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CDP 13-004 – HSR&D Study

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CDP 13-004
Comparative Effectiveness of Strategies to Control S. Aureus Infections (CDA 11-215)
Marin L. Schweizer-Looby PhD BS
Iowa City VA Health Care System, Iowa City, IA
Iowa City, IA
Funding Period: May 2013 - April 2018

BACKGROUND/RATIONALE:
It is unknown which strategies, and in which patient populations, work best at reducing S. aureus infections. Additionally, there is little consensus on the optimal treatment for S. aureus infections.

OBJECTIVE(S):
The three aims are: 1) Complete meta-analyses of the effectiveness of different S. aureus infection prevention strategies; 2) Compare the effectiveness of anti-staphylococcal antibiotics for the treatment of invasive S. aureus infections; and 3) Create a decision model to compare strategies to prevent and treat S. aureus infections.

METHODS:
Aim 1, we performed 2 systematic literature reviews and meta-analyses. The first evaluated which non-surgical patient populations would most benefit from mupirocin decolonization. The second evaluated whether universal glove use was more effective than glove use only for multidrug-resistant organism (MDRO) infected patients or standard precautions. For the meta-analyses, we conducted a systematic search to identify all publications. The pooled odds ratios (pOR) or pooled rate ratios were pooled using a random-effects model.

Aim 2, the outcomes are 30-day mortality and recurrent infection. Cox proportional hazard models were used to assess mortality hazards (stated as a hazard ratio [HR]). Optimal beta-lactam therapy was defined as cefazolin or nafcillin/oxacillin. We compared the effectiveness of different antibiotics to treat S. aureus infections.

Aim 3, we are creating a mathematical model to evaluate the effectiveness of adding mupirocin decolonization to the current VA MRSA Initiative. Data from Aim 1 is being used to parameterize the model.

FINDINGS/RESULTS:
Aim 1: The first meta-analysis found that mupirocin decolonization was protective for ICU patients (pOR=0.44, 95% CI: 0.26, 0.73), peritoneal dialysis patients (pOR=0.23, 95% CI: 0.15, 0.36) and hemodialysis patients (pOR=0.15, 95% CI: 0.06, 0.36). These results were published in Clinical Infectious Diseases. The second meta-analysis found that universal gloving was not more effective than current practices at reducing the incidence of MDRO acquisition or healthcare-associated infection (pooled rate ratio=0.87, 95% CI: 0.69, 1.09). These results were presented at the ECCMID conference in April 2016.

Aim 2: We created a retrospective cohort of 16,973 Veterans with methicillin-susceptible S. aureus (MSSA) bacteremia who were admitted to one of 122 VA medical centers. We found that definitive treatment with any beta-lactam was associated with a 26% decreased hazard of mortality compared with definitive treatment with vancomycin (adjusted HR: 0.74; CI: 0.61-0.90). These results were published in Clinical Infectious Diseases. Among a similar cohort of 3,303 patients who received only optimal beta-lactam treatment, we found that cefazolin use was associated with decreased 30-day mortality compared with nafcillin/oxacillin (adjusted HR: 0.74; 95% CI: 0.60-0.91). However, cefazolin was associated with an increased risk of recurrence compared with nafcillin/oxacillin (adjusted HR: 1.09; 95% CI: 0.91-1.31), although this was not statistically significant. These results were published in Clinical Infectious Diseases.

We compiled a cohort of 664 Veterans with S. aureus prosthetic joint infections (PJI) after hip or knee surgery. We compared the effectiveness of rifampin combination antibiotic therapy to antibiotic therapy without rifampin. We found that 45% of S. aureus PJI patients received rifampin therapy. Rifampin treatment was observed to have a trend towards decreased risk for treatment failure, although this was not statistically significant (adjusted HR=0.85, 95%CI 0.66-1.09). These results were presented at the ICAAC conference in September 2015. The manuscript is written and will be submitted for publication soon.

Aim 3, I am currently collaborating with my colleagues at the Salt Lake City VA to complete the mathematical model.

IMPACT:
This study is consistent with the mission of the VHA in attempting to determine the most effective and cost-effective strategies that can be implemented by the VHA MRSA Prevention Initiative to prevent and treat S. aureus infections.

PUBLICATIONS:

Journal Articles

  1. Branch-Elliman W, Ripollone JE, O'Brien WJ, Itani KMF, Schweizer ML, Perencevich E, Strymish J, Gupta K. Risk of surgical site infection, acute kidney injury, and Clostridium difficile infection following antibiotic prophylaxis with vancomycin plus a beta-lactam versus either drug alone: A national propensity-score-adjusted retrospective cohort study. PLoS Medicine. 2017 Jul 1; 14(7):e1002340.
  2. Carrel M, Goto M, Schweizer ML, David MZ, Livorsi D, Perencevich EN. Diffusion of clindamycin-resistant and erythromycin-resistant methicillin-susceptible Staphylococcus aureus (MSSA), potential ST398, in United States Veterans Health Administration Hospitals, 2003-2014. Antimicrobial resistance and infection control. 2017 Jun 5; 6:55.
  3. McDanel JS, Perencevich EN, Diekema DJ, Winokur PL, Johnson JK, Herwaldt LA, Smith TC, Chrischilles EA, Dawson JD, Schweizer ML. Association between microbial characteristics and poor outcomes among patients with methicillin-resistant Staphylococcus aureus pneumonia: a retrospective cohort study. Antimicrobial resistance and infection control. 2015 Dec 14; 4:51.
  4. Nair R, Ammann E, Rysavy M, Schweizer ML. Mortality among patients with methicillin-resistant Staphylococcus aureus USA300 versus non-USA300 invasive infections: a meta-analysis. Infection control and hospital epidemiology. 2014 Jan 1; 35(1):31-41.
  5. Schweizer ML, Reisinger HS, Ohl M, Formanek MB, Blevins A, Ward MA, Perencevich EN. Searching for an optimal hand hygiene bundle: a meta-analysis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2014 Jan 1; 58(2):248-59.
Conference Presentations

  1. Branch-Elliman W, Strymish J, Schweizer ML, Itani K, Ho M, Gupta K. Effectiveness of Vancomycin versus Vancomycin plus Beta-Lactams for Prevention of Surgical Site Infections. Paper presented at: ID Week Annual Conference; 2015 Oct 9; San Diego, CA.
  2. McDanel JS, Roghmann MC, Perencevich EN, Ohl M, Goto M, Livorsi D, Jones MP, Albertson J, Nair R, O'Shea AM, Schweizer ML. Comparative Effectiveness of Third Generation Cephalosporins versus Penicillinase-Stable Penicillins for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort Study. Poster session presented at: ID Week Annual Conference; 2015 Oct 9; San Diego, CA.
  3. McDanel J, Roghmann MC, Perencevich EN, Ohl M, Goto M, Livorsi D, Jones MP, Albertson J, Nair R, O'Shea AM, Schweizer ML. Comparative Effectiveness of Cefazolin versus Penicillinase-Stable Penicillins for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort Study. Oral Presentation. Paper presented at: ID Week Annual Conference; 2015 Oct 8; San Diego, CA.
  4. Nair R, Perencevich EN, Diekema DJ, Torner J, Burns T, Cavanaugh J, Jiang L, Alexander B, Richardson KK, Beck B, Goto M, McDanel J, Schweizer ML. Exchange Arthroplasty is Associated with Reduced Risk for All-cause Mortality in Staphylococcus aureus Prosthetic Joint Infection. Paper presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy / Infectious Diseases Society of America Joint Meeting; 2015 Sep 21; San Diego, CA.
  5. Nair R, Perencevich EN, Diekema DJ, Torner J, Burns T, Cavanaugh J, Jiang L, Alexander B, Beck B, Goto M, McDanel J, Schweizer ML. Association of Rifampin Use with the Risk for Treatment Failure in Staphylococcus aureus Prosthetic Joint Infections. Paper presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy / Infectious Diseases Society of America Joint Meeting; 2015 Sep 19; San Diego, CA.
  6. Nair R, Perencevich EN, Blevins A, Goto M, Schweizer ML. Clinical effectiveness of mupirocin for preventing S. aureus infections in non-surgical settings: A Meta-analysis. Paper presented at: International Biennial Consortium for Prevention and Infection Control; 2015 Jun 17; Geneva, Switzerland.
  7. Schweizer ML, Nelson R, Samore M, Nelson S, Khader K, Slayton RB, Jernigan J, Chiang HY, Chorazy ML, Herwaldt L, Diekema DJ, Formanek MB, Malhotra A, Blevins A, Ward MA. US Costs and Outcomes Associated with Clostridium difficile Infections: a Systematic Literature Review, Meta-analysis, and Mathematical Model. Paper presented at: International Biennial Consortium for Prevention and Infection Control; 2015 Jun 17; Geneva, Switzerland.
  8. Schweizer ML, Nelson R, Samore M, Nelson S, Khader K, Slayton RB, Jernigan J, Chiang HY, Chorazy ML, Herwaldt L, Diekema DJ, Formanek MB, Malhotra A, Blevins A, Ward MA, Perencevich EN. US Costs and Outcomes Associated with Clostridium difficile Infections: a Systematic Literature Review, Meta-analysis, and Mathematical Model. Poster session presented at: ID Week: A Joint Meeting of IDSA, SHEA, HIVMA, and PIDS; 2014 Oct 11; Philadelphia, PA.
  9. Nair R, Perencevich EN, Blevins A, Goto M, Schweizer ML. Clinical effectiveness of mupirocin for preventing S. aureus infections in non-surgical settings: A Meta-analysis. Poster session presented at: ID Week: A Joint Meeting of IDSA, SHEA, HIVMA, and PIDS; 2014 Oct 9; Philadelphia, PA.


DRA: Infectious Diseases
DRE: Epidemiology, Prevention
Keywords: Career Development
MeSH Terms: none