Enterobacter Bacteremia Research Articles

Ceftriaxone versus cefepime or carbapenems for definitive treatment of low-risk AmpC-Harboring Enterobacterales bloodstream infections in hospitalized adults: A retrospective cohort study

ObjectiveTo compare outcomes of ceftriaxone to AmpC-stable therapies in patients with bacteremia caused by low-risk AmpC harboring Enterobacterales. MethodsIRB-approved, retrospective cohort of hospitalized patients ≥18 years old with Serratia marcescens, Morganella morganii, or Providencia spp. bacteremia from 1/1/2017-2/28/2024. Patients were compared by definitive therapy with ceftriaxone vs AmpC-stable therapy (cefepime, carbapenem). The primary endpoint was 30-day all-cause mortality; secondary endpoints were clinical failure and development of ceftriaxone resistance. Results163 patients were included; 33.1 % received ceftriaxone, 66.9 % AmpC-stable therapies. 30-day all-cause mortality was 9.3 % ceftriaxone vs 10.1 % AmpC stable patients (P = 0.87); ceftriaxone definitive therapy was not associated with 30-day all-cause mortality (adjOR, 0.79; 95 %CI, 0.23-2.3). There were no differences in clinical failure (9.3 % vs 21.1 %, P = 0.059) or relapsing infection (5.6 % vs 9.3 %, P = 0.55) between ceftriaxone and AmpC-stable treated patients. ConclusionsPatients treated with definitive ceftriaxone for low-risk AmpC Enterobacterales bacteremia had similar outcomes to AmpC stable therapies.

Amikacin treatment in patients with Enterobacterales bacteraemia: impact of MIC on mortality.

Recently, breakpoints of Enterobacterales to amikacin were changed from MIC ≤ 16 mg/L to MIC ≤ 4 mg/L based mainly on laboratory data with little supporting clinical evidence. Our aim was to investigate the relation between MIC of Enterobacterales to amikacin and mortality among patients with Enterobacterales bacteraemia from a urinary tract source treated with amikacin. This retrospective, single-centre study included patients with Enterobacterales urinary source bacteraemia treated with amikacin, with Low (MIC ≤ 4 mg/L) and High (MIC 8 or 16 mg/L) MICs. A cohort of patients treated with ertapenem was used to assess if amikacin MIC is a marker of severity independent of antimicrobial treatment. The primary outcome was 30-day mortality. Multivariate logistic regression analysis was done to assess risk factors for mortality. We included 85 patients, 46 (54.1%) were male, and mean age was 79.0 years (SD 11.7). Sixty-one patients (71.8%) had Low MIC and 24 (28.2%) had High MIC. Thirty-day mortality was 8.2% and 29.2% in the Low and High MIC groups, respectively (P = 0.031). Risk factors for 30-day mortality were age, infection by Enterobacterales other than Escherichia coli and high amikacin MIC. In a cohort of 88 patients treated with ertapenem, amikacin MIC was not associated with 30-day mortality. We demonstrated a relation between higher amikacin MIC levels (8 and 16 mg/L) and increased 30-day mortality in patients treated with amikacin for bacteraemia secondary to a urinary source. These findings support the new CLSI breakpoint change of Enterobacterales to amikacin.

Early antibiotic de-escalation in patients with severe infections due to bloodstream infection by enterobacterales: A post hoc analysis of a prospective multicentre cohort

Data about antibiotic de-escalation in sepsis associated with the bloodstream and caused by Enterobacterales are scarce. The objectives of this study are to identify factors associated with early de-escalation and to analyse the impact of de-escalation on mortality in patients with Enterobacterales bloodstream infection (BSI) with a Sequential Organ Failure Assessment (SOFA) score ≥ 2. A prospective, multicentre cohort study was performed including episodes of BSI due to Enterobacterales and a SOFA score ≥ 2 who were receiving an active antipseudomonal β-lactam; the isolate should be susceptible to at least 1 narrower-spectrum antibiotic. Variables associated with de-escalation were identified using logistic binary regression. The association of de-escalation with 30-day mortality was investigated. Confounding was controlled by calculating a propensity score used as covariate, as matching variable, and for inverse probability treatment weighting. Of the 582 patients included, de-escalation was performed in 311 (53.4%). Neutropenia (adjusted odds ratio [aOR] = 0.37; 95% confidence interval [95% CI] = 0.18-0.75), central venous catheter (aOR = 0.52; 95% CI = 0.32-0.83), and extended-spectrum β-lactamase (ESBL)-producing isolate (aOR = 0.28; 95% CI = 0.17-0.48) were negatively associated with de-escalation, and urinary tract source was positively associated (aOR = 2.27; 95% CI = 1.56-3.33). The 30-day mortality was 6.8% (21 patients) in de-escalated patients and 14.4% (39) in not de-escalated patients (relative risk, 0.63; 95% CI = 0.44-0.89). In multivariate analysis including the propensity score, de-escalation was not associated with mortality (AOR = 0.98; 95% CI = 0.39-2.47) and was protective in the case of urinary or biliary tract source (AOR = 0.31, 95% CI = 0.09-1.06). Matched and inverse probability treatment weighting analysis showed similar results. These results suggest that early de-escalation from antipseudomonal β-lactams is safe in patients with Enterobacterales bacteremia and SOFA ≥ 2.

Seven-day antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients: toward a new paradigm.

Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14days. This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14days of AT. Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9days (IQR: 7-15) vs. 14days (IQR: 13-22) (p = < 0.001). These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.

Opportunity for Early De-escalation in Enterobacterales Bacteremia with Rapid Blood Culture Identification Technology

Background: The BioFire FilmArray Blood Culture Identification 2 (BCID2) Panel is used to identify organisms present in positive blood cultures within hours of detection at Virginia Commonwealth University Health System (VCUHS). BCID2 is also able to detect common resistance mechanisms including CTX-M, the most common extended-spectrum beta-lactamase (ESBL) in the United States, and several carbapenemases. The Antimicrobial Stewardship Program (ASP) at VCUHS established optimal treatment recommendations for each organism identified by BCID2 based on the detection of a resistance mechanism and local resistance patterns. The recommendation for the majority of Enterobacterales without a detected resistance mechanism is ceftriaxone. However, providers are often reluctant to de-escalate antibiotics without confirmed susceptibility testing, as there may be other mechanisms of antibiotic resistance in Gram-negative organisms. The objective of this evaluation was to measure the degree of congruence between BCID2 resistance mechanism detection and susceptibility testing by disk diffusion, and to validate the adequacy of the VCUHS ASP BCID2 treatment recommendations for Enterobacterales bacteremia. Methods: Patients with positive Enterobacterales BCID2 results from March 12 to June 19, 2023 were retrospectively identified. Organisms identified by BCID2 that were considered high-risk for clinically significant AmpC production due to an inducible AmpC gene (i.e., K. aerogenes, E. cloacae complex) were excluded. Results: A total of 270 results were included. The most commonly identified organism was E. coli (n = 139, 51.5%), followed by K. pneumoniae (n = 74, 27.4%). There were 27 (10%) isolates positive for CTX-M and 1 (0.4%) isolate positive for KPC. All CTX-M isolates were ceftriaxone resistant, and the KPC isolate was meropenem resistant. The remaining 242 isolates were negative for all resistance markers detected by BCID2. Of these, only 3 (1.2%) were resistant to ceftriaxone and notably, 8 (3.3%) were resistant to piperacillin/tazobactam. Overall, BCID2 CTX-M detection was 90% sensitive and 100% specific for predicting ceftriaxone resistance in Enterobacterales. Conclusion: CTX-M detection by BCID2 is highly sensitive and specific for predicting ceftriaxone resistance in Enterobacterales. CTX-M negative isolates were more often susceptible to ceftriaxone than to piperacillin/tazobactam, which is commonly used as empiric therapy for Gram-negative organisms at our institution. This highlights an excellent opportunity for safe and effective early de-escalation of antibiotics for treatment of Enterobacterales bacteremia.

The impact of colistin-based regimens on mortality compared to other antimicrobials in patients with carbapenem-resistant Enterobacterales bacteremia in South African hospitals: a cross-sectional study

BackgroundTreatment of carbapenem-resistant Enterobacterales (CRE) infections in low-resource settings is challenging particularly due to limited treatment options. Colistin is the mainstay drug for treatment; however, nephrotoxicity and neurotoxicity make this drug less desirable. Thus, mortality may be higher among patients treated with alternative antimicrobials that are potentially less efficacious than colistin. We assessed mortality in patients with CRE bacteremia treated with colistin-based therapy compared to colistin-sparing therapy.MethodsWe conducted a cross-sectional study using secondary data from a South African national laboratory-based CRE bacteremia surveillance system from January 2015 to December 2020. Patients hospitalized at surveillance sentinel sites with CRE isolated from blood cultures were included. Multivariable logistic regression modeling, with multiple imputations to account for missing data, was conducted to determine the association between in-hospital mortality and colistin-based therapy versus colistin-sparing therapy.ResultsWe included 1 607 case-patients with a median age of 29 years (interquartile range [IQR], 0–52 years) and 53% (857/1 607) male. Klebsiella pneumoniae caused most of the infections (82%, n=1 247), and the most common carbapenemase genes detected were blaOXA-48-like (61%, n=551), and blaNDM (37%, n=333). The overall in-hospital mortality was 31% (504/1 607). Patients treated with colistin-based combination therapy had a lower case fatality ratio (29% [152/521]) compared to those treated with colistin-sparing therapy 32% [352/1 086]) (p=0.18). In our imputed model, compared to colistin-sparing therapy, colistin-based therapy was associated with similar odds of mortality (adjusted odds ratio [aOR] 1.02; 95% confidence interval [CI] 0.78-1.33, p=0.873).ConclusionIn our resource-limited setting, the mortality risk in patients treated with colistin-based therapy was comparable to that of patients treated with colistin-sparing therapy. Given the challenges with colistin treatment and the increasing resistance to alternative agents, further investigations into the benefit of newer antimicrobials for managing CRE infections are needed.

In Enterobacterales bacteremia, antipseudomonal β-lactam de-escalation was noninferior to continuation for clinical cure at 3 to 5 d.

López-Cortés LE, Delgado-Valverde M, Moreno-Mellado E, et al; SIMPLIFY study group. Efficacy and safety of a structured de-escalation from antipseudomonal β-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial. Lancet Infect Dis. 2024;24:375-385. 38215770.

Ceftazidime-Avibactam Improves Outcomes in High-Risk Neutropenic Patients with Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales Bacteremia.

Few studies have evaluated the efficacy of ceftazidime-avibactam (CA) for Klebsiella pneumoniae carbapenemase-producing Enterobacterales bacteremia (KPC-PEB) in high-risk neutropenic patients. This is a prospective multicenter observational study in high-risk neutropenic patients with multi-drug resistant Enterobacterales bacteremia. They were compared according to the resistance mechanism and definitive treatment provided: KPC-CPE treated with CA (G1), KPC-CPE treated with other antibiotics (G2), and patients with ESBL-producing Enterobacterales bacteremia who received appropriate definitive therapy (G3). Thirty-day mortality was evaluated using a logistic regression model, and survival was analyzed with Kaplan-Meier curves. A total of 238 patients were included: 18 (G1), 52 (G2), and 168 (G3). Klebsiella spp. (60.9%) and Escherichia coli (26.4%) were the Enterobacterales most frequently isolated, and 71% of the bacteremias had a clinical source. The resistance profile between G1 and G2 was colistin 35.3% vs. 36.5%, amikacin 16.7% vs. 40.4%, and tigeclycline 11.1% vs. 19.2%. The antibiotics prescribed in combination with G2 were carbapenems, colistin, amikacin, fosfomycin, tigecycline, and fluoroquinolones. Seven-day clinical response in G1 vs. G2 vs. G3 was 94.4% vs. 42.3% vs. 82.7%, respectively (p < 0.001). Thirty-day overall mortality in G1 vs. G2 vs. G3 was 22.2% vs. 53.8% vs. 11.9%, respectively (p < 0.001), and infection-related mortality was 5.5% vs. 51.9% vs. 7.7% (p < 0.001). The independent risk factors for mortality were Pitt score > 4: OR 3.63, 95% CI, 1.18-11.14 (p = 0.025) and KPC-PEB treated with other antibiotics: OR 8.85, 95% CI, 2.58-30.33 (p = 0.001), while 7-day clinical response was a protective factor for survival: OR 0.02, 95% CI, 0.01-0.08 (p < 0.001). High-risk neutropenic patients with KPC-CPE treated with CA had an outcome similar to those treated for ESBL-producing Enterobacterales, with higher 7-day clinical response and lower overall and infection-related mortality than those treated with other antibiotics. In view of these data, CA may be considered the preferred therapeutic option for KPC-PEB in high-risk neutropenic patients.

Efficacy and safety of a structured de-escalation from antipseudomonal β-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial

De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal β-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal β-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal β-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. De-escalation from an antipseudomonal β-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

Switch to oral antibiotics in Gram-negative bacteraemia: a randomized, open-label, clinical trial

ObjectivesTo evaluate the safety and efficacy of switching from intravenous (IV) to oral antimicrobial therapy in patients with Enterobacterales bacteraemia, after completion of 3–5 days of microbiologically active IV therapy. MethodsA multicentre, open-label, randomized trial of adults with monomicrobial Enterobacterales bacteraemia caused by a strain susceptible to ≥1 oral beta-lactam, quinolone, or trimethoprim/sulfamethoxazole. Inclusion criteria included completion of 3–5 days of microbiologically active IV therapy, being afebrile and haemodynamically stable for ≥48 hours, and absence of an uncontrolled source of infection. Pregnancy, endocarditis, and neurological infections were exclusion criteria. Randomization, stratified by urinary source of bacteraemia, was to continue IV (IV Group) or to switch to oral therapy (Oral Group). Agents and duration of therapy were determined by the treating physicians. The primary endpoint was treatment failure, defined as death, need for additional antimicrobial therapy, microbiological relapse, or infection-related re-admission within 90 days. Non-inferiority threshold was set at 10% in the 95% CI for the difference in the proportion with treatment failure between the Oral and IV Groups in the modified intention-to-treat population. The protocol was registered at ClinicalTrials.gov (NCT04146922). ResultsIn the modified intention-to-treat population, treatment failure occurred in 21 of 82 (25.6%) in the IV Group, and 18 of 83 (21.7%) in the Oral Group (risk difference –3.7%, 95% CI –16.6% to 9.2%). The proportions of subjects with any adverse events (AE), serious AE, or AE leading to treatment discontinuation were comparable. DiscussionIn patients with Enterobacterales bacteraemia, oral switch, after initial IV antimicrobial therapy, clinical stability, and source control, is non-inferior to continuing IV therapy.

Using antibiotics wisely.

This review will describe role of shorter antibiotic therapies, early switch from intravenous to oral therapy, and artificial intelligence in infectious diseases. There is evidence that shorter courses of antibiotics are noninferior to standard durations of therapy. This has been demonstrated with Enterobacterales bacteremia that can be treated with 7 days of therapy, community acquired pneumonia with 3 days and ventilator associated pneumonia with just 7 days of antibiotic therapy. The conversion from intravenous to oral therapy in treating bacteremia, endocarditis and bone and joint infections is safe and effective and reduces line complications and costs. Also, for clean surgical procedures only one dose of antibiotic is needed, but it should be the most effective antibiotic which is cefazolin. This means avoiding clindamycin, removing penicillin allergies where possible for improved outcomes. Finally, the role of artificial intelligence to incorporate into using antibiotics wisely is rapidly emerging but is still in early stages. In using antibiotics wisely, targeting such as durations of therapy and conversion from intravenous antibiotic therapy to oral are low hanging fruit. The future of artificial intelligence could automate a lot of this work and is exciting but needs to be proven. http://links.lww.com/COID/A50.

Clinical Characteristics of and Risk Factors for Subsequent Carbapenemase-producing Enterobacterales (CPE) Bacteraemia in Rectal CPE Carriers

BackgroundDue to high mortality and limited treatment options, the rise in carbapenemase-producing Enterobacterales (CPE) has become a major concern. This study aimed to evaluate the incidence and characteristics of subsequent CPE bacteraemia in rectal CPE carriers and investigate the risk factors for CPE bacteraemia compared with non-carbapenemase-producing (non-CP) Enterobacterales bacteraemia. MethodsA retrospective analysis was conducted on adult patients who were confirmed to have CPE colonisation by stool surveillance culture at a tertiary hospital from January 2018 to February 2022. All episodes of Enterobacterales bacteraemia up to 6 months after CPE colonisation were identified. ResultsOf 1174 patients identified as rectal CPE carriers, 69 (5.8%; 95% CI 4.6–7.3%) experienced subsequent CPE bacteraemia during the 6 months after the diagnosis of CPE colonisation. Colonisation by a Klebsiella pneumoniae carbapenemase (KPC) producer (or CP-K. pneumoniae), colonisation by multiple CPE species, chronic kidney disease and haematological malignancy were independently associated with CPE bacteraemia in CPE carriers. When CPE carriers developed Enterobacterales bacteraemia, the causative agent was more frequently non-CP Enterobacterales than CPE (63.6% vs. 36.4%). Among these patients, colonisation with a KPC producer, CPE colonisation at multiple sites, shorter duration from colonisation to bacteraemia (< 30 days) and recent intraabdominal surgery were independent risk factors for CPE bacteraemia rather than non-CP Enterobacterales bacteraemia. ConclusionsIn CPE carriers, non-CP Enterobacterales were more often responsible for bacteraemia than CPE. Empirical antibiotic therapy for CPE should be considered when sepsis is suspected in a CPE carrier with risk factors for CPE bacteraemia.

Carbapenem alternatives for treatment of bloodstream infections due to AmpC producing enterobacterales

IntroductionCarbapenems (CR) have traditionally been the first line treatment for bacteremia caused by AmpC-producing Enterobacterales. However, CR have a high ecological impact, and carbapenem-resistant strains continue rising. Thus, other treatment alternatives like Piperacillin-Tazobactam (P-T) or Cefepime (CEF) and oral sequential therapy (OST) are being evaluated.MethodsWe conducted a retrospective, single-centre observational study. All adult patients with AmpC-producing Enterobacterales bacteremia were included. The primary endpoint was clinical success defined as a composite of clinical cure, 14-day survival, and no adverse events. We evaluated the evolution of patients in whom OST was performed.ResultsSeventy-seven patients were included, 22 patients in the CR group and 55 in the P-T/CEF group (37 patients received CEF and 18 P-T). The mean age of the patients was higher in the P-T/CEF group (71 years in CR group vs. 76 years in P-T/CEF group, p = 0.053). In the multivariate analysis, age ≥ 70 years (OR 0.08, 95% CI [0.007–0.966], p = 0.047) and a Charlson index ≥ 3 (OR 0.16, 95% CI [0.026–0.984], p = 0.048), were associated with a lower clinical success. Treatment with P-T/CEF was associated with higher clinical success (OR 7.75, 95% CI [1.273–47.223], p = 0.026). OST was performed in 47% of patients. This was related with a shorter in-hospital stay (OST 14 days [7–22] vs. non-OST 18 days [13–38], p = 0.005) without difference in recurrence (OST 3% vs. non-OST 5%, p = 0.999).ConclusionsTargeted treatment with P-T/CEF and OST could be safe and effective treatments for patients with AmpC-producing Enterobacterales bacteremia.

Simplified antibiotic guidelines in urology are associated with decreased multidrug-resistant Enterobacterales

PurposeA simplified therapeutic guideline (STG) was established in our urology ward in 2019 for urinary infections. Our aim was to describe the level of physician adherence to STG and the impact of a limited number of antibiotic compounds on the rate of multidrug-resistant (MDR) bacteria. As guidelines should improve patient care, unfavorable outcomes were also reported. MethodsThe STG for community-acquired and nosocomial urinary infections, including six antibiotics, was established in November 2019 and has been officially applied since January 2020. Treatment duration has to be ≤14 days. We conducted a before-after study to measure physician adherence to the STG for bacteremia treatment between January 2017 and December 2022. Adherence was defined as exclusive use of STG antibiotics. All isolated bacteria from blood cultures were recorded, including MDR Enterobacterales, defined as AmpC β-lactamase- or ESBL-producing strains. Unfavorable outcomes were defined as uncontrolled infection, a second surgical procedure, ICU requirement, and/or death. ResultsSeventy-six cases of bacteremia occurred between January 2017 and December 2019, and ninety between January 2020 and December 2022. The main comorbid condition was urological cancer (46%). The main reason for surgery was ureteral stent (32%). Antibiotic management in accordance with STG increased from 18% to 52%, p < 0.001, and treatments > 14 days decreased from 53% to 28%, p < 0.001. MDR Enterobacterales bacteremia was reduced from 52% to 35%, p = 0.027. The rate of unfavorable outcomes was unchanged. ConclusionSTG adherence in urology was satisfactory and associated with reduced MDR Enterobacterales bacteremia.

Clinical characteristics and outcomes of carbapenem-resistant Enterobacterales bacteremia in pediatric patients.

Clinical data on carbapenem-resistant Enterobacterales (CRE) bacteremia in the pediatric population are limited. This study investigated the clinical characteristics and outcomes of pediatric CRE bacteremia. Clinical data on bacteremia caused by carbapenem-susceptible and carbapenem-resistant Enterobacterales, including Escherichia coli, Klebsiella spp., Enterobacter spp., Serratia marcescens, Proteus mirabilis, Citrobacter spp., and Morganella spp., in pediatric patients from a children's hospital in Taiwan were retrospectively retrieved and analyzed. From January 2013 to December 2021, 471 clinical isolates of Enterobacterales bacteremia were identified in 451 episodes from 379 pediatric patients. Among all the isolates, the predominant species were E. coli (199/471, 42.2%), Klebsiella spp. (168/471, 35.6%), and Enterobacter spp. (59/471, 12.5%), with carbapenem-resistance rates of 1.5%, 11.9%, and 25.0%, respectively. Overall, 40 (8.4%) showed a carbapenem resistance phenotype. Patients' all-cause mortality rate at 14 days was significantly higher in CRE bacteremia episodes than non-CRE ones (12.5% vs. 3.6%, p<0.05). The predicting factor of a CRE bacteremia episode was the causative agent of Enterobacter spp. (adjusted OR of 2.551, CI 1.073-6.066, p<0.05) and ESBL-producing phenotype (adjusted OR 14.268, CI 5.120-39.762, p<0.001). Bloodstream infections caused by CRE are associated with a higher mortality rate in the pediatric population. Attention must be paid to preventing and managing pediatric patients with CRE infections.

Development of a Clinical Score to Stratify the Risk for Carbapenem-Resistant Enterobacterales Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation

Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88-8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29-9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74-93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80-0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia.

Oral step-down with β-lactams for uncomplicated Enterobacterales bacteraemia

The preferred definitive treatments for invasive Enterobacterales infections, parenteral antibiotics, oral fluoroquinolones, and oral trimethoprim-sulfamethoxazole, are increasingly limited leading to interest in additional options [1–3]. Oral beta-lactams are a conceptionally attractive option because of their high tolerability and activity against Enterobacterales that do not meaningfully express ampC beta-lactamases, but views on their role are mixed due to concerns for subtherapeutic serum concentrations [1].

1839. Impact of Hypoalbuminemia on Ceftriaxone Treatment Failure in Patients With Enterobacterales Bacteremia

Abstract Background Ceftriaxone (CRO) is a third-generation cephalosporin that is commonly prescribed due to its robust Gram-negative activity and lack of renal dose adjustments. It is also highly protein bound allowing for once daily dosing. In patients with hypoalbuminemia, however, the proportion of free drug is increased thus increasing the rate at which CRO is renally eliminated. This increased clearance could lead to lower serum concentrations and increased risk of treatment failure. Methods We performed a retrospective, cohort study to assess the impact of hypoalbuminemia (serum albumin ≤ 2.5 g/dL) on treatment failure among patients with monomicrobial Enterobacterales bacteremia. Adult patients who received &amp;gt; 72 hours of CRO therapy for susceptible Enterobacterales bacteremia between May 1, 2016 and April 30, 2021 were eligible for inclusion. The primary outcome of treatment failure was a composite of inpatient mortality or escalation to an intravenous anti-pseudomonal antibiotic or ertapenem. Secondary outcomes included hospital length of stay, total duration of antibiotic therapy, and time to infection resolution. Baseline characteristics and outcomes were compared using R Studio (Version 4.1.0) in a 1:1 propensity-matched cohort. Results After propensity score matching, 142 patients were included in each study group. The most common organisms in our cohort were Escherichia coli (71.5%), Klebsiella pneumoniae (14.1%), and Proteus mirabilis (5.3%). The most frequently implicated source of infection was the urinary tract (71.5%). Interestingly, treatment failure was numerically higher in the hypoalbuminemia group but was not statistically significant (12.0% vs. 7.7%, p = 0.23). All secondary outcomes were similar between groups. Among the subgroup of patients admitted to the ICU at baseline, the difference in treatment failure was even greater between patients with hypoalbuminemia and those without (23.3% vs. 7.5%, P = 0.07). Conclusion Hypoalbuminemia did not appear to have a significant impact on clinical outcomes among patients with Enterobacterales bacteremia treated with CRO. However, critically ill patients may be subject to higher incidence of treatment failure in the presence of hypoalbuminemia. Disclosures All Authors: No reported disclosures.

1822. Clinical Outcomes Associated with Oral Beta-Lactam Therapy versus Oral Fluoroquinolones/TMP-SMX for Uncomplicated Gram-Negative Bacteremia

Abstract Background Agents commonly used as oral step-down therapy in Enterobacterales bacteremia include fluoroquinolones and TMP-SMX. The use of these oral agents have been associated with adverse events. Oral β-lactams are not recommended to treat Enterobacterales bacteremia because of concerns for sub-therapeutic serum concentrations. Given the limited data on clinical effectiveness of oral β-lactams and increased limitations with fluoroquinolones and TMP-SMX, oral β-lactams may be an alternative option. The purpose of this study is to evaluate the clinical effectiveness in patients transitioned to oral β-lactams versus fluoroquinolones or TMP-SMX for the step-down treatment of uncomplicated Enterobacterales bacteremia. Methods A multi-center, retrospective, propensity-score matched, observational cohort study was conducted from July 1, 2017 to December 31, 2020, at 11 Memorial Hermann Health System hospitals among 690 patients with uncomplicated Enterobacterales bacteremia. Patients were included if they received &amp;gt; 1 day of intravenous antibiotic therapy followed by definitive oral step-down therapy with a β-lactam, fluoroquinolone, or TMP-SMX. The primary outcome was treatment failure within 30 days of starting oral antibiotics, defined as at least one of the following: recurrent bacteremia, transition to IV antibiotics, new-onset sepsis, 30-day readmission, or 30-day all-cause mortality. Results After the patients were propensity score matched 1:1, a total of 199 patients with uncomplicated Enterobacterales bacteremia were included in each group. Treatment failure occurred in 8 patients (4%) who received β-lactams and 10 patients (5%) who received fluoroquinolones or TMP-SMX (OR, 0.79 [95% CI, 0.306-2.04] p-value 0.629). Median length of hospital stay was 5 days for both groups (p-value 0.911), and median duration of oral antibiotics was 10 days in the fluoroquinolone or TMP-SMX group and 11 days in the β-lactam group (p-value 0.377). Conclusion Based on the results of this study, no significant difference in treatment failure was seen in patients who were transitioned to β-lactams versus fluoroquinolones or TMP-SMX as oral step-down therapy for uncomplicated Enterobacterales bacteremia. Oral β-lactams appear to be a safe and effective option. Disclosures All Authors: No reported disclosures.

Ceftriaxone 1 g Versus 2 g Daily for the Treatment of Enterobacterales Bacteremia: A Retrospective Cohort Study.

Background: Ceftriaxone is a commonly used antibiotic for the treatment of susceptible Enterobacterales infections. There is currently limited clinical data on the optimal dose of ceftriaxone for Enterobacterales bacteremia. Objectives: To evaluate the rate of clinical failure of ceftriaxone 1 g versus 2 g daily in patients with Enterobacterales bacteremia. Methods: This was a retrospective cohort study of patients admitted to any of the 3 New York University Hospitals: Long Island, Tisch, or Brooklyn, with ceftriaxone-susceptible Enterobacterales bacteremia, receiving ceftriaxone 1 or 2 g daily from October 2019 to September 2020. The primary outcome was 90-day rate of clinical failure. Clinical failure was defined as escalation of therapy, relapse of infection, or all-cause mortality. Results: A total of 124 patients, 58% in the 1-g group and 42% in the 2-g group, were included. There was no statistically significant difference found in the primary outcome. The 90-day rate of clinical failure was 16.7% versus 9.6%, P = 0.260. There were no statistically significant secondary outcomes, although infection relapse rates at 90 days were numerically greater in the 1-g group (11.1% vs 1.9%, P = 0.078). Hypoalbuminemia was the only variable associated with an increased risk of clinical failure (odds ratio = 4.03; 95% confidence interval [CI] = 1.12-14.50, P = 0.033). Conclusion: In our exploratory findings, there was no statistically significant difference with the 90-day rate of clinical failure between ceftriaxone 1 g versus 2 g daily, although there was a numeric trend toward an increased rate of infection relapse within the 1-g group. Hypoalbuminemia was associated with an increased risk of clinical failure. Prospective studies are warranted to confirm these findings.