-
JAMA Feb 2020Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a β-lactam antibiotic has... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal β-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial.
IMPORTANCE
Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a β-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted.
OBJECTIVE
To determine whether combining an antistaphylococcal β-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia.
DESIGN, SETTING, AND PARTICIPANTS
Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018.
INTERVENTIONS
Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal β-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the β-lactam was administered for 7 days.
MAIN OUTCOMES AND MEASURES
The primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics.
RESULTS
The data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, -4.2%; 95% CI, -14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, -3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, -8.9%; 95% CI, -16.6% to -1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%).
CONCLUSIONS AND RELEVANCE
Among patients with MRSA bacteremia, addition of an antistaphylococcal β-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02365493.
Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cefazolin; Cloxacillin; Daptomycin; Drug Therapy, Combination; Endocarditis, Bacterial; Female; Floxacillin; Follow-Up Studies; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Staphylococcal Infections; Treatment Failure; Vancomycin; beta-Lactams
PubMed: 32044943
DOI: 10.1001/jama.2020.0103 -
The Cochrane Database of Systematic... May 2021Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality....
BACKGROUND
Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis.
OBJECTIVES
To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis.
SEARCH METHODS
We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.
SELECTION CRITERIA
We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up.
MAIN RESULTS
We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors.
AUTHORS' CONCLUSIONS
Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted.
Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; Aztreonam; Bias; Cefazolin; Clavulanic Acid; Drug Therapy, Combination; Floxacillin; Gentamicins; Humans; Infant, Newborn; Neonatal Sepsis; Randomized Controlled Trials as Topic; Ticarcillin; Vancomycin
PubMed: 33998665
DOI: 10.1002/14651858.CD013836.pub2 -
Clinical Medicine (London, England) Jul 2019
Topics: Acetaminophen; Drug-Related Side Effects and Adverse Reactions; Floxacillin; Humans
PubMed: 31308126
DOI: 10.7861/clinmedicine.19-4-357 -
Clinical Microbiology and Infection :... May 2020To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis.
METHODS
This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90.
RESULTS
Between August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12- and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: -15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI: -8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05).
CONCLUSIONS
Given the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies.
Topics: Administration, Intravenous; Aged; Anti-Bacterial Agents; Cellulitis; Double-Blind Method; Duration of Therapy; Female; Floxacillin; Humans; Male; Middle Aged; Treatment Outcome
PubMed: 31618678
DOI: 10.1016/j.cmi.2019.09.019 -
Lakartidningen Jan 2018Automatic infectious disease consultant alert is associated with decreased mortality and readmission rate in Staphylococcus aureus bacteriemia A management plan was...
Automatic infectious disease consultant alert is associated with decreased mortality and readmission rate in Staphylococcus aureus bacteriemia A management plan was implemented at a 2000 bed teaching hospital where positive blood cultures with growth of Staphylococcus aureus were reported simultaneously to the ordering unit and to the Infectious Disease Consultant. Readmission rate and 30-day mortality were compared one year before and one year after introduction of the management plan. Out of totally 320 respectively 321 patients with SAB 252 and 244 were included in the study. 30-day mortality decreased from 26/252 (10%) to 14/244 (5,7%) (p=0.059) when all patients with SAB were included and to 9/193 (4,7%) (p=0,026) when only patients who received a formal consultation after introduction of the management plan were included. The rate of readmission within 30 days declined from 38/227 (17%) in 2014-2015 to 24/230 (10%) in 2015-2016 (p=0,049).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Child; Child, Preschool; Cloxacillin; Comorbidity; Female; Humans; Infant; Infection Control Practitioners; Male; Middle Aged; Patient Readmission; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Time Factors; Young Adult
PubMed: 29337337
DOI: No ID Found -
Tidsskrift For Den Norske Laegeforening... Oct 2023While standard blood tests are often sufficient for an anaemia workup, sometimes more invasive diagnostic testing is required to exclude rare conditions.
BACKGROUND
While standard blood tests are often sufficient for an anaemia workup, sometimes more invasive diagnostic testing is required to exclude rare conditions.
CASE PRESENTATION
A man in his forties contacted his general practitioner because of increasing functional dyspnoea. He had completed a course of dicloxacillin a few months previously for a skin abscess on his abdomen. Bloodwork revealed severe anaemia (haemoglobin 5.4 g/dL), which required transfusion. Subsequent testing excluded iron and vitamin deficiency anaemia, haemolysis and malignancy. Initial bone marrow biopsy was of suboptimal quality. However, repeat tissue sample supported a diagnosis of pure red cell aplasia. The patient improved with ciclosporin treatment, which was gradually tapered.
INTERPRETATION
Pure red cell aplasia should be considered in patients with new onset isolated anaemia with severe reticulocytopenia. Diagnosis depends on obtaining representative tissue from bone marrow biopsy. It is difficult to conclude for this patient whether the aetiology of his pure red cell aplasia was idiopathic or secondary to recent dicloxacillin use.
Topics: Humans; Male; Anemia; Bone Marrow; Dicloxacillin; Neoplasms; Red-Cell Aplasia, Pure; Adult
PubMed: 37874056
DOI: 10.4045/tidsskr.23.0022 -
The Netherlands Journal of Medicine Sep 2019
Topics: Administration, Oral; Anti-Bacterial Agents; Drug Monitoring; Floxacillin; Gastrointestinal Absorption; Humans; Staphylococcal Infections
PubMed: 31582583
DOI: No ID Found -
Nature Medicine Oct 2023Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin... (Randomized Controlled Trial)
Randomized Controlled Trial
Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .
Topics: Adult; Humans; Anti-Bacterial Agents; Bacteremia; Cloxacillin; Fosfomycin; Methicillin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Drug Therapy, Combination
PubMed: 37783969
DOI: 10.1038/s41591-023-02569-0 -
International Journal of Infectious... Dec 2023This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National...
OBJECTIVES
This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP).
METHODS
Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately.
RESULTS
We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors.
CONCLUSION
Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective.
Topics: Humans; Cefazolin; Prospective Studies; Retrospective Studies; Staphylococcal Infections; Treatment Outcome; Bacteremia; Anti-Bacterial Agents; Cloxacillin; Endocarditis, Bacterial; Staphylococcus aureus; Renal Insufficiency; Recurrence
PubMed: 37926195
DOI: 10.1016/j.ijid.2023.10.019 -
The Medical Journal of Malaysia Jun 2012Lemierre syndrome is an uncommon disease which commonly arise from acute bacterial oropharyngeal infection. This disease was first described in 1900 by Courmont and Cade...
Lemierre syndrome is an uncommon disease which commonly arise from acute bacterial oropharyngeal infection. This disease was first described in 1900 by Courmont and Cade Lemierre. It is commonly caused by Fusobacterium necrophorum. Lemierre syndrome has been reported to be serious and potentially fatal in the preantibiotic era. It is characterized by an oropharyngeal infection leading to secondary septic thrombophlebitis of the internal jugular vein with embolization to the lungs and other organs. The incidence has become relatively rare at present and is usually only diagnosed when unsuspected culture results are available. We report a case of Lemierre syndrome which was recently diagnosed in our centre.
Topics: Anti-Bacterial Agents; Ceftriaxone; Cloxacillin; Humans; Lemierre Syndrome; Male; Metronidazole; Middle Aged; Penicillins
PubMed: 23082433
DOI: No ID Found