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Journal of Clinical Pharmacology Feb 2024Macrolides and tetracyclines are antibiotics that have a range of anti-inflammatory properties beyond their microbial capabilities. Although these antibiotics have been... (Meta-Analysis)
Meta-Analysis Review
Macrolides and tetracyclines are antibiotics that have a range of anti-inflammatory properties beyond their microbial capabilities. Although these antibiotics have been in widespread use, the long-term safety profiles are limited. We performed a systematic review and meta-analysis of randomized clinical trials that compared macrolides or tetracyclines with placeboes to provide long-term safety information. We searched Medline and EMBASE from inception to October 2022 and identified studies that reported study drug-related death, serious adverse events (SAEs), or withdrawal rates, and common adverse effects of each drug. Relative risk (RR) and number needed to harm were calculated. Of the 52 randomized clinical trials included, there are 3151 participants on doxycycline, 2519 participants on minocycline, 3049 participants on azithromycin, 763 participants on clarithromycin, 262 participants on erythromycin, and 100 participants on roxithromycin. There was no death related to any study drugs and rates of SAE were not significantly different from placebo in any drug. Overall withdrawal rates were slightly higher than placebo in doxycycline (RR, 1.30; 95% CI, 1.12-1.52) and minocycline (RR, 1.29; 95% CI, 1.15-1.46). Withdrawal rates due to adverse events were higher in doxycycline (RR, 2.82; 95% CI, 1.88-4.22), minocycline (RR, 1.48; 95% CI, 1.09-1.98), and azithromycin (RR, 1.53; 95% CI, 1.13-2.08). Gastrointestinal disturbances are the most common tolerable adverse effects for every drug. Photosensitivity and rash are the second most common adverse effects for doxycycline and minocycline. We found no evidence that long-term use up to 2 years of macrolides or tetracyclines was associated with increased risk of SAEs.
Topics: Humans; Macrolides; Azithromycin; Doxycycline; Minocycline; Anti-Bacterial Agents
PubMed: 37751595
DOI: 10.1002/jcph.2358 -
Asian Pacific Journal of Cancer... Feb 2023Tacrolimus is a powerful macrolide calcineurin inhibitor that has low adverse effects which lead to a rapid response in the control of signs and symptoms in comparison... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Topical Tacrolimus in Comparison with Topical Corticosteroids, Calcineurin Inhibitors, Retinoids and Placebo in Oral Lichen Planus: An Updated Systematic Review and Meta-Analysis.
BACKGROUND
Tacrolimus is a powerful macrolide calcineurin inhibitor that has low adverse effects which lead to a rapid response in the control of signs and symptoms in comparison to that of corticosteroids in Oral Lichen Planus(OLP). There have been increasing number of studies establishing the use of topical tacrolimus in oral lichen planus. Still, there is a need to find evidence of the successful use of tacrolimus in comparison to other drugs used in the treatment of OLP, by means of a systematic review and meta-analysis, so that an informed and accurate approach can be utilized.
METHODS
A comprehensive literature review was performed, including PubMed, the Cochrane Library, published up to and including December 2021. There were no restrictions on date of publication. Articles available in English language were included. Using the Cochrane Collaboration tool, we assessed the risk of bias for randomized controlled trials. A meta-analysis was performed on the relevant studies.
RESULTS
A total of 11 RCTs evaluating the effects of tacrolimus were included in this study after application of inclusion and exclusion criteria. Seven studies revealed a low bias risk, three presented a moderate risk and one had a high risk of bias. The results revealed no significant difference in clinical resolution and adverse effects between tacrolimus and corticosteroids. The pooled data from our meta-analysis shows that there is not sufficient evidence to prove that Tacrolimus is better in efficacy than other topical corticosteroids.
CONCLUSION
According to the current systematic study and meta-analysis, there is not sufficient evidence to prove that Tacrolimus is better in efficacy than other drugs. Uniform trials are required with larger sample sizes and standardized methodology are required for a better analysis.
Topics: Humans; Calcineurin Inhibitors; Tacrolimus; Retinoids; Lichen Planus, Oral; Macrolides; Drug-Related Side Effects and Adverse Reactions
PubMed: 36853285
DOI: 10.31557/APJCP.2023.24.2.389 -
Mycoses Mar 2017Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional... (Meta-Analysis)
Meta-Analysis Review
Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional and lipid-based (liposomal, lipid complex, colloidal dispersion and Intralipid infusion). The aim of our study was to determine the efficacy and safety of conventional amphotericin B vs its lipid-based formulations. A systematic review followed by pairwise meta-analysis was performed, including randomised controlled trials (RCTs) that evaluated the use of lipid-based amphotericin B in patients with any degree of immunosuppression and susceptibility to invasive fungal infection. An electronic search was conducted using PubMed, Scopus, Web of Science and Scielo databases. Extracted outcomes were related to efficacy (cure) and safety (incidence of adverse events). Results were evaluated and meta-analyses were performed. Twenty-three RCTs were identified (n=2677 participants) for meta-analysis. No significant differences between conventional amphotericin B and any of the five formulations evaluated were observed, with regard to the efficacy analysis. With respect to the adverse events of nephrotoxicity, fever, chills and vomiting, all lipid formulations presented better profiles than the conventional formulation. The present systematic review and meta-analysis showed that conventional amphotericin B presents the same efficacy profile as lipid-based formulations, although the latter were associated with a safer profile.
Topics: Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Colloids; Drug Compounding; Emulsions; Fever; Humans; Invasive Fungal Infections; Lipids; Phospholipids; Soybean Oil
PubMed: 27878878
DOI: 10.1111/myc.12585 -
Journal of Neurology Nov 2017To evaluate the efficacy and safety of tacrolimus in patients with myasthenia gravis (MG), a systematic review and meta-analysis was performed. We searched PubMed and... (Meta-Analysis)
Meta-Analysis Review
To evaluate the efficacy and safety of tacrolimus in patients with myasthenia gravis (MG), a systematic review and meta-analysis was performed. We searched PubMed and Embase for randomized controlled trials and clinical controlled trials in English language. Demographic and clinical characteristics of the MG patients were extracted. Differences in the current glucocorticoids (GC) dose in each included study were the primary outcome measure. The adverse events reported in each included study were used as safety evaluation. There were 5 trials included involving 683 patients. In this systematic review, we identified treatment with tacrolimus did not exhibit a statistically significant difference in the GC dose reduction at 6 months and 12 months compared with placebo. The standard mean differences in the GC dose reduction were -1.95 [(-4.20 to 0.30); p = 0.09] at 6 months and -1.72 [(-4.21 to 0.77); p = 0.18] at 12 months. But GC dose reduction from baseline in the tacrolimus group exceeded that in the controlled group. The weighted mean differences were -1.34 [(-2.46 to 0.23); p = 0.02] in the quantitative myasthenia gravis score and -1.10 [(-1.84 to -0.36); p = 0.004] in the myasthenia gravis activities of daily living score at 6 months. Adverse events were recorded in 80 of 347 patients (23%) treated with tacrolimus and most of them were mild. This meta-analysis proves that tacrolimus therapy is beneficial to improve clinical symptoms in MG patients. Tacrolimus may be a worthy therapy to relieve MG symptoms.
Topics: Humans; Immunosuppressive Agents; Myasthenia Gravis; Tacrolimus
PubMed: 28921038
DOI: 10.1007/s00415-017-8616-7 -
Pulmonary Pharmacology & Therapeutics Aug 2014Macrolides has been studied as a potential therapeutic anti-inflammatory agent for bronchiectasis patients, which has used as an immunoregulation agent. However, the... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Macrolides has been studied as a potential therapeutic anti-inflammatory agent for bronchiectasis patients, which has used as an immunoregulation agent. However, the efficacy and safety results of macrolides across available randomized controlled trials (RCTs) are controversial. The aim of this systematic review is to evaluate the efficacy and safety of macrolides in bronchiectasis.
METHODS
RCTs of macrolides treatment for the patients of bronchiectasis published in PubMed and Cochrane Library were searched. Two authors independently extracted data and assessment the methodological quality. The primary efficacy outcome was the impact on the number of pulmonary exacerbation. Safety outcomes included adverse events and mortality.
RESULTS
Seven RCTs were found in the systematic review and six studies were included in the present meta-analysis. Macrolides treatment showed a significant reduced rate of pulmonary exacerbation (RR = 0.55, 95%CI = 0.43-0.70) compared with control groups. However, subgroup analysis failed to find any significant changes in total 46 patients (RR = 0.20, 95%CI = 0.03-1.58) for treatment not more than 3 months. The incidence rates of total adverse events showed no significant difference among the macrolides group and control groups.
CONCLUSIONS
Long-term treatment of bronchiectasis with macrolides can reduce incidence of pulmonary exacerbation, especially in the subgroup treatment 6 months or more. There was no evidence of increased adverse events with macrolides. However, to verify the best macrolides regimen, more studies based on larger sample size and stratified by ethnicity are still needed.
CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE
Erythromycin (PubChem CID 12560); Azithromycin (PubChem CID: 447043); Clarithromycin (PubChem CID: 84029); Roxithromycin (PubChem CID: 5480431).
Topics: Anti-Inflammatory Agents; Bronchiectasis; Humans; Macrolides; Randomized Controlled Trials as Topic; Time Factors
PubMed: 24076368
DOI: 10.1016/j.pupt.2013.09.003 -
The Cochrane Database of Systematic... Jan 2015Background. Mycoplasma pneumoniae (M. pneumoniae) is widely recognised as an important cause of community-acquired lower respiratory tract infection (LRTI) in children.... (Meta-Analysis)
Meta-Analysis Review
Background. Mycoplasma pneumoniae (M. pneumoniae) is widely recognised as an important cause of community-acquired lower respiratory tract infection (LRTI) in children. Pulmonary manifestations are typically tracheobronchitis or pneumonia but M. pneumoniae is also implicated in wheezing episodes in both asthmatic and non-asthmatic individuals. Although antibiotics are used to treat LRTIs, are view of several major textbooks offers conflicting advice for using antibiotics in the management of M. pneumoniae LRTI in children.Objectives To determine whether antibiotics are effective in the treatment of childhood LRTI secondary to M. pneumoniae infections acquired in the community.Search methods We searched CENTRAL (2014, Issue 3), MEDLINE (1966 to July week 4, 2014), EMBASE (1980 to July, 2014), and both WHOICTRP and ClinicalTrials.gov (13 August 2014).Selection criteria Randomised controlled trials (RCTs) comparing antibiotics commonly used for treating M. pneumoniae (i.e. macrolide, tetracycline or quinolone classes) versus placebo, or antibiotics from any other class in the treatment of children under 18 years of age with community acquired LRTI secondary to M. pneumoniae.Data collection and analysis The review authors independently selected trials for inclusion and assessed methodological quality. We extracted and analysed relevant data separately and resolved disagreements by consensus.Main results A total of 1912 children were enrolled from seven studies. Data interpretation was limited by the inability to extract data that referred to children with M. pneumoniae. In most studies, clinical response did not differ between children randomised to a macrolide antibiotic and children randomised to a non-macrolide antibiotic. In one controlled study (of children with recurrent respiratory infections, whose acute LRTI was associated with Mycoplasma, Chlamydia or both, by polymerase chain reaction and/or paired sera) 100% of children treated with azithromycin had clinical resolution of their illness compared to 77% not treated with azithromycin at one month. Authors' conclusions There is insufficient evidence to draw any specific conclusions about the efficacy of antibiotics for this condition in children (although one trial suggests macrolides may be efficacious in some children with LRTI secondary to Mycoplasma). The use of antibiotics has to be balanced with possible adverse events. There is still a need for high quality, double-blinded RCTs to assess the efficacy and safety of antibiotics for LRTI secondary to M. pneumoniae in children.
Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azithromycin; Bronchitis; Child; Community-Acquired Infections; Erythromycin; Humans; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Randomized Controlled Trials as Topic
PubMed: 25566754
DOI: 10.1002/14651858.CD004875.pub5 -
JAMA Sep 2015Chronic sinusitis is a common inflammatory condition defined by persistent symptomatic inflammation of the sinonasal cavities lasting longer than 3 months. It accounts... (Review)
Review
IMPORTANCE
Chronic sinusitis is a common inflammatory condition defined by persistent symptomatic inflammation of the sinonasal cavities lasting longer than 3 months. It accounts for 1% to 2% of total physician encounters and is associated with large health care expenditures. Appropriate use of medical therapies for chronic sinusitis is necessary to optimize patient quality of life (QOL) and daily functioning and minimize the risk of acute inflammatory exacerbations.
OBJECTIVE
To summarize the highest-quality evidence on medical therapies for adult chronic sinusitis and provide an evidence-based approach to assist in optimizing patient care.
EVIDENCE REVIEW
A systematic review searched Ovid MEDLINE (1947-January 30, 2015), EMBASE, and Cochrane Databases. The search was limited to randomized clinical trials (RCTs), systematic reviews, and meta-analyses. Evidence was categorized into maintenance and intermittent or rescue therapies and reported based on the presence or absence of nasal polyps.
FINDINGS
Twenty-nine studies met inclusion criteria: 12 meta-analyses (>60 RCTs), 13 systematic reviews, and 4 RCTs that were not included in any of the meta-analyses. Saline irrigation improved symptom scores compared with no treatment (standardized mean difference [SMD], 1.42 [95% CI, 1.01 to 1.84]; a positive SMD indicates improvement). Topical corticosteroid therapy improved overall symptom scores (SMD, -0.46 [95% CI, -0.65 to -0.27]; a negative SMD indicates improvement), improved polyp scores (SMD, -0.73 [95% CI, -1.0 to -0.46]; a negative SMD indicates improvement), and reduced polyp recurrence after surgery (relative risk, 0.59 [95% CI, 0.45 to 0.79]). Systemic corticosteroids and oral doxycycline (both for 3 weeks) reduced polyp size compared with placebo for 3 months after treatment (P < .001). Leukotriene antagonists improved nasal symptoms compared with placebo in patients with nasal polyps (P < .01). Macrolide antibiotic for 3 months was associated with improved QOL at a single time point (24 weeks after therapy) compared with placebo for patients without polyps (SMD, -0.43 [95% CI, -0.82 to -0.05]).
CONCLUSIONS AND RELEVANCE
Evidence supports daily high-volume saline irrigation with topical corticosteroid therapy as a first-line therapy for chronic sinusitis. A short course of systemic corticosteroids (1-3 weeks), short course of doxycycline (3 weeks), or a leukotriene antagonist may be considered in patients with nasal polyps. A prolonged course (3 months) of macrolide antibiotic may be considered for patients without polyps.
Topics: Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Antifungal Agents; Chronic Disease; Doxycycline; Histamine Antagonists; Humans; Leukotriene Antagonists; Macrolides; Maintenance Chemotherapy; Nasal Polyps; Quality of Life; Sinusitis; Sodium Chloride; Therapeutic Irrigation
PubMed: 26325561
DOI: 10.1001/jama.2015.7544 -
European Archives of... Aug 2023This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on... (Review)
Review
PURPOSE
This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on treatment efficacy but also on possible treatment-related adverse events, and treatment combinations with other techniques.
METHODS
Search criteria were applied to MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases and included all studies published up to March 2022 reporting paediatric lymphatic malformations treated with sirolimus. We selected all original studies that included treatment outcomes. After the removal of duplicates, selection of abstracts and full-text articles, and quality assessment, we reviewed eligible articles for patient demographics, lymphatic malformation type, size or stage, site, clinical response rates, sirolimus administration route and dose, related adverse events, follow-up time, and concurrent treatments.
RESULTS
Among 153 unique citations, 19 studies were considered eligible, with reported treatment data for 97 paediatric patients. Most studies (n = 9) were case reports. Clinical response was described for 89 patients, in whom 94 mild-to-moderate adverse events were reported. The most frequently administered treatment regimen was oral sirolimus 0.8 mg/m twice a day, with the aim of achieving a blood concentration of 10-15 ng/mL.
CONCLUSION
Despite promising results for sirolimus treatment in lymphatic malformation, the efficacy and safety profile of remains unclear due to the lack of high-quality studies. Systematic reporting of known side effects, especially in younger children, should assist clinicians in minimising treatment-associated risks. At the same time, we advocate for prospective multicentre studies with minimum reporting standards to facilitate improved candidate selection.
Topics: Humans; Child; Sirolimus; Prospective Studies; Treatment Outcome; Neck; Head; Lymphatic Abnormalities; Vascular Malformations
PubMed: 37115326
DOI: 10.1007/s00405-023-07991-1 -
Transplantation Reviews (Orlando, Fla.) Dec 2023There is lack of consensus on non-tuberculous mycobacteria pulmonary disease (NTM-PD) treatment regimen and duration in patient listed for lung transplantation (LTx). We... (Review)
Review
BACKGROUND
There is lack of consensus on non-tuberculous mycobacteria pulmonary disease (NTM-PD) treatment regimen and duration in patient listed for lung transplantation (LTx). We conducted a systematic review on treatment regimen and duration pre- and directly post-LTx, for patients with known NTM-PD pre-LTx. Additionally, we searched for risk factors for NTM disease development post-LTx and for mortality.
METHODS
Literature was reviewed on PubMed, Embase and the Cochrane Library, for articles published from inception to January 2022. Individual patient data were sought.
RESULTS
Sixteen studies were included reporting 92 patients. Most frequent used agents were aminoglycosides and macrolides for Mycobacterium abscessus (M. abscessus) and macrolides and tuberculostatic agents for Mycobacterium avium complex (M. avium complex). The median treatment duration pre-LTx was 10 months (IQR 6-17) and 2 months (IQR 2-8) directly post-LTx. Longer treatment duration pre-LTx was observed in children and in patients with M. abscessus. 46% of the patients with NTM-PD pre-LTx developed NTM disease post-LTx, related mortality rate was 10%. Longer treatment duration pre-LTx (p < 0.001) and sputum non-conversion pre-LTx (p = 0.003) were significantly associated with development of NTM-disease post-LTx. Longer treatment duration pre-LTx (p = 0.004), younger age (p < 0.001) and sputum non-conversion (p = 0.044) were risk factors for NTM related death.
CONCLUSIONS
The median treatment duration pre-LTx was 10 months (IQR 6-17) and 2 months (IQR 2-8) directly post-LTx. Patients with longer treatment duration for NTM-PD pre-LTx and with sputum non-conversion are at risk for NTM disease post-LTx and for NTM-related death. Children were particularly at risk for NTM related death.
Topics: Child; Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Lung Diseases; Lung Transplantation; Anti-Bacterial Agents; Macrolides
PubMed: 37832509
DOI: 10.1016/j.trre.2023.100800 -
The Cochrane Database of Systematic... Sep 2014Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or empirically to patients with persistent fever.
OBJECTIVES
To compare the effect of fluconazole and amphotericin B on morbidity and mortality in patients with cancer complicated by neutropenia.
SEARCH METHODS
We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles.
SELECTION CRITERIA
Randomised clinical trials comparing fluconazole with amphotericin B.
DATA COLLECTION AND ANALYSIS
The two review authors independently assessed trial eligibility and risk of bias, and abstracted data.
MAIN RESULTS
Seventeen trials (3798 patients, 381 deaths) were included. In two large three-armed trials, results for amphotericin B were combined with results for nystatin in a 'polyene' group. Because nystatin is an ineffective drug in these circumstances, this approach creates a bias in favour of fluconazole. Furthermore, most patients were randomised to oral amphotericin B, which is poorly absorbed and poorly documented. There was overlap among the 'polyene' trials but we were unable to obtain any information from the trial authors or from Pfizer, the manufacturer of fluconazole, to clarify these issues. There were no significant differences in effect between fluconazole and amphotericin B, but the confidence intervals were wide. More patients dropped out of the study when they received amphotericin B, but as none of the trials were blinded decisions on premature interruption of therapy could have been biased. Furthermore, amphotericin B was not given under optimal circumstances, with premedication to reduce infusion-related toxicity, slow infusion, and with fluid, potassium and magnesium supplements to prevent nephrotoxicity. The major harms were hepatic impairment and gastrointestinal adverse effects with fluconazole and infusion-related toxicity, renal impairment and gastrointestinal adverse effects with amphotericin B. For the 2011 and 2014 updates no additional trials were identified for inclusion.
AUTHORS' CONCLUSIONS
Amphotericin B has been disfavoured in several of the trials through their design or analysis, or both. Since intravenous amphotericin B is the only antifungal agent for which an effect on mortality has been shown, and since it is considerably cheaper than fluconazole, it should be the preferred agent.
Topics: Administration, Oral; Amphotericin B; Antifungal Agents; Confidence Intervals; Fluconazole; Humans; Injections, Intravenous; Mycoses; Neoplasms; Neutropenia; Nystatin; Odds Ratio; Randomized Controlled Trials as Topic
PubMed: 25188769
DOI: 10.1002/14651858.CD000239.pub2