Re: ‘Estimation of missed bloodstream infections without the third blood culture set’ by Collazos et al.
Authors: R. Mahieu, H. Pailhoriès, A. Kouatchet, V. Dubée
Journal: Clinical Microbiology and Infection (2019)

In the study by Collazos-Blanco et al. [[1]Collazos-Blanco A. Pérez-García F. Sánchez-Carrillo C. de Egea V. Muñoz P. Bouza E. Estimation of missed bloodstream infections without the third blood culture set: a retrospective observational single-centre study.Clin Microbiol Infect. 2019; 25: 469-473Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar], the authors found that without performing a third blood culture (BC), 7.5% of bloodstream infections (BSIs) would have been missed. The high number of BSIs included, and the prospective part of the study with a particular attention on the blood volume cultured, adds substantial strength to their conclusions. However, some issues must be discussed before making routine recommendations for performing three BCs in a patient with suspected BSI. The increased yield of subsequent BCs for the diagnostic of BSI has been discussed for decades, with a percentage ranging from 2.4% to 15.3% for third BCs [2Khatib R. Simeunovic G. Sharma M. Fakih M.G. Johnson L.B. Briski L. et al.Blood culture series benefit may be limited to selected clinical conditions: time to reassess.Clin Microbiol Infect. 2015; 21: 332-336Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 3Cockerill F.R. Wilson J.W. Vetter E.A. Goodman K.M. Torgerson C.A. Harmsen W.S. et al.Optimal testing parameters for blood cultures.Clin Infect Dis. 2004; 38: 1724-1730Crossref PubMed Scopus (248) Google Scholar, 4Dargère S. Parienti J.J. Roupie E. Gancel P.E. Wiel E. Smaiti N. et al.Unique blood culture for diagnosis of bloodstream infections in emergency departments: a prospective multicentre study.Clin Microbiol Infect. 2014; 20: O920-O927Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar]. The findings of Collazos-Blanco et al. are consistent with these previous data. Nevertheless, few data on specimen volume were available in previous studies, while BC yield increases with the volume cultured. The prospective monitoring of BC volume performed in their study establishes a new standard for future comparison. However, these results are somewhat confusing because BC contaminants were not systematically excluded. Because contaminants are not considered bacteraemia, this may lead to an overestimation of the number of true BSIs. The rate of missed pathogens is therefore between 5.5% (while excluding all microorganism of doubtful significance) and 6.4% (if some of these microorganisms are considered to be significant pathogens). Considering the very low positive rate of BSI identified by BC (2.5%, 4000 BSI for 159<thinsp>006 BCs) with a high proportion of contaminants (up to 46.3% of all positive BC), these differences matter for future analysis [[5]Eskira S. Gilad J. Schlaeffer P. Hyam E. Peled N. Karakis I. et al.Reduction of blood culture contamination rate by an educational intervention.Clin Microbiol Infect. 2006; 12: 818-821Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar]. For some infections, the identification of bacteraemia would probably have little or no consequence for the patient, as this does not affect the clinical outcome [6Alqarni A. Kantor E. Grall N. Tanaka S. Zappella N. Godement M. et al.Clinical characteristics and prognosis of bacteraemia during postoperative intra-abdominal infections.Crit Care. 2018; 22: 175Crossref PubMed Scopus (14) Google Scholar, 7Karakonstantis S. Kalemaki D. Blood culture useful only in selected patients with urinary tract infections—a literature review.Infect Dis. 2018; 50: 584-592Crossref PubMed Scopus (11) Google Scholar]. The most frequent sample positive with an identical bacteria was urine (58.4%). For pyelonephritis, no difference in mortality has been reported between patients with or without positive BC [[7]Karakonstantis S. Kalemaki D. Blood culture useful only in selected patients with urinary tract infections—a literature review.Infect Dis. 2018; 50: 584-592Crossref PubMed Scopus (11) Google Scholar]. The same remark can be made for intra-abdominal infections, in which it has been observed that the presence of bacteraemia does not change the overall management or outcome of patient (these infections are probably included in ‘deep tissue, abscess, biopsy’) [[6]Alqarni A. Kantor E. Grall N. Tanaka S. Zappella N. Godement M. et al.Clinical characteristics and prognosis of bacteraemia during postoperative intra-abdominal infections.Crit Care. 2018; 22: 175Crossref PubMed Scopus (14) Google Scholar]. Hence, after eliminating patients with another positive sample with the same pathogen, a maximum of 5% of BSI would have been missed without a third BC. In other words, at least 95% of these third BCs have no clinical consequence. This must be discussed in light of the increased cost of these additional examinations. Conversely, a substantial number of these third BCs may have induced unnecessary treatments and diagnostic procedures. Indeed, 14% (43/298) of the ‘missed BSI episodes’ were eventually considered to be contaminated, which can result in unnecessary antibiotic treatment and additional hospital costs [[8]Alahmadi Y.M. Aldeyab M.A. McElnay J.C. Scott M.G. Darwish Elhajji F.W. Magee F.A. et al.Clinical and economic impact of contaminated blood cultures within the hospital setting.J Hosp Infect. 2011; 77: 233-236Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar]. These results should be put in perspective with the 12% (37/298) of potentially contaminant bacteria for which an antibiotic treatment was initiated or changed by the clinician. We agree with the general conclusion of Collazos-Blanco et al. that a third BCs improves the yield of BC, but our strategy would slightly differ from theirs. Instead of immediately performing three BCs for every patient, we prefer collecting two samples. For the marginal proportion of patients (in particular those with no empiric treatment) with two first sets of negative BCs, further consideration is needed before performing a subsequent BC. First, when a microorganism has already been identified in a significant sample, we stop BC collection for the vast majority of patients (e.g. a patient with uncomplicated pyelonephritis with positive urine culture). Hence, we reserve the right to perform an additional BC only in patients with a high suspicion of BSI, a negative first blood collection (two BCs) and no other positive results. In these situations, we perform a new sample (one BC) within a very short time frame, conventionally after 24 hours, because current blood culture systems are able to detect the growth of bacteria at a median of 12 hours [[9]Jacobs M.R. Mazzulli T. Hazen K.C. Good C.E. Abdelhamed A.M. Lo P. et al.Multicenter clinical evaluation of BacT/Alert Virtuo blood culture system.J Clin Microbiol. 2017; 55: 2413-2421Crossref PubMed Scopus (27) Google Scholar]. It has been shown that a 48-hour delay in empirical antibiotic administration does not increase mortality in non–critically ill patients with BSI. Therefore, this strategy decreases the risk of contaminants and cost by limiting the need for a third BC to the very small number of patients without additional risk [[10]Lee C.C. Lee C.H. Hong M.Y. Tang H.J. Ko W.C. Timing of appropriate empirical antimicrobial administration and outcome of adults with community-onset bacteremia.Crit Care. 2017; 21: 119Crossref PubMed Scopus (55) Google Scholar]. Finally, we would like to question the method of BC collection chosen by Collazos-Blanco et al. They decided to perform three different phlebotomies for each patient. This technique is associated with an increased risk of contaminations, as the risk of contamination mathematically increases with the number of venipunctures. In 2014, Dargère et al. [[4]Dargère S. Parienti J.J. Roupie E. Gancel P.E. Wiel E. Smaiti N. et al.Unique blood culture for diagnosis of bloodstream infections in emergency departments: a prospective multicentre study.Clin Microbiol Infect. 2014; 20: O920-O927Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar] compared a unique blood culture (40 mL of blood collected in a single phlebotomy and distributed in two aerobic and two anaerobic bottles) to a multiple blood culture strategy (multiple set of two bottles). By combining the efficiency in detection of microorganisms and the minimization of contaminants, this ‘unique blood culture’ strategy was far better than the standard strategy. In our institution, unique blood culture has become the preferred method for BC collection. In conclusion, a third BC for each patient with suspected BSI may not be mandatory. Collecting two BCs during a single phlebotomy seems to be an effective alternative for most patients, while allowing for detection of most true pathogens with a reduced risk of contaminants. For the few patients with a high suspicion of having BSI and two negative BCs, a new set of BCs should be considered quickly—within 24 hours. Above all, special attention should be paid to better selecting of patients requiring blood cultures, as occurrence of bacteraemia has few therapeutic consequences in most infections. All authors report no conflicts of interest relevant to this article. Estimation of missed bloodstream infections without the third blood culture set: a retrospective observational single-centre studyClinical Microbiology and InfectionVol. 25Issue 4PreviewThe question of whether to obtain two or three sets of blood cultures to assess the aetiology of bloodstream infections (BSIs) remains open to debate. Few studies have assessed the proportion of BSIs missed without the third blood culture set (BCS). The aim of our study was to determine the proportion of BSIs that would be missed without the third BCS in a hospital where obtaining three BCSs is the standard of care. Full-Text PDF Open Archive