Sensitivity of Surveillance Testing for Multidrug-Resistant Gram-Negative Bacteria in the

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1 JCM Accepts, published online ahead of print on 20 August 2014 J. Clin. Microbiol. doi: /jcm Copyright 2014, American Society for Microbiology. All Rights Reserved. 1 2 Sensitivity of Surveillance Testing for Multidrug-Resistant Gram-Negative Bacteria in the Intensive Care Unit Jessica P. Ridgway, MD 1# ; Lance R. Peterson, MD 2,3,4,5 ; Richard B. Thomson, Jr., PhD 2,5 ; Becky A. Miller, MD 3,4 ; Marc-Oliver Wright, MT(ASCP), MS, CIC 4 ; Donna M. Schora, MT(ASCP) 2 ; Ari Robicsek, MD 3,4,5,6 1. University of Chicago, Department of Medicine, Chicago, IL, USA 2. NorthShore University HealthSystem, Department of Pathology, Evanston, IL, USA 3. NorthShore University HealthSystem, Department of Medicine, Evanston, IL, USA 4. NorthShore University HealthSystem, Department of Infection Control, Evanston, IL, USA 5. The University of Chicago Pritzker School of Medicine, Chicago, IL, USA 6. NorthShore University HealthSystem, Department of Clinical Analytics, Evanston, IL, USA Running Head: MDR GNB Surveillance Test Sensitivity # Address correspondence to Jessica P. Ridgway, jessica.ridgway@uchospitals.edu. 1

2 Abstract: We tested ICU patients for colonization with multidrug-resistant Gram-negative bacilli (MDR GNB) and compared results with concurrent clinical cultures. The sensitivity of the surveillance test for detecting MDR GNB was 58.8% (95% CI, %). Among 133 patients with positive surveillance tests, 61% had no prior clinical culture with MDR GNB. 29 Downloaded from on October 4, 2018 by guest 2

3 There is little evidence regarding the utility of inpatient surveillance for multidrug-resistant Gram-negative bacilli (MDR GNB) as it pertains to Infection Control. This study aimed to: 1) determine the sensitivity of surveillance testing for MDR GNB in the intensive care unit (ICU); 2) identify the factors (e.g. antibiotic use) that affect the sensitivity of surveillance testing for MDR GNB; and 3) determine the undetected ratio: i.e. the proportion of patients with a positive surveillance test for MDR GNB who did not have a prior positive clinical culture for MDR GNB (1). This is a measure of how often the surveillance test provides new information regarding a patient s colonization status. This study took place in the adult ICUs of four affiliated hospitals from August 3, 2009 through July 31, Once a month, ICU patients were tested for MDR GNB-colonization with three swabs taken from the upper respiratory tract (throat or endotracheal tube), axillae, and perirectal area. Samples were collected with double-headed culture swabs with Liquid Amies media (BD, Sparks, MD). The swabs were then collectively inoculated onto a single vancomycin, amphotericin B, ceftazidime, and clindamycin (VACC) agar (Remel, Lenexa, KS). After 24 hours of inoculation, colonies resembling GNB were subcultured on MacConkey agar. Colonies then underwent identification via the Vitek 2 System (Durham, NC). Susceptibility testing was performed using Kirby Bauer disk diffusion method. An organism was defined as MDR if it was susceptible to at most two tested antibiotic classes. Pseudomonas aeruginosa and Acinetobacter baumanii isolates were also considered MDR if they were resistant to meropenem. Patients identified as colonized with MDR GNB were placed in contact isolation to prevent transmission. Some patients in whom surveillance testing was done had incidentally undergone clinical cultures (i.e. cultures obtained owing to a clinical indication) at a facility within our healthcare 3

4 network around the time of the surveillance test, where those clinical cultures had been positive for MDR GNR. It is these patients in whom the test sensitivity was determined. The sensitivity of the surveillance test was defined as the proportion of all patients known to be colonized with MDR GNR (denominator) in whom surveillance testing demonstrated these organisms (numerator). Patients were known to be colonized (denominator population) when a clinical culture was positive for MDR GNR in the period from 30 days before to 30 days after the surveillance test. The undetected ratio was determined as follows: among patients who had a positive surveillance test, the proportion that had no previous corresponding positive clinical culture for MDR GNB was calculated. Over the study period, 3,197 surveillance tests were performed on 2,164 patients. In 102 instances, a patient who had a positive clinical culture for MDR GNB had undergone surveillance testing within 30 days of the clinical culture. The sensitivity of the surveillance test for detecting any MDR GNB (not necessarily the same organism that grew in clinical culture) was 58.8% (60/102), (95% CI, %). The sensitivity of the surveillance test for detecting the same species of MDR GNB that grew in clinical culture was 43.1% (44/102) (95% CI, %). Table 1 describes surveillance test sensitivity based on the organism that grew in clinical culture. Receipt of at least one dose of a fluoroquinolone was associated with a significant decrease in the sensitivity of the surveillance test (49.0% vs. 68.6%, p=0.04), but receipt of at least one dose of piperacillin/tazobactam was associated with increased sensitivity (67.6% vs. 41.2%, p=0.01) (Table 2). Other classes of antibiotics were not significantly associated with test sensitivity. 4

5 Over the four-year study period, 6.1% (133/2,164) of patients had a positive surveillance test. Of these patients, 50% (67/133) had no positive clinical culture for MDR GNB. 11% (14/133) only had a positive clinical culture for MDR GNB after the surveillance test was performed. Thus, the undetected ratio was 61% (81/133). This study demonstrates that routine surveillance testing for MDR GNB in the ICU is fairly sensitive: nearly 60% of surveillance tests performed within 30 days of a positive clinical culture for MDR GNB were positive. The true sensitivity of the surveillance test is likely even higher. In the study, the sensitivity was determined by using a gold standard of a positive clinical culture within 30 days of the surveillance test; ideally, if the information were available, we would have used a positive clinical culture collected the same day as the surveillance test. Some patients may not have been actually colonized or infected with the MDR GNB at the time of the test, meaning that the false negative rate might be inflated. If so, then the calculated sensitivity would be an underestimate. Thus, the results in this study represent a floor estimate of sensitivity. In addition to being fairly sensitive, surveillance testing for MDR GNB in the ICU revealed a relatively high undetected ratio: more than 60% had no previous positive clinical culture for MDR GNB. This study has limitations. Patients may be colonized with MDR GNB at body sites other than those sampled by the surveillance test. Furthermore, MDR GNB were identified phenotypically. This precludes definite conclusions about surveillance test sensitivity for organisms with specific mechanisms of resistance (e.g. specific carbapenemases) (2). A final limitation is that our data are based on culture testing. Others have reported that using PCRbased surveillance for MDR GNB enhances the sensitivity of surveillance testing (2, 3). 5

6 This work suggests that routine surveillance has a fair sensitivity for identifying patients harboring MDR GNB. Given that the majority of colonized patients would have gone undetected without this testing, our findings suggest that such a surveillance method may be a beneficial component of a MDR GNB infection control program in the ICU. Further work is needed to evaluate the impact of MDR GNB detection on transmission and the cost effectiveness of such a surveillance strategy (4, 5). Acknowledgments We thank the NorthShore infection preventionists and ICU staff for collecting surveillance cultures which provided the data for this study. RT reports receiving research grants from GlaxoSmithKline, and Nanosphere, consulting for GlaxoSmithKline and Copan, receiving lecture honoraria from BD GeneOhm and Nanosphere, and receiving a project grant from Jones Group. LP reports receiving research grants from BD Diagnostics, Cepheid, MicroPhage, Nanogen, Nanosphere, NIAID, Roche, Synetzza, 3M, AHRQ, Wyeth (Pfizer), and the Washington Square Health Foundation for work in molecular diagnostics and consulting for BD Diagnostics, Cepheid, Nanosphere, Wyeth (Pfizer), and Roche. JR, BM, MW, DS, and AR report no potential conflicts of interest relevant to this article. 6

7 References 1. Harris AD, McGregor JC, Furuno JP What infection control interventions should be undertaken to control multidrug-resistant gramnegative bacteria? Clin Infect Dis 43 Suppl 2:S Singh K, Mangold KA, Wyant K, Schora DM, Voss B, Kaul KL, Hayden MK, Chundi V, Peterson LR Rectal screening for Klebsiella pneumoniae carbapenemases: comparison of real-time PCR and culture using two selective screening agar plates. J Clin Microbiol 50: Mangold KA, Voss BL, Singh K, Thomson RB, Jr., Schora DM, Peterson LR, Kaul KL Multiple broad-spectrum Beta-lactamase targets for comprehensive surveillance. J Clin Microbiol 51: Gardam MA, Burrows LL, Kus JV, Brunton J, Low DE, Conly JM, Humar A Is surveillance for multidrug-resistant enterobacteriaceae an effective infection control strategy in the absence of an outbreak? J Infect Dis 186: Troche G, Joly LM, Guibert M, Zazzo JF Detection and treatment of antibiotic-resistant bacterial carriage in a surgical intensive care unit: a 6- year prospective survey. Infect Control Hosp Epidemiol 26: Downloaded from on October 4, 2018 by guest 7

8 Table 1: Sensitivity of surveillance test by multidrug-resistant organism* Organism Proportion detected Sensitivity 95% CI Acinetobacter baumanii 4/8 50.0% % Enterobacter species 4/5 80.0% % Escherichia coli 11/ % % Klebsiella species Proteus mirabilis Pseudomonas aeruginosa *Among organisms with 5 or more positive clinical cultures 8/ % % 1/9 11.1% % 16/ % % p=0.08 Downloaded from on October 4, 2018 by guest 8

9 Table 2: Association between antibiotic exposure and sensitivity of the surveillance test Antibiotic Sensitivity among patients who received antibiotic Sensitivity among patients who did not receive antibiotic P value Aminoglycosides 16/22 (72.7%) 44/80 (55.0%) 0.13 Anti-pseudomonal cephalosporins 16/29 (55.2%) 44/73 (60.3%) 0.63 Carbapenems 18/34 (52.9%) 42/68 (61.8%) 0.39 Fluoroquinolones 25/51 (49.0%) 35/51 (68.6%) 0.04 Piperacillin/tazobactam 46/68 (67.6%) 14/34 (41.2%) 0.01 Tigecycline 6/11 (54.5%) 54/91 (59.3%) 0.76 Trimethoprim/sulfamethoxazole 5/8 (62.5%) 55/94 (58.5%) 0.82 Downloaded from on October 4, 2018 by guest 9