Person:

Goldmann, Donald

Staphylococcus epidermidis (SE) causes late onset sepsis and significant morbidity in catheterized preterm newborns. Animal models of SE infection are useful in characterizing disease mechanisms and are an important approach to developing improved diagnostics and therapeutics. Current murine models of neonatal bacterial infection employ intraperitoneal or subcutaneous routes at several days of age, and may, therefore, not accurately reflect distinct features of innate immune responses to bacteremia. In this study we developed, validated, and characterized a murine model of intravenous (IV) infection in neonatal mice <24 hours (h) old to describe the early innate immune response to SE. C57BL/6 mice <24 h old were injected IV with 106, 107, 108 colony-forming units (CFU) of SE 1457, a clinical isolate from a central catheter infection. A prospective injection scoring system was developed and validated, with only high quality injections analyzed. Newborn mice were euthanized between 2 and 48 h post-injection and spleen, liver, and blood collected to assess bacterial viability, gene expression, and cytokine production. High quality IV injections demonstrated inoculum-dependent infection of spleen, liver and blood. Within 2 h of injection, SE induced selective transcription of TLR2 and MyD88 in the liver, and increased systemic production of plasma IL-6 and TNF-α. Despite clearance of bacteremia and solid organ infection within 48 h, inoculum-dependent impairment in weight gain was noted. We conclude that a model of IV SE infection in neonatal mice <24 h old is feasible, demonstrating inoculum-dependent infection of solid organs and a pattern of bacteremia, rapid and selective innate immune activation, and impairment of weight gain typical of infected human neonates. This novel model can now be used to characterize immune ontogeny, evaluate infection biomarkers, and assess preventative and therapeutic modalities.

Background In October 2008, the Centers for Medicare and Medicaid Services (CMS) discontinued additional payments for certain hospital-acquired conditions that were deemed preventable. The effect of this policy on rates of health care–associated infections is unknown. Methods Using a quasi-experimental design with interrupted time series with comparison series, we examined changes in trends of two health care–associated infections that were targeted by the CMS policy (central catheter–associated bloodstream infections and catheter-associated urinary tract infections) as compared with an outcome that was not targeted by the policy (ventilator-associated pneumonia). Hospitals participating in the National Healthcare Safety Network and reporting data on at least one health care–associated infection before the onset of the policy were eligible to participate. Data from January 2006 through March 2011 were included. We used regression models to measure the effect of the policy on changes in infection rates, adjusting for baseline trends. Results A total of 398 hospitals or health systems contributed 14,817 to 28,339 hospital unit– months, depending on the type of infection. We observed decreasing secular trends for both targeted and nontargeted infections long before the policy was implemented. There were no significant changes in quarterly rates of central catheter– associated bloodstream infections (incidence-rate ratio in the postimplementation vs. preimplementation period, 1.00; P=0.97), catheter-associated urinary tract infections (incidence-rate ratio, 1.03; P=0.08), or ventilator-associated pneumonia (incidence-rate ratio, 0.99; P=0.52) after the policy implementation. Our findings did not differ for hospitals in states without mandatory reporting, nor did it differ according to the quartile of percentage of Medicare admissions or hospital size, type of ownership, or teaching status. Conclusions We found no evidence that the 2008 CMS policy to reduce payments for central catheter–associated bloodstream infections and catheter-associated urinary tract infections had any measurable effect on infection rates in U.S. hospitals.

The Centers for Medicare and Medicaid Services (CMS) implemented a policy in October 2008 to eliminate additional Medicare payment for mediastinitis following coronary artery bypass graft (CABG) surgery. To evaluate the impact of this policy on mediastinitis rates, using Medicare claims and National Healthcare Safety Network (NHSN) prospective surveillance data. We used an interrupted time series design to compare mediastinitis rates before and after the policy, adjusted for secular trends. Billing rates came from Medicare inpatient claims following 638,761 CABG procedures in 1,234 US hospitals (January 2006-September 2010). Prospective surveillance rates came from 151 NHSN hospitals in 29 states performing 94,739 CABG procedures (January 2007-September 2010). Logistic regression mixed-effects models estimated trends for mediastinitis rates. We found a sudden drop in coding for index admission mediastinitis at the time of policy implementation (odds ratio, 0.36 [95% confidence interval (CI), 0.23-0.57]) and a decreasing trend in coding for index admission mediastinitis in the postintervention period compared with the preintervention period (ratio of slopes, 0.83 [95% CI, 0.74-0.95]). However, we saw no impact of the policy on infection rates as measured using NHSN data. Our results were not affected by changes in patient risk over time, heterogeneity in hospital demographics, or timing of hospital participation in NHSN. The CMS policy of withholding additional Medicare payment for mediastinitis on the basis of claims-based evidence of infection was associated with changes in coding for infections but not with changes in actual infection rates during the first 2 years after policy implementation.

Policymakers may wish to align healthcare payment and quality of care while minimizing unintended consequences, particularly for safety net hospitals. To determine whether the 2008 Centers for Medicare and Medicaid Services Hospital-Acquired Conditions policy had a differential impact on targeted healthcare-associated infection rates in safety net compared with non–safety net hospitals. Interrupted time-series design. Nonfederal acute care hospitals that reported central line–associated bloodstream infection and ventilator-associated pneumonia rates to the Centers for Disease Control and Prevention’s National Health Safety Network from July 1, 2007, through December 31, 2013. We did not observe changes in the slope of targeted infection rates in the postpolicy period compared with the prepolicy period for either safety net (postpolicy vs prepolicy ratio, 0.96 [95% CI, 0.84–1.09]) or non–safety net (0.99 [0.90–1.10]) hospitals. Controlling for prepolicy secular trends, we did not detect differences in an immediate change at the time of the policy between safety net and non–safety net hospitals (P for 2-way interaction, .87). The Centers for Medicare and Medicaid Services Hospital-Acquired Conditions policy did not have an impact, either positive or negative, on already declining rates of central line–associated bloodstream infection in safety net or non–safety net hospitals. Continued evaluations of the broad impact of payment policies on safety net hospitals will remain important as the use of financial incentives and penalties continues to expand in the United States.