Harvey's Garden

Antibiotics

3 min read

Penicillin

  • Syphilis (Treponema pallidum):

    • Drug of Choice: Penicillin G is the only effective treatment for all stages, especially neurosyphilis and syphilis in pregnancy.
    • Regimen: Single IM dose of Benzathine Penicillin G for primary/secondary syphilis.

  • Streptococcal Pharyngitis (Strep Throat - Group A Strep):

    • Drug of Choice: Oral Penicillin V or Amoxicillin for 10 days.
    • Key Goal: Prevent acute rheumatic fever. No known resistance of GAS to penicillin.

  • Rheumatic Fever Prophylaxis:

    • Drug of Choice: Long-acting IM Benzathine Penicillin G (e.g., every 3-4 weeks) for secondary prevention after an initial episode.

  • Actinomycosis (Actinomyces israelii):

    • Drug of Choice: High-dose IV Penicillin G for an extended period, followed by oral therapy.
    • Buzzwords: “Sulfur granules,” jaw/cervicofacial abscess.

  • Leptospirosis (Leptospira spp.):

    • Drug of Choice: IV Penicillin G is used for severe disease.
    • Presentation: Flu-like illness, conjunctival suffusion, myalgias, often with animal/water exposure.

  • Meningococcal Disease (Neisseria meningitidis):

    • Drug of Choice: Penicillin G is effective if the isolate is susceptible (though ceftriaxone is often used empirically first).

Cephalosporins

Mnemonic

Cephalosporins are LAME: 1st–4th generation cephalosporins do not act against

  • Listeria
  • Atypical organisms (e.g., Chlamydia, Mycoplasma)
    • No cell wall
  • MRSA
  • Enterococci (with the exception of ceftaroline, which does act against MRSA).

Nitrofurans

  • Examples: nitrofurantoin
  • Mechanism of action: reduced by bacterial nitroreductases to reactive metabolites → bind to bacterial ribosomes → impaired metabolism, impaired synthesis of protein, DNA, and RNA → cell death (bactericidal effect)
  • Treatment and prophylaxis of acute uncomplicated UTIs (e.g., urethritis, cystitis)

Drug resistance

Mechanisms

Type of resistanceExample mechanismsExample antibiotics affected
Increased drug efflux pump• New membrane transport system• Tetracyclines, fluoroquinolones
Drug-inactivating enzyme• Beta-lactamase
• Acetyltransferase		• Penicillins, cephalosporins
• Aminoglycosides
Decreased drug uptake• Mutated porin protein• Penicillins, fluoroquinolones
Modified drug target• Altered penicillin-binding protein
• Altered ribosomal protein
• Altered DNA gyrase		• Penicillins
• Aminoglycosides, macrolides
• Fluoroquinolones

Examples

1. MRSA (Methicillin-Resistant Staphylococcus aureus)

  • Clues: Purulent skin/soft tissue infections (SSTIs) often looking like “spider bites” (CA-MRSA); hospital-acquired pneumonia, post-op infections, line infections (HA-MRSA). Post-influenza pneumonia.
  • Mechanism: mecA gene (altered PBP2a).
  • Tx:
    • SSTI (CA): TMP-SMX, Doxycycline, Clindamycin (after I&D).
    • Severe/Hospital (HA): Vancomycin, Linezolid, Daptomycin.

2. VRE (Vancomycin-Resistant Enterococci)

  • Clues: UTI, bacteremia in hospitalized patients with prolonged antibiotic use (especially vancomycin/cephalosporins) or indwelling catheters.
  • Mechanism: D-Ala-D-Ala to D-Ala-D-Lac/Ser.
  • Tx: Linezolid, Daptomycin. (Nitrofurantoin/Fosfomycin for cystitis if susceptible).

3. Extended-Spectrum Beta-Lactamase (ESBL)-Producing Enterobacterales (E. coli, Klebsiella)

  • Clues: Recurrent UTIs despite cephalosporins; hospital/LTCF-acquired infections (UTI, intra-abdominal).
  • Mechanism: Beta-lactamases hydrolyzing most penicillins & cephalosporins.
  • Tx: Carbapenems (Imipenem, Meropenem). (Fosfomycin/Nitrofurantoin for cystitis if susceptible).

4. CRE (Carbapenem-Resistant Enterobacterales - e.g., Klebsiella pneumoniae carbapenemase/KPC)

  • Clues: Critically ill ICU patients; multiple prior antibiotics (including carbapenems); invasive devices. High mortality.
  • Mechanism: Carbapenemase enzymes.
  • Tx: Very limited; often combination therapy with newer agents (e.g., Ceftazidime-avibactam, Meropenem-vaborbactam) or Colistin/Tigecycline.

5. Drug-Resistant Streptococcus pneumoniae

  • Clues: CAP, meningitis, otitis media failing first-line beta-lactams. Risk factors: age extremes, daycare, recent antibiotics.
  • Mechanism: Altered PBPs (penicillin resistance); ribosomal methylation/efflux (macrolide resistance).
  • Tx:
    • CAP (non-meningeal): Respiratory Fluoroquinolones (Levofloxacin, Moxifloxacin), Vancomycin (if severe/highly resistant). Ceftriaxone (if lower-level penicillin resistance).
    • Meningitis: Vancomycin + 3rd gen Cephalosporin (e.g., Ceftriaxone).

6. MDR-TB & XDR-TB (Multidrug/Extensively Drug-Resistant Tuberculosis)

  • Clues: Prior TB treatment failure; from high-prevalence area; HIV co-infection; persistent TB symptoms despite standard therapy.
  • MDR: Resistant to Isoniazid (INH) + Rifampin (RIF).
  • XDR: MDR + resistance to a fluoroquinolone AND ≥1 injectable second-line drug.
  • Mechanism: Chromosomal mutations (e.g., katG, rpoB).
  • Tx: Complex, prolonged multi-drug regimens with second-line drugs (e.g., Bedaquiline, Linezolid, Fluoroquinolones) based on DST. Expert consultation mandatory.

7. Multidrug-Resistant Pseudomonas aeruginosa

  • Mechanism: High intrinsic and acquired resistance using multiple strategies simultaneously, including efflux pumps, mutations in porin channels (reducing drug entry), and production of various β-lactamases.

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