Comparative activity of telavancin and other antimicrobial agents against methicillin-resistant Staphylococcus aureus isolates collected from 1991 to 2006.

BACKGROUND: Increasingly frequent reports of vancomycin treatment failures for serious methicillin-resistant Staphylococcus aureus (MRSA) infections provide impetus for comparative in vitro studies to assess the activity of newer antimicrobial agents against a range of MRSA isolates. METHODS: A sample of 168 MRSA derived from a long-term MRSA collection was subjected to susceptibility testing to telavancin, daptomycin, linezolid, tigecycline and vancomycin by broth micro-dilution. Data were reviewed for sporadic occurrence of isolates with reduced susceptibility. Analyses were performed to test for temporal trends toward decreasing susceptibility and to compare susceptibility of isolates from different infection sites. RESULTS: No MRSA isolate from any time period was resistant to test antibiotics. For daptomycin, linezolid and tigecycline, there were no susceptibility differences between the pre- and postclinical availability periods. All newer agents were active against MRSA isolates with minimum inhibitory concentrations (MICs) of vancomycin >1 mg/l, but there were significant correlations in susceptibility among several pairs of antibiotics. CONCLUSIONS: Telavancin and other newer antistaphylococcal agents were fully active against MRSA from various infection sites including isolates with vancomycin MIC >1 mg/l.

Modeling the spread of infectious disease using genetic information within a marked branching process.

Accurate assessment of disease dynamics requires a quantification of many unknown parameters governing disease transmission processes. While infection control strategies within hospital settings are stringent, some disease will be propagated due to human interactions (patient-to-patient or patient-to-caregiver-to-patient). In order to understand infectious transmission rates within the hospital, it is necessary to isolate the amount of disease that is endemic to the outside environment. While discerning the origins of disease is difficult when using ordinary spatio-temporal data (locations and time of disease detection), genotypes that are common to pathogens, with common sources, aid in distinguishing nosocomial infections from independent arrivals of the disease. The purpose of this study was to demonstrate a Bayesian modeling procedure for identifying nosocomial infections, and quantify the rate of these transmissions. We will demonstrate our method using a 10-year history of Morexella catarhallis. Results will show the degree to which pathogen-specific, genotypic information impacts inferences about the nosocomial rate of infection.

Bacterial activation of mast cells.

Mast cells often are found in a perivascular location but especially in mucosae, where they may response to various stimuli. They typically associate with immediate hypersensitive responses and are likely to play a critical role in host defense. In this chapter, a common airway pathogen, Moraxella catarrhalis, and a commensal bacterium, Neiserria cinerea, are used to illustrate activation of human mast cells. A human mast cell line (HMC-1) derived from a patient with mast cell leukemia was activated with varying concentrations of heat-killed bacteria. Active aggregation of bacteria over mast cell surfaces was detected by scanning electron microscopy. The activation of mast cells was analyzed by nuclear factor-kappaB (NF-kappaB) activation and cytokine production in culture supernatants. Both M. catarrhalis and N. cinerea induce mast cell activation and the secretion of two key inflammatory cytokines, interleukin-6 and MCP-1. This is accompanied by NF-kappaB activation. Direct bacterial contact with mast cells appears to be essential for this activation because neither cell-free bacterial supernatants nor bacterial lipopolysaccharide induce cytokine secretion.

Mupirocin-resistant, methicillin-resistant Staphylococcus aureus: does mupirocin remain effective?

OBJECTIVE: To determine the efficacy of mupirocin ointment in reducing nasal colonization with mupirocin-susceptible, methicillin-resistant Staphylococcus aureus (MS MRSA) as well as mupirocin-resistant MRSA (MR MRSA). DESIGN: Prospective evaluation in which patients colonized with MRSA were treated twice daily with 2% topical mupirocin ointment for 5 days. SETTING: James H. Quillen Veterans' Affairs Medical Center. PATIENTS: Forty hospitalized patients with two anterior nares cultures positive for MRSA within a 7-day period. METHODS: Treated patients had post-treatment cultures at day 3 and weeks 1, 2, and 4. Isolates underwent mupirocin-susceptibility testing and DNA typing. MRSA clearance and type turnover were assessed for isolates that were mupirocin-susceptible, low-level (LL) MR MRSA and high-level (HL) MR MRSA. RESULTS: Post-treatment nares cultures on day 3 were negative for 78.5%, 80%, and 27.7% of patients with MS MRSA, LL-MR MRSA, and HLMR MRSA, respectively. Sustained culture negativity at 1 to 4 weeks was more common in the MS MRSA group (91%) than in the LL-MR MRSA group (25%) or the HL-MR MRSA group (25%). Positive post-treatment cultures usually showed the same DNA pattern relative to baseline. Plasmid curing of 18 HL-MR MRSA resulted in 15 MS MRSA and 3 LL-MR MRSA. CONCLUSIONS: Mupirocin was effective in eradicating MS MRSA, but strains of MR MRSA often persisted after treatment. This appeared to reflect treatment failure rather than exogenous recolonization. MR MRSA is now more prevalent and it is appropriate to sample MRSA populations for mupirocin susceptibility prior to incorporating mupirocin into infection control programs.

A decline in mupirocin resistance in methicillin-resistant Staphylococcus aureus accompanied administrative control of prescriptions.

Susceptibility to mupirocin was assessed in methicillin-resistant Staphylococcus aureus isolates selected from eras corresponding to differences in usage rate and prescription policies at a Veterans Affairs medical center. The eras studied encompassed from the time of introduction of the drug to its widespread use, through recommended judicious use, and finally to subsequent stringent administrative control. Prescriptions declined from 3.0 to 0.1 per 1,000 patient days. Precipitous declines first in the numbers of isolates with high-level resistance (from 31% to 4%) and then in those with low-level resistance (from 26% to 10%) accompanied prescription control.