When treating patients with renal failure, the probable benefits of therapy should be considered in the context of probable
risks. If the standard dose and dose interval of drugs dependent on the kidneys for elimination or metabolism are given to
patients with reduced renal function, increased serum concentrations of these drugs might predispose the patient to adverse
drug reactions. When therapy of renal failure patients with drugs dependent on renal excretion is essential, consider adjusting
the dose or dose interval in context of the magnitude of renal dysfunction and potential toxicity of the drug. The goal is
to maintain comparable serum (or plasma) concentrations of the drug known to be safe and effective in patients with normal
renal function. The decision as to whether to alter the drug dose or the maintenance interval between doses should be based
on the best balance of efficacy and potential toxicity. Because the serum half-life of amoxicillin is prolonged in patients
with renal failure and because the efficacy of amoxicillin is dependent on the time the concentration of this drug remains
above the minimum inhibitory concentration, the dose was reduced by 50 percent and given twice per day. [See the "Chronic
Kidney Disease" chapter in the second volume, sixth edition of the textbook of Veterinary Internal Medicine (Elsevier Saunders)
for further information about modification of drug doses and maintenance intervals in patients with renal failure].
How would you monitor response to therapy?
Follow-up bacterial culture of a urine sample collected by cystocentesis three to five days after initiation of antibacterial
therapy was recommended because complete inhibition of bacterial growth in urine at that time provides evidence of effectiveness
Although there might be viable bacteria in surrounding tissues, the urine should be sterile. Hematuria, pyuria and proteinuria
associated with compensatory inflammation may still be present even though the urine contains no viable microbes. Treatment
is considered to be ineffective, and relapse will likely occur if the bacterial colony count only has been reduced, for example,
from 105 colony forming units (CFU) per ml to 102 CFU/ml. In this situation, re-evaluate the therapeutic protocol, including
the basis for selection and dosage of antimicrobic drugs and the likelihood of client compliance with treatment instructions.
A urine sample collected from the cat five days (day 247) after initiation of amoxicillin therapy was bacteriologically sterile;
the magnitude of the inflammatory response was substantially less (Table 2). Likewise, the leukocytosis (Table 1), immature
neutrophilia, and the magnitude of azotemia and hyperphosphatemia were also reduced.
Length of treatment
How long should the patient be treated for bacterial infection of the kidneys?
Because response to treatment of bacterial UTI varies from patient to patient, it is not possible to establish rigid generalities
about the optimum duration of therapy. Duration of antimicrobial therapy should be individualized by monitoring each patient's
response via serial evaluation of clinical and laboratory findings. For patients with upper UTI, therapy is usually continued
for a minimum of three weeks. Deep-seated or severe renal infections may require more prolonged therapy. Re-evaluations of
urinalyses and urine cultures within seven to 10 days after discontinuation of therapy are recommended to detect recurrent
UTIs (relapses or re-infections) at a subclinical stage. Ultimately duration of therapy for each patient should be based on
persistent elimination of UTI as determined by urine culture in addition to amelioration of pyuria and clinical signs.
The owners were instructed to continue amoxicillin therapy for an additional three weeks, to continue feeding the renal-failure
diet indefinitely and to give subcutaneous fluids as needed. Re-evaluation of the patient one month (day 273) after initiation
of treatment of the bacterial UTI revealed that the magnitude of the azotemia had continued to decline (Table 1). Because
there was no evidence of E. coli UTI (Table 2), the owners were advised to discontinue therapy with amoxicillin. Follow-up evaluation of a urine sample collected
by cystocentesis 10 days later revealed no evidence of bacteria or inflammation. Likewise, re-evaluation of the cat four months
later (day 395) revealed no evidence of recurrent UTI (Table 2); the magnitude of renal dysfunction was stable (Table 1).
There was no significant change in the size, number or location of the nephroliths. The owners were advised to continue with
dietary therapy and to give subcutaneous fluids as needed to minimize dehydration. Re-evaluation of the cat every two to three
months was recommended.
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.