Blood culture is the microbiological gold standard method in diagnosis of sepsis and/or fever of unknown origin. It’s important to remember that the presence of microorganisms in the blood can be: transient, as in the case of invasive procedures such as, for example, tooth extractions or bladder catheterization; intermittent, associated, for example, to infections localized; or continuous, a typical example of endovascular or CVC-related infections. Bacteria or fungi isolation from the blood has a diagnostic value, as it allows the confirmation of a clinical suspicion, and it is essential to set a targeted therapy based on susceptibility test. When to take a blood-culture?The sampling should be carried out during the febrile episode, as early as possible and preferably before empirical therapy, or prior to its new administration (when the drug’s concentration in the blood should be at a minimum). Only few studies tried to assess the correct timing of blood-cultures. Often, it is common to collect the samples at ranges of 30-60 minutes, but it is an arbitrary timing; instead, can be useful to do it close to the onset of fever or, however, whenever there is a clinical suspicion of sepsis. In fact, there aren’t significant evidence in the positivity rate of samples taken at fever peak, and this is due to the fact that some bacteremic patients may be hypothermic or otherwise without fever, because unable to develop a febrile response to infection. Fever alone is not a useful indicator, other parameters should be always be considered, such as vital parameters (tachycardia, tachypnea, and hypotension), presence of leukocytosis, chills, increase of inflammatory markers (such as C-reactive protein and procalcitonin). In patients with acute endocarditis may be useful the same considerations to repeat blood-cultures in monitoring therapeutic success. Instead, in sub-acute endocarditis it is recommended to perform 3 sets of blood-cultures in 30-60 minutes, and in case of negativity should run another 3 set after 24 hours. How perform blood-culture collection?It is recommended to carry out 2-3 sets of samples (each sample must consists of a bottle for aerobic and one for anaerobic) to have a greater sensitivity. In fact, in case of sepsis the probability of isolating a pathogen with a single sample is of 65-80%, with two samples is of 80-88%, and 96-99% with three samples. How much blood should be drawn? Some studies suggest that there is a direct relationship between blood volume withdrawn and the blood-culture diagnostic yield. Altogether, should be taken 20-30 ml of blood, to be divided in different phial, putting about 8 ml of blood per bottle (and not to exceed 10 ml). Precautions to be followed are as follows:
In case of suspected CVC-related sepsis is indispensable perform blood-cultures simultaneously from both peripheral vein and from the venous catheter, after the disinfection of the insertion of CVC with an alcohol solution (verify compatibility with the material). The first ml taken from the CVC should not be totally discarded, because it contains the highest concentration of germs. When possible, the sample from peripheral vein should be done on the arm opposite the one in which the CVC is inserted. It is important to distribute the same amount of blood in each bottle, allowing us a correct interpretation of the time to positivity. In fact in cases of CVC-associated bacteremia, the time of CVC positivity must anticipate at least two hours the positivity of bottle drawn from peripheral vein. Delaying transport of the samples to the laboratory should be avoided. The bottles should arrive to microbiology laboratory as quickly as possible because a long time of stay outside the automatic incubation system may result in the failure of test. In fact, the microbial growth may reach the plateau outside of the incubation system, and then no longer be detectable by machine. Instead, an early incubation of bottles allows to bacteria or fungi to grow under optimal conditions, shortening the time to positivity of blood cultures. Under special circumstances it is possible to hold the bottles up to a maximum of 16-18 hours at normal ambient temperature, while the refrigeration is absolutely contraindicated. Why perform blood-culture?Blood culture is the best tool for the diagnosis of septicemia. From this examination, although relatively expensive, it is used to confirm the suspected diagnosis and to have an etiologic diagnosis and sensitivity, allowing you to set a antimicrobial targeted therapy. Learn more about learning and understanding an antibiogram References: – Wayne PA. Clinical and Laboratory Standards Institute (CLSI). Principles and Procedures for Blood Cultures; Approved guideline. CLSI M47-A, 2007. – Baron EJ et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). Clin Infect Dis. 2013 Aug; 57(4): e22-e121 – Dellinger RP et al. Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb; 41(2): 580-63 – Jaimes F et al. Predicting bacteremia at the bedside. Clin Infect Dis. 2004 38: 357-62 – Riedel S et al. Timing of specimen collection for blood cultures from febrile patients with bacteremia. J Clin Microbiol. 2008; 46(4): 1381-5 – Grohs P et al. Relevance of Routine Use of the Anaerobic Blood Culture Bottle. J. Clin Microbiol, 2007, 45: 2711-15 – PDF infezioni el torrente circolatorio FONTANA 2014
Many physicians have followed the historical practice of ordering blood cultures to be drawn as close as possible to the time of the peak of the febrile episode (fever spike).
When is the Best Time to Obtain Blood Cultures from My Potentially Septic Patient? Abstract & Commentary Ellen Jo Baron, PhD, D(ABBM), Professor of Pathology and Medicine, Stanford University Medical School Director; Clinical Microbiology Laboratory, Stanford University Medical Center, is Associate Editor for Infectious Disease Alert Dr. Baron reports no financial relationships relevant to this field of study. Many physicians have followed the historical practice of ordering blood cultures to be drawn as close as possible to the time of the peak of the febrile episode (fever spike). In the absence of prescient knowledge of this moment, physicians order blood cultures to be drawn at intervals ranging from 30 minutes to 2 hours. A paper by Jaimes et al suggested that many factors, other than fever, such as shaking chills, WBC counts, hypotension, and more were needed to better predict whether a patient was experiencing bacteremia.3 For many years, the only data comparing the yield of blood cultures in relationship to the patient's fever was from a study that was presented as an abstract but never officially published. Dr. Richard Thomson performed the study when he was a new microbiology laboratory director in Akron, Ohio, soon after leaving his post-doctoral fellowship at the Mayo Clinic.6 The results were presented in the abstracts of the 1989 American Society for Microbiology Annual Meeting and included in an American Society for Clinical Pathology Check Sample exercise distributed in 1991.6 Only a few contemporary microbiologists ever even had a copy of the report. Thomson et al looked at numbers of clinically relevant positive blood cultures obtained during four different time periods relative to a patient's fever spike. Although there was a trend toward more true positive blood cultures being obtained in the period directly before the fever spike, there were no statistically significant differences among the four time periods. These data served as the basis for most microbiologists' recommendation to obtain all of the blood cultures as soon as a patient becomes febrile, without any time period between draws. A 1994 publication by Li et al basically corroborated the Thomson results.4 The 1994 study showed that the yield of clinically significant blood cultures performed during a 24-hour period did not vary whether the blood was obtained all at once or over a period of several time intervals. Without stronger data, physicians have continued to pursue their idiosyncratic blood culture ordering practices. By asking phlebotomists to obtain blood cultures at intervals spanning several hours, unnecessary additional time is spent in the process and the overall cost and inefficiency of procuring blood cultures is increased. And if antibiotic therapy is withheld while blood cultures are being obtained, patient care also suffers. Dr. Gary Doern set out to perform the definitive study to answer the question without nuance. He enlisted the aid of six additional medical centers in addition to his own, University of Iowa. Workers collaborating from Geisinger Medical Center (Danville, PA), VA Boston Healthcare System, Johns Hopkins University School of Medicine, Barnes-Jewish Hospital Washington University School of Medicine (St. Louis), University of Texas Health Science Center in San Antonio, TX, and the VA Medical Center (Portland) enrolled 1,436 adult patients with clinically significant episodes of bacteremia and fungemia during 2006.5 For each patient enrolled, the workers noted the time at which the highest temperatures were recorded in both the 24 hours preceding and those following the time that the first positive blood culture was obtained, as well as the temperature of the patient recorded closest to the time of that blood culture. Clinical relevance was determined by criteria in place at each medical center. The patients were two-thirds male, average age 59 years, and their blood cultures grew a variety of microorganisms, including 54% gram-positive bacteria such as staphylococci (38%, 42% of which were coagulase negative) and Enterococcus (10%); 38% gram-negative bacteria such as Enterobacteriaceae (> 23%) and Pseudomonas aeruginosa (4%); 3% anaerobic bacteria; and 5% yeast. The highest recorded fevers, determined as the one of the three temperatures that was 0.5° C higher than the other two, occurred during the time of the blood culture draw in 44% of episodes. It was noted that 10%-31% of maximum fevers occurred before or after the blood draw in the remaining patients. In general, none of the results were statistically significantly different from each other. In addition, no significant associations were found between temperatures of patients and their genders, white blood counts, or even when organism types were evaluated. Unfortunately, not enough cultures yielded fungi to allow reliable statistical analysis. One caveat was that for patients 18- to 30-years-old, the maximum temperature was significantly more likely to occur one to < 24 hours after the first positive blood culture. For other age groups (majority of patients enrolled), there were no differences. Riedel et al concluded that the best practices for collecting blood cultures are to obtain enough blood volume (recent studies summarized in the ASM Cumitech and the CLSI guideline on blood cultures have suggested from 40-60 mL), to obtain suitable numbers of separate blood cultures (at least two), and to use stringent aseptic technique to avoid contamination. References cited:
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What is the ideal time to collect blood sample for blood culture
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