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Antibiotics: Complete Reference Guide

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What Are Antibiotics?

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Master Classification

1. Mechanism of action (most clinically useful)
2. Chemical structure
3. Spectrum (narrow vs. broad)
4. Bactericidal vs. bacteriostatic

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CLASS 1: BETA-LACTAMS

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1A. Penicillins

Mechanism of Action

Sub-Groups

• Spectrum: Gram-positive cocci (streptococci, penicillin-susceptible pneumococci), Neisseria meningitidis, Treponema pallidum, Actinomyces, Clostridia, non-β-lactamase anaerobes
• Penicillin G (IV/IM):
  • Dose: 4–24 million units/day IV in 4–6 divided doses for severe infections; can be given as continuous infusion
  • Benzathine penicillin G 1.2 million units IM × 1 dose for streptococcal pharyngitis; 2.4 million units IM weekly × 1–3 weeks for syphilis
• Penicillin V (oral): For minor infections only; narrow spectrum and poor bioavailability → mostly replaced by amoxicillin
• Pregnancy: ✅ Safe (Category B) — no known teratogenicity

• Resist staphylococcal beta-lactamase
• Spectrum: MSSA (methicillin-susceptible Staph. aureus), streptococci; NOT MRSA, enterococci, Listeria
• Uses: Staph. aureus skin/soft tissue infections, endocarditis, osteomyelitis
• Doses:
  • Oxacillin/Nafcillin: 1–2 g IV every 4–6 hours (8–12 g/day) for serious infections
  • Dicloxacillin: 0.25–0.5 g orally every 4–6 hours (take on empty stomach — food reduces absorption)
• Adverse effects: Hepatotoxicity (nafcillin), interstitial nephritis (methicillin — no longer used), phlebitis (IV)
• Pregnancy: ✅ Safe (Category B)

• Extended spectrum: Gram-negatives (H. influenzae, E. coli, Salmonella, Listeria) + gram-positives
• Inactivated by beta-lactamases
• Amoxicillin: 250–500 mg orally every 8 hours, or 875 mg every 12 hours; better absorbed than ampicillin
• Ampicillin: 1–3 g IV every 6 hours
• Beta-lactamase inhibitor combos:
  • Amoxicillin-clavulanate (Augmentin): 875/125 mg orally every 12 hours; broad anaerobe/gram-negative coverage
  • Ampicillin-sulbactam (Unasyn): 1.5–3 g IV every 6 hours
• Uses: Otitis media, sinusitis, pneumonia, UTI, H. pylori (triple therapy), Listeria meningitis, endocarditis prophylaxis
• Adverse effects: GI (diarrhea, nausea), ampicillin rash (maculopapular, non-allergic — especially in EBV/mono), C. difficile colitis, hypersensitivity
• Pregnancy: ✅ Safe (Category B)

• Spectrum: Broad gram-negative including Pseudomonas, anaerobes, gram-positives
• Dose: 3.375 g IV every 6 hours or 4.5 g IV every 6–8 hours; extended infusion over 4 hours used in ICU settings
• Uses: Nosocomial pneumonia, intra-abdominal infections, febrile neutropenia, sepsis
• Adverse effects: Hypokalemia (high doses), platelet dysfunction, C. difficile, neurotoxicity (very high doses)
• Pregnancy: ✅ Safe (Category B)

Penicillin Adverse Effects (Common to All)

• Hypersensitivity: Most important — ranges from mild rash to anaphylaxis (IgE-mediated)
• Anaphylaxis risk: ~0.05% of courses
• Hemolytic anemia (IgG-mediated, high doses)
• Interstitial nephritis
• Seizures (very high IV doses, especially in renal failure)
• C. difficile-associated diarrhea
• Cross-reactivity with cephalosporins: Low (~1–2%); avoid first-generation cephalosporins in documented penicillin anaphylaxis

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1B. Cephalosporins

First Generation

• Drugs: Cefazolin (IV), Cephalexin (oral)
• Spectrum: Gram-positive (MSSA, streptococci), limited gram-negative (E. coli, Klebsiella, Proteus)
• Uses: Surgical prophylaxis (cefazolin is gold standard), skin/soft tissue infections, uncomplicated UTI
• Dose:
  • Cefazolin: 1–2 g IV every 8 hours; poor CNS penetration
  • Cephalexin: 250–500 mg orally every 6 hours
• Pregnancy: ✅ Safe (Category B)

Second Generation

• Drugs: Cefuroxime, Cefoxitin, Cefotetan
• Spectrum: Better gram-negative than 1st gen; Cefoxitin/cefotetan add anaerobe coverage (Bacteroides fragilis)
• Uses: Community-acquired pneumonia, intra-abdominal/pelvic infections (surgical prophylaxis for gynecological procedures), H. influenzae infections
• Dose: Cefuroxime 750 mg–1.5 g IV every 8 hours; cefoxitin 1–2 g IV every 6 hours
• Cefotetan note: Contains methylthiotetrazole group → hypoprothrombinemia and bleeding (give Vitamin K 10 mg twice weekly to prevent); disulfiram-like reaction with alcohol → alcohol must be avoided
• Pregnancy: ✅ Safe (Category B)

Third Generation

• Drugs: Ceftriaxone, Cefotaxime, Ceftazidime, Cefdinir (oral)
• Spectrum: Excellent gram-negative; ceftazidime covers Pseudomonas; good CNS penetration
• Uses:
  • Ceftriaxone: pneumonia, meningitis, gonorrhea, pyelonephritis, Lyme disease — half-life 6 hours (once-daily dosing), biliary/renal excretion; standard dose 1–2 g IV once daily (2 g for meningitis)
  • Ceftazidime: Pseudomonas infections; dose 1–2 g IV every 8 hours
  • Cefdinir oral: acute otitis media, strep pharyngitis — 300 mg every 12 hours
• Adverse effects: Ceftriaxone causes biliary sludging/pseudolithiasis (especially in neonates/children)
• Pregnancy: ✅ Safe (Category B)

Fourth Generation

• Drug: Cefepime (IV)
• Spectrum: Broad — gram-positive, gram-negative including Pseudomonas; stable against chromosomal beta-lactamases
• Uses: Febrile neutropenia, nosocomial pneumonia, severe UTIs, Pseudomonas infections
• Dose: 1–2 g IV every 8–12 hours
• Pregnancy: ✅ Safe (Category B)
• Adverse effect note: Associated with encephalopathy/neurotoxicity, especially in renal impairment — dose-adjust

Fifth Generation

• Drug: Ceftaroline
• Spectrum: Covers MRSA (unique among cephalosporins) + gram-negatives; NOT Pseudomonas
• Uses: MRSA skin infections, community-acquired pneumonia
• Dose: 600 mg IV every 12 hours
• Pregnancy: Limited data — use only if clearly needed

Cephalosporin Adverse Effects (All Generations)

• Hypersensitivity (rash, anaphylaxis — less common than penicillins)
• Local thrombophlebitis (IV), pain (IM)
• Renal toxicity (interstitial nephritis, tubular necrosis — uncommon)
• C. difficile colitis
• Hypoprothrombinemia/bleeding (methylthiotetrazole-containing agents)

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1C. Carbapenems

Mechanism

Drugs

• Imipenem-cilastatin (cilastatin prevents hydrolysis by renal dehydropeptidase)
• Meropenem (inherently stable; no cilastatin needed; lower seizure risk)
• Ertapenem (no Pseudomonas/Acinetobacter activity; once-daily dosing)
• Doripenem

Spectrum

Uses

Doses

• Imipenem: 0.5–1 g IV every 6–8 hours; infused over 30–60 min
• Meropenem: 1–2 g IV every 8 hours (up to 2 g every 8 hours for CNS infections)
• Ertapenem: 1 g IV/IM once daily

Adverse Effects

• Seizures (most significant — especially imipenem, particularly at high doses or in renal failure; dose-adjust!)
• Nausea, vomiting, diarrhea
• Hypersensitivity (cross-react with penicillins in ~1% of cases)
• C. difficile
• Thrombophlebitis (IV)
• Meropenem has significantly lower seizure risk than imipenem

Pregnancy

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1D. Monobactams

Drug: Aztreonam

• Mechanism: Same as other beta-lactams — binds PBPs; monocyclic beta-lactam ring
• Spectrum: Aerobic gram-negatives only (including Pseudomonas); no gram-positive or anaerobe activity
• Key advantage: Safe in confirmed penicillin anaphylaxis (no cross-reactivity — different ring structure); minimal cross-reactivity except with ceftazidime
• Uses: Gram-negative infections in penicillin-allergic patients, Pseudomonas infections
• Dose: 1–2 g IV every 6–8 hours; renal excretion — adjust in renal failure
• Adverse effects: Local phlebitis, skin rash, GI, rarely hepatotoxicity
• Pregnancy: ✅ Safe (Category B)

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CLASS 2: GLYCOPEPTIDES

Vancomycin

Mechanism

Spectrum

Uses

• MRSA infections (bacteremia, endocarditis, pneumonia, osteomyelitis)
• C. difficile colitis (oral vancomycin — not absorbed)
• Gram-positive infections in penicillin-allergic patients

Dosage

• IV: 15–20 mg/kg every 8–12 hours (AUC-guided dosing now preferred over trough-based monitoring)
• Oral (for C. diff): 125 mg every 6 hours × 10 days (not absorbed systemically)
• Requires TDM (therapeutic drug monitoring) — target AUC/MIC ratio 400–600

Adverse Effects

• Nephrotoxicity (especially with aminoglycosides — synergistic toxicity)
• Ototoxicity (tinnitus, hearing loss — particularly with sustained high levels)
• Red man syndrome — flushing, erythema, hypotension from histamine release during rapid infusion (NOT a true allergy); prevented by slow infusion over ≥60 min and premedication with antihistamines
• Thrombophlebitis (IV)
• Neutropenia (prolonged use)

Pregnancy

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CLASS 3: AMINOGLYCOSIDES

Drugs: Gentamicin, Tobramycin, Amikacin, Streptomycin, Neomycin

Mechanism

Spectrum

Uses

• Serious gram-negative infections (sepsis, pneumonia, pyelonephritis)
• Synergistic with penicillins/vancomycin for endocarditis (enterococcal, viridans streptococci)
• Tobramycin: preferred for Pseudomonas (inhaled form for cystic fibrosis)
• Streptomycin: tuberculosis, plague, brucellosis
• Amikacin: resistant gram-negative organisms (stable to many aminoglycoside-modifying enzymes)
• Neomycin: oral for hepatic encephalopathy (reduces ammonia-producing gut bacteria), topical wounds

Dosing

• Once-daily (extended-interval) dosing preferred to maximize peak/MIC ratio and reduce nephrotoxicity:
  • Gentamicin/tobramycin: 5–7 mg/kg IV once daily
  • Amikacin: 15–20 mg/kg IV once daily
• Traditional dosing (for synergy in endocarditis): 1–1.7 mg/kg IV every 8 hours
• Adjust for renal function (renally cleared)
• Serum levels must be monitored (peak and trough)

Adverse Effects

• Nephrotoxicity — proximal tubular damage; usually reversible; risk ↑ with prolonged use, loop diuretics, amphotericin B, vancomycin, pre-existing renal disease
• Ototoxicity — cochleotoxicity (hearing loss, tinnitus) and/or vestibulotoxicity (vertigo, ataxia); often irreversible; risk ↑ with cumulative dose, loop diuretics (furosemide), pre-existing hearing loss
• Neuromuscular blockade (risk at high doses, especially post-anesthesia) — can cause respiratory paralysis; avoid in myasthenia gravis
• Streptomycin: vestibular > cochlear toxicity specifically

Pregnancy

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CLASS 4: TETRACYCLINES

Drugs: Tetracycline, Doxycycline, Minocycline, Tigecycline, Omadacycline

Mechanism

Pharmacokinetics Notes

• Doxycycline: Long half-life 16–18 hours → once or twice daily dosing; eliminated by non-renal mechanisms → no dose adjustment in renal failure (unlike tetracycline); good oral bioavailability
• Minocycline: Half-life 16–18 hours; excellent tissue penetration including CNS; used for MRSA (community-acquired), acne
• Tigecycline: IV only; half-life 36 hours; very broad spectrum (MRSA, VRE, MDR gram-negatives); NOT Pseudomonas; associated with increased mortality in VAP — use cautiously
• Food interactions: Tetracycline absorbed is reduced by calcium (dairy, antacids, iron) → must take 1 hour before or 2 hours after meals; doxycycline less affected

Spectrum

Uses

• Drug of choice: Rocky Mountain spotted fever (Rickettsia), Lyme disease (Borrelia), Chlamydia (STI), Mycoplasma pneumonia, atypical pneumonia
• Community-acquired pneumonia
• Acne vulgaris (doxycycline/minocycline)
• Malaria prophylaxis (doxycycline 100 mg daily)
• H. pylori eradication (part of quadruple therapy)
• Brucellosis, tularemia, plague (with other agents)
• Cholera
• MRSA skin/soft tissue infections (doxycycline/minocycline — community-acquired)

Dosage

• Doxycycline: 100 mg orally/IV twice daily (standard); 200 mg on day 1 as loading dose for some indications
• Tetracycline: 250–500 mg orally 4× daily (take on empty stomach)
• Minocycline: 100 mg orally twice daily

Adverse Effects

• GI: Nausea, vomiting, diarrhea, esophageal ulceration (take with full glass of water, remain upright)
• Photosensitivity: Skin rash on sun exposure — especially doxycycline and demeclocycline; warn patients to use sunscreen
• Hepatotoxicity: Fatty liver, especially with IV high doses or in pregnant women → dangerous in pregnancy
• Intracranial hypertension (pseudotumor cerebri): Headache, visual changes — rare
• Vestibular toxicity: Dizziness, vertigo — especially minocycline
• C. difficile colitis
• Tigecycline: nausea/vomiting very common (47%); increased mortality in VAP

Pregnancy

1. Permanent yellow-brown staining of teeth in the fetus (deposited during tooth development, 2nd trimester onward)
2. Inhibition of bone growth — deposits in fetal long bones → temporary growth retardation
3. Maternal hepatotoxicity — pregnant women especially vulnerable to IV tetracycline-induced acute fatty liver of pregnancy (can be fatal)
4. Exception: Doxycycline is used in Rocky Mountain spotted fever even in pregnancy because the risk of untreated infection outweighs the dental staining risk (per CDC/dermatology guidelines).

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CLASS 5: MACROLIDES

Drugs: Erythromycin, Clarithromycin, Azithromycin

Mechanism

Spectrum

Uses

• Atypical pneumonia (Mycoplasma, Chlamydia, Legionella)
• Community-acquired pneumonia (in combination or as monotherapy in low-risk patients)
• STIs: Chlamydia trachomatis — azithromycin 1 g single dose or doxycycline 7 days
• Pertussis (whooping cough): azithromycin preferred
• H. pylori: clarithromycin in triple therapy (with omeprazole + amoxicillin)
• MAC prophylaxis/treatment in HIV: azithromycin or clarithromycin
• Streptococcal pharyngitis in penicillin allergy
• Erythromycin: gastroparesis (stimulates motilin receptors) — off-label
• Azithromycin: Z-pak (5-day course) for community infections

Doses

• Erythromycin: 250–500 mg orally/IV every 6 hours; poorly tolerated GI
• Clarithromycin: 250–500 mg orally twice daily (or 1000 mg extended-release once daily); half-life 6 hours
• Azithromycin: 500 mg day 1, then 250 mg once daily × 4 days (Z-pak); single 1 g dose for Chlamydia; 500 mg IV once daily for serious infections

Adverse Effects

• QTc prolongation → risk of fatal arrhythmia (torsades de pointes) — avoid with other QT-prolonging drugs; erythromycin and azithromycin carry highest risk
• GI: Nausea, vomiting, diarrhea, abdominal cramping — common with erythromycin (direct motilin receptor agonist); less with azithromycin
• Hepatotoxicity: Cholestatic hepatitis with erythromycin estolate (fever, jaundice, abnormal LFTs) — avoid in liver disease
• Drug interactions: Erythromycin and clarithromycin are strong CYP3A4 inhibitors → increase levels of statins (rhabdomyolysis risk), warfarin, cyclosporine, digoxin, benzodiazepines, many others; azithromycin is a weak inhibitor (safer drug-interaction profile)
• Reduced effectiveness of oral contraceptives
• Transient hearing loss (erythromycin at high doses)
• Ototoxicity (rare)

Pregnancy

• Azithromycin: ✅ Considered safe in pregnancy (Category B) — commonly used for Chlamydia and respiratory infections in pregnant women
• Erythromycin (base or stearate): ✅ Generally considered safe for the mother (however, the estolate formulation is contraindicated in pregnancy — associated with subclinical hepatotoxicity in ~10% of pregnant women)
• Clarithromycin: ⚠️ Avoid (Category C) — animal studies show teratogenicity (cardiovascular defects, cleft palate); limited human data but risk cannot be excluded. Use azithromycin instead.

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CLASS 6: FLUOROQUINOLONES

Drugs: Ciprofloxacin, Levofloxacin, Moxifloxacin, Ofloxacin, Norfloxacin

Mechanism

Spectrum

• Ciprofloxacin: Gram-negatives including Pseudomonas; atypicals; limited gram-positive and NO anaerobe coverage
• Levofloxacin (respiratory fluoroquinolone): MSSA, Streptococcus pneumoniae, gram-negatives, atypicals — "respiratory fluoroquinolone"
• Moxifloxacin: Best gram-positive and anaerobe coverage; no Pseudomonas; no renal excretion (do not use for UTI); "respiratory fluoroquinolone"
• Norfloxacin: Limited to UTIs (oral only)

Uses

• UTIs (ciprofloxacin, norfloxacin, levofloxacin)
• Community/healthcare-acquired pneumonia (levofloxacin, moxifloxacin)
• Intra-abdominal infections (moxifloxacin, ciprofloxacin + metronidazole)
• Traveler's diarrhea, typhoid fever, Salmonella, Shigella (ciprofloxacin)
• Anthrax prophylaxis/treatment (ciprofloxacin)
• Pseudomonas infections (ciprofloxacin — only oral agent with reliable Pseudomonas activity)
• Gonococcal infections (ciprofloxacin — if susceptible; increasing resistance)
• Atypical mycobacteria, TB (second-line: levofloxacin, moxifloxacin)
• Prostatitis, pyelonephritis (ciprofloxacin 500 mg twice daily × 7–14 days)

Doses

• Ciprofloxacin: 250–750 mg orally twice daily; 400 mg IV every 8–12 hours
• Levofloxacin: 500–750 mg orally/IV once daily
• Moxifloxacin: 400 mg orally/IV once daily

Adverse Effects

• Tendinopathy and tendon rupture (Achilles most common) — boxed warning; risk ↑ in elderly, corticosteroids, renal failure; pain may begin during or after treatment
• QTc prolongation — especially moxifloxacin; avoid with other QT-prolonging agents
• CNS toxicity: Headache, dizziness, insomnia, rare seizures, peripheral neuropathy (can be irreversible — boxed warning), agitation, confusion, delirium — especially in elderly
• Phototoxicity: Sun exposure → severe sunburn rash
• Stevens-Johnson syndrome / TEN (rare but severe)
• Arthropathy: Cartilage damage in weight-bearing joints — major concern in children → use restricted in pediatric populations
• GI: nausea, vomiting, diarrhea, C. difficile
• Hyperglycemia/hypoglycemia (especially with antidiabetic drugs)
• Aortic aneurysm/dissection: FDA warning (2018) — black box warning for fluoroquinolones increasing risk of aortic aneurysm; avoid in patients with known aortic aneurysm
• Drug interactions: antacids/dairy significantly reduce oral absorption (take 2 hours apart)

Pregnancy

1. Arthropathy in animal models — fluoroquinolones damage developing cartilage in immature animals; potential risk of fetal joint/cartilage damage
2. Potential CNS effects on fetal development
3. Inadequate human safety data for routine use
4. Levofloxacin and moxifloxacin are sometimes used in multidrug-resistant TB in pregnancy (risk-benefit analysis)

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CLASS 7: SULFONAMIDES AND TRIMETHOPRIM

Mechanism

• Sulfonamides (e.g., sulfamethoxazole): Structural analog of para-aminobenzoic acid (PABA) → competitively inhibit dihydropteroate synthetase → block conversion of PABA to dihydropteroic acid → impair folate synthesis → bacteriostatic
• Trimethoprim: Inhibits dihydrofolate reductase → blocks conversion of dihydrofolic acid to tetrahydrofolic acid → folate deficiency in bacteria
• TMP-SMX (Co-trimoxazole): Sequential double blockade of the folate pathway → synergistic, often bactericidal

Spectrum

Uses

• First-line for PCP pneumonia (Pneumocystis jirovecii) — 15–20 mg/kg/day TMP-SMX IV/orally divided every 6–8 hours × 21 days
• PCP prophylaxis in HIV (CD4 <200): TMP-SMX 1 DS tablet (160/800 mg) daily
• Uncomplicated UTI: TMP-SMX DS twice daily × 3 days
• Community-acquired MRSA skin/soft tissue infections: TMP-SMX DS twice daily × 5–7 days
• Nocardia infections: high-dose, prolonged
• Toxoplasmosis: combined with pyrimethamine
• Traveler's diarrhea (increasing resistance limits use)

Dose

• Standard: TMP-SMX DS (160/800 mg) orally twice daily; adjust for renal function (CrCl <30: reduce or avoid)

Adverse Effects

• Stevens-Johnson syndrome / TEN — severe hypersensitivity — monitor for rash, mucous membrane involvement
• Hematologic: Megaloblastic anemia (folate deficiency), hemolytic anemia (G6PD deficiency patients), agranulocytosis, thrombocytopenia, aplastic anemia
• Nephrotoxicity: Crystalluria/urolithiasis (ensure adequate hydration), interstitial nephritis, tubular toxicity (inhibits creatinine secretion → raises serum creatinine without true GFR change)
• Hyperkalemia (TMP blocks potassium secretion similar to amiloride — especially important in HIV/transplant patients on ACE inhibitors)
• Hepatitis (jaundice, elevated LFTs)
• GI: Nausea, vomiting, anorexia
• Drug interactions: Increases warfarin effect, increases phenytoin and methotrexate levels
• Photosensitivity

Pregnancy

• First trimester: Trimethoprim folate antagonism → risk of neural tube defects and cardiovascular malformations → contraindicated in 1st trimester
• Third trimester: Sulfonamides displace bilirubin from albumin in neonates → risk of neonatal kernicterus (bilirubin encephalopathy) → contraindicated near term
• Second trimester: Relative cautious use possible if no safer alternative, with folate supplementation
• Category C/D

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CLASS 8: METRONIDAZOLE (NITROIMIDAZOLES)

Mechanism

Spectrum

Uses

• C. difficile colitis: 500 mg orally 3× daily × 10–14 days (second-line; vancomycin/fidaxomicin now preferred for initial and recurrent disease)
• Bacterial vaginosis: 500 mg orally twice daily × 7 days, or 2 g single dose
• Trichomonas vaginitis: 2 g single dose or 500 mg twice daily × 7 days
• Giardiasis/amebiasis: 750 mg orally 3× daily × 5–10 days
• Intra-abdominal/pelvic infections: IV 500 mg every 8 hours (usually combined with cephalosporin or fluoroquinolone for gram-negatives)
• H. pylori: part of triple/quadruple therapy
• Anaerobic/mixed infections: brain abscess, aspiration pneumonia, pelvic inflammatory disease

Adverse Effects

• GI: Nausea, metallic taste, anorexia, vomiting — very common
• Disulfiram-like reaction with alcohol → flushing, tachycardia, nausea, vomiting — alcohol must be avoided during and 48 hours after treatment
• Peripheral neuropathy (prolonged high-dose use) — numbness, tingling
• CNS toxicity (rare): Seizures, encephalopathy, cerebellar dysfunction — especially with high doses
• Dark urine (harmless — drug metabolite discoloration)
• Drug interactions: increases warfarin anticoagulation effect (inhibits CYP2C9)
• Headache

Pregnancy

• First trimester: Historically avoided — theoretical concern about mutagenicity/teratogenicity based on high-dose animal studies; avoid in 1st trimester if possible (especially for non-urgent indications like BV)
• Second/Third trimester: Considered acceptable/safe by most guidelines (CDC, WHO) for treating Trichomonas and serious anaerobic infections; studies have not confirmed teratogenicity in humans
• Breastfeeding: Excreted in breast milk — pause breastfeeding for 12–24 hours after single-dose therapy
• Overall: Category B (limited risk in 2nd/3rd trimester; avoid in 1st trimester)

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CLASS 9: LINCOSAMIDES (CLINDAMYCIN)

Mechanism

Spectrum

Uses

• Skin/soft tissue infections (MSSA, CA-MRSA) — especially cellulitis, abscesses, necrotizing fasciitis
• Aspiration pneumonia/lung abscess (excellent anaerobe coverage)
• Pelvic inflammatory disease (combined with other agents)
• Osteomyelitis (excellent bone penetration)
• Toxin suppression in severe streptococcal/staphylococcal infections (TSS, necrotizing fasciitis) — clindamycin suppresses exotoxin production
• Malaria (with quinine): resistant P. falciparum
• Toxoplasmosis (with pyrimethamine) in sulfa allergy
• Dental/oral infections (anaerobes)
• Topical: acne, bacterial vaginosis

Dose

• 300–450 mg orally every 6–8 hours
• 600–900 mg IV every 8 hours
• Topical 1% gel/lotion for acne

Adverse Effects

• C. difficile-associated diarrhea and colitis — historically clindamycin was most commonly implicated (now fluoroquinolones/cephalosporins lead); most severe complication; monitor for diarrhea
• GI: diarrhea, nausea, abdominal pain (common)
• Cross-resistance with macrolides (same 50S binding site — inducible clindamycin resistance tested by D-zone test before prescribing for MRSA)
• Hepatotoxicity (rare)
• Hypersensitivity reactions (rash)
• Neuromuscular blockade (rare, high doses)

Pregnancy

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CLASS 10: CHLORAMPHENICOL

Mechanism

Spectrum

Uses (Now rarely used due to toxicity)

• Bacterial meningitis (in countries without cephalosporins or as alternative)
• Typhoid fever (replaced by fluoroquinolones)
• Rickettsial disease (alternative to doxycycline)
• Brain abscess
• Typhus, brucellosis

Dose

Adverse Effects

• Dose-related bone marrow suppression (reversible): At >50 mg/kg/day — suppresses erythropoiesis; reversible when stopped
• Aplastic anemia (irreversible, idiosyncratic): 1 in 24,000–40,000 courses; not dose-related; often fatal → black box warning; this is the primary reason chloramphenicol is rarely used
• Gray baby syndrome (neonates/infants): Neonates lack glucuronyl transferase to metabolize chloramphenicol → drug accumulates → vomiting, flaccidity, hypothermia, gray cyanosis, cardiovascular collapse → fatal if not stopped
• Drug interactions: inhibits CYP450 → increases levels of phenytoin, warfarin, sulfonylureas

Pregnancy

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CLASS 11: OXAZOLIDINONES (LINEZOLID)

Mechanism

Spectrum

Uses

• VRE infections (vancomycin-resistant enterococcus) — one of few options
• MRSA infections (alternative to vancomycin)
• Healthcare-associated pneumonia
• Complicated skin/soft tissue infections
• Off-label: MDR-TB, Nocardia

Dose

Adverse Effects

• Thrombocytopenia (most common — ~3%; especially >2 weeks of treatment)
• Anemia, neutropenia (myelosuppression — monitor CBC weekly)
• Serotonin syndrome risk: Linezolid is a weak MAO inhibitor → combined with SSRIs, SNRIs, meperidine, tramadol → potentially fatal serotonin syndrome (hyperthermia, agitation, myoclonus, tachycardia) → avoid these combinations
• Peripheral neuropathy (prolonged use — can be irreversible)
• Optic neuropathy (prolonged use — visual changes; monitor)
• Lactic acidosis (rare — mitochondrial toxicity)
• GI: nausea, diarrhea, headache

Pregnancy

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CLASS 12: GLYCOPEPTIDE/LIPOPEPTIDE — DAPTOMYCIN

Mechanism

Spectrum

Uses

• MRSA bacteremia, endocarditis (right-sided — preferred over vancomycin in some guidelines)
• MRSA/VRE skin and soft tissue infections
• VRE bacteremia

Dose

Adverse Effects

• Myopathy/rhabdomyolysis — monitor CPK weekly; avoid statins during treatment
• Eosinophilic pneumonia (rare)
• Peripheral neuropathy
• GI disturbances

Pregnancy

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CLASS 13: RIFAMYCINS (RIFAMPIN/RIFAMPICIN)

Mechanism

Spectrum

Uses

• First-line TB treatment (HRZE regimen: isoniazid + rifampin + pyrazinamide + ethambutol)
• Meningococcal prophylaxis: 600 mg twice daily × 2 days
• H. influenzae type b prophylaxis
• MRSA biofilm infections (adjunctive with other agents)
• Leprosy (dapsone + rifampin)

Dose

Adverse Effects

• Drug interactions (most important adverse effect): Rifampin is a powerful inducer of CYP450 (1A2, 2C9, 2C19, 3A4), P-glycoprotein → dramatically reduces levels of antiretrovirals (HIV), OCP (contraceptive failure), warfarin, cyclosporine, oral hypoglycemics, many drugs → massive drug interaction risk
• Discoloration of secretions: Orange-red staining of urine, sweat, saliva, tears, contact lenses — harmless but warn patients
• Hepatotoxicity — elevated LFTs, hepatitis (especially with isoniazid)
• Flu-like syndrome (with intermittent dosing)
• Thrombocytopenia, hemolytic anemia (high-dose, intermittent)
• Renal failure (high-dose intermittent)

Pregnancy

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CLASS 14: NITROFURANTOIN

Mechanism

Spectrum

Uses

• Uncomplicated lower UTI (cystitis) — first-line option
• Suppressive therapy for recurrent UTI
• NOT for pyelonephritis, prostatitis, or systemic infections

Dose

• Macrocrystalline (Macrobid): 100 mg orally twice daily × 5–7 days
• Microcrystalline: 50–100 mg 4× daily × 7 days
• Requires adequate renal function (CrCl ≥30 mL/min) — not effective if kidneys can't concentrate drug in urine

Adverse Effects

• Pulmonary toxicity: Acute: hypersensitivity pneumonitis (fever, eosinophilia, cough) — resolves on stopping; Chronic: pulmonary fibrosis (long-term use) — potentially irreversible; monitor in long-term prophylaxis
• Peripheral neuropathy (prolonged use — especially in renal impairment)
• Hemolytic anemia (G6PD-deficient patients)
• GI: nausea, vomiting — take with food to reduce
• Hepatotoxicity (rare)
• Brown discoloration of urine (harmless)

Pregnancy

• ✅ Safe in 2nd trimester and most of pregnancy for UTI treatment
• ⚠️ Avoid in 1st trimester — potential fetal toxicity (neural tube defects in some animal studies, though human risk is debated)
• 🚫 Avoid at ≥38 weeks / near term — risk of neonatal hemolytic anemia (immature neonatal erythrocytes are more susceptible to oxidative damage from nitrofurantoin metabolites)

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CLASS 15: POLYMYXINS (COLISTIN/POLYMYXIN B)

Mechanism

Spectrum

Uses

• Multidrug-resistant (MDR) gram-negative infections — carbapenem-resistant organisms, XDR infections
• Typically last resort when all other options exhausted
• Sometimes used intrathecally for MDR CNS infections

Dose

• Colistin (polymyxin E): loading dose 9 million units IV, then maintenance based on CrCl; TDM required
• Polymyxin B: 1.5–2.5 mg/kg/day IV divided every 12 hours (non-renal excretion — no renal adjustment)

Adverse Effects

• Nephrotoxicity — major; dose-limiting; acute tubular necrosis; up to 60% of patients; monitor creatinine daily
• Neurotoxicity — paresthesias (circumoral/peripheral), confusion, ataxia, neuromuscular blockade
• Hypersensitivity

Pregnancy

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Pregnancy Safety Summary Table

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Key Concepts: Bactericidal vs. Bacteriostatic

Clinical note: Bacteriostatic agents are generally NOT used for endocarditis, meningitis, or immunocompromised patients — these require bactericidal drugs.

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Resistance Mechanisms (Brief Overview)

1. Beta-lactamase production — enzymes that hydrolyze the beta-lactam ring (combated by beta-lactamase inhibitors: clavulanate, sulbactam, tazobactam, avibactam)
2. PBP modification — altered penicillin-binding proteins with low antibiotic affinity (MRSA: PBP2a encoded by mecA gene)
3. Efflux pumps — actively pump antibiotic out of cell (gram-negatives: tetracycline, fluoroquinolone resistance)
4. Reduced permeability — decreased porin expression (Pseudomonas: beta-lactam resistance)
5. Target modification — altered DNA gyrase/topoisomerase IV (fluoroquinolone resistance), altered D-Ala-D-Ala terminal (vancomycin resistance in VRE: D-Ala-D-Lactate)
6. Enzymatic modification — aminoglycoside-modifying enzymes (acetylation, phosphorylation, adenylation)

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