High concentrations of ciprofloxacin have been shown to persist in the faeces of volunteers for several days after a week of oral treatment with this drug, which was also found to have a prolonged effect on aerobic Gram-negative intestinal bacteria. To determine whether a shorter course of ciprofloxacin would have the same prolonged effect, we treated ten healthy adult volunteers with a single oral dose of 750 mg ciprofloxacin and found that this was not followed by any significant changes in the counts of anaerobes or streptococci, but that there was a mean decrease of 2.5 log10 cfu/ml in the counts of faecal Enterobacteriaceae, which lasted for a full week. We attributed this to the persistence of high faecal ciprofloxacin concentrations for several days in all the volunteers. We did not observe any significant increase in the MICs of ciprofloxacin for faecal Enterobacteriaceae, or any faecal overgrowth of staphylococci, fungi, Pseudomonas aeruginosa or Clostridium difficile.

Early in vitro investigations have shown that ciprofloxacin is concentrated within human neutrophils (polymorphonuclear leukocytes [PMNs]) at between 3 and 11 times the extracellular concentration. The elution of ciprofloxacin from cells is relatively rapid when the extracellular concentration is reduced. In order to estimate the in vivo intracellular penetration of ciprofloxacin and to determine its intracellular pharmacokinetics' PMNs were recovered from blood samples drawn from healthy volunteers at different times during a 24-h period after they were given a 750-mg oral dose. High-performance liquid chromatographic determination of ciprofioxacin in serum and'cells showed that the intracellular/serum ratio was 3.7 at 1.5 h (maximum concentration of drug in serum), 5.7 at 12 h, and 20 at 24 h. The area under the curve ratio was 3.73. The mean ehimination half-lives of ciprofloxacin were 3.7 and 6.2 h in serum and PMNs, respectively. These data show that in vivo findings are in agreement with in vitro findings. The large uptake of ciprofloxacin by PMNs combined with a prolonged intracellular half-life described under the conditions of human therapy should provide the basis for the use of ciprofloxacin in infections caused by susceptible intracellular bacteria.Fluoroquinolones represent a new group of compounds that exhibit very high activity against a broad spectrum of bacteria, including those that develop intracellularly and that have important extravascular diffusion. Moreover, among the currently marketed compounds, ciprofloxacin has the lowest MICs and the greatest apparent volume of distribution. Thus, it should be one of the most promising agents for the treatment of intracellular infections. Because the ability of an antimicrobial agent to penetrate into phagocytic cells is the first essential step for activity against facultative intracellular organisms (7), in this study we examined the ability of ciprofloxacin to enter human polymorphonuclear leukocytes (PMNs). The uptake of ciprofloxacin by several cell types has been studied previously. These were in vitro experiments only (2, 3), i.e., they were done under experimental conditions, which is very different from the in vivo interactions between the antibiotic and cells. However, these data can be considered very informative, and they demonstrate that ciprofloxacin has a high degree of intracellular penetration followed by a rapid release into the extracellular medium. At present, no information regarding the intracellular behavior of ciprofloxacin in patients receiving the drug has been published.The purpose of this study was to determine whether the pattern of ciprofloxacin penetration into cells observed in vivo corroborates the in vitro data and which findings might be made regarding the clinical use of ciprofloxacin. MATERIALS AND METHODSThe first part of this study was devoted to characterization of the principal parameters of ciprofloxacin penetration into human PMNs in vitro. Following this, the drug was administered to humans and the intracel...

No abstract

No abstract

No abstract