Comparative serum bactericidal activities of three doses of ciprofloxacin administered intravenously

Dan, Michael; Poch, F.; Quassem, C.; Kitzes, R

doi:10.1128/aac.38.4.837

Cited by 7 publications

(3 citation statements)

References 29 publications

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“…Similarly, the AUC range was from 6.4 to 57.0 g ⅐ h/ml, a ninefold difference. Similar variability has been noted in other studies of ciprofloxacin pharmacokinetics (3,5,10). A strong correlation between CL CR and both ciprofloxacin CL (r ϭ 0.85) and CL R (r ϭ 0.84) was noted.…”

Section: Resultssupporting

confidence: 86%

Ciprofloxacin pharmacokinetics in burn patients

Garrelts

Jost

Kowalsky

et al. 1996

Antimicrob Agents Chemother

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Many drugs exhibit altered pharmacokinetic parameters in burn patients. We prospectively evaluated the pharmacokinetics of ciprofloxacin in eight burn patients with active infections. Each patient received a 400-mg dose of ciprofloxacin intravenously (i.v.) every 8 h, with each dose infused over 1 h by using a rate control device. Blood samples for analysis of plasma ciprofloxacin concentrations, determined by high-performance liquid chromatography, were obtained immediately predose, at the end of the infusion, and 1, 2, 3, 4, 5, 6, and 7 h after the end of the infusion. Urine was collected from 0 to 2, 2 to 4, and 4 to 8 h following the same dose, and an aliquot was saved for determination of the ciprofloxacin concentration. Urine was also collected for 24 h prior to this dose for measurement of creatinine clearance (CLCR). Pharmacokinetic parameters were estimated by noncompartmental analysis. Mean maximum and minimum plasma ciprofloxacin concentrations were 4.2 +/- 1.1 and 0.70 +/- 0.55 microgram/ml, respectively. Mean values for clearance (CL), renal clearance (CLR), volume of distribution, terminal elimination rate constant, half-life (t1/2), and area under the concentration-time curve (AUC) were 29.1 +/- 17.5 liters/h, 13.5 +/- 10.1 liters/h, 1.75 +/- 0.41 liters/kg, 0.222 +/- 0.098 h-1, 4.5 +/- 3.9 h, and 20.7 +/- 16.6 micrograms.h/ml, respectively. CL was higher and t1/2 was shorter than noted in previous studies of acutely ill, hospitalized patients. A good correlation was noted between creatinine clearance CL(CR) and both total ciprofloxacin CL (r = 0.85) and CLR (r = 0.84). A moderate inverse correlation was noted between percent body surface area burned and total ciprofloxacin CL (r = -0.55). An AUC/MIC ratio above 125 SIT-1 (where SIT is serum inhibitory titer), which has been strongly correlated with clinical response and time to bacterial eradication, was achieved in five of eight patients (63%) with a MIC of 0.25 microgram/ml. At a ciprofloxacin dosage of 400 mg i.v. every 12 h, an AUC/MIC ratio above 125 SIT-1 would have been achieved in only two of eight patients (25%). We conclude that ciprofloxacin CL is highly variable, but generally increased, in burn patients compared with that in acutely ill, general medical and surgical patients. Because of an increase in CL, a ciprofloxacin dosage of 400 mg i.v. every 8 h is more likely to produce the desired response in burn patients than the same dose given every 12 h.

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Section: Resultssupporting

confidence: 86%

Ciprofloxacin pharmacokinetics in burn patients

Garrelts

Jost

Kowalsky

et al. 1996

Antimicrob Agents Chemother

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“…Fluoroquinolones in general have killing characteristics that differ from those of both these classes of antibiotics. They have a dose-dependent killing initially and then a slower killing curve (4,5,19) and also exhibit a PAE (4)(5)(6)(7)19).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Profiles of High-Dose Intravenous Ciprofloxacin in Severe Sepsis

Lipman

Scribante

Gous

et al. 1998

Antimicrob Agents Chemother

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The pharmacokinetics of 400 mg of ciprofloxacin given intravenously (i.v.) every 8 h (q8h) in severely septic adults was documented in a multidisciplinary, tertiary referral intensive care unit (ICU). Sixteen evaluable patients (three pharmacokinetic profiles) without renal dysfunction and with severe sepsis were studied. Ciprofloxacin at a dosage of 400 mg given i.v. q8h was administered over 1 h. Plasma samples for assay (high-pressure liquid chromatography) were taken at timed intervals (preinfusion, at the end of infusion, and at 1, 2, 3, 5, and 7 h postinfusion) for first-dose kinetics (day 0 [D0]), D2, and between D6 and D8. All pharmacokinetic variables were calculated by noncompartmental methods. Standard intensive care was provided. Peak ciprofloxacin concentrations were as follows: D0, 6.01 ± 1.93 mg/liter; D2, 6.68 ± 2.01 mg/liter; and D6 to D8 6.45 ± 1.54 mg/liter. Trough levels were as follows: D0, 0.6 ± 0.5 mg/liter; D2, 0.7 ± 0.4 mg/liter; and D6 to D8 0.6 ± 0.4 mg/liter. The areas under the concentration curves (8 h) were as follows: D0, 13.3 ± 3.8 mg · h/liter; D2, 16.8 ± 5.4 mg · h/liter; and D6 to D8, 15.5 ± 4.7 mg · h/liter. No drug-related serious adverse events occurred. For 17 of 18 patients enrolled in the study, the causative organisms were susceptible to ciprofloxacin. One patient developed renal failure (non-drug related) after the administration of three doses of ciprofloxacin. One patient was infected with ciprofloxacin-resistant organisms on enrollment. Nine of 16 evaluable patients had clinical cures, and 8 had bacteriological cures. One patient developed a ciprofloxacin-resistant superinfection. In two patients the clinical course was indeterminate. Two bacteriological failures occurred. We conclude that in critically ill adults ciprofloxacin at a dosage of 400 mg given i.v. q8h is safe. Its pharmacokinetic profile provides bactericidal activity against most organisms encountered in an ICU. Except for some initial accumulation on D2, no further accumulation occurred in patients without renal failure. Ciprofloxacin should be administered i.v. at a dosage of 400 mg q8h for severe sepsis.

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“…A suggested "target" parameter for a good clinical bactericidal effect is a peak concentration (C max ) up to eight times the MIC 89 . Quinolones exhibit a PAE [90][91][92][93][94] . Therefore peak concentrations alone may not correspond with optimal in vivo killing.…”

Section: Ciprofloxacin (As Representative Of the Fluoroquinolones)mentioning

confidence: 99%

Pharmacological Principles of Antibiotic Prescription in the Critically Ill

Pinder¹,

Bellomo

Lipman³

2002

Anaesth Intensive Care

112

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The goal of antimicrobial prescription is to achieve effective drug concentrations. Standard antimicrobial dosing regimens are based on research performed often decades ago and for the most part with patients who were not critically ill. More recent insights into antibiotic activity (e.g. the importance of high peak/MIC ratios for aminoglycosides and time above MIC for β-lactam antibiotics), drug pharmacokinetics (e.g. increased volume of distribution and altered clearances) and the pathogenesis of sepsis (e.g. third space losses and altered creatinine clearances) have made re-evaluation of dosing regimens necessary for the critically ill.The inflammatory response associated with sepsis results in a rapid decrease in serum albumin levels, large fluid shifts and third space losses, initially with a high cardiac output. In turn these changes result in increased creatinine clearance and increased renal drug clearance. Unless these effects are offset by ensuing renal and/or hepatic impairment, with subsequent drug accumulation, antibiotic levels may be too low for optimal efficacy. The institution of continuous renal replacement therapy separately affects antibiotic clearances, and therefore dosing, even further.This article reviews relevant literature and offers principles for more effective and appropriate antibiotic dosing in the critically ill, based on the pharmacokinetic and pharmacodynamic principles of the main antibiotic groups (aminoglyosides, glycopeptides, β-lactams, carbapenems and quinolones) and knowledge of the pathophysiology of the inflammatory response syndrome. Finally it also provides some guidance on the basic principles of drug prescription for patients receiving continuous renal replacement therapy. FIGURE 2: Creatinine clearance vs 4th generation cephalosporin clearance ( • ) combination of cefepime (x) and cefpirome (data points -from references 9 and 10). Creatinine clearance (ml/min) Drug clearance (ml/min)

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Comparative serum bactericidal activities of three doses of ciprofloxacin administered intravenously

Cited by 7 publications

References 29 publications

Ciprofloxacin pharmacokinetics in burn patients

Ciprofloxacin pharmacokinetics in burn patients

Pharmacokinetic Profiles of High-Dose Intravenous Ciprofloxacin in Severe Sepsis

Pharmacological Principles of Antibiotic Prescription in the Critically Ill

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