Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant Acinetobacter baumannii Among Patients From Different Global Regions.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. METHODS: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. RESULTS: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. CONCLUSIONS: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.

Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. METHODS: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality. FINDINGS: We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses. INTERPRETATION: The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. FUNDING: National Institutes of Health.

Characteristics of community-acquired carbapenem-resistant Enterobacterales.

BACKGROUND: Community-acquired carbapenem-resistant Enterobacterales (CA-CRE) are an important threat. METHODS: In CRACKLE-2, we defined patients with CA-CRE as admitted from home, without pre-existing conditions, and a positive culture within 48 h of admission. Healthcare-associated CRE (HA-CRE) were those with the lowest likelihood of community acquisition, not admitted from home and cultured >48 h after admission. Specific genetic markers in carbapenemase-producing Klebsiella pneumoniae were evaluated through random forest modelling. RESULTS: CA-CRE and HA-CRE were detected in 83 (10%) and 208 (26%) of 807 patients. No significant differences were observed in bacterial species or strain type distribution. K. pneumoniae (204/291, 70%) was the most common CRE species, of these 184/204 (90%) were carbapenemase producers (CPKP). The top three genetic markers in random forest models were kpi_SA15, fimE, and kpfC. Of these, kpi_SA15 (which encodes a chaperone/usher system) was positively associated (OR 3.14, 95% CI 1.13-8.87, P = 0.026), and kpfC negatively associated (OR 0.21, 95% CI 0.05-0.72, P = 0.015) with CA-CPKP. CONCLUSIONS: Ten percent of CDC-defined CRE were CA. The true proportion of CA-CRE in hospitalized patients is likely lower as patients may have had unrecorded prior healthcare exposure. The kpi_SA15 operon was associated with the CA phenotype.

Impact of a Rapid Molecular Test for Klebsiella pneumoniae Carbapenemase and Ceftazidime-Avibactam Use on Outcomes After Bacteremia Caused by Carbapenem-Resistant Enterobacterales.

BACKGROUND: Patients with bacteremia due to carbapenem-resistant Enterobacterales (CRE) experience delays until appropriate therapy and high mortality rates. Rapid molecular diagnostics for carbapenemases and new ß-lactam/ß-lactamase inhibitors may improve outcomes. METHODS: We conducted an observational study of patients with CRE bacteremia from 2016 to 2018 at 8 New York and New Jersey medical centers and assessed center-specific clinical microbiology practices. We compared time to receipt of active antimicrobial therapy and mortality between patients whose positive blood cultures underwent rapid molecular testing for the Klebsiella pneumoniae carbapenemase (KPC) gene (blaKPC) and patients whose cultures did not undergo this test. CRE isolates underwent antimicrobial susceptibility testing by broth microdilution and carbapenemase profiling by whole-genome sequencing. We also assessed outcomes when ceftazidime-avibactam and polymyxins were used as targeted therapies. RESULTS: Of 137 patients with CRE bacteremia, 89 (65%) had a KPC-producing organism. Patients whose blood cultures underwent blaKPC PCR testing (n = 51) had shorter time until receipt of active therapy (median: 24 vs 50 hours; P = .009) compared with other patients (n = 86) and decreased 14-day (16% vs 37%; P = .007) and 30-day (24% vs 47%; P = .007) mortality. blaKPC PCR testing was associated with decreased 30-day mortality (adjusted odds ratio: .37; 95% CI: .16-.84) in an adjusted model. The 30-day mortality rate was 10% with ceftazidime-avibactam monotherapy and 31% with polymyxin monotherapy (P = .08). CONCLUSIONS: In a KPC-endemic area, blaKPC PCR testing of positive blood cultures was associated with decreased time until appropriate therapy and decreased mortality for CRE bacteremia, and ceftazidime-avibactam is a reasonable first-line therapy for these infections.

Evaluation of Clinical Outcomes After Introduction of a Dedicated Infectious Diseases-Critical Care Medicine Service in Critical Care Units.

BACKGROUND: Infection is a leading cause of admission to intensive care units (ICUs), with critically ill patients often receiving empiric broad-spectrum antibiotics. Nevertheless, a dedicated infectious diseases (ID) consultation and stewardship team is not routinely established. An ID-critical care medicine (ID-CCM) pilot program was designed at a 400-bed tertiary care hospital in which an ID attending was assigned to participate in daily rounds with the ICU team, as well as provide ID consultation on select patients. We sought to evaluate the impact of this dedicated ID program on antibiotic utilization and clinical outcomes in patients admitted to the ICU. METHODS: In this single-site retrospective study, we analyzed antibiotic utilization and clinical outcomes in patients admitted to an ICU during the postintervention period from January 1 to December 31, 2017, and compared it to antibiotic utilization in the same ICUs during the preintervention period from January 1 to December 31, 2015. RESULTS: Our data showed a statistically significant reduction in usage of most frequently prescribed antibiotics including vancomycin, piperacillin-tazobactam, and cefepime during the intervention period. When compared to the preintervention period there was no difference in-hospital mortality, hospital length of stay, and readmission. CONCLUSIONS: With this multidisciplinary intervention, we saw a decrease in the use of the most frequently prescribed broad-spectrum antibiotics without a negative impact on clinical outcomes. Our study shows that the implementation of an ID-CCM service is a feasible way to promote antibiotic stewardship in the ICU and can be used as a strategy to reduce unnecessary patient exposure to broad-spectrum agents.

Bacterial and fungal coinfections in COVID-19 patients hospitalized during the New York City pandemic surge.

We observed bacterial or fungal coinfections in COVID-19 patients admitted between March 1 and April 18, 2020 (152 of 4,267, 3.6%). Among these patients, mortality was 57%; 74% were intubated; 51% with bacteremia had central venous catheters. Time to culture positivity was 6-7 days, and 79% had received prior antibiotics. Metallo-ß-lactamase-producing E. cloacae coinfections occurred in 5 patients.

Analysis of catheter utilization, central line associated bloodstream infections, and costs associated with an inpatient critical care-driven vascular access model.

BACKGROUND: Central line-associated bloodstream infections (CLABSI) carry serious risks for patients and financial consequences for hospitals. Avoiding unnecessary temporary central venous catheters (CVC) can reduce CLABSI. Critical Care Medicine (CCM) is often consulted to insert CVC when alternatives are unavailable. We aim to describe clinical and financial implications of a CCM-driven vascular access model. METHODS: In this retrospective, observational cohort study, all CLABSI and a sample of CCM consults for CVC insertion on adult medical-surgical inpatient units were reviewed in 2019. Assessment of CVC appropriateness and financial analysis of labor, reimbursement, and attributable CLABSI cost was conducted. RESULTS: Of 554 CCM consult requests, 75 (13.5%) were for CVC and 36 (48.0%) resulted in CVC insertion; 6 (16.7%) CVC were avoidable. Three CLABSI occurred in avoidable CVC with estimated annual attributable cost of $165,099. Estimated annual CCM consultant cost for CVC was $78,094 generating $110,733 in reimbursement. Overall estimated annual loss was $132,460. DISCUSSION: Reliance on CCM for intravenous access resulted in avoidable CVC, CLABSI, inefficient physician effort, and financial losses; nurse-driven vascular access models offer potential cost savings and risk reduction. CONCLUSIONS: CCM-driven vascular access models may not be cost-effective; alternatives should be considered for utilization reduction, CLABSI prevention, and financial viability.

Derivation of a Model to Guide Empiric Therapy for Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infection in an Endemic Area.

BACKGROUND: Appropriate therapy for carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) is often given late in the course of infection, and strategies for identifying CRKP BSI earlier are needed. METHODS: A retrospective case-control study was performed at a tertiary care hospital, university hospital, and community hospital in Bronx, New York. All participants had a blood culture sent and received an antibiotic within 48 hours of the culture. The case group (n = 163) had a blood culture with CRKP. The control group (n = 178) had a blood culture with carbapenem-susceptible Klebsiella. Data were obtained by electronic or conventional medical record abstraction. A multiple logistic regression model was built to identify associated factors and develop a clinical model for CRKP BSI. Model performance characteristics were estimated using a 10-fold cross-validation analysis. RESULTS: A prior nonblood culture with carbapenem-resistant Enterobacteriaceae, skilled nursing facility (SNF) residence, mechanical ventilation, and admission >3 days were strongly associated risk factors. A significant interaction led to development of separate clinical models for subjects admitted <3 days at the time of positive blood culture from those admitted at least 3 days. The derived models had a good ability to discriminate between subjects with and without CRKP BSI. A clinical classification rule to guide therapy can prioritize sensitivity or specificity. CONCLUSIONS: Prior nonblood cultures showing resistance and exposure to SNF and health care settings are factors associated with carbapenem resistance. The clinical classification rules derived in this work should be validated for ability to guide therapy.

Inferior vena cava filters do not increase the risk of blood stream infections in patients with newly diagnosed VTE.

BACKGROUND: The association between inferior vena cava (IVC) filter presence and subsequent bloodstream infection (BSI) is unknown. We hypothesized among patients with a new diagnosis of venous thromboembolism (VTE), incidence of BSI after 1 year would be higher in patients who had presence of an IVC filter. METHODS: We performed a retrospective cohort study of patients with newly diagnosed VTE but no IVC filter (N = 4,053) and patients with IVC filter (N = 635) admitted to a metropolitan hospital system from 2006 to 2009 comparing incidence of BSI within 1 year of inclusion. Multivariable regression modeling was used to evaluate the association of IVC filter placement with BSI 1 year after placement. RESULTS: Patients with an IVC filter placed were more likely to be older with higher Charlson co-morbidity score (median 4 vs 1; P < .001). The incidence of BSI was not different between the group with IVC filter and the group without (10.7% vs 8.8%; P = .12). There was no association with IVC filter placement and BSI before or after multivariable adjustment. CONCLUSIONS: In patients newly diagnosed with VTE, we found no association between IVC filter placement and increased incidence of BSI after 1 year.

Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are a global threat. We aimed to describe the clinical and molecular characteristics of Centers for Disease Control and Prevention (CDC)-defined CRE in the USA. METHODS: CRACKLE-2 is a prospective, multicentre, cohort study. Patients hospitalised in 49 US hospitals, with clinical cultures positive for CDC-defined CRE between April 30, 2016, and Aug 31, 2017, were included. There was no age exclusion. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Clinical data and bacteria were collected, and whole genome sequencing was done. This trial is registered with ClinicalTrials.gov, number NCT03646227. FINDINGS: 1040 patients with unique isolates were included, 449 (43%) with infection and 591 (57%) with colonisation. The CDC-defined CRE admission rate was 57 per 100 000 admissions (95% CI 45-71). Three subsets of CDC-defined CRE were identified: carbapenemase-producing Enterobacterales (618 [59%] of 1040), non-carbapenemase-producing Enterobacterales (194 [19%]), and unconfirmed CRE (228 [22%]; initially reported as CRE, but susceptible to carbapenems in two central laboratories). Klebsiella pneumoniae carbapenemase-producing clonal group 258 K pneumoniae was the most common carbapenemase-producing Enterobacterales. In 449 patients with CDC-defined CRE infections, DOOR outcomes were not significantly different in patients with carbapenemase-producing Enterobacterales, non-carbapenemase-producing Enterobacterales, and unconfirmed CRE. At 30 days 107 (24%, 95% CI 20-28) of these patients had died. INTERPRETATION: Among patients with CDC-defined CRE, similar outcomes were observed among three subgroups, including the novel unconfirmed CRE group. CDC-defined CRE represent diverse bacteria, whose spread might not respond to interventions directed to carbapenemase-producing Enterobacterales. FUNDING: National Institutes of Health.

Understanding drivers of influenza-like illness presenteeism within training programs: A survey of trainees and their program directors.

BACKGROUND: Working with influenza-like illness (ILI) is pervasive throughout health care. We assessed knowledge, attitudes, and practices regarding ILI presenteeism of both postgraduate trainees and program leaders. METHODS: This survey study was conducted at the Montefiore Medical Center, Albert Einstein College of Medicine, a large academic center in the Bronx, New York. Internal medicine and subspecialty house staff and program directors completed an anonymous electronic survey between April 23 and June 15, 2018. RESULTS: A total of 197 of 400 (49%) house staff and 23 of 39 (59%) program leaders participated; 107 (54%) trainees and 6 (26%) program leaders self-reported ILI presenteeism in the past 12 months. More than 90% of trainees and program leaders reported that ILI presenteeism places others at risk. Only 9% of program leaders accurately estimated trainee ILI presenteeism prevalence. Both cited "not wanting to burden colleagues" as the top reason for ILI presenteeism. Twenty-six (24%) trainees practiced ILI presenteeism on critical care units. The majority reported that they would provide patient care with upper respiratory symptoms without fever. Most trainees incorrectly answered influenza knowledge questions. CONCLUSIONS: ILI presenteeism prevalence is high within training programs at our medical center. Program leaders can model best practices, enforce nonpunitive sick-leave policies, and ensure infection prevention competencies are met annually.

Bundle in the Bronx: Impact of a Transition-of-Care Outpatient Parenteral Antibiotic Therapy Bundle on All-Cause 30-Day Hospital Readmissions.

BACKGROUND: A streamlined transition from inpatient to outpatient care can decrease 30-day readmissions. Outpatient parenteral antibiotic therapy (OPAT) programs have not reduced readmissions; an OPAT bundle has been suggested to improve outcomes. We implemented a transition-of-care (TOC) OPAT bundle and assessed the effects on all-cause, 30-day hospital readmission. METHODS: Retrospectively, patients receiving postdischarge intravenous antibiotics were evaluated before and after implementation of a TOC-OPAT program in Bronx, New York, between July, 2015 and February, 2016. Pearson's χ2 test was used to compare 30-day readmissions between groups, and logistic regression was used to adjust for covariates. Time from discharge to readmission was analyzed to assess readmission risk, using log-rank test to compare survival curves and Cox proportional hazards model to adjust for covariates. Secondary outcomes, 30-day emergency department (ED) visits, and mortality were analyzed similarly. RESULTS: Compared with previous standard care (n = 184), the TOC-OPAT group (n = 146) had significantly lower 30-day readmissions before (13.0% vs 26.1%, P < .01) and after adjustment for covariates (odds ratio [OR] = 0.51; 95% confidence interval [CI], 0.27-0.94; P = .03). In time-dependent analyses, TOC-OPAT patients were at significantly lower risk for readmission (log-rank test, P < .01; hazard ratio = 0.56; 95% CI, 0.32-0.97; P = .04). Propensity-matched sensitivity analysis showed lower readmissions in the TOC-OPAT group (13.6% vs 24.6%, P = .04), which was attenuated after adjustment (OR = 0.51; 95% CI, 0.25-1.05; P = .07). Mortality and ED visits were similar in both groups. CONCLUSIONS: Our TOC-OPAT patients had reduced 30-day readmissions compared with the previous standard of care. An effective TOC-OPAT bundle can successfully improve patient outcomes in an economically disadvantaged area.

Rapidly growing Mycobacterium infections after cosmetic surgery in medical tourists: the Bronx experience and a review of the literature.

BACKGROUND: Medical tourism is increasingly popular for elective cosmetic surgical procedures. However, medical tourism has been accompanied by reports of post-surgical infections due to rapidly growing mycobacteria (RGM). The authors' experience working with patients with RGM infections who have returned to the USA after traveling abroad for cosmetic surgical procedures is described here. METHODS: Patients who developed RGM infections after undergoing cosmetic surgeries abroad and who presented at the Montefiore Medical Center (Bronx, New York, USA) between August 2015 and June 2016 were identified. A review of patient medical records was performed. RESULTS: Four patients who presented with culture-proven RGM infections at the sites of recent cosmetic procedures were identified. All patients were treated with a combination of antibiotics and aggressive surgical treatment. CONCLUSIONS: This case series of RGM infections following recent cosmetic surgeries abroad highlights the risks of medical tourism. Close monitoring of affected patients by surgical and infectious disease specialties is necessary, as aggressive surgical debridement combined with appropriate antibiotic regimens is needed to achieve cure. Given the increasing reports of post-surgical RGM infections, consultants should have a low threshold for suspecting RGM, as rapid diagnosis may accelerate the initiation of targeted treatment and minimize morbidity.

Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States.

Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 µg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.

Explaining savings for visuomotor adaptation: linear time-invariant state-space models are not sufficient.

Adaptation of the motor system to sensorimotor perturbations is a type of learning relevant for tool use and coping with an ever-changing body. Memory for motor adaptation can take the form of savings: an increase in the apparent rate constant of readaptation compared with that of initial adaptation. The assessment of savings is simplified if the sensory errors a subject experiences at the beginning of initial adaptation and the beginning of readaptation are the same. This can be accomplished by introducing either 1) a sufficiently small number of counterperturbation trials (counterperturbation paradigm [CP]) or 2) a sufficiently large number of zero-perturbation trials (washout paradigm [WO]) between initial adaptation and readaptation. A two-rate, linear time-invariant state-space model (SSM(LTI,2)) was recently shown to theoretically produce savings for CP. However, we reasoned from superposition that this model would be unable to explain savings for WO. Using the same task (planar reaching) and type of perturbation (visuomotor rotation), we found comparable savings for both CP and WO paradigms. Although SSM(LTI,2) explained some degree of savings for CP it failed completely for WO. We conclude that for visuomotor rotation, savings in general is not simply a consequence of LTI dynamics. Instead savings for visuomotor rotation involves metalearning, which we show can be modeled as changes in system parameters across the phases of an adaptation experiment.