UTI is a common cause of problems of LUTD in dogs and, less frequently, in cats. The infection is usually caused by a single organism as a consequence of variable situations that can depend from an alteration of the host defences system, alteration of the normal urination, underlines diseases, anatomical defects, presence of stones in the upper or lower urinary tract, use of improper technique to take urine sample, the presence of indwelling catheters or wrong surgical procedures.
Host defenses are of important value in controlling the development of UTI: they include anatomical natural defenses, like ureteral peristalsis, prostatic secretion, urethral length, normal capability of bladder to void; mucosal defences barrier like GAG (glycosaminoglycans as surface layers), antibody production, intrinsic mucosal antibacterial properties, interference by commensal bacteria on the distal urinary tract; antimicrobial properties of urine, high or low pH, hyperosmolality, high concentration of urea, organic acids, and finally also the systemic immunocompetence plays his role through cell-mediated immunity and humoral-mediated immunity.
Diagnosis of infection: Infection may involve a single or more anatomical part: urethra, prostate gland in the male, bladder, ureters and the kidney (pyelonephritis). The presence of bacteria in the urine does not guarantee the existence of UTI, since the bacteria may be contaminants or pathogens. The diagnosis should be based on quantitative and qualitative methods; detection of bacteria in the sediment may be indicative of infection however the way the urine has been sampled is very important to validate the test results; cystocentesis remains the most reliable system to collect urine for infection studies.
Host defenses are of important value in controlling the development of UTI. Bacterial UTI is more frequent in dogs, affecting 14% of all the dogs during their life, whereas in cat the estimate is quite lower, and several investigations demonstrate that FLUTD associated to bacterial infection is only 1-3%.
Several strain of bacteria affect commonly the urinary tract of both dogs and cats: E.Coli; Proteus mirabilis, Staphylococcus spp, Streptococccus spp, are the most frequent pathogens isolated by urine culture other types may be found as well: Enterobacter Sp.; Klebsiella pneumoniae; Pseudomonas aeruginosa;
Kirby-Bauer disc diffusion susceptibility testing methods are reliable predictors of sensitivity but not of resistance. This is because the methods are related to the presence of bacteria in the serum. In urine the levels of drugs used to treat UTI are often 10 to 100 times higher than in the serum.
The MIC (minimum inhibitory concentration) defines the lowest antibacterial concentration without bacterial growth, usually a urine concentration of antibacterial that is four times the MIC is effective to treat the infection. For this reason the preferred method to perform susceptibility testing for UTI is to evaluate the MIC and compare the results with average urine drug level. For instance, if the average urine level for a drug is 100µg/ml, bacteria that have a MIC = 25µg/ml should be susceptible to the drug.
Selection of the proper drug and dosage
Once the proper drug has been selected it is important to decide about the amount, frequency and timing of treatments. The amount is based if possible on the evaluation of the MIC, the frequency depends on the type of the chosen drug, some of the antibiotics should be given every eight hours (e.g., amoxicillin, cephalexin), other once or twice a day (gentamicin, fluoroquinolones). The optimum time for drug administration is immediately after the patient has been allowed to urinate (easier in dogs then in cats).
Duration of therapy is another important aspect for the success of the therapy; for acute urethrocystitis, antimicrobial treatment may be 7-10 days long; for chronic urethrocystitis, up to 4 weeks of treatment may be necessary; in case of pyelonephritis 4 to 8 weeks may be adequate. In case of complicated UTI antibiotic therapy may need to be continued for months. In some case ancillary therapy (urine acidifiers, antispasmodics or analgesic, should be considered.
During and after the therapy it is important to perform periodical control on the urine, both urinalysis and bacteriological evaluation, to monitor the effectiveness of the chosen therapy, in particular urine culture should be performed 7-14 days after the end of the therapeutic regimen.
Recurrent UTI
After cessation of the treatment, complications may occur with persistent infection, relapsing infection and reinfection; different bacteria can be the cause and reinfection can happen weeks or months following discontinuation of drug therapy.
The patient should be completely revaluated to discover the cause of this complication. Physical examination, abdomen palpation, with particular attention to urinary organs and prostate, routine haematological and serum biochemical tests will be performed along with urinalysis and urine culture.
Diagnostic imaging is very helpful in detecting new change in the anatomy or stone presence; with abdominal radiograph survey, using or not simple or double contrast (cystography, descendent intravenous urography or DIU)) and ultrasound scanning, it is possible to give useful information about abnormalities of kidneys, ureters (in particular with DIU), bladder, prostate in males and urethra.
Indwelling catheterisation, neurogenic disorders of micturition, urethrostomy in male cat may be common cause of recurrent UTI
Modification of drug dosage in renal failure
Conventional dosage rates may be appropriate for initial or loading dose, because volume of drug distribution are usually the same to normal in patients presenting renal failure. However dosage schedules for maintenance therapy must be modified in renal failure, in order to avoid drug accumulation and toxicity; this result may be achieved in two ways:
1. reduce the dose for subsequent treatments at conventional intervals
2. increase the interval between subsequent treatments using conventional doses.
Reducing the dosage amount, with constant interval of administration, produces a more constant plasma concentration, has greater safety since minimize toxic potential, but may produce suboptimal drug level.
Increasing the dosing interval, keeping constant dose, produces large variation in plasma drug levels, with high peak drug level after treatment, and risk of toxicity, and period of suboptimal drug level.
This method is suggested in case of use of nephrotoxic drug like aminoglycosides. Drugs with a narrow margin of safety, require more precise adjustment of the dosage that may be based on GFR (e.g., : creatinine clearance), using the ratio of normal creatinine clearance divided by the patient's creatinine clearance. If we increase the dosage intervals, we multiply the conventional dosage interval by this ratio; if we decrease the dosage, we have to divide the conventional amount by this ratio. A second method to adjust the dosage is based on serum creatinine concentration; because serum creatinine concentration is inversely proportional to GFR serum creatinine can be used instead the creatinine clearance to calculate the adjustment ratio. The patient serum creatinine value is divide by the normal creatinine value and this ratio is used in the same way dividing to decrease dosage or multiplying to increase intervals.
Specific consideration related to the safety of choose drugs, in case of renal failure:
1. Antibiotics with wide margin of safety for which is sufficient to half dosage or doubling treatment intervals:
a. Ampicillin
b. Amoxocillin/Clav. Ac.
c. Cephalotin
d. Enrofloxacin
e. Penicillin G
f. Lincomycin (mostly bacteriostatic)
2. Antibiotics with a narrow margin of safety that require calculation of dosage, proportional to the degree of renal failure:
a. Carbenicillin
b. Cephalexin
c. Aminoglycosides (amikacin, gentamicin, netilmicin, tobramycin)
d. Sulfonamides
3. Antibiotics that should be avoided in severe renal failure.
a. Nitrofurantoin
b. Tetracyclines (except Doxycycline)
Table 1. Some antimicrobial agents used for the treatment of UTI in dogs and cats
Agent |
Spectrum of Activity |
Effect in Urine |
Dog |
Cat |
Route of Administration |
Amoxicillin |
Broad |
Bactericidal |
11mg/kg q8h |
same |
oral |
Amox./Clavul. Ac. |
Broad |
Bactericidal |
10-20mg/kg q8h |
same |
oral |
Ampicillin |
Broad |
Bactericidal |
25mg/kg q8h |
same |
oral |
|
|
|
8mg/kg q8h |
same |
S.C./I.M./I.V. |
Penicillin G (Na or K) |
Moderately broad |
Bactericidal |
40,000U/kg
q8h (*) |
same |
oral
S.C./I.M. |
Cefadroxil |
Broad |
Bactericidal |
10-20mg/kg q8h |
same |
oral |
Cephalexin |
Broad |
Bactericidal |
30-40mg/kg q8h |
same |
oral |
Cephazolin |
Broad |
Bactericidal |
10-20mg/kg q12h |
same |
S.C/ I.M./I.V. |
Amikacin |
Broad |
Bactericidal |
10mg/kg q12h |
5-10mg/kg q8h |
S.C. |
Gentamicin |
Broad |
Bactericidal |
0.5-3mg/kg q12h |
same |
S.C./I.M. |
Kanamycin |
Moderately Broad |
Bactericidal |
6mg/kg q12h |
same |
S.C./I.M. |
Tobramycin |
Moderately Broad |
Bactericidal |
1-2mg/kg q8h |
same |
S.C. |
Enrofloxacin |
Broad |
Bactericidal |
2.5-5 mg/kg q12h |
same |
oral |
Marbofloxacin |
Broad |
Bactericidal |
2.5-5mg/kg q24h |
not defined |
oral |
Norfloxacin |
Broad |
Bactericidal |
5.20mg/kg q12h |
same |
oral |
Nitrofurantoin |
Moderately Broad |
Bacteriostatic |
4mg/kg q6-8h |
same |
oral |
Doxycycline |
Broad |
Bacteriostatic |
5-11mg/kg q12h |
same |
oral |
Tetracycline |
Broad |
Bacteriostatic |
20mg/kg q8h 5-10mg/kg q8h |
same |
Oral
I.M/ I.V. |
Trimethoprim-Sulfadiazine |
Broad |
Bacteriostatic bactericidal |
15mg/kg q12h |
not defined |
oral |
Baquiloprim Sulfadimethoxine |
Broad |
Bacteriostatic Bactericidal |
30mg/kg q24-48h |
same |
oral |
(*) this dosage is useful for the treatment of Leprospirosis infection also