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Respiratory Research Sep 2021The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear.
METHODS
We performed comprehensive searches of randomized control trials (RCTs) that compared the clinical efficacy of additional antimicrobial agents to those of placebo or usual care in the treatment of IPF patients. The primary outcome was all-cause mortality, and the secondary outcomes were changes in forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and the risk of adverse events (AEs).
RESULTS
Four RCTs including a total of 1055 patients (528 receiving additional antibiotics and 527 receiving placebo or usual care) were included in this meta-analysis. Among the study group, 402 and 126 patients received co-trimoxazole and doxycycline, respectively. The all-cause mortality rates were 15.0% (79/528) and 14.0% (74/527) in the patients who did and did not receive additional antibiotics, respectively (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.76 to 1.51; p = 0.71). No significant difference was observed in the changes in FVC (mean difference [MD], 0.01; 95% CI - 0.03 to 0.05; p = 0.56) and DLCO (MD, 0.05; 95% CI - 0.17 to 0.28; p = 0.65). Additional use of antimicrobial agents was also associated with an increased risk of AEs (OR 1.65; 95% CI 1.19 to 2.27; p = 0.002), especially gastrointestinal disorders (OR 1.54; 95% CI 1.10 to 2.15; p = 0.001).
CONCLUSIONS
In patients with IPF, adding antimicrobial therapy to usual care did not improve mortality or lung function decline but increased gastrointestinal toxicity.
Topics: Anti-Infective Agents; Drug Therapy, Combination; Gastrointestinal Diseases; Humans; Idiopathic Pulmonary Fibrosis; Mortality; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34526011
DOI: 10.1186/s12931-021-01839-0 -
International Dental Journal Aug 2018To evaluate the effects of systemic antibiotics as adjuncts to nonsurgical periodontal treatment (NSPT), as opposed to using NSPT alone, on periodontal clinical... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To evaluate the effects of systemic antibiotics as adjuncts to nonsurgical periodontal treatment (NSPT), as opposed to using NSPT alone, on periodontal clinical parameters of diabetic patients with periodontitis.
MATERIALS AND METHODS
Randomised controlled trials with a follow-up of 3 months or more, assessing the effects of NSPT in combination with antibiotics, in diabetic patients with periodontitis were included. Trials published up to August 2016 were identified from MEDLINE, EMBASE and LILACS databases. Meta-analyses were conducted to determine changes in clinical attachment level (CAL), probing pocket depth (PPD), bleeding on probing (BOP) and gingival index (GI). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in this review.
RESULTS
Of the 164 papers potentially admissible to this systematic review, 15 articles on 11 randomised clinical trials were considered as eligible. The results of the meta-analyses presented a modest additional benefit of 0.14 mm (95% confidence interval: 0.08-0.20) in reducing PPD but no further benefit in CAL gain.
CONCLUSION
When the data for all antibiotic protocols were considered together for the treatment of periodontitis patients with DM, a significant, albeit small, reduction of PPD and no improvement in CAL gain was observed. When the antibiotic protocols were analysed separately, the combination of amoxicillin plus metronidazole yielded the best results for PPD.
Topics: Amoxicillin; Anti-Bacterial Agents; Dental Scaling; Diabetes Mellitus; Doxycycline; Drug Therapy, Combination; Humans; Metronidazole; Periodontal Diseases; Periodontal Pocket
PubMed: 29492963
DOI: 10.1111/idj.12384 -
BMC Infectious Diseases Mar 2023Ureaplasma urealyticum is the most prevalent genital mycoplasma isolated from the urogenital tract of females, but there is no unified treatment plan. This study aimed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ureaplasma urealyticum is the most prevalent genital mycoplasma isolated from the urogenital tract of females, but there is no unified treatment plan. This study aimed to evaluate the efficacy of azithromycin in treating Ureaplasma urealyticum.
METHODS
From the earliest to June 2022, published randomized controlled trials (RCTs) on azithromycin treatment of Ureaplasma urealyticum were retrieved by searching PubMed, Embase, Cochrane Library, and Web of Science. Two reviewers independently extracted the data. We utilized the Cochrane risk-of-bias assessment technique to assess the quality of included RCTs. The data were analyzed using the R language (version 4.0.4) software.
RESULTS
Seven RCTs were finally included, involving 512 participants (240 in the experimental group, 272 in the control group). The experimental group was treated with azithromycin monotherapy, while the control group was treated with doxycycline or a placebo. Meta-analysis results suggested that azithromycin has a comparable therapeutic effect on Ureaplasma urealyticum in comparison to that of controls (risk ratio [RR] = 1.03, 95% confidence interval [CI] 0.94-1.12). Subgroup analysis showed that the dose and duration of azithromycin may don't affect its efficacy.
CONCLUSION
Regarding the meta-analysis that we performed based on existing clinical studies, azithromycin is quite effective in treating Ureaplasma urealyticum.
Topics: Female; Humans; Azithromycin; Ureaplasma urealyticum; Doxycycline; Ureaplasma Infections; Anti-Bacterial Agents; Ureaplasma
PubMed: 36927441
DOI: 10.1186/s12879-023-08102-5 -
JMIR Public Health and Surveillance Jan 2024Drug-induced suicide (DIS) is a severe adverse drug reaction (ADR). Although clinical trials have provided evidence on DIS, limited investigations have been performed on... (Review)
Review
BACKGROUND
Drug-induced suicide (DIS) is a severe adverse drug reaction (ADR). Although clinical trials have provided evidence on DIS, limited investigations have been performed on rare ADRs, such as suicide.
OBJECTIVE
We aimed to systematically review case reports on DIS to provide evidence-based drug information.
METHODS
We searched PubMed to obtain case reports regarding DIS published until July 2021. Cases resulting from drugs that are no longer used or are nonapproved, substance use, and suicidal intentions were excluded. The quality of each case report was assessed using the CASE (Case Reports) checklist. We extracted data regarding demographics, medication history, suicide symptoms, and symptom improvement and evaluated the causality of DIS using the Naranjo score. Furthermore, to identify the potential suicidal risk of the unknown drugs, we compared the results of the causality assessment with those of the approved drug labels.
RESULTS
In 83 articles, we identified 152 cases involving 61 drugs. Antidepressants were reported as the most frequent causative drugs of DIS followed by immunostimulants. The causality assessment revealed 61 cases having possible, 89 cases having probable, and 2 cases having definite relationships with DIS. For approximately 85% of suspected drugs, the risk of suicidal ADRs was indicated on the approved label; however, the approved labels for 9 drugs, including lumacaftor/ivacaftor, doxycycline, clozapine, dextromethorphan, adalimumab, infliximab, piroxicam, paclitaxel, and formoterol, did not provide information about these risks.
CONCLUSIONS
We found several case reports involving drugs without suicide risk information on the drug label. Our findings might provide valuable insights into drugs that may cause suicidal ADRs.
Topics: Humans; Doxycycline; Drug Labeling; Drug-Related Side Effects and Adverse Reactions; Suicidal Ideation; Suicide; Case Reports as Topic
PubMed: 38289650
DOI: 10.2196/49755 -
BMJ Open Sep 2020The gut microbiota influences many aspects of human health. We investigated the magnitude and duration of changes in gut microbiota in response to antibiotics commonly... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The gut microbiota influences many aspects of human health. We investigated the magnitude and duration of changes in gut microbiota in response to antibiotics commonly prescribed in UK primary care.
METHODS
We searched MEDLINE, EMBASE and AMED, all years up to May 2020 including all study designs, collecting and analysing data on the effect of antibiotics prescribed for respiratory and urinary tract infections. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane standard methods. Risk of bias was evaluated using the Critical Appraisal Skills Programme. Narrative synthesis was used to report the themes emerging from the data.
MAIN OUTCOME MEASURES
Primary outcomes were antibiotic-induced changes in the composition and/or diversity of the gut microbiota. Secondary outcome was the time for the microbiota to return to baseline.
RESULTS
Thirty-one articles with low or unclear risk of bias showed that antibiotics impact the gut microbiota by causing rapid and diminished levels of bacterial diversity and changes in relative abundances. After cessation of treatment, gut bacteria recover, in most individuals, to their baseline state within a few weeks. Some studies suggested longer term effects from 2 to 6 months. Considerable heterogeneity in methodology makes the studies prone to biases and other confounding factors. Doxycycline was associated with a marked short-term decrease in diversity. Clarithromycin decreased the populations of Enterobacteria, and the anaerobic bacteria sp and sp in numbers and diversity for up to 5 weeks. Phenoxymethylpenicillin, nitrofurantoin and amoxicillin had very little effect on the gut microbiome.
CONCLUSIONS
Despite substantial heterogeneity of the studies and small sample sizes, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal microbiota. Larger population-based studies are needed to fully understand how antibiotics modulate the microbiota, and to determine if these are associated with (longer term) health consequences.
PROSPERO REGISTRATION NUMBER
CRD42017073750.
Topics: Amoxicillin; Anti-Bacterial Agents; Gastrointestinal Microbiome; Humans; Primary Health Care; United Kingdom
PubMed: 32958481
DOI: 10.1136/bmjopen-2019-035677 -
BMC Neurology Sep 2016Many aspects of pharmacological treatment of Lyme neuroborreliosis in children, such as choice of drug, dosage, and duration are subject to intense debates, leading to...
BACKGROUND
Many aspects of pharmacological treatment of Lyme neuroborreliosis in children, such as choice of drug, dosage, and duration are subject to intense debates, leading to uncertainties in patients' parents and healthcare providers alike. To assess the available evidence for pharmacological treatment for children with Lyme neuroborreliosis we conducted a systematic review.
METHODS
The comprehensive systematic literature search included randomized-controlled trials (RCTs) and non-randomized studies (NRS) on treatment of Lyme neuroborreliosis in children (age <18 years). Our primary outcome was neurological symptoms after treatment. Risk of bias was assessed with the Cochrane risk of bias tools for RCTs and NRS. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Two RCTs and four NRS were eligible for inclusion. Risk of bias in RCTs and NRS was generally high. Reporting of studies was generally poor. Regarding the primary outcome neurological symptoms at 1-3 months, no statistically significant difference could be found in cohort studies between doxycycline and beta-lactam antibiotics. In two RCTs comparing penicillin G and ceftriaxone, no patient experienced residual neurological symptoms at the last reported time points. Quality of evidence according to GRADE was judged very low.
CONCLUSIONS
Data is scarce and with limited quality. Several issues could not be addressed due to scarcity of information. No eligible study compared different treatment durations. According to the available evidence, there seems to be no difference between different antibiotic agents for the treatment of Lyme neuroborreliosis in children regarding neurological symptoms. We found no evidence that supports extended antibiotic regimes.
REVIEW REGISTRATION
Systematic review registration: CRD42014008839 .
PubMed: 27686962
DOI: 10.1186/s12883-016-0708-y -
Reviews in Medical Virology Nov 2021The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ...
The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C-reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI-PubMed database to find articles related to Covid-19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid-19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro-inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid-19. From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid-19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials.
Topics: ADAM17 Protein; Angiotensin-Converting Enzyme 2; Anti-Inflammatory Agents; Biomarkers; C-Reactive Protein; COVID-19; Celecoxib; Complement System Proteins; Cytokine Release Syndrome; Cytokines; Disease Progression; Doxycycline; Gene Expression Regulation; Humans; Randomized Controlled Trials as Topic; SARS-CoV-2; Severity of Illness Index; Survival Analysis; COVID-19 Drug Treatment
PubMed: 34773448
DOI: 10.1002/rmv.2221 -
Frontiers in Veterinary Science 2021Bacterial meningitis in dogs and cats is a rare disease associated with a high lethality rate. The spectrum of causative bacteria includes a diverse set of gram...
Bacterial meningitis in dogs and cats is a rare disease associated with a high lethality rate. The spectrum of causative bacteria includes a diverse set of gram positive, gram negative and anaerobic species. Currently, no veterinary medicinal product is approved for this indication in these species in Europe. The objective of this review was to collect the available pharmacokinetic data for antibiotics approved in dogs and cats to enable a preliminary analysis of their potential effectiveness for the treatment of bacterial meningitis. This analysis yielded data for 13 different antibiotics in dogs and two in cats. Additionally, data about frequently recommended cephalosporines not approved in dogs and cats were included. The collected data was used to assess the potential of the respective antibiotics to attain certain simple pharmacokinetic-pharmacodynamic (PK-PD) indexes in the cerebrospinal fluid (CSF). A more sophisticated investigation using modern methods was not possible due to the limited data available. For this purpose, data about the sensitivity of four bacterial species commonly associated with meningitis in dogs and cats to these antibiotics were included. The analysis provided evidence for the potential effectiveness of ampicillin, doxycycline, enrofloxacin, ceftriaxone and cefoxitin against bacteria frequently detected in bacterial meningitis in dogs. Data were not available or insufficient for the assessment of several antibiotics, including frequently recommended substances like metronidazole and trimethoprim-sulphonamide. Little evidence is available for the use of antibiotics in cats afflicted with this disease, highlighting the need for further research to obtain data for evidence based therapeutic recommendations.
PubMed: 35118150
DOI: 10.3389/fvets.2021.769588 -
Sexually Transmitted Infections Feb 2019To assess the effectiveness and safety of antibiotic regimens used to treat pelvic inflammatory disease (PID). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the effectiveness and safety of antibiotic regimens used to treat pelvic inflammatory disease (PID).
DESIGN
This is a systematic review and meta-analysis of randomised controlled trials (RCTs). Risk of bias was assessed using the criteria outlined in the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation.
DATA SOURCES
Eight electronic databases were searched from date of inception up to July 2016. Database searches were complemented by screening of reference lists of relevant studies, trial registers, conference proceeding abstracts and grey literature.
ELIGIBILITY CRITERIA
RCTs comparing the use of antibiotics with placebo or other antibiotics for the treatment of PID in women of reproductive age, either as inpatient or outpatient treatment.
RESULTS
We included 37 RCTs (6348 women). The quality of evidence ranged from very low to high, the main limitations being serious risk of bias (due to poor reporting of study methods and lack of blinding), serious inconsistency and serious imprecision. There was no clear evidence of a difference in the rates of cure for mild-moderate or for severe PID for the comparisons of azithromycin versus doxycycline, quinolone versus cephalosporin, nitroimidazole versus no use of nitroimidazole, clindamycin plus aminoglycoside versus quinolone, or clindamycin plus aminoglycoside versus cephalosporin. No clear evidence of a difference between regimens in antibiotic-related adverse events leading to discontinuation of therapy was observed.
CONCLUSIONS
We found no conclusive evidence that one regimen of antibiotics was safer or more effective than any other for the treatment of PID, and there was no clear evidence for the use of nitroimidazoles (metronidazole) compared with the use of other drugs with activity against anaerobes. More evidence is needed to assess treatments for women with PID, particularly comparing regimens with or without the addition of nitroimidazoles and the efficacy of azithromycin compared with doxycycline.
Topics: Aminoglycosides; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Clindamycin; Doxycycline; Female; Humans; Metronidazole; Pelvic Inflammatory Disease; Quinolones; Randomized Controlled Trials as Topic
PubMed: 30341232
DOI: 10.1136/sextrans-2018-053693 -
The Cochrane Database of Systematic... Jan 2019The genital infection caused by Chlamydia trachomatis (CT) is a common sexually transmitted infection (STI) globally. The infection is mainly asymptomatic in women, thus... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The genital infection caused by Chlamydia trachomatis (CT) is a common sexually transmitted infection (STI) globally. The infection is mainly asymptomatic in women, thus it can produce infertility and chronic pelvic pain. In men infection is mainly symptomatic, but can evolve to prostatitis. Clinical practice guidelines for CT urogenital infections do not give any specific recommendation about which antibiotic use as first option OBJECTIVES: To assess the efficacy and safety of antibiotic treatment for CT genital infection in men and non-pregnant women.
SEARCH METHODS
The Cochrane Sexually Transmitted Infections' (STI) Information Specialist developed the electronic searches in electronic databases (CENTRAL, MEDLINE, Embase and LILACS), and trials registers. We searched studies published from inception to June 2018.
SELECTION CRITERIA
We included parallel, randomised controlled trials (RCTs) of men, and sexually-active, non-pregnant women with CT infection (urethritis or uterine cervicitis or asymptomatic), diagnosed by cell culture for CT, nucleic acid amplification tests (NAAT) or antigen-based detection methods, who had been treated with any of the antibiotic regimens recommended by any of the updated to 2013 CT Guidelines.
DATA COLLECTION AND ANALYSIS
Four review authors screened evidence according to selection criteria and independently extracted data and assessed risk of bias. Two authors developed the 'Summary of findings' tables. We used a fixed-effect meta-analysis model for combining data where it was reasonable to assume that studies were estimating the same underlying treatment effect. We estimated the pooled risk ratio in order to establish the effects of the comparisons. Our primary outcomes were microbiological failure and adverse events, and our secondary outcomes were clinical failure, antimicrobial resistance and reinfection.
MAIN RESULTS
We selected 14 studies ( 2715 participants: 2147 (79.08%) men and 568 (20.92%) women). The studies were conducted mainly at STD clinics. Sample sizes ranged from 71 to 606 participants; follow-up was 29.7 days on average.For the comparison: azithromycin single dose versus doxycycline once or twice daily for 7 days, in men treated for CT, the risk of microbiological failure was higher in the azithromycin group (RR 2.45, 95% CI 1.36 to 4.41; participants = 821; studies = 9; moderate-quality evidence), but regarding clinical failure, the results showed that the effect is uncertain (RR 0.94, 95% CI 0.43 to 2,05; I² = 55%; participants = 525; studies = 3; low-quality evidence). Regarding adverse events (AE) in men there could be little or no difference between the antibiotics (RR 0.83, 95% CI 0.67 to 1.02; participants = 1424; studies = 6; low-quality evidence). About women treated for CT, the effect on microbiological failure was uncertain (RR = 1.71, 95% CI 0.48 to 6.16; participants = 338; studies = 5; very low-quality evidence). There were no studies assessing clinical failure or adverse events in women, however, we found that azithromycin probably has fewer adverse events in both genders (RR 0.83, 95% CI 0.71 to 0.98; I² = 0%; participants = 2261; studies = 9; moderate-quality evidence).For the second comparison: doxycycline compared to ofloxacin, for men treated for CT the effect on microbiological failure was uncertain (RR 8.53, 95% CI 0.43 to 167.38, I² not applicable; participants = 80; studies = 2; very low-quality evidence), as also it was on clinical failure (RR 0.85, 95% CI 0.28 to 2.62; participants = 36; studies = 1; very low-quality evidence). The effect of in women on clinical failure was uncertain (RR 0.94, 95% CI 0.39 to 2.25; I² = 39%; participants = 127; studies = 2; very low-quality evidence).Regarding adverse events, the effect in both men and women was uncertain (RR 1.02 95% CI 0.66 to 1.55; participants = 339 studies = 3; very low-quality evidence). The effect on microbiological failure in women and in men and women together, the effect on microbiological failure was not estimable. The most frequently AE reported were not serious and of gastrointestinal origin.No studies assessed antimicrobial resistance or reinfection in either comparison.
AUTHORS' CONCLUSIONS
In men, regimens with azithromycin are probably less effective than doxycycline for microbiological failure, however, there might be little or no difference for clinical failure. For women, we are uncertain whether azithromycin compared to doxycycline increases the risk of microbiological failure. Azithromycin probably slightly reduces adverse events compared to doxycycline in men and women together but may have little difference in men alone. We are uncertain whether doxycycline compared to ofloxacin reduces microbiological failure in men or women alone, or men and women together, nor if it reduces clinical failure or adverse events in men or women.Based on the fact that women suffer mainly asymptomatic infections, and in order to test the effectiveness and safety of the current recommendations (azithromycin, doxycycline and ofloxacin), for CT infection, especially in low and middle income countries, future RCTs should be designed and conducted to include a large enough sample size of women, and with low risk of bias. It is also important that future RCTs include adherence, CT resistance to antibiotic regimens, and risk of reinfection as outcomes to be measured. In addition, it is important to conduct a network meta-analysis in order to evaluate all those studies that included in one arm only the current antibiotic treatments for CT infection that are recommended by the updated clinical practice guidelines.
Topics: Anti-Bacterial Agents; Asymptomatic Infections; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Doxycycline; Female; Humans; Male; Ofloxacin; Randomized Controlled Trials as Topic; Sex Factors; Treatment Outcome; Urinary Tract Infections
PubMed: 30682211
DOI: 10.1002/14651858.CD010871.pub2