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					Antibiotic Choices
Gary Skankey, MD, FACP
            Outline
When to use and when not to use
antibiotics
Interpreting cultures
Choosing appropriate empiric
antibiotics
Using antibiograms
Appropriate Use of Antibiotics
Employ empirically when there is a reasonable
clinical suspicion of infection
Choose antibiotics active against the most likely
organism(s)
Choose antibiotics known to penetrate involved
tissue
Use correct doses of antibiotics – don’t underdose
Know when bacterostatic antibiotics are adaquate
or bacterocidal drugs are required
In serious, potentially life-threatening infections,
start broad, then de-escalate after cultures back
Stop antibiotics when infection resolved or when
evidence accumulates against existence of
infection
Inappropriate Uses of Antibiotics
Using wrong antibiotic for apparent infection
Using wrong dose of right drug
Using a 2nd or 3rd line drug when a first line drug
could still be used
Using antibiotics in situations when antibiotics are
not indicated – “just in case”
Continuing antibiotics when infection is resolved
or not likely
Keeping coverage broad when cultures reveal a
single organism
Reacting to culture results by starting antibiotics
without considering the significance of the culture
 Results of Antibiotic Misuse
Incomplete, delayed, or failed
resolution of infection
Prolonged or unnecessary
hospitalizations
Increased incidence of antibiotic side
effects
Development of multi-drug resistant
strains of bacteria
Increased cost of health care
Knowing When and When Not to Use
          an Antibiotic
Infection is Diagnosed Clinically
 Based on Multiple Data Points
Pneumonia
• Fever
• Leukocytosis
• Purulent sputum
• New infiltrate
• Cough, chest pain, dyspnea
• Hypoxia
• Sputum gram stain shows many WBCs,
  few epithelial cells
Infection is Diagnosed Clinically
 Based on Multiple Data Points
UTI
• Dysuria
• Urinary frequency
• Fever
• Pelvic or flank pain
• Pyuria
      Watch the number of epithelial cells in U/A
Infection is Diagnosed Clinically
 Based on Multiple Data Points
Wound infection
• Wound is foul smelling
• Skin surrounding wound is red,
  indurated, tender
• Pus draining from wound
• Fever
• leukocytosis
Infection is Diagnosed Clinically
 Based on Multiple Data Points

Infections are not diagnosed by
culture alone
    Mistakes Doctors Make in
      Diagnosing Infection
Base their diagnosis on a single positive
data point when other data points are
negative
React to a positive culture when there is
no clinical evidence of infection
Use serial cultures to determine when
infection has resolved
Obtain cultures randomly when clinical
suspicion of infection is low
Interpreting cultures
  First Step: Determine Whether
Culture Represents Real Pathogen
 Colonizer
 • And organism actually present in or on
   patient, but does not invade tissue or
   cause clinical disease
 Contaminant
 • And organism growing in culture that is
   not actually present in or on the patient,
   but came from the environment directly
   to the culture medium
  First Step: Determine Whether
Culture Represents Real Pathogen
 Every positive culture needs to be
 interpreted with respect to other
 data points
 Example:
 • A wound culture taken from a clean-
   appearing, granulating wound that is
   not painful, has no purulence in a
   patient with no fever and a normal WBC
   is a colonizer and should not be treated
  First Step: Determine Whether
Culture Represents Real Pathogen
 Example:
 • A sputum culture taken from a patient
   without fever, leukocytosis, new
   infiltrate or pulmonary symptoms is a
   colonizer
 Example:
 • A urine culture taken from a patient
   without dysuria, frequency, and with a
   small to moderate amount of WBC in
   the U/A has asymptomatic bacteriuria
Interpreting Individual Cultures
            Blood Cultures
Pathogen if:              Contaminant if:
Patient is febrile when   Patient is afebrile
culture drawn             when culture drawn
Fever persists without    No fever despite lack
appropriate antibiotics   of appropriate
Organism is a known       antibiotic
pathogen                  Organism is a skin
Grows in 2 of 2 sets      colonizer
Grows in 24 to 48         Grows in only one set
hours                     Grows after 48 hours
                          Note: Increased risk
                          of contamination if
                          drawn through line
        Sputum Cultures
A pathogen if:       A colonizer if:
Sputum is grossly    Sputum is scant,
purulent             clear or white
Patient is febrile   Patient is afebrile
Infiltrates on CXR   No infiltrates on
> 5-10 WBC per       CXR
hpf                  < 5-10 WBC per
< 5-10 epithelial    hpf
cells per hpf        > 5-10 epithelial
                     cells per hpf
             Urine Cultures
A pathogen if:            A contaminant if:
> 100,000 cfu             10,000 cfu or less
If urinalysis             If urinalysis
reveals:                  reveals:
•   > 10 WBC              •   < 10 WBC
•   Pos. leuk. esterase   •   Neg. leuk. esterase
•   Pos. nitrite          •   Neg. nitrite
•   Few or no epi’s       •   Many epi’s
If patient                If patient
symptomatic               asymptomatic
   Asymptomatic bacteriuria
> 100,000 cfu bacteria in urine
culture in a patient with no
symptoms
Incidence increases in women by 1%
per decade
• 70 – 80 year olds have 7 – 8% annual
  incidence
Prevalence in elderly
• Men – 10%
• Women – 20%
• In nursing homes, prevalence is higher
  Asymptomatic bacteriuria
NO increased morbidity or mortality
if left untreated
Spontaneously resolves
If treated, patient subjected to
potential side effects of antibiotics
and selective pressure for MDR
organisms unnecessarily
Don’t culture urine if no symptoms
Choosing the Right Empiric Antibiotic
    Antibiotics for Head and Neck
               Infections
Organisms
• Streptococcus viridans group, Lancefield group
  streptococci, staphylococcus,
  peptostrepococcus, Veillonella, fusobacterium,
  bacteroides spp, eikonella, etc.
Antibiotics
•   Beta lactam/beta lactamase inhibitor combos
•   Clindamycin
•   2nd generation cephalosporins
•   4th generation Quinolones (moxifloxacin)
   Antibiotics for Meningitis
Organisms
• Most common - Streptococcus pneumoniae,
  Neisseria meningitidis
• Less common (in very young, elderly, or
  immunecompromised) – Haemophilus
  influenzae, Klebsiella pneumoniae, Listeria
  monocytogenes
Antibiotics
• High dose ceftriaxone, cefotaxime, and
  vancomycin (+ ampicillin)
Antibiotics for Community-Acquired
         Pneumonia (CAP)
 Organisms:
 • S. pneumoniae, H. influenzae, M.
   catarhalis, K. pneumoniae, M.
   pneumoniae, C. pneumoniae, L.
   pneumophila
 Antibiotics
 • 2nd or 3rd generation cephalosporins
 • Respiratory quinolones (Levofloxacin,
   Gatifloxacin)
 • Advanced macrolides (clarithromycin,
   azithromycin)
  IDSA Guidelines for Empiric
  Treatment of Outpatient CAP
Previously healthy, no use of abx in past 3
months
• A macrolide (Biaxin, Azithromycin)
• Doxycycline
Comorbidities, immune suppression, abx
in last 3 months
• Respiratory FQ (Avelox, Tequin, Levaquin [750
  mg])
• Beta-lactam (cefuroxime, amox/clav) plus
  macrolide (clarithromycin, azithromycin)
If high incidence of macrolide-resistant
pneumococcus, substitute FQ for
macrolide
  IDSA Guidelines for empiric
   treatment of Inpatient CAP
Non-ICU
• Respiratory FQ
• Beta-lactam (ceftriaxone, amp/sulb) or
  ertapenem plus macrolide
ICU
• Beta-lactam or ertapenem plus
  macrolide or resp FQ
• (I add vancomycin to cover
  cephalosporin-resistant pneumococcus
  or CA-MRSA)
Timing and duration of therapy for
             CAP
First dose must be given in ER
 • Outcome dependent on early institution
   of appropriate antibiotics
Switch from IV to PO abx when pt
hemodynamically stable and
improving clinically, is able to ingest
medications, and has a normally
functioning gastrointestinal tract
Timing and duration of therapy for
             CAP
Rx for a minimum of 5 days, should be
afebrile for 48–72 h, and should have no
more than 1 CAP-associated sign of
clinical instability before discontinuation of
therapy
Criteria for clinical stability
 • 1) Temperature 37.8°C, 2) Heart rate 100
   beats/min, 3) Respiratory rate 24 breaths/min,
   4) Systolic blood pressure 90 mm Hg, 5)
   Arterial oxygen saturation 90% or pO2 60
   mm Hg on room air, 6) Ability to maintain oral
   intake, 7) Normal mental status
Healthcare Associated Pneumonia
            (HCAP)
                   HCAP
Healthcare associated pneumonia (HCAP)
• Any hospitalization in the past 90 days
• Any IV antibiotics in the past 30 days
• Resident of or transferred from a long term
  acute care facility or skilled nursing facility
Likely to be due to MDR hospital-acquired
organisms
• Pseudomonas, MDR acinetobacter, ESBL
  Klebsiella, MDR enterobacter, etc
• MRSA
These patients are too frequently started
on standard CAP empiric antibiotics
    Empiric Therapy for HAP, VAP and HCAP in
Patients With Late-onset Disease or Risk Factors for
     MDR Pathogens and all Disease Severity
    Potential Pathogens                                 Combination Therapy
    MDR pathogens                                       Antipseudomonal cephalosporin
       • P aeruginosa                                      (cefepime, ceftazidime)       or
       • K pneumoniae                                   Antipseudomonal carbepenem
         (ESBL+)                                           (imipenem or meropenem) or
       • Enterobacter                                   Beta-lactam/beta-lactamase inhibitor
       • Acinetobacter sp                                  (piperacillin-tazobactam)
                                                           plus
                                                        Antipseudomonal fluoroquinolone*
                                                           (ciprofloxacin or levofloxacin)
                                                                or
                                                        Aminoglycoside
                                                           (amikacin, gent, tobra)
          • MRSA                                          plus

                                                          Linezolid suspected, a carbepenem
      *If an ESBL+ strain (eg, K pneumoniae or an Acinetobacter sp) is or vancomycin is a reliable choice. If L
                                                                                                  †
      pneumophila is suspected, the combination regimen should include a macrolide (eg, azithromycin) or a
      fluoroquinolone (eg, ciprofloxacin or levofloxacin) rather than an aminoglycoside. † If MRSA risk factors are present, or
      there is a high incidence locally.
ATS. Am J Respir Crit Care Med. 2005;171:388-416.
 Antibiotics for Intra-abdominal
            Infections
Organisms
• Enteric gram negatives, gram negative
  anaerobes, gram positive anaerobes,
  oral anaerobes, yeast
Antibiotics
• Zosyn, Unasyn, Primaxin, Meropenem
• Ceftriaxone or Cefotaxime + Flagyl +
  Vancomycin
• + Fluconazole
Antibiotics for Urinary Tract Infections

  Organisms
   • Gram negative enterics, enterococcus
  Antibiotics
   • Ciprofloxacin, Levafloxacin, 2nd or 3rd
     generation cephalosporins,
     amoxacillin/ampicillin (if sensitive)
Antibiotics for Skin and Soft Tissue
              Infections
Organisms
 • Staphylococcus (75% MRSA),
   streptococcus
Antibiotics
 • PO – TMP/SMX, Clindamycin, Linezolid
 • IV – Vancomycin, Daptomycin
Antibiogram – HA-MRSA vs CA-MRSA

 HA-MRSA              CA-MRSA
 • Sensitive to:      • Sensitive to:
     Vancomycin           Vancomycin
     TMP/SMX              TMP/SMX
     Rifampin             Rifampin
 • Resistant to:          Tetracyclines
     Oxacillin            Erythromycin
     Cephalosporins       Clindamycin
     Quinolones           Quinolones
     Tetracyclines    • Resistant to:
     Erythromycin         Oxacillin
     clindamycin          Cephalosporins
Antibiotic Resistance
       Things that promote drug
              resistance
Using antibiotics when no infection is present
• The “just-in-case” syndrome
Treating cultures, not patients
• Colonizations or contaminants
Using the incorrect empiric antibiotic
• Example: using Levaquin for cellulitis
Continuing antibiotics past the point that infection has
resolved
Failing to de-escalate antibiotic coverage after cultures are
finalized
Underdosing antibiotics
Using an antibiotic that does not penetrate to the focus of
infection
• Example: using doxycycline for UTI
Using a bacterostatic antibiotic when an infection calls for
bacterocidal action
 Spread of MDR Organisms
Study at Johns Hopkins Medical
Center
• Only 40% of HCWs wash hands
  regularly and appropriately between
  every patient
• Of HCWs doctors were the worst
  washing hands only 18% of the time
MDRs are also transmitted on
medical instruments
• stethoscopes
Cultured-Based Antibiotic Choice
Know Your Local Antibiograms
Sensitivities of community-acquired
and hospital-acquired organisms
vary from region to region
Knowledge of the general
sensitivities will aid in choosing
appropriate antibiotics and early
institution of therapy
                     Inappropriate Antibiotic Therapy
                                Increases Mortality
                                 Appropriate therapy     Inappropriate therapy
                    100
                     90
                     80
           Mortality (%)



                     70
                     60
                     50
                     40
                     30
                     20
                     10
                      0
                           Ibrahim    Leibovici        Luna   Alvarez-Lerma   Rello
                           Bloodstream Infections      Nosocomial Pneumonia/VAP

Ibrahim, et al. Chest. 2000;118:146–155.
Leibovici, et al. J Intern Med. 1998;244:379–386.
Luna, et al. Chest. 1997;111:676–685.
Alvarez-Lerma, et al. Intensive Care Med.1996;22:387–394.
Rello, et al. AJRCCM.1997;156:196–200.
          Hospital Mortality Rate of
             Infected Patients

2000 consecutive patients                               60      52.1%
admitted to an MICU or                                  50
SICU                                                                     N = 312




                                          Mortality %
                                                                         P<.001
Pneumonia in 411 cases                                  40

 • 305 with adequate therapy   30
 • 106 with inadequate therapy 20                                         12.2%

                                                        10

                                                        0
                                                             Inadequate Adequate

                                                              Antibiotic Treatment


Kollef, et al. Chest. 1999;115:462–474.
Interpreting in vitro Sensitivity
MIC – minimum inhibitory concentration
In order to adequately kill bacteria, serum
concentration must be at least 8x the MIC
Sensitivity break-points vary among
different antibiotics, because of
differences in pharmacodynamics
Best drugs to use are those with lowest
MIC
  Interpreting in vitro Sensitivity
              Panels
Not every antibiotic listed as sensitive in
vitro will be effective in vivo
Must consider tissue penetration
• Ancef does not penetrate CSF
• Tetracycline is not excreted in urine
Must consider killing power
• Clindamycin is too slowly bacterocidal to be
  useful in treating bacteremia
• Any bacterostatic antibiotic is contraindicated
  in treating serious infections like endocarditis
  and meningitis
Antibiograms
 Sensitivity to Hospital-Acquired
  Gram Negatives – City Wide
100
90
80
70
60                                                 Meropenem
50                                                 Cefepime
40                                                 Pip/Tazo
30                                                 Levaquin
20
10
 0
      Pseudo   E. cloacae   Acinetob   K. pneumo
Sensitivity to Gram Positives – City
                Wide
100
 90
 80
 70
 60                                     Ceftriaxone
 50                                     Vancomycin
 40                                     Penicillin
 30                                     Linezolid
 20
 10
  0
      S.aureus   S.pneumo   E.faecium
Hospital-Specific Antibiogram
100
90
80
70
60                               Meropenem
50                               Cefepime
40                               Pip/Tazo
30                               Cipro
20
10
 0
      Pseudo-City   Pseudo-UMC
Hospital-Specific Antibiogram
100
90
80
70
60                                   Oxacillin
50                                   Vancomycin
40                                   Clindamycin
30                                   Levaquin
20
10
 0
      S.aureus-City   S.aureus-UMC
           Summary
Use antibiotics judiciously to
minimize treatment failure, higher
morbidity and mortality and reduce
development of resistance
Know the antibiograms of you
respective hospitals to guide choice
of antibiotics
Thoroughly evaluate every patient so
that correct diagnosis is made

				
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