Antimicrobial Susceptibility of the 

 Legionnaires' Disease Bacterium 



Clyde Thornsberry and Linda A. Kirreii 



In 1976 an outbreak of acute respiratory disease, later called "Legionnaires' disease," 

 occurred among people who had attended a convention in Pliiladelpiiia, Pennsylvania (5). The 

 causative agent, later identified as a bacterium (9), is referred to as the Legionnaires" disease 

 bacterium (LDB). Since 1976, more than 500 cases with 79 fatalities have been identified from 

 outbreaks (2). As of October 31, 1978, 453 sporadic cases with 86 fatalities had been confirmed 

 in 43 states and the District of Columbia (4). 



A review of the antimicrobial therapy used for patients with Legionnaires' disease showed 

 that case-fatahty rates were highest for those treated with cephalosporins and were intermediate 

 for those treated with aminoglycosides, chloramphenicol, ampicillin. or penicillin. Lowest rates 

 were for patients who received tetracycline or erythromycin (5). Some patients have been success- 

 fully treated with a combination of intravenous oxytetracycline and rifamycin ilO). Doxy- 

 cycline was effective in another patient, but gentamicin was not (7). 



In vivo studies have been performed with a guinea pig animal model {.\ 6. 11 ) and with 

 an embryonated hens' egg model (S). In the first in vivo study of therapy for an infection in an 

 animal model, erythromycin was demonstrated to be effective in treating infected guinea pigs iS). 

 All of the guinea pigs treated witli erythromycin survived, whereas all the infected controls died. 

 Later the same investigators used five other antimicrobial agents to treat guinea pigs infected 

 with lethal doses of the LDB (77). The most effective drug was minocycline hydrochloride, 

 which was associated with a 50^''f survival rate. Rifampin was less effective than minocycline, and 

 the aminoglycosides (gentamicin, tobramycin, and amikacin) were essentially ineffective, even 

 though they are very active in vitro. 



In another in vivo study, guinea pigs were infected with the LDB and then treated with 

 antibiotics (6). Erythromycin and rifampin were the most effective drugs in preventing mortahty. 

 Penicillin, chloramphenicol, tetracycline, and gentamicin had no significant effect (6). 



In the embryonated hens' egg model studies (6'), rifampin (followed by gentamicin, strepto- 

 mycin, erythromycin, sulfadiazine, and chloramphenicol, in that order) most effectively pre- 

 vented death of the embryo. The least effective drugs were cephalothin. which protected only if 

 large amount were used, and oxytetracycline, whicii partially protected embryos. Ampicillin at 

 the highest levels tested did not prevent or delay death of the embryo (A). 



In vitro studies, with agar dilution and broth microdilution techniques, showed that rifam- 

 pin was the most active agent, but that the macrolides (erythromycin and rosamicin), the amino- 

 glycosides (gentamicin, tobramycin, and amikacin), cotrimoxazole (sulfamethoxozole, 19 parts 

 plus trimethoprim, 1 part), and chloramphenicol were very active (J J. 13). Minimum inhibitory 

 concentrations (MICs) obtained in these studies indicate that the LDB would be only slightly 

 susceptible to commonly used (3-lactam antibiotics (cephalosporins and penicillins). The most 

 active |3-lactam antibiotic tested was cefoxitin (a cefamycin, which has only recently been ap- 

 proved by the Food and Drug Administration for general use) {IJ). 



56 



