No. 1 Post-Transplant Infection: UTIs

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George Alangaden, MD
George Alangaden, MD

They now account for up to 72% of all infections after renal transplantation, according to recent data.

WASHINGTON, D.C.—UTIs continue to be the most common infections following kidney transplantation, with female gender and duration of urinary catheterization among the strongest risk factors.

“Urinary tract infections occur in kidney transplant recipients at rates far greater than in any other population,” said George Alangaden, MD, professor of medicine at Wayne State University in Detroit. “We also know that most UTIs will occur early, usually within the first three months after kidney transplantation.”

At a joint meeting here of the International Conference on Antimicrobial Agents and Chemotherapy and Infectious Diseases Society of America, Dr. Alangaden reviewed the recent epidemiology of UTIs in adult kidney transplant recipients in the United States. He also described current trends in UTI microbiology and the management of UTIs and asymptomatic bacteriuria in kidney transplant recipients.

UTIs now account for 45%-72% of all infections following kidney transplantation, recent data suggest. The broad range in rates relates in part to varying criteria for defining UTI. Other factors include the use of trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis, duration of follow-up, and frequency of urine testing. In terms of recurrent UTIs after kidney transplantation, the frequency is estimated at 26%-64%.

In addition to female gender and duration of urinary catheterization, risk factors for UTIs after kidney transplantation include diabetes mellitus, older age, polycystic kidney disease, vesicoureteral reflux, prolonged dialysis prior to transplantation, pre-transplantation UTIs, allograft contamination/trauma, the presence of ureteral stents, acute rejection, type of immunosuppression, retransplantation, and cytomegalovirus infection. UTI risk also is higher among patients receiving a deceased-donor organ compared with those receiving a living-donor allograft.

With respect to duration of urinary catheterization, the UTI rate is estimated to be 2.6 episodes per 100 catheter-days compared with 1.4 episodes per 100 days without catheter.

The estimated UTI rate in the first 30 days following transplantation is 14% when the catheter is in place for 2.4 days compared with 74% when the catheter is in place for 8.2 days. The estimated time of UTI onset when a catheter is present is five to nine days.

Another important aspect is the changing microbiology. “What we have noticed in recent reports over the past 10 years is that even though Escherichia coli remains the predominant uropathogen, we have seen the additional gram-negative uropathogens, such as Klebsiella species,  Pseudomonas aeruginosa, and others, play an increasingly important role, unlike in other populations,” Dr. Alangaden said.

“What is more important is that gram-positives account for almost 40% of uropathogens, which is remarkable for this population.” Among the gram-positives, the predominant pathogen in recent studies appears to be Enterococcus species. Conversely, Candida does not appear to be a common uropathogen; it is the culprit in only 0%-11% of UTIs.

Prophylaxis with TMP/SMX, which is primarily used to prevent Pneumocystis jiroveci infection, has also been shown to prevent UTIs in kidney transplant recipients, with doses ranging from 80/400 mg to 320/1,600 mg. The duration of TMP/SMX therapy ranges from 3-12 months. High rates of resistance to TMP/SMX (28%-84%) have emerged in E. coli isolated from UTIs in this population. Resistance to ciprofloxacin also is increasing.

With respect to managing symptomatic UTIs, Dr. Alangaden said empiric therapy should include antibiotics likely to be active against Enterobacteriaceae. Broad-spectrum cephalosporins or penicillins are recommended for hospitalized patients, and fluoroquinolones are recommended for outpatient management. Subsequent therapy should always be guided by susceptibility test results given the high rates of antibiotic resistance.

“The second important point to make about treatment is the duration,” he said. “All UTIs in this population should be considered complicated due to the structural abnormalities that result after transplant and the underlying immunosuppression. So the minimum duration of therapy for both cystitis and pyelonephritis should be at least two weeks.”

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