Factors Associated with Poor Clinical and Microbiologic Outcomes in C. auris Bloodstream Infection: A Multicenter Retrospective Cohort Study.

BACKGROUND: C. auris has become a growing concern worldwide due to increases in incidence of colonization and reports of invasive infections. There are limited data on clinical factors associated with poor outcomes in patients with C. auris bloodstream infection (BSI). METHODS: We assembled a multicenter retrospective cohort of patients with C. auris BSI from two geographics areas in US healthcare settings. We collected data on demographic, clinical, and microbiologic characteristics to describe the cohort and constructed multivariate logistic regression models to understand risk factors for two clinical outcomes, all-cause mortality during facility admission, and blood culture clearance. RESULTS: Our cohort consisted of 187 patients with C. auris BSI (56.1% male, 55.6% age >65 years); 54.6% died by facility discharge and 66.9% (of 142 with available data) experienced blood culture clearance. Pitt bacteremia score at infection onset was associated with mortality (odds-ratio [95% confidence interval]: 1.19 [1.01,1.40] per 1-point increase). Hemodialysis was associated with a reduced odds of microbiologic clearance (0.15 [0.05,0.43]) and with mortality (3.08 [1.27,7.50]). CONCLUSIONS: The Pitt bacteremia score at the onset of C. auris BSI may be a useful tool in identifying patients at risk for mortality. Targeted infection prevention practices in patients receiving hemodialysis may be useful to limit poor outcomes.

Difficult-to-treat (DTR) Pseudomonas aeruginosa harboring Verona-Integron metallo-ß-lactamase (blaVIM): infection management and molecular analysis.

Pseudomonas aeruginosa harboring Verona Integron-encoded metallo-ß-lactamase enzymes (VIM-CRPA) have been associated with infection outbreaks in several parts of the world. In the US, however, VIM-CRPA remain rare. Starting in December 2018, we identified a cluster of cases in our institution. Herein, we present our epidemiological investigation and strategies to control/manage these challenging infections. This study was conducted in a large academic healthcare system in Miami, FL, between December 2018 and January 2022. Patients were prospectively identified via rapid molecular diagnostics when cultures revealed carbapenem-resistant P. aeruginosa. Alerts were received in real time by the antimicrobial stewardship program and infection prevention teams. Upon alert recognition, a series of interventions were performed as a coordinated effort. A retrospective chart review was conducted to collect patient demographics, antimicrobial therapy, and clinical outcomes. Thirty-nine VIM-CRPA isolates led to infection in 21 patients. The majority were male (76.2%); the median age was 52 years. The majority were mechanically ventilated (n = 15/21; 71.4%); 47.6% (n = 10/21) received renal replacement therapy at the time of index culture. Respiratory (n = 20/39; 51.3%) or bloodstream (n = 13/39; 33.3%) were the most common sources. Most infections (n = 23/37; 62.2%) were treated with an aztreonam-avibactam regimen. Six patients (28.6%) expired within 30 days of index VIM-CRPA infection. Fourteen isolates were selected for whole genome sequencing. Most of them belonged to ST111 (12/14), and they all carried blaVIM-2 chromosomally. This report describes the clinical experience treating serious VIM-CRPA infections with either aztreonam-ceftazidime/avibactam or cefiderocol in combination with other agents. The importance of implementing infection prevention strategies to curb VIM-CRPA outbreaks is also demonstrated.

Community-acquired pneumonia: a US perspective on the guideline gap.

Community-acquired pneumonia continues to be one of the most common causes of morbidity and mortality due to infectious disease. The aetiologies, clinical presentations, diagnostic modalities and therapeutic options are changing and outpacing the creation of management guidelines. This educational article summarizes a roundtable activity sponsored by an unrestricted educational grant by Paratek that included US experts discussing these changes and identifying gaps in the current guidelines.

A Multicenter Retrospective Cohort Study to Characterize Patients Hospitalized With Multisystem Inflammatory Syndrome in Adults and Coronavirus Disease 2019 in the United States, 2020-2021.

BACKGROUND: The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute coronavirus disease 2019 (COVID-19) and may affect clinical management. METHODS: In this retrospective cohort study, we applied the US Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at 6 academic medical centers from 1 March 2020 to 31 December 2021. Patients MIS-A were matched by age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographic characteristics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts. RESULTS: Through medical record review of 10 223 patients hospitalized with SARS-CoV-2-associated illness, we identified 53 MIS-A cases. Compared with 106 matched patients with COVID-19, those with MIS-A were more likely to be non-Hispanic black and less likely to be non-Hispanic white. They more likely had laboratory-confirmed COVID-19 ≥14 days before hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, patients with MIS-A had higher neutrophil-to-lymphocyte ratio and higher levels of C-reactive protein, ferritin, procalcitonin, and D-dimer than patients with COVID-19. They also had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. The mortality rate was 6% in both cohorts. CONCLUSIONS: Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management.

Disrupting the infectious disease ecosystem in the digital precision health era innovations and converging emerging technologies.

This commentary explores the convergence of precision health and evolving technologies, including the critical role of artificial intelligence (AI) and emerging technologies in infectious diseases (ID) and microbiology. We discuss their disruptive impact on the ID ecosystem and examine the transformative potential of frontier technologies in precision health, public health, and global health when deployed with robust ethical and data governance guardrails in place.

Multisite Detection of Tn1549-Mediated vanB Vancomycin Resistance in Multidrug-Resistant Enterococcus faecalis ST6 in Texas and Florida.

In the United States, vanB-mediated resistance in enterococci is rare. We characterized three sequence type (ST) 6, vancomycin-resistant Enterococcus faecalis isolates causing bacteremia in unique patients in spatiotemporally distinct settings. Isolates were recovered between 2018 and 2020 in two cities in the United States (Houston, TX; Miami, FL). The isolates harbored the vanB operon on a chromosomally located Tn1549 transposon, and epidemiological data suggested multiple introductions of the vanB gene cluster into ST6 E. faecalis.

Difference between SARS-CoV-2, seasonal coronavirus, influenza, and respiratory syncytial virus infection in solid organ transplant recipients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been raging since the end of 2019 and has shown worse outcomes in solid organ transplant (SOT) recipients. The clinical differences as well as outcomes between respiratory viruses have not been well defined in this population. METHODS: This is a retrospective cohort study of adult SOT recipients with nasopharyngeal swab or bronchoalveolar lavage PCR positive for either SARS-CoV-2, seasonal coronavirus, respiratory syncytial virus (RSV) or influenza virus from January 2017 to October 2020. The follow up period was 3 months. Clinical characteristics and outcomes were evaluated. RESULTS: A total of 377 recipients including 157 SARS-CoV-2, 70 seasonal coronavirus, 50 RSV and 100 influenza infections were identified. The most common transplanted organ was kidney 224/377 (59.4%). Lower respiratory tract infection (LRTI) was found in 210/377 (55.7%) and the risk factors identified with multivariable analysis were SARS-CoV-2 infection, steroid use, and older age. Co- and secondary infections were seen in 77/377 (20.4%) recipients with bacterial pathogens as dominant. Hospital admission was seen in 266/377 (67.7%) recipients without significant statistical difference among viruses, however, ICU admission, mechanical ventilation and mortality were higher with SARS-CoV-2 infection. In the multivariable model, the risk factors for mortality were SARS-CoV-2 infection and older age. CONCLUSIONS: We found higher incidence of ICU admission, mechanical ventilation, and mortality among SARS-CoV-2 infected recipients. Older age was found to be the risk factor for lower respiratory tract infection and mortality for SARS-CoV-2, coronaviruses, RSV and influenza virus groups.

Clinical characteristics and outcomes in CMV infection in intestinal transplant recipients: A single-center experience.

BACKGROUND: Cytomegalovirus (CMV) infection is one of the most common posttransplantation infections and has been associated with increased rejection and mortality. Data in intestinal transplants recipients are limited. METHODS: This is a single-center, retrospective cohort study of all intestinal transplants performed between January 1, 2009, and August 31, 2020. We included recipients of all ages who were at risk of CMV infection. To identify the risk factors, we conducted at first univariate and multivariate analysis. For the multivariate analysis, we developed a logistic regression model based on the result of univariate analysis. RESULTS: Ninety five patients with a median age of 32 (interquartile range [IQR] 4, 50) were included. CMV donor seropositive/recipient seronegative were 17 (17.9%). Overall, 22.1% of the recipients developed CMV infection at a median time of 155 (IQR 28-254) days from transplant, including 4 CMV syndrome and 6 CMV end-organ disease. Overall, 90.4%, (19/21) developed DNAemia while on prophylaxis. Median peak viral load and time to negativity was 16 000 (IQR 1034-43 892) IU/mL and 56 (IQR 49-109) days, respectively. (Val)ganciclovir and foscarnet were utilized in 17 (80.9%) and 1 (4.76%) recipients, respectively. Recurrences of CMV DNAemia and graft rejection were observed in three and six recipients, respectively. Younger age was identified as a risk factor (p = .032, odds ratio 0.97, 95% confidence interval 0.95-0.99) to develop CMV DNAemia. CONCLUSION: A significant proportion of intestinal transplant recipients developed CMV infection while on prophylaxis. Better methods such as CMV cell mediated immunity guided prophylaxis should be used to prevent infections in this population.

Validation of the INCREMENT-SOT-CPE score in a large cohort of liver transplant recipients with carbapenem-resistant Enterobacterales infection.

BACKGROUND: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking. METHODS: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out. RESULTS: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score ≥ 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE ≥ 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score ≥ 11 and SOFA score ≥ 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective. CONCLUSIONS: Both INCREMENT-SOT-CPE ≥ 11 and SOFA ≥ 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.

Evaluation of the Infectious Diseases Society of America's Core Antimicrobial Stewardship Curriculum for Infectious Diseases Fellows.

BACKGROUND: Antimicrobial stewardship (AS) programs are required by Centers for Medicare and Medicaid Services and should ideally have infectious diseases (ID) physician involvement; however, only 50% of ID fellowship programs have formal AS curricula. The Infectious Diseases Society of America (IDSA) formed a workgroup to develop a core AS curriculum for ID fellows. Here we study its impact. METHODS: ID program directors and fellows in 56 fellowship programs were surveyed regarding the content and effectiveness of their AS training before and after implementation of the IDSA curriculum. Fellows' knowledge was assessed using multiple-choice questions. Fellows completing their first year of fellowship were surveyed before curriculum implementation ("pre-curriculum") and compared to first-year fellows who complete the curriculum the following year ("post-curriculum"). RESULTS: Forty-nine (88%) program directors and 105 (67%) fellows completed the pre-curriculum surveys; 35 (64%) program directors and 79 (50%) fellows completed the post-curriculum surveys. Prior to IDSA curriculum implementation, only 51% of programs had a "formal" curriculum. After implementation, satisfaction with AS training increased among program directors (16% to 68%) and fellows (51% to 68%). Fellows' confidence increased in 7/10 AS content areas. Knowledge scores improved from a mean of 4.6 to 5.1 correct answers of 9 questions (P = .028). The major hurdle to curriculum implementation was time, both for formal teaching and for e-learning. CONCLUSIONS: Effective AS training is a critical component of ID fellowship training. The IDSA Core AS Curriculum can enhance AS training, increase fellow confidence, and improve overall satisfaction of fellows and program directors.

White paper on antimicrobial stewardship in solid organ transplant recipients.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a "one-size-fits-all" style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Rapid molecular testing for antimicrobial stewardship and solid organ transplantation.

BACKGROUND: Several molecular platforms now exist for early detection of infectious pathogens. In this review, we present the currently available literature summarizing clinical outcomes using rapid diagnostic tests (RDTs) in the solid organ transplant (SOT) population. We also present potential benefits and drawbacks of these technologies for SOT patients. METHODS: We completed a PubMed search querying for 31 specific RDTs AND ("SOT"). We also queried PubMed for studies on RDT outcomes in the general population. References of the resulting relevant studies were reviewed and incorporated if the study population included at least one SOT patient. All culture specimen types were included. Only full-text peer-reviewed publications in English were examined. RESULTS: Our search yielded eleven studies. Across these studies, integrating RDTs with ASP intervention led to faster species identification and susceptibility results, faster time-to-optimal therapy, decreased hospital length-of-stay and costs, and decreased mortality. Potential drawbacks of RDTs in the SOT population included: overdiagnosis due to increased sensitivity (i.e., Clostridium difficile), decreased yield of tests for respiratory pathogens, and lack of identification of important pathogens in this population such as, Aspergillus species. CONCLUSIONS: Although there is a scarcity of studies involving SOT patients, current available data suggests that the use of RDTs helps improve patient outcomes and minimizes inappropriate antimicrobial use when coupled with proactive ASPs. Future studies should focus on clinical outcomes in SOT patients specifically, as well as how to optimize the use of RDTs in conjunction with traditional microbiology methods.

Challenges and opportunities in stewardship among solid organ transplant recipients with Candida auris bloodstream infections.

BACKGROUND: Candida auris is an emerging nosocomial pathogen worldwide. However, there has been little published on the management of C. auris in solid organ transplant recipients. METHODS: A single-center, retrospective cohort study was conducted to evaluate C. auris bloodstream infections in solid organ transplant recipients between January 2020 and December 2021. Patient-related and outcomes data were extracted from electronic medical records. RESULTS: Of the 42 patients identified with C. auris bloodstream infections, five were in solid organ transplant recipients (1 heart, 3 liver, and 1 combined liver-kidney). The median time to fungemia from hospital admission was 43 days, and the median time to fungemia from transplant was 18 days. All patients received micafungin as initial treatment, at a median of 6 hours from pathogen detection. Four patients achieved blood clearance, two patients had persistent fungemia, and two patients developed secondary complications from hematogenous spread. One patient died, resulting in a mortality rate of 20%. CONCLUSIONS: Solid organ transplant recipients are at high risk for developing C. auris bloodstream infections. In order to prevent graft loss and mortality, best practices for the management of C.auris should include rapid screening, diagnosis, and treatment. While echinocandins are considered first-line, antifungal selection should be based on susceptibilities and site of infection. Data to support routine use of combination therapy are lacking, however there may be a role for refractory cases. Prevention efforts against C. auris infection are especially important given the lack of effective decolonization strategies. For transplant recipients, hospitals should seek opportunities to restore patients' gut microbiome by curtailing unnecessary hospital procedures and inappropriate antimicrobial use. Further research and national guidelines are needed to better direct stewardship in this field.

Reinfection with SARS-CoV-2 in solid-organ transplant recipients: Incidence density and convalescent immunity prior to reinfection.

BACKGROUND: Long-term protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains poorly characterized, particularly in solid organ transplant (SOT) patients. METHOD: We determined the incidence density of SARS-CoV-2 reinfection in a cohort of adult SOT recipients initially infected between March 1st, 2020 and March 30th, 2021 and included those with initial infection before or after transplantation. Incidence density was the total cases divided by total days after initial diagnosis with active graft. RESULTS: Of 210 infected recipients, five (2.4%) developed reinfection, including two who had received full mRNA vaccination, but none developed hypoxia. The incidence density for reinfection was 9.4 (95% confidence interval [CI] 3.9-22.6) and for primary infection the density was 9.1 (95% CI 7.9-10.5) cases/100,000 patient days. Two recipients had immunity evaluated in the weeks prior to reinfection, by measuring immunoglobulin-G (IgG) antibody titer to the SARS-CoV-2 receptor binding domain and virus-specific CD4+ and CD8+ T-cell reactivity following stimulation with SARS-CoV-2 peptide pools. Both mounted virus specific CD4 T-cell responses prior to reinfection (1.19% and 0.28% of total CD4 T cells) and both had reactive IgG testing (1.30 and 4.99 signal/cut off ratio). CONCLUSIONS: This suggests that SOT recipients infected with SARS-CoV-2 remain at high risk for reinfection even after generating cellular and humoral immune responses.

Is the Omicron variant truly less virulent in solid organ transplant recipients?

Solid organ transplant (SOT) recipients are at high risk for severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Emerging variants of concern have disproportionately affected this population. Data on severity and outcomes with the Omicron variant in SOT recipients are limited. Thus we conducted this single-center, retrospective cohort study of SOT recipients diagnosed with SARS-CoV-2 infection from December 18, 2021 to January 18, 2022, when prevalence of the Omicron variant was more than 80%-95% in the community. Univariate and multivariate logistic regression analysis was performed to identify risk factors for hospital admission. We identified 166 SOT patients: 112 (67.5%) kidney, 22 (13.3%) liver, 10 (6.0%) lung, seven (4.2%) heart, and 15 (9.0%) combined transplants. SARS-CoV-2 vaccine series was completed in 59 (35.5%) recipients. Ninety-nine (59.6%) and 13 (7.8%) recipients received casirivimab/imdevimab and sotrovimab, respectively. Fifty-three (32%) recipients required hospital admission, of which 19 (35.8%) required intensive care unit level of care. Median follow-up was 50 (interquartile range, 25-59) days, with mortality reported in six (3.6%) patients. Risk factors identified for hospital admission were African American race (p < .001, odds ratio [OR] 4.00, 95% confidence interval [CI] 1.84-8.70), history of coronary artery disease (p = .031, OR 3.50, 95% CI 1.12-10.87), and maintenance immunosuppression with corticosteroids (p = .048, OR 2.00, 95% CI 1.01-4.00). In conclusion, contrary to that in the general population, we found a higher hospital admission rate in SOT recipients with omicron variant infection. Further studies to investigate the efficacy of newer treatments are necessary, even as outcomes continue to improve.

Infected chylopericardium: An unexpected cause of cardiac tamponade.

A 22-year-old immunocompetent female with a history of small pericardial effusion while infant presented with fever and hemodynamic collapse 4 days after facial trauma. She was found to have cardiac tamponade secondary to infected chylopericardium from bacterial translocation. We report this very unusual case and review of the literature on chylopericardium infections.

Development of a Risk Prediction Model for Carbapenem-resistant Enterobacteriaceae Infection After Liver Transplantation: A Multinational Cohort Study.

BACKGROUND: Patients colonized with carbapenem-resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT), with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies. METHODS: Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray subdistribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created. RESULTS: A total of 840 LT recipients found to be colonized with CRE before (n = 203) or after (n = 637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (interquartile range [IQR], 9-42) days after LT. Pre- and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical reintervention were retained in the prediction model. Median 30- and 60-day predicted risk was 15% (IQR, 11-24) and 21% (IQR, 15-33), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (area under the curve [AUC], 74.6; Brier index, 16.3) and bootstrapped validation dataset (AUC, 73.9; Brier index, 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/. CONCLUSIONS: Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.

When is it safe to perform abdominal transplantation in patients with prior SARS-CoV-2 infection: A case series.

BACKGROUND: The Coronavirus disease 2019(COVID-19) pandemic has negatively impacted worldwide organ transplantation. However, there is limited information on recipients transplanted after SARS-CoV-2 infection. A full understanding of this scenario is required, as transplantation is a life-saving procedure and COVID-19 remains an ongoing threat. METHODS: Abdominal organ transplant recipients diagnosed with COVID-19 prior to transplantation were identified by chart review and clinical data were collected. The primary outcome was the transplant outcome including graft loss, rejection and death, and reactivation of infection post-transplant. RESULTS: We identified 14 patients who received abdominal organ transplants after symptomatic PCR confirmed SARS-CoV-2 infection; four patients had a positive PCR at the time of admission for transplantation. The median time of follow-up was 79 (22-190) days. One recipient with negative PCR before transplant tested positive 9 days after transplant. One of 14 transplanted patients developed disseminated mold infection and died 86 days after transplant. During the follow-up, only one patient developed rejection; thirteen patients had favorable graft outcomes. CONCLUSIONS: We were able to perform abdominal transplantation for patients with COVID-19 before transplant, even with positive PCR at the time of transplant. Larger studies are needed to determine the time to safe transplant after SARS-CoV-2 infection.

KPC-3-Producing Serratia marcescens Outbreak between Acute and Long-Term Care Facilities, Florida, USA.

We describe an outbreak caused by Serratia marcescens carrying blaKPC-3 that was sourced to a long-term care facility in Florida, USA. Whole-genome sequencing and plasmid profiling showed involvement of 3 clonal lineages of S. marcescens and 2 blaKPC-3-carrying plasmids. Determining the resistance mechanism is critical for timely implementation of infection control measures.

Opportunities to Improve Antibiotic Appropriateness in U.S. ICUs: A Multicenter Evaluation.

OBJECTIVES: To use a standardized tool for a multicenter assessment of antibiotic appropriateness in ICUs and identify local antibiotic stewardship improvement opportunities. DESIGN: Pilot point prevalence conducted on October 5, 2016; point prevalence survey conducted on March 1, 2017. SETTING: ICUs in 12 U.S. acute care hospitals with median bed size 563. PATIENTS: Receiving antibiotics on participating units on March 1, 2017. INTERVENTIONS: The Centers for Disease Control and Prevention tool for the Assessment of Appropriateness of Inpatient Antibiotics was made actionable by an expert antibiotic stewardship panel and implemented across hospitals. Data were collected by antibiotic stewardship program personnel at each hospital, deidentified and submitted in aggregate for benchmarking. hospital personnel identified most salient reasons for inappropriate use by category and agent. MEASUREMENTS AND MAIN RESULTS: Forty-seven ICUs participated. Most hospitals (83%) identified as teaching with median licensed ICU beds of 70. On March 1, 2017, 362 (54%) of 667 ICU patients were on antibiotics (range, 8-81 patients); of these, 112 (31%) were identified as inappropriate and administered greater than 72 hours among all 12 hospitals (range, 9-82%). Prophylactic antibiotic regimens and PICU patients demonstrated a statistically significant risk ratio of 1.76 and 1.90 for inappropriate treatment, respectively. Reasons for inappropriate use included unnecessarily broad spectrum (29%), no infection or nonbacterial syndrome (22%), and duration longer than necessary (21%). Of patients on inappropriate antibiotic therapy in surgical ICUs, a statistically significant risk ratio of 2.59 was calculated for noninfectious or nonbacterial reasons for inappropriate therapy. CONCLUSIONS: In this multicenter point prevalence study, 31% of ICU antibiotic regimens were inappropriate; prophylactic regimens were often inappropriate across different ICU types, particularly in surgical ICUs. Engaging intensivists in antibiotic stewardship program efforts is crucial to sustain the efficacy of antibiotics and quality of infectious diseases care in critical care settings. This study underscores the value of standardized assessment tools and benchmarking to be shared with local leaders for targeted antibiotic stewardship program interventions.