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Comparative Effectiveness of Trimethoprim-Sulfamethoxazole Vs

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Comparative Effectiveness of Trimethoprim-Sulfamethoxazole Vs Poster # 776 Comparative Effectiveness of Trimethoprim-Sulfamethoxazole vs. Levofloxacin for Stenotrophomonas maltophilia Bacteremia: Analysis of targeted therapy at 90 US Hospitals, 2000-2015 Yi Ling Lai, MPH1, Jennifer Adjemian, PhD1,2, Emily E. Ricotta, ScM1, John P. Dekker3, Robert L. Danner, MD4, Sameer S. Kadri, MD, MS4 1Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA; 2United States Public Health Service, Commissioned Corps, Rockville, MD, USA; National Institutes of Health 3Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD 4Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD INTRODUCTION RESULTS • Stenotrophomonas maltophilia is an opportunistic pathogen with overall low virulence, Figure 2. Proportion of TMP-SMX patients vs. LVX patients with ICU stays during hospitalization Figure 2. Adjusted relative risk (aRR) of targeted therapy choice on mortality controlling for empiric use but is commonly associated with nosocomial infections in immune compromised and and other patient-and facility level factors among a cohort of patients with S. maltophilia bacteremia critically ill populations with ventilator–associated pneumonia and central line- associated bloodstream infections being the most common presentations. ICU Status • The prevalence of S. maltophilia bloodstream infections (BSIs) is estimated between 80 0.70% and 0.95% of all pathogens of BSI worldwide, and is greater in the ICU setting (1.6 - 3.0%)1. 60 • Despite low prevalence, S. maltophilia infections are difficult to treat due to intrinsic or 40 acquired resistance to many antibiotic classes including aminoglycosides, β-lactams, tetracycline, quinolones, and other antibiotic classes2. Therefore, empiric antibiotic 20 regimens often do not include S. maltophilia active agents. P=0.95 0 • Most S. maltophilia isolates are generally susceptible to trimethoprim-sulfamethoxazole TMP-SMX Levofloxacin (TMP-SMX) and levofloxacin (LVX) by in vitro susceptibility testing, but their relative effectiveness in treating S. maltophilia infections is still unclear. Yes No Figure 3. Proportion of TMP-SMX patients vs. LVX patients with central venous catheter use METHODS during hospital stay Data source: A retrospective cohort study was conducted in the CernerTM Healthfacts Central Venous Catheter Use Database: a large multicenter data repository with linked electronic records of patient 40 encounter-level data, medication administrations and microbiology and susceptibility results. 30 Hospitals are well distributed by bed size, geographic region, and teaching status. 20 Figure 1. Selection of Study Population 10 P=0.97 0 • aRR for ICU stay, pulmonary source, Elixhauser score, facility teaching status, geographic region, gender, facility TMP-SMX Levofloxacin indicator, age, urban-rural setting, and empiric therapy of either fluoroquinolones or TMP-SMX are not significant Figure 4. Proportion of TMP-SMX patients vs. LVX patients having pulmonary source of blood stream infection RESULTS Pulmonary Source • Of 171,909 patients with bacteremia from 2000 to 2015, 660 (0.4%) at 102/185 hospitals had S. maltophilia. 20 • Most bloodstream isolates were susceptible to TMP-SMX (99%), and to FQs (97%). • Of 600 evaluable patients, 122 (20%) received targeted therapy with TMP-SMX and 107 (18%) with LVX. 15 • S. maltophilia bacteremia occurs more frequently in patients at >200 beds, urban, and teaching hospitals. • Nearly a third of S. maltophilia patients had ICU stays, and over a third had a central venous catheter placed. 10 • S. maltophilia patients with central venous catheter or with pulmonary source of bacteremia were more likely to have received LVX. 5 • The use of TMP-SMX as target therapy treating S. maltophilia bacteremia peaked in 2006 and subsequently P=0.33 decreased, while the use of LVX as target therapy has progressively increased from 2000 to 2015. 0 • Crude Mortality was 17% in TMP-SMX and 14% in LVX treated patients. Adjusted mortality risk was 3 times TMP-SMX Levofloxacin greater in recipients of targeted therapy with TMP-SMX vs. LVX (aRR=2.9 95%CI[1.4-5.8]). Figure 5. Distribution of TMP-SMX vs. LVX treated S. maltophilia bacteremia cases from 2000 • Risk of mortality for TMP-SMX vs. LVX recipients is analyzed after excluding recipients of empiric therapy with to 2015 TMP-SMX or FQ, and it remains significant (aRR=3.4 95% CI [1.1-10.0]). CONCLUSIONS • In this multicenter cohort of S. maltophilia bacteremia, targeted treatment with LVX was associated with a lower relative risk of mortality compared to TMP-SMX, even when these agents were used empirically. • Overall TMP-SMX use for S. maltophilia bacteremia has decreased and the converse is true for LVX. • Factors affecting the decision to use LVX vs. TMP-SMX should be included in future analysis in order to further pinpoint the true risk associated with using each agent for the targeted therapy of S. maltophilia bacteremia. REFERENCE 1 Chang et al. (2015) Update on infections caused by Stenotrophomonas maltophilia with particular attention to resistance mechanisms and therapeutic options. Front. Microbiol. 6:893. doi: 10.3389/fmicb.2015.00893 2 Sánchez MB (2015) Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia. Front. • Modified Poisson regression was used to estimate the adjusted relative risk (aRR) of Microbiol. 6:658. doi: 10.3389/fmicb.2015.00658 therapy choice on mortality, controlling for empiric use, patient and facility-level factors Support: Division of Intramural Research, NIAID, NIH; Clinical Center, NIH.
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