Hospital-acquired infections among adult patients admitted for coronavirus disease 2019 (COVID-19).

In a multicenter cohort of 963 adults hospitalized due to coronavirus disease 2019 (COVID-19), 5% had a proven hospital-acquired infection (HAI) and 21% had a proven, probable, or possible HAI. Risk factors for proven or probable HAIs included intensive care unit admission, dexamethasone use, severe COVID-19, heart failure, and antibiotic exposure upon admission.

The role of procalcitonin results in antibiotic decision-making in coronavirus disease 2019 (COVID-19).

OBJECTIVE: To evaluate the role of procalcitonin (PCT) results in antibiotic decisions for COVID-19 patients at hospital presentation. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective observational study of patients ≥18 years hospitalized due to COVID-19 at the Johns Hopkins Health system. Patients who were transferred from another facility with >24 hours stay and patients who died within 48 hours of hospitalization were excluded. METHODS: Elevated PCT values were determined based on each hospital's definition. Antibiotic therapy and PCT results were evaluated for patients with no evidence of bacterial community-acquired pneumonia (bCAP) and patients with confirmed, probable, or possible bCAP. The added value of PCT testing to clinical criteria in detecting bCAP was evaluated using receiving operating curve characteristics (ROC). RESULTS: Of 962 patients, 611 (64%) received a PCT test. ROC curves for clinical criteria and clinical criteria plus PCT test were similar (at 0.5 ng/mL and 0.25 ng/mL). By bCAP group, median initial PCT values were 0.58 ng/mL (interquartile range [IQR], 0.24-1.14), 0.23 ng/mL (IQR, 0.1-0.63), and 0.15 ng/mL (IQR, 0.09-0.35) for proven/probable, possible, and no bCAP groups, respectively. Among patients without bCAP, an elevated PCT level was associated with 1.8 additional days of CAP therapy (95% CI, 1.01-2.75; P < .01) compared to patients with a negative PCT result after adjusting for potential confounders. Duration of CAP therapy was similar between patients without a PCT test ordered and a low PCT level for no bCAP and possible bCAP groups. CONCLUSIONS: PCT results may be abnormal in COVID-19 patients without bCAP and may result in receipt of unnecessary antibiotics.

Administration of a ß-Lactam Prior to Vancomycin as the First Dose of Antibiotic Therapy Improves Survival in Patients With Bloodstream Infections.

BACKGROUND: Prompt initiation of antibiotic therapy improves the survival of patients with bloodstream infections (BSIs). We sought to determine if the sequence of administration of the first dose of antibiotic therapy (ie, ß-lactam or vancomycin, if both are deemed necessary and cannot be administered simultaneously) impacts early mortality for patients with BSI. METHODS: We conducted a multicenter, observational study of patients ≥13 years with BSIs to evaluate the association of the sequence of antibiotic administration with 7-day mortality using inverse probability of treatment weighting (IPTW) incorporating propensity scores. Propensity scores were generated based on demographics, Pitt bacteremia score, intensive care unit status, highest lactate, highest white blood cell count, Charlson comorbidity index, severe immunocompromise, administration of active empiric therapy, combination therapy, and time from emergency department arrival to first antibiotic dose. RESULTS: Of 3376 eligible patients, 2685 (79.5%) received a ß-lactam and 691 (20.5%) received vancomycin as their initial antibiotic. In the IPTW cohort, exposed and unexposed patients were similar on all baseline variables. Administration of a ß-lactam agent prior to vancomycin protected against 7-day mortality (adjusted odds ratio [aOR], 0.48 [95% confidence interval {CI}, .33-.69]). Similar results were observed when evaluating 48-hour mortality (aOR, 0.45 [95% CI, .24-.83]). Administration of vancomycin prior to a ß-lactam was not associated with improved survival in the subgroup of 524 patients with methicillin-resistant Staphylococcus aureus BSI (aOR, 0.93 [95% CI, .33-2.63]). CONCLUSIONS: For ill-appearing patients likely to be experiencing a BSI, prioritizing administration of a ß-lactam over vancomycin may reduce early mortality, underscoring the significant impact of a relatively simple practice change on improving patient survival.

Development of an Electronic Algorithm to Identify in Real Time Adults Hospitalized With Suspected Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a major driver of hospital antibiotic use. Efficient methods to identify patients treated for CAP in real time using the electronic health record (EHR) are needed. Automated identification of these patients could facilitate systematic tracking, intervention, and feedback on CAP-specific metrics such as appropriate antibiotic choice and duration. METHODS: Using retrospective data, we identified suspected CAP cases by searching for patients who received CAP antibiotics AND had an admitting International Classification of Diseases, Tenth Revision (ICD-10) code for pneumonia OR chest imaging within 24 hours OR bacterial urinary antigen testing within 48 hours of admission (denominator query). We subsequently explored different structured and natural language processing (NLP)-derived data from the EHR to identify CAP cases. We evaluated combinations of these electronic variables through receiver operating characteristic (ROC) curves to assess which best identified CAP cases compared to cases identified by manual chart review. Exclusion criteria were age <18 years, absolute neutrophil count <500 cells/mm3, and admission to an oncology unit. RESULTS: Compared to the gold standard of chart review, the area under the ROC curve to detect CAP was 0.63 (95% confidence interval [CI], .55-.72; P < .01) using structured data (ie, laboratory and vital signs) and 0.83 (95% CI, .77-.90; P < .01) when NLP-derived data from radiographic reports were included. The sensitivity and specificity of the latter model were 80% and 81%, respectively. CONCLUSIONS: Creating an electronic tool that effectively identifies CAP cases in real time is possible, but its accuracy is dependent on NLP-derived radiographic data.

StenoSCORE: Predicting Stenotrophomonas maltophilia Bloodstream Infections in the Hematologic Malignancy Population.

Stenotrophomonas maltophilia bloodstream infections (BSI) are associated with considerable mortality in the hematologic malignancy population. Trimethoprim-sulfamethoxazole (TMP-SMX) is the treatment of choice; however, it is not routinely included in empirical treatment regimens, both because of its adverse event profile and the relative rarity of S. maltophilia infections. We developed a risk score to predict hematologic malignancy patients at increased risk for S. maltophilia BSI to guide early (TMP-SMX) therapy. Patients ≥12 years of age admitted to five hospitals between July 2016 and December 2019 were included. Two separate risk scores were developed, (i) a "knowledge-driven" risk score based upon previously identified risk factors in the literature in addition to variables identified by regression analysis using the current cohort, and (ii) a risk score based upon automatic variable selection. For both scores, discrimination (receiver operator characteristic [ROC] curves and C statistics) and calibration (Hosmer-Lemeshow goodness-of-fit test and graphical calibration plots) were assessed. Internal validation was assessed using leave-one-out cross-validation. In total, 337 unique patients were included; 21 (6.2%) had S. maltophilia BSI. The knowledge-driven risk score (acute leukemia, absolute neutrophil count category, mucositis, central line, and ≥3 days of carbapenem therapy) had superior performance (C statistic = 0.75; 0.71 after cross-validation) compared to that of the risk score utilizing automatic variable selection (C statistic = 0.63; 0.38 after cross-validation). A user-friendly risk score incorporating five variables easily accessible to clinicians performed moderately well to predict hematologic malignancy patients at increased risk for S. maltophilia BSI. External validation using a larger cohort is necessary to create a refined risk score before broad clinical application.

Prevalence of Co-infection at the Time of Hospital Admission in COVID-19 Patients, A Multicenter Study.

BACKGROUND: Bacterial infections may complicate viral pneumonias. Recent reports suggest that bacterial co-infection at time of presentation is uncommon in coronavirus disease 2019 (COVID-19); however, estimates were based on microbiology tests alone. We sought to develop and apply consensus definitions, incorporating clinical criteria to better understand the rate of co-infections and antibiotic use in COVID-19. METHODS: A total of 1016 adult patients admitted to 5 hospitals in the Johns Hopkins Health System between March 1, 2020, and May 31, 2020, with COVID-19 were evaluated. Adjudication of co-infection using definitions developed by a multidisciplinary team for this study was performed. Both respiratory and common nonrespiratory co-infections were assessed. The definition of bacterial community-acquired pneumonia (bCAP) included proven (clinical, laboratory, and radiographic criteria plus microbiologic diagnosis), probable (clinical, laboratory, and radiographic criteria without microbiologic diagnosis), and possible (not all clinical, laboratory, and radiographic criteria met) categories. Clinical characteristics and antimicrobial use were assessed in the context of the consensus definitions. RESULTS: Bacterial respiratory co-infections were infrequent (1.2%); 1 patient had proven bCAP, and 11 (1.1%) had probable bCAP. Two patients (0.2%) had viral respiratory co-infections. Although 69% of patients received antibiotics for pneumonia, the majority were stopped within 48 hours in patients with possible or no evidence of bCAP. The most common nonrespiratory infection was urinary tract infection (present in 3% of the cohort). CONCLUSIONS: Using multidisciplinary consensus definitions, proven or probable bCAP was uncommon in adults hospitalized due to COVID-19, as were other nonrespiratory bacterial infections. Empiric antibiotic use was high, highlighting the need to enhance antibiotic stewardship in the treatment of viral pneumonias.

Antibiotic-Associated Adverse Events in Hospitalized Children.

BACKGROUND: Antibiotic-associated adverse events (AEs) in hospitalized children have not been comprehensively characterized. METHODS: We conducted a retrospective observational study of children hospitalized at The Johns Hopkins Hospital receiving ≥24 hours of systemic antibiotics. Consensus regarding antibiotic-associated AE definitions was established by 5 infectious diseases specialists prior to data collection. Two physicians reviewed potential AEs and determined whether they were more likely than not related to antibiotics after comprehensive manual chart review. Inpatient and post-discharge AEs were identified using the Epic Care Everywhere network. AEs evaluated from the initiation of antibiotics until 30 days after antibiotic completion included gastrointestinal, hematologic, hepatobiliary, renal, neurologic, dermatologic, cardiac, myositis, vascular access device-related events, and systemic reactions. Ninety-day AEs included Clostridioides difficile infections, multidrug-resistant organism infections, and clinically significant candidal infections. The impact of AEs was categorized as necessitating additional diagnostic testing, changes in medications, unplanned medical encounters, prolonged or new hospitalizations, or death. RESULTS: Among 400 antibiotic courses, 21% were complicated by at least one AE and 30% occurred post-discharge. Each additional day of antibiotics was associated with a 7% increased odds of an AE. Of courses complicated by an AE, 66% required further intervention. Hematologic, gastrointestinal, and renal AEs were the most common, accounting for 31%, 15%, and 11% of AEs, respectively. AEs complicated 35%, 35%, 19%, and 18% of courses of piperacillin-tazobactam, tobramycin, ceftazidime, and vancomycin, respectively. CONCLUSIONS: More than 1 in 5 courses of antibiotics administered to hospitalized children are complicated by AEs. Clinicians should weigh the risk of harm against expected benefit when prescribing antibiotics.

The Association of Antibiotic Duration With Successful Treatment of Community-Acquired Pneumonia in Children.

BACKGROUND: National guidelines recommend 10 days of antibiotics for children with community-acquired pneumonia (CAP), acknowledging that the outcomes of children hospitalized with CAP who receive shorter durations of therapy have not been evaluated. METHODS: We conducted a comparative effectiveness study of children aged ≥6 months hospitalized at The Johns Hopkins Hospital who received short-course (5-7 days) vs prolonged-course (8-14 days) antibiotic therapy for uncomplicated CAP between 2012 and 2018 using an inverse probability of treatment weighted propensity score analysis. Inclusion was limited to children with clinical and radiographic criteria consistent with CAP, as adjudicated by 2 infectious diseases physicians. Children with tracheostomies; healthcare-associated, hospital-acquired, or ventilator-associated pneumonia; loculated or moderate to large pleural effusion or pulmonary abscess; intensive care unit stay >48 hours; cystic fibrosis/bronchiectasis; severe immunosuppression; or unusual pathogens were excluded. The primary outcome was treatment failure, a composite of unanticipated emergency department visits, outpatient visits, hospital readmissions, or death (all determined to be likely attributable to bacterial pneumonia) within 30 days after completing antibiotic therapy. RESULTS: Four hundred and thirty-nine patients met eligibility criteria; 168 (38%) patients received short-course therapy (median, 6 days) and 271 (62%) received prolonged-course therapy (median, 10 days). Four percent of children experienced treatment failure, with no differences observed between patients who received short-course vs prolonged-course antibiotic therapy (odds ratio, 0.48; 95% confidence interval, .18-1.30). CONCLUSIONS: A short course of antibiotic therapy (approximately 5 days) does not increase the odds of 30-day treatment failure compared with longer courses for hospitalized children with uncomplicated CAP.

Impact of Continuation of Parenteral Nutrition on Outcomes of Patients with Blood Stream Infections.

Background: The impact of continuing parenteral nutrition (PN) in patients who develop blood stream infections (BSI) while receiving PN is largely unknown. Patients and Methods: Adult patients admitted to a large academic center over three consecutive years and seven months who had a positive blood culture while receiving PN were included in the study. The cohort was divided into those who had PN continued (PN-c) or discontinued (PN-dc) after the positive culture. We evaluated the effect of continuing PN on clinical outcomes by comparing a composite outcome of recurrent BSI, severe sepsis/septic shock, and death within 30 days between the two groups using a propensity score-weighting regression analysis. Results: Of 154 patients included in the study, approximately 70% of whom were surgical patients, 65 (42%) had PN discontinued whereas 89 (58%) had PN continued. Cohort characteristics were similar between the two groups including the Pitt bacteremia score and source control. There were more cases of candidemia (18% vs 6%, p = 0.03) and more cases of intra-abdominal infections (IAI; 42% vs 25%, p = 0.02) in the PN-c group compared with the PN-dc group. The most common sites of infection were endovascular and IAI in both groups. The median duration of bacteremia for both groups was one day. After applying propensity score weighting, the composite outcome of recurrent BSI, severe sepsis/septic shock, and death within 30 days was similar between the PN-dc and PN-c groups (43% and 49%, respectively; p = 0.61). Conclusions: Continuing PN in patients with bacteremia or candidemia was not associated with worse clinical outcomes.

A Diagnostic Stewardship Intervention To Improve Blood Culture Use among Adult Nonneutropenic Inpatients: the DISTRIBUTE Study.

Interventions to optimize blood culture (BCx) practices in adult inpatients are limited. We conducted a before-after study evaluating the impact of a diagnostic stewardship program that aimed to optimize BCx use in a medical intensive care unit (MICU) and five medicine units at a large academic center. The program included implementation of an evidence-based algorithm detailing indications for BCx use and education and feedback to providers about BCx rates and indication inappropriateness. Neutropenic patients were excluded. BCx rates from contemporary control units were obtained for comparison. The primary outcome was the change in BCxs ordered with the intervention. Secondary outcomes included proportion of inappropriate BCx, solitary BCx, and positive BCx. Balancing metrics included compliance with the Centers for Medicare and Medicaid Services (CMS) SEP-1 BCx component, 30-day readmission, and all-cause in-hospital and 30-day mortality. After the intervention, BCx rates decreased from 27.7 to 22.8 BCx/100 patient-days (PDs) in the MICU (P = 0.001) and from 10.9 to 7.7 BCx/100 PD for the 5 medicine units combined (P < 0.001). BCx rates in the control units did not decrease significantly (surgical intensive care unit [ICU], P = 0.06; surgical units, P = 0.15). The proportion of inappropriate BCxs did not significantly change with the intervention (30% in the MICU and 50% in medicine units). BCx positivity increased in the MICU (from 8% to 11%, P < 0.001). Solitary BCxs decreased by 21% in the medicine units (P < 0.001). Balancing metrics were similar before and after the intervention. BCx use can be optimized with clinician education and practice guidance without affecting sepsis quality metrics or mortality.

Comparative Effectiveness of Antibiotic Treatment Duration in Children With Pyelonephritis.

Importance: National guidelines recommend treating children with pyelonephritis for 7 to 14 days of antibiotic therapy, yet data are lacking to suggest a more precise treatment duration. Objective: To compare the clinical outcomes of children receiving a short-course vs a prolonged-course of antibiotic treatment for pyelonephritis. Design, Setting, and Participants: Retrospective observational study using inverse probability of treatment weighted propensity score analysis of data from 5 hospitals in Maryland between July 1, 2016, and October 1, 2018. Participants were children aged 6 months to 18 years with a urine culture growing Escherichia coli, Klebsiella species, or Proteus mirabilis with laboratory and clinical criteria for pyelonephritis. Exposures: Treatment of pyelonephritis with a short-course (6 to 9 days) vs a prolonged-course (10 or more days) of antibiotics. Main Outcomes and Measures: Composite outcome of treatment failure within 30 days of completing antibiotic therapy: (a) unanticipated emergency department or outpatient visits related to urinary tract infection symptoms, (b) hospital readmission related to UTI symptoms, (c) prolongation of the planned, initial antibiotic treatment course, or (d) death. A subsequent urinary tract infection caused by a drug-resistant bacteria within 30 days was a secondary outcome. Results: Of 791 children who met study eligibility criteria (mean [SD] age 9.2 [6.3] years; 672 [85.0%]) were girls, 297 patients (37.5%) were prescribed a short-course and 494 patients (62.5%) were prescribed a prolonged-course of antibiotics. The median duration of short-course therapy was 8 days (interquartile range, 7-8 days), and the median duration of prolonged-course therapy was 11 days (interquartile range, 11-12 days). Baseline characteristics were similar between the groups in the inverse probability of treatment weighted cohort. There were 79 children (10.1%) who experienced treatment failure. The odds of treatment failure were similar for patients prescribed a short-course vs a prolonged-course of antibiotics (11.2% vs 9.4%; odds ratio, 1.22; 95% CI, 0.75-1.98). There was no significant difference in the odds of a drug-resistant uropathogen for patients with a subsequent urinary tract infection within 30 days when prescribed a short-courses vs prolonged-course of antibiotics (40% vs 64%; odds ratio, 0.36; 95% CI, 0.09-1.43). Conclusions and Relevance: The study findings suggest that short-course antibiotic therapy may be as effective as prolonged-courses for children with pyelonephritis, and may mitigate the risk of future drug-resistant urinary tract infections. Additional studies are needed to confirm these findings.

The Role of Healthcare Worker-Mediated Contact Networks in the Transmission of Vancomycin-Resistant Enterococci.

BACKGROUND: User- and time-stamped data from hospital electronic health records (EHRs) present opportunities to evaluate how healthcare worker (HCW)-mediated contact networks impact transmission of multidrug-resistant pathogens, such as vancomycin-resistant enterococci (VRE). METHODS: This is a retrospective analysis of incident acquisitions of VRE between July 1, 2016 and June 30, 2018. Clinical and demographic patient data were extracted from the hospital EHR system, including all recorded HCW contacts with patients. Contacts by an HCW with 2 different patients within 1 hour was considered a "connection". Incident VRE acquisition was determined by positive clinical or surveillance cultures collected ≥72 hours after a negative surveillance culture. RESULTS: There were 2952 hospitalizations by 2364 patients who had ≥2 VRE surveillance swabs, 112 (4.7%) patients of which had incident nosocomial acquisitions. Patients had a median of 24 (interquartile range [IQR], 18-33) recorded HCW contacts per day, 9 (IQR, 5-16) of which, or approximately 40%, were connections that occurred <1 hour after another patient contact. Patients that acquired VRE had a higher average number of daily connections to VRE-positive patients (3.1 [standard deviation {SD}, 2.4] versus 2.0 [SD, 2.1]). Controlling for other risk factors, connection to a VRE-positive patient was associated with increased odds of acquiring VRE (odds ratio, 1.64; 95% confidence interval, 1.39-1.92). CONCLUSIONS: We demonstrated that EHR data can be used to quantify the impact of HCW-mediated patient connections on transmission of VRE in the hospital. Defining incident acquisition risk of multidrug-resistant organisms through HCWs connections from EHR data in real-time may aid implementation and evaluation of interventions to contain their spread.

Comparing Propensity Score Methods Versus Traditional Regression Analysis for the Evaluation of Observational Data: A Case Study Evaluating the Treatment of Gram-Negative Bloodstream Infections.

BACKGROUND: Propensity score methods are increasingly being used in the infectious diseases literature to estimate causal effects from observational data. However, there remains a general gap in understanding among clinicians on how to critically review observational studies that have incorporated these analytic techniques. METHODS: Using a cohort of 4967 unique patients with Enterobacterales bloodstream infections, we sought to answer the question "Does transitioning patients with gram-negative bloodstream infections from intravenous to oral therapy impact 30-day mortality?" We conducted separate analyses using traditional multivariable logistic regression, propensity score matching, propensity score inverse probability of treatment weighting, and propensity score stratification using this clinical question as a case study to guide the reader through (1) the pros and cons of each approach, (2) the general steps of each approach, and (3) the interpretation of the results of each approach. RESULTS: 2161 patients met eligibility criteria with 876 (41%) transitioned to oral therapy while 1285 (59%) remained on intravenous therapy. After repeating the analysis using the 4 aforementioned methods, we found that the odds ratios were broadly similar, ranging from 0.84-0.95. However, there were some relevant differences between the interpretations of the findings of each approach. CONCLUSIONS: Propensity score analysis is overall a more favorable approach than traditional regression analysis when estimating causal effects using observational data. However, as with all analytic methods using observational data, residual confounding will remain; only variables that are measured can be accounted for. Moreover, propensity score analysis does not compensate for poor study design or questionable data accuracy.

Corrigendum to: Oral Vancomycin May Be Associated With Earlier Symptom Resolution Than Metronidazole for Hospitalized Children With Nonsevere Clostridioides difficile Infections.

[This corrects the article DOI: 10.1093/ofid/ofz492.].

Is Piperacillin-Tazobactam Effective for the Treatment of Pyelonephritis Caused by Extended-Spectrum ß-Lactamase-Producing Organisms?

BACKGROUND: Limited data exist regarding the efficacy of piperacillin-tazobactam (TZP) for the management of nonbacteremic pyelonephritis caused by extended-spectrum ß-lactamase (ESBL)-producing organisms. METHODS: We conducted a multicenter observational study comparing clinical outcomes of adults hospitalized with ESBL-producing pyelonephritis who were receiving TZP versus carbapenems, using an inverse probability of treatment weighted propensity score analysis. Patients were eligible for inclusion if all of the following criteria were met: (1) urine cultures growing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis at ≥50 000 colony-forming units/mL; (2) identification of an ESBL gene; (3) pyuria (≥10 white blood cells per high powered field in the urine); and (4) dysuria and fever plus at least 1 of the following symptoms: emesis, rigors, hypotension, or flank pain. RESULTS: There were 186 patients included in the propensity score-weighted cohort; 45 (24%) received TZP and 141 (76%) received a carbapenem. Of these 186 patients, 27% were admitted to the intensive care unit, 48% were immunocompromised, and 45% had underlying urologic abnormalities. There were no differences between the 2 groups in the proportion of patients (20% vs 25%) with recurrent cystitis or pyelonephritis with the same ESBL-producing organism within 30 days (odds ratio, 0.75; 95% confidence interval, .31-1.81; P = .52). There were no differences in the resolution of clinical symptoms by Day 7 or in 30-day mortality. There was 1 (2%) patient in the TZP arm and 11 (8%) patients in the carbapenem arm who had incident carbapenem-resistant organisms isolated within 30 days (P = .09). CONCLUSIONS: TZP may be a reasonable alternative to carbapenems for the management of ESBL-producing pyelonephritis and may mitigate the risk of emergence of carbapenem-resistant organisms, compared with carbapenem therapy.

Molecular Epidemiology of Ceftriaxone Non-Susceptible Enterobacterales Isolates in an Academic Medical Center in the United States.

BACKGROUND: Knowledge of whether Enterobacterales are not susceptible to ceftriaxone without understanding the underlying resistance mechanisms may not be sufficient to direct appropriate treatment decisions. As an example, extended-spectrum ß-lactamase (ESBL)-producing organisms almost uniformly display non-susceptibility to ceftriaxone. Regardless of susceptibility to piperacillin-tazobactam or cefepime, carbapenem antibiotics are the treatment of choice for invasive infections. No such guidance exists for ceftriaxone non-susceptible organisms with mechanisms other than ESBL production. We sought to investigate the molecular epidemiology of ceftriaxone non-susceptible Enterobacterales. METHODS: All consecutive Escherichia coli, Klebsiellapneumoniae, Klebsiella oxytoca, or Proteus mirabilis clinical isolates with ceftriaxone MICs of ≥2 mcg/mL from unique patients at a United States hospital over an 8-month period were evaluated for ß-lactamase genes using a DNA microarray-based assay. RESULTS: Of 1929 isolates, 482 (25%) had ceftriaxone MICs of ≥2 mcg/mL and were not resistant to any carbapenem antibiotics. Of the 482 isolates, ESBL (blaCTX-M, blaSHV, blaTEM) and/or plasmid-mediated ampC (p-ampC) genes were identified in 376 (78%). ESBL genes were identified in 310 (82.4%), p-ampC genes in 2 (0.5%), and both ESBL and p-ampC genes in 64 (17.0%) of the 376 organisms. There were 211 (56%), 120 (32%), 41 (11%), and 4 (1%) isolates with 1, 2, 3, or 4 or more ESBL or p-ampC genes. The most common ESBL genes were of the blaCTX-M-1 group (includes blaCTX-M-15) and the most common p-ampC gene was the blaCMY-2. CONCLUSIONS: There is considerable diversity in the molecular epidemiology of ceftriaxone non-susceptible Enterobacterales. An understanding of this diversity can improve antibiotic decision-making.

The Likelihood of Developing a Carbapenem-Resistant Enterobacteriaceae Infection during a Hospital Stay.

Of 1,455 unique patients in U.S. intensive care units (ICUs), 4% were rectally colonized with CRE on admission. A total of 297 patients were initially negative for carbapenem-resistant Enterobacteriaceae (CRE) and remained in the ICU long enough to contribute additional swabs; 22% of these patients had a subsequent CRE-positive swab, with a median time to CRE colonization of 13 days (interquartile range, 7 to 21 days). Patients colonized with carbapenemase-producing CRE were more likely than those colonized with non-carbapenemase-producing CRE to develop CRE infections during their hospitalizations (36% versus 3%; P < 0.05).

Antibiotic Therapy for Pseudomonas aeruginosa Bloodstream Infections: How Long Is Long Enough?

In a multicenter, observational, propensity-score-weighted cohort of 249 adults with uncomplicated Pseudomonas aeruginosa bacteremia, patients receiving short-course (median, 9 days; interquartile range [IQR], 8-10) therapy had a similar odds of recurrent infection or death within 30 days as those receiving longer courses (median, 16 days; IQR, 14-17).

Association of 30-Day Mortality With Oral Step-Down vs Continued Intravenous Therapy in Patients Hospitalized With Enterobacteriaceae Bacteremia.

Importance: Conversion to oral therapy for Enterobacteriaceae bacteremia has the potential to improve the quality of life of patients by improving mobility, eliminating catheter-associated discomfort, decreasing the risk for noninfectious and infectious catheter-associated adverse events, and decreasing health care costs. Objective: To compare the association of 30-day mortality with early oral step-down therapy vs continued parenteral therapy for the treatment of Enterobacteriaceae bloodstream infections. Design, Setting, and Participants: This retrospective multicenter cohort study included a 1:1 propensity score-matched cohort of 4967 unique patients hospitalized with monomicrobial Enterobacteriaceae bloodstream infection at 3 academic medical centers from January 1, 2008, through December 31, 2014. Eligibility criteria included appropriate source control measures, appropriate clinical response by day 5, active antibiotic therapy from day 1 until discontinuation of therapy, availability of an active oral antibiotic option, and ability to consume other oral medications or feeding. Statistical analysis was performed from March 2, 2018, to June 2, 2018. Exposures: Oral step-down therapy within the first 5 days of treatment of Enterobacteriaceae bacteremia. Main Outcomes and Measures: The main outcome was 30-day all-cause mortality. Results: Of the 2161 eligible patients, 1185 (54.8%) were male and 1075 (49.7%) were white; the median (interquartile range [IQR]) age was 59 (48-68) years. One-to-one propensity-score matching yielded 1478 patients, with 739 in each study arm. Sources of bacteremia included urine (594 patients [40.2%]), gastrointestinal tract (297 [20.1%]), central line-associated (272 [18.4%]), pulmonary (58 [3.9%]), and skin and soft tissue (41 [2.8%]). There were 97 (13.1%) deaths in the oral step-down group and 99 (13.4%) in the intravenous (IV) group within 30 days (hazard ratio [HR], 1.03; 95% CI, 0.82-1.30). There were no differences in recurrence of bacteremia within 30 days between the groups (IV, 6 [0.8%]; oral, 4 [0.5%]; HR, 0.82 [0.33-2.01]). Patients transitioned to oral step-down therapy were discharged from the hospital an average of 2 days (IQR, 1-6) sooner than patients who continued to receive IV therapy (5 days [IQR, 3-8 days] vs 7 days [IQR, 4-14 days]; P < .001). Conclusions and Relevance: In this study, 30-day mortality was not different among hospitalized patients who received oral step-down vs continued parenteral therapy for the treatment of Enterobacteriaceae bloodstream infections. The findings suggest that transitioning to oral step-down therapy may be an effective treatment approach for patients with Enterobacteriaceae bacteremia who have received source control and demonstrated an appropriate clinical response. Early transition to oral step-down therapy may be associated with a decrease in the duration of hospital stay for patients with Enterobacteriaceae bloodstream infections.

The Role of Ertapenem for the Treatment of Complicated Intra-abdominal Infections With a Positive Culture for Enterococcus faecalis.

Controversy remains as to whether Enterococcus faecalis recovered from intra-abdominal infections (IAIs) requires targeted therapy. In a multicenter study comparing patients with IAIs from which E. faecalis was identified in intra-abdominal cultures, no difference in clinical outcomes was observed between patients receiving ertapenem vs those receiving piperacillin/tazobactam.