Innovative Medicines Initiative.

Extensive antibiotic use over the years has led to the emergence and spread of antibiotic resistant bacteria (ARB). Antibiotic resistance poses a major threat to public health since for many infections antibiotic treatment is no longer effective. Hospitals are focal points for ARB spread. Antibiotic use in hospitals exerts selective pressure, accelerating the spread of ARB. We used an agent-based model to explore the impact of antibiotics on the transmission dynamics and to examine the potential of stewardship interventions in limiting ARB spread in a hospital. Agents in the model consist of patients and health care workers (HCW). The transmission of ARB occurs through contacts between patients and HCW and between adjacent patients. In the model, antibiotic use affects the risk of transmission by increasing the vulnerability of susceptible patients and the contagiousness of colonized patients who are treated with antibiotics. The model shows that increasing the proportion of patients receiving antibiotics increases the rate of acquisition non-linearly. The effect of antibiotics on the spread of resistance depends on characteristics of the antibiotic agent and the density of antibiotic use. Antibiotic's impact on the spread increases when the bacterial strain is more transmissible, and decreases as resistance prevalence rises. The individual risk for acquiring ARB increases in parallel with antibiotic density both for patients treated and not treated with antibiotics. Antibiotic treatment in the hospital setting plays an important role in determining the spread of resistance. Interventions to limit antibiotic use have the potential to reduce the spread of resistance, mainly by choosing an agent with a favorable profile in terms of its impact on patient's vulnerability and contagiousness. Methods to measure these impacts of antibiotics should be developed, standardized, and incorporated into drug development programs and approval packages.

A national, coordinated intervention resulted in a sustained decrease in CRE incidence and prevalence in LTCFs. These results support the assumption that centrally coordinated intervention is an essential public health tool in reducing CRE in healthcare facilities.

objective. Carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are extremely drug-resistant pathogens. Screening of contacts of newly identified CP-CRE patients is an important step to limit further transmission. We aimed to determine the risk factors for CP-CRE acquisition among patients exposed to a CP-CRE index patient.methods. A matched case-control study was performed in a tertiary care hospital in Israel. The study population was comprised of patients who underwent rectal screening for CP-CRE following close contact with a newly identified CP-CRE index patient. Cases were defined as positive tests for CP-CRE. For each case patient, 2 matched controls were randomly selected from the pool of contacts who tested negative for CP-CRE following exposure to the same index case. Bivariate and multivariate analyses were conducted using conditional logistic regression.results. In total, 53 positive contacts were identified in 40 unique investigations (896 tests performed on 735 contacts) between October 6, 2008, and June 7, 2012. bla KPC was the only carbapenemase identified. In multivariate analysis, risk factors for CP-CRE acquisition among contacts were (1) contact with an index patient for ≥3 days (odds ratio [OR], 9.8; 95% confidence interval [CI], 2.0-48.9), (2) mechanical ventilation (OR, 4.1; 95% CI, 1.4-11.9), and (3) carriage or infection with another multidrug-resistant organism (MDRO; OR, 2.6; 95% CI, 1.0-7.1). Among patients who received antibiotics, cephalosporins were associated with a lower risk of acquisition.conclusions. Patient characteristics (ventilation and carriage of another MDRO) as well as duration of contact are risk factors for CP-CRE acquisition among contacts. The role of cephalosporins requires further study.

ESBL-PE carriers who receive cephalosporin-based prophylaxis are at increased risk of SSI following colorectal surgery.