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Myelosuppression is major treatment-related adverse events of linezolid therapy and result in treatment termination in some cases. We aimed to identify the risk factors for linezolid-induced thrombocytopenia and anemia. We retrospectively retrieved demographic and laboratory data from the medical records of 221 Japanese patients who were undergoing linezolid therapy. Thrombocytopenia and anemia were defined as an unexplained reduction of30% in the patient's platelet count and hemoglobin level, respectively, from the baseline. Thrombocytopenia developed in 48.4% of patients, and anemia developed in 10.4% of patients during linezolid therapy. In multivariate analysis, creatinine clearance (adjusted odds ratio = 0.94 [0.92-0.95], P 0.001), hemodialysis (3.32 [1.14-9.67], P = 0.011), and the duration of linezolid therapy (1.14 [1.07-1.21], P 0.001) were found to be significant risk factors for linezolid-induced thrombocytopenia. Patients with creatinine clearance rates of60 mL/min and those on hemodialysis were found to be at high risk of linezolid-induced thrombocytopenia. In addition, a high incidence of linezolid-induced thrombocytopenia was even detected among the patients that had received linezolid therapy for7 days. As for anemia, the duration of linezolid therapy (1.04 [1.01-1.07], P = 0.011) was shown to be a risk factor for anemia, and a high incidence of anemia was seen among the patients who received linezolid for15 days. In conclusion, we recommend that among patients receiving linezolid therapy the platelet counts of those with risk factors for linezolid-induced thrombocytopenia should be monitored closely throughout treatment, and the hemoglobin levels of patients that receive linezolid for15 days should be carefully monitored on a weekly basis to detect anemia.

We evaluated the drug interaction between Cyclosporine A (CsA) and both fluconazole (FCZ) and clarithromycin (CAM) using absorption profiling monitoring in a renal transplant recipient. The concentrations at 0 hr and 2 hr after the administration were monitored as C0 and C2, respectively.A 53-year-old woman was receiving oral CsA (NeoralTM), methylpredonisolone, and mycophenolate mofetil. Oral FCZ was then added to this regimen for the treatment of oral Candidiasis. The next day, the patients C0/D and C2/D ratios increased 1.6 and 2.4-fold, respectively. Moreover, the CsA clearance decreased by approximately 45%. After altering the administration routes and drug combinations (intravenous FCZ and intravenous CsA, intravenous FCZ and oral CsA), the CsA clearance decreased to 30% of the baseline. These results suggest that FCZ appears to inhibit both the liver and intestinal function by means of the cytochrome P450 system, thereby increasing the bioavailability of CsA. Ten days later, the patient received the concomitant oral administration of CAM for an H. pylori infection. The C0/D and C2/D ratios increased by approximately 3-fold and the CsA clearance decreased by 35%, but these pharmacokinetic parameters normalized within a few days of initiating coadministration. The drug interaction between CsA and CAM may inhibit liver metabolism of CsA. Therefore, the mechanisms responsible for FCZ and CAM interaction with CsA differ.Our findings show that monitoring the C0 and C2 levels was useful in determining the CsA absorption profile, which allowed for a detailed evaluation of drug interaction. Consequently, we were able to adequately control the CsA blood concentration without either graft rejection or any adverse effects.

The fluoroquinolone antibiotic ciprofloxacin has been reported to block delayed rectifier K+ channels at much higher concentrations than those at which it exerts its bactericidal activity. In this study using the halothane-anesthetized guinea pig, we assessed whether ciprofloxacin has a proarrhythmic activity. Ciprofloxacin at a clinically relevant dose of 3 mg/kg, i.v. did not affect any electrocardiographic parameters. At 10 mg/kg, it prolonged the QT interval and the duration of the monophasic action potential of the ventricle under sinus rhythm and constant ventricular pacing (n = 6). The extents of its effects on the ventricular repolarization phase were comparable to those of another fluoroquinolone antibiotic moxifloxacin at a clinically relevant dose of 3 mg/kg (n = 6). Meanwhile, the PR interval and QRS width were also increased by ciprofloxacin at 10 mg/kg, suggesting that the drug inhibited cardiac K+ channels as well as Na+ and Ca2+ channels in vivo. These results suggest that ciprofloxacin exerted a multi-ion channel–blocking action in the heart within the supra-therapeutic dose range. Therefore, careful observation may be necessary for patients with heart disease receiving a higher dose of ciprofloxacin in order to prevent the emergence of resistance. Keywords:: ciprofloxacin, fluoroquinolone antibiotic, QT interval, monophasic action potential

PURPOSE. Infection control is particularly vital in hospitals, and proper use of antimicrobial drugs is one of the most important roles of hospital pharmacists. In this study, we surveyed patients who had been prescribed single-use ciprofloxacin (CPFX), and evaluated the blood concentration of CPFX from the predictive AUC (area under the concentration curve). METHODS. This study was performed retrospectively to 112 adult patients diagnosed as having respiratory infections who had been treated as inpatients with intravenous CPFX for more than 3 days at Toho University Omori Hospital in Tokyo. The predictive AUC of each patient was obtained from the modified formulae reported by Forrest et al. (1993) [1]. The relation between the antimicrobial activity of CPFX and pharmacokinetic/pharmacodynamic (Cmax, AUC and AUC/MIC (minimum inhibitory concentration)) was studied. RESULTS. Although CPFX is excreted from the kidney, standard treatment with this drug does not take renal function into consideration. Our results indicated that CPFX was effective in less than 50% of the patients who received it. Moreover, the AUC/MIC ratio in both the effective group and the failure group was less than 125 when the clinical target was gram-negative bacteria. CONCLUSION. These results suggest that the clinical use of CPFX for the treatment of infectious diseases does not reach the target AUC/MIC ratio, and that the concentration of CPFX is not within the range to which many pathogens are susceptible in a large proportion of patients. To ensure the effective treatment of patients with infectious diseases and to prevent the development of resistance in bacteria, we recommend therapeutic drug monitoring (TDM) of CPFX in hospitals.