Clinical Outcomes Associated With Methylprednisolone in Mechanically Ventilated Patients With COVID-19.

BACKGROUND: The efficacy and safety of methylprednisolone in mechanically ventilated patients with acute respiratory distress syndrome resulting from coronavirus disease 2019 (COVID-19) are unclear. In this study, we evaluated the association between use of methylprednisolone and key clinical outcomes. METHODS: Clinical outcomes associated with the use of methylprednisolone were assessed in an unmatched, case-control study; a subset of patients also underwent propensity-score matching. Patients were admitted between 1 March and 12 April, 2020. The primary outcome was ventilator-free days by 28 days after admission. Secondary outcomes included extubation, mortality, discharge, positive cultures, and hyperglycemia. RESULTS: A total of 117 patients met inclusion criteria. Propensity matching yielded a cohort of 42 well-matched pairs. Groups were similar except for hydroxychloroquine and azithromycin use, which were more common in patients who did not receive methylprednisolone. Mean ventilator-free days were significantly higher in patients treated with methylprednisolone (6.21 ±â€…7.45 vs 3.14 ±â€…6.22; P = .044). The probability of extubation was also increased in patients receiving methylprednisolone (45% vs 21%; P = .021), and there were no significant differences in mortality (19% vs 36%; P = .087). In a multivariable linear regression analysis, only methylprednisolone use was associated with a higher number of ventilator-free days (P = .045). The incidence of positive cultures and hyperglycemia were similar between groups. CONCLUSIONS: Methylprednisolone was associated with increased ventilator-free days and higher probability of extubation in a propensity-score matched cohort. Randomized, controlled studies are needed to further define methylprednisolone use in patients with COVID-19.

Carbapenemase-producing Enterobacterales causing secondary infections during the COVID-19 crisis at a New York City hospital.

BACKGROUND: Patients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE). OBJECTIVES: We sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with COVID-19. METHODS: We retrospectively identified CPE clinical isolates collected from patients testing positive for SARS-CoV-2 between March and April 2020 at our medical centre in New York City. Available isolates underwent nanopore sequencing for rapid genotyping, antibiotic resistance gene detection and phylogenetic analysis. RESULTS: We identified 31 CPE isolates from 13 patients, including 27 Klebsiella pneumoniae and 4 Enterobacter cloacae complex isolates. Most patients (11/13) had a positive respiratory culture and 7/13 developed bacteraemia; treatment failure was common. Twenty isolates were available for WGS. Most K. pneumoniae (16/17) belonged to ST258 and encoded KPC (15 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. E. cloacae isolates belonged to ST270 and encoded NDM-1. Nanopore sequencing enabled identification of at least four distinct ST258 lineages in COVID-19 patients, which were validated by Illumina sequencing data. CONCLUSIONS: While CPE prevalence has declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a re-emergence of these highly resistant pathogens in the wake of the global pandemic. Increased surveillance and antimicrobial stewardship efforts, as well as identification of optimal treatment approaches for CPE, will be needed to mitigate their future impact.

Emergence of Polymyxin Resistance in Clinical Klebsiella pneumoniae Through Diverse Genetic Adaptations: A Genomic, Retrospective Cohort Study.

BACKGROUND: Polymyxins are antimicrobials of last resort for the treatment of carbapenem-resistant Enterobacteriaceae, but resistance in 5% to >40% isolates has been reported. We conducted a genomic survey of clinical polymyxin-resistant (PR) Klebsiella pneumoniae to determine the molecular mechanisms of PR and the role of polymyxin exposure versus transmission in PR emergence. METHODS: We included 88 patients with PR K. pneumoniae from 2011-2018 and collected demographic, antimicrobial exposure, and infection data. Whole-genome sequencing was performed on 388 isolates, including 164 PR isolates. Variant calling and insertion sequence detection were performed, focusing on key genes associated with PR (mgrB, crrAB, phoPQ, and pmrAB). We conducted phylogenetic analyses of key K. pneumoniae multi-locus sequence types (ST258, ST17, ST307, and ST392). RESULTS: Polymyxin exposure was documented in 53/88 (60%) patients prior to PR detection. Through an analysis of key PR genes, we detected 129 individual variants and 72 unique variant combinations in PR isolates. This included multiple, distinct changes in 36% of patients with serial PR isolates. Insertion sequence disruption was limited to mgrB (P < .001). Polymyxin minimum inhibitory concentrations showed stepwise increases with the number of PR genes affected (P < .001). When clusters containing PR isolates in ≥2 patients were analyzed, 10/14 had multiple genetic events leading to PR. CONCLUSIONS: Molecular mechanisms leading to PR in clinical K. pneumoniae isolates are remarkably heterogenous, even within clusters or individual patients. Polymyxin exposure with de novo PR emergence led to PR in the majority of patients, rather than transmission. Optimizing polymyxin use should be a key strategy in stopping the spread of PR.

A culture of compassion: How timeless principles of kindness and empathy become powerful tools for confronting today's most pressing healthcare challenges.

The role of compassion in healthcare is receiving increased attention as emerging research demonstrates how compassionate patient care can improve health outcomes and reduce workplace stress and burnout. To date, proposals to encourage empathy, kindness, and compassion in healthcare have focused primarily on training individual care providers. This article argues that increasing the awareness and skills of individuals is necessary but insufficient. Compassionate care becomes an organizational norm only when health leaders create and nurture a "culture of compassion" that actively supports, develops, and recognizes the role of compassion in day-to-day management and practice. The article profiles four organizations that have adopted compassionate healthcare as an explicit organizational priority and implemented practical measures for building and sustaining a culture of compassion. Common principles and practices are identified. These organizations demonstrate how compassion can lead directly to improved outcomes of primary importance to healthcare organizations, including quality and safety, patient experience, employee and physician engagement, and financial performance. They show how compassion can be a powerful yet often underappreciated tool for helping organizations successfully manage current challenges.

Population Pharmacokinetics of Intravenous Polymyxin B from Clinical Samples.

A retrospective study was conducted in hospitalized patients receiving intravenous polymyxin B who underwent therapeutic drug monitoring during treatment. The aim of this study was to assess the population pharmacokinetics (PK) of intravenous polymyxin B in patients with variable total body weights and create a population model for clinical use. Nonlinear mixed-effects modeling analyses were performed. A total of 43 patients were included, and 70% of these patients were male. The median age was 58 years, and the median weight was 78 kg. The median polymyxin B dose was 180 mg/day or 2.8 mg/kg/day. A one-compartment model described the polymyxin B PK well with conditional mean parameter estimates of a clearance (CL) of 2.37 liters/h and a volume of distribution of 34.4 liters and can be employed for clinical population modeling. Total body weight was not significantly associated with CL (Akaike information criterion, 361.6 for the weight-based model versus 359.5 for the non-weight-based model). These data suggest that dosing according to patient body weight requires further exploration. Greater study is needed to assess the relationships between polymyxin B exposures and efficacy and toxicity.

Population Pharmacokinetics of Polymyxin B in Acutely Ill Adult Patients.

Polymyxin B (PB) has reemerged as a common treatment against multidrug-resistant Gram-negative pathogens. However, nephrotoxicity remains a significant dose-limiting side effect, and contemporary pharmacokinetic (PK) data are limited. This study sought to evaluate PB exposure differences in various loading and nonloading strategies according to total body weight (TBW) and adjusted body weight (ABW). Patients treated with PB had plasma samples obtained for clinical care and analyzed using liquid chromatography-tandem mass spectrometry. Compartmental PK models with linear and allometric scaling of TBW were explored. Semiparametric Monte Carlo simulation evaluated the total (i.e., protein bound plus unbound) area under the plasma concentration-time curve (AUCtotal) during the first 24 h of therapy and at 96 h posttherapy for each regimen at the 10th, 50th, and 90th percentiles of TBW and ABW in the derivation cohort. Literature-based values of the 24-h total AUC/MIC ratio (AUC/MICtotal) of ≥50 defined efficacy, and literature-based values of the 72- to 96-h AUCtotal of ≥100 µg · h/ml defined toxicity. Fifty-two patients contributed 156 PB plasma samples. A two-compartment model with allometric scaling of TBW produced a comparable fit (Akaike information criterion [AIC] = 376.7) to that achieved with linear scaling (AIC = 378). The regimen of a loading dose of 2.5 mg/kg of body weight plus a fixed dose of 100 mg every 12 h had the highest probability of achieving a 24-h AUC/MICtotal of ≥50 with the lowest probability of toxicity in all groups at 24 h, aside from those with the lowest 10th percentile of body weight. This is the first study to suggest that a weight-based loading and fixed maintenance (i.e., weight-independent) dosing strategy for polymyxin B may maximize efficacy while balancing toxicity concerns for most patients.

Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC ß-Lactamase-Producing Enterobacteriaceae.

In vivo induction of AmpC beta-lactamases produces high-level resistance to many beta-lactam antibiotics in Enterobacteriaceae, often resulting in the need to use carbapenems or cefepime (FEP). The clinical effectiveness of piperacillin-tazobactam (TZP), a weak inducer of AmpC beta-lactamases, is poorly understood. Here, we conducted a case-control study of adult inpatients with bloodstream infections (BSIs) due to Enterobacter, Serratia, or Citrobacter species from 2009 to 2015 to assess outcomes following treatment with TZP compared to FEP or meropenem (MEM). We collected clinical data and screened all isolates for the presence of ampC alleles by PCR. Primary study outcomes were 30-day mortality and persistent bacteremia at ≥72 h from the time of treatment initiation. Of 493 patients with bacteremia, 165 patients met the inclusion criteria, of which 88 were treated with TZP and 77 with FEP or MEM. To minimize differences between covariates, we carried out propensity score matching, which yielded 41 matched pairs. Groups only differed by age, with patients in the TZP group significantly older (P = 0.012). There were no significant differences in 30-day mortality, persistent bacteremia, 7-day mortality, or treatment escalation between the two treatment groups, including in the propensity score-matched cohort. PCR amplification and sequencing of ampC genes revealed the presence of ampC in isolates with cefoxitin MICs below 16 µg/ml, in particular in Serratia spp., and demonstrated that these alleles were highly genetically diverse. Taken together, TZP may be a valuable treatment option for BSIs due to AmpC beta-lactamase-producing Enterobacteriaceae, diminishing the need for broader-spectrum agents. Future studies are needed to validate these findings.

High reliability in healthcare: creating the culture and mindset for patient safety.

Occurrences of patient harm in healthcare represent a significant burden, with serious implications for patients and families and for the capacity of health systems to manage patient access, flow, and wait times. Interest in the science of high reliability, developed originally in industries such as commercial airlines that have demonstrated exceptional safety records, is an emerging trend in healthcare with the potential to help organizations and systems achieve the ultimate goal of zero patient harm. This article argues that zero patient harm is a fundamental imperative, and that high-reliability science can help to accelerate and sustain progress toward this vital goal. Although the practices used in other industries are not readily transferable to healthcare, and no single proven model for High Reliability Organizations in healthcare is yet available, leading organizations are beginning to demonstrate effective healthcare-specific strategies. Experience from Studer Group's international network of partner organizations is used to illustrate and understand these early efforts. Studer Group's Evidence-Based LeadershipSM framework is applied in diverse healthcare settings to provide a foundation of culture transformation and change management to support high reliability. It offers an approach and resources for moving forward toward the goal of zero patient harm, with concurrent benefits related to the efficient use of our valuable healthcare resources.

La haute fiabilité en soins de santé: la création d'une culture et d'une mentalité favorisant la sécurité des patients.

Les préjudices que subissent les patients recevant des soins de santé représentent un fardeau considérable et peuvent avoir de graves répercussions sur les patients et les familles ainsi que sur la capacité des systèmes de santé de gérer l'accès des patients, leurs déplacements dans le système et les temps d'attente. L'intérêt pour la science de la haute fiabilité, mise au point à l'origine dans des secteurs comme l'aviation commerciale, qui ont un bilan exceptionnel en matière de sécurité, est une nouvelle tendance en soins de santé qui pourrait aider les organisations et les systèmes à atteindre le but ultime : zéro préjudice subi par les patients. Cet article fait valoir que zéro préjudice au patient est un impératif fondamental et que la science de la haute fiabilité peut aider à accélérer et à soutenir les progrès vers ce but vital. Bien que les pratiques utilisées dans d'autres secteurs ne soient pas facilement transférables aux soins de santé et qu'il n'existe pas encore un seul modèle éprouvé pour les organisations à haute fiabilité en santé, des organisations de premier plan commencent à faire la démonstration de stratégies efficaces propres aux soins de santé. L'expérience du réseau international d'organisations partenaires du groupe Studer est utilisée pour illustrer et comprendre ces premiers efforts. Le cadre Evidence-Based LeadershipSM (leadership fondé sur les données probantes) du groupe Studer est appliqué dans différents milieux de soins de santé pour transformer la culture et la gestion du changement visant à favoriser une haute fiabilité. Il propose une démarche et des ressources pour progresser vers le but zéro préjudice subi par les patients et tous les avantages liés à l'utilisation efficiente de nos précieuses ressources en soins de santé.

Clinical outcomes associated with polymyxin B dose in patients with bloodstream infections due to carbapenem-resistant Gram-negative rods.

There is significant variation in the use of polymyxin B (PMB), and optimal dosing has not been defined. The purpose of this retrospective study was to evaluate the relationship between PMB dose and clinical outcomes. We included patients with bloodstream infections (BSIs) due to carbapenem-resistant Gram-negative rods who received ≥48 h of intravenous PMB. The objective was to evaluate the association between PMB dose and 30-day mortality, clinical cure at day 7, and development of acute kidney injury (AKI). A total of 151 BSIs were included. The overall 30-day mortality was 37.8% (54 of 151), and the median PMB dosage was 1.3 mg/kg (of total body weight)/day. Receipt of PMB dosages of <1.3 mg/kg/day was significantly associated with 30-day mortality (46.5% versus 26.3%; P = 0.02), and this association persisted in multivariable analysis (odds ratio [OR] = 1.58; 95% confidence interval [CI] = 1.05 to 1.81; P = 0.04). Eighty-two percent of patients who received PMB dosages of <1.3 mg/kg/day had baseline renal impairment. Clinical cure at day 7 was not significantly different between dosing groups. AKI was more common in patients receiving PMB dosages of ≥250 mg/day (66.7% versus 32.0%; P = 0.03), and this association persisted in multivariable analysis (OR = 4.32; 95% CI = 1.15 to 16.25; P = 0.03). PMB dosages of <1.3 mg/kg/day were administered primarily to patients with renal impairment, and this dosing was independently associated with 30-day mortality. However, dosages of ≥250 mg/day were independently associated with AKI. These data support the use of PMB without dose reduction in the setting of renal impairment.

Back to the future: Patient experience and the link to quality, safety, and financial performance.

Improving patient experience has emerged as an important healthcare policy priority across Canada. Tools and systems for monitoring patient experience metrics are becoming increasingly refined and standardized, and the trend toward greater accountability for improvements that are sustainable and affordable is well underway. For many healthcare professionals, this represents a renewed focus on core patient needs and priorities, following decades during which structural and technological changes have dominated healthcare agendas. Improving patient experience in our contemporary healthcare environment presents major challenges-and opportunities-for Canadian health leaders. The experience of Studer Group partner organizations in Canada is relevant and instructive in this context. These organizations have adopted a model known as Evidence-Based Leadership (EBL) that enables and supports the alignment of all activities and behaviours toward specific organizational goals, including measurable patient experience improvements. This article reviews case studies of organizations that have adopted EBL. These organizations are demonstrating rapid progress in patient experience indicators while simultaneously making gains in critical areas such as clinical outcomes, safety, physician and staff engagement, and financial performance. Emerging evidence concerning the factors and processes that underlie these improvements is also discussed.

Retour vers le futur: l'expérience des patients et le lien avec la qualité, la sécurité et le rendement financier.

Au Canada, l'amélioration de l'expérience des patients est devenue une priorité des politiques de santé. Le perfectionnement et la normalisation des outils et systèmes pour surveiller les mesures de l'expérience des patients augmentent, tandis que la tendance vers une plus grande reddition de compte sur des améliorations durables et abordables se confirme. Pour de nombreux professionnels de la santé, ce phénomène fait foi d'un intérêt renouvelé pour les besoins et priorités fondamentaux des patients, après des décennies où les changements structurels et technologiques ont dominé les programmes de santé. Pour les leaders en santé canadiens, l'amélioration de l'expérience des patients comporte actuellement de grands défis et de belles possibilités. À cet égard, l'expérience des organisations partenaires du groupe Studer au Canada est à la fois pertinente et instructive. Ces organisations ont adopté un modèle, du nom de Evidence-Based Leadership (EBL, ou leadership fondé sur des données probantes), qui favorise et soutient l'harmonisation de l'ensemble des activités et des comportements, conformément à des objectifs organisationnels précis, y compris des améliorations mesurables de l'expérience des patients. Le présent article expose des études de cas d'organisations qui ont adopté l'EBL. Ces organisations ont réalisé des progrès rapides en matière d'indicateurs de l'expérience des patients, ainsi que dans des secteurs essentiels comme les résultats cliniques, la sécurité et le rendement financier. Les données émergentes sur les facteurs et processus qui sous-tendent ces améliorations sont également abordées.

The role of envelope shape in the localization of multiple sound sources and echoes in the barn owl.

Echoes and sounds of independent origin often obscure sounds of interest, but echoes can go undetected under natural listening conditions, a perception called the precedence effect. How does the auditory system distinguish between echoes and independent sources? To investigate, we presented two broadband noises to barn owls (Tyto alba) while varying the similarity of the sounds' envelopes. The carriers of the noises were identical except for a 2- or 3-ms delay. Their onsets and offsets were also synchronized. In owls, sound localization is guided by neural activity on a topographic map of auditory space. When there are two sources concomitantly emitting sounds with overlapping amplitude spectra, space map neurons discharge when the stimulus in their receptive field is louder than the one outside it and when the averaged amplitudes of both sounds are rising. A model incorporating these features calculated the strengths of the two sources' representations on the map (B. S. Nelson and T. T. Takahashi; Neuron 67: 643-655, 2010). The target localized by the owls could be predicted from the model's output. The model also explained why the echo is not localized at short delays: when envelopes are similar, peaks in the leading sound mask corresponding peaks in the echo, weakening the echo's space map representation. When the envelopes are dissimilar, there are few or no corresponding peaks, and the owl localizes whichever source is predicted by the model to be less masked. Thus the precedence effect in the owl is a by-product of a mechanism for representing multiple sound sources on its map.

The contributions of onset and offset echo delays to auditory spatial perception in human listeners.

In echoic environments, direct sounds dominate perception even when followed by their reflections. As the delay between the direct (lead) source and the reflection (lag) increases, the reflection starts to become localizable. Although this phenomenon, which is part of the precedence effect, is typically studied with brief transients, leading and lagging sounds often overlap in time and are thus composed of three distinct segments: the "superposed" segment, when both sounds are present together, and the "lead-alone" and "lag-alone" segments, when leading and lagging sounds are present alone, respectively. Recently, it was shown that the barn owl (Tyto alba) localizes the lagging sound when the lag-alone segment, not the lead-alone segment, is lengthened. This was unexpected given the prevailing hypothesis that a leading sound may briefly desensitize the auditory system to sounds arriving later. The present study confirms this finding in humans under conditions that minimized the role of the superposed segment in the localization of either source. Just as lengthening the lag-alone segment caused the lagging sound to become more salient, lengthening the lead-alone segment caused the leading sound to become more salient. These results suggest that the neural representations of the lead and lag are independent of one another.

Long-term α1A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood, and longevity.

The role of α(1)-adrenergic receptors (α(1)ARs) in cognition and mood is controversial, probably as a result of past use of nonselective agents. α(1A)AR activation was recently shown to increase neurogenesis, which is linked to cognition and mood. We studied the effects of long-term α(1A)AR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM) form of the α(1A)AR. CAM-α(1A)AR mice showed enhancements in several behavioral models of learning and memory. In contrast, mice that have the α(1A)AR gene knocked out displayed poor cognitive function. Hippocampal brain slices from CAM-α(1A)AR mice demonstrated increased basal synaptic transmission, paired-pulse facilitation, and long-term potentiation compared with wild-type (WT) mice. WT mice treated with the α(1A)AR-selective agonist cirazoline also showed enhanced cognitive functions. In addition, CAM-α(1A)AR mice exhibited antidepressant and less anxious phenotypes in several behavioral tests compared with WT mice. Furthermore, the lifespan of CAM-α(1A)AR mice was 10% longer than that of WT mice. Our results suggest that long-term α(1A)AR stimulation improves synaptic plasticity, cognitive function, mood, and longevity. This may afford a potential therapeutic target for counteracting the decline in cognitive function and mood associated with aging and neurological disorders.

A prospective blinded comparison of second trimester fetal measurements by expert and novice readers using low-cost novice-acquired 3D volumetric ultrasound.

RATIONALE AND OBJECTIVES: Two-dimensional (2D) ultrasound (US) is operator dependent, requiring operator skill and experience to selectively identify and record planes of interest for subsequent interpretation. This limits the utility of US in settings in which expert sonographers are unavailable. Three-dimensional (3D) US acquisition of an anatomic target, which enables reconstruction of any plane through the acquired volume, might reduce operator dependence by providing any desired image plane for interpretation, without identification of target planes of interest at the time of acquisition. We applied a low-cost 3DUS technology because of the wider potential application compared with dedicated 3DUS systems. We chose second trimester fetal biometric parameters for study because of their importance in maternal-fetal health globally. We hypothesized that expert and novice interpretations of novice-acquired 3D volumes would not differ from each other nor from expert measurements of expert-acquired 2D images, the clinical reference standard. MATERIALS AND METHODS: This was a prospective, blinded, observational study. Expert sonographers blinded to 3DUS volumes acquired 2DUS images of second trimester fetuses from 32 subjects, and expert readers performed interpretation, during usual care. A novice sonographer blinded to other clinical data acquired oriented 3DUS image volumes of the same subjects on the same date. Expert readers blinded to other data assessed placental location (PL), fetal presentation (FP), and amniotic fluid volume (AFV) in novice-acquired 3D volumes. Novice and expert raters blinded to other data independently measured biparietal diameter (BPD), humerus length (HL), and femur length (FL) for each fetus from novice-acquired 3D volumes. Corresponding gestational age (GA) estimates were calculated. Inter-rater reliability of measurements and GAs (expert 3D versus expert 2D, novice 3D versus expert 2D, and expert 3D versus novice 3D) were assessed by intraclass correlation coefficient (ICC). Mean inter-rater measurement differences were analyzed using one-way ANOVA. RESULTS: 3D volume acquisition and reconstruction required mean 30.4 s (±5.7) and 70.0 s (±24.0), respectively. PL, FP, and AFV were evaluated from volumes for all subjects; mean time for evaluation was 16 s (±0.0). PL, FP, and AFV could be evaluated for all subjects. At least one biometric measurement was possible for 31 subjects (97%). Agreement between rater pairs for a composite of all measures was excellent (ICCs ≥ 0.95), and for individual measures was good to excellent (ICCs ≥ 0.75). Inter-rater differences were not significant (p > .05). CONCLUSIONS: Expert and novice interpretations of novice-acquired 3DUS volumes of second trimester fetuses provided reliable biometric measures compared with expert interpretation of expert-acquired 2DUS images. 3DUS volume acquisition with a low-cost system may reduce operator dependence of ultrasound.

Characterization of Bacterial and Fungal Infections in Hospitalized Patients With Coronavirus Disease 2019 and Factors Associated With Health Care-Associated Infections.

BACKGROUND: Patients hospitalized with coronavirus disease 2019 (COVID-19) are at increased risk of health care-associated infections (HAIs), especially with prolonged hospital stays. We sought to identify incidence, antimicrobial susceptibilities, and outcomes associated with bacterial/fungal secondary infections in a large cohort of patients with COVID-19. METHODS: We evaluated adult patients diagnosed with COVID-19 between 2 March and 31 May 2020 and hospitalized >24 hours. Data extracted from medical records included diagnoses, vital signs, laboratory results, microbiological data, and antibiotic use. Microbiologically confirmed bacterial and fungal pathogens from clinical cultures were evaluated to characterize community- and health care-associated infections, including describing temporal changes in predominant organisms on presentation and throughout hospitalization. Univariable and multivariable logistic regression analyses were performed to investigate risk factors for HAIs. RESULTS: A total of 3028 patients were included and accounted for 899 positive clinical cultures. Overall, 516 (17%) patients with positive cultures met criteria for infection. Community-associated coinfections were identified in 183 (6%) patients, whereas HAIs occurred in 350 (12%) patients. Fifty-seven percent of HAIs were caused by gram-negative bacteria and 19% by fungi. Antibiotic resistance increased with longer hospital stays, with incremental increases in the proportion of vancomycin resistance among enterococci and ceftriaxone and carbapenem resistance among Enterobacterales. Intensive care unit stay, invasive mechanical ventilation, and steroids were associated with HAIs. CONCLUSIONS: HAIs occur in a small proportion of patients hospitalized with COVID-19 and are most often caused by gram-negative and fungal pathogens. Antibiotic resistance is more prevalent with prolonged hospital stays. Antimicrobial stewardship is imperative in this population to minimize unnecessary broad-spectrum antibiotic use.