Key Facts

Antibiotics are among the most prescribed drugs in the UK. Appropriate use is critical to maximise efficacy, minimise side effects, and combat antimicrobial resistance. Local formularies and guidelines should always be consulted.

Epidemiology

• ~40 million antibiotic prescriptions/year in England
• ~20% of antibiotic prescriptions considered inappropriate
• AMR: ~5,000 deaths/year in UK attributed to drug-resistant infections
• C. difficile: ~13,000 cases/year — strongly associated with broad-spectrum antibiotics

Classification by Mechanism

• Cell wall synthesis inhibitors: penicillins, cephalosporins, carbapenems, glycopeptides (vancomycin)
• Protein synthesis inhibitors: macrolides (30S/50S), tetracyclines (30S), aminoglycosides (30S), chloramphenicol (50S), linezolid (50S)
• DNA synthesis inhibitors: fluoroquinolones (DNA gyrase/topoisomerase IV), metronidazole (DNA damage)
• Folate synthesis inhibitors: trimethoprim, sulfamethoxazole
• Cell membrane disruptors: colistin, daptomycin

Key Principles

• Bactericidal: kills bacteria — penicillins, cephalosporins, aminoglycosides, fluoroquinolones, metronidazole
• Bacteriostatic: inhibits growth — macrolides, tetracyclines, trimethoprim, chloramphenicol, linezolid
• Spectrum: narrow (flucloxacillin, benzylpenicillin) → broad (co-amoxiclav, meropenem) — use narrowest effective spectrum
• Time-dependent killing: penicillins, cephalosporins — efficacy depends on time above MIC
• Concentration-dependent killing: aminoglycosides, fluoroquinolones — efficacy depends on peak concentration/MIC ratio

Common Antibiotic Indications

• Community-acquired pneumonia: amoxicillin ± clarithromycin (NICE NG138)
• UTI (uncomplicated): nitrofurantoin 100 mg MR BD for 3 days (NICE NG109)
• Skin/soft tissue: flucloxacillin 500 mg–1 g QDS
• Dental infection: amoxicillin 500 mg TDS or metronidazole 400 mg TDS
• Acute exacerbation of COPD: amoxicillin, doxycycline, or clarithromycin (NICE NG115)
• Sepsis: empirical broad-spectrum per local protocol (often piperacillin-tazobactam ± gentamicin)

Common Side Effects

• Penicillins: rash, diarrhoea, anaphylaxis (rare)
• Cephalosporins: diarrhoea, rash, C. difficile risk
• Macrolides: GI upset, QT prolongation, CYP3A4 inhibition
• Fluoroquinolones: tendon rupture, QT prolongation, C. difficile, CNS effects — MHRA restricted use
• Aminoglycosides: nephrotoxicity, ototoxicity — TDM mandatory
• Metronidazole: metallic taste, disulfiram-like reaction with alcohol, peripheral neuropathy

Red Flags

• Anaphylaxis to any antibiotic — immediate management, document allergy
• C. difficile (antibiotic-associated diarrhoea): watery diarrhoea + fever → stool CDT, isolate, oral vancomycin
• Tendon pain on fluoroquinolone → stop immediately (rupture risk)
• Aminoglycoside: rising creatinine or hearing loss → stop and review

Before Prescribing

• Blood cultures: BEFORE starting antibiotics in severe infection/sepsis
• Specimen culture: urine MC&S, sputum, wound swab — guide targeted therapy
• CRP/WBC: markers of infection (though non-specific)

During Treatment

• Clinical response: review at 48–72 hours (Start Smart — Then Focus)
• TDM: gentamicin (trough <1 mg/L; or Hartford nomogram for once-daily), vancomycin (trough 10–15 mg/L or AUC-guided)
• Renal function: if on nephrotoxic antibiotics
• C. difficile testing: if diarrhoea develops

Special Tests

• Allergy testing: penicillin allergy assessment at allergy clinic (most labelled patients are NOT allergic)

Antimicrobial Stewardship

• Start Smart: only start antibiotics when there is clinical evidence of bacterial infection; document indication, dose, route, duration
• Then Focus (48–72 hour review): stop if no evidence of infection; switch IV→oral if improving; narrow spectrum based on culture results; change if not responding; consider OPAT
• Duration: use shortest effective course — many infections require only 5 days (NICE)

Key Prescribing by Class

• Penicillins: amoxicillin 500 mg TDS (community infections); flucloxacillin 500 mg–1 g QDS (staphylococcal); benzylpenicillin 1.2 g QDS IV (meningitis, streptococcal)
• Co-amoxiclav 625 mg TDS: bite wounds, aspiration pneumonia, intra-abdominal
• Cephalosporins: cefalexin 500 mg TDS (UTI, skin); ceftriaxone 2 g OD IV (meningitis, severe sepsis)
• Macrolides: clarithromycin 500 mg BD (atypical pneumonia, penicillin allergy); erythromycin (pregnancy)
• Tetracyclines: doxycycline 100–200 mg OD (atypical pneumonia, Lyme, acne)
• Fluoroquinolones: ciprofloxacin 500 mg BD (Pseudomonas, pyelonephritis — restricted use due to MHRA safety warnings)
• Metronidazole: 400 mg TDS oral or 500 mg TDS IV (anaerobes, C. difficile — if vancomycin unavailable, dental infections)
• Nitrofurantoin: 100 mg MR BD for 3 days (uncomplicated lower UTI)
• Trimethoprim: 200 mg BD for 3 days (UTI alternative); caution with co-trimoxazole + methotrexate

Referral Criteria

• Microbiology: suspected resistant organisms, complex infections, empirical failure
• Infectious diseases: endocarditis, osteomyelitis, prosthetic joint infection
• Allergy clinic: penicillin allergy testing/delabelling

• Most bacterial infections respond well to appropriate antibiotics
• Delay in appropriate antibiotics in sepsis: mortality increases ~7% per hour of delay
• AMR: increasing threat — appropriate prescribing is the key intervention
• C. difficile: mortality ~5–10%; recurrence ~20–25%
• Antibiotic stewardship reduces inappropriate prescribing, resistance, and C. difficile rates

Common Antibiotic Spectra

Start Smart — Then Focus Actions at 48–72 Hours