Title: Risk of hospital-acquired infections and drug resistance caused by gram-negative bacteria in patients with multiple hospitalizations
Description: Patients who experience multiple hospitalizations over short periods of time may be at greater risk of hospital-acquired infections (HAIs). While it is known that prior hospitalizations are associated with HAIs, there is a gap in knowledge regarding which factors of prior hospitalizations have an impact on the risk of HAIs in subsequent hospitalizations. HAIs caused by gram-negative bacteria (GNB) are of particular concern due to their propensity to develop drug resistance and the limited antibiotics available to treat them. The aims of this dissertation are to: 1) examine clinical and patient risk factors associated with acquiring at least one gram-negative hospital-acquired infection in adult patients with multiple hospitalizations; 2) systematically review the literature assessing the association between repeat gram-negative bacterial infections and changes in antibiotic susceptibility patterns; and 3) assess the association between repeat infections with three common gram-negative pathogens and risk of subsequent drug resistant infections with the same species among patients with multiple hospitalizations.

A retrospective cohort study was conducted to identify risk factors from prior hospitalizations associated with incident HAIs caused by three common GNB. Of the 129,372 patients with multiple hospitalizations, 1,672 (1.3%) acquired K. pneumoniae, 1,127 (0.9%) acquired P. aeruginosa, and 262 (0.2%) acquired A. baumannii infections. In survival analyses, older age, mechanical ventilation, history of chronic diseases, and increasing days of use of antibiotics decreased the time to infection for all 3 pathogens. This study highlights potential modifiable risk factors for infection control. Patients with multiple hospitalizations are also inherently at greater risk for repeat HAIs which may result in decreased antibiotic susceptibility, making them more difficult to treat. A systematic review was conducted to evaluate if there is an association between repeat GNB HAIs and drug resistance. From 2000 to 2015, only seven studies explicitly examined repeat GNB HAIs and change in antibiotic susceptibility, five of which reported decreased susceptibility in later infections.

The association between repeat GNB HAIs and risk of drug resistance among patients with multiple hospitalizations was then investigated with available electronic medical record data. The risk of a drug-resistant K. pneumoniae HAI increased by 1.14 times (95%CI: 1.04-1.24) with each prior K. pneumoniae HAI, after adjusting for potential confounders and antibiotic use. Similarly, patients with repeat P. aeruginosa infections had a 1.23 times increased risk of a subsequent drug-resistant infection (95%CI: 1.12-1.36) with each prior P. aeruginosa HAI as compared to patients with only one infection. Repeat A. baumannii infections were not analyzed due to limited sample size. The studies in this dissertation demonstrate that patients with multiple hospitalizations are a high-risk population for GNB HAIs. Prevention of GNB HAIs in this group is critical in order to reduce complications to medical care and limit transmission of infections to others in healthcare facilities and the community. Patient medical history can be used for infection risk assessment and to guide future medical care to reduce risk of infection in patients with multiple hospitalizations.