Avelumab for the treatment of metastatic Merkel cell carcinoma.

Avelumab is a promising new therapeutic agent for patients with metastatic Merkel cell carcinoma, a rare and aggressive type of neuroendocrine tumor of the skin. Until the recent approval of avelumab (Bavencio), no therapies were approved by the U.S. Food and Drug Administration for the treatment of metastatic Merkel cell carcinoma. In a recent trial, avelumab, an anti-programmed death ligand-1 antibody, demonstrated an objective response in 28 of 88 patients (31.8% [95.9% CI, 21.9-43.1]) with advanced, chemotherapy-refractory Merkel cell carcinoma. Overall, avelumab was well tolerated at a dose of 10 mg/kg administered intravenously every 2 weeks. Serious treatment-related adverse events were reported in 5 patients (6%), but no grade 4 adverse events or treatment-related deaths were reported. Preliminary data evaluating avelumab in chemotherapy-naive patients is also encouraging.

Microtubule nucleating capacity of centrosomes in tissue sections.

We used a novel adaptation of methods for microtubule polymerization in vitro to assess the MTOC activity of centrosomes in frozen-sectioned tissues. Remarkably, centrosomes of tissue sections retain the ability to nucleate microtubules even after several years of storage as frozen tissue blocks. Adaptations of these methods allow accurate counts of microtubules from individual cells and the quantitative estimation the MTOC activity of the intact tissue. These methods can be utilized to characterize MTOC activity in normal and diseased tissues and in particular tissues at different stages of development. (J Histochem Cytochem 47:1265-1273, 1999)

Susceptibility of Pittsburgh pneumonia agent (Legionella micdadei) and other newly recognized members of the genus Legionella to nineteen antimicrobial agents.

The susceptibilities of 11 strains representing the five recognized species of Legionella were determined by agar dilution testing on buffered charcoal-yeast extract agar. All of the legionellae tested were susceptible to rifampin, erythromycin, rosaramycin, chloramphenicol, and the aminoglycosides and were resistant to clindamycin and vancomycin. Susceptibilities to penicillins and cephalosporins were variable. Legionella micdadei, Legionella bozemanii, and Legionella gormanii were susceptible to these agents, but minimal inhibitory concentrations for each species were different. Legionella dumoffii resembled Legionella pneumophila in being resistant to penicillin, cephalothin, and cephamandole and susceptible to moxalactam and cefoxitin. All species except L. micdadei produced beta-lactamase.

A cluster of Acinetobacter Pneumonia in foundry workers.

In a 3-month period, three men who had worked for 5 to 19 years as welders or grinders of steel castings in a foundry acquired pneumonia caused by Acinetobacter calcoaceticus variety anitratus serotype 7J. Two of the men died, and postmortem examination showed mixed-dust pneumoconiosis with iron particles in the lungs. A calcoaceticus variety anitratus serotype 7J was isolated from the air in the foundry but the source was not found. The prevalence of antibody titers of 64 or greater to the 7J strain was significantly higher among foundry workers (15%) than among community controls (2%) (p less than 0.01). Sampling showed that the concentrations of total and metallic particles (especially iron) and of free silica in air inhaled by welders and grinders at the foundry frequently exceeded acceptable levels. These findings suggest that chronic exposure to such particles may increase susceptibility to infection by this organism, which rarely affects healthy people.

Primary isolation of a new strain of the TATLOCK/Pittsburgh pneumonia agent (Legionella micdadei).

Pneumonia, empyema and lung abscesses developed in a patient following a neurosurgical procedure and associated short-term corticosteroid therapy. An organism identical to the TATLOCK/Pittsburgh pneumonia agent (Legionella micdadei) was the only organism isolated from multiple specimens from lung aspirates and chest tube drainage. The organism was isolated directly on charcoal yeast extract (CYE) agar and classified as identical to the TATLOCK bacterium by direct immunofluorescent staining and by gas-liquid chromatography of cellular fatty acids. The patient's pulmonary infection improved during treatment with penicillin. Serum specimens obtained from the patient during convalescence showed an indirect fluorescent antibody reciprocal titer of 16,000 to his homologous antigen, but he also had titers that were potentially diagnostic against antigens of the six serogroups of Legionella pneumophila and three other Legionella-like organisms. Legionella can be isolated from clinical specimens by the routine use of CYE agar, which should be incorporated as the primary isolation medium for chest fluids and lung specimens. It appears that a large battery of antigens will be required for serological testing to diagnose infections caused by L micadei, L pneumophila and Legionella-like organisms.

Legionella micdadei (Pittsburgh pneumonia agent): direct fluoresent-antibody examination of infected human lung tissue and characterization of clinical isolates.

Legionella micdadei (Pittsburgh pneumonia agent) was identified by direct fluorescent-antibody (DFA) examination of lung tissue in six of seven persons diagnosed previously as having L. micdadei pneumonia only by histopathology and in four persons who also had positive cultures of the organism. No cross-reactions occurred with monospecific DFA conjugates prepared against Legionella pneumophila serogroups 1 to 6, Legionella bozemanii, Legionella dumoffii, and Legionella gormanii. One person had L. pneumophila serogroup 6 identified by DFA examination of lung tissue and subsequent culture of stored pulmonary secretions. Characterization of the four strains of L. micdadei revealed specific DFA reactions, bacteriological behavior, and cellular fatty acid composition that allow identification of the organism. DFA testing appears to be a sensitive method for identifying L. micdadei prescent in human lung tissue or cultured on artificial media.

Isolation of Legionella pneumophila from hospital shower heads.

Legionella pneumophila serogroup 6 was isolated from nine of 16 shower heads in a Chicago hospital ward where three patients had contracted Legionnaires' disease caused by serogroup 6 L. pneumophila. Each patient had showered there 2 to 10 days before the onset of disease symptoms. We also isolated the bacteria in two other hospitals, and found the same serogroups as had been causing Legionnaires' disease in those hospitals: serogroup 1 in Pittsburgh and serogroups 1 and 4 in Los Angeles. However, showers from hospital wards where no patients had contracted Legionnaires' disease also yielded L. pneumophila. Shower heads at the Chicago hospital were sterilized with ethylene oxide but rapidly became recontaminated, suggesting that the potable water at these hospitals may have contained the organism. The question of whether aerosols of shower water or other exposures to potable water containing L. pneumophila may cause nosocomial Legionnaires' disease has not been resolved but deserves further study.

Pittsburgh pneumonia agent: direct isolation from human lung tissue.

Pittsburgh pneumonia agent (PPA) was recently cultivated from infected egg yold on charcoal yeast extract agar. PPA has now been isolated both from infected egg yolk and human lung tissue on charcoal yeast extract agar and on a new medium, buffered charcoal yeast extract agar. PPA resembles Legionella pneumophila and other Legionella-like organisms in requirements for growth and composition of fatty acids. It differs in genetic relatedness, antigenic composition, and colonial morphology and has distinctive characteristics that allow it to be identified. The name Legionella pittsburgensis species nova is proposed for this organism.

Legionnaires' disease outbreak at an Atlanta, Georgia, Country Club: evidence for spread from an evaporative condenser.

During July 1978 an outbreak of Legionnaires' disease characterized by high fever, prostration, and pneumonia occurred at an Atlanta, Georgia, country club. All eight cases involved club members whose primary club activity was golfing. The degree of golfing activity during the likely exposure period was a risk factor for acquiring the illness. Legionella pneumophila was isolated from the evaporative condenser within the clubhouse. The fact that the stream of air blowing from the exhaust duct of the evaporative condenser was directed toward a nearby practice green and the 10th and 16th tees supports the hypothesis that this outbreak represents airborne dissemination of L. pneumophila from the evaporative condenser to an outdoor site where susceptible golfers contracted the illness.

Atypical Legionella-like organisms: fastidious water-associated bacteria pathogenic for man.

A group of related bacteria designated atypical Legionella-like organisms (ALLO) has been identified. ALLO, like L. pneumophila, are fastidious gram-negative rods that grow well on charcoal yeast extract (CYE) agar and produce ground glass colonies and browning of modified yeast extract agar. Unlike L. pneumophila, ALLO do not grow well on Feeley-Gorman (FG) agar, and on CYE agar they fluoresce under longwave ultraviolet light. ALLO and L. pneumophila have a similar predominance of branched-chain forms among total cellular fatty acids but have distinctive fatty-acid profiles. 2 patients with culture-verified ALLO pneumonia and 10 with pneumonia of uncertain aetiology who seroconverted to ALLO offer evidence that ALLO may be a cause of community-acquired pneumonia. Like L. pneumophila, ALLO appear to be water-associated; both persons with culture-verified ALLO infection were exposed to fresh water or its contents before becoming ill, and two strains of ALLO were isolated from water or wet environments.