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The Cochrane Database of Systematic... Dec 2016Choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection due to Pseudomonas aeruginosa in cystic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection due to Pseudomonas aeruginosa in cystic fibrosis (CF). Advantages of combination therapy include wider range of modes of action, possible synergy and reduction of resistant organisms; advantages of monotherapy include lower cost, ease of administration and reduction of drug-related toxicity. Current evidence does not provide a clear answer and the use of intravenous antibiotic therapy in cystic fibrosis requires further evaluation. This is an update of a previously published review.
OBJECTIVES
To assess the effectiveness of single compared to combination intravenous anti-pseudomonal antibiotic therapy for treating people with cystic fibrosis.
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: 14 October 2016.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing a single intravenous anti-pseudomonal antibiotic with a combination of that antibiotic plus a second anti-pseudomonal antibiotic in people with CF.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data.
MAIN RESULTS
We identified 45 trials, of which eight trials (356 participants) comparing a single anti-pseudomonal agent to a combination of the same antibiotic and one other, were included.There was a wide variation in the individual antibiotics used in each trial. In total, the trials included seven comparisons of a beta-lactam antibiotic (penicillin-related or third generation cephalosporin) with a beta-lactam-aminoglycoside combination and three comparisons of an aminoglycoside with a beta-lactam-aminoglycoside combination. These two groups of trials were analysed as separate subgroups.There was considerable heterogeneity amongst these trials, leading to difficulties in performing the review and interpreting the results. The meta-analysis did not demonstrate any significant differences between monotherapy and combination therapy, in terms of lung function; symptom scores; adverse effects; and bacteriological outcome measures.These results should be interpreted cautiously. Six of the included trials were published between 1977 and 1988; these were single-centre trials with flaws in the randomisation process and small sample size. Overall, the methodological quality was poor.
AUTHORS' CONCLUSIONS
The results of this review are inconclusive. The review raises important methodological issues. There is a need for an RCT which needs to be well-designed in terms of adequate randomisation allocation, blinding, power and long-term follow up. Results need to be standardised to a consistent method of reporting, in order to validate the pooling of results from multiple trials.
Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Cephalosporins; Cystic Fibrosis; Drug Therapy, Combination; Humans; Injections, Intravenous; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Tract Infections; beta-Lactams
PubMed: 27907224
DOI: 10.1002/14651858.CD002007.pub4 -
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 -
Chronic Respiratory Disease May 2017To provide an update on efficacy and safety of antibiotic treatments for stable non-cystic fibrosis (CF) bronchiectasis (BE). Systematic review based on the Preferred... (Review)
Review
To provide an update on efficacy and safety of antibiotic treatments for stable non-cystic fibrosis (CF) bronchiectasis (BE). Systematic review based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was done. Twenty-six studies (1.898 patients) fulfilled the inclusion criteria. Studies of inhaled tobramycin have revealed conflicting results regarding quality of life (QoL), exacerbations and admissions, but may result in sputum cultures negative for Pseudomonas aeruginosa, whereas studies investigating the effect of inhaled gentamycin have shown positive effects on sputum bacterial density, decrease in sputum cultures positive for P. aeruginosa, QoL and exacerbation rate, but no improvement in forced expiratory volume in first second (FEV). Oral azithromycin can reduce exacerbations, together with minor improvements in QoL and FEV. Furthermore, oral erythromycin reduces exacerbations, but has no effect on lung function, symptoms or QoL. Inhaled ciprofloxacin may reduce P. aeruginosa in sputum cultures, but without changes in lung function, exacerbations or QoL. Although with limited evidence, inhaled colistin may have effects on P. aeruginosa density, exacerbations and QoL, whereas studies on aztreonam revealed no significant clinical improvements in the outcomes of interest, including exacerbation rate. Adverse events, including bronchospasm, have been reported in association with tobramycin and aztreonam. Several antibiotic treatment regimens have been shown to improve QoL and exacerbation rate, whereas findings regarding sputum production, lung function and admissions have been conflicting. Evidence-based treatment algorithms for antibiotic treatment of stable non-CF BE will have to await large-scale, long-term controlled studies.
Topics: Aminoglycosides; Anti-Bacterial Agents; Aztreonam; Bronchiectasis; Ciprofloxacin; Colistin; Disease Progression; Forced Expiratory Volume; Humans; Macrolides; Pseudomonas Infections; Pseudomonas aeruginosa; Quality of Life; Sputum
PubMed: 27507832
DOI: 10.1177/1479972316661923 -
Le Infezioni in Medicina Sep 2020The present study aims to investigate the prevalence of Pseudomonas aeruginosa in Iranian Cystic Fibrosis (CF) patients. We conducted a systematic search on this topic... (Meta-Analysis)
Meta-Analysis
The present study aims to investigate the prevalence of Pseudomonas aeruginosa in Iranian Cystic Fibrosis (CF) patients. We conducted a systematic search on this topic in Web of Science, PubMed, Embase, Scopus, and Google Scholar electronic databases to the end of July 2019. Then, 14 articles with eligible criteria were selected for data extraction and analysis by Comprehensive Meta-Analysis Software. The pooled prevalence of P. aeruginosa was 40.6% (95% CI: 32.4%-49.4%) ranging from 32.4% to 49.4%. There was a significant heterogeneity among the studies (χ2 =21.02; p <0.001; I2 = 86.07%). The funnel plot for publication bias showed no evidence of asymmetry. Based on the results of Begg's and Egger's test no significant publication bias was observed. The study demonstrated a relative prevalence of P. aeruginosa among CF patients in Iran. Due to the rapid spread and infection severity of P. aeruginosa and other opportunistic pathogens, efforts are required to identify risk factors, reservoirs, transmission routes and source of infection.
Topics: Cystic Fibrosis; Humans; Iran; Prevalence; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 32920566
DOI: No ID Found -
Infectious Diseases and Therapy Sep 2021Gram-negative nosocomial pneumonia (NP), including hospital-acquired bacterial pneumonia (HABP), ventilated HABP (vHABP), and ventilator-associated bacterial pneumonia... (Review)
Review
INTRODUCTION
Gram-negative nosocomial pneumonia (NP), including hospital-acquired bacterial pneumonia (HABP), ventilated HABP (vHABP), and ventilator-associated bacterial pneumonia (VABP), is a significant cause of morbidity and mortality. Common pathogens, including Enterobacterales and Pseudomonas aeruginosa, are prevalent in healthcare settings and have few effective treatment options due to high rates of antibacterial resistance. Resistant pathogens are associated with significantly worse outcomes, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials of patients with NP. This review aims to collate data on C/T use for HABP/vHABP/VABP infections in real-world clinical practice.
METHODS
This systematic literature review searched online biomedical databases for real-world studies of C/T used to treat Gram-negative respiratory tract infections (RTIs) between January 2009 and June 2020.
RESULTS
Thirty-three studies comprising 658 patients were identified. Pneumonia was the most common infection treated with C/T (85%), with a smaller number of unspecified RTIs (9%) and tracheobronchitis (5%) reported. The majority of patients had respiratory infections caused by P. aeruginosa (92.8%), of which 88.1% were multidrug-resistant. Examination of these studies demonstrated an increase in the percentage of patients receiving the recommended dose of C/T for respiratory infections (3 g q8h or renal impairment-adjusted) over time (36.8% of patients in 2017 to 71.5% in 2020). Clinical success rates ranged from 51.4 to 100%, with 10 studies (55.6% of studies reporting clinical success) reporting clinical success rates of > 70%; microbiological success rates ranged from 57.0 to 100.0%, with three studies (60.0% of studies reporting microbiological success) reporting microbiological success rates of > 70%. Thirty-day mortality ranged from 0.0 to 33.0%, with nine studies (90% of studies reporting mortality) reporting 30-day mortality of < 30%.
CONCLUSIONS
The studies identified in this review demonstrate that C/T shows similar outcomes as those seen in clinical trials, despite the higher frequency of multidrug-resistant pathogens, and comorbidities that may have been excluded from the trials.
PubMed: 34278551
DOI: 10.1007/s40121-021-00491-x -
Indian Journal of Ophthalmology Aug 2017The purpose of this study was to review the incidence and microbiology of acute postcataract surgery endophthalmitis in India. (Review)
Review
PURPOSE
The purpose of this study was to review the incidence and microbiology of acute postcataract surgery endophthalmitis in India.
METHODS
Systematic review of English-language PubMed referenced articles on endophthalmitis in India published in the past 21 years (January 1992-December 2012), and retrospective chart review of 2 major eye care facilities in India in the past 5 years (January 2010-December 2014) were done. The incidence data were collected from articles that described "in-house" endophthalmitis and the microbiology data were collected from all articles. Both incidence and microbiological data of endophthalmitis were collected from two large eye care facilities. Case reports were excluded, except for the articles on cluster infection.
RESULTS
Six of 99 published articles reported the incidence of "in-house" acute postcataract surgery endophthalmitis, 8 articles reported the microbiology spectrum, and 11 articles described cluster infection. The clinical endophthalmitis incidence was between 0.04% and 0.15%. In two large eye care facilities, the clinical endophthalmitis incidence was 0.08% and 0.16%; the culture proven endophthalmitis was 0.02% and 0.08%. Gram-positive cocci (44%-64.8%; commonly, Staphylococcus species), and Gram-negative bacilli (26.2%-43%; commonly Pseudomonas species) were common bacteria in south India. Fungi (16.7%-70%; commonly Aspergillus flavus) were the common organisms in north India. Pseudomonas aeruginosa (73.3%) was the major organism in cluster infections.
CONCLUSIONS
The incidence of postcataract surgery clinical endophthalmitis in India is nearly similar to the world literature. There is a regional difference in microbiological spectrum. A registry with regular and uniform national reporting will help formulate region specific management guidelines.
Topics: Cataract Extraction; Endophthalmitis; Eye Infections; Forecasting; Humans; Incidence; India; Microbial Sensitivity Tests; Surgical Wound Infection
PubMed: 28820151
DOI: 10.4103/ijo.IJO_509_17 -
Journal of Cystic Fibrosis : Official... Jan 2015Cystic Fibrosis (CF) is a severe genetic disorder that is common among the Caucasian population. Bacterial respiratory infections are the main cause of morbidity and... (Review)
Review
BACKGROUND
Cystic Fibrosis (CF) is a severe genetic disorder that is common among the Caucasian population. Bacterial respiratory infections are the main cause of morbidity and mortality in CF patients. Pseudomonas aeruginosa is the main pathogen of lower airways (LAW) decline.
METHOD
To understand chronic broncho-pulmonary colonization, a systematic review is conducted. The aim of our article is to identify the pathways of contamination in the upper aero-digestive tract.
RESULTS
A large number of articles report that P. aeruginosa is established first at nasopharyngeal sites. The vast majority of authors agree that the upper aero-digestive tract is the first location of colonization by P. aeruginosa and its presence appears to be predictive of subsequent broncho-pulmonary colonization.
CONCLUSION
This review supports the possible involvement of the nasal and paranasal sinuses and oral cavity as means of contamination.
Topics: Cystic Fibrosis; Female; Humans; Incidence; Male; Mouth; Paranasal Sinuses; Prognosis; Pseudomonas Infections; Pseudomonas aeruginosa; Respiratory Tract Infections; Risk Assessment; Survival Rate
PubMed: 24933711
DOI: 10.1016/j.jcf.2014.04.008 -
Veterinary Medicine and Science Mar 2022Housefly (Musca domestica) is an excellent candidate for the distribution of susceptible and resistant bacterial strains that potentially threaten public health. To... (Meta-Analysis)
Meta-Analysis
Housefly (Musca domestica) is an excellent candidate for the distribution of susceptible and resistant bacterial strains that potentially threaten public health. To date, there is a paucity of information on the global distribution of pathogenic bacteria of medical and veterinary importance from diverse environmental settings. Therefore, this study was undertaken to conduct a systemic review and meta-analysis to estimate occurrence of various bacterial species of medical and veterinary importance harboured by houseflies around the world. Published articles from 1980 to 2020 were retrieved from electronic databases and assessed for eligibility according to Preferred Reporting Items for Systemic Reviews and Meta-Analysis guidelines. Seventy-eight studies were included in the review with only 44 studies being eligible for meta-analysis. Results indicated that eligible studies used in this review were from four continents, i.e., Asia (47.4%) America (23.1%), Africa (20.5%) and Europe (8.9%). The majority of the studies (56.4%) used the culture method for the identification of bacterial pathogens, while 30.7% used both culture and PCR techniques. For meta-analysis, we focused on five pathogenic bacterial species including Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. High heterogeneity was found among studies investigating different pathogens including E. coli (Q = 10,739.55; I = 99.60; Q-p 0.0001), E. faecium (Q = 317.61; I = 86.46; Q-p < 0.0001), K. pneumonia (Q = 1,576.61; I = 97.27; Q-p < 0.0001), S. aureus (Q = 2,439.12; I = 98.24; Q-p < 0.0001) and P. aeruginosa (Q = 1,283.0; I = 96.65; Q-p < 0.0001). Furthermore, it was observed that houseflies carried a considerable number of susceptible and antibiotic-resistant bacterial strains that pose considerable threats to public health. Findings from this study have provided more insight on the vectoral potential of houseflies in the transmission of significant bacterial pathogens from different regions across the world. Further investigation is required to quantify the bacterial contamination and dissemination by houseflies.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Escherichia coli; Houseflies; Humans; Staphylococcus aureus
PubMed: 33955703
DOI: 10.1002/vms3.496 -
The Cochrane Database of Systematic... Mar 2017People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside... (Meta-Analysis)
Meta-Analysis Review
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: 24 June 2016.
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
Fifteen studies were identified for possible inclusion in the review. Four studies reporting results from a total of 328 participants (aged 5 to 50 years) were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One study had a low risk of bias for all criteria assessed; the remaining three 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 no significant difference between treatment groups in: forced expiratory volume in one second, mean difference 0.33 (95% confidence interval -2.81 to 3.48, moderate quality evidence); forced vital capacity, mean difference 0.29 (95% confidence interval -6.58 to 7.16, low quality evidence); % weight for height, mean difference -0.82 (95% confidence interval -3.77 to 2.13, low quality evidence); body mass index, mean difference 0.00 (95% confidence interval -0.42 to 0.42, low quality evidence); or in the incidence of ototoxicity, relative risk 0.56 (95% confidence interval 0.04 to 7.96, moderate quality evidence). The percentage change in creatinine significantly favoured once-daily treatment in children, mean difference -8.20 (95% confidence interval -15.32 to -1.08, moderate quality evidence), but showed no difference in adults, mean difference 3.25 (95% confidence interval -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: Adolescent; Adult; Aminoglycosides; Anti-Bacterial Agents; Body Mass Index; Child; Child, Preschool; Cystic Fibrosis; Drug Administration Schedule; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Injections, Intravenous; Male; Middle Aged; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Tobramycin; Vital Capacity; Young Adult; beta-Lactams
PubMed: 28349527
DOI: 10.1002/14651858.CD002009.pub6