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CEPHEID ON-DEMAND REPORT A Quarterly Publication by Cepheid Volume 1, Issue 3 IN THIS ISSUE… Cover Story: A New Paradigm for the Management of Skin and Soft Tissue Infections (SSTI) in the Era of MRSA Inside: Highlights from ICAAC/IDSA a Summary of Selected Presentations with a Focus on Healthcare-Associated Infections Online: www.cepheidondemand.com A New Paradigm for the Management of Skin and Soft Tissue Infections (SSTI) in the Era of MRSA How will rapid MRSA/SA test results affect treatment algorithms? Ellen Jo Baron, Ph.D. Director, Clinical Microbiology Lab, SHC Professor, Dept. of Pathology, Stanford Med School Recently, Cepheid convened a panel of experts in emergency medicine, surgery, infectious disease, and epidemiology to discuss how treatment algorithms might change in response to having rapid test results available. Doctors David Alland, MD, Samir Awad, MD, Stanley Deresinski, MD, FACP, and David Talan, MD, FACEP, FIDSA expressed their perspectives on being able to know whether a patient’s infection was caused by MSSA or MRSA while the patient is still in the emergency room. Emergency department (ED) physicians thrive on action. Their practice is exemplified by constant multiple demands for their attention and their decisions, and they like it that way. So defining on-demand molecular diagnostics. when patients show up with infected lesions that the patients describe as “spider bites,” if the patients are not systemically ill and the lesions are not considered severe, emergency department physicians instinctively want to take action. “Drain and refrain” (from See RAPID TESTING on next page December – February 2008 – 2009 Rapid Testing, a New Paradigm Affecting ON-DEMAND CEPHEID Executive Editor David Persing, M.D., Ph.D. Managing Editor Stripe Demarest Lead Author Ellen Jo Baron, Ph.D. Contributing Author Fred Tenover, Ph.D Production Manager Gregory Birgfeld Newsletter Design Bijal Patel Print/Web Design & Production Tori Muir prescribing antimicrobials) has been at least one publicized approach to such situations.1 And in fact, in most cases (90.5% in one study), the patient without other risk factors does well with drainage alone.2 But wouldn’t it be helpful to know the identity of the offending organism? If infected patients knew that their infection was caused by the infamous methicillin-resistant Staphylococcus aureus (MRSA), for example, they might take precautions to avoid reinfection, or they might modify their personal hygiene practices to prevent spreading the infection to family members, friends, or close contacts. REPORT Cepheid’s ON‑DEMAND Report is distributed four times a year. We welcome communication from users of Cepheid systems and tests and invite suggestions for articles in future issues. Send correspondence to: Cepheid ON‑DEMAND Report 1327 Chesapeake Terrace Sunnyvale, CA 94089 [email protected] To sign up for email notification of new issues of Cepheid’s ON‑DEMAND Report, visit www.cepheidondemand.com Contents are ©2008 by Cepheid unless otherwise indicated. Rights reserved on all guest columns. The contents of this publication may not be reproduced in any form without written permission of the editor. The mention of trade names, commercial products, or organizations does not imply endorsement by Cepheid. physician who saw that patient is no longer responsible for the care of that patient. So either that physician must attempt to contact the patient on his day off, or an ED nurse, with many other more pressing tasks, must spend precious time trying to locate and speak with the patient. If the lesion has healed properly, the patient may not appreciate the call. What if the infection is severe enough that the patient is admitted to the hospital? Of course cultures will be obtained. If the cultures show the patient is infected with MRSA, then the patient is placed on contact precautions or moved to a private room—but this information isn’t available for at least two days. 53% of North American respondents would treat a young athlete’s wound infection with an anti-MRSA antibiotic after incision and drainage— NEJM poll MRSA patients have a dramatically higher risk of reinfection. One study showed that 29% of MRSA-colonized or infected patients became reinfected, often at a different site and sometimes with very serious, even fatal, infections, within 18 months of their initial infection.3 Colonized patients and healthcare workers can also pass the organism to family members or other close contacts.4-5 A recent New England Journal of Medicine poll found that even without culture results, 53% of North American respondents would treat a young athlete with a wound infection with an anti-MRSA antibiotic after incision and drainage.6 A problem with those culture results remains. The results are available two days after the ED visit, and the 2 The patient and his or her family will certainly wonder why they, the nurses, and the doctors could go in and out of the room freely for two days, and suddenly now they need to put on gowns and gloves. Suddenly there are fewer visits for patient care, and the sense of worry and concern grows and grows.7 Understandably, everyone involved is just a bit grumpier and the previously non-colonized roommate possibly even unhappier. For nearly three decades, the Star Trek Tricorder used by Dr. McCoy to get an instantaneous diagnosis of a patient’s malady with a single, non-invasive pass over the patient’s body was the best of medical science fiction. With FDA clearance of Cepheid’s moderatecomplexity Xpert™ MRSA/SA Skin and Soft Tissue Infection (SSTI) on-demand Cepheid On-Demand Report Patient Treatment Algorithms in the Era of MRSA molecular test, we are one step closer to real-time diagnosis —although we still have to use a swab! A new diagnostic paradigm is emerging, and ED doctors will have to rethink their practices. Starting now, the presence of either Staphylococcus aureus (i.e., MSSA) or MRSA in a swab from a wound lesion can be determined within one hour of sample collection—right in the ED, if desired. This test offers an exciting new option for diagnosing infections rapidly and accurately. If surgeons knew that a patient’s wound was infected with MSSA and not MRSA, they could be confident that their cephalosporin or extended-spectrum penicillin therapy would be effective. Alternatively, they could avoid using vancomycin, which is not as effective as beta-lactam drugs for MSSA. If they knew that the wound carried MRSA, they could opt for vancomycin or one of several newer antimicrobial agents that are highly effective against MRSA. Recent studies have shown that appropriate treatment improves patient outcomes, which is the major goal of all healthcare institutions.8 The most widely used algorithm for SSTIs today is the one developed by Centers for Disease Control and Prevention (CDC), the American Medical Association, and the Infectious Diseases Society of America (Figure 1). Empiric therapy options are listed in the algorithm for presumptive treatment of MRSA. Figure 2 provides an often-used algorithm for pediatric patients presents more details on the lesion size and location.9 Using these references as guidelines, our panel had a freeflowing discussion about how the use of rapid results for MSSA and MRSA might change their practices. See RAPID TESTING on next page In one institution, having MRSA/MSSA information within one hour would prevent the overutilization of anti-MRSA therapy in approximately 30% of patients Outpatient† management of skin and soft tissue infections in the era of community-associated MRSA‡ Patient presents with signs/ symptoms of skin infection: • Redness • Swelling • Warmth • Pain/tenderness • Complaint of “spider bite” Is the lesion purulent (i.e., are any of the following signs present)? YES • Fluctuance—palpable fluid-filled cavity, movable, compressible • Yellow or white center • Central point or “head” • Draining pus • Possible to aspirate pus with needle and syringe Possible cellulitis without abscess: NO • Provide antimicrobial therapy with coverage for Streptococcus spp. and/or other suspected pathogens • Maintain close follow-up • Consider adding coverage for MRSA (if not provided initially), if patient does not respond YES † For severe infections requiring inpatient management, consider consulting an infectious disease specialist. ‡ Visit www.cdc.gov/mrsa .for more information 1. Drain the lesion 2. Send wound drainage for culture and susceptibility testing 3. Advise patient on wound care and hygiene 4. Discuss follow-up plan with patient Abbreviations: I&D—incision and drainage MRSA—methicillin-resistant S. aureus SSTI—skin and soft tissue infection If systemic symptoms, severe local symptoms, immunosuppression, or failure to respond to I&D, consider antimicrobial therapy with coverage for MRSA in addition to I&D (see below for options). Options for empiric outpatient antimicrobial treatment of SSTIs when MRSA is a consideration* Drug Name Considerations Precautions** Clindamycin •FDA-approved to treat serious infections due to S. aureus •D-zone test should be performed to identify inducible clindamycin resistance in erythromycin-resistant isolates •Clostridium difficile-associated disease, while uncommon, may occur more frequently in association with clindamycin compared to other agents. Tetracyclines •Doxycycline •Minocycline •Doxycycline is FDA-approved to treat S. aureus skin infections. •Not recommended during pregnancy. •Not recommended for children under the age of 8. •Activity against group A streptococcus, a common cause of cellulitis, unknown. TrimethoprimSulfamethoxazole •Not FDA-approved to treat any staphylo‑ coccal infection •May not provide coverage for group A streptococcus, a com‑ mon cause of cellulitis •Not recommended for women in the third trimester of pregnancy. •Not recommended for infants less than 2 months. Rifampin •Use only in combination with other agents. •Drug-drug interactions are common. Linezolid •Consultation with an infectious disease specialist is suggested. •FDA-approved to treat complicated skin in‑ fections, including those caused by MRSA. •Has been associated with myelosuppression, neuropathy and lactic acidosis during prolonged therapy. •MRSA is resistant to all currently available beta-lactam agents (penicillins and cephalosporins) •Fluoroquinolones (e.g., ciprofloxacin, levofloxacin) and macrolides (erythromycin, clarithromycin, azithromycine) are not optimal for treatment of MRSA SSTIs because resistance is common or may develop rapidly. * Data from controlled clinical trials are needed to establish the comparative efficacy of these agents in treating MRSA SSTIs. Patients with signs and symptoms of severe illness should be treated as inpatients. ** Consult product labeling for a complete list of potential adverse effects associated with each agent. Role of decolonization Regimens intended to eliminate MRSA colonization should not be used in patients with active infections. Decolonization regimens may have a role in preventing recurrent infections, but more data are needed to establish their efficacy and to identify optimal regimens for use in community settings. After treating active infections and reinforcing hygiene and appropriate wound care, consider consultation with an infectious disease specialist regarding use of decolonization when there are recurrent infections in an individual patient or members of a household. Figure 1. Treatment algorithm flowchart based on CDC guidelines. 3 December – February 2008 – 2009 Rapid Testing, a New Paradigm Affecting Patient Treatment Common Algorithm for Treatment of Skin/Soft Tissue Infections in Children OUTPATIENT INPATIENT Clindamycin 20–30 mg/kg/day PO Clindamycin 30–40 mg/kg/day IV; if life-threatening, add Vancomycin 40 mg/ kg/day IV Penicillin Penicillin + clindamycin in severe soft-tissue infections Sensitive (MSSA) Cephalexin or dicloxicillin 50–75 mg/kg/day Nafcillin 150–200 mg/kg/day; D/C vancomycin and/or clindamycin Resistant Trimethoprimsulfamethoxazole or linezolid, if susceptible Vancomycin 40 mg/kg/day IV; potential role for linezolid, other agents Susceptible Continue clindamycin Continue clindamycin and/or vancomycin, depending on site & severity of infection Trimethoprimsulfamethoxazole or linezolid, if susceptible Vancomycin 40 mg/kg/day IV Culture & susceptibility (very important) Empiric therapy Positive culture Staph or Strep? Strep. pyogenes (group A streptococcus) Staph. aureus Methicillin/oxacillin susceptibility Resistant (MRSA) Clindamycin susceptibility Susceptible Erythromycin susceptibility Resistant (inducible resistance to clindamycin is possible) Negative D Test (measures inducible resistance to clindamycin; this may lead to clindamycin treatment failures) Positive Please note that these are general recommendations; therapy for children with skin/soft tissue infections must be individualized. Figure 2. A standard pediatric treatment algorithm. David Talan, MD, FACEP, FIDSA Professor, Medicine/ Emergency Medicine Chair, Dept. of Emer‑ gency Medicine, Olive View-UCLA Medical Center Dr. David Talan started the discussion with his assertion that there are three types of patients. First, there are those who are critically ill, further characterized by Dr. Stanley Deresinski as patients with immediate life- or limb-threatening conditions, for whom physicians must start antimicrobial therapy immediately. There is no time to wait for the results of a rapid microbiology diagnostic test, no matter how quickly the results are available. Empiric treatment must be immediate to decrease mortality in this very ill group of patients. The second group of patients is one for which an algorithm that includes a rapid diagnostic arm makes sense. These patients present with an SSTI but they are not systemically ill and the infection is not necrotizing or a bite wound. Dr. Deresinski agrees that this is the type of patient for whom a rapid MRSA result would impact therapy. A rapid result showing the presence of MSSA and not MRSA, for example, would indicate that treatment with vancomycin or a newer, more expensive anti-MRSA agent, such as linezolid, daptomycin, or tigecycline is unnecessary. Knowing up front that nafcillin or cephalexin will be effective both simplifies and lowers the cost of treatment. Dr. Talan and Dr. Samir Awad noted that a third type of patient presents with an SSTI that is chronic (not necrotizing Stanley Deresinski, MD, FACP Clinical Professor, Med. in Infectious Diseases, Stanford Medical School Associate Chief, Infec‑ tious Diseases at Santa Clara Valley Medical Center Senior Editor,Infectious Disease Alert Newsletter 4 Samir Awad, MD Associate Professor of Surgery; Chief, Section of Critical Care for the Michael E. DeBakey Dept. of Surgery Associate Chief of Surgery Medical Direc‑ tor, SICU MED VAMC Houston, TX fasciitis) and likely to be polymicrobial. Such patients require debridement of the wound and long-term antimicrobial therapy. For these patients, a rapid result showing the presence of MSSA or MRSA will help the physician to target the antistaphylococcal therapy. In Dr. Awad’s institution, having this information within one hour would prevent the overutilization of anti-MRSA therapy in approximately 30% of the patients. Dr. David Alland concurred with this assessment. He pointed out that anti-MSSA therapy is not only less expensive, but is given for shorter duration. According to Dr. Alland, the negative predictive value of a rapid test has to be extremely good to reap these benefits. Cepheid On-Demand Report Algorithms in the Era of MRSA David Alland, MD Director, Center for Emerging & Re-Emerging Pathogens Professor, Department of Medicine, Infectious Diseases at the Univ. of Medicine and Dentistry, Newark, NJ The panel also discussed how the use of a rapid test would alter the management of hospitalized patients. One obvious arena for immediate utilization of the results is for the patient undergoing surgery. Vancomycin as a preemptive prophylactic agent could be avoided, with two positive consequences: • Lessening the risk of driving up the rate of vancomycin-resistant Enterococcus species (in that patient and in the hospital environment) • Allowing the use of a potentially more effective prophylactic agent Another positive outcome would be institution of appropriate infection control measures before the patient was placed in a room. Until all hospitals in the United States have migrated to allprivate rooms, the problem of patient placement and proper isolation will remain a key infection control issue.10 A less-recognized benefit of knowing that MRSA is the cause of an SSTI is that an antimicrobial agent known to have anti-toxin activity, such as linezolid or clindamycin could be used to potentially reduce the severity of the infection.11 Even before the organism is destroyed, its toxin-producing abilities are inhibited by these ribosomal-active agents. MRSA toxins, including Panton-Valentine leukocidin, alpha toxin, and toxic shock toxin, contribute to virulence of the organisms that carry them. The findings of the Institute for Healthcare Improvement, new guidelines from CDC and professional societies, and the plethora of states enacting legislation mandating MRSA surveillance and subsequent action have magnified the need for cost-effective strategies in healthcare settings. Cost-effectiveness studies such as those of Forrest and colleagues can be cited to mitigate the perceived price barriers to enacting the new molecular technology-based tests.12 New antimicrobial agents that are due to be released in the coming year, such as ceftibiprole, dalbavancin, televancin, and oritavancin, are highly effective but are likely to be expensive, emphasizing the need for such costbenefit studies. on the need for vigilance with regard to personal hygiene and the possibility of chronic problems. • Trimethoprim-sulfamethoxazole was mentioned as a good choice for initial therapy, but anti-MRSA therapy in general should be used, with different agents based on factors as indicated in the table shown on page 6. • Children in particular dislike the bad taste of clindamycin, so although it is an excellent drug for MRSA because of its anti-toxic properties, it is not the best choice for pediatric patients. New requirements for MRSA surveillance and subsequent action have magnified the need for cost-effective strategies in healthcare settings Finally, the experts noted that they could simplify a protocol for outpatient treatment of SSTI if they knew up front that MRSA was the etiological agent. The following points were discussed: • If diabetic foot ulcers were encountered, they would require debridement and scraping (no swabs) for complete culture. Good studies have shown that such infections involve only 14% S. aureus and 4% MRSA. • Similarly, abscesses rarely involve streptococci, so testing for presence of S. aureus or MRSA alone is appropriate. • Even those patients presenting with furuncles which previously would have been incised and drained and not treated should be seen in a new light. Now, knowing the furuncle contained MRSA, the patient could be educated 5 • Patients without pus (those with lumps, bumps, or cellulitis) are difficult to culture or test by PCR, as there is no easily obtained sample to test. Cellulitis is not likely to yield MRSA at any rate, as most cellulitis is due to streptococci. The current IDSA Guidelines state “Therapy for the typical case of erysipelas or cellulitis should include an antibiotic active against streptococci. Many clinicians choose an agent that is also effective against S. aureus, although this organism rarely causes cellulitis unless associated with an underlying abscess or penetrating trauma. A large percentage of patients can receive oral medications from the start. Suitable agents include dicloxacillin, cephalexin, clindamycin, or erythromycin, unless streptococci or staphylococci resistant to these agents are common in the community (A-I).” December – February 2008 – 2009 • Overall, the algorithms were appropriate except that instead of suspicion of MRSA triggering the use of anti-MRSA therapy, the actual presence of MRSA would do so. Given the excellent predictive value of negative results (as seen in beta trials), presence of S. aureus would suggest use of cephalexin, nafcillin, or other anti-S. aureus antibiotics. In summary, our panel of experts expressed great enthusiasm for the ability to quickly identify those patients with skin and soft tissue infections who harbored either S. aureus or MRSA. These distinguished clinicians anticipate a new era in which more rapid information will lead to better initial treatment choices. Anti-MRSA Anti-MSSA Choices in Antimicrobial Treatment (Based on CDC Algorithm) Antimicrobial Agent Drug Class Comments Cephalexin Cephalosporin - oral Also has anti-streptococcal activity; should be considered when cellulitis is present Dicloxacillin Penicillin - oral Nafcillin Penicillin – IM orIV Levofloxacin Fluoroquinolone – oral or IV Not first-line drug; not recommended for children TrimethoprimSulfamethoxazole Folate pathway in‑ hibitors - oral or IV Oral, usually active against MRSA but not FDA-cleared for use against MRSA; choice for SSTI in otherwise healthy patients, not for pregnant women (i.e., >12 weeks) or babies; some studies suggest less efficacy than clindamycin Clindamycin Lincosamide - oral, IM, or IV Has anti-toxin activity; requires special laboratory test to detect inducible resistance; bad taste disliked by children Linezolid Oxazolidinone oral or IV Has anti-toxin activity; more expensive than other agents; both oral and IV formulas available Doxycycline Tetracycline - oral or IV May have side-effects; not for use in children <5 years of age Minocycline Tetracycline - oral or IV Under-appreciated agent; similar to tetracycline Vancomycin Glycopeptide oral or IV May be less effective than other agents, particularly for bloodstream infections; levels should be monitored; overutilization can contribute to development of VRE; CDC recommends ef‑ forts to reduce use of vancomycin; recent studies suggest mean MRSA vancomycin MICs are increasing Daptomycin Lipopeptide - IV Effective against MRSA; not active in respiratory tract; more expensive than other agents Oritavancin Lipoglycopeptide - IV New agent currently in clinical trials; appears to have excellent anti-MRSA activity Ceftobiprole Cephalosporin – IV New extended spectrum cephalosporin that has anti-MRSA activity References 1. Chambers, Moellering. Clinical Decisions: Management of Skin and Soft-Tissue Infection. New England Journal of Medicine. 2008; 359(10):1063–1065. 2. Rajendran PM, Young D, Maurer T, et al. Randomized, double-blind, placebo-controlled trial of cephalexin for treatment of uncomplicated skin abscesses in a population at risk for community-acquired meth‑ icillin-resistant Staphylococcus aureus infection. Antimicrob Agents Chemotherapy. 2007; 51:4044–8. 3. Huang SS, Platt R. Risk of Methicillin-Resistant Staphylococcus aureus Infection after Previous Infection or Colonization. Clinical Infectious Diseases. 2003; 36:281–5 4. Bonness S, Szekat C, Novak N, Bierbaum G. Pulsed-Field Gel Elec‑ trophoresis of Staphylococcus aureus Isolates from Atopic Patients Revealing Presence of Similar Strains in Isolates from Children and Their Parents. Journal of Clinical Microbiology. 2008; 46:456–461. 5. Lu P-L, Tsai J-C, Chiu Y-W, Chang F-Y, Chen Y-W, Hsiao C-F, Siu LK. Methicillin-resistant Staphylococcus aureus carriage, infection and transmission in dialysis patients, healthcare workers and their family members Nephrol Dial Transplant. 2008; 23:1659–1665. 6. Hammond SP, Baden LR: Management of Skin and Soft-Tissue Infection — Polling Results. New England Journal of Medicine. 2008; 359:e20. 7. Kirkland KB, Weinstein JM. Adverse effects of contact isolation. Lancet. 1999; 354(9185):1177–1178. 8. Ruhe JJ, Smith N, Bradsher RW, Menon A. Community-Onset Methicillin-Resistant Staphylococcus aureus Skin and Soft-Tissue Infections: Impact of Antimicrobial Therapy on Outcome. Clinical Infectious Diseases. 2007; 44:777–784. 9. Lee, MC, Rios AM, Aten MF, Mejias A, Cavuoti D, McCracken GH Jr, Hardy RD. Management and outcome of children with skin and soft tissue abscesses caused by community-acquired methicillin-resistant Staphylococcus aureus. Pediatric Infectious Disease Journal. 2004; 23(2):123–7. 10.Huang SS, Datta R, Platt, R. Risk of Acquiring Antibiotic-Resistant Bacteria From Prior Room Occupants. Archives of Internal Medicine. 2006; 166:1945–1951. 11.Stevens DL, Ma Y, Salmi DB, McIndoo E, Wallace RJ, Bryant AE. Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus. Journal of Infectious Diseases. 2007; 195(2):202–11. 12.Forrest GN, Mehta S, Weekes E, Lincalis DP, Johnson JK, Venezia RA. Impact of rapid in situ hybridization testing on coagulase-negative staphylococci positive blood cultures. Journal of Antimicrobial Chemotherapy. 2006; 58:154–158. 6 Cepheid On-Demand Report Highlights from ICAAC/IDSA Focusing on Healthcare-Associated Infections Ellen Jo Baron, Ph.D. The American Society for Microbiology’s Interscience Congress on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America’s annual meeting were combined and held in Washington, DC this October. More than 14,000 attendees acquired the latest information on new diagnostics, new therapies, microbial pathogenesis, and more. Here is a summary of a few abstracts whose findings focus on healthcare-associated infections. The majority of recent studies are proving that infection control based on surveillance is cost-effective and beneficial, even when surveillance is restricted to limited inpatient units. C2-106. Detection of Oxacillin/Methicillin Resistant and Susceptible Staphylococcus aureus by Culture and RT-PCR in Patients Scheduled for Orthopedic Surgery Halstead DC, Kirspel CE, Mckean KA, Meyer KS, Boland BJ Nasal swabs from 275 patients scheduled for orthopedic surgery at Baptist Hospital (Jacksonville, FL) were tested by CHROMagar and BD GeneOhm MRSA in Phase I and another 137 patients by the Xpert™ MRSA test (using a frozen swab obtained at the same time) during Phase II. Rates of positivity more than doubled with the Xpert MRSA test. Both molecular systems usually agreed. The authors concluded that molecular methods were more sensitive than culture and that the GeneXpert® System gave more rapid results with less hands-on time than did the SmartCycler® System. C2-1066. Real-Time PCR (RT-PCR) for Methicillin-Resistant Staphylococcus aureus (MRSA) Detection: Implications in a Neonatal Intensive Care (NIC) Setting Song X, Campos J, Short B, Singh N In 2005, National Childrens’ Hospital in Washington DC tested for MRSA at admission and weekly thereafter using cultures. After they switched to rt-PCR (GeneXpert, Cepheid) in 2007 the incidence of MRSA increased from 6.9% to 10.8%. This enhanced detection led to a statistically significant reduction in hospital acquisitions of colonizing MRSA. During the time of culture surveillance 30.4% of MRSA-colonized patients developed an MRSA infection, whereas during PCR-based testing, only 9.1% of MRSA-positive patients developed MRSA infection. They concluded that PCR-based testing enhanced infection control measures for MRSA. K-3367. A Pilot Study of Active Surveillance for MRSA by PCR on Admission to ICUs at a Tertiary Care Center Espinoza C, Fisher V, Jean W, Gaines B, Davis K, Wanger A, Schaeffer M, Ostrosky-Zeichner L Mem. Hermann TX Medical Ctr., Houston, performed the BD GeneOhm assay once daily on all patients admitted to the adult ICU. Patients were initially all placed on modified contact precautions and positive patients were placed on full contact precautions and flagged for future infection control actions. During the 3-month intervention period, 11.6% of patients tested were MRSA positive. There was a statistically significant decrease in healthcare-associated ventilator-associated pneumonias and bloodstream infections overall in the ICU, from 59 to 38 per 1000 admissions. MRSA infections dropped from 9% to 5%. Importantly, the authors extrapolated costs to one year. Even considering the cost of testing and isolation, the cost avoidance associated with preventing healthcare-associated infections by PCR screening and subsequent isolation was estimated at $567,000. What’s good and what’s disappointing about the various surveillance methods? D-1137. Comparison of Direct Plating and Broth Enhanced Culture for Recovery of MRSA from PCR Positive Nasal Swabs Vonrentzell JE, Schreckenberger PC To resolve discrepancies between positive GeneXpert (Cepheid) MRSA results and negative culture results, Loyola scientists evaluated enhanced culture methods for recovery of MRSA. During Phase I, the second swab from patients whose first swab yielded a positive or inconclusive PCR was plated directly onto blood agar, two types of MRSA selective CHROMagars and then incubated in 1 mL of 6.5% NaCl in trypticase-soy broth (TSB) overnight. Broths from negative plate cultures 7 were plated to the same 3 agars. In Phase II, the second swab was vortexed in sterile saline, and inoculated onto the 3 agars and into 6.5% and 3.25%NaCl TSBs. Broths were subcultured if direct plating did not yield MRSA. In Phase I, direct plating recovered 68% of those with positive results in the Xpert MRSA test. Seven more MRSA were recovered from TSB subcultures (total 76% recovery). However, 13 of 21 MRSA culture negative samples grew MSSA. In Phase II, cultures overall yielded 87% on blood agar and 92-93% on CHROMagars. Of 20 MRSA-negative cultures , 13 grew MSSA. The MSSA isolates were further characterized; 2/3 were found to have a deletion in the mecA region. The isolation of MRSA from PCR-positive patients was increased 10% by vortexing swabs in saline before plating and 7% by enriching overnight in TSB. These results further support the superior sensitivity of molecular methods for detection of MRSA colonized patients. D-1136. Surveillance Swabs for Detection of Methicillin-Resistant Staphylococcus aureus (MRSA): Diagnostic Yield of Different Anatomic Sites and Comparison of Provider and Patient-Collected Samples Lautenbach E, Fishman N, Nachamkin I, Hu B, Tolomeo P, Prasad P, Bilker W, Zaoutis T Using cultures, workers at the Univ. of Pennsylvania (Philadelphia) compared swabs from different sites collected by healthcare workers and by the patients themselves. Axillae, nares, throat, perineum, and groin swabs were evaluated. Patient-collected swabs compared favorably with professionally collected samples. The best agreement between patient- and provider-collected samples was 95% for the groin. To achieve >90% detection of colonized persons, >1 site had to be sampled. In this population, the best single sites were nares (84% sensitive) and throat (65% sensitive). Groin and perineum cultures were more likely to be positive in community-onset patients (81%) than hospital-onset patients (41%). Nares, throat, and groin together achieved 100% sensitivity and either nares and throat or nares and groin reached 91% sensitivity for recovery of MRSA. K-3355. A Targeted Approach to MRSA Colonization Screening Using a PCR Assay and Multi-Site Sampling Strategy Metzger BS, Leung SS, Currie BP Colleagues at Montefiore Medical Center in the Bronx increased the sensitivity of December – February 2008 – 2009 surveillance cultures almost 24% by collecting swabs from axilla, nares, and groin vs. nares alone. 268 patients, of whom 21.3% were positive from at least one site: 17.2% nares, 10.1% axilla, and 13.4% groin, were evaluated. Targeting screening to those patients who had either long-term care residence, a previous MRSA isolate, or antibacterial use within the last 6 months, yielded a sensitivity of 80.7% and the need to test 43.7% of admissions. By adding the risk factor of hospitalization within the last 6 months, sensitivity increased to 91.2% with the need to screen 57.8% of admissions. They concluded that a targeted approach to surveillance and a two-swab (nares and skin) sample could result in near-complete capture of MRSA-colonized patients. Use of PCR as a point-of-care test: at this time, there is only one moderate complexity PCR assay FDA-cleared for use in the United States. Admissions wards of two hospitals in Birmingham, UK. Double swabs were collected from patients in the wards and one swab was used for near-patient testing, the other was sent to the central laboratory. Valid paired results were available for 735 swabs, 62 of which were MRSA positive. There was 97.1% agreement. Sampling errors were thought to account for all discrepancies. The results of tests performed at the wards were available in ≤ 2 hours for 97.7% of the swabs collected. The authors said that the use of the GeneXpert System at the patient point of care dramatically reduced the time to result compared with testing in the laboratory. Late Breaker: First look at the new Xpert MRSA/SA test for SSTI and blood culture broths. D-1139. Potential Use of the Cepheid Xpert™ MRSA Test for Near-Patient Testing Brenwald NP, Baker N, Oppenheim B D-2250a. Automated PCR to Detect Methicillin-Resistant (MR) or -Susceptible (MS) Staphylococcus aureus (SA) in Blood Cultures (BC) and Wound Swabs (WS) Musher DM, Goebel M, Matloobi M, Stager C, Parta M Computer-interfaced Cepheid GeneXpert® Systems were installed in the Critical Care and 132 blood cultures yielding gram-positive cocci in clusters were tested using the Xpert MRSA/SA CEPHEID REPORT ON-DEMAND A Quarterly Publication 1327 Chesapeake Terrace Sunnyvale, CA 94089 toll free: 1.888.336.2743 Volume 1, Issue 3 test. All 25 MRSA and 7 MSSA were correctly identified by the Xpert test in 50 minutes. One blood culture (negative for S. aureus) was identified as MRSA by the Xpert test. The sensitivities of the Xpert test for blood cultures were 100% for MRSA and MSSA and 99% for no S. aureus. Specificities were 99% for MRSA and 100% for MSSA. Sensitivity of the Xpert test for wounds culture-positive for MRSA was 99%. Sensitivities for wounds yielding MSSA and no S. aureus on culture were 91% and 79%; and specificities were all >91%. Of 80 MRSA cultured from 235 wound swabs, the Xpert test correctly identified 79. The Xpert MRSA/SA test correctly identified 30 of 33 MSSA isolates from wounds; 2 were incorrectly called MRSA, and one was not detected. From 122 wound cultures where no S. aureus were isolated, the Xpert test detected MRSA in 12 samples and MSSA in 14 samples. Because resolving tests were not performed, the true nature of the discrepant results is not known yet. Dr. Musher suggested that previously treated patients may account for some of the inconsistencies.