Antibiotics in Liver Disease

Antibiotic prescribing in liver disease covers treatment and prophylaxis of infections that are frequent and lethal in cirrhosis, while avoiding nephrotoxicity, hepatotoxicity and sodium overload. Bacterial infection triggers acute-on-chronic liver failure, and delay in effective antibiotics raises mortality.

Common infections. Spontaneous bacterial peritonitis, urinary tract infection, pneumonia, cellulitis and bacteraemia.

Pharmacokinetics. Ascites increases volume of distribution of beta-lactams and aminoglycosides. Hepatic clearance falls for metronidazole, clindamycin, macrolides and tigecycline.

Resistance. Healthcare exposure, prophylactic quinolones and prior admissions raise the risk of extended-spectrum beta-lactamase producers and resistant enterococci.

Spontaneous bacterial peritonitis (ascitic neutrophils 250 cells/mm3 or more). Third-generation cephalosporin for community-acquired infection. Piperacillin-tazobactam or a carbapenem for healthcare-associated infection or recent antibiotic exposure.

Variceal bleeding. Ceftriaxone prophylaxis for all patients.

Long-term prophylaxis. Norfloxacin, ciprofloxacin or co-trimoxazole after a first episode, and in selected patients with low ascitic protein.

Avoid. Aminoglycosides; long-term nitrofurantoin; co-amoxiclav where an alternative exists; intravenous tetracyclines at high dose.

Use with caution. Flucloxacillin, macrolides (cholestasis, QT prolongation), rifampicin and isoniazid, and linezolid (thrombocytopenia worsens in hypersplenism).

Antifungals. Echinocandins are preferred over azoles in Child-Pugh C.

Spontaneous bacterial peritonitis treatment. - Cefotaxime 2 g intravenously every 8 hours, or ceftriaxone 2 g intravenously once daily, for 5 to 7 days. - Healthcare-associated: piperacillin-tazobactam 4.5 g intravenously every 6 to 8 hours, or meropenem 1 g intravenously every 8 hours. - Albumin 1.5 g/kg intravenously within 6 hours of diagnosis (maximum 150 g) and 1 g/kg on day 3 (maximum 100 g).

Variceal bleeding. Ceftriaxone 1 g intravenously once daily for up to 7 days.

Long-term prophylaxis. Norfloxacin 400 mg orally once daily; or ciprofloxacin 500 mg orally once daily; or co-trimoxazole 960 mg orally once daily.

Hepatic adjustments.

Sodium content. Piperacillin-tazobactam and some intravenous formulations add significant sodium; account for it in refractory ascites.

Special groups. - Kidney impairment: adjust cefotaxime, piperacillin-tazobactam, meropenem, ciprofloxacin and co-trimoxazole to creatinine clearance. - Pregnancy: avoid quinolones and tetracyclines; ceftriaxone and cefotaxime are suitable. - Breastfeeding: beta-lactams are compatible. - Older adults: quinolones raise risk of delirium and tendon rupture.

Treatment response. Repeat diagnostic paracentesis at 48 hours. A fall in ascitic neutrophils of less than 25% indicates treatment failure; broaden cover and review cultures.

Monitoring. Creatinine every 1 to 2 days during spontaneous bacterial peritonitis, given the risk of hepatorenal syndrome. Liver tests weekly on flucloxacillin, macrolides or antituberculous drugs.

Prophylaxis review. Stop quinolone prophylaxis after transplant, or when ascites resolves on treatment of the cause, for example sustained alcohol abstinence or antiviral therapy.

Referral and escalation. Escalate urgently for septic shock, rising creatinine or new encephalopathy. Involve microbiology for resistant organisms.