Knowledge, attitudes and perceptions of Latin American healthcare workers relating to antibiotic stewardship and antibiotic use: a cross-sectional multi-country study.

BACKGROUND: The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers' (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region. METHODS: HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March-April 2023. FINDINGS: Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% "other"). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term "antibiotic stewardship". Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (< 30%) or AMR (< 50%) were a problem in their HCF. Lack of access to antibiogram and to locally endorsed guidelines was reported by 51% and 34% of HCWs, respectively. Among prescribers, 53% did not consider non-physicians' opinions to make antibiotic-related decisions, 22% reported not receiving education on how to select antibiotics based on culture results and 60% stated patients and families influence their antibiotic decisions. CONCLUSIONS: Although HCWs perceived improving AU as a priority, they did not perceive AU or AMR as a problem in their HCF. AS opportunities include improved access to guidelines, access to AMR/AU data, teamwork, and education on AS for HCWs and patients and families.

A comparison of strategies for identifying patients at risk for carbapenem-resistant or extended ß-lactam-resistant Pseudomonas aeruginosa.

OBJECTIVES: To assess risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR) and extended-ß-lactam-resistant P. aeruginosa (EBR) infection/colonization, and to develop and compare tools for predicting isolation of CR and EBR from clinical cultures. METHODS: This retrospective study analysed hospitalized patients with positive P. aeruginosa cultures between 2015 and 2021. Two case-control analyses were performed to identify risk factors and develop scoring tools for distinguishing patients with CR versus carbapenem-susceptible (CS) P. aeruginosa and EBR versus CS P. aeruginosa. The performance of institutionally derived scores, externally derived scores and the presence/absence of key risk factors to predict CR and EBR were then compared. RESULTS: A total of 2379 patients were included. Of these, 8.3% had a positive culture for CR, 5.0% for EBR and 86.7% for CS P. aeruginosa. There was substantial overlap in risk factors for CR and EBR. Institutional risk scores demonstrated modestly higher area under the ROC curve values than external scores for predicting CR (0.67 versus 0.58) and EBR (0.76 versus 0.70). Assessing the presence/absence of ≥1 of the two strongest predictors (prior carbapenem use or CR isolation within 90 days) was slightly inferior to scoring tools for predicting CR, and comparable for predicting EBR. CONCLUSIONS: Clinicians concerned about CR in P. aeruginosa should consider the likelihood of EBR when making treatment decisions. A simple approach of assessing recent history of CR isolation or carbapenem usage performed similarly to more complex scoring tools and offers a more pragmatic way of identifying patients who require coverage for resistant P. aeruginosa.

Defining access without excess: expanding appropriate use of antibiotics targeting multidrug-resistant organisms.

Antimicrobial resistance remains a significant global public health threat. Although development of novel antibiotics can be challenging, several new antibiotics with improved activity against multidrug-resistant Gram-negative organisms have recently been commercialised. Expanding access to these antibiotics is a global public health priority that should be coupled with improving access to quality diagnostics, health care with adequately trained professionals, and functional antimicrobial stewardship programmes. This comprehensive approach is essential to ensure responsible use of these new antibiotics.

Trends in Inpatient Antibiotic Use Among Adults Hospitalized During the Coronavirus Disease 2019 Pandemic in Argentina, Brazil, and Chile, 2018-2021.

BACKGROUND: High rates of antibiotic use (AU) among inpatients with coronavirus disease 2019 (COVID-19) despite low rates of bacterial coinfection and secondary infection have been reported. We evaluated the impact of the COVID-19 pandemic on AU in healthcare facilities (HCFs) in South America. METHODS: We conducted an ecologic evaluation of AU in inpatient adult acute care wards in 2 HCFs each in Argentina, Brazil, and Chile. The AU rates for intravenous antibiotics were calculated as the defined daily dose per 1000 patient-days, using pharmacy dispensing records and hospitalization data from March 2018-February 2020 (prepandemic) and March 2020-February 2021 (pandemic). Differences in median AU were compared between the prepandemic and pandemic periods, using the Wilcoxon rank sum test to determine significance. Interrupted time series analysis was used to analyze changes in AU during the COVID-19 pandemic. RESULTS: Compared with the prepandemic period, the median difference in AU rates for all antibiotics combined increased in 4 of 6 HCFs (percentage change, 6.7%-35.1%; P < .05). In the interrupted time series models, 5 of 6 HCFs had significant increases in use of all antibiotics combined immediately at the onset of the pandemic (immediate effect estimate range, 15.4-268), but only 1 of these 5 HCFs experienced a sustained increase over time (change in slope, +8.13; P < .01). The effect of the pandemic onset varied by antibiotic group and HCF. CONCLUSIONS: Substantial increases in AU were observed at the beginning of the COVID-19 pandemic, suggesting the need to maintain or strengthen antibiotic stewardship activities as part of pandemic or emergency HCF responses.

Deep Dive Into Gaps and Barriers to Implementation of Antimicrobial Stewardship Programs in Hospitals in Latin America.

BACKGROUND: Antimicrobial resistance has worsened in Latin America. There is an urgent need to understand the development of antimicrobial stewardship programs (ASPs) and the barriers to implementing effective ASPs in light of limited national action plans or policies to promote ASPs in the region. METHODS: We performed a descriptive mixed-methods study of ASPs in 5 Latin American countries in March-July 2022. An electronic questionnaire with an associated scoring system (hospital ASP self-assessment) was used, and ASP development was classified based on the scores (inadequate, 0-25; basic, 26-50; intermediate, 51-75; or advanced, 76-100). Interviews among healthcare workers (HCWs) involved in antimicrobial stewardship (AS) inquired about behavioral and organizational factors that influence AS activities. Interview data were coded into themes. Results from the ASP self-assessment and interviews were integrated to create an explanatory framework. RESULTS: Twenty hospitals completed the self-assessment, and 46 AS stakeholders from these hospitals were interviewed. ASP development was inadequate/basic in 35% of hospitals, intermediate in 50%, and advanced in 15%. For-profit hospitals had higher scores than not-for-profit hospitals. Interview data validated the self-assessment findings and provided further insight into ASP implementation challenges, which included limited formal hospital leadership support, inadequate staffing and tools to perform AS work more efficiently, limited awareness of AS principles by HCWs, and limited training opportunities. CONCLUSIONS: We identified several barriers to ASP development in Latin America, suggesting the need to create accurate business cases for ASPs to obtain the necessary funding for their effective implementation and sustainability.

Prescribing of Outpatient Antibiotics Commonly Used for Respiratory Infections Among Adults Before and During the Coronavirus Disease 2019 Pandemic in Brazil.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic may have impacted outpatient antibiotic prescribing in low- and middle-income countries such as Brazil. However, outpatient antibiotic prescribing in Brazil, particularly at the prescription level, is not well-described. METHODS: We used the IQVIA MIDAS database to characterize changes in prescribing rates of antibiotics commonly prescribed for respiratory infections (azithromycin, amoxicillin-clavulanate, levofloxacin/moxifloxacin, cephalexin, and ceftriaxone) among adults in Brazil overall and stratified by age and sex, comparing prepandemic (January 2019-March 2020) and pandemic periods (April 2020-December 2021) using uni- and multivariate Poisson regression models. The most common prescribing provider specialties for these antibiotics were also identified. RESULTS: In the pandemic period compared to the prepandemic period, outpatient azithromycin prescribing rates increased across all age-sex groups (incidence rate ratio [IRR] range, 1.474-3.619), with the greatest increase observed in males aged 65-74 years; meanwhile, prescribing rates for amoxicillin-clavulanate and respiratory fluoroquinolones mostly decreased, and changes in cephalosporin prescribing rates varied across age-sex groups (IRR range, 0.134-1.910). For all antibiotics, the interaction of age and sex with the pandemic in multivariable models was an independent predictor of prescribing changes comparing the pandemic versus prepandemic periods. General practitioners and gynecologists accounted for the majority of increases in azithromycin and ceftriaxone prescribing during the pandemic period. CONCLUSIONS: Substantial increases in outpatient prescribing rates for azithromycin and ceftriaxone were observed in Brazil during the pandemic with prescribing rates being disproportionally different by age and sex. General practitioners and gynecologists were the most common prescribers of azithromycin and ceftriaxone during the pandemic, identifying them as potential specialties for antimicrobial stewardship interventions.

Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing Klebsiella pneumoniae Lineages Among Inpatients in a Chilean Hospital: A Time-Series Study and Phylogenomic Analysis.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) on antimicrobial use (AU) and resistance has not been well evaluated in South America. These data are critical to inform national policies and clinical care. METHODS: At a tertiary hospital in Santiago, Chile, between 2018 and 2022, subdivided into pre- (3/2018-2/2020) and post-COVID-19 onset (3/2020-2/2022), we evaluated intravenous AU and frequency of carbapenem-resistant Enterobacterales (CRE). We grouped monthly AU (defined daily doses [DDD]/1000 patient-days) into broad-spectrum ß-lactams, carbapenems, and colistin and used interrupted time-series analysis to compare AU during pre- and post-pandemic onset. We studied the frequency of carbapenemase-producing (CP) CRE and performed whole-genome sequencing analyses of all carbapenem-resistant (CR) Klebsiella pneumoniae (CRKpn) isolates collected during the study period. RESULTS: Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P < .001), 50.9 to 110.1 (P < .001), and 4.1 to 13.3 (P < .001) for broad-spectrum ß-lactams, carbapenems, and colistin, respectively. The frequency of CP-CRE increased from 12.8% pre-COVID-19 to 51.9% after pandemic onset (P < .001). The most frequent CRE species in both periods was CRKpn (79.5% and 76.5%, respectively). The expansion of CP-CRE harboring blaNDM was particularly noticeable, increasing from 40% (n = 4/10) before to 73.6% (n = 39/53) after pandemic onset (P < .001). Our phylogenomic analyses revealed the emergence of two distinct genomic lineages of CP-CRKpn: ST45, harboring blaNDM, and ST1161, which carried blaKPC. CONCLUSIONS: AU and the frequency of CP-CRE increased after COVID-19 onset. The increase in CP-CRKpn was driven by the emergence of novel genomic lineages. Our observations highlight the need to strengthen infection prevention and control and antimicrobial stewardship efforts.

Leptospirosis Manifesting as HELLP (Hemolysis, Elevated Liver Enzymes, and Low Platelets) Syndrome: A Rare Case of Leptospirosis During Pregnancy.

Pregnancy is characterized by a reduced immune response, making pregnant women more susceptible to infections. We present a case of a 24-year-old woman in her second pregnancy who arrived at the hospital at 36 weeks gestation in active labor. The patient had received regular antenatal care including routine prenatal check-ups, screenings, and appropriate vaccinations. She complained of abdominal pain for 5-6 hours, sudden onset of hematuria, and a history of low-grade fever for two days. Physical examination revealed paleness, grade three pedal edema, and elevated blood pressure. Diagnostic tests showed mild anemia, thrombocytopenia, proteinuria, elevated liver enzymes, and kidney dysfunction. The patient was admitted to the labor ward, and a tentative diagnosis of hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome was made. Shortly after arrival, she spontaneously delivered a healthy baby. However, post-delivery, her fever profile indicated the presence of leptospira IgM antibodies, leading to a diagnosis of leptospirosis mimicking HELLP syndrome. Immediate medical treatment resulted in symptom resolution within two weeks and normal biochemical values within a month. Leptospirosis, caused by the gram-negative spirochete bacteria leptospira, is a zoonotic infection rarely observed during pregnancy and can be misdiagnosed due to its atypical presentation. It can mimic other pregnancy-related conditions such as viral hepatitis, obstetric cholestasis, HELLP syndrome, and acute fatty liver of pregnancy. Early detection and treatment are crucial as this disease can have serious consequences for both the mother and fetus. Therefore, leptospirosis should be considered a potential differential diagnosis, particularly in endemic areas.

Impact of number of lumens in central-venous catheters on central-line bloodstream infection (CLABSI) and venous thromboembolism (VTE) risk in patients with acute leukemia.

This retrospective study was conducted to determine whether the number of peripherally inserted central-catheter lumens affected the rate of central-line associated bloodstream infections (CLABSIs) in adult patients with acute leukemia. The results show that CLABSI rates were not significantly different between patients with triple-lumen or double-lumen PICCs (22.1% vs 23.4%; P = .827).

Antimicrobial stewardship in Latin America: Past, present, and future.

Implementation of antimicrobial stewardship programs (ASPs) in well-resourced countries has been associated with reductions in antibiotic-resistant infections and improved patient outcomes. Several guidance documents providing recommendations on how to structure antimicrobial stewardship activities at the national and hospital level in resource-limited settings have been published. However, few hospitals in Latin America report having a structure or resources needed for a successful ASP. Given the alarming increases in antimicrobial resistance in Latin America, better understanding of barriers to promote implementation of effective ASPs is urgently needed. We have summarized past and present antimicrobial stewardship activities in Latin American hospitals, and we describe key elements needed in future efforts to strengthen antimicrobial stewardship in the region.

Identifying context-specific domains for assessing antimicrobial stewardship programmes in Asia: protocol for a scoping review.

INTRODUCTION: Antimicrobial stewardship (AMS) is an important strategy to control antimicrobial resistance. Resources are available to provide guidance for design and implementation of AMS programmes, however these may have limited applicability in resource-limited settings including those in Asia. This scoping review aims to identify context-specific domains and items for the development of a healthcare facility (HCF)-level tool to guide AMS implementation in Asia. METHODS AND ANALYSIS: This review is the first step in a larger project to assess AMS implementation, needs and gaps in Asia. We will employ a deductive qualitative approach to identify locally appropriate domains and items of AMS implementation guided by Nilsen and Bernhardsson's contextual dimensions. This process is also informed by discussions from a technical advisory group coordinated by the US Centers for Disease Control and Prevention to develop an AMS HCF-level assessment tool for low-income and middle-income countries. We will review English-language documents that discuss HCF-level implementation, including those describing frameworks, components/elements or recommendations for design, implementation or assessment globally and specific to Asia. We have performed the search in August-September 2021 including general electronic databases (MEDLINE, Embase, Web of Science and Google Scholar), region-specific databases, national action plans, grey literature sources and reference lists to identify eligible documents. Country-specific documents will be restricted to countries in three subregions: South Asia, East Asia and Southeast Asia. Codes and themes will be derived through a content analysis, classified following the predefined context dimensions and used for developing domains and items of the assessment tool. ETHICS AND DISSEMINATION: Results from this review will feed into our stepwise process for developing a context-specific HCF-level assessment tool for AMS programmes to assess the implementation status, identify intervention opportunities and monitor progress over time. The process will be done in consultation with local stakeholders, the end-users of the generated knowledge.

Acute kidney injury in cystic fibrosis patients treated with intravenous colistimethate sodium or tobramycin.

OBJECTIVES: Colistimethate sodium and tobramycin are important systemic antibiotics for treatment of cystic fibrosis (CF) pulmonary exacerbations but can induce acute kidney injury (AKI). We characterize the rate of AKI in CF patients treated with systemic colistimethate sodium compared with tobramycin. METHODS: This single-centre, retrospective cohort study included hospitalized CF patients treated with IV colistimethate sodium or tobramycin. The primary outcome was AKI defined using the RIFLE criteria. Multivariate logistic regression using a mixed model was performed to identify variables that were independently associated with AKI. RESULTS: Overall, 156 patients representing 507 care encounters were included. The OR of AKI was not increased with IV colistimethate sodium relative to IV tobramycin after adjusting for other potential predictor variables (aOR 1.00; 95% CI 0.16-6.03). The frequency of AKI was 9.5% across all encounters, 6.9% with IV colistimethate sodium and 9.9% with IV tobramycin, with RIFLE category R (risk) being the most common stage, accounting for 4.2% of encounters with IV colistimethate sodium and 9.2% with IV tobramycin. The concomitant use of another nephrotoxin (aOR 2.51; 95% CI 1.27-4.95) or the combination of vancomycin and piperacillin/tazobactam (aOR 5.95; 95% CI 2.05-17.3) were both associated with increased odds of AKI. CONCLUSIONS: Systemic treatment with colistimethate sodium or tobramycin in the CF patient population is associated with a similar rate of nephrotoxicity. However, clinicians should be mindful of the increased risk for AKI in patients treated with either IV colistimethate sodium or IV tobramycin when used concurrently with other nephrotoxic agents, particularly the combination of vancomycin and piperacillin/tazobactam.

The Clinical Impact of Implementation of a Multidisciplinary Endocarditis Team.

BACKGROUND: Infectious endocarditis is associated with substantial in-hospital mortality of 15%-20%. Effective management requires coordination between multiple medical and surgical subspecialties, which can often lead to disjointed care. Previous European studies have identified multidisciplinary endocarditis teams as a tool for reducing endocarditis mortality. METHODS: The multidisciplinary endocarditis team was formed in May 2018. The group developed an evidence-based algorithm for management of endocarditis that was used to provide recommendations for hospitalized patients over a 1-year period. Mortality outcomes were then retroactively assessed and compared to a historical control utilizing propensity matching. RESULTS: Between June 2018 and June 2019 the team provided guideline-based recommendations on 56 patients with Duke Criteria-definite endocarditis and at least 1 American Heart Association indication for surgery. The historical control included 68 patients with definite endocarditis and surgical indications admitted between July 1, 2014, and June 30, 2015. In-hospital mortality decreased significantly from 29.4% in 2014-2015 to 7.1% in 2018-2019 (P < .0001). There was a non-significant increase in the rate of surgical intervention after implementation of the team (41.2% vs 55.4%; P = 0.12). Propensity score matching demonstrated similar results. CONCLUSIONS: Implementation of a multidisciplinary endocarditis team was associated with a significant 1-year decrease in all-cause in-hospital mortality for patients with definite endocarditis and surgical indications, in the presence of notable differences between the 2 studied cohorts. In conjunction with previous studies demonstrating their effectiveness, these data support the idea that widespread adoption of endocarditis teams in North America could improve outcomes for this patient population.

Spontaneous Expulsion of a Prolapsed Pedunculated Uterine Leiomyoma: A Rare Gynecologic Enigma.

Uterine leiomyomas, also known as uterine fibroids, are smooth muscle tumors in the uterus, mostly benign in nature. They occur in the reproductive age group i.e. between 15 and 49 years. Asymptomatic in nature; rarely, they may be associated with symptoms like abnormal uterine bleeding, pelvic pain, and compression symptoms or secondary changes. Patients of the reproductive age group may be associated with infertility and recurrent pregnancy loss. Fibroids run in families and are associated with both estrogen and progesterone levels. Myomas produce symptoms depending on their site, size, position, number, or any secondary changes. The submucosal type of fibroid is associated with symptoms more commonly. Based on presenting symptoms, uterine leiomyoma can be managed medically or surgically. Here we present a case of a 32-year-old multigravida who had a spontaneous vaginal expulsion of a pedunculated intramural fibroid. Very rarely as in this case, complete expulsion of leiomyoma is seen. When it occurs in the reproductive age group, it may mimic many clinical conditions like incomplete or inevitable abortion. Such a case may also be associated with excess hemorrhage and can cause significant morbidity to the patient; hence it is essential to make an early diagnosis and necessary timely intervention.

A step-by-step guide to implementing a multidisciplinary endocarditis team.

Over the last several years multiple studies, primarily from European centers have demonstrated the clinical and outcomes benefits of multidisciplinary endocarditis teams. Despite this literature, adoption of this approach to patient care has been slower in the United States. While there is literature outlining the optimal composition of an endocarditis team, there is little information to guide providers as they attempt to transform practice from a fragmented, disjointed process to an efficient, collaborative care model. In this review, the authors will outline the steps they took to create and implement a successful multidisciplinary endocarditis team at the University of Michigan. In conjunction with existing data, this piece can be used as a resource for clinicians seeking to improve the care of patients with endocarditis at their institutions.

Utility of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening in patients with acute myeloid leukemia (AML).

BACKGROUND: Current literature has demonstrated the utility of the MRSA nasal screen as a de-escalation tool to decrease unnecessary anti-MRSA antibiotic therapy. However, data on the applicability of this test in patients with hematologic malignancy is lacking. METHODS: This is a single-center, retrospective cohort study of patients with acute myeloid leukemia (AML) with or without a history of hematopoietic cell transplant (HCT), with pneumonia and MRSA nasal screening with respiratory cultures obtained. The primary outcome was to determine the negative predictive value (NPV) of the MRSA nasal screen for MRSA pneumonia. Secondary outcomes included sensitivity, specificity, positive predictive value (PPV) of the MRSA nasal screen and prevalence of MRSA pneumonia. RESULTS: Of 98 patients with AML and pneumonia, the prevalence of MRSA pneumonia was 4.1% with confirmed positive MRSA respiratory cultures observed in 4 patient cases. In patients with confirmed MRSA pneumonia, 3 had positive MRSA nasal screens while 1 had a false negative result, possibly due to a long lag time (21 days) between MRSA nasal screen and pneumonia diagnosis. Overall, the MRSA nasal screen demonstrated 75% sensitivity and 100% specificity, with a PPV of 100% and a NPV of 98.9%. CONCLUSIONS: Given the low prevalence, empiric use of anti-MRSA therapy in those AML and HCT patients with pneumonia may not be warranted in clinically stable patients. For patients in whom empiric anti-MRSA antibiotics are initiated, nasal screening for MRSA may be utilized to de-escalate anti-MRSA antibiotics in patients with AML with or without HCT.

Management of anticoagulation in patients with human immunodeficiency virus/acquired immunodeficiency virus.

PURPOSE: Limited guidance is available to assist practitioners in managing complex human immunodeficiency virus (HIV) related pharmacotherapy. Management recommendations of oral anticoagulation (warfarin and direct oral anticoagulants [DOACs]) and highly active antiretroviral therapy (HAART) based on drug-drug interactions (DDI) studies and pharmacokinetic (PK) data are provided. METHODS: Search of PubMed, EMBASE, and Google Scholar (01/1985 to 12/2018) using the terms "HIV," "DDI," and names of HAART. PK information and DDI screening were obtained from medication package inserts and drug information resources: Micromedex, Lexicomp, HIV-DDI Checker- University of Liverpool. All English literature on DDI or PK interactions was considered for inclusion. In the absence of data, PK principles were used to predict the likelihood of interactions. RESULTS: No clinically significant DDI are expected to occur between DOACs and nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), maraviroc, enfuvirtide, or integrase strand inhibitors (INSTIs) that do not include a pharmacologic booster. Potent cytochrome P (CYP) 450 enzyme inhibition by protease inhibitors (PIs) or pharmacologic boosters may lead to higher concentrations of the DOAC and potentially increase the risk of bleeding. CYP450 enzyme induction by non-nucleoside reverse transcriptase inhibitors (NNRTIs) may lower concentrations of DOACs, which may lead to treatment failure. Warfarin DDIs are variable, therefore close monitoring of the INR is recommended. CONCLUSIONS: The potential for DDIs between HAART and oral anticoagulation exists based on PK profiles. Management of these interactions should involve careful selection based on patient characteristics and HAART and anticoagulants with a low potential for DDI should be selected.

Evaluation of targeted versus universal prophylaxis for the prevention of invasive fungal infections following lung transplantation.

BACKGROUND: Antifungal prophylaxis to prevent invasive fungal infections (IFI) is widely used following lung transplantation, but the optimal strategy remains unclear. We compared universal with targeted antifungal prophylaxis for effectiveness in preventing IFI. METHODS: Adult patients who underwent lung transplantation at the University of Michigan from /1 July 2014-31 December 2017 were studied for 18 months post-transplant. Universal prophylaxis consisted of itraconazole with or without inhaled liposomal amphotericin B. Using specific criteria, targeted prophylaxis was given with voriconazole for patients at risk for invasive pulmonary aspergillosis (IPA) and with fluconazole or micafungin for patients at risk for invasive candidiasis. Risk factors, occurrence of proven/probable IFI, and mortality were analyzed for the two prophylaxis cohorts. RESULTS: Of 105 lung transplant recipients, 84 (80%) received a double lung transplant, and 38 (36%) of patients underwent transplant for pulmonary fibrosis. Fifty-nine (56%) patients received universal antifungal prophylaxis, and 46 (44%), targeted antifungal prophylaxis. Among 20 proven/probable IFI, there were 14 IPA, 4 invasive candidiasis, 1 cryptococcosis, and 1 deep sternal mold infection. Six (10%) IFI occurred in the universal prophylaxis cohort and 14 (30%) in the targeted prophylaxis cohort. Five of 6 (83%) IFI in the universal prophylaxis cohort, compared with 9/14 (64%) in the targeted prophylaxis cohort, were IPA Candida infections occurred only in the targeted prophylaxis cohort. The development of IFI was more likely in the targeted prophylaxis cohort than the universal prophylaxis cohort, HR = 4.32 (1.51-12.38), P = .0064. CONCLUSIONS: Universal antifungal prophylaxis appears to be more effective than targeted antifungal prophylaxis for prevention of IFI after lung transplant.

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.

Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment. METHODS: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW). RESULTS: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia. CONCLUSIONS: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.