Antibiotic Use and Resistance by 667pn8

VIEWS: 21 PAGES: 86

									Antibiotic Use and Resistance
   Ask Questions, Then Shoot…


      Michael J. Pistoria, DO, FACP, SFHM
                  Outline
■   History

■   Antibiotic classes

■   General principles

■   Preventing Resistance
Special thanks…
History
Antibiotic Classes
          Antibiotic Classes
■ Aminoglycosides        ■   Glycylcyclines
■ Β-lactams              ■   Lincosamides
    ●   Penicillins      ■   Lipopeptides
    ●   Cephalosporins   ■   Macrolides
    ●   Carbapenems
                         ■   Oxazolidinones
    ●   Monobactams
                         ■   Sulfonamides
■ Fluoroquinolones
                         ■   Tetracyclines
■ Glycopeptides
Aminoglycosides
              Aminoglycosides
■   Bind irreversibly to     ■   Coverage
    30S ribosome                   ●   Gram-negative
      ●   Inhibits protein         ●   Pseudomonas
          synthesis
                             ■   Adverse effects
■   Common drugs                   ●   Renal damage
      ●   Amikacin                 ●   Hearing loss
      ●   Gentamicin               ●   Vertigo
      ●   Tobramycin
β-lactams
         β-lactams: Penicillins
■   Disrupt synthesis of cell wall
■   Wide range of coverage, especially
    gram-positive
■   Most are renally excreted
■   Adverse effects
     ● Allergy and anaphylactic reactions
     ● GI upset and diarrhea
    β-lactams: Cephalosporins
■   Disrupt synthesis of cell wall
■   Bactericidal
■   Coverage shifts with higher generations
      ●   Cefepime adds Pseudomonas
■   Most are renally excreted
■   Adverse effects similar to penicillins
      ●   10-15% cross-reactivity
    β-lactams: Carbapenams
■ Inhibit cell wall        ■ Intrinsic resistance
  synthesis                  to MRSA
■ Common drugs             ■ Adverse effects
      ● Ertapenem              ●   Rash and allergic
      ● Imipenem                   reactions
      ● Meropenem              ●   Headache
                               ●   Seizures
■   Bactericidal against
    gram-positive and          ●   GI upset and
                                   diarrhea
    gram-negative
                               ●   Nausea
    β-Lactams: Monobactams
■   Aztreonam
     ● Disrupts synthesis of cell wall
     ● Coverage against gram-negative
     ● Similar to aminoglycosides, but without
       the nephrotoxicity
Fluoroquinolones
Fluoroquinolones
              Fluoroquinolones
■   Inhibit DNA gyrase      ■   Coverage
                                  ●   Cipro strong against
                                      GNRs
■   Common drugs
                                  ●   Levo/Moxi have greater
      ●   Ciprofloxacin               gram-(+) coverage
      ●   Levofloxacin
      ●   Moxifloxacin
                            ■   Adverse effects
                                  ●   GI upset
■   Good bioavailability!         ●   QT prolongation
                                  ●   Achilles tendon rupture
                                  ●   Phototoxicity
Glycopeptides
              Glycopeptides
■   Vancomycin
     ●   Coverage against gram-(+) aerobes and
         anaerobes
         – Bacteristatic against enterococci
         – Synergistic with gentamicin against
           enterococci and staph
         – Emerging resistance: VRE and VISA
              Glycopeptides
■   Vancomycin
     ● Good penetration of serous membranes
     ● CSF penetration ONLY with inflamed
       meninges
     ● Poor PO absorption
     ● Mostly renal excretion
         – Cautious dosing in renal patients
                Glycylcyclines
■   Derived from tetracyclines
      ●   Bind more effectively to 30S ribosomal subunit
■   Tigecycline
      ●   Active against many gram-(+), gram-(-) and
          anaerobic bacteria
      ●   Effective against MDR Acinetobacter
      ●   Approved for complicated cSSSIs and intra-
          abdominal infections
      ●   Adverse effects similar to tetracyclines
      ●   2010 safety announcement
Lincosamides
                Lincosamides
■   Clindamycin
     ● Binds 50S subunit, inhibiting protein
       synthesis
     ● Coverage
         – Strong anaerobic coverage
         – Staph, strep and pneumococcal infections in
           PCN-allergic patients
     ●   Adverse effects
         – C. difficile
    Lipopeptides: Daptomycin
■   Novel drug
■   Disrupts cell membrane function
■   Coverage against resistant gram-(+)
    organisms
■   Limited use
     ● cSSSIs
     ● Right-sided endocarditis due to MRSA or
       MSSA
    Lipopeptides: Daptomycin
■   Adverse effects
     ● Myopathy
     ● Peripheral neuropathy


■   Do not use to treat pneumonia
Macrolides
               Macrolides
■ Reversibly bind to   ■   Coverage
  50S subunit                ● Strep infections
■ Common drugs               ● Mycoplasma

    ● Azithromycin           ● Lyme

    ● Claithromycin          ● Syphilis

    ● Erythromycin
    ● Telithromycin*   ■   Adverse effects
                             ●   Nausea, vomiting
                                 and diarrhea
    Oxazolidinones: Linezolid
■   Coverage                      ■   Good bioavailability
      ●   Bacteristatic against   ■   Adverse effects
          Staph and
                                        ●   Serotonin syndrome
          enterococcus
                                        ●   Long-term use can
      ●   Bactericidal versus
                                            lead to:
          most Strep spp.
                                            – Myelosuppression
■   Approved for:                           – Peripheral neuropathy
      ●   HAP/CAP                           – Optic neuritis
      ●   VRE and MRSA
      ●   cSSSI
      ●   SBE (not 1st line!)
Oxazolidinones: Linezolid
Sulfonamides
              Sulfonamides
■ Trimethoprim-            ■   Adverse effects
  sulfamethoxazole               ●   Allergy (skin rash)\
■ Coverage                           – SJS
                                 ●   Nausea, vomiting
    ● Strep, staph, E.
      coli, H. flu, oral             and diarrhea
      anaerobes                  ●   Neutropenia
    ● Excellent UTI              ●   Thrombocytopenia
      coverage
    ● Pneumocystis
Tetracyclines
            Tetracyclines
■ Bind 30s subunit    ■   Adverse effects
■ Reduced efficacy          ●   GI upset
  due to resistance         ●   Phototoxicity
    ● Acne                  ●   Teeth discoloration
    ● Rosacea
    ● Syphilis        ■   Demeclocycline
    ● Chlamydial
      infections
General Principles
    Remember Your ABCs…

■ Allergies
■ Bacterial target
■ Co-morbidities
■ Destination
■ Excretion
■ Formulary
                 Allergies
■   True reaction or intolerance?
     ●   Hives
     ●   Fevers
     ●   Nausea
     ●   Anaphylaxis
     ●   Red man’s syndrome
                 Allergies
■   True reaction or intolerance?
     ●   Hives
     ●   Fevers
     ●   Nausea
     ●   Anaphylaxis
     ●   Red man’s syndrome
                 Bacterial Target
■   Biliary               ■   Urinary
      ●    E. coli              ●   Community
      ●    Klebsiella               – E. coli
      ●    Enterobacter             – Staph saprophyticus
      ●    Enterococci
      ●    Salmonella           ●   Hospital and long-term
      ●    Clostridium              care facilities
      ●    Bacteroides              –   Proteus
                                    –   Klebsiella
■   Skin                            –   Pseudomonas
      ● MSSA                        –   Enterobacter
      ● MRSA
      ● Group A Strep
             Co-morbidities
■   Renal function
     ●   Measure GFR and creatinine clearance
■   Hepatic function
■   Drug interactions
     ● QT prolongation
     ● P450 system
     ● Coumadin
■   Pregnancy/breast feeding
Destination
      ■   Daptomycin

      ■   Vancomycin
           ●   Oral
           ●   CSF


      ■   Gentamicin
                   Excretion
■   Relates back to the destination
■   Helps with drug dosing
     ●   Will the drug and/or metabolites
         accumulate?
         – Methotrexate and TMP/Sulfa
         – Voriconazole and its substrate
Formulary
Cardinal Rules
       ■   Check your
           antibiogram
             ●   Know your
                 institution’s
                 sensitivity and
                 resistance patterns
Examples
               Cellulitis
■   55-year old with two days of lower
    extremity erythema
■   The patient has no known medication
    allergies or intolerances
■   Has a baseline creatinine of 2mg/dl
    secondary to long-standing
    hypertension
          Which Antibiotic?
1.   Vancomycin

2.   Cefazolin

3.   Ciprofloxacin

4.   Piperacillin/tazo
     Remember Your ABCs…
A:      None known
B:      Skin → Staph (MRSA/MSSA)
             and GAS
C:      CKD secondary to HTN
D:      Do those agents penetrate the
             skin and soft tissue?
          Which Antibiotic?
1.   Vancomycin

2.   Cefazolin

3.   Ciprofloxacin

4.   Piperacillin/tazo
      Urinary Tract Infection
■   A 68-year old female presents with
    urgency, frequency, and dysuria
■   She has a history of recurrent UTIs
■   She denies fever, chills, nausea,
    vomiting, headaches
■   She was on antibiotics six weeks ago
    for similar symptoms
     ●   Developed a rash on sulfa
          Which Antibiotic?
1.   Doxycycline

2.   Cephalexin
     (Keflex)

3.   T-Sulfa (Bactrim)

4.   Ciprofloxacin
     Remember Your ABCs…
A:       Sulfa drugs!
B:       E. coli, Klebsiella, Proteus,
              enterococcus
C:       None
D and E: Doxycycline has less excretion
              via kidney than β-lactams
            Urine culture
Urine: >100,000 colonies Proteus mirabilis

    Cefazolin               <=1 susceptible
    Gentamicin              <=1 susceptible
    Ampicillin              8 susceptible
    Cipro                   2 intermediate
    TMP/SMX                 <= 20 susceptible
    Cefepime                <=1 susceptible
    Meropenem               <=0.25 susceptible
    Pip/tazo                <=4 susceptible
          Which Antibiotic?
1.   Doxycycline
2.   Cephalexin
     (Keflex)
3.   T-Sulfa (Bactrim)
4.   Ciprofloxacin
      Ascending Cholangitis
■   55-year old male admitted with right
    upper quadrant pain and fever
■   His history is significant for atrial
    fibrillation
     ●   Takes warfarin (Coumadin)
■   Diagnosed with ascending cholangitis
          Which Antibiotic?
1.   Cefazolin + MTNZ

2.   Vancomycin +
     MTNZ

3.   Levofloxacin +
     MTNZ
     Remember Your ABCs…
A:       None
B:       E. coli, Klebsiella, Enterobacter,
               Enterococci, Salmonella,
               Clostridium, Bacteroides
C:       AF on anticoagulation
D and E: All have good biliary tract
               absorption
      Ascending Cholangitis
■   Remember your antibiogram!
      Ascending Cholangitis
■   Culture returns positive for E. coli

      ● Cefazolin      91% sensitive
      ● Levofloxacin   79% sensitivity (cipro)


■   Therefore, cefazolin + MTNZ is the
    better choice at our institution
          Which Antibiotic?
1.   Cefazolin + MTNZ

2.   Vancomycin +
     MTNZ

3.   Levofloxacin +
     MTNZ
  Remember your ABCs…
 Think about the location of the infection,
                  AND...
   The common organisms found there,
                 AND…
 Whether the antibiotic gets to that spot,
                 AND…
Is there a reason NOT to use that agent?
Preventing
Resistance
Impact of Antibiotic Resistance

■   Treatment failure
■   Poor outcomes
■   Increased mortality
■   Need for combination therapy
■   Increased costs
      Preventing Resistance
■   Prevent Infection
     ● Vaccinate
     ● Get the catheters out


■   Diagnose and Treat Effectively
     ● Target the pathogen
     ● Access the experts
      Preventing Resistance
■   Use Antimicrobials Wisely
     ●   Practice local antimicrobial control
     ●   Use local data
     ●   Treat infection, not contamination
     ●   Treat infection, not colonization
     ●   Know when to say “no” to Vanco
     ●   Stop treatment when cured
      Preventing Resistance
■   Prevent Transmission
     ● Isolate the pathogen
     ● Contain your contagion
Importance of De-escalation
              ■ Does the patient still
                need antibiotics?
              ■ Does the antibiotic
                work against the
                organism?
              ■ Can I narrow my
                coverage?
Importance of De-escalation
■   Rely on your culture and sensitivity data
■   Modify your initial selection based upon
    susceptibility
■   Use the context of the patient’s
    improvement (or lack thereof) when
    making your decision
■   Individualize treatment duration based
    on patient factors and clinical response
Guideline-Based De-escalation

■   Culture result
■   Empiric treatment
■   Reassess in 24-48 hours
■   7-day treatment duration




            Ibrahim EH, et al. Crit Care Med. 2001;29:1109-1115.
                               Pre-    Post-
                             (n = 50) (n = 52)
Initial adequate therapy
                              48.0      94.2
(%)
                             14.8 ±
Duration of therapy (days)            8.6 ± 5.1
                               8.1
                             23.1 ±    21.7 ±
ICU length-of-stay (days)
                              17.4      12.9

Mortality (%)                 51.9      42.0

Secondary VAP (%)             24.0      7.7
                               Pre-    Post-
                             (n = 50) (n = 52)
Initial adequate therapy
                              48.0      94.2
(%)
                             14.8 ±
Duration of therapy (days)            8.6 ± 5.1
                               8.1
                             23.1 ±    21.7 ±
ICU length-of-stay (days)
                              17.4      12.9

Mortality (%)                 51.9      42.0

Secondary VAP (%)             24.0      7.7
        Take Home Messages
■ Remember your
  ABCs
■ Document “dose,
  duration and
  indication”
■ Get cultures
■ Take a timeout
    ●   De-escalation
       Take Home Messages
■   Bioavailability


■   Restrict use of:
         –   Carbapenems
         –   Daptomycin
         –   Linezolid
         –   Tigecycline
Contact Information:
                 Who We Are
■   Largest academic community   ■   Magnet Hospital
    hospital in PA               ■   143,850 ED visits /
■   Largest Level 1 Trauma           49,300 admissions
    Center in PA                 ■   988 acute care beds
■   Certified Stroke Center      ■   3 hospital campuses
■   Employees – 9,500            ■   Revenues over
    Medical Staff – 1,100+           $1 Billion
    Nurses – 2,334

								
To top