The challenge of multidrug resistance in hospitalized pediatric patients with urinary tract infections

Abstract

Background: The choice of empirical treatment in pediatric urinary tract infections (UTIs) is increasingly complicated by the emergence of antibiotic resistance and the growing prevalence of multidrug-resistant organisms (MDROs). The aim of this study is to assess the resistance patterns of isolated uropathogens among children and adolescents hospitalized with UTIs in Lebanon; and determine the risk factors associated with MDRO-related UTIs over a 10-year period.

Methods: A retrospective chart review was conducted at two tertiary medical centers in Beirut. Children and adolescents less than 18 years who were admitted, between January 1, 2011, and December 31, 2021, with the following ICD-10 codes: "urinary tract infection", "cystitis" and/or "pyelonephritis " were included. A case was excluded if the urine culture was polymicrobial or did not meet the definition of UTI we used. Univariate and multivariable logistic regression analyses were performed to identify risk factors for MDRO infections.

Results: Among the 876 pediatric UTI cases included, 85% were above 2 months of age and 74.1% were females. 64.5% of 644 Escherichia coli and 61.9% of 114 Klebsiella spp. isolates met international MDR criteria. After a period of fluctuation, the proportion of MDROs began to steadily increase starting 2019 eventually surpassing the 2011 percentage by nearly 10% in 2021 (67.9%, p = 0.248). Only 2.1% of MDR E. coli and 2.9% of MDR Klebsiella spp. were resistant to carbapenems. However, aminoglycoside resistance was high ranging between 28.3% and 48.6%. Children aged ≥ 5 years were nearly twice as likely to present with an MDR uropathogen compared to those < 5 years of age (p < 0.001). Only a history of leukemia (p = 0.010, AOR = 4.248, 95% CI [1.412-12.778]) and antibiotic use in the preceding 30 days (p = 0.012, AOR = 2.045, 95% CI [1.167-3.582]) were found as independent risk factors for UTIs caused by MDROs in multivariable logistic regression.

Conclusion: This study highlights the increasing threat of MDROs among pediatric UTIs. Recent antibiotic use was strongly associated with MDRO infections highlighting the urgent need for effective antimicrobial stewardship, re-evaluation of empiric treatment guidelines, and strict abidance by infection control measures.

Keywords: Lebanon; antimicrobial resistance; children; extended-spectrum beta lactamase; multidrug resistant organisms; urinary tract infection.

Figure 1

Percentage of multi drug resistant isolates within each species. MDR, multi-drug resistant; Spp., species.

Figure 2

Trend of multi-drug resistance among identified pathogens over the study period. MDRO: multi-drug-resistant organism. A binary logistic regression analysis was performed to compare the proportion of MDROs across the years from 2011 to 2021, with 2011 serving as the reference year. After a period of fluctuation, the proportion of MDROs began to steadily increase starting in 2019, eventually surpassing the 2011 percentage by nearly 10% in 2021; however, this increase was not statistically significant (67.9%, p = 0.248, OR = 1.560, 95% CI = [0.733–3.322]). The y-axis represents the number of non-MDRO and MDRO cases. Error bars indicate 95% confidence intervals.

Figure 3

Distribution of resistance to different antimicrobial classes within multi-drug resistant (MDR) isolates of (A) E. coli and (B) Klebsiella spp. Antimicrobial Categories: Penicillins + beta-lactamase inhibitors (amoxicillin-clavulanic acid), antipseudomonal penicillins + betalactamase inhibitors (piperacillin-tazobactam), third generation cephalosporins (cefixime, ceftazidime, and cefotaxime), fourth generation cephalosporins (cefepime), folate pathway inhibitors (trimethoprim/sulfamethoxazole), fluoroquinolones (ciprofloxacin and levofloxacin), carbapenems (imipenem), aminoglycosides (amikacin and gentamicin). Pearson’s Chi-square test or Fisher’s exact test (for subgroups with fewer than five cases) was used to compare the percentage of multidrug-resistant (Escherichia coli and Klebsiella spp.) cases between antibiotic-sensitive and -resistant groups. All comparisons were statistically significant (p < 0.05), except for Carbapenems (p > 0.05). The y-axis represents the percentage of MDR E. coli and Klebsiella spp. cases by antibiotic resistance status. Error bars indicate 95% confidence intervals.

Figure 4

Trends of resistance to third generation cephalosporins, folate pathway inhibitors, and antipseudomonal penicillins + beta lactamase inhibitors between 2011-2021. Third generation cephalosporins (cefixime, ceftazidime, and cefotaxime), folate pathway inhibitors (trimethoprim/sulfamethoxazole), antipseudomonal penicillins + betalactamase inhibitors (piperacillin-tazobactam). *Compared to 2011: Resistance to third generation cephalosporins significantly increased in 2014: p=0.018, 2.237 [1.148- 4.357], 2016: p=0.007, 2.483 [1.288- 4.785], and 2017: p=0.035, 2.022 [1.051- 3.893]. Resistance to folate pathway inhibitors significantly increased in 2013: p=0.047, 2.026 [1.009- 4.069].Resistance to antipseudomonal penicillins + Beta lactamase inhibitors significantly decreased in 2014: p=0.008,0.2 [0.061- 0.655], 2015: p=0.008, 0.168 [0.045-0.627], 2017:p=0.016, 0.258 [0.086- 0.777], 2019: p=0.033,0.353 [0.135- 0.919], and 2021:p=0.041, 0.288 [0.087- 0.950].