Prevalence, regional distribution, and trends of antimicrobial resistance among female outpatients with urine Klebsiella spp. isolates: a multicenter evaluation in the United States between 2011 and 2019

Abstract

Background: Antimicrobial resistance research in uncomplicated urinary tract infection typically focuses on the main causative pathogen, Escherichia coli; however, little is known about the antimicrobial resistance burden of Klebsiella species, which can also cause uncomplicated urinary tract infections. This retrospective cohort study assessed the prevalence and geographic distribution of antimicrobial resistance among Klebsiella species and antimicrobial resistance trends for K. pneumoniae in the United States (2011-2019).

Methods: K. pneumoniae and K. oxytoca urine isolates (30-day, non-duplicate) among female outpatients (aged ≥ 12 years) with presumed uUTI at 304 centers in the United States were classified by resistance phenotype(s): not susceptible to nitrofurantoin, trimethoprim/sulfamethoxazole, or fluoroquinolone, extended-spectrum β-lactamase-positive/not susceptible; and multidrug-resistant based on ≥ 2 and ≥ 3 resistance phenotypes. Antimicrobial resistance prevalence by census division and age, as well as antimicrobial resistance trends over time for Klebsiella species, were assessed using generalized estimating equations.

Results: 270,552 Klebsiella species isolates were evaluated (250,719 K. pneumoniae; 19,833 K. oxytoca). The most frequent resistance phenotypes in 2019 were nitrofurantoin not susceptible (Klebsiella species: 54.0%; K. pneumoniae: 57.3%; K. oxytoca: 15.1%) and trimethoprim/sulfamethoxazole not susceptible (Klebsiella species: 10.4%; K. pneumoniae: 10.6%; K. oxytoca: 8.6%). Extended-spectrum β-lactamase-positive/not susceptible prevalence was 5.4%, 5.3%, and 6.8%, respectively. K. pneumoniae resistance phenotype prevalence varied (p < 0.0001) geographically and by age, and increased over time (except for the nitrofurantoin not susceptible phenotype, which was stable and > 50% throughout).

Conclusions: There is a high antimicrobial resistance prevalence and increasing antimicrobial resistance trends among K. pneumoniae isolates from female outpatients in the United States with presumed uncomplicated urinary tract infection. Awareness of K. pneumoniae antimicrobial resistance helps to optimize empiric uncomplicated urinary tract infection treatment.

Keywords: Antimicrobial resistance; Klebsiella oxytoca; Klebsiella pneumoniae; Uncomplicated urinary tract infection.

Fig. 1

Prevalence of AMR among 30-day non-duplicate K. pneumoniae isolates in 2019 by US census division. For panel A, data are shown for ESBL+/NS, FQ NS, SXT NS; NTF NS are not depicted to provide greater clarity for the three other AMR phenotypes. By US census division, the NTF NS prevalence was 53.3% in New England, 58.2% in the Middle Atlantic, 56.6% in East North Central, 54.5% in West North Central, 60.4% in the South Atlantic, 57.6% in East South Central, 56.0% in West South Central, 53.8% in Mountain, and 56.3% in the Pacific. New England: CT, MA, ME, NH, RI, VT; Middle Atlantic: NJ, NY, PA; East North Central: IL, IN, MI, OH, WI; West North Central: IA, KS, MN, MO, ND, NE, SD; South Atlantic: DE, DC, FL, GA, MD, NC, SC, VA, WV; East South Central: AL, KY, MS, TN; West South Central: AR, LA, OK, TX; Mountain: AZ, CO, ID, MT, NM, NV, UT, WY; Pacific: AK, CA, OR, WA. AMR, Antimicrobial resistance; ESBL+/NS, Extended spectrum β-lactamase-producing or not susceptible to ceftriaxone, cefotaxime, ceftazidime, or cefepime; FQ, Fluoroquinolone; MDR-2/-3, Multidrug-resistant if resistant to ≥ 1 antibiotic in ≥ 2 or ≥ 3 drug classes (including NTF, SXT, FQ, or the ESBL+/NS phenotype); NS, Not susceptible; NTF, Nitrofurantoin; SXT, Trimethoprim/sulfamethoxazole; US, United States

Fig. 2

Observed AMR prevalence trends among 30-day non-duplicate Klebsiella spp. isolates from US female outpatients. Data for NTF NS are not depicted to provide greater clarity for the five other AMR phenotypes (NTF NS prevalence was > 50.0% throughout; these data can be found in Additional file 1: Fig. S2). AMR, Antimicrobial resistance; ESBL+/NS, Extended spectrum β-lactamase-producing or not susceptible to ceftriaxone, cefotaxime, ceftazidime, or cefepime; FQ, Fluoroquinolone; MDR-2/-3, Multidrug-resistant if resistant to ≥ 1 antibiotic in ≥ 2 or ≥ 3 drug classes (including NTF, SXT, FQ, or the ESBL+/NS phenotype); NS, not susceptible; NTF, Nitrofurantoin; SXT, Trimethoprim-sulfamethoxazole; US, United States