ID: How Infection Happens

• Basics: How Infection Happens | Host Defences and Who Is at Risk | Bacteria — A Working Classification | Viruses, Fungi and Parasites
• Investigations: Taking Good Samples | Microscopy, Culture, PCR and Serology | Inflammatory Markers and Imaging
• Antimicrobials: Principles of Antimicrobial Prescribing | How Antibiotics Work | Antimicrobial Resistance | Penicillins | Cephalosporins, Carbapenems and Aztreonam | Macrolides, Tetracyclines and Clindamycin | Aminoglycosides, Glycopeptides and Other Gram-Positive Drugs | Quinolones, Trimethoprim, Nitrofurantoin, Metronidazole and Others | Penicillin Allergy | Antivirals | Antifungals | Antiparasitic Drugs | Therapeutic Drug Monitoring | Antimicrobials in Special Groups
• Prevention: Infection Prevention and Control | Notifiable Diseases
• Revision: Antimicrobial Reference Table | Spot the Answer | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🦠 Infectious diseases — principles, microbiology and antimicrobials — this is the first page of the Infectious Diseases chapter. It covers how infections happen, how to classify organisms, how to get good samples, and how to use antimicrobials well. The other pages cover sepsis and serious bacterial infections; HIV and viral hepatitis; viral, fungal and parasitic infections; tropical and travel medicine; and hospital infection, the immunocompromised host and vaccination. Pneumonia and TB, sexually transmitted infections, skin infections and childhood infections have their own chapters.
Your four questions for every infection: Where is the infection (the source)? What is the likely organism? Which antimicrobial — the narrowest one that works, by the right route, for the right time? Does the patient need source control, isolation or public health action?

How Infection Happens

• Infection — an organism invades tissue and causes harm. Colonisation — an organism lives on or in the body without causing harm (e.g. MRSA in the nose, bacteria in a catheter bag, Candida in sputum). Treat infection, not colonisation — swabbing and treating colonisation drives resistance.
• The chain of infection — organism → reservoir (people, animals, environment) → way out → route of spread → way in → susceptible host. Infection control breaks a link in the chain.
• Routes of spread:
  • Contact — direct (hands, skin) or indirect (equipment, surfaces) — MRSA, C. difficile, norovirus, CPE.
  • Droplet — large droplets over about 1–2 metres — influenza, meningococcus, pertussis, mumps.
  • Airborne — tiny particles that hang in the air — TB, measles, chickenpox, COVID-19 (especially with aerosol-generating procedures).
  • Faecal–oral — food and water — hepatitis A and E, typhoid, cholera, norovirus.
  • Blood and body fluids — HIV, hepatitis B and C (sharps, sex, transfusion, mother to baby).
  • Vectors — mosquitoes (malaria, dengue), ticks (Lyme disease), fleas, sandflies.
  • Vertical — mother to baby (HIV, hepatitis B, syphilis, CMV, toxoplasma, group B strep, rubella).
• Virulence — how much harm an organism can do: toxins (exotoxins in toxic shock, tetanus, diphtheria, cholera; endotoxin from Gram-negative cell walls in sepsis), capsules (resist engulfment — pneumococcus, meningococcus), biofilms on devices (staphylococci on lines and joints), invasion enzymes.
• Incubation period — time from exposure to symptoms; useful in travel and outbreak history (e.g. food poisoning in hours suggests a toxin; malaria rarely within 7 days of exposure).

Host Defences and Who Is at Risk

• Barriers — intact skin, mucus, cilia, stomach acid, normal bacteria (microbiome), urine flow. Broken by wounds, burns, lines and catheters, intubation, surgery, PPIs, antibiotics.
• Innate immunity — neutrophils, macrophages, complement, fever, inflammation.
• Adaptive immunity — B cells (antibodies) and T cells (cell-mediated).
• What goes wrong and what follows:
  • Neutropenia (chemotherapy) — bacterial sepsis (Gram-negatives including Pseudomonas, staphylococci), fungal infection (Candida, Aspergillus).
  • Low antibodies (CLL, myeloma, rituximab, inherited) — recurrent bacterial chest and sinus infections (pneumococcus, Haemophilus).
  • T-cell problems (HIV, steroids, transplant drugs, lymphoma) — viruses (CMV, VZV), Pneumocystis, TB, fungi (Cryptococcus), Toxoplasma, Listeria.
  • Complement deficiency (or complement inhibitor drugs) — meningococcal infection.
  • No spleen — overwhelming infection with encapsulated bacteria, severe malaria.
• Other risk factors — older age, diabetes, CKD, liver disease, alcohol, malnutrition, smoking, pregnancy (Listeria, malaria, varicella and influenza are more severe), newborns.
• Older people often present atypically — no fever, just confusion, falls, reduced mobility or poor eating; a low or normal white count doesn't exclude sepsis.
• The immunocompromised host is covered in more detail on the final page of this chapter.

Bacteria — A Working Classification

• Gram stain — Gram-positive bacteria have a thick cell wall (stain purple); Gram-negatives have a thin wall with an outer membrane (stain pink) — the outer membrane keeps many drugs out (e.g. vancomycin doesn't work on Gram-negatives).
• Haemolysis on blood agar (streptococci) — beta (clear — group A and B), alpha (green — pneumococcus, viridans), none (enterococci).
• S. aureus in blood is never a contaminant — needs an infection specialist review, echocardiogram and at least 14 days of IV treatment.

Viruses, Fungi and Parasites

• Viruses — live inside cells; antibiotics don't work. Classified as DNA viruses (herpes family — HSV, VZV, EBV, CMV; hepatitis B; adenovirus; poxviruses) and RNA viruses (influenza, RSV, coronaviruses, measles, mumps, enteroviruses, norovirus, hepatitis A, C and E; HIV — a retrovirus).
  • Herpesviruses become latent and can reactivate (shingles, cold sores, CMV after transplant).
• Fungi:
  • Yeasts — Candida (thrush, line infections, candidaemia), Cryptococcus (meningitis in HIV).
  • Moulds — Aspergillus (lung disease in neutropenia, ABPA, aspergilloma), Mucorales (mucormycosis — diabetic ketoacidosis, iron overload).
  • Dermatophytes — skin, hair and nail tinea.
  • Pneumocystis jirovecii — pneumonia in immunosuppression.
• Parasites:
  • Protozoa (single-celled) — Plasmodium (malaria), Giardia, Entamoeba (amoebic dysentery and liver abscess), Cryptosporidium, Toxoplasma, Leishmania, Trypanosoma.
  • Helminths (worms) — roundworms (Ascaris, threadworm, Strongyloides — can cause hyperinfection with steroids), tapeworms (cysticercosis, hydatid), flukes (schistosomiasis). Worms often cause eosinophilia.
  • Ectoparasites — scabies, lice.
• Prions — misfolded proteins (CJD) — not killed by normal sterilisation.

Taking Good Samples

• Take samples before antibiotics where possible — but never delay antibiotics in sepsis or suspected meningitis to get them.
• Blood cultures:
  • Two sets (each an aerobic and an anaerobic bottle) from separate venepunctures (or one peripheral and one from each line lumen if line infection is suspected).
  • Strict asepsis — clean skin with 2% chlorhexidine in alcohol and let it dry; don't palpate after cleaning; clean bottle tops.
  • Fill bottles properly (about 8–10 mL each in adults) — volume is the biggest factor in detecting bacteraemia.
  • Take them when sepsis is suspected, not just at a fever spike; send to the lab quickly.
  • Coagulase-negative staphylococci in one of several sets usually means contamination; S. aureus, Candida, streptococci and Gram-negatives almost never are.
• Urine — midstream urine; from a catheter, sample from the sampling port, not the bag (and only if symptomatic); don't dipstick urine in people over 65 or with catheters to diagnose UTI.
• Sputum — a deep cough sample before antibiotics; TB needs 3 samples (including an early morning one).
• Swabs — wound swabs only if clinically infected (pus, spreading redness); pus or tissue is better than a swab.
• Stool — culture and C. difficile testing for diarrhoea (type 5–7 on the Bristol scale); ova, cysts and parasites after travel.
• CSF — cells, protein, glucose (with paired blood glucose), Gram stain, culture, PCR (meningococcus, pneumococcus, HSV, VZV, enterovirus); see the Neurology chapters.
• Other — joint aspirate (before antibiotics in septic arthritis), ascitic and pleural fluid (in blood culture bottles), bone biopsy (osteomyelitis), throat and nasopharyngeal swabs for viral PCR.
• Give the lab clinical details — travel, immunosuppression, antibiotics given, suspected organism — it changes what they look for (and alerts them to hazard group 3 organisms such as brucella or typhoid).

Microscopy, Culture, PCR and Serology

• Microscopy — fast: Gram stain (shape and Gram reaction), Ziehl–Neelsen or auramine stain (acid-fast bacilli — TB), white cells in urine or CSF, thick and thin blood films (malaria — three negative films over 72 hours to exclude it).
• Culture and sensitivity — grows the organism (24–48 hours for most bacteria; weeks for TB) and tests which antibiotics work ("S" — sensitive, "I" — sensitive at increased exposure (higher dose), "R" — resistant). Use the result to narrow treatment.
• Antigen tests — urinary pneumococcal and Legionella antigen, cryptococcal antigen, malaria rapid tests, galactomannan (Aspergillus), C. difficile toxin, rapid flu and COVID-19 tests.
• PCR (nucleic acid tests) — detects DNA or RNA quickly and sensitively — respiratory viruses, CSF organisms, chlamydia and gonorrhoea, HIV and hepatitis viral loads, TB (GeneXpert — also detects rifampicin resistance). A positive PCR may detect dead organisms or carriage — interpret with the clinical picture.
• Serology (antibodies):
  • IgM — usually recent infection (false positives occur).
  • IgG — past infection or immunity (or vaccination); a four-fold rise between acute and convalescent samples confirms recent infection.
  • Used for HIV, hepatitis, syphilis, EBV, CMV, toxoplasma, measles, rubella, Lyme disease, many tropical infections; may be falsely negative early (window period) or in immunosuppression.
• Interferon-gamma release assays (IGRA) — detect latent TB infection (can't distinguish latent from active disease).
• Typing and genomics — whole genome sequencing tracks outbreaks and detects resistance genes.

Inflammatory Markers and Imaging

• White cell count — high neutrophils in bacterial infection (also steroids, stress); low counts in overwhelming sepsis, viral infection, typhoid, brucellosis; lymphopenia in severe viral infection and HIV; eosinophilia in worm infections (and allergy, drugs).
• CRP — rises within 6–8 hours, peaks at about 48 hours; useful for trends (response to treatment) more than diagnosis; raised by many non-infective causes (surgery, inflammation, cancer); can be normal early, and lower in immunosuppression and liver failure.
• Procalcitonin — rises more in bacterial than viral infection; sometimes used to guide stopping antibiotics in ITU and lower respiratory infection.
• Lactate — marker of tissue hypoperfusion in sepsis (over 2 mmol/L abnormal; 4 or more is high risk); also raised by metformin, liver failure, seizures, salbutamol.
• ESR — slow to change; high in osteomyelitis, endocarditis, TB, myeloma, autoimmune disease.
• Imaging to find the source:
  • Chest X-ray — pneumonia, empyema, TB.
  • Ultrasound — biliary sepsis, abscesses, joint effusions, kidney obstruction (infected obstructed kidney — emergency drainage).
  • CT — abdominal and pelvic abscesses, perforation, deep neck infection, sinusitis.
  • MRI — osteomyelitis, discitis, epidural abscess, encephalitis, brain abscess.
  • Echocardiography — endocarditis (TOE more sensitive than TTE).
  • PET-CT and white cell scans — pyrexia of unknown origin, prosthetic infections, vasculitis.
• Source control — drainage of pus, removal of infected lines and devices, debridement of dead tissue and relief of obstruction are often more important than the choice of antibiotic.

Principles of Antimicrobial Prescribing

• "Start Smart — Then Focus" (UKHSA):
  • Start smart — only start antibiotics if there is clinical evidence of bacterial infection; take cultures first; follow local guidelines; give within 1 hour in sepsis or septic shock; document the indication, duration or review date and route on the chart; check allergies.
  • Then focus — review at 48–72 hours with the results, and record one of five decisions: Stop (no infection), Switch IV to oral, Change (narrow, or broaden if needed), Continue (and set a review date), or OPAT (outpatient parenteral antimicrobial therapy).
• Choose the narrowest effective drug — broad-spectrum drugs (co-amoxiclav, cephalosporins, quinolones, carbapenems, clindamycin) cause more C. difficile and resistance.
• IV-to-oral switch (UK national criteria) — consider once the patient is improving, temperature normal for 24 hours or so, observations stable (no sepsis), able to swallow and absorb, with a suitable oral option — unless an infection needs prolonged IV treatment (e.g. endocarditis, meningitis, S. aureus bacteraemia, undrained abscess, neutropenic sepsis, some bone and joint infections at first).
• Oral drugs with excellent absorption — quinolones, doxycycline, linezolid, metronidazole, co-trimoxazole, fluconazole, rifampicin, clindamycin — often as good as IV.
• Duration — shorter courses are often as effective: e.g. 5 days for most community-acquired pneumonia and cellulitis, 3 days for uncomplicated lower UTI in women, 7 days for men; longer for endocarditis, bone and joint infections, TB, S. aureus bacteraemia.
• Dose correctly — by weight (gentamicin, vancomycin), kidney and liver function; under-dosing causes treatment failure and resistance.
• Check interactions — especially macrolides, quinolones, rifampicin, azoles and linezolid.
• Don't treat — colonisation, asymptomatic bacteriuria (except in pregnancy), a raised CRP alone, viral upper respiratory infections, most acute bronchitis, uninfected leg ulcers.
• Delayed (back-up) prescriptions in primary care for self-limiting infections (sore throat, otitis media, sinusitis) reduce antibiotic use (NICE).

How Antibiotics Work

• Bactericidal (kill) versus bacteriostatic (stop growth) — killing matters most in endocarditis, meningitis and neutropenia.
• Time-dependent killing (beta-lactams, vancomycin) — keep levels above the minimum inhibitory concentration (MIC) for as long as possible (frequent doses or prolonged infusions); concentration-dependent killing (aminoglycosides, quinolones) — high peak levels (once-daily gentamicin).
• Protein synthesis inhibitors (clindamycin, linezolid) switch off toxin production — added in necrotising fasciitis and toxic shock syndrome.
• Synergy — a cell wall drug helps an aminoglycoside get in (e.g. amoxicillin plus gentamicin in enterococcal endocarditis).
• Tissue penetration — nitrofurantoin reaches only the bladder (not for pyelonephritis); daptomycin is inactivated in the lungs (not for pneumonia); some drugs penetrate CSF poorly unless meninges are inflamed.

Antimicrobial Resistance

• Why it matters — resistant infections are harder to treat, need more toxic drugs, and kill more people; antibiotic use (including in animals) drives resistance. Every prescription counts.
• How bacteria resist — enzymes that destroy the drug (beta-lactamases), altered targets (MRSA's altered penicillin-binding protein), pumps that push the drug out, reduced entry, and sharing resistance genes between bacteria (plasmids).
• Key resistant organisms:
  • MRSA (meticillin-resistant S. aureus) — resistant to flucloxacillin and most beta-lactams; treat with vancomycin, teicoplanin, linezolid, daptomycin, or doxycycline or co-trimoxazole for milder infections (depending on sensitivities); decolonise (nasal mupirocin and chlorhexidine body wash) before some surgery.
  • ESBL-producing Gram-negatives (E. coli, Klebsiella) — resistant to most penicillins and cephalosporins; serious infections need a carbapenem (or other options by sensitivity); oral options for UTI may include nitrofurantoin, fosfomycin, pivmecillinam.
  • CPE (carbapenemase-producing Enterobacterales — e.g. KPC, OXA-48, NDM) — resistant to carbapenems too; very limited options (e.g. ceftazidime–avibactam, colistin); screen patients admitted after hospital care abroad or in affected UK units; strict isolation.
  • VRE (vancomycin-resistant enterococci) — linezolid, daptomycin.
  • Pseudomonas — naturally resistant to many drugs; options include piperacillin–tazobactam, ceftazidime, meropenem, ciprofloxacin, aminoglycosides.
  • Drug-resistant TB (MDR and XDR), resistant gonorrhoea, azole-resistant Candida auris (spreads in hospitals).
• Stewardship — prescribe only when needed, choose narrow drugs, review at 48–72 hours, keep courses short, follow guidelines, and support vaccination and infection control.

Penicillins

• Side effects of penicillins — rash, allergy (including anaphylaxis), diarrhoea and C. difficile, thrush, interstitial nephritis, seizures or encephalopathy at high doses in kidney failure, haemolytic anaemia (rare).
• Penicillins are safe in pregnancy and breastfeeding.
• Probenecid slows penicillin excretion (raises levels) — occasionally used deliberately.

Cephalosporins, Carbapenems and Aztreonam

• Cephalosporins — the "generations" broadly gain Gram-negative activity:
  • Cefalexin (oral) — UTI (including pregnancy), skin infections.
  • Cefuroxime — surgical prophylaxis, some respiratory and UTIs.
  • Ceftriaxone (once daily — useful for OPAT) and cefotaxime — bacterial meningitis, severe pneumonia, pyelonephritis, gonorrhoea (1 g IM), Lyme neuroborreliosis, typhoid; ceftriaxone can cause biliary sludge and must not be mixed with calcium in neonates.
  • Ceftazidime — Pseudomonas.
  • Newer agents (specialist use for resistant organisms) — ceftaroline (MRSA), ceftazidime–avibactam, ceftolozane–tazobactam, cefiderocol.
• Gaps — cephalosporins don't cover enterococci, Listeria, MRSA (except ceftaroline) or atypicals.
• Side effects — allergy, high C. difficile risk, diarrhoea, positive Coombs test and haemolysis (ceftriaxone), encephalopathy and seizures at high levels in kidney failure (cefepime).
• Carbapenems — meropenem, imipenem, ertapenem (once daily; no Pseudomonas cover):
  • Very broad; used for ESBL infections and severe hospital sepsis — reserve to protect against CPE.
  • Lower the seizure threshold (especially imipenem); greatly lower valproate levels — avoid the combination.
• Aztreonam (monobactam) — Gram-negative only (including Pseudomonas); can usually be given in penicillin allergy (except with ceftazidime allergy — shared side chain).

Macrolides, Tetracyclines and Clindamycin

• Macrolides — clarithromycin, erythromycin, azithromycin:
  • Uses — atypical pneumonia, alternative for streptococcal and respiratory infections in penicillin allergy, H. pylori, Campylobacter, pertussis, long-term azithromycin in bronchiectasis and COPD.
  • Side effects — GI upset (erythromycin also speeds stomach emptying), QT prolongation, hearing loss (high doses), liver injury.
  • Interactions — clarithromycin and erythromycin are strong CYP3A4 inhibitors: simvastatin and atorvastatin (myopathy — pause the statin), warfarin, DOACs, colchicine (dangerous), theophylline, carbamazepine, ciclosporin and tacrolimus, some calcium channel blockers; azithromycin has fewer interactions.
  • Erythromycin in newborns is linked to pyloric stenosis.
• Tetracyclines — doxycycline, lymecycline, minocycline:
  • Uses — community pneumonia and COPD exacerbations, cellulitis in penicillin allergy, chlamydia, Lyme disease, rickettsial infections, leptospirosis, Q fever, some MRSA, malaria prophylaxis, acne, rosacea.
  • Avoid in children under 12 and in pregnancy and breastfeeding (tooth discolouration, bone effects).
  • Side effects — photosensitivity, pill oesophagitis (swallow upright with plenty of water), GI upset, raised intracranial pressure; minocycline — skin pigmentation, drug-induced lupus, hepatitis.
  • Absorption reduced by milk, calcium, iron, zinc, magnesium and antacids — separate doses.
• Clindamycin:
  • Uses — Gram-positive (staphylococci, streptococci) and anaerobic infections; toxin suppression in necrotising fasciitis and toxic shock; bone penetration; alternative in penicillin allergy.
  • The highest C. difficile risk of any antibiotic — stop if diarrhoea develops.

Aminoglycosides, Glycopeptides and Other Gram-Positive Drugs

• Aminoglycosides — gentamicin, amikacin, tobramycin:
  • Uses — serious Gram-negative sepsis (often a single empirical dose while cultures are awaited), pyelonephritis, Pseudomonas, synergy in endocarditis; tobramycin nebulised in CF.
  • Not absorbed orally. Dosing — once daily by weight (ideal or adjusted for obesity) and kidney function, with levels interpreted on a nomogram (e.g. Hartford); lower "synergy" doses in endocarditis.
  • Nephrotoxicity (usually reversible) and ototoxicity (hearing loss and vestibular damage — often permanent); higher risk with long courses, high levels, older age, and with loop diuretics, vancomycin, ciclosporin or cisplatin.
  • Mitochondrial variant m.1555A>G — greatly increases deafness risk even with normal levels; ask about family history of aminoglycoside-induced deafness; consider rapid genetic testing in neonatal units (MHRA).
  • Neuromuscular blockade — avoid in myasthenia gravis.
  • Avoid in pregnancy unless essential (fetal ototoxicity); limit courses (often 3 days or less) where possible.
• Vancomycin:
  • IV for serious Gram-positive infections including MRSA; oral vancomycin (not absorbed) is first-line for C. difficile.
  • Levels — trough-guided or AUC-guided dosing (check local targets).
  • Side effects — nephrotoxicity (especially with piperacillin–tazobactam or high levels), ototoxicity, infusion reaction (flushing and itch of the face and upper body if infused too fast — slow the infusion; not an allergy), neutropenia with long courses.
• Teicoplanin — glycopeptide; once daily after loading doses; less nephrotoxic; useful for OPAT; levels in severe infection.
• Daptomycin — S. aureus bacteraemia, endocarditis, skin infections; not for pneumonia (inactivated by surfactant); raised CK and myopathy (weekly CK; pause statins), eosinophilic pneumonia.
• Linezolid — MRSA, VRE; 100% oral bioavailability:
  • Marrow suppression (thrombocytopenia — especially beyond 10–14 days — weekly FBC), optic and peripheral neuropathy (long courses), lactic acidosis, hypoglycaemia.
  • It is a weak MAO inhibitor — serotonin syndrome with SSRIs and other serotonergic drugs; avoid large amounts of tyramine-rich foods.

Quinolones, Trimethoprim, Nitrofurantoin, Metronidazole and Others

• Fluoroquinolones — ciprofloxacin (Gram-negatives, Pseudomonas — the only oral anti-Pseudomonal), levofloxacin and moxifloxacin (respiratory, TB):
  • Excellent oral absorption — but MHRA: use only when other antibiotics are inappropriate, because of serious, sometimes long-lasting side effects — tendinitis and tendon rupture (older people, steroids, kidney or organ transplant), aortic aneurysm and dissection and heart valve regurgitation, peripheral neuropathy, psychiatric effects, fatigue and memory problems.
  • Also QT prolongation, seizures, low and high blood glucose, C. difficile, worsening myasthenia, confusion in older people.
  • Interactions — raise theophylline and tizanidine levels, increase warfarin effect; absorption blocked by calcium, iron, zinc, magnesium and antacids.
  • Generally avoid in children and pregnancy.
• Trimethoprim — lower UTI; folate antagonist; raises potassium and creatinine; dangerous with methotrexate; avoid in the first trimester.
• Co-trimoxazole (trimethoprim + sulfamethoxazole) — Pneumocystis treatment and prophylaxis, Stenotrophomonas, Nocardia, toxoplasmosis prophylaxis, some MRSA and UTIs; side effects — severe rashes (SJS/TEN), marrow suppression, high potassium, liver injury, haemolysis in G6PD deficiency; avoid near term (neonatal jaundice).
• Nitrofurantoin — lower UTI only (doesn't reach kidney tissue — not for pyelonephritis or sepsis); avoid if eGFR under 45; lung, liver and nerve toxicity with long courses; avoid at term; harmless brown urine.
• Metronidazole — anaerobes (abdominal and pelvic sepsis, dental and aspiration infections), protozoa (Giardia, amoebiasis, Trichomonas), bacterial vaginosis, H. pylori; metallic taste, nausea; avoid alcohol during and for 48 hours after (flushing, vomiting); peripheral neuropathy and encephalopathy with long courses; increases warfarin effect.
• Fosfomycin — single 3 g oral dose for uncomplicated lower UTI in women (including some ESBL); IV for specialist use.
• Rifampicin — TB, adjunct for staphylococcal prosthetic infections, meningococcal contact prophylaxis (ciprofloxacin is usually preferred), brucellosis; never used alone for treatment (resistance develops fast); potent enzyme inducer (contraception, warfarin, DOACs, steroids, antiretrovirals, tacrolimus); orange body fluids.
• Fusidic acid — topical or oral for staphylococcal skin infections (with another drug orally); contraindicated with statins (rhabdomyolysis — stop the statin during treatment and for 7 days after).
• Others — mupirocin (nasal MRSA decolonisation), chloramphenicol (eye drops; systemic use rare — marrow suppression, "grey baby" syndrome), colistin (resistant Gram-negatives — kidney and nerve toxicity), tigecycline.

Penicillin Allergy

• About 1 in 10 people carry a penicillin allergy label, but over 90% of them are not allergic when tested. A false label leads to broader, less effective and more toxic antibiotics, more C. difficile and MRSA, and worse outcomes.
• Take a proper allergy history:
  • Which drug, when, what happened, how soon, how it was treated, and whether a similar drug has been tolerated since.
  • Immediate reactions (within about 1 hour) — urticaria, angioedema, wheeze, low blood pressure, anaphylaxis — true allergy likely.
  • Delayed benign rash (maculopapular, days into treatment) — often low risk (many are viral rashes, e.g. amoxicillin with EBV).
  • Severe delayed reactions — Stevens–Johnson syndrome, toxic epidermal necrolysis, DRESS, blistering, organ involvement — never rechallenge; avoid related drugs; specialist advice.
  • Side effects (nausea, diarrhoea, thrush) and family history are not allergy.
• Cross-reactivity:
  • Cephalosporins — low overall (about 1–2%), higher with similar side chains (e.g. amoxicillin with cefalexin or cefadroxil); many guidelines allow cephalosporins with dissimilar side chains after non-severe reactions.
  • Carbapenems — under 1%; usually given with caution unless the reaction was severe.
  • Aztreonam — negligible (except with ceftazidime).
• De-labelling — low-risk histories can be removed by a direct oral challenge (e.g. amoxicillin) under supervision; higher-risk histories need allergy clinic testing (BSACI guidance).
• Record allergies accurately — the drug, the reaction, the date and the certainty; distinguish allergy from intolerance.

Antivirals

• Aciclovir and valaciclovir (prodrug — better absorbed) — HSV and VZV:
  • IV aciclovir (10 mg/kg every 8 hours, adjusted for kidney function) — HSV encephalitis (start on suspicion), disseminated or severe VZV, chickenpox in immunocompromised people.
  • Oral — shingles (within 72 hours, or later if new lesions or eye involvement), genital herpes, chickenpox in adults; prophylaxis in immunosuppression.
  • Side effects — crystal nephropathy (hydrate well), neurotoxicity (confusion, hallucinations, tremor — especially with kidney impairment and older people).
• CMV drugs — ganciclovir (IV) and valganciclovir (oral) — marrow suppression, teratogenic (handle with care); foscarnet — kidney toxicity, low calcium, magnesium and potassium; letermovir (prophylaxis after stem cell transplant), maribavir (resistant CMV).
• Influenza — oseltamivir (oral) within 48 hours of symptoms for people at risk of complications, all hospitalised patients with suspected influenza, and as post-exposure prophylaxis in at-risk groups when flu is circulating (NICE); zanamivir (inhaled — bronchospasm; IV for resistant or severe cases).
• COVID-19 (for people at high risk of severe disease — check current NICE guidance):
  • Nirmatrelvir–ritonavir (Paxlovid) — oral, within 5 days of symptoms; ritonavir is a strong CYP3A4 inhibitor — major interactions with statins, DOACs, amiodarone, tacrolimus and ciclosporin, some antiseizure drugs, sildenafil, salmeterol, many others — always check (e.g. the Liverpool COVID-19 interaction checker).
  • Sotrovimab (neutralising antibody), remdesivir (IV, hospital use).
• HIV and hepatitis B and C antivirals are covered on the HIV and Viral Hepatitis page.
• RSV — prevention by vaccination (older adults, pregnancy) and monoclonal antibodies for infants (nirsevimab).

Antifungals

• Candida in a blood culture is never a contaminant — start an echinocandin, remove central lines, repeat cultures, echocardiogram and eye examination (endophthalmitis), and treat for at least 14 days after the first negative culture.
• Candida in sputum or urine is usually colonisation — don't treat unless there is clear infection (or in neutropenia or certain urological procedures).

Antiparasitic Drugs

• Malaria (see the Tropical and Travel Medicine page):
  • Artemisinin combination therapy (artemether–lumefantrine) — uncomplicated falciparum malaria; IV artesunate — severe malaria (watch for delayed haemolysis).
  • Chloroquine (where sensitive) or ACT for non-falciparum malaria, then primaquine or tafenoquine to clear liver stages of vivax and ovale — check G6PD first (haemolysis).
  • Prophylaxis — atovaquone–proguanil, doxycycline, mefloquine (neuropsychiatric side effects — MHRA; avoid with psychiatric history), chloroquine–proguanil (limited areas).
• Ivermectin — Strongyloides, crusted or difficult scabies, some filarial infections.
• Albendazole and mebendazole — roundworms, hookworm, threadworm (mebendazole — treat the whole household), some tapeworm infections (albendazole — neurocysticercosis, hydatid disease with surgery); avoid in early pregnancy where possible.
• Praziquantel — schistosomiasis (repeat after the larvae mature), tapeworms.
• Metronidazole and tinidazole — Giardia, amoebiasis (followed by a luminal agent such as paromomycin for cysts), Trichomonas.
• Pyrimethamine with sulfadiazine (plus folinic acid) — toxoplasmosis in immunosuppression; co-trimoxazole for prophylaxis.
• Permethrin and malathion — scabies and head lice (see the Skin Infections and Infestations chapter).