In Vitro Activity of Antimicrobial Agents on Legionnaires Disease Bacterium

Abstract

Six isolates of Legionnaires disease bacteria were tested for their susceptibility to 22 antimicrobial agents. The most active agent was rifampin (minimal inhibitory concentration, ≤0.01 μg/ml). On the basis of minimal inhibitory concentration breakpoints that have been used to categorize susceptibility for most of these drugs, the organisms were susceptible to rifampin, cefoxitin, erythromycin, the aminoglycosides, minocycline and doxycycline, chloramphenicol, ampicillin, penicillin G, carbenicillin, colistin, and sulfamethoxazole-trimethoprim (19:1 ratio); sensitive to intermediate in susceptibility to tetracycline, methicillin, cefamandole, cephalothin, and clindamycin; and resistant to vancomycin. More clinical data must be obtained before an optimal therapeutic regimen can be recommended.

Inhibition of Legionella pneumophila multiplication within human macrophages by antimicrobial agents

“…This fact is well illustrated by the discrepancy between the conventional MIC and the MIEC of cefoxitin as demonstrated in the macrophage model. Cefoxitin, which among the cephalosporins has the lowest MIC (23) and is resistant to the P-lactamase of L. pneumophila (11), had no bacteriostatic effect on intracellu-0(1.0) lar L. pneumophila even at a concentration as high as 64 ,ug/ml. Similar results have been obtained with peritoneal macrophages of guinea pigs (26).…”

“…However, the clinical efficacy of sulfamethoxazole-trimethoprim against Legionnaires disease is still to be confirmed (17). The determination of the MICs of sulfamethoxazole-trimethoprim and sulfarnethoxazole against L. pneumophila remains an unresolved question with large variations (3,5,20,23) caused by the nature and compounds of the culture medium (5). This emphasizes the interest of the MIEC determination in a cell culture model.…”

Intracellular multiplication of Legionnaires' disease bacteria (Legionella pneumophila) in human monocytes is reversibly inhibited by erythromycin and rifampin.

“…Several antibiotics active against L. pneumophila growing on artificial medium have been found to lack efficacy against L. pneumophila in vivo (8)(9)(10)(11). It is noteworthy that one such antibiotic, penicillin G, was reported by Johnson et al (22) to be taken up very poorly by rabbit alveolar macrophages; in contrast, erythromycin and rifampin, which are active against L. pneumophila both in vivo and under cell-free conditions, were taken up readily by rabbit alveolar macrophages (8)(9)(10)(11)22). In fact, erythromycin and rifampin were among the few antibiotics tested that were concentrated in rabbit alveolar macrophages-erythromycin 20-fold and rifampin twofold (22).…”

“…Egg yolk buffer (EYB), with (EYB-BSA) or without 1% bovine serum albumin, and RPMI 1640 medium were prepared or obtained as described previously (1). Buffered yeast extract (BYE) broth, pH 6.9, was prepared with 5 g/ liter bovine serum albumin fraction V (Reheis Co., Inc., Armour Pharmaceutical Co., Phoenix, AZ), 10 in methanol, diluted in water to 1,000 Ag activity/ml, and stored in small aliquots in vials at -70'C. On the day of the experiments the frozen preparation was thawed and diluted to the desired concentration in RPMI 1640 medium.…”

“…Both clinical experience and in vivo studies indicate that these antibiotics are efficacious in treating Legionnaires' disease (6)(7)(8)(9). L. pneumophila grown under cell-free conditions on artificial media is inhibited from multiplying by these antibiotics and is killed by concentrations of these antibiotics that are the same or somewhat higher than the minimal inhibitory concentration (MIC)' (10,11).…”