Micafungin does not influence the concentration of tacrolimus in patients after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Tacrolimus is commonly used in stem cell transplant recipients for prophylaxis of graft-vs-host disease. Micafungin is widely used as a strong antifungal agent in empirical therapy in patients with febrile neutropenia. Both tacrolimus and micafungin are substrates of cytochrome P450 3A4 in vitro. Therefore, there is risk of drug interaction with concomitant administration of these drugs. OBJECTIVE: To estimate the drug interaction of tacrolimus and micafungin by evaluating the pharmacokinetics in 6 patients who had undergone allogeneic stem cell transplantation. RESULTS: The mean (SD) concentration-dose ratio of tacrolimus in all patients at 1, 4, 8, and 24 hours after concomitant administration of micafungin was 607 ± 306, 653 ± 328, 699 ± 340 and 671 ± 403 (ng/mL)/(mg/kg/d), respectively, and without micafungin was 756 ± 314 (ng/mL)/(mg/kg/d). The percentage of the concentration-dose ratio in patients treated with tacrolimus and micafungin vs patients treated with tacrolimus alone was 98%, 105%, 112%, and 108% at 1, 4, 8, and 24 hours, respectively. For both tacrolimus and micafungin, the 90% confidence intervals for the primary pharmacokinetic parameters (ie, the concentration-dose ratio at each point) ranged from 80% to 125%. CONCLUSION: We conclude that there is no drug interaction between tacrolimus and concomitantly administered micafungin in stem cell transplantation recipients.

Problems associated with prophylactic use of erythromycin in 1566 staff to prevent hospital infection during the outbreak of pertussis.

BACKGROUND AND OBJECTIVE: Pertussis developed in Kagawa University Medical School and University Hospital in May 2007. To control the outbreak and prevent the infection of hospital inpatients, the Infection Control Team (ICT) carried out the prophylactic administration of erythromycin (EM) to hospital staff (1566 staff) who might be exposed to Bordetella pertussis. METHODS: An oral dose of 1000 mg/day EM was given for 10 days. To assess compliance and estimate the frequency of adverse effect, the ICT conducted a questionnaire survey. RESULTS AND DISCUSSION: Of 942 respondents (response rate: 60.2%), 264 (28.0%) experienced some form of EM adverse effects, of which the most commonly reported involved digestive organ symptoms, e.g. diarrhoea (15.6%), stomachache (7.5%), nausea (3.6%), epigastric distress (2.1%) and abdominal distention (1.8%). More importantly, 246 participants (26.1%) stopped taking the EM before completing 10 days because of perceived adverse effects. CONCLUSION: These results indicate that EM appears to cause adverse effects more frequently than reported in the package insert in Japan. The prophylactic use of EM for pertussis infection is recognized in the guideline of the Centers for Disease Control and Prevention. However, this study suggests that attention should be paid to EM non-compliance during a pertussis outbreak, which could extend the duration of the outbreak and increase the number of affected patients.

Recommended dose of arbekacin, an aminoglycoside against methicillin-resistant Staphylococcus aureus, does not achieve desired serum concentration in critically ill patients with lowered creatinine clearance.

OBJECTIVE: To define the pharmacokinetics of arbekacin (ABK), an aminoglycoside, in patients with acutely lowered renal function. METHODS: We measured the serum concentrations of ABK, using fluorescence polarization immunoassay, in 10 critically ill patients (patient group) and six healthy volunteers (control group). Data were analysed with a two-compartment model and parameters were estimated by the Bayesian method. The Mann-Whitney U-test or chi-squared test was used as appropriate (P < 0.05). RESULTS: Creatinine clearance (CCR), measured or estimated using Cockcroft and Gault's formula of the patient group (CCR: 58 +/- 13 mL/min), was significantly lower than that of the control group (CCR: 99 +/- 8 mL/min). However, despite the low CCR, even the maintenance ABK dosage for normal CCR did not elevate the highest serum level (C(max)) to the effective range in the patient group. Although the ABK clearance (CL) did not differ between the groups, the patients' distribution volume (V(d)) increased significantly compared with the control. The transfer rate constant from central to peripheral compartment (k(12)) in the patient group was much higher than that in the control. CONCLUSION: In critically ill patients with lowered CCR, the ABK dose for normal CCR subjects does not elevate its serum concentration to effective levels because of augmented V(d) caused by increased k(12). The present results hypothesize that adjustment of antibiotic dosing according to CCR further lowers C(max) in critically ill patients with reduced CCR.

[Evaluation of specificity of EIA kit (ED-007)].

EIA (Eitest: Eisai) and Gelatin Particle Agglutination: PA (SERODIA: Fujirebio) assays were performed for the detection of HTLV-I antibodies with 10,780 sera from patients since 1986. Eleven point five percent were reactive by both EIA and PA, while 1.1% was PA(+), EIA(-), these PA false positive occurred on low titer. Conversely 0.2% on EIA positive seems PA false negative because of Western blot (WB) positivity. Zero point nine percent was EIA(+), PA(-), of these 80.6% were not inhibited by EIA confirmatory test. The main cause of EIA false positive was due to reactivity of auto antibody with MT-2 cell lysate. We used new EIA (ED-007: Eisai) coated with HTLV-I antigen purified from supernatant of culture medium of MT-2 cell. The results completely matched with EIA confirmatory test and WB. Cut off index value of sera from SLE patients were down to 0.2 (mean +/- SD) from 0.7 +/- 0.4 of Eitest ATL. EIA (ED-007) are probably useful and more specific assays for the detection of HTLV-I antibodies, especially, the sera of patients with autoimmune diseases.