title: Effectiveness of Practices To Increase Timeliness of Providing Targeted Therapy for Inpatients with Bloodstream Infections: a Laboratory Medicine Best Practices Systematic Review and Meta-analysis.
abstract: BACKGROUND
  Bloodstream infection (BSI) is a major cause of morbidity and mortality throughout the world. Rapid identification of bloodstream pathogens is a laboratory practice that supports strategies for rapid transition to direct targeted therapy by providing for timely and effective patient care. In fact, the more rapidly that appropriate antimicrobials are prescribed, the lower the mortality for patients with sepsis. Rapid identification methods may have multiple positive impacts on patient outcomes, including reductions in mortality, morbidity, hospital lengths of stay, and antibiotic use. In addition, the strategy can reduce the cost of care for patients with BSIs.
  
  
  OBJECTIVE
  The purpose of this review is to evaluate the evidence for the effectiveness of three rapid diagnostic practices in decreasing the time to targeted therapy for hospitalized patients with BSIs. The review was performed by applying the Centers for Disease Control and Prevention's (CDC's) Laboratory Medicine Best Practices Initiative (LMBP) systematic review methods for quality improvement (QI) practices and translating the results into evidence-based guidance (R. H. Christenson et al., Clin Chem 57:816-825, 2011, http://dx.doi.org/10.1373/clinchem.2010.157131).
  
  
  METHODS
  A comprehensive literature search was conducted to identify studies with measurable outcomes. A search of three electronic bibliographic databases (PubMed, Embase, and CINAHL), databases containing "gray" literature (unpublished academic, government, or industry evidence not governed by commercial publishing) (CIHI, NIHR, SIGN, and other databases), and the Cochrane database for English-language articles published between 1990 and 2011 was conducted in July 2011.
  The dates of our search were from 1990 to July 2011.
  
  
  METHODS
  Animal studies and non-English publications were excluded. The search contained the following medical subject headings: bacteremia; bloodstream infection; time factors; health care costs; length of stay; morbidity; mortality; antimicrobial therapy; rapid molecular techniques, polymerase chain reaction (PCR); in situ hybridization, fluorescence; treatment outcome; drug therapy; patient care team; pharmacy service, hospital; hospital information systems; Gram stain; pharmacy service; and spectrometry, mass, matrix-assisted laser desorption-ionization. Phenotypic as well as the following key words were searched: targeted therapy; rapid identification; rapid; Gram positive; Gram negative; reduce(ed); cost(s); pneumoslide; PBP2; tube coagulase; matrix-assisted laser desorption/ionization time of flight; MALDI TOF; blood culture; EMR; electronic reporting; call to provider; collaboration; pharmacy; laboratory; bacteria; yeast; ICU; and others. In addition to the electronic search being performed, a request for unpublished quality improvement data was made to the clinical laboratory community.
  
  
  RESULTS
  Rapid molecular testing with direct communication significantly improves timeliness compared to standard testing. Rapid phenotypic techniques with direct communication likely improve the timeliness of targeted therapy. Studies show a significant and homogeneous reduction in mortality associated with rapid molecular testing combined with direct communication.
  
  
  CONCLUSIONS
  No recommendation is made for or against the use of the three assessed practices of this review due to insufficient evidence. The overall strength of evidence is suggestive; the data suggest that each of these three practices has the potential to improve the time required to initiate targeted therapy and possibly improve other patient outcomes, such as mortality. The meta-analysis results suggest that the implementation of any of the three practices may be more effective at increasing timeliness to targeted therapy than routine microbiology techniques for identification of the microorganisms causing BSIs. Based on the included studies, results for all three practices appear applicable across multiple microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive S. aureus (MSSA), Candida species, and Enterococcus species.
authors.affiliation: Battelle Center for Analytics and Public Health, Atlanta, Georgia, USA.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Buehler
authors.affiliation: Battelle Center for Analytics and Public Health, Atlanta, Georgia, USA.
authors.forename: Bereneice
authors.initials: B
authors.lastname: Madison
authors.affiliation: Battelle Center for Analytics and Public Health, Atlanta, Georgia, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Snyder
authors.affiliation: Battelle Center for Analytics and Public Health, Atlanta, Georgia, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Derzon
authors.affiliation: Centers for Disease Control and Prevention, Center for Surveillance, Epidemiology and Laboratory Services (CSELS), Atlanta, Georgia, USA NCornish@cdc.gov.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Cornish
authors.affiliation: Banner Good Samaritan Medical Center, Banner Health, Phoenix, Arizona, USA, and University of Arizona College of Medicine, Phoenix, and University of Arizona College of Medicine, Tucson, Arizona, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Saubolle
authors.affiliation: Microbiology Specialists Incorporated, Houston, Texas, USA.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Weissfeld
authors.affiliation: Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
authors.forename: Melvin P
authors.initials: MP
authors.lastname: Weinstein
authors.affiliation: Battelle Center for Analytics and Public Health, Atlanta, Georgia, USA.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Liebow
authors.affiliation: Geisinger Health System, Danville, Pennsylvania, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Wolk
mesh_terms: D055499:Catheter-Related Infections / Q000175:diagnosis* / Q000188:drug therapy*; D003955:Diagnostic Tests, Routine / Q000379:methods*; D006801:Humans; D007297:Inpatients; D017410:Practice Guidelines as Topic; D057285:Precision Medicine / Q000379:methods*; D018805:Sepsis / Q000175:diagnosis* / Q000188:drug therapy*; D013997:Time Factors