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BMJ Open Respiratory Research Aug 2023Current evidence on the effectiveness of SARS-CoV-2 prophylaxis is inconclusive. We aimed to systematically evaluate published studies on repurposed drugs for the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Current evidence on the effectiveness of SARS-CoV-2 prophylaxis is inconclusive. We aimed to systematically evaluate published studies on repurposed drugs for the prevention of laboratory-confirmed SARS-CoV-2 infection and/or COVID-19 among healthy adults.
DESIGN
Systematic review.
ELIGIBILITY
Quantitative experimental and observational intervention studies that evaluated the effectiveness of repurposed drugs for the primary prevention of SARS-CoV-2 infection and/or COVID-19 disease.
DATA SOURCE
PubMed and Embase (1 January 2020-28 September 2022).
RISK OF BIAS
Cochrane Risk of Bias 2.0 and Risk of Bias in Non-Randomised Studies of Interventions tools were applied to assess the quality of studies.
DATA ANALYSIS
Meta-analyses for each eligible drug were performed if ≥2 similar study designs were available.
RESULTS
In all, 65 (25 trials, 40 observational) and 29 publications were eligible for review and meta-analyses, respectively. Most studies pertained to hydroxychloroquine (32), ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) (11), statin (8), and ivermectin (8). In trials, hydroxychloroquine prophylaxis reduced laboratory-confirmed SARS-CoV-2 infection (risk ratio: 0.82 (95% CI 0.74 to 0.90), I=48%), a result largely driven by one clinical trial (weight: 60.5%). Such beneficial effects were not observed in observational studies, nor for prognostic clinical outcomes. Ivermectin did not significantly reduce the risk of SARS-CoV-2 infection (RR: 0.35 (95% CI 0.10 to 1.26), I=96%) and findings for clinical outcomes were inconsistent. Neither ACEi or ARB were beneficial in reducing SARS-CoV-2 infection. Most of the evidence from clinical trials was of moderate quality and of lower quality in observational studies.
CONCLUSIONS
Results from our analysis are insufficient to support an evidence-based repurposed drug policy for SARS-CoV-2 prophylaxis because of inconsistency. In the view of scarce supportive evidence on repurposing drugs for COVID-19, alternative strategies such as immunisation of vulnerable people are warranted to prevent the future waves of infection.
PROSPERO REGISTRATION NUMBER
CRD42021292797.
Topics: Adult; Humans; COVID-19; Pandemics; SARS-CoV-2; Angiotensin Receptor Antagonists; Hydroxychloroquine; Ivermectin; Angiotensin-Converting Enzyme Inhibitors; Primary Prevention
PubMed: 37640510
DOI: 10.1136/bmjresp-2023-001674 -
Scientific Reports Aug 2023The purpose of this study is to evaluate the efficacy of prophylactic use amphotericin B in patients with hematologic disorders complicated by neutropenia. We searched... (Meta-Analysis)
Meta-Analysis
The purpose of this study is to evaluate the efficacy of prophylactic use amphotericin B in patients with hematologic disorders complicated by neutropenia. We searched the PubMed, EMBASE, The Cochrane Library, CBM, CNKI, VIP and WanFang Data database and the China Clinical Trials Registry ( www.chictr.org.cn ) to collect randomized controlled trials (RCTs) of amphotericin B for patients with hematologic disorders complicated by neutropenia from inception to May 2023. The Cochrane risk-of-bias tool for RCTs was used to assess the bias risk of the included studies. The meta-analysis was performed using RevMan 5.3 software. A total of 6 studies with a total of 1019 patients were included. The results of the meta-analysis showed that the treatment group was superior to the control group in terms of the fungal infection rate, and the differences were statistically significant [RR = 0.47, 95% CI (0.32, 0.69), P < 0.0001]. There was no significant difference between the two groups in terms of the mortality [RR = 0.87, 95% CI (0.61, 1.23), P = 0.43] and the incidence of colonization [OR = 0.51, 95% CI (0.25, 1.03), P = 0.06]. The evidence shows that amphotericin B prophylactic use for patients with hematologic disorders complicated by neutropenia can decrease the fungal infection rate. However, there was no significant difference in reducing mortality or the incidence of colonization. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.
Topics: Humans; Amphotericin B; Neutropenia; Hematologic Diseases; China; Databases, Factual
PubMed: 37635176
DOI: 10.1038/s41598-023-41268-1 -
Annals of Clinical Microbiology and... Aug 2023Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. The two stages of melioidosis treatment are the intense intravenous phase and the... (Review)
Review
BACKGROUND
Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. The two stages of melioidosis treatment are the intense intravenous phase and the oral eradication phase. Although co-trimoxazole has been in use for several years, the literature does not demonstrate uniformity of the drug doses, combinations, or durations suitable for the eradication phase of melioidosis. The safety profile of co-trimoxazole was not documented in the literature, nor have systematic studies of its effectiveness been done. This systematic review sought to study on the dose, duration and combination of co-trimoxazole therapy in view of clinical efficacy and safety in the eradication phase of melioidosis.
MAIN BODY
This systematic review included all of the published articles that employed co-trimoxazole in the eradication phase after 1989, including, randomized clinical trials, case-control studies, cohorts, case reports, and case series. Throughout the eradication (maintenance) phase, co-trimoxazole usage was permissible in any dose for any period. A total of 40 results were included in the analysis which contained six clinical trials, one cohort study, one Cochrane review, and thirty-two case series/case reports. Clinical and microbial relapse rates are low when co-trimoxazole is used in single therapy than in combination. There were several adverse events of co-trimoxazole, however, a quantitative analysis was not conducted as the data did not include quantitative values in most studies.
SHORT CONCLUSION
The dose of co-trimoxazole, duration of the eradication phase, and other combinations used in the treatment was varying between studies. Compared to combined therapy patients treated with co-trimoxazole alone the mortality and relapse rates were low. The lowest relapse rate and lowest mortality rate occur when using co-trimoxazole 1920 mg twice daily. The duration of therapy varies on the focus of melioidosis and it is ranged from 2 months to one year and minimum treatment duration associated with low relapse rate is 3 months. The use of co-trimoxazole over the maintenance phase of melioidosis is associated with clinical cure but has adverse effects.
Topics: Humans; Melioidosis; Cohort Studies; Administration, Intravenous; Case-Control Studies; Drug-Related Side Effects and Adverse Reactions; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 37592339
DOI: 10.1186/s12941-023-00620-z -
Annals of Clinical Microbiology and... Aug 2023Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations.... (Review)
Review
Pan-American Guidelines for the treatment of SARS-CoV-2/COVID-19: a joint evidence-based guideline of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API).
BACKGROUND
Since the beginning of the COVID-19 pandemic, therapeutic options for treating COVID-19 have been investigated at different stages of clinical manifestations. Considering the particular impact of COVID-19 in the Americas, this document aims to present recommendations for the pharmacological treatment of COVID-19 specific to this population.
METHODS
Fifteen experts, members of the Brazilian Society of Infectious Diseases (SBI) and the Pan-American Association of Infectious Diseases (API) make up the panel responsible for developing this guideline. Questions were formulated regarding prophylaxis and treatment of COVID-19 in outpatient and inpatient settings. The outcomes considered in decision-making were mortality, hospitalisation, need for mechanical ventilation, symptomatic COVID-19 episodes, and adverse events. In addition, a systematic review of randomised controlled trials was conducted. The quality of evidence assessment and guideline development process followed the GRADE system.
RESULTS
Nine technologies were evaluated, and ten recommendations were made, including the use of tixagevimab + cilgavimab in the prophylaxis of COVID-19, tixagevimab + cilgavimab, molnupiravir, nirmatrelvir + ritonavir, and remdesivir in the treatment of outpatients, and remdesivir, baricitinib, and tocilizumab in the treatment of hospitalised patients with severe COVID-19. The use of hydroxychloroquine or chloroquine and ivermectin was discouraged.
CONCLUSION
This guideline provides recommendations for treating patients in the Americas following the principles of evidence-based medicine. The recommendations present a set of drugs that have proven effective in the prophylaxis and treatment of COVID-19, emphasising the strong recommendation for the use of nirmatrelvir/ritonavir in outpatients as the lack of benefit from the use of hydroxychloroquine and ivermectin.
Topics: Humans; United States; COVID-19; SARS-CoV-2; Ritonavir; Hydroxychloroquine; Pandemics; Brazil; Ivermectin; Communicable Diseases; Antiviral Agents
PubMed: 37550690
DOI: 10.1186/s12941-023-00623-w -
BMC Microbiology Jul 2023While trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line therapy of Stenotrophomonas maltophilia infections, colistin is one of the therapeutic options in cases... (Meta-Analysis)
Meta-Analysis
While trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line therapy of Stenotrophomonas maltophilia infections, colistin is one of the therapeutic options in cases of allergy or resistance to TMP-SMX. However, understanding the global status of resistance to colistin amongst S. maltophilia isolates could be helpful for appropriate antibiotic prescription. This study aimed to conduct a systematic review and meta-analysis to examine the prevalence of colistin resistance in clinical S. maltophilia isolates worldwide. According to eligibility criteria, a total of 61 studies were included in the analysis. The pooled prevalence for colistin resistance was 42% (95% CI: 35-49%), ranging from 0.1 to 97%. Subgroups analysis indicated that, the pooled prevalence of colistin resistance was 44% (95% CI: 29-60%) in 15 studies during 2000-2010, and it was estimated to be 41% (95% CI: 33-50%) in 46 articles from 2011 to 2021. It was 46% (95% CI: 35-58%) in the studies that used broth microdilution method, and 39% (95% CI: 30-49%) in the studies with other used methods. The resistance rate in Asian countries was 45% (95% CI: 31-60%), in European countries was 45% (95% CI: 34-56%) and in the countries of North and South America was 33% (95% CI: 20-46%). Our review showed notable resistance to colistin in clinical S. maltophilia isolates. Given the estimated resistance rates, alternative antibiotics could be preferred to treat serious infections due to S. maltophilia.
Topics: Humans; Colistin; Trimethoprim, Sulfamethoxazole Drug Combination; Stenotrophomonas maltophilia; Prevalence; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 37507660
DOI: 10.1186/s12866-023-02950-6 -
PLoS Neglected Tropical Diseases Jul 2023Nocardia species can cause local or disseminated infection. Prompt diagnosis and appropriate treatment of nocardiosis are required, because it can cause significant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nocardia species can cause local or disseminated infection. Prompt diagnosis and appropriate treatment of nocardiosis are required, because it can cause significant morbidity and mortality. Knowledge of local species distribution and susceptibility patterns is important to appropriate empiric therapy. However, knowledge on the epidemiology and antimicrobial susceptibility profiles of clinical Nocardia species remains limited in China.
METHODS
The data of isolation of Nocardia species were collected from databases such as Pubmed, Web of Science, Embase as well as Chinese databases (CNKI, Wanfang and VIP). Meta-analysis was performed using RevMan 5.3 software. Random effect models were used and tested with Cochran's Q and I2 statistics taking into account the possibility of heterogeneity between studies.
RESULTS
In total, 791 Nocardia isolates were identified to 19 species levels among all the recruited studies. The most common species were N. farcinica (29.1%, 230/791), followed by N. cyriacigeorgica (25.3%, 200/791), N. brasiliensis (11.8%, 93/791) and N. otitidiscaviarum (7.8%, 62/791). N. farcinica and N. cyriacigeorgica were widely distributed, N. brasiliensis mainly prevalent in the south, N. otitidiscaviarum mainly distributed in the eastern coastal provinces of China. Totally, 70.4% (223/317) Nocardia were cultured from respiratory tract specimens, 16.4% (52/317) from extra-pulmonary specimens, and 13.3% (42/317) from disseminated infection. The proportion of susceptible isolates as follows: linezolid 99.5% (197/198), amikacin 96.0% (190/198), trimethoprim-sulfamethoxazole 92.9% (184/198), imipenem 64.7% (128/198). Susceptibility varied by species of Nocardia.
CONCLUSIONS
N. farcinica and N. cyriacigeorgica are the most frequently isolated species, which are widely distributed in China. Pulmonary nocardiosis is the most common type of infection. Trimethoprim-sulfamethoxazole can still be the preferred agent for initial Nocardia infection therapy due to the low resistance rate, linezolid and amikacin could be an alternative to treat nocardiosis or a choice in a combination regimen.
Topics: Humans; Nocardia; Anti-Bacterial Agents; Trimethoprim, Sulfamethoxazole Drug Combination; Linezolid; Amikacin; Microbial Sensitivity Tests; Drug Resistance, Bacterial; Nocardia Infections; China
PubMed: 37428800
DOI: 10.1371/journal.pntd.0011432 -
The American Journal of Tropical... Aug 2023Little is known about the adverse health, economic, and social impacts of substandard and falsified medicines (SFMs). This systematic review aimed to identify the...
Little is known about the adverse health, economic, and social impacts of substandard and falsified medicines (SFMs). This systematic review aimed to identify the methods used in studies to measure the impact of SFMs in low- and middle-income countries (LMICs), summarize their findings, and identify gaps in the reviewed literature. A search of eight databases for published papers, and a manual search of references in the relevant literature were conducted using synonyms of SFMs and LMICs. Studies in the English language that estimated the health, social, or economic impacts of SFMs in LMICs published before June 17, 2022 were considered eligible. Search results generated 1,078 articles, and 11 studies were included after screening and quality assessment. All included studies focused on countries in sub-Saharan Africa. Six studies used the Substandard and Falsified Antimalarials Research Impact model to estimate the impact of SFMs. This model is an important contribution. However, it is technically challenging and data demanding, which poses challenges to its adoption by national academics and policymakers alike. The included studies estimate that substandard and falsified antimalarial medicines can account from 10% to ∼40% of total annual malaria costs, and SFMs affect rural and poor populations disproportionately. Evidence on the impact of SFMs is limited in general and nonexistent regarding social outcomes. Further research needs to focus on practical methods that can serve local authorities without major investments in terms of technical capacity and data collection.
Topics: Humans; Counterfeit Drugs; Developing Countries; Social Change; Antimalarials; Malaria
PubMed: 37339762
DOI: 10.4269/ajtmh.22-0525 -
BMJ Open Jun 2023We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised controlled trials (RCTs).
DATA SOURCES
PubMed and EMBASE databases were searched to identify randomised trials studying HCQ.
STUDY SELECTION
Ten RCTs were identified (n=5079 participants).
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and meta-analysis between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis plan was written.
MAIN OUTCOMES
The primary efficacy outcome was PCR-confirmed SARS-CoV-2 infection and the primary safety outcome was incidence of adverse events. The secondary outcome included clinically suspected SARS-CoV-2 infection.
RESULTS
Compared with placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected SARS-CoV-2 infection (OR 0.78, 95% CI: 0.57, 1.10), but significant difference in adverse events (OR 1.35, 95% CI: 1.03, 1.73).
CONCLUSIONS AND RELEVANCE
Our meta-analysis of 10 RCTs investigating the safety and efficacy of HCQ as pre-exposure prophylaxis in HCWs found that compared with placebo, HCQ does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 infection, while HCQ significantly increases adverse events.
PROSPERO REGISTRATION NUMBER
CRD42021285093.
Topics: Humans; COVID-19; COVID-19 Drug Treatment; Health Personnel; Hydroxychloroquine; SARS-CoV-2; Pre-Exposure Prophylaxis
PubMed: 37328184
DOI: 10.1136/bmjopen-2022-065305 -
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 -
PLoS Neglected Tropical Diseases Jun 2023This systematic review and network meta-analysis (NMA) aimed to compare the efficacy of all available treatments for severe melioidosis in decreasing hospital mortality... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and network meta-analysis (NMA) aimed to compare the efficacy of all available treatments for severe melioidosis in decreasing hospital mortality and to identify eradication therapies with low disease recurrence rates and minimal risk of adverse drug events (AEs).
METHODOLOGY
Relevant randomized controlled trials (RCT) were searched from Medline and Scopus databases from their inception until July 31, 2022. RCTs that compared the efficacy between treatment regimens for severe melioidosis or eradication therapy of melioidosis, measured outcomes of in-hospital mortality, disease recurrence, drug discontinuation, or AEs, were included for review. A two-stage NMA with the surface under the cumulative ranking curve (SUCRA) was used to estimate the comparative efficacy of treatment regimens.
PRINCIPAL FINDINGS
Fourteen RCTs were included in the review. Ceftazidime plus granulocyte colony-stimulating factor (G-CSF), ceftazidime plus trimethoprim-sulfamethoxazole (TMP-SMX), and cefoperazone-sulbactam plus TMP-SMX had a lower mortality rate than other treatments and were ranked as the top three most appropriate treatments for severe melioidosis with the SUCRA of 79.7%, 66.6%, and 55.7%, respectively. However, these results were not statistically significant. For eradication therapy, treatment with doxycycline monotherapy for 20 weeks was associated with a significantly higher risk of disease recurrence than regimens containing TMP-SMX (i.e.,TMP-SMX for 20 weeks, TMP-SMX plus doxycycline plus chloramphenicol for more than 12 weeks, and TMP-SMX plus doxycycline for more than 12 weeks). According to the SUCRA, TMP-SMX for 20 weeks was ranked as the most efficacious eradication treatment (87.7%) with the lowest chance of drug discontinuation (86.4%), while TMP-SMX for 12 weeks had the lowest risk of AEs (95.6%).
CONCLUSION
Our results found a non-significant benefit of ceftazidime plus G-CSF and ceftazidime plus TMP-SMX over other treatments for severe melioidosis. TMP-SMX for 20 weeks was associated with a lower recurrence rate and minimal risk of adverse drug events compared to other eradication treatments. However, the validity of our NMA may be compromised by the limited number of included studies and discrepancies in certain study parameters. Thus, additional well-designed RCTs are needed to improve the therapy of melioidosis.
Topics: Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Melioidosis; Doxycycline; Ceftazidime; Network Meta-Analysis; Granulocyte Colony-Stimulating Factor; Drug-Related Side Effects and Adverse Reactions
PubMed: 37307278
DOI: 10.1371/journal.pntd.0011382