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Life (Basel, Switzerland) May 2021Ceftolozane/tazobactam (C/T) is a β-lactam/β-lactamase inhibitor combination that mainly targets Gram-negative bacteria. The current international guidelines recommend... (Review)
Review
BACKGROUND
Ceftolozane/tazobactam (C/T) is a β-lactam/β-lactamase inhibitor combination that mainly targets Gram-negative bacteria. The current international guidelines recommend including C/T treatment in the empirical therapy for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). (PA) is one of the most challenging Gram-negative bacteria. We conducted a systematic review of all cases reported in the literature to summarize the existing evidence.
METHODS
The main electronic databases were screened to identify case reports of patients with drug-resistant PA respiratory infections treated with C/T.
RESULTS
A total of 22 publications were included for a total of 84 infective episodes. The clinical success rate was 72.6% across a wide range of comorbidities. The 45.8% of patients treated with C/T presented colonization by PA. C/T was well tolerated. Only six patients presented adverse events, but none had to stop treatment. The most common therapeutic regimens were 1.5 g every 8 h and 3 g every 8 h.
CONCLUSION
C/T may be a valid therapeutic option to treat multidrug-resistant (MDR), extensively drug-resistant (XDR), pandrug-resistant (PDR), and carbapenem-resistant (CR) PA infections. However, further data are necessary to define the optimal treatment dosage and duration.
PubMed: 34073847
DOI: 10.3390/life11060474 -
Chemosphere Jul 2023Antibiotic resistance in drinking water systems poses human health risks. Earlier studies, including reviews on antibiotic resistance in drinking water systems are... (Review)
Review
Antibiotic resistance in drinking water systems poses human health risks. Earlier studies, including reviews on antibiotic resistance in drinking water systems are limited to the occurrence, behaviour and fate in bulk raw water and drinking water treatment systems. By comparison, reviews on the bacterial biofilm resistome in drinking water distribution systems are still limited. Therefore, the present systematic review investigates the occurrence, behaviour and fate and, detection methods of bacterial biofilm resistome in the drinking water distribution systems. A total of 12 original articles drawn from 10 countries were retrieved and analyzed. Antibiotic resistant bacteria and antibiotic resistance genes detected in biofilms include those for sulfonamides, tetracycline, and beta-lactamase. The genera detected in biofilms include Staphylococcus, Enterococcus, Pseudomonas, Ralstonia, Mycobacteria, as well as Enterobacteriaceae family and other gram-negative bacteria. The presence of Enterococcus faecium, Staphylococcusaureus, Klebsiella pneumoniae, Acinetobacterbaumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE bacteria) among the detected bacteria points to potential human exposure and health risks especially for susceptible individuals via the consumption of drinking water. Besides, the effects of water quality parameter and residual chlorine, the physico-chemical factors controlling the emergence, persistence and fate of the biofilm resistome are still poorly understood. Culture-based methods, and molecular methods, and their advantages and limitations are discussed. The limited data on the bacterial biofilm resistome in drinking water distribution system points to the need for further research. To this end, future research directions are discussed including understanding the formation, behaviour, and fate of the resistome and the controlling factors.
Topics: Humans; Drinking Water; Renal Dialysis; Bacteria; Biofilms; Genes, Bacterial; Anti-Bacterial Agents
PubMed: 37059195
DOI: 10.1016/j.chemosphere.2023.138642 -
Current Pharmaceutical Biotechnology Apr 2023Pseudomonas aeruginosa is an opportunistic gram-negative pathogen with multiple mechanisms of resistance to antibiotics. This systematic review aimed to study the...
BACKGROUND
Pseudomonas aeruginosa is an opportunistic gram-negative pathogen with multiple mechanisms of resistance to antibiotics. This systematic review aimed to study the antibacterial effects of nanocomposites on efflux pump expression and biofilm production in P. aeruginosa.
METHODS
The search was conducted from January 1, 2000, to May 30, 2022, using terms such as (P. aeruginosa) AND (biofilm) AND (antibiofilm activity) AND (anti-Efflux Pump Expression activity) AND (nanoparticles) AND (Efflux Pump Expression) AND (Solid Lipid NPS) AND (Nano Lipid Carriers). Many databases are included in the collection, including ScienceDirect, PubMed, Scopus, Ovid, and Cochrane.
RESULTS
A list of selected articles was retrieved by using the relevant keywords. A total of 323 published papers were selected and imported into the Endnote library (version X9). Following the removal of duplicates, 240 were selected for further processing. Based on the titles and abstracts of the articles, 54 irrelevant studies were excluded. Among the remaining 186 articles, 54 were included in the analysis because their full texts were accessible. Ultimately, 74 studies were selected based on inclusion/exclusion criteria.
CONCLUSION
Recent studies regarding the impact of NPs on drug resistance in P. aeruginosa found that various nanostructures were developed with different antimicrobial properties. The results of our study suggest that NPs may be a feasible alternative for combating microbial resistance in P. aeruginosa by blocking flux pumps and inhibiting biofilm formation.
PubMed: 37132134
DOI: 10.2174/1389201024666230428121122 -
The Yale Journal of Biology and Medicine Dec 2022: Antibiotic resistance in cystic fibrosis (CF) is a well-known phenomenon. However, the comprehensive epidemiological impact of antibiotic resistance in CF is not... (Meta-Analysis)
Meta-Analysis Review
: Antibiotic resistance in cystic fibrosis (CF) is a well-known phenomenon. However, the comprehensive epidemiological impact of antibiotic resistance in CF is not clearly documented. So, this meta-analysis evaluated the proportion rates of carbapenem resistance (imipenem, meropenem, and doripenem) in CF based on publication date (1979-2000, 2001-2010, and 2011-2021), continents, pathogens, and antimicrobial susceptibility testing (AST). : We searched studies in PubMed, Scopus, and Web of Science (until April 2021). Statistical analyses were conducted using STATA software (version 14.0). : The 110 studies included in the analysis were performed in 25 countries and investigated 13,324 pathogens associated with CF. The overall proportion of imipenem, meropenem, and doripenem resistance in CF were 43% (95% CI 36-49), 48% (95% CI 40-57), 28% (95% CI 23-33), and 45% (95% CI 32-59), respectively. Our meta-analysis showed that trends of imipenem, meropenem, and doripenem-resistance had gradual decreases over time (1979-2021). This could be due to the limited clinical effectiveness of these antibiotics to treat CF cases over time. Among the opportunistic pathogens associated with CF, the highest carbapenem resistance rates were shown in , spp., , and . The highest and lowest carbapenem resistance rates among in CF patients were shown against meropenem (23%) and doripenem (39%). : We showed that trends of carbapenem resistance had decreased over time (1979-2021). This could be due to the limited clinical effectiveness of these antibiotics to treat CF cases over time. Plans should be directed to fight biofilm-associated infections and prevent the emergence of mutational resistance. Systematic surveillance for carbapenemase-producing pathogens in CF by molecular surveillance is necessitated.
Topics: Humans; Meropenem; Doripenem; Carbapenems; Cystic Fibrosis; Microbial Sensitivity Tests; Anti-Bacterial Agents; Imipenem; Pseudomonas aeruginosa
PubMed: 36568834
DOI: No ID Found -
Journal of Pharmaceutical Policy and... Dec 2022There is limited data to describe the point-prevalence of healthcare-associated infections (HAIs) among patients at a regional level in Africa. This study estimated the... (Review)
Review
BACKGROUND
There is limited data to describe the point-prevalence of healthcare-associated infections (HAIs) among patients at a regional level in Africa. This study estimated the pooled prevalence of HAIs and described the distribution of HAIs as well as the pathogens identified from African studies.
METHODS
PubMed, Scopus and Google Scholar databases were searched to find point-prevalence studies of HAIs in Africa. Studies conducted in Humans that reported the prevalence of HAIs among hospitalized patients and published in English language from January 2010 to March 2022 were selected. Longitudinal studies of HAIs and unpublished studies were excluded. The reference list of the selected studies was checked to find additional studies. A meta-analysis was conducted using RevMan 5.4 and the pooled prevalence of HAIs was determined using a random effect model.
RESULTS
Of the 6094 articles identified from the databases, fifteen eligible articles were selected. The studies were conducted in the North, South, East and West African regions with Tunisia (n = 4) and South Africa (n = 2) having the highest number of studies. Most of the studies (n = 12, 80.0%) had good quality. The pooled prevalence of HAIs was 12.76% (95% confidence interval [CI] 10.30-15.23) with a high degree of heterogeneity (I = 90.0%). The prevalence of HAIs varied between wards with the highest rate found in the ICU (25.2%-100%), followed by neonatal ICU/ward (7.0%-53.6%) and paediatric medical ward (2.7%-33.0%). Surgical site infection was the most common HAIs and accounted for 41.6% of all HAIs (95% CI 23.55-59.80), followed by bloodstream infection (17.07%, 95% CI 11.80-22.33) and respiratory tract infections/pneumonia (17.04%, 95% CI 13.21-20.87). Recent hospitalization (adjusted odds ratio [AOR]: 4.17, 95% CI 1.85-9.41), presence of peripheral vascular catheter (AOR: 2.87, 95% CI 1.54-5.36) and having diabetes mellitus (AOR: 2.46, 95% CI 1.45-4.17) were the strongest predictors of HAIs in Africa. Only 37.9% of HAIs had documented positive microbiological culture result with gram negative bacteria including Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii and Citrobacter been the most common microorganisms and accounted for 40%-100% of the pathogens.
CONCLUSIONS
The pooled point-prevalence of HAIs in Africa is more than two times higher than the rate reported in developed countries. The prevalence varied between the countries and was highest in the ICU and neonatal ICU/ward. Surgical site infection and bloodstream infection were the most common HAIs reported in African studies. Recent hospitalization, presence of peripheral vascular catheter and having diabetes mellitus were the strongest predictors of HAIs in African studies. Most of the HAIs are preventable with appropriate infection control measures and antimicrobial stewardship. Additional studies are needed especially in the Central African region. Future studies should be designed using standardized protocol and standardized definition to reduce heterogeneity among the studies.
PubMed: 36494700
DOI: 10.1186/s40545-022-00500-5 -
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 -
The Cochrane Database of Systematic... Sep 2020Staphylococcus aureus causes pulmonary infection in young children with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent such infection and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Staphylococcus aureus causes pulmonary infection in young children with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent such infection and lung damage. Antibiotics have adverse effects and long-term use might lead to infection with Pseudomonas aeruginosa. This is an update of a previously published review.
OBJECTIVES
To assess continuous oral antibiotic prophylaxis to prevent the acquisition of Staphylococcus aureus versus no prophylaxis in people with cystic fibrosis, we tested the following hypotheses to investigate whether prophylaxis: 1. improves clinical status, lung function and survival; 2. leads to fewer isolates of Staphylococcus aureus; 3. causes adverse effects (e.g. diarrhoea, skin rash, candidiasis); 4. leads to fewer isolates of other common pathogens from respiratory secretions; 5. leads to the emergence of antibiotic resistance and colonisation of the respiratory tract with Pseudomonas aeruginosa.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Companies manufacturing anti-staphylococcal antibiotics were contacted. Most recent search of the Group's Register: 27 February 2020. Online trials registries were also searched. Most recent search of online trials registries: 15 September 2020.
SELECTION CRITERIA
Randomised trials of continuous oral prophylactic antibiotics (given for at least one year) compared to intermittent antibiotics given 'as required', in people with cystic fibrosis of any disease severity.
DATA COLLECTION AND ANALYSIS
The authors assessed studies for eligibility and methodological quality and extracted data. The quality of the evidence was assessed using the GRADE criteria. The review's primary outcomes of interest were lung function by spirometry (forced expiratory volume in one second (FEV)) and the number of people with one or more isolates of Staphylococcus aureus (sensitive strains).
MAIN RESULTS
We included four studies, with a total of 401 randomised participants aged zero to seven years on enrolment; one study is ongoing. The two older included studies generally had a higher risk of bias across all domains, but in particular due to a lack of blinding and incomplete outcome data, than the two more recent studies. We only regarded the most recent study as being generally free of bias, although even here we were not certain of the effect of the per protocol analysis on the study results. Evidence quality was judged to be low for all outcomes assessed after being downgraded based on GRADE assessments. Downgrading decisions were due to limitations in study design (all outcomes), for imprecision and for inconsistency . Prophylactic anti-staphylococcal antibiotics probably make little or no difference to lung function measured as FEV % predicted after six years (mean difference (MD) -2.30, 95% confidence interval (CI) -13.59 to 8.99, one study, n = 119, low-quality evidence); but may reduce the number of children having one or more isolates of Staphylococcus aureus at two years (odds ratio (OR) 0.21, 95% CI 0.13 to 0.35, three studies, n = 315, low-quality evidence). At the same time point, there may be little or no effect on nutrition as reported using weight z score (MD 0.06, 95% CI -0.33 to 0.45, two studies, n = 140, low-quality evidence), additional courses of antibiotics (OR 0.18, 95% CI 0.01 to 3.60, one study, n = 119, low-quality evidence) or adverse effects (low-quality evidence). There was no difference in the number of isolates of Pseudomonas aeruginosa between groups at two years (OR 0.74, 95% CI 0.45 to 1.23, three studies, n = 312, low-quality evidence), though there was a trend towards a lower cumulative isolation rate of Pseudomonas aeruginosa in the prophylaxis group at two and three years and towards a higher rate from four to six years. As the studies reviewed lasted six years or less, conclusions cannot be drawn about the long-term effects of prophylaxis.
AUTHORS' CONCLUSIONS
Anti-staphylococcal antibiotic prophylaxis may lead to fewer children having isolates of Staphylococcus aureus, when commenced early in infancy and continued up to six years of age. The clinical importance of this finding is uncertain. Further research may establish whether the trend towards more children with CF with Pseudomonas aeruginosa, after four to six years of prophylaxis, is a chance finding and whether choice of antibiotic or duration of treatment might influence this.
Topics: Antibiotic Prophylaxis; Bias; Child; Child, Preschool; Cystic Fibrosis; Drug Resistance, Bacterial; Forced Expiratory Volume; Growth; Humans; Infant; Infant, Newborn; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus aureus
PubMed: 32997797
DOI: 10.1002/14651858.CD001912.pub5 -
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 -
Cureus Mar 2021Cystic fibrosis is an autosomal recessive disorder caused by a mutation in genes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR gene is... (Review)
Review
Cystic fibrosis is an autosomal recessive disorder caused by a mutation in genes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR gene is responsible for the production of sweat, digestive fluids, and mucus, and any mutation in this would lead to the thickening of these secretions. Cystic fibrosis is a multi-organ disorder, but 80% of patients suffer from respiratory problems due to chronic infections most commonly caused by . Eradication of these infections has become a challenge as has developed resistance to multiple antibiotics. In several studies, iron has been shown to play an integral role in biofilm formation which is the predominant resistance mechanism used by to combat antibiotics. The increased iron content in cystic fibrosis patients' sputum samples explains their increased susceptibility to infections. Hence in this review article, we have used the research data available on therapeutic agents that target iron as an adjuvant treatment for chronic infection. We systematically screened three databases using focused words and Medical Subject Headings (MeSH) terms for relevant articles. Further, we applied the inclusion and exclusion criteria and performed a thorough quality appraisal. Thirty shortlisted relevant studies were meticulously reviewed. In our opinion, novel therapeutic approaches targeting iron such as iron chelators, gallium, and cefiderocol have potent anti-biofilm properties. Future studies and clinical trials using these approaches in the management of chronic infection might help in decreasing morbidity and mortality in patients with cystic fibrosis. Exploring these approaches might also help to combat other resistant organisms whose survival is dependent on iron.
PubMed: 33833927
DOI: 10.7759/cureus.13716 -
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