Chapter 114 Urosepsis
Urosepsis, uncommonly reported in veterinary medicine, refers to sepsis associated with a complicated urinary tract infection (UTI). In humans, the source of the infection can be the kidney, bladder, prostate, or genital tract.1 More specifically, urosepsis in humans has been associated with acute bacterial pyelonephritis, emphysematous pyelonephritis, pyonephrosis, renal abscess formation, fungal infections, bladder perforation, and prostatic and testicular infections.2-5 Additionally in human patients, urinary catheter-associated infections have also resulted in sepsis.6-8 Although many of these conditions are often diagnosed in the veterinary patient, little information exists in the veterinary literature regarding the incidence of urosepsis as a complication of these conditions. In one retrospective study looking at sepsis in small animal surgical patients, the urogenital tract was identified as the source of infection in approximately 50% of the cases.9 Of 61 dogs included in the study, sources of urosepsis included pyometra (14), prostatic abscess formation or suppuration (12), testicular abscess formation (3), renal abscess formation (3), and vaginal abscess formation (1). Of four cats included in the study, one had a pyometra and a second cat had a ruptured uterus. This chapter will discuss the pathogenesis of urosepsis, as well as review the veterinary literature to determine what conditions in veterinary medicine have been associated with this disease. Accurate recognition of these complicated UTIs and appropriate, timely treatment are necessary to prevent morbidity and mortality.
Urosepsis is a clinical condition that occurs secondary to a systemic bacterial infection originating in the urogenital tract and the associated inflammatory response. In most cases of urosepsis, bacteria isolated from the rectal, genital, and perineal areas serve as the principal source of infection.10 These bacteria can then migrate from the genital tract to the lower and then upper urinary tracts.10 As in human patients, E. coli is the most common uropathogen affecting dogs and cats and accounts for up to one half of the urine isolates.10-16 Gram-positive cocci, including Staphylococci, Streptococci, and Enterococci, account for up to one third of bacteria isolated and, although uncommonly diagnosed, Pseudomonas, Klebsiella, Pasteurella, Corynebacterium, and Mycoplasma account for the remaining isolates.12,17-19 In humans, gram-negative sepsis is frequently caused by infections originating in the urinary tract.6,13
Because Escherichia coli is the most common pathogen affecting the urinary tract of both human and veterinary patients, and consequently the most common pathogen leading to urosepsis, its virulence has been investigated extensively. Although several hundred serotypes of E. coli are known, fewer than 20 account for most bacterial UTIs.20 In dogs and humans, most of the strains that cause symptomatic UTIs belong to a small number of serogroups (O, K, and H) (see Chapter 109, Gram-Negative Infections).13 Certain properties that may enhance bacterial virulence include the presence of a particular pilus that mediates attachment to uroepithelium, hemolysin, aerobactin, resistance to the bactericidal action of serum, and rapid replication time in urine.10-13 In patients with structural or functional abnormalities of the urinary tract or those with altered defenses, infections can be caused by gram-negative aerobic bacilli other than E. coli, gram-positive cocci, and bacterial strains that normally lack uropathogenic properties.5,14 In patients that have a septic peritonitis associated with a urinary tract disorder, the visceral and parietal peritoneum provides a large surface area for absorption of bacteria and endotoxins, resulting in septic shock.21
Development of a UTI and subsequent urosepsis in both human and veterinary patients often represent a balance between the quantity and pathogenicity of the infectious agents and host defenses. Local host defense mechanisms, including normal micturition, extensive renal blood supply, normal urinary tract anatomy (i.e., urethral length and high-pressure zones within the urethra), urethral and ureteral peristalsis, mucosal defense barriers, antimicrobial properties of the urine, and systemic immunocompetence, are the initial defenses that prevent ascending infection.10,12 Systemic defenses are important in preventing hematogenous spread from the urinary tract.10 A patient with a UTI and a risk factor such as an anatomic abnormality, urinary tract obstruction, nephrolithiasis, prior urinary tract disease, renal failure, neurologic disease, diabetes, Cushing disease, or immunosuppression has a complicated UTI and is more prone to urosepsis.2,5,10,22-24 Additionally, UTIs diagnosed in pregnant or intact dogs and cats should be considered complicated.
Clinical and laboratory findings in a patient diagnosed with urosepsis are often similar to those found in a patient whose sepsis originated from another source. These may include lethargy, fever or hypothermia, hyperemic mucous membranes, tachycardia, tachypnea, bounding pulses, positive blood culture results, and a leukogram that reveals leukocytosis or leukopenia with or without a left shift (see Chapter 106, Sepsis).25 In patients with urosepsis, however, early laboratory tests may identify abnormalities specifically related to the urinary tract, including azotemia, active urine sediment formation, and a positive urine culture result. It is important to perform blood cultures in these patients to confirm that the organism in the urinary tract is identical to that in the blood.6 In cases of severe sepsis, multiple organ dysfunction may be present along with pale mucous membranes, weak pulses, and prolonged capillary refill time. Additionally in cats, diffuse abdominal pain, bradycardia, anemia, and icterus may be identified.25
Although treatment protocols vary in these patients depending on the source of the infection and the complications resulting from sepsis, aggressive treatment is necessary. Treatment often includes a combination of intravenous fluids and broad-spectrum antimicrobial therapy. Once the culture and sensitivity information is available, antibiotic coverage should be changed if necessary, to appropriately treat the isolated organism(s). Additionally, the clinician should address the underlying condition and attempt to correct any complicating factors.14 Although there is some overlap in the clinical presentation for various causes of urosepsis in the veterinary patient, some clinical findings, laboratory results, and treatments are unique to each condition. The rest of this chapter discusses causes of urosepsis that have been identified in veterinary medicine.
The kidneys and ureters are affected more commonly by ascending bacteria than via hematogenous infections. Renal trauma or a urinary tract obstruction may increase the incidence of hematogenous spread of infection to the urinary tract because of interference with the renal microcirculation.26,27 In human patients, hematogenous pyelonephritis occurs most commonly in those who are debilitated from chronic illness or those receiving immunosuppressive therapy.13 Urosepsis resulting from pyelonephritis has been reported uncommonly in the veterinary literature. In a retrospective study evaluating 61 dogs with severe sepsis, a renal abscess in conjunction with pyelonephritis was the source of the infection in only three dogs.9 In a second retrospective study evaluating 29 cats with sepsis, pyelonephritis was the cause of sepsis in only two cats.25 The author has identified seven cats with obstructive calcium oxalate urolithiasis that were also diagnosed with pyelonephritis based on a positive bacteriologic culture result from urine collected by pyelocentesis (unpublished results). None of the identified cats were septicemic. In humans, patients with infected stones or renal pelvic urine were at greater risk for urosepsis than those with a lower tract UTI.28
Dogs and cats with pyelonephritis and urosepsis may be febrile, anorexic, lethargic, dehydrated, and have a history of recent weight loss. If the disease is acute, one or both kidneys may be enlarged and painful, and the animal may have signs of polyuria, polydipsia, and vomiting. Azotemia secondary to renal failure may be present, and blood work often reveals a neutrophilic leukocytosis with a left shift and a metabolic acidosis. In both acute and chronic cases, abdominal ultrasonography, intravenous pyelography, or both, may reveal mild to moderate pelvic dilation and ureteral dilation. The renal cortex and the surrounding retroperitoneal space may be hyperechoic. Renal enlargement often is identified in cases of acute pyelonephritis, and poor corticomedullary definition, distortion of the renal collecting system, and an irregular renal shape and reduced size may be seen with chronic cases. The urinalysis may reveal impaired urine concentrating ability, bacteriuria, pyuria, proteinuria, hematuria, and white blood cells or granular casts.10,29
As previously mentioned, treatment includes removal of predisposing factors, intravenous fluid administration, and broad-spectrum antibiotic therapy until a specific organism is identified. Antibiotic therapy targeted against the isolated organism should continue for 4 to 8 weeks. A urinalysis and culture should be performed after 1 week of treatment and before antibiotic therapy is discontinued to determine whether the infection has resolved. Additionally, a urine culture should be performed 2 to 3 days after therapy has been discontinued. In animals with unilateral advanced pyelonephritis, pyonephrosis, or a renal abscess, partial or total nephrectomy in addition to antibiotic therapy is the treatment of choice.30