Pulsatile Delivery of Clarithromycin Alone or in Combination with Amoxicillin against Streptococcus pneumoniae

We evaluated pulsatile dosing of clarithromycin and amoxicillin alone or combined against Streptococcus pneumoniae with various susceptibilities. When combined, pulsatile amoxicillin with clarithromycin was superior to either 8- or 12-h dosing against the intermediate strain and was identical for the susceptible strain. Pulse dosing of antimicrobials warrants further investigation

Activities of Ceftobiprole, Linezolid, Vancomycin, and Daptomycin against Community-Associated and Hospital-Associated Methicillin-Resistant Staphylococcus aureus▿

We evaluated the activity of ceftobiprole against 100 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and 100 hospital-associated MRSA (HA-MRSA) isolates. Eight isolates were evaluated by time-kill studies for kill rate and potential for synergy with tobramycin. Ceftobiprole MIC50 and MIC90 values were 1 and 2 μg/ml, respectively, against CA-MRSA and HA-MRSA. In time-kill analysis, ceftobiprole was bactericidal at all concentrations tested

Antimicrobial Activities of Ceragenins against Clinical Isolates of Resistant Staphylococcus aureus

The rise in the rates of glycopeptide resistance among Staphylococcus aureus isolates is concerning and underscores the need for the development of novel potent compounds. Ceragenins CSA-8 and CSA-13, cationic steroid molecules that mimic endogenous antimicrobial peptides, have previously been demonstrated to possess broad-spectrum activities against multidrug-resistant bacteria. We examined the activities of CSA-8 and CSA-13 against clinical isolates of vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), as well as vancomycin-resistant S. aureus (VRSA) and compared them to those of daptomycin, linezolid, and vancomycin by susceptibility testing and killing curve analysis. We also examined CSA-13 for its concentration-dependent activity, inoculum effect, postantibiotic effect (PAE), and synergy in combination with various antimicrobials. Overall, the MICs and minimal bactericidal concentrations of CSA-13 were fourfold lower than those of CSA-8. Time-kill curve analysis of the VRSA, VISA, and hVISA clinical isolates demonstrated concentration-dependent bactericidal killing. An inoculum effect was also observed when a higher starting bacterial density was used, with the time required to achieve 99.9% killing reaching 1 h with a 6-log(10)-CFU/ml starting inoculum, whereas it was ≥24 h with a 8- to 9-log(10)-CFU/ml starting inoculum with 10× the MIC (P ≤ 0.001). A concentration-dependent PAE was demonstrated with CSA-13, nearly doubling from 2× to 4× the MIC (P = 0.03). With respect to the CSA-13 antimicrobial combinations, time-kill curve analysis showed no difference in the log(10) CFU/ml at 24 h for the majority of the organisms tested. However, early synergy at 4 to 8 h was detected against the VRSA Pennsylvania strain (2002) when CSA-13 was tested in combination with gentamicin, while early additivity was demonstrated against all of the other organisms

Characterization of Vancomycin-Heteroresistant Staphylococcus aureus from the Metropolitan Area of Detroit, Michigan, over a 22-Year Period (1986 to 2007)▿

We screened for heteroresistant, vancomycin-intermediate Staphylococcus aureus (hVISA) among clinical isolates of methicillin-resistant S. aureus collected from three hospitals (two urban teaching hospitals and one community hospital) in the Detroit metropolitan area over a 22-year period. The Macro Etest method was used to screen all available isolates. Confirmation of hVISA-positive screens were confirmed by population-area under the concentration-time curve (AUC) analysis. A total of 1,499 isolates revealed hVISA/VISA rates of 2.2/0.4% (n = 225; 1986 to 1993), 7.6/2.3% (n = 356; 1994 to 2002), and 8.3/0.3% (n = 917; 2003 to 2007). Population-AUC analysis confirmed 92.6% of the hVISA-positive strains determined by the Macro Etest method. For the isolates with known sources (1,208), the predominant source of hVISA was blood (60%), followed by lung (21%), skin and wound infections (14%), abscess (1%), and other (4%). The percentage of hVISA-positive strains appeared to increase as a function of the vancomycin MIC. Staphylococcal cassette chromosome mec (SCCmec) typing revealed that the majority (56.9%) of the hVISA strains were SCCmec type II and 39.4% were type IV; the majority of these strains were collected from 2000 to 2007. Our data indicate that the prevalence of hVISA may be increasing. Based on the association of vancomycin treatment failure in patients with hVISA, surveillance of hVISA strains is warranted