Blood Culture Contamination Rates after Skin Antisepsis with Chlorhexidine Gluconate versus Povidone-Iodine in a Pediatric Emergency Department

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1 infection control and hospital epidemiology february 2010, vol. 31, no. 2 original article Blood Culture Contamination Rates after Skin Antisepsis with Chlorhexidine Gluconate versus Povidone-Iodine in a Pediatric Emergency Department Lauren Marlowe, MD; Rakesh D. Mistry, MD, MS; Susan Coffin, MD, MPH; Kateri H. Leckerman, MS; Karin L. McGowan, PhD; Dingwei Dai, PhD; Louis M. Bell, MD; Theoklis Zaoutis, MD, MSCE objective. To determine blood culture contamination rates after skin antisepsis with chlorhexidine, compared with povidone-iodine. design. Retrospective, quasi-experimental study. setting. Emergency department of a tertiary care children s hospital. patients. Children aged 2 36 months with peripheral blood culture results from February 2004 to June Control patients were children younger than 2 months with peripheral blood culture results. methods. Blood culture contamination rates were compared using segmented regression analysis of time-series data among 3 patient groups: (1) patients aged 2 36 months during the 26-month preintervention period, in which 10% povidone-iodine was used for skin antisepsis before blood culture; (2) patients aged 2 36 months during the 26-month postintervention period, in which 3% chlorhexidine gluconate was used; and (3) patients younger than 2 months not exposed to the chlorhexidine intervention (ie, the control group). results. Results from 11,595 eligible blood cultures were reviewed (4,942 from the preintervention group, 4,274 from the postintervention group, and 2,379 from the control group). For children aged 2 36 months, the blood culture contamination rate decreased from to contaminated cultures per 1,000 cultures ( P!.05) after implementation of chlorhexidine. This decrease of 7.62 contaminated cultures per 1,000 cultures (95% confidence interval, to 15.16) represented a 30% relative decrease from the preintervention period and was sustained over the entire postintervention period. No change in contamination rate was observed in the control group ( P p.337). conclusion. Skin antisepsis with chlorhexidine significantly reduces the blood culture contamination rate among young children, as compared with povidone-iodine. Infect Control Hosp Epidemiol 2010; 31: Blood culture is an important diagnostic test in the emergency evaluation of young children who may have bacteremia. However, bacteremia is rare and is the source of fever for only 0.4% 1.9% of young children. 1,2 In this population, cultures are more likely to grow skin contaminants than true pathogens. 1,3,4 The overall blood culture contamination rate across all populations is 0.9% 9.1%. 5,6 Patients who have contaminants isolated from blood culture experience significant clinical consequences, including the need for follow-up care and repeat blood cultures, and increased healthcare costs. 7,8 Because skin organisms represent the most common blood culture contaminants, the appropriate use of skin antiseptics is among the most important methods to minimize contamination. While the use of aqueous povidone-iodine remains the standard of care, many advantages of chlorhexidine over povidone-iodine have been described. Chlorhexidine achieves a greater reduction in skin flora, has residual activity for hours, and requires less drying time 9 ; therefore, it is believed to have improved ease of use. For adults, chlorhexidine is more effective than povidone-iodine in reducing central line associated bloodstream infections, 10 and the Centers for Disease Control and Prevention (CDC) recommends the use of From the Divisions of General Pediatrics (L.M., L.M.B.), Emergency Medicine (R.D.M.), and Infectious Diseases (S.C., K.H.L., L.M.B., T.Z.), the Department of Pathology and Laboratory Medicine (K.L.M.), and the Center for Pediatric Clinical Effectiveness (S.C., D.D., T.Z.), Children s Hospital of Philadelphia, and the Department of Pediatrics (R.D.M., S.C., L.M.B., T.Z.) and the Center for Clinical Epidemiology and Biostatistics (S.C., T.Z.), University of Pennsylvania School of Medicine (L.M.), Philadelphia, Pennsylvania. Received May 18, 2009; accepted August 11, 2009; electronically published December 21, by The Society for Healthcare Epidemiology of America. All rights reserved X/2010/ $ DOI: /650201

2 172 infection control and hospital epidemiology february 2010, vol. 31, no. 2 chlorhexidine for central venous catheter placement for both adults and children. 11 Adverse reactions to chlorhexidine are rare. 12,13 Several adult studies have shown that alcoholic chlorhexidine achieves lower blood culture contamination rates than does povidone-iodine Although these studies have shown the superiority of chlorhexidine, there are few data on the use of this antiseptic as the standard of care in the pediatric emergency department. The aim of this study was to compare the blood culture contamination rates before and after a change in skin antisepsis practice, from 10% povidone-iodine to 3% chlorhexidine gluconate, among children aged 2 36 months in a pediatric emergency department. methods We performed a retrospective, quasi-experimental study with a nonequivalent control group. The institutional review board of the Children s Hospital of Philadelphia approved this study. Patients were identified by a computerized search of hospital laboratory records. Patients 2 36 months of age were included, and single peripheral blood culture samples (1 aerobic bottle each) were obtained from them as part of their routine evaluation in the emergency department of this large urban tertiary care children s hospital during the period from February 1, 2004, through June 30, Patients with indwelling catheters at the time of blood culture were excluded because of the potential misclassification of centrally obtained culture samples as peripherally obtained culture samples. Blood culture samples were obtained by registered nurses, phlebotomists, or physicians, either by dedicated venipuncture or in conjunction with intravenous catheter insertion, in accordance with a standard protocol. A venipuncture site was identified, hand hygiene was performed, and the insertion site was scrubbed with the appropriate antiseptic agent before the needle was inserted. A 1 4 ml sample of blood was aspirated via sterile tubing with gentle negative pressure into a syringe and was directly inoculated into a single highly enriched sterile pediatric blood culture bottle (Pedi-Bac T; Organon Teknika). During the 26-month preintervention phase (February 1, 2004 March 31, 2006), a 10% povidoneiodine swab (Betadine; Purdue Pharma) was applied to the venipuncture site and was allowed to dry. With evidence of the increased efficacy and greater ease of chlorhexidine use, the Infection Prevention and Control Committee at the Children s Hospital of Philadelphia instituted a practice change effective April 1, 2006, that requires the use of 3.15% (wt/vol) chlorhexidine gluconate in 70% isopropanol (Chlorascrub; Professional Disposables International) for skin antisepsis before blood culture for children 2 months or older. During the 26-month postintervention phase (May 1, 2006 June 30, 2008), a chlorhexidine gluconate swab was applied to the venipuncture site and was allowed to dry. Other than the change in the antiseptic agent, no other changes were made in blood culture collection practices or in laboratory techniques during the study period. Data from the implementation phase (April 1 30, 2006) were excluded from the analysis because of the concern about a delayed uptake of the practice change by staff members. The nonequivalent control group included all children younger than 2 months for whom blood culture was performed as part of routine evaluation in the same emergency department during the study period. Because of incomplete safety data for neonates exposed to greater than 1% chlorhexidine and theoretical concern for percutaneous absorption, 17 children younger than 2 months were not exposed to the chlorhexidine intervention. Povidone-iodine was used for skin antisepsis in this group throughout the study. Blood culture results were collected from hospital laboratory records and were categorized as no growth, true positive, or contaminant. Isolates classified as contaminants were coagulase-negative staphylococci (CoNS), viridans group and nonhemolytic streptococci, Corynebacteria, micrococci, and nonpathogenic Bacillus and Neisseria species. 18 Gemella, Lactococcus, and Lactobacillus, which commonly colonize the oropharynx and frequently contaminate the skin via oral secretions, were also classified as contaminants because these organisms rarely cause disease. Cultures growing 2 or more organisms were considered contaminated if at least 1 organism was one of the contaminants listed above. All other isolated organisms were considered true pathogens. Emergency department and inpatient records of all patient cultures growing at least 1 contaminant were abstracted by a single investigator (L.M.) for review of the patient s clinical disease. CoNS was considered a true pathogen only in specific clinical circumstances: (1) ventriculoperitoneal shunt associated bacteremia, (2) comorbid Staphylococcus epidermidis sternotomy wound infection, (3) respiratory failure secondary to S. epidermidis sepsis, (4) comorbid CoNS urosepsis, and (5) compromised immune system. Data Analysis Blood culture contamination rates (ie, number of contaminated cultures per 1,000 cultures) were aggregated into monthly intervals. We used interrupted time-series analysis to estimate the effect of the chlorhexidine intervention on the contamination rate, adjusting for preintervention trends and other autocorrelation, including seasonal effects. 19,20 Segmented regression models were constructed by means of the Proc Autoreg procedure in the SAS software, release 9.13 (SAS Institute). The models contained 2 segments, 1 for the preintervention phase and 1 for the postintervention phase. Each segment was described by 2 independent variables. One variable represented the level of the segment, and the second represented the trend. A change in the level variable represented an immediate change at the beginning of the period;

3 blood culture contamination rates 173 figure 1. Time series of blood culture contamination rates, defined as the number of contaminated blood cultures per 1,000 cultures, by month. Fitted trend lines show predicted values from the segmented regression analysis. a change in the trend variable represented a change over time during the period. Nonsignificant level and trend variables ( P 1.05) were excluded from the models by stepwise backward elimination. Autocorrelation was assessed by means of the Durbin-Watson statistic. 21 The adequacy of each model was tested by standard methods of residual analysis. 22 results A total of 11,832 single blood cultures were obtained during the study period, including 4,942 during the preintervention period, 4,274 during the postintervention period, and 2,379 from the control group. Of these, 17 cultures were excluded because of the presence of an indwelling catheter identified during chart review, and an additional 220 cultures were excluded because they were obtained during the implementation phase (April 2006). This left 11,595 blood cultures for our study. During the preintervention phase, the median age was 12.1 months (interquartile range, months), and patients were 54.1% male. During the postintervention phase, the median age was 12.9 months (interquartile range, months), and patients were 56.3% male. During the preintervention phase, there were 193 positive cultures. Of these, 122 (63.2%) grew contaminant organisms. The proportion of all blood cultures obtained during this period that grew contaminant organisms was 122 (2.5%) of 4,942 (95% confidence interval [CI], 2.1% 2.9%). During the postintervention phase, there were 125 positive cultures. Of these, 72 (57.6%) grew contaminant organisms. The proportion of all blood cultures that grew contaminant organisms after the practice change to chlorhexidine decreased to 72 (1.7%) of 4,274 (95% CI, 1.3% 2.1%). When the preintervention period trends were controlled for, an immediate reduction in the blood culture contamination rate, from to contaminated cultures per 1,000 cultures ( P!.05), was observed after the chlorhexidine intervention (Figure 1). This decrease of 7.62 contaminated cultures per 1,000 blood cultures (95% CI, to 0.781) represented a relative decrease of 30% from the month before the intervention and was sustained over the entire 26-month postintervention period. In the control group, no significant change in the contamination rate was observed ( P p.337). During both phases, the most common organisms isolated from contaminated cultures were CoNS, viridans group Streptococcus, and Micrococcus (Table 1). Two or more organisms were isolated from 17.1% of contaminated cultures. Of the 143 cultures growing CoNS, 5 (3.5%) were classified as true positives after review of the patient s clinical disease. The rate of true-positive bacteremia was 1.4% (71 of 4,942 cultures) and 1.3% (54 of 4,274 cultures) during the pre- and

4 174 infection control and hospital epidemiology february 2010, vol. 31, no. 2 table 1. Type of organism Frequency of Microorganisms Recovered from Contaminated Blood Cultures No. (%) of organisms Preintervention ( n p 173) Postintervention ( n p 96) Coagulase-negative staphylococci 88 (50.9) 55 (57.3) Viridans or nonhemolytic streptococci 33 (19.1) 17 (17.7) Micrococcus species 14 (8.1) 6 (6.3) Corynebacterium species 7 (4.0) 2 (2.1) Bacillus species, nonpathogenic 4 (2.3) 1 (1.0) Neisseria species, nonpathogenic 2 (1.2) 1 (1.0) Multiple a 21 (12.1) 12 (12.5) Gemella, Lactococcus, orlactobacillus species 4 (2.3) 2 (2.1) a Cultures growing x2 organisms with x1 contaminant and classified as contaminated cultures. During the preintervention phase, 122 contaminated cultures yielded 173 organisms. During the postintervention phase, 72 contaminated cultures yielded 96 organisms. postintervention periods, respectively. Among the true-positive blood cultures, the most common pathogens were Streptococcus pneumoniae (24.0%); Staphylococcus aureus, including methicillin-resistant S. aureus (13.6%); Escherichia coli (8.8%); Streptococcus pyogenes (8.0%); Salmonella species (6.4%); Klebsiella species (6.4%); Enterobacter species (6.4%); and Enterococcus species. (4.8%). Four cultures, each growing 2 pathogenic organisms and no contaminants, were classified as true positives. discussion To our knowledge, we report the largest study of blood culture contamination rates to date in children aged 2 36 months, from whom the majority of emergent pediatric blood culture samples are obtained. We found that antisepsis with chlorhexidine before blood culture significantly reduces the rate of blood culture contamination, compared with antisepsis with povidone-iodine. In this population, the incidence of bacteremia has decreased since the introduction of the conjugated S. pneumoniae and Haemophilus influenza type b vaccines, 2-4,23 and skin contaminants are isolated more frequently than are true pathogens. Therefore, reducing blood culture contamination in this age group is important to be able to best evaluate patients at risk for bacteremia and to reduce unnecessary testing and treatment. In our study, the majority (57.6% 63.2%) of blood cultures with positive results grew contaminants rather than true pathogens, irrespective of the type of skin antisepsis used, consistent with other recent studies of pediatric occult bacteremia. 2-4 The identity of organisms recovered from blood cultures in our study is also consistent with other pediatric studies, with CoNS being the most common contaminant. 2,5,6 To our knowledge, this is the first study comparing use of povidone-iodine with use of chlorhexidine for skin antisepsis in the 2 36-month age group. Although we have studied a different population and setting, the results of our study are consistent with existing infection control literature. In adult acute care settings, 0.5% 2% alcoholic chlorhexidine is superior to aqueous povidone-iodine for blood culture antisepsis in 2 randomized control trials 14,15 and a retrospective study. 16 Additionally, alcohol-based iodine tincture is superior to povidine-iodine in reducing blood culture contamination. 24,25 Two small adult studies compared iodine tincture with alcoholic chlorhexidine for skin antisepsis and found no statistically significant difference between the blood culture contamination rates with either product. 26,27 These studies conclude that, given equivalent antisepsis with chlorhexidine and with iodine tincture, chlorhexidine may be preferable because of its greater ease of use and the avoidance of common adverse effects associated with systemic absorption of iodine. Adverse reactions to chlorhexidine, including contact dermatitis, photosensitivity, and anaphylaxis, are rare. 12,13 Our study has many important strengths. First, the quasiexperimental design is the strongest study design to demonstrate causal links between infectious disease interventions and outcomes when a randomized control trial is not practical. 28 Second, to our knowledge, this study is the first to use time-series analysis to evaluate the effect of an intervention on blood culture contamination rates. Time-series analysis is the strongest quasi-experimental method for analyzing the effect of an intervention over time in nonrandomized settings. 20 Moreover, segmented regression is a robust method for modeling time-series data to assess chance and to control for secular trends. Additionally, the use of a nonequivalent control group allowed us to account for secular temporal changes, regression to the mean, and confounding events unrelated to the intervention in question. The stable contamination rate in the control group throughout the study period strengthens our conclusion that the observed decrease in contamination in the intervention group was due to the chlorhexidine intervention and not to secular trends. Our findings should be considered in light of certain limitations. The first is the retrospective nature of this study.

5 blood culture contamination rates 175 However, we believe that our microbiology records are accurate and are unlikely to have missed positive blood cultures. Second, factors other than skin antisepsis have been shown to reduce blood culture contamination rates, including using dedicated venipuncture for blood culture, 6,29 using a specialized team of phlebotomists, 30 obtaining culture samples preferentially from the antecubital fossa, 29 and changing needles before inoculating culture bottles. 31,32 Although our study was unable to control for these variables, there were no other known practice changes during the study period. Finally, a higher concentration of chlorhexidine gluconate (3.15%) was used in our study than in previous studies (0.5% 2%). It is unclear whether the concentration of chlorhexidine affects its antiseptic properties or its toxicity profile. Further study is warranted. We conclude that the blood culture contamination rate is significantly lower after skin antisepsis with chlorhexidine than after skin antisepsis with povidone-iodine. Consideration should be given to the use of chlorhexidine for skin antisepsis before blood culture in young children. Reducing the rates of blood culture contamination will decrease the need for repeat blood cultures, the need for repeat evaluations, and overall healthcare costs. acknowledgments Financial support. National Institutes of Health (grant 1K23 AI to T.Z.). Potential conflicts of interest. All authors report no conflicts of interest relevant to this article. Address reprint requests to Theoklis Zaoutis, MD, MSCE, Children s Hospital of Philadelphia, 34th and Civic Center Boulevard, CHOP North, Room 1527, Philadelphia, PA (zaoutis@ .chop.edu). Presented in part: Pediatric Academic Societies Annual Meeting; Baltimore, Maryland; May 2 5, 2009 (poster ). references 1. 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