Urinary Pathogens Changing in Renal Transplant Patients

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SAN FRANCISCO—Over the past decade, gram-negative organisms have become more prevalent when organisms are isolated from the urine of renal transplant recipients, and resistance to levofloxacin and ceftriaxone has increased among Escherichia coli, the most frequently isolated urinary pathogen in these patients, a new study suggests.

“Increases in multidrug-resistance, especially among gram-negative organisms, are complicating treatment of straight forward infections, like urinary tract infections,” said lead investigator Christine J. Kubin, PharmD, Clinical Pharmacy Manager at New York-Presbyterian Hospital, Columbia University Medical Center in New York. “At our institution and nationwide, we have noticed increases in resistance among cephalosporins and quinolones among urinary isolates. Renal transplant recipients are at increased risk post-transplant and increases in multidrug-resistance may increase the need for readmissions to receive intravenous antimicrobials.”

Dr. Kubin presented study findings at the 52nd Annual Meeting of Interscience Conference on Antimicrobial Agents and Chemotherapy. 

She and her colleagues conducted a retrospective review of unique urine isolates (ISO) identified in 2002-2011 from renal transplant recipients up to 12 months post-transplant.  In this study, unique ISO were separated by14 days or more. The researchers defined multidrug resistance as resistance to three or more classes of antibiotics and recurrence as a patient with two or more ISO within six months or three or more within 12 months.

The study included 1,595 renal transplant patients. Among these patients, 1,250 ISO were identified in 571 patients (36%).  Gram-negative organisms were more common than gram-positive organisms or Candida species (67% vs. 32% and 0.5%, respectively).

The most common organisms were Escherichia coli (31% of ISO), Enterococcus faecalis (19%), Klebsiella pneumoniae (16%), and Enterococcus faecium (12%). The median time to first ISO was 29 days. The initial ISO was gram negative in 383 patients (67%). Of these patients, 23% had multidrug-resistant ISO. Recurrent infection occurred in 232 patients (41%).

The investigators compared two time periods (2002-2006 and 2007-2011) and found that the proportion of gram-negative organisms increased from 62% in the first period to 72% in the second period. The biggest increase occurred among E. coli (from 25% to 36%).

“Bacteriuria most often occurs one to six months post-transplant, and increases in gram-negative organisms as a cause of bacteriuria have occurred over the last 10 years,” Dr. Kubin told Renal & Urology News. “Increases in cephalosporin and quinolone resistance, especially among E. coli, have occurred during this time period. Therefore, the early post-transplant period (the first month) may be a time of opportunity to limit unnecessary antibiotic use.”

Among all gram-negative organisms, resistance was similar between the two periods, but E. coli resistance to levofloxacin increased from 39% to 57% of ISO and E. coli resistance to ceftriaxone increased 10% to 21% of ISO.

Among K. pneumoniae, carbapenem resistance did not change significantly (18% vs. 20%) and vancomycin resistance did not increase in E. faecium (78% vs. 75%). “It was surprising that carbapenem resistance has not significantly increased,” Dr. Kubin said. 

Overall, the investigators found more multidrug resistance among gram-negative organisms in the second period (27% versus 33%). Bacteriuria did not significantly impact graft survival at one year compared to those without bacteriuria (94% vs. 96%).

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