Page 984 - Equine Clinical Medicine, Surgery and Reproduction, 2nd Edition

Urinary system 959

VetBooks.ir Aminoglycosides cephalosporins or trimethoprim/sulphonamides in
the urine and are not used routinely in urinary tract
Aminoglycoside antimicrobials have an excellent
gram-negative spectrum, but less gram- positive
Fluoroquinolones (enrofloxacin: 2.5–5 mg/kg i/v
activity and no activity against anaerobes. infection.
Aminoglycosides are excreted by glomerular or i/m q24 h, or 7.5–10 mg/kg p/o q24 h; orbifloxacin:
filtration and they achieve high concentrations in 2.5–5 mg/kg p/o q24 h) are bactericidal and effec-
urine, which may result in activity against certain tive against many gram-negative and gram-positive
organisms that are resistant in vitro, including gram- organisms. Based on the importance of fluoroquino-
positive organisms, but not anaerobes. The main lones in human medicine, they should be considered
concern about the use of aminoglycosides in uri- second-line drugs and used only when there is resis-
nary tract disease is the potential for nephrotoxicity. tance to first-line drugs. Fluoroquinolones should
The accumulation of aminoglycosides in proximal not be used in growing animals because of effects
tubular cells interferes with normal cell lysosomal on cartilage development. In human medicine a
activity, which activates the intrinsic pathway of cell small, but significantly increased risk of AKI was
apoptosis. Aminoglycosides also alter glomerular found with the use of oral fluoroquinolones. Similar
filtration influencing metabolic, physical and mor- problems have not been reported or investigated in
phological cellular changes. These events also cause horses.
renal vasoconstriction, which is enhanced by direct
effect of aminoglycosides on renal vascular cells. Non-steroidal anti-inflammatory
The development of AKI secondary to amino- drugs
glycoside nephrotoxicity is related to dosing and NSAIDs, especially when given to hypotensive or
the duration of therapy. One dose per day is accept- dehydrated patients, may induce medullary isch-
able treatment for horses. It causes less accumula- aemia and renal papillary necrosis. The nephro-
tion in the tubular cells once the saturation point is toxicity is related to the vasodilatory effects of
reached. Once-daily aminoglycoside administration prostaglandins on renal arterioles. In patients with
also exhibits: normal physiological control of renal blood flow the
role of prostaglandins in preservation of renal blood
• Longer post-antibiotic effect (continued flow is negligible, whereas in hypovolaemic patients,
suppression of bacterial growth despite decline prostaglandins are necessary to maintaining GFR.
of the antimicrobial concentration). Therefore, NSAIDs should be used judiciously in
• Enhanced bactericidal action, which in urinary tract disease. Their use should be reserved
aminoglycosides is concentration dependent. for animals that are not hypovolaemic, hypotensive
• Reduced bacterial adaptive post-exposure or dehydrated.
resistance (multiple-day dosing tends to reduce
aminoglycoside uptake into the bacterial cell). Mannitol
Mannitol is an osmotic diuretic that is used in some
Aminoglycosides should not be used routinely in cases of oliguric AKI. Mannitol is filtered into the
urinary tract infection because of their nephrotoxic tubular space, where it increases tubular fluid osmo-
activity. Extending the dose interval to >24 hours in lality. This impairs fluid resorption, with resultant
patients with renal disease may reduce the incidence increased excretion primarily of water, although
of irreversible nephrotoxicity, although the evidence modest amounts of sodium and potassium are also
for this in the equine is limited. excreted. Mannitol should only be given i/v via a
blood filter administration set.
Other antimicrobials The major potential adverse effects of mannitol
Tetracyclines have been associated with renal tox- administration are consequences of increased plasma
icity, do not achieve levels similar to penicillins, osmolality. When GFR is reduced, as in renal failure