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P0300CEPHALOSPORINS COMPARED TO OTHER ANTIMICROBIALS FOR CKD-PATIENTS WITH PYELONEPHRITIS INFECTED BY PMRG-PRODUCING ENTEROBACTERIACAE OR NOT


 
 
 Chronic kidney disease (CKD) is assоciated with significant majоr infectiоus complicatiоns, which оccur at rаtes 3 to 4 times the generаl population. Urinary tract infection (UTI) is one of the major nosocomial infections, reaching 150 million episodes per year and accounting for $6 billion. Pyelonephritis is the leading cause of hospitalization among all UTIs. Recent years, steady increase in the rate of uropathogen resistance to commonly prescribed antibiotics is associated with plasmid-mediated resistance genes (PMRG) existence. The aim of the study is to compare the effectiveness of cephalosporins versus fluoroquinolones for pyelonephritis among non-dialysis CKD-patients.
 
 
 
 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 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) intravenously. The treatment duration was 7-10 days. After IV treatment, patients were switched to oral levofloxacin 500 mg up to 3-5 days.
 
 
 
 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 PMQR. Clinical outcome was assessed at the day 5 (D5), end of treatment (EOT), test of cure visit (TOC). At the D5, 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 EOT, 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]). At the TOC, 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]). There was no significant difference between levofloxacin and ceftriaxone efficiency, except for the D5, when the clinical efficacy of levofloxacin was significantly higher. In the cephtriaxone group, clinical cure rates were significantly higher among patients, infected with PMRG-negative strains compare to patients infected with resistant bacteria at the D3 (p≤0.001), D5 (p≤0.001), EOT (p=0.013), TOC (p=0.016) visits. In the levofloxacine group, there wasn’t find any significant differences between patients infected with PMRG-producers or not. Rates of microbiologic eradication were significantly higher among patients infected with PMRG-negative strains at the day 5 (OR 0.05; 95% CI [0.01;0.25]), EOT (OR 0.05; [0.01;0.21]), TOC visits (OR 0.03 [0.01;0.13]).
 
 
 
 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.
