As discussed in last month's Diagnote, protocols designed to safely and effectively eliminate urinary tract infections (UTIs) should include:
How should relapsing UTIs be treated?
If the relapse occurred following a brief period of therapy, continue treatment for a longer period. If the relapse occurred 10 or more days following therapy, repeat therapy with a different antimicrobial agent selected on the basis of susceptibility tests. Then, continue therapy for a longer period (three to four weeks). The procedures to evaluate treatment efficacy described above should be repeated.
Caveat: Relapses are indicative of antimicrobic treatment failure, and are of considerable significance in terms of potential morbidity. Special consideration should be given to the likelihood that the drug selected will reach therapeutic concentrations at the site of infection in the urinary tract.
How should UTIs caused by reinfection be treated?
Provided the urinary tract has had sufficient time to repair damaged tissues, reinfection caused by different pathogenic microbes would be expected to occur later following discontinuation of treatment than a relapse (Table 1). Therefore the results of a urinalysis and culture should be re-evaluated approximately two to three weeks after cessation of antimicrobial therapy.
Detection of frequent reinfection following antimicrobial therapy warrants evaluation of the patient for one or more predisposing causes (Table 3). The goal is to correct the predisposing cause. reinfection should be managed by choosing antimicrobial agents on the basis of antimicrobial susceptibility tests. Each product should be used for a sufficient period of time (three to five days) to evaluate its effectiveness in sterilizing urine.
Caveat: Elimination of bacterial pathogens associated with reinfection may require therapy of shorter duration (10 to 14 days) than recurrences associated with relapses. In fact, treatment of reinfection with therapeutic doses of antibiotics for long periods is usually not warranted. Why? Because, when recurrences due to reinfection occur the antimicrobial drugs are effectively eradicating bacterial pathogens. Infrequent reinfection (two or three times per year) may be treated as single episodes (i.e. short course of a suitable antimicrobial agent).
How can frequent reinfection be minimized?
In some patients with recurrent UTIs, it may be impossible to identify and/or correct underlying disorders in host defenses that permit bacteria to infect the urinary tract (Table 3). The result is often frequent reinfection. In such cases it may be helpful to provide low-dose (so-called preventative) antibacterial therapy for six months or more with bacteriocidal drugs primarily eliminated in urine.
Drugs that have been used for this purpose include amoxicillin, ampicillin cephalexin and trimethoprim-sulfadiazine. Consider selection of drugs to use for preventative therapy on the basis of results of the most recent antimicrobial susceptibility test. Reduced dosages (about one-third to one-half of the therapeutic dosage) of drugs excreted in high concentration in urine may be used provided there has been complete eradication of bacterial pathogens by therapeutic dosages of appropriate drugs. Logically, low-dose preventive antimicrobial therapy would be inappropriate for management of patients with recurrent bacterial UTI due to relapses, since they have persistent infection.
It is best to give one daily preventive dose of the antibiotic at a time when the drug is likely to be retained in the urinary tract for six to eight hours (for example, prior to bedtime). Even though this preventive dosage regimen does not result in MICs throughout the day, low concentrations of some drugs augment innate host defenses.
In some patients, this strategy appears to interfere with production of fimbriae by some uropathogens. This in turn interferes with the ability of potential pathogens to adhere to and colonize uroepithial cells.
During preventative therapy, urine samples collected by cystocentesis should be recultured at appropriate intervals (so-called surveillance cultures). Samples should not be collected by catheterization, as catheters may cause iatrogenic infection. Urine samples should not be collected by voiding as it may be impossible to distinguish bacterial contaminants in voided samples from pathogens.
Surveillance cultures of urine for bacteria should be performed at shorter intervals initially (after first week of treatment and, if sterile, after the fourth week of treatment). If there are no signs of bacteria-induced urinary tract disease, and the urine is sterile, surveillance intervals may be extended to every eight to 12 weeks.
Any time bacteria are identified, a "breakthrough" infection should be suspected. Recurrences during prophylactic therapy may be associated with poor compliance (Table 4).
Compare bacterial culture results to previous bacterial isolates to determine whether a relapse or reinfection has occurred. The recurrent infection should be treated for an appropriate period with therapeutic dosages (so-called "full dose") of an antimicrobial drug selected on the basis of susceptibility tests. Once the infection has been eradicated and the associated inflammatory response subsides, preventative therapy may be resumed.
Following six to nine months of consecutive negative urine cultures and urinalysis results indicating that the host defenses are functioning adequately, therapy may be discontinued on a trial basis to determine if re-infection will occur. If abnormalities in host defenses have healed, UTI may not recur. If UTI develops within a short period, the procedures outlined above should be repeated.
Caveat: Bacterial infections should be eradicated from the urinary tract prior to prophylactic therapy. Therefore, low-dose preventative antimicrobial therapy would be inappropriate for management of patients with recurrent bacterial UTI due to relapses since by definition viable bacteria are still present in the urinary tract.
Dr. Osborne, a diplomate of the American College of Veterinary Internal Medicine, is professor of medicine in the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota.