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Journal of Clinical Microbiology Nov 2021The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing (AST) develops and publishes standards and guidelines for AST... (Review)
Review
The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing (AST) develops and publishes standards and guidelines for AST methods and results interpretation in an annual update to the (M100). This minireview will discuss changes to M100 for the 31st edition, including new and revised breakpoints and testing recommendations. New MIC and disk diffusion breakpoints are described for azithromycin ( spp.), imipenem-relebactam (, Pseudomonas aeruginosa, and anaerobes), and lefamulin (Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pneumoniae), and disk breakpoints are described for azithromycin and Neisseria gonorrhoeae. The rationale behind revised oxacillin MIC breakpoints for select staphylococci is discussed. Updates to test methods include a method for disk diffusion using positive blood culture broth and use of linezolid to predict tedizolid susceptibility. There is clarification on which drugs to suppress on bacteria isolated from the cerebrospinal fluid and clarification on the use of a caret symbol attached to the intermediate category ("I^") to indicate those antimicrobials that concentrate in the urine.
Topics: Anti-Bacterial Agents; Humans; Laboratories; Microbial Sensitivity Tests; Oxacillin; Pseudomonas aeruginosa
PubMed: 34550809
DOI: 10.1128/JCM.00213-21 -
Acta Medica Portuguesa Mar 2021Non-necrotizing acute dermo-hypodermal infections are infectious processes that include erysipela and infectious cellulitis, and are mainly caused by group A... (Review)
Review
Non-necrotizing acute dermo-hypodermal infections are infectious processes that include erysipela and infectious cellulitis, and are mainly caused by group A β-haemolytic streptococcus. The lower limbs are affected in more than 80% of cases and the risk factors are disruption of cutaneous barrier, lymphoedema and obesity. Diagnosis is clinical and in a typical setting we observe an acute inflammatory plaque with fever, lymphangitis, adenopathy and leucocytosis. Bacteriology is usually not helpful because of low sensitivity or delayed positivity. In case of atypical presentations, erysipela must be distinguished from necrotizing fasciitis and acute vein thrombosis. Flucloxacillin and cefradine remain the first line of treatment. Recurrence is the main complication, so correct treatment of the risk factors is crucial.
Topics: Anti-Bacterial Agents; Cellulitis; Cephradine; Erysipelas; Floxacillin; Humans; Recurrence; Soft Tissue Infections
PubMed: 33971117
DOI: 10.20344/amp.12642 -
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 -
BMC Microbiology Nov 2019Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are now accepted as suitable alternatives to...
BACKGROUND
Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are now accepted as suitable alternatives to antibiotics in the control of animal infections and improving animal production. Lactic acid bacteria (LAB) with remarkable functional properties have been evaluated in different studies as possible probiotic candidates. The purpose of this study was to isolate, characterize and assess the potentials of LAB from poultry gastrointestinal tract as potential poultry probiotics.
RESULTS
Potential LAB probiotics were isolated from broilers, characterized and evaluated for probiotic properties including antagonistic activity (against Escherichia coli, E. coli O157: H7, Enterococcus faecalis, Salmonella Typhimurium, S. Enteritidis and Listeria monocytogenes), survivability in simulated gastric juice, tolerance to phenol and bile salts, adhesion to ileum epithelial cells, auto and co-aggregation, hydrophobicity, α-glucosidase inhibitory activity, and antibiotic susceptibility tests. Most promising LAB strains with excellent probiotic potentials were identified by API 50 CHL and 16S rRNA sequencing as Lactobacillus reuteri I2, Pediococcus acidilactici I5, P. acidilactici I8, P. acidilactici c3, P. pentosaceus I13, and Enterococcus faecium c14. They inhibited all the pathogens tested with zones of inhibition ranging from 12.5 ± 0.71 to 20 ± 0 mm, and competitively excluded (P < 0.05) the pathogens examined while adhering to ileum epithelial cells with viable counts of 3.0 to 6.0 Log CFU/ml. The selected LAB strains also showed significant (P < 0.005) auto and co-aggregation abilities with α-glucosidase inhibitory activity ranging from 12.5 to 92.0%. The antibiotic susceptibility test showed 100.00% resistance of the LAB strains to oxacillin, with multiple antibiotic resistance indices above 0.5.
CONCLUSION
The selected LAB strains are ideal probiotic candidates which can be applied in the field for the improvement of poultry performance and control of pathogens in poultry, hence curtailing further transmission to humans.
Topics: Animals; Chickens; DNA, Ribosomal; Drug Resistance, Bacterial; Gastric Juice; Gastrointestinal Tract; Lactobacillales; Microbial Viability; Oxacillin; Poultry; Probiotics; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 31718570
DOI: 10.1186/s12866-019-1626-0 -
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 -
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