Little evidence exists addressing the clinical value of adding gentamicin to ampicillin for invasive listeriosis. A multicenter retrospective observational study of nonpregnant adult patients with invasive listeriosis (primary bacteremia, central nervous system (CNS) disease, and others) in 11 hospitals in Israel between the years 2008 and 2014 was conducted. We evaluated the effect of penicillin-based monotherapy compared with early combination therapy with gentamicin, defined as treatment started within 48 h of culture results and continued for a minimum of 7 days. Patients who died within 48 h of the index culture were excluded. The primary outcome was 30-day all-cause mortality. A total of 190 patients with invasive listeriosis were included. Fifty-nine (30.6%) patients were treated with early combination therapy, 90 (46.6%) received monotherapy, and 44 (22.8%) received other treatments. Overall 30-day mortality was 20.5% (39/190). Factors associated with mortality included lower baseline functional status, congestive heart failure, and higher sequential organ failure assessment score. Source of infection, treatment type, and time from culture taken date to initiation of effective therapy were not associated with mortality. In multivariable analysis, monotherapy was not significantly associated with increased 30-day mortality compared with early combination therapy (OR 1.947, 95% CI 0.691–5.487). Results were similar in patients with CNS disease (OR 3.037, 95% CI 0.574–16.057) and primary bacteremia (OR 2.983, 95% CI 0.575–15.492). In our retrospective cohort, there was no statistically significant association between early combination therapy and 30-day mortality. A randomized controlled trial may be necessary to assess optimal treatment.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Charlier C, Perrodeau E, Leclercq A et al (2017) Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study. Lancet Infect Dis 17(5):510–519
de Noordhout CM, Devleesschauwer B, Angulo FJ et al (2014) The global burden of listeriosis: a systematic review and meta-analysis. Lancet Infect Dis 14(11):1073–1082
Elinav H, Hershko-Klement A, Valinsky L et al (2014) Pregnancy-associated listeriosis: clinical characteristics and geospatial analysis of a 10-year period in Israel. Clin Infect Dis 59(7):953–961
Gerner-Smidt P, Ethelberg S, Schiellerup P et al (2005) Invasive listeriosis in Denmark 1994-2003: a review of 299 cases with special emphasis on risk factors for mortality. Clin Microbiol Infect 11(8):618–624
Goulet V, Hebert M, Hedberg C et al (2012) Incidence of listeriosis and related mortality among groups at risk of acquiring listeriosis. Clin Infect Dis 54(5):652–660
Guevara RE, Mascola L, Sorvillo F (2009) Risk factors for mortality among patients with nonperinatal listeriosis in Los Angeles County, 1992-2004. Clin Infect Dis 48(11):1507–1515
Koopmans MM, Bijlsma MW, Brouwer MC, van de Beek D, van der Ende A (2017) Listeria monocytogenes meningitis in the Netherlands, 1985-2014: a nationwide surveillance study. J Infect 75(1):12–19
van de Beek D, Cabellos C, Dzupova O et al (2016) ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect 22(Suppl 3):S37–S62
Gordon RC, Barrett FF, Yow MD (1970) Ampicillin treatment of listeriosis. J Pediatr 77(6):1067–1070
Lavetter A, Leedom JM, Mathies AW Jr, Ivler D, Wehrle PF (1971) Meningitis due to Listeria monocytogenes. A review of 25 cases. N Engl J Med 285(11):598–603
Macnair DR, White JE, Graham JM (1968) Ampicillin in the treatment of Listeria monocytogenes meningitis. Lancet 1(7532):16–17
Azimi PH, Koranyi K, Lindsey KD (1979) Listeria monocytogens: synergistic effects of ampicillin and gentamicin. Am J Clin Pathol 72(6):974–977
Gordon RC, Barrett FF, Clark DJ (1972) Influence of several antibiotics, singly and in combination, on the growth of Listeria monocytogenes. J Pediatr 80(4):667–670
McCracken GH Jr, Nelson JD, Thomas ML (1973) Discrepancy between carbenicillin and ampicillin activities against enterococci and Listeria. Antimicrob Agents Chemother 3(3):343–349
Moellering RC Jr, Medoff G, Leech I, Wennersten C, Kunz LJ (1972) Antibiotic synergism against Listeria monocytogenes. Antimicrob Agents Chemother 1(1):30–34
Mohan K, Gordon RC, Beaman TC et al (1977) Synergism of penicillin and gentamicin against Listeria monocytogenes in ex vivo hemodialysis culture. J Infect Dis 135(1):51–54
Wiggins GL, Albritton WL, Feeley JC (1978) Antibiotic susceptibility of clinical isolates of Listeria monocytogenes. Antimicrob Agents Chemother 13(5):854–860
Edmiston CE Jr, Gordon RC (1979) Evaluation of gentamicin and penicillin as a synergistic combination in experimental murine listeriosis. Antimicrob Agents Chemother 16(6):862–863
Hof H, Guckel H (1987) Lack of synergism of ampicillin and gentamicin in experimental listeriosis. Infection 15(1):40–41
Kim KS (1986) In vitro and in vivo studies of imipenem-cilastatin alone and in combination with gentamicin against Listeria monocytogenes. Antimicrob Agents Chemother 29(2):289–293
Scheld WM, Fletcher DD, Fink FN, Sande MA (1979) Response to therapy in an experimental rabbit model of meningitis due to Listeria monocytogenes. J Infect Dis 140(3):287–294
Amaya-Villar R, Garcia-Cabrera E, Sulleiro-Igual E et al (2010) Three-year multicenter surveillance of community-acquired Listeria monocytogenes meningitis in adults. BMC Infect Dis 10:324
Mitja O, Pigrau C, Ruiz I et al (2009) Predictors of mortality and impact of aminoglycosides on outcome in listeriosis in a retrospective cohort study. J Antimicrob Chemother 64(2):416–423
Mylonakis E, Hohmann EL, Calderwood SB (1998) Central nervous system infection with Listeria monocytogenes. 33 years’ experience at a general hospital and review of 776 episodes from the literature. Medicine (Baltimore) 77(5):313–336
Suarez MM, Bautista RM, Almela M et al (2007) Listeria monocytogenes bacteremia: analysis of 110 episodes. Med Clin (Barc) 129(6):218–221
Thonnings S, Knudsen JD, Schonheyder HC et al (2016) Antibiotic treatment and mortality in patients with Listeria monocytogenes meningitis or bacteraemia. Clin Microbiol Infect 22(8):725–730
Arslan F, Meynet E, Sunbul M et al (2015) The clinical features, diagnosis, treatment, and prognosis of neuroinvasive listeriosis: a multinational study. Eur J Clin Microbiol Infect Dis 34(6):1213–1221
Pelegrin I, Moragas M, Suarez C et al (2014) Listeria monocytogenes meningoencephalitis in adults: analysis of factors related to unfavourable outcome. Infection 42(5):817–827
Fernandez Guerrero ML, Torres R, Mancebo B et al (2012) Antimicrobial treatment of invasive non-perinatal human listeriosis and the impact of the underlying disease on prognosis. Clin Microbiol Infect 18(7):690–695
Salama M, Amitai Z, Ezernitchi AV et al (2018) Surveillance of listeriosis in the Tel Aviv District, Israel, 2010-2015. Epidemiol Infect 146(3):283–290
Vasilev V, Japheth R, Andorn N et al (2009) A survey of laboratory-confirmed isolates of invasive listeriosis in Israel, 1997-2007. Epidemiol Infect 137(4):577–580
Jerusalem: Israeli Ministry of Health (2016) Licensed hospitalization beds and sites. Department of Information, Health Division. https://www.health.gov.il/PublicationsFiles/beds2016.pdf. Accessed 28.10.2018.
Paul M, Lador A, Grozinsky-Glasberg S, Leibovici L (2014) Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev 1:CD003344
Paul M, Dickstein Y, Schlesinger A, Grozinsky-Glasberg S, Soares-Weiser K, Leibovici L (2013) Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropenia. Cochrane Database Syst Rev 6:CD003038
Baddour LM, Wilson WR, Bayer AS et al (2015) Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation 132(15):1435–1486
Leibovici L (2010) Aminoglycoside-containing antibiotic combinations for the treatment of bacterial endocarditis: an evidence-based approach. Int J Antimicrob Agents 36(Suppl 2):S46–S49
Paul M, Leibovici L (2013) Editorial commentary: combination therapy for Pseudomonas aeruginosa bacteremia: where do we stand? Clin Infect Dis 57(2):217–220
Kortebi M, Milohanic E, Mitchell G et al (2017) Listeria monocytogenes switches from dissemination to persistence by adopting a vacuolar lifestyle in epithelial cells. PLoS Pathog 13(11):e1006734
Bakardjiev AI, Theriot JA, Portnoy DA (2006) Listeria monocytogenes traffics from maternal organs to the placenta and back. PLoS Pathog 2(6):e66
Jones EM, Howe RA, MacGowan AP (1997) Treatment of listeria meningitis. Lancet 350(9083):1034
Hawkins AE, Bortolussi R, Issekutz AC (1984) In vitro and in vivo activity of various antibiotics against Listeria monocytogenes type 4b. Clin Invest Med 7(4):335–341
Marklein G, Hafelein J (1981) In vitro susceptibility of Listeria monocytogenes with special reference to newer beta lactam antibiotics (author’s transl). Zentralbl Bakteriol Mikrobiol Hyg A 251(1):40–53
Conflict of interest
The authors declare that they have no conflict of interest.
The study was approved by the ethics committees of all participating institutions.
Informed consent was not applicable given the retrospective observational nature of the study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
All authors have seen and approved the manuscript and contributed significantly to the work, and the manuscript has not been previously published nor is not being considered for publication elsewhere.
Data from this article were presented as a poster at the 29th European Congress of Clinical Microbiology and Infectious Diseases, April 2019.
Electronic supplementary material
About this article
Cite this article
Dickstein, Y., Oster, Y., Shimon, O. et al. Antibiotic treatment for invasive nonpregnancy-associated listeriosis and mortality: a retrospective cohort study. Eur J Clin Microbiol Infect Dis 38, 2243–2251 (2019). https://doi.org/10.1007/s10096-019-03666-0
- CNS infection
- Combination therapy