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The Journal of Antimicrobial... Feb 2020The literature on the epidemiology, mortality and treatment of pandrug-resistant (PDR) Gram-negative bacteria (GNB) is scarce, scattered and controversial.
BACKGROUND
The literature on the epidemiology, mortality and treatment of pandrug-resistant (PDR) Gram-negative bacteria (GNB) is scarce, scattered and controversial.
OBJECTIVES
To consolidate the relevant literature and identify treatment options for PDR GNB infections.
METHODS
A systematic search in MEDLINE, Scopus and clinical trial registries was conducted. Studies reporting PDR clinical isolates were eligible for review if susceptibility testing for all major antimicrobials had been performed. Characteristics and findings of retrieved studies were qualitatively synthesized.
RESULTS
Of 81 studies reviewed, 47 (58%) were published in the last 5 years. The reports reflected a worldwide dissemination of PDR GNB in 25 countries in 5 continents. Of 526 PDR isolates reported, Pseudomonas aeruginosa (n=175), Acinetobacter baumannii (n=172) and Klebsiella pneumoniae (n=125) were most common. PDR GNB were typically isolated in ICUs, but several studies demonstrated wider outbreak potential, including dissemination to long-term care facilities and international spread. All-cause mortality was high (range 20%-71%), but appeared to be substantially reduced in studies reporting treatment regimens active in vitro. No controlled trial has been performed to date, but several case reports and series noted successful use of various regimens, predominantly synergistic combinations, and in selected patients increased exposure regimens and newer antibiotics.
CONCLUSIONS
PDR GNB are increasingly being reported worldwide and are associated with high mortality. Several treatment regimens have been successfully used, of which synergistic combinations appear to be most promising and often the only available option. More pharmacokinetic/pharmacodynamic and outcome studies are needed to guide the use of synergistic combinations.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacterial Infections; Humans; Klebsiella pneumoniae; Prognosis; Pseudomonas aeruginosa
PubMed: 31586417
DOI: 10.1093/jac/dkz401 -
Infection, Genetics and Evolution :... Nov 2019Pseudomonas aeruginosa (PA) is an opportunistic pathogen that produces widespread and often overwhelming infections. Among different virulence factors, toxins are... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Pseudomonas aeruginosa (PA) is an opportunistic pathogen that produces widespread and often overwhelming infections. Among different virulence factors, toxins are important bacterial agent which increases PA pathogenesis especially in immunocompromised patients. The aim of this meta-analysis was to determine the prevalence of exotoxin production in PA isolates in the world. Also according to the importance of drug resistance in isolates with more pathogenicity this estimation was conducted in resistant isolates.
METHODS
A systematic search was conducted in international database like PubMed, Scopus, Web of Science and Embase up to December 2018. Joanna Briggs Institute Checklist was used to evaluate the quality assessment of studies. Random effect model was applied to pool the prevalence data. Stata 13 software was used to analyze the data.
RESULTS
Total of 58 eligible studies that fulfilled the inclusion criteria of the study were selected for qualitative synthesis. Among exotoxins; the highest prevalence was related to exoT (0.83 (CI95%: 0.64-0.96)). Lowest prevalence rate was seen in exoU with estimated prevalence 0.32 (CI95%: 0.24-0.41). In Carbapenem resistance isolates exoA and exoT had the highest prevalence (1.00 (CI95%: 0.98-1.00)).
CONCLUSION
This first meta-analysis on PA isolates with toxin potency indicated high prevalence of exotoxin production in clinical isolates of PA which is an alarming point as a clinical aspect. It was found that the ExoT has the most prevalence rate among toxins. The results of simultaneous evaluation of exotoxins and antimicrobial resistance can develop treatment policies against PA infections in hospitals and hospitalized patients.
Topics: Bacterial Toxins; Cross Infection; Exotoxins; Humans; Prevalence; Pseudomonas Infections; Pseudomonas aeruginosa; Virulence Factors
PubMed: 31518698
DOI: 10.1016/j.meegid.2019.104037 -
The Cochrane Database of Systematic... Sep 2019People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside...
BACKGROUND
People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often. This is an update of a previously published review.
OBJECTIVES
To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis.
SEARCH METHODS
We searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.Date of the most recent search: 31 January 2019.We also searched online trial registries. Date of latest search: 25 February 2019.
SELECTION CRITERIA
All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The two authors independently selected the studies to be included in the review and assessed the risk of bias of each study; authors also assessed the quality of the evidence using the GRADE criteria. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies.
MAIN RESULTS
We identified 15 studies for possible inclusion in the review. Five studies reporting results from a total of 354 participants (aged 5 to 50 years) were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One cross-over trial had 26 participants who received the first-arm treatment but only 15 received the second arm. One study had a low risk of bias for all criteria assessed; the remaining included studies had a high risk of bias from blinding, but for other criteria were judged to have either an unclear or a low risk of bias.There was little or no difference between treatment groups in: forced expiratory volume in one second, mean difference (MD) 0.33 (95% confidence interval (CI) -2.81 to 3.48, moderate-quality evidence); forced vital capacity, MD 0.29 (95% CI -6.58 to 7.16, low-quality evidence); % weight for height, MD -0.82 (95% CI -3.77 to 2.13, low-quality evidence); body mass index, MD 0.00 (95% CI -0.42 to 0.42, low-quality evidence); or in the incidence of ototoxicity, relative risk 0.56 (95% CI 0.04 to 7.96, moderate-quality evidence). Once-daily treatment in children probably improved the percentage change in creatinine, MD -8.20 (95% CI -15.32 to -1.08, moderate-quality evidence), but showed no difference in adults, MD 3.25 (95% CI -1.82 to 8.33, moderate-quality evidence). The included trials did not report antibiotic resistance patterns or quality of life.
AUTHORS' CONCLUSIONS
Once- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis. There is evidence of less nephrotoxicity in children.
Topics: Aminoglycosides; Anti-Bacterial Agents; Cystic Fibrosis; Drug Administration Schedule; Drug Therapy, Combination; Forced Expiratory Volume; Humans; Injections, Intravenous; Lung Diseases; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Vital Capacity
PubMed: 31483853
DOI: 10.1002/14651858.CD002009.pub7 -
Antimicrobial Resistance and Infection... 2019Antibiotic resistance (ABR) is one of the biggest threats to global health. Infections by ESKAPE (, , , , , and ) organisms are the leading cause of healthcare-acquired...
BACKGROUND
Antibiotic resistance (ABR) is one of the biggest threats to global health. Infections by ESKAPE (, , , , , and ) organisms are the leading cause of healthcare-acquired infections worldwide. ABR in ESKAPE organisms is usually associated with significant higher morbidity, mortality, as well as economic burden. Directing attention towards the ESKAPE organisms can help us to better combat the wide challenge of ABR, especially multi-drug resistance (MDR).
OBJECTIVE
This study aims to systematically review and evaluate the evidence of the economic consequences of ABR or MDR ESKAPE organisms compared with susceptible cases or control patients without infection/colonization in order to determine the impact of ABR on economic burden.
METHODS
Both English-language databases and Chinese-language databases up to 16 January, 2019 were searched to identify relevant studies assessing the economic burden of ABR. Studies reported hospital costs (charges) or antibiotic cost during the entire hospitalization and during the period before/after culture among patients with ABR or MDR ESKAPE organisms were included. The costs were converted into 2015 United States Dollars. Disagreements were resolved by a third reviewer.
RESULTS
Of 13,693 studies identified, 83 eligible studies were included in our review. The most studied organism was , followed by , , , or/and , , and . There were 71 studies on total hospital cost or charge, 12 on antibiotic cost, 11 on hospital cost or charge after culture, 4 on ICU cost, 2 on hospital cost or charge before culture, and 2 on total direct and indirect cost. In general, ABR or MDR ESKAPE organisms are significantly associated with higher economic burden than those with susceptible organisms or those without infection or colonization. Nonetheless, there were no differences in a few studies between the two groups on total hospital cost or charge (16 studies), antibiotic cost (one study), hospital cost before culture (one study), hospital cost after culture (one study). Even, one reported that costs associated with MSSA infection were higher than the costs for similar MRSA cases.
CONCLUSIONS
ABR in ESKAPE organisms is not always, but usually, associated with significantly higher economic burden. The results without significant differences may lack statistical power to detect a significant association. In addition, study design which controls for severity of illness and same empirical antibiotic therapy in the two groups would be expected to bias the study towards a similar, even negative result. The review also highlights key areas where further research is needed.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Enterococcus; Escherichia coli; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Hospital Costs; Humans; Klebsiella pneumoniae; Pseudomonas aeruginosa; Staphylococcus aureus
PubMed: 31417673
DOI: 10.1186/s13756-019-0590-7 -
Journal of Burn Care & Research :... Oct 2019The role of integrons has been highlighted in antibiotic resistance among Pseudomonas aeruginosa isolates. Therefore, we here reviewed the prevalence of class 1... (Meta-Analysis)
Meta-Analysis
The role of integrons has been highlighted in antibiotic resistance among Pseudomonas aeruginosa isolates. Therefore, we here reviewed the prevalence of class 1 integrons and their correlations with antibiotic resistance of P. aeruginosa isolated from Iranian burn patients. This review was conducted according to the guidelines of Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). Cross-sectional and cohort studies published from January 1, 2000 until December 31, 2018 were enrolled. Meta-analysis was performed by Comprehensive Meta-Analysis (CMA) software using the random effects model, Cochran's Q, and I2 tests. Publication bias was estimated by Funnel plot and Egger's linear regression test. Nine out of 819 studies met the eligibility criteria. The overall combined prevalence of class 1 integrons in P. aeruginosa isolates was 69% (95% confidence interval [CI]: 50.5-83%). The highest combined resistance was reported against Cloxacillin (87.7%), followed by Carbenicillin (79.1%) and Ceftriaxone (77.3%). The combined prevalence of multidrug-resistant (MDR) isolates was 79.3% (95% CI: 31.1-97%). Also, a significant correlation was noted between the presence of class 1 integrons and antibiotic resistance in 55.5% of the included studies (P < .05). The results showed high prevalence of class 1 integrons, antibiotic resistance, and MDR strains in P. aeruginosa isolated from Iranian burn patients. Also, most of the included studies showed a significant correlation between the presence of class 1 integrons and antibiotic resistance.
Topics: Anti-Bacterial Agents; Burns; Drug Resistance, Multiple, Bacterial; Humans; Integrons; Prevalence; Pseudomonas Infections; Pseudomonas aeruginosa; Wound Infection
PubMed: 31326983
DOI: 10.1093/jbcr/irz135 -
The European Respiratory Journal Sep 2019Pleural infection is a major cause of morbidity and mortality among adults. Identification of the offending organism is key to appropriate antimicrobial therapy. It is...
BACKGROUND AND OBJECTIVES
Pleural infection is a major cause of morbidity and mortality among adults. Identification of the offending organism is key to appropriate antimicrobial therapy. It is not known whether the microbiological pattern of pleural infection is variable temporally or geographically. This systematic review aimed to investigate available literature to understand the worldwide pattern of microbiology and the factors that might affect such pattern.
DATA SOURCES AND ELIGIBILITY CRITERIA
Ovid MEDLINE and Embase were searched between 2000 and 2018 for publications that reported on the microbiology of pleural infection in adults. Both observational and interventional studies were included. Studies were excluded if the main focus of the report was paediatric population, tuberculous empyema or post-operative empyema.
STUDY APPRAISAL AND SYNTHESIS METHODS
Studies of ≥20 patients with clear reporting of microbial isolates were included. The numbers of isolates of each specific organism/group were collated from the included studies. Besides the overall presentation of data, subgroup analyses by geographical distribution, infection setting (community hospital) and time of the report were performed.
RESULTS
From 20 980 reports returned by the initial search, 75 articles reporting on 10 241 patients were included in the data synthesis. The most common organism reported worldwide was . Geographically, pneumococci and viridans streptococci were the most commonly reported isolates from tropical and temperate regions, respectively. The microbiological pattern was considerably different between community- and hospital-acquired infections, where more Gram-negative and drug-resistant isolates were reported in the hospital-acquired infections. The main limitations of this systematic review were the heterogeneity in the method of reporting of certain bacteria and the predominance of reports from Europe and South East Asia.
CONCLUSIONS
In pleural infection, the geographical location and the setting of infection have considerable bearing on the expected causative organisms. This should be reflected in the choice of empirical antimicrobial treatment.
Topics: Acinetobacter; Adult; Aged; Anti-Bacterial Agents; Enterobacteriaceae; Global Health; Humans; Klebsiella; Middle Aged; Pleural Diseases; Pseudomonas; Risk; Staphylococcal Infections; Staphylococcus aureus; Streptococcus pneumoniae; Viridans Streptococci
PubMed: 31248959
DOI: 10.1183/13993003.00542-2019 -
Journal of Global Antimicrobial... Dec 2019Recently, multidrug-resistant (MDR) Gram-negative bacteria (GNB) have become a serious concern causing infections in hospitalised burn patients. This meta-analysis was... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Recently, multidrug-resistant (MDR) Gram-negative bacteria (GNB) have become a serious concern causing infections in hospitalised burn patients. This meta-analysis was conducted to detect the prevalence of infections caused by MDR-GNB in hospitalised burn patients in Iran.
METHODS
An electronic search was performed using PubMed, Scopus, Web of Science, EMBASE and Iranian databases. Statistical analysis was performed using STATA13. According to the results of the heterogeneity test, a fixed- or random-effects model was used. Publication bias was detected based on Egger's test. Of 1292 articles identified in the initial search, 107 studies were included in this review.
RESULTS
According to the results, the lowest resistance rate was observed in Acinetobacter baumannii and Pseudomonas aeruginosa to colistin, estimated at 21% [95% confidence interval (CI) 2-49%; I=97.30%] and 27% (95% CI 0-82%; I=99.27%), respectively. Moreover, the highest rate was to cefepime, estimated 98% (95% CI 93-100%; I=88.28%) and 87% (95% CI 81-92%; I=96.27%).
CONCLUSION
The prevalence of MDR-GNB in Iranian burn patients is very high. Thus, a comprehensive infectious control programme, a reduction in the use of antibiotic prophylaxis, and thorough information regarding antimicrobial resistance patterns is required.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Burns; Colistin; Databases, Factual; Drug Resistance, Multiple, Bacterial; Escherichia coli; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitalization; Humans; Infection Control; Iran; Microbial Sensitivity Tests; Prevalence; Pseudomonas aeruginosa
PubMed: 31063845
DOI: 10.1016/j.jgar.2019.04.017 -
Clinical Microbiology and Infection :... Aug 2019Pseudomonas aeruginosa is mostly a nosocomial pathogen affecting predisposed patients. However, community-onset bloodstream infections (CO-BSI) caused by this organism... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pseudomonas aeruginosa is mostly a nosocomial pathogen affecting predisposed patients. However, community-onset bloodstream infections (CO-BSI) caused by this organism are not exceptional.
OBJECTIVES
To assess the predisposing factors for CO-BSI due to P. aeruginosa (CO-BSI-PA) and the impact in mortality of inappropriate empirical antimicrobial therapy.
DATA SOURCE
A systematic literature search was performed in the Medline, Embase, Cochrane Library, Scopus and Web of Science databases. Study eligibility criteria and participants: Articles published between 1 January 2002 and 31 January 2018 reporting at least of 20 adult patients with CO-BSI due to P. aeruginosa were considered.
INTERVENTION
Empiric antimicrobial therapy for CO-BSI-PA.
METHODS
A systematic review and a meta-analysis were conducted for risk factors and to evaluate if inappropriate empiric antimicrobial therapy increased mortality in CO-BSI-PA using a Mantel-Haenszel effects model.
RESULTS
Twelve studies assessing data of 1120 patients were included in the systematic review. Solid tumour (33.1%), haematologic malignancy (26.4%), neutropenia (31.7%) and previous antibiotic use (44.8%) were the most prevalent predisposing factors. Septic shock was present in 42.3% of cases, and 30-day crude mortality was 33.8%. Mortality in meta-analysis (four studies) was associated with septic shock at presentation (odds ratio, 22.31; 95% confidence interval, 3.52-141.35; p 0.001) and with inappropriate empiric antibiotic therapy (odds ratio, 1.83; 95% confidence interval, 1.12-2.98l p 0.02).
CONCLUSIONS
CO-BSI-PA mostly occurred in patients with predisposing factors and had a 30-day mortality comparable to hospital-acquired cases. Inappropriate empirical antibiotic therapy was associated with increased mortality. Appropriate identification of patients at risk for CO-BSI-PA is needed for empirical treatment decisions.
Topics: Anti-Bacterial Agents; Bacteremia; Cross Infection; Humans; Inappropriate Prescribing; Pseudomonas Infections; Pseudomonas aeruginosa; Risk Factors; Shock, Septic
PubMed: 30995530
DOI: 10.1016/j.cmi.2019.04.005 -
Clinical Microbiology and Infection :... Oct 2019There is an ongoing controversy on the role of the healthcare-associated pneumonia (HCAP) label in the treatment of patients with pneumonia.
BACKGROUND
There is an ongoing controversy on the role of the healthcare-associated pneumonia (HCAP) label in the treatment of patients with pneumonia.
OBJECTIVE
To provide an update of the literature on patients meeting criteria for HCAP between 2014 and 2018.
SOURCES
The review is based on a systematic literature search using PubMed-Central full-text archive of biomedical and life sciences literature at the U.S. National Institutes of Health's National Library of Medicine (NIH/NLM).
CONTENT
Studies compared clinical characteristics of patients with HCAP and community-acquired pneumonia (CAP). HCAP patients were older and had a higher comorbidity. Mortality rates in HCAP varied from 5% to 33%, but seemed lower than those cited in the initial reports. Criteria behind the HCAP classification differed considerably within populations. Microbial patterns differed in that there was a higher incidence of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, and, to a lesser extent, enterobacteriaceae. Definitions and rates of multidrug-resistant (MDR) pneumonia also varied considerably. Broad-spectrum guideline-concordant treatment did not reduce mortality in four observational studies. The HCAP criteria performed poorly as a predictive tool to identify MDR pneumonia or pathogens not covered by treatment for CAP. A new score (Drug Resistance in Pneumonia, DRIP) outperformed HCAP in the prediction of MDR pathogens. Comorbidity and functional status, but not different microbial patterns, seem to account for increased mortality.
IMPLICATIONS
HCAP should no longer be used to identify patients at risk of MDR pathogens. The use of validated predictive scores along with implementation of de-escalation strategies and careful individual assessment of comorbidity and functional status seem superior strategies for clinical management.
Topics: Aged; Aged, 80 and over; Bacterial Infections; Clinical Decision Rules; Disease Management; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Female; Healthcare-Associated Pneumonia; Humans; Incidence; Male; Pseudomonas aeruginosa; Staphylococcus aureus; United States
PubMed: 30825674
DOI: 10.1016/j.cmi.2019.02.022 -
Journal of Global Antimicrobial... Sep 2019This meta-analysis aimed to evaluate the current prevalence and trends over the past 10 years of Pseudomonas aeruginosa (P. aeruginosa) antimicrobial resistance. Two... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This meta-analysis aimed to evaluate the current prevalence and trends over the past 10 years of Pseudomonas aeruginosa (P. aeruginosa) antimicrobial resistance. Two researches independently searched two national (ULAKBİM, Türk Medline) and two international databases (PubMed, Web of Science) to identify studies on P. aeruginosa resistance to antimicrobials from 2007 to 2017.
METHODS
Homogeneity across studies was assessed using Cochrane guidelines, and total variability due to between-study variations was reflected in the I index. A random effects model was developed to estimate the antimicrobial resistance rates and their corresponding 95% CI. Pooled antibiotic resistance rates between 2007-2011 and 2012-2016 were compared to calculate the change in antibiotic resistance over time. Electronic searches with MeSH terms and text words identified 1017 papers. After applying exclusion and inclusion criteria, 45 articles were selected.
RESULTS
Pooled resistance prevalence of P. aeruginosa to piperacillin-tazobactam, ceftazidime, cefepime, meropenem, imipenem, ciprofloxacin, gentamicin, amikacin, tobramycin and colistin were 33.9%, 38.6%, 35.6%, 30.1%, 28.0%, 30.7%, 28.2%, 17.8%, 15.7% and 2.2%, respectively. The resistance rates of piperacillin, piperacillin-tazobactam, imipenem, meropenem, amikacin and colistin significantly increased in the second 5 years (P<0.05); however, gentamicin, tobramycin and ciprofloxacin resistance rates significantly decreased (P<0.05). Comparing the resistance rates between the isolates of intensive care unit (ICU) patients and non-ICU patients, meropenem and piperacillin-tazobactam resistance in ICU isolates were significantly higher than non-ICU (P<0.05).
CONCLUSIONS
These results suggest that antibiotic resistance is high in P. aeruginosa and the trends in antimicrobial resistance continue to increase, mainly in carbapenems and penicillins, in Turkey.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Humans; Intensive Care Units; Microbial Sensitivity Tests; Prevalence; Pseudomonas Infections; Pseudomonas aeruginosa; Turkey
PubMed: 30753904
DOI: 10.1016/j.jgar.2019.01.032