Household Influenza Transmission and Healthcare Resource Utilization Among Patients Treated with Baloxavir vs Oseltamivir: A United States Outpatient Prospective Survey.

INTRODUCTION: Influenza is a common, seasonal infectious disease with broad medical, economic, and social consequences. Real-world evidence on the effect of influenza treatment on household transmission and healthcare resource utilization is limited in outpatient settings in the USA. This study examined the real-world effectiveness of baloxavir vs oseltamivir in reducing influenza household transmission and healthcare resource utilization. METHODS: This prospective electronic survey on patient-reported outcomes was conducted between October 2022 and May 2023 via CVS Pharmacy in the USA. Adult participants (≥ 18 years old) were eligible if they filled a prescription for baloxavir or oseltamivir at a CVS Pharmacy within 2 days of influenza symptom onset. Participant demographics, household transmission, and all-cause healthcare resource utilization were collected. Transmission and utilization outcomes were assessed using χ2 and Fisher exact tests. RESULTS: Of 87,871 unique patients contacted, 1346 (1.5%) consented. Of 374 eligible patients, 286 (90 baloxavir- and 196 oseltamivir-treated patients) completed the survey and were included in the analysis. Mean age of participants was 45.4 years, 65.6% were female, and 86.7% were White. Lower household transmission was observed with baloxavir compared with oseltamivir therapy (17.8% vs 26.5%; relative risk = 0.67; 95% CI 0.41-1.11). Healthcare resource utilization, particularly emergency department visits (0.0% vs 4.6%), was also numerically lower in the baloxavir-treated group; no hospitalizations were reported in either cohort. CONCLUSIONS: The findings from this real-world study suggest that antiviral treatment of influenza with baloxavir may decrease household transmission and reduce healthcare resource utilization compared with oseltamivir.

Exebacase in Addition to Standard-of-Care Antibiotics for Staphylococcus aureus Bloodstream Infections and Right-Sided Infective Endocarditis: A Phase 3, Superiority-Design, Placebo-Controlled, Randomized Clinical Trial (DISRUPT).

BACKGROUND: Novel treatments are needed for Staphylococcus aureus bacteremia, particularly for methicillin-resistant S. aureus (MRSA). Exebacase is a first-in-class antistaphylococcal lysin that is rapidly bactericidal and synergizes with antibiotics. METHODS: In DISRUPT, a superiority-design phase 3 study, patients with S. aureus bacteremia/endocarditis were randomly assigned to receive a single dose of IV exebacase or placebo in addition to standard-of-care antibiotics. The primary efficacy outcome was clinical response at Day 14 in the MRSA population. RESULTS: A total of 259 patients were randomized before the study was stopped for futility based on the recommendation of the unblinded Data Safety Monitoring Board. Clinical response rates at Day 14 in the MRSA population (n = 97) were 50.0% (exebacase + antibiotics; 32/64) vs. 60.6% (antibiotics alone; 20/33) (P = 0.392). Overall, rates of adverse events were similar across groups. No adverse events of hypersensitivity related to exebacase were reported. CONCLUSIONS: Exebacase + antibiotics failed to improve clinical response at Day 14 in patients with MRSA bacteremia/endocarditis. This result was unexpected based on phase 2 data that established proof-of-concept for exebacase + antibiotics in patients with MRSA bacteremia/endocarditis. In the antibiotics alone group, the clinical response rate was higher than that seen in phase 2. Heterogeneity within the study population and a relatively small sample size in either the phase 2 or phase 3 studies may have increased the probability of imbalances in the multiple components of Day 14 clinical outcome. This study provides lessons for future superiority studies in S. aureus bacteremia/endocarditis.

Aminopenicillins vs non-aminopenicillins for treatment of enterococcal lower urinary tract infections.

Aminopenicillins (APs) achieve urinary concentrations that exceed typical minimum inhibitory concentrations for enterococcal lower urinary tract infection (UTI). The local clinical microbiology laboratory discontinued routine susceptibilities on enterococcal urine isolates, and reports that 'APs are predictably reliable for uncomplicated enterococcal UTI'. The objective of this study was to compare outcomes of APs with non-APs (NAPs) for enterococcal lower UTIs. This was an institutional-review-board-approved, retrospective cohort of adults hospitalized with symptomatic enterococcal lower UTIs from 2013 to 2021. The primary endpoint was composite clinical success at 14 days, defined as resolution of symptoms without new symptoms and no repeat culture growth of the index organism. A non-inferiority analysis was utilized with a 15% margin, and logistic regression evaluated characteristics associated with 14-day failure. In total, 178 subjects were included: 89 AP patients and 89 NAP patients. Vancomycin-resistant enterococci (VRE) were identified in 73 (82%) AP patients and 76 (85%) NAP patients (P=0.54); in total, 34 (38.2%) AP patients and 66 (74.2%) NAP patients had confirmed Enterococcus faecium (P<0.001). Amoxicillin (n=36, 40.5%) and ampicillin (n=36, 40.5%) were the most commonly used APs, and linezolid (n=41, 46%) and fosfomycin (n=30, 34%) were the most commonly used NAPs. Fourteen-day clinical success rates for APs and NAPs were 83.1% and 82.0%, respectively [1.1% difference, 97.5% confidence interval (CI) -0.117 to 0.139]. Among the E. faecium subgroup, 14-day clinical success was observed in 27/34 (79.4%) AP patients and 53/66 (80.3%) NAP patients (P=0.916). On logistic regression, APs were not associated with 14-day clinical failure (adjusted odds ratio 0.84, 95% CI 0.38-1.86). APs were non-inferior to NAPs for treating enterococcal lower UTIs, and may be considered irrespective of susceptibility results.

Pandemic response gaps: Infection prevention and control lessons learned during coronavirus disease 2019 (COVID-19) outbreaks in skilled nursing facilities in Detroit, Michigan.

BACKGROUND: Hospitalizations among skilled nursing facility (SNF) residents in Detroit increased in mid-March 2020 due to the coronavirus disease 2019 (COVID-19) pandemic. Outbreak response teams were deployed from local healthcare systems, the Centers for Disease Control and Prevention (CDC), and the Detroit Health Department (DHD) to understand the infection prevention and control (IPC) gaps in SNFs that may have accelerated the outbreak. METHODS: We conducted 2 point-prevalence surveys (PPS-1 and PPS-2) at 13 Detroit SNFs from April 8 to May 8, 2020. The DHD and partners conducted facility-wide severe acute respiratory coronavirus virus 2 (SARS-CoV-2) testing of all residents and staff and collected information regarding resident cohorting, staff cohorting, and personnel protective equipment (PPE) utilized during that time. RESULTS: Resident cohorting had been implemented in 7 of 13 (58.3%) SNFs prior to point-prevalence survey 1 (PPS-1), and other facilities initiated cohorting after obtaining PPS-1 results. Cohorting protocols of healthcare practitioners and environmental service staff were not established in 4 (31%) of 13 facilities, and in 3 facilities (23.1%) the ancillary staff were not assigned to cohorts. Also, 2 SNFs (15%) had an observation unit prior to PPS-1, 2 (15%) had an observation unit after PPS-1, 4 (31%) could not establish an observation unit due to inadequate space, and 5 (38.4%) created an observation unit after PPS-2. CONCLUSION: On-site consultations identified gaps in IPC knowledge and cohorting that may have contributed to ongoing transmission of SARS-CoV-2 among SNF residents despite aggressive testing measures. Infection preventionists (IPs) are critical in guiding ongoing IPC practices in SNFs to reduce spread of COVID-19 through response and prevention.

PROPHETIC EU: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit in European and United States Cohorts.

Background: The prospective identification of patients at high risk for hospital-acquired/ventilator-associated bacterial pneumonia may improve clinical trial feasibility and foster antibacterial development. In a prior study conducted in the United States, clinical criteria were used to prospectively identify these patients; however, these criteria have not been applied in a European population. Methods: Adults considered high risk for pneumonia (treatment with ventilation or high levels of supplemental oxygen) in the intensive care units of 7 European hospitals were prospectively enrolled from June 12 to December 27, 2017. We estimated the proportion of high-risk patients developing pneumonia according to US Food and Drug Administration guidance and a subset potentially eligible for antibacterial trial enrollment. We compared patient characteristics, treatment exposures, and pneumonia incidence in a European cohort and a previously described US cohort. Results: Of 888 high-risk patients, 211/888 (24%) were treated for possible pneumonia, and 150/888 (17%) met the Food and Drug Administration definition for hospital-acquired/ventilator-associated bacterial pneumonia. A higher proportion of European patients treated for possible pneumonia met the pneumonia definition (150/211 [71%] vs 537/1464 [37%]; P < .001). Among patients developing pneumonia, a higher proportion of European patients met antibacterial trial eligibility criteria (124/150 [83%] vs 371/537 [69%]; P < .001). Conclusions: Clinical criteria prospectively identified high-risk patients with high rates of pneumonia in the European cohort. Despite higher rates of established risk factors and incident pneumonia, European patients were significantly less likely to receive antibiotics for possible pneumonia than US patients. Different treatment practices may contribute to lower rates of antibacterial trial enrollment in the United States.

Association Between Implementation of a Universal Face Mask Policy for Healthcare Workers in a Health Care System and SARS-CoV-2 Positivity Testing Rate in Healthcare Workers.

OBJECTIVE: Examine the effect of a universal facemask policy for healthcare workers (HCW) and incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity. METHODS: Daily number of symptomatic HCW tested, SARS-CoV-2 positivity rates, and HCW job-descriptions were collected pre and post Universal HCW facemask policy (March 26, 2020). Multiple change point regression was used to model positive-test-rate data. SARS-CoV-2 testing and positivity rates were compared for pre-intervention, transition, post-intervention, and follow-up periods. RESULTS: Between March 12 and August 10, 2020, 19.2% of HCW were symptomatic for COVID-19 and underwent SARS-CoV-2 testing. A single change point was identified ∼March 28-30 (95% probability). Before the change point, the odds of a tested HCW having a positive result doubled every 4.5 to 7.5 days. Post-change-point, the odds of a tested HCW having a positive result halved every 10.5 to 13.5 days. CONCLUSIONS: Universal facemasks were associated with reducing HCW's risk of acquiring COVID-19.

Impact of pre-transplant carbapenem-resistant Enterobacterales colonization and/or infection on solid organ transplant outcomes.

The impact of pre-transplant (SOT) carbapenem-resistant Enterobacterales (CRE) colonization or infection on post-SOT outcomes is unclear. We conducted a multi-center, international, cohort study of SOT recipients, with microbiologically diagnosed CRE colonization and/or infection pre-SOT. Sixty adult SOT recipients were included (liver n = 30, hearts n = 17). Klebsiella pneumoniae (n = 47, 78%) was the most common pre-SOT CRE species. Median time from CRE detection to SOT was 2.32 months (IQR 0.33-10.13). Post-SOT CRE infection occurred in 40% (n = 24/60), at a median of 9 days (IQR 7-17), and most commonly due to K pneumoniae (n = 20/24, 83%). Of those infected, 62% had a surgical site infection, and 46% had bloodstream infection. Patients with post-SOT CRE infection more commonly had a liver transplant (16, 67% vs. 14, 39%; p =.0350) or pre-SOT CRE BSI (11, 46% vs. 7, 19%; p =.03). One-year post-SOT survival was 77%, and those with post-SOT CRE infection had a 50% less chance of survival vs. uninfected (0.86, 95% CI, 0.76-0.97 vs. 0.34, 95% CI 0.08-1.0, p =.0204). Pre-SOT CRE infection or colonization is not an absolute contraindication to SOT and is more common among abdominal SOT recipients, those with pre-SOT CRE BSI, and those with early post-SOT medical and surgical complications.

Antibiotics and antimicrobial resistance in the COVID-19 era: Perspective from resource-limited settings.

The dissemination of COVID-19 around the globe has been followed by an increased consumption of antibiotics. This is related to the concern for bacterial superinfection in COVID-19 patients. The identification of bacterial pathogens is challenging in low and middle income countries (LMIC), as there are no readily-available and cost-effective clinical or biological markers that can effectively discriminate between bacterial and viral infections. Fortunately, faced with the threat of COVID-19 spread, there has been a growing awareness of the importance of antimicrobial stewardship programs, as well as infection prevention and control measures that could help reduce the microbial load and hence circulation of pathogens, with a reduction in dissemination of antimicrobial resistance. These measures should be improved particularly in developing countries. Studies need to be conducted to evaluate the worldwide evolution of antimicrobial resistance during the COVID-19 pandemic, because pathogens do not respect borders. This issue takes on even greater importance in developing countries, where data on resistance patterns are scarce, conditions for infectious pathogen transmission are optimal, and treatment resources are suboptimal.

The Impact of Sociodemographic Factors, Comorbidities, and Physiologic Responses on 30-Day Mortality in Coronavirus Disease 2019 (COVID-19) Patients in Metropolitan Detroit.

BACKGROUND: The relationship of health disparities and comorbidities in coronavirus disease 2019 (COVID-19)-related outcomes are an ongoing area of interest. This report assesses risk factors associated with mortality in patients presenting with COVID-19 infection and healthcare disparities. METHODS: We conducted a retrospective cohort study of consecutive patients presenting to emergency departments within an integrated health system who tested positive for COVID-19 between 7 March and 30 April 2020 in metropolitan Detroit. The primary outcomes were hospitalization and 30-day mortality. RESULTS: A total of 3633 patients with a mean age of 58 years were included. The majority were female and Black non-Hispanic. Hospitalization was required for 64% of patients, 56% of whom were Black. Hospitalized patients were older, more likely to reside in a low-income area, and had a higher burden of comorbidities. By 30 days, 433 (18.7%) hospitalized patients died. In adjusted analyses, the presence of comorbidities, an age >60 years, and more severe physiological disturbance were associated with 30-day mortality. Residence in low-income areas (odds ratio [OR], 1.02; 95% confidence interval [CI], .76-1.36) and public insurance (OR, 1.24; 95% CI, .76-2.01) were not independently associated with a higher risk of mortality. Black female patients had a lower adjusted risk of mortality (OR, 0.46; 95% CI, .27-.78). CONCLUSIONS: In this large cohort of COVID-19 patients, those with comorbidities, advanced age, and physiological abnormalities on presentation had higher odds of death. Disparities in income or source of health insurance were not associated with outcomes. Black women had a lower risk of dying.

Assessment of invitrosynergy of daptomycin or vancomycin plus ceftaroline for daptomycin non-susceptible Staphylococcus aureus.

The combination of vancomycin or daptomycin plus ceftaroline has showed synergistic results in vitro. This study aimed to investigate in vitro synergy of vancomycin or daptomycin plus ceftaroline for seven patients with daptomycin non-susceptible Staphylococcus aureus (SA) bacteremia Thirteen isolates from seven patients were evaluated: two methicillin-susceptible and five methicillin-resistant SA infections. All patients were treated with daptomycin and became non-susceptible (minimum inhibitory concentration (MIC) >1 µg/mL) with therapy or had resistant strains initially. Time kill experiments were completed with 0.25 × MIC, 0.5 × MIC, and 0.75 × MIC concentrations. No synergy was seen at 0.25 × MIC. Synergy was observed for 4 isolates with vancomycin plus ceftaroline and with daptomycin plus ceftaroline for 2 isolates at 0.5 × MIC. These results are in accordance with literature that supports synergistic combinations of daptomycin or vancomycin with ceftaroline for SA bacteremia. Daptomycin non-susceptible SA bacteremia presents a treatment challenge.

PROPHETIC: Prospective Identification of Pneumonia in Hospitalized Patients in the ICU.

BACKGROUND: Pneumonia is the leading infection-related cause of death. The use of simple clinical criteria and contemporary epidemiology to identify patients at high risk of nosocomial pneumonia should enhance prevention efforts and facilitate development of new treatments in clinical trials. RESEARCH QUESTION: What are the clinical criteria and contemporary epidemiology trends that are helpful in the identification of patients at high risk of nosocomial pneumonia? STUDY DESIGN AND METHODS: Within the ICUs of 28 US hospitals, we conducted a prospective cohort study among adults who had been hospitalized >48 hours and were considered high risk for pneumonia (defined as treatment with invasive or noninvasive ventilatory support or high levels of supplemental oxygen). We estimated the proportion of high-risk patients who experienced the development of nosocomial pneumonia. Using multivariable logistic regression, we identified patient characteristics and treatment exposures that are associated with increased risk of pneumonia development during the ICU admission. RESULTS: Between February 6, 2016, and October 7, 2016, 4,613 high-risk patients were enrolled. Among 1,464 high-risk patients (32%) who were treated for possible nosocomial pneumonia, 537 (37%) met the study pneumonia definition. Among high-risk patients, a multivariable logistic model was developed to identify key patient characteristics and treatment exposures that are associated with increased risk of nosocomial pneumonia development (c-statistic, 0.709; 95% CI, 0.686-0.731). Key factors associated with increased odds of nosocomial pneumonia included an admission diagnosis of trauma or cerebrovascular accident, receipt of enteral nutrition, documented aspiration risk, and receipt of systemic antibacterials within the preceding 90 days. INTERPRETATION: Treatment for nosocomial pneumonia is common among patients in the ICU who are receiving high levels of respiratory support, yet more than one-half of patients who are treated do not fulfill standard diagnostic criteria for pneumonia. Application of simple clinical criteria may improve the feasibility of clinical trials of pneumonia prevention and treatment by facilitating prospective identification of patients at highest risk.

Initial and Repeated Point Prevalence Surveys to Inform SARS-CoV-2 Infection Prevention in 26 Skilled Nursing Facilities - Detroit, Michigan, March-May 2020.

Skilled nursing facilities (SNFs) are focal points of the coronavirus disease 2019 (COVID-19) pandemic, and asymptomatic infections with SARS-CoV-2, the virus that causes COVID-19, among SNF residents and health care personnel have been described (1-3). Repeated point prevalence surveys (serial testing of all residents and health care personnel at a health care facility irrespective of symptoms) have been used to identify asymptomatic infections and have reduced SARS-CoV-2 transmission during SNF outbreaks (1,3). During March 2020, the Detroit Health Department and area hospitals detected a sharp increase in COVID-19 diagnoses, hospitalizations, and associated deaths among SNF residents. The Detroit Health Department collaborated with local government, academic, and health care system partners and a CDC field team to rapidly expand SARS-CoV-2 testing and implement infection prevention and control (IPC) activities in all Detroit-area SNFs. During March 7-May 8, among 2,773 residents of 26 Detroit SNFs, 1,207 laboratory-confirmed cases of COVID-19 were identified during three periods: before (March 7-April 7) and after two point prevalence surveys (April 8-25 and April 30-May 8): the overall attack rate was 44%. Within 21 days of receiving their first positive test results, 446 (37%) of 1,207 COVID-19 patients were hospitalized, and 287 (24%) died. Among facilities participating in both surveys (n = 12), the percentage of positive test results declined from 35% to 18%. Repeated point prevalence surveys in SNFs identified asymptomatic COVID-19 cases, informed cohorting and IPC practices aimed at reducing transmission, and guided prioritization of health department resources for facilities experiencing high levels of SARS-CoV-2 transmission. With the increased availability of SARS-CoV-2 testing, repeated point prevalence surveys and enhanced and expanded IPC support should be standard tools for interrupting and preventing COVID-19 outbreaks in SNFs.

Clinical Characteristics and Morbidity Associated With Coronavirus Disease 2019 in a Series of Patients in Metropolitan Detroit.

Importance: In late December 2019, an outbreak caused by a novel severe acute respiratory syndrome coronavirus 2 emerged in Wuhan, China. Data on the clinical characteristics and outcomes of infected patients in urban communities in the US are limited. Objectives: To describe the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and to perform a comparative analysis of hospitalized and ambulatory patient populations. Design, Setting, and Participants: This study is a case series of 463 consecutive patients with COVID-19 evaluated at Henry Ford Health System in metropolitan Detroit, Michigan, from March 9 to March 27, 2020. Data analysis was performed from March to April 2020. Exposure: Laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Main Outcomes and Measures: Demographic data, underlying comorbidities, clinical presentation, complications, treatment, and outcomes were collected. Results: Of 463 patients with COVID-19 (mean [SD] age, 57.5 [16.8] years), 259 (55.9%) were female, and 334 (72.1%) were African American. Most patients (435 [94.0%]) had at least 1 comorbidity, including hypertension (295 patients [63.7%]), chronic kidney disease (182 patients [39.3%]), and diabetes (178 patients [38.4%]). Common symptoms at presentation were cough (347 patients [74.9%]), fever (315 patients [68.0%]), and dyspnea (282 patients [60.9%]). Three hundred fifty-five patients (76.7%) were hospitalized; 141 (39.7%) required intensive care unit management and 114 (80.8%) of those patients required invasive mechanical ventilation. Male sex (odds ratio [OR], 2.0; 95% CI, 1.3-3.2; P = .001), severe obesity (OR, 2.0; 95% CI, 1.4-3.6; P = .02), and chronic kidney disease (OR, 2.0; 95% CI, 1.3-3.3; P = .006) were independently associated with intensive care unit admission. Patients admitted to the intensive care unit had longer length of stay and higher incidence of respiratory failure and acute respiratory distress syndrome requiring invasive mechanical ventilation, acute kidney injury requiring dialysis, shock, and mortality (57 patients [40.4%] vs 15 patients [7.0%]) compared with patients in the general practice unit. Twenty-nine (11.2%) of those discharged from the hospital were readmitted and, overall, 20.0% died within 30 days. Male sex (OR, 1.8; 95% CI, 1.1-3.1; P = .03) and age older than 60 years (OR, 5.3; 95% CI, 2.9-9.7; P < .001) were significantly associated with mortality, whereas African American race was not (OR, 0.98; 95% CI, 0.54-1.8; P = .86). Conclusions and Relevance: In this review of urban metropolitan patients with COVID-19, most were African American with a high prevalence of comorbid conditions and high rates of hospitalization, intensive care unit admission, complications, and mortality due to COVID-19.

Interplay Between Patient Colonization and Environmental Contamination With Vancomycin-Resistant Enterococci and Their Association With Patient Health Outcomes in Postacute Care.

BACKGROUND: The clinical utility of patient and environmental surveillance screening for vancomycin-resistant enterococci (VRE) in the postacute care setting has not been definitively clarified. We assessed the longitudinal relationship between patient colonization and room contamination, and we established their association with unfavorable health outcomes. METHODS: Four hundred sixty-three postacute care patients were followed longitudinally from enrollment to discharge for up to 6 months. Multiple body and environmental sites were sampled at regular intervals to establish correlation between environmental contamination and patient colonization and with longer than expected stay, unplanned hospitalization, and infections adjusting for sex, age, race, Charlson's comorbidity index, and physical self-maintenance score. RESULTS: New VRE acquisition was more likely in patients residing in contaminated rooms (multivariable odds ratio [OR] = 3.75; 95% confidence interval [CI], 1.98-7.11) and vice versa (OR = 3.99; 95% CI, 2.16-7.51). New acquisition and new contamination were associated with increased length of stay (OR = 4.36, 95% CI = 1.86-10.2 and OR = 4.61, 95% CI = 1.92-11.0, respectively) and hospitalization (OR = 2.42, 95% CI = 1.39-4.22 and OR = 2.80, 95% CI = 1.52-5.12). New-onset infections were more common with higher VRE burdens (15% in the absence of VRE, 20% when after VRE isolation only on the patient or only in the room, and 29% after VRE isolation in both the patient and the room). CONCLUSIONS: Room contamination with VRE is a risk factor for patient colonization, and both are associated with future adverse health outcomes in our postacute care patients. Further research is warranted to establish whether VRE screening may contribute to better understanding of risk assessment and adverse outcome prevention in postacute care.

Multicenter Cohort of Patients With Methicillin-Resistant Staphylococcus aureus Bacteremia Receiving Daptomycin Plus Ceftaroline Compared With Other MRSA Treatments.

BACKGROUND: Daptomycin and ceftaroline (DAP-CPT) have been used for persistent methicillin-resistant Staphylococcus aureus bacteremia (MRSAB), but have rarely been compared with other therapies. This study provides an exploratory analysis of patients placed on DAP-CPT vs standard of care (SOC) for MRSAB. METHODS: This is a retrospective, matched cohort study MRSAB patients at 4 hospitals in the United States. Patients receiving DAP-CPT for ≥72 hours at any point in therapy were matched 2:1 when possible, 1:1 otherwise, to SOC, first by infection source, then age and renal function. SOC was empiric treatment with vancomycin or daptomycin and any subsequent combination antibiotic(s), except for DAP-CPT. RESULTS: Fifty-eight patients received DAP-CPT with 113 matched SOC. Ninety-six percent of SOC received vancomycin, and 56% (63/113) escalated therapy at least once in the treatment course. Twenty-four patients received DAP-CPT within 72 hours of index culture; 2 (8.3%) died within 30 days vs 14.2% (16/113) with SOC (P > .05). Subgroup analysis identified numerically lower mortality in DAP-CPT patients with a Charlson comorbidity index ≥3, endovascular source, and receipt of DAP-CPT within 72 hours of index culture. The median MRSAB duration was 9.3 vs 4.8 days for DAP-CPT and SOC, respectively. DAP-CPT was initiated on day 6 on average; after receipt of DAP-CPT, MRSAB duration was 3.3 days. CONCLUSIONS: DAP-CPT treatment is often delayed in MRSAB. Combination therapy may be more beneficial if initiated earlier, particularly in patients at higher risk for mortality. Blinded, randomized, prospective studies are needed to eliminate selection bias inherent in retrospective analyses when examining DAP-CPT vs SOC.

The Emperor's New Clothes: PRospective Observational Evaluation of the Association Between Initial VancomycIn Exposure and Failure Rates Among ADult HospitalizEd Patients With Methicillin-resistant Staphylococcus aureus Bloodstream Infections (PROVIDE).

BACKGROUND: Vancomycin is the most commonly administered antibiotic in hospitalized patients, but optimal exposure targets remain controversial. To clarify the therapeutic exposure range, this study evaluated the association between vancomycin exposure and outcomes in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. METHODS: This was a prospective, multicenter (n = 14), observational study of 265 hospitalized adults with MRSA bacteremia treated with vancomycin. The primary outcome was treatment failure (TF), defined as 30-day mortality or persistent bacteremia ≥7 days. Secondary outcomes included acute kidney injury (AKI). The study was powered to compare TF between patients who achieved or did not achieve day 2 area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds previously found to be associated with lower incidences of TF. The thresholds, analyzed separately as co-primary endpoints, were AUC/MIC by broth microdilution ≥650 and AUC/MIC by Etest ≥320. RESULTS: Treatment failure and AKI occurred in 18% and 26% of patients, respectively. Achievement of the prespecified day 2 AUC/MIC thresholds was not associated with less TF. Alternative day 2 AUC/MIC thresholds associated with lower TF risks were not identified. A relationship between the day 2 AUC and AKI was observed. Patients with day 2 AUC ≤515 experienced the best global outcomes (no TF and no AKI). CONCLUSIONS: Higher vancomycin exposures did not confer a lower TF risk but were associated with more AKI. The findings suggest that vancomycin dosing should be guided by the AUC and day 2 AUCs should be ≤515. As few patients had day 2 AUCs <400, further study is needed to define the lower bound of the therapeutic range.

Impact of Reported ß-Lactam Allergy on Management of Methicillin-Sensitive Staphylococcus aureus Bloodstream Infections.

BACKGROUND: Antistaphylococcal ß-lactams antibiotics are the preferred treatment for methicillin-sensitive Staphylococcus aureus (MSSA) infections. Patient-reported ß-lactam allergies may complicate antibiotic decision-making and delay optimal therapy, with potential implications on patient outcomes. OBJECTIVE: To determine the impact of reported ß-lactam allergies on the receipt of optimal therapy and outcomes for MSSA bloodstream infections (BSI). METHODS: Retrospective, matched cohort of MSSA BSI patients with and without a reported ß-lactam allergy. The primary end point was receipt of optimal therapy, defined as an antistaphylococcal ß-lactam. RESULTS: Two hundred twelve patients were included: 53 with reported ß-lactam allergy and 159 without ß-lactam allergy. Commonly reported ß-lactam allergies were 26 (49%) immune-mediated reaction and 8 (15%) intolerance, with 19 (36%) having no documented reaction. Optimal antibiotics were given to 135 patients without a ß-lactam allergy and 37 patients with a reported ß-lactam allergy (85% vs 70%, P = .015). Among reported ß-lactam allergy patients, those without a documented reaction were less likely to receive optimal therapy (47% vs 79%, P = .042). Reported ß-lactam allergy was not associated with clinical response (P = .61) or MSSA-related mortality (P = .83). When adjusting for immunosuppression, variables independently associated with optimal therapy were ß-lactam allergy (adjusted odds ratio [adjOR], 0.3; 95% confidence interval [CI], 0.1-0.6) and infectious diseases consultation (adjOR, 6.1; 95%CI, 2.7-13.9). Optimal antibiotic use was associated with decreased all-cause 90-day mortality (adjOR, 0.23; 95%CI, 0.09-0.54). CONCLUSIONS: Patients with reported ß-lactam allergies, particularly those without a documented reaction, were less likely to receive optimal antibiotics for MSSA BSI. Patient outcomes may be improved with enhanced quality of allergy history and routine infectious disease consultation.

Reduced Production of Bacterial Membrane Vesicles Predicts Mortality in ST45/USA600 Methicillin-Resistant Staphylococcus aureus Bacteremia.

Immune biomarkers can stratify mortality risk in staphylococcal bacteremia. Microbial biomarkers may provide more consistent signals during early infection. We demonstrate that in ST45/USA600 bacteremia, bacterial membrane vesicle production in vitro predicts clinical mortality (773 vs. 116 RFU, survivors vs. decedents, p < 0.0001). Using a threshold of 301 relative fluorescence units (RFU), the sensitivity and specificity of the membrane vesicles to predict mortality are 78% and 90%, respectively. This platform is facile, scalable and can be integrated into clinical microbiology lab workflows.

Impact of an antimicrobial stewardship intervention in India: Evaluation of post-prescription review and feedback as a method of promoting optimal antimicrobial use in the intensive care units of a tertiary-care hospital.

OBJECTIVE: Antimicrobial stewardship programs (ASPs) are effective in developed countries. In this study, we assessed the effectiveness of an infectious disease (ID) physician-driven post-prescription review and feedback as an ASP strategy in India, a low middle-income country (LMIC). DESIGN AND SETTING: This prospective cohort study was carried out for 18 months in 2 intensive care units of a tertiary-care hospital, consisting of 3 phases: baseline, intervention, and follow up. Each phase spanned 6 months. PARTICIPANTS: Patients aged ≥15 years receiving 48 hours of study antibiotics were recruited for the study. METHODS: During the intervention phase, an ID physician reviewed the included cases and gave alternate recommendations if the antibiotic use was inappropriate. Acceptance of the recommendations was measured after 48 hours. The primary outcome of the study was days of therapy (DOT) per 1,000 study patient days (PD). RESULTS: Overall, 401 patients were recruited in the baseline phase, 381 patients were recruited in the intervention phase, and 379 patients were recruited in the follow-up phase. Antimicrobial use decreased from 831.5 during the baseline phase to 717 DOT per 1,000 PD in the intervention phase (P < .0001). The effect was sustained in the follow-up phase (713.6 DOT per 1,000 PD). De-escalation according to culture susceptibility improved significantly in the intervention phase versus the baseline phase (42.7% vs 23.6%; P < .0001). Overall, 73.3% of antibiotic prescriptions were inappropriate. Recommendations by the ID team were accepted in 60.7% of the cases. CONCLUSION: The ID physician-driven implementation of an ASP was successful in reducing antibiotic utilization in an acute-care setting in India.

Combatting resistant enterococcal infections: a pharmacotherapy review.

INTRODUCTION: The role of enterococci in infectious diseases has evolved from a gut and urinary commensal to a major pathogen of concern. Few options exist for resistant enterococci, and appropriate use of the available agents is crucial. AREAS COVERED: Herein, the authors discuss antibiotics with clinically useful activity against Enterococcus faecalis and E. faecium. The article specifically discusses: antibiotics active against enterococci and their mechanism of resistance, pharmacokinetic and pharmacodynamic principles, in vitro combinations, and clinical studies which focus on urinary tract, intra-abdominal, central nervous system, and bloodstream infections due to enterococci. EXPERT OPINION: Aminopenicillins are preferred over all other agents when enterococci are susceptible and patients can tolerate them. Daptomycin and linezolid have demonstrated clinical efficacy against vancomycin-resistant enterococci (VRE). Synergistic combinations are often warranted in complex infections of high inoculum and biofilms while monotherapies are generally appropriate for uncomplicated infections. Although active against resistant enterococci, the pharmacokinetics, efficacy and safety of tigecycline and quinupristin/dalfopristin can problematical for severe infections. For cystitis, amoxicillin, nitrofurantoin, or fosfomycin are ideal. Recently, approved agents such as tedizolid and oritavancin have good in vitro activity against VRE but clinical studies against other resistant enterococci are lacking.