Learn — Antimicrobials

6 notes · 26 questions on the topic

First-line treatment for pulmonary TB

Under India's National Tuberculosis Elimination Programme a new case of drug-sensitive pulmonary tuberculosis is treated with four first-line drugs daily in fixed-dose combinations: 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol, followed by 4 months of isoniazid, rifampicin and ethambutol, written as 2HRZE and 4HRE. Daily weight-band dosing replaced the old thrice-weekly intermittent regimen, and treatment is free, notified on Nikshay and backed by treatment adherence support, because irregular therapy is what creates drug resistance.

The regimen: an intensive phase of 2 months of HRZE daily and a continuation phase of 4 months of HRE daily. India keeps ethambutol in the continuation phase, and treatment is extended only on specialist advice, for example to 10 to 12 months in tuberculous meningitis or bone and joint disease.
Daily doses: isoniazid 5 mg/kg with a range of 4 to 6, rifampicin 10 mg/kg with a range of 8 to 12, pyrazinamide 25 mg/kg with a range of 20 to 30, and ethambutol 15 mg/kg with a range of 15 to 20, delivered as adult fixed-dose combination tablets by weight band: 2 tablets for 25 to 39 kg, 3 for 40 to 54 kg, 4 for 55 to 69 kg and 5 at 70 kg and above.
Pyridoxine 10 mg daily is given alongside to prevent isoniazid-induced peripheral neuropathy, and the weight is rechecked every month so that the patient moves up a band as he regains weight.
The tablets are taken as a single daily dose on an empty stomach, about an hour before food, and the patient is warned that rifampicin turns the urine, tears and sweat orange-red, a harmless effect that must be explained or he will stop the drug.
Every presumptive case now gets an upfront molecular test, CBNAAT or Truenat, rather than smear alone, because it detects rifampicin resistance the same day; universal drug susceptibility testing is programme policy, and a rifampicin-resistant result moves the patient to an all-oral bedaquiline-containing regimen rather than to a repeat of first-line drugs.
Follow-up sputum smears are done at the end of the intensive phase at 2 months and at the end of treatment; a positive smear at the end of the intensive phase triggers repeat drug susceptibility testing rather than an automatic extension of the phase.
Every diagnosed patient is notified on Nikshay, notification being mandatory for private practitioners as well, is tested for HIV and for diabetes, is offered nutritional support through direct benefit transfer, and has household contacts screened and offered preventive treatment.
TB preventive treatment for eligible contacts and for people living with HIV uses 6 months of daily isoniazid, or the shorter rifapentine-based options of 3 months of weekly isoniazid with rifapentine or 3 months of daily isoniazid with rifampicin, which the programme is scaling up because short courses are completed more often.
Adherence is supported by a treatment supporter with digital tools such as 99DOTS and medication event monitors; an interruption of a month or more is managed as loss to follow-up, with retrieval and re-evaluation rather than simply restarting the tablets.

Side effects of anti-TB drugs

Anti-tuberculosis treatment is long, multi-drug and given to people who feel well within a few weeks, so adverse effects are the main reason patients stop taking it, and stopping is what breeds resistance. The nurse's task is to know which effect belongs to which drug, which effects are harmless and need only explanation, and which ones, meaning hepatitis, visual loss, hearing loss and severe rash, mean the drug must be stopped that day.

Isoniazid: hepatitis, whose risk rises with age and alcohol; peripheral neuropathy from pyridoxine antagonism, prevented by pyridoxine 10 mg daily and treated with 100 mg daily; and rarely psychosis, seizures and a lupus-like syndrome. In overdose it causes refractory seizures with metabolic acidosis, and the antidote is pyridoxine given gram for gram with the amount ingested.
Rifampicin: harmless orange-red discolouration of urine, tears and sweat that permanently stains soft contact lenses; mainly cholestatic hepatitis; a flu-like syndrome, thrombocytopenia and acute kidney injury with intermittent or restarted dosing; and powerful cytochrome P450 induction that lowers levels of oral contraceptives, warfarin, oral hypoglycaemics, phenytoin, corticosteroids, azole antifungals and antiretrovirals.
Pyrazinamide: the most hepatotoxic of the first-line drugs, together with hyperuricaemia and arthralgia, which is usually managed with analgesia while treatment continues, plus photosensitivity and worsening glycaemic control.
Ethambutol: dose-dependent retrobulbar optic neuritis with loss of visual acuity and of red-green discrimination; ask about vision at every visit, avoid it where vision cannot be assessed, reduce the dose in renal impairment, and stop it at the first symptom, when recovery is usually complete.
Streptomycin and other injectable aminoglycosides: vestibular damage before cochlear damage, giving vertigo and then deafness, with nephrotoxicity and neuromuscular blockade, and contraindication in pregnancy because of fetal eighth-nerve damage. The programme has moved to all-oral regimens, so injectables are now rarely used.
Second-line drugs to recognise: bedaquiline prolongs the QT interval and needs baseline and monthly ECG with potassium and magnesium; linezolid causes myelosuppression with peripheral and optic neuropathy; clofazimine causes reddish-brown skin pigmentation and QT prolongation; and cycloserine causes psychosis, depression and suicidal ideation.
Drug-induced hepatitis follows a rule: stop all the drugs when transaminases exceed three times the upper limit of normal with symptoms or five times without, or when the bilirubin rises; give a non-hepatotoxic holding regimen if the tuberculosis is severe, and reintroduce the drugs one at a time with monitoring once the enzymes settle.
Every adverse event is recorded and reported through the programme's active drug-safety monitoring and to the Pharmacovigilance Programme of India, and the patient is counselled rather than simply told to carry on.
Monitoring parameters: monthly weight, which also re-bands the dose, symptom enquiry about jaundice, vision and hearing at every visit, liver function tests whenever symptoms appear or when there is pre-existing liver disease or alcohol use, and colour vision testing where it is available.

Tetracycline

Tetracyclines are broad-spectrum bacteriostatic antibiotics that enter bacteria by active transport and bind reversibly to the 30S ribosomal subunit, blocking attachment of aminoacyl-tRNA to the A site and halting protein synthesis. They cover the intracellular and atypical organisms that beta-lactams cannot touch, including rickettsiae, chlamydiae, mycoplasma, brucella, leptospira and spirochaetes, which is why doxycycline remains a front-line drug in Indian practice for scrub typhus and leptospirosis.

Members: tetracycline itself, the long-acting doxycycline given as 100 mg twice on the first day and then once or twice daily, and minocycline; tigecycline is the intravenous glycylcycline kept for resistant hospital infections.
Uses: rickettsial infection including scrub typhus, where doxycycline is the drug of choice; leptospirosis for both treatment and weekly 200 mg prophylaxis in outbreaks; chlamydial urethritis and pelvic inflammatory disease; atypical pneumonia; brucellosis with streptomycin or rifampicin; cholera as an adjunct to rehydration; plague; Lyme disease; acne vulgaris; and the bismuth quadruple regimen for Helicobacter pylori.
Absorption decides how it is given: calcium, magnesium and aluminium antacids, milk and dairy products, iron, zinc and sucralfate chelate the drug and block its absorption, so doses are separated from them by at least 2 hours; doxycycline is least affected and may be taken with food.
The adverse effect that decides nursing action is oesophageal ulceration, because the capsule sticks and burns: the drug is swallowed with a full glass of water while sitting or standing, and the patient does not lie down for 30 minutes afterwards.
Other adverse effects: permanent yellow-brown staining of teeth with enamel hypoplasia and inhibition of bone growth, photosensitivity with severe sunburn, gastrointestinal upset with candidal superinfection, hepatotoxicity especially with high intravenous doses in pregnancy, vestibular disturbance with minocycline, benign intracranial hypertension, and Fanconi-like renal tubular damage from expired, degraded tetracycline.
Contraindications: pregnancy and lactation, and children under 8 years for conventional courses; tetracycline itself is avoided in renal failure, though doxycycline is safe there because it is eliminated mainly through the gut.
Patient teaching: a full glass of water, upright for half an hour, no milk or antacid around the dose, sunscreen and covering clothing, completion of the course, and immediate reporting of severe retrosternal pain on swallowing or of persistent headache with visual disturbance.

Antimalarials

Antimalarials are the drugs that kill the malaria parasite at its different life-cycle stages: blood schizonticides clear the fever-producing erythrocytic forms, tissue schizonticides clear the dormant liver hypnozoites of Plasmodium vivax and P. ovale, and gametocytocides stop transmission back to the mosquito. They matter at the bedside because the drug is chosen by species, severity and pregnancy rather than by symptom, and because two of them cause emergencies of their own — primaquine haemolysis in G6PD deficiency and quinine-induced hypoglycaemia.

Mechanism: chloroquine and quinine act inside the parasite food vacuole by blocking the polymerisation of toxic haem into inert haemozoin, while the artemisinins are activated by parasite iron and cleave their endoperoxide bridge into free radicals; primaquine is the only tissue schizonticide in routine use and the only drug that kills the vivax hypnozoite.
Uncomplicated P. falciparum in India is treated with an artemisinin-based combination — artesunate 4 mg/kg once daily for 3 days with sulfadoxine-pyrimethamine on day 1 in most of the country, and artemether-lumefantrine in the North-eastern states — plus a single gametocytocidal dose of primaquine 0.75 mg/kg on day 2.
Uncomplicated P. vivax is treated with chloroquine 25 mg/kg spread over 3 days as 10, 10 and 5 mg/kg for the blood stage, followed by primaquine 0.25 mg/kg daily for 14 days as radical cure; without the full 14-day course the hypnozoites survive and the patient relapses.
Severe malaria is an intravenous artesunate case: 2.4 mg/kg IV at 0, 12 and 24 hours and then once daily until the patient can swallow, after which a full 3-day oral ACT course is completed, because artemisinin left as monotherapy breeds resistance.
Onset and duration differ enormously: artesunate gives the fastest parasite clearance of any antimalarial and acts within hours, chloroquine has a half-life of days to weeks and accumulates in tissues, and mefloquine is long-acting enough to be dosed once a week for prophylaxis.
The adverse effects that decide nursing action are acute haemolysis with primaquine in G6PD deficiency, cinchonism with quinine (tinnitus, deafness, headache, blurred vision) together with hypoglycaemia from quinine-driven insulin release, irreversible retinopathy with long-term chloroquine, and neuropsychiatric reactions with mefloquine.
Monitoring: check blood glucose in every patient on intravenous quinine and in every child with severe malaria and keep it above 70 mg/dL, follow parasite density and haemoglobin daily, and screen for G6PD deficiency before a 14-day primaquine course wherever testing is available.
Contraindications: primaquine is not given in pregnancy, in infants under 1 year or in known G6PD deficiency. In pregnancy chloroquine is used for vivax; for falciparum the Indian national policy has used quinine with clindamycin in the first trimester and ACT later, while WHO now recommends artemether-lumefantrine in the first trimester as well, so follow the current local protocol.

Cephalosporins — generations

Cephalosporins are beta-lactam antibiotics that kill bacteria by binding penicillin-binding proteins and blocking the cross-linking of the peptidoglycan cell wall, and they are grouped into generations that trace a steady move from Gram-positive cover towards Gram-negative and antipseudomonal cover. They matter at the bedside because they are the commonest parenteral antibiotics on an Indian ward and the standard surgical prophylaxis, and because they carry a real anaphylaxis risk as well as the penicillin cross-reactivity question the nurse is asked to answer at the drug trolley.

Mechanism: cephalosporins are bactericidal and time-dependent — they bind penicillin-binding proteins and inhibit transpeptidation, so efficacy depends on how long the free drug stays above the minimum inhibitory concentration, which is why the daily dose is divided rather than given as one large dose.
First generation (cefazolin injectable, cephalexin oral) covers staphylococci and streptococci and is the standard surgical prophylaxis; second generation (cefuroxime) adds Haemophilus influenzae and Moraxella for respiratory infection, and cefoxitin adds anaerobic cover for bowel surgery.
Third generation (ceftriaxone, cefotaxime, ceftazidime) crosses the inflamed blood-brain barrier and is the workhorse for bacterial meningitis, enteric fever, gonorrhoea and severe community-acquired pneumonia, with ceftazidime the antipseudomonal member; fourth generation cefepime covers Pseudomonas and regains Gram-positive activity, and fifth generation ceftaroline is the only cephalosporin active against MRSA.
Standard adult doses: cefazolin 1 to 2 g IV within 60 minutes before skin incision for prophylaxis, ceftriaxone 1 to 2 g IV once daily and 2 g twelve-hourly for meningitis, cefotaxime 1 to 2 g IV six- to eight-hourly, and cephalexin 500 mg orally six-hourly.
Onset and duration: intravenous doses peak at the end of the infusion, and ceftriaxone's half-life of about 8 hours is what allows once-daily dosing, while cefotaxime and cefepime must be repeated through the day to keep concentrations above the minimum inhibitory concentration.
The adverse effect that decides nursing action is immediate hypersensitivity — urticaria, wheeze, angio-oedema and hypotension within minutes of the dose; the others to watch are Clostridioides difficile diarrhoea after any broad-spectrum course, neutropenia and a positive Coombs test on prolonged use, and biliary sludging with ceftriaxone.
There is no antidote to a cephalosporin, so the reversal is for the emergency it causes: intramuscular adrenaline 0.5 mg (0.5 mL of 1 in 1000) into the anterolateral thigh for anaphylaxis, repeated every 5 minutes as needed, with high-flow oxygen and a rapid fluid bolus.
Monitoring: check renal function because almost all cephalosporins are renally cleared and need dose reduction as creatinine clearance falls (ceftriaxone and cefoperazone are the biliary exceptions), watch the neutrophil count on courses beyond 10 days, and record the stool pattern for C. difficile.
Contraindication: a previous immediate or anaphylactic reaction to a cephalosporin. Cross-reactivity with penicillin is low and is driven by a shared side chain rather than the beta-lactam ring, but penicillin anaphylaxis still rules out the agents with similar side chains; and ceftriaxone must never be given to a neonate who is receiving calcium-containing intravenous fluid, because the precipitate can be fatal.

Vaccine diluent and storage

Reconstitution is the mixing of a freeze-dried (lyophilised) vaccine with the exact diluent supplied by the same manufacturer for that product, and storage is the holding of every vaccine within its own temperature window from the factory to the child's arm. It matters because the wrong diluent, a warm diluent or a frozen vaccine destroys potency invisibly — the vial looks unchanged — and the child goes home unprotected while everyone believes she is immunised.

Only the diluent supplied with that vaccine by that manufacturer is used, and it is chilled to +2 to +8 °C before mixing so the cold vaccine is not shocked; a diluent is never swapped between vaccines and never replaced with saline or water drawn from a bottle. BCG is reconstituted with the normal saline supplied with it, measles or MR with the sterile water supplied with it.
Reconstituted BCG, measles or MR and JE vaccines are discarded 4 hours after reconstitution or at the end of the session, whichever is earlier, because they contain no preservative; write the time of reconstitution on the vial the moment the diluent goes in.
Open-vial policy: opened multi-dose vials of OPV, Pentavalent, Td, Hepatitis B, IPV and PCV may be used for up to 28 days if the vaccine vial monitor is usable, the expiry date has not passed, the vial stayed at +2 to +8 °C and the septum was never submerged in water.
The ice-lined refrigerator holds +2 °C to +8 °C for every vaccine at the session and PHC level (BCG, Hep B, Pentavalent, Rotavirus, PCV, fIPV, MR, JE, Td) and for the diluents; the deep freezer holds −15 °C to −25 °C for OPV and for freezing ice packs, and diluents are never frozen.
The freeze-sensitive vaccines are those with an aluminium adjuvant — Hepatitis B, Pentavalent, DPT, Td, IPV, PCV and Rotavirus. A vial suspected of freezing is tested with the shake test against a known frozen control, and rapid flaky sedimentation means the batch is discarded.
Vaccine vial monitor: the inner square is lighter than the outer ring at stages 1 and 2 and the vial is usable; once the inner square matches or is darker than the outer ring (stages 3 and 4) the vial is discarded whatever the printed expiry date says.
At the session the vials sit in the vaccine carrier on conditioned ice packs with the lid closed, out of direct sunlight, and stock is used earliest-expiry-first; diluents are stored with their vaccine at +2 to +8 °C for at least 24 hours before use.
The nurse's own checks before drawing a dose are the expiry date, the vaccine vial monitor, the appearance of the solution, the time written on a reconstituted vial and the label of the diluent ampoule in her other hand.

Free today: the 10-question daily quiz · the NORCET 11 recall paper · what ₹999 unlocks — once, no auto-renewal.