Beta-Lactam antibiotic-induced leukopenia in severe hepatic dysfunction: risk factors and implications for dosing in patients with liver disease

Am J Med. 1993 Mar;94(3):251-6. doi: 10.1016/0002-9343(93)90056-u.


Purpose: To determine if an association could be established for leukopenia and administration of beta-lactam antibiotic therapy in patients with hepatic dysfunction. If such an association could be found, to determine the incidence, timing, and risk factors for beta-lactam antibiotic-induced leukopenia.

Patients and methods: Patients with hepatic dysfunction, i.e., liver transplant recipients as well as patients with end-stage liver disease awaiting liver transplantation, seen at our institution between October 1989 and October 1991, who received 7 or more days of antibiotics, were studied in a prospective observational fashion. Complete blood count was determined at baseline and followed until the completion of the antibiotic course or until the resolution of leukopenia in leukopenic patients.

Results: Leukopenia occurred after a mean of 6 days with 23% of the beta-lactam antibiotic courses as compared with 0% with the non-beta-lactam antibiotic courses (p = 0.046). Development of leukopenia correlated with the severity of liver disease. Patients developing leukopenia had worse synthetic hepatic function as evidenced by a lower serum albumin level (p < 0.01), a lower serum cholesterol level (p < 0.05), and a higher prothrombin time (p < 0.01) as compared with the patients without leukopenia. Leukopenic patients had a lower baseline white blood cell count (p < 0.051) and a lower baseline platelet count (p < 0.01) indicative of a greater degree of hypersplenism. Leukopenic patients received a higher mean daily dosage of cephalosporins as compared with nonleukopenic patients.

Conclusion: beta-Lactam antibiotics when administered in usually recommended dosages can induce leukopenia in patients with hepatic dysfunction. The probable mechanism is impaired hepatic metabolism of the beta-lactam antibiotics resulting in bone marrow suppression of white cell precursors from excessive antibiotic concentrations. The more severe the hepatic dysfunction, the greater the risk. We propose a reduction in dosages of beta-lactam antibiotics when used in patients with hepatic dysfunction. Finally, we raise the possibility that this adverse drug effect is more common than currently recognized by physicians.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects*
  • Chronic Disease
  • Follow-Up Studies
  • Humans
  • Leukopenia / blood
  • Leukopenia / chemically induced*
  • Liver Failure / blood
  • Liver Failure / drug therapy*
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Severity of Illness Index
  • beta-Lactams


  • Anti-Bacterial Agents
  • beta-Lactams