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The lower urinary tract has a variety of host defense mechanisms to prevent bacterial urinary tract infection (UTI). Physical barriers such as the length of the urethra; high pressure zones within the urethra; bacteria-trapping longitudinal folds in the proximal urethra; and urethral peristalsis resulting in a unidirectional urine flow, form the first line of defense. These are supported by mucosal defense barriers, including a glycosaminoglycan layer and intrinsic mucosal antimicrobial properties, to prevent bacterial migration and colonization, and by the composition of the urine (Blanco et al, 2001; Bartges, 2005).
Normal cat urine is highly concentrated, with urine specific gravity often exceeding 1.045 and an associated high osmolality (Lees et al., 1979). High concentrations of urea and organic acids and secreted antimicrobial peptides that inhibit bacterial colonization work together with the acquired cell-mediated and antibody-mediated immune response (Blanco et al, 2001; Bartges, 2005), making it a remarkably hostile environment for bacterial growth. It is not surprising therefore, that bacterial urinary tract infections in cats are relatively rare events (Bartges et al, 2000). The reported prevalence is variable, depending on the inclusion criteria of investigating studies. Studies of cats with clinical signs of lower urinary tract disease (dysuria, stranguria, pollakiuria) have consistently shown that the overall prevalence of positive bacterial urine cultures is less than 3% (Kruger et al., 1991; Buffington et al., 1997; Lekcharoensuk et al., 2001). However, some studies have reported much higher prevalences (15-43%) in cats that have normal urinary tract defense mechanisms against infection compromised by the effects of other diseases and/or the treatment (e.g., urinary catheterization, perineal urethrostomy) of such conditions (Lees, 1996; Mayer-Roenne et al., 2007).
Newly Reported Bacterial Pathogens of the Feline Urinary Tract
Our group recently published a study detailing bacterial isolates which caused bacterial urinary tract infection in 107 cats, their prevalence, and their antimicrobial susceptibility data (Litster et al, 2007a). The majority of gram-negative bacterial isolates were E. coli, echoing the results of other published studies in cats (Davidson et al., 1992; Bartges et al., 2000), while the most common gram-positive bacterial isolate was E. faecalis (Table 1). In 84.1% (90/107) of specimens there was a pure growth of a single bacterial isolate; in 14.9% (16/107) of specimens two bacterial isolates were cultured; and in one specimen (0.93%) four different isolates including a multi-drug resistant E. coli were identified.
Table 1. Bacterial isolates (n=126) from 107 cats with lower urinary tract infections.
Total number of isolates
1 Enterococcus faecalis (n=34) and Enterococcus faecium (n=2). 2 Proteus mirabilis (n=5) and one isolate identified as Proteus vulgaris. 3 One isolate identified as Enterobacter aerogenes, two isolates identified as Enterobacter cloacae and one Klebsiella pneumoniae subspecies oxytoca isolate.
We attempted to identify all Staphylococcal isolates to species level using standard biochemical protocols, but in the case of the coagulase-negative Staphylococci (CNS), the current commercial phenotypic identification systems were not discriminatory and could not differentiate between Staphylococcus felis and the other CNS species, in particular Staphylococcus simulans. This necessitated the use of partial 16S rDNA sequencing, which identified all the coagulase-negative isolates as S. felis. S. felis was first recognized from feline clinical specimens in 1989 (Igimi et al., 1989) and is regarded as a normal commensal organism present on the skin (Lilenbaum et al., 1998), the conjunctival sac and eyelid margins (Espinola et al., 1996) and in the saliva of normal healthy cats (Lilenbaum et al., 1999). Igimi (1989, 1994) describes strains of S. felis isolated from clinical specimens from cats with cystitis, but there is no description of the method of specimen collection, the clinical history of the cats, or the degree or purity of growth. CNS are not widely known to be feline pathogens and individual species are difficult to identify (Takahashi et al., 1997). However, in our study, all S. felis-positive specimens were obtained aseptically by cystocentesis from cats with clinical signs of lower urinary tract disease, thereby minimizing the possibility of sample contamination by commensal organisms from the skin or lower urethra. The prevalence of S. felis-positive UTIs reported in our study suggests that S. felis is a common urinary tract pathogen of cats. However, further work, such as analysis of the isolates for virulence factors, would be required to confirm this. As S. felis is not found on the databases of most of the commercial Staphylococcal identification systems currently used by veterinary pathology laboratories, it is likely to be reported as a CNS species. The majority of S. felis isolates were susceptible to all antimicrobials tested, with only two strains resistant to penicillin/ampicillin and only one strain resistant to tetracycline, erythromycin, clindamycin and penicillin/ampicillin.
There have recently been case reports of Corynebacterium urealyticum (previously known as Corynebacterium group D2) in association with lower urinary tract infections in cats (Bailiff et al., 2005; Cavana et al., 2008). These non-hemolytic gram-positive, rapid urea-splitting bacilli are uncommon causes of urinary tract infections in cats and in dogs and they present diagnostic and therapeutic challenges because of slow in vitro growth and the multidrug resistant nature of the pathogen (Bailiff et al., 2005). Risk factors for this type of infection include urological procedures, foreign bodies, bladder mucosa abnormalities, immuno-suppressed states and antibiotic treatment (Cavana et al., 2008). In particular, because of the ability of this organism to hydrolyze urea, infection may be associated with encrusting cystitis, a condition causing precipitation of struvite or calcium phosphate crystals on the bladder mucosa. Treatment should be based on the results of the most recent antimicrobial susceptibility patterns available and treatment of any predisposing factors (Bailiff et al., 2005).
Feline Bacterial Utis: A Newly Reported Clinical Presentation
Although clinical signs of lower urinary tract disease (e.g., dysuria, stranguria, pollakiuria, hematuria) are common in feline practice (Buffington et al., 2006), bacterial urinary tract infections (UTI) in cats are relatively rare (Bartges et al., 2000). However, numerous studies have shown that risk factors such as age (> 10 years), urinary catheterization and perineal urethrostomy can increase this rate markedly (Gregory et al., 1983; Barsanti et al., 1985; Davidson et al., 1992; Lekcharoensuk et al., 2001). Interestingly, a recent study which examined whether decreasing urine specific gravity was associated with positive urine culture reported that no such association existed, but pyuria, bacteriuria and hematuria were all associated with increased likelihood of positive urine culture (Bailiff et al., 2008).
Our group recently published a study that specifically examined bacterial lower UTI in cats in the absence of lower urinary tract clinical signs, a history of inappropriate urination, or previous UTI (including pyelonephritis) (Litster et al., 2009). Asymptomatic bacteriuria is a common but usually benign finding in women, and risk factors include pregnancy, diabetes mellitus, spinal cord injury, indwelling urinary catheterization and being an elderly resident of a nursing home (Nicolle, 2006). Occult bacterial UTIs have also been reported in diabetic dogs, but urinalysis results could reliably predict urine culture status and the presence of bacteriuria was inconsistent (McGuire et al., 2002). Care was taken in our study design to include only urine specimens that were collected by cystocentesis and yielded moderate or heavy growth on bacterial culture, so that iatrogenic bacterial contamination was not a confounding factor. All of our specimens met the widely used interpretive criteria for significant bacteriuria in feline urine (>1,000 CFU/mL of bacteria grown from a quantitative culture of urine collected by cystocentesis; Osborne et al 1999).
Culture positive urine specimens in our study of occult lower UTIs were more likely to be from older female cats (Litster et al., 2009), confirming the results of a previous large epidemiologic study of symptomatic cats (Lekcharoensuk et al., 2001). This finding is also echoed in studies of asymptomatic bacteriuria in humans (Nicholle, 2006) and occult canine UTIs (McGuire et al., 2002) and is not surprising given the relative ease with which resident gastrointestinal flora can ascend the relatively short and wide female urethra from the perineum and establish an infection. The bacteria cultured from urine specimens in asymptomatic cats also appeared to have initiated an inflammatory response in the urinary tract as positive cultures were accompanied by high urine erythrocyte and leukocyte counts (Litster et al., 2009). Asymptomatic bacteriuria in humans is also usually accompanied by pyuria (Nicolle, 2006).
Determination of urine bacterial culture status is increasingly becoming part of a minimum database of laboratory information collected for a wide variety of clinical presentations. In our study, approximately 10-15% of cats that presented for hyperthyroidism, diabetes mellitus or chronic renal disease had a bacterial lower UTI, confirming the findings of other studies (Bailiff et al., 2006; Elliott, 2007; Mayer-Roenne et al., 2007; Bailiff et al., 2008). Also, some cats that presented for routine geriatric checkups had culture positive urine, but these cats had no clinical signs of illness of any kind. The positive relationship between age and positive urine culture status reported in our study and another other study (Lekcharoensuk et al., 2001) may, at least in part, explain this finding.
While healthy women identified with asymptomatic bacteriuria on population screening subsequently experience more frequent episodes of symptomatic infection, antimicrobial treatment of asymptomatic bacteriuria does not decrease the occurrence of these episodes (Nicolle, 2006). Clinical trials have consistently found no benefits with antimicrobial treatment of human asymptomatic bacteriuria and negative outcomes can occur, such as adverse drug effects and re-infection with organisms of increasing antimicrobial resistance (Nicolle, 2006). Prospective clinical trials comparing clinical outcomes in cats with occult UTIs treated with antimicrobials with an untreated control group would be necessary to decide the optimal management recommendations for these cats.
New Antimicrobial Treatments For Bacterial Urinary Tract Infections In Cats
An important concept in modern antimicrobial chemotherapeutics is the mutant prevention concentration (MPC), which is the drug concentration required to prevent selection of first-step resistant variants naturally present in large bacterial populations. Such mutants may be amplifiedby consecutive steps of clonal enrichment under selective drugpressure during therapy (Wetzstein et al., 2005). Our group recently performed a controlled clinical trial to assess the efficacy and palatability of pradofloxacin 2.5% oral suspension compared to two other commonly prescribed antimicrobials (doxycycline and amoxicillin/clavulanic acid) for the treatment of feline bacterial lower UTI (Litster et al., 2007b). Pradofloxacin is an 8-cyano-fluoroquinolone developed to treat bacterial infections in dogs and cats(Körber B, et al., 2002). Molecular substitutions at positions C-7 and C-8 have greatly enhanced the bactericidal activity of pradofloxacin compared to earlier fluoroquinolones, especially for pathogens with reduced fluoroquinolone susceptibility, as its molecular structure restricts bacterial selection for antimicrobial resistance. Pradofloxacin has been shown in vitro to be highly active against a range of canine and feline urinary tract pathogens, including E. coli and Staphylococcus spp.(Körber B, et al., 2002). In our clinical trial, the post-treatment urine specimen in all cats in the pradofloxacin group (n=27) was negative for bacteria on urine culture. In each of the other 2 treatment groups (doxycycline, n=23; amoxicillin/clavulanic acid, n=28), there were 3 cats (doxycycline, 13.0%; amoxicillin/clavulanic acid, 10.7%) in which the post-treatment urine specimen was positive for bacteria on urine culture. The difference in proportions of treatment failure among groups was not statistically significant (p>0.05). Adverse events that were attributed to drug exposure by the attending veterinarian were not reported in the pradofloxacin or doxycycline groups. Three cats initially allocated to the amoxicillin/clavulanic acid treatment group developed gastrointestinal signs that were attributed by the attending veterinarian to drug exposure, resulting in their exclusion from the trial. None of the cats in the pradofloxacin group had pupillary light reflex test abnormalities during therapy (Litster et al., 2007b).
There is an emerging need for palatable oral pharmaceutical formulations for companion animals, and this factor has a major impact on issues such as owner convenience and compliance, particularly for chronically administered medications (Thombre et al., 2004). Our clinical trial also assessed the ease of administration by owners of each of the three antimicrobials used, all of which were presented in palatable liquid form. All three antimicrobials tested performed equally well, and none of the participating owners reported inability to medicate their cat during the trial. Owners' perceptions of the difficulty of administering oral medication to their cats was more positive post-treatment than pre-treatment (P=0.001) (Litster et al., 2007b).
Cefovecin, a new extended spectrum semi-synthetic cephalosporin, has a 14-day dosing interval after a single subcutaneous injection and combines rapid absorption with slow elimination due to the protein bound fraction of the drug acting as a reservoir with slow release of free (unbound) drug (Stegemann et al., 2006a). Concentrations of cefovecin in urine collected from cats with normal renal function are maintained above the MIC90 of E coli for at least 10 days (Stegemann et al., 2006a). A recent in vitro study reported that cefovecin exhibited in vitro activity against all major aerobic and anaerobic bacterial pathogens associated with skin, urinary tract, and periodontal infections in dogs and cats (Stegemann et al., 2006b). Subsequently, multi-center, masked, randomized study was performed to compare the efficacy and safety of cefovecin with cephalexin for the treatment of feline bacterial UTIs (Passmore et al., 2008). Post-treatment urine cultures revealed that cefovecin eliminated 75.9% of all pathogens (41/54); 76.7% of single and mixed infections with E. coli (23/30); and 72.7% of single infections with E. coli (16/22)--a lower efficacy than that reported for cefovecin in canine UTIs (Passmore et al., 2007). There were no suspected adverse drug reactions attributable to treatment with cefovecin or cephalexin UTIs (Passmore et al., 2008).
In both studies performed by our group to examine bacterial lower UTI in cats, Enterococcus spp. and E. coli were the most common isolates (Litster et al, 2007a; Litster et al., 2009). These were also the most common bacteria isolated from cats with clinical signs of lower urinary tract disease in other published studies (Davidson et al., 1992; Bartges et al., 2000; Gottlieb et al, 2008). In our studies, the E. coli isolates were sensitive to the majority of the antimicrobials tested, whereas the Enterococcus isolates were uniformly sensitive to amoxycillin/clavulanic acid and penicillin/ampicillin and mostly resistant to cephalothin and clindamycin. Based on these findings, in a clinical situation, if high numbers of bacteria are visualized on microscopic examination of a cystocentesis-obtained urine specimen from a cat without lower urinary tract signs, and it is decided that immediate antimicrobial treatment is warranted, it would seem reasonable to prescribe amoxycillin/clavulanic acid for gram-negative infections and amoxicillin for gram-positive infections. Of course, regional variations in bacterial prevalence, bacterial sensitivity patterns and registered drug availability and palatability could affect this recommendation and quantitative urine culture and antimicrobial susceptibility testing is still the recommended "gold standard" to confirm a bacterial UTI and to determine the appropriate antimicrobial treatment.
Disclosure for Annette Litster: Support for some of the work reported in this presentation was provided by: Bayer Animal Health, Leverkusen, Germany; Consultant: Bayer USA
I need a fprmat close to this as possible:
ex. staphyococcus intermedius
Disease potential: #1 cause of canine pyoderma, otitis externa
Diagnostic procedures; beta hemolysis on BAP, catalase and coagulase+, positive in mannitol salt agar
Treatment protocol: whatever if any (I can't find this either)
I need info in this format for staph felis and staph warneri. Thanks