Bioquimica

ANTIMICROBIAL AGENTS

AND

CHEMOTHERAPY, Aug. 1982, p. 289-294

Vol. 22, No. 2

0066-4804/82/080289-06$02.00/0

Effects of Erythromycin in Combination with Penicillin, Ampicillin, or Gentamicin on the Growth of Listeria monocytogenes
ROBERT L. PENN,t THOMAS T. WARD,t AND ROY T. STEIGBIGEL* Infectious Diseases Unit, Department of Medicine, University of Rochester School of Medicine,Rochester,
New York 14642

Received 1 March 1982/Accepted 26 May 1982

Since the optimal antimicrobial therapy for infections caused by Listeria monocytogenes, particularly in patients allergic to penicillin, is uncertain, we investigated the in vitro effects of erythromycin, alone and in combination with other antibiotics, on listeriae. Seven strains of listeriae were inhibited but not killedby erythromycin, penicillin G, or ampicillin when tested by a microtiter broth dilution method. Susceptibility to gentamicin decreased when tryptose phosphate broth was substituted for Mueller-Hinton broth, but was independent of their calcium and magnesium concentrations. Quantitative killing studies performed with erythromycin combined with either penicillin G or ampicillin yielded antagonism forall strains, in contrast to microtiter checkerboard determinations, which did not indicate antagonism in all instances. Antagonism occurred with strains in both the stationary and log phases of growth and was slightly reversed by a 120-min preincubation of the listeriae with penicillin before the addition of erythromycin. Erythromycin and gentamicin were antagonistic in quantitative killingstudies. Based on these in vitro findings, we conclude that the addition of gentamicin to erythromycin offers no advantage in the treatment of listeriosis in the penicillin-allergic patient.
There is a need to optimize the antibiotic therapy of infections due to Listeria monocytogenes since this species has a predilection for causing life-threatening illness in the infirm, the neonate, and theimmunosuppressed (2, 7, 14). Furthermore, L. monocytogenes is inhibited in growth but not killed by easily achievable concentrations of those antibiotics to which it is most susceptible (12, 21). Erythromycin on a weight basis has the greatest inhibitory activity against listeriae and is the most commonly suggested therapeutic alternative for the penicillin-allergic patient. Recommendations for thetherapy of serious listeriosis have included antibiotic combinations, such as penicillin combined with gentamicin and erythromycin combined with penicillin (7, 14). In addition, erythromycin is often combined with other antimicrobial agents given to immunosuppressed patients because of its minor side effects and its activity against major respiratory pathogens (3). The effects of potentially usefulantibit Present address: Infectious Diseases, Medical Service (111), Veterans Adiinistration Medical Center, Shreveport, LA 71130. t Present address: Infectious Disease Section, Department of Medicine, Veterans Administration K'edical Center, Portland, OR 97201.

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otic combinations which include erythromycin have not been evaluated for theirinteractions with listeriae. Therefore, we investigated the in vitro effects on L. monocytogenes of erythromycin when combined with penicillin G, ampicilllin, or gentamicin, to evaluate the potential of combination therapy of listeriosis in the penicillin-allergic patient.
MATERIAL AND METHODS Bacterial strains. The seven strains of L. monocytogenes were isolated from either blood or cerebrospinalfluid submitted to the Clinical Microbiology Laboratory, Strong Memorial Hospital, Rochester, N.Y. Confirmation of the identity and serotyping were performed by the Centers for Disease Control. Listeriae were stored at 4°C on Trypticase (BBL Microbiology Systems, Cockeysville, Md.) soy agar (TSA) slants. In preparation for each experiment, listeriae were incubated at 37°C in Trypticase soy broth...