The positive rate of blood culture is related to the type and concentration of microorganisms in the blood. Slow growth of fastidious bacteria, low bacterial count in the blood, and treatment with antibiotics can all affect the positive rate. The fundamental reason for false positive blood culture is contamination of the blood culture. The widespread use of central venous catheters and vascular implants has made blood culture contamination more common. Therefore, clinical doctors must comprehensively consider the patient's clinical manifestations when facing positive blood culture reports and distinguish between true and false positives.
1: The incidence of blood culture contamination
The actual incidence of blood culture contamination varies in literature reports, ranging from 0 6% to over 6%. The Quality Improvement Group (CAP QProbe) of the American Society of Pathology (CAP) conducted a survey of 497134 adult blood specimens from 640 health care institutions in the United States, and found an average contamination rate of 2 5%
[1] ; The CAP Quality Tracking Research Group collected blood culture specimen data from 356 hospitals in the United States from 1999 to 2003, with a total average contamination rate of 2 92%. The pollution rate has been on the rise recently, mainly due to improvements in cultivation techniques that have enabled the detection of a relatively small number of pathogens. The result of blood culture contamination will inevitably lead to an increase in medical expenses and affect the rational use of antibiotics. Almost half of the patients with false positive reports were treated with antibiotics. Staphylococcus is the most common contaminating bacteria, and vancomycin is also the most commonly used in clinical practice. This abuse of antibiotics not only wastes medical resources, but also increases bacterial resistance
[2] . Scholars have proposed three different solutions for this: (1) identifying contaminated bacteria: as contamination cannot be completely eliminated, reliable predictive factors must be found to distinguish between positive and false; (2) Prevention: Improve the aseptic operation technology for blood sample collection; (3) Reasonable application of blood culture: Patients with minimal probability of bacteremia should reduce blood culture to improve the positive predictive value of blood culture, reduce resource waste and patient economic burden caused by pollution. Factors for Judging Blood Culture Pollution
2.1 Microbial identification The type of microorganisms that grow in blood culture is the most important basis for determining true or false positive results.
Weinstein et al. analyzed 843 blood culture positive pathogens and thought that the following pathogens could be considered as true positive: Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and other Enterobacteriaceae bacteria, Pseudomonas aeruginosa and Candida albicans [3]. According to his personal observation, he believes that the following pathogens are also real infections: Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, some Bacteroides fragilis, Candida and Cryptococcus neoformans [3]. The growth of some pathogens suggests that it may be pollution, such as coagulase negative Staphylococcus (CNS), Corynebacterium, Bacillus (excluding anthrax), Propionibacterium, Micrococcus, Streptococcus viridis, Enterococcus and Clostridium perfringens [3]. However, it must be pointed out that the possible "contaminating bacteria" mentioned above can sometimes cause true bacteremia, and if not analyzed, it will have terrifying consequences. CNS is the most common contaminating bacterium, accounting for 70% to 80% of all contaminating bacteria. However, with the development of medical technology, this bacterium has gradually become an important pathogen in bacteremia caused by catheterization and vascular repair surgery. So, when separating CNS from blood culture, it cannot be simply attributed to contaminated bacteria. Similarly, the clinical significance of other microorganisms cannot be judged solely by the identification of the bacterial species themselves. For example, the same study [3] found that 78% of Enterococcus and 38% of Streptococcus viridis were pathogenic bacteria; 77% of Clostridium perfringens were contaminating bacteria, and 80% of Clostridium were pathogenic bacteria.
2. Two sets of blood culture sets: Two sets of blood culture (two different blood collection sites). If only one bottle of CNS is positive, it should be considered contaminated. If more than two bottles of blood culture are positive, it can be considered bacteremia.
Among the 11 167 CNS positive specimens from the CAP-Q Probe research group, the contamination rate was 27. 7% among the 2 sets of positive specimens 8%, up to 75% in 1 set of positive cases 2%. A study on patients with CNS positive blood cultures with central venous catheters found that the positive predictive value (PPV) for single bottle positive individuals was 55% when only one set of culture was performed, 20% for single bottle positive individuals when two sets of culture were performed, and only 5% for single bottle positive individuals when three sets of culture were performed [4]. Therefore, in order to improve the true positive rate, at least two sets of blood samples should be collected simultaneously for blood culture. Due to the fact that CNS often implies contamination rather than true infection, even if both sets are positive, clinical judgment still needs to be combined.
In theory, only 1 out of 2 bottles in a set of 3 blood culture positive bottles is positive, which has a high possibility of contamination.
Mirrett et al. conducted research on the number of bottles cultured for CNS and found that the number of positive bottles is not related to infection [5]. Two bottles of 486 sets of specimens were collected, and only one bottle had a positive diagnosis of sepsis with a PPV of 18%, while both bottles were positive with a PPV of 37%; 235 sets were collected from 3 bottles, with positive PPV rates of 28%, 52%, and 30% for 1, 2, and 3 bottles, respectively; 303 cases were collected with 4 bottles, and the positive PPV rates for 1-4 bottles were 27%, 28%, 19%, and 27%, respectively. It seems that the higher the number of positive bottles, the higher the predicted positive value, so the authenticity of a positive should not be judged solely based on the number of positive bottles.
The positive reporting time of blood culture is inversely proportional to the original amount of bacteria in the inoculated sample.
When bacteremia occurs, the number of pathogenic bacteria in the blood is generally high, and the corresponding amount of bacteria inoculated in the blood culture bottle is relatively large, so the positive time for growth alarm is faster; However, the amount of contaminated bacteria is generally relatively small, and the amount planted in the culture bottle is also small, so the growth time will be slower than that of pathogenic bacteria. Most of the instruments currently used for bacteremia generally generate a positive alarm within 24 hours. If a positive alarm occurs after 3-5 days, it may indicate contamination. Due to the difficulty in collecting more than one set of blood cultures for children, Haimi Cohen et al. believe that if the positive time is ≤ 15 hours, the PPV of bacteremia is 84%, which can be used to identify contaminated bacteria [6]. However, due to the overlap in the growth time of pathogenic and polluting bacteria, and the influence of various factors such as bacterial species, bacterial quantity, and culture conditions, this method can only be used as a reference. With the continuous improvement of the nutrient composition of the blood culture system culture medium, the speed of microbial reproduction accelerates, and the positive time of instrument alarm will also be correspondingly shortened. It is more difficult to grasp the scale by distinguishing whether it is contaminated based solely on the positive alarm time. There is still a lack of gold standard for distinguishing between pathogenic microorganisms and polluting bacteria when blood culture is positive. The combination of patient clinical manifestations and laboratory results may be the most reliable method. Strengthening quality control before and during analysis, and close communication between clinical and laboratory departments, is possible to minimize the incidence of blood culture contamination.
