The inhibitory and bactericidal activities of daptomycin, vancomycin, and teicoplanin against a collection of 479 methicillin-resistant Staphylococcus aureus isolates were assessed. The isolates were collected from U.S. and European hospitals from 1985 to 2007 and were primarily from blood and abscess cultures. The MICs and minimum bactericidal concentrations (MBCs) of the three agents were determined, and the MBC/MIC ratios were calculated to determine the presence or absence of tolerance. Tolerance was defined as an MBC/MIC ratio of >32 or an MBC/MIC ratio of >16 when the MBC was greater than or equal to the breakpoint for resistance. Tolerance to vancomycin and teicoplanin was observed in 6.1% and 18.8% of the strains, respectively. Tolerance to daptomycin was not observed.Although vancomycin and teicoplanin are the standard therapies for staphylococcal bacteremia, tolerance to vancomycin and teicoplanin has been demonstrated in both coagulasenegative staphylococci and Staphylococcus aureus as well as in various Streptococcus species (2,3,7,10,13,15,20,21,23,25). Daptomycin, a lipopeptide antibiotic, has been demonstrated to have rapid bactericidal activity against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and tolerance to this drug has not been demonstrated (2,9,10,19,21,24,26,28).The issue of antibiotic tolerance is a complicated one. Some studies have suggested that infections caused by tolerant strains may be more difficult to treat, especially when they cause complicated infections such as endocarditis, meningitis, or osteomyelitis or cause infections in immunocompromised patients (7,8,14,15,16,18,20,22,23,25). Other investigators' expert analyses do not agree that there is proof of a correlation between tolerant strains and treatment failures or that bactericidal activity is required for the treatment of serious MRSA infections (17,25,26,27,28). Controversy concerning the appropriate methods for the determination of tolerance in clinical isolates and in the practicality of testing isolates for tolerance in the clinical laboratory also exists.This study looked at MRSA isolates obtained primarily from blood and abscess cultures collected between 1985 and 2007. The main purpose of the study was to determine the in vitro inhibitory and bactericidal activities and the level of tolerance to the three drugs observed by standardized MIC and minimum bactericidal concentration (MBC) tests (4,5,19).(This study was presented in part at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 17 to 20 September 2007.) MATERIALS AND METHODS Microorganisms.A collection of 479 MRSA isolates, primarily from blood and abscess sources of infection, collected from U.S. and European hospitals between 1985 and 2007 were tested. The isolates were unique and nonconsecutive and were collected for a variety of studies. All of the strains were susceptible to daptomycin, vancomycin, and teicoplanin and resistant to oxacillin by previous MIC testing. Vancomy...

cViridans group streptococci (VGS) are part of the normal flora that may cause bacteremia, often leading to endocarditis. We evaluated daptomycin against four clinical strains of VGS (MICs ‫؍‬ 1 or 2 g/ml) using an in vitro-simulated endocardial vegetation model, a simulated bacteremia model, and kill curves. Daptomycin exposure was simulated at 6 mg/kg of body weight and 8 mg/kg every 24 h for endocardial and bacteremia models. Total drug concentrations were used for analyses containing protein (albumin and pooled human serum), and free (unbound) drug concentrations (93% protein bound) were used for analyses not containing protein. Daptomycin MICs in the presence of protein were significantly higher than those in the absence of protein. Despite MICs below or at the susceptible breakpoint, all daptomycin regimens demonstrated limited kill in both pharmacodynamic models. A reduction of approximately 1 to 2 log 10 CFU was seen for all isolates and dosages except daptomycin at 6 mg/kg, which achieved a reduction of 2.7 log 10 CFU/g against one strain (Streptococcus gordonii 1649) in the endocardial model. Activity was similar in both pharmacodynamic models in the presence or absence of protein. Similar activity was noted in the kill curves over all multiples of the MIC. Regrowth by 24 h was seen even at 8؋ MIC. Postexposure daptomycin MICs for both pharmacodynamic models increased to >256 g/ml for all isolates by 24 and 72 h. Despite susceptibility to daptomycin by standard MIC methods, these VGS developed high-level daptomycin resistance (HLDR) after a short duration following drug exposure not attributed to modification or inactivation of daptomycin. Further evaluation is warranted to determine the mechanism of resistance and clinical implications.

Aim:  To compare the inactivation rates of male‐specific bacteriophage‐2 (MS2), hepatitis A HM‐175/18f (HM‐175) and reovirus T1 Lang (T1 L) during alkaline stabilization of wastewater residues. Methods and Results:  A bench scale alkaline stabilization model was used to evaluate the inactivation of MS2 seeded into raw sludge simultaneously with HM‐175 or T1 L. Stabilization was performed in triplicate at 28 and 4°C for both viral combinations. During stabilization at 28 and 4°C, MS2 and T1 L concentrations were similar at each time point (t = 0·1, 2, 12 and 24 h). MS2 and HM‐175 concentrations were also similar at each time point during stabilization at 28°C. At 4°C, MS2 and HM‐175 concentrations were not similar at the first two time points (t = 0·1 and 2 h), but were similar at later time points (t = 12 and 24 h). Conclusions:  The inactivation rates of T1 L at 4°C and both T1 L and HM‐175 at 28°C were similar to the inactivation rate of MS2 at all time points. At 4°C, MS2 was inactivated at a faster rate during the first two time points (t = 0·1 and 2 h) than HM‐175, but was inactivated similarly at later time points (t = 12 and 24 h). Significance and Impact of the Study:  Phages, such as MS2, would be ideal indicators for the presence of enteric viruses in wastewater residues because of their ubiquity, nonpathogenic nature, low cost and time associated with their detection. The findings of this study suggest that MS2 could serve as an indicator for monitoring the persistence of enteric viruses, such as HM‐175 and T1 L, during alkaline stabilization performed at moderate temperatures (28°C), but may not serve as an indicator for HM‐175 at reduced temperature (4°C). The utility of MS2 as an indicator of viral persistence during biosolids treatment should be further evaluated, as the increased efficiency and frequency of pathogen monitoring associated with their use may reduce the potential public health risk associated with biosolids, facilitating a greater acceptance for their land application.

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