Ciprofloxacin pharmacokinetics in critically ill patients: a prospective cohort study.
OBJECTIVE
Optimal dosing of antibiotics is important for efficacy and avoidance of resistance. Fluoroquinolones are frequently used to treat severe infections in critically ill patients. We studied ciprofloxacin pharmacokinetics after administration of 400 mg twice a day (bid) intravenously (IV).


METHODS
Serum concentrations were measured in 32 intensive care unit patients (age, 68.7 +/- 17.4 years; Sepsis-related Organ Failure Assessment (SOFA) scores, 7.3 +/- 3.4). Blood samples were drawn at 7 time points after ciprofloxacin infusion. We evaluated whether areas under the curve (AUCs) exceeded minimal inhibitory concentration (MIC) values of 0.125, 0.25, 0.5, 1.0, and 2.0 mg/L by 125 times and peak concentrations (C(max)) 10 x MIC (C(max)/MIC >10).


RESULTS
The AUC/MIC more than 125 was achieved in 100% for MIC 0.125. For MIC values 0.25, 0.5, 1.0, and 2.0, results were 84%, 31%, 3%, and 0%, respectively (P < .01). The C(max)/MIC more than 10 for MIC values of 0.125, 0.25, 0.5, 1.0, and 2.0 was realized in 100%, 97%, 69%, 25%, and 0%, respectively (P < .01). Female sex, SOFA(pulmonary) points, and SOFA(renal) points predicted higher AUC. Cumulative SOFA scores were most predictive of high AUCs.


CONCLUSIONS
Ciprofloxacin 400 mg bid IV leads to inadequate AUC/MIC and C(max)/MIC ratios in many cases. Effective killing concentrations were only achieved in pathogens with MIC less than 0.25. As bacteria in intensive care unit patients often exceed this threshold, we recommend to use higher doses of ciprofloxacin (1200 mg daily) to ensure optimal bacterial killing and avoid antibiotic resistance.
van Zanten
Arthur R H
AR
Department of Intensive Care, Gelderse Vallei Hospital, 6710 HN Ede, The Netherlands.
Polderman
Kees H
KH
van Geijlswijk
Ingeborg M
IM
van der Meer
Gert Y G
GY
Schouten
Marinus A
MA
Girbes
Armand R J
AR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D016638:Critical Illness; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007362:Intensive Care Units; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin