Relationship between Target Time above Minimum Inhibitory Concentration Achievement Rate of Meropenem Using Monte Carlo Simulation and In-Hospital Survival in Patients with Pseudomonas aeruginosa Bacteremia.

Pseudomonas aeruginosa bacteremia is associated with a high mortality rate, and meropenem (MEPM) is commonly used to treat it. However, the relationship between the time above the minimum inhibitory concentration (fT>MIC) of MEPM and its therapeutic efficacy in P. aeruginosa bacteremia has not been explored. This study aimed to investigate this relationship by defining the target % fT>MIC of MEPM as 75%. The retrospective study spanned 14 years and included hospitalized patients treated with MEPM for P. aeruginosa bacteremia. Monte Carlo simulation was used to calculate the probability of target attainment (PTA) for each patient, and the threshold for a PTA of 75% fT>MIC associated with in-hospital survival was determined using receiver operating characteristic (ROC) curves. The ROC curve-derived PTA associated with improved in-hospital survival was 65.0%, a significant finding in multivariate logistic regression analysis adjusted for patient background factors (odds ratio: 20.49, 95% confidence interval: 3.02-245.23, p = 0.005). This result suggests a dosing regimen that achieves a PTA of at least 65% when the target fT>MIC of MEPM for treating P. aeruginosa bacteremia is defined as 75%.

Probability of target attainment of oral antimicrobials for Escherichia coli and Klebsiella pneumoniae based on Monte Carlo simulations.

Although early transition from intravenous to oral antimicrobials can reduce hospitalization duration, susceptibility breakpoints have not been established for many oral antimicrobials against Escherichia coli and Klebsiella pneumoniae bacteremia. Thus, we used population pharmacokinetic models, pharmacokinetic/pharmacodynamic indices, and Monte Carlo simulations to evaluate the probability of target attainment (PTA) for common oral antimicrobial dosages against E. coli and K. pneumoniae. The oral antimicrobial agents evaluated included cephalexin, cefaclor, cefditoren, amoxicillin/clavulanic acid, faropenem, and levofloxacin. For E. coli, the percentage of isolates with minimum inhibitory concentrations for which a PTA >90% was achieved was 53% and less than 20% for levofloxacin and the ß-lactams, respectively. For K. pneumoniae, the percentages of isolates for which a PTA >90% was achieved were comparatively higher (cephalexin, 73%; amoxicillin/clavulanic acid, 83%; levofloxacin, 96%). Our results suggest clinicians should check if pharmacokinetic/pharmacodynamic indices are achieved in individual patients before transitioning to oral antimicrobial therapy.

Prediction of Apnea Testing Duration to Ensure Safety During Brain Death Assessment.

BACKGROUND: Apnea testing is the last step of brain death assessment. This study aimed to determine whether apnea testing is safer when performed over a shorter duration. METHODS: The medical records of 200 brain-dead donors were retrospectively evaluated. All the records were anonymously registered in the Japanese Ministry of Health, Labor, and Welfare from 1999 to 2012. The rate of [Formula: see text] increase was analyzed to calculate the duration required for apnea testing. RESULTS: At baseline, body temperature and [Formula: see text] significantly affected the increase rate of [Formula: see text]. At baseline, the apnea testing durations were 4.7 min with normal body temperature and higher [Formula: see text] ([Formula: see text] 40-60 mm Hg, body temperature 36.5°C, [Formula: see text] 400 mm Hg); further, it was 3.0 min with higher body temperature and lower [Formula: see text] at baseline ([Formula: see text] 40-60 mm Hg, body temperature 38.0°C, [Formula: see text] 100 mm Hg). CONCLUSIONS: The specific duration of apnea testing during brain death assessment may be predicted by measuring the increase rate of [Formula: see text].

False Prolongation of Prothrombin Time in the Presence of a High Blood Concentration of Daptomycin.

Prothrombin time (PT) can reportedly be falsely prolonged by the antimicrobial drug daptomycin (DAP), and concomitant use of phosphatidylglycerol (PG). Although high doses of DAP (>6 mg/kg/day) are recommended for severe infection and result in a high blood concentration, the extent to which high blood concentrations of DAP interfere with PT, in the presence or absence of PG, has yet to be determined when using the HemosIL RecombiPlasTin 2G (Werfen Japan, Tokyo, Japan). We examined the effects of high doses of DAP on PT using this reagent. DAP (0-500 mg/L) was added to normal plasma and plasma with an already prolonged PT in the presence or absence of liposomal amphotericin B (L-AMB, 5-50 mg/L) or COATSOME EL-01 empty cationic liposomes (CS, 25-250 mg/L). Furthermore, we undertook a Monte Carlo simulation to calculate the probability of achieving DAP concentrations >100, >200 and >500 mg/L 0-48 hr after administering 6-12 mg/kg of DAP. Apparent PT increased with increasing DAP concentration, but neither L-AMB nor CS appeared to further elevate PT when co-administered with DAP. The probability of achieving DAP concentrations >100 and >200 mg/L increased with DAP dose. Higher doses of DAP than the approved dose caused false prolongation of PT. PT should be monitored carefully in patients taking high doses of DAP; ideally, PT should be measured at the trough blood concentration of DAP. Concomitant use of L-AMB and CS did not generally further elevate PT when co-administered with DAP.