Assessing Rates of Co-Resistance and Patient Outcomes in Multidrug-Resistant Pseudomonas aeruginosa

Abstract

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are associated with poor patient outcomes due to complex co-resistance patterns. We described common co-resistance patterns, clinical characteristics, and associated outcomes in patients admitted with an MDR P. aeruginosa. This national, multicenter, retrospective cohort study within the Veterans Affairs included adults hospitalized with a MDR P. aeruginosa infection (January 2015-December 2020) per Centers for Disease Control definition. Clinical outcomes were compared among those with differing MDR P. aeruginosa co-resistance: resistant to carbapenems and extended-spectrum cephalosporins and piperacillin-tazobactam (CARB/ESC/PT) versus without CARB/ESC/PT resistance; resistant to carbapenems and extended-spectrum cephalosporins and fluoroquinolone (CARB/ESC/FQ) versus without CARB/ESC/FQ resistance. We included 3,763 hospitalized patients. Co-resistance to CARB/ESC/PT was observed in 42.7%, and to CARB/ESC/FQ in 40.7%. The lowest co-resistance rates were observed with ceftolozane-tazobactam (6.2%, n = 6/97; 12.5%, n = 10/80, respectively) and ceftazidime-avibactam (5.2%, n = 5/97; 12.5%, n = 10/80, respectively). Overall, 14.2% of patients died during hospitalization, 59.7% had an extended length of stay, and 14.9% had reinfection with hospitalization. Outcomes were similar between patients with MDR P. aeruginosa strains with and without co-resistance to CARB/ESC/PT and CARB/ESC/FQ. Among a national cohort of patients hospitalized with MDR P. aeruginosa infections, co-resistance to three classes of standard of care antibiotics, such as carbapenem, extended-spectrum cephalosporins, and piperacillin-tazobactam or fluoroquinolones, exceeded 40% in our study population, posing great concerns for selecting appropriate empirical therapy. Clinical outcomes were poor for all patients, regardless of different co-resistance patterns. New treatment options are needed for hospitalized patients with suspected or confirmed MDR P. aeruginosa infections. IMPORTANCE We studied antibiotic co-resistance patterns in a national group of hospitalized patients with infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa, a type of bacteria that resists treatment to at least three classes of antibiotics. Co-resistance to antibiotic classes most typically used for treatment was common, which makes selecting appropriate antibiotics to successfully treat the infections difficult. Outcomes, including death, were poor for all patients in our study, regardless of the different patterns of co-resistance to common antibiotic classes. New antibiotics are needed to help treat hospitalized patients with MDR P. aeruginosa infections.

Keywords: Pseudomonas aeruginosa; antibiotic resistance; antipseudomonal antibiotics; co-resistance; multidrug resistance.

FIG 1

Resistance and co-resistance in MDR Pseudomonas aeruginosa. Bubbles represent percent resistance or co-resistance for the antibiotic class/classes indicated among multidrug-resistant (MDR, tested either intermediate or resistant to at least one antibiotic in at least three categories [AMG, CARB, ESC, FQ, PT]) Pseudomonas aeruginosa isolates. Colors represent antibiotic class/classes of resistance. Yellow bubbles represent co-resistance to CARB/ESC/PT and additional classes (as indicated with the + sign). Green bubbles represent co-resistance to CARB/ESC/FQ and additional classes (as indicated with the + sign). Size of bubbles represent the number of isolates tested. AMG = aminoglycosides (amikacin, gentamicin, tobramycin); CA = ceftazidime-avibactam; CARB = carbapenems (imipenem, meropenem, doripenem); CT = ceftolozane-tazobactam; ESC = extended-spectrum cephalosporins (cefepime, ceftazidime); FQ = fluoroquinolone (ciprofloxacin, levofloxacin); PT = piperacillin-tazobactam.