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Antibiotics (Basel, Switzerland) Aug 2022(1) Background: Infections caused by multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria represent a challenge in the neonatal population due to... (Review)
Review
(1) Background: Infections caused by multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria represent a challenge in the neonatal population due to disease severity and limited therapeutic possibilities compared to adults. The spread of antimicrobial resistance and drug availability differ significantly worldwide. The incidence of MDR bacteria has constantly risen, causing an increase in morbidity, mortality, and healthcare costs in both high-income (HIC) and low- and middle-income countries (LMIC). Therefore, more evidence is needed to define the possible use of newer molecules and to optimize combination regimens for the oldest antimicrobials in neonates. This systematic review aims to identify and critically appraise the current antimicrobial treatment options and the relative outcomes for MDR and XDR Gram-negative bacterial infections in the neonatal population. (2) Methods: A literature search for the treatment of MDR Gram-negative bacterial infections in neonates (term and preterm) was conducted in Embase, MEDLINE, and Cochrane Library. Studies reporting data on single-patient-level outcomes related to a specific antibiotic treatment for MDR Gram-negative bacterial infection in children were included. Studies reporting data from adults and children were included if single-neonate-level information could be identified. We focused our research on four MDROs: producing extended-spectrum beta-lactamase (ESBL) or carbapenemase (CRE), and . PROSPERO registration: CRD42022346739 (3) Results: The search identified 11,740 studies (since January 2000), of which 22 fulfilled both the inclusion and exclusion criteria and were included in the analysis. Twenty of these studies were conducted in LMIC. Colistin is the main studied and used molecule to treat Gram-negative MDR bacteria for neonate patients in the last two decades, especially in LMIC, with variable evidence of efficacy. Carbapenems are still the leading antibiotics for ESBL , while newer molecules (i.e., beta-lactam agents/beta-lactamase inhibitor combination) are promising across all analyzed categories, but data are few and limited to HICs. (4) Conclusions: Data about the treatment of Gram-negative MDR bacteria in the neonatal population are heterogeneous and limited mainly to older antimicrobials. Newer drugs are promising but not affordable yet for many LMICs. Therefore, strategies cannot be generalized but will differ according to the country's epidemiology and resources. More extensive studies are needed to include new antimicrobials and optimize the combination strategies for the older ones.
PubMed: 36009956
DOI: 10.3390/antibiotics11081088 -
BMC Infectious Diseases Mar 2020Treatment of resistant Pseudomonas aeruginosa infection continues to be a challenge in Latin American countries (LATAM). We synthesize the literature on the use of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Treatment of resistant Pseudomonas aeruginosa infection continues to be a challenge in Latin American countries (LATAM). We synthesize the literature on the use of appropriate initial antibiotic therapy (AIAT) and inappropriate initial antibiotic therapy (IIAT) in P. aeruginosa infections, and the literature on risk factors for acquisition of resistant P. aeruginosa among hospitalized adult patients in LATAM.
METHODS
MEDLINE, EMBASE, Cochrane, and LILAC were searched between 2000 and August 2019. Abstracts and full-text articles were screened in duplicate. Random effects meta-analysis was conducted when studies were sufficiently similar.
RESULTS
The screening of 165 citations identified through literature search yielded 98 full-text articles that were retrieved and assessed for eligibility, and 19 articles conducted in Brazil (14 articles), Colombia (4 articles), and Cuba (1 article) met the inclusion criteria. Of 19 eligible articles, six articles (840 subjects) examined AIAT compared to IIAT in P. aeruginosa infections; 17 articles (3203 total subjects) examined risk factors for acquisition of resistant P. aeruginosa; and four articles evaluated both. Four of 19 articles were rated low risk of bias and the remaining were deemed unclear or high risk of bias. In meta-analysis, AIAT was associated with lower mortality for P. aeruginosa infections (unadjusted summary OR 0.48, 95% CI 0.28-0.81; I = 59%), compared to IIAT and the association with mortality persisted in subgroup meta-analysis by low risk of bias (3 articles; unadjusted summary OR 0.46, 95% CI 0.28-0.81; I = 0%). No meta-analysis was performed for studies evaluating risk factors for acquisition of resistant P. aeruginosa as they were not sufficiently similar. Significant risk factors for acquisition of resistant P. aeruginosa included: prior use of antibiotics (11 articles), stay in the intensive care unit (ICU) (3 articles), and comorbidity score (3 articles). Outcomes were graded to be of low strength of evidence owing to unclear or high risk of bias and imprecise estimates.
CONCLUSION
Our study highlights the association of AIAT with lower mortality and prior use of antibiotics significantly predicts acquiring resistant P. aeruginosa infections. This review reinforces the need for rigorous and structured antimicrobial stewardship programs in the LATAM region.
Topics: Adult; Anti-Bacterial Agents; Comorbidity; Drug Resistance, Bacterial; Hospitalization; Humans; Intensive Care Units; Latin America; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 32220233
DOI: 10.1186/s12879-020-04973-0 -
BMJ Open Respiratory Research Sep 2023Epidemiological information is essential in providing appropriate empiric antimicrobial therapy for pneumonia. This study aimed to clarify the epidemiology of...
OBJECTIVE
Epidemiological information is essential in providing appropriate empiric antimicrobial therapy for pneumonia. This study aimed to clarify the epidemiology of community-acquired pneumonia (CAP) by conducting a systematic review of published studies in Japan.
DESIGN
Systematic review.
DATA SOURCE
PubMed and Ichushi web database (January 1970 to October 2022).
ELIGIBILITY CRITERIA
Clinical studies describing pathogenic micro-organisms in CAP written in English or Japanese, excluding studies on pneumonia other than adult CAP, investigations limited to specific pathogens and case reports.
DATA EXTRACTION AND SYNTHESIS
Patient setting (inpatient vs outpatient), number of patients, concordance with the CAP guidelines, diagnostic criteria and methods for diagnosing pneumonia pathogens as well as the numbers of each isolate. A meta-analysis of various situations was performed to measure the frequency of each aetiological agent.
RESULTS
Fifty-six studies were included and 17 095 cases of CAP were identified. Pathogens were undetectable in 44.1% (95% CI 39.7% to 48.5%). was the most common cause of CAP requiring hospitalisation or outpatient care (20.0% (95% CI 17.2% to 22.8%)), followed by (10.8% (95% CI 7.3% to 14.3%)) and (7.5% (95% CI 4.6% to 10.4%)). However, when limited to CAP requiring hospitalisation, was the third most common at 4.9% (95% CI 3.9% to 5.8%). was more frequent in hospitalised cases, while atypical pathogens were less common. Methicillin-resistant accounted for 40.7% (95% CI 29.0% to 52.4%) of cases. In studies that used PCR testing for pan-respiratory viral pathogens, human enterovirus/human rhinovirus (9.4% (95% CI 0% to 20.5%)) and several other respiratory pathogenic viruses were detected. The epidemiology varied depending on the methodology and situation.
CONCLUSION
The epidemiology of CAP varies depending on the situation, such as in the hospital versus outpatient setting. Viruses are more frequently detected by exhaustive genetic searches, resulting in a significant variation in epidemiology.
PubMed: 37751988
DOI: 10.1136/bmjresp-2023-001800 -
The Cochrane Database of Systematic... Aug 2015Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review.
OBJECTIVES
To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013).
SELECTION CRITERIA
Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The authors independently selected trials, assessed them and extracted data.
MAIN RESULTS
Six trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P < 0.0001).
AUTHORS' CONCLUSIONS
Vaccines against Pseudomonas aeruginosa cannot be recommended.
Topics: Cystic Fibrosis; Humans; Pseudomonas Infections; Pseudomonas Vaccines; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic
PubMed: 26298311
DOI: 10.1002/14651858.CD001399.pub4 -
Antibiotics (Basel, Switzerland) Dec 2021(PA) is a leading cause of healthcare-associated infections. A variety of antibiotic classes are used in the treatment of PA infections, including beta-lactams (BLs)...
INTRODUCTION
(PA) is a leading cause of healthcare-associated infections. A variety of antibiotic classes are used in the treatment of PA infections, including beta-lactams (BLs) and fluoroquinolones (FQs), given either together in combination therapy or alone in monotherapy. A systematic review and meta-analysis were performed to evaluate the therapeutic efficacy of BL agents versus FQ agents as active, definitive monotherapy in PA infections in adults.
METHODS
Comprehensive literature searches of the Medline and Scopus electronic databases, alongside hand searches of the Cochrane Database of Systematic Reviews, PubMed, and Google Scholar, were performed without a time restriction to identify studies published in English comparing BL and FQ agents given as monotherapy for PA infection in hospitalized adults for which mortality, bacteriological eradication, or clinical response was evaluated. One reviewer screened search results based on pre-defined selection criteria. Two reviewers independently assessed included studies for methodological quality using NIH assessment tools. Two fixed-effects meta-analyses were performed.
RESULTS
A total of 368 articles were screened, and six studies involving 338 total patients were included in the meta-analysis. Upon evaluation of methodological quality, two studies were rated good, three fair, and one poor. A meta-analysis of three studies demonstrates FQ monotherapy is associated with significantly improved survival compared to BL monotherapy for patients with PA bacteremia (OR, 3.65; 95% CI, 1.27-10.44; = 0.02). A meta-analysis of three studies demonstrates FQ monotherapy is associated with equivalent bacteriological eradication compared to BL monotherapy for PA pneumonia or skin and soft tissue infection (RD, 0.07; 95% CI, -0.09 to 0.24; = 0.39).
CONCLUSION
The meta-analyses demonstrate FQ monotherapy significantly improves survival in PA bacteremia and is associated with similar rates of bacteriological eradication in pneumonia and skin and soft tissue infection caused by PA compared to BL monotherapy. However, more research is needed to make meaningful clinical recommendations.
PubMed: 34943695
DOI: 10.3390/antibiotics10121483 -
Antimicrobial Resistance and Infection... Sep 2023Antimicrobial resistance (AMR) is on the rise worldwide. Tools such as dynamic regression (DR) models can correlate antimicrobial consumption (AMC) with AMR and predict... (Review)
Review
Usefulness of dynamic regression time series models for studying the relationship between antimicrobial consumption and bacterial antimicrobial resistance in hospitals: a systematic review.
BACKGROUNG
Antimicrobial resistance (AMR) is on the rise worldwide. Tools such as dynamic regression (DR) models can correlate antimicrobial consumption (AMC) with AMR and predict future trends to help implement antimicrobial stewardship programs (ASPs).
MAIN BODY
We carried out a systematic review of the literature up to 2023/05/31, searching in PubMed, ScienceDirect and Web of Science. We screened 641 articles and finally included 28 studies using a DR model to study the correlation between AMC and AMR at a hospital scale, published in English or French. Country, bacterial species, type of sampling, antimicrobials, study duration and correlations between AMC and AMR were collected. The use of β-lactams was correlated with cephalosporin resistance, especially in Pseudomonas aeruginosa and Enterobacterales. Carbapenem consumption was correlated with carbapenem resistance, particularly in Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Fluoroquinolone use was correlated with fluoroquinolone resistance in Gram-negative bacilli and methicillin resistance in Staphylococcus aureus. Multivariate DR models highlited that AMC explained from 19 to 96% of AMR variation, with a lag time between AMC and AMR variation of 2 to 4 months. Few studies have investigated the predictive capacity of DR models, which appear to be limited.
CONCLUSION
Despite their statistical robustness, DR models are not widely used. They confirmed the important role of fluoroquinolones, cephalosporins and carbapenems in the emergence of AMR. However, further studies are needed to assess their predictive capacity and usefulness for ASPs.
Topics: Humans; Anti-Bacterial Agents; Time Factors; Drug Resistance, Bacterial; Anti-Infective Agents; Carbapenems; Fluoroquinolones; Hospitals
PubMed: 37697357
DOI: 10.1186/s13756-023-01302-3 -
JAC-antimicrobial Resistance Feb 2023Antimicrobial resistance (AMR) causes substantial health and economic burden to individuals, healthcare systems and societies globally. Understanding the temporal... (Review)
Review
BACKGROUND
Antimicrobial resistance (AMR) causes substantial health and economic burden to individuals, healthcare systems and societies globally. Understanding the temporal relationship between antibiotic consumption and antibiotic resistance in hospitalized patients can better inform antibiotic stewardship activities and the time frame for their evaluation.
OBJECTIVES
This systematic review examined the temporal relationship between antibiotic use and development of antibiotic resistance for 42 pre-defined antibiotic and pathogen combinations in hospitalized adults in Europe.
METHODS
Searches in MEDLINE, Embase, Cochrane Library and NIHR Centre for Reviews and Dissemination were undertaken from 2000 to August 2021. Pathogens of interest were , , , , , CoNS, and complex.
RESULTS
Twenty-eight ecological studies and one individual-level study were included. Ecological studies were predominantly retrospective in design (19 studies) and of reasonable (20 studies) to high (8 studies) methodological quality. Of the eight pathogens of interest, no relevant data were identified for . and CoNS. Across all pathogens, the time-lag data from the 28 ecological studies showed a similar pattern, with the majority of studies reporting lags ranging from 0 to 6 months.
CONCLUSIONS
Development of antibiotic resistance for the investigated antibiotic/pathogen combinations tends to occur over 0 to 6 months following exposure within European hospitals. This information could inform planning of antibiotic stewardship activities in hospital settings.
PubMed: 36694849
DOI: 10.1093/jacamr/dlad001 -
The Cochrane Database of Systematic... Dec 2015Recurrent endobronchial infection in cystic fibrosis requires treatment with intravenous antibiotics for several weeks usually in hospital, affecting health costs and... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Recurrent endobronchial infection in cystic fibrosis requires treatment with intravenous antibiotics for several weeks usually in hospital, affecting health costs and quality of life for patients and their families. This is an update of a previously published review.
OBJECTIVES
To determine whether home intravenous antibiotic therapy in cystic fibrosis is as effective as inpatient intravenous antibiotic therapy and if it is preferred by individuals or families or both.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search of the Group's Trials Register: 23 November 2015.
SELECTION CRITERIA
Randomized and quasi-randomized controlled studies of intravenous antibiotic treatment for adults and children with cystic fibrosis at home compared to in hospital.
DATA COLLECTION AND ANALYSIS
The authors independently selected studies for inclusion in the review, assessed methodological quality of each study and extracted data using a standardised form.
MAIN RESULTS
Eighteen studies were identified by the searches. Only one study could be included which reported results from 17 participants aged 10 to 41 years with an infective exacerbation of Pseudomonas aeruginosa. All their 31 admissions (18 hospital and 13 at home after two to four days of hospital treatment) were analysed as independent events. Outcomes were measured at 0, 10 and 21 days after initiation of treatment. Home participants underwent fewer investigations than hospital participants (P < 0.002) and general activity was higher in the home group. No significant differences were found for clinical outcomes, adverse events, complications or change of intravenous lines,or time to next admission. Home participants received less low-dose home maintenance antibiotic.Quality of life measures showed no significant differences for dyspnoea and emotional state, but fatigue and mastery were worse for home participants, possibly due to a higher general activity and need of support. Personal, family, sleeping and eating disruptions were less important for home than hospital admissions.Home therapy was cheaper for families and the hospital. Indirect costs were not determined.
AUTHORS' CONCLUSIONS
Current evidence is restricted to a single randomized clinical trial. It suggests that, in the short term, home therapy does not harm individuals, entails fewer investigations, reduces social disruptions and can be cost-effective. There were both advantages and disadvantages in terms of quality of life. The decision to attempt home treatment should be based on the individual situation and appropriate local resources. More research is urgently required.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Cystic Fibrosis; Home Care Services; Hospitalization; Humans; Injections, Intravenous; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Self Care; Staphylococcal Infections; Staphylococcus aureus
PubMed: 26671062
DOI: 10.1002/14651858.CD001917.pub4 -
International Journal of Microbiology 2020Studies have reported that the existence of CP bacteria in Africa, but, in general, comprehensive data about the molecular epidemiology of CP organisms are limited.... (Review)
Review
BACKGROUND
Studies have reported that the existence of CP bacteria in Africa, but, in general, comprehensive data about the molecular epidemiology of CP organisms are limited. Therefore, this systematic review and meta-analysis expound the pooled prevalence of CP and CP clinical isolates in Africa. It also identified the diversity of carbapenemases or their encoding genes among the isolates in Africa. Lastly, the review observed the trends of these CP isolates in Africa.
METHODS
A comprehensive search was performed between July 2019 and October 2019 in the following databases: PubMed, Google Scholar, and African Journal online. The included articles were published only in English. The screening was done by two authors independently. The data extracted on Excel spreadsheet were transferred to STATA 11 software for analysis.
RESULTS
From a total of 1,454 articles searched, 42 articles were eligible. Most of the studies were conducted in the North Africa region. But there was no report from Central Africa. The pooled prevalence of CP and CP among the clinical specimens in Africa was 21.36% and 56.97%, respectively. OXA-23 and VIM were the most prevailing carbapenemase among and respectively. The cumulative meta-analysis revealed a relative increment of the prevalence of CP over time in Africa but it showed a higher prevalence of CP isolates across years.
CONCLUSION
The review revealed a high pooled prevalence of CP clinical isolates in Africa which needs urgent action. Moreover, the emergence of concomitant carbapenemases, especially OXA-23 + NDM among CP , was also an alarming problem.
PubMed: 33204275
DOI: 10.1155/2020/9461901 -
The Cochrane Database of Systematic... Sep 2018The diagnosis of bronchiectasis is defined by abnormal dilation of the airways related to a pathological mechanism of progressive airway destruction that is due to a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The diagnosis of bronchiectasis is defined by abnormal dilation of the airways related to a pathological mechanism of progressive airway destruction that is due to a 'vicious cycle' of recurrent bacterial infection, inflammatory mediator release, airway damage, and subsequent further infection. Antibiotics are the main treatment option for reducing bacterial burden in people with exacerbations of bronchiectasis and for longer-term eradication, but their use is tempered against potential adverse effects and concerns regarding antibiotic resistance. The comparative effectiveness, cost-effectiveness, and safety of different antibiotics have been highlighted as important issues, but currently little evidence is available to help resolve uncertainty on these questions.
OBJECTIVES
To evaluate the comparative effects of different antibiotics in the treatment of adults and children with bronchiectasis.
SEARCH METHODS
We identified randomised controlled trials (RCTs) through searches of the Cochrane Airways Group Register of trials and online trials registries, run 30 April 2018. We augmented these with searches of the reference lists of published studies.
SELECTION CRITERIA
We included RCTs reported as full-text articles, those published as abstracts only, and unpublished data. We included adults and children (younger than 18 years) with a diagnosis of bronchiectasis by bronchography or high-resolution computed tomography who reported daily signs and symptoms, such as cough, sputum production, or haemoptysis, and those with recurrent episodes of chest infection; we included studies that compared one antibiotic versus another when they were administered by the same delivery method.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial selection, data extraction, and risk of bias. We assessed overall quality of the evidence using GRADE criteria. We made efforts to collect missing data from trial authors. We have presented results with their 95% confidence intervals (CIs) as mean differences (MDs) or odds ratios (ORs).
MAIN RESULTS
Four randomised trials were eligible for inclusion in this systematic review - two studies with 83 adults comparing fluoroquinolones with β-lactams and two studies with 55 adults comparing aminoglycosides with polymyxins.None of the included studies reported information on exacerbations - one of our primary outcomes. Included studies reported no serious adverse events - another of our primary outcomes - and no deaths. We graded this evidence as low or very low quality. Included studies did not report quality of life. Comparison between fluoroquinolones and β-lactams (amoxicillin) showed fewer treatment failures in the fluoroquinolone group than in the amoxicillin group (OR 0.07, 95% CI 0.01 to 0.32; low-quality evidence) after 7 to 10 days of therapy. Researchers reported that Pseudomonas aeruginosa infection was eradicated in more participants treated with fluoroquinolones (Peto OR 20.09, 95% CI 2.83 to 142.59; low-quality evidence) but provided no evidence of differences in the numbers of participants showing improvement in sputum purulence (OR 2.35, 95% CI 0.96 to 5.72; very low-quality evidence). Study authors presented no evidence of benefit in relation to forced expiratory volume in one second (FEV₁). The two studies that compared polymyxins versus aminoglycosides described no clear differences between groups in the proportion of participants with P aeruginosa eradication (OR 1.40. 95% CI 0.36 to 5.35; very low-quality evidence) or improvement in sputum purulence (OR 0.16, 95% CI 0.01 to 3.85; very low-quality evidence). The evidence for changes in FEV₁ was inconclusive. Two of three trials reported adverse events but did not report the proportion of participants experiencing one or more adverse events, so we were unable to interpret the information.
AUTHORS' CONCLUSIONS
Limited low-quality evidence favours short-term oral fluoroquinolones over beta-lactam antibiotics for patients hospitalised with exacerbations. Very low-quality evidence suggests no benefit from inhaled aminoglycosides verus polymyxins. RCTs have presented no evidence comparing other modes of delivery for each of these comparisons, and no RCTs have included children. Overall, current evidence from a limited number of head-to-head trials in adults or children with bronchiectasis is insufficient to guide the selection of antibiotics for short-term or long-term therapy. More research on this topic is needed.
Topics: Adult; Aminoglycosides; Amoxicillin; Anti-Bacterial Agents; Bronchiectasis; Child; Fluoroquinolones; Forced Expiratory Volume; Humans; Polymyxins; Pseudomonas Infections; Randomized Controlled Trials as Topic; beta-Lactams
PubMed: 30184243
DOI: 10.1002/14651858.CD012590.pub2