Dataset Information

Survey of infectious diseases providers reveals variability in duration of antibiotic therapy for the treatment of Gram-negative bloodstream infections.

ABSTRACT:

Background

Trials supporting shorter durations of antibiotic therapy for Gram-negative bloodstream infections (GN-BSI) have recently been published. However, adoption of these findings into practice is unclear given limited eligibility criteria and relatively large non-inferiority margins of these studies. To better understand contemporary management of GN-BSI, we conducted an international survey of infectious diseases (ID) specialists.

Methods

We developed and disseminated an online survey to assess practice patterns involving treatment duration of GN-BSI, including providers from 28 countries. χ² tests, t-tests and multivariable linear regression with generalized estimating equations were used to identify factors associated with treatment duration.

Results

In total, 277 ID specialists completed the survey (64% physicians, 31% pharmacists). The median reported duration of antibiotics was 7 days (IQR, 7-10 days) for all GN-BSI sources. Thirty percent of providers typically recommend durations that differ by ≥7 days depending on the source of GN-BSI, and 71% treat ≥10 days for at least one source. In an adjusted model, factors associated with increased duration included intra-abdominal (+1.01 days, 95% CI 0.57-1.45 days; P < 0.0001), vascular catheter (+0.74 days; 0.33-1.15 days; P = 0.0004), and respiratory (+0.76 days; 0.38-1.14 days; P < 0.0001) sources of GN-BSI relative to urinary sources. Providers that transition patients to oral therapy report shorter durations than those who treat with full IV therapy (-0.60 days; -1.12 to -0.09 days; P = 0.02).

Conclusions

There is extensive heterogeneity in duration of therapy for treating GN-BSI, particularly with respect to source of GN-BSI. Investigations into appropriate treatment durations for different GN-BSI sources are needed.

SUBMITTER: Thaden JT

PROVIDER: S-EPMC8827556 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Survey of infectious diseases providers reveals variability in duration of antibiotic therapy for the treatment of Gram-negative bloodstream infections.

Thaden Joshua T JT Tamma Pranita D PD Pan Qing Q Doi Yohei Y Daneman Nick N

JAC-antimicrobial resistance 20220209 1

<h4>Background</h4>Trials supporting shorter durations of antibiotic therapy for Gram-negative bloodstream infections (GN-BSI) have recently been published. However, adoption of these findings into practice is unclear given limited eligibility criteria and relatively large non-inferiority margins of these studies. To better understand contemporary management of GN-BSI, we conducted an international survey of infectious diseases (ID) specialists.<h4>Methods</h4>We developed and disseminated an on ...[more]

PMID: 35156030

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Project description:ImportanceManagement of gram-negative bloodstream infections (GN-BSIs) with oral antibiotics is highly variable.ObjectiveTo examine the transition from intravenous (IV) to oral antibiotics, including selection, timing, and associated clinical and microbial characteristics, among hospitalized patients with GN-BSIs.Design, setting, and participantsA retrospective cohort study was conducted of 4581 hospitalized adults with GN-BSIs at 24 US hospitals between January 1 and December 31, 2019. Patients were excluded if they died within 72 hours. Patients were excluded from the oral therapy group if transition occurred after day 7. Statistical analysis was conducted from July 2022 to October 2023.ExposuresAdministration of antibiotics for GN-BSIs.Main outcomes and measuresBaseline characteristics and clinical parameters reflecting severity of illness were evaluated in groups receiving oral and IV therapy. The prevalence of transition from IV to oral antibiotics by day 7, median day of transition, sources of infection, and oral antibiotic selection were assessed.ResultsOf a total of 4581 episodes with GN-BSIs (median age, 67 years [IQR, 55-77 years]; 2389 men [52.2%]), 1969 patients (43.0%) receiving IV antibiotics were transitioned to oral antibiotics by day 7. Patients maintained on IV therapy were more likely than those transitioned to oral therapy to be immunosuppressed (833 of 2612 [31.9%] vs 485 of 1969 [24.6%]; P < .001), require intensive care unit admission (1033 of 2612 [39.5%] vs 334 of 1969 [17.0%]; P < .001), have fever or hypotension as of day 5 (423 of 2612 [16.2%] vs 49 of 1969 [2.5%]; P < .001), require kidney replacement therapy (280 of 2612 [10.7%] vs 63 of 1969 [3.2%]; P < .001), and less likely to have source control within 7 days (1852 of 2612 [70.9%] vs 1577 of 1969 [80.1%]; P < .001). Transitioning patients from IV to oral therapy by day 7 was highly variable across hospitals, ranging from 25.8% (66 of 256) to 65.9% (27 of 41). A total of 4109 patients (89.7%) achieved clinical stability within 5 days. For the 3429 episodes (74.9%) with successful source control by day 7, the median day of source control was day 2 (IQR, 1-3 days) for the oral group and day 2 (IQR, 1-4 days) for the IV group (P < .001). Common infection sources among patients administered oral therapy were the urinary tract (1277 of 1969 [64.9%]), hepatobiliary (239 of 1969 [12.1%]), and intra-abdominal (194 of 1969 [9.9%]). The median day of oral transition was 5 (IQR, 4-6 days). Total duration of antibiotic treatment was significantly shorter among the oral group than the IV group (median, 11 days [IQR, 9-14 days] vs median, 13 days [IQR, 8-16 days]; P < .001]. Fluoroquinolones (62.2% [1224 of 1969]), followed by β-lactams (28.3% [558 of 1969]) and trimethoprim-sulfamethoxazole (11.5% [227 of 1969]), were the most commonly prescribed oral antibiotics.Conclusions and relevanceIn this cohort study of 4581 episodes of GN-BSIs, transition to oral antibiotic therapy by day 7 occurred in fewer than half of episodes, principally with fluoroquinolones, although this practice varied significantly between hospitals. There may have been additional opportunities for earlier and more frequent oral antibiotic transitions because most patients demonstrated clinical stability by day 5.

Project description:BackgroundClusters of bloodstream infections caused by Burkholderia cepacia and Stenotrophomonas maltophilia are uncommon, but have been previously identified in hemodialysis centers that reprocessed dialyzers for reuse on patients. We investigated an outbreak of bloodstream infections caused by B cepacia and S maltophilia among hemodialysis patients in clinics of a dialysis organization.Study designOutbreak investigation, including matched case-control study.Setting & participantsHemodialysis patients treated in multiple outpatient clinics owned by a dialysis organization.PredictorsMain predictors were dialyzer reuse, dialyzer model, and dialyzer reprocessing practice.OutcomesCase patients had a bloodstream infection caused by B cepacia or S maltophilia; controls were patients without infection dialyzed at the same clinic on the same day as a case; results of environmental cultures and organism typing.Results17 cases (9 B cepacia and 8 S maltophilia bloodstream infections) occurred in 5 clinics owned by the same dialysis organization. Case patients were more likely to have received hemodialysis with a dialyzer that had been used more than 6 times (matched OR, 7.03; 95% CI, 1.38-69.76) and to have been dialyzed with a specific reusable dialyzer (Model R) with sealed ends (OR, 22.87; 95% CI, 4.49-∞). No major lapses during dialyzer reprocessing were identified that could explain the outbreak. B cepacia was isolated from samples collected from a dialyzer header-cleaning machine from a clinic with cases and was indistinguishable from a patient isolate collected from the same clinic, by pulsed-field gel electrophoresis. Gram-negative bacteria were isolated from 2 reused Model R dialyzers that had undergone the facility's reprocessing procedure.LimitationsLimited statistical power and overmatching; few patient isolates and dialyzers available for testing.ConclusionsThis outbreak was likely caused by contamination during reprocessing of reused dialyzers. Results of this and previous investigations demonstrate that exposing patients to reused dialyzers increases the risk for bloodstream infections. To reduce infection risk, providers should consider implementing single dialyzer use whenever possible.

Project description:ObjectiveTo describe antibiotic treatment durations that pediatric infectious diseases (ID) and critical care clinicians usually recommend for bloodstream infections in critically ill children.DesignAnonymous, online practice survey using five common pediatric-based case scenarios of bloodstream infections.SettingPediatric intensive care units in Canada, Australia and New Zealand.ParticipantsPediatric intensivists, nurse practitioners, ID physicians and pharmacists.Main outcome measuresRecommended treatment durations for common infectious syndromes associated with bloodstream infections and willingness to enrol patients into a trial to study treatment duration.ResultsAmong 136 survey respondents, most recommended at least 10 days antibiotics for bloodstream infections associated with: pneumonia (65%), skin/soft tissue (74%), urinary tract (64%) and intra-abdominal infections (drained: 90%; undrained: 99%). For central vascular catheter-associated infections without catheter removal, over 90% clinicians recommended at least 10 days antibiotics, except for infections caused by coagulase negative staphylococci (79%). Recommendations for at least 10 days antibiotics were less common with catheter removal. In multivariable linear regression analyses, lack of source control was significantly associated with longer treatment durations (+5.2 days [95% CI: 4.4-6.1 days] for intra-abdominal infections and +4.1 days [95% CI: 3.8-4.4 days] for central vascular catheter-associated infections). Most clinicians (73-95%, depending on the source of bloodstream infection) would be willing to enrol patients into a trial of shorter versus longer antibiotic treatment duration.ConclusionsThe majority of clinicians currently recommend at least 10 days of antibiotics for most scenarios of bloodstream infections in critically ill children. There is practice heterogeneity in self-reported treatment duration recommendations among clinicians. Treatment durations were similar across different infectious syndromes. Under appropriate clinical conditions, most clinicians would be willing to enrol patients into a trial of shorter versus longer treatment for common syndromes associated with bloodstream infections.

Project description:Rationale & objectiveContaminated water and other fluids are increasingly recognized to be associated with health care-associated infections. We investigated an outbreak of Gram-negative bloodstream infections at 3 outpatient hemodialysis facilities.Study designMatched case-control investigations.Setting & participantsPatients who received hemodialysis at Facility A, B, or C from July 2015 to November 2016.ExposuresInfection control practices, sources of water, dialyzer reuse, injection medication handling, dialysis circuit priming, water and dialysate test findings, environmental reservoirs such as wall boxes, vascular access care practices, pulsed-field gel electrophoresis, and whole-genome sequencing of bacterial isolates.OutcomesCases were defined by a positive blood culture for any Gram-negative bacteria drawn July 1, 2015 to November 30, 2016 from a patient who had received hemodialysis at Facility A, B, or C.Analytical approachExposures in cases and controls were compared using matched univariate conditional logistic regression.Results58 cases of Gram-negative bloodstream infection occurred; 48 (83%) required hospitalization. The predominant organisms were Serratia marcescens (n=21) and Pseudomonas aeruginosa (n=12). Compared with controls, cases had higher odds of using a central venous catheter for dialysis (matched odds ratio, 54.32; lower bound of the 95% CI, 12.19). Facility staff reported pooling and regurgitation of waste fluid at recessed wall boxes that house connections for dialysate components and the effluent drain within dialysis treatment stations. Environmental samples yielded S marcescens and P aeruginosa from wall boxes. S marcescens isolated from wall boxes and case-patients from the same facilities were closely related by pulsed-field gel electrophoresis and whole-genome sequencing. We identified opportunities for health care workers' hands to contaminate central venous catheters with contaminated fluid from the wall boxes.LimitationsLimited patient isolates for testing, on-site investigation occurred after peak of infections.ConclusionsThis large outbreak was linked to wall boxes, a previously undescribed source of contaminated fluid and biofilms in the immediate patient care environment.

Project description:ImportanceCurrent evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes.ObjectiveTo investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI).Design, setting, and participantsThis cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion β-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023.ExposuresEI-BL (ie, ≥3-hour infusion).Main outcomes and measuresEI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the β-lactam used to treat the index GN-BSI).ResultsAmong the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35).Conclusions and relevanceIn this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.

Project description:Bloodstream infections (BSI) caused by antimicrobial-resistant (AMR) Gram-negative bacteria (GNB) are a significant cause of morbidity and mortality. Third-generation cephalosporins (3GCs) have been used as empiric treatment for BSI and other invasive infections for years; however, their overuse could promote the emergence of extended-spectrum beta-lactamases (ESBLs). Thus, this study aimed to determine the epidemiological, clinical and microbiological features and the effects of antimicrobial resistance on the outcomes of BSIs at a referral hospital in Lusaka, Zambia. This was a six-month prospective facility-based study undertaken at a referral hospital in Lusaka, Zambia. As part of the routine diagnosis and patient care, blood samples for bacteriological culture were collected from patients presenting with fever and processed for pathogen identification and antimicrobial susceptibility testing using the VITEK 2 Compact instrument. ESBLs and plasmid-mediated quinolone resistance (PMQR) associated genes were determined using the polymerase chain reaction method. Patient information was collected using a structured data collection sheet and entered in CSpro 7.6. Data were analysed in WHOnet and STATA version 14. A total of 88 GNB were isolated, of which 76% were Enterobacterales, 14% Acinetobacter baumannii and 8% Pseudomonas aeruginosa. Resistance to third and fourth-generation cephalosporins was 75% and 32%, respectively. Noteworthy was the high prevalence (68%) of inappropriate empirical treatment, carbapenem resistance (7%), multi-drug resistance (83%) and ESBL-producers (76%). In comparison to E. coli as a causative agent of BSI, the odds of death were significantly higher among patients infected with Acinetobacter baumannii (OR = 3.8). The odds of death were also higher in patients that received 3GCs as empiric treatment than in those that received 4GCs or other (none cephalosporin) treatment options. Structured surveillance, yearly antibiogram updates, improved infection control and a well functional antimicrobial stewardship (AMS) program, are of utmost importance in improving appropriate antimicrobial treatment selection and favourable patient outcomes.

Dataset Information

Survey of infectious diseases providers reveals variability in duration of antibiotic therapy for the treatment of Gram-negative bloodstream infections.

Background

Methods

Results

Conclusions

Publications

Survey of infectious diseases providers reveals variability in duration of antibiotic therapy for the treatment of Gram-negative bloodstream infections.

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