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Pharmacological Research Aug 2022We aimed to assess the effect of second-line anti-TB treatment and determine which drugs can achieve the greatest clinical benefit for DR-TB-HIV patients by comparing... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We aimed to assess the effect of second-line anti-TB treatment and determine which drugs can achieve the greatest clinical benefit for DR-TB-HIV patients by comparing multiple chemotherapy regimens, to provide a basis for evidence-based practice.
METHODS
We searched three electronic databases (PubMed, Web of Science and Cochrane) for related English studies published since 2010. A random-effect model was used to estimate the pooled result for the treatment outcomes. Subgroup analysis based on possible factors, such as ART, baseline CD4 T-cell count, treatment regimens, and profiles of drug resistance, was also conducted to assess factors for favorable outcome. Outcomes were treatment success and mortality.
RESULTS
38 studies, 40 cohorts with 9279 patients were included. The pooled treatment success, mortality, treatment failure, and default rates were 57.5 % (95 % CI 53.1-61.9), 21 % (95 % CI 17.8-24.6), 4.8 % (95 % CI 3.5-6.5), and 10.7 % (95 % CI 8.7-13.1), respectively, in patients with DR-TB and HIV co-infection. Subgroup analysis showed that BDQ and LZD based regimen, and ≥ 2 Group A drugs were associated with a higher treatment success rate. Besides, higher CD4 T-cell count at baseline was also correlated with higher treatment success rate, too.
CONCLUSIONS
Suboptimal anti-TB outcomes underlining the need to expand the application of effective drugs and better regimen in high HIV setting. BDQ and LZD based all-oral regimen and early ART could contribute to higher treatment success, particularly among XDR-TB-HIV patients. Given that all included studies were observational, our findings emphasize the need for high-quality studies to further investigate the optimal treatment regimen for DR-TB-HIV.
Topics: Antitubercular Agents; Diarylquinolines; Extensively Drug-Resistant Tuberculosis; HIV Infections; Humans; Linezolid; Treatment Outcome; Tuberculosis, Multidrug-Resistant
PubMed: 35779814
DOI: 10.1016/j.phrs.2022.106336 -
The Cochrane Database of Systematic... Nov 2022Inhaled antibiotics are commonly used to treat persistent airway infection with Pseudomonas aeruginosa that contributes to lung damage in people with cystic fibrosis.... (Review)
Review
BACKGROUND
Inhaled antibiotics are commonly used to treat persistent airway infection with Pseudomonas aeruginosa that contributes to lung damage in people with cystic fibrosis. Current guidelines recommend inhaled tobramycin for individuals with cystic fibrosis and persistent Pseudomonas aeruginosa infection who are aged six years or older. The aim is to reduce bacterial load in the lungs so as to reduce inflammation and deterioration of lung function. This is an update of a previously published review.
OBJECTIVES
To evaluate the effects of long-term inhaled antibiotic therapy in people with cystic fibrosis on clinical outcomes (lung function, frequency of exacerbations and nutrition), quality of life and adverse events (including drug-sensitivity reactions and survival).
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched ongoing trials registries. Date of last search: 28 June 2022.
SELECTION CRITERIA
We selected trials where people with cystic fibrosis received inhaled anti-pseudomonal antibiotic treatment for at least three months, treatment allocation was randomised or quasi-randomised, and there was a control group (either placebo, no placebo or another inhaled antibiotic).
DATA COLLECTION AND ANALYSIS
Two authors independently selected trials, judged the risk of bias, extracted data from these trials and judged the certainty of the evidence using the GRADE system.
MAIN RESULTS
The searches identified 410 citations to 125 trials; 18 trials (3042 participants aged between five and 45 years) met the inclusion criteria. Limited data were available for meta-analyses due to the variability of trial design and reporting of results. A total of 11 trials (1130 participants) compared an inhaled antibiotic to placebo or usual treatment for a duration between three and 33 months. Five trials (1255 participants) compared different antibiotics, two trials (585 participants) compared different regimens of tobramycin and one trial (90 participants) compared intermittent tobramycin with continuous tobramycin alternating with aztreonam. One trial (18 participants) compared an antibiotic to placebo and also to a different antibiotic and so fell into both groups. The most commonly studied antibiotic was tobramycin which was studied in 12 trials. Inhaled antibiotics compared to placebo We found that inhaled antibiotics may improve lung function measured in a variety of ways (4 trials, 814 participants). Compared to placebo, inhaled antibiotics may also reduce the frequency of exacerbations (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.47 to 0.93; 3 trials, 946 participants; low-certainty evidence). Inhaled antibiotics may lead to fewer days off school or work (quality of life measure) (mean difference (MD) -5.30 days, 95% CI -8.59 to -2.01; 1 trial, 245 participants; low-certainty evidence). There were insufficient data for us to be able to report an effect on nutritional outcomes and there was no effect on survival. There was no effect on antibiotic resistance seen in the two trials that were included in meta-analyses. We are uncertain of the effect of the intervention on adverse events (very low-certainty evidence), but tinnitus and voice alteration were the only events occurring more often in the inhaled antibiotics group. The overall certainty of evidence was deemed to be low for most outcomes due to risk of bias within the trials and imprecision due to low event rates. Different antibiotics or regimens compared Of the eight trials comparing different inhaled antibiotics or different antibiotic regimens, there was only one trial for each unique comparison. We found no differences between groups for any outcomes except for the following. Aztreonam lysine for inhalation probably improved forced expiratory volume at one second (FEV) % predicted compared to tobramycin (MD -3.40%, 95% CI -6.63 to -0.17; 1 trial, 273 participants; moderate-certainty evidence). However, the method of defining the endpoint was different to the remaining trials and the participants were exposed to tobramycin for a long period making interpretation of the results problematic. We found no differences in any measure of lung function in the remaining comparisons. Trials measured pulmonary exacerbations in different ways and showed no differences between groups except for aztreonam lysine probably leading to fewer people needing treatment with additional antibiotics than with tobramycin (RR 0.66, 95% CI 0.51 to 0.86; 1 trial, 273 participants; moderate-certainty evidence); and there were fewer hospitalisations due to respiratory exacerbations with levofloxacin compared to tobramycin (RR 0.62, 95% CI 0.40 to 0.98; 1 trial, 282 participants; high-certainty evidence). Important treatment-related adverse events were not very common across comparisons, but were reported less often in the tobramycin group compared to both aztreonam lysine and colistimethate. We found the certainty of evidence for these comparisons to be directly related to the risk of bias within the individual trials and varied from low to high.
AUTHORS' CONCLUSIONS
Long-term treatment with inhaled anti-pseudomonal antibiotics probably improves lung function and reduces exacerbation rates, but pooled estimates of the level of benefit were very limited. The best evidence available is for inhaled tobramycin. More evidence from trials measuring similar outcomes in the same way is needed to determine a better measure of benefit. Longer-term trials are needed to look at the effect of inhaled antibiotics on quality of life, survival and nutritional outcomes.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Middle Aged; Young Adult; Anti-Bacterial Agents; Aztreonam; Cystic Fibrosis; Lysine; Quality of Life; Tobramycin; Randomized Controlled Trials as Topic
PubMed: 36373968
DOI: 10.1002/14651858.CD001021.pub4 -
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 -
The Lancet Regional Health. Southeast... Jul 2022A major driver of antimicrobial resistance (AMR) and poor clinical outcomes is suboptimal antibiotic use, although data are lacking in low-resource settings. We...
BACKGROUND
A major driver of antimicrobial resistance (AMR) and poor clinical outcomes is suboptimal antibiotic use, although data are lacking in low-resource settings. We reviewed studies on systemic antibiotic use (WHO ATC/DDD category J01) for human health in Indonesia, and synthesized available evidence to identify opportunities for intervention.
METHODS
We systematically searched five international and national databases for eligible peer-reviewed articles, in English and Indonesian, published between 1 January 2000 and 1 June 2021 including: (1) antibiotic consumption; (2) prescribing appropriateness; (3) antimicrobial stewardship (AMS); (4) consumers' and providers' perceptions. Two independent reviewers included studies and extracted data. Study-level data were summarized using random-effects model meta-analysis for consumption and prescribing appropriateness, effect direction analysis for antimicrobial stewardship (AMS) interventions, and qualitative synthesis for perception surveys. (PROSPERO: CRD42019134641).
FINDINGS
Of 9323 search hits, we included 100 reports on antibiotic consumption (20), prescribing appropriateness (49), AMS interventions (13), and/or perception (25) (8 categorized in >1 domain). The pooled estimate of overall antibiotic consumption was 134.8 DDD per 100 bed-days (95%CI 82.5-187.0) for inpatients and 121.1 DDD per 1000 inhabitants per day (10.4-231.8) for outpatients. Ceftriaxone, levofloxacin, and ampicillin were the most consumed antibiotics in inpatients, and amoxicillin, ciprofloxacin, and cefadroxil in outpatients. Pooled estimates for overall appropriate prescribing (according to Gyssens method) were 33.5% (18.1-53.4) in hospitals and 49.4% (23.7-75.4) in primary care. Pooled estimates for appropriate prescribing (according to reference guidelines) were, in hospitals, 99.7% (97.4-100) for indication, 84.9% (38.5-98.0) for drug choice, and 6.1% (0.2-63.2) for overall appropriateness, and, in primary care, 98.9% (60.9-100) for indication, 82.6% (50.5-95.7) for drug choice and 10.5% (0.8-62.6) for overall appropriateness. Studies to date evaluating bundled AMS interventions, although sparse and heterogeneous, suggested favourable effects on antibiotic consumption, prescribing appropriateness, guideline compliance, and patient outcomes. Key themes identified in perception surveys were lack of community antibiotic knowledge, and common non-prescription antibiotic self-medication.
INTERPRETATION
Context-specific intervention strategies are urgently needed to improve appropriate antibiotic use in Indonesian hospitals and communities, with critical evidence gaps concerning the private and informal healthcare sectors.
FUNDING
Wellcome Africa Asia Programme Vietnam.
PubMed: 37383293
DOI: 10.1016/j.lansea.2022.05.002 -
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 -
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 -
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 -
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 -
Gastroenterology Research Dec 2020(HP) is the most common cause of gastritis worldwide. Clarithromycin-based triple therapy or bismuth-based quadruple therapy is usually considered the first-line...
BACKGROUND
(HP) is the most common cause of gastritis worldwide. Clarithromycin-based triple therapy or bismuth-based quadruple therapy is usually considered the first-line treatment, however with around 30% failure rate for both regimens. Drug resistance of clarithromycin and metronidazole is a growing concern in some parts of the world. Therefore, there is a need for effective eradication regimen for HP. Nitazoxanide, a bactericidal thiazolide antibiotic, has been shown to be effective in HP infection. We conducted a systematic review and meta-analysis to evaluate the efficacy of nitazoxanide-based regimen for the eradication of HP.
METHODS
We have searched PubMed, Embase, Ovid Medline and Cochrane library database from inception to December 9, 2020 to identify studies that utilized nitazoxanide in the treatment regimen for HP eradication. Our primary outcome was pooled eradication rate of HP.
RESULTS
Thirteen studies including 1,028 patients met our inclusion criteria and were analyzed in a meta-analysis. HP eradication was successful in 867 patients with a pooled eradication rate of 86% (95% confidence interval (CI): 79-90%) with 84% heterogeneity. A subgroup analysis that included 230 patients who failed other prior eradication regimens revealed a pooled eradication rate of 85% (95% CI: 69-94%) without heterogeneity. In a subgroup analysis, highest eradication rates were achieved with levofloxacin, doxycycline, nitazoxanide and proton pump inhibitor with a pooled eradication rate of 92% (88-95%).
CONCLUSION
Nitazoxanide-based regimen is safe and effective in the eradication of HP infection. It is also successful as a salvage therapy in patients who have failed prior treatments.
PubMed: 33447305
DOI: 10.14740/gr1342 -
International Journal of Microbiology 2022Carbapenems are the last-line therapy for multidrug-resistant (MDR) infections caused by including those caused by species. However, the recent emergence of...
BACKGROUND
Carbapenems are the last-line therapy for multidrug-resistant (MDR) infections caused by including those caused by species. However, the recent emergence of carbapenem-resistant (CR) and extended-spectrum -lactamase (ESBL)-producing pathogens, which are resistant to nearly all antibiotics, has raised concerns among international healthcare organizations. Hence, because there is no comprehensive data in Iran, the current study aimed to evaluate the prevalence of antibiotic resistance among species, especially CR and ESBL-producing strains, in Iran.
METHODS
The literature search was performed up to June 21, 2021, in national and international databases using MeSH-extracted keywords, i.e., , antibiotic resistance, carbapenem, ESBL, and Iran. Study selection was done based on the predefined inclusion and exclusion criteria, and data analysis was carried out using the Comprehensive Meta-Analysis (CMA) software.
RESULTS
The pooled prevalence of species resistant to various antibiotics is as follows: imipenem 16.6%, meropenem 16.2%, aztreonam 40.9%, ciprofloxacin 35.3%, norfloxacin 31%, levofloxacin 48%, gentamicin 42.1%, amikacin 30.3%, tobramycin 37.2%, tetracycline 50.1%, chloramphenicol 25.7%, trimethoprim/sulfamethoxazole 52%, nalidixic acid 49.1%, nitrofurantoin 43%, ceftriaxone 49.3%, cefixime 52.4%, cefotaxime 52.7%, ceftazidime 47.9%, cefepime 43.6%, and ceftizoxime 45.5%. The prevalence rates of MDR and ESBL-producing species in Iran were 63.1% and 32.8%, respectively.
CONCLUSION
In accordance with the warning of international organizations, our results revealed a high prevalence of ESBL-producing species in Iran, which is probably associated with the high prevalence of species resistant to most of the assessed antibiotics, especially MDR strains. However, the resistance rate to carbapenems was relatively low, and these drugs can still be considered as drugs of choice for the treatment of infections in Iran. Nevertheless, continuous monitoring of drug resistance along with antibiotic therapy based on the local data and evaluation of the therapeutic efficacy of new antibiotics or combination therapeutic strategies, such as ceftazidime/avibactam, meropenem/vaborbactam, plazomicin, and eravacycline, is recommended.
PubMed: 36312785
DOI: 10.1155/2022/8367365