Dataset Information

Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial.

ABSTRACT: Importance:Antibiotic overuse drives antibiotic resistance. Gram-negative bacteremia is a common infection that results in substantial antibiotic use.

Objective:To compare the clinical effectiveness of C-reactive protein (CRP)-guided, 7-day, and 14-day antibiotic durations 30, 60, and 90 days after treatment initiation.

Design, setting, and participants:Multicenter, noninferiority, point-of-care randomized clinical trial including adults hospitalized with gram-negative bacteremia conducted in 3 Swiss tertiary care hospitals between April 2017 and May 2019, with follow-up until August 2019. Patients and physicians were blinded between randomization and antibiotic discontinuation. Adults (aged ?18 years) were eligible for randomization on day 5 (±1 d) of microbiologically efficacious therapy for fermenting, gram-negative bacteria in blood culture(s) if they were afebrile for 24 hours without evidence for complicated infection (eg, abscess) or severe immunosuppression.

Intervention:Randomization in a 1:1:1 ratio to an individualized CRP-guided antibiotic treatment duration (discontinuation once CRP declined by 75% from peak; n?=?170), fixed 7-day treatment duration (n?=?169), or fixed 14-day treatment duration (n?=?165).

Main outcomes and measures:The primary outcome was the clinical failure rate at day 30, defined as the presence of at least 1 of the following, with a non-inferiority margin of 10%: recurrent bacteremia, local suppurative complication, distant complication (growth of the same organism causing the initial bacteremia), restarting gram-negative-directed antibiotic therapy due to clinical worsening suspected to be due to the initial organism, or death due to any cause. Secondary outcomes included the clinical failure rate on day 90 of follow-up.

Results:Among 504 patients randomized (median [interquartile range] age, 79 [68-86] years; 306 of 503 [61%] were women), 493 (98%) completed 30-day follow-up and 448 (89%) completed 90-day follow-up. Median antibiotic duration in the CRP group was 7 (interquartile range, 6-10; range, 5-28) days; 34 of the 164 patients (21%) who completed the 30-day follow-up had protocol violations related to treatment assignment. The primary outcome occurred in 4 of 164 (2.4%) patients in the CRP group, 11 of 166 (6.6%) in the 7-day group, and 9 of 163 (5.5%) in the 14-day group (difference in CRP vs 14-day group, -3.1% [1-sided 97.5% CI, -? to 1.1]; P?
Conclusions and relevance:Among adults with uncomplicated gram-negative bacteremia, 30-day rates of clinical failure for CRP-guided antibiotic treatment duration and fixed 7-day treatment were noninferior to fixed 14-day treatment. However, interpretation is limited by the large noninferiority margin compared with the low observed event rate, as well as low adherence and wide range of treatment durations in the CRP-guided group.

Trial registration:ClinicalTrials.gov Identifier: NCT03101072.

SUBMITTER: von Dach E

PROVIDER: S-EPMC7267846 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial.

von Dach Elodie E Albrich Werner C WC Brunel Anne-Sophie AS Prendki Virginie V Cuvelier Clémence C Flury Domenica D Gayet-Ageron Angèle A Huttner Benedikt B Kohler Philipp P Lemmenmeier Eva E McCallin Shawna S Rossel Anne A Harbarth Stephan S Kaiser Laurent L Bochud Pierre-Yves PY Huttner Angela A

JAMA 20200601 21

<h4>Importance</h4>Antibiotic overuse drives antibiotic resistance. Gram-negative bacteremia is a common infection that results in substantial antibiotic use.<h4>Objective</h4>To compare the clinical effectiveness of C-reactive protein (CRP)-guided, 7-day, and 14-day antibiotic durations 30, 60, and 90 days after treatment initiation.<h4>Design, setting, and participants</h4>Multicenter, noninferiority, point-of-care randomized clinical trial including adults hospitalized with gram-negative bact ...[more]

PMID: 32484534

Similar Datasets

Project description:BackgroundOptimal antibiotic treatment strategies of Haemophilus infections are still needed. Therefore, 30-day case fatality rate (CFR) of Haemophilus bacteremia and efficacy of various antibiotic treatment regimes were studied.MethodsAll episodes of Haemophilus bacteremia in the former Copenhagen County during the period 2000-9 were included in the study. Clinical and biochemical findings and outcome were collected retrospectively from medical records.Results105 consecutive episodes were identified (median age: 69 years, with only 4 children <16 years), 72% were due to non-typeable -, 16% to typeable H. influenzae, and 11% to other Haemophilus species. Pneumonia was the most common primary focus (in 48%), and 58% of the patients had Charlson comorbidity index > 1. Definitive antibiotic therapy was in 26 cases benzylpenicillin, in 12 cases aminopenicillins, in 50 cases cefuroxime and in 16 cases broadspectrum antibiotics, whereas 1 palliative case died without start of therapy. Whereas the use of broadspectrum antibiotics was related to the severity of the disease (admittance to ICU, need for assisted ventilation or hemodialysis, septic shock), no significant difference in clinical features was demonstrated for therapy with benzylpenicillin, aminopenicillin or cefuroxime, except benzylpenicillin was rarely administered to immunosuppressed patients. The CFR was 22% (23/105). The choice of empiric antibiotic therapy was not significantly associated with mortality (adequate vs. inadequate treatment: 23% (21/93) vs. 17% (2/12), respectively, P > 0.05). In contrast, definite antibiotic therapy with cefuroxime or aminopenicillins resulted in a significantly lower CFR than treatment with benzylpenicillin (12% (6/50) or 0% (0/12) vs. 39% (10/26), respectively, Log rank test P < 0.02). When adjustments were made for other identified risk factors in bivariate logistic regression analysis, treatment with cefuroxime was still were found to be associated with a significantly lower CFR than for benzylpenicillin: OR: 0.21 (0.06-0.69), P = 0.01 (hospital-acquired bacteremia), OR: 0.27 (0.08-0.91), P = 0.04 (polymicrobial episodes), OR: 0.16 (0.04-0.59), P = 0.006 (admittance at intensive care unit), OR: 0.22 (0.06-0.82), P = 0.02 (alcohol abuse), OR: 0.15 (0.04-0.60), P = 0.008 (altered mental state), OR: 0.22 (0.07-0.71), P = 0.01 (temperature < 38 °C), OR: 0.23 (0.07-0.79), P = 0.02 (septic shock), OR: 0.21 (0.06-0.69), P = 0.01 (mechanical ventilation).ConclusionOur results suggest that, after susceptibility testing, cefuroxime or aminopenicillins are preferable to benzylpenicillins as definitive therapy for Haemophilus bacteremia.

Project description:BackgroundWe aim to compare the effect of short versus long treatment duration in Gram-negative bacteremia on all-cause mortality in pre-specified sub-groups.MethodsIndividual participant data meta-analysis of randomized controlled trials (RCTs) comparing short (≤7) versus longer (>7 days) antibiotic treatment for Gram-negative bacteremia. Participants were adults (≥18 years), with Gram-negative bacteremia during hospital stay. We searched PubMed, Cochrane Central Register of Controlled Trials, and Web of Science to identify trials conducted up to May 2022. Primary outcome was 90-day all-cause mortality. Secondary outcomes were 30-day mortality, relapse of bacteremia, length of hospital stay, readmission, local or distant infection complications, adverse events, and resistance emergence.Outcomes were assessed in pre-specified subgroups: women vs men; non-urinary vs urinary source; presence vs absence of hypotension on initial presentation; immunocompromised patients versus non-immunocompromised patients, and age (above/below 65). Fixed-effect meta-analysis model was used to estimate pooled odds ratio (OR) and 95% confidence interval (CI). All three trials had low risk of bias for allocation generation and concealment.FindingsThree RCTs (1186 patients) were included; 1121 with enterobacterales bacteremia. No significant difference in mortality was demonstrated between 7- and 14-days treatment (90-day mortality: OR 1.08, 95% CI 0.73-1.58; 30-day mortality: 1.08, 0.62-1.91). Relapse (1.00, 0.50-1.97); length of hospital stay (P = 0.78); readmission (0.96, 0.80-1.22); and infection complications (local: 1.62 0.76-3.47; distant: 2.00, 0.18-22.08), were without significant difference, and so were adverse events or resistance emergence.No significant difference in clinical outcomes between 7 and 14 days of antibiotics was demonstrated in the subgroups of gender, age, hemodynamic status, immune status, and source of infection.InterpretationFor patients hemodynamically stable and afebrile at 48 h prior to discontinuation, seven days of antibiotic therapy for enterobacterales bacteremia result in similar outcomes as 14 days, in terms of mortality, relapse, length of hospital stay, complications of infection, resistance emergence, and adverse events. These results apply for any adult age group, gender, source of infection, immune status, and hemodynamic status on presentation.FundingThere was no funding source for this study.

Project description:What is known and objectiveGram-negative bacteremia remains a major health problem around the world. The optimal duration of antibiotic treatment has been poorly defined, and there are significant differences of opinion between clinicians. We conducted this systematic review and meta-analysis to compare the clinical outcomes of short-course and long-course treatments in patients with uncomplicated gram-negative bacteremia.MethodsWe searched public databases (PubMed, EMBASE and Cochrane Library) to identify eligible studies. The primary outcomes were all-cause mortality and the incidence of recurrent bacteremia through day 30. We used the Cochrane risk of bias assessment tool to evaluate the risk of bias for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale for non-RCTs.Results and discussionSix studies involving 2689 patients were included in the systematic review and meta-analysis. No significant difference was found between short-course and long-course antibiotic treatments in 30-day mortality (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.65-1.13; P = .26), 30-day recurrent bacteremia (RR 1.07; 95% CI 0.68-1.67; P = .78), 90-day mortality (RR 0.84; 95% CI 0.57-1.24; P = .38), 90-day recurrent bacteremia (RR 0.98; 95% CI 0.50-1.89; P = .94), adverse events (RR 1.14; 95% CI 0.89-1.45; P = .30), Clostridium difficile infection (RR 0.86; 95% CI 0.40-1.86; P = .71) or resistance development (RR 1.19; 95% CI 0.66-2.14; P = .57).What is new and conclusionShort-course was non-inferior to long-course antibiotic treatments for patients with uncomplicated gram-negative bacteremia. Considering the drug-related side effects and cost-effectiveness, a shorter duration of antibiotic treatment may be preferable for this particular population. However, additional high-quality RCTs are needed to further assess whether a shorter course of antibiotic treatment is of greater benefit for patients with uncomplicated gram-negative bacteremia.

Project description:BackgroundNeonatal sepsis is a global public health problem. There is no consensus regarding the optimum duration of antibiotics for culture-proven neonatal sepsis. Published randomized controlled trials (RCTs) comparing shorter versus longer courses of antibiotics provide low-quality evidence with serious risk of bias. We hypothesized that among neonates with uncomplicated culture-proven sepsis, antibiotic duration of 7 days is not inferior to 14 days.MethodsThis is a multi-centric, parallel-group, stratified, block-randomized, active-controlled, non-inferiority trial with outcome assessment blinded. Stratification is by center and birth weight. Neonates weighing ≥1000 g at birth, with blood-culture-proven sepsis (barring Staphylococcus aureus and fungi), without conditions warranting > 14 days antibiotics, and who clinically remit, are enrolled in the RCT on day 7 of administration of sensitive antibiotics. They are randomly allocated to no further antibiotics (intervention arm: total 7 days) or 7 more days of the same antibiotics (control arm: total 14 days). Allocation is concealed by opaque, sealed envelopes. The primary outcome is "definite or probable relapse" within 21 days after antibiotic completion. Secondary outcomes include definite and probable relapses at various timepoints until day 35 post-randomization, secondary infections, and adverse events. The neonatologist adjudicating probable relapses and lab personnel are blinded. Three hundred fifty subjects will be recruited in each arm, assuming a non-inferiority margin of 7%, one-sided alpha error 5%, and power of 90%. Analysis will be per protocol and by intention-to-treat. An independent Data Safety Monitoring Board monitors adverse events and will perform one interim analysis when 50% of expected primary outcomes have occurred or 50% of subjects have completed follow-up, whichever is earlier. O'Brien-Fleming criteria will be used to stop for mid-term benefit and Pocock's to stop for mid-term harm. A priori subgroup analyses are planned by birth weight categories, gram-stain status of pathogens, and radiological pneumonia.DiscussionThis trial will provide evidence to guide practice regarding optimum duration of antibiotics for culture-proven neonatal bacterial sepsis. If a 7-day regime is proved to be non-inferior to a 14-day regime, it is likely to reduce hospital stay, costs, adverse effects of drugs, and nosocomial infections.Trial registrationClinical Trials Registry India CTRI/2017/09/009743 . Registered on 13 September 2017.

Project description:ImportanceStaphylococcus aureus bacteremia (SAB) is a common and potentially severe infectious disease (ID). Retrospective studies and derived meta-analyses suggest that bedside infectious disease consultation (IDC) for SAB is associated with improved survival; however, such IDCs might not always be possible because of the lack of ID specialists, particularly at nonacademic hospitals.ObjectivesTo investigate whether unsolicited telephone IDCs (triggered by an automated blood stream infection reporting system) to nonacademic hospitals improved 30-day all-cause mortality in patients with SAB.Design, setting, and participantsThis patient-blinded, multicenter, interventional, cluster randomized, controlled, crossover clinical trial was conducted in 21 rural, nonacademic hospitals in Thuringia, Germany. From July 1, 2016, to December 31, 2018, 1029 blood culture reports were assessed for eligibility. A total of 386 patients were enrolled, whereas 643 patients were not enrolled for the following reasons: death before enrollment (n = 59); palliative care (n = 41); recurrence of SAB (n = 9); discharge from the hospital before enrollment (n = 77); age younger than 18 years (n = 5); duplicate report from a single patient (n = 26); late report (n = 17); blood culture reported during the washout phase (n = 48); and no signed informed consent for other or unknown reasons (n = 361).InterventionsDuring the ID intervention phase, ID specialists from Jena University Hospital provided unsolicited telephone IDCs to physicians treating patients with SAB. During the control phase, patients were treated according to local standards. Crossover was performed after including 15 patients or, at the latest, 1 year after the first patient was included.Main outcomes and measuresThirty-day all-cause mortality.ResultsA total of 386 patients (median [IQR] age, 75 [63-82] years; 261 [67.6%] male) were included, with 177 randomized to the IDC group and 209 to the control group. The 30-day all-cause mortality rate did not differ between the IDC and control groups (relative risk reduction [RRR], 0.12; 95% CI, -2.17 to 0.76; P = .81). No evidence was found of a difference in secondary outcomes, including 90-day mortality (RRR, 0.17; 95% CI, -0.59 to 0.57; P = .62), 90-day recurrence (RRR, 0.10; 95% CI, -2.51 to 0.89; P = .89), and hospital readmission (RRR, 0.04; 95% CI, -0.63 to 0.48; P = .90). Exploratory evidence suggested that indicators of quality of care were potentially realized more often in the IDC group than in the control group (relative quality improvement, 0.16; 95% CI, 0.08-0.26; P = .01).Conclusions and relevanceIn this cluster randomized clinical trial, unsolicited telephone IDC, although potentially enhancing quality of care, did not improve 30-day all-cause mortality in patients with SAB.Trial registrationdrks.de Identifier: DRKS00010135.

Project description:IntroductionThis exploratory analysis assessed efficacy and safety outcomes in patients with Gram-negative bacteremia treated with ceftazidime-avibactam or comparator across five phase 3, randomized, controlled, multi-center trials in adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI)/pyelonephritis, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP).MethodsIn each trial, RECLAIM and RECLAIM 3 (cIAI; NCT01499290/NCT01726023), REPRISE (cIAI/cUTI; NCT01644643), RECAPTURE (cUTI; NCT01595438/NCT01599806), and REPROVE (HAP/VAP; NCT01808092), patients were randomized 1:1 to intravenous ceftazidime-avibactam (plus metronidazole for those with cIAI) or comparators (carbapenems in > 97% patients) for 5-21 days. Efficacy assessments included clinical and microbiological responses at the test-of-cure visit in the pooled Gram-negative extended microbiologically evaluable (GNeME) population (bacteremia subset). Safety outcomes were summarized for patients with positive bacterial blood culture(s) at baseline who received ≥ 1 dose of study treatment.ResultsThe overall safety population included 4050 patients (ceftazidime-avibactam, n = 2024; comparator, n = 2026). The GNeME population (bacteremia subset) comprised 101 patients (ceftazidime-avibactam, n = 54; comparator, n = 47). Clinical cure rates (all indications combined) were 47/54 (87.0%) for ceftazidime-avibactam and 39/47 (83.0%) for comparators; favorable microbiological response rates were 43/54 (79.6%) and 32/47 (68.1%), respectively. Clinical and microbiological responses in the bacteremia subset were generally similar to those in the overall set. The pattern of adverse events in patients with bacteremia was similar between treatment groups and was consistent with the known safety profile of ceftazidime-avibactam.ConclusionThis analysis provides supportive evidence of the efficacy and safety of ceftazidime-avibactam in patients with Gram-negative bacteremia associated with cIAI, cUTI/pyelonephritis, or HAP/VAP.

Dataset Information

Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial.

Publications

Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets