Molecular Characterization of Beta-lactams Resistance in Pseudomonas aeruginosa Isolated from Clinical Sources at the Nairobi Hospital

The increase of Beta-lactamases producing organisms can cause major therapeutic failure and poses a significant clinical challenge in healthcare settings.  A total of 185 clinical isolates of Pseudomonas aeruginosa strains were collected from in-and out-patients at The Nairobi Hospital, 74.1 % were inpatients and 25.9% were outpatients with the high prevalence of this bacterium among the male gender (61.1%) than female(38.9%); and preponderantly comprising the patients above 45 years old (64.3%). The highest numbers of P. aeruginosa were isolated from pus swab (39.5%), respiratory secretions (25.9%), and urine (18.9%). The resistance rate of P. aeruginosa against carbapenem was 31.5% among the isolates. The prevalence of MBL producing P. aeruginosa was 22.7% as compared to non-MBL isolates (77.3%). The MBL isolates were resistant to the examined antibiotics. There were two predominant genes VIM-2 (28.57%) and NDM-1 (66.67%) types among MBL P. aeruginosa, and more prevalent genes were isolated from Critical care nursing ward; Intensive Care Unit (45.2%) and High Dependency Unite (28.6%) at The Nairobi Hospital. These findings suggest that the early detection of   Metallo-Beta-Lactamases-producing isolates and the cooperation between medical professionals and infection control team may help in appropriate antimicrobial therapy and avoid further spread of these multidrug resistance strains. Keywords: Pseudomonas aeruginosa, Metallo-Beta-Lactamases, Resistance, Beta-lactams

The glucose transporter PfHT1 is an antimalarial target of the HIV protease inhibitor lopinavir

Malaria and HIV infection are coendemic in a large portion of the world and remain a major cause of morbidity and mortality. Growing resistance of Plasmodium species to existing therapies has increased the need for new therapeutic approaches. The Plasmodium glucose transporter PfHT is known to be essential for parasite growth and survival. We have previously shown that HIV protease inhibitors (PIs) act as antagonists of mammalian glucose transporters. While the PI lopinavir is known to have antimalarial activity, the mechanism of action is unknown. We report here that lopinavir blocks glucose uptake into isolated malaria parasites at therapeutically relevant drug levels. Malaria parasites depend on a constant supply of glucose as their primary source of energy, and decreasing the available concentration of glucose leads to parasite death. We identified the malarial glucose transporter PfHT as a target for inhibition by lopinavir that leads to parasite death. This discovery provides a mechanistic basis for the antimalarial effect of lopinavir and provides a direct target for novel drug design with utility beyond the HIV-infected population

Renal function and the effects of vericiguat in patients with worsening heart failure with reduced ejection fraction : insights from the VICTORIA (Vericiguat Global Study in Subjects with HFrEF) trial

Aims Vericiguat reduced the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization in patients with worsening HF with reduced ejection fraction (HFrEF) and a lower limit of baseline estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73 m(2). We evaluated the relationship between the efficacy of vericiguat and baseline and subsequent changes in renal function. Methods and results In VICTORIA, core laboratory serum creatinine was measured at baseline (n = 4956) and weeks 16, 32, and 48. Worsening renal function (WRF), defined as an increase >= 0.3 mg/dL in creatinine from baseline to week 16, was assessed via a Cox model with respect to subsequent primary events. Mean age was 69 years, 24% were female, and mean baseline eGFR was 61 mL/min/1.73 m(2). During 48 weeks of treatment, the trajectories in eGFR and creatinine with vericiguat were similar to placebo (P = 0.50 and 0.18). The beneficial effects of vericiguat on the primary outcome were not influenced by baseline eGFR (interaction P = 0.48). WRF occurred in 15% of patients and was associated with worse outcomes (adjusted hazard ratio 1.28, 95% confidence interval 1.11-1.47; P < 0.001), but the beneficial effects of vericiguat on the primary outcome were similar in patients with or without WRF (interaction P = 0.76). Conclusion Renal function trajectories were similar between vericiguat- and placebo-treated patients and the beneficial effects of vericiguat on the primary outcome were consistent across the full range of eGFR and irrespective of WRF.Peer reviewe

A Pilot Online Survey Assessing Risk Factors for HIV Acquisition in the Navy and Marine Corps, 2005-2010

The Department of Defense policy Don\u27t Ask, Don\u27t Tell (DADT) ended in September, 2011. The Navy Bloodborne Infection Management Center conducted a post-DADT pilot survey of HIV seroconverters identified when the DADT policy was in effect. Sailors and Marines newly diagnosed as HIV positive from 2005 to 2010 were invited to participate in an online survey. A structured questionnaire elicited risk information about the 3-year period before HIV diagnosis. Respondents reported engaging commonly in same sex sexual activity, having concurrent partners, and poor condom use for anal sex. In this first post-DADT repeal report of self-reported behaviors, male-to-male sexual contact was a much more common mode of infection than previously reported. Several opportunities for primary prevention messaging now possible after DADT repeal are evident