Medline ® Abstracts for References 40-43
of 'Treatment of community-acquired pneumonia in adults who require hospitalization'
A worldwide perspective of atypical pathogens in community-acquired pneumonia.
Arnold FW, Summersgill JT, Lajoie AS, Peyrani P, Marrie TJ, Rossi P, Blasi F, Fernandez P, File TM Jr, Rello J, Menendez R, Marzoratti L, Luna CM, Ramirez JA, Community-Acquired Pneumonia Organization (CAPO) Investigators
Am J Respir Crit Care Med. 2007;175(10):1086.
RATIONALE: Controversy still exists in the international literature regarding the need to use antimicrobials covering atypical pathogens when initially treating hospitalized patients with community-acquired pneumonia (CAP). In different regions of the world, monotherapy with a beta-lactam antimicrobial is common.
OBJECTIVES: We sought to correlate the incidence of CAP due to atypical pathogens in different regions of the world with the proportion of patients treated with an atypical regimen in those same regions. In addition, we sought to compare clinical outcomes of patients with CAP treated with and without atypical coverage.
METHODS: A secondary analysis was performed using two comprehensive international databases. World regions were defined as North America (I), Europe (II), Latin America (III), and Asia and Africa (IV). Time to reach clinical stability, length of hospital stay, and mortality were compared between patients treated with and without atypical coverage.
MEASUREMENTS AND MAIN RESULTS: The incidence of CAP due to atypical pathogens from 4,337 patients was 22, 28, 21, and 20% in regions I-IV, respectively. The proportion of patients treated with atypical coverage from 2,208 patients was 91, 74, 53, and 10% in regions I-IV, respectively. Patients treated with atypical coverage had decreased time to clinical stability (3.7 vs. 3.2 d, p<0.001), decreased length of stay (7.1 vs. 6.1 d, p<0.01), decreased total mortality (11.1 vs. 7%, p<0.01), and decreased CAP-related mortality (6.4 vs. 3.8%, p = 0.05).
CONCLUSIONS: The significant global presence of atypical pathogens and the better outcomes associated with antimicrobial regimens with atypical coverage support empiric therapy for all hospitalized patients with CAP with a regimen that covers atypical pathogens.
Division of Infectious Diseases, University of Louisville, Louisville, KY 40292, USA. firstname.lastname@example.org
Does empiric therapy for atypical pathogens improve outcomes for patients with CAP?
File TM Jr, Marrie TJ
Infect Dis Clin North Am. 2013 Mar;27(1):99-114.
The present controversy regarding the need to cover atypical pathogens in the empiric therapy of community-acquired pneumonia is related to several issues, including the relevance of terminology, imprecise diagnostic methods, and perceived contradictory results of published evidence. Studies evaluating the time to clinical recovery and the use of earlier endpoints for evaluation suggest that appropriate therapy provides a benefit if an atypical pathogen is a pathogen. Because recent surveillance studies suggest these pathogens are common and until there is the availability of accurate, cost-effective, and easily interpreted laboratory tests to provide the etiologic diagnosis at the time of point of care, empiric therapy of atypical pathogens is supported.
Infectious Disease Section, Department of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH 44272, USA. email@example.com
Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults.
Eliakim-Raz N, Robenshtok E, Shefet D, Gafter-Gvili A, Vidal L, Paul M, Leibovici L
Cochrane Database Syst Rev. 2012;
BACKGROUND: 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.
OBJECTIVES: 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.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2012 which includes the Acute Respiratory Infection Group's Specialized Register, MEDLINE (January 1966 to April week 1, 2012) and EMBASE (January 1980 to April 2012).
SELECTION CRITERIA: 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.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data from included trials. We estimated risk ratios (RRs) with 95% confidence intervals (CIs). We assessed heterogeneity using a Chi(2) test.
MAIN RESULTS: We included 28 trials, encompassing 5939 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. There was no difference in mortality between the atypical arm and the non-atypical arm (RR 1.14; 95% CI 0.84 to 1.55), RR<1 favors the atypical arm. The atypical arm showed an insignificant trend toward clinical success and a significant advantage to bacteriological eradication, which disappeared when evaluating methodologically high quality studies alone. Clinical success for the atypical arm was significantly higher for Legionella pneumophilae (L. pneumophilae) and non-significantly lower for pneumococcal pneumonia. There was no significant difference between the groups in the frequency of (total) adverse events, or those requiring discontinuation of treatment. However, gastrointestinal events were less common in the atypical arm (RR 0.70; 95% CI 0.53 to 0.92). Although the trials assessed different antibiotics, no significant heterogeneity was detected in the analyses.
AUTHORS' CONCLUSIONS: No benefit of survival or clinical efficacy was shown with empirical atypical coverage in hospitalized patients with CAP. 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.
Department of Medicine E, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel. firstname.lastname@example.org.
Oral gemifloxacin versus sequential therapy with intravenous ceftriaxone/oral cefuroxime with or without a macrolide in the treatment of patients hospitalized with community-acquired pneumonia: a randomized, open-label, multicenter study of clinical efficacy and tolerability.
Lode H, File TM Jr, Mandell L, Ball P, Pypstra R, Thomas M, 185 Gemifloxacin Study Group
Clin Ther. 2002;24(11):1915.
OBJECTIVE: This study aimed to compare the efficacy and safety of oral gemifloxacin, an enhanced-affinity quinolone, with sequential therapy with IV ceftriaxone followed by oral cefuroxime (with or without a macrolide) in patients hospitalized for community-acquired pneumonia (CAP).
METHODS: A randomized, open-label, multicenter study comprised adults hospitalized with a clinical and radiologic diagnosis of CAP. Patients were randomized 1:1 to receive either (1) oral gemifloxacin 320 mg once daily (7-14 days); or (2) IV ceftriaxone 2 g once daily (1-7 days) followed by oral cefuroxime 500 mg twice daily (1-13 days) for a total of<or = 14 days. Patients receiving ceftriaxone/cefuroxime were allowed concomitant macrolide treatment.
RESULTS: A total of 345 patients were randomized, of whom 341 received at least 1 dose of study medication (gemifloxacin, 169/172; ceftriaxone/cefuroxime, 172/173). Clinical success rates in the clinically evaluable (CE) population at follow-up (day 21-28 post-therapy), the primary end point, were 92.2% (107/116) for gemifloxacin and 93.4% (113/121) for ceftriaxone/cefuroxime (treatment difference, -1.15; 95% CI, -7.73 to 5.43). In patients in Fine risk classes IV and V, the clinical success rate was 87.0% (20/23) for gemifloxacin versus 83.3% (20/24) for ceftriaxone/cefuroxime. No difference in clinical response at follow-up was noted based on macrolide use. Bacteriologic success rates at follow-up in the bacteriologically evaluable (BE) population were 90.6% (58/64) for gemifloxacin and 87.3% (55/63) for ceftriaxone/cefuroxime (treatment difference 3.32; 95% CI, -7.57 to 14.21). The clinical success rate in bacteremic patients at follow-up (BE population) was 100.0%. Both treatments were generally well tolerated. The frequency and types of adverse events were similar between the 2 groups. The most common treatment-related adverse events with gemifloxacin were diarrhea, liver-function adverse events, and rash; with ceftriaxone/cefuroxime, they were diarrhea, elevated hepatic-enzyme activity, and moniliasis.
CONCLUSION: The clinical efficacy and tolerability of oral gemifloxacin 320 mg once daily were similar to those of IV ceftriaxone followed by oral cefuroxime (with or without a macrolide) in the treatment of adult patients hospitalized with moderate to severe CAP. Both treatments were effective in bacteremic patients and those at increased risk of mortality.
Department of Chest and Infectious Diseases, Hospital Heckeshorn, Akademisches Lehrkrankenhaus, Free University Berlin, Berlin, Germany. email@example.com