Therapeutic drug monitoring of meropenem and pharmacokinetic-pharmacodynamic target assessment in critically ill pediatric patients from a prospective observational study.

OBJECTIVES: To compare the unbound plasma meropenem concentrations at mid-dosing intervals (Cmid, 50%fT), end-dosing intervals (Ctrough, 100%fT), and proportions of patients achieving 50%fT and 100%fT above minimum inhibitory concentration (MIC) (50%fT>MIC and 100%fT>MIC) between extended infusion (EI) and intermittent bolus (IB) administration in a therapeutic drug monitoring (TDM) program in children. METHODS: A prospective observational study was conducted in children aged 1 month to 18 years receiving meropenem every 8 hours by either EI or IB. Meropenem Cmid, Ctrough, and proportions of patients achieving 50%fT>MIC and 100%fT>MIC were compared. RESULTS: TDM data from 72 patients with a median age (interquartile range [IQR]) of 12 months (3-37) were used. Meropenem dose was 120 and 60 mg/kg/day in EI and IB groups, respectively. Geometric mean (95% confidence interval [CI]) Cmid of EI versus IB was 17.3 mg/L (13.7-21.8) versus 3.4 mg/L (1.7-6.7) (P <0.001). Geometric mean (95% CI) Ctrough of EI versus IB was 2.3 mg/L (1.6-3.4) versus 0.8 mg/L (0.4-1.5) (P=0.005). Greater proportions of patients achieving 50%fT>MIC and 100%fT>MIC were observed in the EI group. CONCLUSIONS: A meropenem dose of 20 mg/kg/dose given by IB should not be used in critically ill children, even if they are not suspected of having a central nervous system infection. A dose of 40 mg/kg/dose given by EI resulted in higher Cmid, Ctrough, and proportions of patients achieving 50%fT>MIC and 100%fT>MIC.

Pharmacokinetics and 48-week safety and efficacy of generic ritonavir tablet-boosted atazanavir in HIV-1-infected Thai adults.

BACKGROUND: Ritonavir (RTV) tablets were not available in Thailand until they were manufactured by the Government Pharmaceutical Organization of Thailand. We assessed pharmacokinetics (PK), safety and efficacy of generic RTV-boosted atazanavir (ATV) in virologically suppressed HIV-1-infected Thai adults. METHODS: Virologically suppressed HIV-1-infected Thai adults who currently use ATV (either 200 or 300 mg) with Norvir® soft gel capsule (SGC) 100-mg-based regimen were enrolled into this prospective, 48-week single-arm study. Participants switched from Norvir® SGC to generic RTV. Plasma trough concentration (Ctrough) was assessed at baseline before switching to generic RTV and week 24 in all participants, with the target ATV Ctrough of 0.15 mg/l. Plasma HIV-1 RNA and other laboratory safety parameters were assessed until week 48. RESULTS: Of 100 participants (51% male) enrolled, 50% was using ATV 200 mg and 50% was using 300 mg at the time RTV SGC were changed into generic tablets. All participants used two nucleoside reverse transcriptase inhibitors (NRTIs) as backbone. There were no significant changes in mean (sd) Ctrough of RTV (0.20 [0.33] versus 0.23 [0.39]; P=0.21) and ATV (0.83 [0.93] versus 0.88 [0.95]; P=0.62) between baseline and week 24. From entry to week 48, median alanine aminotransferase significantly increased from 25 to 30 IU/l (P=0.001) and total bilirubin significantly decreased from 1.7 to 1.3 (P=0.04). One study drug related grade 3 adverse event was reported. All but one participant maintained plasma HIV-1 RNA <50 copies/ml after 48 weeks. CONCLUSIONS: Generic RTV-boosted ATV showed adequate levels, good tolerability and great efficacy after 48 weeks.

Real-Life Clinical Practice of Using the Xpert MTB/RIF Assay in Thailand.

BACKGROUND: Delayed diagnosis of tuberculosis (TB) and drug-resistant TB are major challenges of TB control in Thailand. This study assessed the practicality of the Xpert MTB/RIF assay in a real-life setting with high prevalence of human immunodeficiency virus (HIV) infection and pulmonary tuberculosis (PTB). METHODS: This prospective study was conducted at 3 large tertiary care hospitals. Patients who had suspected PTB were enrolled into the study. Expectorated sputum samples were sent for staining, mycobacterial culture, and Xpert MTB/RIF. RESULTS: Four hundred ninety-four patients were enrolled. From 355 cases with final diagnosis of PTB, 263 (71.8%) had definite diagnosis and 92 cases had probable diagnosis. Among TB culture-positive cases, Xpert MTB/RIF had 100% and 81% sensitivity in sputum smear-positive and smear-negative groups, respectively. The specificity was 95.7%. The sensitivity and positive predictive value of Xpert MTB/RIF in culture-negative but clinically diagnosed PTB was 37.8% and 83.8%, respectively. Centrifugation was required in 59% cases with scanty sputum. Five cases were false-positive by Xpert MTB/RIF in patients with nontuberculous mycobacteria, old PTB scar, and immune reconstitution syndrome. Discordant rifampicin susceptibility results of Xpert MTB/RIF and mycobacteria growth indicator tube (MGIT) were confirmed by using rpoB gene sequencing, which raised the sensitivity of Xpert MTB/RIF in detecting rifampicin resistance to 93.8%. CONCLUSIONS: Xpert MTB/RIF is an effective tool in diagnosing PTB but will be more cost-effective for sputum-negative patients and in settings with high prevalence of rifampicin resistance. Early diagnosis of TB results in early treatment and implementation of strategies to limit spreading of TB. Sputum centrifugation may increase the yield of Xpert MTB/RIF.