Antimicrobials work because they hit a target that bacteria have and human cells lack or have in a different form (selective toxicity).

Key terms

• Bactericidal drugs kill bacteria (beta-lactams, aminoglycosides, fluoroquinolones, vancomycin); bacteriostatic drugs stop growth and rely on host defenses (tetracyclines, macrolides, clindamycin, linezolid, sulfonamides). Bactericidal drugs are preferred in endocarditis, meningitis, and severe immunosuppression
• Spectrum: narrow (e.g., penicillin G, cefazolin) versus broad (e.g., piperacillin–tazobactam, carbapenems). Broad-spectrum use disrupts normal flora and drives resistance
• Minimum inhibitory concentration (MIC): the lowest concentration that inhibits growth; susceptibility reports classify organisms as susceptible, intermediate, or resistant
• Time-dependent killing (beta-lactams): effect depends on how long the level stays above the MIC → give doses on time; extended or continuous infusions are sometimes used. Vancomycin effect is best predicted by total exposure (AUC/MIC), so it is dosed by AUC
• Concentration-dependent killing (aminoglycosides, fluoroquinolones, daptomycin): effect depends on peak height → large, less frequent doses (e.g., once-daily aminoglycosides); post-antibiotic effect allows long intervals
• Synergy: a cell-wall drug helps an aminoglycoside enter the cell (e.g., ampicillin + gentamicin for enterococcal endocarditis)

Resistance develops by mutation or by transfer of genes (plasmids). Mechanisms: enzymes that destroy the drug (beta-lactamases, extended-spectrum beta-lactamases [ESBL], carbapenemases [CRE]), altered targets (MRSA's altered penicillin-binding protein; VRE's altered cell-wall precursor), reduced entry, and efflux pumps. Every exposure — especially unnecessary or broad-spectrum use — selects resistant organisms.

Empiric versus definitive therapy

• Empiric therapy covers the likely organisms before culture results, based on infection site, severity, local resistance patterns (antibiogram), recent antibiotic use, and host factors
• Definitive (targeted) therapy follows culture and susceptibility results — de-escalate to the narrowest effective drug
• Prophylaxis prevents infection: surgical prophylaxis (e.g., cefazolin) within 60 minutes before incision (120 minutes for vancomycin and fluoroquinolones), usually stopped within 24 hours; endocarditis prophylaxis only for high-risk clients before certain dental procedures; post-exposure prophylaxis (e.g., meningococcal contacts)

Collect cultures first — but do not delay treatment in severe infection. For probable septic shock or a high likelihood of sepsis, the Surviving Sepsis Campaign (2021) recommends antimicrobials within 1 hour of recognition; with possible sepsis without shock, a rapid assessment and antibiotics within 3 hours if concern persists. Draw two sets of blood cultures (from separate sites) before the first dose whenever this causes no significant delay.

Choosing a drug — the host

• Allergy history (drug, reaction, timing, severity)
• Kidney function (most antibiotics need renal dose adjustment) and liver function
• Age: neonates (immature liver and kidneys; avoid ceftriaxone with hyperbilirubinemia), older adults (lower kidney function, higher toxicity)
• Pregnancy and lactation: penicillins, cephalosporins, and azithromycin are generally preferred; avoid tetracyclines (teeth, bone), fluoroquinolones (cartilage concerns), and TMP-SMX in the first trimester and near term (folate antagonism; kernicterus); use aminoglycosides only when clearly indicated — fetal ototoxicity is reported mainly with streptomycin, and gentamicin is used (e.g., intraamniotic infection, pyelonephritis) with level monitoring
• Site of infection: drug must reach it (e.g., blood–brain barrier for meningitis; daptomycin is inactivated in lungs)
• Immune status, genetic factors (e.g., G6PD deficiency with sulfonamides and nitrofurantoin), drug interactions, QT risk, cost, route

Stewardship (CDC Core Elements) — the right drug, dose, route, and duration, only when needed:

• Antibiotic time-out at 48–72 hours: review diagnosis, cultures, and response; stop, narrow, or switch
• IV-to-oral switch when the client is stable, afebrile, and can absorb oral drugs (high bioavailability drugs: fluoroquinolones, linezolid, TMP-SMX, metronidazole, doxycycline)
• Shorter courses are effective for many common infections (e.g., 5 days for uncomplicated community-acquired pneumonia in many adults)
• Antibiotics do not treat viral infections (colds, most sore throats and bronchitis)
• Delabel inaccurate penicillin allergy labels through allergy evaluation or direct oral challenge

Effects shared by many antibacterials:

• Hypersensitivity — rash, urticaria, angioedema, anaphylaxis (usually within an hour of a dose); severe delayed reactions — Stevens–Johnson syndrome/toxic epidermal necrolysis, DRESS
• GI upset — nausea, diarrhea
• Superinfection — Clostridioides difficile infection (any antibiotic; highest risk with clindamycin, fluoroquinolones, cephalosporins, and broad-spectrum drugs), oral thrush and vaginal candidiasis
• Organ toxicity — nephrotoxicity (aminoglycosides, vancomycin, polymyxins), ototoxicity (aminoglycosides), hepatotoxicity, bone marrow suppression, neurotoxicity and seizures (high-dose beta-lactams in kidney failure), QT prolongation (macrolides, fluoroquinolones)
• Photosensitivity (tetracyclines, fluoroquinolones, sulfonamides)
• Infusion reactions (vancomycin with rapid infusion)
• Drug interactions (enzyme inhibition by macrolides; rifampin induction; chelation of fluoroquinolones and tetracyclines)

Distinguish true allergy from intolerance: nausea, diarrhea, or headache are not allergies. About 10% of people report a penicillin allergy, but fewer than 1% of the population have a true IgE-mediated penicillin allergy; an inaccurate label leads to broader, more toxic, costlier drugs.

• Previous severe reaction to the drug (anaphylaxis, SJS/TEN, DRESS) → avoid the drug; SJS/TEN or DRESS to a beta-lactam → avoid the whole class unless an allergist advises otherwise
• Cross-reactivity: penicillin–cephalosporin cross-reactivity is low (about 1–2%) and depends mainly on similar side chains; carbapenem cross-reactivity is below 1%; aztreonam does not cross-react except with ceftazidime (shared side chain)
• Kidney impairment: adjust dose or interval using creatinine clearance for most beta-lactams, vancomycin, aminoglycosides, fluoroquinolones, TMP-SMX; nitrofurantoin is avoided with low clearance
• Liver impairment: caution with drugs cleared by the liver or hepatotoxic (e.g., amoxicillin–clavulanate, macrolides, tetracyclines, isoniazid)
• Key interactions: warfarin effect increased by metronidazole, TMP-SMX, fluoroquinolones, macrolides → check INR; rifampin decreases levels of many drugs, including hormonal contraceptives; carbapenems sharply lower valproic acid levels; linezolid + serotonergic drugs → serotonin syndrome; antacids, calcium, iron, zinc chelate fluoroquinolones and tetracyclines; aminoglycosides + other nephrotoxic or ototoxic drugs (loop diuretics, vancomycin, NSAIDs, contrast) → additive toxicity
• Pregnancy: see section 2; always check pregnancy status in people who can become pregnant

1. Before the first dose
   • Obtain a detailed allergy history (drug, reaction, timing, treatment) and record it precisely
   • Collect ordered cultures before the first dose (blood, urine, sputum, wound) without significantly delaying treatment in sepsis
   • Baseline creatinine/eGFR, CBC, liver tests as indicated; pregnancy status; current drugs (warfarin, QT drugs, serotonergic drugs)
2. First dose and anaphylaxis readiness: observe closely during and after the first dose, especially IV; have epinephrine available; stop the infusion at the first sign of a reaction
3. Give doses on time to maintain levels (critical for time-dependent drugs); use correct dilution and infusion rate; check compatibility (e.g., aminoglycosides and penicillins inactivate each other if mixed; ceftriaxone must not be given with IV calcium solutions in neonates)
4. Therapeutic drug monitoring
   • Trough level: drawn just before the next dose (reflects accumulation and toxicity risk)
   • Peak level: drawn after distribution (for IV aminoglycosides, commonly 30 minutes after the end of a 30-minute infusion)
   • Vancomycin: AUC-guided dosing (target AUC about 400–600 mg·h/L for serious MRSA infections) is now preferred over trough-only monitoring; many protocols still use troughs
   • Label specimens with exact draw and dose times
5. Monitor response: temperature curve, WBC count (normal about 4,500–11,000/mm³ (4.5–11.0 × 10⁹/L)), procalcitonin or CRP where used, vital signs, wound appearance, mental status; report no improvement within 48–72 hours
6. Monitor toxicity: urine output and creatinine (normal about 0.6–1.2 mg/dL (53–106 µmol/L)); hearing, tinnitus, balance; new diarrhea (three or more unformed stools in 24 hours → C. difficile testing, contact precautions, soap-and-water hand hygiene); rash; mouth and vaginal candidiasis; INR on warfarin
7. Support stewardship: prompt the 48–72-hour review, IV-to-oral switch, and stop dates

• Take every dose as prescribed, for the full prescribed course, at evenly spaced times; do not stop early unless the prescriber says so, and never save or share antibiotics or use leftovers for a new illness
• Antibiotics do not work for colds and most viral infections
• Report rash, hives, swelling, or difficulty breathing at once; tell every provider about true drug allergies and describe the reaction
• Report severe or persistent watery diarrhea, especially with fever or abdominal pain, even weeks after finishing — do not self-treat with loperamide
• Food and drug timing: follow label instructions (with or without food; separate from antacids, calcium, iron when required)
• Hormonal contraception: rifampin and rifabutin reduce effectiveness — use backup; most other antibiotics do not
• Avoid sun exposure with photosensitizing drugs; avoid alcohol with metronidazole during and for 72 hours after
• Dispose of unused antibiotics through take-back programs

Most antibacterials have no specific antidote; many are removed by hemodialysis.

• Cultures before the first dose — but do not delay antibiotics in sepsis (within 1 hour for septic shock or probable sepsis)
• Empiric → definitive: de-escalate at the 48–72-hour time-out
• Time-dependent drugs (beta-lactams): give on time; vancomycin dosed by AUC; concentration-dependent (aminoglycosides): high peaks, once-daily dosing
• Trough = just before the next dose; peak = after distribution
• Take the full prescribed course; never share or save antibiotics; no antibiotics for viral infections
• Anaphylaxis → stop drug, epinephrine IM 0.01 mg/kg (max 0.5 mg adult)
• C. difficile: new diarrhea after antibiotics → test, contact precautions, soap and water
• Pregnancy: avoid tetracyclines and fluoroquinolones, TMP-SMX in first trimester and near term; gentamicin only when indicated, with levels
• Adjust most antibiotics for kidney function
• Metronidazole, TMP-SMX, fluoroquinolones, macrolides raise INR with warfarin