Validation of Active Surveillance Testing for Clostridium difficile Colonization Using the cobas Cdiff Test.

Clostridium difficile infection (CDI) is not declining in the United States. Nucleic acid amplification tests (NAAT) are used as part of active surveillance testing programs to prevent health care-associated infection. The objective of this study was to validate the cobas Cdiff Test on the cobas 4800 System (cobas) within a four-hospital system using prospectively collected perirectal swabs from asymptomatic patients at admission and during monthly intensive care unit (ICU) screening in an infection control CDI reduction program. Performance of the cobas was compared to that of toxigenic culture. Each positive cobas sample and the next following negative patient swab were cultured. The study design gave 273 samples processed by both cobas (137 positive and 136 negative) and culture (one negative swab was not cultured). Discrepant analysis was performed using a second NAAT, the Xpert C. difficile Epi test (Xpert). This strategy was compared to a medical record review for antibiotic receipt that would inhibit growth of C. difficile in colonic stool. None of the cobas-negative samples were culture positive. The cobas positive predictive value was 75.2% (95% confidence interval [CI], 66.9% to 82%) and positive percent agreement was 100% (95% CI, 96.0% to 100%). Overall agreement between cobas and direct toxigenic culture was 87.6% (95% CI, 83.1% to 91%). For the cobas-positive/culture-negative (discrepant) samples, 7 Xpert-positive samples were from patients receiving inhibitory antimicrobials; only 4 of 23 Xpert-negative samples received these agents (P = 0.00006). Our results support use of the cobas as a reliable assay for an active surveillance testing program to detect asymptomatic carriers of toxigenic C. difficile.

Prospective observational study on central line-associated bloodstream infections and central venous catheter occlusions using a negative displacement connector with an alcohol disinfecting cap.

BACKGROUND: Major complications of central venous catheter (CVC) use include bloodstream infection and occlusion. We performed a prospective, observational study to determine the rate of central line-associated bloodstream infection (CLABSI) and CVC occlusion using a negative displacement connector with an alcohol disinfecting cap. METHODS: Patients were followed from the time of CVC insertion through 2 days after removal, at the time of hospital discharge if there was no documentation of removal, or 90 days after the insertion of the CVC if it was not removed. CLABSI was defined using National Healthcare Safety Network criteria. Data for evidence of lumen occlusions were extracted from the electronic health record. Direct observations were performed to assess adherence to hospital policy regarding CVC insertion practice. RESULTS: A total of 2,512 catheters from 2,264 patients were enrolled for this study. There were 21 CLABSIs (0.84%; 95% confidence interval [CI], 0.48%-1.19%; 0.62 per 1,000 line days) and 378 occlusions (15.05%; 95% CI, 13.65%-16.45%; 11.23 per 1,000 line days). Eighty-five direct observations demonstrated insertion protocol adherence in 881 of 925 (95.24%; 95% CI, 93.87%-96.61%) measured criteria. CONCLUSIONS: Lines placed following a standardized protocol using a negative displacement connector with an alcohol cap have low rates of infection compared with historically published findings. We also established that the occlusion rate is >15-fold the CLABSI rate.

Reduction of methicillin-resistant Staphylococcus aureus infection in long-term care is possible while maintaining patient socialization: A prospective randomized clinical trial.

BACKGROUND: Antibiotic resistance is a challenge in long-term care facilities (LTCFs). The objective of this study was to demonstrate that a novel, minimally invasive program not interfering with activities of daily living or socialization could lower methicillin-resistant Staphylococcus aureus (MRSA) disease. METHODS: This was a prospective, cluster-randomized, nonblinded trial initiated at 3 LTCFs. During year 1, units were stratified by type of care and randomized to intervention or control. In year 2, all units were converted to intervention consisting of universal decolonization using intranasal mupirocin and a chlorhexidine bath performed twice (2 decolonization-bathing cycles 1 month apart) at the start of the intervention period. Subsequently, after initial decolonization, all admissions were screened on site using real-time polymerase chain reaction, and those MRSA positive were decolonized, but not isolated. Units received annual instruction on hand hygiene. Enhanced bleach wipe cleaning of flat surfaces was done every 4 months. RESULTS: There were 16,773 tests performed. The MRSA infection rate decreased 65% between baseline (44 infections during 365,809 patient days) and year 2 (12 infections during 287,847 patient days; P <.001); a significant reduction was observed at each of the LTCFs (P <.03). CONCLUSIONS: On-site MRSA surveillance with targeted decolonization resulted in a significant decrease in clinical MRSA infection among LTCF residents.

Nonimpact of Decolonization as an Adjunctive Measure to Contact Precautions for the Control of Methicillin-Resistant Staphylococcus aureus Transmission in Acute Care.

This was an observational study comparing methicillin-resistant Staphylococcus aureus (MRSA) transmission with no decolonization of medical patients to required decolonization of all MRSA carriers during two consecutive periods: baseline with no decolonization of medical patients (16 months) and universal MRSA carrier decolonization (13 months). The setting was a one-hospital, 156-bed facility with 9,200 annual admissions. Regression models were used to compare rates of MRSA acquisition. The chi-square test was used to compare event frequencies. We used rates of MRSA clinical disease as an outcome monitor of the program. Analysis was done on 15,666 patients who had admission and discharge tests; 27.9% of inpatient days were occupied by a MRSA-positive patient (colonized patient-days) who received decolonization while hospitalized during the baseline period (this 27.9% represented those who had planned surgery) compared to 76.0% during the intervention period (P < 0.0001). The rate of MRSA transmission was 97 events (1.0%) for 9,415 admissions (2.0 transmission events/1,000 patient-days) during baseline and was 87 (1.4%) for 6,251 admissions (2.7 transmission events/1,000 patient-days) during intervention (P = 0.06; rate ratio, 0.74; 95% confidence interval [CI], 0.55 to 1.00). The MRSA nosocomial clinical disease rate was 5.9 infections/10,000 patient-days in the baseline period and was 7.2 infections/10,000 patient-days for the intervention period (rate ratio, 0.82; 95% CI, 0.46 to 1.45; P = 0.49). Decolonization of MRSA patients does not add benefit when contact precautions are used for patients colonized with MRSA in acute (hospital) care.

Evaluation of multiple real-time PCR tests on nasal samples in a large MRSA surveillance program.

OBJECTIVES: We evaluated the LightCycler MRSA Advanced Test (Roche Molecular Diagnostics, Pleasanton, CA), the BD MAX MRSA assay (Becton Dickinson, Franklin Lakes, NJ), and the Xpert MRSA assay (Cepheid, Sunnyvale, CA) on nasal samples using the same population. METHODS: Admission and discharge nasal swabs were collected from inpatients using a double-headed swab. One swab was plated onto CHROMagar MRSA (CMA; Becton Dickinson, Sparks, MD) and then broken off into tryptic soy broth (TSB) for enrichment. TSB was incubated for 24 hours and then plated to CMA. The molecular tests were performed on the second swab. We analyzed the cost benefit of testing to evaluate what parameters affect hospital resources. RESULTS: A total of 27,647 specimens were enrolled. The sensitivity/specificity was 98.3%/98.9% for the LightCycler MRSA Advanced Test and 95.7%/98.8% for the Xpert MRSA assay, but the difference was not significant. The positive predictive value was 86.7% for the LightCycler MRSA Advanced Test, 82.7% for the Xpert MRSA assay (P > .1), and 72.2% and for the BD MAX MRSA test (P < .001 compared with the LightCycler MRSA Advanced Test). All three assays were cost-effective, with the LightCycler MRSA Advanced Test having the highest economic return. CONCLUSIONS: Our results suggest that the performance of the three commercial assays is similar. When assessing economic cost benefit of methicillin-resistant Staphylococcus aureus screening, the two measures with the most impact are the cost of the test and the specificity of the assay results.

Impact of Detection, Education, Research and Decolonization without Isolation in Long-term care (DERAIL) on methicillin-resistant Staphylococcus aureus colonization and transmission at 3 long-term care facilities.

We tested infection prevention strategies to limit exposure of long-term care facility residents to drug-resistant pathogens in a prospective, cluster randomized 2-year trial involving 3 long-term care facilities (LTCFs) using methicillin-resistant Staphylococcus aureus (MRSA) as a model. We hypothesized that nasal MRSA surveillance using rapid quantitative polymerase chain reaction and decolonization of carriers would successfully lower overall MRSA colonization. In year 1, randomly assigned intervention units received decolonization with nasal mupirocin and chlorhexidine bathing and enhanced environmental cleaning with bleach every 4 months. Newly admitted MRSA nares-positive residents were decolonized on admission. Control units were screened but not decolonized. All units received periodic bleach environmental cleaning and instruction on hand hygiene. In year 2, all units followed intervention protocol caused by failure of the cluster randomized approach to sufficiently segregate patients. MRSA colonization was monitored using point prevalence testing every 4-6 months. Colonization status at admission and discharge was performed 1 quarter per year to determine acquisition. Fisher exact test was used for statistical analysis. Baseline MRSA colonization rate was 16.64%. In year 1, the colonization rate of intervention units was 11.61% (P = .028) and 17.85% in control units (P = .613) compared with baseline. Intervention unit rate difference compared with the controls was significant (P = .001). In year 2, the colonization rate was 10.55% (P < .001) compared with baseline. The transmission rates were 1.66% and 3.52% in years 1 and 2, respectively (P = .034). The planned interventions of screening and decolonization were successful at lowering MRSA colonization.

Performance of the Cepheid Xpert® SA Nasal Complete PCR assay compared to culture for detection of methicillin-sensitive and methicillin-resistant Staphylococcus aureus colonization.

Sensitivity, specificity, positive predictive value, and negative predictive value for the Cepheid Xpert® SA Nasal Complete detection (N = 971) of methicillin-sensitive Staphylococcus aureus was 86.5%, 98.5%, 94.6%, and 96.1%; detection of methicillin-resistant S. aureus was 89.3%, 97.9%, 79.8%, and 99.0%, respectively. Our results show that testing on long-term care facility patients had lower sensitivity and specificity compared to acute care patient results.

Laboratory testing for Clostridium difficile infection: light at the end of the tunnel.

Clostridium difficile infection (CDI) is changing as evidenced by increasing virulence, rising incidence, unresponsiveness to metronidazole therapy, and worse outcomes. Thus, it is critical that CDI diagnosis be accurate so ongoing epidemiology, disease prevention, and treatment remain satisfactory. We tested 10 diagnostic assays, including 1 commercial real-time polymerase chain reaction (qPCR) test for the laboratory detection of toxigenic C difficile on 1,000 stool samples. Sensitive culture for toxigenic C difficile using 2 types of media with broth enrichment defined the reference standard. For the study, 1,000 tests were performed on samples from 919 patients. Of the samples, 146 contained evidence for toxigenic C difficile and represented the true-positive results. Only the US Food and Drug Administration-cleared qPCR assay (Becton Dickinson, Franklin Lakes, NJ) and 1 glutamate dehydrogenase test (TechLab, Blacksburg, VA) were not statistically inferior to culture in sensitivity. The common enzyme immunoassay tests all had sensitivity values less than 50%. Clinical laboratory professionals need to seriously consider their diagnostic testing and use the assays that perform best for the detection of CDI.

Performance of the BD GeneOhm MRSA achromopeptidase assay for real-time PCR detection of methicillin-resistant Staphylococcus aureus in nasal specimens.

We evaluated the BD GeneOhm MRSA achromopeptidase (ACP) assay, which incorporates a new specimen preparation approach. A total of 1,216 leftover nasal samples were tested; using culture as the gold standard, the sensitivity and specificity were 92% and 94.6%, respectively. The new lysis method provides good sensitivity and simplifies specimen preparation.

Multicenter evaluation of the LightCycler methicillin-resistant Staphylococcus aureus (MRSA) advanced test as a rapid method for detection of MRSA in nasal surveillance swabs.

The rate of methicillin-resistant Staphylococcus aureus (MRSA) infection continues to rise in many health care settings. Rapid detection of MRSA colonization followed by appropriate isolation can reduce transmission and infection. We compared the performance of the new Roche LightCycler MRSA advanced test to that of the BD GeneOhm MRSA test and culture. Double-headed swabs were used to collect anterior nasal specimens from each subject. For both tests, DNA was extracted and real-time PCR was performed according to manufacturer's instructions. For culture, one swab of the pair was plated directly to CHROMagar MRSA. The swab paired with the BD GeneOhm MRSA test was also placed into an enrichment broth and then plated to CHROMagar MRSA. Colonies resembling staphylococci were confirmed as S. aureus by standard methods. Discrepant specimens had further testing with additional attempts to grow MRSA as well as sample amplicon sequencing. Agreement between results for the two swabs was 99.3% for those with valid results. A total of 1,402 specimens were tested using direct culture detection of MRSA as the gold standard; 187 were culture positive for MRSA. The LightCycler MRSA advanced test had relative sensitivity and specificity of 95.2% (95% confidence interval [CI]: 91.1% to 97.8%) and 96.4% (95% CI: 95.2% to 97.4%), respectively. The BD GeneOhm assay had relative sensitivity and specificity of 95.7% (95% CI: 91.7% to 98.1%) and 91.7% (95% CI: 90.0% to 93.2%), respectively. Following discrepancy analysis, the relative sensitivities of the LightCycler MRSA advanced test and the BD GeneOhm MRSA assay were 92.2 and 93.2%, respectively; relative specificities were 98.9 and 94.2%, respectively. Specificity was significantly better (P<0.001) with the LightCycler MRSA advanced test. The sensitivity of direct culture was 80.4%. The LightCycler MRSA advanced test is a useful tool for sensitive and rapid detection of MRSA nasal colonization.