Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial: A Post Hoc Analysis.

Background: The Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial ceased recruitment in July 2018, noting that a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analyzed the long-term outcomes of participants in CAMERA2 to understand the impact of combination antibiotic therapy and AKI. Methods: Trial sites obtained additional follow-up data. The primary outcome was all-cause mortality, censored at death or the date of last known follow-up. Secondary outcomes included kidney failure or a reduction in kidney function (a 40% reduction in estimated glomerular filtration rate to <60 mL/minute/1.73 m2). To determine independent predictors of mortality in this cohort, adjusted hazard ratios were calculated using a Cox proportional hazards regression model. Results: This post hoc analysis included extended follow-up data for 260 patients. Overall, 123 of 260 (47%) of participants died, with a median population survival estimate of 3.4 years (235 deaths per 1000 person-years). Fifty-five patients died within 90 days after CAMERA2 trial randomization; another 68 deaths occurred after day 90. Using univariable Cox proportional hazards regression, mortality was not associated with either the assigned treatment arm in CAMERA2 (hazard ratio [HR], 0.84 [95% confidence interval [CI], .59-1.19]; P = .33) or experiencing an AKI (HR at 1 year, 1.04 [95% CI, .64-1.68]; P = .88). Conclusions: In this cohort of patients hospitalized with methicillin-resistant S aureus bacteremia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality.

Penicillin versus anti-staphylococcal beta-lactams for penicillin-susceptible Staphylococcus aureus blood stream infections: a retrospective cohort study.

The objective of the study is to assess the efficacy and tolerability of penicillins compared to anti-staphylococcal beta-lactams for treatment of penicillin-susceptible Staphylococcus aureus bloodstream infections (PSSA BSI). A retrospective cohort study was conducted of 140 sequential PSSA BSI presenting to a local health district (90 cases included). Penicillin susceptibility was confirmed by disc diffusion, Vitek® and Nitrocefin beta-lactamase methods. Clinical information regarding comorbidities and infection complexity was recorded. Antibiotic choice, dosage and duration were reviewed. Outcomes were compared according to the definitive treatment with either penicillin or ASBLs. The primary outcome was 30-day mortality. Secondary outcomes included renal injury, microbiological relapse and treatment tolerability. Ninety patients met inclusion criteria and were included in subsequent analysis. Of PSSA BSI, 69% were community acquired. Eighty-two percent had complex PSSA infections. The average duration of bacteraemia was 2.8 days (SD = 1.8 days). Sixty-six patients received definitive penicillin treatment, with a mean of 3.5 days of empiric antibiotics prior to penicillin. Twenty-four patients received definitive ASBL treatment (11 cefazolin, 13 flucloxacillin). There was no difference in 30-day mortality between groups (p = 1). There was no difference in renal injury (p > 0.5), hospital length of stay (p = 0.59) or microbiological relapse within 1 year (p = 0.17). Penicillin treatment was well tolerated. Our data supports penicillin as a suitable and well-tolerated alternative to ASBL in managing complex PSSA BSI.

Peritonsillar abscess and concomitant COVID-19 in a 21-year-old male.

Transoral drainage of peritonsillar abscess during the COVID-19 pandemic is a high-risk procedure due to potential aerosolisation of SARS-CoV-2. This case describes conservative management of peritonsillar abscess in a 21-year-old male with COVID-19.

Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal ß-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial.

Importance: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a ß-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. Objective: To determine whether combining an antistaphylococcal ß-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018. Interventions: Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal ß-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the ß-lactam was administered for 7 days. Main Outcomes and Measures: The primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. Results: The data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, -4.2%; 95% CI, -14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, -3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, -8.9%; 95% CI, -16.6% to -1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%). Conclusions and Relevance: Among patients with MRSA bacteremia, addition of an antistaphylococcal ß-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02365493.

Exploring the binding dynamics of etoricoxib with human hemoglobin: A spectroscopic, calorimetric, and molecular modeling approach.

Etoricoxib, widely used for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and related conditions has ample affinity to bind with globular proteins. Here, the molecular interaction between purified human hemoglobin (HHb), a major heme protein and etoricoxib, a cyclooxygenase-2 inhibitor was studied by various spectroscopic, calorimetric, and molecular modeling techniques. The binding affected hypochromic changes in the Soret band of hemoglobin (Hb) and induced remarkable quenching of the intrinsic fluorescence property of protein molecules. Synchronous fluorescence studies revealed alterations in tryptophan (Trp) and tyrosine (Tyr) microenvironments of HHb molecule in presence of etoricoxib. Flouremetric and isothermal titration calorimetric studies suggested two binding sites in HHb for etoricoxib at three different temperatures (298.15, 303.15, and 310.15 K). Negative values of Gibbs energy change (ΔG0) and enthalpy change (ΔH0) strongly suggest that it is spontaneous and exothermic reaction, mainly stabilized by hydrogen bonding as evidenced by sucrose binding assay. These findings support our in silico molecular docking study, which specified the binding site and the non-covalent interactions involved in the association. Moreover, the interaction impacts on structural integrity and functional aspects of HHb as confirmed by decreased α helicity, increased free iron release, increased rate of co-oxidation, and decreased rate of esterase activity. Overall, these studies conclude that etoricoxib leads to a remarkable alteration in the conformational aspects of binding to HHb. Communicated by Ramaswamy H. Sarma.

Buruli ulcer disease in travelers and differentiation of Mycobacterium ulcerans strains from northern Australia.

Buruli ulcer (BU) is a necrotizing infection of skin and soft tissue caused by Mycobacterium ulcerans. In Australia, most cases of BU are linked to temperate, coastal Victoria and tropical, northern Queensland, and strains from these regions are distinguishable by variable-number tandem repeat (VNTR) typing. We present an epidemiological investigation of five patients found to have been infected during interstate travel and describe two nucleotide polymorphisms that differentiate M. ulcerans strains from northern Australia.

Combined cation-exchange and extraction chromatographic method of preconcentration and concomitant separation of bismuth(III) with high molecular mass liquid cation exchanger.

A selective method has been developed for the extraction chromatographic separation of Bi(III) with Versatic 10 coated on silanized silica gel (SSG). Bi(III) has been quantitatively extracted from 0.1 M acetate buffer at the range of pH 5.0-5.5. The result showed that the solution pH, influent volume, flow-rate and solution temperature would affect the sorption of Bi(III). The sorbed Bi(III) was eluted with 0.1 M H(2)SO(4). The extractor system has got good values of exchange capacity (1.42 meq. of H(+) g(-1) of dry exchanger at 25 degrees C), break-through capacity (19.75 mg g(-1) at pH 5.5) and column efficiencies (300) with respect to Bi(III). The positive value of DeltaH (12.63 kJ mol(-1)) and DeltaS (0.271 kJ mol(-1) K(-1)) and negative value of DeltaG (-68.241 kJ mol(-1)) indicated that the sorption process was endothermic, entropy gaining and spontaneous in nature. P.F. has been optimized at 76.4+/-0.3 and the desorption constants K(desorption) (8x10(-3)) and K'(desorption) (1.4x10(-1)) have been determined. R(f) values and selectivity factors for diverse metal ions with respect to that of Bi(III) have been determined by ion-exchange paper chromatography. Bi(III) has been separated from synthetic mixtures containing its congeners and other metal ions associated with it in ores and alloy samples. The method was found effective for removal of Bi(III) from different water samples. A plausible mechanism for the extraction of Bi(III) has been suggested.