-
Open Forum Infectious Diseases Jul 2019Beta-lactam antibiotics are recommended as first-line for treatment of methicillin-sensitive (MSSA) bacteremia. The objective of this study was to compare effectiveness...
Comparative Effectiveness of Exclusive Exposure to Nafcillin or Oxacillin, Cefazolin, Piperacillin/Tazobactam, and Fluoroquinolones Among a National Cohort of Veterans With Methicillin-Susceptible Bloodstream Infection.
OBJECTIVE
Beta-lactam antibiotics are recommended as first-line for treatment of methicillin-sensitive (MSSA) bacteremia. The objective of this study was to compare effectiveness of anti-MSSA therapies among bacteremia patients exclusively exposed to 1 antimicrobial.
METHOD
This was a national retrospective cohort study of patients hospitalized in Veterans Affairs medical centers with MSSA bacteremia from January 1, 2002, to October 1, 2015. Patients were included if they were treated exclusively with nafcillin, oxacillin, cefazolin, piperacillin/tazobactam, or fluoroquinolones (moxifloxacin and levofloxacin). We assessed 30-day mortality, time to discharge, inpatient mortality, 30-day readmission, and 30-day reinfection. Hazard ratios (HRs) and 95% confidence intervals (CI) were calculated using propensity-score (PS) matched Cox proportional hazards regression model.
RESULTS
When comparing nafcillin/oxacillin (n = 105) with cefazolin (n = 107), 30-day mortality was similar between groups (PS matched n = 44; HR, 0.67; 95% CI, 0.11-4.00), as were rates of the other outcomes assessed. As clinical outcomes did not vary between nafcillin/oxacillin and cefazolin, they were combined for comparison with piperacillin/tazobactam (n = 113) and fluoroquinolones (n = 103). Mortality in the 30 days after culture was significantly lower in the nafcillin/oxacillin/cefazolin group compared with piperacillin/tazobactam (PS matched n = 48; HR, 0.10; 95% CI, 0.01-0.78), and similar when compared with fluoroquinolones (PS matched n = 32; HR, 1.33; 95% CI, 0.30-5.96).
CONCLUSIONS
In hospitalized patients with MSSA bacteremia, no difference in mortality was observed between nafcillin/oxacillin and cefazolin or fluoroquinolones. However, higher mortality was observed with piperacillin/tazobactam as compared with nafcillin/oxacillin/cefazolin, suggesting it may not be as effective as a monotherapy in MSSA bacteremia.
PubMed: 31281864
DOI: 10.1093/ofid/ofz270 -
The Cochrane Database of Systematic... May 2020Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but due to the differences in... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but due to the differences in presentation, populations affected, and the wide variety of micro-organisms that can be responsible, their use is not standardised. This is an update of a review previously published in 2016.
OBJECTIVES
To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Classic and Embase, LILACS, CINAHL, and the Conference Proceedings Citation Index - Science on 6 January 2020. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) assessing the effects of antibiotic regimens for treating definitive infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates, and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, 'Risk of bias' assessment, and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of the evidence. We described the included studies narratively.
MAIN RESULTS
Six small RCTs involving 1143 allocated/632 analysed participants met the inclusion criteria of this first update. The included trials had a high risk of bias. Three trials were sponsored by drug companies. Due to heterogeneity in outcome definitions and different antibiotics used data could not be pooled. The included trials compared miscellaneous antibiotic schedules having uncertain effects for all of the prespecified outcomes in this review. Evidence was either low or very low quality due to high risk of bias and very low number of events and small sample size. The results for all-cause mortality were as follows: one trial compared quinolone (levofloxacin) plus standard treatment (antistaphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin), and rifampicin) versus standard treatment alone and reported 8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; risk ratio (RR) 1.12, 95% confidence interval (CI) 0.49 to 2.56. One trial compared fosfomycin plus imipenem 3/4 (75%) versus vancomycin 0/4 (0%) (RR 7.00, 95% CI 0.47 to 103.27), and one trial compared partial oral treatment 7/201 (3.5%) versus conventional intravenous treatment 13/199 (6.53%) (RR 0.53, 95% CI 0.22 to 1.31). The results for rates of cure with or without surgery were as follows: one trial compared daptomycin versus low-dose gentamicin plus an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) or vancomycin and reported 9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus antistaphylococcal penicillin or vancomycin; RR 0.89, 95% CI 0.42 to 1.89. One trial compared glycopeptide (vancomycin or teicoplanin) plus gentamicin with cloxacillin plus gentamicin (13/23 (56%) versus 11/11 (100%); RR 0.59, 95% CI 0.40 to 0.85). One trial compared ceftriaxone plus gentamicin versus ceftriaxone alone (15/34 (44%) versus 21/33 (64%); RR 0.69, 95% CI 0.44 to 1.10), and one trial compared fosfomycin plus imipenem versus vancomycin (1/4 (25%) versus 2/4 (50%); RR 0.50, 95% CI 0.07 to 3.55). The included trials reported adverse events, the need for cardiac surgical interventions, and rates of uncontrolled infection, congestive heart failure, relapse of endocarditis, and septic emboli, and found no conclusive differences between groups (very low-quality evidence). No trials assessed quality of life.
AUTHORS' CONCLUSIONS
This first update confirms the findings of the original version of the review. Limited and low to very low-quality evidence suggests that the comparative effects of different antibiotic regimens in terms of cure rates or other relevant clinical outcomes are uncertain. The conclusions of this updated Cochrane Review were based on few RCTs with a high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis.
Topics: Anti-Bacterial Agents; Endocarditis, Bacterial; Female; Fosfomycin; Humans; Imipenem; Levofloxacin; Male; Penicillins; Randomized Controlled Trials as Topic; Vancomycin
PubMed: 32407558
DOI: 10.1002/14651858.CD009880.pub3 -
The Journal of Antimicrobial... Nov 2022Anti-staphylococcal penicillins (ASPs) are among the most commonly prescribed antibiotics in children and are associated with a risk of drug-induced liver injury (DILI).... (Review)
Review
INTRODUCTION
Anti-staphylococcal penicillins (ASPs) are among the most commonly prescribed antibiotics in children and are associated with a risk of drug-induced liver injury (DILI). Despite the frequent use of ASPs in children, there is no consensus on whether liver function tests (LFTs) should be routinely monitored during treatment.
OBJECTIVES
To review the literature on the frequency of ASP-related DILI in children to determine the incidence, risk factors and outcomes of hepatotoxicity.
METHODS
PubMed, MEDLINE and Embase were searched in January 2022 for original studies of children who received cloxacillin, dicloxacillin, flucloxacillin, methicillin, nafcillin or oxacillin that included ≥10 children aged up to 18 years, and presented data on the incidence of DILI in children exposed to ASPs.
RESULTS
Overall, two studies of oral flucloxacillin, two of intravenous (IV) methicillin, three of IV nafcillin and four of IV oxacillin were included. The mean onset of DILI ranged between 7.0 and 19.0 days following commencement of antibiotic treatment and all episodes resolved between 14.2 and 16.0 days after drug discontinuation, with no specific treatment required. This review found that the incidence of DILI in children was 1 in 50 000 for oral flucloxacillin and ranged from 1 in 3 to 13 for IV oxacillin, methicillin and nafcillin.
CONCLUSIONS
This review found that routine LFT monitoring is not required in children receiving low dose oral flucloxacillin in a primary care setting, although pharmacovigilance is critical. For IV preparations, the existing data support routine LFT monitoring in those receiving treatment for at least 7 days.
Topics: Child; Humans; Nafcillin; Methicillin; Penicillins; Floxacillin; Oxacillin; Cloxacillin; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury
PubMed: 36203386
DOI: 10.1093/jac/dkac325 -
Pediatric Reports Jun 2022Myelosuppression, a potential adverse reaction of nafcillin and rifampin, is rarely documented in pediatric populations. The objective of this study is to describe the...
Myelosuppression, a potential adverse reaction of nafcillin and rifampin, is rarely documented in pediatric populations. The objective of this study is to describe the incidence of myelosuppression in pediatric patients receiving nafcillin or a combination of nafcillin and rifampin therapy. This retrospective chart review identified patients who received nafcillin alone or in combination with rifampin. The primary endpoint was the incidence of myelosuppression as a composite outcome. The secondary endpoints were the incidence of thrombocytopenia, anemia, and neutropenia individually. Of 199 patients in this study, 98 received nafcillin alone. There was no difference in the rates of myelosuppression between patients receiving nafcillin alone or in combination with rifampin ( = 0.0763), and the use of combination therapy did not affect the development of neutropenia ( = 0.2764) or thrombocytopenia ( = 0.1672). Patients receiving combination therapy were more likely to be anemic at the end of therapy (odds ratio [OR] = 2.333, 95% confidence interval [CI] 0.999, 5.446). Similarly, patients receiving longer durations of nafcillin were more likely to experience anemia (OR 1.774, 95% CI 1.382, 2.370) and neutropenia (OR 1.256, 95% CI 1.024, 1.540). The use of nafcillin does not significantly affect myelosuppression in pediatric patients, although longer durations of therapy may result in increased rates of neutropenia and anemia. Combination therapy with rifampin may result in increased rates of neutropenia.
PubMed: 35736658
DOI: 10.3390/pediatric14020036 -
International Journal of Antimicrobial... Jun 2023Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis failing conventional therapy has been successfully treated with nafcillin plus daptomycin in the...
Nafcillin Augmentation of Daptomycin and Cathelicidin LL-37 Killing of Methicillin-resistant Staphylococcus epidermidis: Foundations of Successful Therapy of Endocarditis.
Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis failing conventional therapy has been successfully treated with nafcillin plus daptomycin in the clinic. In vitro studies showed that nafcillin enhanced daptomycin killing of MRSE in both planktonic cells and biofilm. Nafcillin exposure also sensitized MRSE to killing by human neutrophils and cathelicidin antimicrobial peptide LL-37. Fluorescent microscopy showed increased daptomycin and LL-37 binding to the MRSE bacterial surface upon nafcillin treatment. Ceftaroline also increased MRSE killing by daptomycin in planktonic cultures and biofilms, as well as daptomycin and LL-37 binding on the bacterial surface. Nafcillin, ceftaroline, and possibly other β-lactams, may serve an important role in the therapy of MRSE endocarditis through augmentation of cationic peptide, the innate immune system, and daptomycin killing. Clinical studies will be needed to determine how early these regimens should be deployed to optimize clinical outcome.
Topics: Humans; Daptomycin; Nafcillin; Cathelicidins; Anti-Bacterial Agents; Staphylococcus epidermidis; Methicillin-Resistant Staphylococcus aureus; Methicillin Resistance; Staphylococcal Infections; Endocarditis; Microbial Sensitivity Tests; Ceftaroline
PubMed: 36775256
DOI: 10.1016/j.ijantimicag.2023.106758 -
American Family Physician Mar 2000Most cases of bacterial endocarditis involve infection with viridans streptococci, enterococci, coagulase-positive staphylococci or coagulase-negative staphylococci. The... (Review)
Review
Most cases of bacterial endocarditis involve infection with viridans streptococci, enterococci, coagulase-positive staphylococci or coagulase-negative staphylococci. The choice of antibiotic therapy for bacterial endocarditis is determined by the identity and antibiotic susceptibility of the infecting organism, the type of cardiac valve involved (native or prosthetic) and characteristics of the patient, such as drug allergies. Antibiotic therapies discussed in this report are based on recommendations of the American Heart Association. Treatment with aqueous penicillin or ceftriaxone is effective for most infections caused by streptococci. A combination of penicillin or ampicillin with gentamicin is appropriate for endocarditis caused by enterococci that are not highly resistant to penicillin. Vancomycin should be substituted for penicillin when high-level resistance is present. Resistance of enterococci to multiple antibiotics including vancomycin is becoming an increasing problem. Native valve infection by methicillin-susceptible staphylococci is treated with nafcillin, oxacillin or cefazolin. The addition of gentamicin for the first three to five days may accelerate clearing of bacteremia. Infection of a prosthetic valve by a staphylococcal organism should be treated with three antibiotics: oral rifampin and gentamicin and either nafcillin, oxacillin, cefazolin or vancomycin, depending on susceptibility to methicillin. Vancomycin is substituted for penicillin in patients with a history of immediate-type hypersensitivity to penicillin.
Topics: Endocarditis, Bacterial; Enterococcus; Gram-Positive Bacterial Infections; Humans; Patient Education as Topic; Staphylococcal Infections; Streptococcal Infections; Teaching Materials
PubMed: 10750879
DOI: No ID Found -
Data in Brief Apr 2020Ampicillin and nafcillin antibiotics were treated by high frequency ultrasound (at 375 kHz and 24.4 W). Degradations followed pseudo-first order kinetics, which...
Ampicillin and nafcillin antibiotics were treated by high frequency ultrasound (at 375 kHz and 24.4 W). Degradations followed pseudo-first order kinetics, which constants were k: 0.0323 min for AMP and k: 0.0550 min for NAF. Accumulation of sonogenerated hydrogen peroxide and inhibition degree of sonochemical removal (IDS) in presence of a radical scavenger were also stablished. Afterwards, ultrasound was combined with UVC light (sono-photolysis), with ferrous ion (sono-Fenton), and with ferrous ion plus UVC light (sono-photo-Fenton) to degrade the antibiotics. Furthermore, treatment of the pollutants in a complex matrix and removal of antimicrobial activity (AA) were considered. The antibiotics evolution was followed by HPLC-DAD technique and the accumulation of sonogenerated HO was measured by an iodometry-spectrophotometry methodology (77.6 and 57.3 μmol L of HO after 30 min of sonication were accumulated in presence of AMP and NAF, respectively). IDS was analyzed through treatment of the antibiotics in presence of 2-propanol (87.1% for AMP and 56 % for NAF) and considering the hydrophobic character of pollutants (i.e., Log P values). Antimicrobial activity evolution was assessed by the Kirby-Bauer method using as indicator microorganism (sono-photo-Fenton process removed 100% of AA after 60 and 20 min for AMP and NAF, respectively). Finally, for degradations in the complex matrix, a simulated effluent of municipal wastewater treatment plant was utilized (sono-photo-Fenton led to degradations higher than 90 % at 60 min of treatment for both antibiotics). The data from the present work can be valuable for people researching on treatment of wastewaters containing antibiotics, application of advanced oxidation technologies and combination of sonochemical process with photochemical systems.
PubMed: 32195299
DOI: 10.1016/j.dib.2020.105361