Surveillance of iclaprim activity: In vitro susceptibility of gram-positive pathogens collected from 2012 to 2014 from the United States,Asia Pacific,Latin American and Europe

Iclaprim is a diaminopyrimidine, which inhibits bacterial dihydrofolate reductase, and it is highly active against Gram-positive pathogens including emerging drug-resistant pathogens. In vitro activity of iclaprim and comparators against 2814 Gram-positive clinical isolates from the United States, Asia Pacific, Latin American and Europe collected between 2012 and 2014 were tested. Susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum inhibitory concentration (MIC) interpretations were based on CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. MIC₅₀/MIC₉₀ for all S. aureus, methicillin susceptible S. aureus, methicillin resistant S. aureus, beta-hemolytic streptococci, and Streptococcus pneumoniae were 0.06/0.12, 0.06/0.12, 0.06/0.5, 0.06/0.25, and 0.06/2 μg/mL, respectively. Iclaprim was 8 to 32-fold more potent than trimethoprim, the only FDA approved dihydrofolate reductase inhibitor, against all Gram-positive isolates including resistant phenotypes. The MIC₉₀ of iclaprim was also lower than most of the comparators including linezolid and vancomycin against Gram-positive pathogens. Iclaprim demonstrated potent activity against a contemporary collection (2012–2014) of Gram-positive clinical isolates from the United States, Asia Pacific, Latin America and Europe.     

A brief review of the management of platinum-resistant–platinum-refractory ovarian cancer

Ovarian cancer, which ranks fifth in cancer deaths among women, is the most lethal gynecologic malignancy. Epithelial ovarian cancer (EOC) is the most common histologic type, with the 5-year survival for all stages estimated at 45.6%. This rate increases to more than 70% in the minority of patients who are diagnosed at an early stage, but declines to 35% in the vast majority of patients diagnosed at advanced stage. Recurrent EOC is incurable. Platinum sensitivity (or lack thereof) is a major determinant of prognosis. The current standard treatment is primary surgery followed by platinum-based chemotherapy. In recurrent platinum-resistant/platinum-refractory EOC, sequential single-agent salvage chemotherapy is superior to multiagent chemotherapy. Multiagent regimens increase toxicity without clear benefit; however, no preferred sequence of single agents is recommended. The impact of targeted therapies and immunotherapies on progression-free survival and overall survival, which remains dismal, is under active investigation. Currently, clinical trials offer the best hope for the development of a new treatment paradigm in this recalcitrant disease.     

Hot Off the Press: Peripheral Intravenous Cannula Insertion and Use in the Emergency Department

This is a prospective before–after study comparing peripheral intravenous cannulation (PIVC) placement and usage rates following a 10‐week‐long multimodal intervention provided to medical and nursing staff working in a tertiary emergency department (ED). The intervention focused on improving appropriate use of PIVCs in an emergency setting by emphasizing to clinicians that a PIVC should only be placed if it was believed there was more than an 80% chance that it would be used. Patients were eligible for the study if they presented to the ED and were >18 years of age. Patients were excluded from the study if they were triage category 1, already had a PIVC placed in an ambulance, or were transferred from another hospital. Among the 4,172 patients included in the analysis, there was a 9.8% reduction in the number of PIVCs inserted (95% confidence interval [CI] = 6.8–12.87) and a 12% increase in PIVC usage (95% CI = 8.7%–17.0%) in the postintervention cohort.     

Cardiac Strain in a Swine Model of Regional Hibernating Myocardium: Effects of CoQ10 on Contractile Reserve Following Bypass Surgery

There is conflicting clinical evidence whether administration of coenzyme Q10 (CoQ10) improves function following coronary artery bypass graft surgery (CABG). Using a swine model of hibernating myocardium, we tested whether daily CoQ10 would improve contractile function by MRI at 4-week post-CABG. Twelve pigs underwent a thoracotomy and had a constrictor placed on the left anterior descending (LAD). At 12 weeks, they underwent off-pump bypass and received daily dietary supplements of either CoQ10 (10 mg/kg/day) or placebo. At 4-week post-CABG, circumferential strain measurements in the hibernating LAD region from placebo and CoQ10 groups were not different and increased to a similar extent with dobutamine (?14.7?±?0.6 versus ?14.8?±?0.1, respectively (NS)). Post-sacrifice, oxidant stress markers were obtained in the mitochondrial isolates and protein carbonyl in the placebo, and CoQ10 groups were 6.14?±?0.36 and 5.05?±?0.32 nmol/mg, respectively (NS). In summary, CoQ10 did not improve contractile reserve or reduce oxidant stress at 4-week post-CABG.     

Performance of a novel real-time respirator seal integrity monitor on firefighters: Simulated workplace pilot study

Millions of workers, including firefighters, use respiratory protective device. The key aspect in assuring the intended protection level of a respirator is its fit. However, even if the respirator originally fits well, the faceseal may be breached during its use. Until now, there have been no practically viable, inexpensive means to monitor the performance of a respirator during actual use. A novel Respirator Seal Integrity Monitor (ReSIM) was developed and recently evaluated on manikins by our team. The objective of this study was to evaluate the ReSIM effectiveness on respirator-wearing firefighters exposed to aerosols while performing simulated routine operational activities. Initially, 15 subjects were recruited for the study. Following a preliminary investigation that resulted in modifications in the ReSIM prototype and testing protocol, a subset of nine firefighters was chosen for a full-scale evaluation. The testing was conducted in a 24.3-m³ exposure chamber using NaCl as the challenge aerosol. Controlled faceseal leaks were established by opening a solenoid valve for 10, 15, or 20?sec. Leaks were also established as the tested firefighter slightly repositioned the respirator on his/her face. During the testing, the ReSIM measured particles inside a full-face elastomeric respirator with a 72.7% leak detection sensitivity (probability of correct leak identification) and an 84.2% specificity (probability of correct identification of the intervals which are absent of any leak). After adjusting for false negatives and persistent false positives, sensitivity and specificity increased to 83.6% and 92.2%, respectively. The factors causing minor limitations in leak detection sensitivity and specificity can be attributed to variability among subjects, moisture’s effect on the particle sensor, and some in-mask sampling bias. In conclusion, the ReSIM can promptly detect the breach in a respirator faceseal with high sensitivity and specificity. Due to its capability to alert the wearer of possible overexposure to hazardous aerosols, the ReSIM concept has a remarkable potential to be applied in various working environments, where respirators are used.     

Cervicovaginal shedding of hepatitis C viral RNA is associated with the presence of menstrual or other blood in cervicovaginal fluids

BackgroundThe role of sexual activity in hepatitis C virus (HCV) transmission remains controversial. Studies to date have not explored the relationship between HCV shedding in cervicovaginal fluids and the presence of menstrual or other blood.ObjectivesSince cross-sectional studies may underestimate the prevalence of viral shedding, we performed a 56-day longitudinal study of cervical HCV shedding.Study designWomen self-collected cervicovaginal swabs for 56 consecutive days, while keeping a diary of menses and genital symptoms. Swabs were tested for HCV RNA and cellular DNA by quantitative PCR, and hemoglobin by spectrophotometry.ResultsSixteen women contributed a total of 701 cervicovaginal swabs (mean collection period 48 days, range 18–56). Detection of HCV RNA was associated with detection of hemoglobin. Premenopausal women were more likely than post-menopausal women to have HCV RNA detected in cervicovaginal fluids. For premenopausal women, detection of HCV RNA was more likely during menstruation (OR = 56.4) or when hemoglobin was detected in cervicovaginal fluids, even if menstruation was not occurring (OR = 35.4). No woman post-hysterectomy had HCV RNA detected in cervicovaginal fluids on any day, regardless of whether hemoglobin was detected.ConclusionsOur findings are consistent with a low likelihood of sexual transmission of HCV. The results suggest that shedding of HCV RNA in the female genital tract is associated with the presence of blood, and requires the presence of a cervix. Clinicians should consider advising premenopausal women who are concerned about transmitting infection that infectivity may increase during menstruation.