First United States Outbreak of Mycobacterium abscessus Hand and Foot Disease Among Children Associated With a Wading Pool.

BACKGROUND: Mycobacterium abscessus, an emerging pathogen in healthcare settings, has rarely been associated with community outbreaks. During February-May 2013, Idaho public health officials and pediatric infectious disease physicians investigated an outbreak of M abscessus skin infections in children whose only common exposure was an indoor wading pool. METHODS: Healthcare providers and parents reported possible M abscessus cases. We used a standardized questionnaire to interview parents of affected children. Clinical specimens were submitted for mycobacterial examination. We conducted an environmental investigation of the pool. Microbial isolates from clinical and environmental samples were identified by sequencing polymerase chain reaction amplicons and underwent pulsed-field gel electrophoresis. RESULTS: Twelve cases were identified. Specimens from 4 of 7 children grew M abscessus or Mycobacterium abscessus/Mycobacterium chelonae . Ten (83%) of 12 children were female; median age was 3 years (range, 2 to 6 years); and all were immunocompetent. Pool maintenance did not fully comply with Idaho state rules governing pool operation. Mycobacterium abscessus/chelonae was isolated from pool equipment. Pulsed-field gel electrophoresis composite patterns were 87% similar between isolates from the pool ladder and 1 patient, and they were 90% similar between isolates from 2 patients. Environmental remediation included hyperchlorination, scrubbing and disinfection of pool surfaces, draining the pool, and replacement of worn pool materials. CONCLUSIONS: Immunocompetent children acquired M abscessus cutaneous infection involving hands and feet after exposure to a wading pool. Environmental remediation and proper pool maintenance likely halted transmission. Medical and public health professionals' collaboration effectively detected and controlled an outbreak caused by an emerging recreational waterborne pathogen.

Reduction of 13-deoxydoxorubicin and daunorubicinol anthraquinones by human carbonyl reductase.

Carbonyl reductase (CR) catalyzes the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of several carbonyls. Anthracyclines used to treat cancer are reduced by CR at the C13 carbonyl and the resulting metabolites are implicated in the cardiotoxicity associated with anthracycline therapy. CR also is believed to have a role in detoxifying quinones, raising the question whether CR catalyzes reduction of anthracycline quinones. Steady-state kinetic studies were done with several anthraquinone-containing compounds, including 13-deoxydoxorubicin and daunorubicinol, which lack the C13 carbonyl, thus unmasking the anthraquinone for study. k(cat) and k(cat)/K(m) values for 13-deoxydoxorubicin and daunorubicinol were nearly identical, indicating that that the efficiency of quinone reduction was unaffected by the differences at the C13 position. k(cat) and k(cat)/K(m) values were much smaller for the analogs than for the parent compounds, suggesting that the C13 carbonyl is preferred as a substrate over the quinone. CR also reduced structurally related quinone molecules with less favorable catalytic efficiency. Modeling studies with doxorubicin and carbonyl reductase revealed that methionine 234 sterically hinder the rings adjacent to the quinone, thus accounting for the lower catalytic efficiency. Reduction of the anthraquinones may further define the role of CR in anthracycline metabolism and may influence anthracycline cytotoxic and cardiotoxic mechanisms.