Infectious Disease (ID) on NAPLEX: Stop Memorizing Every Antibiotic, This Is the High-Yield "Bug-to-Drug" Chart You Actually Need

Infectious Disease (ID) on NAPLEX: Stop Memorizing Every Antibiotic, This Is the High-Yield “Bug-to-Drug” Chart You Actually Need

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The NAPLEX loves infectious disease because it tests whether you can pick a rational empiric therapy quickly and safely. You do not need to memorize every antibiotic. You need a short “bug-to-drug” map, plus the reasons those pairings work. Below is the high-yield chart and the rules behind it, so you can adapt to any stem that throws in allergies, renal impairment, or resistant organisms.

How to think on ID questions

  • Empiric vs. targeted: Start broad when the source is unclear or life-threatening, then narrow when cultures return. The exam expects you to de-escalate correctly.
  • Host matters: Pregnancy, age, renal/hepatic function, and immune status change the drug. For example, avoid tetracyclines in pregnancy/children; adjust renally cleared drugs.
  • Site matters: Drugs must penetrate where the bug lives. Nitrofurantoin is great in bladder but useless for pyelonephritis. Daptomycin fails in lungs due to surfactant binding.
  • Local resistance patterns: The test often implies resistance risk (prior antibiotics, healthcare exposure). Respond by adding MRSA or Pseudomonas coverage as needed.

The high-yield bug-to-drug map (with “why”)

Gram-positive cocci

  • Streptococcus pneumoniae (CAP, meningitis):
    • First-line: High-dose amoxicillin (outpatient), ceftriaxone (inpatient), or a respiratory fluoroquinolone (levofloxacin/moxifloxacin) if beta-lactam allergy. Add vancomycin for meningitis until susceptibilities known.
    • Why: S. pneumo has altered PBPs; high-dose beta-lactams overcome this. Macrolide resistance is common, so avoid macrolide monotherapy if moderate/high local resistance.
  • Group A Strep (S. pyogenes; strep throat, cellulitis):
    • First-line: Penicillin or amoxicillin; cephalexin for skin/soft tissue.
    • Alternatives: Clindamycin or azithromycin for severe beta-lactam allergy, but check local macrolide resistance.
    • Why: GAS remains universally susceptible to penicillin; macrolide resistance is rising.
  • MSSA (skin/soft tissue, bacteremia):
    • First-line: Anti-staphylococcal penicillins (nafcillin/oxacillin/dicloxacillin) or cefazolin/cephalexin.
    • Why: Beta-lactams kill MSSA faster than vancomycin and reduce failures.
  • MRSA:
    • Community SSTI: TMP-SMX, doxycycline, or clindamycin (ensure D-test negative if inducible resistance suspected).
    • Serious/hospital-acquired: Vancomycin first; alternatives include daptomycin (not pneumonia), linezolid, or ceftaroline.
    • Why: mecA alters PBPs; beta-lactams don’t bind. Daptomycin is inactivated by pulmonary surfactant, so never use for pneumonia.
  • Enterococcus (E. faecalis/faecium):
    • First-line: Ampicillin for faecalis if susceptible; vancomycin if resistant to ampicillin.
    • VRE: Linezolid or daptomycin (higher doses for bacteremia).
    • Endocarditis: Add gentamicin for synergy when susceptible.
    • Why: Enterococcus has low-level beta-lactam susceptibility and often requires synergy for deep-seated infections.

Gram-negative rods

  • Enterobacterales (E. coli, Klebsiella, Proteus):
    • Uncomplicated cystitis: Nitrofurantoin (5 days), TMP-SMX (3 days) if local resistance <20%, or single-dose fosfomycin.
    • Pyelonephritis/sepsis: Ceftriaxone, cefepime, piperacillin/tazobactam; use a carbapenem for ESBL producers.
    • Avoid: Moxifloxacin for UTI (poor urine levels).
    • Why: Nitrofurantoin concentrates in bladder only; ESBL enzymes destroy most beta-lactams except carbapenems.
  • Pseudomonas aeruginosa:
    • Active drugs: Piperacillin/tazobactam, cefepime, ceftazidime, aztreonam, meropenem/imipenem (not ertapenem), ciprofloxacin/levofloxacin, aminoglycosides. Newer options: ceftolozane/tazobactam, ceftazidime/avibactam.
    • Severe infections: Start with two active classes until susceptibilities return, then de-escalate to one.
    • Why: Pseudomonas has multiple efflux pumps and porin mutations; combination empiric therapy reduces the risk of inadequate coverage.
  • Acinetobacter baumannii:
    • Options: Ampicillin/sulbactam (sulbactam has intrinsic activity), meropenem/imipenem (not ertapenem), high-dose tigecycline or polymyxins if MDR.
    • Why: Intrinsic resistance is common; sulbactam is uniquely active beyond enzyme inhibition.

Atypicals (no cell wall):

  • Mycoplasma, Chlamydophila, Legionella:
    • Active drugs: Macrolides (azithromycin), doxycycline, respiratory fluoroquinolones (levofloxacin/moxifloxacin).
    • Avoid: All beta-lactams (no cell wall target).
    • Why: Intracellular pathogens require drugs that penetrate cells and bind ribosomes or DNA enzymes.

Anaerobes

  • Mouth/aspiration (Peptostreptococcus, oral flora): Penicillin/amoxicillin, amoxicillin–clavulanate, or clindamycin. Why: Clindamycin covers oral anaerobes well and concentrates in tissues.
  • Gut anaerobes (Bacteroides fragilis): Metronidazole, beta-lactam/beta-lactamase inhibitors (amp/sulb, pip/tazo), or carbapenems. Why: B. fragilis produces beta-lactamases; choose agents stable to these enzymes.
  • Clostridioides difficile: Oral vancomycin or fidaxomicin; metronidazole only if others unavailable in non-severe disease. Why: Oral vancomycin stays in the gut lumen and achieves high concentrations.

Other high-yield organisms

  • H. influenzae, M. catarrhalis (sinusitis/otitis/CAP): Amoxicillin–clavulanate or a second/third-generation cephalosporin; doxycycline if allergy. Why: Beta-lactamase production is common.
  • Neisseria gonorrhoeae: Ceftriaxone; add doxycycline if chlamydia not excluded. Why: Rising resistance eliminates older regimens.
  • Neisseria meningitidis (meningitis): Ceftriaxone or high-dose penicillin G if susceptible. Close-contact prophylaxis: rifampin, ciprofloxacin, or ceftriaxone. Why: Rapid transmission and severe disease demand prompt coverage and prophylaxis.
  • Listeria monocytogenes (neonates, elderly, pregnancy, immunocompromised): Ampicillin (± gentamicin for synergy). Avoid all cephalosporins. Why: Listeria is intrinsically resistant to cephalosporins.
  • Treponema pallidum (syphilis): Penicillin G benzathine (IM). Why: Remains the most reliable curative therapy.
  • Tick-borne (Rickettsia, Ehrlichia, Lyme early disseminated): Doxycycline. Why: Intracellular pathogens respond best to tetracyclines.

Site-based anchor regimens you should recognize

  • Outpatient CAP, healthy adult: Amoxicillin high-dose or doxycycline; use azithromycin only if local pneumococcal resistance is low. Comorbidities: amox/clav plus azithro/doxy, or a respiratory fluoroquinolone.
  • Inpatient CAP (non-ICU): Ceftriaxone plus azithromycin, or monotherapy with levofloxacin/moxifloxacin.
  • HAP/VAP with MRSA and Pseudomonas risk: Vancomycin (or linezolid) plus one antipseudomonal beta-lactam (pip/tazo, cefepime, meropenem). Add a second antipseudomonal class if high resistance risk; de-escalate when cultures return.
  • Uncomplicated cystitis (female): Nitrofurantoin 5 days, TMP-SMX 3 days, or fosfomycin single dose.
  • Pyelonephritis: Ceftriaxone initial dose, then oral step-down based on susceptibilities; avoid nitrofurantoin and fosfomycin.
  • Nonpurulent cellulitis (likely streptococcal): Cephalexin or amoxicillin; if MRSA suspected or purulent, use TMP-SMX or doxycycline plus a beta-lactam for strep coverage, or clindamycin alone if D-test negative.
  • Intra-abdominal infection: Pip/tazo or ceftriaxone plus metronidazole; carbapenem if ESBL risk.
  • Bacterial meningitis (empiric):
    • Age <1 month: Ampicillin + cefotaxime (avoid ceftriaxone) or gentamicin.
    • Age 1 month–50 years: Ceftriaxone + vancomycin.
    • Age >50 or immunocompromised: Ceftriaxone + vancomycin + ampicillin (for Listeria).

Quick rules that save you points

  • Daptomycin is not for pneumonia. Surfactant inactivates it.
  • Cephalosporins do not cover Listeria or atypicals. Add ampicillin for Listeria risk; use macrolide/doxy/FQ for atypicals.
  • Ertapenem misses Pseudomonas and Acinetobacter. All other carbapenems cover Pseudomonas.
  • Aztreonam: Gram-negative only, including Pseudomonas; safe in IgE-mediated penicillin allergy.
  • Nitrofurantoin is bladder-only. Do not use for pyelonephritis or CrCl <30 mL/min.
  • Use a carbapenem for ESBL. De-escalate if susceptibility allows.
  • MSSA prefers beta-lactams. Avoid vancomycin if a beta-lactam is an option.
  • Toxicities to remember: Macrolides and fluoroquinolones prolong QT; fluoroquinolones cause tendinopathy/CNS effects; TMP-SMX raises potassium and interacts with warfarin; linezolid can cause thrombocytopenia and serotonin syndrome risk; clindamycin carries high C. difficile risk.
  • Pregnancy cautions: Avoid tetracyclines, fluoroquinolones, and TMP-SMX near term; use beta-lactams or azithromycin when possible.
  • Neonates: Avoid ceftriaxone (biliary sludging, calcium precipitation); use cefotaxime instead.
  • Penicillin allergy: Non-severe reactions usually tolerate cephalosporins; true anaphylaxis may need aztreonam or desensitization for syphilis.

Pharmacodynamics in one minute

  • Time-dependent killers (beta-lactams, clindamycin): Efficacy tracks time above MIC. Prolonged/continuous infusions can help in severe infections.
  • Concentration-dependent killers (aminoglycosides): Higher peaks kill better; use extended-interval dosing when appropriate. Strong post-antibiotic effect.
  • AUC/MIC (vancomycin, fluoroquinolones, linezolid): Target vancomycin AUC/MIC 400–600 for serious MRSA to balance efficacy and nephrotoxicity.

If you remember nothing else

  • MSSA: cefazolin/nafcillin; MRSA: vancomycin (no lungs for daptomycin).
  • Pseudomonas: pip/tazo, cefepime, meropenem, cipro/levo, ± aminoglycoside.
  • ESBL: carbapenem. Atypicals: macrolide/doxy/FQ, never beta-lactam alone.
  • UTI cystitis: nitrofurantoin, TMP-SMX, fosfomycin; pyelo: ceftriaxone or equivalent.
  • Intra-abdominal: ceftriaxone + metronidazole or pip/tazo.
  • Meningitis by age: add ampicillin for Listeria risk in neonates/elderly.

How to study this efficiently

  • Build your own one-page chart: List the organisms above with two go-to drugs and one backup for allergy.
  • Tie each pairing to a “why” line: e.g., “ESBL → carbapenem because beta-lactamases hydrolyze others.” This cements recall.
  • Drill site-based regimens: CAP, HAP/VAP, cystitis vs pyelo, cellulitis vs abscess, intra-abdominal, meningitis.
  • Flash the red flags daily: daptomycin-not-lungs, ceftriaxone-not-neonates, nitrofurantoin-not-pyelo.
  • Practice de-escalation: Read a culture report and switch to the narrowest effective agent.

Master these patterns and the reasons behind them, and you will stop guessing. You will pick appropriate empiric coverage, avoid common pitfalls, and safely narrow therapy—the exact skills NAPLEX wants to see.

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