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BACTERIAL PYELONEPHRITIS Jennifer Good, DVM Resident, Emergency and Critical Care Mark P. Rondeau, DVM, DACVIM (SAIM) Staff Veterinarian Department of Clinical Studies Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania Douglass K. Macintire, DVM, MS, DACVIM, DACVECC Professor Department of Clinical Sciences Auburn University P yelonephritis is an inflammation of the renal parenchyma and renal pelvis that may be acute or chronic. The terms acute and chronic refer to the nature of the host response rather than the duration of inflammation. Most cases of pyelonephritis in dogs and cats are caused by bacterial infection. Bacterial pyelonephritis is most often caused by ascending urinary tract infection (UTI); however, hematogenous spread is also possible. Disruption of local mechanical or immunologic defense mechanisms in the urinary tract is fundamental to the development of most cases of canine and feline bacterial pyelonephritis. Disruption of local mechanical defense mechanisms may lead to ascending UTI. For example, vesicoureteral reflux may result in bacterial cystitis, leading to bacterial pyelonephritis. During normal micturition, the detrusor muscle contracts and occludes the ureter so that vesicoureteral reflux cannot occur. This preventive mechanism has been shown to be much weaker in animals with preexisting UTIs or obstructive urinary disorders. Congenital ureteral defects (e.g., ectopic ureter) are other common predisposing causes of bacterial pyelonephritis. Other local mechanisms against infection are normal uroepithelium and well-concentrated urine. Therefore, epithelial disruption and diseases that lead to chronically dilute urine may predispose dogs or cats to UTIs. It has been shown that up to 30% of cats with chronic renal failure develop bacterial UTIs. Frequent voiding of urine also helps prevent bacteria from colonizing the lower urinary tract. Disruption of local immunologic defenses can allow bacterial colonization of the urinary tract. Diseases that alter the function of the immune system may lead to decreased neutrophil chemotaxis and a hampered ability to fight off infection. Use of immunosuppressive medications may also decrease immune function. Either endogenous or exogenous insults to the normal competency of the immune system may predispose dogs and cats to bacterial pyelonephritis. Bacteria implicated in the development of pyelonephritis in dogs and cats are usually normal inhabitants of the gastrointestinal tract or skin that have managed to colSTANDARDS of CARE: E M E R G E N C Y onize the urinary tract. The most common causative pathogen identified in dogs and cats is Escherichia coli derived from the normal flora of the gastrointestinal tract. Certain strains of E. coli appear to have particular virulence characteristics that allow them to avoid being flushed out by normal micturition. These bacteria may also survive in acidic urine and actively ascend up the ureters and into the kidneys. Other common pathogens reported to cause bacterial pyelonephritis in dogs and cats include Staphylococcus, Streptococcus, and Enterococcus spp. Proteus, Klebsiella, Pasteurella, Pseudomonas, Corynebacterium, and Mycoplasma spp are less commonly reported. Pyelonephritis may be unilateral (ascending UTI) or bilateral (ascending UTI, hematogenous infection). Clinical signs of pyelonephritis are varied or may be absent altogether, making diagnosis a challenge. DIAGNOSTIC CRITERIA Historical Information Gender Predisposition • Females are more often affected (dogs and cats). Age Predisposition • Dogs: None. • Cats: Older cats with preexisting renal insufficiency may be more predisposed. Breed Predisposition • None recorded. Owner Observations • Polyuria and polydipsia. • Lethargy. • Vomiting (with acute pyelonephritis). • Stranguria and/or hematuria. • Anorexia. • Weight loss (with chronic pyelonephritis). Other Historical Considerations/Predispositions • History of infection: — Bacterial cystitis, especially if recurrent. 7 AND CRITICAL CARE MEDICINE — Sepsis. — Bacterial endocarditis. — Diskospondylitis. — Septic arthritis. • Presence of a local condition predisposing to infection: — Urolithiasis. — Urinary tract neoplasia. — Urine retention: Urethral obstruction or neurologic disease (upper motor neuron bladder with spinal cord lesions above the sacral spinal cord or lower motor neuron bladder with S1–S3 spinal cord lesions). — Congenital ureteral defect. — Juvenile vulvar conformation. — Chronically dilute urine. • Presence of a systemic condition predisposing to infection: — Diabetes mellitus. — Hyperadrenocorticism. — Chronic renal failure. • Use of immunosuppressive medication. Physical Examination Findings • Large, painful kidneys. • Small, irregular kidneys. • Fever. Laboratory Findings Serum Biochemistry Panel $ • Increased blood urea nitrogen, creatinine, and phosphorus. Complete Blood Count $ • Increased white blood cell count. • Immature leukocytosis. Urinalysis $ • Urine sample collection should be done using a sterile technique. • Pyuria, bacteriuria, or proteinuria. • Inappropriately concentrated urine (often isosthenuric). • Leukocyte and/or granular casts. Urine Culture $ • Sampling via cystocentesis or pyelocentesis before initiation of antibiotic therapy is ideal. In patients with bleeding tendencies, uncooperative patients that are not stable enough for sedation, or patients in which repeated attempts at cystocentesis have been unsuccessful, it may be prudent to obtain the sample using a sterile urinary catheter. 8 J U N E 2 0 0 8 V O L U M E 1 0 . 5 • Documentation of infection. • Antimicrobial susceptibility testing. Other Diagnostic Findings Radiography $ • Bilateral or unilateral renomegaly (acute pyelonephritis). • Small, irregular kidneys (chronic pyelonephritis). • Perinephric gas or loss of detail. • Evidence of nephroliths, ureteroliths, cystic calculi, or urethral calculi. • Proximal ureteral dilation or complete dilation if the patient has a concurrent ectopic ureter. • Radiography results may be normal. Ultrasonography $$ • Renal pelvic dilation: Pyelectasis (usually >2 mm). • Renomegaly (acute pyelonephritis). • Perirenal gas or fluid. • Hyperechoic renal cortices (more likely in patients with chronic pyelonephritis). • Decreased corticomedullary distinction (more likely in patients with chronic pyelonephritis). Contrast-Enhanced Computed Tomography $$$–$$$$ • Unilateral or bilateral renomegaly (acute pyelonephritis). • Poor definition of calyceal architecture. • Blunting of diverticuli. • Patchy nephrographic appearance on angiography caused by an atrophied or asymmetric renal cortex. • Poorly demarcated ischemic areas secondary to infarction. • Homogeneous or heterogeneous enhancement of renal parenchyma. Excretory Urography (Intravenous Urography or Pyelography) $$ • Excretory urography helps to rule out ureteral obstruction as a cause of pyelectasis. • Dilation of the renal pelvis and/or ureter. • Blunting of diverticuli. • Filling defects or fragmentation of contrast within the collecting system because of accumulation of exudate. Histopathology $$ • Samples for histopathology may be obtained via exploratory laparotomy or laparoscopy or using an ultrasound-guided Tru-Cut biopsy needle. • Scarring of capsular surface. • Interstitial mononuclear inflammation. TA B L E 1 A n t i b i o t i c s f o r I n i t i a l Tr e a t m e n t Spectrum and Efficacy Route of Elimination Route of Administration Canine Dosage Feline Dosage Rational Empiric Use Ampicillin Gram +: Excellent Gram –: Fair Anaerobes: Excellent Other: Leptospirosis Renal filtration into urine IV, SC, or IM 22 mg/kg q8h 22 mg/kg q8h Good first choice for hospitalized patient with suspected grampositive infection or suspected leptospirosis Amoxicillin Gram +: Excellent Gram –: Fair Anaerobes: Excellent Other: Leptospirosis Renal filtration into urine PO, IM, or SC 20 mg/kg q12h 20 mg/kg q12h Good first choice for suspected grampositive infection or suspected leptospirosis Amoxicillin– clavulanic acid Gram +: Excellent Gram -: Good Anaerobes: Excellent Renal filtration into urine PO 13.75 mg/kg q12h 62.5 mg q12h Good broad spectrum for possible mixed infection while awaiting culture results Cefoxitin Gram +: Good Gram -: Good Anaerobes: Excellent Renal filtration into urine SC, IM, or IV 20 mg/kg q8h 20 mg/kg q8h Good broadspectrum choice for hospitalized patient Cefotaxime Gram +: Fair Gram -: Excellent Anaerobes: Excellent Renal filtration into urine IV, IM, or SC 30 mg/kg q8h 30 mg/kg q8h Excellent choice for suspected resistant infection in hospitalized patients Cephalexin Gram +: Excellent Gram -: Good Anaerobes: Good Renal filtration into urine Some secretion into bile PO 30 mg/kg q8h 30 mg/kg q8h Good first choice with suspected grampositive infection Doxycycline Gram +: Fair Gram -: Good Anaerobes: Fair Other: Leptospirosis ~75% eliminated in feces ~20% eliminated in urine <5% excreted in bile PO or IV 5–10 mg/kg q12h 5 mg/kg q12h Good choice if underlying leptospirosis is suspected Enrofloxacin Gram +: Good Renal filtration Gram -: into urine Excellent Anaerobes: Fair PO, IM, or IV 10 mg/kg q24h 5 mg/kg q24h Excellent first choice for suspected gramnegative infection Ticarcillin– clavulanic acid Gram +: Excellent Gram -: Good Anaerobes: Excellent IV or IM 50 mg/kg q6–8h 50 mg/kg q6–8h Excellent broad spectrum for suspected resistant organisms Drug Renal filtration into urine • Increased interstitial fibrous tissue. • Leukocyte casts in collecting tubules. • Pelvis and calyx involvement (infiltration of subenSTANDARDS of CARE: E M E R G E N C Y dothelial connective tissue with inflammatory cells). • Interstitial deposits of Tamm-Horsfall protein precipitates with chronic pyelonephritis. 9 AND CRITICAL CARE MEDICINE Summary of Diagnostic Criteria • Positive urine culture (ideally from the renal pelvis but may also be from the lower urinary tract) with appropriate antimicrobial susceptibility testing. • Dilated renal pelvis. • Painful, large kidneys or small, irregular kidneys. • Immature leukocytosis. • Azotemia. • History of polyuria and polydipsia. • Hyperechoic renal cortices. Diagnostic Differentials • Other causes of lower urinary tract signs (hematuria, stranguria): Bacterial cystitis, urolithiasis, sterile cystitis (feline urinary tract disease), urinary tract neoplasia, hemorrhagic cystitis from cyclophosphamide therapy, disorders of primary hemostasis. • Other causes of renal failure: Leptospirosis, nephrotoxins, bilateral ureteral obstruction, hypoperfusion, renal lymphoma, renal dysplasia, chronic interstitial nephritis. • Other causes of renomegaly: Hydronephrosis (as with ureteral obstruction), feline infectious peritonitis, neoplasia. • Other causes of polyuria and polydipsia: Diabetes mellitus, hyperadrenocorticism, hypoadrenocorticism, diabetes insipidus, psychogenic water drinking, hypercalcemia, liver disease, hyperthyroidism, pyometra. TREATMENT RECOMMENDATIONS Initial Treatment • Antibiotic treatment should be based on culture and sensitivity. Gram stain may help guide initial antibiotic choices. Reasonable initial choices are listed in Table 1. $ • Ideally, all antibiotics should initially be given intravenously, especially in cases of acute pyelonephritis. • Scientific evidence for the appropriate duration of antibiotic treatment for dogs and cats is lacking. Current recommendations are to treat initial episodes for a total of 4 to 6 weeks. Recurrent episodes may warrant longer treatment times. Alternative/Optional Treatments/Therapy Surgery $$$–$$$$ • Renal or perirenal abscess formation may warrant surgical intervention. • Cystic, ureteral, renal, or urethral calculi may need to be surgically removed if they are serving as a nidus for recurrent infection, obstructing urine flow, or causing patient discomfort. 10 J U N E 2 0 0 8 V O L U M E 1 0 . 5 Lithotripsy $$$–$$$$ • Cystoscopic laser lithotripsy may be used to remove cystic calculi in patients that are large enough to accept the instruments (excluding small male dogs and cats). • Extracorporeal shock-wave lithotripsy may be used to fragment uroliths in any site. Minimally Invasive Procedures $$–$$$$ • Ureteral or urethral stents may be placed with fluoroscopic guidance to facilitate passage of calculi. • Voiding urohydropulsion may be performed to remove small cystic and urethral calculi. • Furosemide, mannitol, amitriptyline, or glucagon may be used to facilitate passage of ureteral calculi. • Percutaneous nephrolithotomy may be used when indicated. • Cystoscopic laser surgery may be performed for correction of ureteral ectopy. Supportive Treatment Fluid Diuresis $ • If renal failure is present, the animal should be hospitalized and given IV fluids until the renal values have normalized or stabilized. Pain Medication $ • Tramadol: 2 mg/kg PO bid. • Buprenorphine: 0.01 mg/kg IV or PO q6–8h. • Butorphanol: 0.1–0.3 mg/kg IV q6h. Gastric Antacids $ • Famotidine: 0.5 mg/kg PO or IV sid. • Ranitidine: 2 mg/kg PO or IV bid. • Omeprazole: 0.5–1.0 mg/kg PO sid. • Esomeprazole: 0.5–1.0 mg/kg PO or IV sid. Phosphate Binders $ • Phosphate binders should be used in patients with hyperphosphatemia. • Aluminum hydroxide: 10–30 mg/kg PO with each meal. • Aluminum carbonate: 10–30 mg/kg PO with each meal. Antihypertensive Agents (If Indicated) $ • Antihypertensive therapy should not be instituted until the animal is stable and any dehydration has been resolved with fluid therapy. • Amlodipine: — Dogs: 0.1–0.5 mg PO sid or bid. — Cats: 0.625–2.5 mg PO sid or bid. Cats weighing more than 4 kg may require a higher dosage. • Enalapril or benazepril: — Dogs: 0.25–0.5 mg/kg PO sid or bid. — Cats: 0.25–1 mg/kg PO sid or bid. Dietary Modifications $ • If renal failure is present, protein- and phosphorusrestricted diets may be useful for long-term management. • If urolithiasis is present, dietary manipulation may be indicated depending on the type of stone. Patient Monitoring • For patients without a history of UTIs, urine culture and urinalysis should be performed 3 to 5 days into therapy (or sooner if desired) and repeated 1 and 4 weeks after cessation of antibiotic therapy. • For patients with a history of recurrent UTIs, urine culture should be repeated approximately 1 week before cessation of antibiotic therapy. A follow-up urine culture at 8, 12, and 24 weeks after cessation of therapy is also appropriate. • For patients with renal failure and any of its sequelae, routine monitoring is indicated as for other patients in renal failure. • For patients with urolithiasis being treated medically for dissolution, follow-up radiography should be conducted, with the interval depending on the type of stone. Home Management • For patients with persistent renal failure, provision of adequate amounts of water is necessary to help maintain hydration. • For cats with persistent renal failure, feeding wet food provides another source of water. • Subcutaneous fluid administration may be useful to provide fluid support to patients in renal failure that are unable to maintain adequate hydration with their own intake. • Dietary and other supportive management of chronic renal failure should be provided if indicated. Milestones/Recovery Time Frames • The animal should stop straining to urinate after a few days of appropriate antibiotic therapy. • Resolution of hematuria should be seen within days of starting therapy. • Appetite and general attitude should improve over the first few days of therapy. STANDARDS of CARE: E M E R G E N C Y Treatment Contraindications • Nephrotoxic drugs. • Aminoglycosides. • NSAIDs are usually not recommended because of concomitant renal insufficiency. • Placement of urinary catheters should be avoided because their use may introduce further infection into the lower urinary tract. If acute renal failure is present and urine output needs to be measured, use of a urinary catheter should be strongly considered because it is imperative to ensure that the animal is not going into oliguric or anuric renal failure. PROGNOSIS Favorable Criteria • A negative urine culture after cessation of antibiotic therapy indicates that the infection has cleared. • Normal renal values on recheck chemistry panels. • Successful identification and treatment of predisposing factors. Unfavorable Criteria • • • • • • • • Persistent azotemia. Positive urine culture despite antibiotic therapy. Urine casts on subsequent urinalysis. Urolithiasis may result in recurrent or persistent infection if uroliths are not removed. Underlying neoplasia. Recurrent infections. Multiple drug-resistant infections. Oliguria or anuria. RECOMMENDED READING Allen TA, Jaenke RS: Pyelonephritis in the dog. Compend Contin Educ Pract Vet 7(5):421–428, 1985. Bartges JW: Urinary tract infections, in Ettinger, Feldman EC (eds): Textbook of Veterinary Internal Medicine. Philadelphia, WB Saunders, 2005, pp 1800–1808. O’Brian TR: Radiographic Diagnosis of Abdominal Disorders in the Dog and Cat: Radiographic Interpretation, Clinical Signs and Pathophysiology. Philadelphia, WB Saunders, 1978, pp 520–521. Osborne CA, Lees GE: Bacterial infections of the canine and feline urinary tract, in Osborne CA, Delmar FR (eds): Canine and Feline Nephrology and Urology. Philadelphia, Lea & Febiger, 1995, pp 759–797. Senior DF: Management of urinary tract infections, in Elliott J, Grauer GF (eds): BSAVA Manual of Canine and Feline Nephrology and Urology. Gloucester, BSAVA, 2007, pp 282–290. 11 AND CRITICAL CARE MEDICINE