DIAGN MICROBIOL INFECT DIS 311 1991 ;14:311-317 Susceptibility Testing of Listeria monocytogenes A Reassessment of Bactericidal Activity as a Predictor for Clinical Outcome Maria D. Appleman, Charles E. Peter N.R. Heseltine, and Charles W. Stratton Cherubin, In vitro susceptibility testing of Listeria monocytogenes most often reveals both ampicillin and penicillin as inhibito~ as opposed to bactericidal with activity comparable to chloram- phenicol and tetracycline. Yet, the former two penicillins are more effective for Listeria meningitis than are the latter agents. Accordingly, we reassessed the bactericidal activity of agents used in listeriosis in order to determine in vitro meth- odology that would be more predictive of clinical outcome. We found that bactericidal activity for > 48 hr by either minimum inhibitory-minimum bactericidal concentration (MIC-MBC) testing or time-kill kinetic studies was the best predictor of clinical efficacy. This correlation may be due to Listeria being a slow-growing microorganism. In addition to ampicillin and penicillin, we found trimethoprim-sulfamethoxazole, vancomy- cin, and imipenem to exhibit bactericidal activity for 48 hr. For the first two agents, this is in agreement with the results of clinical experience. INTRODUCTION Infections with Listeria monocytogenes have been in- creasing in incidence over the past decade (Gellin and Broome, 1989). Ampicillin or penicillin is con- sidered to be the preferred agent for the treatment of listeriosis, including sepsis and meningitis (Gor- larom the Departments of Pathology (M.D.A.) and Medicine (P.N.R.H.), Los Angeles County/University of Southern Cali- fornia Medical Center, Los Angeles, California; Department of Pathology (C.W.S.), Vanderbilt University Medical Center, Nashville, Tennessee; and Department of Medicine (C.E.C.), Mercy Hospital and Medical Center, and Infectious Disease Section (C.E.C.), Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA. Address reprint requests to Dr. C.W. Stratton, Department of Pathology, C-3217 MCN, Vanderbilt University Medical Center, Nashville, TN 37232-2561, USA. Received 16 July 1990; revised and accepted 6 November 1990. © 1991 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 0732-8893/91/$3.50 don et al., 1970; MacNair and White, 1968; Medoff et al., 1971). The addition of an aminoglycoside to ampicillin or penicillin often is done because of the in vitro demonstration of synergy between these combinations (Gordon et al., 1972 and 1980; Moell- ering et al., 1972). There is the need for alternative therapy for lis- teriosis in penicillin-allergic patients. In addition, there is some evidence that penicillins (with or without an aminoglycoside) may not be the most effective ther- apy for listeriosis. A recent review of Listeria endo- carditis (Carvajal and Frederiksen, 1988) reported a mortality rate of 48% in 44 patients despite the use of penicillins alone or in combination with an ami- noglycoside for the majority of these cases. Also, a recent report of transferable plasmid-mediated an- tibiotic resistance in Listeria monocytogenes (Poyart- Salmeron et al., 1990) suggest that future therapy of listeriosis may require alternate agents because of resistance. Finally, there are older antibiotics, such