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Clinical Microbiology and Infection :... Apr 2022These ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant...
European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine).
SCOPE
These ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy.
METHODS
An expert panel was convened by ESCMID. A systematic review was performed including randomized controlled trials and observational studies, examining different antibiotic treatment regimens for the targeted treatment of infections caused by the 3GCephRE, carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii. Treatments were classified as head-to-head comparisons between individual antibiotics and between monotherapy and combination therapy regimens, including defined monotherapy and combination regimens only. The primary outcome was all-cause mortality, preferably at 30 days and secondary outcomes included clinical failure, microbiological failure, development of resistance, relapse/recurrence, adverse events and length of hospital stay. The last search of all databases was conducted in December 2019, followed by a focused search for relevant studies up until ECCMID 2021. Data were summarized narratively. The certainty of the evidence for each comparison between antibiotics and between monotherapy and combination therapy regimens was classified by the GRADE recommendations. The strength of the recommendations for or against treatments was classified as strong or conditional (weak).
RECOMMENDATIONS
The guideline panel reviewed the evidence per pathogen, preferably per site of infection, critically appraising the existing studies. Many of the comparisons were addressed in small observational studies at high risk of bias only. Notably, there was very little evidence on the effects of the new, recently approved, β-lactam/β-lactamase inhibitors on infections caused by carbapenem-resistant Gram-negative bacteria. Most recommendations are based on very-low- and low-certainty evidence. A high value was placed on antibiotic stewardship considerations in all recommendations, searching for carbapenem-sparing options for 3GCephRE and limiting the recommendations of the new antibiotics for severe infections, as defined by the sepsis-3 criteria. Research needs are addressed.
Topics: Anti-Bacterial Agents; Carbapenems; Communicable Diseases; Critical Care; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans
PubMed: 34923128
DOI: 10.1016/j.cmi.2021.11.025 -
International Journal of Environmental... Sep 2022One of the public health issues faced worldwide is antibiotic resistance (AR). During the novel coronavirus (COVID-19) pandemic, AR has increased. Since some studies... (Review)
Review
One of the public health issues faced worldwide is antibiotic resistance (AR). During the novel coronavirus (COVID-19) pandemic, AR has increased. Since some studies have stated AR has increased during the COVID-19 pandemic, and others have stated otherwise, this study aimed to explore this impact. Seven databases-PubMed, MEDLINE, EMBASE, Scopus, Cochrane, Web of Science, and CINAHL-were searched using related keywords to identify studies relevant to AR during COVID-19 published from December 2019 to May 2022, according to PRISMA guidelines. Twenty-three studies were included in this review, and the evidence showed that AR has increased during the COVID-19 pandemic. The most commonly reported resistant Gram-negative bacteria was , followed by , , and . and were highly resistant to tested antibiotics compared with and . Moreover, showed high resistance to colistin. Commonly reported Gram-positive bacteria were and . The resistance of to ampicillin, erythromycin, and Ciprofloxacin was high. Self-antibiotic medication, empirical antibiotic administration, and antibiotics prescribed by general practitioners were the risk factors of high levels of AR during COVID-19. Antibiotics' prescription should be strictly implemented, relying on the Antimicrobial Stewardship Program (ASP) and guidelines from the World Health Organization (WHO) or Ministry of Health (MOH).
Topics: Ampicillin; Anti-Bacterial Agents; Ciprofloxacin; Colistin; Drug Resistance, Bacterial; Erythromycin; Escherichia coli; Humans; Microbial Sensitivity Tests; Pandemics; Pseudomonas aeruginosa; COVID-19 Drug Treatment
PubMed: 36231256
DOI: 10.3390/ijerph191911931 -
Journal of Thoracic Oncology : Official... Jul 2020Immune checkpoint inhibitors (ICIs) have dramatically improved patient outcomes in a variety of tumor types, but with variable efficacy. Recent research has suggested... (Meta-Analysis)
Meta-Analysis Review
Immune checkpoint inhibitors (ICIs) have dramatically improved patient outcomes in a variety of tumor types, but with variable efficacy. Recent research has suggested that antibiotic-induced disruption of the microbiota may impact ICI efficacy. We performed a systematic review and meta-analysis of studies that assessed the impact of antibiotic use on the survival of patients diagnosed with NSCLC and treated with ICI. We systematically searched Medline, the Cochrane Library, and major oncology conferences proceedings. Eligible studies mentioned hazard ratio or Kaplan-Meier curves for progression-free survival (PFS) or overall survival (OS) based on antibiotic exposure before or during ICI treatment. We identified 23 eligible studies. The impact of antibiotics was then evaluated in 2208 patients for PFS and 5560 for OS. For both PFS and OS meta-analyses, the between-study heterogeneity was high (Higgins and Thompson I of 69% and 80%, respectively). The pooled hazard ratio was 1.47 (95% confidence interval [CI]: 1.13-1.90) for PFS and 1.69 (95% CI: 1.25-2.29) for OS revealing a significantly reduced survival in patients with NSCLC exposed to antibiotics. The median OS was reduced on average by 6.7 months (95% CI: 5.1-8.4) in the patients exposed to antibiotics. The effect seems to depend on the time window of exposure with stronger effects reported when the patients took antibiotics [-60 days; +60 days] around ICI initiation. In patients with NSCLC, the findings of the meta-analysis indicate that antibiotic use before or during treatment with ICI leads to a median OS decreased by more than 6 months. Specifically, exposure shortly before or after ICI initiation seems to be particularly detrimental, whereas antibiotic use later during disease course does not seem to alter survival. Because PFS and OS were difficult to compare between studies owing to heterogeneity and the multiple confounding factors identified, further studies are needed to strengthen the understanding of this phenomenon.
Topics: Anti-Bacterial Agents; Carcinoma, Non-Small-Cell Lung; Humans; Immunotherapy; Lung Neoplasms; Proportional Hazards Models
PubMed: 32173463
DOI: 10.1016/j.jtho.2020.03.002 -
BMJ Evidence-based Medicine Apr 2021Antibiotic over prescription for upper respiratory tract infections (URTIs) in primary care exacerbates antimicrobial resistance. There is a need for effective... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antibiotic over prescription for upper respiratory tract infections (URTIs) in primary care exacerbates antimicrobial resistance. There is a need for effective alternatives to antibiotic prescribing. Honey is a lay remedy for URTIs, and has an emerging evidence base for its use. Honey has antimicrobial properties, and guidelines recommended honey for acute cough in children.
OBJECTIVES
To evaluate the effectiveness of honey for symptomatic relief in URTIs.
METHODS
A systematic review and meta-analysis. We searched Pubmed, Embase, Web of Science, AMED, Cab abstracts, Cochrane Library, LILACS, and CINAHL with a combination of keywords and MeSH terms.
RESULTS
We identified 1345 unique records, and 14 studies were included. Overall risk of bias was moderate. Compared with usual care, honey improved combined symptom score (three studies, mean difference -3.96, 95% CI -5.42 to -2.51, I=0%), cough frequency (eight studies, standardised mean difference (SMD) -0.36, 95% CI -0.50 to -0.21, I=0%) and cough severity (five studies, SMD -0.44, 95% CI -0.64 to -0.25, I=20%). We combined two studies comparing honey with placebo for relieving combined symptoms (SMD -0.63, 95% CI -1.44 to 0.18, I=91%).
CONCLUSIONS
Honey was superior to usual care for the improvement of symptoms of upper respiratory tract infections. It provides a widely available and cheap alternative to antibiotics. Honey could help efforts to slow the spread of antimicrobial resistance, but further high quality, placebo controlled trials are needed.
PROSPERO REGISTRATION NO
Study ID, CRD42017067582 on PROSPERO: International prospective register of systematic reviews (https://www.crd.york.ac.uk/prospero/).
Topics: Anti-Bacterial Agents; Child; Cough; Honey; Humans; Respiratory Tract Infections
PubMed: 32817011
DOI: 10.1136/bmjebm-2020-111336 -
Pediatrics Jul 2023The use of antibiotics in young children is widespread and may lead to adverse effects on dental health, including staining, developmental defects, and dental caries.
CONTEXT
The use of antibiotics in young children is widespread and may lead to adverse effects on dental health, including staining, developmental defects, and dental caries.
OBJECTIVE
To systematically review the effects of early childhood antibiotic exposure on dental health.
DATA SOURCES
Medline (Ovid/PubMed), Embase (Ovid) and Cochrane databases. Study bias was assessed using the Newcastle-Ottawa Scale.
STUDY SELECTION
English language articles that reported antibiotic exposure before 8 years of age and 1 or more of the relevant outcomes (dental caries, intrinsic tooth staining, or developmental defects of enamel) were included.
DATA EXTRACTION
Data on study population, design, type of antibiotic, outcome measurement, and results were extracted from the identified studies.
RESULTS
The initial search yielded 1003 articles of which 34 studies were included. Five of the 18 studies on tetracycline described a dose response relationship between exposure to tetracycline doses of > 20 mg/kg per day and dental staining. Early childhood exposure to doxycycline (at any dose) was not associated with dental staining. There was no clear association between any early childhood antibiotic exposure and dental caries or enamel defects.
LIMITATIONS
In all included studies, the main limitations and sources of bias were the lack of comparison groups, inconsistent outcome measures, and lack of adjustment for relevant confounders.
CONCLUSIONS
There was no evidence that newer tetracycline formulations (doxycycline and minocycline) at currently recommended dosages led to adverse effects on dental health. Findings regarding antibiotic exposure and developmental defects of enamel or dental caries were inconsistent. Further prospective studies are warranted.
Topics: Child; Child, Preschool; Humans; Infant; Anti-Bacterial Agents; Doxycycline; Dental Caries; Bias; Databases, Factual
PubMed: 37264510
DOI: 10.1542/peds.2023-061350 -
The Cochrane Database of Systematic... Jun 2022Diverticulitis is a complication of the common condition, diverticulosis. Uncomplicated diverticulitis has traditionally been treated with antibiotics, as diverticulitis... (Review)
Review
BACKGROUND
Diverticulitis is a complication of the common condition, diverticulosis. Uncomplicated diverticulitis has traditionally been treated with antibiotics, as diverticulitis has been regarded as an infectious disease. Risk factors for diverticulitis, however, may suggest that the condition is inflammatory rather than infectious which makes the use of antibiotics questionable.
OBJECTIVES
The objectives of this systematic review were to determine if antibiotic treatment of uncomplicated acute diverticulitis affects the risk of complications (immediate or late) or the need for emergency surgery.
SEARCH METHODS
For this update, a comprehensive systematic literature search was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov and WHO International Clinical Trial Registry Platform on February 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs), including all types of patients with a radiologically confirmed diagnosis of left-sided uncomplicated acute diverticulitis. Comparator and interventions included antibiotics compared to no antibiotics, placebo, or to any other antibiotic treatment (different regimens, routes of administration, dosage or duration of treatment). Primary outcome measures were complications and emergency surgery. Secondary outcomes were recurrence, late complications, elective colonic resections, length of hospital stay, length to recovery of symptoms, adverse events and mortality.
DATA COLLECTION AND ANALYSIS
Two authors performed the searches, identification and assessment of RCTs and data extraction. Disagreements were resolved by discussion or involvement of the third author. Authors of trials were contacted to obtain additional data if needed or for preliminary results of ongoing trials. The Cochrane Collaboration's tool for assessing risk of bias was used to assess the methodological quality of the identified trials. The overall quality of evidence for outcomes was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Effect estimates were extracted as risk ratios (RRs) with 95% confidence intervals. Random-effects meta-analyses were performed with the Mantel-Haenzel method.
MAIN RESULTS
The authors included five studies. Three studies compared no antibiotics to antibiotics; all three were original RCTs of which two also published long-term follow-up information. For the outcome of short-term complications there may be little or no difference between antibiotics and no antibiotics (RR 0.89; 95% CI 0.30 to 2.62; 3 studies, 1329 participants; low-certainty evidence). The rate of emergency surgery within 30 days may be lower with no antibiotics compared to antibiotics (RR 0.47; 95% CI 0.13, 1.71; 1329 participants; 3 studies; low-certainty evidence). However, there is considerable imprecision due to wide confidence intervals for this effect estimate causing uncertainty which means that there may also be a benefit with antibiotics. One of the two remaining trials compared single to double compound antibiotic therapy and, due to wide confidence intervals, the estimate was imprecise and indicated an uncertain clinical effect between these two antibiotic regimens (RR 0.70; 95% CI 0.11 to 4.58; 51 participants; 1 study; low-certainty evidence). The last trial compared short to long intravenous administration of antibiotics and did not report any events for our primary outcomes. Both trials included few participants and one had overall high risk of bias. Since the first publication of this systematic review, an increasing amount of evidence supporting the treatment of uncomplicated acute diverticulitis without antibiotics has been published, but the total body of evidence is still limited.
AUTHORS' CONCLUSIONS
The evidence on antibiotic treatment for uncomplicated acute diverticulitis suggests that the effect of antibiotics is uncertain for complications, emergency surgery, recurrence, elective colonic resections, and long-term complications. The quality of the evidence is low. Only three RCTs on the need for antibiotics are currently available. More trials are needed to obtain more precise effect estimates.
Topics: Anti-Bacterial Agents; Colon; Diverticulitis; Humans; Length of Stay
PubMed: 35731704
DOI: 10.1002/14651858.CD009092.pub3 -
The Lancet. Infectious Diseases Aug 2022According to the latest reports from WHO, the incidence of antibiotic-resistant bacterial infections is increasing worldwide, resulting in increased morbidity and... (Review)
Review
According to the latest reports from WHO, the incidence of antibiotic-resistant bacterial infections is increasing worldwide, resulting in increased morbidity and mortality and a rising pressure on health-care systems. However, the development of new antibiotics is an expensive and time-consuming process, urging scientists to seek alternative antimicrobial strategies. Over the past few decades, the concept of therapeutic administration of bacteriophages (also known as phages) has gained popularity worldwide. Although conceptually promising, the widespread implementation of phage therapy in routine clinical practice is restricted by the scarcity of safety and efficacy data obtained according to the strict standards of the applicable clinical trial regulations. In this systematic review, we list clinical data published between Jan 1, 2000 and Aug 14, 2021 on the safety and efficacy of phage therapy for difficult-to-treat bacterial infections, and provide an overview of trials and case studies on the use of phage therapy in several medical disciplines.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriophages; Humans; Phage Therapy
PubMed: 35248167
DOI: 10.1016/S1473-3099(21)00612-5 -
JAMA Pediatrics Dec 2022Short-course antibiotic therapy could enhance adherence and reduce adverse drug effects and costs. However, based on sparse evidence, most guidelines recommend a longer... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Short-course antibiotic therapy could enhance adherence and reduce adverse drug effects and costs. However, based on sparse evidence, most guidelines recommend a longer course of antibiotics for nonsevere childhood community-acquired pneumonia (CAP).
OBJECTIVE
To determine whether a shorter course of antibiotics was noninferior to a longer course for childhood nonsevere CAP.
DATA SOURCES
MEDLINE, Embase, Web of Science, the Cochrane Library, and 3 Chinese databases from inception to March 31, 2022, as well as clinical trial registries and Google.com.
STUDY SELECTION
Randomized clinical trials comparing a shorter- vs longer-course therapy using the same oral antibiotic for children with nonsevere CAP were included.
DATA EXTRACTION AND SYNTHESIS
Random-effects models were used to pool the data, which were analyzed from April 15, 2022, to May 15, 2022. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the quality of the evidence.
MAIN OUTCOMES AND MEASURES
Treatment failure, defined by persistence of pneumonia or the new appearance of any general danger signs of CAP (eg, lethargy, unconsciousness, seizures, or inability to drink), elevated temperature (>38 °C) after completion of treatment, change of antibiotic, hospitalization, death, missing more than 3 study drug doses, loss to follow-up, or withdrawal of informed consent.
RESULTS
Nine randomized clinical trials including 11 143 participants were included in this meta-analysis. A total of 98% of the participants were aged 2 to 59 months, and 58% were male. Eight studies with 10 662 patients reported treatment failure. Treatment failure occurred in 12.8% vs 12.6% of participants randomized to a shorter vs a longer course of antibiotics. High-quality evidence showed that a shorter course of oral antibiotic was noninferior to a longer course with respect to treatment failure for children with nonsevere CAP (risk ratio, 1.01; 95% CI, 0.92-1.11; risk difference, 0.00; 95% CI, -0.01 to 0.01; I2 = 0%). A 3-day course of antibiotic treatment was noninferior to a 5-day course for the outcome of treatment failure (risk ratio, 1.01; 95% CI, 0.91-1.12; I2 = 0%), and a 5-day course was noninferior to a 10-day course (risk ratio, 0.87; 95% CI, 0.50-1.53; I2 = 0%). A shorter course of antibiotics was associated with fewer reports of gastroenteritis (risk ratio, 0.79; 95% CI, 0.66-0.95) and lower caregiver absenteeism (incident rate ratio, 0.74; 95% CI, 0.65-0.84).
CONCLUSIONS AND RELEVANCE
Results of this meta-analysis suggest that a shorter course of antibiotics was noninferior to a longer course in children aged 2 to 59 months with nonsevere CAP. Clinicians should consider prescribing a shorter course of antibiotics for the management of pediatric nonsevere CAP.
Topics: Humans; Male; Child; Female; Community-Acquired Infections; Pneumonia; Anti-Bacterial Agents; Fever; Randomized Controlled Trials as Topic
PubMed: 36374480
DOI: 10.1001/jamapediatrics.2022.4123 -
JAMA Dermatology Apr 2023Antibiotics are an important risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most severe types of drug hypersensitivity... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antibiotics are an important risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), which are the most severe types of drug hypersensitivity reaction with a mortality rate up to 50%. To our knowledge, no global systematic review has described antibiotic-associated SJS/TEN.
OBJECTIVE
To evaluate the prevalence of antibiotics associated with SJS/TEN worldwide.
DATA SOURCES
The MEDLINE and Embase databases were searched for experimental and observational studies that described SJS/TEN risks since database inception to February 22, 2022.
STUDY SELECTION
Included studies adequately described SJS/TEN origins and specified the antibiotics associated with SJS/TEN.
DATA EXTRACTION AND SYNTHESIS
Two reviewers (E.Y.L. and C.K.) independently selected the studies, extracted the data, and assessed the risk of bias. A meta-analysis using a random-effects model was performed in the studies that described patient-level associations. Subgroup analyses were performed to explore the heterogeneity. The risk of bias was assessed using the Joanna Briggs Institute checklist, and the certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
MAIN OUTCOMES AND MEASURES
Prevalence of antibiotic-associated SJS/TEN was presented as pooled proportions with 95% CIs.
RESULTS
Among the 64 studies included in the systematic review, there were 38 studies that described patient-level associations; the meta-analysis included these 38 studies with 2917 patients to determine the prevalence of single antibiotics associated with SJS/TEN. The pooled proportion of antibiotics associated with SJS/TEN was 28% (95% CI, 24%-33%), with moderate certainty of evidence. Among antibiotic-associated SJS/TEN, the sulfonamide class was associated with 32% (95% CI, 22%-44%) of cases, followed by penicillins (22%; 95% CI, 17%-28%), cephalosporins (11%; 95% CI, 6%-17%), fluoroquinolones (4%; 95% CI, 1%-7%), and macrolides (2%; 95% CI, 1%-5%). There was a statistically significant heterogeneity in the meta-analysis, which could be partially explained in the subgroup analysis by continents. The overall risk of bias was low using the Joanna Briggs Institute checklist for case series.
CONCLUSION AND RELEVANCE
In this systematic review and meta-analysis of all case series, antibiotics were associated with more than one-quarter of SJS/TEN cases described worldwide, and sulfonamide antibiotics remained the most important association. These findings highlight the importance of antibiotic stewardship, clinician education and awareness, and weighing the risk-benefit assessment of antibiotic choice and duration.
Topics: Humans; Stevens-Johnson Syndrome; Anti-Bacterial Agents; Prevalence; Sulfanilamide; Retrospective Studies
PubMed: 36790777
DOI: 10.1001/jamadermatol.2022.6378 -
Gut Microbes 2021Antibiotics in childhood have been linked with diseases including asthma, juvenile arthritis, type 1 diabetes, Crohn's disease and mental illness. The underlying... (Meta-Analysis)
Meta-Analysis
Antibiotics in childhood have been linked with diseases including asthma, juvenile arthritis, type 1 diabetes, Crohn's disease and mental illness. The underlying mechanisms are thought related to dysbiosis of the gut microbiome. We conducted a systematic review of the association between antibiotics and disruption of the pediatric gut microbiome. Searches used MEDLINE, EMBASE and Web of Science. Eligible studies: association between antibiotics and gut microbiome dysbiosis; children 0-18 years; molecular techniques of assessment; outcomes of microbiome richness, diversity or composition. Quality assessed by Newcastle-Ottawa Scale or Cochrane Risk of Bias Tool. Meta-analysis where possible. A total of 4,668 publications identified: 12 in final analysis (5 randomized controlled trials (RCTs), 5 cohort studies, 2 cross-sectional studies). Microbiome richness was measured in 3 studies, species diversity in 6, and species composition in 10. Quality of evidence was good or fair. 5 studies found a significant reduction in diversity and 3 a significant reduction in richness. Macrolide exposure was associated with reduced richness for twice as long as penicillin. Significant reductions were seen in (5 studies) and (2 studies), and significant increases in Proteobacteria such as (4 studies). A meta-analysis of RCTs of the effect of macrolide (azithromycin) exposure on the gut microbiome found a significant reduction in alpha-diversity (Shannon index: mean difference -0.86 (95% CI -1.59, -0.13). Antibiotic exposure was associated with reduced microbiome diversity and richness, and with changes in bacterial abundance. The potential for dysbiosis in the microbiome should be taken into account when prescribing antibiotics for children.: CRD42018094188.
Topics: Anti-Bacterial Agents; Bacteria; Child; Child, Preschool; Dysbiosis; Gastrointestinal Microbiome; Humans; Infant; Infant, Newborn
PubMed: 33651651
DOI: 10.1080/19490976.2020.1870402