High urine concentrations of antimicrobials are correlated with efficacy in treatment of uncomplicated cystitis. But in complicated cases and in pyelonephritis, tissue concentrations may be equally important. Most antimicrobials undergo renal elimination to a great extent, so urine concentrations may be up to 100 times peak plasma concentrations. H in the tubular fluid, and degree of protein binding.
The flow of urine through the urinary tract is part of the defense against invading pathogens, because the flow of fluid rinses the epithelial linings. High urine antimicrobial concentrations are important for eradication of bacteria in the urine, but for infection of the bladder wall or renal tissue it is necessary to use antimicrobials that have active concentrations in the tissues. Serum or plasma concentrations are useful surrogate markers for antimicrobial concentrations in the renal or bladder tissues. In addition to having the appropriate antimicrobial activity and achieving effective concentrations in urine, the selected antimicrobial should be easy for owners to administer, have few adverse effects, and be relatively inexpensive. As penicillins, they are weak acids with a low volume of distribution, so they do not achieve therapeutic concentrations in prostatic fluid. Like the penicillins, they are bactericidal, acidic drugs with a low volume of distribution and are relatively nontoxic. Vomiting and other GI signs may occur in dogs and cats treated with cephalosporins.
Cephalosporins have greater stability to β-lactamases than penicillins, so they have greater activity against staphylococci and gram-negative bacteria. In cats, it is only approved for skin infections but may be used in an extra-label manner for UTIs. With SC dosing, therapeutic concentrations are achieved for 14 days, making this an attractive treatment choice for fractious animals. Ceftiofur has pharmacokinetic properties very different from those of other cephalosporins. After injection, ceftiofur is immediately metabolized to desfuroylceftiofur, which has different antimicrobial activity than the parent compound. Because of the instability of desfuroylceftiofur, microbiology services use a ceftiofur disk when performing susceptibility testing, so a false expectation of therapeutic efficacy may result for some pathogens.
Ceftiofur is associated with a duration- and dose-related thrombocytopenia and anemia in dogs, which would not be expected with the recommended dosage regimen. It is active against a wide range of gram-positive and many gram-negative bacteria, against which it is usually bacteriostatic. North America, but it is approved for treatment of UTI in dogs in Europe and is used to treat feline UTI. The fluoroquinolones are bactericidal, amphoteric drugs. All fluoroquinolones usually have excellent activity against staphylococci and gram-negative bacteria, but they may have variable activity against streptococci and enterococci. The therapeutic advantages of these drugs are their gram-negative antimicrobial activity and high degree of lipid solubility. UTIs in intact male dogs and cats because of their excellent penetration into the prostate gland and activity in abscesses.
They are concentration-dependent killers with a long postadministration effect, so once daily, high-dose therapy for a relatively short duration of treatment is effective. Fluoroquinolones should be avoided for chronic, low-dose therapy, because this encourages emergence of resistant bacteria that are cross-resistant to other antimicrobial drugs as well. They are not absorbed orally and must be given by SC, IM, or IV injection. The aminoglycosides have a similar spectrum of activity to that of the fluoroquinolones, but their use for UTI is limited because of the necessity of parenteral injections and the risk of toxicity with anything but short-term use. Like the fluoroquinolones, the aminoglycosides are concentration dependent, bactericidal killers with a long postadministration effect, so once-daily therapy of short duration is effective and minimizes the risk of nephrotoxicity. It is not commonly used in veterinary medicine.
It is typically used only for treatment of UTI in people, because it has a very low volume of distribution, and therapeutic concentrations are attained only in urine. It is considered a carcinogen, so it is banned for use in food-producing animals, but its use in small animals is increasing with the rising rates of antimicrobial resistance to veterinary antimicrobials. It is increasingly indicated for treatment of UTIs caused by multidrug-resistant bacteria, which are otherwise difficult to treat using conventional veterinary antimicrobial agents. However, the tetracyclines are excreted unchanged in urine, so high urinary concentrations may result in therapeutic efficacy. If capsules are administered, it is critical to have the animal drink afterward to ensure passage into the stomach. If capsules remain in the esophagus, severe local necrosis with subsequent esophageal stricture can occur. These drugs are formulated in a 1:5 ratio of TMP to sulfa, although the optimal bactericidal concentration is a ratio of 1:20 TMP:sulfa.
1:20 ratio at the infection site. Although the combination does penetrate the blood-prostate barrier, sulfa drugs are ineffective in purulent material because of freely available para-aminobenzoic acid from dead neutrophils. TMP-sulfas are associated with a number of adverse effects, and chronic low-dose therapy may result in bone marrow suppression and keratoconjunctivitis sicca in dogs. Currently, the duration of therapy for UTI is controversial. 14 days, shorter duration antimicrobial regimens are routinely prescribed in human patients, including single-dose fluoroquinolone therapy. However, further studies are needed to determine the optimal dosage regimens for different classes of antimicrobials, and it is inappropriate to use fluoroquinolones as first-line therapy for simple UTIs. Animals with complicated UTI may require longer courses of therapy, and underlying pathology must be addressed. 6 wk, with the risk of selecting for antimicrobial resistance. 7 days of therapy to determine efficacy.