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Journal of Global Antimicrobial... Sep 2023The aim of the study was to update the classification of drugs used in multidrug-resistant tuberculosis (MDR-TB) regimens. Group A drugs (fluoroquinolones, bedaquiline... (Meta-Analysis)
Meta-Analysis Review
Evaluation of genetic mutations associated with phenotypic resistance to fluoroquinolones, bedaquiline, and linezolid in clinical Mycobacterium tuberculosis: A systematic review and meta-analysis.
OBJECTIVES
The aim of the study was to update the classification of drugs used in multidrug-resistant tuberculosis (MDR-TB) regimens. Group A drugs (fluoroquinolones, bedaquiline (BDQ), and linezolid (LZD)) are crucial drugs for the control of MDR-TB. Molecular drug resistance assays could facilitate the effective use of Group A drugs.
METHODS
We summarised the evidence implicating specific genetic mutations in resistance to Group A drugs. We searched PubMed, Embase, MEDLINE, and the Cochrane Library for studies published from the inception of each database until July 1, 2022. Using a random-effects model, we calculated the odds ratios and 95% confidence intervals as our measures of association.
RESULTS
A total of 5001 clinical isolates were included in 47 studies. Mutations in gyrA A90V, D94G, D94N, and D94Y were significantly associated with an increased risk of a levofloxacin (LFX)-resistant phenotype. In addition, mutations in gyrA G88C, A90V, D94G, D94H, D94N, and D94Y were significantly associated with an increased risk of a moxifloxacin (MFX)-resistant phenotype. In only one study, the majority of gene loci (n = 126, 90.65%) in BDQ-resistant isolates were observed to have unique mutations in atpE, Rv0678, mmpL5, pepQ, and Rv1979c. The most common mutations occurred at four sites in the rrl gene (g2061t, g2270c, g2270t, and g2814t) and at one site in rplC (C154R) in LZD-resistant isolates. Our meta-analysis demonstrated that there were no mutations associated with BDQ- or LZD-resistant phenotypes.
CONCLUSION
The mutations detected by rapid molecular assay were correlated with phenotypic resistance to LFX and MFX. The absence of mutation-phenotype associations for BDQ and LZD hindered the development of a rapid molecular assay.
Topics: Humans; Mycobacterium tuberculosis; Linezolid; Fluoroquinolones; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Levofloxacin; Phenotype
PubMed: 37172764
DOI: 10.1016/j.jgar.2023.05.001 -
BMC Infectious Diseases Jun 2022The role of Helicobacter pylori (H. pylori) virulence factors of such as vacA s1m1 and cagA in designating clinical outcomes and eradication rate has been deeply... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of Helicobacter pylori (H. pylori) virulence factors of such as vacA s1m1 and cagA in designating clinical outcomes and eradication rate has been deeply challenged in the last decade. The goal of this analysis was to identify the potential relevance between cagA and vacA genotypes with reported antibiotic resistance observed in clinical H. pylori isolates.
METHODS
This literature search was conducted in databases such as Clarivate analytics, PubMed, Scopus, EMBASE, DOAJ, and Google Scholar by April 2022, regardless of language restrictions and publication date. Quality of the included studies was assessed by the Newcastle-Ottawa scale. Statistical analysis of retrieved studies was fulfilled using Comprehensive Meta-Analysis software version 2.2. Following quality appraisal of eligible studies, potential association between the status of cagA and vacA genes with resistance to clarithromycin, metronidazole, amoxicillin, tetracycline, and levofloxacin was measured using odds ratio with 95% confidence interval. We also used sensitivity analyses and meta-regression to eliminate the source of heterogeneity from the overall estimates. Publication bias was assessed using funnel plot, Egger's test, Begg's test with the trim and fill procedure to assess the presence and magnitude of publication bias in the included studies.
RESULTS
Our findings suggested that a significant relationship between cagA status and increase resistance to metronidazole (OR: 2.69; 95% CI: 1.24-5.83). In subgroup analysis, we found that in the Western population, infection with cagA-positive strains could be led to increase in the resistance to metronidazole (OR: 1.59; 95% CI: 0.78-3.21), amoxicillin (OR: 19.68; 95% CI: 2.74-141.18), and levofloxacin (OR: 11.33; 95% CI: 1.39-91.85). After implementation of trim and fill method, the adjusted OR was not significantly differed from original estimates which in turn represented our subgroup analysis was statistically robust. On the other hand, vacA genotypes usually reduce the antibiotic resistance of this bacterium, so that vacA s1m1 significantly reduces the resistance to metronidazole (OR: 0.41; 95% CI: 0.20-0.86). Surprisingly, resistance of vacA s2m2 strains to antibiotics was low, the reason may be due to the non-inflammatory properties of strains containing vacA s2m2. The meta-regression and sensitivity analyses successfully reduced the effect of heterogeneity from the overall estimates. In addition, although the pooled OR is reduced after trim and fill adjustment but results do not change the conclusion regarding vacA genotypes and antibiotic resistance.
CONCLUSIONS
According to our findings, it was clearly demonstrated that cagA-positive strains are resistance to metronidazole, especially in Western countries. In Western countries, vacA s1m1 increases resistance to amoxicillin and levofloxacin. Based on the present findings, the vacA s1m1 genotype significantly increases resistance to metronidazole, while the vacA s1m2 decreases resistance to clarithromycin and metronidazole. Resistance to antibiotics in less virulent (vacA s2m2) strains is statistically significant lower than others.
Topics: Amoxicillin; Anti-Bacterial Agents; Antigens, Bacterial; Bacterial Proteins; Clarithromycin; Drug Resistance, Microbial; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole
PubMed: 35752757
DOI: 10.1186/s12879-022-07546-5 -
Journal of Global Antimicrobial... Sep 2023The incidence of Helicobacter pylori (HP) is 25-50% in developed countries and 80% in developing countries, including 56.2% in China. However, antibiotic resistance of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The incidence of Helicobacter pylori (HP) is 25-50% in developed countries and 80% in developing countries, including 56.2% in China. However, antibiotic resistance of HP is a threat to HP control. The purpose of this study was to comprehensively evaluate primary drug resistance of HP in China.
METHODS
The full text of reports of the primary antibiotic resistance prevalence of HP was obtained from multiple databases (PubMed, Web of Science, Evimed, Cochrane Library, and China National Knowledge Internet). Review Manager 5.2 was adopted for meta-analysis, sensitivity analysis, and bias analysis. The Newcastle-Ottawa Scale was used to assess the article quality.
RESULTS
In total, 38804 HP samples from 22 trials were extracted. The results suggested that the overall prevalence of amoxicillin, clarithromycin, metronidazole, and levofloxacin resistance among HP in adults was as follows: mean difference (MD) = 1.35%, 95% confidence interval (CI) [1.03%, 1.68%]; MD = 23.76%, 95% CI [20.23%, 27.3%]; MD = 69.32%, 95% CI [64.85%, 73.8%]; and MD = 29.45%, 95% CI [4.90, 176.96], respectively. From the results of sensitivity and publication bias, we find that these results are robust and had little publication bias.
CONCLUSION
Our research showed that in China, the prevalence of HP resistance to primary antibiotics warrants attention, especially with regard to metronidazole, levofloxacin, and clarithromycin.
Topics: Adult; Humans; Metronidazole; Clarithromycin; Levofloxacin; Helicobacter pylori; Helicobacter Infections; Drug Resistance, Bacterial; Anti-Bacterial Agents; China
PubMed: 37315738
DOI: 10.1016/j.jgar.2023.05.014 -
Clinical Infectious Diseases : An... Oct 2022Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies.
METHODS
We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans.
RESULTS
We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx.
CONCLUSIONS
These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.
Topics: Amoxicillin-Potassium Clavulanate Combination; Animals; Anthrax; Anti-Bacterial Agents; Anti-Infective Agents; Bacillus anthracis; Cilastatin, Imipenem Drug Combination; Ciprofloxacin; Doxycycline; Glycopeptides; Humans; Levofloxacin; Lipopeptides; Models, Animal; Tetracyclines; United States; beta-Lactams
PubMed: 36251546
DOI: 10.1093/cid/ciac591 -
EClinicalMedicine Jun 2022Pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are empirically used. However, the quantitative comparative effectiveness and...
BACKGROUND
Pharmacological treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are empirically used. However, the quantitative comparative effectiveness and safety of multiple pharmacological treatments is lacking.
METHODS
PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to March 22, 2022. Randomised controlled trials comparing two or more oral pharmacological treatments for patients with CP/CPPS were included. Title, abstract, and full-text screening were independently screened by four reviewers. Primary outcomes were efficacy (the National Institutes of Health Chronic Prostatitis Symptom Index [NIH-CPSI] total score, pain score, urinary score, and quality of life score [QoL]) and safety (adverse events). This study was registered with PROSPERO, CRD42020184106.
FINDINGS
25 studies (3514 patients) assessed 26 treatments. Low to very low quality evidence indicated that doxazosin (Mean difference [MD], -11.4, 95% Credible interval [CrI], -17.5 to -5.1) and the doxazosin, ibuprofen, and thiocolchicoside combination (MD, -11.6, CrI, -18.1 to -5.3) were significantly more effective than placebo in the NIH-CPSI total score. Other NIH-CPSI relative outcomes (pain, urinary, and QoL scores) showed a similar pattern. Low and very low quality evidence suggested that combination treatment including doxazosin, ibuprofen, and thiocolchicoside (odds ratios [OR], 3.2, CrI, 0.5 to 19.3) and the tamsulosin and dapoxetine combination (OR, 6.0, CrI, 0.7 to 67.3) caused more adverse events. In half of all comparisons regarding NIH-CPSI pain scores and quality of life scores, heterogeneity was minimal or low. Heterogeneity was high in both NIH-CPSI total symptom scores ( = 78.0%) and pain scores ( = 87. 0%) for tamsulosin versus placebo. There was also high heterogeneity in NIH-CPSI urine scores for the combination of tamsulosin and ciprofloxacin versus tamsulosin ( = 66.8%), tamsulosin and levofloxacin versus tamsulosin ( = 93.3%), and tamsulosin versus placebo ( = 83%).
INTERPRETATION
Pharmacological treatments have little evidence supporting efficacy in CP/CPPS. Future studies could personalise therapy for individuals according to specific symptoms and identify non-pharmacological targets for CP/CPPS.
FUNDING
Dr Jiani Wu received funding for this project from the China Association for Science and Technology (2017QNRC001), the China Academy of Chinese Medical Sciences (ZZ13-YQ-027), and the National Natural Science Foundation of China (82105037).
PubMed: 35706494
DOI: 10.1016/j.eclinm.2022.101457 -
European Journal of Internal Medicine Feb 2024The optimal antimicrobial regimen for adults with respiratory failure due to Legionella pneumonia remains controversial. A systematic review was performed to assess the...
The optimal antimicrobial regimen for adults with respiratory failure due to Legionella pneumonia remains controversial. A systematic review was performed to assess the impact on outcomes comparing quinolones versus macrolides. A literature search was conducted in PubMed, Cochrane Library and Web of Science between 2012 and 2022. It yielded 124 potentially articles and ten observational studies met the inclusion criteria. A total of 4271 patients were included, 2879 (67 %) were male. A total of 1797 (42 %) subjects required intensive care unit (ICU) admission and 942 (52 %) mechanical ventilation. Fluoroquinolones and macrolides alone were administered in 1397 (33 %) and 1500 (35 %) subjects, respectively; combined therapy in 204 (4.8 %) patients. Overall mortality was 7.4 % (319 patients), with no difference between antibiotics. When data from the three studies with severe pneumonia were pooled together, mortality with fluoroquinolones alone was statistically superior to macrolides alone (72.8 % vs 30.8 %, p value 0.027). Hospital length of stay and complications were comparable. Our findings suggest that macrolides and quinolones were comparable for hospitalized Legionella pneumonia. However, in severe pneumonia, a randomized clinical trial is an unmet clinical need. PROSPERO registration number: CRD42023389308.
Topics: Adult; Humans; Male; Female; Macrolides; Quinolones; Anti-Bacterial Agents; Legionnaires' Disease; Fluoroquinolones; Legionella; Respiratory Insufficiency; Randomized Controlled Trials as Topic
PubMed: 37730517
DOI: 10.1016/j.ejim.2023.09.013 -
Medicine Sep 2022Tuberculosis (TB) is one of the serious epidemics that highly threaten the global public health. To explore the treatment effect of Levofloxacin, Moxifloxacin, and... (Meta-Analysis)
Meta-Analysis
The treatment effect of Levofloxacin, Moxifloxacin, and Gatifloxacin contained in the conventional therapy regimen for pulmonary tuberculosis: Systematic review and network meta-analysis.
BACKGROUND
Tuberculosis (TB) is one of the serious epidemics that highly threaten the global public health. To explore the treatment effect of Levofloxacin, Moxifloxacin, and Gatifloxacin contained in the conventional therapy regimen for pulmonary tuberculosis.
METHODS
Medline, PubMed, Embase, and Cochrane Library were searched with the keyword such as "Levofloxacin," "Moxifloxacin," "Gatifloxacin," and "tuberculosis", through June 1992 to 2017. According to the inclusion and exclusion criteria, 2 researchers independently screened the literature, extracted the data, and evaluated the quality of the included studies. The Cochrane system was evaluated by RevMan5.2 and the network meta-analysis was performed by Stata 15.
RESULTS
A total of 891 studies were included, with a total of 6565 patients. The results of network meta-analysis showed that Moxifloxacin + conventional therapy (CT) regimen was superior to CT regimen only on the spectrum culture negative. Both Levofloxacin + CT and Moxifloxacin + CT were superior to the CT regimen in treatment success rate. For the adverse events, the Levofloxacin + CT showed much safer results than CT group, while Moxifloxacin + CT had more adverse events than CT group.
CONCLUSION
Levofloxacin, Moxifloxacin, and Gatifloxacin have different superiority, comparing to CT regimen in spectrum culture negative, treatment success rate, and adverse events. Hence, combined utilization of these quinolone is important on the clinical treatment for tuberculosis.
Topics: Antitubercular Agents; Fluoroquinolones; Gatifloxacin; Humans; Levofloxacin; Moxifloxacin; Network Meta-Analysis; Tuberculosis; Tuberculosis, Pulmonary
PubMed: 36197231
DOI: 10.1097/MD.0000000000030412 -
The American Journal of Gastroenterology Aug 2022Antimicrobial resistance among Helicobacter pylori strains has been rising globally, leading to declining eradication rates. We performed a systematic review and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Antimicrobial resistance among Helicobacter pylori strains has been rising globally, leading to declining eradication rates. We performed a systematic review and meta-analysis of the resistance patterns of H. pylori strains in the United States between 2011 and 2021.
METHODS
Ovid MEDLINE, Embase, CINAHL, and Cochrane CENTRAL databases were searched for manuscripts and conference abstracts published between 2011 and 2021 reporting H. pylori antibiotic resistance. A mixed-effects model estimated pooled rates of resistance to clarithromycin, amoxicillin, metronidazole, tetracycline, rifabutin, levofloxacin, or a combination of these, with 95% confidence intervals (CIs).
RESULTS
A total of 19 studies including 2,660 samples, met inclusion criteria. The pooled rate of resistance to metronidazole was 42.1% (95% CI 27.3%-58.6%), levofloxacin 37.6% (95% CI 26.3%-50.4%), clarithromycin 31.5% (95% CI 23.6%-40.6%), amoxicillin 2.6% (95% CI 1.4%-5.0%), tetracycline 0.87% (95% CI 0.2%-3.8%), rifabutin 0.17% (95% CI 0.00%-10.9%), and dual clarithromycin and metronidazole 11.7% (95% CI 0.1%-94.0%). Considerable data heterogeneity was evident for pooled resistance prevalence rates (I 2 > 50%), with the exception of rifabutin resistance.
DISCUSSION
Metronidazole, levofloxacin, and clarithromycin resistance rates each exceed 30%; thus, choosing an empiric antibiotic regimen without knowledge of the likely pattern of antibiotic resistance is not appropriate. Resistance to tetracycline, rifabutin, and amoxicillin remains low. Given the scarcity of available data with considerable heterogeneity among studies, continued surveillance, ideally with a more systematic approach to data collection, is an increasingly important goal in H. pylori management.
Topics: Amoxicillin; Anti-Bacterial Agents; Clarithromycin; Drug Resistance, Bacterial; Drug Resistance, Microbial; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Metronidazole; Rifabutin; Tetracycline; United States
PubMed: 35509128
DOI: 10.14309/ajg.0000000000001828 -
Emergency Medicine International 2022Levofloxacin has been widely used in clinical anti-infection treatment; however, its adverse reactions to levofloxacin were also obvious in patients. Herein we aimed to...
Clinical Efficacy and Safety Analysis of Levofloxacin for the Prevention of Infection after Traumatic Osteoarthrosis and Internal Fixation: Systematic Review and Meta-Analysis.
OBJECTIVE
Levofloxacin has been widely used in clinical anti-infection treatment; however, its adverse reactions to levofloxacin were also obvious in patients. Herein we aimed to systematically evaluate the clinical efficacy and safety of systemic administration of levofloxacin in the prevention of postoperative infection after traumatic osteoarthrosis and internal fixation.
METHODS
PubMed, Cochrane Library, OVID, EBSCO, CNKI, VIP database, and Wanfang Database were searched from December 1993 to December 2021. Meanwhile, China ADR Information Bulletin and WHO Pharmaceutical were searched manually. Newsletter and FDA Drug Safety Newsletter, also to retrieve the Websites of Chinese, Chinese, and drug regulatory authorities; To obtain data on adverse events in children with systemic administration of levofloxacin. The literature was screened according to inclusion and exclusion criteria. The risk of bias was evaluated for the included RCT literature.
RESULTS
There was a statistical difference in the comparison of the incidence of fever between the experimental group and the control group (OR = 2.29, 95% CI (1.75,2.98), < 0.00001, I = 0%, = 6.11); elevated white blood cell count (OR = 1.82, 95% CI (1.31,2.52),=0.0003, I = 0%, = 3.60); incidence of wound infection (OR = 2.11, 95% CI (1.54,2.90), < 0.00001, I = 0%, = 4.64); adverse drug reaction (OR = 1.82, 95% CI (1.21,2.74),=0.004, I = 0%, = 2.86).
CONCLUSION
In the clinical use of levofloxacin, adverse drug reactions including fever, elevated white blood cell count, and wound infection should be concerned.
PubMed: 36213001
DOI: 10.1155/2022/8788365 -
Journal of Global Antimicrobial... Jun 2022Despite excessive resistance of Helicobacter pylori to clarithromycin among the Iranian population, clarithromycin-based therapy is still prescribed in Iran. Recent... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Despite excessive resistance of Helicobacter pylori to clarithromycin among the Iranian population, clarithromycin-based therapy is still prescribed in Iran. Recent studies have shown high rates of H. pylori eradication in patients treated with levofloxacin. The main purpose of this study was to compare the effect of levofloxacin with clarithromycin on the eradication of H. pylori infection in the Iranian population.
METHODS
A comprehensive meta-analysis was done for relevant cohort studies and clinical trials to compare the therapeutic effects of levofloxacin and clarithromycin in the Iranian population. We pooled the data using odds ratio (OR) and corresponding 95% confidence interval (CI) to determine the clinical efficacy of levofloxacin versus clarithromycin to treat H. pylori infection. Heterogeneity and publication bias were also measured for the included studies.
RESULTS
Thirteen studies were included in the quantitative synthesis. The eradication rate was significantly higher in patients receiving levofloxacin compared with clarithromycin (75.2% vs. 66.3%; OR = 1.76, 95% CI 1.40-2.20). Additionally, in the subgroup analyses it was confirmed that the cure rate was relatively higher in levofloxacin-treated cases. However, there was significant heterogeneity and publication bias, thus the results should be interpreted with caution.
CONCLUSION
We found that the success of levofloxacin treatment was significantly higher than clarithromycin. Therefore, it is suggested that clarithromycin-based triple therapy be replaced by levofloxacin-based triple therapy in countries with high resistance to clarithromycin such as Iran. Nevertheless, the findings of this study need to be approved with a larger investigation on the Iranian population.
Topics: Anti-Bacterial Agents; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Iran; Levofloxacin
PubMed: 34788690
DOI: 10.1016/j.jgar.2021.10.019