Analysis of pathogens and antimicrobial resistance of sodium-glucose cotransporter 2 inhibitors in treatment of urinary tract infection in patients with type 2 diabetes
ZHANG Chun1, YU Li2, CUI Long2, WEI Wang3, WANG Xiaohong4
1. Department of Emergency Medicine, 2. Department of Endocrinology, 3. Department of Clinical Pharmacology, 4. Department of Hand and Foot Surgery, Chongqing Municipal Corps Hospital of Chinese People's Armed Police Force, Chongqing 400061, China
Abstract:Objective To investigate the distribution and drug resistance of pathogens associated with urinary tract infections (UTIs) in the treatment of type 2 diabetes with sodium-glucose cotransporter 2 (SGLT-2) inhibitors. Methods A retrospective analysis was conducted on 231 patients with type 2 diabetes who were treated with SGLT-2 inhibitors and developed UTIs from January 2020 to December 2023 in Chongqing Municipal Corps Hospital of Chinese People's Armed Police Force. The distribution of pathogens and the resistance of the main isolates were analyzed using routine urine analysis, urine microbial culture and antimicrobial susceptibility testing. Results A total of 231 strains of pathogens were isolated, of which 37 were Gram-positive bacteria (16.02%), 182 were Gram-negative bacteria (78.79%), and 12 were fungi (5.19%). Among the Gram-positive bacteria, 18 strains were Enterococcus faecium (48.65%, 18/37) and 9 strains were Enterococcus faecalis (24.32%, 9/37); 14 strains were multidrug-resistant bacteria (37.84%, 14/37), including 7 strains each of enterococcus faecium and enterococcus faecalis. Among the Gram-negative bacteria, there were 156 strains of Escherichia coli (85.71%, 156/182) and 13 strains of Klebsiella pneumoniae (7.14%, 13/182); 84 strains were multidrug-resistant (46.15%, 84/182), of which 81 strains of Escherichia coli and 3 strains of Klebsiella pneumoniae produced extended-spectrum beta-lactamases (ESBLs).Antimicrobial susceptibility test showed that Escherichia coli had the highest resistance rate to ampicillin and ciprofloxacin (81.94% and 79.35%, respectively), but was more sensitive to carbapenems, tigecycline, and nitrofurantoin. Klebsiella pneumoniae demonstrated a resistance rate of 76.92% to quinolone antibiotics, but was completely sensitive to carbapenems, tigecycline, and cefepime/sulbactam. Both Enterococcus faecium and Enterococcus faecalis exhibited high resistance to a variety of antibiotics, yet showed high sensitivity to vancomycin, teicoplanin, and linezolid. Conclusions The main pathogenic bacteria in the treatment of type 2 diabetes patients with urinary tract infection by SGLT-2 inhibitors are Gram-negative bacteria such as Escherichia coli, with some infections also involving Gram-positive bacteria and a small amount of fungi. Due to the pharmacological mechanism of SGLT-2 inhibitors, there is a higher proportion of multidrug-resistant bacteria, and it is clinically essential to use medication rationally based on antibiogram results.
张春, 余丽, 崔龙, 杨威, 王晓宏. 钠-葡萄糖协同转运蛋白2抑制剂治疗2型糖尿病并发尿路感染患者的病原菌分布和耐药性分析[J]. 武警医学, 2024, 35(9): 754-757.
ZHANG Chun, YU Li, CUI Long, WEI Wang, WANG Xiaohong. Analysis of pathogens and antimicrobial resistance of sodium-glucose cotransporter 2 inhibitors in treatment of urinary tract infection in patients with type 2 diabetes. Med. J. Chin. Peop. Armed Poli. Forc., 2024, 35(9): 754-757.
Go A,Daisuke K,Kenji O, et al.Sodium-glucose cotransporter-2 inhibitors increase urinary tract infections-a cross sectional analysis of a nationwide Japanese claims database[J].Endocr J,2023,70(11):1103-1107.
[5]
Keisuke T,Masahiko G.Increased risk of urinary tract infection and pyelonephritis under concomitant use of sodium-dependent glucose cotransporter 2 inhibitors with antidiabetic, antidyslipidemic, and antihypertensive drugs: an observational study[J].Fundam Clin Pharmacol,2022,36(6):1106-1114.
[6]
Despoina V,Thomas K,Eleni A, et al.Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis.[J].Ann Intern Med,2013,159(4):262-274.
Fone J H,John S.Analysis and presentation of cumulative antibiograms: a new consensus guideline from the clinical and laboratory standards institute[J].Clin Infect Dis,2007,44(6):867-873.
[11]
Giri B,Dey S,Das T, et al.Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: an update on glucose toxicity[J].Biomed Pharmacother,2018,107:306-328.
[12]
Fatma H,Makram K,Amal C, et al.1697. The burden of multidrug-resistant urinary tract infections[J].Open Forun Infect Dis,2020,7(Suppl 1):S831-S831.
Louise S.Effect of high glucose on E coli[J].Nat Rev Urol,2023,20(1):7.
[15]
Eickhoff K M,Dekkers J C,Kramers J B, et al.Effects of dapagliflozin on volume status when added to renin-angiotensin system inhibitors[J].J. Clin Med,2019,8(6):779-779.
[16]
Eleazar B C.Functional linkage between genes that regulate osmotic stress responses and multidrug resistance transporters: challenges and opportunities for antibiotic discovery[J]. Antimicrob Agents Chemother,2014,58(2):640-646.
[17]
Dantas T P,Gastalho C L,Luciene C, et al.Functional role of glucose metabolism, osmotic stress, and sodium-glucose cotransporter isoform-mediated transport on Na+/H+ exchanger isoform 3 activity in the renal proximal tubule[J].JASN,2014,25(9):2028-2039.
[18]
S D I,Ella H,C G U.The basics of bacteriuria: strategies of microbes for persistence in urine[J].Front Cell Infect Microbiol,2016,8(6):14.
[19]
Hiroshige M,Yuka Y,Hiroyuki S, et al.High glucose-mediated overexpression of ICAM-1 in human vaginal epithelial cells increases adhesion of Candida albicans[J].J Obstet Gynaecol,2018,38(2):226-230.
[20]
Hu R,Xia C,Butfiloski E, et al.Effect of high glucose on cytokine production by human peripheral blood immune cells and type I interferon signaling in monocytes: Implications for the role of hyperglycemia in the diabetes inflammatory process and host defense against infection[J].Clin Immunol,2018,195:139-148.