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The Journal of Infection May 2019To assess the utility of the neutrophil:lymphocyte (NLR), lymphocyte:monocyte (LMR) and platelet:lymphocyte ratios (PLR) as infection biomarkers. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the utility of the neutrophil:lymphocyte (NLR), lymphocyte:monocyte (LMR) and platelet:lymphocyte ratios (PLR) as infection biomarkers.
METHODS
PubMed/MEDLINE, Embase and Cochrane databases were searched to identify eligible articles. Studies of diagnosis, severity or outcome were included. PROSPERO systematic review registration CRD42017075032.
RESULTS
Forty studies were included, reporting on bacterial and viral infections, malaria, and critical illness due to sepsis. Ten studies reported an association of higher NLR with bacteraemia, supported by meta-analysis of patient-level data (five studies, n = 3320; AUC 0.72, p<0.0001) identifying a cut-off of >12.65. Two studies reported an association with lower LMR and diagnosis of influenza virus infection in patients with respiratory tract infection. Meta-analysis of patient-level data (n = 85; AUC 0.66, p = 0.01) identified a cut-off of ≤2.06. The directionality of associations between NLR and outcomes in heterogeneous cohorts of critically ill adults with sepsis varied. Potential clinical utility was also demonstrated in pneumonia (NLR), pertussis (NLR), urinary tract infection (NLR), diabetic foot infections (NLR) and Crimean Congo Haemorrhagic Fever (PLR). Longitudinal measurement of LMR during respiratory virus infection reflected symptoms and NLR during sepsis and bacteraemia predicted mortality.
CONCLUSIONS
Peripheral blood leucocyte ratios are useful infection biomarkers, with the most evidence related to diagnosis of bacteraemia and influenza virus infection. In critical illness due to sepsis, a signal towards an association with NLR and outcomes exists, and NLR should be evaluated in future stratification models. Longitudinal measurement of ratios during infection could be informative. Overall, these biomarkers warrant further recognition and study in infectious diseases.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Child; Child, Preschool; Communicable Diseases; Female; Humans; Infant; Infant, Newborn; Leukocyte Count; Male; Middle Aged; Young Adult
PubMed: 30802469
DOI: 10.1016/j.jinf.2019.02.006 -
Critical Care (London, England) Dec 2017An optimal therapy for the treatment of pneumonia caused by drug-resistant Acinetobacter baumannii remains unclear. This study aims to compare various antimicrobial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An optimal therapy for the treatment of pneumonia caused by drug-resistant Acinetobacter baumannii remains unclear. This study aims to compare various antimicrobial strategies and to determine the most effective therapy for pneumonia using a network meta-analysis.
METHODS
Systematic search and quality assessment were performed to select eligible studies reporting one of the following outcomes: all-cause mortality, clinical cure, and microbiological eradication. The primary outcome was all-cause mortality. A network meta-analysis was conducted with a Bayesian approach. Antimicrobial treatments were ranked based on surface under the cumulative ranking curve (SUCRA) value along with estimated median outcome rate and corresponding 95% credible intervals (CrIs). Two treatments were considered significantly different if a posterior probability of superiority (P) was greater than 97.5%.
RESULTS
Twenty-three studies evaluating 15 antimicrobial treatments were included. Intravenous colistin monotherapy (IV COL) was selected as a common comparator, serving as a bridge for developing the network. Five treatments ranked higher than IV COL (SUCRA, 57.1%; median all-cause mortality 0.45, 95% CrI 0.41-0.48) for reducing all-cause mortality: sulbactam monotherapy (SUL, 100.0%; 0.18, 0.04-0.42), high-dose SUL (HD SUL, 85.7%; 0.31, 0.07-0.71), fosfomycin plus IV COL (FOS + IV COL, 78.6%; 0.34, 0.19-0.54), inhaled COL plus IV COL (IH COL + IV COL, 71.4%; 0.39, 0.32-0.46), and high-dose tigecycline (HD TIG, 71.4%; 0.39, 0.16-0.67). Those five treatments also ranked higher than IV COL (SUCRA, 45.5%) for improving clinical cure (72.7%, 72.7%, 63.6%, 81.8%, and 90.9%, respectively). Among the five treatments, SUL (P = 98.1%) and IH COL + IV COL (P = 99.9%) were significantly superior to IV COL for patient survival and clinical cure, respectively. In terms of microbiological eradication, FOS + IV COL (P = 99.8%) and SUL (P = 98.9%) were significantly superior to IV COL.
CONCLUSIONS
This Bayesian network meta-analysis demonstrated the comparative effectiveness of fifteen antimicrobial treatments for drug-resistant A. baumannii pneumonia in critically ill patients. For survival benefit, SUL appears to be the best treatment followed by HD SUL, FOS + IV COL, IH COL + IV COL, HD TIG, and IV COL therapy, in numerical order.
Topics: Acinetobacter baumannii; Anti-Infective Agents; Bayes Theorem; Colistin; Critical Illness; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests
PubMed: 29262831
DOI: 10.1186/s13054-017-1916-6 -
Advances in Therapy Mar 2020Studies assessing the effect of high dose tigecycline on severe infections are limited and remain controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies assessing the effect of high dose tigecycline on severe infections are limited and remain controversial.
OBJECTIVES
To assess systematically the effectiveness and safety of high dose tigecycline in the treatment of severe infections.
METHODS
Pubmed, Web of Science, Embase, MEDLINE, Cochrane Library and ClinicalTrials were searched up to February 20, 2019 for studies that compared the effectiveness and safety of high dose tigecycline with standard dose tigecycline or other non-tigecycline-containing regimens in the treatment of severe infections. Rates for all-cause mortality, clinical cure, microbiological eradication and adverse events were analysed.
RESULTS
Ten studies with 593 patients were included. The results indicated that using high dose tigecycline resulted in better outcomes compared with controls with lower all-cause mortality (OR 0.44, 95% CI 0.30-0.66, p < 0.0001), higher clinical cure (OR 3.43, 95% CI 2.09-5.63, p < 0.00001), higher microbiological eradication (OR 2.25, 95% CI 1.44-3.50, p = 0.0003), and without increasing adverse events rates. Subgroup analysis showed that high dose tigecycline reduced all-cause mortality in nosocomial acquired pneumonia (OR 0.39, 95% CI 0.22-0.70, p = 0.002), bloodstream infections (OR 0.19, 95% CI 0.06-0.58, p = 0.004) and mixed infections (OR 0.20, 95% CI 0.07-0.59, p = 0.003), with no statistical differences in complicated intra-abdominal infections (OR 2.04, 95% CI 0.80-5.23, p = 0.14). In carbapenem-resistant pathogens, the microbiological eradication rate in those given high dose tigecycline did not differ from controls (OR 1.07, 95% CI 0.44-2.60, p = 0.87), although mortality was reduced (OR 0.20, 95% CI 0.09-0.45, p = 0.0001). The main limitation of the review is that most of the included studies are observational studies with small sample sizes and high risks of bias.
CONCLUSIONS
High dose tigecycline treatment is effective and safe for severe infections owing to its lower all-cause mortality, higher clinical cure, microbiological eradication and comparable adverse events. However, as a result of the high risks of bias of the included studies, well-designed randomised clinical trials are warranted to establish the effectiveness and safety of high dose tigecycline compared with standard dose tigecycline and other commonly used antibiotics.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Infections; Observational Studies as Topic; Severity of Illness Index; Tigecycline
PubMed: 32006240
DOI: 10.1007/s12325-020-01235-y -
The Cochrane Database of Systematic... Jan 2016Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged length of hospital stay and increased healthcare costs in critically ill... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged length of hospital stay and increased healthcare costs in critically ill patients. Guidelines recommend a semi-recumbent position (30º to 45º) for preventing VAP among patients requiring mechanical ventilation. However, due to methodological limitations in existing systematic reviews, uncertainty remains regarding the benefits and harms of the semi-recumbent position for preventing VAP.
OBJECTIVES
To assess the effectiveness and safety of semi-recumbent positioning versus supine positioning to prevent ventilator-associated pneumonia (VAP) in adults requiring mechanical ventilation.
SEARCH METHODS
We searched CENTRAL (2015, Issue 10), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1946 to October 2015), EMBASE (2010 to October 2015), CINAHL (1981 to October 2015) and the Chinese Biomedical Literature Database (CBM) (1978 to October 2015).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing semi-recumbent versus supine positioning (0º to 10º), or RCTs comparing alternative degrees of positioning in mechanically ventilated patients. Our outcomes included clinically suspected VAP, microbiologically confirmed VAP, intensive care unit (ICU) mortality, hospital mortality, length of ICU stay, length of hospital stay, duration of ventilation, antibiotic use and any adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently and in duplicate screened titles, abstracts and full texts, assessed risk of bias and extracted data using standardised forms. We calculated the mean difference (MD) and 95% confidence interval (95% CI) for continuous data and the risk ratio (RR) and 95% CI for binary data. We performed meta-analysis using the random-effects model. We used the grading of recommendations, assessment, development and evaluation (GRADE) approach to grade the quality of evidence.
MAIN RESULTS
We included 10 trials involving 878 participants, among which 28 participants in two trials did not provide complete data due to loss to follow-up. We judged all trials to be at high risk of bias. Semi-recumbent position (30º to 60º) versus supine position (0° to 10°) A semi-recumbent position (30º to 60º) significantly reduced the risk of clinically suspected VAP compared to a 0º to 10º supine position (eight trials, 759 participants, 14.3% versus 40.2%, RR 0.36; 95% CI 0.25 to 0.50; risk difference (RD) 25.7%; 95% CI 20.1% to 30.1%; GRADE: moderate quality evidence).There was no significant difference between the two positions in the following outcomes: microbiologically confirmed VAP (three trials, 419 participants, 12.6% versus 31.6%, RR 0.44; 95% CI 0.11 to 1.77; GRADE: very low quality evidence), ICU mortality (two trials, 307 participants, 29.8% versus 34.3%, RR 0.87; 95% CI 0.59 to 1.27; GRADE: low quality evidence), hospital mortality (three trials, 346 participants, 23.8% versus 27.6%, RR 0.84; 95% CI 0.59 to 1.20; GRADE: low quality evidence), length of ICU stay (three trials, 346 participants, MD -1.64 days; 95% CI -4.41 to 1.14 days; GRADE moderate quality evidence), length of hospital stay (two trials, 260 participants, MD -9.47 days; 95% CI -34.21 to 15.27 days; GRADE: very low quality evidence), duration of ventilation (four trials, 458 participants, MD -3.35 days; 95% CI -7.80 to 1.09 days), antibiotic use (three trials, 284 participants, 84.8% versus 84.2%, RR 1.00; 95% CI 0.97 to 1.03) and pressure ulcers (one trial, 221 participants, 28% versus 30%, RR 0.91; 95% CI 0.60 to 1.38; GRADE: low quality evidence). No other adverse events were reported. Semi-recumbent position (45°) versus 25° to 30° We found no statistically significant differences in the following prespecified outcomes: clinically suspected VAP (two trials, 91 participants, RR 0.74; 95% CI 0.35 to 1.56; GRADE: very low quality evidence), microbiologically confirmed VAP (one trial, 30 participants, RR 0.61; 95% CI 0.20 to 1.84: GRADE: very low quality evidence), ICU mortality (one trial, 30 participants, RR 0.57; 95% CI 0.15 to 2.13; GRADE: very low quality evidence), hospital mortality (two trials, 91 participants, RR 1.00; 95% CI 0.38 to 2.65; GRADE: very low quality evidence), length of ICU stay (one trial, 30 participants, MD 1.6 days; 95% CI -0.88 to 4.08 days; GRADE: very low quality evidence) and antibiotic use (two trials, 91 participants, RR 1.11; 95% CI 0.84 to 1.47). No adverse events were reported.
AUTHORS' CONCLUSIONS
A semi-recumbent position (≧ 30º) may reduce clinically suspected VAP compared to a 0° to 10° supine position. However, the evidence is seriously limited with a high risk of bias. No adequate evidence is available to draw any definitive conclusion on other outcomes and the comparison of alternative semi-recumbent positions. Adverse events, particularly venous thromboembolism, were under-reported.
Topics: Adult; Anti-Bacterial Agents; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Patient Positioning; Pneumonia, Ventilator-Associated; Pressure Ulcer; Randomized Controlled Trials as Topic; Respiration, Artificial; Supine Position
PubMed: 26743945
DOI: 10.1002/14651858.CD009946.pub2 -
Journal of Clinical Medicine Dec 2022Extra-pulmonary features sometimes occur in association with atypical bacterial pneumonia and include neurologic manifestations, diarrhea, rashes, altered liver enzymes,... (Review)
Review
BACKGROUND
Extra-pulmonary features sometimes occur in association with atypical bacterial pneumonia and include neurologic manifestations, diarrhea, rashes, altered liver enzymes, or kidney injury, among other conditions. Acute pancreatitis has been associated with atypical pneumonias since 1973.
METHODS
We performed a systematic review of the literature in the Excerpta Medica, National Library of Medicine, and Web of Science databases. We retained 27 reports published between 1973 and 2022 describing subjects with an otherwise unexplained pancreatitis temporally associated with an atypical pneumonia.
RESULTS
The reports included 33 subjects (19 males, and 14 females; 8 children and 25 adults) with acute pancreatitis temporally associated with atypical pneumonia caused by ( = 18), species ( = 14), or ( = 1). Approximately 90% of patients ( = 29) concurrently presented with respiratory and pancreatic diseases. No cases associated with , , or species were found.
CONCLUSIONS
Acute pancreatitis has been associated with various infectious agents. The present review documents the association with atypical pneumonia induced by , species, and .
PubMed: 36498822
DOI: 10.3390/jcm11237248 -
Clinical Infectious Diseases : An... Feb 2023The optimal treatment duration of community-acquired pneumonia (CAP) in children has been controversial in high-income countries. We conducted a meta-analysis to compare... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The optimal treatment duration of community-acquired pneumonia (CAP) in children has been controversial in high-income countries. We conducted a meta-analysis to compare short antibiotic treatment (3-5 days) with longer treatment (7-10 days) among children aged ≥6 months.
METHODS
On 31 January 2022, we searched PubMed, Scopus, and Web of Science databases for studies published in English from 2003 to 2022. We included randomized controlled trials focusing on antibiotic treatment duration in children with CAP treated as outpatients. We calculated risk differences (RDs) with 95% confidence intervals and used the fixed-effect model (low heterogeneity). Our main outcome was treatment failure, defined as need for retreatment or hospitalization within 1 month. Our secondary outcome was presence of antibiotic-related harms.
RESULTS
A total of 541 studies were screened, and 4 studies with 1541 children were included in the review. Three studies had low risk of bias, and one had some concerns. All 4 studies assessed treatment failures, and the RD was 0.1% (95% confidence interval, -3.0% to 2.0%) with high quality of evidence. Two studies (1194 children) assessed adverse events related to antibiotic treatment, and the RD was 0.0% (-5.0% to 5.0%) with moderate quality of evidence. The diagnostic criteria varied between the included studies.
CONCLUSIONS
A short antibiotic treatment duration of 3-5 days was equally effective and safe compared with the longer (current) recommendation of 7-10 days in children aged ≥6 months with CAP. We suggest that short antibiotic courses can be implemented in treatment of pediatric CAP.
Topics: Child; Humans; Anti-Bacterial Agents; Outpatients; Duration of Therapy; Developed Countries; Pneumonia; Community-Acquired Infections
PubMed: 35579504
DOI: 10.1093/cid/ciac374 -
BMJ Clinical Evidence Aug 2010In the northern hemisphere about 12/1000 people a year (on average) contract pneumonia while living in the community, with most cases caused by Streptococcus pneumoniae.... (Review)
Review
INTRODUCTION
In the northern hemisphere about 12/1000 people a year (on average) contract pneumonia while living in the community, with most cases caused by Streptococcus pneumoniae. Mortality ranges from about 5% to 35% depending on severity of disease, with a worse prognosis in older people, men, and people with chronic diseases.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent community-acquired pneumonia? What are the effects of treatments for community-acquired pneumonia in outpatient settings, in people admitted to hospital, and in people receiving intensive care? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (oral, intravenous), different combinations, and prompt administration of antibiotics in intensive-care settings, early mobilisation, influenza vaccine, and pneumococcal vaccine.
Topics: Administration, Oral; Anti-Bacterial Agents; Community-Acquired Infections; Evidence-Based Medicine; Hospitalization; Humans; Incidence; Pneumonia; Severity of Illness Index; Streptococcus pneumoniae
PubMed: 21418681
DOI: No ID Found -
The Lancet. Microbe Dec 2022Antimicrobial resistance of bacterial pathogens is an increasing clinical problem and alternative approaches to antibiotic chemotherapy are needed. One of these... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antimicrobial resistance of bacterial pathogens is an increasing clinical problem and alternative approaches to antibiotic chemotherapy are needed. One of these approaches is the use of lytic bacterial viruses known as phage therapy. We aimed to assess the efficacy of phage therapy in preclinical animal models of bacterial infection.
METHODS
In this systematic review and meta-analysis, MEDLINE/Ovid, Embase/Ovid, CINAHL/EbscoHOST, Web of Science/Wiley, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Google Scholar were searched from inception to Sept 30, 2021. Studies assessing phage efficacy in animal models were included. Only studies that assessed the efficacy of phage therapy in treating established bacterial infections in terms of survival and bacterial abundance or density were included. Studies reporting only in-vitro or ex-vivo results and those with incomplete information were excluded. Risk-of-bias assessment was performed using the Systematic Review Centre for Laboratory Animal Experimentation tool. The main endpoints were animal survival and tissue bacterial burden, which were reported using pooled odds ratios (ORs) and mean differences with random-effects models. The I measure and its 95% CI were also calculated. This study is registered with PROSPERO, CRD42022311309.
FINDINGS
Of the 5084 references screened, 124 studies fulfilled the selection criteria. Risk of bias was high for 70 (56%) of the 124 included studies; therefore, only studies classified as having a low-to-moderate risk of bias were considered for quantitative data synthesis (n=32). Phage therapy was associated with significantly improved survival at 24 h in systemic infection models (OR 0·08 [95% CI 0·03 to 0·20]; I=55% [95% CI 8 to 77]), skin infection (OR 0·08 [0·04 to 0·19]; I = 0% [0 to 79]), and pneumonia models (OR 0·13 [0·06 to 0·31]; I=0% [0 to 68]) when compared with placebo. Animals with skin infections (mean difference -2·66 [95% CI -3·17 to -2·16]; I = 95% [90 to 96]) and those with pneumonia (mean difference -3·35 [-6·00 to -0·69]; I = 99% [98 to 99]) treated with phage therapy had significantly lower tissue bacterial loads at 5 ± 2 days of follow-up compared with placebo.
INTERPRETATION
Phage therapy significantly improved animal survival and reduced organ bacterial loads compared with placebo in preclinical animal models. However, high heterogeneity was observed in some comparisons. More evidence is needed to identify the factors influencing phage therapy performance to improve future clinical application.
FUNDING
Swiss National Foundation and Swiss Heart Foundation.
Topics: Humans; Phage Therapy; Bacterial Infections; Anti-Bacterial Agents
PubMed: 36370748
DOI: 10.1016/S2666-5247(22)00288-9 -
Clinical Microbiology and Infection :... Dec 2016Antibiotic de-escalation is an appealing strategy in antibiotic stewardship programmes. We aimed to assess its safety and effects using a systematic review and... (Meta-Analysis)
Meta-Analysis Review
Antibiotic de-escalation is an appealing strategy in antibiotic stewardship programmes. We aimed to assess its safety and effects using a systematic review and meta-analysis. We included randomized controlled trials (RCTs) and observational studies assessing adults with bacteraemia, microbiologically documented pneumonia or severe sepsis, comparing between antibiotic de-escalation and no de-escalation. De-escalation was defined as changing an initially covering antibiotic regimen to a narrower spectrum regimen based on antibiotic susceptibility testing results within 96 hours. The primary outcome was 30-day all-cause mortality. A search of published articles and conference proceedings was last updated in September 2015. Crude and adjusted ORs with 95% CI were pooled in random-effects meta-analyses. Sixteen observational studies and three RCTs were included. Risk of bias related to confounding was high in the observational studies. De-escalation was associated with fewer deaths in the unadjusted analysis (OR 0.53, 95% CI 0.39-0.73), 19 studies, moderate heterogeneity. In the adjusted analysis there was no significant difference in mortality (adjusted OR 0.83, 95% CI 0.59-1.16), 11 studies, moderate heterogeneity and the RCTs showed non-significant increased mortality with de-escalation (OR 1.73, 95% 0.97-3.06), three trials, no heterogeneity. There was a significant unadjusted association between de-escalation and survival in bacteraemia/severe sepsis (OR 0.45, 95% CI 0.30-0.67) and ventilator-associated pneumonia (OR 0.49, 95% CI 0.26-0.95), but not with other pneumonia (OR 0.97, 95% CI 0.45-2.12). Only two studies reported on the emergence of resistance with inconsistent findings. Observational studies suggest lower mortality with antibiotic susceptibility testing-based de-escalation for bacteraemia, severe sepsis and ventilator-associated pneumonia that was not demonstrated in RCTs.
Topics: Anti-Bacterial Agents; Bacteremia; Bias; Communicable Diseases; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Observational Studies as Topic; Pneumonia, Ventilator-Associated; Randomized Controlled Trials as Topic; Risk Assessment; Sepsis; Treatment Outcome
PubMed: 27283148
DOI: 10.1016/j.cmi.2016.05.023 -
The Cochrane Database of Systematic... Mar 2018Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation and distortion of the smaller airways. Bacterial colonisation of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiectasis is a chronic respiratory disease characterised by abnormal and irreversible dilatation and distortion of the smaller airways. Bacterial colonisation of the damaged airways leads to chronic cough and sputum production, often with breathlessness and further structural damage to the airways. Long-term macrolide antibiotic therapy may suppress bacterial infection and reduce inflammation, leading to fewer exacerbations, fewer symptoms, improved lung function, and improved quality of life. Further evidence is required on the efficacy of macrolides in terms of specific bacterial eradication and the extent of antibiotic resistance.
OBJECTIVES
To determine the impact of macrolide antibiotics in the treatment of adults and children with bronchiectasis.
SEARCH METHODS
We identified trials from the Cochrane Airways Trials Register, which contains studies identified through multiple electronic searches and handsearches of other sources. We also searched trial registries and reference lists of primary studies. We conducted all searches on 18 January 2018.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of at least four weeks' duration that compared macrolide antibiotics with placebo or no intervention for the long-term management of stable bronchiectasis in adults or children with a diagnosis of bronchiectasis by bronchography, plain film chest radiograph, or high-resolution computed tomography. We excluded studies in which participants had received continuous or high-dose antibiotics immediately before enrolment or before a diagnosis of cystic fibrosis, sarcoidosis, or allergic bronchopulmonary aspergillosis. Our primary outcomes were exacerbation, hospitalisation, and serious adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of 103 records. We independently screened the full text of 40 study reports and included 15 trials from 30 reports. Two review authors independently extracted outcome data and assessed risk of bias for each study. We analysed dichotomous data as odds ratios (ORs) and continuous data as mean differences (MDs) or standardised mean differences (SMDs). We used standard methodological procedures as expected by Cochrane.
MAIN RESULTS
We included 14 parallel-group RCTs and one cross-over RCT with interventions lasting from 8 weeks to 24 months. Of 11 adult studies with 690 participants, six used azithromycin, four roxithromycin, and one erythromycin. Four studies with 190 children used either azithromycin, clarithromycin, erythromycin, or roxithromycin.We included nine adult studies in our comparison between macrolides and placebo and two in our comparison with no intervention. We included one study with children in our comparison between macrolides and placebo and one in our comparison with no intervention.In adults, macrolides reduced exacerbation frequency to a greater extent than placebo (OR 0.34, 95% confidence interval (CI) 0.22 to 0.54; 341 participants; three studies; I = 65%; moderate-quality evidence). This translates to a number needed to treat for an additional beneficial outcome of 4 (95% CI 3 to 8). Data show no differences in exacerbation frequency between use of macrolides (OR 0.31, 95% CI 0.08 to 1.15; 43 participants; one study; moderate-quality evidence) and no intervention. Macrolides were also associated with a significantly better quality of life compared with placebo (MD -8.90, 95% CI -13.13 to -4.67; 68 participants; one study; moderate-quality evidence). We found no evidence of a reduction in hospitalisations (OR 0.56, 95% CI 0.19 to 1.62; 151 participants; two studies; I = 0%; low-quality evidence), in the number of participants with serious adverse events, including pneumonia, respiratory and non-respiratory infections, haemoptysis, and gastroenteritis (OR 0.49, 95% CI 0.20 to 1.23; 326 participants; three studies; I = 0%; low-quality evidence), or in the number experiencing adverse events (OR 0.83, 95% CI 0.51 to 1.35; 435 participants; five studies; I = 28%) in adults with macrolides compared with placebo.In children, there were no differences in exacerbation frequency (OR 0.40, 95% CI 0.11 to 1.41; 89 children; one study; low-quality evidence); hospitalisations (OR 0.28, 95% CI 0.07 to 1.11; 89 children; one study; low-quality evidence), serious adverse events, defined within the study as exacerbations of bronchiectasis or investigations related to bronchiectasis (OR 0.43, 95% CI 0.17 to 1.05; 89 children; one study; low-quality evidence), or adverse events (OR 0.78, 95% CI 0.33 to 1.83; 89 children; one study), in those receiving macrolides compared to placebo. The same study reported an increase in macrolide-resistant bacteria (OR 7.13, 95% CI 2.13 to 23.79; 89 children; one study), an increase in resistance to Streptococcus pneumoniae (OR 13.20, 95% CI 1.61 to 108.19; 89 children; one study), and an increase in resistance to Staphylococcus aureus (OR 4.16, 95% CI 1.06 to 16.32; 89 children; one study) with macrolides compared with placebo. Quality of life was not reported in the studies with children.
AUTHORS' CONCLUSIONS
Long-term macrolide therapy may reduce the frequency of exacerbations and improve quality of life, although supporting evidence is derived mainly from studies of azithromycin, rather than other macrolides, and predominantly among adults rather than children. However, macrolides should be used with caution, as limited data indicate an associated increase in microbial resistance. Macrolides are associated with increased risk of cardiovascular death and other serious adverse events in other populations, and available data cannot exclude a similar risk among patients with bronchiectasis.
Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Child, Preschool; Clarithromycin; Erythromycin; Humans; Macrolides; Randomized Controlled Trials as Topic; Roxithromycin
PubMed: 29543980
DOI: 10.1002/14651858.CD012406.pub2