True Pathogen or Contamination: Validation of Blood Cultures for the Diagnosis of Nosocomial Infections in a Developing Country

True Pathogen or Contamination: Validation of Blood Cultures for the Diagnosis of Nosocomial... Abstract Background Blood culture results are frequently used to guide antibiotic decision-making, but culture contaminants need to be distinguished from true pathogens. Aims To assess the contamination rate of blood cultures and validate a method to distinguish between true bacteraemia and contamination. Methods We analysed blood culture results from children who were admitted to the paediatric ICU and paediatric wards at the Sardjito Hospital, Yogyakarta, Indonesia between December 2010 and February 2013. For each positive culture result, the type of isolated organism, time to positivity, and the number of positive culture sites were considered to classify the isolate as representing a true bacteraemia or contaminant. Results There were 1293 cultures obtained from blood and 308 (23.8%) were positive for bacterial growth. Fifty-three (4.1%) of the total cultures drawn fulfilled criteria for contaminants. The most common blood culture contaminants were coagulase-negative staphylococci. Conclusion Using standardized criteria, it is possible to implement a working method to identify true nosocomial infection from blood culture contaminant, and thus limit the effect of contaminated blood culture on irrational antibiotic use. true pathogen, contamination, blood culture, nosocomial infection, children, developing countries INTRODUCTION The development of bacteraemia has major significance for hospitalized children, increasing morbidity and the risk of mortality several-fold. Nosocomial infections are common in hospitalized children in developing countries but often go undiagnosed. Blood culture results are frequently used to direct antimicrobial therapy [1], but differentiating a true pathogen from a contaminant can be challenging. Blood cultures are frequently contaminated by skin flora inoculated into the blood culture medium at the time of blood collection. The rational use of antibiotics based on culture results would be helped by a standardized method to distinguish true pathogens from contaminants. This would also assist countries to have standardized surveillance systems for community- and hospital-acquired bacterial infections. This study aimed to assess the contamination rate of blood cultures using standardized criteria, and in doing so evaluate the feasibility of a method to distinguish between true bacteraemia and a contaminated blood culture. METHODS Setting and time The blood culture results from the children who were admitted to the paediatric intensive care unit (PICU) and paediatric wards (one infectious ward and one non-infectious ward) at the Dr Sardjito Hospital, Yogyakarta, Indonesia between 1 December 2010 and 28 February 2013 were analysed. Data collection Specimens were taken for bacterial culture when nosocomial infection was suspected. Where appropriate to the clinical situation, cultures were taken from blood specimens. Nosocomial bloodstream infections (BSIs) were defined using the US Centers for Disease Control and Prevention (CDC) criteria. All isolates of a pathogen cultured from blood collected >48 h after hospitalization were considered as nosocomial BSI when there were corresponding clinical symptoms of infection and there was no contamination. If the same organism was found on repeat blood cultures collected within 14 days, the isolates were counted as one infection episode. Culture-positive nosocomial BSI must meet at least one of the following criteria: (i) the patient had an organism cultured from one or more blood cultures unrelated to another site of infection; or (ii) the patient had at least either fever (>38.5 °C) or hypotension and positive laboratory results not related to another site of infection and common skin contaminant organisms [i.e. diphtheroids (Corynebacterium spp.), Bacillus (not Bacillusanthracis) spp., Propionibacterium spp., coagulase-negative staphylococci (including Staphylococcusepidermidis), viridans group streptococci, Aerococcus spp., Micrococcus spp.] on culture from two or more blood samples drawn on separate occasions; or (iii) patients aged  ≤1 year had at least one of the following signs or symptoms: fever (>38.5 °C), hypothermia (<36.5 °C), apnea and bradycardia, as well as positive laboratory results not related to another site of infection and common skin contaminant organisms [i.e. diphtheroids (Corynebacterium spp.), Bacillus (not B. anthracis) spp., Propionibacterium spp., coagulase-negative staphylococci (including S. epidermidis), viridans group streptococci, Aerococcus spp., Micrococcus spp.] on culture from two or more blood samples drawn on separate occasions [2]. We used standard culture techniques that had been validated using BACTEC® 9120 (BD Diagnostics, Sparks, MD, USA). Bacterial isolation and antibiotic susceptibility testing were performed according to Clinical Pathology standard procedure [3]. When obtaining blood cultures, the skin was cleaned using 70% isopropyl alcohol from the centre to the periphery of the needle insertion site after the vein was palpated. This was followed by cleaning with 2% of iodine tincture or povidone-iodine, and the site was left to dry. A non-touch method was used, meaning that when venipuncture site had been sterilized, the skin should not be touched. When the vein needed to be palpated, sterilization of skin over the vein was conducted. For blood cultures, 3–5 ml of blood was obtained and inoculated into a culture bottle. Before inoculating the culture bottles, the tops were disinfected with 70% alcohol. Blood culture bottles were processed in a semi-automated blood culture system. Assessment criteria for blood culture contaminants True pathogen was defined combining of blood culture plus clinical and laboratory indexes. These included positive blood culture (presence of bacteria) plus hypothermia or hyperthermia and leucocytosis or leucopenia or immature-to-total neutrophil ratio (IT ratio) > 0.2 or hypotension [4]. For each positive culture result, the type of isolated organism, time to positivity, and the number of positive culture sites were considered to determine if the isolate was a contaminant (Table 1). Table 1 Method for differentiation between true pathogen and contaminant [4] Detection of contaminated blood cultures True pathogen Potential contaminants Types of organism Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and other Enterobacteriaceae, P. aeruginosa, Candida albicans, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Bacteroides fragilis group and Cryptococcus neoformans Coagulase-negative staphylococci, Corynebacterium species, Bacillus species other than B. anthracis, Propionibacterium acnes, Propionibacterium species, Micrococcus species, viridians group streptococci, Aerococcus species, Diphtheroid species Time to culture positivity ≤5 days >5 days Number of positive culture sites When the same organism grows on multiple culture setsa When different organisms grows on the same culture set Clinical or laboratory parameters Hypothermia <36°C or hyperthermia ≥39°C, peripheral leukocyte < 4000/μl or > 20 000/μl, IT ratio >0.2, or hypotension Normothermia, peripheral leukocyte ≥4000/μl or ≤ 20 000/μl, IT ratio ≤0.2 or no hypotension Detection of contaminated blood cultures True pathogen Potential contaminants Types of organism Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and other Enterobacteriaceae, P. aeruginosa, Candida albicans, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Bacteroides fragilis group and Cryptococcus neoformans Coagulase-negative staphylococci, Corynebacterium species, Bacillus species other than B. anthracis, Propionibacterium acnes, Propionibacterium species, Micrococcus species, viridians group streptococci, Aerococcus species, Diphtheroid species Time to culture positivity ≤5 days >5 days Number of positive culture sites When the same organism grows on multiple culture setsa When different organisms grows on the same culture set Clinical or laboratory parameters Hypothermia <36°C or hyperthermia ≥39°C, peripheral leukocyte < 4000/μl or > 20 000/μl, IT ratio >0.2, or hypotension Normothermia, peripheral leukocyte ≥4000/μl or ≤ 20 000/μl, IT ratio ≤0.2 or no hypotension a This should be applied to potential contaminants such as coagulase-negative Staphylococcus. If we grew any true pathogen once, then that was considered sufficient. Table 1 Method for differentiation between true pathogen and contaminant [4] Detection of contaminated blood cultures True pathogen Potential contaminants Types of organism Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and other Enterobacteriaceae, P. aeruginosa, Candida albicans, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Bacteroides fragilis group and Cryptococcus neoformans Coagulase-negative staphylococci, Corynebacterium species, Bacillus species other than B. anthracis, Propionibacterium acnes, Propionibacterium species, Micrococcus species, viridians group streptococci, Aerococcus species, Diphtheroid species Time to culture positivity ≤5 days >5 days Number of positive culture sites When the same organism grows on multiple culture setsa When different organisms grows on the same culture set Clinical or laboratory parameters Hypothermia <36°C or hyperthermia ≥39°C, peripheral leukocyte < 4000/μl or > 20 000/μl, IT ratio >0.2, or hypotension Normothermia, peripheral leukocyte ≥4000/μl or ≤ 20 000/μl, IT ratio ≤0.2 or no hypotension Detection of contaminated blood cultures True pathogen Potential contaminants Types of organism Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and other Enterobacteriaceae, P. aeruginosa, Candida albicans, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Bacteroides fragilis group and Cryptococcus neoformans Coagulase-negative staphylococci, Corynebacterium species, Bacillus species other than B. anthracis, Propionibacterium acnes, Propionibacterium species, Micrococcus species, viridians group streptococci, Aerococcus species, Diphtheroid species Time to culture positivity ≤5 days >5 days Number of positive culture sites When the same organism grows on multiple culture setsa When different organisms grows on the same culture set Clinical or laboratory parameters Hypothermia <36°C or hyperthermia ≥39°C, peripheral leukocyte < 4000/μl or > 20 000/μl, IT ratio >0.2, or hypotension Normothermia, peripheral leukocyte ≥4000/μl or ≤ 20 000/μl, IT ratio ≤0.2 or no hypotension a This should be applied to potential contaminants such as coagulase-negative Staphylococcus. If we grew any true pathogen once, then that was considered sufficient. The organisms that were considered as potential contaminants include coagulase-negative staphylococci, Corynebacterium species, Bacillus species other than B.anthracis, Propionibacterium acnes, Micrococcus species, viridians group streptococci, enterococci and Clostridium perfringens [4]. Time to culture positivity was defined as an interval from specimen collection and examination to a positive bacterial culture result. Cultures of potential contaminants that became positive after >5 days were considered as likely contaminants. We also considered as a contaminant different organisms growing on the same culture set. If we considered any potential contaminant, such as coagulase-negative Staphylococcus, then it was assumed that the same organism grows on multiple culture sets. However, if any true pathogen grew once, then that was considered sufficient. Outcome measure The proportion of contaminated blood culture results was defined as the culture isolates classified as contaminants divided by the number of all blood samples taken. Data analysis Data were analysed using STATA V.12.1 (StataCorp LP, Texas, USA). Contaminated blood culture results were presented as proportions. The χ2 statistic was used to analyse the results when comparing proportions. A probability value <0.05 was considered to denote statistical significance. RESULTS During the study period, there were 1293 cultures obtained from blood. In total, 308 cultures (23.8%) were positive for bacterial growth (Table 2). Using the standardized criteria, 53 (17.2% of all positive cultures and 4.1% of all blood samples) drawn were contaminants (Table 3). Table 2 Baseline characteristics of all admissions Characteristics n = 2646 (%) Age  ≤12 months 640 (24.2)  >12–60 months 736 (27.8)  >60–120 months 574 (21.7)  >120 months 696 (26.3) Male sex 1480 (55.9) Ward of origin  PICU 509 (19.2)  Infectious ward 916 (34.6)  Non-infectious ward 1221 (46.1) Developing nosocomial infection 400 (15.1) Nosocomial BSI 170 (6.4) Taking blood sample 1293 (48.9) Positive culture result 308 (23.8) Characteristics n = 2646 (%) Age  ≤12 months 640 (24.2)  >12–60 months 736 (27.8)  >60–120 months 574 (21.7)  >120 months 696 (26.3) Male sex 1480 (55.9) Ward of origin  PICU 509 (19.2)  Infectious ward 916 (34.6)  Non-infectious ward 1221 (46.1) Developing nosocomial infection 400 (15.1) Nosocomial BSI 170 (6.4) Taking blood sample 1293 (48.9) Positive culture result 308 (23.8) Table 2 Baseline characteristics of all admissions Characteristics n = 2646 (%) Age  ≤12 months 640 (24.2)  >12–60 months 736 (27.8)  >60–120 months 574 (21.7)  >120 months 696 (26.3) Male sex 1480 (55.9) Ward of origin  PICU 509 (19.2)  Infectious ward 916 (34.6)  Non-infectious ward 1221 (46.1) Developing nosocomial infection 400 (15.1) Nosocomial BSI 170 (6.4) Taking blood sample 1293 (48.9) Positive culture result 308 (23.8) Characteristics n = 2646 (%) Age  ≤12 months 640 (24.2)  >12–60 months 736 (27.8)  >60–120 months 574 (21.7)  >120 months 696 (26.3) Male sex 1480 (55.9) Ward of origin  PICU 509 (19.2)  Infectious ward 916 (34.6)  Non-infectious ward 1221 (46.1) Developing nosocomial infection 400 (15.1) Nosocomial BSI 170 (6.4) Taking blood sample 1293 (48.9) Positive culture result 308 (23.8) Table 3 Blood culture results by ward PICU (n) Infectious ward (n) Non-infectious ward (n) Total Number of cultures performed from blood 651 437 205 1293 Number of positive blood cultures (%) 181 (27.8) 95 (21.7) 32 (15.6) 308 (23.8) Contaminated blood culture (%) 24 (3.7) 22 (5) 7 (3.4) 53 (4.1) PICU (n) Infectious ward (n) Non-infectious ward (n) Total Number of cultures performed from blood 651 437 205 1293 Number of positive blood cultures (%) 181 (27.8) 95 (21.7) 32 (15.6) 308 (23.8) Contaminated blood culture (%) 24 (3.7) 22 (5) 7 (3.4) 53 (4.1) Table 3 Blood culture results by ward PICU (n) Infectious ward (n) Non-infectious ward (n) Total Number of cultures performed from blood 651 437 205 1293 Number of positive blood cultures (%) 181 (27.8) 95 (21.7) 32 (15.6) 308 (23.8) Contaminated blood culture (%) 24 (3.7) 22 (5) 7 (3.4) 53 (4.1) PICU (n) Infectious ward (n) Non-infectious ward (n) Total Number of cultures performed from blood 651 437 205 1293 Number of positive blood cultures (%) 181 (27.8) 95 (21.7) 32 (15.6) 308 (23.8) Contaminated blood culture (%) 24 (3.7) 22 (5) 7 (3.4) 53 (4.1) The proportion of blood culture contamination in the PICU was similar to the non-infectious wards of 3.7% (24 of 651) and 3.4% (7 of 205), respectively. In the infectious ward, the proportion of contamination was higher at 5% (22 of 437) (Table 3). The most common blood culture contaminants were coagulase-negative staphylococci followed by Streptococcus spp., Pseudomonasaeruginosa and other Pseudomonas spp. (Table 4). Table 4 Organisms yielded from the contaminated blood cultures Contaminant organisms n (%) Coagulase-negative staphylococci 48 (90.5) Streptococcus spp. 3 (5.7) Pseudomonas aeruginosa 1 (1.9) Pseudomonas spp. 1 (1.9) Total 53 Contaminant organisms n (%) Coagulase-negative staphylococci 48 (90.5) Streptococcus spp. 3 (5.7) Pseudomonas aeruginosa 1 (1.9) Pseudomonas spp. 1 (1.9) Total 53 Table 4 Organisms yielded from the contaminated blood cultures Contaminant organisms n (%) Coagulase-negative staphylococci 48 (90.5) Streptococcus spp. 3 (5.7) Pseudomonas aeruginosa 1 (1.9) Pseudomonas spp. 1 (1.9) Total 53 Contaminant organisms n (%) Coagulase-negative staphylococci 48 (90.5) Streptococcus spp. 3 (5.7) Pseudomonas aeruginosa 1 (1.9) Pseudomonas spp. 1 (1.9) Total 53 We showed the proportion of clinical and laboratory indicators in children with a contaminant or a true pathogen. These indicators included hypothermia <36 °C or hyperthermia ≥39 °C, peripheral leukocyte < 4000/µl or >20 000/µl, IT ratio  >0.2 or hypotension (Table 5). Table 5 The proportion of clinical or laboratory parameters in children with true bacteraemia and contamination Clinical or laboratory parameters True bacteraemia n = 170 (%) Contamination n = 53 (%) Hypothermia or hyperthermia 143 (83.6) 2 (3.8) Leukopenia (<4000) or leucocytosis (>20 000) 62 (36.3) 1 (1.9) IT ratio > 0.2 5 (2.9) 0 Hypotension 5 (2.9) 0 Clinical or laboratory parameters True bacteraemia n = 170 (%) Contamination n = 53 (%) Hypothermia or hyperthermia 143 (83.6) 2 (3.8) Leukopenia (<4000) or leucocytosis (>20 000) 62 (36.3) 1 (1.9) IT ratio > 0.2 5 (2.9) 0 Hypotension 5 (2.9) 0 Table 5 The proportion of clinical or laboratory parameters in children with true bacteraemia and contamination Clinical or laboratory parameters True bacteraemia n = 170 (%) Contamination n = 53 (%) Hypothermia or hyperthermia 143 (83.6) 2 (3.8) Leukopenia (<4000) or leucocytosis (>20 000) 62 (36.3) 1 (1.9) IT ratio > 0.2 5 (2.9) 0 Hypotension 5 (2.9) 0 Clinical or laboratory parameters True bacteraemia n = 170 (%) Contamination n = 53 (%) Hypothermia or hyperthermia 143 (83.6) 2 (3.8) Leukopenia (<4000) or leucocytosis (>20 000) 62 (36.3) 1 (1.9) IT ratio > 0.2 5 (2.9) 0 Hypotension 5 (2.9) 0 DISCUSSION False-positive contaminated culture results are a significant problem in clinical practice. Blood culture contaminants should be identified, as significant healthcare costs and effects on patient outcomes can occur from the over-use of antibiotics and extended hospital stays [5]. In this study, approximately a quarter of all blood cultures obtained were positive. Even though low-level bacteraemia is generally common in children [6], the positive rate in our study was high compared with a study in Taiwan, which had a positivity rate of 4.2% of all performed cultures [7]. This low positivity might be explained by low organism concentration because of smaller blood volumes collected from children [6]. Other possible explanations could be prior antibiotic treatment, the severity of disease, different patient populations, and different species and strain of organisms that lead to transient or intermittent bacteraemia [6, 8–10]. To increase the true positivity of culture results, the use of antibiotic–adsorbent resin may be added to the medium [11]. In the paediatric population, a smaller volume of blood is often sufficient compared with adults because the number of organisms per millilitre of blood is larger [9, 11]. However, an adequate amount of blood should be taken, depending on the patients’ body weight, which is 1–2 ml in neonates, 2–3 ml in infants, 3–5 ml in children and up to 10 ml in adolescents [9]. The proportion of contaminated blood cultures in this study, with the standardized definition we used, was acceptable. Previous studies recommended that the proportions of blood culture contamination should not exceed 3%; however, contamination rates reported in hospitals ranged from 0.6 to 6% [4, 12], and it is likely that in routine settings outside trial conditions, the contamination rates may be even higher. Our findings correspond with previous studies where the reported contamination rates were 3.4% [6, 7]. Coagulase-negative staphylococci were the most common contaminants in our study. This was similar to other studies where gram-positive bacteria were common, representing skin contaminants [13–15]. In 3.8% of cases, we identified gram-negative bacteria as contaminants based on our criteria. These patients were directly admitted from the community rather than also including patients who had spent some time in hospitals, as in our study. We included several standardized criteria to indicate a contaminant, and these criteria reflect the factors behind blood cultures becoming contaminated: when the yielded pathogen may be part of skin flora, or isolated after prolonged incubation or there is more than one bacteria isolated in the culture [4, 11–14]. Time required for the organism to grow is shorter in children with nosocomial BSI compared with children with contaminated blood cultures. This indicates a higher bacterial concentration in the blood among children with true BSI than those with contaminated cultures. A review conducted by Myllote and Tayara indicates that isolating the organism after 5 days incubation increases the probability of culture results being contaminated [16]. A study conducted in Taiwan also suggests that a 5-day incubation period is more efficient in identifying true pathogens and cost-effective in settings with limited resources [17]. Ideally, two or three sets of blood cultures should be taken within 24 h because this increases the yield of detecting a pathogen in the blood. This also increases the probability of detecting pathogens when there are low levels of bacteraemia. However, obtaining multiple blood cultures in a child is challenging, when the procurement technique is not easy and when healthcare resources are limited. Some high-yield studies of bacteraemia have been done with only a single blood sample collected [18].Weinstein et al. [14] indicated that the first blood culture detected 91.5% of all bacteraemia, and a second blood culture detected an additional 7.8%. Adequate skin disinfection reduces the probability of contaminated culture results, although around 20% of skin flora is not removed even after disinfecting [12]. Insufficient skin preparation leads to skin contaminants, such as coagulase-negative staphylococci in blood cultures [11]. Direct collection from a vein rather than an intravenous catheter also reduces contamination rates [13, 15, 19]. In our study, clinical indicators of infection or systemic inflammation are associated with true bacteraemia and fungaemia [14]. Because of this finding, clinical and laboratory markers should be included to distinguish blood culture positivity from contamination. In our study, only a single blood sample was collected in most patients to diagnose a nosocomial infection. However, in the paediatric setting, this may be appropriate, as taking blood more than once leads to additional costs, discomfort and time, and adds minimal value when the volume of blood culture is adequate [9]. CONCLUSIONS Differentiating contaminated blood cultures from true bacteraemia is essential to ensure the validity of nosocomial infection diagnosis. Our criteria are simple to apply and represent a valid workable algorithm for identifying true bacteraemia from blood culture contamination. To reduce contamination and improve the yield of true bacteraemia in children in settings with limited resources, blood samples should only be taken when bacterial infection is clinically suspected, the skin should be disinfected properly before taking blood samples and percutaneous collection from a vein rather than a venous catheter should be the standard method. Applying this method and these criteria for identifying true bacteraemia from contaminants would save significant healthcare costs and improve patient care. ACKNOWLEDGEMENTS The authors would like to thank the Infection Control team at the Dr Sardjito Hospital, Yogyakarta, Indonesia. FUNDING IKM was supported by an Australian Development Scholarship, AusAid for the duration of the study. The Centre for International Child Health was supported by the Knowledge Hubs for Health initiative of the Australian Government and is a WHO Collaborating Centre for Research and Training in Child and Neonatal Health. Ethics approval: The Ethics Committees of the Universitas Gadjah Mada (Application KE/FK/532/EC) and the University of Melbourne (Application #1033316) approved the study. References 1 Murni IK , Duke T , Kinney S , et al. Antibiotic resistance and mortality in children with nosocomial bloodstream infection in a teaching hospital in Indonesia . Southeast Asian J Trop Med Public Health 2016 ; 47 : 983 – 93 . 2 Horan TC , Andrus M , Dudeck MA. CDC/NHSN surveillance definition of healthcare–associated infection and criteria for specific types of infections in the acute care setting . Am J Infect Control 2008 ; 36 : 309 – 32 . Google Scholar CrossRef Search ADS PubMed 3 Clinical Laboratory and Standard Institute (CLSI) . Performance standards for antimicrobial susceptibility testing; twenty-first informational supplement . CLSI document M100-S21 , Wayne, PA: Clinical and Laboratory Standards Institute; 2011 , p. 31 (1). 4 Weinstein MP. Blood culture contamination: persisting problems and partial progress . J Clin Microbiol 2003 ; 41 : 2275 – 8 . Google Scholar CrossRef Search ADS PubMed 5 Murni IK , Duke T , Kinney S , et al. Reducing hospital-acquired infections and improving the rational use of antibiotics in a developing country: an effectiveness study . Arch Dis Child 2015 ; 100 : 454 – 9 . Google Scholar CrossRef Search ADS PubMed 6 Kellogg JA , Manzella JP , Bankert DA. Frequency of low-level bacteremia in children from birth to fifteen years of age . J Clin Microbiol 2000 ; 38 : 2181 – 5 . Google Scholar PubMed 7 Chiu YH , Chen TJ , Chen CT , et al. Positive blood cultures in pediatric emergency department patients: epidemiological and clinical characteristics . Acta Paediatr Taiwan 2005 ; 46 : 11 – 6 . Google Scholar PubMed 8 Bennett I , Beeson R. Bacteremia: a consideration of some experimental and clinical aspects . Yale J Biol Med 1954 ; 26 : 241. Google Scholar PubMed 9 Paisley JW , Lauer BA. Pediatric blood cultures . Clin Lab Med 1994 ; 14 : 17 – 30 . Google Scholar PubMed 10 Riedel S , Bourbeau P , Swartz B , et al. Timing of specimen collection for blood cultures from febrile patients with bacteremia . J Clin Microbiol 2008 ; 46 : 1381 – 5 . Google Scholar CrossRef Search ADS PubMed 11 Chandrasekar PH , Brown WJ. Clinical issues of blood cultures . Arch Intern Med 1994 ; 154 : 841 – 9 . Google Scholar CrossRef Search ADS PubMed 12 Hall KK , Lyman JA. Updated review of blood culture contamination . Clin Microbiol Rev 2006 ; 19 : 788 – 802 . Google Scholar CrossRef Search ADS PubMed 13 Bates DW , Goldman L , Lee TH. Contaminant blood cultures and resource utilization: the true consequences of false-positive results . Jama 1991 ; 265 : 365 – 9 . Google Scholar CrossRef Search ADS PubMed 14 Weinstein MP , Towns ML , Quartey SM , et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults . Clin Infect Dis 1997 ; 24 : 584 – 602 . Google Scholar CrossRef Search ADS PubMed 15 Ramsook C , Childers K , Cron SG , et al. Comparison of blood-culture contamination rates in a pediatric emergency room: newly inserted intravenous catheters versus venipuncture . Infect Control Hosp Epidemiol 2000 ; 21 : 649 – 51 . Google Scholar CrossRef Search ADS PubMed 16 Mylotte JM , Tayara A. Blood cultures: clinical aspects and controversies . Eur J Clin Microbiol Infect Dis 2000 ; 19 : 157 – 63 . Google Scholar CrossRef Search ADS PubMed 17 Huang AH , Yan JJ , Wu JJ. Comparison of five days versus seven days of incubation for detection of positive blood cultures by the Bactec 9240 system . Eur J Clin Microbiol Infect Dis 1998 ; 17 : 637 – 41 . Google Scholar CrossRef Search ADS PubMed 18 Schifman RB , Bachner P , Howanitz PJ. Blood culture quality improvement: a College of American Pathologists Q-Probes Study involving 909 institutions and 289572 blood culture sets . Arch Pathol Lab Med 1996 ; 120 : 999 – 1002 . Google Scholar PubMed 19 McBryde ES , Tilse M , McCormack J. Comparison of contamination rates of catheter-drawn and peripheral blood cultures . J Hosp Infect 2005 ; 60 : 118 – 21 . Google Scholar CrossRef Search ADS PubMed © The Author [2017]. 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True Pathogen or Contamination: Validation of Blood Cultures for the Diagnosis of Nosocomial Infections in a Developing Country

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Abstract

Abstract Background Blood culture results are frequently used to guide antibiotic decision-making, but culture contaminants need to be distinguished from true pathogens. Aims To assess the contamination rate of blood cultures and validate a method to distinguish between true bacteraemia and contamination. Methods We analysed blood culture results from children who were admitted to the paediatric ICU and paediatric wards at the Sardjito Hospital, Yogyakarta, Indonesia between December 2010 and February 2013. For each positive culture result, the type of isolated organism, time to positivity, and the number of positive culture sites were considered to classify the isolate as representing a true bacteraemia or contaminant. Results There were 1293 cultures obtained from blood and 308 (23.8%) were positive for bacterial growth. Fifty-three (4.1%) of the total cultures drawn fulfilled criteria for contaminants. The most common blood culture contaminants were coagulase-negative staphylococci. Conclusion Using standardized criteria, it is possible to implement a working method to identify true nosocomial infection from blood culture contaminant, and thus limit the effect of contaminated blood culture on irrational antibiotic use. true pathogen, contamination, blood culture, nosocomial infection, children, developing countries INTRODUCTION The development of bacteraemia has major significance for hospitalized children, increasing morbidity and the risk of mortality several-fold. Nosocomial infections are common in hospitalized children in developing countries but often go undiagnosed. Blood culture results are frequently used to direct antimicrobial therapy [1], but differentiating a true pathogen from a contaminant can be challenging. Blood cultures are frequently contaminated by skin flora inoculated into the blood culture medium at the time of blood collection. The rational use of antibiotics based on culture results would be helped by a standardized method to distinguish true pathogens from contaminants. This would also assist countries to have standardized surveillance systems for community- and hospital-acquired bacterial infections. This study aimed to assess the contamination rate of blood cultures using standardized criteria, and in doing so evaluate the feasibility of a method to distinguish between true bacteraemia and a contaminated blood culture. METHODS Setting and time The blood culture results from the children who were admitted to the paediatric intensive care unit (PICU) and paediatric wards (one infectious ward and one non-infectious ward) at the Dr Sardjito Hospital, Yogyakarta, Indonesia between 1 December 2010 and 28 February 2013 were analysed. Data collection Specimens were taken for bacterial culture when nosocomial infection was suspected. Where appropriate to the clinical situation, cultures were taken from blood specimens. Nosocomial bloodstream infections (BSIs) were defined using the US Centers for Disease Control and Prevention (CDC) criteria. All isolates of a pathogen cultured from blood collected >48 h after hospitalization were considered as nosocomial BSI when there were corresponding clinical symptoms of infection and there was no contamination. If the same organism was found on repeat blood cultures collected within 14 days, the isolates were counted as one infection episode. Culture-positive nosocomial BSI must meet at least one of the following criteria: (i) the patient had an organism cultured from one or more blood cultures unrelated to another site of infection; or (ii) the patient had at least either fever (>38.5 °C) or hypotension and positive laboratory results not related to another site of infection and common skin contaminant organisms [i.e. diphtheroids (Corynebacterium spp.), Bacillus (not Bacillusanthracis) spp., Propionibacterium spp., coagulase-negative staphylococci (including Staphylococcusepidermidis), viridans group streptococci, Aerococcus spp., Micrococcus spp.] on culture from two or more blood samples drawn on separate occasions; or (iii) patients aged  ≤1 year had at least one of the following signs or symptoms: fever (>38.5 °C), hypothermia (<36.5 °C), apnea and bradycardia, as well as positive laboratory results not related to another site of infection and common skin contaminant organisms [i.e. diphtheroids (Corynebacterium spp.), Bacillus (not B. anthracis) spp., Propionibacterium spp., coagulase-negative staphylococci (including S. epidermidis), viridans group streptococci, Aerococcus spp., Micrococcus spp.] on culture from two or more blood samples drawn on separate occasions [2]. We used standard culture techniques that had been validated using BACTEC® 9120 (BD Diagnostics, Sparks, MD, USA). Bacterial isolation and antibiotic susceptibility testing were performed according to Clinical Pathology standard procedure [3]. When obtaining blood cultures, the skin was cleaned using 70% isopropyl alcohol from the centre to the periphery of the needle insertion site after the vein was palpated. This was followed by cleaning with 2% of iodine tincture or povidone-iodine, and the site was left to dry. A non-touch method was used, meaning that when venipuncture site had been sterilized, the skin should not be touched. When the vein needed to be palpated, sterilization of skin over the vein was conducted. For blood cultures, 3–5 ml of blood was obtained and inoculated into a culture bottle. Before inoculating the culture bottles, the tops were disinfected with 70% alcohol. Blood culture bottles were processed in a semi-automated blood culture system. Assessment criteria for blood culture contaminants True pathogen was defined combining of blood culture plus clinical and laboratory indexes. These included positive blood culture (presence of bacteria) plus hypothermia or hyperthermia and leucocytosis or leucopenia or immature-to-total neutrophil ratio (IT ratio) > 0.2 or hypotension [4]. For each positive culture result, the type of isolated organism, time to positivity, and the number of positive culture sites were considered to determine if the isolate was a contaminant (Table 1). Table 1 Method for differentiation between true pathogen and contaminant [4] Detection of contaminated blood cultures True pathogen Potential contaminants Types of organism Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and other Enterobacteriaceae, P. aeruginosa, Candida albicans, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Bacteroides fragilis group and Cryptococcus neoformans Coagulase-negative staphylococci, Corynebacterium species, Bacillus species other than B. anthracis, Propionibacterium acnes, Propionibacterium species, Micrococcus species, viridians group streptococci, Aerococcus species, Diphtheroid species Time to culture positivity ≤5 days >5 days Number of positive culture sites When the same organism grows on multiple culture setsa When different organisms grows on the same culture set Clinical or laboratory parameters Hypothermia <36°C or hyperthermia ≥39°C, peripheral leukocyte < 4000/μl or > 20 000/μl, IT ratio >0.2, or hypotension Normothermia, peripheral leukocyte ≥4000/μl or ≤ 20 000/μl, IT ratio ≤0.2 or no hypotension Detection of contaminated blood cultures True pathogen Potential contaminants Types of organism Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and other Enterobacteriaceae, P. aeruginosa, Candida albicans, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Bacteroides fragilis group and Cryptococcus neoformans Coagulase-negative staphylococci, Corynebacterium species, Bacillus species other than B. anthracis, Propionibacterium acnes, Propionibacterium species, Micrococcus species, viridians group streptococci, Aerococcus species, Diphtheroid species Time to culture positivity ≤5 days >5 days Number of positive culture sites When the same organism grows on multiple culture setsa When different organisms grows on the same culture set Clinical or laboratory parameters Hypothermia <36°C or hyperthermia ≥39°C, peripheral leukocyte < 4000/μl or > 20 000/μl, IT ratio >0.2, or hypotension Normothermia, peripheral leukocyte ≥4000/μl or ≤ 20 000/μl, IT ratio ≤0.2 or no hypotension a This should be applied to potential contaminants such as coagulase-negative Staphylococcus. If we grew any true pathogen once, then that was considered sufficient. Table 1 Method for differentiation between true pathogen and contaminant [4] Detection of contaminated blood cultures True pathogen Potential contaminants Types of organism Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and other Enterobacteriaceae, P. aeruginosa, Candida albicans, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Bacteroides fragilis group and Cryptococcus neoformans Coagulase-negative staphylococci, Corynebacterium species, Bacillus species other than B. anthracis, Propionibacterium acnes, Propionibacterium species, Micrococcus species, viridians group streptococci, Aerococcus species, Diphtheroid species Time to culture positivity ≤5 days >5 days Number of positive culture sites When the same organism grows on multiple culture setsa When different organisms grows on the same culture set Clinical or laboratory parameters Hypothermia <36°C or hyperthermia ≥39°C, peripheral leukocyte < 4000/μl or > 20 000/μl, IT ratio >0.2, or hypotension Normothermia, peripheral leukocyte ≥4000/μl or ≤ 20 000/μl, IT ratio ≤0.2 or no hypotension Detection of contaminated blood cultures True pathogen Potential contaminants Types of organism Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli and other Enterobacteriaceae, P. aeruginosa, Candida albicans, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Bacteroides fragilis group and Cryptococcus neoformans Coagulase-negative staphylococci, Corynebacterium species, Bacillus species other than B. anthracis, Propionibacterium acnes, Propionibacterium species, Micrococcus species, viridians group streptococci, Aerococcus species, Diphtheroid species Time to culture positivity ≤5 days >5 days Number of positive culture sites When the same organism grows on multiple culture setsa When different organisms grows on the same culture set Clinical or laboratory parameters Hypothermia <36°C or hyperthermia ≥39°C, peripheral leukocyte < 4000/μl or > 20 000/μl, IT ratio >0.2, or hypotension Normothermia, peripheral leukocyte ≥4000/μl or ≤ 20 000/μl, IT ratio ≤0.2 or no hypotension a This should be applied to potential contaminants such as coagulase-negative Staphylococcus. If we grew any true pathogen once, then that was considered sufficient. The organisms that were considered as potential contaminants include coagulase-negative staphylococci, Corynebacterium species, Bacillus species other than B.anthracis, Propionibacterium acnes, Micrococcus species, viridians group streptococci, enterococci and Clostridium perfringens [4]. Time to culture positivity was defined as an interval from specimen collection and examination to a positive bacterial culture result. Cultures of potential contaminants that became positive after >5 days were considered as likely contaminants. We also considered as a contaminant different organisms growing on the same culture set. If we considered any potential contaminant, such as coagulase-negative Staphylococcus, then it was assumed that the same organism grows on multiple culture sets. However, if any true pathogen grew once, then that was considered sufficient. Outcome measure The proportion of contaminated blood culture results was defined as the culture isolates classified as contaminants divided by the number of all blood samples taken. Data analysis Data were analysed using STATA V.12.1 (StataCorp LP, Texas, USA). Contaminated blood culture results were presented as proportions. The χ2 statistic was used to analyse the results when comparing proportions. A probability value <0.05 was considered to denote statistical significance. RESULTS During the study period, there were 1293 cultures obtained from blood. In total, 308 cultures (23.8%) were positive for bacterial growth (Table 2). Using the standardized criteria, 53 (17.2% of all positive cultures and 4.1% of all blood samples) drawn were contaminants (Table 3). Table 2 Baseline characteristics of all admissions Characteristics n = 2646 (%) Age  ≤12 months 640 (24.2)  >12–60 months 736 (27.8)  >60–120 months 574 (21.7)  >120 months 696 (26.3) Male sex 1480 (55.9) Ward of origin  PICU 509 (19.2)  Infectious ward 916 (34.6)  Non-infectious ward 1221 (46.1) Developing nosocomial infection 400 (15.1) Nosocomial BSI 170 (6.4) Taking blood sample 1293 (48.9) Positive culture result 308 (23.8) Characteristics n = 2646 (%) Age  ≤12 months 640 (24.2)  >12–60 months 736 (27.8)  >60–120 months 574 (21.7)  >120 months 696 (26.3) Male sex 1480 (55.9) Ward of origin  PICU 509 (19.2)  Infectious ward 916 (34.6)  Non-infectious ward 1221 (46.1) Developing nosocomial infection 400 (15.1) Nosocomial BSI 170 (6.4) Taking blood sample 1293 (48.9) Positive culture result 308 (23.8) Table 2 Baseline characteristics of all admissions Characteristics n = 2646 (%) Age  ≤12 months 640 (24.2)  >12–60 months 736 (27.8)  >60–120 months 574 (21.7)  >120 months 696 (26.3) Male sex 1480 (55.9) Ward of origin  PICU 509 (19.2)  Infectious ward 916 (34.6)  Non-infectious ward 1221 (46.1) Developing nosocomial infection 400 (15.1) Nosocomial BSI 170 (6.4) Taking blood sample 1293 (48.9) Positive culture result 308 (23.8) Characteristics n = 2646 (%) Age  ≤12 months 640 (24.2)  >12–60 months 736 (27.8)  >60–120 months 574 (21.7)  >120 months 696 (26.3) Male sex 1480 (55.9) Ward of origin  PICU 509 (19.2)  Infectious ward 916 (34.6)  Non-infectious ward 1221 (46.1) Developing nosocomial infection 400 (15.1) Nosocomial BSI 170 (6.4) Taking blood sample 1293 (48.9) Positive culture result 308 (23.8) Table 3 Blood culture results by ward PICU (n) Infectious ward (n) Non-infectious ward (n) Total Number of cultures performed from blood 651 437 205 1293 Number of positive blood cultures (%) 181 (27.8) 95 (21.7) 32 (15.6) 308 (23.8) Contaminated blood culture (%) 24 (3.7) 22 (5) 7 (3.4) 53 (4.1) PICU (n) Infectious ward (n) Non-infectious ward (n) Total Number of cultures performed from blood 651 437 205 1293 Number of positive blood cultures (%) 181 (27.8) 95 (21.7) 32 (15.6) 308 (23.8) Contaminated blood culture (%) 24 (3.7) 22 (5) 7 (3.4) 53 (4.1) Table 3 Blood culture results by ward PICU (n) Infectious ward (n) Non-infectious ward (n) Total Number of cultures performed from blood 651 437 205 1293 Number of positive blood cultures (%) 181 (27.8) 95 (21.7) 32 (15.6) 308 (23.8) Contaminated blood culture (%) 24 (3.7) 22 (5) 7 (3.4) 53 (4.1) PICU (n) Infectious ward (n) Non-infectious ward (n) Total Number of cultures performed from blood 651 437 205 1293 Number of positive blood cultures (%) 181 (27.8) 95 (21.7) 32 (15.6) 308 (23.8) Contaminated blood culture (%) 24 (3.7) 22 (5) 7 (3.4) 53 (4.1) The proportion of blood culture contamination in the PICU was similar to the non-infectious wards of 3.7% (24 of 651) and 3.4% (7 of 205), respectively. In the infectious ward, the proportion of contamination was higher at 5% (22 of 437) (Table 3). The most common blood culture contaminants were coagulase-negative staphylococci followed by Streptococcus spp., Pseudomonasaeruginosa and other Pseudomonas spp. (Table 4). Table 4 Organisms yielded from the contaminated blood cultures Contaminant organisms n (%) Coagulase-negative staphylococci 48 (90.5) Streptococcus spp. 3 (5.7) Pseudomonas aeruginosa 1 (1.9) Pseudomonas spp. 1 (1.9) Total 53 Contaminant organisms n (%) Coagulase-negative staphylococci 48 (90.5) Streptococcus spp. 3 (5.7) Pseudomonas aeruginosa 1 (1.9) Pseudomonas spp. 1 (1.9) Total 53 Table 4 Organisms yielded from the contaminated blood cultures Contaminant organisms n (%) Coagulase-negative staphylococci 48 (90.5) Streptococcus spp. 3 (5.7) Pseudomonas aeruginosa 1 (1.9) Pseudomonas spp. 1 (1.9) Total 53 Contaminant organisms n (%) Coagulase-negative staphylococci 48 (90.5) Streptococcus spp. 3 (5.7) Pseudomonas aeruginosa 1 (1.9) Pseudomonas spp. 1 (1.9) Total 53 We showed the proportion of clinical and laboratory indicators in children with a contaminant or a true pathogen. These indicators included hypothermia <36 °C or hyperthermia ≥39 °C, peripheral leukocyte < 4000/µl or >20 000/µl, IT ratio  >0.2 or hypotension (Table 5). Table 5 The proportion of clinical or laboratory parameters in children with true bacteraemia and contamination Clinical or laboratory parameters True bacteraemia n = 170 (%) Contamination n = 53 (%) Hypothermia or hyperthermia 143 (83.6) 2 (3.8) Leukopenia (<4000) or leucocytosis (>20 000) 62 (36.3) 1 (1.9) IT ratio > 0.2 5 (2.9) 0 Hypotension 5 (2.9) 0 Clinical or laboratory parameters True bacteraemia n = 170 (%) Contamination n = 53 (%) Hypothermia or hyperthermia 143 (83.6) 2 (3.8) Leukopenia (<4000) or leucocytosis (>20 000) 62 (36.3) 1 (1.9) IT ratio > 0.2 5 (2.9) 0 Hypotension 5 (2.9) 0 Table 5 The proportion of clinical or laboratory parameters in children with true bacteraemia and contamination Clinical or laboratory parameters True bacteraemia n = 170 (%) Contamination n = 53 (%) Hypothermia or hyperthermia 143 (83.6) 2 (3.8) Leukopenia (<4000) or leucocytosis (>20 000) 62 (36.3) 1 (1.9) IT ratio > 0.2 5 (2.9) 0 Hypotension 5 (2.9) 0 Clinical or laboratory parameters True bacteraemia n = 170 (%) Contamination n = 53 (%) Hypothermia or hyperthermia 143 (83.6) 2 (3.8) Leukopenia (<4000) or leucocytosis (>20 000) 62 (36.3) 1 (1.9) IT ratio > 0.2 5 (2.9) 0 Hypotension 5 (2.9) 0 DISCUSSION False-positive contaminated culture results are a significant problem in clinical practice. Blood culture contaminants should be identified, as significant healthcare costs and effects on patient outcomes can occur from the over-use of antibiotics and extended hospital stays [5]. In this study, approximately a quarter of all blood cultures obtained were positive. Even though low-level bacteraemia is generally common in children [6], the positive rate in our study was high compared with a study in Taiwan, which had a positivity rate of 4.2% of all performed cultures [7]. This low positivity might be explained by low organism concentration because of smaller blood volumes collected from children [6]. Other possible explanations could be prior antibiotic treatment, the severity of disease, different patient populations, and different species and strain of organisms that lead to transient or intermittent bacteraemia [6, 8–10]. To increase the true positivity of culture results, the use of antibiotic–adsorbent resin may be added to the medium [11]. In the paediatric population, a smaller volume of blood is often sufficient compared with adults because the number of organisms per millilitre of blood is larger [9, 11]. However, an adequate amount of blood should be taken, depending on the patients’ body weight, which is 1–2 ml in neonates, 2–3 ml in infants, 3–5 ml in children and up to 10 ml in adolescents [9]. The proportion of contaminated blood cultures in this study, with the standardized definition we used, was acceptable. Previous studies recommended that the proportions of blood culture contamination should not exceed 3%; however, contamination rates reported in hospitals ranged from 0.6 to 6% [4, 12], and it is likely that in routine settings outside trial conditions, the contamination rates may be even higher. Our findings correspond with previous studies where the reported contamination rates were 3.4% [6, 7]. Coagulase-negative staphylococci were the most common contaminants in our study. This was similar to other studies where gram-positive bacteria were common, representing skin contaminants [13–15]. In 3.8% of cases, we identified gram-negative bacteria as contaminants based on our criteria. These patients were directly admitted from the community rather than also including patients who had spent some time in hospitals, as in our study. We included several standardized criteria to indicate a contaminant, and these criteria reflect the factors behind blood cultures becoming contaminated: when the yielded pathogen may be part of skin flora, or isolated after prolonged incubation or there is more than one bacteria isolated in the culture [4, 11–14]. Time required for the organism to grow is shorter in children with nosocomial BSI compared with children with contaminated blood cultures. This indicates a higher bacterial concentration in the blood among children with true BSI than those with contaminated cultures. A review conducted by Myllote and Tayara indicates that isolating the organism after 5 days incubation increases the probability of culture results being contaminated [16]. A study conducted in Taiwan also suggests that a 5-day incubation period is more efficient in identifying true pathogens and cost-effective in settings with limited resources [17]. Ideally, two or three sets of blood cultures should be taken within 24 h because this increases the yield of detecting a pathogen in the blood. This also increases the probability of detecting pathogens when there are low levels of bacteraemia. However, obtaining multiple blood cultures in a child is challenging, when the procurement technique is not easy and when healthcare resources are limited. Some high-yield studies of bacteraemia have been done with only a single blood sample collected [18].Weinstein et al. [14] indicated that the first blood culture detected 91.5% of all bacteraemia, and a second blood culture detected an additional 7.8%. Adequate skin disinfection reduces the probability of contaminated culture results, although around 20% of skin flora is not removed even after disinfecting [12]. Insufficient skin preparation leads to skin contaminants, such as coagulase-negative staphylococci in blood cultures [11]. Direct collection from a vein rather than an intravenous catheter also reduces contamination rates [13, 15, 19]. In our study, clinical indicators of infection or systemic inflammation are associated with true bacteraemia and fungaemia [14]. Because of this finding, clinical and laboratory markers should be included to distinguish blood culture positivity from contamination. In our study, only a single blood sample was collected in most patients to diagnose a nosocomial infection. However, in the paediatric setting, this may be appropriate, as taking blood more than once leads to additional costs, discomfort and time, and adds minimal value when the volume of blood culture is adequate [9]. CONCLUSIONS Differentiating contaminated blood cultures from true bacteraemia is essential to ensure the validity of nosocomial infection diagnosis. Our criteria are simple to apply and represent a valid workable algorithm for identifying true bacteraemia from blood culture contamination. To reduce contamination and improve the yield of true bacteraemia in children in settings with limited resources, blood samples should only be taken when bacterial infection is clinically suspected, the skin should be disinfected properly before taking blood samples and percutaneous collection from a vein rather than a venous catheter should be the standard method. Applying this method and these criteria for identifying true bacteraemia from contaminants would save significant healthcare costs and improve patient care. ACKNOWLEDGEMENTS The authors would like to thank the Infection Control team at the Dr Sardjito Hospital, Yogyakarta, Indonesia. FUNDING IKM was supported by an Australian Development Scholarship, AusAid for the duration of the study. The Centre for International Child Health was supported by the Knowledge Hubs for Health initiative of the Australian Government and is a WHO Collaborating Centre for Research and Training in Child and Neonatal Health. Ethics approval: The Ethics Committees of the Universitas Gadjah Mada (Application KE/FK/532/EC) and the University of Melbourne (Application #1033316) approved the study. References 1 Murni IK , Duke T , Kinney S , et al. Antibiotic resistance and mortality in children with nosocomial bloodstream infection in a teaching hospital in Indonesia . Southeast Asian J Trop Med Public Health 2016 ; 47 : 983 – 93 . 2 Horan TC , Andrus M , Dudeck MA. CDC/NHSN surveillance definition of healthcare–associated infection and criteria for specific types of infections in the acute care setting . Am J Infect Control 2008 ; 36 : 309 – 32 . Google Scholar CrossRef Search ADS PubMed 3 Clinical Laboratory and Standard Institute (CLSI) . Performance standards for antimicrobial susceptibility testing; twenty-first informational supplement . CLSI document M100-S21 , Wayne, PA: Clinical and Laboratory Standards Institute; 2011 , p. 31 (1). 4 Weinstein MP. Blood culture contamination: persisting problems and partial progress . J Clin Microbiol 2003 ; 41 : 2275 – 8 . Google Scholar CrossRef Search ADS PubMed 5 Murni IK , Duke T , Kinney S , et al. Reducing hospital-acquired infections and improving the rational use of antibiotics in a developing country: an effectiveness study . Arch Dis Child 2015 ; 100 : 454 – 9 . Google Scholar CrossRef Search ADS PubMed 6 Kellogg JA , Manzella JP , Bankert DA. Frequency of low-level bacteremia in children from birth to fifteen years of age . J Clin Microbiol 2000 ; 38 : 2181 – 5 . Google Scholar PubMed 7 Chiu YH , Chen TJ , Chen CT , et al. Positive blood cultures in pediatric emergency department patients: epidemiological and clinical characteristics . Acta Paediatr Taiwan 2005 ; 46 : 11 – 6 . Google Scholar PubMed 8 Bennett I , Beeson R. Bacteremia: a consideration of some experimental and clinical aspects . Yale J Biol Med 1954 ; 26 : 241. Google Scholar PubMed 9 Paisley JW , Lauer BA. Pediatric blood cultures . Clin Lab Med 1994 ; 14 : 17 – 30 . Google Scholar PubMed 10 Riedel S , Bourbeau P , Swartz B , et al. Timing of specimen collection for blood cultures from febrile patients with bacteremia . J Clin Microbiol 2008 ; 46 : 1381 – 5 . Google Scholar CrossRef Search ADS PubMed 11 Chandrasekar PH , Brown WJ. Clinical issues of blood cultures . Arch Intern Med 1994 ; 154 : 841 – 9 . Google Scholar CrossRef Search ADS PubMed 12 Hall KK , Lyman JA. Updated review of blood culture contamination . Clin Microbiol Rev 2006 ; 19 : 788 – 802 . Google Scholar CrossRef Search ADS PubMed 13 Bates DW , Goldman L , Lee TH. Contaminant blood cultures and resource utilization: the true consequences of false-positive results . Jama 1991 ; 265 : 365 – 9 . Google Scholar CrossRef Search ADS PubMed 14 Weinstein MP , Towns ML , Quartey SM , et al. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults . Clin Infect Dis 1997 ; 24 : 584 – 602 . Google Scholar CrossRef Search ADS PubMed 15 Ramsook C , Childers K , Cron SG , et al. Comparison of blood-culture contamination rates in a pediatric emergency room: newly inserted intravenous catheters versus venipuncture . Infect Control Hosp Epidemiol 2000 ; 21 : 649 – 51 . Google Scholar CrossRef Search ADS PubMed 16 Mylotte JM , Tayara A. Blood cultures: clinical aspects and controversies . Eur J Clin Microbiol Infect Dis 2000 ; 19 : 157 – 63 . Google Scholar CrossRef Search ADS PubMed 17 Huang AH , Yan JJ , Wu JJ. Comparison of five days versus seven days of incubation for detection of positive blood cultures by the Bactec 9240 system . Eur J Clin Microbiol Infect Dis 1998 ; 17 : 637 – 41 . Google Scholar CrossRef Search ADS PubMed 18 Schifman RB , Bachner P , Howanitz PJ. Blood culture quality improvement: a College of American Pathologists Q-Probes Study involving 909 institutions and 289572 blood culture sets . Arch Pathol Lab Med 1996 ; 120 : 999 – 1002 . Google Scholar PubMed 19 McBryde ES , Tilse M , McCormack J. Comparison of contamination rates of catheter-drawn and peripheral blood cultures . J Hosp Infect 2005 ; 60 : 118 – 21 . Google Scholar CrossRef Search ADS PubMed © The Author [2017]. 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Journal of Tropical PediatricsOxford University Press

Published: Nov 21, 2017

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