P2463 Antibiotic treatment for invasive listeriosis and patient outcome: a retrospective cohort study Yaakov Dickstein*1, Yonatan Oster2, Orit Shimon3, Lior Nesher4, Dafna Yahav5,3, Yonit Wiener-Well6, Regev Cohen7,8, Ronen Ben-Ami9,3, Miriam Weinberger10,3, Galia Rahav11,3, Yasmin Maor12,3, Michal Chowers13,3, Ran Nir-Paz2, Mical Paul8,14

1 Rambam Healthcare Campus, , , 2 Hadassah University - Ein Kerem, , Israel, 3 University, Sackler Faculty of Medicine, Ramat Aviv, Israel, 4 , , Israel, 5 , , Israel, 6 Shaare Zedek, Jerusalem, Israel, 7 Laniado Hospital, , Israel, 8 Technion, The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel, 9 Tel Aviv Sourasky Medical Center , Tel Aviv, Israel, 10 Assaf Harofeh Medical Center, Be’er Ya’akov, Israel, 11 , , Israel, 12 , , Israel, 13 Meir Medical Center, Kefar Sava, Israel, 14 Infectious Diseases Unit, Rambam Health Care Campus, Haifa, Israel Background: Current recommendations for treatment of invasive listeriosis suggest ampicillin-based therapy with the addition of an aminoglycoside. However, several reports have suggested higher morbidity and mortality with this regimen as compared with beta-lactam monotherapy. We aimed to evaluate the association between penicillin-aminoglycoside combination therapy and mortality in patients with invasive listeriosis while adjusting for timing of treatment onset. Materials/methods: This is a multicenter retrospective observational study of adult patients with invasive listeriosis (primary bacteremia, central nervous system [CNS] disease and pregnancy-associated listeriosis) in 11 in Israel between the years 2008-2014. We evaluated the effect of penicillin-based monotherapy compared with early combination therapy with gentamicin, defined as treatment started within 48 hours of culture results and continued for a minimum duration of 7 days. Patients who died within 48 hours of the index culture were excluded. The primary outcome was 30-day all-cause mortality. Subgroup analyses were performed by diagnosis. Results: A total of 246 invasive listeriosis patients were identified of whom 243 were included in the analyses. Seventy-two (29.6%) patients were treated with early combination therapy, 117 (48.1%) received monotherapy and 54 (22.2%) received other treatments. Overall 30-day mortality was 16.0% (39/243). Factors associated with mortality included age, functional capacity, no pregnancy, renal function, congestive heart failure, clinical diagnosis, Sequential Organ Failure Assessment (SOFA) score, elevated liver-function tests and therapy. Time from culture-taken-date to initiation of appropriate therapy was not associated with mortality. In multivariable analysis, a non-significant trend was observed between monotherapy and higher 30-day mortality compared with early combination therapy (OR 1.867, 95%CI 0.653-5.334). Results were similar in patients with non-pregnancy- associated listeriosis (OR 2.069, 95%CI 0.694-6.163), CNS disease (OR 3.037, 95%CI 0.574-16.057) and primary bacteremia (OR 2.983, 95%CI 0.575-15.492). Conclusions: In our retrospective cohort there was no statistically-significant difference between monotherapy and combination therapy, but possibly a clinically-significant benefit to combination therapy. Our results were limited by sample size which may have been insufficient to show superiority of one antibiotic regimen to the other. A randomized controlled trial may be necessary to assess optimal treatment. Figure 1: Survival function based on treatment group

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