Updates in Management of Complicated Urinary Tract Infections: A Focus on Multidrug-Resistant Organisms

Abstract

Background: Urinary tract infection treatment can be difficult in the geriatric population. These patients often require a more nuanced approach due to recurrent, resistant, and catheter-associated infections. Areas of Uncertainty: Although some attempts have been made to prevent urinary tract infections using cranberry products, probiotics, and nonpharmacologic means, current interest lies largely with the development of new antibiotics to treat increasingly resistant organisms. Therapeutic Advances: Efforts to reduce the development of resistance starts with judicious and appropriate empiric use of antibiotics. Fluoroquinolones are no longer recommended as first-line therapy due to adverse reactions and the development of resistance. Complicated and upper urinary tract infections require broader empiric coverage and measures should be taken to de-escalate treatment as early as possible. Antimicrobial stewardship programs are recommended to aid in these efforts in addition to antibiotic selection in the presence of multidrug-resistant organisms such as those producing extended spectrum beta-lactamase or carbapenemase. Multidrug-resistant organisms are often present in catheter-associated urinary tract infections so broad empiric coverage should be initially started. Catheter-associated urinary tract infections should generally be treated for 7–14 days depending on the rate of clinical improvement, and fungal coverage is often also necessary. Ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam were recently approved in the US for treating multidrug-resistant organisms and several more agents are in development, such as parenteral fosfomycin. Ceftolozane/tazobactam is effective for treating Pseudomonas aeruginosa and other gram-negative organisms, even those that produce extended spectrum beta-lactamases. Ceftazidime/avibactam is effective solely for gram-negative organisms, including those that produce various carbapenemases, but efficacy for P. aeruginosa is variable. Both combinations are approved for complicated urinary tract infections in addition to complicated intra-abdominal infections. Several medications are currently in the pipeline to treat multidrug-resistant organisms. Meropenem/vaborbactam was approved for complicated urinary tract infections and its coverage includes carbapenem-resistant Enterobacteriaceae. Fosfomycin, currently available orally and first line for uncomplicated urinary tract infections, is being evaluated for intravenous use for methicillin-resistant Staphylococcus, vancomycin-resistant Enterococcus, and gram-negative bacilli that produce both extended spectrum beta-lactamase and carbapenemase. Conclusions: Urinary Tract Infections are a common cause of hospitalization in older adults. Antibiotic selection and antimicrobial stewardship programs are important given the increasing prevalence of multidrug-resistant organisms.