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Treatment of Citrobacter koseri Infection with Ciprofloxacin and Cefotaxime in a Preterm Infant

Neonatal Pharmacotherapy Fellow, Departments of Neonatal Medicine and Pharmacy, Women's Hospital, Greensboro, NC

Peter Gal, PharmD BCPS FCCP FASHP

Director, Graduate Pharmacy Education, Greensboro Area Health Education Center; Clinical Professor, School of Pharmacy, University of North Carolina; Pharmacotherapy Specialist, Department of Neonatal Medicine, Women's Hospital, Greensboro

J Laurence Ransom, MD

Director, Department of Neonatal Medicine, Women's Hospital, Greensboro

Reprints: Dr. Gal, Greensboro AHEC, Department of Graduate Pharmacy Education, Suite 100, 200 E. Northwood St., Greensboro, NC 27401, fax 336/832-2851, peter.gal{at}mosescone.com

OBJECTIVE: To report a case of successful treatment of Citrobacter koseri infection in a preterm infant as a means of challenging the current treatment recommendations on the basis of pharmacodynamic and pharmacokinetic considerations.

CASE SUMMARY: A premature infant was diagnosed with C. koseri sepsis after 3 weeks in intensive care. Concern for meningitis was based on the propensity for central nervous system (CNS) involvement with Citrobacter infection along with new findings of ventriculomegaly and hydrocephalus shown on cranial ultrasound (CUS). The infant was treated with ciprofloxacin 10–20 mg/day and cefotaxime 100 mg/day for 21 days. After treatment, lumbar puncture was normal, follow-up CUS returned to baseline, and the infant passed a hearing screen after discharge. A favorable outcome was achieved in this case.

DISCUSSION: Approximately 76% of neonatal patients infected with C. koseri develop brain abscesses. The mortality rate for meningitis due to Citrobacter spp. is approximately 30%, and of the infants who survive, more than 80% have some degree of mental retardation. Third-generation cephalosporins and aminoglycosides are traditional therapies against this infection. The current antibiotic strategies have failed to prevent the high rates of morbidity and mortality associated with Citrobacter infections. A possible basis for these poor outcomes is failure to apply appropriate pharmacokinetic and pharmacodynamic principles in selecting antibiotics that will achieve adequate concentrations to kill the bacteria in granulocytes within the CNS. Based on favorable sensitivity data, penetration into neutrophils and the CNS, and favorable toxicity profiles, ciprofloxacin and meropenem would appear to be the most appropriate antibiotic treatment options for systemic infection or meningitis caused by C. koseri.

CONCLUSIONS: Ciprofloxacin and meropenem should be considered antibiotic treatment options for systemic infection or meningitis caused by C. koseri.

Key Words: Citrobacter koseri, meningitis, neonates, pharmacokinetics

Published Online, June 24, 2008. www.theannals.com, DOI 10.1345/aph.1L008