INFECTIONS

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					INFECTIONS
Peter Burke 2003 (Updated by Christopher Tracey 2008)



Contents
Definitions .................................................................................................................................................................2
Classification .............................................................................................................................................................3
     Isolated Infections..............................................................................................................................................3
     Unresolved Bacteriuria during Therapy .............................................................................................................3
     Recurrent Urinary Tract Infections ....................................................................................................................3
Incidence and Epidemiology .....................................................................................................................................4
Pathogenesis ............................................................................................................................................................4
  Routes of Infection ................................................................................................................................................4
  Urinary Pathogens ................................................................................................................................................4
  Fastidious Organisms ...........................................................................................................................................5
  Bacterial Virulence Factors ...................................................................................................................................5
  Bacterial Adherence and Colonization ..................................................................................................................5
Diagnosis ..................................................................................................................................................................5
  Urine Collection .....................................................................................................................................................5
  Urinalysis ...............................................................................................................................................................5
  Urine Culture .........................................................................................................................................................6
  Localization ...........................................................................................................................................................6
Imaging Techniques .................................................................................................................................................7
  Indications .............................................................................................................................................................7
Principles of Antimicrobial Therapy ..........................................................................................................................8
  Antimicrobial Formulary ........................................................................................................................................8
     Trimethoprim-Sulfamethoxazole .......................................................................................................................9
     Nitrofurantoin .....................................................................................................................................................9
     Cephalosporins ..................................................................................................................................................9
     Aminopenicillins .................................................................................................................................................9
     Aminoglycosides............................................................................................................................................. 10
     Aztreonam ...................................................................................................................................................... 10
     Fluoroquinolones ............................................................................................................................................ 10
  Choice of Antimicrobial Agents .......................................................................................................................... 10
  Duration of Therapy ........................................................................................................................................... 10
  Antimicrobial Prophylaxis for Transurethral Procedures .................................................................................... 11
  Antimicrobial Prophylaxis for Transrectal Prostatic Needle Biopsy ................................................................... 11
  Asymptomatic Bacteriuria .................................................................................................................................. 11
Factors Increasing Morbidity and/or Mortality........................................................................................................ 12
     Obstruction ..................................................................................................................................................... 12
     Urea-Splitting Bacteria That Cause Struvite Renal Stones ............................................................................ 12
     Congenital Urinary Tract Anomalies............................................................................................................... 12
     Catheter Drainage .......................................................................................................................................... 12
     Renal Papillary Necrosis ................................................................................................................................ 12
     Diabetes Mellitus ............................................................................................................................................ 13
     Spinal Cord Injury with High-Pressure Bladders ............................................................................................ 13
     Pregnancy ...................................................................................................................................................... 13
     Acute Bacterial Prostatitis .............................................................................................................................. 13
Upper Tract Infections ........................................................................................................................................... 13
  Acute Pyelonephritis .......................................................................................................................................... 13
  Chronic Pyelonephritis ....................................................................................................................................... 14
  Emphysematous Pyelonephritis ......................................................................................................................... 15
  Renal Abscess ................................................................................................................................................... 16
  Infected Hydronephrosis and Pyonephrosis ...................................................................................................... 17
  Perinephric Abscess .......................................................................................................................................... 17
  Xanthogranulomatous Pyelonephritis ................................................................................................................ 18
     Pathogenesis .................................................................................................................................................. 18
     Clinical Presentation ....................................................................................................................................... 18
    Bacteriology and Laboratory Findings ............................................................................................................ 19
    Radiologic Findings ........................................................................................................................................ 19
    Management................................................................................................................................................... 19
  Malacoplakia ...................................................................................................................................................... 19
    Pathogenesis .................................................................................................................................................. 20
    Pathology........................................................................................................................................................ 20
    Clinical Presentation ....................................................................................................................................... 20
    Radiologic Findings ........................................................................................................................................ 20
    Management................................................................................................................................................... 21
  Renal Echinococcosis ........................................................................................................................................ 21
Bacteremia, Sepsis, and Septic Shock .................................................................................................................. 22
  Pathophysiology ................................................................................................................................................. 22
Lower Tract Infections ........................................................................................................................................... 23
  Uncomplicated Cystitis ....................................................................................................................................... 23
  Recurrent Urinary Tract Infections ..................................................................................................................... 24
  Symptomatic Infections versus Infections Detected on Screening Surveys for Bacteriuria .............................. 26
  Urethral Syndrome ............................................................................................................................................. 26
Urinary Tract Infections During Pregnancy............................................................................................................ 26
  Anatomic and Physiologic Changes during Pregnancy ..................................................................................... 26
  Natural History of Bacteriuria during Pregnancy ................................................................................................ 27
  Complications Associated with Bacteriuria during Pregnancy ........................................................................... 27
  Management of Bacteriuria during Pregnancy .................................................................................................. 27
Urinary Tract Infections in the Elderly.................................................................................................................... 28
Urinary Tract Infections in Patients with Spinal Cord Injury .................................................................................. 29
Other Infections ..................................................................................................................................................... 30
  Fournier's Gangrene .......................................................................................................................................... 30
  Periurethral Abscess .......................................................................................................................................... 31




DEFINITIONS
     Urinary tract infection
       inflammatory response of the urothelium to bacterial invasion that is usually associated with bacteriuria
          and pyuria
     Bacteriuria
       presence of bacteria in the urine
           implies that these bacteria are from the urinary tract and are not contaminants from the skin, vagina,
               or prepuce
     Pyuria
       presence of white blood cells (WBCs)
           without bacteriuria warrants evaluation for tuberculosis, stones, or cancer
     Acute pyelonephritis
       clinical syndrome of chills, fever, and flank pain accompanied by bacteriuria and pyuria
     Chronic pyelonephritis
       shrunken, scarred kidney, diagnosed by morphologic/radiologic/functional evidence of renal disease
       may be postinfectious but is frequently not associated with UTI
     Cystitis
       inflammation of the bladder
           may be histologic, bacteriologic, or cystoscopic description, or a clinical syndrome that is usually
               accompanied by an abrupt onset of dysuria, increased frequency, urgency, and suprapubic pain
     Urethritis
       inflammation of the urethra
     Uncomplicated
       infection in a healthy patient with a structurally and functionally normal urinary tract
     Complicated
       infection in a patient who is compromised and/or has a urinary tract with a structural or functional
          abnormality
   Recurrent infections
     due to either reinfection or bacterial persistence
        reinfection
            recurrent infection with different bacteria from outside the urinary tract
            each infection is a new event; the urine must show no growth after the preceding infection
        bacterial persistence
            recurrent UTI caused by the same bacteria from a focus within the urinary tract
   Prophylactic antimicrobial therapy
     prevention of reinfections of the urinary tract by the administration of antimicrobial drugs
   Suppressive antimicrobial therapy
     suppression of a focus of bacterial persistence that cannot be eradicated

CLASSIFICATION
   four categories
     isolated infections
     unresolved infections
     recurrent UTIs that are reinfections
     recurrent infections resulting from bacterial persistence

Isolated Infections
   first infections or those isolated from previous infections by at least 6 months
   occur in 25% to 30% of women between the ages of 30 and 40 years

Unresolved Bacteriuria during Therapy
   indicates that the initial therapy has been inadequate
   causes of unresolved bacteriuria
     bacterial resistance
          tetracyclines, sulfonamides, and penicillins are notorious for producing resistance in the fecal
            bacteria
          nitrofurantoin and the quinolones do not cause plasmid-mediated (R factor) resistance
     development of bacterial resistance in initially susceptible organism
     2 different organisms with mutually excusive susceptibilities
     rapid reinfection with a new, resistant species
     azotemia
          diseased kidney cannot achieve bactericidal concentrations of the antimicrobial agent
     papillary necrosis
     giant staghorn
     self-inflicted infections or non-compliance

Recurrent Urinary Tract Infections
   either reinfection from outside the urinary tract or bacterial persistence in a focus
   Reinfections
     >95% of all recurrent infections in females are reinfections of the urinary tract
   Bacterial Persistence
     correctable urologic abnormalities that cause bacteria to persist within the urinary tract between
        episodes of recurrent bacteriuria
         infection stones
         chronic bacterial prostatitis
         unilateral infected atrophic kidneys
         duplicated/ectopic ureters
         foreign bodies
         urethral diverticula and infected paraurethral glands
         unilateral MSK
         nonrefluxing infected ureteric stumps after nephrectomy
         infected urachal cysts
         papillary necrosis
         perivesical abscess with fistula to bladder
       Categorised (by chris)
         Foreign bodies
            Foreign bodies (IDC), stones, necrotic papilla
         Fistula / abscess
         Sumps
            Kidney
                MSK, atrophic kidney, calyceal diverticulum
            Ureter
                Duplication, ectopic, stumps
            Bladder
                Diverticulum, urachal remnants, prostatitis
            Urethra
                Diverticulum, prostatitis, paraurethral glands


INCIDENCE AND EPIDEMIOLOGY
   overall prevalence of bacteriuria ~3.5%, with prevalence generally increasing with age
   symptomatic UTI affects 30% of women 20-40 years (30 times men)
   with increasing age, the ratio of women to men with bacteriuria progressively decreases
   at least 20% of women and 10% of men >65 years have bacteriuria
   57-80% of bacteriuric women who are untreated or treated with placebo clear their infections spontaneously
   70% of recurrent infections are caused by reinfection with different organisms
   antimicrobial treatment appears to alter only the time until recurrence


PATHOGENESIS

Routes of Infection
   Ascending Route
     bacteria enter the urinary tract from the fecal reservoir via ascent through the urethra
     enhanced in individuals with significant soilage of the perineum with feces, women using spermicidal
       agents, and patients with intermittent or IDCs
     evidence strongly suggests that most episodes of pyelonephritis are caused by retrograde ascent of
       bacteria from the bladder through the ureter to the renal pelvis and parenchyma
   Hematogenous Route
     uncommon in normal individuals
     occasionally secondary infection occurs in patients with Staphylococcus aureus bacteremia from oral
       sites or with Candida fungemia
   Lymphatic Route
     in unusual circumstances such as a severe bowel infection or retroperitoneal abscesses

Urinary Pathogens
   most UTIs are caused by facultative anaerobes that are able to grow under either anaerobic or aerobic
    conditions and usually originate in the bowel flora
   E. coli 85% of community-acquired and 50% of hospital-acquired infections
   others
     gram-negative Enterobacteriaceae including Proteus and Klebsiella
     gram-positive E. faecalis and Staphylococcus saprophyticus are responsible for the remainder of most
        community-acquired infections
   diabetics are more likely to have urinary tract infections caused by Klebsiella, group B streptococci,
    Aerococcus and non–albicans Candida
   less common organisms such as Gardnerella vaginalis, Mycoplasma species, and Ureaplasma urealyticum
    may infect patients with intermittent or IDCs
Fastidious Organisms
   symptomatic anaerobic infections are uncommon
   must be suspected when a patient with bladder irritative symptoms has cocci or gram-negative rods seen on
    microscopic examination of the centrifuged urine
   frequently found in suppurative infections of the genitourinary tract
   usually Bacteroides species including Bacteroides fragilis, Fusobacterium species, anaerobic cocci, and
    Clostridium perfringens

Bacterial Virulence Factors
   uropathogenic bacteria are selected from the fecal flora by the presence of virulence factors that enable
    them to adhere to and colonize the perineum and urethra and migrate to the urinary tract

Bacterial Adherence and Colonization
   extent to which bacteria adhere is a critical event in colonization and infection
   adhesins on the bacterial surface help dictate the tissue specificity of invading bacteria and can modulate
    host cell response to infection
   bacterial cell structures most important in binding of bacteria to epithelial cells are long, filamentous protein
    appendages called pili or fimbriae
   E. coli produces a number of antigenically and functionally different types of pili on the same cell
   Primary Bladder and Vaginal Defences
     flow of urine + voiding are the primary bladder defences against infection
     others
         low pH and osmolarity of urine
         salts, urea, and organic acids present in urine
         lactoferrin within urine can scavenge essential iron away from bacteria
         soluble and cell-associated factors within the bladder, including low-molecular-weight sugars, and
             secretory immunoglobulin A (IgA) can act as antiadherence factors competitively inhibiting bacterial
             attachment to the bladder surface
         antibacterial effects of bladder mucosa
              urinary and local antibodies, polymorphonuclear neutrophils, and cytokines such as interleukin
                 (IL)-6 and IL-8
         vaginal flora
              lactobacilli make up the majority of the vaginal flora in healthy, premenopausal women
              sexual intercourse, use of antibiotics and intravaginal antimicrobials including antimycotics, and
                 spermicides have been identified as factors that reduce the normal lactobacillus-dominant
                 vaginal flora and increase susceptibility to UTI


DIAGNOSIS

Urine Collection
   Suprapubic Aspiration
     highest degree of reliability
     highly useful in newborn infants and in patients with paraplegia
   Urethral Catheterization in the Female Patient
     some nonbacteriuric bladder urine specimens will be contaminated by urethral bacteria
     incidence of introduction of infection varies with the type of patient catheterized
     can prevent catheter-induced infections with single dose oral antimicrobial agent
   Segmented Voided Urine Specimens
     self-caught, midstream voided urine specimen

Urinalysis
   microscopic urinalysis for bacteriuria, pyuria, and hematuria should be performed
   most important error is a false-negative result
     imposed by the microscope on the volume of urine that can be observed
   second error of urinalysis (i.e., a false-positive result) is the reverse of the first error
   bacteria are seen in the microscopic sediment but the urine culture shows no growth
     absence of pyuria should cause the diagnosis of UTI to be questioned until urine culture data are
        available
     microscopic hematuria is found in 40-60% of cases of cystitis and is uncommon in other dysuric
        syndromes

Urine Culture
   two techniques available
     direct surface plating
         known amount of urine on split-agar disposable plates
     dip-slides
         simpler but somewhat less accurate
         plastic slides attached to screw-top caps
         urine must be refrigerated immediately on collection and should be cultured within 24 hours
         most bacteria allowed to incubate for several hours in bladder urine reach cfu counts of 10 /ml
                                                                                                     5

             nb 20-40% of women with symptomatic UTIs present with bacteria counts of 10 -10 cfu/ml of
                                                                                              2    4

                 urine
     overdiagnosis
         women susceptible to infection often carry large numbers of pathogenic bacteria on the perineum
            that contaminate otherwise sterile bladder urine
         uncircumcised men may harbor uropathogenic bacteria on their foreskins

Localization
   Kidney
     Fever and Flank Pain
         thought to indicate pyelonephritis
     Ureteral Catheterization
         allows separation of bacterial persistence into upper/lower urinary tracts and laterality
         when applied to large numbers of bacteriuric patients, 45% were found to have bladder infection
           only; 27%, unilateral renal bacteriuria; and 28%, bilateral renal bacteriuria
     Fairley Bladder Washout Test
     washing the bladder free of bacteria and then collecting serial cultures that would essentially represent
        upper tract urine

   Immunologic Responses
     both cellular and humoral
        humoral immunity is characterized by the formation of antibodies (immunoglobulins) in response to
          invasive bacterial antigens
     Direct Agglutination Tests
        mixing dilutions of serum with bacterial suspensions
        presence of serum antibodies to the bacteria (antigen-specific antibodies) is detected by
          agglutination of particles
        primarily multivalent antibodies, such as IgM, combine with surface bacterial antigens to cause the
          clumping
     Passive Agglutination Tests
        red blood cells with their attached antigens mixed with dilutions of serum
        antigen-specific antibodies can be detected by measuring agglutination of the red blood cells
     Antibody-coated Bacteria
        bacteria mixed with fluorescein-conjugated anti–human globulin demonstrate antibody coating under
          a fluorescence microscope
        false-positives
           local production of bladder antibody in children
           prostatitis
           hemorrhagic cystitis
             cystitis associated with many submucosal, lymphoid follicles at cystoscopy
       Enzyme-linked Immunosorbent Assays and Radioimmunoassays for Immunoglobulins
         in the urinary tract used to detect and measure serum, urine, and prostatic fluid, total
            immunoglobulins, and antigen-specific antibodies
         more sensitive and quantitative than agglutination or HA tests
       Immunoglobulin Response in Pyelonephritis
         serum levels of antibodies (primarily IgM) against the infecting bacteria are elevated in human acute
            clinical pyelonephritis
         antigen-specific antibodies stimulated by UTI have also been identified both directly and indirectly
       Diagnostic Use of Antibody Titers
         measurements of antigen-specific antibody in serum or urine may be more useful in chronic
            bacterial infections than in acute infections


IMAGING TECHNIQUES

Indications
   patients with risk factors that may require intervention in addition to antimicrobial treatment
   calculi, especially infection (struvite) stones; ureteral tumors; ureteral strictures; congenital obstructions; or
    previous genitourinary surgery, such as ureteral reimplantation or urinary diversion procedures, that may
    have caused obstruction
   diagnose a focus of bacterial persistence

   Plain Film of the Abdomen
     radiopaque calculi and unusual gas patterns in emphysematous pyelonephritis
   Plain Film Renal Tomograms
     small or poorly calcified stones despite overlying gas and fecal shadows
     localize findings (calcifications or gas) to the kidney
   Excretory Urogram
     not required in uncomplicated infections
     useful to determine the exact site and extent of urinary tract obstruction
   Voiding Cystourethrogram
     important in assessing VUR
     may be used to evaluate patients with neuropathic bladders and the rare female patient who has a
        urethral diverticulum causing her persistent infections
   Renal USS
     useful in eliminating the concern of hydronephrosis associated with UTI, pyonephrosis, and perirenal
        abscesses
   CT and MRI
     offer the best anatomic detail but cost prevents them from being screening procedures
     more sensitive than IVP or USS in the diagnosis of acute focal bacterial nephritis and renal and perirenal
        abscesses
   Radionuclide Studies
     gallium 67 and indium 111 have been used to detect renal or perirenal infections
         Gallium
              has been used to distinguish some upper tract from lower tract infections
              disadvantage of being unable to differentiate simple inflammatory processes from
                 pyelonephritis, pyonephrosis, perirenal abscess, or renal tumors
         Indium
              111–labeled leukocytes accumulate only in sites of inflammation and not in normal kidneys or in
                 tumors
              highly specific for inflammation
     Agent              Target            Mechanism of Action               Major Mechanisms of Resistance




PRINCIPLES OF ANTIMICROBIAL THERAPY
   Initial Elimination of Bacteriuria
     if the proper antimicrobial agent is used urine will show no bacterial growth within hours
     principle of no bacterial growth in urine during treatment is the basis for successful antimicrobial therapy
   Serum versus Urinary Levels of Antimicrobial Agents
     urinary levels and not serum concentrations are important in the cure of UTI
   Bacterial Resistance
     three categories
          natural Resistance
                absence of drug-susceptible substrate in some species of bacteria
                eg all Proteus species are resistant to nitrofurantoin, and E. fecalis is always resistant to
                  cephalexin
          selection of resistant mutants within the urinary tract during therapy
                within 48 hours of therapy the susceptible population is replaced in the urine by an equal
                                              5
                  population of bacteria (≥10 ) of the original strain, which is now resistant to the antimicrobial
                  agent
                occurs 5-10% of the time
                classic way to prevent selection of these resistant clones is to treat a susceptible infection with
                  two or even three antimicrobial agents simultaneously
          transferable, extrachromosomal, plasmid-mediated (R factor) resistance
                more important to the urologist than selection of resistant clones within urinary tract because
                   much more common
                   transferable or "infectious" nature of R factors produces multiply resistant strains, making
                       therapy more difficult
                   R-factor resistance occurs only in the fecal flora, never within the urinary tract, which makes
                       the latter amenable to the intelligent use of antimicrobial drugs with regard to their influence
                       on the fecal flora
     Factors Modifying Resistance
          amount and duration of antimicrobial used
          reduction in duration of therapy and amount of drug used can lead to reemergence of more
               susceptible strains

Antimicrobial Formulary
β-Lactams           Cell wall        Inhibit cell-wall cross-linking    1. Drug inactivation (β-lactamase)
                                                                        2. Insensitivity of target (altered penicillin-binding
(penicillins and
                                                                        proteins)
cephalosporins)                                                         3. Decreased permeability (altered gram-negative
                                                                        outer-membrane porins)
                                                                        4. Active efflux

Aminoglycosides     Protein          Binds to 30S ribosomal subunit 1. Drug inactivation (aminoglycoside-modifying
                                                                        enzyme)
(gentamicin)        synthesis
                                                                        2. Decreased permeability through gram-negative
                                                                        outer membrane
                                                                        3. Active efflux

Sulfonamides and Cell                Competitively inhibit enzymes      Production of insensitive targets [dihydropteroate
                                                                        synthetase (sulfonamides) and dihydrofolate
trimethoprim     metabolism          involved in two steps of folic     reductase (trimethoprim)] that bypass metabolic
                                     acid biosynthesis                  block

Quinolones          DNA              Inhibit DNA gyrase (A subunit)     1. Insensitivity of target (mutation of gyrase genes)
                                                                        2. Decreased intracellular drug accumulation (active
(ciprofloxacin)     synthesis        and topoisomerase IV
                                                                        efflux)

Vancomycin          Cell wall        Interferes with addition of new    Alteration of target (substitution of terminal amino
                                                                        acid of peptidoglycan subunit)
                                     cell-wall subunits (muramyl
                                     pentapeptides)

Trimethoprim-Sulfamethoxazole
       TMP alone is as effective as the combination for most uncomplicated infections and may be associated
        with fewer side effects
       SMX contributes to efficacy in the treatment of upper tract infection via a synergistic bactericidal effect
        and may diminish the emergence of resistance
       TMP alone or in combination with SMX is effective against most common uropathogens with the notable
        exception of enterococci and Pseudomonas species
       disadvantages are relatively frequent adverse effects, consisting primarily of skin rashes and
        gastrointestinal complaints
Nitrofurantoin
       effective against most uropathogens including Enterobacteriaceae
       not effective against Pseudomonas and Proteus species
       rapidly excreted from the urine but does not obtain therapeutic levels in most body tissues including
        those of the urinary and gastrointestinal tracts
       therefore not useful for upper tract or complicated infections
       minimal effects on the resident fecal and vaginal flora
       acquired bacterial resistance exceedingly low
Cephalosporins
       activity high against Enterobacteriaceae
       do not provide activity against enterococci (or serratia)
       first-generation cephalosporins have greater activity against gram-positive organisms
       second-generation cephalosporins have activity against anaerobes
       third-generation cephalosporins are more reliably active against community-acquired and nosocomial
        gram-negative organisms than other β-lactam antibiotics
Aminopenicillins
       ampicillin/amoxicillin
       resistance in up to 30% of common urinary isolates has lessened the utility of these drugs
       effects on the normal fecal and vaginal flora can predispose to reinfection with resistant strains and
        frequently lead to Candida vaginitis
       addition of the β-lactamase inhibitor clavulanate to amoxicillin greatly improves activity against β-
        lactamase–producing bacteria that are resistant to amoxicillin alone
       high cost and frequent gastrointestinal side effects argue against its use for first-line therapy of
        uncomplicated UTIs
       extended-spectrum penicillin derivatives (e.g., piperacillin, mezlocillin, azlocillin) retain ampicillin's
        activity against enterococci and offer activity against many ampicillin-resistant gram-negative bacilli
Aminoglycosides
       when combined with TMP-SMX, or ampicillin, are the first drugs of choice for patients with urosepsis
       nephrotoxicity is well recognized, and careful monitoring of patients with renal impairment associated
        with infection is indicated
       once-daily regimens maximize bacterial killing by optimizing the peak concentration–to–MIC ratio and
        reduce potential for toxicity
Aztreonam
       activity only against gram-negative aerobes, and, like all β-lactams, it is not nephrotoxic
       spectrum of activity is less broad than that of the third-generation cephalosporins
       should be used primarily in patients who have penicillin allergies
Fluoroquinolones
       broad spectrum
       highly effective against Enterobacteria as well as P. aeruginosa
       resistance to staphylococci may develop while the patient is on therapy
       most anaerobic bacteria are resistant to these drugs, and, therefore, the normal vaginal and fecal flora
        are not altered
       for most uncomplicated UTIs only slightly more effective than TMP-SMX
       as resistance to TMP-SMX increases, the fluoroquinolones have distinct advantages in empirical
        treatment of patients recently exposed to antimicrobials, in the outpatient treatment of complicated UTIs
        or in difficult-to-treat pathogens such as P. aeruginosa
       first-line agents in areas in which a significant level of bacterial resistance (>20%) exists to agents like
        ampicillin and TMP-SMX
       all can be administered orally and ciprofloxacin, ofloxacin, and levofloxacin can also be administered
        parenterally
       not nephrotoxic but renal insufficiency prolongs the serum half-life, requiring adjusted dosing in patients
        with creatinine clearances of less than 30 ml/min
       adverse reactions uncommon; gastrointestinal disturbances are more frequent
       hypersensitivity, skin reactions, mild CNS and peripheral nervous system reactions, and even acute
        renal failure have been reported
       contraindicated in children, adolescents, and pregnant or nursing women

Choice of Antimicrobial Agents
   determined by
     complicated or uncomplicated
     spectrum of activity of the drug against the probable pathogen
     history of hypersensitivity
     potential side effects, including renal and hepatic toxicity
     cost
     favorable or unfavorable effects of the antimicrobial on the vaginal and fecal flora are important in
        women with recurrent UTIs

Duration of Therapy
   Symptomatic Acute Cystitis
     compared to 7-10 days, 3-day therapy appears to be optimal because there is no difference in cure
       rates, side effects are reduced, and the cost is decreased
     7-day regimen should be considered in the presence of mitigating circumstances such as symptoms for
       over 7 days, recent UTI, age older than 65 years, diabetes, or pregnancy
     single-dose therapy
        convenient and inexpensive but
        resolution of symptoms is slower and failure/recurrence rates greater than with longer therapy
     young healthy men 7-day course of TMP-SMX, TMP, or a fluoroquinolone
        if recurrent infection, they should be referred for urologic evaluation
        in older men, all UTIs should be treated as if they are complicated
   Acute Uncomplicated Pyelonephritis in Women
     broad-spectrum antibiotics until culture and susceptibilities available
     outpatient-acquired infection
           without sepsis, nausea, and vomiting and who are not pregnant
             oral 7-day therapy with a fluoroquinolone is more effective than TMP-SMX
         sufficiently ill to require hospitalization
             parenteral fluoroquinolone, an aminoglycoside, or an extended-spectrum cephalosporin
             single parenteral dose of an antimicrobial (ceftriaxone, gentamicin, or a fluoroquinolone) before
                 initiating oral therapy can also be used
             when stable, parenteral therapy may be converted to oral therapy for 10-14 days
   Patients with Unresolved or Complicated Infections
     14-21 day regimen should be used in patients who remain bacteriuric on antimicrobial therapy or who
        have structural or functional abnormalities of the urinary tract or abnormal host defences
     more extended therapy of up to 6 weeks does not appear to be superior to 14-21-day therapy

Antimicrobial Prophylaxis for Transurethral Procedures
   preoperative UTI should be eradicated before the procedure is started
   failure to eradicate bacteriuria results in bacteremia in 50% of patients

   patients with risk of endocarditis
     ampicillin + gentamicin IM ½ hour before the procedure or IV immediately before, followed by amoxicillin
        1.5 g orally, 6 hours after the initial dose
     alternatively, the parenteral regimen may be repeated once, 8 hours after the initial dose.
     allergic to penicillin
         vancomycin + gentamicin IM or IV 1 hour before the procedure
         may be repeated once, 8 hours after the initial dose.

   patients without risk of endocarditis
     controversial
     if no preoperative or postoperative antimicrobial agents are used in transurethral resection of the
        prostate (TURP), postoperative bacteriuria is found in 11-45% of patients up to 1 month postoperatively
     all but one study suggest that postoperative UTIs decrease from a range of 26-42% to a range of 0-12%
        when various antimicrobial agents are used prophylactically

       prophylaxis should be broken into two parts
         prophylaxis to prevent operative and perioperative bacteremia
         prophylaxis to prevent postoperative UTIs
       if no growth in preoperative urine and no gram-negative organisms in the urethra
         probably no prophylaxis to prevent bacteremia is needed
         if not known, 6-12% of patients may be considered to have unsuspected bacteriuria and up to 66%
             risk of becoming bacteremic if not treated prophylactically
       any patient with an IDC should be assumed to be infected and must achieve no growth in the urine
        preoperatively through administration of at least two doses of a drug that has broad coverage against
        gram-negative organisms

Antimicrobial Prophylaxis for Transrectal Prostatic Needle Biopsy
   complications include cystitis, prostatitis, epididymitis, pyelonephritis, local abscess, osteomyelitis, and
    sepsis
   5 minutes after transrectal biopsy 76% of patients (16 of 21) had bacteremia proved by blood culture >50%
    anaerobic (mainly Bacteroides species and anaerobic streptococci)
   fluoroquinolone given several hours before the procedure and continued for 24 hours after the procedure is
    effective

Asymptomatic Bacteriuria
   although 80% of patients with asymptomatic bacteriuria can be cured with a 7-day course of oral
    antimicrobial therapy, long-term cure rates are no better than those of placebo therapy because of
    reinfections in treated patients and spontaneous cures in untreated subjects
   patients at risk for increased morbidity from bacteriuria, such as patients with severe diabetes, pregnant
    women, and others, should be treated
FACTORS INCREASING MORBIDITY AND/OR MORTALITY

Obstruction
Urea-Splitting Bacteria That Cause Struvite Renal Stones
      P. mirabilis not uncommon cause of bacteriuria
      struvite stones form in patients who have a protracted infection with P. mirabilis, an infection that is often
       asymptomatic or minimally symptomatic
      causes intense alkalinization of the urine with precipitation of calcium, magnesium, ammonium, and
       phosphate salts and the subsequent formation of branched struvite renal stones
      when ESWL is used to fragment infection stones, patient should be maintained on appropriate
       antimicrobial therapy until the fragments pass
      any fragments left behind at the time of surgical removal leave residual bacteria within the interstices of
       the stone; these bacteria ensure recurrence of the staghorn calculus with its attendant morbidity
Congenital Urinary Tract Anomalies
      recurrent bacteriuria is characterized by the same organism until the anomalous colonized structure is
       surgically removed
      include
        nonfunctioning duplications of the renal collecting system, which accompany ectopic ureters
        pericalyceal diverticula that lose their free communication with pelvic urine
        urachal cysts of the dome of the bladder
        unilateral medullary sponge kidneys
        congenital obstructions that have produced nonfunctioning kidneys into which effective urinary
            concentrations of antimicrobial agents cannot be delivered
Catheter Drainage
      most common predisposing factor for hospital-acquired UTIs is urethral instrumentation
      UTIs in patients with IDCs directly related to the duration of catheterization
      daily rate of acquired bacteriuria is about 5% per day of catheterization
      any patient who risks endocarditis or who has a prosthesis that might become infected should receive
       antimicrobial prophylaxis before catheter manipulation
      aetiology (three sources)
        periurethral and perineal organism
        organisms colonizing the collecting bag or collecting device
        breaks in the drainage system caused by opening the closed system for irrigation, changes in
           tubing, or emptying the collecting bag
      E. coli predominates, others Candida species, Enterococci, P. aeruginosa, Klebsiella, Enterobacter, and
       S. aureus
      Methods to Decrease Catheter-Associated Urinary Tract Infections
        closed drainage systems
      Antimicrobial Therapy
        depends on the circumstances of the catheterization
        IDCs that will be removed after only a few days require the same treatment as patients undergoing
           TURP
        antimicrobial should be given just before catheter removal, and the urine should be cultured after
           removal of the catheter to verify no growth
        chronic indwelling urethral catheters, no methods totally eliminate catheter-associated infections
        asymptomatic bladder bacteriuria, funguria, or pyuria should not be treated as long as the catheter
           remains and the patient is asymptomatic
        if a urea-splitting bacteriuria is identified, it should be eradicated by a 3- to 5-day course of
           antimicrobial therapy
        if elevated temperature or flank pain who has a catheter-associated infection must be treated for
           clinical acute pyelonephritis with the appropriate antimicrobial agent until asymptomatic
Renal Papillary Necrosis
      role of infection in development/progression of RPN is controversial
       multiple predisposing conditions have been associated with the development of RPN
         DM
         pyelonephritis
         urinary tract obstruction
         analgesic abuse
         sickle-cell haemoglobinopathies
         renal transplant rejection
         cirrhosis of the liver
         dehydration, hypoxia and jaundice of infants
       RPN is a spectrum of disease
       may have an acute fulminating illness with rapid progression or may have a chronic disease that is
        incidentally discovered on IVP
       some may chronically pass necrotic tissue in their urine
       diagnosis may be made from the passage of necrotic papillae in the urine, most often made from the
        excretory urogram
       show various degrees of renal involvement with either medullary or papillary changes causing irregular
        sinuses or medullary cavities or classic ring shadows
Diabetes Mellitus
       emphysematous pyelonephritis is an uncommon complication of acute pyelonephritis that occurs in
        diabetic patients, with an overall mortality of 43%
Spinal Cord Injury with High-Pressure Bladders
Pregnancy
Acute Bacterial Prostatitis


UPPER TRACT INFECTIONS

Acute Pyelonephritis
   Clinical Presentation
     ranges from gram-negative sepsis to cystitis with mild flank pain
     classic presentation is abrupt onset of chills, fever, and costovertebral angle tenderness
     75% of patients give a history of previous lower UTIs
     frequently tenderness to deep palpation in the costovertebral angle
     may also simulate GIT abnormalities with abdominal pain, nausea, vomiting, and diarrhea
   Laboratory Findings
     urine cultures are positive
         20% of patients have urine cultures with fewer than 10 cfu/ml and, therefore, negative results on
                                                                    5

             gram staining of the urine
     blood tests may show a polymorphonuclear leukocytosis, increased erythrocyte sedimentation rate,
        elevated C-reactive protein levels, and elevated creatinine levels if renal failure is present
   Bacteriology
     E. coli 80%
     other Enterobacteriaceae family are also cultured from the urine
     of the gram-positive organisms, only E. faecalis, less commonly, S. aureus and S. epidermidis
   Radiologic Findings
     IVP
         generalized or focal renal enlargement
         contralateral kidney may be enlarged as well
         length of 15 cm or >1.5 cm greater than that of the unaffected side consistent with acute
             pyelonephritis
         obstruction of the renal tubules from parenchymal edema and vasoconstriction may impair contrast
             agent excretion
         dilatation of the ureter and renal pelvis without any obstructive cause may be seen
     Renal USS
         useful to show renal size and collecting system obstruction and to delineate focal bacterial nephritis
       Computed Tomography
         not indicated unless the diagnosis cannot be established by an intravenous urogram or if the patient
            does not respond after 72 hours of therapy
   Pathology
     kidney may be grossly enlarged
     usually small, yellow-white cortical abscesses mixed with parenchymal hyperemia
     parenchyma shows a focal, patchy infiltrate of neutrophils
     abscesses may cause tubular destruction; the glomeruli are usually spared
   Treatment
     subdivided
         uncomplicated infection that does not warrant hospitalization
             fluoroquinolones attractive for outpatient therapy
             if gram-positive bacteria are suspected, amoxicillin or amoxicillin–clavulanic acid is
                recommended
         uncomplicated infection in patients with normal urinary tracts who are ill enough to warrant
            hospitalization for parenteral therapy
             for patients requiring parenteral therapy for uncomplicated pyelonephritis, a fluoroquinolone, an
                aminoglycoside with or without ampicillin, or an extended-spectrum cephalosporin with or
                without an aminoglycoside has proven efficacy against enterobacteriaceae, pseudomonas, and
                other gram-negative bacilli
             if symptoms persist beyond 72 hours the possibility of perinephric or intrarenal abscesses,
                urinary tract abnormalities, or obstruction should be considered and radiologic investigation with
                USS or CT performed
             duration of therapy for acute uncomplicated pyelonephritis generally should be 7 days for a
                fluoroquinolone or 14 days for tmp-smx
         complicated infection associated with hospitalization, catheterization, urologic surgery, or urinary
            tract abnormalities
             complicated pyelonephritis and positive blood cultures should be treated for 7 days with
                parenteral therapy
             if blood cultures are negative, 2-3-day parenteral therapy is sufficient
             appropriate oral therapy should be continued for an additional 7-14 days
             repeat urine cultures should be performed 5-7 days after initiation of therapy and 4-6 weeks
                after discontinuation of antimicrobial therapy to ensure that the urinary tract remains free of
                infection
             10-30% of individuals with acute pyelonephritis relapse after a 14-day course of therapy
     in all, antimicrobial therapy should be initiated that will be active against potential uropathogens and
        achieve antimicrobial levels in renal tissue as well as urine

Chronic Pyelonephritis
   definition controversial
   has been used to refer to a variety of chronic renal lesions and has been used synonymously with interstitial
    nephritis, reflux nephropathy, chronic atrophic pyelonephritis, and focal coarse renal scarring
   diagnosed by radiologic and pathologic means
   here the term chronic pyelonephritis refers to the small, contracted, atrophic kidney or to the coarsely
    scarred kidney that has been produced by bacterial infection, whether recent or remote.
   Pathogenesis
     Immunologic Response to Infection
     Bacterial infection of the kidneys in both humans and animals stimulates humoral and cellular immune
        responses
     cause of the renal scarring that unpredictably follows infection is unclear
     leukocyte response is at least partially responsible for renal scarring
     children <4 years with intrarenal reflux commonly have renal scarring present before they have their first
        documented UTI
     if histories of undiagnosed febrile illnesses in early childhood do, indeed, represent pyelonephritis,
        untreated infections may be the cause of scarring in the "chronic pyelonephritic" kidney
     Association with Reflux Neuropathy
         role that bacterial infection of the urinary tract plays in reflux nephropathy is controversial
         natural history and prevalence of reflux nephropathy found incidentally in adults is unknown
   Clinical Presentation
     many have no urologic symptoms, and the condition is discovered incidentally
   Laboratory Findings
     urinary sediment may show leukocytes, proteinuria, and, rarely, leukocyte casts
     urinary concentrating capacity is impaired
     creatinine levels may be increased and creatinine clearance may be decreased
   Radiologic Findings
     IVP
         best technique for diagnosing chronic pyelonephritis
         kidneys are usually small and atrophic
         focal coarse renal scarring with clubbing of the underlying calyx is characteristic
         since the scarring and atrophy commonly affect the renal poles, the renal parenchyma is especially
             thin in these areas
         localized areas of normal renal tissue within a scarred kidney may undergo compensatory
             hypertrophy, suggesting a renal mass
     Voiding Cystourethrogram
         useful, particularly in children, to show VUR, which may be associated with focal renal scarring
   Pathology
     kidney is often diffusely contracted, scarred, and pitted
     scarring is often polar with underlying calyceal blunting
     parenchyma is thin, and the corticomedullary demarcation is lost
     histologic changes are patchy
         interstitial infiltrate of lymphocytes, plasma cells, and occasional polymorphonuclear cells
         portions of the parenchyma may be replaced by fibrosis
         glomeruli may be preserved, completely fibrosed and tubules atrophied
         in general, the changes are nonspecific; they also may be seen in toxic exposures, postobstructive
             atrophy, hematologic disorders, postirradiation nephritis, ischemic renal disease, and
             nephrosclerosis
   Sequelae of Pyelonephritis
     most of the changes of chronic pyelonephritis seem to occur in infancy, probably because the growing
        kidney is most susceptible to scarring

Emphysematous Pyelonephritis
   acute necrotizing parenchymal and perirenal infection caused by gas-forming uropathogens
   pathogenesis is poorly understood
   usually occurs in diabetic patients
     postulated that the high tissue glucose levels provide the substrate for microorganisms
   should be considered a complication of severe pyelonephritis rather than a distinct entity
   overall mortality is 43%
   Clinical Presentation
     severe, acute pyelonephritis that fails to resolve during the first 3 days of treatment
     almost all patients display the classic triad of fever, vomiting, and flank pain
     pneumaturia absent unless the infection involves the collecting system
     urine cultures are invariably positive
     E. coli is most frequently identified; Klebsiella and Proteus are less common
   Radiologic Findings
     diagnosis is established radiographically
     hallmark is intraparenchymal gas
     as the infection progresses, gas extends to the perinephric space and retroperitoneum
     should not be confused with cases of pyelonephritis in which air is in the collecting system of the kidney
     IVP rarely of value because the affected kidney usually is nonfunctioning or poorly functioning
     obstruction demonstrated in 25%
     USS usually demonstrates strong focal echoes, suggesting the presence of intraparenchymal gas
   Management
       usually acutely ill, and rapid supportive measures are required
       appropriate antimicrobial agents, and treatment of diabetes must be initiated
       obstruction must be eliminated
       function of the contralateral kidney must be established (10% bilateral)
       persistent intraparenchymal renal gas documents ineffective treatment
         then surgical drainage or nephrectomy is needed
       surgical treatment must be complete extirpation, because most attempts at renal sparing have been
        unsuccessful in retaining renal function or decreasing patient morbidity
       selected cases, percutaneous drainage combined with medical therapy can produce complete recovery
        and preserve renal function

Renal Abscess
   collection of purulent material confined to the renal parenchyma
   gram-negative organisms implicated in majority
   ascending infection associated with tubular obstruction from prior infections or calculi appears to be the
    primary pathway for the establishment of gram-negative abscesses
   ⅔ of gram-negative abscesses in adults are associated with renal calculi or damaged kidneys
   Clinical Presentation
     may present with fever, chills, abdominal or flank pain, and, occasionally, weight loss and malaise
     symptoms may be vague and delay diagnosis until surgical exploration or autopsy
     may have recent gram-positive source of infection 1 to 8 weeks before
          carbuncles, intravenous drug abuse, mouth, lungs, and bladder
     complicated urinary tract infections associated with stasis, calculi, pregnancy, neurogenic bladder, and
         diabetes mellitus also appear to predispose the patient to abscess formation
   Laboratory Findings
     marked leukocytosis
     blood cultures usually positive
     pyuria and bacteriuria may not be evident unless the abscess communicates with the collecting system
   Radiologic Findings
     generalized renal enlargement with distortion of the renal contour on the affected side
     scoliosis is often present, with a concavity of the curve facing the affected kidney
     more chronic abscess
          renal mass lesion
          calyceal system may be poorly defined or show distortion or even amputation
     USS
          echo-free or low–echo-density space-occupying lesion with increased transmission
          margins indistinguishable in the acute phase, but the structure contains a few echoes, and the
              surrounding renal parenchyma is edematous
          internal appearance may vary from a virtually solid lucent mass to one with large numbers of low-
              level internal echoes
     CT
          well defined both before and after contrast agent enhancement
          initially, renal enlargement and focal, rounded areas of decreased attenuation
          after several days, thick fibrotic wall begins to form around the abscess
          echo-free or slightly echogenic mass due to the presence of necrotic debris is seen
          chronic abscess shows obliteration of adjacent tissue planes, thickening of Gerota's fascia, a round
              or oval parenchymal mass of low attenuation, and a surrounding inflammatory wall of slightly higher
              attenuation that forms a ring when the scan is enhanced with contrast material
   Management
     IV antimicrobials and careful observation of a small abscess <3cm, if begun early enough in the course
         of the process, may obviate surgical procedures
     CT- or US-guided needle aspiration may be necessary to differentiate an abscess from a hypervascular
         tumor
     empirical antimicrobial therapy is dependent on the presumed source of the infection
     3-5 cm diameter and smaller abscesses in immunocompromised hosts or those that do not respond to
         antimicrobial therapy should be drained percutaneously
       surgical drainage procedure of choice for most renal abscesses greater than 5 cm in diameter

Infected Hydronephrosis and Pyonephrosis
   infected hydronephrosis
     bacterial infection in a hydronephrotic kidney
   pyonephrosis
     infected hydronephrosis associated with suppurative destruction of the parenchyma of the kidney, in
        which there is total or nearly total loss of renal function
   Clinical Presentation
     usually very ill, with high fever, chills, flank pain, and tenderness
   Radiologic Findings
     urographic findings are those of urinary tract obstruction and depend on degree and duration of
        obstruction
     IVP
         poorly functioning/nonfunctioning hydronephrotic kidney in 50%
     USS
         echoes from inferior portion of collecting system
         fluid-debris level with dependent echoes that shift when patient changes position
         strong echoes with acoustic shadowing from air in the collecting system
         weak echoes throughout a dilated collecting system
     RGP
         usually shows ureteral obstruction with an irregular filling defect in the renal pelvis caused by
             purulent sediment
   Management
     appropriate antimicrobial drugs and drainage of the infected pelvis

Perinephric Abscess
   mortality rate up to 56% caused in part by delay in diagnosis
   thought to arise from hematogenous seeding from sites of infection or from renal extension of an ascending
    UTI
   located within Gerota's fascia
   Clinical Presentation
     classic patient who has a cutaneous infection or UTI that is followed in 1-2 weeks by fever and unilateral
        flank pain is uncommon
     most common complaints fever, flank or abdominal pain, chills, and dysuria; physical findings showed
        flank or abdominal tenderness and fever
   Bacteriology and Laboratory Findings
     urine cultures identified the infecting pathogen in only one third of cases
     blood culture more frequently indicative of perinephric abscess but identified the pathogen in less than
        half of the cases
   Radiologic Findings
     plain film
         missing psoas shadows, apparent renal masses, absent renal outlines, calculi, and retroperitoneal
             gas
     IVP
         little or no function, calicectasis, calculi in 14%, renal displacement in 4%
         renal mobility by fluoroscopy or inspiration-expiration films
         normal kidneys that have not been operated on should move 2-6 cm with respiration
         kidney with a perinephric abscess is fixed to surrounding tissues and does not move with respiration
     USS
         ranges from nearly anechoic mass displacing the kidney to an echogenic collection that tends to
             blend with normally echogenic fat within Gerota's fascia
         CT defines renal distortion and perirenal fluid or gas associated with perinephric abscesses in
             excellent anatomic detail
   Management
     primary treatment is drainage
         reports of successful treatment by antimicrobial agents alone are unusual
       renal sonography and CT make percutaneous aspiration and drainage of small perirenal collections
        possible
       percutaneous drainage contraindicated in large abscess cavities filled with thick, purulent fluid

   Perinephric Abscess versus Acute Pyelonephritis
     two factors differentiated perinephric abscess and acute pyelonephritis
     most patients with uncomplicated pyelonephritis symptomatic for <5 days before hospitalization,
        whereas most with perinephric abscesses were symptomatic for longer than 5 days
     no patient with an acute pyelonephritis remained febrile for longer than 4 days once appropriate
        antimicrobial agents were started
     all patients with perinephric abscesses had a fever for at least 5 days, with a median of 7 days

Xanthogranulomatous Pyelonephritis
   rare, severe, chronic renal infection typically resulting in diffuse renal destruction
   most cases unilateral and result in a nonfunctioning, enlarged kidney associated with obstructive uropathy
    secondary to nephrolithiasis
   gross renal examination reveals yellow nodules and pericalyceal granulation
   found in ~1% of patients with renal inflammation who are evaluated pathologically
   often misdiagnosed as a renal tumor

Pathogenesis
   primary factors necessary
     obstruction
     UTI
     nephrolithiasis
   pathogenesis is unknown
     proposed that the obstruction is primary and followed by infection with E. coli, which leads to tissue
         destruction and collections of lipid material by histiocytes
     lipid-laden macrophages (xanthoma cells) are distributed in sheets around parenchymal abscesses and
         calyces and are intermixed with lymphocytes, giant cells, and plasma cells
     fibrous tissue reaction ensues to form a granulomatous process initially in the renal pelvis and calyces
         that infiltrates, destroys, and replaces the renal parenchyma
   nephrolithiasis has been noted in as many as 83% of the patients in various series
   ~50% staghorns
   divided into three extents of retroperitoneal involvement
     kidney alone
     kidney and perinephric fat
     kidney, perinephric fat, and extensive retroperitoneum
   otherwise may involve the kidney diffusely or the pericalyceal tissue alone

   Grossly
     kidney shows yellow-white nodules, pyonephrosis, and hemorrhage
   Microscopic
     xanthoma cells, associated necrosis and inflammation, hemosiderin in the histiocytes
     xanthoma cells are not specific to XGPN but also appear in other conditions, such as obstructive
         pneumonia, in which inflammation and obstruction are associated
   in the majority of cases, diagnosis is made postoperatively by the pathologist
   some investigators have shown that preoperative cytologic studies of the urinary sediment in four of five
    patients with pathologically proven XGPN showed renal xanthoma cells

Clinical Presentation
   most patients present with flank pain, fever and chills, and persistent bacteriuria
   vague symptoms, such as malaise, may be present
   2/3 have flank mass, 1/3 have previous calculi
Bacteriology and Laboratory Findings
   Proteus most common organism, E. coli next most common
   anaerobes also have been cultured
   10% of patients have mixed cultures
   1/3 of patients have no growth in their urine, probably because many patients have recently taken or are
    taking antimicrobial agents when cultures are obtained
   blood tests often reveal anemia and may show hepatic dysfunction in up to 50% of the patients
   XGPN is almost always unilateral; therefore, azotemia or frank renal failure is uncommon

Radiologic Findings
   IVP
     renal calculi 38-70%, lack of excretion 27-80%, renal mass in 62%, calyceal deformity in 46%
   USS
     enlarged kidney with a large central echogenic area and increased parenchymal anechoic pattern
   CT
     most useful radiologic technique in evaluating patients with XGPN
     usually demonstrates a large, reniform mass with the renal pelvis tightly surrounding a central
        calcification but without pelvic dilatation
     parenchyma is replaced by multiple water-density masses representing dilated calyces and abscess
        cavities filled with varied amounts of pus and debris
     on enhanced scans, the walls of these cavities demonstrate a prominent blush owing to the abundant
        vascularity within the granulation tissue
     helpful in demonstrating the extent of renal involvement and may indicate whether adjacent organs or
        the abdominal wall are involved
   Radionuclide renal scanning
    
        99m                               99m
           Tc-dimercaptosuccinic acid ( Tc-DMSA) is used to confirm and quantify the differential lack of
        function in the involved kidney
   MR
     not yet superseded CT in the evaluation of renal inflammation, but it provides some advantages in
        delineating extrarenal extension of inflammation

   radiologic studies, often cannot differentiate between XGPN and renal cell carcinoma

Management
   primary obstacle is incorrect diagnosis
   in most patients, the diagnosis is made postoperatively
   antimicrobial therapy may be necessary to stabilize the patient preoperatively, and occasionally, long-term
    antimicrobial therapy will eradicate the infection and restore renal function

   lipid-laden macrophages associated with XGPN, however, closely resemble clear cell adenocarcinoma and
    may be difficult to distinguish solely on the basis of frozen section
   XGPN has been associated with renal cell carcinoma, papillary transitional cell carcinoma of the pelvis or
    bladder, and infiltrating squamous cell carcinoma of the pelvis
   when diffuse and extensive disease into the retroperitoneum exists, removal of the kidney and perinephric
    fat may be needed
     important to remove the entire inflammatory mass
     incision and drainage alone may not resolve inflammation, may develop a renal cutaneous fistula, may
         make even more difficult nephrectomy


Malacoplakia
   Greek word meaning "soft plaque"
   unusual inflammatory disease that was originally described to affect the bladder but has been found to affect
    the genitourinary and gastrointestinal tracts, skin, lungs, bones, and mesenteric lymph nodes
   urinary tract involved in 58% (bladder, 40%; ureter, 11%; renal parenchyma, 16%)
   retroperitoneum involved in 16%
   patients with genitourinary malacoplakia have chronic coliform bacteriuria

Pathogenesis
   pathogenesis is unknown
   ~90% have coliform infections
   up to 50% have an immunodeficiency syndrome, autoimmune disease, carcinoma, or another systemic
    disorder
   hypothesized that bacteria or bacterial fragments form the nidus for the calcium phosphate crystals that
    laminate the Michaelis-Gutmann bodies

Pathology
   diagnosis is made by biopsy
   characterized by
     large histiocytes, known as von Hansemann cells
     small basophilic, extracytoplasmic, or intracytoplasmic calculospherules called Michaelis-Gutmann
        bodies, which are pathognomonic
         may be absent in early malacoplakia and are not necessary for the diagnosis
     EM reveals intact coliform bacteria and bacterial fragments within phagolysosomes of the foamy-
        appearing malacoplakic histiocytes
     macrophages contain large amounts of immunoreactive alpha 1-antitrypsin, uncommon in macrophages
        from other pathologic processes, immunohistochemical staining for alpha 1-antitrypsin may be a useful
        test for an early and accurate differential diagnosis of malacoplakia

Clinical Presentation
   most >50 years
   F:M within urinary tract 4:1, but not in other body tissues
   often debilitated, immunosuppressed, and have other chronic diseases
   symptoms of bladder malacoplakia are bladder irritability and haematuria
   cystoscopy reveals mucosal plaques or nodules
   may progress to fungating, firm, sessile masses that cause filling defects of the bladder, ureter, or pelvis on
    intravenous urograms
   distal ureter may become strictured or stenotic and cause subsequent renal obstruction or nonfunction
   extension of renal parenchymal malacoplakia into the perirenal space is uncommon
   renal parenchymal malacoplakia may be complicated by renal vein thrombosis and inferior vena cava
    thrombosis

Radiologic Findings
   Multifocal malacoplakia
     IVP
         enlarged kidneys with multiple filling defects
         calcification, lithiasis, and hydronephrosis absent
         multifocal nature is best appreciated by using ultrasonography, CT, or arteriography
     USS
         renal enlargement and distortion of the central echo complex
     CT
         foci of malacoplakia are less dense than the surrounding enhanced parenchyma
     Arteriography
         hypovascular mass without peripheral neovascularity
   Unifocal malacoplakia
     IVP
         noncalcified mass that is indistinguishable from other inflammatory or neoplastic lesions
     USS/CT
         solid or cystic structure, depending on the degree of internal necrosis
     Angiography
         neovascularity
Management
   control of UTIs should stabilize the disease process
     sulfonamides, rifampin, doxycycline, and TMP are thought to be especially useful because of their
        intracellular bactericidal activity
     other investigators have used ascorbic acid and cholinergic agents, such as bethanechol in conjunction
        with antimicrobial therapy, and have reported good results
   surgical intervention
     may be necessary if the disease progresses in spite of antimicrobial treatment
     nephrectomy is usually performed for the treatment of symptomatic unilateral renal lesions
   long-term prognosis appears to be related to the extent of the disease
     if parenchymal renal malacoplakia is bilateral or occurs in the transplanted kidney, death usually occurs
        within 6 months
     patients with unilateral disease usually have a long-term survival after nephrectomy

Renal Echinococcosis
   parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus
   prevalent in dogs, sheep, cattle, and humans in South Africa, Australia, New Zealand, Mediterranean
    countries (especially Greece), and some parts of the Soviet Union
   Pathogenesis
     produced by the larval form of the tapeworm, which in its adult form resides in the intestine of the dog,
        the definitive host
     adult worm is 3-9 mm long
     ova in dog faeces contaminate grass and farmlands and are ingested by sheep, pigs, or humans, the
        intermediate hosts
     larvae hatch, penetrate venules in the wall of the duodenum, and are carried by the blood stream to the
        liver
     larvae that escape the liver are next filtered by the lungs
     3% of the organisms that escape entrapment in the liver and lungs may then enter the systemic
        circulation and infect the kidneys
     larvae undergo vesiculation, and the resultant hydatid cyst gradually develops at a rate of about 1 cm/yr.
        cyst may take 5 to 10 years to reach pathologic size
   Pathology
     cysts usually single and located in the cortex
     wall has three zones
         peripheral zone of fibroblasts derived from tissues of the host becomes the adventitia and may
             calcify
         intermediate laminated layer becomes hyalinized
         single inner layer composed of nucleated epithelium and is called the germinal layer
   Clinical Findings
     symptoms are those of a slowly growing tumor
     most asymptomatic or have a flank mass, dull pain, or hematuria
     rarely, the cyst ruptures into the collecting system, and the patient may experience severe colic and
        passage of debris resembling grape skins in the urine (hydatiduria)
   Laboratory Findings
     definitive diagnosis can be established by identifying daughter cysts in the urine or by identifying the
        laminated wall of the cyst
     most reliable diagnostic test uses partially purified hydatid arc 5 antigens in a double-diffusion test
     complement fixation, HA, and the Casoni intradermal skin tests are less reliable but, when combined,
        are positive in about 90% of patients
   Radiologic Findings
     IVP
         thick-walled cystic mass, occasionally calcified
         occasionally direct filling of the cyst with contrast medium occurs
     USS
         multicystic or multiloculated mass
     CT
            cystic mass with discrete, round daughter cysts and a well-defined enhancing membrane
            less specific pattern is that of a thick-walled multiloculated cystic mass
            diagnostic aspiration should not be performed because of the danger of rupture and spillage of the
             highly antigenic cyst contents and risk of fatal anaphylaxis
   Management
     medical treatment with mebendazole has shown limited success with significant side effects
     surgery remains the mainstay of treatment
     cyst should be removed without rupture to reduce the chance of seeding and recurrence
     if the cyst ruptures or cannot be removed and marsupialization is required, the contents of the cyst
       initially should be aspirated and filled with a scolecoidal agent such as 30% sodium chloride, 0.5% silver
       nitrate, 2% formalin, or 1% iodine for approximately 5 minutes to kill the germinal portion


BACTEREMIA, SEPSIS, AND SEPTIC SHOCK

Pathophysiology
   Bacterial Cell Wall Components in Septic Shock
     bacteria and cell wall components are primarily responsible for the development of septic shock
     exotoxins can also initiate septic shock
     prime initiator of gram-negative bacterial septic shock is endotoxin, an LPS component of the bacterial
        outer membrane
   Cytokine Network
     monocytic cells have a pivotal role in mediation of the biologic effects of LPS
     can remove and detoxify LPS and be beneficial to the host
     LPS-stimulated monocytes produce cytokines such as tumor necrosis factor (TNF) and IL-1
     intravascular activation of inflammatory systems involved in septic shock is mainly the consequence of
        an overproduction of these and other cytokines
   Clinical Presentation
     classic fever/chills followed by hypotension manifest in 30% with gram-negative bacteremia
     earliest metabolic change in septicemia is respiratory alkalosis from hyperventilation
     mental state also important
         lethargy,obtundation, excited, agitated, or combative
     bull's-eye lesion associated with P. aeruginosa may be identified
   Bacteriology
     gram-negative in 30-80%
     gram-positive 5-24%
   Diagnosis and Management
     overall mortality 10-90%
     40% of deaths occurred within 24 hours and 60% within 48 hours
     5 factors associated with a high probability of bacteremia
         fever
         leukocyte count
         creatinine level
         diabetes mellitus
         low serum albumin level
     3 clinical factors predictive of the subsequent isolation of a resistant pathogen
         use of an antibiotic drug in the last month
         advanced age
         male sex
     once culture available, antibiotic should be lowest cost, least toxic antibiotic with the narrowest
        antimicrobial coverage
     should be continued until afebrile for 3-4 days and clinically stable
     vasoactive agents may be necessary to maintain adequate cardiac perfusion
LOWER TRACT INFECTIONS

Uncomplicated Cystitis
   patients without physiologic or anatomic abnormalities of the urinary tract and in the absence of recent
    urologic surgery or instrumentation
   female
     increased incidence in late adolescence and during the second and fourth decades of life
     risk factors include sexual intercourse and use of condoms
     remarkably narrow spectrum of etiologic agents
          E. coli in 80%, and S. saprophyticus in 5% to 15%
          less commonly Klebsiella species, P. mirabilis, or enterococci
   male
     often in association with not being circumcised, with sexual activity, or with HIV infection.
     E. coli and other Enterobacteriaceae most commonly identified
   Clinical Presentation
     dysuria, frequency, urgency, voiding of small urine volumes
     suprapubic or lower abdominal pain
     haematuria or foul-smelling urine
     suprapubic tenderness
     males may have a syndrome resembling nongonococcal urethritis (urethral discharge and dysuria)
   Laboratory Diagnosis
     microscopic urinalysis indicates bacteriuria, pyuria, and hematuria
     dip-stick tests for bacteriuria (nitrite) or pyuria (leukocyte esterase) may also be informative but are less
         sensitive than microscopic examination
     culture remains the definitive test, and, in symptomatic patients, the presence of 10 or more cfu/ml of
                                                                                               2

         urine usually indicates infection
   Differential Diagnosis
     must be differentiated from other inflammatory infectious conditions, including vaginitis, urethral
         infections, and miscellaneous noninflammatory causes of urethral discomfort
     vaginitis
          irritative voiding associated with vaginal irritation and is subacute in onset
     urethritis
          dysuria that is usually subacute in onset and is associated with a history of discharge and new or
             multiple sexual partners
          common causes of urethritis include gonorrhea, Chlamydia infection, herpes simplex, and
             trichomoniasis
     others
          urethral injury associated with sexual intercourse, chemical irritants, or allergy
   Management
     Antimicrobial Selection
          resistance to TMP and TMP-SMX is 9-18%
          TMP alone is as efficacious as TMP-SMX and is associated with fewer side effects
          ⅓ of bacterial strains causing uncomplicated cystitis demonstrate in vitro resistance to amoxicillin,
             cephalothin, and sulfonamides, and 15-20% are resistant to nitrofurantoin
          high cost of amoxicillin-clavulanate and the cephalosporins limits their usefulness
              drugs of choice for treatment of cystitis during pregnancy
          fluoroquinolones offer excellent activity, and they are well tolerated
              resistance <5% in most places
              use for uncomplicated cystitis should be limited to patients with allergy to less costly drugs or
                  with previous exposure to antibiotics causing bacterial resistance and to areas in which the
                  prevalence of resistance to TMP-SMX or TMP is 20% or greater
     Duration of Therapy
          with most antimicrobial agents, 3-days appears optimal, with efficacy comparable with that of 7-day
             regimens, but with fewer side effects and lower cost
          single-dose therapy generally results in lower rates of cure and more frequent recurrences
           follow-up visit, urinalysis, and urine culture are recommended in older women or those with potential
            risk factors and in men
           urologic evaluation is unnecessary in women and is usually unnecessary in young men who respond
            to therapy

Recurrent Urinary Tract Infections
   most commonly new infections from bacteria outside the urinary tract (reinfection)
   infections due to re-emergence of bacteria from a site within the urinary tract (persistence) are uncommon
     must be due to the same organism, and infections generally occur at close intervals
     patients can usually be cured of recurrent infections by identification and surgical removal or correction
         of the focus of infection
   at a minimum endoscopic evaluation is indicated in men
   Reinfections
     women
          associated with increased vaginal mucosal receptivity for uropathogens and ascending colonization
              from the fecal flora
          risk factors
               first UTI before age 15 years
               maternal history of UTI
               diaphragm-spermicide
               tampon use
               nonoxynol-9 may provide a selective advantage in colonizing the vagina, perhaps by a reduction
                   in colonization population of vaginal lactobacilli and through enhancement of adherence of E.
                   coli to epithelial cells
               postmenopausal women
                    residual urine after voiding, which is often associated with bladder or uterine prolapse
                    lack of oestrogen causes marked changes in the vaginal microflora
                    oestrogen replacement restores the normal vaginal environment, allows recolonization with
                        lactobacilli, and eliminates bacterial uropathogenic colonization
     men
          may be associated with a urinary tract abnormality
     vesicoenteric or vesicovaginal fistula should be considered when there is any history of pneumaturia,
         fecaluria, diverticulitis, obstipation, previous pelvic surgery, or radiation therapy
     Evaluation
          IVP
               in patients with risk factors such as a history of unexplained hematuria, obstructive symptoms,
                   neurogenic bladder dysfunction, renal calculi, fistula, analgesic abuse, and/or severe diseases
                   such as diabetes mellitus
          Cystoscopy
               all men
               women who have frequent reinfections and symptoms suggestive of obstruction, bladder
                   dysfunction, and fistula
                    little evidence that repeated urethral dilatation is indicated in the routine management of
                        most women
     Low-Dose Prophylaxis
          success of prophylaxis depends on the effect antibiotic agent has on the introital and fecal reservoirs
              of pathogenic bacteria
          agents that eliminate pathogenic bacteria from these sites and/or do not cause bacterial resistance
              at the sites can be effective for antimicrobial prophylaxis of UTIs
          Effective Drugs
               Trimethoprim-Sulfamethoxazole
                    eradicates gram-negative aerobic flora from the gut and vaginal fluid
                    these effects occur in addition to the bactericidal levels of TMP-SMX that are present in the
                        urine during nightly prophylaxis
               Trimethoprim
                    alone should be as effective as TMP-SMX for prophylactic prevention of recurrent UTIs
                 minimal fecal resistance
               Nitrofurantoin
                 does not alter gut flora
                 present for brief periods at high concentrations in urine and leads to repeated elimination of
                     bacteria from the urine
                 produces minimal fecal resistance
                 unlike TMP, colonization of the vaginal introitus with Enterobacteriaceae continues
                     throughout therapy
                 bacteria colonizing the vagina nearly always remain susceptible because of the lack of
                     bacterial resistance in the fecal flora
                 adverse reactions
                      acute pulmonary reactions (43%) allergic reactions (42%)
                      neuropathy, blood dysurias, liver damage, and chronic pulmonary reactions constituted
                          the remainder
                      risk of an adverse reaction increases with age
             Cephalexin
                 250mg or less nightly is an excellent prophylactic agent because fecal resistance does not
                     develop at this low dosage
             Fluoroquinolones
                 short-course therapy eradicates Enterobacteriaceae from the fecal and vaginal flora
                 in addition to preventing symptomatic UTIs, norfloxacin virtually eradicates periurethral and
                     fecal colonization with aerobic gram-negative organisms
                 expensive and can be used only in nonpregnant women
                 favored only when antimicrobial resistance or patient intolerance to TMP-SMX, TMP,
                     nitrofurantoin, or cephalexin occurs
        Efficacy of Prophylaxis
             women with recurrent UTIs
                 recurrences decrease by 95% when compared with placebo or with the patients' prior
                     experiences as controls
                 reduce reinfection rate from 2.0 to 3.0 per patient-year to 0.1 to 0.4 per patient-year
                 antiseptics, such as methenamine mandelate or hippurate, have resulted in some decrease
                     in recurrences, but they are not as effective as antimicrobial agents
        Postintercourse Prophylaxis
             intercourse is an important risk factor for acute cystitis in women
             diaphragm users have a significantly greater risk of UTI than women who use other
                contraceptive methods
             postintercourse therapy with antimicrobials such as nitrofurantoin, cephalexin, or TMP-SMX
                taken as a single dose effectively reduces the incidence of reinfection
        Intermittent Self-Start Therapy
             in patients reluctant to continue long-term antimicrobial prophylaxis
             may be managed with repeated courses of self-administered, single-dose therapy
             self-diagnosis and self-start therapy
             dip-slide device to culture the urine and instructed to perform a urine culture when symptoms of
                UTI occur
             patient given a 3-day course of empirical full-dose antimicrobial therapy to be started
                immediately after performing the culture
             Fluoroquinolones ideal
             Nitrofurantoin and TMP-SMX acceptable alternatives
             culture is brought to the office as soon as possible
   Bacterial Persistence
     uncommon
     surgically curable cause of recurrent UTIs
        infection stones
        chronic bacterial prostatitis
        unilateral infected atrophic kidneys
        ureteral duplication and ectopic ureters
         foreign bodies
         urethral diverticula and infected periurethral glands
         unilateral medullary sponge kidneys
         non-refluxing, normal appearing infected ureteral stumps after nephrectomy
         infected urachal cysts
         infected communicating cysts of the renal calyces
         papillary necrosis
         perivesical abscess with fistula to bladder
       most common bacterial persistence within infection stones
       IVP and cystoscopy provide initial screening
       in selected patients, CT and bacterial localization cultures are indicated
       in selected cases, ureteral catheterization studies should be performed to verify that upper tract
        abnormality harbors the bacteria
       if focus of infection cannot be eradicated, long-term, low-dose antimicrobial suppression is necessary to
        prevent symptoms of infections

Symptomatic Infections versus Infections Detected on Screening Surveys for Bacteriuria
   3-6% of sexually active women of childbearing age are bacteriuric on screening surveys
   Are Adult Women with Screening Bacteriuria at Risk of Serious Renal Damage?
     studies clearly established that, although women with ScBU have three times the number of
        abnormalities in their kidneys as matched control subjects (of the same age and parity) without
        bacteriuria, these abnormalities do not represent serious renal disease
   Do Women with Screening Bacteriuria Differ from Those with Symptomatic Bacteriuria?
     probability of acquiring a symptomatic infection is seven times greater in women with known ScBU than
        in those without
   Is Detection of Screening Bacteriuria in Adult Women a Worthwhile Public Health Effort?
     successful therapy in ScBU little different in the long run from the natural history of spontaneous
        remissions
     screening for bacteriuria in the first trimester of pregnancy probably represents the only time that
        screening for bacteriuria is worthwhile

Urethral Syndrome
   any symptoms or combination of symptoms suggestive of UTI occurring in patients considered to be
    uninfected
     three subgroups:
         infectious (microbial) cause, nearly always accompanied by an inflammatory response
         interstitial cystitis, rarely accompanied by inflammatory cells
         "pure" urethral syndrome, ie patients who have neither a microbial cause nor interstitial cystitis



URINARY TRACT INFECTIONS DURING PREGNANCY
   prevalence of bacteriuria does not change with the occurrence of pregnancy
   anatomic and physiologic alterations associated with this state probably do change the course of bacteriuria
    during pregnancy

Anatomic and Physiologic Changes during Pregnancy
   Increase in Renal Size
   Smooth Muscle Atony of the Collecting System and Bladder
     collecting system, especially the ureters, undergoes decreased peristalsis during pregnancy, and most
        women in their third trimester show significant ureteral dilatation
     attributed both to the muscle-relaxing effects of increased progesterone during pregnancy and to
        mechanical obstruction of the ureters by the enlarging uterus at the pelvic brim
     progesterone-induced smooth muscle relaxation also may cause an increased bladder capacity
   Bladder Changes
     bladder becomes hyperemic and may appear congested endoscopically
     oestrogen stimulation probably causes bladder hypertrophy as well as squamous changes of the urethra
   Augmented Renal Function
     transient increases in GFR and RPF during pregnancy
     probably secondary to the increase in cardiac output

Natural History of Bacteriuria during Pregnancy
   recurrent bacteriuria in the pregnant female merely reflects a segment of the natural history of recurrent
    infections in females and is not a peculiarity of pregnancy
   incidence of acute clinical pyelonephritis in pregnant women with bacteriuria is significantly increased over
    that in nonpregnant women
     60-75% during the third trimester
   treatment of ScBUP decreases the incidence of acute pyelonephritis during pregnancy from a range of 13.5-
    65% to a range of 0-5.3%

Complications Associated with Bacteriuria during Pregnancy
   prematurity and perinatal mortality
     whether women who have been treated for pyelonephritis or scbu during pregnancy still deliver infants
       with increased prematurity and perinatal mortality is controversial
   maternal anemia
     although several studies suggest that bacteriuria untreated during pregnancy is associated with maternal
       anemia, not all studies support this
   maternal hypertension and eclampsia
     data inconclusive

Management of Bacteriuria during Pregnancy
   Diagnosis of Bacteriuria
     should be sought at the initial prenatal visit
     risk of bacteriuria increases with the duration of pregnancy
     pregnant women with a history of recurrent UTIs and/or VUR may benefit from reculture and/or
        antimicrobial prophylaxis
   Treatment of Urinary Tract Infections during Pregnancy
     when symptomatic or asymptomatic bacteriuria of pregnancy is diagnosed, the bacteriuria should be
        treated to avoid the complications already discussed
     antimicrobial selection must be made with special considerations given to maternal and fetal toxicity
     physiologic changes of pregnancy may decrease tissue and serum drug concentrations
     certain antimicrobial agents should be avoided in pregnancy
         tetracyclines contraindicated throughout pregnancy
         chloramphenicol may accumulate to toxic concentrations in the neonate because infants may lack
            the ability to metabolize or excrete the drug
         may cause cardiovascular collapse and high neonatal mortality
         fluoroquinolones contraindicated because of potential adverse effects on cartilage formation
         sulfa preparations should be avoided during the third trimester because they compete for fetal
            bilirubin-binding sites on albumin and can cause neonatal hyperbilirubinemia and kernicterus
         most investigators believe that TMP, a folic acid antagonist, should be avoided during the first
            trimester of pregnancy because of its potential teratogenic activity
         nitrofurantoin can cause a hemolytic anemia in patients and fetuses with a glucose-6-phosphate
            dehydrogenase deficiency
         aminoglycosides have no specific complications associated with pregnancy, but they may cause
            ototoxicity and nephrotoxicity in both fetus and mother
     agents relatively safe during pregnancy
         penicillins and cephalosporins inhibit growth of the bacterial cell wall, and human cells have a
            cytoplasmic membrane without a cell wall, these drugs act specifically on the bacteria
         only the penicillins (penicillin, ampicillin, and synthetic penicillins) and cephalosporins are thought to
            be safe and effective during any phase of pregnancy
         short-acting sulfonamides can be safely used during the first two trimesters of pregnancy, because
            the fetus in utero handles excess unconjugated bilirubin through the placenta
           nitrofurantoin has been commonly used in pregnancy during the first two trimesters but may be
            contraindicated at term because it can cause a hemolytic anemia in neonates with an immature
            enzyme system
           pregnant women with acute clinical pyelonephritis should be admitted to the hospital for treatment
            with parenteral agents
           after treatment should be monitored closely for recurrent bacteriuria or be given prophylaxis for the
            remainder of the pregnancy

   Pregnancy in Women with Renal Insufficiency
     renal function should be carefully evaluated by both serum creatinine levels and creatinine clearance
       before a woman is counseled about conceiving or continuing a pregnancy
     normal pregnancy is rare if the preconception serum creatinine level exceeds 3 mg/dl (about 30 ml/min
       clearance)
     conception is ill advised in patients with less than 50% of normal renal function (serum creatinine levels
       > 1.7 mg/dl or < about 50 ml/min clearance)


URINARY TRACT INFECTIONS IN THE ELDERLY

   Epidemiology
     at least 20% of women and 10% of men older than 65 years have bacteriuria
     ratio in women to men with bacteriuria progressively decreases to 2:1

   Clinical Presentation
     majority have no urinary tract symptoms
     other symptoms such as lethargy, confusion, anorexia, and incontinence may be caused by bacteriuria
        and lead to missed or delayed diagnosis and increased morbidity and mortality
     urinalysis and cultures are valid only if the urine has been collected without contamination
     >60% of women with pyuria of 10 WBC/ml or greater noted in midstream specimens do not have
                                                    3

        concurrent bacteriuria
     renal dysfunction, calculi, hydronephrosis, urinary retention, neurogenic bladder dysfunction, and other
        abnormalities should be identified by serum creatinine measurement, IVP, USS, urodynamics, and/or
        cystoscopy

   Bacteriology
     E. coli causes only 75% of these infections; Proteus, Klebsiella, Enterobacter, Serratia, and
       Pseudomonas species and enterococci are also frequently encountered
     gram-positive bacteria much more common in elderly men than in elderly women

   Pathophysiology
     factors contributing to UTIs in the elderly are complex and poorly understood
     age-related changes include a decline in cell-mediated immunity; altered bladder defences owing to
        obstructive uropathy; neurogenic dysfunction; increased receptivity of uroepithelial cells; an increased
        risk of contamination owing to fecal and urinary incontinence and urethral instrumentation and
        catheterization; and a decrease in prostatic and vaginal antibacterial factors associated with changes in
        pH and levels of zinc and hormones

   Significance
     UTIs in elderly subjects in the presence of underlying structural urinary tract abnormalities or systemic
        conditions (e.g., diabetes mellitus) are clinically significant, can lead to renal failure, and require prompt
        therapy
     UTIs caused by urea-splitting bacteria, such as Proteus or Klebsiella species that cause formation of
        infection stones, may also lead to severe renal damage
     bacteriuria has been associated with increased mortality
         may result either from a direct effect on mortality of the bacteriuria itself or from such factors as
             aging or underlying disease that increase both bacteriuria and mortality
       treatment of asymptomatic bacteriuria to improve incontinence has not been justified

   Management
     elderly more susceptible than young patients to the toxic and adverse effects of antimicrobial agents
       because the metabolism and excretion of antimicrobial agents may be impaired, and resulting increased
       serum levels can further damage renal function
     no question that symptomatic UTIs should be treated
     merit of antimicrobial therapy in asymptomatic bacteriuria is debatable
        treatment of asymptomatic bacteriuria in the absence of obstruction does not appear warranted


URINARY TRACT INFECTIONS IN PATIENTS WITH SPINAL CORD INJURY

   Epidemiology
     ~33% of spinal cord injury patients have bacteriuria at any time
     eventually almost all spinal cord injury patients will become bacteriuric
     UTI is the most common cause of fever in the spinal cord injury patient
     risk factors
         overdistention of the bladder, elevated intravesical pressure, increased risk of urinary obstruction,
           VUR, impaired voiding, instrumentation, and increased incidence of stones
         other: decreased fluid intake, poor hygiene, perineal colonization, decubiti and other evidence of
           local tissue trauma, and reduced host defence associated with chronic illness

   Pathogenesis
     method of bladder management has a profound impact on UTI
     vast majority of patients with an IDC for 30 days are bacteriuric
     SPCs and IDCs eventually have an equivalent infection rate
         onset of bacteriuria may be delayed using a SPC compared with an IDC
     CISC
         has been shown to decrease lower tract complications by maintaining low intravesical pressure and
           reducing the incidence of stones
         also appears to reduce complications associated with an IDC, such as UTI, fever, bacteremia, and
           local infections such as epididymitis and prostatitis

   Clinical Presentation
     majority of spinal cord injury patients with bacteriuria are asymptomatic

   Bacteriology and Laboratory Findings
     urinalysis bacteriuria and pyuria
     any detectable bacteria from indwelling or suprapubic catheter aspirates is significant because majority
                                                                                               5
       of patients with an IDC and low-level bacteriuria showed an increase to greater than 10 cfu/ml within a
       short period of time
     E. coli is isolated in approximately 20% of patients
     Enterococci, P. mirabilis, and Pseudomonas are more common among spinal cord injury patients than
       patients with intact spinal cords
     other common organisms are Klebsiella species, Serratia species, Staphylococcus, and Candida
       species

   Management
     urine culture must be obtained before initiating empirical therapy
     afebrile patients
     oral fluoroquinolone is the agent of choice
     β-Lactams, TMP-SMX, and nitrofurantoin are not recommended because of the high prevalence of
       bacterial resistance to these drugs
     IDC should be changed to ensure maximum drainage and eliminate bacterial foci in catheter
       encrustations
       duration of therapy is not established, but 4 to 5 days is recommended for the mildly symptomatic patient
        and 10 to 14 days for sicker patients
       post-therapy cultures are usually not necessary because asymptomatic recolonization is common and
        not clinically significant


OTHER INFECTIONS

Fournier's Gangrene
   form of necrotizing fasciitis occurring about the male genitalia
   initially characterized by an abrupt onset of a rapidly fulminating genital gangrene of idiopathic origin in
    previously healthy young patients, which resulted in gangrenous destruction of the genitalia
   now involves a broader age range, including older patients, follows a more indolent course, and has a less
    abrupt onset, and, in approximately 95% of the cases, a source can now be identified
   most commonly arises from the skin, urethra, or rectal regions
   association between urethral obstruction associated with strictures and extravasation and instrumentation
   predisposing factors
     diabetes mellitus, local trauma, paraphimosis, periurethral extravasation or urine, perirectal or perianal
          infections, and surgery such as circumcision or herniorrhaphy
   bacteriology
     major role for anaerobic bacteria is likely
     cultures generally yield multiple organisms, implicating anaerobic-aerobic synergy
     mixed cultures containing facultative organisms (E. coli, Klebsiella, enterococci) along with anaerobes
          (Bacteroides, Fusobacterium, Clostridium, microaerophilic streptococci) have been obtained
   Clinical Presentation
     history of recent perineal trauma, instrumentation, urethral stricture associated with sexually transmitted
          disease, or urethral cutaneous fistula
     pain, rectal bleeding, and a history of anal fissures suggest a rectal source of infection
     dermal sources are suggested by history of acute and chronic infections of the scrotum and spreading
          recurrent hidradenitis suppurativa or balanitis
     commonly starts as cellulitis adjacent to the portal of entry
     swelling and crepitus of the scrotum quickly increase, and dark purple areas develop and progress to
          extensive gangrene
   Laboratory Studies
     anaemia
     elevated serum creatinine levels, hyponatremia, and hypocalcemia
   Diagnostic Tests
     AXR/scrotal USS can identify air
   Management
     prompt diagnosis is critical because of the rapidity with which the process can progress
     clinical differentiation of necrotizing fasciitis from cellulitis may be difficult because the initial signs
          including pain, edema, and erythema are not distinctive
     presence of marked systemic toxicity out of proportion to the local finding should alert the clinician
     IV hydration and antibiotic therapy are indicated in preparation for surgical débridement
     antibiotic regimens include combinations of ampicillin plus sulbactam or a parenteral third-generation
          cephalosporin such as ceftriaxone, gentamicin, and clindamycin
     immediate débridement is essential
           extensive incision should be made through the skin and subcutaneous tissues, going beyond the
               areas of involvement until normal fascia is found
           necrotic fat and fascia should be excised, and the wound should be left open
     second procedure 24-48 hours later is indicated if there is any question about the adequacy of initial
          débridement
   Outcome
     mortality 20%
     higher mortality in diabetics, alcoholics, and those with colorectal sources of infection who often have a
          less typical presentation, greater delay in diagnosis, and more widespread extension
Periurethral Abscess
   life-threatening infection of the male urethra and periurethral tissues
   initially, the area of involvement can be small and localized by Buck's fascia
   when Buck's fascia is penetrated, there can be extensive necrosis of the subcutaneous tissue and fascia
   Pathophysiology
     frequently a sequela of gonorrhea, urethral stricture disease, or urethral catheterization
     source of the infecting organism is the urine
     Gram-negative rods, enterococci, and anaerobes are most frequently identified
   Clinical Presentation
     scrotal swelling in 94% of patients, fever (70%), acute urinary retention (19%), spontaneously drained
          abscess (11%), and dysuria or urethral discharge (5% to 8%)
     average interval between initial symptoms and presentation is 21 days
   Management
     immediate suprapubic urinary drainage and wide débridement
     therapy with an aminoglycoside and a cephalosporin is usually adequate for empirical coverage
     perineal urethrostomy or chronic suprapubic diversion occasionally has been helpful to prevent
          recurrences, and it should be considered in patients with diffuse stricture disease

				
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