Follow-up duration was specified in 21 studies, of which 16 defined a specific time for outcome measurement.
Follow-up ranged from the end of treatment to 3 months after. Overall mortality was assessed at the end of treatment or at follow-up in all studies. Data at the furthest point in time, up to 30 days, was chosen for analysis. At least 18 of the 24 studies were sponsored by pharmaceutical companies, all of which manufactured the drug with atypical coverage.
Twenty-three of the 24 studies could be evaluated for mortality, encompassing of randomized patients Six studies reported no deaths, whereas 10 reported mortality rates of 0.
The difference was nonsignificant when evaluating quinolones RR, 0. No heterogeneity was seen for the overall comparison. Mortality was further analyzed by age, geographic area, and sample size, and the results disclosed no significant difference. Overall mortality in both arms was similar when analyzing studies per allocation generation, allocation concealment, blinding, and the ITT analysis Table 2.
In the funnel plot for overall mortality, results are symmetrically centered around the combined RR. Clinical failure was the primary outcome in all studies, encompassing patients.
No significant difference between study arms was observed RR, 0. When we evaluated the different drug regimens, opposing trends were noticeable, with an advantage for quinolone monotherapy RR, 0. Reanalysis by the random-effects model did not alter the results. Relative risks were similar regardless of age or sample size. An advantage for coverage of atypical pathogens was statistically significant in the 13 European studies RR, 0. When we analyzed studies by methodological quality, an advantage toward coverage of atypical pathogens was accentuated in studies of unclear or inadequate allocation concealment and allocation generation.
In the analysis of studies of high methodological quality, the effect was nearly identical in the 2 arms for adequate allocation generation, RR, 0. In an ITT vs per-protocol design sensitivity analysis, no significant difference was found.
Clinical treatment failure rates were evaluated among patients with microbiologically documented infections. No significant difference between the study arms in the treatment of documented pneumococcal infections was detected RR, 1. Data were insufficient to analyze cases of pneumococcal bacteremia. For atypical pathogens, a trend in favor of atypical coverage did not reach statistical significance RR, 0.
A significant advantage to coverage of atypical pathogens was found for eradication of Legionella species, with an RR of 0. Sixty-one of 78 atypical cases and 9 of 20 cases of L pneumophila were successfully resolved in the arm without coverage of atypical pathogens.
There was a statistically significant advantage to bacteriological eradication for the arm covering atypical pathogens RR, 0. However, in an analysis restricted to studies of adequate allocation generation and concealment, this advantage disappeared RR, 0.
Adverse events per treatment arm were reported for patients. Total adverse events RR, 1. However, the definitions of gastrointestinal events differed, some including abdominal pain and some diarrhea alone, thereby precluding an accurate comparison of antibiotic-associated diarrhea.
The objective of our review was to assess empirical antibiotic coverage of atypical pathogens in hospitalized patients with CAP, in terms of mortality and successful treatment. We found no difference in mortality between regimens with coverage of atypical pathogens and regimens without such coverage, persisting in all subgroup analyses. There was a nonsignificant trend toward clinical success to coverage of atypical pathogens, accentuated with quinolone monotherapy.
The advantage disappeared when we evaluated high-quality methodological studies alone. A significant advantage in bacteriological eradication was detected in the coverage of atypical pathogens, especially in reference to Legionella species.
This advantage was not demonstrated in an analysis restricted to studies of adequate allocation generation and concealment. There was no difference in the frequency of total adverse events between the 2 groups, although more gastrointestinal events but not explicitly diarrhea were noted in the arm without atypical coverage. Mortality data were obtained for The overall mortality rate adjusted mean mortality rate, 3. This is surprising because nearly half of the studies target relatively severe pneumonia cases.
Thus, patients recruited to randomized trials may not adequately represent all patients hospitalized with CAP. Although mortality is the most significant outcome in a potentially lethal infection, all studies chose clinical failure as their primary outcome.
This end point is subjective and should be studied with care. Our review clearly demonstrates its potential for bias. A trend in favor of clinical success for the arm covering atypical pathogens originated in studies with unclear allocation generation. Similarly, the clear statistical advantage of that arm, found in the overall analysis of bacteriological eradication rates, did not exist in an analysis restricted to studies of adequate allocation generation. Thus, we should be wary about relying solely on subjective outcomes when comparing treatment regimens for pneumonia, especially because pharmaceutical companies sponsored most studies and many studies were nonblinded.
The similar response of the young and old is somewhat surprising, as an advantage to atypical coverage would be expected in younger people with a higher prevalence of atypical pneumonia. Perhaps this prevalence diminishes in the hospitalized population. The clear advantage of the arm with atypical pathogen coverage in the successful treatment of L pneumophila infections is not surprising, although cases of atypical pneumonia including L pneumophila often resolved without such coverage.
Coinfections with typical pathogens may explain some of these cases. We had set out to investigate the contribution of coverage of atypical pathogens to empirical treatment of CAP in hospitalized patients. Furthermore, many studies included treatment arms that do not adhere to current guidelines.
Therefore, our meta-analysis is chiefly based on comparison of various regimens without coverage of atypical pathogens to monotherapy, mainly quinolone monotherapy. Regarding this comparison, we found no advantage to coverage of atypical pathogens in terms of mortality or clinical success. Our conclusion of no benefit might be due to lack of power when using available randomized trials.
Large observational studies showed benefit for atypical coverage. However, correction for the baseline differences between patients given or not given atypical coverage in these studies may be impossible. Studies designed specifically to evaluate the necessity of atypical coverage are needed.
Studies must be of adequate generation concealment and allocation, and patients included should resemble more closely the general population of inpatients with CAP.
Additional Information: A detailed protocol of the methodology used for this study was published in The Cochrane Library, where the full review has been accepted for publication. Our website uses cookies to enhance your experience.
By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy Continue. Figure 1. View Large Download. This conclusion relates mostly to the comparison of quinolone monotherapy to beta-lactams.
Further trials, comparing beta-lactam monotherapy to the same combined with a macrolide, should be performed. Community-acquired pneumonia CAP is caused by various pathogens, traditionally divided into 'typical' and 'atypical'.
Initial antibiotic treatment of CAP is usually empirical, customarily covering both typical and atypical pathogens. To date, no sufficient evidence exists to support this broad coverage, while limiting coverage is bound to reduce toxicity, resistance and expense. The main objective was to estimate the mortality and proportion with treatment failure using regimens containing atypical antibiotic coverage compared to those that had typical coverage only. Secondary objectives included the assessment of adverse events.
Randomized controlled trials RCTs of adult patients hospitalized due to CAP, comparing antibiotic regimens with atypical coverage quinolones, macrolides, tetracyclines, chloramphenicol, streptogramins or ketolides to a regimen without atypical antibiotic coverage. Two review authors independently assessed the risk of bias and extracted data from included trials. We assessed heterogeneity using a Chi 2 test.
We included 28 trials, encompassing randomized patients. The atypical antibiotic was administered as monotherapy in all but three studies. Only one study assessed a beta-lactam combined with a macrolide compared to the same beta-lactam.
Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med. Scoring the severity of illness can help to determine whether the patient can be treated as an outpatient or requires hospitalization or intensive care.
A prediction rule to identify low-risk patients with community-acquired pneumonia. Twenty factors are assessed, including age, respiratory rate, pulse, blood pressure, and temperature, and total points are added together. New scoring systems might have some advantage on the PSI and the CURB, in identifying patients who need intensive care and hospital admission. Prospective comparison of severity scores for predicting clinically relevant outcomes for patients hospitalized with community-acquired pneumonia.
Development and validation of a clinical prediction rule for severe community-acquired pneumonia. Towards a sensible comprehension of severe community-acquired pneumonia. Intensive Care Med. The use of corticosteroids in patients with severe community-acquired pneumonia has been a long-debated issue. Current guidelines generally recommend against the use of corticosteroids in patients with nonsevere or severe community-acquired pneumonia.
This recommendation is based on the fact that there are no data suggesting benefit in patients with nonsevere community-acquired pneumonia with respect to mortality or organ failure, and only limited data to support their use in patients with severe community-acquired pneumonia. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock Meta-analyses of studies of hospitalized adults with community-acquired pneumonia found that the use of corticosteroids was associated with reduced need for mechanical ventilation, reduced hospital stay, lower clinical failure rates, fewer complications including septic shock , decreased C-reactive protein CRP levels, and reduced all-cause mortality.
However, it appears that the reduction in mortality applies only to patients with severe community-acquired pneumonia. In patients with nonsevere disease, adjunctive corticosteroids reduce morbidity, but not mortality. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis.
Ann Intern Med. Efficacy and safety of adjunctive corticosteroids therapy for severe community-acquired pneumonia in adults: an updated systematic review and meta-analysis.
PLoS One. Corticosteroids in patients hospitalized with community-acquired pneumonia: systematic review and individual patient data meta-analysis. Corticosteroids for pneumonia. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis.
Am J Emerg Med. Efficacy and safety of adjunctive corticosteroids therapy for patients with severe community-acquired pneumonia: A systematic review and meta-analysis. Medicine Baltimore. Efficacy and safety of glucocorticoids in the treatment of severe community-acquired pneumonia: a meta-analysis.
A study from Japan suggests that corticosteroids may not offer any advantage in the treatment of M pneumoniae pneumonia. Recent trends in practice patterns and impact of corticosteroid use on pediatric Mycoplasma pneumoniae-related respiratory infections. Respir Investig. Efficacy of glucocorticoids for the treatment of macrolide refractory mycoplasma pneumonia in children: meta-analysis of randomized controlled trials. BMC Pulm Med. Patients treated with corticosteroids have an increased risk for hyperglycemia.
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