Orris

Explain antibiotics in detail classification, each class with their mechanism of action, uses,adverse effects,side effects, example, dosage, how to use it, pregnancy safe or not and if not then why?, literally every little detail

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Here is a comprehensive, detailed reference on antibiotics — every major class, with mechanism, uses, adverse effects, dosage, administration, and pregnancy safety.

Antibiotics: Complete Reference

How Antibiotics Are Classified

Antibiotics are classified by three overlapping schemes:
  1. Chemical structure — e.g., β-lactams, aminoglycosides
  2. Mechanism of action — e.g., cell wall inhibitors, protein synthesis inhibitors
  3. Spectrum of activity — narrow, extended, or broad spectrum
Bactericidal drugs kill bacteria; bacteriostatic drugs inhibit growth and rely on host immune clearance.

Master Classification by Mechanism of Action

MechanismClasses
Cell wall synthesis inhibitionPenicillins, Cephalosporins, Carbapenems, Monobactams, Glycopeptides
Cell membrane disruptionPolymyxins, Daptomycin
Protein synthesis inhibition (30S)Aminoglycosides, Tetracyclines, Tigecycline
Protein synthesis inhibition (50S)Macrolides, Lincosamides, Chloramphenicol, Oxazolidinones, Streptogramins
DNA/RNA synthesis inhibitionFluoroquinolones, Rifamycins, Metronidazole
Folate synthesis inhibitionSulfonamides, Trimethoprim

CLASS 1 — PENICILLINS (β-Lactams)

Mechanism of Action

Penicillins bind irreversibly to penicillin-binding proteins (PBPs) — particularly transpeptidase enzymes — on the bacterial cell membrane. This blocks the cross-linking of peptidoglycan strands in the cell wall. The weakened wall cannot resist osmotic pressure, and the cell lyses. They are bactericidal and work best on actively dividing bacteria.

Subclasses, Examples & Coverage

SubclassExamplesSpectrum
Natural penicillinsPenicillin G (IV/IM), Penicillin V (oral)Streptococci, Treponema pallidum, Neisseria meningitidis
Penicillinase-resistantOxacillin, Nafcillin, DicloxacillinMSSA, staphylococci producing penicillinase
AminopenicillinsAmoxicillin, AmpicillinExtended: H. influenzae, E. coli, Listeria
Antipseudomonal penicillinsPiperacillin, TicarcillinPseudomonas aeruginosa, broader GN coverage
β-Lactamase inhibitor combosAmoxicillin-clavulanate, Ampicillin-sulbactam, Piperacillin-tazobactamBroader GN + anaerobes; overcomes beta-lactamase

Uses

  • Streptococcal pharyngitis, skin infections, pneumococcal pneumonia
  • Syphilis (Penicillin G — drug of choice)
  • Endocarditis prophylaxis (amoxicillin)
  • Urinary tract infections (ampicillin, amoxicillin)
  • Intra-abdominal infections, aspiration pneumonia (piperacillin-tazobactam)
  • Otitis media — amoxicillin is first-line per AAP guidelines

Dosage & Administration

DrugDoseRoute
Amoxicillin (adult)500 mg every 8 h OR 875 mg every 12 hOral
Amoxicillin-clavulanate875/125 mg every 12 hOral
Ampicillin1–2 g every 4–6 hIV/IM
Piperacillin-tazobactam3.375–4.5 g every 6–8 hIV
Penicillin G2–4 million units every 4 hIV
Penicillin V500 mg every 6 hOral
  • Take amoxicillin with or without food
  • Amoxicillin-clavulanate should be taken with food to reduce GI upset
  • IV penicillins require extended infusion for time-dependent killing

Adverse Effects & Side Effects

  • Hypersensitivity (most important): urticaria, rash, angioedema, anaphylaxis (IgE-mediated, 0.05% of doses); cross-reactivity with cephalosporins (~1–2%)
  • GI upset: nausea, diarrhea (especially amoxicillin-clavulanate — clavulanate causes diarrhea)
  • Clostridioides difficile–associated diarrhea (CDAD)
  • Maculopapular rash with ampicillin in mononucleosis (~80–100%)
  • Seizures at very high doses (especially in renal failure)
  • Neutropenia, thrombocytopenia (prolonged therapy)
  • Beta-lactamase inhibitors may cause cholestatic jaundice (amoxicillin-clavulanate)

Pregnancy Safety

✅ Generally SAFE — Category B (FDA legacy)
Penicillins cross the placenta but have not demonstrated teratogenicity in decades of use. They are the drugs of choice for GBS prophylaxis in labor, syphilis in pregnancy, and dental procedures in pregnancy. No known fetal harm.

CLASS 2 — CEPHALOSPORINS (β-Lactams)

Mechanism of Action

Same as penicillins — bind PBPs → inhibit peptidoglycan cross-linking → bactericidal cell lysis. Classified into five generations based on spectrum.

Generations, Examples & Coverage

GenerationKey DrugsSpectrum
1stCephalexin (PO), Cefazolin (IV), CefadroxilMSSA, Streptococci, basic GN (E. coli, Klebsiella, Proteus)
2ndCefuroxime, Cefprozil, Cefoxitin, CefotetanMore GN coverage; cefoxitin/cefotetan cover anaerobes (B. fragilis)
3rdCeftriaxone (IV/IM), Cefotaxime, Ceftazidime, Cefdinir, CefpodoximeEnhanced GN; CSF penetration; Ceftazidime covers Pseudomonas
4thCefepimePseudomonas + GN; greater stability against β-lactamases than 3rd gen
5thCeftarolineMRSA + broad GN coverage

Uses

  • Surgical prophylaxis: Cefazolin is the workhorse (1st generation)
  • Community-acquired pneumonia: Ceftriaxone (3rd gen, IV)
  • Meningitis: Ceftriaxone or cefotaxime (3rd gen; cross blood-brain barrier)
  • Gonorrhea: Ceftriaxone 500 mg IM single dose (3rd gen)
  • MRSA: Only ceftaroline (5th gen) covers MRSA
  • UTI: Cephalexin (oral, 1st gen)
  • Sepsis/febrile neutropenia: Cefepime (4th gen)
  • Otitis media (PCN-allergic): Cefdinir, cefuroxime, cefpodoxime (3rd gen)

Dosage

DrugDoseRoute
Cephalexin500 mg every 6 hOral
Cefazolin1–2 g every 8 h (prophylaxis: 1–2 g × 1 dose)IV
Ceftriaxone1–2 g every 12–24 hIV/IM
Cefepime1–2 g every 8–12 hIV
Ceftaroline600 mg every 12 hIV

Adverse Effects & Side Effects

  • Hypersensitivity (cross-reactivity with penicillins ~1–2%; avoid in history of severe PCN anaphylaxis)
  • GI: nausea, diarrhea, CDAD
  • Cefotetan/cefoxitin: disulfiram-like reaction with alcohol (MTT side chain), hypoprothrombinemia
  • Neutropenia, eosinophilia
  • Nephrotoxicity (rare; increased with aminoglycoside co-administration)

Pregnancy Safety

✅ Generally SAFE — Category B
Cephalosporins cross the placenta but are not teratogenic. Widely used in pregnancy for UTIs, GBS prophylaxis (in PCN-allergic patients), and pneumonia.

CLASS 3 — CARBAPENEMS (β-Lactams)

Mechanism of Action

Same PBP-binding / peptidoglycan cross-linking inhibition as other β-lactams, but carbapenems are broadest-spectrum β-lactams and are highly stable against most β-lactamases (including extended-spectrum β-lactamases, ESBLs). Bactericidal.

Examples

Imipenem-cilastatin, Meropenem, Ertapenem, Doripenem
  • Cilastatin is co-administered with imipenem to block renal tubular dehydropeptidase, which would otherwise degrade imipenem.

Uses

  • Severe nosocomial infections, sepsis
  • ESBL-producing GN organisms
  • Polymicrobial intra-abdominal infections
  • Febrile neutropenia, hospital-acquired pneumonia
  • Ertapenem: NOT effective against Pseudomonas (used for ESBL community-acquired)
  • Meropenem/imipenem: cover Pseudomonas aeruginosa

Dosage

DrugDoseRoute
Imipenem-cilastatin500 mg every 6 hIV
Meropenem1–2 g every 8 hIV
Ertapenem1 g every 24 hIV/IM

Adverse Effects & Side Effects

  • Seizures (imipenem > meropenem — imipenem lowers seizure threshold; avoid in CNS infections)
  • GI: nausea, vomiting, diarrhea, CDAD
  • Hypersensitivity (cross-react with penicillins <1%)
  • Eosinophilia, transaminase elevation
  • Thrombophlebitis at IV site

Pregnancy Safety

⚠️ Use with caution — Category B/C
Limited human data but animal studies do not show harm. Used when no safer alternative exists for serious infection. Generally considered acceptable when benefit outweighs risk.

CLASS 4 — MONOBACTAMS (β-Lactams)

Key Drug: Aztreonam

Mechanism of Action

Binds specifically to PBP3 of gram-negative bacteria only → inhibits cell wall synthesis → bactericidal. Has no activity against gram-positive bacteria or anaerobes.

Uses

  • Gram-negative aerobic infections in patients with serious penicillin/cephalosporin allergy (minimal cross-reactivity)
  • Pseudomonas aeruginosa infections
  • UTI, lower respiratory tract infections by GN organisms
  • Meningitis caused by susceptible GN bacilli

Dosage

  • 1–2 g IV/IM every 6–12 h

Adverse Effects

  • Generally well tolerated
  • GI: nausea, diarrhea
  • Hepatotoxicity (transaminase elevation)
  • Rare hypersensitivity

Pregnancy Safety

✅ Category B — Safe to use Good alternative for serious GN infections in PCN-allergic pregnant patients.

CLASS 5 — GLYCOPEPTIDES

Key Drugs: Vancomycin, Teicoplanin

Mechanism of Action

Glycopeptides bind the D-Ala-D-Ala terminus of peptidoglycan precursors → physically block transglycosylation and transpeptidation → cell wall synthesis fails → bactericidal against most gram-positive organisms. They do not penetrate the outer membrane of gram-negative bacteria.

Spectrum

Gram-positive only: MRSA, MRSE, Enterococcus (VRE are resistant), Streptococci, C. difficile (oral vancomycin only — not absorbed systemically)

Uses

  • MRSA infections (skin, bacteremia, endocarditis, pneumonia, osteomyelitis)
  • Gram-positive infections in beta-lactam–allergic patients
  • C. difficile colitis — oral vancomycin (stays in gut; NOT absorbed)
  • Febrile neutropenia with suspected gram-positive source
  • Endocarditis caused by resistant enterococci

Dosage

  • Vancomycin IV: 15–20 mg/kg every 8–12 h (dose by AUC/MIC targeting in current guidelines; trough monitoring or AUC monitoring used)
  • Oral vancomycin (for C. diff): 125 mg every 6 h × 10 days
  • Doses adjusted for renal function

Administration

  • Must be infused slowly over ≥60 minutes — rapid infusion causes "Red Man Syndrome" (flushing, erythema, hypotension) — due to non-immune mast cell degranulation, not true allergy
  • Therapeutic drug monitoring (TDM) required for IV use

Adverse Effects & Side Effects

  • Nephrotoxicity — dose-dependent; risk increased with concomitant aminoglycosides or NSAIDs
  • Ototoxicity — tinnitus, hearing loss (high serum levels)
  • Red Man Syndrome — rate-related infusion reaction; prevented by slowing infusion and pre-treating with antihistamines
  • Thrombophlebitis at IV site
  • Neutropenia, thrombocytopenia (prolonged use)
  • Note: "Vancomycin allergy" is frequently mislabeled — most reactions are Red Man Syndrome, not true IgE-mediated allergy

Pregnancy Safety

⚠️ Category C — Use with caution
Vancomycin crosses the placenta. No confirmed teratogenicity in humans, but fetal ototoxicity and nephrotoxicity are theoretically possible given the drug's mechanism. Used in pregnancy only when absolutely indicated (MRSA with no alternative); requires careful TDM.

CLASS 6 — LIPOGLYCOPEPTIDES

Drugs: Telavancin, Oritavancin, Dalbavancin

Mechanism

Similar to vancomycin (D-Ala-D-Ala binding) plus membrane depolarization via lipid tail anchoring. More potent than vancomycin; active against some vancomycin-intermediate/resistant strains.

Uses

  • Acute bacterial skin and skin structure infections (ABSSSI) from resistant gram-positive organisms including MRSA
  • Hospital-acquired pneumonia (telavancin)
  • Oritavancin and dalbavancin: prolonged half-lives (204–245 hours) → single-dose IV treatment for ABSSSI

Adverse Effects

  • Nephrotoxicity (telavancin)
  • QTc prolongation (avoid with fluoroquinolones, macrolides)
  • Infusion reactions
  • Oritavancin/telavancin interfere with coagulation assays (phospholipid-based; avoid with heparin)

Pregnancy Safety

❌ CONTRAINDICATED in pregnancy (telavancin)
Telavancin has confirmed fetal harm in animal studies and carries a boxed warning regarding risk of fetal harm. Pregnancy must be excluded before use. Oritavancin and dalbavancin also lack safety data — avoid unless no alternatives.

CLASS 7 — AMINOGLYCOSIDES

Examples

Gentamicin, Tobramycin, Amikacin, Streptomycin, Neomycin

Mechanism of Action

Aminoglycosides are concentration-dependent bactericidal agents. They enter bacteria (requires oxygen — inactive against obligate anaerobes) and bind irreversibly to the 30S ribosomal subunit → misreading of mRNA → production of aberrant/nonfunctional proteins → membrane disruption → cell death. They also have a prolonged post-antibiotic effect (PAE).

Uses

  • Serious gram-negative aerobic infections: Pseudomonas aeruginosa, Acinetobacter, Klebsiella
  • Synergy with beta-lactams for gram-positive endocarditis (e.g., Enterococcal or Streptococcal endocarditis)
  • Streptomycin: tuberculosis, plague, tularemia
  • Topical neomycin: wound/skin infections
  • Tobramycin: Pseudomonas in cystic fibrosis (inhaled)
  • Amikacin: drug-resistant TB; resistant GN organisms

Dosage

DrugDoseNotes
Gentamicin5–7 mg/kg/day (once daily, extended-interval)Adjust for renal function; monitor levels
Tobramycin5–7 mg/kg/daySame as gentamicin
Amikacin15–20 mg/kg/dayReserve for resistant organisms
Streptomycin15 mg/kg/day IMTB: combination regimen
  • Extended-interval (once-daily) dosing is preferred — exploits concentration-dependent killing and PAE while reducing toxicity
  • Peak and trough levels (or AUC) must be monitored
  • Dose reduction required in renal impairment

Adverse Effects & Side Effects

  • Nephrotoxicity — proximal tubular damage; reversible if caught early; risk increased with duration, pre-existing renal disease, volume depletion, NSAIDs, vancomycin
  • Ototoxicity — cochlear (hearing loss, tinnitus) and vestibular damage; may be irreversible. Cochlear: amikacin > kanamycin. Vestibular: tobramycin > gentamicin
  • Neuromuscular blockade — rare; can potentiate effects of neuromuscular blocking agents; risk in myasthenia gravis
  • Hypersensitivity (rare)
  • Neomycin topical: contact dermatitis

Pregnancy Safety

❌ CONTRAINDICATED (Category D)
Aminoglycosides cross the placenta and can cause irreversible sensorineural hearing loss (8th cranial nerve damage) in the fetus. Streptomycin is the most documented for fetal ototoxicity. Avoid throughout pregnancy unless life-threatening infection with no safer alternative.

CLASS 8 — TETRACYCLINES

Examples

Tetracycline, Doxycycline, Minocycline, Tigecycline (glycylcycline subclass)

Mechanism of Action

Bacteriostatic. Bind reversibly to the 30S ribosomal subunit → block attachment of aminoacyl-tRNA to the ribosomal acceptor site → inhibit protein synthesis. Active against a wide range of bacteria, including atypicals.

Spectrum

Broad: gram-positive, gram-negative, Rickettsia, Chlamydia, Mycoplasma, Borrelia (Lyme disease), Brucella, Vibrio cholerae, H. pylori (part of triple therapy)

Uses

  • Doxycycline (most commonly used):
    • Community-acquired pneumonia (atypicals: Mycoplasma, Chlamydophila)
    • Lyme disease (all stages)
    • Chlamydia, gonorrhea
    • Rickettsia (Rocky Mountain Spotted Fever — drug of choice)
    • Malaria prophylaxis and treatment
    • Acne (topical and oral)
    • Anthrax prophylaxis and treatment
    • MRSA skin infections (community-acquired)
  • Tigecycline: reserved for complicated skin/soft tissue infections, intra-abdominal infections; covers MRSA, many resistant GN organisms
  • Minocycline: acne, MRSA skin infections

Dosage

DrugDoseRoute
Doxycycline100 mg every 12 hOral or IV
Tetracycline250–500 mg every 6 hOral
Minocycline100–200 mg/day (divided doses)Oral
Tigecycline100 mg loading, then 50 mg every 12 hIV

Administration

  • Take doxycycline with a full glass of water and remain upright for 30 minutes to prevent esophageal ulceration
  • Dairy products, antacids (calcium, magnesium, aluminum), and iron chelate tetracyclines → take 2 h apart
  • Doxycycline can be taken with food (unlike older tetracyclines)

Adverse Effects & Side Effects

  • GI: nausea, vomiting, diarrhea, esophageal ulceration (if taken lying down)
  • Photosensitivity: increased sunburn risk — use sunscreen
  • Hepatotoxicity: dose-dependent, especially with IV tetracycline or in pregnancy
  • Tooth discoloration and enamel hypoplasia in children under 8 (permanent teeth affected)
  • Fanconi syndrome with expired tetracycline (degradation products toxic to proximal tubules)
  • Pseudotumor cerebri (benign intracranial hypertension): rare, minocycline > others
  • Vestibular toxicity: dizziness, ataxia with minocycline
  • Tigecycline: increased all-cause mortality in some indications (FDA warning), nausea most common adverse effect

Pregnancy Safety

❌ CONTRAINDICATED after first trimester (Category D)
Tetracyclines deposit in fetal teeth and bones during calcification (from week 20 of gestation through 8 years of age post-birth). They cause yellow-brown permanent tooth staining and enamel hypoplasia. They can also cause hepatotoxicity in pregnant women, particularly at high IV doses. Avoid in all trimesters if possible; absolutely avoid in 2nd and 3rd trimesters.

CLASS 9 — MACROLIDES

Examples

Erythromycin, Azithromycin (Z-pack), Clarithromycin

Mechanism of Action

Bacteriostatic. Bind irreversibly to the 50S ribosomal subunit (23S rRNA) → block translocation step of elongation → inhibit protein synthesis. Concentration in tissues and macrophages (especially azithromycin — very long half-life, distributes intracellularly).

Spectrum

Streptococcus, Staphylococcus (MSSA), Corynebacterium, Chlamydia, Legionella, Mycoplasma, Moraxella, H. pylori, Mycobacterium avium complex (azithromycin, clarithromycin)

Uses

  • Community-acquired pneumonia (atypical pathogens)
  • Pharyngitis in PCN-allergic patients
  • STIs: Chlamydia (azithromycin 1 g single dose)
  • Legionella, Mycoplasma pneumonia
  • MAC prophylaxis/treatment in HIV (azithromycin, clarithromycin)
  • H. pylori (clarithromycin-based triple therapy: PPI + clarithromycin + amoxicillin)
  • Pertussis (whooping cough)
  • Prophylaxis in PCN-allergic patients undergoing dental procedures (azithromycin 500 mg PO × 1)

Dosage

DrugDoseNotes
Azithromycin500 mg day 1, then 250 mg days 2–5 (Z-pack) OR 500 mg/day × 3 daysOral/IV
Clarithromycin250–500 mg every 12 hOral
Erythromycin250–500 mg every 6 hOral; also IV for gastroparesis (prokinetic)
  • Adjust clarithromycin in CKD
  • Azithromycin: avoid in hepatic disease (excreted in bile)

Adverse Effects & Side Effects

  • QTc prolongation — risk of torsades de pointes, especially azithromycin + other QT-prolonging drugs (antiarrhythmics, fluoroquinolones, antipsychotics)
  • GI: nausea, vomiting, abdominal cramping (erythromycin most common — also a motilin receptor agonist → gastroparesis treatment)
  • Hepatotoxicity: cholestatic jaundice (erythromycin estolate form most common)
  • Hearing loss: high-dose IV erythromycin (reversible)
  • Drug interactions: potent CYP3A4 inhibitors (erythromycin, clarithromycin) → increase levels of statins, warfarin, cyclosporine, carbamazepine. Azithromycin does NOT inhibit CYP3A4 (major advantage)
  • Reduced contraceptive effectiveness (erythromycin, clarithromycin — alter gut flora affecting enterohepatic recycling)
  • CDAD

Pregnancy Safety

⚠️ Mixed safety:
  • Azithromycin: Category B — generally considered safe; most data support use in pregnancy (Chlamydia treatment, pneumonia)
  • Clarithromycin: ❌ Category C / avoid — animal studies show teratogenicity (cardiovascular defects, cleft palate). Avoid in 1st trimester if possible; use only when no alternative
  • Erythromycin: Category B — considered acceptable, but erythromycin estolate is contraindicated (cholestatic hepatitis in pregnant women)

CLASS 10 — FLUOROQUINOLONES

Examples

Ciprofloxacin, Levofloxacin, Moxifloxacin, Ofloxacin, Norfloxacin

Mechanism of Action

Bactericidal, concentration-dependent. Inhibit bacterial type II topoisomerases:
  • DNA gyrase (topoisomerase II) — primarily in gram-negative bacteria
  • Topoisomerase IV — primarily in gram-positive bacteria
These enzymes are essential for DNA replication, transcription, and repair. Quinolones stabilize the enzyme-DNA cleavage complex → accumulation of double-strand DNA breaks → cell death.

Spectrum

  • Ciprofloxacin: excellent GN (including Pseudomonas), moderate GP
  • Levofloxacin, Moxifloxacin: "respiratory fluoroquinolones" — excellent GP (including S. pneumoniae), GN, atypicals
  • Moxifloxacin: additional anaerobic coverage; no Pseudomonas coverage
  • All active against Mycobacterium tuberculosis (2nd-line TB drugs)

Uses

  • Urinary tract infections (cipro, levofloxacin — UTI)
  • Community-acquired pneumonia (levofloxacin, moxifloxacin)
  • Hospital-acquired pneumonia, Pseudomonas infections (ciprofloxacin)
  • Traveler's diarrhea, Salmonellosis, Shigellosis
  • Anthrax (ciprofloxacin — drug of choice)
  • Gonorrhea (resistance common — use with caution)
  • Atypical pneumonia, Legionella
  • Bone and joint infections
  • Prostatitis (ciprofloxacin)
  • TB (2nd-line, in MDR-TB regimens)

Dosage

DrugDoseRoute
Ciprofloxacin250–750 mg every 12 h (PO) or 200–400 mg every 8–12 h (IV)Oral/IV
Levofloxacin500–750 mg every 24 hOral/IV (bioequivalent)
Moxifloxacin400 mg every 24 hOral/IV
  • Avoid antacids, calcium, iron, zinc within 2 hours (chelation reduces absorption)
  • Excellent oral bioavailability — oral = IV efficacy for levofloxacin

Adverse Effects & Side Effects

  • Tendinopathy and tendon rupture — Achilles tendon most common (boxed warning); risk increased with age >60, corticosteroids, renal failure
  • QTc prolongation — avoid with other QT-prolonging drugs
  • CNS toxicity: headache, dizziness, insomnia, confusion, seizures (especially in elderly)
  • Cartilage damage in developing animals (basis for avoiding in children and pregnancy)
  • Photosensitivity: sunburn — use sunscreen
  • Peripheral neuropathy: may be irreversible (boxed warning)
  • Hypoglycemia: especially in patients on sulfonylureas
  • Hepatotoxicity: elevated LFTs; rare severe hepatitis (moxifloxacin)
  • Aortic dissection/aneurysm — FDA safety communication; avoid in patients at risk
  • Drug interactions: inhibit CYP1A2 (ciprofloxacin) — increases theophylline, caffeine levels

Pregnancy Safety

❌ CONTRAINDICATED — Category C
Fluoroquinolones damage developing cartilage in animal models. While not definitively proven teratogenic in humans, they are avoided due to potential fetal cartilage and musculoskeletal toxicity. The FDA advises against use in pregnancy and lactation. Used only in life-threatening infections with no alternative.

CLASS 11 — CLINDAMYCIN (Lincosamide)

Mechanism of Action

Bacteriostatic (bactericidal at high concentrations against staphylococci, streptococci, and anaerobes). Binds the 50S ribosomal subunit → inhibits elongation of peptide chains → protein synthesis stopped.

Spectrum

Gram-positive: MSSA, community-acquired MRSA (CA-MRSA), Streptococcus, anaerobes (Bacteroides fragilis, Prevotella, Clostridium — but NOT C. difficile)

Uses

  • Skin and soft tissue infections (MRSA, Streptococcus)
  • Anaerobic infections (aspiration pneumonia, intra-abdominal)
  • Pelvic inflammatory disease (combined with other agents)
  • Dental infections (PCN-allergic)
  • Toxin-mediated infections (toxic shock syndrome — inhibits toxin production even when bactericidal activity is incomplete)
  • Bone and joint infections
  • Pneumocystis pneumonia (PCP) — combined with primaquine
  • Malaria (combined with quinine)

Dosage

  • Adult: 150–450 mg every 6 h (oral); 600–900 mg every 8 h (IV)
  • Topical (gel, lotion, solution): for acne
  • Vaginal cream/suppositories: bacterial vaginosis

Adverse Effects & Side Effects

  • C. difficile-associated diarrhea (CDAD) / pseudomembranous colitis — historically the most notorious cause; very important risk
  • GI: nausea, vomiting, diarrhea (common)
  • Metallic taste (IV administration)
  • Hepatotoxicity (elevated LFTs)
  • Rash, urticaria

Pregnancy Safety

✅ Category B — Generally safe
Considered acceptable for use in pregnancy. Widely used for bacterial vaginosis, dental infections, and soft tissue infections in PCN-allergic pregnant women. No known teratogenicity.

CLASS 12 — SULFONAMIDES & TRIMETHOPRIM

Mechanism of Action

These drugs target folate synthesis — a pathway humans do not have (we obtain folate from diet), so selective toxicity is high.
  • Sulfonamides: inhibit dihydropteroate synthase → block conversion of PABA to dihydropteroic acid → no dihydrofolate
  • Trimethoprim: inhibits dihydrofolate reductase (DHFR) → blocks conversion of dihydrofolic acid to tetrahydrofolate → no active folate
  • TMP-SMX (co-trimoxazole): sequential blockade of two steps → synergistic bactericidal activity

Spectrum

Broad: gram-positive (MSSA, CA-MRSA), gram-negative (E. coli, Klebsiella, Enterobacter), Pneumocystis jirovecii, Toxoplasma, Nocardia

Uses

  • UTI (most common use — TMP-SMX 1 double-strength tablet BID × 3 days)
  • PCP treatment and prophylaxis (HIV patients — TMP-SMX is drug of choice)
  • CA-MRSA skin infections (TMP-SMX)
  • Toxoplasmosis treatment (with pyrimethamine; TMP-SMX for prophylaxis)
  • Nocardiosis
  • Traveler's diarrhea
  • Prophylaxis in immunocompromised patients (post-transplant, HIV CD4 <200)

Dosage

DrugDoseNotes
TMP-SMX (Bactrim DS)1 DS tablet (160/800 mg) every 12 hOral
TMP-SMX for PCP treatment15–20 mg/kg/day of TMP component (IV or PO)High dose
Trimethoprim alone100 mg every 12 h or 200 mg every 24 hUTI

Adverse Effects & Side Effects

  • Stevens-Johnson syndrome (SJS) / Toxic epidermal necrolysis (TEN): most feared hypersensitivity reaction — potentially life-threatening; blistering, skin sloughing
  • Hematologic: megaloblastic anemia (folate deficiency), neutropenia, thrombocytopenia, agranulocytosis — especially in folate-deficient patients
  • Crystalluria / urolithiasis: sulfonamides precipitate in urine (maintain good hydration)
  • Hyperkalemia: trimethoprim blocks ENaC channels in distal nephron (same mechanism as amiloride) → hyponatremia in elderly
  • Hepatotoxicity: cholestatic jaundice
  • Nausea, vomiting, diarrhea
  • Drug interactions: increases warfarin levels (inhibits CYP2C9); increases methotrexate toxicity; increases phenytoin levels

Pregnancy Safety

❌ AVOID — Category C/D depending on trimester
  • 1st trimester: folate antagonism raises concern for neural tube defects (folic acid supplement recommended if unavoidable)
  • 3rd trimester / near term: sulfonamides displace bilirubin from albumin in the neonate → neonatal jaundice and kernicterus
  • Avoid at term; use only with clear indication in early pregnancy with folic acid supplementation

CLASS 13 — METRONIDAZOLE (Nitroimidazole)

Mechanism of Action

Bactericidal and antiprotozoal. In anaerobic organisms (and anaerobic microenvironments), metronidazole is reduced by bacterial ferredoxin or NADH → reactive nitro-radical intermediates → DNA strand breaks and disruption → cell death. Active only in anaerobic/microaerophilic environments (reason it is selective).

Spectrum

Obligate anaerobes: Bacteroides fragilis, Clostridium difficile, Clostridium perfringens, Prevotella Protozoa: Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica

Uses

  • C. difficile colitis (oral or IV)
  • Bacterial vaginosis (metronidazole is drug of choice)
  • Trichomoniasis (2 g single oral dose)
  • Giardiasis, amebiasis
  • Intra-abdominal and pelvic infections (combined with cephalosporins or fluoroquinolones)
  • Aspiration pneumonia / lung abscess (anaerobic coverage)
  • H. pylori (part of quadruple therapy)
  • Dental infections (anaerobes)
  • Brain abscess

Dosage

IndicationDoseRoute
C. diff500 mg every 8 h × 10–14 daysOral
Bacterial vaginosis500 mg BID × 7 days (or 0.75% gel intravaginal)Oral/Topical
Trichomoniasis2 g single dose OR 500 mg BID × 7 daysOral
Intra-abdominal500 mg every 8 hIV/Oral

Adverse Effects & Side Effects

  • Disulfiram-like reaction: severe flushing, nausea, vomiting, tachycardia if alcohol consumed during or within 48–72 h of therapy — absolutely no alcohol
  • Metallic taste (very common — patients report a strong metallic taste throughout therapy)
  • GI: nausea, vomiting, diarrhea
  • Peripheral neuropathy: with prolonged use (numbness, tingling in extremities)
  • CNS: headache, dizziness, seizures (high doses or prolonged use)
  • Dark/reddish-brown urine (harmless metabolite)
  • Warfarin interaction: inhibits CYP2C9 → increased INR; monitor closely

Pregnancy Safety

⚠️ Category B — but controversial:
  • 1st trimester: traditionally avoided — older concerns about theoretical teratogenicity (though well-designed studies have not confirmed this)
  • 2nd/3rd trimester: generally considered safe
  • At term: avoid systemic use for trichomoniasis in 1st trimester per some guidelines; use vaginal gel as alternative
  • Currently, most guidelines (including CDC) consider metronidazole safe in all trimesters when indicated (e.g., bacterial vaginosis to reduce preterm labor risk)

CLASS 14 — AMINOGLYCOSIDES (see Class 7 above) — RIFAMYCINS

Key Drug: Rifampin (Rifampicin)

Mechanism of Action

Bactericidal. Binds the β-subunit of bacterial DNA-dependent RNA polymerase → blocks DNA transcription → no mRNA → no protein synthesis. Excellent intracellular penetration (kills intracellular organisms).

Uses

  • Tuberculosis — cornerstone of first-line regimen (RIPE: Rifampin + Isoniazid + Pyrazinamide + Ethambutol)
  • Meningococcal prophylaxis (contacts of meningitis)
  • H. influenzae type b prophylaxis
  • Leprosy (rifampin-based regimens)
  • MRSA — as part of combination therapy (adjunct; never monotherapy due to rapid resistance development)
  • Staphylococcal prosthetic valve endocarditis / implant infections

Dosage

  • TB treatment: 10 mg/kg/day (max 600 mg/day) × months (part of combination regimen)
  • Meningococcal prophylaxis: 600 mg every 12 h × 2 days (adults)

Adverse Effects & Side Effects

  • Orange-red discoloration of urine, tears, saliva, sweat, sputum — harmless but startling; stains soft contact lenses permanently
  • Hepatotoxicity (transaminase elevation, jaundice) — monitor LFTs
  • GI: nausea, vomiting
  • Flu-like syndrome (intermittent dosing)
  • Powerful CYP450 inducer — induces CYP3A4, CYP2C9, CYP2C19, CYP2D6, and P-glycoprotein → dramatically reduces levels of: oral contraceptives (OCP failure), warfarin, antiretrovirals (especially PIs and NNRTIs), tacrolimus, cyclosporine, methadone, phenytoin, and many others

Pregnancy Safety

⚠️ Category C — Use with caution
Rifampin crosses the placenta. Limited human data on teratogenicity. May cause postnatal bleeding in the newborn (vitamin K-dependent clotting factors reduced through CYP induction) — give vitamin K prophylaxis. Used in TB during pregnancy because untreated TB poses greater risk to mother and fetus.

CLASS 15 — OXAZOLIDINONES

Key Drug: Linezolid (Zyvox)

Mechanism of Action

Bacteriostatic. Binds the 23S ribosomal RNA of the 50S subunit at a unique site → prevents formation of the 70S initiation complex → protein synthesis cannot begin. Novel mechanism with no cross-resistance to other antibiotic classes.

Spectrum

Gram-positive only: MRSA, VRE (Enterococcus faecium and faecalis), MRSE, penicillin-resistant Streptococcus pneumoniae

Uses

  • VRE infections (one of few drugs active)
  • MRSA pneumonia (may be superior to vancomycin for lung penetration)
  • Skin and soft tissue infections by resistant gram-positive organisms
  • Diabetic foot infections (oral bioavailability allows step-down from IV)
  • MRSA osteomyelitis (oral option)
  • Alternative when vancomycin toxicity is a concern

Dosage

  • 600 mg every 12 h, oral or IV
  • Excellent oral bioavailability (~100%) — IV and oral are equivalent
  • No dose adjustment needed for renal/hepatic impairment

Adverse Effects & Side Effects

  • Myelosuppression — thrombocytopenia is most common (monitor CBC weekly)
  • Serotonin syndrome — CRITICAL: linezolid is a monoamine oxidase inhibitor (MAOI). Combining with SSRIs, SNRIs, tricyclics, meperidine, tramadol, triptans → life-threatening serotonin syndrome (hyperthermia, agitation, myoclonus, autonomic instability)
  • Peripheral neuropathy with prolonged use
  • Optic neuropathy: visual impairment, color vision loss (usually reversible)
  • GI: nausea, diarrhea
  • Lactic acidosis (rare, mitochondrial toxicity)
  • Drug interactions: avoid tyramine-rich foods (aged cheese, wine) — MAO inhibition

Pregnancy Safety

⚠️ Category C — Limited data; use only if benefit outweighs risk
Limited human data. Animal studies suggest potential fetal toxicity (decreased fetal weight). Use only when no alternative exists.

CLASS 16 — DAPTOMYCIN

Mechanism of Action

Bactericidal, concentration-dependent. Cyclic lipopeptide that inserts into the bacterial cell membrane in a calcium-dependent manner → causes depolarization → efflux of intracellular ions (K+) → membrane potential lost → cell death. Unique mechanism — no cross-resistance.

Spectrum

Gram-positive only: MRSA, VRE, S. aureus (including bacteremia with right-sided endocarditis), Streptococci
Critical: Daptomycin is inactivated by pulmonary surfactant — NEVER use for pneumonia.

Uses

  • Complicated skin and soft tissue infections (cSSTI)
  • S. aureus bacteremia and right-sided endocarditis
  • VRE infections (alternative)
  • Left-sided endocarditis: not proven effective — avoid

Dosage

  • cSSTI: 4 mg/kg IV once daily
  • Bacteremia/endocarditis: 6 mg/kg IV once daily
  • Adjust for renal function (CrCl <30 mL/min: dose every 48 h)

Adverse Effects & Side Effects

  • Myopathy / rhabdomyolysis: elevated CPK → muscle pain/weakness; monitor CPK weekly; discontinue if symptomatic or CPK >5× ULN; risk increased with statins (hold statins during therapy)
  • GI: nausea, constipation
  • Eosinophilic pneumonia (rare)
  • Peripheral neuropathy (rare)

Pregnancy Safety

⚠️ Category B — Limited data
Animal studies show no fetal harm. Limited human data; use only when clearly indicated.

CLASS 17 — POLYMYXINS

Drugs: Polymyxin B, Colistin (Polymyxin E)

Mechanism of Action

Bactericidal. Cationic polypeptides that bind lipopolysaccharide (LPS) of gram-negative outer membranes via electrostatic interaction → displace divalent cations (Ca²⁺, Mg²⁺) → disrupt outer and inner membrane integrity → cell contents leak out → cell death. Like a detergent effect on the membrane.

Spectrum

Gram-negative only (narrow): Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae (including carbapenem-resistant strains — CRE, CRAB, CRPA)

Uses

  • Last-resort agents for multidrug-resistant (MDR) and extensively drug-resistant (XDR) gram-negative infections
  • CRE (carbapenem-resistant Enterobacteriaceae) infections
  • MDR Acinetobacter baumannii
  • Inhaled colistin for Pseudomonas in cystic fibrosis

Dosage

  • Colistin (colistimethate sodium, CMS): 2.5–5 mg/kg/day in 2–4 divided doses IV (based on colistin base activity)
  • Polymyxin B: 15,000–25,000 units/kg/day IV divided every 12 h
  • Both: critical dose adjustments for renal function

Adverse Effects & Side Effects

  • Nephrotoxicity — major dose-limiting toxicity; acute tubular necrosis; occurs in 20–60% of patients; reversible
  • Neurotoxicity: dizziness, paresthesia, perioral numbness, ataxia, neuromuscular blockade
  • GI: nausea
  • Significant toxicity limits use to resistant infections only

Pregnancy Safety

⚠️ Category C — Use with caution; last resort only
Limited human data. Nephrotoxicity potential is a concern for fetal renal development. Used only when all other options exhausted for MDR infections threatening maternal life.

CLASS 18 — CHLORAMPHENICOL

Mechanism of Action

Bacteriostatic (bactericidal against some organisms: S. pneumoniae, H. influenzae, N. meningitidis). Binds the 23S rRNA of the 50S ribosomal subunit → inhibits peptidyl transferase → prevents peptide bond formation → protein synthesis stops.

Spectrum

Broad: gram-positive, gram-negative, anaerobes, Rickettsia, Salmonella

Uses

  • Bacterial meningitis (alternative when beta-lactams unavailable/allergic)
  • Typhoid fever (salmonellosis) in resource-limited settings
  • Rickettsial diseases (Rocky Mountain Spotted Fever — alternative to doxycycline; preferred in children <8 years when tetracycline is contraindicated)
  • Ophthalmic preparations (eye drops/ointment) — widely used topically
  • Brain abscess

Dosage

  • 50–100 mg/kg/day in 4 divided doses (IV or oral)
  • Monitor serum levels (desired peak 10–25 mcg/mL)

Adverse Effects & Side Effects

  • Gray baby syndrome — in neonates: accumulation due to immature glucuronyl transferase → high serum levels → cardiovascular collapse, ashen-gray skin, hypothermia, cyanosis, flaccidity; can be fatal
  • Aplastic anemia — rare (1:20,000–40,000) but potentially fatal; idiosyncratic, dose-independent
  • Reversible bone marrow suppression — dose-dependent; anemia, leukopenia, thrombocytopenia (monitor CBC)
  • Optic neuritis (prolonged use)
  • GI: nausea, vomiting, diarrhea

Pregnancy Safety

❌ AVOID — especially near term
Risk of gray baby syndrome in neonates exposed near delivery. Use topical ophthalmic formulations (minimal systemic absorption) cautiously. Systemic use only as last resort.

QUICK PREGNANCY SAFETY SUMMARY TABLE

Antibiotic ClassPregnancy SafetyKey Reason if Unsafe
Penicillins✅ SAFE (Category B)No known harm; drug of choice in pregnancy
Cephalosporins✅ SAFE (Category B)No known harm
Aztreonam✅ SAFE (Category B)No teratogenicity
Carbapenems⚠️ Use if needed (B/C)Limited data; generally acceptable
Vancomycin⚠️ Use with caution (C)Fetal oto/nephrotoxicity risk
Clindamycin✅ SAFE (Category B)No known harm
Metronidazole✅ Generally safe (B)Avoid in 1st trimester per some guidelines
Azithromycin✅ SAFE (Category B)Preferred macrolide in pregnancy
Clarithromycin❌ AVOID (Category C)Teratogenic in animals
Erythromycin base⚠️ Acceptable (B)Estolate form avoided (hepatotoxicity)
Aminoglycosides❌ AVOID (Category D)Irreversible fetal sensorineural deafness
Tetracyclines❌ AVOID (Category D)Tooth discoloration, enamel defects, hepatotoxicity
Fluoroquinolones❌ AVOID (Category C)Fetal cartilage damage (animal data)
TMP-SMX❌ AVOID near termKernicterus risk; folate antagonism
Rifampin⚠️ Use for TB (C)Neonatal bleeding risk; essential for TB
Linezolid⚠️ Category CLimited data; use only if necessary
Daptomycin⚠️ Category BLimited data; animal studies OK
Polymyxins⚠️ Last resort (C)Nephrotoxicity concern
Chloramphenicol❌ AVOID near termGray baby syndrome in neonate
Telavancin❌ CONTRAINDICATEDConfirmed fetal harm (boxed warning)

KEY CONCEPTS TO REMEMBER

Resistance mechanisms (why antibiotics fail):
  1. Beta-lactamase production — destroys beta-lactam ring (penicillinase, ESBL, carbapenemase)
  2. PBP modification — MRSA uses PBP2a (encoded by mecA gene) with low affinity for beta-lactams
  3. Porin downregulation — reduces drug entry (Pseudomonas)
  4. Efflux pumps — actively expel antibiotic from cell
  5. Target site modification — ribosome methylation (macrolide resistance), D-Ala-D-Lac (vancomycin resistance in VRE)
  6. Enzymatic modification — aminoglycoside-modifying enzymes
Concentration-dependent vs. time-dependent killing:
  • Concentration-dependent (aminoglycosides, fluoroquinolones, daptomycin): larger doses less frequently; peak/MIC ratio drives efficacy
  • Time-dependent (beta-lactams, vancomycin, macrolides): keep levels above MIC for maximum % of dosing interval; extended infusions used
Post-antibiotic effect (PAE): continued suppression of bacterial growth after drug levels fall below MIC — prolonged PAE with aminoglycosides and fluoroquinolones justifies once-daily dosing.
Sources: Lippincott Illustrated Reviews: Pharmacology; K.J. Lee's Essential Otolaryngology, Chapter 9 (Antimicrobial Therapy)
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