For education and revision only. Not individual medical advice; check current NICE/BNF and local guidance before clinical use. Clinical safety and terms.
🦠 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).
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).
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.
Atypical pneumonia, STIs -beta-lactams don't work; use macrolides, tetracyclines or quinolones
Mycobacteria (acid-fast)
M. tuberculosis, non-tuberculous mycobacteria, M. leprae
TB, lung and skin infections
Spirochaetes
Treponema pallidum, Borrelia, Leptospira
Syphilis, Lyme disease, leptospirosis
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 -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.
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.
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.
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 -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.
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.
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.
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.
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).
Quinolones (DNA gyrase -ciprofloxacin), metronidazole (damages DNA in anaerobes), nitrofurantoin
RNA synthesis
Rifampicin (RNA polymerase)
Folate synthesis
Trimethoprim, sulfonamides (sulfamethoxazole -together as co-trimoxazole)
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.
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.
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.
Streptococci, meningococcal disease (IM in the community before transfer), syphilis, cellulitis (with flucloxacillin in some guidelines), anthrax
Phenoxymethylpenicillin (penicillin V, oral)
Streptococcal sore throat, prophylaxis after splenectomy and in sickle cell disease, rheumatic fever prophylaxis
Amoxicillin
Community pneumonia, otitis media, sinusitis, enterococci, Listeria (with ceftriaxone in meningitis in at-risk adults), H. pylori; rash with glandular fever (not true allergy)
Co-amoxiclav (amoxicillin + clavulanic acid)
Beta-lactamase producers and anaerobes -bites, aspiration, abdominal, diabetic foot, severe pneumonia; cholestatic jaundice (may start weeks after the course -older men, long courses); high C. difficile risk
Flucloxacillin
S. aureus (not MRSA) and streptococci -cellulitis, wounds, bone and joint, staphylococcal bacteraemia; take on an empty stomach; cholestatic jaundice (older people, courses over 2 weeks)
Piperacillin–tazobactam (IV)
Broad-spectrum including Pseudomonas and anaerobes -hospital-acquired and neutropenic sepsis, severe abdominal infection; AKI more common when combined with vancomycin; low potassium
Pivmecillinam, temocillin
Gram-negative UTIs including some ESBL producers; pivmecillinam -oral; temocillin -IV
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.
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.
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).
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.
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.
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).
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.
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.
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).
Candida (thrush, UTI, step-down for candidaemia), cryptococcal maintenance
CYP inhibitor -warfarin, sulfonylureas, statins, phenytoin; QT; some Candida resistant (C. krusei, C. glabrata, C. auris); avoid high doses in pregnancy
Itraconazole
ABPA, chronic aspergillosis, dermatophytes, some endemic fungi
Heart failure (negative inotrope), liver toxicity, many interactions; absorption varies by formulation
Voriconazole
Invasive aspergillosis (first-line)
Level monitoring; visual disturbance, hallucinations, photosensitivity and skin cancer, liver toxicity, periostitis, QT; many interactions
Posaconazole, isavuconazole
Prophylaxis in AML and GvHD (posaconazole); invasive mould infections; mucormycosis
Levels (posaconazole); interactions (especially with chemotherapy and immunosuppressants)
Candidaemia and invasive candidiasis (first-line), some aspergillosis
IV only; few interactions; well tolerated
Amphotericin B (liposomal)
Severe fungal infections, cryptococcal meningitis (with flucytosine), mucormycosis, visceral leishmaniasis
Kidney toxicity, low potassium and magnesium, infusion reactions; doses of different formulations are not interchangeable (fatal errors)
Flucytosine
With amphotericin for cryptococcal meningitis
Levels; marrow suppression; kidney dosing
Nystatin, miconazole, clotrimazole
Topical and oral thrush, vaginal candidiasis
Nystatin not absorbed; miconazole oral gel raises INR with warfarin
Terbinafine
Dermatophyte nail and skin infections
Liver toxicity, taste loss, skin reactions
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).
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).
Level 6–14 hours after the first dose plotted on a nomogram, or a pre-dose (trough) level -follow local protocol
Toxicity (kidneys, ears) rises with high troughs; adjust the interval
Gentamicin (synergy dosing in endocarditis)
Pre-dose and 1-hour post-dose levels
Low targets to limit toxicity over long courses
Amikacin
As for gentamicin (different targets)
Ototoxicity, nephrotoxicity
Vancomycin
Trough before the 3rd or 4th dose, or continuous infusion levels, or AUC-based software -follow local targets
Too low -failure and resistance; too high -AKI
Teicoplanin
Trough in severe, bone and joint infections and endocarditis
Ensure adequate levels
Voriconazole, posaconazole
Trough after about 5–7 days
Wide variation in levels (genetics, interactions); toxicity and failure
Flucytosine
Peak and trough
Marrow toxicity
Don't withhold a first dose of gentamicin or vancomycin in sepsis while waiting for kidney function -give the first dose, then adjust.
Timing errors (wrong sample time, sample taken from the line the drug was given through) are common causes of misleading levels -record the exact dose and sample times.
Most antibiotics (penicillins, cephalosporins, macrolides) -check the BNF
Some quinolones and tetracyclines (prolonged use), chloramphenicol
Children
Weight-based doses of penicillins, cephalosporins, macrolides
Tetracyclines under 12, quinolones (usually), chloramphenicol in neonates, ceftriaxone with calcium in neonates
Older people
Narrow-spectrum drugs, careful dosing
C. difficile risk (broad-spectrum), quinolones (tendons, delirium), nitrofurantoin with low eGFR, interactions, aminoglycosides (hearing)
Kidney impairment
No dose change usually -ceftriaxone, doxycycline, clindamycin, linezolid, moxifloxacin, metronidazole
Reduce -most penicillins and cephalosporins at low eGFR (seizures), aminoglycosides, vancomycin, aciclovir, co-trimoxazole, fluconazole; avoid nitrofurantoin if eGFR under 45
Liver impairment
Most beta-lactams (except below)
Flucloxacillin and co-amoxiclav (cholestasis), TB drugs, azoles, high-dose tetracyclines, macrolides
Standard precautions for every patient, every time (National Infection Prevention and Control Manual):
Hand hygiene -the single most important measure; the WHO "5 moments" (before patient contact, before a clean or aseptic procedure, after body fluid exposure, after patient contact, after touching the patient's surroundings); bare below the elbows.
Alcohol gel doesn't kill C. difficile spores or norovirus -use soap and water.
Personal protective equipment (PPE) according to risk; safe sharps use and disposal; safe care of equipment, linen, waste and the environment; respiratory hygiene ("catch it, bin it, kill it").
Transmission-based precautions:
Type
Examples
Measures
Contact
MRSA, C. difficile, CPE and ESBL, norovirus, scabies
Side room (or cohort), gloves and apron, dedicated equipment, enhanced cleaning (chlorine for C. difficile)
Droplet
Influenza, meningococcal disease (first 24 hours of antibiotics), pertussis, mumps, group A strep
Side room, fluid-resistant surgical mask within about 2 metres
Airborne
Pulmonary TB (smear-positive, or MDR suspected), measles, chickenpox and disseminated shingles, aerosol-generating procedures in respiratory viral infection
Negative-pressure room where available, FFP3 respirator (fit-tested), keep door closed; non-immune staff avoid measles and chickenpox
Sharps and splash injuries -encourage bleeding, wash with soap and water (don't scrub or suck), report immediately to occupational health or the emergency department; risk-assess the source (HIV, hepatitis B and C); HIV post-exposure prophylaxis as soon as possible (ideally within 1 hour, up to 72 hours); hepatitis B vaccination or booster ± immunoglobulin; follow-up testing.
Device care -remove unnecessary urinary catheters and cannulas early (daily review; VIP score for cannulas), aseptic non-touch technique (ANTT), care bundles for central lines and ventilators.
Staff health -vaccination (influenza, hepatitis B, MMR, varicella, COVID-19), staying off work with diarrhoea and vomiting until 48 hours symptom-free.
Registered medical practitioners must notify the local UKHSA health protection team (the "proper officer") on clinical suspicion of a notifiable disease -don't wait for laboratory confirmation. Urgent cases (e.g. meningococcal disease, diphtheria) should be phoned through.
Any other infection or contamination that could present a significant risk to human health.
Not notifiable by clinicians -HIV and other sexually transmitted infections (confidential surveillance through sexual health services); laboratories separately report many organisms.
Why notify -contact tracing, prophylaxis (e.g. ciprofloxacin and vaccination for meningococcal contacts), outbreak control (food sources, water, nurseries, care homes), surveillance.
1. A 74-year-old woman was started on IV piperacillin–tazobactam for urosepsis 3 days ago. She is now afebrile, eating and drinking, with normal observations. Blood and urine cultures grew E. coli sensitive to co-amoxiclav, cefalexin and ciprofloxacin. Answer: 48–72 hour review -switch to a narrow oral agent.
Record the review decision ("Switch"); she meets IV-to-oral switch criteria.
Choose a narrower oral option guided by sensitivity and local policy (e.g. cefalexin or co-amoxiclav); avoid a quinolone if a suitable alternative exists (MHRA -older age).
Set a total duration (e.g. 7 days in total for pyelonephritis-type infection) and a stop date.
2. A 45-year-old man with cellulitis has a "penicillin allergy" label. On questioning, he had a mild rash at age 6 while taking amoxicillin for an ear infection, and has never taken a penicillin since. Answer: Low-risk history -likely not truly allergic.
Benign delayed rash in childhood (often viral) with no features of anaphylaxis or severe skin reaction.
He may be suitable for direct oral challenge and de-labelling (local pathway); meanwhile use a suitable alternative per guidelines (e.g. clarithromycin or doxycycline).
Document the allergy history accurately; explain the benefits of removing a false label.
3. A 68-year-old man on IV vancomycin for MRSA bacteraemia has a trough level well above target and his creatinine has risen from 90 to 160. He is also on furosemide. Answer: Vancomycin toxicity with AKI.
Withhold the next dose; recheck level and creatinine; review fluid balance and stop or reduce other nephrotoxins (diuretic, NSAIDs, contrast).
Redose when the level falls into range, using kidney-adjusted dosing (pharmacy and microbiology advice); consider alternatives (e.g. daptomycin) if kidney function keeps worsening.
Continue the bacteraemia bundle -echo, repeat cultures, source control, 14 days or more of treatment.
4. A 30-year-old woman with a central line for parenteral nutrition has a fever. Blood cultures from the line and a peripheral vein both grow yeast. Answer: Candidaemia -catheter-related.
Start an echinocandin; remove the line; repeat cultures until negative.
Echocardiogram and dilated eye examination (endocarditis and endophthalmitis).
Step down to fluconazole if sensitive and stable; treat for 14 days after the first negative culture.
5. A patient with cirrhosis and a seizure disorder on sodium valproate develops hospital-acquired pneumonia with an ESBL Klebsiella. The team propose meropenem. Answer: Carbapenems drastically reduce valproate levels -seizure risk.
Discuss with microbiology -choose an alternative effective agent by sensitivity if possible.
If a carbapenem is essential, involve neurology and pharmacy -switch to another antiseizure medicine for the duration (increasing valproate doses doesn't overcome the interaction).
Always check interactions for antimicrobials with narrow-range drugs.