Medline ® Abstracts for References 40-43
of 'Treatment of community-acquired pneumonia in adults who require hospitalization'
Excess deaths associated with tigecycline after approval based on noninferiority trials.
Prasad P, Sun J, Danner RL, Natanson C
Clin Infect Dis. 2012;54(12):1699.
BACKGROUND: On the basis of noninferiority trials, tigecycline received Food and Drug Administration (FDA) approval in 2005. In 2010, the FDA warned in a safety communication that tigecycline was associated with an increased risk of death.
METHODS: PubMed, EMBASE, Scopus, and ClinicalTrials.gov were searched using the terms "tigecycline" and "randomized controlled trial (RCT)" through April 2011. Excess deaths and noncure rates for both approved and nonapproved indications were examined using meta-analysis.
RESULTS: Ten published and 3 unpublished studies met inclusion criteria (N = 7434). No significant heterogeneity was seen for mortality (I(2 )= 0%; P = .99) or noncure rates (I(2 )= 25%; P = .19). Across randomized controlled trials, tigecycline was associated with increased mortality (risk difference [RD], 0.7%; 95% confidence interval [CI], 0.1%-1.2%; P = .01) and noncure rates (RD, 2.9%; 95% CI, 0.6%-5.2%; P = .01). Effects were not isolated to type of infection or comparator antibiotic regimen, and the impact on survival remained significant when limited to trials of approved indications (I(2 )= 0%; RD, 0.6%; P = .04). A pooled analysis of the 5 trials completed by early 2005 before tigecycline was approved would have demonstrated a similar harmful effect of tigecycline on survival (I(2 )= 0%; RD, 0.7%; P = .06).
CONCLUSIONS: Pooling noninferiority studies to examine survival may help ensure the safety and efficacy of new antibiotics. The association of tigecycline with excess deaths and noncure includes indications for which it is approved and marketed. Tigecycline cannot be relied on in serious infections.
Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland, USA. email@example.com
US Food and Drug Administration (FDA). FDA drug safety communication: FDA warns of increased risk of death with IV antibacterial Tygacil (tigecycline) and approves new boxed warning. http://www.fda.gov/Drugs/DrugSafety/ucm369580.htm (Accessed on October 09, 2013).
no abstract available
Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF, Infectious Diseases Society of America
Clin Infect Dis. 2011;52(3):e18.
Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.
Department of Medicine, Division of Infectious Diseases, University of California-San Francisco, San Francisco, California94102, USA. firstname.lastname@example.org
What is the best antimicrobial treatment for severe community-acquired pneumonia (including the role of steroids and statins and other immunomodulatory agents).
Sibila O, Restrepo MI, Anzueto A
Infect Dis Clin North Am. 2013 Mar;27(1):133-47. Epub 2012 Dec 21.
Community-acquired pneumonia (CAP) is the leading cause of death from infectious diseases in the United States. The mortality rate due to severe CAP has shown little improvement over the past few years, with a rate as high as 50% mainly in patients admitted to intensive care units. Death and adverse outcomes from CAP result from a complex interplay between the pathogen and the host. Several therapies have been tested in patients with severe CAP in recent years. This article reviews recent data regarding different treatments including antimicrobials and adjunctive therapies in patients with severe CAP.
University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.