Antibacterial drugs

Why antibiotics spare human cells

Selective toxicity depends on targets that humans lack or that differ: the peptidoglycan cell wall, 70S ribosomes (30S plus 50S; humans have 80S), bacterial DNA gyrase, and folate synthesis (humans take folate from food). Mitochondrial ribosomes resemble bacterial ones, which explains some toxicity (aminoglycoside ototoxicity, linezolid and chloramphenicol marrow effects).

Growth phase, killing pattern and combinations

• β-lactams kill by blocking cell wall building during growth: walls weakened while the cell enlarges burst osmotically. They are most effective in the logarithmic (exponential) phase and poorly active against dormant cells.
• Adding a bacteriostatic drug (tetracycline) to penicillin in pneumococcal meningitis is a poor combination: stopping growth blunts penicillin's killing; the bacteriostatic-plus-penicillin arm had higher mortality.
• Concentration-dependent killing (aminoglycosides, quinolones): high peaks, once-daily dosing, post-antibiotic effect. Time-dependent (β-lactams, vancomycin): time above MIC matters.
• Jarisch–Herxheimer reaction: fever, rigors, headache and a worse rash hours after the first dose of penicillin for syphilis (or other spirochaetes), from cytokines released as organisms die. Continue treatment; give antipyretics.

Classes, spectra and toxicities

• Grey baby syndrome: premature neonates have immature glucuronyl transferase and poor renal excretion, so chloramphenicol accumulates and poisons mitochondria: floppy, ashen, cyanosed, hypotensive.
• Sulphonamides near term and in newborns displace bilirubin from albumin; free bilirubin crosses the immature BBB and causes kernicterus. Ceftriaxone does the same.
• Gentamicin monitoring: the trough (pre-dose) level reflects accumulation between doses, which drives kidney and ear toxicity. A high trough means the drug is not being cleared: extend the dosing interval (do not just lower the dose). Gentamicin is hydrophilic: in obese patients it distributes poorly into fat, so dose by adjusted body weight; in the elderly, reduced renal excretion is the main issue. Avoid in CKD and myasthenia.
• In renal failure, macrolides such as azithromycin and doxycycline need no adjustment.
• Enterohepatic circulation: some drugs (oestrogens, mycophenolate) are conjugated in the liver, excreted in bile, deconjugated by gut bacteria and reabsorbed. Broad-spectrum antibiotics kill those bacteria and reduce recirculation, lowering levels.
• Long courses of antibiotics with poor diet or TPN kill vitamin K-producing gut flora: bruising with prolonged PT and normal platelets. Antibiotic-associated diarrhoea with fever suggests C. difficile pseudomembranous colitis.

Resistance mechanisms

• Genes spread by plasmids (conjugation), transposons, transformation and transduction. Stewardship: right drug, dose and duration; review at 48–72 hours. Uncomplicated community pneumonia (CURB-65 0–1) needs 5 days of amoxicillin.
• Penicillin "allergy" labels: a mild delayed itchy rash in childhood is a non-severe reaction, so a cephalosporin is reasonable; only immediate anaphylaxis, angioedema or severe skin reactions exclude β-lactams. Wrong labels push patients onto broader drugs.

Surgical prophylaxis

• Indicated for clean-contaminated and contaminated surgery, and clean surgery with implants or where infection would be catastrophic. Dirty wounds need treatment. Elective laparoscopic cholecystectomy in a low-risk patient does not routinely need prophylaxis.
• Timing: IV within 60 minutes before incision, at induction. Vancomycin must be infused slowly (red man syndrome), so it is started 60–120 minutes before incision.
• Redose if surgery lasts beyond two half-lives or blood loss exceeds 1.5 L; do not continue beyond 24 hours.
• Cefazolin (first generation) for clean orthopaedic surgery: better antistaphylococcal activity and less resistance selection than a third-generation drug. Add metronidazole for colorectal surgery; teicoplanin or vancomycin plus gentamicin for MRSA or penicillin allergy.
• Do not shave with a razor the night before: microscopic cuts let bacteria colonise the skin. Clip just before surgery if needed.
• Endocarditis prophylaxis for dental extraction is not routine even with a prosthetic valve under UK-style guidance; follow cardiology advice; oral hygiene matters more.

Source control, tetanus and splenectomy

• Pus needs drainage: an abscess (after checking that a groin swelling in a drug user is not pulsatile) needs incision and drainage; a pelvic collection after perforated appendicitis needs image-guided drainage with antibiotics.
• In a diabetic foot, culture deep tissue or bone taken at surgery, not surface swabs.
• Tetanus: a clean minor wound with a full primary course and a booster within 10 years needs nothing. A tetanus-prone wound in an unvaccinated person needs vaccine plus tetanus immunoglobulin; tetanus does not leave immunity.
• After splenectomy: pneumococcal, Hib, meningococcal and annual influenza vaccines (2 weeks before elective or 2 weeks after emergency surgery) and long-term penicillin prophylaxis.

Exam trap A high gentamicin trough means extend the interval; a high peak means lower the dose.

Drugs from other anti-infective chapters tested here

Remember β-lactams need growing bacteria; give them alone, early and at the right time.

How FCPS asks about this

• Why β-lactams work best in log phase: they block wall building during growth.
• Grey baby syndrome: immature glucuronidation of chloramphenicol.
• Sulphonamides near term: displace bilirubin from albumin (kernicterus).
• Vancomycin and VRE: binds D-Ala-D-Ala; VRE makes D-Ala-D-Lac.
• ESBL Klebsiella failing ceftriaxone: enzyme hydrolyses cephalosporins; use a carbapenem.
• Clarithromycin mechanism: blocks translocation at the 50S subunit.
• Prophylaxis timing: within 60 minutes before incision; vancomycin 60–120 minutes before.