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Gram Positive Pathogens

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Gram Positive Pathogens Powered By Docstoc
					Gram Positive & Gram Negative
     Bacterial Pathogens
 Ted Morton, Pharm.D., BCPS (AQ-ID)
      Clinical Pharmacist – Regional Medical Center at Memphis
   Associate Professor of Medicine & Clinical Pharmacy UT Memphis
Objectives
  •   Understand the general classification and taxonomy of
      pathogenic bacteria
  •   For each pathogenic organism, know & clinically apply:
      – The organisms cell wall staining characteristics, morphology, and other
        factors useful in classification (including spore formation, toxin
        production, and requiring an anaerobic environment for growth)
      – The major diseases states caused by the organism
      – Major mechanisms of resistance and general trends in antibiotic
        susceptibility
      – Usual drug and/or regimen of choice and alternative specifically
        recommended.
Bacteria                                  (Prokaryotes)

  •   Differentiated by
      –   Cell wall staining
           »   Gram Positive         Gram Positive Cocci
           »   Gram Negative
           »   Acid Fast
      –   Morphology
           »   Cocci
           »   Bacilli               Gram Negative Rod
      –   Chemical Reactions
           »   Coagulase, Catalase
Gram Positive
  •   Thick Peptidoglycan Cell Wall
  •   Cytoplasmic Membrane
      –   Penicillin Binding Proteins


                           Cell Wall
                           (purple on Gram Stain)

                            Cytoplasmic             PBP
                                                          PBP
                            Membrane
Gram Positives

                 Staphylococci
                 (catalase positive)
                                        Common
       Cocci                           Pathogens
                 Streptococci
                 (catalase negative)


                 Clostridium
                 & Bacillus
                 (spore formers)        Rare but
       Bacilli                          Serious
                                       Pathogens
                 Corynebacterium
                 & Listeria
                 (non-spore formers)
Clostridium & Bacillus

   •   Gram Positive Spore Forming Rods
       –   Spore protects from heat, cold


   •   ExoToxins!
       –   antibiotics can’t stop poisons once made
Clostridium
  an-aerobic spore forming gram-positive rod
  •   botulinum     neurotoxic food poison
                    flaccid paralysis
  •   difficile     Diarrhea/enterocolitis
                    antibiotic-associated (clinda, any Beta-lactam)
  •   perfringens   gas gangrene
  •   tetani        lockjaw
Clostridium
Bacillus
   aerobic spore-forming gram-positive rod

   •   anthracis   Pulmonary & Gastrointestinal: Lethal
                   Cutaneous: responds to antibiotics
                   usually was from cows & sheep,
                   now agent of bioterrorism
   •   cereus      food poisoning
B. anthracis
Corynebacterium diphtheriae
  Diphtheria (pediatrics)
  • Colonizes Throat
  •   Exotoxin to Head & Heart
      – Prevent with Diphtheria-Pertussis-Tetanus (DPT)
        vaccine
      – Treat with antitoxin
               plus penicillin (or erythromycin)
               plus DPT vaccine
Listeria monocytogenes
  Meningitis
  • Pediatrics, Immunocompromised
      –  Elderly, Cancer, AIDS
  •   Drug of Choice: Ampicillin IV
  •   Alternative: Trimethoprim/Sulfamethoxazole
      – (aka TMP/SMX, Co-trimoxazole, Septra, Bactrim)
  Gastroenteritis
Staphylococci



                              aureus
                   Positive
       Coagulase
                   Negative

                              "CoNS"
                                Epidermidis
                                Saprophyticus
S. aureus
Disease caused by Staph. aureus
       Meningitis
                        Endocarditis (IV-DA)

        Pneumonia
                       Toxic Shock Syndrome
  Food Poisoning

                      Osteomyelitis
         Cellulitis   #1 cause




                      Chews up tissue
Staph. aureus
  •    99% Resistant to Penicillin, Amoxicillin...
  •    70% Resistant to Methicillin (MR-SA)...
  •     0% Resistant to Vancomycin for now
        – but case reports of VISA...
             Penicillin     Methicillin
                            (anti-staphylococcal penicillin)
                        MS-SA           MR-SA
       Beta-lactamase
          Enzyme
                                                        Vancomycin
                                        PBP
      PBP                       PBP
                                         2a
Treatment:           Methicillin Susceptible
                     S. aureus (MS-SA)
   •   Anti-Staphylococcal Penicillins
       –   faster than Vancomycin for MS-SA endocarditis
       –   Combine with low dose gentamicin for endocarditis for
           synergy (& rifampin if mechanical valve)
   •   1st generation Cephalosporins
       –   Surgical prophylaxis, cellulitis
   •   a Penicillin with Beta-lactamase inhibitor (BL-I)
       –   Amoxicillin/Clavulanate, Ampicillin/Sulbactam,
           Ticarcillin/Clavulanate, Piperacillin/Tazobactam
       –   not a penicillin (amoxicillin, ampicillin, etc) alone
Treatment of Staph. aureus
  •   Less Effective but OK vs MS-SA
      –   Clindamycin > erythromycin
          Tetracyclines, TMP/SMX (static)
  •   Methicillin Resistant S. aureus (MR-SA)
      –   Drug of Choice:Vancomycin (IV only)
           »   Used empirically in high risk patients (ICU)
           »   Linezolid equivalent in SSTI, Bacteremia, and Pneumonia
                 •   Excluded endocarditis & Osteomyelitis
           »   Daptomycin for endocarditis et al
      –   Promising:
           »   Clinda, TMP/SMX, & Tetracyclines (minocycline) in vitro
Coagulase Negative Staph.
  •   saprophyticus - UTI’s in healthy females
  •   epidermidis - common skin flora
          contaminates blood cultures
          Sticks to prosthesis and catheters - line sepsis
          Treatment: Remove source
          Drugs: Like Staph. aureus but more resistance
                77% MR-CoNS
  •   haemolyticus - sometimes Vanco Resistant
S. pneumoniae
Strep. pneumoniae
      Meningitis      Upper Respiratory Tract Infections
        #1 cause      Otitis Media, Sinusitis etc.

                           Pneumonia
    Bacteriemia            #1 cause
    20 pneumonia




                           Common cause
                    of life threatening infections
Definitive Treatment
   •   Penicillin: Drug of choice if susceptible
       –   61% fully susceptible in Memphis
   •   Cephalosporins: 3rd >2nd >1st generation, (not ceftaz)
       –   75% fully susceptible (CNS criteria) in Memphis;
       –   The MED = 99%
   •   Quinolones: Levo >90% susceptible, Moxi > 99%
   •   Vancomycin
       –   100% but doesn’t get into CNS
   •   Less Active but ok if susceptible to penicillins
       –   Macrolides, TMP/SMX, Doxycycline
S. pneumoniae resistance in Memphis
                       Penicillin        Ceftriaxone
                                         (non-CNS)
    S                  71%               97%

    I                  25%               3%

    R                  4%                0%
        Outside the Central Nervous System (ie Lungs),
can treat “I” strains with high dose penicillin or cephalosporins
  Resistance is from change in PBP (lower binding affinity)
Other Streptococcus
           viridans              pyogenes
           Endocarditis          (aka B-hemolytic, Group A)
                                 Strep Throat
                                 Toxic Shock Syndrome
                                 Scarlet Fever
post-pyogenes                    Necrotizing Fasciitis
(delayed-immune mediated)        Skin infections
Rheumatic fever (heart)
Glomerulonephritis (kidneys)
                                         Cellulitis, impetigo
                                  Treat with PCN
                                If Allergic: Erythromycin
                               (some resistance in Europe)
                                   add Clinda if fasciitis
                                  add gent if endocarditis
Enterococci
Formerly Group D Streptococcus

    •   Gut Flora - causes UTI’s
    •   Also bacteremia, found in wounds, urine
        –   May be pathogen or just there because pt sick
             faecalis- common, susceptible
             faecium- nosocomial, resistant (VRE, HLARE)
    •   Blood: (Amp or Vanc) + (Gent or Strep)
    •   Urine: Amp IV or Amox PO , FQ (nitrofurantoin)
    •   Resistance to Vancomycin esp E. faecium
        –   Usually also resistant to ampicillin and or aminoglycosides
        –   Linezolid or Daptomycin now DOC (previously Chloro & Doxy)
Gram Negative
                                      Porin Channel
    –   Outer Membrane
         LPS = endotoxin = septic shock         LPS
    –   Thin Cell Wall
    –   Cytoplasmic Membrane                                Periplasmic Space


                         Outer
                                                                  PBP
                         Membrane                     PBP




                          Cell Wall
                          (Red/Pink on Gram Stain)

                        Cytoplasmic Membrane
Gram Negative Taxonomy
                  Neisseria
         Cocci    gonorrhoeae, meningitidis


                  Enterics
                  Enterobacteriaceae: EPK-SE

                  Diarrhea
                  Salmonella, Shigella, Yersinia
        Bacilli   Vibrio, Campy, Helicobacter

                  Nosocomials
                  Pseudomonads, Acinetobacter

                  Respiratory
                  Hemophilus, Moraxella
Neisseria
gonorrhoeae
- STD/PID               meningitidis
- Bacteremia            meningitis
- Septic arthritis      sepsis (petechial rash)
DOC                     DOC: Penicillin (high dose IV)
 Ceftriaxone            Alt: 3rd generation cephalosporin
STD:                             (ceftriaxone, cefotaxime)
 Ceftriaxone IM/IV        Need to prophylax contacts
 Cefixime PO              rifampin, cipro, ceftriaxone
 Quinolone Resistance
Enteric Anaerobic Gram Negs
  •   Bacteroides
      –   fragilis
           »   Normal gut flora, pathogenic if gets into peritoneum
           »   Abscesses, intra-abdominal infection
      –   melaninogenicus
         Mouth, pathogenic if aspirated
           »
       » Necrotizing aspiration pneumonia
  DOC: Metronidazole
  Alt: Clindamycin (not as good for fragilis as metronidazole)
       Any Penicillin/Beta-Lactamase inhibitor combination,
       Carbapenem (imipenem),
Enterobacteriaceae
                                          Normal Gut Flora
  •   Common, “sensitive”
      –   Escherichia coli
      –   Proteus mirabilis
      –   Klebsiella pneumonia
  •   Nosocomial, “resistant”
      –   Serratia marcescens
      –   Enterobacter sps, Citrobacter
E. coli
E.coli
   •   Normal Gut Flora - But can acquire virulence factors!
       –   Mucosal interaction
       –   Exotoxin or Endotoxin production
   •   Then can cause
       –   UTI’s: acquire pili & move up urethra into bladder
            »   Most common cause in women & can lead to pyelonephritis
       –   Meningitis: in neonates, post CNS surgery
       –   Sepsis: from pyelonephritis, also nosocomial
       –   Pneumonia: nosocomial, some times community acquired
       –   Diarrhea….
Diarrhea from E. coli
   •   Toxigenic (ET-EC)
       –   Exotoxins (like cholera) w/ intestinal binding
       –   Travelers diarrhea
   •   Hemorrhagic (EH-EC)
       –   Exotoxins (like shigella) w/ intestinal binding
       –   bloody diarrhea, HUS w/O157:H7
   •   Invasive (EI-EC)
       –   Exotoxins (like shigella) w/ epithelial infection
       –   Bloody w/WBC and Fever
Proteus & Klebsiella
   •   Proteus
       –   mirabilis (indole - ) and vulgaris (indole + )
       –   UTI’s, nosocomial pneumonia

   •   Klebsiella pneumoniae
       –   Pneumonia in alcoholics, debilitated,
           hospitalized
            »   Cavitary w/ bright red sputum
       –   Nosocomial UTI’s with urethral catheter
    Treating EPK
Cephalosporin Susceptibility: 3rd Gen: 96%, 1st Gen 86%
•   E.coli                  3rd Generation Cephalosporins
                            +/- an aminoglycoside (gentamicin)
                            Quinolones (80%); Carbapenems (100%),
                            Any Cephalosporin, TMP/SMX (75%), Aztreonam
                            Antipseudomonal Penicillin
                            with or without a Beta-lactamase Inhibitor
•   Proteus mirabilis       Ampicillin, any E. coli treatment
           vulgaris         3rd Gen Ceph, Carbapenem, Antipseudomonal PCN
                            (+/- Quinolone or Aminoglycoside)
•   Kleb. pneumoniae        Any E. Coli treatment except Ampicillin
Serratia & Enterobacter
  Nosocomial Pneumonia
  • Serratia marcescens
      –   3rd Gen Ceph, Carbapenem, (+/- gentamicin or
          quinolone); Quinolone
  •   Enterobacter aerogenes, cloacae; Citrobacter
      cephalosporin-ases inactivates ceftazidime et al
      –   Carbapenem or Antipseudomonal penicillin
          with an aminoglycoside or quinolone); quinolone
      –   Cefepime OK?
Gram-Negs that cause Diarrhea
  always pathogenic if found in stool
  • Shigella - via fecal-oral
      –   Shiga toxin: bloody diarrhea w/ WBC; fever
  •   Salmonella - Turtles, eggs (man-typhi)
      –   diarrhea, Typhoid fever +/- carrier state,
      –   sepsis, osteo in asplenic patients
  •   Yersinia enterocolitica - via fecal-oral
      –   invasive w/enterotoxin, survives refrigeration
Other GI Gram-Negatives
  •   Vibrio cholera via fecal-oral (water)
      –   like ET-EC (rice water) but worse

  •   Campylobacter jejuni animals (water)
      –   like S.typhi, Y. enterocolitica (bloody diarrhea)

  •   Helicobacter pylori
      –   Most common cause of duodenal ulcers
Other Pathogenic Zoonotic GNR
  •   Yersinia pestis - Plague
      – Bubonic from rat bites
      – Pneumonic from bioterrorism
  •   Francisella tularensis - Tularemia
      – Pneumonia, Skin & lymph nodes; from rabbits
  •   Brucella sps - Brucellosis
      – Undulant fever; from goats, cows, pigs & dogs
  •   Pasteurella multocida - Pasteurella
      – Common cause of bite wounds; dogs & cats
Pseudomonas aeruginosa
Pseudomonas aeruginosa
                              Post-op Meningitis
Malignant
Otitis External

 Endocarditis                 Pneumonia
 (Intravenous drug abusers)    Cystic fibrosis
                               Nosocomial

 Sepsis
                               UTI’s
 Nosocomial
                                Catheter/nosocomial
 (from lungs/UTI)




                               Osteomyelitis
                                IVDA (vertebral)
                                Nail, Diabetic Foot
Treatment:
Beta-lactam +/- Aminoglycoside
   •   Add Aminoglycoside for empiric antipseudomonal coverage
       unless the Beta-lactam is really good (>85% S)
   •   Beta-lactams IV
       –   Penicillins:           92%    Piperacillin ( > Ticarcillin)
       –   Cephalosporins:        93%    Cefepime, Ceftazidime
       –   Other:                 83,67% Carbapenem, Aztreonam
   •   Aminoglycosides IV
       –   Amikacin (99%) > Tobramycin (89% S) > Gentamicin (82% S)
   •   Quinolones IV & PO
       –   Cipro (74% S) > Levo NOT Moxi
Nosocomial Gram-Negatives
Pneumonia & Sepsis

   Things that used to be a Pseudomonas
      Burkholderia cepacia         Ceftazidime or TMP/SMX
      Stenotrophomonas maltophilia
                      TMP/SMX and/or Ticarcillin/Clavulanate

   Acinetobacter calcoaceticus-baumannii
      –   Bad Bug: Tx:
      –   Carbapenem (or Ampicillin/Sulbactam) with amikacin

   Wash Your Hands (to prevent)
“Respiratory” Pathogens
  •   Haemophilus influenzae
      –   type b: covered by vaccine, effective at >18 months
            meningitis, epiglottitis, septic arthritis, sepsis
           »   Ceftriaxone or Cefotaxime w/steroids in meningitis (peds)
           »   TMP/SMX, Carbapenem, quinolone, Chloramphenicol
      –   Otitis (pediatric); bronchitis, Pneumonia (smokers)
           »   Amoxicillin; Amoxicillin/Clavulanate, TMP/SMX,
               Clarithro/Azithromycin, 2-3 cephPO
      –   19% Resistant Amoxicillin via Beta-lactamase
           (100% susceptible to Amoxicillin w/ Clavulanate)
Haemophilus influenzae
Respiratory Pathogens
  •   Moraxella catarrhalis
      –   Otitis, sinusitis, bronchitis, pneumonia
           Amoxicillin/Clavulanate, 2-3 CephPO ,
           Clarith/Azithromycin, TMP/SMX
          70% resistant to Amoxicillin via beta-lactamase
  •   Legionella sps
      –   Severe (atypical) pneumonia
          DOC: Erythromycin (1g IV Q6) +/- rifampin
          New options: Azithromycin, Levofloxacin
Legionella

				
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