BackgroundVancomycin therapeutic drug monitoring (TDM) is based on achieving 24-h area under the concentration–time curve to minimum inhibitory concentration cure breakpoints (AUC24/MIC). Approaches to vancomycin TDM vary, with no head-to-head randomized controlled trial (RCT) comparisons to date.ObjectivesWe aimed to compare clinical and pharmacokinetic outcomes between peak–trough-based and trough-only-based vancomycin TDM approaches and to determine the relationship between vancomycin AUC24/MIC and cure rates.MethodsA multicentered pragmatic parallel-group RCT was conducted in Hamad Medical Corporation hospitals in Qatar. Adult non-dialysis patients initiated on vancomycin were randomized to peak–trough-based or trough-only-based vancomycin TDM. Primary endpoints included vancomycin AUC24/MIC ratio breakpoint for cure and clinical effectiveness (therapeutic cure vs therapeutic failure). Descriptive, inferential, and classification and regression tree (CART) statistical analyses were applied. NONMEM.v.7.3 was used to conduct population pharmacokinetic analyses and AUC24 calculations.ResultsSixty-five patients were enrolled [trough-only-based-TDM (n = 35) and peak–trough-based-TDM (n = 30)]. Peak–trough-based TDM was significantly associated with higher therapeutic cure rates compared to trough-only-based TDM [76.7% vs 48.6%; p value = 0.02]. No statistically significant differences were observed for all-cause mortality, neutropenia, or nephrotoxicity between the two groups. Compared to trough-only-based TDM, peak–trough-based TDM was associated with less vancomycin total daily doses by 12.05 mg/kg/day (p value = 0.027). CART identified creatinine clearance (CLCR), AUC24/MIC, and TDM approach as significant determinants of therapeutic outcomes. All patients [n = 19,100%] with CLCR ≤ 7.85 L/h, AUC24/MIC ≤ 1256, who received peak–trough-based TDM achieved therapeutic cure. AUC24/MIC > 565 was identified to be correlated with cure in trough-only-based TDM recipients [n = 11,84.6%]. No minimum AUC24/MIC breakpoint was detected by CART in the peak–trough-based group.ConclusionMaintenance of target vancomycin exposures and implementation of peak–trough-based vancomycin TDM may improve vancomycin-associated cure rates. Larger scale RCTs are warranted to confirm these findings.

Rabies is a zoonotic disease with the highest fatality rate of any infectious disease. The clinical features of rabies encephalopathy are highly nonspecific at the onset and clinicians from low endemic areas usually face difficulties in recognizing cases during the early stages. The need for establishing a rapid and accurate test to identify rabies during the ante-mortem period is important. However, in actual clinical practice, the latter may remain difficult for various reasons. In human rabies, positively identifying the antigen, antibody or genetic material by various diagnostic methods during the symptomatic period is affected by the unpredictable nature of viremia, levels of antibody immune response of the host, and the virulence of the infecting strain. Also, more advanced testing with greater sensitivity may not be readily available at all centers. Here we describe a case of a young male who was bitten by a rabid dog and developed progressive encephalopathy with a fatal outcome, with negative antibodies in the cerebrospinal fluid (CSF). A review of the literature on the clinical features, diagnostic tests, treatment and prevention of rabies is also presented.

No abstract

Brain abscess is a collection of pus in the parenchyma of brain. Most common infecting organisms are streptococci, staphylococci and anaerobes, depending upon the source from which it originates. Clostridium cadaveris and Clostridium sporogenes are common organisms found in the gastrointestinal tract of humans, rarely producing disease. Few cases of bacteremia and abscesses are reported with these organisms. We hereby report the first case of brain abscess with C cadaveris and C. sporogenes in a young male with good outcome by surgical and medical management. J Microbiol Infect Dis 2019; 9(3):129-132.