Michael A. Saubolle

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

SUMMARY 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. Objectives. 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 Preventions (CDCs) 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). Search strategy. 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of three electronic bibliographic databases (PubMed, Embase, and CINAHL), databases containing “gray” literature (unpublished academic, government, or industry evidence not governed by commercial publishing) (CIHI, NIHR, SIGN, and other databases), and the Cochrane database for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. Dates of search. The dates of our search were from 1990 to July 2011. Selection criteria. 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. Main 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. Authors 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.

Laboratory Aspects in the Diagnosis of Coccidioidomycosis

Abstract:  Coccidioides immitis and Coccidioides posadasii, the two recognized causes of coccidioidomycosis, may be detected by direct microscopy, culture, and serologic documentation. Two useful stains include the Grocott methenamine silver (GMS) and the calcofluor white (CFW). Other useful stains used in histopathologic studies include hematoxylin‐eosin (H&E) and periodic acid Schiff (PAS). Nucleic acid amplification tests (NAATs) have been introduced for detection of Coccidioides spp. in specimens, but are not yet commercially available. Isolation of Coccidioides spp. by culture is not difficult as many fungal as well as routine bacteriologic media are available. For the safe isolation of Coccidioides spp., the laboratory should maintain a biological safety level 2 or 3. Identification of Coccidioides spp. uses the organisms’ phenotypic or genotypic characteristics. Phenotypic identification to genus level may be achieved by visualization of spherules in specimens and/or by the presence of arthroconidia in culture. Isolates may be confirmed as Coccidioides spp. by molecular probes. Separation of species into C. immitis and C. posadasii is best achieved by specialized molecular techniques which are not normally available in routine clinical laboratories. Humoral antibodies can be used for the diagnosis and prognosis of coccidioidomycosis. Although positive serologic results may be helpful in the diagnosis of coccidioidomycosis, negative serologic results cannot be used to rule out the disease. Enzyme immunoassays (EIA) and immunodiffusion methods are commonly used for detection of both IgM and IgG antibody groups. Sequential complement fixation (CF) studies for IgG class of antibody are useful for the prognosis of coccidioidomycosis.

Primary amoebic meningoencephalitis with Naegleria fowleri: Clinical review

Two children with primary amoebic meningoencephalitis secondary to Naegleria fowleri are reported. Both children died, and the causative agent was identified at autopsy. Presentation and outcome conformed to the usual course of primary amoebic meningoencephalitis and reaffirm the gravity and rapid progression of this infection. The epidemiology, microbiology, diagnostic considerations, and treatment are discussed. Primary amoebic meningoencephalitis should be considered in the differential diagnosis of children with meningitis or encephalitis.

Dominance of multidrug resistant CC271 clones in macrolide-resistant streptococcus pneumoniae in Arizona

BackgroundRates of resistance to macrolide antibiotics in Streptococcus pneumoniae are rising around the world due to the spread of mobile genetic elements harboring mef(E) and erm(B) genes and post-vaccine clonal expansion of strains that carry them.ResultsCharacterization of 592 clinical isolates collected in Arizona over a 10 year period shows 23.6% are macrolide resistant. The largest portion of the macrolide-resistant population, 52%, is dual mef(E)/erm(B)-positive. All dual-positive isolates are multidrug-resistant clonal lineages of Taiwan19F-14, mostly multilocus sequence type 320, carrying the recently described transposon Tn2010. The remainder of the macrolide resistant S. pneumoniae collection includes 31% mef(E)-positive, and 9% erm(B)-positive strains.ConclusionsThe dual-positive, multidrug-resistant S. pneumoniae clones have likely expanded by switching to non-vaccine serotypes after the heptavalent pneumococcal conjugate vaccine release, and their success limits therapy options. This upsurge could have a considerable clinical impact in Arizona.

Clinical Microbiology and Infection Prevention

Health care-associated infections (HAIs) represent one of the most common complications of care, affecting 5 to 10% of patients admitted to acute-care hospitals worldwide. These HAIs are associated with enormous morbidity and mortality, resulting in more than 90,000 deaths each year in the United

Antimicrobial resistance: current status and future direction.

Background Antimicrobial resistance is initiated through mutations in bacterial genes, culminating in end products that help circumvent the action of specific antimicrobial agents. Resistant mutants can proliferate under a number of circumstances but primarily through the action of selective pressure from the overuse of antimicrobial agents. Methods The results of surveillance studies over approximately the last ten years were evaluated. Conclusion Resistance rates in the group of microorganisms associated with respiratory tract infections had been increasing rapidly over the past 10 years, but, recently, many seem to have reached a plateau. However, newer, more invasive clones of methicillin resistant Staphylococcus aureus (MRSA), differing from health care–associated MRSA (HA-MRSA), and typically associated with community-acquisition (CA-MRSA), recently have begun to proliferate. Burgeoning use of fluoroquinolones has impacted the Gram-negative bacilli (e.g., Pseudomonas aeruginosa, Escherichia coli, and Salmonella), causing their resistance rates to approach the critical point. A better understanding of the epidemiology of resistance and responsible use of antimicrobial agents are mandatory if the continuing rates of increasing resistance are to be abrogated.

Designing Studies Acceptable for Abstraction and Inclusion in Evidence-Based Laboratory Practice Guidelines.

Expansion of technologies, changing infrastructure, and dwindling resources have produced the need for health care reform and changes in clinical laboratories. The health care model will have to shift increasingly from a fee-for-service model to a value-based model. ABSTRACT Expansion of technologies, changing infrastructure, and dwindling resources have produced the need for health care reform and changes in clinical laboratories. The health care model will have to shift increasingly from a fee-for-service model to a value-based model. Laboratories will have to focus more on evidence-based outcome studies evaluating the effects of their preanalytical and postanalytical practices on real patient outcomes. Although well-designed clinical trials and multicenter studies are needed to determine the effects of laboratory processes on outcomes, there has been concern that too few well-designed studies have been published. To help improve the quality of study design and to facilitate reporting transparency, several method statements have been developed. The Standards for Reporting of Diagnostic Accuracy Studies (STARD) initiative was recently updated, listing 30 items deemed crucial for transparent reporting of studies, thereby allowing the creation of a robust database for clinical practice guidelines. Three methods describing the assessment of the quality of data on which to base recommendations for such guidelines are also available. Close attention must be given to study design so that parameters ensuring study quality are met, thereby allowing inclusion of the study data in the formulation of evidence-based laboratory best practices guidelines.