›Start all indicated prophylaxis before source and baseline results return
›Stop HIV prophylaxis if the source is confirmed negative and not in a window period
›Continue rabies prophylaxis unless a dog, cat, or ferret is healthy after 10 days of observation or the animal tests negative
HIV post-exposure prophylaxis regimens
›Preferred regimen for adults and adolescents
›Tenofovir disoproxil fumarate 300 mg with emtricitabine 200 mg, one tablet by mouth once daily
›Plus dolutegravir 50 mg by mouth once daily
›Or plus raltegravir 400 mg by mouth twice daily
›Duration 28 days for all components
›Preferred alternative anchor
›Tenofovir disoproxil fumarate 300 mg with emtricitabine 200 mg once daily
›Plus darunavir 800 mg by mouth once daily with ritonavir 100 mg by mouth once daily
›Take with food; note sulfonamide cross-reactivity and extensive CYP3A4 interactions
›Lamivudine 300 mg once daily may substitute for emtricitabine as the second nucleoside
›Interchangeable cytidine analogues; use whichever the formulary supplies
›The fixed-dose tenofovir plus emtricitabine tablet is preferred for pill burden
›Regimens requiring infectious diseases sign-off rather than routine emergency department use
›Nevirapine 200 mg once daily for 14 days then 200 mg twice daily: do not use for prophylaxis because of fulminant hepatic failure and Stevens-Johnson syndrome in otherwise healthy recipients
›Abacavir 600 mg once daily: hypersensitivity reaction risk without HLA-B*5701 testing
›Efavirenz 600 mg at night: neuropsychiatric effects and adherence loss across a 28-day course
›Stavudine, didanosine, and full-dose ritonavir: unacceptable toxicity
›Anchor choice with a treatment-experienced source
›Obtain the source genotype and current regimen
›Infectious diseases selects the tailored regimen; do not delay the first dose of the standard regimen while waiting
HIV prophylaxis renal dosing, interactions, and adverse-effect management
›Renal impairment
›Avoid tenofovir disoproxil fumarate when estimated GFR is below 60 ml/min
›Substitute zidovudine 300 mg twice daily plus lamivudine 150 mg twice daily, each dose-adjusted for clearance
›Or a tenofovir alafenamide 25 mg with emtricitabine 200 mg once-daily regimen where it is available
›Infectious diseases and pharmacy confirm the interval adjustment
›Avoid concurrent NSAIDs, aminoglycosides, and other nephrotoxins during tenofovir exposure
›Integrase inhibitor cation interactions
›Give dolutegravir 2 hours before or 6 hours after aluminium, magnesium, or calcium antacids, iron, or multivitamins, or take dolutegravir together with a calcium- or iron-containing meal
›Avoid aluminium and magnesium antacids entirely with raltegravir
›Dolutegravir raises metformin concentrations: cap metformin at 1000 mg/day and monitor
›Carbamazepine, phenytoin, oxcarbazepine, phenobarbital, and rifampin lower integrase inhibitor levels; rifampin requires raltegravir 800 mg twice daily and infectious diseases input
›Protease inhibitor interactions if darunavir with ritonavir is used
›Contraindicated with simvastatin and lovastatin; use the lowest dose of atorvastatin or rosuvastatin
›Interactions with inhaled and intranasal fluticasone, ergot alkaloids, several anticonvulsants, quetiapine, and hormonal contraception
›Hyperglycaemia and gastrointestinal intolerance
›Adverse-effect management to protect the 28-day course
›Nausea: ondansetron 4 mg by mouth or IV every 8 hours as needed, maximum single dose 8 mg
›Diarrhoea: loperamide 4 mg once then 2 mg after each loose stool, maximum 16 mg/day
›Take doses with food and at a consistent time; provide antiemetics proactively at the first visit
›Headache and fatigue are common in the first week and usually settle without stopping the regimen
Hepatitis B post-exposure prophylaxis
›Exposed person previously vaccinated with a documented anti-HBs of 10 mIU/ml or higher
›No treatment and no booster needed
›This applies regardless of source status
›Exposed person unvaccinated or incompletely vaccinated
›Source HBsAg-positive or high-risk unknown: hepatitis B immune globulin 0.06 ml/kg intramuscularly once, plus start the hepatitis B vaccine series at a separate site
›Source HBsAg-negative: start or complete the vaccine series, with no immune globulin
›Give immune globulin within 24 hours where possible
›Exposed person vaccinated but with an unknown response
›Draw anti-HBs now
›If the source is HBsAg-positive and results will be delayed, give hepatitis B immune globulin 0.06 ml/kg and a vaccine dose while waiting
›Anti-HBs 10 mIU/ml or higher: stop; below 10 mIU/ml: complete a full second series
›Known vaccine non-responder, defined as anti-HBs below 10 mIU/ml after two full series
›Source HBsAg-positive: hepatitis B immune globulin 0.06 ml/kg in two doses one month apart, or one dose plus reinitiation of vaccination
›Vaccine schedule and route
›Recombinant hepatitis B vaccine intramuscularly into the deltoid at 0, 1, and 6 months for the adult three-dose schedule
›A CpG-adjuvanted two-dose schedule at 0 and 1 month is an alternative in adults
›Do not give in the gluteal region; immunogenicity is reduced there
Rabies post-exposure prophylaxis: immune globulin
›Indication
›All WHO category III exposures in a person not previously vaccinated against rabies
›Never give to a previously vaccinated person; give vaccine only
›Human rabies immune globulin
›20 IU/kg body weight, given once on day 0
›Infiltrate as much of the calculated dose as anatomically feasible into and around every wound
›Give any remainder intramuscularly at a site distant from the vaccine injection site
›Do not exceed 20 IU/kg: excess immune globulin suppresses the vaccine-induced antibody response and has contributed to prophylaxis failure
›Equine rabies immune globulin where the human product is unavailable
›40 IU/kg body weight once, with the same infiltration principle
›Purified F(ab')2 product; monitor for serum sickness at 1 to 3 weeks
›Practical rules
›Never mix immune globulin and vaccine in the same syringe or inject them at the same site
›If wounds are small and the volume needed exceeds what the tissues will hold, dilute human immune globulin two to three-fold with normal saline to allow full wound infiltration
›If immune globulin is not available on day 0, give it through day 7 after the first vaccine dose and not later
Rabies post-exposure prophylaxis: vaccine schedule
›Previously unvaccinated and immunocompetent, using the United States four-dose schedule
›Cell-culture rabies vaccine 1 ml intramuscularly into the deltoid on days 0, 3, 7, and 14
›Use the anterolateral thigh in infants and small children
›Never use the gluteal region: lower antibody titres and documented prophylaxis failures
›Previously unvaccinated and immunocompromised
›Five doses on days 0, 3, 7, 14, and 28
›Check a rabies neutralising antibody titre 1 to 2 weeks after the last dose and revaccinate if it is inadequate
›Avoid corticosteroids and other immunosuppressants during the series if at all possible
›Previously vaccinated, with a documented prior series or a prior adequate titre
›Two doses of 1 ml intramuscularly on days 0 and 3
›No rabies immune globulin
›WHO abbreviated schedules
›WHO also endorses shorter intramuscular and intradermal multi-site regimens, for example a one-week two-site intradermal schedule, where those are the standard of care
›Follow the schedule used by the local rabies programme rather than mixing schedules
›Interruptions and animal testing
›Resume an interrupted series rather than restarting it; minor timing deviations do not require restarting
›Stop the series if a dog, cat, or ferret remains healthy through 10 days of observation, or if brain testing of the animal is negative
Adjunctive wound management, tetanus, and antibiotics
›Tetanus prophylaxis by immunisation status
›Tdap or Td 0.5 ml intramuscularly if the last booster was 5 years ago or more for a tetanus-prone wound, or 10 years for a clean minor wound
›Tetanus immune globulin 250 units intramuscularly, or 500 units if the wound is more than 24 hours old or heavily contaminated, at a separate site, for a tetanus-prone wound in a person with fewer than three lifetime doses or unknown status
›Antibiotic prophylaxis for higher-risk mammalian bites
›Indications: cat bites, hand or foot bites, deep punctures, crush injury, wounds near a joint or bone, genital bites, immunocompromise, asplenia, cirrhosis, and delayed presentation
›Amoxicillin-clavulanate 875/125 mg by mouth twice daily for 3 to 5 days for prophylaxis, and 5 to 14 days for established infection
›Penicillin allergy: doxycycline 100 mg twice daily, or a fluoroquinolone, or trimethoprim-sulfamethoxazole, each combined with metronidazole 500 mg three times daily or clindamycin 300 to 450 mg four times daily for anaerobic cover
›Avoid first-generation cephalosporins, dicloxacillin, clindamycin alone, and macrolides alone: inadequate activity against Pasteurella multocida
›Parenteral antibiotics for established or severe infection
›Ampicillin-sulbactam 3 g IV every 6 hours
›Piperacillin-tazobactam 3.375 g IV every 6 hours for systemic sepsis
›Seek urgent review for suspected Capnocytophaga sepsis in an asplenic host and do not step down early
›Wound closure
›Primary closure only for selected fresh, low-risk facial wounds after copious irrigation
›Leave hand bites, puncture wounds, cat bites, crush wounds, and wounds older than 12 hours open, with delayed primary closure at 72 hours if clean
Anaphylaxis and biologic reaction management
›Recognition
›Rabies immune globulin, hepatitis B immune globulin, and both vaccines can rarely cause anaphylaxis; equine immune globulin also causes serum sickness in 1 to 6% of recipients
›Observe every recipient for 15 to 30 minutes after injection, with epinephrine immediately available
›First-line treatment of anaphylaxis
›Epinephrine 0.5 mg intramuscularly into the anterolateral thigh using the 1 mg/ml concentration, repeated every 5 to 15 minutes as needed
›Paediatric dose 0.01 mg/kg intramuscularly, maximum 0.3 mg in a prepubertal child and 0.5 mg in an adolescent
›Verify against current paediatric guideline before use
›Position supine with the legs raised unless respiratory distress requires sitting
›High-flow oxygen and airway readiness
›Adjuncts, which do not replace epinephrine
›Isotonic crystalloid 1 to 2 litres IV for hypotension in adults
›Paediatric bolus 20 ml/kg isotonic crystalloid, reassessed and repeated to 40 to 60 ml/kg as needed
›Verify against current paediatric guideline before use
›Nebulised salbutamol 5 mg for bronchospasm
›An H1 antihistamine such as cetirizine 10 mg by mouth or diphenhydramine 25 to 50 mg IV for cutaneous symptoms only
›Corticosteroids are not first-line and do not reliably prevent biphasic reactions
›Completing rabies prophylaxis after a reaction
›Rabies is virtually always fatal, so continue prophylaxis under allergy and immunology guidance in a monitored setting with premedication
›Consider switching to a different cell-culture vaccine product
›Known selective IgA deficiency: use an IgA-depleted immune globulin preparation where the diagnosis is established
Iatrogenic risks and interventions to modify or avoid
›Wound closure and exploration
›Tight primary suturing without prior irrigation and immune globulin infiltration drives inoculum deeper and raises rabies and bacterial infection risk
›Local anaesthetic infiltration for wound care is acceptable once irrigation is complete
›Analgesia and antipyresis
›Paracetamol 1 g by mouth every 6 hours, maximum 4 g/day, is the preferred baseline analgesic and antipyretic
›Avoid NSAIDs such as ibuprofen 400 mg while on tenofovir because of additive nephrotoxicity; if unavoidable use the shortest course and monitor creatinine
›Opioids titrated for severe wound pain do not interact with the regimens
›A low-grade fever after vaccination is expected and is not a reason to stop the series
›Sedation and intubation for wound care or trauma
›No interaction with prophylaxis; use standard induction and sedation agents
›Etomidate and other single-dose induction agents are not contraindicated
›Oxygen, fluids, and vasopressors
›No modification for prophylaxis itself
›In biologic anaphylaxis, intramuscular epinephrine and fluids are first-line and vasopressor infusions are reserved for refractory shock
›Corticosteroids and immunosuppressants
›They blunt the rabies vaccine antibody response; avoid them during the series unless clinically essential
›If unavoidable, obtain a post-series rabies neutralising antibody titre and revaccinate if it is inadequate
›Antimalarials
›Chloroquine, hydroxychloroquine, and mefloquine reduce the response to intradermal rabies vaccine; use the intramuscular route in patients taking them
›Live vaccines and passive antibody interference
›Defer measles-mumps-rubella and varicella vaccines for at least 4 months after rabies immune globulin and about 3 months after hepatitis B immune globulin
›If a live vaccine was given in the 2 weeks before immune globulin, repeat it after the deferral interval
›Inactivated rabies and hepatitis B vaccines are unaffected and are co-administered with immune globulin at separate sites
›Anticoagulation and bleeding disorders
›For intramuscular vaccine or immune globulin, use a 23-gauge or finer needle, apply firm pressure for at least 2 minutes, and do not rub
›The rabies and hepatitis B vaccines may be given subcutaneously in a patient with a bleeding disorder; wound infiltration of rabies immune globulin is still required
›Time injections to after clotting factor replacement in haemophilia
›Anticoagulation, fibrinolysis, and mechanical circulatory support
›None are indicated for post-exposure prophylaxis; if they are present for another reason they do not contraindicate prophylaxis but they change injection technique as above
Breakthrough infection, prophylaxis failure, and exposed contacts
›HIV seroconversion despite prophylaxis
›Assess adherence across the full 28 days, the time from exposure to the first dose, and any ongoing exposure
›Send HIV RNA and a genotype; transmitted resistance in the source is a recognised cause of failure
›Transition immediately to a fully suppressive treatment regimen with infectious diseases rather than simply extending prophylaxis
›Hepatitis B breakthrough
›Check HBsAg and HBV DNA if transaminases rise or the follow-up anti-HBs is unexpectedly below 10 mIU/ml
›Confirm every vaccine dose was received on schedule by the intramuscular deltoid route
›Rabies prophylaxis failure
›Almost every documented failure involved a deviation: no wound infiltration of immune globulin, immune globulin dose exceeded, gluteal vaccine administration, delayed start, or an unrecognised immunocompromised state
›Any prodromal pain, paraesthesia, or pruritus at a healed bite site after completed prophylaxis warrants urgent specialist review
›There is no effective rescue once symptoms begin; management becomes palliative
›The prophylaxis course is not being tolerated
›Escalate antiemetic and antidiarrhoeal support before allowing the patient to stop
›Switch the anchor, for example dolutegravir to raltegravir, rather than abandoning prophylaxis
›Renal function falling on tenofovir: switch to zidovudine plus lamivudine or a tenofovir alafenamide regimen rather than discontinuing
›Isolation and exposed contacts
›Standard precautions are adequate for patients receiving prophylaxis for any of the three pathogens
›Human-to-human rabies transmission is effectively limited to tissue and organ transplantation; use standard precautions and avoid contact with the saliva and cerebrospinal fluid of a symptomatic patient
›Identify household and healthcare contacts with a mucosal or non-intact skin exposure to the saliva of a rabies patient and offer them prophylaxis
›Handling of source-patient blood and body fluids follows routine bloodborne pathogen precautions