Article Vol. 8, No. 12 1019 Eur, J. Clin. Microbiol. Infect. Dis., December 1989, p. 1019-1023 0934-9723/89/12 1019-05 $3.00/0 Serum Levels of Ciprofloxacin after Single Oral Doses in Patients with Septicemia M. D'Espine I , F. Bellido 2 , J. C. Pech~re 2 , R. Auckenthaler 1 , P. Rohner 1 , D. Lew I , B. Hirschel 1 * Ciprofloxaein serum levels were measured after administration of the drug to 36 patients with septicemia (at least one positive blood culture) who were able to take oral medication. Patients were randomly allocated to receive ciprofloxacin 500 mg p.o. (n = 21) or 200 nag i.v. over 30 min (n = 15). A first dose was administered 18-30 h after the last positive blood culture (day 1), and a second dose four days later (day 5) in some patients. In addition to ciprofloxacin, standard antibiotics were administered. Organisms isolated were Escherichia coli (15), other gram-negative bacteria (6), Streptococcus pneumoniae (7), Staphylococcus aureus (2), and other gram-positive bacteria (6). None of the patients vomited. Ciprofloxacin serum concentrations 1 h after oral administration were in the range 0.09-2.32 rag/l, and 2 h after administration in the range 0.5-7.27 mg/l. The average terminal half-life was 8.6 h. In individual patients serum concentrations and area-under-the-curve values were compared. Poor correlation was found between values measured on day 1 and day 5 after oral administration, whereas the correlation was excellent after i.v. administration. Serum levels 2 h after oral administration were 30-900 times the MICs for the gram-negative organisms, but were in the range of the MICs for the gram-positive organisms in some cases. In conclusion, ciprofloxacin serum levels are difficult to predict in septicemia patients after oral administration, but probably suffice to treat infections caused by gram-negative or- ganisms. Ciprofloxacin is a fluoroquinolone antibiotic with a wide antibacterial spectrum and especially low MIC values for gram-negative aerobic bacteria (1). tt has potential for use as an oral drug, since in healthy volunteers an oral dose of 500 mg usually produces serum levels of about 1-3 mg/1 (2), which are several hundred times higher than the typical MICs for sus- ceptible Enterobacteriaceae. Pharmacokinetics in patients with serious infections might however be different. Volunteers have with some exceptions (3, 4) been young and healthy (5, 6), whereas infected patients are ill and most are old. Volunteers can be tested after an overnight fast, whereas patients have to be treated at any time, whether they have eaten or not. Volunteers are administered only the drugs to be tested, whereas hospitalized patients typically need other drugs. 1 Division of Infectious Diseases, H6pital Cantonal Universi- take, 24 rue Micheli-du-Crest, CH-1211 Geneva 4, Switzer- land. 2Department of Microbiology, Geneva University Medical School, CH-1211 Geneva, Switzerland. We therefore decided to measure serum levels after a single dose of ciprofloxacin in patients with septicemia who were also treated with conventional antibiotics. Patients and Methods Patients. Patients over 18 years of age hospitalized at the Hdpital Cantonal Universitaire in Geneva were considered for inclusion in the study, provided they were able to give in- formed consent and to take medication by mouth, did not have hypotension, and had at least one positive blood culture showing the same pathogen in both paired bottles, and were not in septic shock. Cultures had to be reported as positive within 24 h after drawing the blood. Pregnant patients and patients allergic to quinolone antibiotics were excluded. The study was approved by the Ethics Committee of Geneva University Hospital. Informed consent was obtained from all patients. Drug Administration. Patients consenting to be studied were randomized (using a table of random numbers: even = p.o., odd = i.v.) to receive either 500mg of eiprofloxacin p.o., or 200 mg i.v. in a 30 min infusion. Blood was drawn after 5 min (i.v. group on/y), 30 rain, 60 rain, 2 h, 6 h, 12 h and 24 h to determine serum levels. Whenever possible, the study was repeated five days later to compare pharmacokinetics at a time when the patients' condition had stabilized. In addi-