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● In the abscence of order entry restrictions, negative C. difficile tests were often repeated within 7 days ● Repeating a negative C. difficile test within 7 days had a low yield (3.3%) for detection of C. difficile infection ● There were no significant differences in the positivity rate from each unit compared to the overall positivity rate ● Restrictions on repeat negative C. difficile testing may have to be modified for specific populations (e.g. HSCT patients) Conclusions Conclusions ● Cohen SH, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults. Infect Control Hosp Epidemiol 2010; 31:431-455 ● Luo, RF, Banaei, N. Is Repeat PCR Needed for Diagnosis of Clostridium difficile Infection? J Clin Micro, Oct. 2010, p. 3738–3741 ● Khanna, S, et al. An Evaluation of Repeat Stool Testing for Clostridium difficile Infection by Polymerase Chain Reaction. J Clin Gastroenterol. 2012; 46:846-9 ● Baron, EJ., et al. A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases. Clin Infect Dis. 2013; 57(4): e22-e121 References References During the study period, 1075 patients had a negative test which was followed by a repeat test in 7 days. In 35 patients, the repeat C. difficile tests turned positive within 7 days (3.3%). Figure 1 shows the distribution of the 35 patients who had NP conversion on days 1 through 7. Figure 2 shows the distribution of the 1040 patients with 2 negative tests in the 7-day period. The highest number of repeat tests occurred on day 2, and steadily declined thereafter. Table 2 shows the positivity rate of repeat testing within the 7-day period at specified testing locations/ medical units. All testing pairs (NP and NN) were broken down into initial- and repeat- test locations. There were no significant differences between unit specific positivity rate and the overall positivity rate. The positivity rate of the HSCT unit, however, was significantly different than that of the ICUs (4.49% vs. 1.15%, P=0.05). The presence of the NAP1/BI/027 “Epi” strain was tested in 219 C. difficile-positive specimens, of which 61 (27.9%) were “Epi”-positive. In the 35 patients with NP conversions within 7 days, 12 were tested for the “Epi” strain, and 3 (25%) were positive. On review of the documentation from a subset of these 35 patients, it was difficult to retrospectively ascertain the severity of the patient’s diarrhea or stool output from the nursing and physician documentation. Furthermore, it was also difficult to determine the clinical progress of these patients from the documentation. All patients in this group received active anti-C. difficile therapy of oral vancomycin, metronidazole, fidaxomicin, or a combination of medications. Our study’s overall 7-day NP conversion rate of 3.3 % is similar to that by Luo and Banaei (1.1% in 7-day period), and Khanna et al (2.7% in 7-day period). Our data supports the general recommendation that a negative C. difficile PCR test should not be repeated within 7 days. However, special consideration may be needed in patients from the hematopoietic stem cell transplantation unit due to the complexity of their underlying disease. * Long Island Veterans State Home - a 350 bed SNF serving honorably discharged veterans and their spouses. § ICUs: Medical ICU 0.17% (0.5/294); Surgical ICU 0.64% (1/156); Cardiothoracic ICU 1.93% (2/103.5); Burn ICU - 0% (0/6.5) ‡ Others: Emergency Room 8.11% (3/37); Outpatient Units 1.89% (0.5/26.5); Pediatric Units 0% (0/1.5); Psychiatry 0% (0/1); Veterans Nursing Home 12.50% (2/16) Results and Discussion Results and Discussion C. difficile tests (age ≥18 y) ● n= 8048 PCR tests ● 4683 patients ● Avg age 63 years ● 49.3% male Single test performed ● n = 3142 test ● C. diffile Rate = 15.6% (491/3142) Multiple tests performed ● n = 4906 ● 1541 patients ● Avg. 3.2 tests per patient Table 1: Locations of 8048 Tests Unit HSCT Cardio ER ICUs Gen Med Ob/Gyn Outpt Peds Psych Gen Surg Vet SNF* No. 483 435 817 1277 3227 17 549 57 8 789 389 % 6.0% 5.4% 10.2% 15.9% 40.1% 0.2% 6.8% 0.7% 0.1% 9.8% 4.8% Table 2: Positivity Rate of Repeat Tests Location HSCT Cardio Gen Med Gen Surg Others ‡ ICUs§ Total NP 7 3.5 12 3.5 5.5 3.5 35 NN 149 63 359.5 90.5 76.5 301.5 1040 Positivity Rate 7/156 (4.5%) 3/66.5 (5.3%) 12/371.5 (3.2%) 3.5/94 (3.7%) 5.5/82 (6.7%) 3.5/305 (1.2%) 3.26/1075 (3.3%) Figure 2: NN within 7 days (1040 test pairs) 0 50 100 150 200 7-day 6-day 5-day 4-day 3-day 2-day 1-day 0 1 2 3 4 5 6 7 8 7-day 6-day 5-day 4-day 3-day 2-day 1-day Figure 1: NP within 7 days (35 test pairs) Freq 2 7 7 4 6 2 7 Day 1 2 3 4 5 6 7 %* 5.7 20% 20% 11.4% 17.1% 5.7% 20% Cum %* 5.7% 25.7% 45.7% 57.1% 74.2% 79.9% 100% * no. are rounded Day 1 2 3 4 5 6 7 Freq 99 196 183 183 138 127 114 %* 9.5% 18.9% 17.6% 17.6% 13.3% 12.2% 11.0% Cum %* 9.5% 28.4% 46.0% 63.6% 76.9% 89.1% 100% Day 1 2 3 4 5 6 7 * no. are rounded Utility of Repeating a Clostridium difficile PCR Test within 7 Days of a Negative Result Utility of Repeating a Clostridium difficile PCR Test within 7 Days of a Negative Result Guo Jun Huang, MD † , Rekha Sivadas, MD † , Silvia Spitzer, PhD ‡ , Eric Spitzer, MD, PhD ¶ † Department of Medicine, ‡ Molecular Genetics Laboratory, and ¶ Department of Clinical Microbiology Stony Brook University Medical Center, Stony Brook, NY Guo Jun Huang, MD † , Rekha Sivadas, MD † , Silvia Spitzer, PhD ‡ , Eric Spitzer, MD, PhD ¶ † Department of Medicine, ‡ Molecular Genetics Laboratory, and ¶ Department of Clinical Microbiology Stony Brook University Medical Center, Stony Brook, NY 101 Nicolls Rd, T15-080 Stony Brook, NY 11794-8153 T 631-444-3490 F 631-444-7518 [email protected] Methods Methods Stony Brook University Hospital is a 603-bed hospital in Long Island, NY, with multiple subspecialty units including a 16-bed (2.65%) hematopoietic stem cell transplant (HSCT) unit. We used the Cepheid® Xpert C. difficile PCR test which has a sensitivity of 93.5% and a specificity of 94.0%. All specimens sent for C. difficile testing from 12/31/2010 to 12/31/2012 were reviewed. We collected demographic data including age, sex, order location, medical service, admission date, discharge date, specimen collection date, and C. difficile result. During the last 4 months of the study period, we used the Xpert C. difficile/Epi PCR test that incorporates markers for the NAP1/BI/027 epidemic strain. We identified 8489 PCR tests in this period. 441 tests were excluded in patient’s age < 18 years, yielding 8048 tests. The average age of the patients was 63 years, SD 18. Table 1 shows the distribution of clinical units where the tests were ordered. Microsoft Excel 2010 was used to analyze the data collected, using logical statements. Descriptive statistics was used to analyze the data. 3142 patients had a solitary test. There were 4906 tests done on 1541 patients, from 2192 admissions. For patients with more than 1 test, we calculated the interval between tests and the total number of tests per patient. We identified patients who had a repeat test within 7 days, and categorized them as either negative to positive (NP) conversion or negative to negative (NN) conversion. The positivity rate” of repeating testing was calculated using the formula: (NP)/[(NP)+(NN)]. To account for any difference in initial- and the repeat test- locations, we took the mean of the number of test from the initial- and repeat test- locations. Outcomes were rounded up, and the Fisher exact test was used to compare the positivity rates. We further identified 35 patients with NP within 7 days and reviewed a subset of their charts. Repeat Clostridium difficile testing is discouraged by the 2010 SHEA-IDSA Clinical guidelines due to its limited clinical value. However, that position is based on results from non-PCR data. Two published studies evaluating repeat testing of negative PCR results showed a 3.2% subsequent positive test in one study and 2.5% subsequent positive test in the second study within the 14-day period. The rates of having a subsequent positive result were decreased to 2.7% and 1.1%, respectively, for these 2 studies within a 7-day period. Despite the high sensitivity and specificity of C. difficile PCR tests, repeat testing is ordered on many patients. The aim of this study was to evaluate how often repeat C. difficile PCR testing was done in our hospital system, and if repeat testing was warranted in certain clinical situations. Introduction Introduction Abstract Abstract Nucleic acid amplification tests (e.g. PCR) for toxigenic Clostridium difficile are much more sensitive than immunoassays; however, there are limited data on whether performing PCR on a second specimen following an initial negative test increases detection of C. difficile. Since switching to a C. difficile PCR test, we have permitted repeat testing >24 hrs. after a negative specimen, or >7 days after a positive. Previous studies suggest that repeating a negative test within 7 days has a low yield. We performed a retrospective review to determine how often a negative C. difficile result was followed by a positive within 7 days and whether there were distinctive clinical features associated with conversions. All Clostridium difficile PCR tests performed at Stony Brook University Hospital during 2011-2012 were reviewed. Samples were tested with the Cepheid® Xpert C. difficile test from Jan 2011 to Aug 2012 and the Xpert C. difficile/Epi test from Sep to Dec 2012. An Excel spreadsheet was used to identify repeat specimens and calculate time intervals. 8048 Clostridium difficile tests were performed on patients ≥ 18 years old. 3142 patients had a single test and 1542 patients had ≥ 2 tests (mean 3.2). Among patients who had a single C. difficile test, 491 (15.6%) had a positive result. A negative specimen was repeated within 7 days in 1075 cases; 35 (3.3%) of these repeats converted to positive; the median repeat interval is 4 days for both negative-to-negative and negative-to-positive. The majority of the conversions occurred in bone marrow transplant and oncology patients (n=11)* or patients on other medical services (n=17).* Chart review did not identify a unique clinical patern. 3/12 of negative-to-positive conversions tested with the C. difficile/Epi assay were positive for the Epi component (NAP1/BI/027). Repeating a negative Clostridium difficile test within 7 days identified a small percentage of infected patients. Restrictions on test ordering may need to be tailored to specific populations. * Table 2 shows updated location specific counts instead of service specific counts.
