Penetration of ciprofloxacin into heart valves, myocardium, mediastinal fat, and sternal bone marrow in humans

Abstract

The penetration of ciprofloxacin into heart tissue (valve and myocardium), mediastinal fat, and sternal bone marrow was the object of a prospective nonrandomized study involving 36 patients undergoing mitral and/or aortic valve replacement. Patients were divided into two groups of 18. Group 1 patients were administered a single 400-mg intravenous dose of ciprofloxacin over a 1-h period. Group 2 patients received a 750-mg dose of ciprofloxacin orally every 12 h over the 48-h period preceding surgery. In this group, the last dose of ciprofloxacin consisted of an intravenous infusion of 400 mg. Concentrations of ciprofloxacin in plasma and tissue were assayed by high-performance liquid chromatography. Peak and trough levels in plasma were, respectively, 6.19 + 1.73 and 0.54 0.25 ,Ig/nd in group 1 patients and 11.59 3.95 and 0.89 0.57 >g/ml in group 2 patients. Levels of ciprofloxacin in plasma remained significantly higher in group 2 than in group 1 until 12 h postinfusion (P < 0.05). Concentrations of ciprofioxacin in heart valves and myocardia rose rapidly by 1 h postinfusion and remained greater than the MICs for usually susceptible pathogens for at least 5 h. Peak concentrations in myocardia were achieved by hour 1 and were 31.6 25.0 g.g/g for group 1 and 21.8 13.0 ,tg/g for group 2. Peak concentrations in heart valves, achieved between hours 1 and 3, were 5.8 3.2 and 8.3 3.1 ,ug/g for groups 1 and 2, respectively. In both groups, peak concentrations in mediastinal fat were lower and achieved later. These were 3.1 + 3.8 ,ug/g in group 1 and 2.0 ± 1.8 gig/g in group 2 and were achieved between hours 3 and 5 and hours 1 and 3, respectively. In conclusion, the good diffusion of ciprofloxacin into heart tissue warrants its use for the treatment of bacterial endocarditis. On the other hand, low and delayed concentrations in mediastinal fat could limit its value as an antibiotic prophylactic agent in a cardiovascular surgical setting when administered immediately (less than 3 h) before surgery.

Effects of cardiopulmonary bypass surgery on intravenous ciprofloxacin disposition

“…Penetration into mediastinal fat tissue was consistent with those presented in other reports, and ciprofloxacin demonstrated adequate tissue penetration (14,18,22,23). Concentrations of ciprofloxacin in mediastinal fat tissue remained above the MIC for 90% of most pathogenic organisms associated with CPB surgery up to 4.5 h after intravenous administrations of ciprofloxacin (Table 4).…”

“…Among currently available antimicrobial agents, cephalosporins have undergone the most extensive evaluations; however, the dispositions of other antibiotics including gentamicin, netilmicin, and vancomycin have been studied (12,17). To date, investigations with ciprofloxacin have dealt primarily with the determination of tissue penetration and not the effect of CPB on ciprofloxacin disposition (18,22).…”

Pharmacokinetics of Intravenously Administered Levofloxacin in Men and Women

“…It is not surprising that lean body weight was found to be a strong predictor of V ss in men, women, and the combined sexes since fluoroquinolones distribute more rapidly and to a greater extent into lean muscle as opposed to adipose tissue. 2,[25][26][27][28] In fact, this property may in part explain the smaller V c and subsequent larger C max after levofloxacin administration in women compared with these parameters in men. Men on average have an increased amount of body water and an increased muscle mass:body fat ratio compared with women.…”

Sex‐Related Differences in the Pharmacokinetics of Oral Ciprofloxacin

“…Fluoroquinolones distribute rapidly and at increased amounts into lean muscle as opposed to adipose tissue. [26][27][28][29] Furthermore, men in general have an increased amount of body water and an increased muscle mass to body fat ratio compared to women. 6 It is therefore expected that males in the current investigation had the aforementioned body composition differences compared to the females, leading to differences in the tissue volume of distribution.…”