Extra-intestinal non-typhoidal Salmonella (NTS) infections are rare in humans. Bacteremia is reported to occur in 5–10% of humans who are infected with NTS, and immunosuppression and young age (< 1 yr) are risk factors for severe clinical outcomes [21, 22]. NTS infections of the urinary tract are uncommon. In a cohort single-center study that reviewed all cases of NTS urinary tract infections, 27% of patients had isolated symptomatic NTS urinary tract infection without gastroenteritis or Salmonella isolated from a fecal sample. These individuals were found to have a higher rate of underlying lower urinary tract malignancies, as well as higher rates of diabetes and underlying immunosuppressive states [23].
Here, we report the second case of Salmonella bacteriuria in a dog. In the previous report, a dog undergoing immunosuppressive treatment for IMPA had non-clinical bacteriuria, and Salmonella enterica serovar Typhimurium was isolated from the dog’s urine culture [24].
Central nervous system infections due to Salmonella spp. are uncommon in humans and have not been previously reported in dogs. In humans, structural brain disease and systemic immunocompromise have been associated with intracranial Salmonella infection [25, 26]. In children, meningitis is of particularly high risk in infants less than 6 months of age [22]. While meningitis is the most common presentation for Salmonella CNS infections, a few case reports have identified NTS as the etiologic agent for acute transverse myelitis [27, 28]. No serotype has been found to have a greater predilection for the CNS compared to others [29], although Salmonella Enteridis Group D1 was reported to be the most common agent in one report of Samonella meningitis in children [30].
The serovar isolated in this case Salmonella enterica subsp. houtenae is a novel serotype in dogs. This serotype is commonly identified in reptiles and amphibians and more than 90% of reptiles are asymptomatic carriers, contaminating their environment via fecal shedding [18]. In this case, geckos, lizards, and turtles are commonly found in the dog’s yard and have access to the dog’s outdoor water bowl. A limitation of this case management is the absence of cultures of various samples from the dog’s environment to support this hypothesis of source of infection. However, it is the authors’ opinion that given the 3-month time course that elapsed between initial culture diagnosis of a Salmonella species and the subsequent genome identification of S. houtenae, there would be low utility of post-hoc collection and culture of samples.
Of the 51 publications of clinical infection with S. houtenae in people, 5 are case reports of meningitis or brain abscess; 4 affected patients were children and 1 was a patient with HIV [14,15,16,17,18]. In all of these cases, CNS infection was recognized without any preluding or concomitant gastrointestinal signs, similar to the dog in this case report.
There is very limited evidence to guide treatment of NTS gastroenteritis, bacteremia, and complicated infections, such as meningitis and osteomyelitis. Given that NTS resides intracellularly within phagocytes after invading the gastrointestinal epithelium, antibiotics with intracellular penetration are often first line [22]. Amoxicillin/ampicillin, trimethoprim-sulfamethoxazole, fluoroquinolones, azithromycin, and third-generation cephalosporins are often recommended; aminoglycosides have poor clinical efficacy despite proven in vitro activity [22, 29]. There are also no universally-accepted guidelines for the duration for which to treat NTS infection, although a minimum of 4–6 weeks is repeatedly cited [22, 26, 29, 31]. Relapses, if they occur, are thought to most likely be recrudescence rather than re-infection, due to the intracellular persistence of NTS and difficulty achieving adequate and prolonged macrophage penetration [22].
Increasing antimicrobial resistance of Salmonella is an emerging concern, especially resistance to fluoroquinolones. Resistance rates varies with different serotypes; S. Enteritidis is reported to have shown less resistance than other serovars whereas S. Typhimurium definitive phage type (DT) 104 has become multidrug-resistant [21]. The authors acknowledge that retrospectively, a more judicious choice regarding initial antibiotic therapy could have been made in this particular case.
It is unclear if the lumbar pain and neutrophilic pleocytosis that occurred 3.5 years after initial SRMA diagnosis was a SRMA relapse or the first manifestation of Salmonella meningomyelitis, although timing suggests the former. In two studies of the clinical course of SRMA, all dogs had cervical pain on presentation, with thoracolumbar being a concurrent clinical sign in 15 and 34% of dogs; isolated lumbar pain in the absence of cervical pain was not reported in these two populations [32, 33]. Description of clinical signs associated with relapses commonly report “recurrence of previous signs,” cervical pain, lethargy, neurological deficits (paresis, ataxia), and fever [11, 33,34,35]. Though first relapses have been reported up to 2176 days, most occur earlier [11, 32].
This case highlights a novel opportunistic infection in an immunocompromised dog. Culture of CSF and urine as well as blood cultures should be considered in any immunocompromised animal with a compromised barrier system (e.g. dog with meningitis) presenting with potential ‘relapsing’ clinical signs attributable to their initial disease. Although Salmonella should be considered as a cause of opportunistic infection, we do not recommend fecal culture as a component of the diagnostic work-up given that Salmonella can be a found in fecal samples of healthy dogs.