Dose-ranging study to assess the application of intranasal 2% mupirocin calcium ointment to eradicate Staphylococcus aureus nasal colonization.

BACKGROUND: Mupirocin nasal ointment may be prescribed for decolonization prior to surgical procedures, especially for carriers of methicillin-resistant Staphylococcus aureus (MRSA). The approved regimen for decolonization of S. aureus from the anterior nares is twice daily for 5 d (10 doses). We performed a two-center, randomized, open-label study to compare the utility of six and 10 doses for decolonization of S. aureus. METHODS: Patients expecting to undergo surgery were screened for S. aureus nasal carriage approximately three weeks prior to the procedure. Those found to be positive were offered enrollment in the study. In the first arm (n=41), patients were randomized to receive 2, 3, or 5 d (six or 10 doses) of treatment prior to their operation. Their anterior nares were swabbed for culture and S. aureus polymerase chain reaction (PCR) during the decolonization therapy period as well as for four weeks after surgery. In the second arm (n=60), all patients were given 5 d (10 doses) of nasal mupirocin treatment, and the patient's anterior nares were swabbed for culture and S. aureus PCR for four weeks after surgery. Data from six of the patients were excluded from analysis because of failure to submit swabs after operation. All S. aureus isolates were tested for susceptibility to mupirocin and the presence of the mecA gene to detect MRSA. RESULTS: In Arm 1, 16 patients received 10 doses of mupirocin, 18 received six doses (twice daily for 3 d), and 7 received six doses (thrice daily for 2 d). In the second arm, all patients received 10 doses of mupirocin (twice a day for 5 d). Overall, 89.5% patients who received 10 doses of mupirocin remained decolonized for at least four weeks after surgery versus 68.0% of patients who received six doses (p=0.016). There was no difference between arms 1 and 2 for those given mupirocin twice daily for 5 d. CONCLUSION: The ten-dose regimen is superior to any six-dose regimen for de-colonizing S. aureus from the anterior nares of patients and for maintaining the decolonized state for at least four weeks after therapy.

Electronic surveillance for infectious disease trend analysis following a quality improvement intervention.

OBJECTIVE: Interventions for reducing methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated disease require outcome assessment; this is typically done by manual chart review to determine infection, which can be labor intensive. The purpose of this study was to validate electronic tools for MRSA healthcare-associated infection (HAI) trending that can replace manual medical record review. DESIGN AND SETTING: This was an observational study comparing manual medical record review with 3 electronic methods: raw culture data from the laboratory information system (LIS) in use by our healthcare organization, LIS data combined with admission-discharge-transfer (ADT) data to determine which cultures were healthcare associated (LIS + ADT), and the CareFusion MedMined Nosocomial Infection Marker (NIM). Each method was used for the same 7-year period from August 2003 through July 2010. PATIENTS: The data set was from a 3-hospital organization covering 342,492 admissions. RESULTS: Correlation coefficients for raw LIS, LIS + ADT, and NIM were 0.976, 0.957, and 0.953, respectively, when assessed on an annual basis. Quarterly performance for disease trending was also good, with R(2) values exceeding 0.7 for all methods. CONCLUSIONS: The electronic tools accurately identified trends in MRSA HAI incidence density when all infections were combined as quarterly or annual data; the performance is excellent when annual assessment is done. These electronic surveillance systems can significantly reduce (93% [in-house-developed program] to more than 99.9999% [commercially available systems]) the personnel resources needed to monitor the impact of a disease control program.

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.

Real-time detection of blaKPC in clinical samples and surveillance specimens.

A real-time PCR assay was developed targeting the bla(KPC) responsible for Klebsiella pneumoniae carbapenemase (KPC)-mediated carbapenem resistance and was validated for testing colonies or enrichment broth cultures. The assay accurately detects KPC-containing strains with high analytical specificity and sensitivity.

Significant impact of terminal room cleaning with bleach on reducing nosocomial Clostridium difficile.

BACKGROUND: We were alerted to increased rates of Clostridium difficile-positive tests at all 3 hospitals in our health care system by MedMined Data Mining Surveillance Service, CareFusion (San Diego, CA). In response, an intervention of terminal room cleaning with dilute bleach was instituted to decrease the amount of C difficile environmental spore contamination from patients with C difficile infection (CDI). METHODS: The intervention consisted of replacing quaternary ammonium compound as a room cleaning agent with dilute bleach to disinfect rooms of patients with CDI upon discharge. All surfaces, floor to ceiling were wiped with dilute bleach applied with towels to thoroughly wet the surfaces. Daily room cleaning remained unchanged. Patients remained on C difficile contact isolation precautions until discharge. To determine the effectiveness of this program, rates of nosocomial CDI for all 3 hospitals were determined using the MedMined Virtual Surveillance Interface for 10 months prior to and 2 years after the cleaning intervention. Statistical significance was determined using Poisson regression analysis. RESULTS: There was a 48% reduction in the prevalence density of C difficile after the bleaching intervention (95% confidence interval: 36%-58%, P < .0001). CONCLUSION: The implementation of a thorough, all-surface terminal bleach cleaning program in the rooms of patients with CDI has made a sustained, significant impact on reducing the rate of nosocomial CDI in our health care system.

Management of a multidrug-resistant Acinetobacter baumannii outbreak in an intensive care unit using novel environmental disinfection: a 38-month report.

BACKGROUND: Between June 1, 2004, and March 14, 2005, 16 patients in the surgical/medical intensive care unit (ICU) were infected and another 2 were colonized with multidrug-resistant (MDR) Acinetobacter baumannii. We describe the systematic investigation initiated to discover an environmental reservoir and a novel measure taken to terminate the outbreak. METHODS: Cultures were taken from moist areas in the ICU, including sink traps, sink and counter surfaces, drains, and faucets. Strains were characterized using restriction endonuclease analysis. A weekly full drainpipe chase cleansing protocol with sodium hypochlorite (bleach) solution for all 24 ICU and waiting room area sinks connected by common plumbing was initiated in March 2005. RESULTS: Eleven of 16 infected patients (69%) had a clonal MDR strain, 1 patient (6%) was infected with an unrelated strain, and in 4 patients (25%) strains were not available for typing. The reservoir for the A baumannii clone was detected in a sink trap within one of the ICU patient rooms that likely represented contamination of the entire horizontal drainage system. The bleaching protocol initiated in March 2005 successfully decontaminated the reservoir and eliminated the MDR A baumannii infections. CONCLUSION: A systematic search for an environmental reservoir followed by decontamination significantly reduced (P < .01) the incidence of MDR A baumannii infection.

Implementation of a universal admission surveillance and decolonization program for methicillin-resistant staphylococcus aureus (MRSA) reduces the number of MRSA and total number of S. aureus isolates reported by the clinical laboratory.

Our three-hospital system began active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization, with decolonization of positive patients, on all admissions starting 1 August 2005. A question not previously addressed is whether reduction of the incidence of MRSA disease would lower the total number of S. aureus clinical isolates recovered by the microbiology laboratory that are reported to health care providers. The decreases in the numbers of MRSA and total S. aureus clinical isolates for each year after August 2005 were highly statistically significant compared to the numbers in each of the prior 3 years (P < 0.0001).

Chromogenic media vs real-time PCR for nasal surveillance of methicillin-resistant Staphylococcus aureus: impact on detection of MRSA-positive persons.

Surveillance for methicillin-resistant Staphylococcus aureus (MRSA) colonization can be an important element for infection control programs when managing a multidrug-resistant pathogen such as MRSA. The sensitivity and speed of laboratory testing affects the proportion of appropriate isolation days captured, which determines the success or failure of a MRSA control program. Chromogenic culture, CHROMagar MRSA (BBL, Becton Dickinson, Sparks, MD) and MRSASelect (Bio-Rad, Hercules, CA), with and without broth enrichment and real-time polymerase chain reaction (PCR; BD GeneOhm MRSA, BD Diagnostics, San Diego, CA), were compared and found to have a wide range of sensitivities (78.5%-98.2%), specificities (91.6%-100.0%), and turnaround times (2-72 hours). Real-time PCR provided the most rapid results and demonstrated the highest sensitivity followed by broth-enriched culture and then direct plating for MRSA detection in nasal swabs. There was no substantial difference in the labor required for any of the 3 approaches.

Optimization of a laboratory-developed test utilizing roche analyte-specific reagents for detection of Staphylococcus aureus, methicillin-resistant S. aureus, and vancomycin-resistant Enterococcus species.

Nasal and perianal swab specimens were tested for detection of Staphylococcus aureus and vancomycin-resistant Enterococcus species (VRE) using a laboratory-developed real-time PCR test and microbiological cultures. The real-time PCR and culture results for S. aureus were similar. PCR had adequate sensitivity, but culture was more specific for the detection of VRE.

Universal surveillance for methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals.

BACKGROUND: The effect of large-scale expanded surveillance for methicillin-resistant Staphylococcus aureus (MRSA) on health care-associated MRSA disease is not known. OBJECTIVE: To examine the effect of 2 expanded surveillance interventions on MRSA disease. DESIGN: Observational study comparing rates of MRSA clinical disease during and after hospital admission in 3 consecutive periods: baseline (12 months), MRSA surveillance for all admissions to the intensive care unit (ICU) (12 months), and universal MRSA surveillance for all hospital admissions (21 months). SETTING: A 3-hospital, 850-bed organization with approximately 40,000 annual admissions. INTERVENTION: Polymerase chain reaction-based nasal surveillance for MRSA followed by topical decolonization therapy and contact isolation of patients who tested positive for MRSA. MEASUREMENTS: Poisson and segmented regression models were used to compare prevalence density of hospital-associated clinical MRSA disease (bloodstream, respiratory, urinary tract, and surgical site) in each period. Rates of bloodstream disease with methicillin-susceptible S. aureus were used as a control. RESULTS: The prevalence density of aggregate hospital-associated MRSA disease (all body sites) per 10,000 patient-days at baseline, during ICU surveillance, and during universal surveillance was 8.9 (95% CI, 7.6 to 10.4), 7.4 (CI, 6.1 to 9.0; P = 0.15 compared with baseline), and 3.9 (CI, 3.2 to 4.7; P < 0.001 compared with baseline and ICU surveillance), respectively. During universal surveillance, the prevalence density of MRSA infection at each body site had a statistically significant decrease compared with baseline. The methicillin-susceptible S. aureus bacteremia rate did not statistically significantly change during the 3 periods. In a segmented regression model, the aggregate hospital-associated MRSA disease prevalence density changed by -36.2% (CI, -65.4% to 9.8%; P = 0.17) from baseline to ICU surveillance and by -69.6% (CI, -89.2% to -19.6%]; P = 0.03) from baseline to universal surveillance. During universal surveillance, the MRSA disease rate decreased during hospitalization and in the 30 days after discharge; no further reduction occurred thereafter. Surveillance with clinical cultures would have identified 17.8% of actual MRSA patient-days, and ICU-based surveillance with polymerase chain reaction would have identified 33.3%. LIMITATION: The findings rely on observational data. CONCLUSION: The introduction of universal admission surveillance for MRSA was associated with a large reduction in MRSA disease during admission and 30 days after discharge.

Staphylococcus aureus nasal decolonization in joint replacement surgery reduces infection.

UNLABELLED: Surgical site infections (SSIs) with Staphylococcus aureus are a recognized adverse event of hip and knee replacements. We evaluated the impact of a program to detect S. aureus nasal carriers before surgery with preoperative decolonization (using mupirocin twice daily for 5 days prior to surgery) of carriers. Nasal swab samples were obtained from patients prior to surgery from 8/1/2003 through 2/28/2005. Samples were tested using real-time PCR technology to detect S. aureus. The group that developed S. aureus SSI was compared to a combined concurrent and historical control for one year following the operation. S. aureus caused 71% of SSIs in the combined control groups. Of the 1495 surgical candidates evaluated, 912 (61.0%) were screened for S. aureus; 223 of those screened (24.5%) were positive and then decolonized with mupirocin. Among the 223 positive and decolonized patients, three (1.3%) developed a SSI. Among the 689 screen-negative patients, four (0.6%) developed SSIs for an overall rate of 0.77%. Among the 583 control patients who were not screened or decolonized, 10 (1.7%) developed S. aureus SSIs. SSIs from other organisms were 0.44% and 0.69%, respectively. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Detection of toxigenic Clostridium difficile in stool samples by real-time polymerase chain reaction for the diagnosis of C. difficile-associated diarrhea.

BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) is the major cause of health care-associated infectious diarrhea. Current laboratory testing lacks a single assay that is sensitive, specific, and rapid. The purpose of this work was to design and validate a sensitive and specific real-time polymerase chain reaction (PCR) diagnostic test for CDAD. METHODS: This observational validation study of a new real-time PCR assay occurred from July 2004 through April 2006 and involved the testing of 1368 stool samples. As the final validation portion of the investigation, 350 inpatients were prospectively interviewed for clinical findings for 365 episodes of diarrheal illness. Test results and clinical criteria were used to assess the performance of 4 assays. RESULTS: Using clinical criteria requiring at least 3 loose stools in 1 day as part of the reference standard for a positive test result supporting CDAD, the sensitivity, specificity, and positive and negative predictive values were 73.3%, 97.6%, 73.3%, and 97.6%, respectively, for enzyme immunoassay; 93.3%, 97.4%, 75.7%, and 99.4%, respectively, for real-time PCR; 76.7%, 97.1%, 69.7%, and 97.9%, respectively, for cell culture cytotoxin assay; and 100.0%, 95.9%, 68.2%, and 100.0%, respectively, for anaerobic culture (for toxigenic C. difficile strains). The real-time PCR and anaerobic culture assays were significantly more sensitive than the enzyme immunoassay (P<.01 to P<.05). CONCLUSIONS: With an assay turnaround time of <4 h, real-time PCR is a more sensitive and equally rapid test, compared with enzyme immunoassay, and is a feasible laboratory option to replace enzyme immunoassay for toxigenic C. difficile detection in clinical practice, as well as for use during the development of new therapeutic agents.

Performance of the BD GeneOhm methicillin-resistant Staphylococcus aureus test before and during high-volume clinical use.

We evaluated the use of the BD GeneOhm MRSA real-time PCR assay (BD Diagnostics, San Diego, CA) for the detection of nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA). The initial evaluation consisted of 403 paired nasal swabs and was done using the specimen preparation provided with the kit and an in-house lysis method that was specifically developed to accommodate large-volume testing using a minimal amount of personnel time. One swab was placed in an achromopeptidase (ACP) lysis solution, and the other was first used for culture and then prepared according to the kit protocol. PCR was performed on both lysates, and results were compared to those for culture. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the PCR assay were 98%, 96%, 77%, and 99.7% with the kit lysate and 98%, 95%, 75%, and 99.7% with the ACP lysate (P, not significant), respectively. The second evaluation was done after implementation of all-admission surveillance using PCR with ACP lysis and a sampling of 1,107 PCR-negative samples and 215 PCR-positive samples that were confirmed by culture. The results of this sampling showed an NPV of 99.9% and a PPV of 73.5% (prevalence, 6%), consistent with our initial findings. The BD GeneOhm MRSA assay is an accurate and rapid way to detect MRSA nasal colonization. When one is dealing with large specimen numbers, the ACP lysis method offers easier processing without negatively affecting the sensitivity or specificity of the PCR assay.

5 Million Lives Campaign. Case study: an MRSA intervention at Evanston Northwestern Healthcare.

PCR-based testing offers superiority to culture in reduction of unisolated days. The ICU-based surveillance intervention had little impact after one year with surveillance compliance at 67%. However, once compliance improved, surveillance was expanded to the entire hospital and decolonization was implemented, MRSA BSIs were significantly reduced. Our experience parallels that of the European countries and other United States facilities that have implemented aggressive MRSA control measures. All successful programs have included active surveillance testing and barrier precautions. Finally, according to the Centers for Disease Control and Prevention's just-released report on invasive MRSA, since most MRSA infections are associated with health care contact, strategies to prevent and control MRSA among inpatients still may have a positive impact on infection, as demonstrated by our intervention.

A laboratory-based, hospital-wide, electronic marker for nosocomial infection: the future of infection control surveillance?

Faced with expectations to improve patient safety and contain costs, the US health care system is under increasing pressure to comprehensively and objectively account for nosocomial infections. Widely accepted nosocomial infection surveillance methods, however, are limited in scope, not sensitive, and applied inconsistently. In 907 inpatient admissions to Evanston Northwestern Healthcare hospitals (Evanston, IL), nosocomial infection identification by the Nosocomial Infection Marker (MedMined, Birmingham, AL), an electronic, laboratory-based marker, was compared with hospital-wide nosocomial infection detection by medical records review and established nosocomial infection detection methods. The sensitivity and specificity of marker analysis were 0.86 (95% confidence interval [CI 95], 0.76-0.96) and 0.984 (CI 95, 0.976, 0.992). Marker analysis also identified 11 intensive care unit-associated nosocomial infections (sensitivity, 1.0; specificity, 0.986). Nosocomial Infection Marker analysis had a comparable sensitivity (P > .3) to and lower specificity (P < .001) than medical records review. It is important to note that marker analysis statistically outperformed widely accepted surveillance methods, including hospital-wide detection by Study on the Efficacy of Nosocomial Infection Control chart review and intensive care unit detection by National Nosocomial Infections Surveillance techniques.

Three surveillance strategies for vancomycin-resistant enterococci in hospitalized patients: detection of colonization efficiency and a cost-effectiveness model.

OBJECTIVE: To evaluate the cost-effectiveness and detection sensitivity associated with three active surveillance strategies for the identification of patients harboring vancomycin-resistant enterococci (VRE) to determine which is the most medically and economically useful. DESIGN: Culture for VRE from 200 consecutive stool specimens submitted for Clostridium difficile culture. Following this, risk factors were assessed for patients whose culture yielded VRE, and a cost-effectiveness evaluation was performed using a decision analytic model with a probabilistic analysis. SETTING: A 688-bed, tertiary-care facility in Chicago, Illinois, with approximately 39,000 annual admissions, 7,000 newborn deliveries, 56,000 emergency department visits, and 115,000 home care and 265,000 outpatient visits. SUBJECTS: All stool specimens submitted to the clinical microbiology laboratory for C. difficile culture from hospital inpatients. RESULTS: From 200 stool samples submitted for C. difficile testing, we identified 5 patients with VRE in non-high-risk areas not screened as part of our routine patient surveillance. Medical record review revealed that all 5 had been hospitalized within the prior 2 years. Three of 5 had a history of renal impairment. The strategy that would involve screening the greatest number of patients (all those with a history of hospital admission in the prior 2 years) resulted in highest screening cost per patient admitted (dollars 2.48), lower per patient admission costs (dollars 480), and the best survival rates. CONCLUSION: An expanded VRE surveillance program that encompassed all patients hospitalized within the prior 2 years was a cost-effective screening strategy compared with a more traditional one focused on high-risk units.

Direct detection of Staphylococcus aureus from adult and neonate nasal swab specimens using real-time polymerase chain reaction.

Nasal carriage of Staphylococcus aureus is considered a source of subsequent infection in health care settings. Utilization of real-time polymerase chain reaction (PCR) for detection of S. aureus has the potential to dramatically affect infection control practice by rapidly identifying S. aureus-colonized patients. We developed and validated the use of real-time PCR for detection of S. aureus colonization in two patient populations. Paired nasal swabs were collected from 299 neonates and from 151 adult patients at Evanston Hospital. One swab was used for culture and the other placed into a bacterial lysis solution containing achromopeptidase. The DNA liberated was used as the template for real-time PCR with primers for the femA gene. SYBR Green was used for amplicon detection. In the neonatal population the sensitivity, specificity, predictive value positive and predictive value negative for culture and PCR was 92% versus 96%, 100% versus 100%, 100% versus 100%, and 98% versus 99%, respectively. In the adults the results were 90% versus 100%, 100% versus 98%, 100% versus 96%, and 95% versus 100%, respectively. Real-time PCR was able to detect S. aureus in 2 hours compared to 1 to 4 days for culture and provided sensitivity equal to or greater than culture.

Improving patient safety by repeating (read-back) telephone reports of critical information.

Reducing the rate of avoidable errors is crucial to patient safety. Telephone calls with misunderstood critical results constitute one area in which opportunities for improvement exist. The aviation industry has dealt with this issue by requiring pilots to repeat instructions received from the air traffic controller. At 3 health care organizations, we tested a program to decrease telephone reporting errors by requiring the recipients of critical results to repeat the message. Of 822 outgoing telephone calls from the laboratory, 29 errors were detected (error rate 3.5%). Calls to physicians had the highest rate of errors (6/95 [5%]). The time required to ask for the information and for the message to be repeated averaged 12.8 seconds per call, which corrected 29 errors. A simple system of repeating telephoned laboratory results has the potential to reduce the risk of medical errors and improve patient safety.

Computer-assisted surveillance for detecting clonal outbreaks of nosocomial infection.

Whole-house surveillance for healthcare-associated infection is no longer the recommended practice because of the large personnel time investment required. We developed a computer-based tracking system using microbiologic data as an aid in detecting potential outbreaks of healthcare-associated infections on a hospital-wide basis. Monthly total isolates of 25 clinically significant hospital pathogens were tallied from 1991 to 1998 to form a database for future comparison. Two different algorithm tools (based on increases of organism numbers over baseline) were applied to determine alert thresholds for suspected outbreaks using this information. The first algorithm (2SD) defined an alert as two standard deviations above the mean monthly number of isolates. The second (MI) defined an alert as either a 100% increase from the baseline organism number over 2 months or a >/=50% increase (compared to baseline) during a three-consecutive-month period. These two methods were compared to standard infection control professional surveillance (ICP) for the detection of clonal outbreaks over 12 months. Overall, a total of seven clonal outbreaks were detected during the 1-year study. Using standard methods, ICP investigated nine suspected outbreaks, four of which were associated with clonal microbes. The 2SD method signaled a suspected outbreak 15 times, of which three were clonal and ICP had detected one. The MI method signaled a suspected outbreak 30 times; four of these were clonal, and ICP had detected one. The sensitivity and specificity values for ICP, 2SD, and MI for detecting clonal outbreaks were 57, 43, and 57% and 17, 83, and 67%, respectively. Statistical methods applied to clinical microbiology laboratory information system data efficiently supplement infection control efforts for outbreak detection.