Evaluating the Role of MRSA Nasal Swabs

Evaluating the Role of MRSA Nasal Swabs Josh Arnold, PharmD PGY1 Pharmacy Resident Pharmacy Grand Rounds February 28, 2017 2016 MFMER slide-1

Objectives Identify the pathophysiology of MRSA nasal colonization Discuss current evidence for the utility of MRSA nasal swabs in specific patient populations Describe the clinical considerations associated with MRSA nasal swabs 2016 MFMER slide-2

The burden of infection Mortality MRSA Cost Drug consequences Marlowe EM, et al. Journal of Clinical Microbiology. 2011;49(9 Supplement):S53. 2016 MFMER slide-3

Pathophysiology Primary reservoir of S. aureus is the vestibulum nasi Shown to be highest colonization site Kluytmans J, et al. Clin Micro Rev. 1997;10(3):505-520. Mulcahy ME, et al. PLoS Pathog. 2012;8(12):e1003092. 2016 MFMER slide-4

Pathophysiology Primary reservoir of S. aureus is the vestibulum nasi Shown to be highest colonization site - S. aureus with ClfB - Loricrin ClfB: clumping factor B Kluytmans J, et al. Clin Micro Rev. 1997;10(3):505-520. Mulcahy ME, et al. PLoS Pathog. 2012;8(12):e1003092. 2016 MFMER slide-5

Epidemiology Rates of Nasal Colonization Community ICU Healthcare Employees MSSA 12-28% 22% 29% MRSA 0.7-2% 3-21% 4-15% Risk Factors for Nasal Colonization Antibiotic use within 3 months Hospitalization within 12 months Diagnosis of SSTI HIV infection Advanced age Long-term care residence SSTI: skin or soft-tissue infection Kenner J, et al. Infect Control Hosp Epidemiol. 2003;24(6):439-44. Porter R, et al. Intensive Care Med. 2003;29(4):655-8. Hidron AI, et al. Clin Infect Dis. 2005;41(2):159-66. Shibabaw A, et al. Antimicrob Resist Infect Control. 2013;2(1):25. 2016 MFMER slide-7

Culture vs. PCR Method Sensitivity Specificity Time to results (h) Cost Required skill level Culture Low 100% 18-48 Low Moderate PCR High <100% 4-12 High Moderate to high Marlowe EM, et al. Journal of Clinical Microbiology. 2011;49(9 Supplement):S53. 2016 MFMER slide-8

What gene detected by PCR is associated with methicillin-resistant S. aureus? A. Loricrin B. meca C. VISA D. ClfB 2016 MFMER slide-9

Universal screening Design Prospective, interventional case-control study Two community hospitals approximately 175 beds Population 15,049 adults All adults admitted during study period Objective Evaluate the clinical effectiveness and cost-benefit of universal versus targeted screening for MRSA to prevent hospital-acquired MRSA infections Intervention 9-month baseline: targeted screening for both hospitals 5-month intervention: universal screening at intervention hospital Leonhardt KK, et al. Infect Control Hosp Epidemiol 2011;32(8):797-803 2016 MFMER slide-10

Universal screening Universal screening was associated with: Increase in MRSA detection (P < 0.01) Non-significant decline in hospital-acquired MRSA infections (P = 0.34) Benefit-to-cost ratio of 0.50 Leonhardt KK, et al. Infect Control Hosp Epidemiol 2011;32(8):797-803 2016 MFMER slide-11

Consequences of screening Costly Isolation precautions Laborious Requires infrastructure 2016 MFMER slide-12

Is screening a poor use of resources? No Screening Start Universal Screening Screening Targeted Screening Tübbicke A, et al. BMC Health Serv Res. 2012;12:438. 2016 MFMER slide-13

Cost in Euros (millions) Is screening a poor use of resources? 25 20 15 10 5 0 Universal Screening No Screening Targeted Screening Tübbicke A, et al. BMC Health Serv Res. 2012;12:438. 2016 MFMER slide-14

MRSA pneumonia CAP HAP Incidence 2-9% 20-40% Risk Factors Prior influenza, ESRD Hospitalization where >20% isolates are MRSA, high risk for mortality Prior antibiotic therapy, IVDA, tobacco use, COPD, HIV infection Mortality 29-55% IVDA: intravenous drug abuse ESRD: end-stage renal disease COPD: chronic obstructive pulmonary disease HIV: human immunodeficiency virus Wooten DA, et al. Respir Med. 2013;107(8):1266-70. Kalil AC, et al. Clin Infect Dis. 2016; Mandell LA, et al. Clin Infect Dis. 2007;44 Suppl 2:S27-72. 2016 MFMER slide-15

The value of prediction Design Retrospective review study 850-bed three-hospital healthcare organization Population 5,779 nasal MRSA tests from patients in either ICU or chronic care units Objective Examine whether MRSA nasal colonization predicts MRSA involvement in a patient with positive cultures from site of suspected infection Inclusion MRSA PCR nasal swab performed within a 24-h period before or after a clinical culture showed the growth of any organism Robicsek A, et al. J Clin Microbiol. 2008;46(2):588-92. 2016 MFMER slide-16

The value of prediction Results Total number of clinical cultures (+)MRSA 5.6% Positive MRSA PCR nasal swab in setting of MRSA clinical cultures 217/323 patients (67.2%) Infectious Source Sensitivity (%) Specificity (%) Positive Predictive Value (%) Negative Predictive Value (%) Total 67 90 27 98 Respiratory 75 90 30 98 Bloodstream 74 88 21 99 Ulcer 70 89 70 89 Urine 77 87 11 99 Robicsek A, et al. J Clin Microbiol. 2008;46(2):588-92. 2016 MFMER slide-17

Definitions Sensitivity Probability that a test result will be positive when the disease is present (true positive rate) Specificity Probability that a test result will be negative when the disease is not present (true negative rate) Positive predictive value Probability that the disease is present when the test is positive Negative predictive value Probability that the disease is not present when the test is negative 2016 MFMER slide-18

Prediction in the ICU Design Prospective cohort study 1252-bed urban teaching hospital Population 749 consecutive patients admitted to the medical ICU Objective Test whether ICU nasal screening for MRSA predicts the presence or absence of MRSA infections requiring antimicrobial treatment Intervention Nasal swabs were obtained at ICU admission and weekly thereafter for MRSA detection Sarikonda KV, et al. Crit Care Med. 2010;38(10):1991-5. 2016 MFMER slide-20

Prediction in the ICU Results Rate of MRSA nasal colonization 24.4% Confirmed MRSA PNA 13.4% Infection Sensitivity (%) Specificity (%) Positive Predictive Value (%) Negative Predictive Value (%) PNA 24.2 78.5 17.7 84.4 BSI 23.1 78.2 11.0 89.7 Either PNA or BSI 25.2 79.2 27.4 77.3 LRTI: lower respiratory tract infection BSI: bloodstream infection PNA: pneumonia Sarikonda KV, et al. Crit Care Med. 2010;38(10):1991-5. 2016 MFMER slide-21

Utility in pneumonia Design Retrospective cohort study 244-bed academic tertiary care hospital Population 435 patients from both ICU and general floor Objective Describe the diagnostic characteristics of the nasal swab MRSA PCR test in predicting culture-confirmed pneumonia Inclusion Patients with confirmed pneumonia who had nasal swab MRSA PCR test and culture specimen obtained Dangerfield B, et al. Antimicrob Agents Chemother. 2014;58(2):859-64. 2016 MFMER slide-22

Utility in pneumonia Results Rate of colonization 14.3% Positive blood cultures 25 cases (5.7%) Pneumonia Type (n) Sensitivity (%) Specificity (%) Positive Predictive Value (%) Negative Predictive Value (%) All (435) 88.0 90.1 35.4 99.2 CAP (149) 77.8 90.7 35.0 98.4 HCAP (238) 100.0 88.9 34.2 100.0 HAP (48) 66.7 95.6 50.0 97.7 Dangerfield B, et al. Antimicrob Agents Chemother. 2014;58(2):859-64. 2016 MFMER slide-23

CAP guidelines 2007 No discussion of utility of MRSA nasal swab culture or PCR technology Mandell LA, et al. Clin Infect Dis. 2007;44 Suppl 2:S27-72. 2016 MFMER slide-24

HAP/VAP guidelines 2016 Observational data suggest that concurrent or recent positive MRSA screens increase the likelihood that clinical infection is due to MRSA. negative MRSA surveillance studies need to be interpreted within the context of the local prevalence of MRSA. There is also some evidence suggesting that a positive MRSA screen may increase the risk of MRSA being cultured from respiratory samples, but not enough evidence to definitively list this as a risk factor for MRSA pneumonia. Kalil AC, et al. Clin Infect Dis. 2016;63:1-51. 2016 MFMER slide-25

Is MRSA detection and de-escalation effective? Design Retrospective analysis Assessed two 1-month periods prior to and following initiation of MRSA PCR swab protocol Population Patients receiving vancomycin or linezolid for pneumonia pre- and post-pcr protocol Intervention MRSA PCR nasal swab ordered on all patients with suspected pneumonia started on vancomycin or linezolid Provider notified of PCR results to make decision of therapy Outcomes 1 : Duration of MRSA-targeted therapy 2 : Length of hospital stay; mortality after conclusion of initial MRSA-targeted regimen Baby N, et al. Antimicrob Agents Chemother. 2017;:AAC.02432-16. 2016 MFMER slide-26

Is MRSA detection and de-escalation effective? 366 patients on vancomycin or linezolid Indication not pneumonia: 263 Pre-PCR Group: 71 PCR Group: 32 MRSA nasal culture: 41 Died during treatment: 3 Died during treatment: 2 Pre-PCR Group: 27 PCR Group: 30 Baby N, et al. Antimicrob Agents Chemother. 2017;:AAC.02432-16. 2016 MFMER slide-27

Is MRSA detection and de-escalation effective? Duration of MRSA-Targeted Therapy (days) Days to Clinical Improvement Pre-PCR (n = 27) 4.0 ± 2.0 PCR (n = 30) 2.13 ± 0.86 Significance P = <0.0001 1.78 ± 2.52 2.27 ± 3.34 P = 0.54 Incidence of AKI 7 (26%) 1 (3.3%) P = 0.02 Hospital LOS (days) 11.04 ± 9.5 8.2 ± 7.8 P = 0.22 Mortality 4 (14.8%) 2 (6.7%) P = 0.41 AKI: acute kidney injury LOS: length of stay Baby N, et al. Antimicrob Agents Chemother. 2017;:AAC.02432-16. 2016 MFMER slide-28

There is evidence to support de-escalating antimicrobial therapy based on MRSA nasal swab results in pneumonia. A. True B. False 2016 MFMER slide-29

Surgical populations S. aureus is the most common pathogen causing surgical site infections (SSIs) S. aureus nasal colonization: Occurs in ~25% of individuals Increases risk of SSI 2-14 fold Screening for MRSA colonization may play a role in: Identifying candidates for decolonization Informing the selection of optimal prophylactic antimicrobials Bratzler DW, et al. Am J Health-Syst Pharm. 2013; 70:195 283. 2016 MFMER slide-30

SCIP guidelines Universal use of mupirocin for nasal decolonization is discouraged Cardiac Procedures 45% reduction in S. aureus SSIs with the use of perioperative mupirocin among patients known to be colonized with S. aureus Orthopedic Procedures Mupirocin decolonization has shown significant decreases in nasal MRSA carriage and overall SSIs Mupirocin should be given intranasally to all patients with documented S. aureus colonization (SOE = A) SCIP: surgical care improvement project Bratzler DW, et al. Am J Health-Syst Pharm. 2013; 70:195 283. 2016 MFMER slide-31

Skin and soft tissue infections MRSA nasal colonization is a risk factor Predictive value increases significantly when paired with MRSA swab from another site Decolonization may play a role in recurrent SSTIs Limited data exists SSTI: skin and soft tissue infection Schleyer AM, et al. Am J Infect Control. 2010;38(8):657-9. 2016 MFMER slide-32

A 51 year-old male presents to the ED with a 2-day history of fever, shortness of breath, and cough and no other PMH. CXR shows new bilateral infiltrates, and he is diagnosed with community-acquired pneumonia. The patient resides at home with his wife and two children, has no recent hospitalizations or antibiotics, and no other risk factors for MRSA pneumonia. He is admitted to the hospital and started on ceftriaxone and azithromycin. An MRSA PCR nasal swab, ordered in the ED, returns positive for MRSA colonization the next morning. On rounds, the attending states she would like to start IV linezolid. What is your response? 2016 MFMER slide-33

A. Recommend starting IV vancomycin due to cost considerations B. Oblige and go check Pyxis to confirm linezolid is available C. Recommend adding oral MRSA coverage with doxycycline D. Discuss likelihood of MRSA pneumonia being present based on patient s presentation, risk factors and the PPV of the nasal swab PCR 2016 MFMER slide-34

Take home points MRSA nasal swabs should not be used to direct antibiotic therapy alone Clinical Presentation Risk Factors MRSA Nasal Swab Screening Clinical Course Cardiac and Orthopedic Surgery Strong Negative Predictor Risk Factor vs. Definitive Diagnostic Tool 2016 MFMER slide-35

Evaluating the Role of MRSA Nasal Swabs Josh Arnold, PharmD PGY1 Pharmacy Resident Pharmacy Grand Rounds February 28, 2017 2016 MFMER slide-36

CA-Pneumonia and Influenza Correlation Jain S, et al. N Engl J Med. 2015;373(5):415-27. 2016 MFMER slide-37

Disease Non Disease Positive A Sensitivity (True Positive) B Specificity (False Positive) Negative C Positive Predictive Value (False Negative) D Negative Predictive Value (True Negative) DA D+B A+C Positive Negative Sensitivity Specificity Predictive = Value = = A D A+B D+C 2016 MFMER slide-38