Antibiotic treatment for invasive listeriosis and patient outcome: a retrospective cohort study Yaakov Dickstein1, Yonatan Oster2, Orit Shimon3, Lior Nesher4, Dafna Yahav3,5, Yonit Wiener-Well6, Regev Cohen7,8, Ronen Ben-Ami3,9, Miriam Weinberger3,10, Galia Rahav3,11, Yasmin Maor3,12, Michal Chowers3,13, Ran Nir-Paz2, Mical Paul1,8 1 Institute of Infectious Diseases, Rambam Health Care Campus, Haifa, Israel 2 Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel 3 Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel 4 Infectious Disease Institute, Soroka Medical Center, Ben-Gurion University of the Negev, Beer Sheba, Israel 5 Infectious Diseases Unit, Rabin Medical Center, Beilinson hospital, Petah-Tikva, Israel 6 Infectious Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel 7 Infectious Diseases Unit, Sanz Medical Center–Laniado Hospital , Netanya, Israel 8 The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel 9 Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel 10 Infectious Diseases Unit, Assaf Harofeh Medical Center, Zerifin, Israel 11 Infectious Disease Unit, Sheba Medical Center, Ramat Gan, Israel 12 Infectious Disease Unit, Wolfson Medical Center, Holon, Israel 13 Infectious Diseases Unit, Meir Medical Center, Kfar Saba, Israel Cumulative survival by treatment group Background: Current treatment started within 48 hours of culture recommendations for treatment of results and continued for a minimum duration invasive listeriosis suggest ampicillin- of 7 days. Patients who died within 48 hours of based therapy with the addition of an the index culture were excluded. The primary aminoglycoside. However, several outcome was 30-day all-cause mortality. reports have suggested higher Subgroup analyses were performed by morbidity and mortality with this diagnosis. regimen as compared with beta-lactam Results: A total of 190 invasive listeriosis monotherapy. We aimed to evaluate patients were included in the analyses. Fifty- the association between penicillin- nine (30.6%) patients were treated with early aminoglycoside combination therapy combination therapy, 90 (46.6%) received and mortality in patients with invasive Early combi – Early combination therapy; Mono – Penicillin monotherapy Primary bacteremia, multiple variable analysis for 30-day mortality listeriosis while adjusting for timing of Variable OR 95% CI Lower 95% CI Upper p associated compared with early Age 1.006 0.971 1.042 0.742 monotherapy and 44 (22.8%) received other treatment onset. Fully functional 0.337 0.119 0.956 0.041 No CKD Reference treatments. Overall 30-day mortality was combination therapy (OR 1.947, 95%CI Materials/methods: We performed a CKD Stage I-II 1.067 0.235 4.851 0.933 CKD Stage III-V 1.416 0.269 7.459 0.682 20.5% (39/190). Factors associated with 0.691-5.487). Results were similar in CHF 1.256 0.344 4.589 0.730 multicenter retrospective observational SOFA 1.149 1.025 1.288 0.017 Early combination therapy Reference mortality included lower baseline functional patients with CNS disease (OR 3.037, study of non-pregnant adult patients Monotherapy 2.983 0.575 15.492 0.193 Other 4.579 0.761 27.563 0.097 status, congestive heart failure and higher 95%CI 0.574-16.057) and primary with invasive listeriosis (primary CHF – Congestive heart failure; CKD – Chronic kidney disease; SOFA – Sequential organ sequential organ failure assessment (SOFA) bacteremia (OR 2.983, 95%CI 0.575- bacteremia, central nervous system failure assessment CNS infection, multiple variable analysis for 30-day mortality score. Source of infection, treatment type and 15.492). [CNS] disease and other) in 11 Variable OR 95% CI Lower 95% CI Upper p Age 1.005 0.969 1.042 0.787 time from culture taken date to initiation of Conclusions: In our retrospective cohort hospitals in Israel between the years Fully functional 0.340 0.120 0.963 0.042 No CKD Reference effective therapy were not associated with there was no statistically-significant 2008-2014. We evaluated the effect of CKD Stage I-II 0.977 0.195 4.881 0.977 CKD Stage III-V 1.450 0.275 7.654 0.662 mortality. In multivariable analysis, lower CHF 1.256 0.344 4.589 0.730 difference between monotherapy and penicillin-based monotherapy SOFA 1.142 1.015 1.286 0.028 Early combination therapy Reference baseline functional status and higher SOFA combination therapy. A randomized compared with early combination Monotherapy 3.037 0.574 16.057 0.191 Other 4.936 0.810 30.086 0.083 score were associated with increased 30-day controlled trial may be necessary to assess therapy with gentamicin, defined as CHF – Congestive heart failure; CKD – Chronic kidney disease; SOFA – Sequential organ failure assessment mortality. Monotherapy was not significantly optimal treatment..