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Treatment of Mycoplasma Pneumonia: a Systematic Review

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Treatment of Mycoplasma Pneumonia: a Systematic Review REVIEW ARTICLE Treatment of Mycoplasma Pneumonia: A Systematic Review AUTHORS: Eric Biondi, MD,a Russell McCulloh, MD,b Brian Alverson, MD,c Andrew Klein, BS,a Angela Dixon, BSN, MLS, abstract a d AHIP, and Shawn Ralston, MD BACKGROUND AND OBJECTIVE: Children with community-acquired aDepartment of Pediatrics, University of Rochester, Rochester, lower respiratory tract infection (CA-LRTI) commonly receive antibiotics New York; bDepartment of Pediatrics, Children’s Mercy Hospitals & Clinics, Kansas City, Missouri; cDepartment of Pediatrics, for Mycoplasma pneumoniae. The objective was to evaluate the effect Hasbro Children’s Hospital, Providence, Rhode Island; and of treating M. pneumoniae in children with CA-LRTI. dDepartment of Pediatrics, Children’s Hospital at Dartmouth– Hitchcock, Hanover, New Hampshire METHODS: PubMed, Cochrane Central Register of Controlled Trials, and bibliography review. A search was conducted by using Medical Subject KEY WORDS pediatric, pneumonia, macrolide, azithromycin, atypical Headings terms related to CA-LRTI and M. pneumoniae and was not pneumonia, mycoplasma restricted by language. Eligible studies included randomized controlled ABBREVIATIONS trials (RCTs) and observational studies of children #17 years old with CA-LRTI—community-acquired lower respiratory tract infection confirmed M. pneumoniae and a diagnosis of CA-LRTI; each must have CAP—community-acquired pneumonia CI—95% confidence interval also compared treatment regimens with and without spectrum of IDSA—Infectious Diseases Society of America activity against M. pneumoniae. Data extraction and quality assessment RCT—randomized controlled trial were completed independently by multiple reviewers before arriving — URTI upper respiratory tract infection at a consensus. Data were pooled using a random effects model. Dr Biondi conceptualized and designed the review, reviewed articles, ran the meta-analysis, and drafted the original RESULTS: Sixteen articles detailing 17 studies were included. The most manuscript; Dr McCulloh conceptualized and designed the commonly selected primary outcome was symptomatic improvement. review, reviewed articles, helped to run the meta-analysis, and Nine studies examined M. pneumoniae treatment in CA-LRTI secondary drafted the original manuscript; Dr Alverson participated in the design, helped interpret the included studies, and critically to M. pneumoniae, and 5 RCTs met criteria for meta-analysis. The reviewed the manuscript; Mr Klein participated in study design, suggested pooled risk difference of 0.12 (95% confidence interval, tabulated articles, and reviewed the manuscript; Ms Dixon 20.04 to 0.20) favoring treatment was not significantly different participated in study design, helped perform the literature and demonstrated significant heterogeneity. Limitations included review, and critically reviewed portions of the manuscript; Dr Ralston participated in study design, supervised Drs Biondi substantial bias and subjective outcomes within the individual and McCulloh in study interpretation and translated 1 study, and studies, difficulty interpreting testing modalities, and the inability to participated in the meta-analysis; and all authors approved the correct for mixed infections or timing of intervention. final manuscript as submitted. fi fi www.pediatrics.org/cgi/doi/10.1542/peds.2013-3729 CONCLUSIONS: We identi ed insuf cient evidence to support or refute treatment of M. pneumoniae in CA-LRTI. These data highlight the need doi:10.1542/peds.2013-3729 for well-designed, prospective RCTs assessing the effect of treating M. Accepted for publication Feb 21, 2014 pneumoniae in CA-LRTI. Pediatrics 2014;133:1081–1090 Address correspondence to Russell McCulloh, MD, Pediatric Infectious Diseases, Children’s Mercy Hospitals & Clinics, 2401 Gillham Rd, Kansas City, MO 64108. E-mail: [email protected] PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2014 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no conflicts of interest to disclose. COMPANION PAPER: A companion to this article can be found on page 1124, and online at www.pediatrics.org/cgi/doi/10.1542/peds. 2014-0871. PEDIATRICS Volume 133, Number 6, June 2014 1081 Downloaded from www.aappublications.org/news by guest on October 2, 2021 Community-acquired pneumonia (CAP) bination therapy decreased length of ,18 years of age with CA-LRTI. The re- accounts for .150 000 pediatric hos- stay by 20% to 30% over b-lactam view was conducted in concordance pitalizations each year in the United monotherapy.2,4 Data on antibiotic treat- with the Preferred Reporting Items for States, and there are great disparities ment of pediatric CA-LRTI caused by Systematic Reviews and Meta-Analyses in patterns of care and outcomes.1 M. pneumoniae are generally consid- statement. Specifically, wide variations in antibi- ered inconclusive,3,4,10,14 yet macro- otic prescribing practices exist among lides remain the most commonly Outcome Types physicians, often because the causa- overprescribed antibiotic at pediatric The primary outcome was clinical im- tive agent is not identified.2 For this clinics in the United States: .6 million provement or cure at follow-up. Clinical reason, recent evidence-based pediat- annual doses for respiratory symp- improvement or cure could include reso- ric CAP practice guidelines published toms without a clear indication.15 lution of fever; resolution or improvement by the Infectious Diseases Society of A Cochrane review on the use of anti- in symptoms such as cough, congestion, America (IDSA) recommend that chil- biotics to treat CA-LRTI secondary to M. shortness of breath, fatigue, or chest pain; dren hospitalized with CAP be tested pneumoniae in children found in- or improvement or cure as defined by the for Mycoplasma pneumoniae.3 M. sufficient evidence to draw any specific authors of the individual studies. pneumoniae is a common cause of CAP conclusions about the efficacy of anti- and other community-acquired lower biotics for the condition.10 However, Literature Search respiratory tract infections (CA-LRTIs), this review omitted at least 3 RCTs With the assistance of a librarian (A.D.), particularly in school-age children and (roughly one-third of the total RCTs) for we performed a comprehensive search adolescents, but there are large gaps which there appeared to be applicable of PubMed (January 1966–August 2012) in our understanding of this disease.3,4 data on the topic,12,16,17 and data from with the Medical Subject Headings Prevalence estimates vary from 10% to observational studies were omitted. terms and keywords (Table 1). After 40% in pediatric CA-LRTI,5–9 and few The objective of our study was to pro- duplicates were removed, we used in- studies address treatment recommenda- vide a more comprehensive review of clusion and exclusion criteria to select tions.4,10 Additionally, the IDSA guidelines all available published literature on the studies based on their title and ab- use of antibiotics in children to treat target the use of macrolides in CA-LRTI as stract to include in our review. Addi- 3 CA-LRTI secondary to M. pneumoniae. an area needing additional research. tional studies were identified through First-line treatment of children hospi- manual search of the bibliographies of METHODS talized with CAP currently includes a qualifying studies. Before manuscript b-lactam to treat common causative Search Design submission, a second search was per- bacterial agents such as Streptococ- This was a systematic review of all formed (August 2012–September 2013) cus pneumoniae and a macrolide to observational and randomized trials to ensure that the review was as up-to- provide additionally treatment of atypi- comparing antibiotics with spectrum of date as possible and any new studies 3 cal pathogens such as M. pneumoniae. activity for M. pneumoniae (eg, mac- were included in the analysis. – Studies of antibiotic use in the pre rolide, tetracycline, or quinolone class) IDSA guidelines era showed marked with placebo or antibiotics from any Study Selection variability in prescription practices,2 other class without spectrum of activ- Studies were considered eligible for probably because the efficacy ity against M. pneumoniae in children inclusion in the review if they met the of macrolides in the treatment of M. pneumoniae remains unclear and treatment recommendations, even in TABLE 1 Medical Subject Headings Used for Primary Literature Search 4,10 major textbooks, are variable. The Mycoplasma pneumoniae pediatrica antibiotica available evidence is also conflicting. pneumonia, mycoplasma infant anti-bacterial agents One small trial suggests that b-lactam respiratory tract infections child macrolidea pneumonia child, preschool roxithromycin use in children with CAP is more cost- recurrent respiratory tract infectiona adolescent erythromycin effective than macrolides,11 several respiratory infectiona telithromycin randomized controlled trials (RCTs) RRTI macrolides community-acquired infections azithromycin fi 12,13 suggest no difference in ef cacy, lower respiratory tract infectiona clarithromycin and 2 recent pediatric cohort studies lower respiratory infectiona suggest that b-lactam–macrolide com- a Represents open-ended term. 1082 BIONDI et al Downloaded from www.aappublications.org/news by guest on October 2, 2021 REVIEW
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