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Frontiers in Pharmacology 2022Postmarketing safety analysis is an effective supplement for new drugs in clinical practice. Therefore, we aimed to systematically assess the safety of oral nemonoxacin...
Postmarketing safety analysis is an effective supplement for new drugs in clinical practice. Therefore, we aimed to systematically assess the safety of oral nemonoxacin malate, the first approved C-8-methoxy non-fluorinated quinolone, in clinical studies and postmarketing safety surveillance. We electronically and manually searched and screened safety data (including premarketing and postmarketing data) of oral nemonoxacin from clinical registries. We standardized and summarized the reported adverse events according to the Medical Dictionary for Regulatory Activities System Organ Class and Preferred Terms. We summarized and reported the number and frequency (%) of the AEs and serious AEs in patients with community-acquired pneumonia and in specific patients. Three Phase II/III comparator studies ( = 670, nemonoxacin), one Phase IV study ( = 461), two special population pharmacokinetic studies ( = 40), four observational studies ( = 1,852), and one 5-year postmarketing surveillance project ( = 257,420) were included in this study. The Phase II/III studies showed that the commonly reported drug-related AEs were similar for oral 500 mg nemonoxacin and levofloxacin treatments, which mainly included increased alanine aminotransferase levels (4.4% vs. 2.5%), neutropenia (2.5% vs. 4.4%), nausea (2.5% vs. 1.6%), and leukopenia (2.3% vs. 3.2%). No drug-related deaths were reported. Postmarketing safety surveillance revealed that known adverse drug reaction characteristics were generally unchanged. Pharmacokinetic data suggested that dose adjustment was not necessary in elderly patients, which was confirmed by a Phase IV study in an elderly population, in patients with renal impairment with CLcr ≥50 ml/min, and in those with mild-to-moderate hepatic impairment. Clinical trial data of approximately 1,450 patients and postmarketing data of >257,420 patients suggest that nemonoxacin is generally well tolerated and can be a suitable alternative to fluoroquinolones for patients with CAP.
PubMed: 36569296
DOI: 10.3389/fphar.2022.1067686 -
Clinical Therapeutics Oct 2016In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparison of Inhaled Antibiotics for the Treatment of Chronic Pseudomonas aeruginosa Lung Infection in Patients With Cystic Fibrosis: Systematic Literature Review and Network Meta-analysis.
PURPOSE
In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). Levofloxacin inhalation solution (LIS) is the most recently approved inhaled antibiotic for adult patients with CF. A systematic literature review and Bayesian network meta-analysis (NMA) was conducted to compare the relative short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics versus LIS.
METHODS
A systematic literature search was conducted on February 16, 2016, using EMBASE and Medline via OvidSP. All randomized controlled trials comparing any of the aforementioned inhaled antibiotics with 4 or 24 weeks of follow-up were evaluated. NMA was performed for the following outcomes: relative and absolute percent changes from baseline in forced expiratory volume in 1 second (FEV%) predicted, change in P aeruginosa sputum density, respiratory symptoms score from the CF questionnaire-revised, hospitalization, additional antibiotics use, and study withdrawal rates.
RESULTS
Of the 685 articles identified, 7 unique studies were included in the 4 weeks' NMA and 9 unique studies were included in the 24 weeks' NMA. Aztreonam was predicted to result in the greatest numerically increase in FEV% predicted at 4 weeks, whereas LIS were predicted to be numerically greater than colistimethate sodium, tobramycin inhaled solution (TIS), and tobramycin inhaled powder (TIP). However, all of the 95% credibility intervals (CrIs) of these comparisons included zero. At 24 weeks, none of the treatments was significantly more effective than LIS. The estimates for the mean change from baseline to 24 weeks in relative FEV% versus LIS was -0.55 (95% CrI, -3.91 to 2.80) for TIS, -2.36 (95% CrI, -7.32 to 2.63) for aztreonam, -2.95 (95% CrI, -10.44 to 4.51) for TIP, and -9.66 (95% CrI, -15.01 to -4.33) for placebo. Compared with LIS, the odds ratio for hospitalization at 24 weeks was 1.92 (95% CrI, 1.01-3.30) for TIS, 2.25 (95% CrI, 1.01-4.34) for TIP, and 3.16 (95% CrI, 1.53-5.78) for placebo, all statistically worse than LIS. P aeruginosa sputum density scores, additional use of antipseudomonal antibiotics, and study withdrawal rates were comparable among all inhaled antibiotics at all times.
IMPLICATIONS
Based on this NMA, the analyses for many of the outcomes did not provide significant evidence to indicate that the other approved inhaled antibiotics were more effective than LIS for the treatment of chronic P aeruginosa lung infection in patients with CF. Study withdrawal rates seemed to be comparable among these inhaled antibiotics.
Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Bayes Theorem; Chronic Disease; Cystic Fibrosis; Europe; Forced Expiratory Volume; Humans; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Tract Infections
PubMed: 27692977
DOI: 10.1016/j.clinthera.2016.08.014 -
BMJ Open Dec 2018To review the literature for non-standard treatment options for uncomplicated (CT) infections in adolescents and adults. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To review the literature for non-standard treatment options for uncomplicated (CT) infections in adolescents and adults.
DESIGN
Systematic review.
DATA SOURCES
Ovid MEDLINE/PubMed, Ovid EMBASE, Cochrane Trials & Systematic Review Databases, CINAHL Plus with Full Text, Web of Science Core Collection, Scopus, ProQuest Dissertations & Theses Global, ClinicalTrials.gov and Health Canada Trials Database were searched for studies in English or French from 1 January 2006 to 6 August 2017. Keywords included CT, anti-infective or anti-bacterial agents, therapy/pharmacotherapy/management.
REVIEW METHODS
Included were primary research studies. Outcome measures included clinical or microbiological cure, treatment failure and adverse events. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were assessed for risk of bias using the Revised Cochrane Risk of Bias V.2.0 tool for randomised and the Newcastle-Ottawa Quality Assessment Scale for non-randomised studies.
FUNDING SOURCE
Public Health Agency of Canada.
RESULTS
Of the 6899 records identified through the database search, 11 studies were included. One randomised controlled trial reported that delayed release doxycycline was non-inferior to azithromycin. Two studies examined higher doses of azithromycin but reported no additional benefit. One study looked at a 5-day azithromycin treatment regimen and reported a high cure rate. Two studies reported efficacy of sitafloxacin, and a single study supports the use of levofloxacin. Two phase 2 studies reported efficacy of single-dose rifalazil in both men and women. Only one retrospective study was identified that examined treatment in pregnant women and reported that efficacy with single-dose azithromycin exceeded that of amoxicillin and erythromycin. A single study examining the efficacy of a beta-lactam antibiotic was stopped early due to high treatment failures.
CONCLUSIONS
The paucity of existing data highlights the need for further adequately powered studies to evaluate rifalazil, delayed release doxycycline, levofloxacin and other agents for the treatment of uncomplicated CT infections.
PROSPERO REGISTRATION NUMBER
CRD42017073096.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Canada; Chlamydia Infections; Chlamydia trachomatis; Databases, Factual; Female; Female Urogenital Diseases; Humans; Lymphogranuloma Venereum; Pregnancy; Prognosis; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome; Young Adult
PubMed: 30518587
DOI: 10.1136/bmjopen-2018-023808 -
Antibiotics (Basel, Switzerland) Sep 2021The emergence of multidrug-resistant poses a public healthcare threat, particularly in low- and middle-income countries. Recently, the World Health Organization has... (Review)
Review
The emergence of multidrug-resistant poses a public healthcare threat, particularly in low- and middle-income countries. Recently, the World Health Organization has classified clarithromycin-resistant as high priority in the research and discovery of novel antibiotics. This study was aimed to systematically review the prevalence of primary antibiotic resistance in in Southeast Asian countries (SEAC) and to review current studies of antimicrobial peptides against . We systematically searched through electronic databases of studies conducted on antimicrobial resistance of in SEA countries. Furthermore, we searched articles that conducted studies on antimicrobial peptides, naturally occurring host's defense molecules, against . After a series of screening processes, 15 studies were included in our systematic review. Our analysis revealed that primary resistance of to metronidazole, clarithromycin, and levofloxacin were high in SEAC, although the primary resistance to amoxicillin and tetracycline remains low. Multidrug-resistant are emerging in SE Asian countries. The antimicrobial peptides show promising antibacterial and antibiofilm activity against drug-resistant . The research and discovery of antimicrobial peptides against in SEAC will help in limiting the spread of antimicrobial resistance of .
PubMed: 34572643
DOI: 10.3390/antibiotics10091061 -
BMC Gastroenterology Jul 2016Approximately half of the world's population is infected with Helicobacter pylori (H.pylori), a bacterium shown to be linked with a series of gastrointestinal diseases.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately half of the world's population is infected with Helicobacter pylori (H.pylori), a bacterium shown to be linked with a series of gastrointestinal diseases. A growing number of systematic reviews (SRs) have been published comparing the effectiveness of different treatments for H.pylori infection but have not reached a consistent conclusion. The objective of this study is to provide an overview of SRs of pharmacological therapies for the eradication of H.pylori.
METHODS
Major electronic databases were searched to identify relevant SRs published between 2002 and February 2016. Studies were considered eligible if they included RCTs comparing different pharmacological regimens for treating patients diagnosed as H.pylori infected and pooled the eradication rates in a meta-analysis. A modified version of the 'A Measurement Tool to Assess Systematic Reviews' (AMSTAR) was used to assess the methodological quality. A Bayesian random effects network meta-analysis (NMA) was conducted to compare the different proton pump inhibitors (PPI) within triple therapy.
RESULTS
30 SRs with pairwise meta-analysis were included. In triple therapy, the NMA ranked the esomeprazole to be the most effective PPI, followed by rabeprazole, while no difference was observed among the three old generations of PPI for the eradication of H.pylori. When comparing triple and bismuth-based therapy, the relative effectiveness appeared to be dependent on the choice of antibiotics within the triple therapy; moxifloxacin or levofloxacin-based triple therapy were both associated with greater effectiveness than bismuth-based therapy as a second-line treatment, while bismuth-based therapy achieved similar or greater eradication rate compared to clarithromycin-based therapy. Inconsistent findings were reported regarding the use of levofloxacin/moxifloxacin in the first-line treatment; this could be due to the varied resistant rate to different antibiotics across regions and populations. Critical appraisal showed a low-moderate level of overall methodological quality of included studies.
CONCLUSIONS
Our analysis suggests that the new generation of PPIs and use of moxifloxacin or levofloxacin within triple therapy as second-line treatment were associated with greater effectiveness. Given the varied antibiotic resistant rate across regions, the appropriateness of pooling results together in meta-analysis should be carefully considered and the recommendation of the choice of antibiotics should be localized.
Topics: Antacids; Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Network Meta-Analysis; Practice Guidelines as Topic; Proton Pump Inhibitors
PubMed: 27460211
DOI: 10.1186/s12876-016-0491-7 -
Journal of Korean Medical Science Aug 2015The efficacy of seven-day clarithromycin-based standard triple therapy (STT) for Helicobacter pylori has decreased in Korea over the past decade. The aim of this... (Meta-Analysis)
Meta-Analysis Review
The efficacy of seven-day clarithromycin-based standard triple therapy (STT) for Helicobacter pylori has decreased in Korea over the past decade. The aim of this meta-analysis was to clarify the efficacy of first-line and second-line therapies in Korea. This systematic review will provide an overview of H. pylori eradication and present new therapeutic strategies used in Korea. An extensive search of the literature concerning STT, sequential therapy (SET), concomitant therapy (CT), bismuth-containing quadruple therapy (BCQT) and various other therapies used in Korea was performed. All selected studies were randomized controlled trials (RCTs). Eighteen RCTs were eligible for systematic review. The alternative regimens comparing seven-day STT as a first-line therapy include SET, CT, levofloxacin-based therapy (LBT), BCQT, and STT with prolonged duration. The results of the meta-analysis suggest that SET is superior to seven-day STT. The overall eradication rate by intention to treat (ITT) analysis was 69.8% for STT and 79.7% for SET. The overall eradication rate by per-protocol (PP) analysis was 77.0% for STT and 85.0% for SET. The odds ratios for the ITT and PP eradication rate were 0.57 (95% confidence interval [CI], 0.43 to 0.74) and 0.52 (95% CI, 0.35 to 0.76), respectively. In the subgroup analysis, however, there were no significant differences between SET and STT with prolonged durations. Alternative regimens to seven-day BCQT as second-line therapy include LBT, moxifloxacin-based therapy and 14-day BCQT. The eradication rates of these alternative regimens were not superior to that of the conventional treatment. SET is superior to seven-day STT but not to STT with prolonged duration.
Topics: Anti-Bacterial Agents; Evidence-Based Medicine; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Practice Patterns, Physicians'; Prevalence; Republic of Korea; Risk Assessment; Treatment Outcome
PubMed: 26240475
DOI: 10.3346/jkms.2015.30.8.1001 -
American Journal of Ophthalmology Aug 2022To summarize key findings from a Cochrane systematic review of the effectiveness and safety of topical pharmacologic interventions compared with active control or... (Review)
Review
PURPOSE
To summarize key findings from a Cochrane systematic review of the effectiveness and safety of topical pharmacologic interventions compared with active control or placebo for epidemic keratoconjunctivitis (EKC).
DESIGN
Systematic review.
METHODS
We included randomized controlled trials that compared antiseptic agents, virustatic agents, or immune-modulating topical therapies with placebo or an active control. We adhered to Cochrane methods for trial selection, data extraction, risk of bias evaluation, and data synthesis.
RESULTS
Ten randomized controlled trials with 892 participants with acute or chronic EKC were included. Eight trials compared interventions with artificial tears or saline (n = 4) or with steroids (n = 4); two 3-arm trials contributed data to both comparisons. Estimates suggested that compared with tears, after povidone-iodine (PVP-I) alone (2 studies, 409 participants) more participants with acute EKC had resolution of symptoms (risk ratio [RR] 1.15 [95% confidence interval {CI} 1.07-1.24]) and signs (RR 3.19 [95% CI 2.29-4.45]) within 10 days. In 2 trials comparing treatments with steroid alone or steroid with levofloxacin, fewer eyes treated with PVP-I or polyvinyl alcohol iodine (PVA-I) plus steroid developed subepithelial infiltrates within 21 days (RR 0.08 [95% CI 0.01-0.55]; 69 eyes). No treatment was shown to improve resolution of infiltrates.
CONCLUSIONS
Low- to very low-level certainty of evidence suggested that PVP-I or PVA-I with steroid may confer some benefit in acute EKC, but imprecision from small sample sizes, the potential risk of bias from inadequate reporting or trial design, and variability in participant selection, outcome measurement, and reporting limit the amount and quality of evidence.
Topics: Anti-Infective Agents, Local; Humans; Keratoconjunctivitis; Lubricant Eye Drops; Povidone-Iodine
PubMed: 35331686
DOI: 10.1016/j.ajo.2022.03.018 -
PloS One 2015Tuberculosis is a major public health problem especially in developing countries, the comparative efficacy and safety of fluroquinolones (FQs) for adult patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculosis is a major public health problem especially in developing countries, the comparative efficacy and safety of fluroquinolones (FQs) for adult patients with newly diagnosed, sputum-positive tuberculosis remains controversial. We aimed to investigate the benefits and risks of FQs-containing (addition/substitution) regimens in this population.
METHODS
A network meta-analysis was performed to compare FQs (C: ciprofloxacin; O: ofloxacin; Lo: levofloxacin; M: moxifloxacin; G: gatifloxacin) addition/substitution regimen with standard HRZE regimen (ie isoniazid, rifampicin, pyrazinamide and ethambutol) in newly diagnosed, sputum-positive tuberculosis. Medline, Embase and Cochrane Central Register of Controlled Trials were systematically searched, randomized trials with duration longer than 8 weeks were included. The primary outcome was week-8 sputum negativity, and secondary outcomes included treatment failure, serious adverse events and death from all cause.
RESULTS
Twelve studies comprising 6465 participants were included in the network meta-analysis. Löwenstein-Jensen culture method showed that HRZEM (OR 4.96, 95% CI 2.83-8.67), MRZE (OR 1.48, 95% CI 1.19-1.84) and HRZM (OR 1.32, 95% CI 1.08-1.62) had more sputum conversion than HRZE by the eighth week, whereas HRC (OR 0.39, 95% CI 0.19-0.77) and HRZO (OR 0.47, 95% CI 0.24-0.92) were worse than HRZE. Moxifloxacin-containing regimens showed more conversion than HRZE by liquid method at the end of two months. But by the end of treatment, FQs-containing regimens didn't show superiority than HRZE on treatment failure. There were no significant differences between any regimens on other outcomes like serious adverse events and all-cause death.
CONCLUSION
This comprehensive network meta-analysis showed that compared with HRZE, moxifloxacin-containing regimens could significantly increase sputum conversion by the eighth week for patients with newly diagnosed pulmonary tuberculosis while HRC and HRZO regimens were inferior. But all the FQs-containing regimens did not show superiority in other outcomes (such as treatment failure, serious adverse events and all-cause death). Thus, HRZE is still an effective regimen for this population. Although moxifloxacin-containing regimens have deomonstrated their potential, FQs-containing regimens should be used with great caution to avoid widespread FQs-resistance worldwide.
Topics: Adult; Antitubercular Agents; Fluoroquinolones; Humans; Publication Bias; Sputum; Treatment Outcome; Tuberculosis, Pulmonary
PubMed: 26669635
DOI: 10.1371/journal.pone.0145066 -
Iranian Journal of Public Health Jun 2021We aimed to review relevant randomized controlled trials to assess the relative clinical effects of antibiotic treatment of patients with community-acquired pneumonia... (Review)
Review
BACKGROUND
We aimed to review relevant randomized controlled trials to assess the relative clinical effects of antibiotic treatment of patients with community-acquired pneumonia (CAP).
METHODS
In this meta-analysis, we identified relevant studies from PubMed, Cochrane, and Embase using appropriate keywords. Key pertinent sources in the literature were also reviewed and all articles published through Oct 2019 were considered for inclusion. For each study, we assessed the risk ratios (RRs) or mean difference combined with the 95% confidence interval (CI) to assess and synthesize outcomes.
RESULTS
Overall, 36 studies were consistent with the meta-analysis, involving 17,076 patients. There was no significant difference in the mortality after subgroup analysis: individualized treatment vs. standard treatment; β-lactams plus macrolides vs. β-lactam and/or fluoroquinolone; ceftaroline fosamil vs. ceftriaxone; combination therapy vs. monotherapy or high-dose vs. low-dose. The drug-related adverse event incidence was significantly higher in the ceftriaxone group than in the other drug groups (<0.05) and also higher in the tigecyline group than in the levofloxacin group (<0.05). Compared with ceftriaxone, ceftaroline fosamil significantly increased the clinical cure rate at the test-of-cure (TOC) visit in the clinically evaluable population, modified intent-to-treat efficacy (MITTE) population, microbiologically evaluable (ME) population and the microbiological MITTE (mMITTE) population (all <0.05). Compared with ceftriaxone, ceftaroline fosamil significantly increased the clinical cure rate at the TOC visit in the mMITTE population of Gram positive- (<0.05) and multidrug-resistant (<0.05).
CONCLUSION
There was a limited number of included studies in the subgroup analysis, but it will still be necessary to conduct more high-quality randomized controlled trials to confirm the clinical efficacy of different antibiotics used to treat CAP.
PubMed: 34540732
DOI: 10.18502/ijph.v50i6.6410 -
Frontiers in Pharmacology 2020To study the prescribing pattern of antibiotics in outpatients and emergency departments in the Gulf region. To compare the appropriateness of prescriptions and...
To study the prescribing pattern of antibiotics in outpatients and emergency departments in the Gulf region. To compare the appropriateness of prescriptions and antibiotics commonly prescribed for respiratory tract infection. The search was limited to the years 2008-2020, and articles had to be in English. Articles were searched from various resources and evaluated using PRISMA. Forty-one articles were selected and screened, and in the end, 17 articles were included in the study. All articles were selected from the gulf region of six countries: UAE, Saudi Arabia, Qatar, Oman, Yemen, and Bahrain. Only primary literature were included. Inpatient and literature from other countries outside the gulf region were excluded. Penicillins, cephalosporins, and macrolides are highly useful antibiotics for respiratory tract infections. Ceftriaxone IV is recommended in acute respiratory tract infection if therapy with penicillin fails. Most of the antibiotic prescriptions in Gulf countries are inappropriate. Inappropriate antibiotic prescribing in the gulf region varies from place to place and reaches a maximum of 80%. Antibiotics may be prescribed with the wrong dosage or frequency and inappropriate guidelines. Penicillins are prescribed at about 50-60%; the most common penicillins prescribed are amoxicillin and co-amoxiclave. Cephalosporins are prescribed at about 30%, and the most common are third-generation. Macrolides are prescribed at about 17-20%, and the most common macrolides are azithromycin and clarithromycin. Fluoroquinolones are prescribed at about 10-12%, of which levofloxacin and ciprofloxacin are more commonly prescribed with metronidazole at 10%. It is suggested that the antibiotic-prescribing pattern in outpatient and emergency departments in the Gulf region are highly inappropriate and need improvement through education, following guidelines, annual vaccination, and stewardship programs; the most prescribed antibiotic is amoxicillin/co-amoxiclave, and the most often encountered infection in outpatients is acute respiratory tract infection.
PubMed: 33424594
DOI: 10.3389/fphar.2020.585051