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The Cochrane Database of Systematic... Feb 2024The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and... (Review)
Review
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and societies worldwide. Favipiravir was suggested by some experts to be effective and safe to use in COVID-19. Although this drug has been evaluated in randomized controlled trials (RCTs), it is still unclear if it has a definite role in the treatment of COVID-19.
OBJECTIVES
To assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID-19.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, and three other databases, up to 18 July 2023.
SELECTION CRITERIA
We searched for RCTs evaluating the efficacy of favipiravir in treating people with COVID-19.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures for data collection and analysis. We used the GRADE approach to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included 25 trials that randomized 5750 adults (most under 60 years of age). The trials were conducted in Bahrain, Brazil, China, India, Iran, Kuwait, Malaysia, Mexico, Russia, Saudi Arabia, Thailand, the UK, and the USA. Most participants were hospitalized with mild to moderate disease (89%). Twenty-two of the 25 trials investigated the role of favipiravir compared to placebo or standard of care, whilst lopinavir/ritonavir was the comparator in two trials, and umifenovir in one trial. Most trials (24 of 25) initiated favipiravir at 1600 mg or 1800 mg twice daily for the first day, followed by 600 mg to 800 mg twice a day. The duration of treatment varied from five to 14 days. We do not know whether favipiravir reduces all-cause mortality at 28 to 30 days, or in-hospital (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.46; 11 trials, 3459 participants; very low-certainty evidence). We do not know if favipiravir reduces the progression to invasive mechanical ventilation (RR 0.86, 95% CI 0.68 to 1.09; 8 trials, 1383 participants; very low-certainty evidence). Favipiravir may make little to no difference in the need for admission to hospital (if ambulatory) (RR 1.04, 95% CI 0.44 to 2.46; 4 trials, 670 participants; low-certainty evidence). We do not know if favipiravir reduces the time to clinical improvement (defined as time to a 2-point reduction in patients' admission status on the WHO's ordinal scale) (hazard ratio (HR) 1.13, 95% CI 0.69 to 1.83; 4 trials, 721 participants; very low-certainty evidence). Favipiravir may make little to no difference to the progression to oxygen therapy (RR 1.20, 95% CI 0.83 to 1.75; 2 trials, 543 participants; low-certainty evidence). Favipiravir may lead to an overall increased incidence of adverse events (RR 1.27, 95% CI 1.05 to 1.54; 18 trials, 4699 participants; low-certainty evidence), but may result in little to no difference inserious adverse eventsattributable to the drug (RR 1.04, 95% CI 0.76 to 1.42; 12 trials, 3317 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
The low- to very low-certainty evidence means that we do not know whether favipiravir is efficacious in people with COVID-19 illness, irrespective of severity or admission status. Treatment with favipiravir may result in an overall increase in the incidence of adverse events but may not result in serious adverse events.
Topics: Adult; Humans; COVID-19; SARS-CoV-2; Amides; Pyrazines
PubMed: 38314855
DOI: 10.1002/14651858.CD015219.pub2 -
Frontiers in Immunology 2024Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined...
BACKGROUND
Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent.
METHODS
Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE).
RESULTS
Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]).
CONCLUSION
Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).
Topics: Humans; Dermatitis, Atopic; Janus Kinase Inhibitors; Nasopharyngitis; Pruritus; Acne Vulgaris; Headache; Herpes Zoster; Immunoglobulin A; Purines; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38464512
DOI: 10.3389/fimmu.2024.1342810 -
The Journal of Pain Nov 2023Transdermal buprenorphine (TBUP) may have some advantages for the management of acute postoperative pain. The aim of this systematic review and meta-analysis was to... (Meta-Analysis)
Meta-Analysis Review
Transdermal buprenorphine (TBUP) may have some advantages for the management of acute postoperative pain. The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of TBUP compared to other analgesics or placebo for acute postoperative pain. A systematic search was conducted using Embase, MEDLINE, and Cochrane Central Register of Controlled Trials (CENTRAL) until December 26, 2022. The search included randomized controlled trials comparing TBUP versus other analgesics or placebo for acute postoperative pain. A certainty assessment was conducted using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. The protocol for this review was registered on Prospective Register of Systematic Reviews (CRD42022318601). In total, 15 studies involving 1,205 participants were included that compared TBUP versus fentanyl (n = 2), celecoxib (n = 3), placebo (n = 2), tramadol (n = 5), diclofenac (n = 3), parecoxib (n = 1), and flurbiprofen (n = 1). Meta-analyses were conducted for 3 comparators that involved 2 studies each. There was no significant difference in pain between TBUP 10 mcg/h versus fentanyl 25 mcg/h (standardized mean difference [SMD] -.03, 95% confidence interval [CI] -.86 to .81, P = .95, I = 85%). TBUP 10 mcg/h was associated with less pain compared to celecoxib 200 mg twice daily (SMD -.32, 95% CI -.58 to -.05, P = .02, I = 0%) and placebo (SMD -2.29, 95% CI -4.32 to -.27, P = .03, I = 94%). The GRADE assessment showed a very low certainty of evidence for all comparisons. There is insufficient evidence that TBUP improves pain control compared to other analgesics for acute postoperative pain. PERSPECTIVE: This systematic review and meta-analysis compared the use of TBUP to other analgesics for postoperative pain. The results showed that there is insufficient evidence to recommend the use of TBUP in this setting. The findings will help clinicians select the most appropriate opioid regimens for postoperative pain.
Topics: Humans; Celecoxib; Analgesics, Opioid; Pain, Postoperative; Fentanyl; Buprenorphine
PubMed: 37442403
DOI: 10.1016/j.jpain.2023.07.001 -
Journal of the American Pharmacists... 2023The 2011 Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases guidelines recommend ciprofloxacin or... (Review)
Review
BACKGROUND
The 2011 Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases guidelines recommend ciprofloxacin or sulfamethoxazole-trimethoprim (SMX-TMP) as first-line agents to treat uncomplicated acute pyelonephritis (APN).
OBJECTIVE
With increasing antimicrobial resistance rates and recent changes in practice patterns, the objective of this systematic review was to describe the effectiveness of cephalosporins for uncomplicated APN in more recently published literature.
METHODS
Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for reporting. We searched PubMed, Embase, and Scopus for publications between January 2010 and September 2022. Eligible articles detailed patients with uncomplicated APN, treated with first- to fourth-generation cephalosporins, and identified a clinical, microbiological, or health care utilization outcome. Studies with more than 30% of complicated APN patients, non-English-language studies, case reports, case series, pharmacodynamic or pharmacokinetic studies, and in vitro laboratory or animal studies were excluded. Screening, review, and extraction were performed independently by 2 researchers, plus a third for conflict resolution. Critical appraisal of studies was performed using Joanna Briggs Institute checklists.
RESULTS
Eight studies met inclusion, including 5 cohort studies (62.5%), 2 randomized controlled trials (25%), and 1 nonrandomized experimental study (12.5%). Cephalosporins most used across the studies included cefazolin, cephalexin, cefuroxime, cefotaxime, cefdinir, cefditoren, and ceftriaxone. Outcomes assessed were diverse, including clinical or microbiological success and time to defervescence or symptom resolution. Cephalosporins displayed effectiveness for the treatment of acute uncomplicated APN regardless of study design or the presence of a comparison group. No trials reported inferiority of clinical treatment outcomes compared with a fluoroquinolone or SMX-TMP.
CONCLUSION
Cephalosporins may be viable treatment options for the management of uncomplicated APN.
Topics: Humans; Anti-Bacterial Agents; Cephalosporins; Communicable Diseases; Pyelonephritis; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 37414282
DOI: 10.1016/j.japh.2023.06.028 -
Reviews on Environmental Health Dec 2023Acrylamide is a known neurotoxic compound for humans. Foods that have high concentrations of acrylamide need to be identified. One of the food products containing... (Meta-Analysis)
Meta-Analysis Review
Acrylamide is a known neurotoxic compound for humans. Foods that have high concentrations of acrylamide need to be identified. One of the food products containing acrylamide is popcorn. Popcorn is an important source of snacks for children, especially students. The presented study is a systematic review and meta-analysis of the level of acrylamide in popcorn. The search was done in different databases with the keywords; acrylamide, popcorn, popped corn. 27 articles were found by searching various databases. After initial screening and full text evaluation, 8 articles were selected for systematic review and 6 articles for meta-analysis. The amount of acrylamide in this product was in the range of 1,017.7-106 μg/kg. Microwaved corn contains lower amounts of acrylamide than other methods of preparation. The type of popcorn also had an effect on the amount of acrylamide with Meta-regression. It was found that sweet popcorn contains higher amounts of acrylamide. The overall value of acrylamide concentration in popcorns was calculated to be 459.6 ± 220.3 μg/kg. This amount is high and requires measures to reduce the amount of acrylamide.
Topics: Child; Humans; Food Contamination; Neurotoxins; Acrylamide; Food; Zea mays
PubMed: 35960600
DOI: 10.1515/reveh-2022-0085 -
Antiviral Research Jan 2024Remdesivir, molnupiravir, and nirmatrelvir/ritonavir are three antiviral agents approved by FDA emergency authorization for treating mild to moderate symptomatic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Remdesivir, molnupiravir, and nirmatrelvir/ritonavir are three antiviral agents approved by FDA emergency authorization for treating mild to moderate symptomatic COVID-19 adult outpatients at high risk for hospitalization and death.
OBJECTIVES
To compare the efficacy and safety of these antivirals based on updated published RCT and real-world data.
STUDY DESIGN
This systematic review followed the preferred reporting items for systematic reviews and meta-analysis framework guidelines. We searched all publications up to January 2023. RRs and 95% CIs for death, hospitalization, and adverse events were calculated.
RESULTS
Six RCTs and seven cohort studies were included, with 1,456,523 participants, of whom 50,979 were treated with antivirals. Remdesivir was associated with the lowest probability of hospitalization and death compared to nirmatrelvir/ritonavir and molnupiravir (P-scores 0.99 and 0.90, respectively, for remdesivir, 0.64 and 0.55, respectively for nirmatrelvir/ritonavir, and 0.26 and 0.49, respectively for molnupiravir). Based on indirect comparisons, remdesivir was associated with a statistically significant decreased risk for hospitalization compared to molnupiravir (RR 0.09; 95% CI 0.02-0.40) and to nirmatrelvir/ritonavir (RR 0.11; 95% CI 0.03-0.73). No statistically significant difference was found between antivirals in the mortality risk reduction and the risk for side effects.
CONCLUSIONS
This is the most comprehensive network meta-analysis integrating RCTs and real-world data. In our indirect comparison, remdesivir was associated with the highest efficacy in preventing hospitalization among high risk symptomatic COVID-19 outpatients, compared to nirmatrelvir/ritonavir and molnupiravir. This finding supports current guidelines, and may have importance when deciding which antiviral to use, together with other important factors.
Topics: Adult; Humans; COVID-19; Network Meta-Analysis; Outpatients; Ritonavir; Antiviral Agents; Hydroxylamines; Cytidine; Nitriles; Lactams; Proline; Leucine
PubMed: 38056602
DOI: 10.1016/j.antiviral.2023.105768 -
CNS Drugs Nov 2023In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium channels and the subsequent release of glutamate. The aim of this systematic review and meta-analysis was to examine the efficacy and safety of both drugs compared with placebo on motor symptoms, cognitive function, and quality of life in patients with Parkinson's disease.
METHODS
We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to March 2023 for randomized controlled trials of adults with Parkinson's disease administered either safinamide or zonisamide and published in English. We excluded single-arm trials or if neither the efficacy nor safety outcomes of interest were reported. Primary outcomes were the change from baseline in Unified Parkinson's Disease Rating Scale section III (UPDRS-III) and serious adverse events. Secondary outcomes included a change from baseline in OFF-time, Parkinson's Disease Questionnaire 39 to evaluate quality of life, and Mini-Mental State Examination for cognitive function assessment. The meta-analysis was conducted using Review Manager 5.4.1. Random-effect models were used to calculate the pooled mean differences (MDs) and risk ratios with 95% confidence intervals (CIs). Subgroup analyses by medication, doses, Parkinson's disease stage, and risk of bias were conducted. We assessed the risk of bias using the Cochrane's risk of bias tool. Sensitivity analysis was conducted, and publication bias were evaluated. This meta-analysis was not externally funded, and the protocol is available on the Open Science Framework Registration ( https://doi.org/10.17605/OSF.IO/AMNP5 ).
RESULTS
Of 3570 screened citations, 16 trials met inclusion criteria (4314 patients with Parkinson's disease). Ten safinamide trials were conducted in several countries. Six zonisamide trials were included, five of which were conducted in Japan and one in India. UPDRS Part III scores were significantly lower with both monoamine oxidase-B inhibitors than with placebo (MD = - 2.18; 95% CI - 2.88 to - 1.49; I =63%; n = 14 studies). A subgroup analysis showed a significant improvement in UPDRS-III in safinamide (MD = - 2.10; 95% CI - 3.09 to - 1.11; I = 71%; n = 8 studies) and zonisamide (MD = - 2.31; 95% CI - 3.35 to - 1.27; I = 52%; n = 6 studies) compared with placebo. Monoamine oxidase-B inhibitors significantly decreased OFF-time compared with placebo. No significant differences in cognitive function (Mini-Mental State Examination), whereas an improvement in quality of life (Parkinson's Disease Questionnaire 39 scores) was observed. There was no significant difference in incidence rates of serious adverse events among all examined doses of zonisamide and safinamide compared with placebo. Two trials were reported as a high risk of bias and sensitivity analyses confirmed the primary analysis results.
CONCLUSIONS
Evidence suggests that novel monoamine oxidase-B inhibitors not only improve motor symptoms but also enhance patients' quality of life. The meta-analysis showed that both medications have a similar safety profile to placebo with regard to serious adverse events. The overall findings emphasize the effectiveness of safinamide and zonisamide in the treatment of Parkinson's disease as adjunct therapy. Further long-term studies examining the impact of these medications on motor and non-motor symptoms are necessary.
Topics: Adult; Humans; Parkinson Disease; Zonisamide; Quality of Life; Randomized Controlled Trials as Topic; Dopamine Agents; Monoamine Oxidase
PubMed: 37973769
DOI: 10.1007/s40263-023-01048-x -
Journal of Drugs in Dermatology : JDD Aug 2023Hidradenitis suppurativa (HS) is an inflammatory skin condition characterized by recurrent abscesses, nodules, and sinus tracts. Hormones are thought to play an...
Hidradenitis suppurativa (HS) is an inflammatory skin condition characterized by recurrent abscesses, nodules, and sinus tracts. Hormones are thought to play an important role in HS pathophysiology, but there is a lack of an updated review on hormonal treatments in HS. Objective: Perform a systematic review of the literature on hormonal treatments in patients with HS. Methods: In April 2022, MEDLINE and EMBASE databases were searched for articles on hormonal treatments in HS. Non-English, duplicate, and irrelevant results were excluded. Data extraction was performed by two reviewers. Results: From 1952 to 2022, 30 articles (634 patients) met the inclusion criteria. Anti-androgen treatments discussed include finasteride (n=8), spironolactone (n=7), cyproterone acetate (CPA) (n=5), flutamide (n=1), leuprolide (n=1), and buserelin acetate (n=1). Metabolic treatments reported include metformin (n=8) and liraglutide (n=2). Three articles on hormonal contraceptives and 2 articles on testosterone were included. Of the articles which reported response rates, 62.8% (27/43) of patients improved with finasteride, 53.3% (32/60) with CPA mono/combination therapy, 50.5% (51/101) with spironolactone, and 46.0% (74/161) with metformin. Improvement in HS was also noted in case reports of patients treated with buserelin acetate, leuprolide, flutamide, and liraglutide. Conclusions: Hormonal treatments for HS, especially finasteride, spironolactone, and metformin, are efficacious and safe; but large-scale randomized controlled trials are needed to determine the patient populations which would benefit from these therapies. Masson R, Shih T, Jeong C, et al. Hormonal treatments in hidradenitis suppurativa: a systematic review. J Drugs Dermatol. 2023;22(8):785-794. doi:10.36849/JDD.7325.
Topics: Humans; Finasteride; Hidradenitis Suppurativa; Flutamide; Spironolactone; Liraglutide; Metformin
PubMed: 37556513
DOI: 10.36849/jdd.7325 -
CNS Drugs Jan 2024Studies have suggested that levetiracetam may help improve cognitive function in patients with epilepsy. Recently, its efficacy in improving cognitive function was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies have suggested that levetiracetam may help improve cognitive function in patients with epilepsy. Recently, its efficacy in improving cognitive function was reported in patients with amnestic mild cognitive impairment, schizophrenia, and Alzheimer's disease. However, the specific cognitive domains affected and the degree of evidence supporting these effects remain unclear. This systematic review and meta-analysis aimed to explore the effects of levetiracetam on different cognitive domains.
METHODS
This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. We defined our inclusion criteria for the systematic review as: (1) randomized placebo-controlled trials (RCTs) involving human subjects, (2) double-blinded RCTs, and (3) RCTs evaluating the quantitative differences in cognitive function between levetiracetam and placebo. We excluded: (1) non-RCT studies, (2) open-label studies, and (3) RCTs lacking cognitive assessments for either intervention. Two authors independently searched electronic databases, including PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov, from inception until 2 July 2023. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Meta-analytic techniques were applied to examine the impact of levetiracetam on cognitive domain tests, with Hedges' g facilitating the comparison with placebo. The domains analyzed comprised multi-domain, executive function, processing speed, working memory, verbal memory/learning (verbal ML), visuospatial memory/learning (visuospatial ML), and language. We used odds ratios to compare the incidence of treatment-emergent adverse events between the groups, including somnolence, fatigue, dizziness, headache, irritability, and cognitive adverse events.
RESULTS
A random-effects model was utilized to perform a meta-analysis of 16 RCTs including 545 participants. Compared with a placebo, levetiracetam was associated with improved executive function [Hedges'g = - 0.390, 95% confidence interval (CI) = - 0.609 to - 0.172, p < 0.001, I = 24.0%]. Subgroup analysis showed that levetiracetam outperformed placebo in patients without epilepsy (Hedges' g = - 0.419, 95% CI = - 0.647 to - 0.191, p < 0.001, I = 26.2%). Meanwhile, low-dose levetiracetam showed a moderate favorable effect over placebo (Hedges' g = -0.544, 95% CI = - 1.085 to - 0.003, p = 0.049, I = 65.3%). In patients without epilepsy, low-dose levetiracetam was associated with improved executive function (Hedges'g = - 0.544, 95% CI = - 1.085 to - 0.003, p = 0.049, I = 65.3%). Concurrently, levetiracetam was associated with more frequent somnolence than a placebo (odds ratio = 4.654, 95% CI = 1.533 to 14.124, p = 0.007, I = 32.9%). Potential publication bias was observed in the executive function domain.
CONCLUSIONS
This exploratory study suggests that levetiracetam might improve executive function in specific populations. However, the diversity in study populations and potential publication bias warrant caution.
Topics: Humans; Cognition; Cognitive Dysfunction; Epilepsy; Levetiracetam; Randomized Controlled Trials as Topic; Sleepiness
PubMed: 38102532
DOI: 10.1007/s40263-023-01058-9 -
The Cochrane Database of Systematic... Mar 2024Leptospirosis is a global zoonotic and waterborne disease caused by pathogenic Leptospira species. Antibiotics are used as a strategy for prevention of leptospirosis, in... (Review)
Review
BACKGROUND
Leptospirosis is a global zoonotic and waterborne disease caused by pathogenic Leptospira species. Antibiotics are used as a strategy for prevention of leptospirosis, in particular in travellers and high-risk groups. However, the clinical benefits are unknown, especially when considering possible treatment-associated adverse effects. This review assesses the use of antibiotic prophylaxis in leptospirosis and is an update of a previously published review in the Cochrane Library (2009, Issue 3).
OBJECTIVES
To evaluate the benefits and harms of antibiotic prophylaxis for human leptospirosis.
SEARCH METHODS
We identified randomised clinical trials through electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and other resources. We searched online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The last date of search was 17 April 2023.
SELECTION CRITERIA
We included randomised clinical trials of any trial design, assessing antibiotics for prevention of leptospirosis, and with no restrictions on age, sex, occupation, or comorbidity of trial participants. We looked for trials assessing antibiotics irrespective of route of administration, dosage, and schedule versus placebo or no intervention. We also included trials assessing antibiotics versus other antibiotics using these criteria, or the same antibiotic but with another dose or schedule.
DATA COLLECTION AND ANALYSIS
We followed Cochrane methodology. The primary outcomes were all-cause mortality, laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (inclusive of asymptomatic cases), clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation, clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (exclusive of asymptomatic cases), and serious adverse events. The secondary outcomes were quality of life and the proportion of people with non-serious adverse events. We assessed the risk of bias of the included trials using the RoB 2 tool and the certainty of evidence using GRADE. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean difference (MD), with their 95% confidence intervals (CI). We used a random-effects model for our main analyses and the fixed-effect model for sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up.
MAIN RESULTS
We identified five randomised clinical trials comprising 2593 participants that compared antibiotics (doxycycline, azithromycin, or penicillin) with placebo, or one antibiotic compared with another. Four trials assessed doxycycline with different durations, one trial assessed azithromycin, and one trial assessed penicillin. One trial had three intervention groups: doxycycline, azithromycin, and placebo. Three trials assessed pre-exposure prophylaxis, one trial assessed postexposure prophylaxis, and one did not report this clearly. Four trials recruited residents in endemic areas, and one trial recruited soldiers who experienced limited time exposure. The participants' ages in the included trials were 10 to 80 years. Follow-up ranged from one to three months. Antibiotics versus placebo Doxycycline compared with placebo may result in little to no difference in all-cause mortality (RR 0.15, 95% CI 0.01 to 2.83; 1 trial, 782 participants; low-certainty evidence). Prophylactic antibiotics may have little to no effect on laboratory-confirmed leptospirosis, but the evidence is very uncertain (RR 0.56, 95% CI 0.25 to 1.26; 5 trials, 2593 participants; very low-certainty evidence). Antibiotics may result in little to no difference in the clinical diagnosis of leptospirosis regardless of laboratory confirmation (RR 0.76, 95% CI 0.53 to 1.08; 4 trials, 1653 participants; low-certainty evidence) and the clinical diagnosis of leptospirosis with laboratory confirmation (RR 0.57, 95% CI 0.26 to 1.26; 4 trials, 1653 participants; low-certainty evidence). Antibiotics compared with placebo may increase non-serious adverse events, but the evidence is very uncertain (RR 10.13, 95% CI 2.40 to 42.71; 3 trials, 1909 participants; very low-certainty evidence). One antibiotic versus another antibiotic One trial assessed doxycycline versus azithromycin but did not report mortality. Compared to azithromycin, doxycycline may have little to no effect on laboratory-confirmed leptospirosis regardless of the presence of an identified clinical syndrome (RR 1.49, 95% CI 0.51 to 4.32; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis regardless of the presence of laboratory confirmation (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), on the clinical diagnosis of leptospirosis confirmed by laboratory diagnosis (RR 4.18, 95% CI 0.94 to 18.66; 1 trial, 137 participants), and on non-serious adverse events (RR 1.12, 95% CI 0.36 to 3.48; 1 trial, 137 participants), but the evidence is very uncertain. The certainty of evidence for all the outcomes was very low. None of the five included trials reported serious adverse events or assessed quality of life. One study is awaiting classification. Funding Four of the five trials included statements disclosing their funding/supporting sources, and the remaining trial did not include this. Three of the four trials that disclosed their supporting sources received the supply of trial drugs directly from the same pharmaceutical company, and the remaining trial received financial support from a governmental source.
AUTHORS' CONCLUSIONS
We do not know if antibiotics versus placebo or another antibiotic has little or have no effect on all-cause mortality or leptospirosis infection because the certainty of evidence is low or very low. We do not know if antibiotics versus placebo may increase the overall risk of non-serious adverse events because of very low-certainty evidence. We lack definitive rigorous data from randomised trials to support the use of antibiotics for the prophylaxis of leptospirosis infection. We lack trials reporting data on clinically relevant outcomes.
Topics: Humans; Antibiotic Prophylaxis; Doxycycline; Azithromycin; Quality of Life; Anti-Bacterial Agents; Penicillins; Leptospirosis
PubMed: 38483067
DOI: 10.1002/14651858.CD014959.pub2