In this randomized controlled trial, active screening was superior to passive screening for discontinuation of contact precautions for methicillin-resistant Staphylococcus aureus, and a single negative nasal swab processed by polymerase chain reaction had a high negative predictive value compared to 3 nasal cultures.
Keywords: MRSA, infection control, contact precautions, isolation, clinical trial
Abstract
Background. There have been no randomized controlled trials comparing active and passive screening for documenting clearance of colonization with methicillin-resistant Staphylococcus aureus (MRSA). We compared the efficacy of active and passive screening using both culture and commercial polymerase chain reaction (PCR) for documentation of MRSA clearance and discontinuation of MRSA contact precautions (CPs).
Methods. Inpatients with a history of MRSA infection or colonization enrolled between December 2010 and September 2011 were randomized to either passive (nonintervention arm; n = 202; observation with local standard of care) or active screening (intervention arm; n = 405; study staff screened using culture and commercial PCR). The primary outcome was discontinuation of CPs by trial arm based on 3 negative cultures. In the intervention arm, sensitivity, specificity, and positive and negative predictive values of the first PCR were compared to cultures.
Results. CPs were discontinued significantly more often (rate ratio [RR], 4.1; 95% confidence interval [CI], 2.3%–7.1%) in the intervention arm, including in an intent-to-screen analysis (RR, 2.6; 95% CI, 1.5%–4.7%). The first PCR, compared to 3 cultures, detected MRSA with a sensitivity of 93.9% (95% CI, 85.4%–97.6%), a specificity of 92.0% (95% CI, 85.9%–95.6%), a positive predictive value of 86.1% (95% CI, 75.9%–93.1%), and a negative predictive value of 96.6% (95% CI, 91.6%–99.1%).
Conclusions. Compared to passive screening using culture methods, active screening resulted in discontinuation of MRSA CPs at a significantly higher frequency. Active screening with a single PCR would significantly increase the completion of the screening process.
Clinical Trials Registration. NCT01234831.
(See the Editorial Commentary by Pegues on pages 185–7.)
Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in hospitals and, increasingly, outpatient settings [1]. Based on guidelines from the Centers for Disease Control and Prevention, inpatients with a positive culture(s) for MRSA should be managed using contact precautions (CPs) [2].
Although data suggest that the majority of individuals clear MRSA colonization spontaneously within months to years, there are currently no national or universally accepted guidelines with respect to when and under what conditions CPs should be discontinued [3–8]. To evaluate a practical algorithm for discontinuation of CPs for MRSA, we randomized eligible inpatients to the current institutional protocol of clinician-initiated screening (primary team) for discontinuation of CPs (nonintervention arm) or to active screening using both culture- and molecular-based methods (intervention arm).
METHODS
Design Overview
We conducted a randomized controlled trial at the Massachusetts General Hospital (MGH), a 947-bed tertiary referral center in Boston, affiliated with Harvard Medical School. MGH has approximately 50 000 admissions per year, and MRSA prevalence among inpatients is approximately 8% as determined by a retrospective analysis of patients flagged as having a history of MRSA on admission. Decolonization protocols and daily skin cleansing with chlorhexidine were not routinely employed.
Settings and Participants
Eligible participants were adult inpatients identified as having a history of MRSA, but not more recently than the prior 90 days. Participants were admitted to the hospital between 6 December 2010 and 16 September 2011. Eligibility was determined by a MRSA Automated Alert System, which identified patients with a history of MRSA without documented clearance (Supplementary Appendix). Concurrent antibiotic use did not preclude enrollment, but was an exclusion criterion for discontinuation of CPs. The study protocol was reviewed and approved by the Partners Human Research Committee, with verbal consent required for participation in the intervention arm.
Randomization and Interventions
Subjects were assigned to the nonintervention arm and intervention arm in a sequential 1:2 fashion in the order of admission to account for expected attrition in the intervention arm.
Nonintervention Arm
The nonintervention arm utilized the local standard of care for discontinuation of CPs. This protocol involved (1) the primary team identifying the patient as eligible based on MRSA history; (2) the primary team completing a series of 3 surveillance nasal cultures negative for MRSA at least 24 hours apart; and (3) cultures obtained without concurrent administration of antibiotics with activity against MRSA in the preceding 48 hours. The primary team was not informed of the subjects’ enrollment; if they obtained surveillance swabs, the timing of their collection and culture results were documented by study staff. The primary team was responsible for referral of subjects to the Infection Control Unit for validation for discontinuation of CPs.
Intervention Arm
Subjects who consented to participate were swabbed by study staff immediately, with one swab processed for culture as in the nonintervention arm, and the second swab processed using a commercially available polymerase chain reaction (PCR) assay. The procedure was employed on subsequent days, at least 24 hours apart. The series continued through to completion when possible, regardless of the results or antibiotic administration. Any subject with 3 negative cultures was immediately referred to the Infection Control Unit. In those subjects not receiving antibiotics with activity against MRSA in the prior 48 hours, CPs were discontinued. Clinical and demographic data for participants were collected from medical and administrative databases.
Swab Collection
The nasal swab procedure was commonly performed under a variety of circumstances throughout the institution, and no additional training of hospital staff in the nonintervention arm was undertaken. In the intervention arm, swabs were obtained by study staff who were trained by the study investigators.
Laboratory Methods
Culture-Based Screening
Nasal swab specimens were collected for both trial arms with the BBL CultureSwab Collection and Transport System (Becton, Dickinson and Company, Franklin Lakes, New Jersey) and were inoculated onto BBL CHROMagar MRSA media plates (“CA,” Becton, Dickinson and Company). Mauve-colored colonies seen by 48 hours were tested by Gram stain, and those with gram-positive cocci were confirmed by a positive tube coagulase test for reporting as MRSA.
PCR-Based Screening
In the intervention arm, specimens were also collected with the Cepheid Collection Device (Copan, Marietta, Georgia) and processed using the Xpert MRSA real-time PCR assay on the GeneXpert platform (“PCR,” Cepheid, Sunnyvale, California; Supplementary Appendix).
Outcomes
The primary outcome was discontinuation of CPs, using culture-based methods. We also examined completion of the series and frequency of clearance. For the intervention arm, outcomes included the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the first PCR compared to 3 negative cultures. We conducted sensitivity analyses to examine the impact of prevalence of MRSA on the NPV. For the small fraction of subjects in whom the CA and PCR were discordant, we applied a protocol for discordancy testing (Supplementary Appendix).
Approach to Antibiotics Received
Using medication administration data, we determined timing of sampling with respect to administration of antibiotics with activity against MRSA. Separate analyses were conducted for all subjects and those with samples obtained in the absence of antibiotics (Supplementary Appendix).
Statistical Analysis
The Fisher exact test was used to compare participant demographics, admission source site and clinical service, and the proportion of subjects with prior hospitalizations; the independent samples t test was used to compare means related to MRSA history. Rate ratios and 95% confidence intervals (CIs) were calculated using the Armitage and Berry method in both the efficacy analysis and the intent-to-screen analysis [9]. The 95% CIs for sensitivity, specificity, PPV, and NPV were calculated based on the exact binomial model. Additional details are provided in the Supplementary Appendix.
Estimation of Contact Precautions Days Averted and Associated Costs
To compute the total estimated decrease in CP days, the frequency of observed CP discontinuation was multiplied by the total length of stay (LOS) minus the specimen-processing time. Applying a total of 5 days of processing for culture and a single day for PCR resulted in the subject-level LOS off CPs, with the sum over all subjects equal to the total number of CP days averted. Published data reporting the cost of CP per patient per day were used, multiplied by study-derived CP days averted, to estimate associated cost savings (Supplementary Appendix) [10, 11].
RESULTS
Study Population
A total of 634 eligible admissions were evaluated for inclusion, of which 202 were randomized to the nonintervention arm and 198 allocated. Of 405 randomized to the intervention arm, 259 were allocated. A total of 457 subjects were included in the efficacy analysis (Figure 1).
Figure 1.
Patient flow diagram. aOnly patients with a history of methicillin-resistant Staphylococcus aureus (MRSA) >90 days at time of admission were assessed for eligibility. bSubjects were assigned to the nonintervention arm and intervention arm in a sequential 1:2 fashion in the order of admission, which was assumed to be random. cOf 202 subjects randomized to the nonintervention arm, 4 were excluded because they were found to be ineligible after enrollment (admission cancelled [n = 2]; found to be MRSA negative based on prior cultures [n = 1]; or determined to have methicillin-susceptible S. aureus, not MRSA [n = 1]). Of 261 randomized to the intervention arm, 2 were excluded because they were found to be ineligible after enrollment (prior enrollment [n = 1]; or found to be MRSA negative based on prior cultures [n = 1]). Abbreviations: CA, chromogenic agar (culture); MRSA, methicillin-resistant Staphylococcus aureus; PCR, polymerase chain reaction.
Baseline characteristics of subjects did not differ significantly between the 2 arms (Table 1). The mean number of days since last documented MRSA culture and the mean LOS in the nonintervention and intervention arms were 749 and 726 (P = .8) and 8 and 7 (P = .2), respectively. Of the 198 subjects in the nonintervention arm and 259 subjects in the intervention arm, 32 (16.2%) and 33 (12.7%), respectively, had an LOS of <48 hours, which would have precluded completion of the series of swabs (data not shown).
Table 1.
Baseline Demographics and Clinical Characteristics of Subjects
| Characteristic | Nonintervention Arm (n = 198) | Intervention Arm (n = 259) |
|---|---|---|
| Age, ya | 63.1 ± 18.3 | 63.8 ± 16.8 |
| Female sex | 84 (42.4) | 91 (35.1) |
| Raceb | ||
| White | 174 (87.9) | 229 (88.4) |
| Black | 13 (6.6) | 14 (5.4) |
| Hispanic/Latino | 8 (4.0) | 9 (3.5) |
| Asian | … | 4 (1.5) |
| Other | … | 2 (0.8) |
| Not identified | 3 (1.5) | 1 (0.4) |
| Admission source | ||
| Walk-in | 51 (25.8) | 65 (25.1) |
| Physician/self-referral | 50 (25.3) | 84 (32.4) |
| Emergency Medical Services transport decision | 64 (32.3) | 76 (29.3) |
| Transfer from acute care hospital | 24 (12.1) | 21 (8.1) |
| Transfer from rehabilitation hospital | 5 (2.5) | 6 (2.3) |
| Transfer from skilled nursing facility | 3 (1.5) | 4 (1.5) |
| Transfer from intermediate care facility | … | 1 (0.4) |
| Clinic/health center referral | 1 (0.5) | 2 (0.8) |
| Admitting site | ||
| Emergency department | 135 (68.2) | 167 (64.5) |
| Scheduled admission | 61 (30.8) | 85 (32.8) |
| Surgical day care unit | 2 (1.0) | 7 (2.7) |
| Admitting service | ||
| Medicine | 135 (68.2) | 169 (65.3) |
| Surgery | 57 (28.8) | 85 (32.8) |
| Emergency departmentc | 6 (3.0) | 5 (1.9) |
| Length of hospital stay, d | ||
| Mean length of stay (25th, 50th, 75th percentiles) | 8 ± 10 (2, 5, 9) | 7 ± 7 (3, 5, 8) |
| No. hospitalizations at MGH in prior mod | ||
| Inpatient, median (0; ≥1) | 0 (183; 15) | 0 (238; 21) |
| Emergency department, median (0; ≥1) | 0 (176; 22) | 0 (240; 19) |
| No. hospitalizations at MGH in prior yd | ||
| Inpatient, median (0; ≥1) | 1 (91; 107) | 1 (121; 138) |
| Emergency department, median (0; ≥1) | 0 (137; 61) | 0 (187; 72) |
| MRSA history | ||
| Mean time since last positive MRSA culture, da | 749 ± 737 | 726 ± 772 |
| Mean time since original MRSA documentation, da | 1078 ± 737 | 1085 ± 772 |
Data are No. (%) unless otherwise specified.
Abbreviations: MGH, Massachusetts General Hospital; MRSA, methicillin-resistant Staphylococcus aureus.
a Values are means ± SD.
b Race was self-reported.
c These subjects were initially admitted to the emergency department observation unit but subsequently admitted to the inpatient service.
d Median and counts for specified ranges of hospitalizations provided. P values calculated using Fisher exact test for proportions.
Outcomes and Estimation
The efficacy analysis included all allocated randomized subjects (Table 2). In the nonintervention arm, 62 of 198 (31.3%) subjects had screening initiated, compared with 259 of 259 (100%) in the intervention arm. Among the 62 subjects in the nonintervention arm, 30 (48.4%) were swabbed on admission to one of the hospital's units that conducted active surveillance for MRSA on admission (data not shown). Once initiated, completion of the series of swabs occurred in 19 of 198 (9.6%) and 191 of 259 (73.7%) in the nonintervention arm and intervention arm, respectively. Of those who completed the series of swabs, the number of subjects for whom all 3 culture swabs were negative did not differ significantly between the nonintervention (78.9%) and intervention arms (65.4%; Table 2). Of the 191 subjects completing the series in the intervention arm, 66 had at least one positive culture. Of those, 60 were positive on the first swab, 63 were positive by the second swab, and all 66 positive on the third. The cumulative sensitivity of the series was thus 90.9% (60/66) based on the first culture, 95.5% (63/66) by the second culture, and 100% (66/66) by the third culture (data not shown).
Table 2.
Implementation of Screening Protocol and Discontinuation of Contact Precautions
| Protocol Implementation | Efficacy Analysis |
Intent-to-Screen Analysis |
||||
|---|---|---|---|---|---|---|
| Nonintervention, No. (%) | Intervention, No. (%) | Rate Ratio (95% CI) | Nonintervention, No. (%) | Intervention, No. (%) | Rate Ratio (95% CI) | |
| Screen initiated | 62/198 (31.3%) | 259/259 (100%) | 3.2 (2.6–3.9) | 62/202 (30.1%) | 259/405 (64.0%) | 2.1 (1.7–2.6) |
| Three swabs obtained | 19/198 (9.6%) | 191/259 (73.7%) | 7.7 (5.0–11.9) | 19/202 (9.4%) | 191/405 (47.2%) | 5.0 (3.2–7.8) |
| All negative, given 3 swabs obtained | 15/19 (78.9%) | 125/191 (65.4%) | 0.8 (.6–1.1) | 15/19 (78.9%) | 125/191 (65.4%) | 0.8 (.6–1.1) |
| Removed from CPs, given negative screen completeda | 13/15 (86.7%) | 69/125 (55.2%) | 0.6 (.5–.8) | 13/15 (86.7%) | 69/125 (55.2%) | 0.6 (.5–.8) |
| Removed from CPs, given allocation/randomization.a | 13/198 (6.6%) | 69/259 (26.6%) | 4.1 (2.3–7.1) | 13/202 (6.4%) | 69/405 (17.0%) | 2.6 (1.5–4.7) |
Abbreviations: CI, confidence interval; CPs, contact precautions.
a Only subjects in whom all 3 cultures were negative were referred to Infection Control Unit for review of record and discontinuation of CPs if criteria were met. The only disqualifying criterion at this level of review for subjects in the intervention arm was whether the samples had been obtained within 48 hours of concurrent exposure to antibiotics with activity against methicillin-resistant Staphylococcus aureus. Because intervention arm subjects were screened regardless of concurrent antibiotic exposure, a smaller proportion of those who screened negative were able to be removed from CPs, compared to the nonintervention arm. See Supplementary Appendix for detailed discussion of restricted antimicrobials.
For the primary outcome of discontinuation of CPs in the absence of anti-MRSA antibiotics, based on culture results, subjects in the intervention arm had CPs discontinued 4.1 times more frequently (95% CI, 2.3–7.1) as those in the nonintervention arm. In the intent-to-screen analysis, which included all randomized subjects (n = 607), there remained significantly more subjects in the intervention than the nonintervention arm who completed screening and had discontinuation of CPs (Table 2).
Concurrent Antistaphylococcal Antibiotic Use by Trial Arm
Roughly half of subjects in the nonintervention arm who had a first swab obtained were off antistaphylococcal antibiotics within the window of screening (32/62 [51.6%]; 95% CI, 38.6%–64.5%). Similarly, almost half of subjects in the intervention arm who had a first swab obtained were off antibiotics within the window of screening (127/259 [49.0%]; 95% CI, 42.8%-55.3%; data not shown).
Performance Characteristics of Single PCR Versus 3 Culture Assays
In the 191 subjects in the intervention arm who completed the series, the sensitivity of the first PCR compared to the set of 3 cultures was 93.9% (95% CI, 85.4%–97.6%), and specificity was 92.0% (95% CI, 85.9%–95.6%). With a prevalence of persistent MRSA of 44.4%, the PPV of the first PCR compared to 3 cultures was 86.1% (95% CI, 75.9%–93.1%), and the NPV was 96.6% (95% CI, 91.6%–99.1%). Subgroup analyses, performed for subjects with all swabs obtained “off antibiotics” (as defined in the Supplementary Appendix), produced similar point-estimates with wider CIs (Table 3).
Table 3.
First Polymerase Chain Reaction Test Performance Compared to 3 Sequential Chromogenic Agar Cultures in Intervention Arm Population
| Study Population | Sensitivity % (95% CI) | Specificity % (95% CI) | PPV % (95% CI) | NPV % (95% CI) |
|---|---|---|---|---|
| All subjects, series of 3 swabs completed (n = 191) | 93.9 (85.4–97.6) | 92.0 (85.9–95.6) | 86.1 (75.9–93.1) | 96.6 (91.6–99.1) |
| All subjects, series of 3 swabs completed, no antibiotics prior 48 h (n = 128)—antibiotic list Aa | 96.9 (89.3–99.1) | 92.2 (83.0–96.6) | 92.5 (83.4–97.5 | 96.7 (88.7–99.6) |
| All subjects, series of 3 swabs completed, no antibiotics prior 48 h (n = 111)—antibiotic list Bb | 96.9 (89.3–99.1) | 89.4 (77.4–95.4) | 92.5 (83.4–97.5) | 95.5 (84.5–99.4) |
Among the 191 subjects who completed all 3 swabs in the intervention arm, 3 received mupirocin at some point during their encounter. The first subject received mupirocin within the 48 hours prior to the second swab. The second and third subjects did not receive mupirocin during the swabbing window (see Supplementary Appendix for details).
Abbreviations: CI, confidence interval; NPV, negative predictive value; PPV, positive predictive value.
a List A: Includes subjects without concurrent exposure to any of the following: trimethoprim/sulfamethoxazole, intravenous, suspension; mupirocin topical; clindamycin oral, intravenous, suspension; daptomycin; doxycycline oral and intravenous; linezolid oral and intravenous; nitrofurantoin oral and suspension; rifampin oral and intravenous; quinupristin/dalfopristin; tetracycline oral; tigecycline; vancomycin intravenous.
b List B: Includes subjects without exposure to ciprofloxacin or levofloxacin in addition to any of the antibiotics from List A.
Clearance by 3 negative cultures or by first negative PCR increased with time since the most recent culture. Comparing subjects by time since most recent MRSA culture (<1 year, 1 to <2 years, and ≤2 years) in the nonintervention arm, there were 8, 3, and 8 subjects in each time frame, of whom 5 of 8 (62.5%), 2 of 3 (66.7%), and 8 of 8 (100%) cleared by sequential cultures at the respective time intervals. Among subjects in the intervention arm, there were 84, 51, and 56 subjects in each time frame, of whom clearance by culture was 46 of 84 (54.8%), 36 of 51 (70.6%), and 43 of 56 (76.8%), and 44 of 84 (52.4%), 34 of 51 (66.7%), and 41 of 56 (73.2%) by single PCR, respectively (data not shown).
Sensitivity Analysis of PCR NPV Examined at Alternative Rates of MRSA Persistence
The NPV was ≥90% at persistent MRSA prevalences of <70% in both the overall analysis and in the subgroup analyses in the absence of antistaphylococcal antibiotics (Figure 2).
Figure 2.
Negative predictive value of a first polymerase chain reaction result across a range of methicillin-resistant Staphylococcus aureus prevalence. Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; NPV, negative predictive value.
Estimated Effect on Unnecessary CP Days Avoided
The 457 subjects accounted for 3339 patient-days in the course of the study. Passive culture screening, active culture screening, and active PCR screening (with respective discontinuation rates of 6.6%, 26.6%, and 63.8%) would have resulted in 104, 418, and 1841 fewer CP patient-days, respectively. The latter strategy represents a 55% reduction in patient-days on CPs. These reductions in CP days resulted in estimated annualized savings of $86 950, $349 472, and $1 539 180 for each respective strategy (Supplementary Appendix).
DISCUSSION
We found, through a randomized trial design, that active screening is superior to passive screening for discontinuation of MRSA CPs. Under the current local standard of care, in the absence of active, targeted screening, few eligible individuals who have cleared MRSA will ever be identified.
That subjects in the nonintervention arm were substantially less likely to have initial screening specimens obtained (31% vs 100%) is likely due to several factors. First, determination of eligibility requires review of historical microbiological data, a process that may deter providers from screening. Increasingly shorter lengths of stay likely serve as a barrier to either initiating or completing the series of 3 swabs, which from start to finalization of cultures is at least a 5-day process. Whereas antibiotic administration did not appear to influence the initiation of the series, the possibility of potential wasted efforts—due either to expedient discharges or antibiotic initiation—may discourage providers from completing the process.
The trend toward a higher proportion of negative swabs in the nonintervention arm could reflect differences in specimen collection practices or the policy guidance to providers to discontinue the series if either the first or second swab returned positive results or if antibiotics had been administered. The reported rate of discontinuation of CPs in the nonintervention arm may underestimate the impact of active screening. For 6 subjects in the nonintervention arm who were not referred to the Infection Control Unit, study staff alerted Infection Control. These subjects were included among those who had CPs discontinued.
In both the nonintervention and intervention arms, a substantial proportion of subjects received at least one antibiotic with activity against MRSA during their entire admission (67.2% and 64.9%, respectively). This observation is in keeping with reports in the literature documenting widespread use of antibiotics among hospitalized patients [12]. Sensitivity, specificity, and NPVs of single PCR were statistically similar in the subset of subjects in whom no documented antibiotics were used in the 48 hours prior to sampling.
Intravenous vancomycin was the most commonly used antimicrobial with activity against MRSA and was administered to 44.4% of subjects in the nonintervention arm and 37.5% of subjects in the intervention arm. Although there is evidence in the literature to support no effect of intravenous vancomycin on MRSA nasal carriage [7, 13], many Infection Control policies consider specimens obtained in the presence of such antibiotics invalid for the purposes of discontinuation of CPs. The data presented here suggest that in programs using PCR for detection of persistent colonization, such restrictions may not be necessary.
We found that a single PCR assay has high sensitivity (93.9%) and specificity (92.0%) compared to 3 cultures. We found a higher PPV (86.1%) than others have documented, although it should be noted that these other studies were conducted in lower-prevalence settings [14, 15]. We also demonstrated a very high NPV (96.6%). Our sensitivity analyses demonstrate excellent NPVs (>90%) over a wide range of MRSA prevalences. Thus, discontinuation of CPs based on a single negative PCR may offer a reasonable and streamlined strategy to address the growing pool of those designated as MRSA-colonized, although acceptance of such an approach is likely to depend upon institutional and patient-mix characteristics.
A single PCR test performed at (or before) hospital admission could result in an increase in CP discontinuation not only because of a reduction in the number of samples needed, but also given the lower likelihood of concurrent antibiotics in this population. Our findings with regard to averted CP days and their associated costs illustrates that the most substantial impact is appreciated when active screening using single PCR is implemented.
Although more expensive than culture assays on a per-test basis, PCR screening offers the advantage of high sensitivity and rapid turn-around time [16, 17]. There are substantial costs to patients and the healthcare system attributable to the lack of an efficient means to document clearance of MRSA colonization and discontinuation of CPs. Given the widespread practice of cohorting patients who have known past histories of infection or colonization [18], or active infection with MRSA, cohorted patients with discordant colonization are at risk of reacquisition of MRSA and the associated costs [19–22]. Decreased satisfaction with care, fewer provider-patient interactions, increased reported symptoms of depression, and delays in care have been documented for patients on CPs [23–25]. Patients with a history of MRSA may also experience delays in time-to-bed-assignment [26] and may block neighboring beds in institutions with semi-private accommodations, limiting capacity. In the absence of a consensus as to when and under what testing circumstances CP can be safely discontinued, the pool of patients identified as MRSA colonized will continue to grow, with attendant adverse effects on patients and resource utilization.
The costs to patients and providers must be considered in the context of the costs of proposed screening strategies. Any active screening approach would incur costs of various types: personnel to implement screening, process assays, and manage patient results; capital investment in commercial PCR technology if active surveillance with PCR is acceptable; and laboratory costs of reagent expenses. The Manufacturers’ Suggested Retail Price (MSRP) of the culture plates is $6, of which 3 would be needed for the series, for a total of $18. The MSRP for the GeneXpert MRSA kit is $42, a >2-fold difference. The use of electronic alerts to identify eligible patients rapidly at the point of care and decision support to assist providers in implementation of such programs might increase the yield, as well as programmatic costs. These costs would need to be weighed against the potential benefits including a reduction in CP days, expanded hospital capacity, decreases in MRSA transmission, and improvements in patient satisfaction. The net result of this analysis is likely to depend on institutional characteristics including MRSA prevalence and capacity constraints.
This trial was conducted at a single academic center and in the absence of any national guidelines on protocols for discontinuation of CP, we implemented the local standard of care, the components of which are found in varying combinations nationally [18]. Nevertheless the demonstrated test performance characteristics, and specifically the high NPV over a wide range of persistent MRSA prevalences, illustrate the generalizability of the findings. We sampled the bilateral nares of subjects in the study. Many patients with nasal colonization with MRSA are also colonized at extranasal body site(s) [27], and extranasal colonization in the absence of nasal colonization has been observed. Single PCR on nasal specimens has been shown to provide similar NPV as when the assay is performed on specimens from additional body sites [28, 29], and, from an operational perspective, a simplified protocol requiring a single nasal swab compared to multiple sites is more efficiently implemented. Finally, we assessed the performance of PCR to an imperfect gold standard—serial culture specimens—which, although commonly used in infection control programs, is not 100% sensitive in detecting MRSA. Thus, our results must be weighed in this context.
In conclusion, active, targeted screening of individuals with a history of MRSA resulted in a significantly higher rate of discontinuation of CPs than the current local standard of clinician-initiated screening. The single PCR offers substantial clinical and operational advantages. These benefits include rapid determination of precaution status, which has the potential to inform clinical care decisions and alleviate capacity constraints.
Supplementary Data
Supplementary materials are available at Clinical Infectious Diseases online (http://cid.oxfordjournals.org/). Supplementary materials consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all supplementary data are the sole responsibility of the authors. Questions or messages regarding errors should be addressed to the author.
Notes
Acknowledgments. The authors thank the subjects for participating in the trial. Study data were collected and managed using the REDCap Electronic Data Capture tools hosted by Partners HealthCare Research Computing, Enterprise Research Infrastructure & Services group [30].
MGH Infection Control Unit. Paula Wright, RN, BSN, CIC, Director; Irene Goldenshtein, MS; Fred Hawkins, RN, MHR, CIC; Kathleen Hoffman, RN, BS, CIC; Katherine Kakwi, RN, MSN, MBA, CIC; Heidi Schleicher, RN, BSN, CIC; Nancy Swanson, RN, BSN, CIC; Judith A. Tarselli, RN. MGH Clinical Research Center Nursing Staff. Daniela Agusti, RN; Karen Branch, RN, BSN; Tammy Carnevale, RN; Catherine A. Griffith, RN; Kathleen A. Grinke, RN; Kathleen Habeeb, RN; Kathryn E. Hall, MS, APRN-BC; Helen Ann Higgins, RN; Sharon Maginnis, RN; Kathleen Martin, RN; June McMorrow, RN; Roseann B. McNamara, RN; Patricia R. Moran, RN; Marjorie A. Noone, RN.
We also acknowledge the MGH Emergency Department staff and Clinical Research Coordinators; the MGH Clinical Research Program; Winston Ware, Clinical Systems Analyst, MGH Clinical Care Management Unit; Keith Jennings and Douglas Kelbaugh, Partners Information Systems; Aaron Sacco, Pharmacy Systems Analyst, MGH Pharmacy IS/Informatics Group; MetaVision Data Use Committee and Clinical Information Technology Systems Team of the Department of Anesthesia, Critical Care, and Pain Medicine; Clinical Information Technology Systems Team; Jerry Petrole and Joy Boulware, Partners Healthcare Enterprise eMAR Information Systems; Lynn A. Simpson, MPH, Partners Information Systems, Research Computing; Fred Tenover, PhD, David Persing, MD, PhD, and Isabella Tickler, Cepheid; and Joseph P. Newhouse, PhD, and Haiden Huskamp, PhD.
Disclaimer. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. The funding sources had no influence on any aspects of the trial including data collection, manuscript preparation, or the decision to submit the manuscript for publication.
Financial support. This work was conducted with support from Harvard Catalyst, National Center for Research Resources and the National Center for Advanced Translational Sciences, and financial contributions from Harvard University and its affiliated academic healthcare centers. This work was supported by MGH 2010–2011 Clinical Innovation Award; National Institutes of Health Training Grant (T32 A107061); and The Harvard Clinical and Translational Science Center, National Institutes of Health (8UL1TR000170-05, 1 UL1 RR025758). Reagents and PCR testing equipment were provided without charge by Cepheid.
Potential conflicts of interest. E. S. R. reports consultancy with T2 Biosystems, Microphage, and royalties from Up To Date, all outside of the scope of the work herein. J. A. C. reports receiving grant support from Pfizer, Inc, unrelated to the scope of the work herein. R. P. W. reports receiving consultancy fees from LeClair Ryan, unrelated to the scope of work herein. D. C. H. reports receiving grant support from Pfizer, Inc, unrelated to the scope of work herein. All other authors report no potential conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References
- 1.Siegel JD, Rhinehart E, Jackson M, Chiarello L Healthcare Infection Control Practices Advisory Committee. Management of multidrug-resistant organisms in health care settings, 2006. Am J Infect Control. 2007;35(10 suppl 2):S165–93. doi: 10.1016/j.ajic.2007.10.006. [DOI] [PubMed] [Google Scholar]
- 2.Siegel JD, Rhinehart E, Jackson M, Chiarello L Health Care Infection Control Practices Advisory Committee. 2007 guideline for isolation precautions: preventing transmission of infectious agents in health care settings. Am J Infect Control. 2007;35(10 suppl 2):S65–164. doi: 10.1016/j.ajic.2007.10.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Robicsek A, Beaumont JL, Peterson LR. Duration of colonization with methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2009;48:910–3. doi: 10.1086/597296. [DOI] [PubMed] [Google Scholar]
- 4.Scanvic A, Denic L, Gaillon S, Giry P, Andremont A, Lucet JC. Duration of colonization by methicillin-resistant Staphylococcus aureus after hospital discharge and risk factors for prolonged carriage. Clin Infect Dis. 2001;32:1393–8. doi: 10.1086/320151. [DOI] [PubMed] [Google Scholar]
- 5.Marschall J, Muhlemann K. Duration of methicillin-resistant Staphylococcus aureus carriage, according to risk factors for acquisition. Infect Control Hosp Epidemiol. 2006;27:1206–12. doi: 10.1086/507917. [DOI] [PubMed] [Google Scholar]
- 6.Vriens MR, Blok HE, Gigengack-Baars AC, et al. Methicillin-resistant Staphylococcus aureus carriage among patients after hospital discharge. Infect Control Hosp Epidemiol. 2005;26:629–33. doi: 10.1086/502592. [DOI] [PubMed] [Google Scholar]
- 7.Vikram HR, Dumigan DG, Kohan C, Havill NL, Tauman A, Boyce JM. Discontinuation of contact precautions for patients no longer colonized with methicillin-resistant Staphylococcus aureus. Infect Control Hosp Epidemiol. 2010;31:541–3. doi: 10.1086/652455. [DOI] [PubMed] [Google Scholar]
- 8.Calfee DP, Salgado CD, Classen D, et al. Strategies to prevent transmission of methicillin-resistant Staphylococcus aureus in acute care hospitals. Infect Control Hosp Epidemiol. 2008;29(suppl 1):S62–80. doi: 10.1086/591061. [DOI] [PubMed] [Google Scholar]
- 9.Armitage P, Berry G. Statistical methods in medical research. 3rd ed. Medford, MA: Blackwell; 1994. [Google Scholar]
- 10.Conterno LO, Shymanski J, Ramotar K, et al. Real-time polymerase chain reaction detection of methicillin-resistant Staphylococcus aureus: impact on nosocomial transmission and costs. Infect Control Hosp Epidemiol. 2007;28:1134–41. doi: 10.1086/520099. [DOI] [PubMed] [Google Scholar]
- 11.Squires DA. Explaining high health care spending in the United States: an international comparison of supply, utilization, prices and quality. The Commonwealth Fund. 2012 [PubMed] [Google Scholar]
- 12.O'Neill E, Morris-Downes M, Rajan L, Fitzpatrick F, Humphreys H, Smyth E. Combined audit of hospital antibiotic use and a prevalence survey of healthcare-associated infection. Clin Microbiol Infect. 2010;16:513–5. doi: 10.1111/j.1469-0691.2009.02822.x. [DOI] [PubMed] [Google Scholar]
- 13.Yu VL, Goetz A, Wagener M, et al. Staphylococcus aureus nasal carriage and infection in patients on hemodialysis. efficacy of antibiotic prophylaxis. N Engl J Med. 1986;315:91–6. doi: 10.1056/NEJM198607103150204. [DOI] [PubMed] [Google Scholar]
- 14.Roisin S, Laurent C, Nonhoff C, et al. Positive predictive value of the Xpert MRSA assay diagnostic for universal patient screening at hospital admission: influence of the local ecology. Eur J Clin Microbiol Infect Dis. 2012;31:873–80. doi: 10.1007/s10096-011-1387-7. [DOI] [PubMed] [Google Scholar]
- 15.Creamer E, Dolan A, Sherlock O, et al. The effect of rapid screening for methicillin-resistant Staphylococcus aureus(MRSA) on the identification and earlier isolation of MRSA-positive patients. Infect Control Hosp Epidemiol. 2010;31:374–81. doi: 10.1086/651093. [DOI] [PubMed] [Google Scholar]
- 16.van Hal SJ, Stark D, Lockwood B, Marriott D, Harkness J. Methicillin-resistant Staphylococcus aureus (MRSA) detection: comparison of two molecular methods (IDI-MRSA PCR assay and GenoType MRSA direct PCR assay) with three selective MRSA agars (MRSA ID, MRSASelect, and CHROMagar MRSA) for use with infection-control swabs. J Clin Microbiol. 2007;45:2486–90. doi: 10.1128/JCM.00139-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Wolk DM, Picton E, Johnson D, et al. Multicenter evaluation of the Cepheid Xpert methicillin-resistant Staphylococcus aureus (MRSA) test as a rapid screening method for detection of MRSA in nares. J Clin Microbiol. 2009;47:758–64. doi: 10.1128/JCM.01714-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Shenoy ES, Hsu H, Noubary F, Hooper DC, Walensky RP. National survey of infection preventionists: policies for discontinuation of contact precautions for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus. Infect Control Hosp Epidemiol. 2012;33:1272–5. doi: 10.1086/668427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Datta R, Platt R, Yokoe DS, Huang SS. Environmental cleaning intervention and risk of acquiring multidrug-resistant organisms from prior room occupants. Arch Intern Med. 2011;171:491–4. doi: 10.1001/archinternmed.2011.64. [DOI] [PubMed] [Google Scholar]
- 20.Hardy KJ, Oppenheim BA, Gossain S, Gao F, Hawkey PM. A study of the relationship between environmental contamination with methicillin-resistant Staphylococcus aureus (MRSA) and patients’ acquisition of MRSA. Infect Control Hosp Epidemiol. 2006;27:127–32. doi: 10.1086/500622. [DOI] [PubMed] [Google Scholar]
- 21.Moore C, Dhaliwal J, Tong A, et al. Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) acquisition in roommate contacts of patients colonized or infected with MRSA in an acute-care hospital. Infect Control Hosp Epidemiol. 2008;29:600–6. doi: 10.1086/588567. [DOI] [PubMed] [Google Scholar]
- 22.Hamel M, Zoutman D, O'Callaghan C. Exposure to hospital roommates as a risk factor for health care-associated infection. Am J Infect Control. 2010;38:173–81. doi: 10.1016/j.ajic.2009.08.016. [DOI] [PubMed] [Google Scholar]
- 23.Day HR, Morgan DJ, Himelhoch S, Young A, Perencevich EN. Association between depression and contact precautions in veterans at hospital admission. Am J Infect Control. 2011;39:163–5. doi: 10.1016/j.ajic.2010.06.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Morgan DJ, Diekema DJ, Sepkowitz K, Perencevich EN. Adverse outcomes associated with contact precautions: a review of the literature. Am J Infect Control. 2009;37:85–93. doi: 10.1016/j.ajic.2008.04.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Stelfox HT, Bates DW, Redelmeier DA. Safety of patients isolated for infection control. JAMA. 2003;290:1899–905. doi: 10.1001/jama.290.14.1899. [DOI] [PubMed] [Google Scholar]
- 26.Shenoy ES, Walensky RP, Lee H, Orcutt B, Hooper DC. Resource burden associated with contact precautions for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus: the patient access managers’ perspective. Infect Control Hosp Epidemiol. 2012;33:849–52. doi: 10.1086/666629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Baker SE, Brecher SM, Robillard E, Strymish J, Lawler E, Gupta K. Extranasal methicillin-resistant Staphylococcus aureus colonization at admission to an acute care veterans affairs hospital. Infect Control Hosp Epidemiol. 2010;31:42–6. doi: 10.1086/649222. [DOI] [PubMed] [Google Scholar]
- 28.Wassenberg MW, Kluytmans JA, Bosboom RW, et al. Rapid diagnostic testing of methicillin-resistant Staphylococcus aureus carriage at different anatomical sites: costs and benefits of less extensive screening regimens. Clin Microbiol Infect. 2011;17:1704–10. doi: 10.1111/j.1469-0691.2011.03502.x. [DOI] [PubMed] [Google Scholar]
- 29.Hombach M, Pfyffer GE, Roos M, Lucke K. Detection of methicillin-resistant Staphylococcus aureus (MRSA) in specimens from various body sites: performance characteristics of the BD GeneOhm MRSA assay, the Xpert MRSA assay, and broth-enriched culture in an area with a low prevalence of MRSA infections. J Clin Microbiol. 2010;48:3882–7. doi: 10.1128/JCM.00670-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–81. doi: 10.1016/j.jbi.2008.08.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.