Current Approaches to the Diagnosis of Bacterial and Fungal Bloodstream Infections in the Intensive Care Unit

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Current Approaches to the Diagnosis of Bacterial and Fungal Bloodstream Infections in the Intensive Care Unit Current approaches to the diagnosis of bacterial and fungal bloodstream infections in the intensive care unit Patrick R. Murray, PhD; Henry Masur, MD Healthcare systems spend considerable resources collecting of organism detection, thus providing valuable guidance to clini- and processing blood cultures for the detection of blood stream cians who strive to initiate the appropriate antimicrobial therapy pathogens. The process is initiated with the collection of blood as rapidly as possible, and who wish to discontinue unnecessary cultures that depend upon proper skin disinfection, collection drugs expeditiously. Molecular and mass spectroscopy techniques of an adequate number of specimens and volume of blood, and are changing sepsis diagnosis rapidly and will provide far more prompt processing in a sensitive culture system. Complement- specific information far more quickly, but the performance char- ing blood cultures and gaining in use are techniques such as acteristics of these systems must be understood by intensivists nucleic acid amplification tests and mass spectroscopy that allow who use such information to guide their patient management. (Crit clinical laboratories to detect and identify organisms from blood Care Med 2012; 00:0–0) cultures substantially faster than conventional systems. Further- KEY WORDS: bacteremia; blood culture; fungemia; matrix-assist- more, certain resistance mutations can be detected within hours ed laser desorption/ionization; molecular; sepsis rompt, accurate detection and must recognize that technology is revo- Instruments were introduced in the early identification of bloodstream lutionizing the tools that are being used. 1970s that could automatically monitor pathogens are essential for opti- For the past 30 yrs, healthcare sys- the bottles for microbial growth (e.g., mal management of intensive tems have relied on techniques in which production of carbon dioxide) and alert staff Pcare unit patients with sepsis syndromes. blood is incubated in various media, when growth was detected. Subsequent Healthcare facilities spend considerable semiautomated instruments are used to refinements in both culture media and resources in terms of labor and equip- monitor microbial growth, and organ- detection systems have improved the overall ment drawing, processing and analyzing isms are identified by Gram stain and recovery and time to detection of organisms blood cultures. Missed opportunities to biochemical tests. In recent years, clinical in septic patients while reducing lab-related document the true cause of blood stream laboratories have begun to move to novel contamination of cultures. infections can adversely affect patient approaches: nucleic acid amplification The value of blood cultures for con- outcome if the true causative organism is tests and mass spectrometry are two of firming the clinical diagnosis of sepsis, not identified and treated with an active the most common approaches that have severe sepsis, and septic shock (i.e., dis- antibiotic. Conversely, the identification been introduced into clinical laboratories seminated infection from a localized of organisms in blood cultures that are for routine detection and identification focus such as meninges, lungs, abdomen, contaminants can lead to the unnecessary of organisms, and molecular tests are urinary tract, or from febrile neutropenia) administration of antimicrobial agents being used increasingly to rapidly iden- is suboptimal. Although most untreated that will increase cost, increase toxicity, tify microbial sequences that confer drug patients with bacterial meningitis have positive blood cultures, only 30% of and distract the clinical team from treat- resistance. Clinicians must understand patients with bacterial pneumonia and ing the true causative agent. Thus, tech- the sensitivities and specificities of results intra-abdominal infections have positive niques that are sensitive, specific, and derived from both conventional diagnos- cultures, and positive blood cultures in rapid for identifying the microbial cause tics and newer molecular approaches. The patients with urologic disease are primar- of sepsis are major operational tools for implications of using these technologies for the assessment of septic patients will ily restricted to those with acute pyelone- all critical care units, and intensivists be evaluated in this review. phritis. Only 5% to 15% of the all cultures drawn for any reason, and only 50% of From the Becton Dickinson Diagnostic Systems patients with septic shock, are positive. (PRM), Sparks, MD; and Department of Critical Care Evolution of Conventional Blood Medicine (HM), Clinical Center, National Institutes of Culture Whether the low rate for positive blood Health, Bethesda, MD. cultures is related to the sensitivity of the Patrick Murray is an employee of Becton Dickinson Historically, blood cultures were per- diagnostic techniques or the biology of and has equity interest. Dr. Masur has not disclosed any formed by inoculating a large volume of the infectious process is unclear. potential conflicts of interest. blood into one or more bottles of a nutrient Contaminants represent 15% to 30% For information regarding this article, E-mail: hma- [email protected] medium after which the bottles were of the isolated organisms in some hos- Copyright © 2012 by the Society of Critical Care examined visually each day for evidence pitals. Overall, the success of recovering Medicine and Lippincott Williams and Wilkins of microbial growth (e.g., visualization of pathogens and eliminating contaminants DOI: 10.1097/CCM.0b013e318270e771 discrete colonies, turbidity, gas production). is directly related to the techniques used Crit Care Med 2012 Vol. 40, No. 12 1 Copyright (c) Society of Critical Care Medicine and Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. to collect and process blood cultures, and multiple bottles or in multiple blood cul- the higher the yield of the process (10– the patient population being evaluated. ture sets, they need to be considered seri- 15). Cockerill et al (13) documented a Blood Culture Contaminants. Careful ously as true pathogens, especially if they 29.8% increase in positive cultures when attention to the blood drawing and bottle are detected in <24–48 hrs (time of blood 20 mL of blood (divided into two bottles) inoculation techniques are important to draw to time of laboratory detection). were cultured compared with 10 mL of maximize culture specificity for the true Cultures Drawn From Catheters. blood. Additional positive cultures were causative organism. This begins with Collection of blood cultures through observed when 30 mL (13.4% increase careful disinfection of the phlebotomy intravascular devices was traditionally vs. 20 mL) and 40 mL of blood (7.2% in- site (1, 2) with 70% ethanol followed by discouraged because the prevalence of crease vs. 30 mL) were cultured. The application of chlorhexidine (30 secs) or contaminated cultures is slightly higher blood culture yield also increases with tincture of iodine (1 min). Betadine prep- compared with venipuncture. However, the collection of additional blood cultures arations are not recommended because as more and more patients have indwell- (consisting of 20 mL of blood divided into they must be applied for 1.5–2 mins to be ing intravascular devices, clinicians have two bottles). Cockerill et al (13) also re- effective, and clinical staff are unlikely to recognized that blood draws through ported that when a minimum of four wait for this long (3). Catheter access sites catheters can increase the likelihood of blood culture sets were collected within as well as the rubber diaphragm on blood identifying the cause of sepsis because a 24-hr period, the yield increased with culture bottles should also be disinfected the catheter is often the infected nidus, each additional culture drawn: 61.4% of with 70% ethanol. The contamination and because patient phlebotomy can be the patients with blood stream pathogens rate should not exceed 2% to 3% of blood difficult and painful when patients are in had the causative organism detected with culture sets (a set consists of two to three intensive care units for many days, have the first collected culture, 78.2% with the bottles inoculated with a single blood col- coagulation disorders, and are subjected first two cultures, and 93.1% with the lection). Focused training for those draw- to many intravascular accesses. In fact, first three cultures. Lee et al (14) reported ing such cultures is likely to result in the likelihood of obtaining contaminants very similar data. substantial savings in terms of reducing by drawing blood through intravascular Whereas patients with catheter-related the prevalence and consequences of con- catheters is only slightly higher than the sepsis, endocarditis, or other intravas- taminated cultures. risk associated with venipuncture (5, 6). cular infections may be persistently It is no longer recommended that the An important concept for interpreting bacteremic, most other infections are needle inserted at the phlebotomy site be the source of bacteremia and fungemia is associated with intermittent bacteremia replaced with a second needle before the the recognition that the “time to positiv- or fungemia. Although it is commonly blood is transferred to the blood culture ity” (time from when the blood culture believed that high-grade seeding of the bottles. Although there is a small decrease was drawn until the positive result was blood corresponds to
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