Outcomes of ceftriaxone use compared to standard of therapy in methicillin susceptible staphylococcal aureus (MSSA) bloodstream infections.

BACKGROUND: Standard of care therapy (SOCT) for the treatment of methicillin susceptible staphylococcal aureus (MSSA) infections requires multiple daily infusions. Despite questionable efficacy due to high protein binding, ceftriaxone (CTX) is frequently used for treatment of MSSA at Hines VA Hospital. OBJECTIVE: The objective of this study was to determine clinical and microbiological outcomes in patients with MSSA bacteremia treated with CTX compared to SOCT. SETTING: This retrospective study was conducted at the Edward Hines, Jr. VA Hospital which is a comprehensive health care center serving the veteran population of the greater metropolitan Chicago and northwest Indiana regions and is institutionally affiliated with the Loyola University Medical Center. The Hines VA provides medical care to over 56,000 veterans and operates approximately 500 hospital beds, including acute care and nursing home beds. METHOD: We conducted a retrospective cohort study of patients with MSSA bacteremia treated at Hines VA Hospital between January 2000 and September 2009. Patients who received either SOCT or CTX for >50% of the treatment course and for the appropriate duration were included. Patients who were on multiple antibiotics concurrently or who received <14 days of therapy were excluded. MAIN OUTCOME MEASURE: The primary outcome of this study is to compare clinical outcomes of patients with MSSA bacteremia who were treated with CTX compared to those who received standard of care agents. RESULTS: Ninety-three patients with MSSA bacteremia were included in the analysis. Fifty-one were treated with SOCT and 42 with CTX. There were no differences in microbiological cure between SOCT (94.1%) and CTX (95.2%) (p = 0.812). Clinical cure was similar between groups (74.5% for SOCT, 83.3% for CTX) (p = 0.303). CTX was used more often to treat Staphylococcus aureus bacteremia associated with osteomyelitis whereas endocarditis and central line associated infections were treated more frequently with SOCT (p = 0.01). More patients treated with CTX were managed in the ambulatory setting (64 vs. 24%; p = <0.001). There was a trend toward a longer hospital stay with SOCT. CONCLUSION: Clinical outcomes for MSSA bacteremia did not differ significantly between patients treated with CTX and SOCT. Findings suggest that CTX may be an alternative for outpatient management of MSSA bacteremia.

Fatal disseminated mouse adenovirus type 1 infection in mice lacking B cells or Bruton's tyrosine kinase.

Mouse adenovirus type 1 (MAV-1) infection of B-cell-deficient and Bruton's tyrosine kinase (Btk)-deficient mice resulted in fatal disseminated disease resembling human adenovirus infections in immunocompromised patients. Mice lacking B cells or Btk were highly susceptible to acute MAV-1 infection, in contrast to controls and mice lacking T cells. To our knowledge, this is the first demonstration that mice with an X-linked immunodeficiency phenotype (Btk deficient) are susceptible to virus-induced disease. Mice lacking B cells or Btk on a C57BL/6 background succumbed with encephalomyelitis, hepatitis, and lymphoid necrosis. Mice lacking B cells on a BALB/c background succumbed with enteritis and hepatitis. Survival of acute MAV-1 infection correlated with early T-cell-independent neutralizing antibody and T-cell-independent antiviral immunoglobulin M. Treatment of MAV-1-infected Btk(-/-) mice 4 to 9 days postinfection with antiserum harvested 6 to 9 days postinfection from MAV-1-infected Btk(+/+) mice was therapeutic. Our findings implicate a critical role for B-cell function in preventing disseminated MAV-1 infection, particularly production of early T-cell-independent antiviral immunoglobulin M.