Antibiotics in Pregnancy

Antibiotic prescribing in pregnancy treats infections that threaten mother and foetus, including bacteriuria, pyelonephritis, sexually transmitted infections, chorioamnionitis, sepsis and tuberculosis. Effective treatment matters more than theoretical drug risk; untreated infection causes preterm birth, foetal loss and maternal death.

Safe core. Penicillins, cephalosporins and macrolides have the most data and are first choice for most infections.

Dosing changes. Higher volume of distribution and faster renal clearance lower beta-lactam and aminoglycoside levels; use full adult doses and weight-based aminoglycoside dosing.

Sepsis. Maternal sepsis needs broad-spectrum IV antibiotics within 1 hour of recognition, with source control.

Asymptomatic bacteriuria and cystitis (treat both). Nitrofurantoin modified release 100 mg orally twice daily for 5 to 7 days (avoid from 36 weeks); cefalexin 500 mg orally 2 to 3 times daily for 5 to 7 days; amoxicillin 500 mg 3 times daily for 5 to 7 days if sensitive. Recurrence: nitrofurantoin 50 to 100 mg at night until birth.

Pyelonephritis. Ceftriaxone 1 to 2 g IV once daily until afebrile for 48 hours, then oral cefalexin 500 mg 3 times daily or amoxicillin-clavulanate 625 mg 3 times daily by sensitivity, total 10 to 14 days.

Syphilis.

• Early (primary, secondary, early latent under 2 years): benzathine benzylpenicillin 2.4 million units IM as a single dose; some regions add a second dose 1 week later in the third trimester.
• Late latent or unknown duration: 2.4 million units IM weekly for 3 weeks; if doses are more than 9 days apart, restart the course.
• Penicillin allergy: desensitise; macrolides do not treat the foetus. Ceftriaxone 1 g IM or IV daily for 10 to 14 days only where desensitisation is impossible.

Chlamydia. Azithromycin 1 g orally as a single dose, or amoxicillin 500 mg 3 times daily for 7 days. Test of cure 4 weeks after treatment.

Gonorrhoea. Ceftriaxone 1 g IM as a single dose (500 mg in some regions) plus chlamydia treatment if not excluded.

Bacterial vaginosis (symptomatic). Metronidazole 400 to 500 mg orally twice daily for 7 days, or clindamycin 2% vaginal cream at night for 7 days.

Trichomoniasis. Metronidazole 400 to 500 mg orally twice daily for 7 days.

Preterm prelabour rupture of membranes. Erythromycin 250 mg orally every 6 hours for 10 days or until labour. Alternative: ampicillin 2 g IV every 6 hours with azithromycin 1 g orally once for 48 hours, then amoxicillin 500 mg orally 3 times daily for 5 days. Avoid amoxicillin-clavulanate (necrotising enterocolitis).

Chorioamnionitis. Ampicillin 2 g IV every 6 hours plus gentamicin 5 mg/kg IV once daily (or 1.5 mg/kg every 8 hours); add metronidazole 500 mg IV every 8 hours or clindamycin 900 mg IV every 8 hours after caesarean birth.

Maternal sepsis, source unclear. Piperacillin-tazobactam 4.5 g IV every 8 hours (every 6 hours in severe sepsis) or a carbapenem, with gentamicin for shock; add clindamycin 1.2 g IV every 6 hours for suspected group A streptococcal infection.

Tuberculosis. Rifampicin, isoniazid, pyrazinamide and ethambutol daily for 2 months, then rifampicin and isoniazid for 4 months, at usual weight-band doses. Add pyridoxine 25 mg daily.

Avoid. Tetracyclines and doxycycline after 15 weeks (short courses may be justified for rickettsial disease or anthrax). Streptomycin, amikacin and kanamycin (foetal ototoxicity). Fluoroquinolones unless no alternative. Trimethoprim in the first trimester. Sulphonamides and chloramphenicol near term. Amoxicillin-clavulanate in preterm membrane rupture.

Acceptable with care. Gentamicin (short courses with levels), vancomycin (levels), azithromycin and clarithromycin (small, inconsistent malformation and miscarriage signals in early pregnancy), metronidazole in all trimesters.

Jarisch-Herxheimer reaction. Fever, myalgia and contractions within 24 hours of penicillin for syphilis can trigger preterm labour or foetal distress; warn, give paracetamol and monitor the foetus after 20 weeks.

Interactions. Rifampicin lowers levels of nifedipine, hormonal contraceptives, dolutegravir (double the dolutegravir dose to 50 mg twice daily), methadone and corticosteroids. Macrolides with ergometrine risk ergotism.

Special groups.

• Kidney impairment: adjust gentamicin, vancomycin, nitrofurantoin (avoid if eGFR under 45 mL/min) and cefalexin.
• Liver impairment: monitor transaminases on tuberculosis therapy; pregnancy and postpartum raise isoniazid hepatotoxicity risk.
• Penicillin allergy: clarify history; most labels do not reflect true allergy and penicillin is first choice for syphilis and group B streptococcus.
• Regional: in HIV continue co-trimoxazole 960 mg daily and give no sulfadoxine-pyrimethamine; syphilis, tuberculosis and malaria screening are core antenatal tasks in East Africa.

Monitoring. Urine culture 7 to 10 days after treatment for bacteriuria and monthly until birth after any positive culture. Gentamicin levels by local nomogram or trough under 1 mg/L before the next dose. Monthly liver tests and symptom review on tuberculosis therapy. Non-treponemal titres at 3, 6 and 12 months or at birth after syphilis treatment.

Adjustment. Narrow therapy on culture results at 48 to 72 hours. Switch IV to oral once afebrile for 24 to 48 hours with improving markers.

Stopping rules. Stop isoniazid, rifampicin and pyrazinamide if transaminases exceed 5 times normal without symptoms or 3 times with symptoms or jaundice. Stop gentamicin after 72 hours unless a continuing indication is confirmed.

Referral and escalation. Escalate maternal sepsis (systolic pressure under 90 mmHg, lactate 2 mmol/L or more, altered mental state) to senior obstetric and critical care staff. Refer drug-resistant tuberculosis and penicillin desensitisation to specialist units.