Analysis of COVID-19 waste management in Vietnam and recommendations to adapt to the 'new normal' period.

Amid the 4th wave of COVID-19, Vietnam reopened its economy, which placed extra burdens on the COVID-19 waste management system. This study analyzed existing issues and recommended adaptations to secure appropriate management of COVID-19 waste under the 'new normal' pandemic period. Results showed changes in COVID-19 waste characteristics (e.g., rapid rise in waste generation, lower percentage of plastic) and multiple other issues (e.g., presence of COVID-19 waste in municipal waste, lack of temporary storage sites and local treatment capacity), along with greater waste-handling responsibilities placed on authorities and higher infection risks. To adapt to the 'new normal', introduction of separate handling routes and collaboration in waste treatment were recommended. Employing the network of pharmacies used for vaccination would require COVID-19 waste collection from scattered, small-scale sources as part of the waste management solution. Also, following the 4R initiatives (reduce, reuse, recycle, recovery) could help ease the burden on the country's waste system and provide additional opportunities to move towards a circular economy in the post-acute COVID-19 era. The findings should contribute to a safer co-existence with the virus through appropriate waste management in Vietnam and could be used to tackle waste problems in other developing countries. Supplementary Information: The online version contains supplementary material available at 10.1007/s10163-022-01563-x.

Capacity assessment to secure COVID-19 waste treatment in Vietnam.

The accelerated generation of COVID-19 waste under the Delta-fuelled outbreak placed a sudden burden on waste disposal in Vietnam. To secure the treatment of COVID-19 waste amid the pandemic uncertainty, treatment capacity was assessed by determining treatment occupancy rate-the ratio of estimated demand to calculated capacity-both nationally and in Ho Chi Minh City. At the general occupancy rate for COVID-19 waste treatment of 7.4%, the country was capable of handling COVID-19 waste, with a capacity to treat 62 191 t month-1. However, Ho Chi Minh City became overwhelmed, indicated by a treatment occupancy rate of up to 780% during the Delta outbreak, as the unanticipated growth of demand for COVID-19 waste treatment caused waste to back up. The assessment results, in addition to current legislation, support collaboration in waste treatment as a solution to using existing resources to address the acute shortage of treatment capacity, so as to secure COVID-19 waste treatment. The findings could be used by other developing countries to tackle the waste problem in the pandemic era. Supplementary Information: The online version contains supplementary material available at 10.1007/s10163-022-01529-z.

Balloon Angioplasty with or without Stenting for Acute Intracranial Atherothrombosis.

Objectives: Due to limited evidence on the optimal strategy for acute atherothrombosis in a large intracranial vessel, we aimed to provide further evidence on the safety and efficacy of balloon angioplasty with or without stenting after failed thrombectomy. Materials & Methods: This single-center retrospective study was performed from June 2017 to February 2021. Patients with acute atherothrombosis in large intracranial vessels treated by balloon angioplasty with or without stenting after failed thrombectomy were enrolled and analyzed. Results: A total of 23 patients were recruited. All patients had a moderate stroke and the majority of them had ASPECTS ≥7 (82.6%). MCA was the most commonly affected artery (13 cases), followed by supraclinoid ICA (6 cases), and BA (4 cases). Balloon angioplasty was firstly performed in 15 cases, of which 8 cases required subsequent stenting. Intracranial stenting was firstly performed in 8 cases. Success-ful recanalization (TICI 2b-3) was achieved in 19/23 cases (82.6%) on the final angiogram. Perforated complications occurred in 1/23 cases (4.3%). Good outcome (mRS 0-2) at 90 days was achieved in 13/23 cases (56.5%) and the mortality rate was 4/23 cases (17.4%). The good clinical outcome rate was significantly higher in patients adapted with balloon angioplasty alone versus intracranial stenting. Conclusions: In the present study, balloon angioplasty with or without stenting was obsversed to be safe and efficient as a rescue therapy after failed thrombectomy for acute atherothrombosis in a large intracranial vessel. Balloon angioplasty should be the first choice and stenting should be performed later in refractory cases.

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

Astroblastomas (ABs) are rare brain tumors of unknown origin. We performed an integrative genetic and epigenetic analysis of AB-like tumors. Here, we show that tumors traceable to neural stem/progenitor cells (radial glia) that emerge during early to later brain development occur in children and young adults, respectively. Tumors with MN1-BEND2 fusion appear to present exclusively in females and exhibit overexpression of genes expressed prior to 25 post-conception weeks (pcw), including genes enriched in early ventricular zone radial glia and ependymal tumors. Other, histologically classic ABs overexpress or harbor mutations of mitogen-activated protein kinase pathway genes, outer and truncated radial glia genes, and genes expressed after 25 pcw, including neuronal and astrocyte markers. Findings support that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors. Selective gene fusion, variable imprinting and/or chromosome X-inactivation escape resulting in biallelic overexpression may contribute to female predominance of AB molecular subtypes.

Multicenter Cohort Study of Ceftaroline Versus Daptomycin for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection.

BACKGROUND: Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin. METHODS: Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied. RESULTS: Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, -5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = .034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = .001). CONCLUSIONS: No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required.

Do biologic therapies reduce aortic inflammation in rheumatoid arthritis patients?

OBJECTIVES: Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD). In the present study, we evaluated the inflammatory activity of the ascending aorta in RA patients who received biological treatment. METHODS: We assessed the aortic wall inflammation of RA patients using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography before and after 6 months of biologic therapies. We also compared the inflammatory activity at the aortic wall in RA patients with remission or low disease activity (RLDA) and those with moderate or high disease activity (MHDA). The aortic uptake was measured by the standardized uptake value (SUV) and the target-to-background ratio (TBR). RESULTS: A total of 64 patients were included in the analysis (mean age, 58.4 ± 13.8 years old; female, 77%). The Disease Activity Score for 28 joints (DAS28) erythrocyte sedimentation rate (ESR) had significantly decreased after 6 months: from 5.0 ± 1.2 to 3.3 ± 1.2 (p < 0.001). The FDG uptake in the ascending aorta changed from baseline to 6 months, showing a maximum SUV (SUVmax) of 1.83 ± 0.34 to 1.90 ± 0.34 (p = 0.059) and TBR of 1.71 ± 0.23 to 1.75 ± 0.24 (p = 0.222). The SUVmax and TBR after 6 months were significantly higher in the RLDA group than in the MHDA group (2.05 ± 0.32 vs. 1.79 ± 0.33 (p = 0.002) and 1.89 ± 0.33 vs. 1.65 ± 0.20 (p = 0.001), respectively). The percentage of monocytes also significantly increased from baseline to 6 months: from 5.9 ± 1.6 to 6.9 ± 2.6 (p = 0.032). CONCLUSION: The inflammation activity at the ascending aorta in RA patients did not change significantly after 6 months of biological treatment. RA patients with a low disease activity or in clinical remission after 6 months of biological treatment still had an increased inflammatory activity at the aortic wall.

Standardized Treatment and Assessment Pathway Improves Mortality in Adults With Methicillin-resistant Staphylococcus aureus Bacteremia: STAPH Study.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) management remains challenging for clinicians. Numerous in vitro studies report synergy when vancomycin (VAN) and daptomycin (DAP) are combined with beta-lactams (BLs), which has led to clinical implementation of these combinations. While shorter durations of bacteremia have often been reported, there has been no significant impact on mortality. METHODS: The Detroit Medical Center (DMC) developed and implemented a clinical pathway algorithm for MRSA BSI treatment in 2016 that included the early use of BL combination therapy with standard of care (VAN or DAP) and a mandatory Infectious Diseases consultation. This was a retrospective, quasi-experimental study at the DMC between 2013 and 2020. Multivariable logistic regression was used to assess the independent association between pathway implementation and 30-day mortality while adjusting for confounding variables. RESULTS: Overall, 813 adult patients treated for MRSA BSI were evaluated. Compared with prepathway (PRE) patients (n = 379), those treated postpathway (POST; n = 434) had a significant reduction in 30-day and 90-day mortality: 9.7% in POST vs 15.6% in PRE (P = .011) and 12.2% in POST vs 19.0% in PRE (P = .007), respectively.The incidence of acute kidney injury (AKI) was higher in the PRE compared with the POST group: 9.6% vs 7.2% (P = .282), respectively. After adjusting for confounding variables including Infectious Diseases consult, POST was independently associated with a reduction in 30-day mortality (adjusted odds ratio [aOR], 0.608; 95% CI, 0.375-0.986). CONCLUSIONS: Implementation of an MRSA BSI treatment pathway with early use of BL reduced mortality with no increased rate of AKI. Further prospective evaluation of this pathway approach is warranted.

Reductions in vancomycin and meropenem following the implementation of a febrile neutropenia management algorithm in hospitalized adults: An interrupted time series analysis.

OBJECTIVE: To evaluate broad-spectrum intravenous antibiotic use before and after the implementation of a revised febrile neutropenia management algorithm in a population of adults with hematologic malignancies. DESIGN: Quasi-experimental study. SETTING AND POPULATION: Patients admitted between 2014 and 2018 to the Adult Malignant Hematology service of an acute-care hospital in the United States. METHODS: Aggregate data for adult malignant hematology service were obtained for population-level antibiotic use: days of therapy (DOT), C. difficile infections, bacterial bloodstream infections, intensive care unit (ICU) length of stay, and in-hospital mortality. All rates are reported per 1,000 patient days before the implementation of an febrile neutropenia management algorithm (July 2014-May 2016) and after the intervention (June 2016-December 2018). These data were compared using interrupted time series analysis. RESULTS: In total, 2,014 patients comprised 6,788 encounters and 89,612 patient days during the study period. Broad-spectrum intravenous (IV) antibiotic use decreased by 5.7% with immediate reductions in meropenem and vancomycin use by 22 (P = .02) and 15 (P = .001) DOT per 1,000 patient days, respectively. Bacterial bloodstream infection rates significantly increased following algorithm implementation. No differences were observed in the use of other antibiotics or safety outcomes including C. difficile infection, ICU length of stay, and in-hospital mortality. CONCLUSIONS: Reductions in vancomycin and meropenem were observed following the implementation of a more stringent febrile neutropenia management algorithm, without evidence of adverse outcomes. Successful implementation occurred through a collaborative effort and continues to be a core reinforcement strategy at our institution. Future studies evaluating patient-level data may identify further stewardship opportunities in this population.

Bennu's near-Earth lifetime of 1.75 million years inferred from craters on its boulders.

An asteroid's history is determined in large part by its strength against collisions with other objects1,2 (impact strength). Laboratory experiments on centimetre-scale meteorites3 have been extrapolated and buttressed with numerical simulations to derive the impact strength at the asteroid scale4,5. In situ evidence of impacts on boulders on airless planetary bodies has come from Apollo lunar samples6 and images of the asteroid (25143) Itokawa7. It has not yet been possible, however, to assess directly the impact strength, and thus the absolute surface age, of the boulders that constitute the building blocks of a rubble-pile asteroid. Here we report an analysis of the size and depth of craters observed on boulders on the asteroid (101955) Bennu. We show that the impact strength of metre-sized boulders is 0.44 to 1.7 megapascals, which is low compared to that of solid terrestrial materials. We infer that Bennu's metre-sized boulders record its history of impact by millimetre- to centimetre-scale objects in near-Earth space. We conclude that this population of near-Earth impactors has a size frequency distribution similar to that of metre-scale bolides and originates from the asteroidal population. Our results indicate that Bennu has been dynamically decoupled from the main asteroid belt for 1.75 ± 0.75 million years.

Corrigendum to: The Impact of Concomitant Empiric Cefepime on Patient Outcomes of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections Treated With Vancomycin.

[This corrects the article DOI: 10.1093/ofid/ofz079.].

Monotherapy with Vancomycin or Daptomycin versus Combination Therapy with ß-Lactams in the Treatment of Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections: A Retrospective Cohort Analysis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with high morbidity and mortality. More in vitro, in vivo, and clinical data suggest that vancomycin (VAN) or daptomycin (DAP) combination therapy with ß-lactams (BL) improves outcomes of MRSA infections. We hypothesize that BL combination with VAN or DAP would reduce the odds of clinical failure compared to VAN or DAP monotherapy. METHODS: A retrospective cohort study of adult patients ≥ 18 years treated with VAN or DAP for MRSA BSI from 2006 to 2019 at Detroit Medical Center. Combination therapy (CT) was defined as VAN or DAP plus any BL for ≥ 24 h within 72 h of index culture. Monotherapy (MT) was defined as ≥ 72 h VAN or DAP within 72 h of index culture and no BL for ≥ 24 h up to 7 days following VAN/DAP initiation. Primary outcome was composite endpoint of clinical failure defined as: (1) 30-day mortality, (2) 60-day recurrence, or (3) persistent bacteremia (PB). PB was defined as bacteremia > 5 days. Multivariable logistic regression was used to evaluate the association between CT and the primary outcome. RESULTS: Overall, 597 patients were included in this analysis, 153 in the MT group and 444 in the CT group. CT was independently associated with reduced odds of clinical failure (adjusted odds ratio, 0.523; 95% confidence interval, 0.348-0.787). The composite endpoint was driven by 60-day recurrence and PB but not 30-day mortality. There were no difference in adverse events including nephrotoxicity between the two study arms. CONCLUSIONS: In hospitalized adults with MRSA BSI, CT with any BL was independently associated with improved clinical outcomes and may ultimately be selected as preferred therapy.

Evaluation of the INCREMENT-CPE, Pitt Bacteremia and qPitt Scores in Patients with Carbapenem-Resistant Enterobacteriaceae Infections Treated with Ceftazidime-Avibactam.

BACKGROUND: The aim of this study was to evaluate the predictive performance of the INCREMENT-CPE (ICS), Pitt bacteremia score (PBS) and qPitt for mortality among patients treated with ceftazidime-avibactam for carbapenem-resistant Enterobacteriaceae (CRE) infections. METHODS: Retrospective, multicenter, cohort study of patients with CRE infections treated with ceftazidime-avibactam between 2015 and 2019. The primary outcome was 30-day all-cause mortality. Predictive performance was determined by assessing discrimination, calibration and precision. RESULTS: In total, 109 patients were included. Thirty-day mortality occurred in 18 (16.5%) patients. There were no significant differences in discrimination of the three scores [area under the curve (AUC) ICS 0.7039, 95% CI 0.5848-0.8230, PBS 0.6893, 95% CI 0.5709-0.8076, and qPitt 0.6847, 95% CI 0.5671-0.8023; P > 0.05 all pairwise comparisons]. All scores showed adequate calibration and precision. When dichotomized at the optimal cut-points of 11, 3, and 2 for the ICS, PBS, and qPitt, respectively, all scores had NPV > 90% at the expense of low PPV. Patients in the high-risk groups had a relative risk for mortality of 3.184 (95% CI 1.35-8.930), 3.068 (95% CI 1.094-8.606), and 2.850 (95% CI 1.016-7.994) for the dichotomized ICS, PBS, and qPitt, scores respectively. Treatment-related variables (early active antibiotic therapy, combination antibiotics and renal ceftazidime-avibactam dose adjustment) were not associated with mortality after controlling for the risk scores. CONCLUSIONS: In patients treated with ceftazidime-avibactam for CRE infections, mortality risk scores demonstrated variable performance. Modifications to scoring systems to more accurately predict outcomes in the era of novel antibiotics are warranted.

Real-World Experience with Ceftolozane-Tazobactam for Multidrug-Resistant Gram-Negative Bacterial Infections.

Our objective was to describe the prescribing practices, clinical characteristics, and outcomes of patients treated with ceftolozane-tazobactam (C/T) for multidrug-resistant (MDR) Gram-negative infections. This was a multicenter, retrospective, cohort study at eight U.S. medical centers (2015 to 2019). Inclusion criteria were age ≥18 years and receipt of C/T (≥72 hours) for suspected or confirmed MDR Gram-negative infection. The primary efficacy outcome, evaluated among patients with MDR Pseudomonas aeruginosa infections, was composite clinical failure, namely, 30-day all-cause mortality, 30-day recurrence, and/or failure to resolve or improve infection signs or symptoms after C/T treatment. In total, 259 patients were included, and P. aeruginosa was isolated in 236 (91.1%). The MDR and extremely drug-resistant phenotypes were detected in 95.8% and 37.7% of P. aeruginosa isolates, respectively. The most common infection source was the respiratory tract (62.9%). High-dose C/T was used in 71.2% of patients with a respiratory tract infection (RTI) overall but in only 39.6% of patients with an RTI who required C/T renal dose adjustment. In the primary efficacy population (n = 226), clinical failure and 30-day mortality occurred in 85 (37.6%) and 39 (17.3%) patients, respectively. New C/T MDR P. aeruginosa resistance was detected in 3 of 31 patients (9.7%) with follow-up cultures. Hospital-acquired infection and Acute Physiological and Chronic Health Evaluation II (APACHE II) score were independently associated with clinical failure (adjusted odds ratio [aOR], 2.472 and 95% confidence interval [CI], 1.322 to 4.625; and aOR, 1.068 and 95% CI, 1.031 to 1.106, respectively). Twenty-five (9.7%) patients experienced ≥1 adverse effect (9 acute kidney injury, 13 Clostridioides difficile infection, 1 hepatotoxicity, 2 encephalopathy, and 2 gastrointestinal intolerance). C/T addresses an unmet medical need in patients with MDR Gram-negative infections.

Daptomycin Plus ß-Lactam Combination Therapy for Methicillin-resistant Staphylococcus aureus Bloodstream Infections: A Retrospective, Comparative Cohort Study.

BACKGROUND: Mounting evidence suggests the addition of a ß-lactam (BL) to daptomycin (DAP) results in synergistic in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and bolsters the innate immune response to infection. This study's objective was to provide clinical translation to these experimental data and determine if DAP+BL combination therapy results in improved clinical outcomes compared with treatment with DAP alone in patients with MRSA bloodstream infections (BSIs). METHODS: This was a retrospective, comparative cohort study conducted at 2 academic medical centers between 2008 and 2018. Adults with MRSA BSI treated with DAP for ≥72 hours and initiated ≤5 days of culture collection were included. Patients who received a BL for ≥24 hours and initiated ≤24 hours of DAP comprised the DAP+BL group. The primary outcome was composite clinical failure (60-day all-cause mortality and/or 60-day recurrence). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). RESULTS: A total of 229 patients were included (72 DAP+BL and 157 DAP). In unadjusted and IPTW-adjusted analyses, DAP+BL was associated with significantly reduced odds of clinical failure (odds ratio [OR], 0.362; 95% confidence interval [CI], .164-.801; adjusted OR, 0.386; 95% CI, .175-.853). Adjusted analyses restricted to prespecified subgroups based on infection complexity and baseline health status were consistent with the main analysis. CONCLUSIONS: The addition of a BL to DAP was associated with improved clinical outcomes in patients with MRSA BSI. This study provides support to ongoing and future studies evaluating the impact of combination therapy for invasive MRSA infections.Patients treated with daptomycin plus a ß-lactam for MRSA bloodstream infection had lower odds of composite clinical failure defined as 60-day all-cause mortality and/or 60-day recurrence compared with patients treated with daptomycin monotherapy after adjusting for confounding variables using inverse probability of treatment weighting.

Parenteral Fosfomycin for the Treatment of Multidrug Resistant Bacterial Infections: The Rise of the Epoxide.

Fosfomycin was initially discovered in 1969 but has recently gained renewed interest for the treatment of multidrug-resistant (MDR) bacterial infections, particularly in the United States. Its unique mechanism of action, bactericidal activity, broad spectrum of activity, and relatively safe and tolerable adverse effect profile make it a great addition to the dwindling antibiotic armamentarium. Fosfomycin contains a three-membered epoxide ring with a direct carbon to phosphorous bond that bypasses the intermediate oxygen bond commonly present in other organophosphorous compounds; this structure makes the agent unique from other antibiotics. Despite nearly 50 years of parenteral fosfomycin use in Europe, fosfomycin has retained stable activity against most pathogens. Furthermore, fosfomycin demonstrated in vitro synergy in combination with other cell wall-active antibiotics (e.g., ß-lactams, daptomycin). These combinations may offer respite for severe infections due to MDR gram-positive and gram-negative bacteria. The intravenous (IV) formulation is currently under review in the United States, and apropos, this review collates more contemporary evidence (i.e., studies published between 2000 and early 2019) in anticipation of this development. The approval of IV fosfomycin provides another option for consideration in the management of MDR infections. Its unique structure will give rise to a promising epoxide epoch in the battle against MDR bacteria.

The Impact of Concomitant Empiric Cefepime on Patient Outcomes of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections Treated With Vancomycin.

Background: Data suggest that vancomycin + ß-lactam combinations improve the clearance of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs). However, it is unclear which specific ß-lactams confer benefit. This analysis evaluates the impact of concomitant empiric cefepime on outcomes of MRSA BSIs treated with vancomycin. Methods: This was a multicenter, retrospective cohort study of adults with MRSA BSIs from 2006 to 2017. Vancomycin + cefepime therapy was defined as ≥24 hours of cefepime during the first 72 hours of vancomycin. The primary outcome was microbiologic failure, defined as BSI duration ≥7 days and/or 60-day recurrence. Multivariable logistic regression was used to evaluate the association between vancomycin + cefepime therapy and binary outcomes. Cause-specific and subdistribution hazard models were used to evaluate the association between vancomycin + cefepime and BSI clearance. Results: Three hundred fifty-eight patients were included, 129 vancomycin and 229 vancomycin + cefepime. Vancomycin + cefepime therapy was independently associated with reduced microbiologic failure (adjusted odds ratio [aOR], 0.488; 95% confidence interval [CI], 0.271-0.741). This was driven by a reduction in BSI duration ≥7 days (vancomycin + cefepime aOR, 0.354; 95% CI, 0.202-0.621). Vancomycin + cefepime had no association with 30-day mortality (aOR, 0.952; 95% CI, 0.435-2.425). Vancomycin + cefepime was associated with faster BSI clearance in both cause-specific (hazard ratio [HR], 1.408; 95% CI, 1.125-1.762) and subdistribution hazard models (HR, 1.264; 95% CI, 1.040-1.536). Conclusions: Concomitant empiric cefepime improved MRSA BSI clearance and may be useful as the ß-lactam component of synergistic vancomycin + ß-lactam regimens when empiric or directed gram-negative coverage is desired.

The Impact of Concomitant Empiric Cefepime on Patient Outcomes of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections Treated With Vancomycin.

BACKGROUND: Data suggest that vancomycin + ß-lactam combinations improve clearance of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs). However, it is unclear which specific ß-lactams confer benefit. This analysis evaluates the impact of concomitant empiric cefepime on outcomes of MRSA BSIs treated with vancomycin. METHODS: Retrospective cohort study of adults with MRSA BSI from 2006 to 2017. Vancomycin + cefepime therapy was defined as ≥24 hours of cefepime during the first 72 hours of vancomycin. The primary outcome was microbiologic failure, defined as BSI duration ≥7 days and/or 60-day recurrence. Multivariable logistic regression was used to evaluate the association between vancomycin + cefepime therapy and binary outcomes. Cause-specific and subdistribution hazard models were used to evaluate the association between vancomycin + cefepime and BSI clearance. RESULTS: Three hundred fifty-eight patients were included, 129 vancomycin and 229 vancomycin + cefepime. Vancomycin + cefepime therapy was independently associated with reduced microbiologic failure (adjusted odds ratio [aOR], 0.488; 95% confidence interval [CI], 0.271-0.741). This was driven by a reduction in the incidence of BSI durations ≥7 days (vancomycin + cefepime aOR, 0.354; 95% CI, 0.202-0.621). Vancomycin + cefepime had no association with 30-day mortality (aOR, 0.952; 95% CI, 0.435-2.425). Vancomycin + cefepime was associated with faster BSI clearance in both cause-specific (HR, 1.408; 95% CI, 1.125-1.762) and subdistribution hazard models (HR, 1.264; 95% CI, 1.040-1.536). CONCLUSIONS: Concomitant empiric cefepime improved MRSA BSI clearance and may be useful as the ß-lactam component of synergistic vancomycin + ß-lactam regimens when empiric or directed gram-negative coverage is desired.

Open-Label Randomized Trial of Early Clinical Outcomes of Ceftaroline Fosamil Versus Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections at Risk of Methicillin-Resistant Staphylococcus aureus.

INTRODUCTION: Acute bacterial skin and skin structure infections (ABSSSIs) remain among the most common infectious processes seen in the clinical setting. For patients with complicated ABSSSIs deemed to require intravenous antibiotics, vancomycin remains the mainstay therapy. Ceftaroline has been shown to be non-inferior to vancomycin and may result in faster resolution of signs of infection. METHODS: Multicenter, prospective, open-label, randomized trial of ceftaroline versus vancomycin for the treatment of adult patients admitted for management of ABSSSIs from April 2012 to May 2016; 166 patients in the clinically evaluable (CE) group were needed to determine a 20% difference in primary outcome of clinical response at day 2 or 3 of antibiotics. Clinical response was defined as cessation of spread of lesion and improvement in systemic signs/symptoms of infection. A secondary outcome was a ≥ 20% reduction in lesion size at day 2 or 3 of antibiotics. RESULTS: One hundred seventy-four patients were enrolled in the intention-to-treat (ITT) group and 108 were CE. Among CE patients, 54 were randomized to ceftaroline and 54 to vancomycin. Baseline characteristics were similar except patients in the ceftaroline arm were older and had a non-significantly higher degree of comorbidities (median Charlson score 2 vs. 4, respectively). Cellulitis was the most common type of ABSSSI (85.2% vs. 79.6%, respectively). Rapid diagnostic testing of available cultures (n = 55) demonstrated high agreement with clinical microbiology for identification of Staphylococcus aureus (100%) and MRSA (100%). There was no significant difference in primary outcome of day 2 or 3 clinical response (50.0% vs. 51.9%). CONCLUSION: Early clinical response between vancomycin- and ceftaroline-treated ABSSSIs was similar. Patients with ABSSSIs rarely remained hospitalized for > 2-3 days, thus limiting our ability to critically assess clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02582203. FUNDING: Allergan plc.

Real-World Experience With Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections.

BACKGROUND: We conducted this study to describe the clinical characteristics, microbiology, and outcomes of patients treated with ceftazidime-avibactam (CZA) for a range of multidrug-resistant Gram-negative (MDR-GN) infections. METHODS: This is a multicenter, retrospective cohort study conducted at 6 medical centers in the United States between 2015 and 2019. Adult patients who received CZA (≥72 hours) were eligible. The primary outcome was clinical failure defined as a composite of 30-day all-cause mortality, 30-day microbiological failure, and/or failure to resolve or improve signs or symptoms of infection on CZA. RESULTS: In total, data from 203 patients were evaluated. Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas spp were isolated from 117 (57.6%) and 63 (31.0%) culture specimens, respectively. The most common infection sources were respiratory (37.4%), urinary (19.7%), and intra-abdominal (18.7%). Blood cultures were positive in 22 (10.8%) patients. Clinical failure, 30-day mortality, and 30-day recurrence occurred in 59 (29.1%), 35 (17.2%), and 12 (5.9%) patients, respectively. On therapy, CZA resistance developed in 1 of 62 patients with repeat testing. Primary bacteremia or respiratory tract infection and higher SOFA score were positively associated with clinical failure (adjusted odds ratio [aOR] = 2.270, 95% confidence interval [CI] = 1.115-4.620 and aOR = 1.234, 95% CI = 1.118-1.362, respectively). Receipt of CZA within 48 hours of infection onset was protective (aOR, 0.409; 95% CI, 0.180-0.930). Seventeen (8.4%) patients experienced a potential drug-related adverse effect (10 acute kidney injury, 3 Clostridioides difficile infection, 2 rash, and 1 each gastrointestinal intolerance and neutropenia). CONCLUSIONS: Ceftazidime-avibactam is being used to treat a range of MDR-GN infections including Pseudomonas spp as well as CRE.