Nosocomial Legionella micdadei infection in transplant patients: fortune favors the prepared mind

In 1977, investigators from the University of Pittsburgh and the University of Virginia observed weakly acid-fast organisms in lung tissue of immunosuppressed patients with pneumonia of unknown causes (1,2). The patients from Pittsburgh were all renal transplant recipients. The organism, however, could not be grown on standard bacteriologic and Mycobacterium tuberculosis culture media, and was named the Pittsburgh Pneumonia Agent because it was unclear if it was a bacterium. After the discovery of Legionella pneumophila, lung tissue specimens containing the Pittsburgh Pneumonia Agent were inoculated into guinea pigs and embryonated eggs, and a bacterium was finally isolated (1). Pittsburgh investigators named this organism Legionella pittsburghensis or Tatlockia micdadei, and Centers for Disease Control (CDC) investigators named it Legionella micdadei (3). Forty-one other Legionella species have since been discovered, 18 of which have been implicated as causes of pneumonia (4). The relative rarity of infection from L. micdadei (and other species) derives from its lower virulence and less favorable growth kinetics in potable water, thus reducing the chance for exposure (4,5). Patients with L. micdadei infection are more likely to be immunocompromised than patients with L. pneumophila infection, and mortality is lower (4,6). In some centers, Legionella is the most frequent cause of pneumonia in transplant recipients, accounting for 25% to 50% of cases (7). Heart, kidney, liver, and lung transplant recipients are at the greatest risk, while bone marrow transplants have the lowest risk. Nosocomial outbreaks in transplant hospitals have been reported, with attack rates as high as 50%. The hospital water system is the usual source. Aspiration of contaminated water, rather than aerosolization, is the dominant mode of transmission. This may explain the relatively lower incidence of Legionella infections in bone marrow recipients; since the organism is usually acquired in the early postoperative period following solid organ transplants, intubation may be the precipitating factor. Nosocomial legionellosis is vastly underdiagnosed, primarily because diagnostic methods are often not available in-house. Less than 19% of transplant hospitals performed routine laboratory testing for Legionella (8). Of greater concern, even among those hospitals that had experienced nosocomial Legionnaires’ disease, only 21% applied routine Legionella testing for respiratory specimens. In this issue of The American Journal of Medicine, Knirsch and colleagues performed a superb epidemiologic investigation of nosocomial L. micdadei infection in transplant patients (9). Isolation of L. micdadei from bronchoscopy specimens from two renal transplant patients who contracted pneumonia during a 1-week period prompted the authors to perform retrospective surveillance for Legionella infection. This surveillance was possible because of the fortuitous availability of stored sera used for white blood cell (HLA) crossmatching. In their initial survey, 11 transplant patients with pneumonia were found to have elevated antibody titers to L. micdadei, and in 3 of these patients L. micdadei was isolated from culture of bronchoscopy specimens, illustrating that fortune favors the prepared mind. The authors then isolated L. micdadei from several sites within the hospital’s hot water supply. The environmental isolates had a DNA banding pattern that was identical to the clinical isolates, supporting the hypothesis that the hospital water supply was the source of the outbreak. A hospital’s ability to perform Legionella cultures in its microbiology laboratories is crucial for uncovering unsuspected nosocomial legionellosis. Knirsch et al were successful in isolating L. micdadei from patient specimens and the hospital water system, even though the medium used—nonselective buffered charcoal yeast extract (BCYE)—was suboptimal for the isolation of L. micdadei from bronchoscopy specimens. The isolation of Legionella usually requires the addition of antimicrobial agents to inhibit competing microflora. For optimal recovery, two selective media—BCYE-alpha supplemented with polymyxin B, anisomycin, vancomycin, and dyes, or BCYE-alpha supplemented with polymyxin B, anisomycin, and cefamandole—should have been used (10). The dyes (bromocresol purple and bromothymol blue) are important additives that allow for visual differentiation of L. pneumophila (light green colonies) and L. micdadei (blue colonies) (4) (Figure). Some Legionella species, including L. micdadei, are inhibited by antibiotics, particularly cefamandole (11); thus the vancomycin-containing Am J Med. 2000;108:346 –348. From the Special Pathogens Laboratory and Infectious Disease Section, VA Medical Center, Pittsburgh, and University of Pittsburgh, Pittsburgh. Requests for reprints should be addressed to Victor L. Yu, MD, VA Medical Center, Infectious Disease Section, University Drive C, Pittsburgh, Pennsylvania 15240.