Modeling Meropenem Treatment, Alone and in Combination with Daptomycin, for KPC-Producing Klebsiella pneumoniae Strains with Unusually Low Carbapenem MICs.

Klebsiella pneumoniae strains producing K. pneumoniae carbapenemase (KPC) cause serious infections in debilitated and immunocompromised patients and are associated with prolonged hospital stays and increased mortality rates. Daptomycin is a lipopeptide used against Staphylococcus aureus infection and considered inactive against Gram-negative bacteria. We investigated the effectiveness of a daptomycin-meropenem combination by synergy kill curve and a pharmacokinetic/pharmacodynamic model. The combination may represent a novel therapeutic strategy against infections caused by KPC-producing K. pneumoniae strains.

Defining daptomycin resistance prevention exposures in vancomycin-resistant Enterococcus faecium and E. faecalis.

Daptomycin is used off-label for enterococcal infections; however, dosing targets for resistance prevention remain undefined. Doses of 4 to 6 mg/kg of body weight/day approved for staphylococci are likely inadequate against enterococci due to reduced susceptibility. We modeled daptomycin regimens in vitro to determine the minimum exposure to prevent daptomycin resistance (Dapr) in enterococci. Daptomycin simulations of 4 to 12 mg/kg/day (maximum concentration of drug in serum [Cmax] of 57.8, 93.9, 123.3, 141.1, and 183.7 mg/liter; half-life [t1/2] of 8 h) were tested against one Enterococcus faecium strain (S447) and one Enterococcus faecalis strain (S613) in a simulated endocardial vegetation pharmacokinetic/pharmacodynamic model over 14 days. Samples were plated on media containing 3× the MIC of daptomycin to detect Dapr. Mutations in genes encoding proteins associated with cell envelope homeostasis (yycFG and liaFSR) and phospholipid metabolism (cardiolipin synthase [cls] and cyclopropane fatty acid synthetase [cfa]) were investigated in Dapr derivatives. Dapr derivatives were assessed for changes in susceptibility, surface charge, membrane depolarization, cell wall thickness (CWT), and growth rate. Strains S447 and S613 developed Dapr after simulations of 4 to 8 mg/kg/day but not 10 to 12 mg/kg/day. MICs for Dapr strains ranged from 8 to 256 mg/liter. Some S613 derivatives developed mutations in liaF or cls. S447 derivatives lacked mutations in these genes. Dapr derivatives from both strains exhibited lowered growth rates, up to a 72% reduction in daptomycin-induced depolarization and up to 6-nm increases in CWT (P<0.01). Peak/MIC and AUC0-24/MIC ratios (AUC0-24 is the area under the concentration-time curve from 0 to 24 h) associated with Dapr prevention were 72.1 and 780 for S447 and 144 and 1561 for S613, respectively. Daptomycin doses of 10 mg/kg/day may be required to prevent Dapr in serious enterococcal infections.

Persistence of influenza vaccine-induced antibodies in lung transplant patients between seasons.

BACKGROUND: Immunization policy-making bodies advised against immunizing too early before the influenza season because vaccine-specific antibody may wane before the end of the influenza season. Lung transplant patients are included in the group of high-risk patients for whom this recommendation had been made. We hypothesized that immunosuppressed lung transplant patients would maintain protective concentrations of influenza antigen-specific antibodies between seasons. METHODS: As part of a planned 5-year study of influenza vaccine responses in lung transplant patients, we measured influenza antibody concentrations by hemagglutination inhibition assay before influenza immunization annually. The fraction of lung transplant patients who maintained seroprotective levels (≥ 40 hemagglutination units) approximately 11 months from last season immunization was calculated. Antibody concentrations and response rates in lung transplant patients were compared with healthy individuals and those waiting for lung transplantation. RESULTS: The majority of lung transplant patients maintained seroprotective influenza antigen-specific antibody concentrations for approximately 11 months after immunization. Seroprotection rates varied greatly with influenza antigens (healthy 68-100%, pretransplant 44-100%, transplant 64-100%), and were similar when groups were compared. More than 70% of lung transplant patients maintained seroprotective antibody concentrations to 10 of 11 vaccine antigens. CONCLUSION: Seroprotective influenza antibody concentrations are maintained at very high rates among immunosuppressed lung transplant patients and depend more on the vaccine virus than the immunostatus of the vaccine recipient. Early seasonal influenza immunization of lung transplant patients is appropriate.

Induced adhesion in Crassostrea virginica larvae.

Normal motile veliger larvae of the oyster, Crassostrea virginica, were observed swimming in pairs or trios. Adhesion between animals is firm and has a specific orientation. This adhesion can be induced in low frequencies by culturing larvae at high densities, and in much higher frequencies by inclusion of an antibiotic mix in the seawater culture medium.