SUN-079 THE PROBLEM OF RESISTANCE UTI IN NON-DIALYSIS CKD PATIENTS: TREARMENT EFFICACY AND OUTCOMES

Abstract

Resistance to common groups of antibiotics has been increasing in the treatment of urinary tract infections worldwide. CDC has estimated that more thаn 2 million infections and 23,000 deaths are due to antibiotic resistance each year. By 2050, it is estimated that antibiotic resistance will cause 10 million deaths every year. CKD is assоciated with significant majоr infectiоus complicatiоns, which оccur at rаtes 3 to 4 times the generаl population. Infection is an importаnt cause of mоrbidity and mоrtality amоng patients with kidney failurе and is the sеcond lеading causе of death following CVD. Recent studies in Europe and the United States have demonstrated that steady increase in the rate of uropathogen resistance to commonly prescribed antibiotics is associated with plasmid-mediated resistance genes (PMRG) existence. A cross-sectional study of 105 adult CKD patients with pyelonephritis, who were admitted in Kharkiv City Clinical Emergency Hospital, Ukraine, was carried out. Antimicrobial susceptibility of bacterial isolates was determined by the Kirby Bauer disk diffusion method and screening for PMRG was performed by the polymerase chain reaction. Subjects were randomized to receive either 3d generation of cephalosporins (n=56), or fluroquinolones (n=49) (levofloxacin) intravenously. The treatment duration was 7-10 days. After IV treatment, patients were switched to oral levofloxacin 500 mg up to 3-5 days. Clinical and bacteriological outcomes were classified as clinical/bacteriological cure or failure. The primary end points of the study were composite cure (clinical cure and microbiologic eradication) at day 5, end of treatment and at the test-of-cure visit (21 day±3 after initiation of antimicrobial therapy). Out of 105 patients, 31 (29.5%) were infected with PMRG-producing bacteria. Among 81 gram negative bacterial isolates, 39 (48.1 %) were identified to carry different types of PMRG, among which 27 (69.2 %) were found to be extended spectrum beta-lactamases producers (ESBLs), and 12 (30.8 %) – were positive for plasmid-mediated quinolone resistance genes (PMQR). Clinical outcome was assessed at the Day 5, end of treatment, test of cure visit. At day 5, clinical cure was observed in 41.9% (13/31) patients infected with resistance bacteria compared to 75.7% (56/74) patients infected with PMRG-negative bacterial strains (RR 0,4 95% CI [0,21; 0,75]). At the end of treatment, the favorable clinical response was seen in 51.6 % (16/31) patients infected with PMRG-bacteria compared to 87.8 % (65/74) patients infected with PMRG-negative bacterial strains (RR 0,91 95% CI [0,8; 1,03]). The hospitalization term was longer for patients infected with PMRG-strains compared to the patients infected with non PMRG-strains (median 10.5 days vs. 8.4 days, P < 0.05). At the test-of-cure visit, composite cure was observed in 82.6% (19/23) and 96.3% (79/82) patients, respectively (RR 0,86 95% CI [0,71; 1,04]). Composite cure rates were significantly higher in patients infected with PMRG-negative bacterial strains. Further clinical studies are needed to establish the guideline for the management of patients with plasmid-mediated resistance and to expand the number of options available for empiric therapy of these multi-drug resistance infections.