Antibiotic Resistance

Aka: Antibiotic Resistance, Antibiotic Resistant Infection, Antimicrobial Resistance, Multidrug-Resistant Organism, Multi-Drug Resistant Bacteria, Beta-Lactamase

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II. Epidemiology

  1. Health Care Associated Infections are caused by multidrug resistant organisms in 16% of cases (especially MRSA)

III. Pathophysiology

  1. Factors Affecting Drug Resistance
    1. Antibiotic Overuse
      1. Viral Upper Respiratory Infections
      2. Agricultural Antibiotic use (animal breeding and enhancing growth, fisheries)
      3. Antimicrobial cleaning solutions
    2. Increasing Incidence of Immunocompromised patients
      1. Prolonged Antibiotic exposure
    3. Food supply globalization
    4. International travel
  2. Common features in Antibiotic Resistance
    1. Antibiotic Resistance is virtually guaranteed given enough time and exposure
    2. Antibiotic Resistance typically progresses over time from low to high levels
    3. Cross-resistance to multiple Antibiotics ocurs frequently
    4. Once drug resistance occurs, it typically remains, or decreases very slowly
    5. Antibiotic exposure affects not only the treated patient, but also others in their environment
  3. Common mechanisms of Microorganism genetic variability
    1. DNA point mutations (may modify antimicrobial target site configuration)
    2. Large segment DNA changes
    3. Foreign DNA via Plasmids, Bacteriophages
  4. Common mechanisms of Antimicrobial Resistance
    1. Enzyme inhibitors (e.g. Beta Lactamases)
    2. Decreased membrane permeability to antimicrobials (e.g. Gram Negative lipid bilayer)
    3. Active cellular pumps facilitate antimicrobial efflux (e.g. Tetracycline resistance)
    4. Protein target modifications (e.g. ribosomal target alteration in Macrolide resistance)
    5. Antimicrobial bypass tracks (e.g. Enterococcus may use exogenous thymidine)

IV. Mechanisms: Beta-Lactamase

  1. More than 300 Beta Lactamases have been identified (e.g. ESBL, KPC, NDM-1, CRE)
  2. Beta-Lactams (Penicillins and Cephalosporins) inhibit transpeptidase
  3. Transpeptidase cross-links peptidoglycan mesh in the synthesis of the Bacterial cell wall
    1. Beta-Lactams inhibition of Transpeptidase results in lysis and death of the Bacterial cell
  4. Beta-Lactams are inactivated by the enzyme Beta-Lactamase
    1. Beta-Lactamase is produced by beta-lactam resistant Bacteria
  5. Several Antibiotics have since been developed to be resistant to Beta-Lactamase
    1. Beta-Lactamase Resistant Penicillins include Dicloxacillin and Nafcillin

V. Causes: Emerging Drug Resistance

  1. Methicillin Resistant Staphylococcus Aureus (MRSA)
  2. Penicillin Resistant Pneumococcus
  3. Vancomycin Resistant Enterococcus (VRE)
  4. Multi-resistant Gram Negative Bacilli
    1. ESBL-Producing Enterobacteriaceae
    2. Carbapenem-Resistant Enterobacteriaceae (CRE)
    3. Carbapenem-Resistant Klebsiella
    4. AmpC Beta-Lactamase-Producing Enterobacteriaceae (typically respond to Cefepime)
      1. Enterobacter cloacae
      2. Klebsiella aerogenes
      3. Citrobacter freundii
    5. Pseudomonas Aeruginosa resistance
    6. Nosocomial outbreaks
    7. Restricted drug use sometimes beneficial
  5. Multi-Resistant Neisseria Gonorrhea
  6. Multi-Resistant Tuberculosis
  7. Carbapenem-Resistant Acinetobacter Baumannii
    1. Lung and Wound Infections or colonization
    2. Treated with high dose Unasyn (>= 6g sulbactam) AND Minocycline, Tigecycline or polymyxin B
    3. May be sensitive to Cefiderocol
  8. Stenotrophomonas Maltophilia
    1. Lung and Wound Infections in Immunocompromised patients (esp. Hematologic Malignancy)
    2. Treated with two of the following: TMP-SMZ, Minocycline, Tigecycline, cifiderocol, Levofloxacin
    3. Alternatively treated with Ceftazidime-Avibactam AND Aztreonam

VI. Prevention

  1. Antibiotic Stewardship
    1. Limit Antibiotics to cases in which they are absolutely indicated
    2. Educate patients and follow guidelines regarding Antibiotic indications (e.g. URI vs Bacterial Sinusitis)
    3. Use the narrowest spectrum antimicrobial appropriate for the indication
    4. Limit broad spectrum Antibiotics to severe illness (e.g, Sepsis)
  2. Prevent spread
    1. See Health Care-Associated Infection
    2. See Personal Protection Equipment
    3. Practice good Hand Hygiene before and after seeing each paint
    4. Follow contact precautions for colonized or infected patients
    5. Consider culturing for nasal MRSA in high risk hospital settings (e.g. ICU)
    6. Consider nasal decolonization with Bactroban of infected patients
  3. Decolonization
    1. Chlorhexidine baths daily for Intensive Care unit patients (esp. MRSA, VRE patients)

VII. Resources

  1. Centers for Disease Control
    1. Patient Education Tools on appropriate Antibiotic use
      1. http://www.cdc.gov/antibioticresistance/tools.htm
  2. Patient Education from FamilyDoctor.org
    1. Antibiotic Resistance
      1. http://www.familydoctor.org/handouts/659.html
    2. Antibiotic Indications
      1. http://www.familydoctor.org/handouts/680.html

VIII. Reference

  1. Gladwin, Trattler and Mahan (2014) Clinical Microbiology, Medmaster, Fl, p. 387-91
  2. (1995) Lecture: M Osterholm, MD, Minneapolis, MN
  3. Hooton (2001) Am Fam Physician 63(6):1087-6 [PubMed]
  4. Hsu (2014) Am Fam Physician 90(6): 377-82 [PubMed]
  5. Sensakovic (2001) Med Clin North Am 85:115-23 [PubMed]
  6. Tamma (2023) Clin Infect Dis +PMID: 37463564 [PubMed]

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