Relationship among sleep, work features, and SARS-cov-2 vaccine antibody response in hospital workers.

STUDY OBJECTIVES: Immunity is influenced by sleep and the circadian rhythm. Healthcare workers are predisposed to both insufficient sleep and circadian disruption. This study aimed to evaluate the relationship between sleep and work characteristics and the antibody response to the mRNA SARS-CoV-2 vaccine BNT162b2. METHODS: The authors' prospective cohort study ("COVI3") evaluated the effect of a third (booster) dose of the BNT162b2 vaccine. A subset of participants provided information on anthropometric measures, sleep, stress and work characteristics including shift work and number of work hours per week. Blood samples for anti-S1-RBD IgG antibody levels were obtained 21 weeks following receipt of the third dose of the vaccine. RESULTS: In total, 201 healthcare workers (73% women) were included. After adjustment for age, body mass index (BMI), shift work, smoking status, and perceived stress, short sleep duration (<7 h per night) was associated with lower anti-S1-RBD IgG levels (Odds ratio 2.36 [95% confidence interval 1.08-5.13]). Participants who performed shift work had higher odds of lower anti-S1-RBD IgG levels compared to those who did not work in shifts [odds ratio = 2.99 (95% confidence interval 1.40, 6.39)] after accounting for age, short sleep duration, BMI, smoking status and perceived stress. CONCLUSIONS: Shift work and self-reported short sleep duration were associated with a lower antibody response following a booster dose of the SARS-CoV-2 vaccine. These findings suggest that the efficacy of vaccination, particularly among healthcare workers, may be augmented by addressing both sleep and circadian alignment.

An Open-Label, Randomized Trial Comparing Fidaxomicin With Oral Vancomycin for the Treatment of Clostridioides difficile Infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections.

BACKGROUND: Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode. METHODS: We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile, and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin. RESULTS: Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P = .195) and rCDI (3.3% vs 4.0%; P > .99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI. CONCLUSIONS: In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT02692651).

Nationwide Outbreak of Candida auris Infections Driven by COVID-19 Hospitalizations, Israel, 2021-2022

We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.

Nosocomial transmission of MPOX virus to health care workers -an emerging occupational hazard: A case report and review of the literature.

We present an unusual case of monkeypox (MPOX) virus transmission to a dermatology resident during examination of affected patients. Viral DNA sequencing led to the identification of the most likely contact. This case, along with a review of all published cases so far, emphasizes the possible hazard of MPOX transmission to health care personnel, even when wearing personal protective equipment. It also emphasizes the need for maintaining high index of suspicion when examining patients with new dermatological lesions and strict compliance with the revised Centers for Disease Control and Prevention recommendations for specimen collection from such patients.

An outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infections among hospital personnel with high mRNA vaccine uptake.

Real-world studies have demonstrated impressive effectiveness of the BNT162b2 COVID-19 vaccine in preventing symptomatic and asymptomatic SARS-CoV-2 infection. We describe an outbreak of SARS-CoV-2 infections in a hospital with high vaccine uptake. We found a low secondary attack rate (7%), suggesting low infectivity of vaccinated persons with vaccine breakthrough SARS-CoV-2 infections.

Outcomes of neutropenic hemato-oncological patients with viridans group streptococci (VGS) bloodstream infection based on penicillin susceptibility.

Viridans group streptococci (VGS) bloodstream infection (BSI) in neutropenic patients can be a severe complication. A higher prevalence of vancomycin use has been reported due to reduced susceptibility to penicillin. We aimed to assess the impact on mortality of both penicillin minimal inhibitory concentration (MIC) and the use of vancomycin. We conducted a retrospective multicenter study including consecutive neutropenic patients with VGS BSI between 2007 and 2019. Univariable and multivariable analyses were conducted to evaluate risk factors for mortality, including penicillin susceptibility as an independent variable. Non-susceptibility to penicillin was defined as MIC ≥ 0.25. We included 125 neutropenic patients with VGS BSI. Mean age was 53 years and ~ 50% were women. Overall, 30-day mortality rate was 25/125 (20%), and 41 patients (33%) had a VGS isolate non-susceptible to penicillin. In univariable analysis, no significant association was demonstrated between penicillin non-susceptibility and mortality (9/25, 26% vs. 32/100, 32%, p = 0.81). Among patients with a non-susceptible strain, the use of vancomycin was not significantly associated with mortality (empirical, p = 0.103, or definitive therapy, p = 0.491). Factors significantly associated with increased mortality in multivariable analysis included functional status (ECOG > 1, adjusted odds ratio [aOR] 12.53, 95% CI 3.64-43.14; p < 0.0001); allogeneic transplantation (aOR 6.33, 95% CI 1.96-20.46; p = 0.002); and co-pathogen in blood cultures (aOR 3.99, 95% CI 1.34-11.89; p = 0.013). Among neutropenic hemato-oncological patients with VGS BSI, penicillin non-susceptibility and the use of vancomycin were not associated with mortality. Thus, vancomycin should not be used routinely as empirical therapy in neutropenic patients with suspected VGS BSI.

Rethinking the "Pan-Culture": Clinical Impact of Respiratory Culturing in Patients With Low Pretest Probability of Ventilator-Associated Pneumonia.

Background: Respiratory cultures are often obtained as part of a "pan-culture" in mechanically ventilated patients in response to new fevers or leukocytosis, despite an absence of clinical or radiographic evidence suggestive of pneumonia. Methods: This was a propensity score-stratified cohort study of hospitalized mechanically ventilated adult patients between 2014 and 2019, with a new abnormal temperature or serum white blood cell count (NATW), but without radiographic evidence of pneumonia, change in ventilator requirements, or documentation of purulent secretions. Two patient groups were compared: those with respiratory cultures performed within 36 hours after NATW and those without respiratory cultures performed. The co-primary outcomes were the proportion of patients receiving >2 days of total antibiotic therapy and >2 days of broad-spectrum antibiotic therapy within 1 week after NATW. Results: Of 534 included patients, 113 (21.2%) had respiratory cultures obtained and 421 (78.8%) did not. Patients with respiratory cultures performed were significantly more likely to receive antibiotics for >2 days within 1 week after NATW than those without respiratory cultures performed (total antibiotic: adjusted odds ratio [OR], 2.57; 95% CI, 1.39-4.75; broad-spectrum antibiotic: adjusted OR, 2.47, 95% CI, 1.46-4.20). Conclusions: Performance of respiratory cultures for fever/leukocytosis in mechanically ventilated patients without increasing ventilator requirements, secretion burden, or radiographic evidence of pneumonia was associated with increased antibiotic use within 1 week after incident abnormal temperature and/or white blood cell count. Diagnostic stewardship interventions targeting performance of unnecessary respiratory cultures in mechanically ventilated patients may reduce antibiotic overuse within intensive care units.

Drivers of adaptive evolution during chronic SARS-CoV-2 infections.

In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient's body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence.

Short-Term Safety of Booster Immunization With BNT162b2 mRNA COVID-19 Vaccine in Healthcare Workers.

This study demonstrated a favorable short-term safety profile after a third dose of the BNT162b2 vaccine among healthcare workers (HCWs). There were more frequent local reactions and less systemic reactions compared to the second dose. The HCWs who reported reactions had higher prebooster titer of anti-S1 antibodies compared to those who reported no reactions.

Association of a Third Dose of BNT162b2 Vaccine With Incidence of SARS-CoV-2 Infection Among Health Care Workers in Israel.

Importance: Administration of a BNT162b2 booster dose (Pfizer-BioNTech) to fully vaccinated individuals aged 60 years and older was significantly associated with lower risk of SARS-CoV-2 infection and severe illness. Data are lacking on the effectiveness of booster doses for younger individuals and health care workers. Objective: To estimate the association of a BNT162b2 booster dose with SARS-CoV-2 infections among health care workers who were previously vaccinated with a 2-dose series of BNT162b2. Design, Setting, and Participants: This was a prospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. The study cohort included 1928 immunocompetent health care workers who were previously vaccinated with a 2-dose series of BNT162b2, and had enrolled between August 8 and 19, 2021, with final follow-up reported through September 20, 2021. Screening for SARS-CoV-2 infection was performed every 14 days. Anti-spike protein receptor binding domain IgG titers were determined at baseline and 1 month after enrollment. Cox regression with time-dependent analysis was used to estimate hazard ratios of SARS-CoV-2 infection between booster-immunized status and 2-dose vaccinated (booster-nonimmunized) status. Exposures: Vaccination with a booster dose of BNT162b2 vaccine. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infection, as confirmed by reverse transcriptase-polymerase chain reaction. Results: Among 1928 participants, the median age was 44 years (IQR, 36-52 years) and 1381 were women (71.6%). Participants completed the 2-dose vaccination series a median of 210 days (IQR, 205-213 days) before study enrollment. A total of 1650 participants (85.6%) received the booster dose. During a median follow-up of 39 days (IQR, 35-41 days), SARS-CoV-2 infection occurred in 44 participants (incidence rate, 60.2 per 100 000 person-days); 31 (70.5%) were symptomatic. Five SARS-CoV-2 infections occurred in booster-immunized participants and 39 in booster-nonimmunized participants (incidence rate, 12.8 vs 116 per 100 000 person-days, respectively). In a time-dependent Cox regression analysis, the adjusted hazard ratio of SARS-CoV-2 infection for booster-immunized vs booster-nonimmunized participants was 0.07 (95% CI, 0.02-0.20). Conclusions and Relevance: Among health care workers at a single center in Israel who were previously vaccinated with a 2-dose series of BNT162b2, administration of a booster dose compared with not receiving one was associated with a significantly lower rate of SARS-CoV-2 infection over a median of 39 days of follow-up. Ongoing surveillance is required to assess durability of the findings.

Use of antibiotics and factors associated with treatment failure among 152,245 patients with pneumonia treated in the community - a retrospective cohort study.

This study aims to evaluate risk factors associated with treatment failure and the antibiotics prescribed by primary care physicians in a large patient cohort treated for pneumonia in the community. A retrospective cohort study based on the databases of Maccabi Healthcare Services that provide healthcare to a quarter of the Israeli population. Included patients were > 12 years and diagnosed with pneumonia in the outpatient setting. Cohort 1 included patients with community-acquired pneumonia (CAP), whereas cohort 2 included patients with a documented pneumonia diagnosis following hospital discharge. Treatment failure (TF) was defined as either the use of a second line antibiotic OR hospital admission within 3-14 days OR death within 30 days of diagnosis. Risk factors for TF in the study cohorts were analyzed using multivariable logistic regression. During the study period, 148,376 patients were included in cohort 1 and 3,869 patients in cohort 2, with mean ages of 46.5 ± 20.3 and 63.8 ± 19.5 years, respectively. The most commonly used antibiotics were cephalosporins (36%) and macrolides (35.5%). TF occurred in 12% of cohort 1 and was associated with older age, comorbid conditions, use of non-respiratory fluoroquinolones, and penicillin. Atypical coverage (either macrolides or tetracyclines) was associated with a lower risk of failure. Among cohort 2, TF was higher (16.4%, p < 0.001) and was associated with older age, prior cancer, and congestive heart failure. Treatment failure was associated with comorbid conditions and increasing age. Among young patients with CAP and no comorbid conditions, macrolides or tetracyclines may suffice.

Unraveling a Nosocomial Outbreak of COVID-19: The Role of Whole-Genome Sequence Analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic poses many epidemiological challenges. The investigation of nosocomial transmission is usually performed via thorough investigation of an index case and subsequent contact tracing. Notably, this approach has a subjective component, and there is accumulating evidence that whole-genome sequencing of the virus may provide more objective insight. METHODS: We report a large nosocomial outbreak in 1 of the medicine departments in our institution. Following intensive epidemiological investigation, we discovered that 1 of the patients involved was suffering from persistent COVID-19 while initially thought to be a recovering patient. She was therefore deemed to be the most likely source of the outbreak. We then performed whole-genome sequencing of the virus of 14 infected individuals involved in the outbreak. RESULTS: Surprisingly, the results of whole-genome sequencing refuted our initial hypothesis. A phylogenetic tree of the samples showed multiple introductions of the virus into the ward, 1 of which led to a cluster of 10 of the infected individuals. Importantly, the results pointed in the direction of a specific index patient that was different from the 1 that arose from our initial investigation. CONCLUSIONS: These results underscore the important added value of using whole-genome sequencing in epidemiological investigations as it may reveal unexpected connections between cases and aid in understanding transmission dynamics, especially in the setting of a pandemic where multiple possible index cases exist simultaneously.

Antibiotic Use during the COVID-19 Pandemic in a Tertiary Hospital with an Ongoing Antibiotic Stewardship Program.

During the recent pandemic, the fact that the clinical manifestation of COVID-19 may be indistinguishable from bacterial infection, as well as concerns of bacterial co-infection, have been associated with an increased use of antibiotics. The objective of this study was to assess the effect of targeted antibiotic stewardship programs (ASP) on the use of antibiotics in designated COVID-19 departments and to compare it to the antibiotic use in the equivalent departments in the same periods of 2018 and 2019. Antibiotic consumption was assessed as days of treatment (DOT) per 1000 patient days (PDs). The COVID-19 pandemic was divided into three periods (waves) according to the pandemic dynamics. The proportion of patients who received at least one antibiotic was significantly lower in COVID-19 departments compared to equivalent departments in 2018 and 2019 (Wave 2: 30.2% vs. 45.6% and 44.9%, respectively; Wave 3: 30.5% vs. 47.8% and 50.1%, respectively, p < 0.001). The DOT/1000PDs in every COVID-19 wave was lower than during similar periods in 2018 and 2019 (179-282 DOT/1000PDs vs. 452-470 DOT/1000PDs vs. 426-479 DOT/1000PDs, respectively). Moreover, antibiotic consumption decreased over time during the pandemic. In conclusion, a strong ASP is effective in restricting antibiotic consumption, particularly for COVID-19 which is a viral disease that may mimic bacterial sepsis but has a low rate of concurrent bacterial infection.

Deferring Amputation in Diabetic Foot Osteomyelitis: Doing More Harm Than Good?

In a cohort of patients with diabetic foot osteomyelitis who were recommended to undergo below-knee amputation, those who deferred amputation and chose medical therapy were more likely to die during the follow-up time compared with those who proceeded with amputation.

Association Between Vaccination With BNT162b2 and Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infections Among Health Care Workers.

IMPORTANCE: Randomized clinical trials have provided estimates of the effectiveness of the BNT162b2 vaccine against symptomatic SARS-CoV-2 infection, but its effect on asymptomatic infections remains unclear. OBJECTIVE: To estimate the association of vaccination with the Pfizer-BioNTech BNT162b2 vaccine with symptomatic and asymptomatic SARS-CoV-2 infections among health care workers. DESIGN, SETTING, AND PARTICIPANTS: This was a single-center, retrospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. Data were collected on symptomatic and asymptomatic SARS-CoV-2 infections confirmed via polymerase chain reaction (PCR) tests in health care workers undergoing regular screening with nasopharyngeal swabs between December 20, 2020, and February 25, 2021. Logistic regression was used to calculate incidence rate ratios (IRRs) comparing the incidence of infection between fully vaccinated and unvaccinated participants, controlling for demographics and the number of PCR tests performed. EXPOSURES: Vaccination with the BNT162b2 vaccine vs unvaccinated status was ascertained from the employee health database. Full vaccination was defined as more than 7 days after receipt of the second vaccine dose. MAIN OUTCOMES AND MEASURES: The primary outcome was the regression-adjusted IRR for symptomatic and asymptomatic SARS-CoV-2 infection of fully vaccinated vs unvaccinated health care workers. The secondary outcomes included IRRs for partially vaccinated health care workers (days 7-28 after first dose) and for those considered as late fully vaccinated (>21 days after second dose). RESULTS: A total of 6710 health care workers (mean [SD] age, 44.3 [12.5] years; 4465 [66.5%] women) were followed up for a median period of 63 days; 5953 health care workers (88.7%) received at least 1 dose of the BNT162b2 vaccine, 5517 (82.2%) received 2 doses, and 757 (11.3%) were not vaccinated. Vaccination was associated with older age compared with those who were not vaccinated (mean age, 44.8 vs 40.7 years, respectively) and male sex (31.4% vs 17.7%). Symptomatic SARS-CoV-2 infection occurred in 8 fully vaccinated health care workers and 38 unvaccinated health care workers (incidence rate, 4.7 vs 149.8 per 100 000 person-days, respectively, adjusted IRR, 0.03 [95% CI, 0.01-0.06]). Asymptomatic SARS-CoV-2 infection occurred in 19 fully vaccinated health care workers and 17 unvaccinated health care workers (incidence rate, 11.3 vs 67.0 per 100 000 person-days, respectively, adjusted IRR, 0.14 [95% CI, 0.07-0.31]). The results were qualitatively unchanged by the propensity score sensitivity analysis. CONCLUSIONS AND RELEVANCE: Among health care workers at a single center in Tel Aviv, Israel, receipt of the BNT162b2 vaccine compared with no vaccine was associated with a significantly lower incidence of symptomatic and asymptomatic SARS-CoV-2 infection more than 7 days after the second dose. Findings are limited by the observational design.

The Effect of ß-Blockers for Burn Patients on Clinical Outcomes: Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the effects and safety of ß-blockers in hospitalized patients with burns. METHODS: A systematic review and meta-analysis of the literature. A broad search was conducted to identify all randomized controlled trials (RCTs) comparing ß-blockers to control in hospitalized patients with burns. The primary outcome was 3-month all-cause mortality. Secondary outcomes were clinical patient-relevant end points. We subgrouped results by children/adults and burn severity. Risk of bias was assessed using the individual domain approach. RESULTS: Four RCTs reported in 11 publications were included. Primary outcome of mortality was assessed in children (2 trials, n = 424) and adults (2 trials, n = 148) with severe burns. No significant difference was found between propranolol and control for mortality (risk ratio [RR] = 0.82, 95% CI = 0.48-1.39, 4 trials with broad confidence intervals in adults and children), sepsis (RR = 0.81, 95% CI = 0.46-1.43, 2 trials), and survivors' length of stay (absolute mean difference = 2.53, 95% CI = -2.58-7.63, 3 trials). There was no significant difference in bradycardia (RR = 1.33, 95% CI = 0.77-2.3, 2 trials), hypotension (RR = 1.26, 95% CI = 0.73-2.17, 3 trials), or cardiac arrhythmia (RR: 2.97, 95% CI: 0.12-71.87, 1 trial). The evidence was graded as very low certainty, due to trial's internal risk of bias, imprecision, and possible selective reporting. CONCLUSIONS: No sufficient evidence was found to support or refute an advantage for ß-blocker use in children or adults after burns. Additional studies are needed to create a consensus and formulate practice guidelines on the optimal ß-blocker to use, indications for initiation, and duration of treatment.

The Performance of Sepsis-3 Criteria to Predict Mortality Among Patients With Hematologic Malignancy and Post-transplant who Have Suspected Infection.

BACKGROUND: Sepsis is a leading cause of death, particularly in immunocompromised people. The revised definition of sepsis (Sepsis-3) uses the Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) to identify patients with sepsis. The aim of this study was to evaluate the performance of SOFA, qSOFA, and systemic inflammatory response syndrome (SIRS) in immunocompromised patients. METHODS: Adult immunocompromised patients admitted to Michigan Medicine between 2012 and 2018 with suspected infection were included based on criteria adopted from the Sepsis-3 study. Each clinical score (SOFA ≥2, qSOFA ≥2, SIRS ≥2) was added to the baseline risk model as an ordinal variable as well as a dichotomous variable, and area under the receiver operating characteristic curve (AUROC) values were calculated. In addition, breakpoints of SOFA between 2 and 10 were assessed to identify the breakpoints with the highest sensitivity and specificity for hospital mortality. The analysis was stratified for intensive care unit (ICU) status. RESULTS: Of 2822 immunocompromised patients with a mean age of 56.8±15.6 years, 213 (7.5%) died during hospitalization. When added to the baseline risk model, SOFA score had the greatest predictive validity for hospital mortality (AUROC,0.802; 95% CI, 0.771-0.832), followed by qSOFA (AUROC,0.783; 95% CI, 0.754-0.812) and SIRS (AUROC,0.741; 95% CI, 0.708-0.774). Among the SOFA breakpoints that were evaluated, SOFA ≥6 had the greatest predictive validity and a moderate positive likelihood ratio (2.75) for hospital mortality. CONCLUSIONS: The predictive validity for hospital mortality of qSOFA was similar among immunocompromised patients as that reported in the Sepsis-3 study. The sensitivity of qSOFA ≥2 for hospital mortality was low. SOFA ≥6 might be an effective tool to identify immunocompromised patients with suspected infection at high risk for clinical deterioration.

The Impact of Multidrug-Resistant Organisms on Outcomes in Patients With Diabetic Foot Infections.

BACKGROUND: Multidrug-resistant organisms (MDROs) are important diabetic foot infection (DFI) pathogens. This study evaluated the impact of DFIs associated with MDRO pathogens (DFI-MDRO) on clinical outcomes. METHODS: Adults admitted to Detroit Medical Center from January 2012 to December 2015 with culture-positive DFI were included. Associations between outcomes and DFI-MDRO (evaluated as a single group that included methicillin-resistant Staphylococcus aureus [MRSA], vancomycin-resistant enterococci, Enterobacteriaceae resistant to third-generation cephalosporin [3GCR-EC], Acinetobacter baumannii, and Pseudomonas aeruginosa) were analyzed. Outcomes included above- and below-knee lower extremity amputation (LEA), readmissions, and mortality within a year after DFI. A propensity score predicting the likelihood of having DFI-MDRO was computed by comparing patients with DFI-MDRO with patients with DFI with non-MDRO pathogens (DFI-non-MDRO). Using conditional logistic regression, DFI-MDRO was analyzed as an independent variable after patients in the MDRO and non-MDRO groups were matched by propensity score. RESULTS: Six hundred forty-eight patients were included, with a mean age ± SD of 58.4 ± 13.7. Most patients in the cohort presented with chronic infection (75%). DFI-MDRO occurred in greater than one-half of the cohort (n = 364, 56%), and MRSA was the most common MDRO (n = 224, 62% of the DFI-MDRO group). In propensity-matched analyses, DFI-MDRO was not associated with 1-year LEA or readmissions, but was associated with recurrent DFI episodes (odds ratio, 2.1; 95% confidence interval, 1.38-3.21). CONCLUSIONS: DFI-MDRO was associated with a 2-fold increased risk of recurrent DFI compared with patients with DFI-non-MDRO.

Clinical Implications of Microbiologic Treatment Failure in the Setting of Clinical Cure of Bacterial Pneumonia.

BACKGROUND: Microbiologic cure is a common outcome in pneumonia clinical trials, but its clinical significance is incompletely understood. METHODS: We conducted a retrospective cohort study of adult patients hospitalized with bacterial pneumonia who achieved clinical cure. Rates of recurrent pneumonia and death were compared between patients with persistent growth of the index pathogen at the time of clinical cure (microbiologic failure) and those with pathogen eradication (microbiologic cure). RESULTS: Among 441 patients, 237 experienced microbiologic cure and 204 experienced microbiologic failure. Prevalences of comorbidities, ventilator dependence, and severity of acute illness were similar between groups. Patients with microbiologic failure experienced significantly higher rates of recurrent pneumonia or death following clinical cure than patients with microbiologic cure, controlling for comorbid conditions, severity of acute illness, appropriateness of empiric antibiotics, intensive care unit placement, tracheostomy dependence, and immunocompromised status (90-day multivariable adjusted odds ratio [OR], 1.56; 95% confidence interval [CI], 1.04-2.35). This association was observed among patients with pneumonias caused by Staphylococcus aureus (90-day multivariable adjusted OR, 3.69; 95% CI, 1.73-7.90). A trend was observed among pneumonias caused by nonfermenting gram-negative bacilli, but not Enterobacteriaceae or other pathogens. CONCLUSIONS: Microbiologic treatment failure was independently associated with recurrent pneumonia or death among patients with bacterial pneumonia following clinical cure. Microbiologic cure merits further study as a metric to guide therapeutic interventions for patients with bacterial pneumonia.