Molecular characterization of endocarditis-associated Staphylococcus aureus

Infective endocarditis (IE) is a life-threatening infection of the heart endothelium and valves. Staphylococcus aureus is a predominant cause of severe IE and is frequently associated with infections in health care settings and device-related infections. Multilocus sequence typing (MLST), spa typing, and virulence gene microarrays are frequently used to classify S. aureus clinical isolates. This study examined the utility of these typing tools to investigate S. aureus epidemiology associated with IE. Ninety-seven S. aureus isolates were collected from patients diagnosed with (i) IE, (ii) bloodstream infection related to medical devices, (iii) bloodstream infection not related to medical devices, and (iv) skin or soft-tissue infections. The MLST clonal complex (CC) for each isolate was determined and compared to the CCs of members of the S. aureus population by eBURST analysis. The spa type of all isolates was also determined. A null model was used to determine correlations of IE with CC and spa type. DNA microarray analysis was performed, and a permutational analysis of multivariate variance (PERMANOVA) and principal coordinates analysis were conducted to identify genotypic differences between IE and non-IE strains. CC12, CC20, and spa type t160 were significantly associated with IE S. aureus. A subset of virulence-associated genes and alleles, including genes encoding staphylococcal superantigen-like proteins, fibrinogen-binding protein, and a leukocidin subunit, also significantly correlated with IE isolates. MLST, spa typing, and microarray analysis are promising tools for monitoring S. aureus epidemiology associated with IE. Further research to determine a role for the S. aureus IE-associated virulence genes identified in this study is warranted.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections : clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin–clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of β-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin–clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3–12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home CI of ticarcillin–clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting.

Current understanding of streptococcal urinary tract infection

Group B streptococcus (GBS), also known as Streptococcus agalactiae is a Gram-positive, β-hemolytic, chain-forming bacterium and a commensal within the genital tract flora in approximately 25% of healthy adult women (Campbell et al., 2000). The organism is a leading cause of serious infection in newborns, pregnant women, and older persons with chronic medical illness (Baker et al., Edwards&Baker, 2005). In neonates GBS infection most commonly causes pneumonia, meningitis, and sepsis. In addition to maternal cervicovaginal colonization and neonatal infection that can result from vertical transmission of GBS from mothers to their infants, the bacterium can also cause urinary tract infection (UTI). The spectrum of GBS UTI includes asymptomatic bacteriuria (ABU), cystitis, pyelonephritis, urethritis, and urosepsis (Bronsema et al., 1993, Edwards&Baker, 2005, Farley et al., 1993, Lefevre et al., 1991, McKenna et al., 2003, Munoz et al., 1992, Ulett et al., 2009). GBS ABU is particularly common among pregnant women, although those most at risk for cystitis due to GBS appear to be elderly individuals (Edwards&Baker, 2005, Falagas et al., 2006, Muller et al., 2006). In addition to acute and asymptomatic UTI other invasive diseases caused by GBS infection include skin infections, bacteraemia, pneumonia, arthritis, and endocarditis (Liston et al., 1979, Patil & Martin, 2010, Tissi et al., 1997, Trivalle et al., 1998). Thus, GBS is considered unique in terms of its ability to cause a spectrum of diseases in newborns and adult humans and its ability to colonize the genital tract of healthy women in a commensal-type manner...