Clinical significance of identification of Sphingomonas paucimobilis on bacterial culture in companion dogs and cats.

Clinical significance of identification of Sphingomonas paucimobilis on bacterial culture in companion dogs and cats. | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 13 September 2025 V1 Latest version Share on Clinical significance of identification of Sphingomonas paucimobilis on bacterial culture in companion dogs and cats. Authors : Perrine Henry 0000-0003-1630-9080 [email protected] , Devon Russell , Gavin Paterson , Silke Salavati 0000-0003-1084-7013 , and Alisdair Boag 0000-0002-3819-1821 Authors Info & Affiliations https://doi.org/10.22541/au.175773075.56404328/v1 465 views 159 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background : Sphingomonas paucimobilis is part of the commensal microbiota of many animals but considered an emerging opportunistic pathogen in humans. Its occurrence and clinical relevance in dogs and cats is unknown. Objectives : We aimed to investigate the clinical significance of identification of S. paucimobilis on bacterial culture samples from dogs and cats. Methods : Retrospective longitudinal study. Medical records of dogs and cats with documented growth of S. paucimobilis from a single veterinary hospital were reviewed. Characteristics of the isolate (site, quantitative assessment, co-infections, sensitivity testing) and potential inciting causes (concurrent antibiotic treatment, immunosuppression, comorbidities) were retrieved. When possible, follow-up data were collected to document response to treatment and outcomes. Results : Ninety microbiology reports from 80 dogs and 10 cats were included. The most common site of isolation was the respiratory tract (33/90) followed by urine and skin (13/90 each). Pure growths were less common (9/90) than mixed. Sensitivity testing was only available from three cases. Most animals were treated with antimicrobials (70/90). Response to treatment was available for 78 animals and outcomes for 87. Most animals experienced a resolution of clinical signs (66/78), of which 12/66 had negative repeat culture. Thirty-four animals died during the follow-up period; five of those (all isolated from the respiratory tract of dogs, one of which a pure growth) were possibly related to S. paucimobilis infection. Conclusion : S. paucimobilis isolated from dogs and cats is often incidental, however it may be clinically significant when isolated from the respiratory tract in dogs. Clinical significance of identification of Sphingomonas paucimobilis on bacterial culture in companion dogs and cats. Perrine M. N. Henry 1 , Devon Russell 1 , Gavin K. Paterson 2 , Silke Salavati Schmitz 1 , Alisdair M. Boag 1 1 Hospital for Small Animals, The Royal (Dick) School of Veterinary Studies, EH25 9RG, Roslin, UK 2 Easter Bush Pathology, The Royal (Dick) School of Veterinary Studies and The Roslin Institute, EH25 9RG, Roslin, UK Correspondence: Perrine Henry, [email protected] , 07904997582, Hospital for Small Animals, The Royal (Dick) School of Veterinary Studies, Easter Bush Campus, EH25 9 RG, Roslin, Midlothian, UK Abstract Background : Sphingomonas paucimobilis is part of the commensal microbiota of many animals but considered an emerging opportunistic pathogen in humans. Its occurrence and clinical relevance in dogs and cats is unknown. Objectives : We aimed to investigate the clinical significance of identification of S. paucimobilis on bacterial culture samples from dogs and cats. Methods : Retrospective longitudinal study. Medical records of dogs and cats with documented growth of S. paucimobilis from a single veterinary hospital were reviewed. Characteristics of the isolate (site, quantitative assessment, co-infections, sensitivity testing) and potential inciting causes (concurrent antibiotic treatment, immunosuppression, comorbidities) were retrieved. When possible, follow-up data were collected to document response to treatment and outcomes. Results : Ninety microbiology reports from 80 dogs and 10 cats were included. The most common site of isolation was the respiratory tract (33/90) followed by urine and skin (13/90 each). Pure growths were less common (9/90) than mixed. Sensitivity testing was only available from three cases. Most animals were treated with antimicrobials (70/90). Response to treatment was available for 78 animals and outcomes for 87. Most animals experienced a resolution of clinical signs (66/78), of which 12/66 had negative repeat culture. Thirty-four animals died during the follow-up period; five of those (all isolated from the respiratory tract of dogs, one of which a pure growth) were possibly related to S. paucimobilis infection. Conclusion : S. paucimobilis isolated from dogs and cats is often incidental, however it may be clinically significant when isolated from the respiratory tract in dogs. Keywords : Sphingomonas paucimobilis , bacteria, pneumonia, contaminant, companion animals Introduction Sphingomonas paucimobilis , formally known as Pseudomonas paucimobilis , ( SP ) is an ubiquitous environmental Gram-negative, non-fermentative, aerobic rod considered as a potential emerging opportunistic pathogen in human medicine (1–4). Its identification is often interpreted as a contaminant while most cases of infection are nosocomial or occur in immunocompromised patients (1,5). Clinical presentations of SP infections are variable with reports of central venous catheter infection with bacteriemia, peritonitis, meningitis, brain abscess, soft tissue infection, wound infection, osteomyelitis, urinary tract infections and pneumonias (6). Despite being generally considered an organism with low virulence, there are sporadic reports of severe infections, leading to septic shock or death (7). Sensitivity testing is strongly recommended in serious infections due to frequent resistance to colistin and poor sensitivity to beta lactam antibiotics (8). Data regarding Sphingomonas spp. is limited in veterinary medicine. The genus Sphingomonas is mainly described as part of the commensal microbiota: in the uterus of cows, intestines of fish, chicken, hare and sheep, in the lungs of pigs and horses, in caprine and bovine ejaculates, in the eyes of healthy horses and turtles, and in snails ( Galba truncatula ) (9–22). It has been reported in blood cultures of sea turtles and Antillean manatees and as a pathogen harbored by ticks (23–26). A potentially clinical infection has been described in a wild boar diagnosed with a diaphragmatic abscess from which SP , Streptococcus suis type I , Carnobacterium divergens , and Lactobacillus sakei were isolated (27). There is scarce information relating to the identification of Sphingomonas spp. in companion animals, with only four reports in dogs and none in cats. Sphingomonas spp. have been isolated as part of the skin flora of healthy and atopic dogs, in approximately 10% of canine samples from a variety of sources (including blood cultures and pleural effusions) send to a commercial veterinary bacterial laboratory, and in joint tissue and joint fluid from dogs with osteoarthritis and/or cruciate rupture (28–31). Sensitivity testing is not routinely performed due to lack of information on the bacteria’s breakpoint and because the clinical significance of isolating Sphingomonas sp. from dogs and cats is unknown. As studies in people suggest that SP isolation can be clinically relevant, the aim of this study was to report the isolation of SP in companion dogs and cats and describe their clinical presentation, including any evidence of underlying immunosuppression, response to treatment and outcomes. Materials and methods The microbiology laboratory database of our institution was interrogated for canine and feline reports obtained between December 2018 and April 2025 featuring the word “ paucimobilis ”. Database interrogation was performed with institutional veterinary ethical review committee (VERC) approval (VERC 19.25). S. paucimobilis was isolated from clinical samples submitted for routine diagnosis to our institution microbiology laboratory by culture on Columbia blood agar with 5% v/v defibrinated horse blood (E & O Laboratories, Bonnyrigg, UK) at 37 o C. Identification and sensitivity testing was performed using Vitek2® following manufacturer’s instructions (bioMérieux, Basingstoke, UK). Sensitivity testing was done using the AST-GN97 Pets card and applying Clinical and Laboratory Standards Institute-based breakpoints for non-fastidious non fermenting organisms (32). For each case with SP identification, information on animal signalment (species, breed, age, sex, neutering status, body weight), site of sampling and details of the described bacterial growth (pure or mixed, light, moderate or heavy, other bacteria identified and sensitivity results when available) were recorded. Medical case files were retrospectively reviewed by a single author (PH) to assess for comorbidities (as recorded on medical files) or treatment that may cause immunosuppression (corticosteroids, ciclosporin, tacrolimus, chemotherapeutics), and to collect data on final diagnosis, antimicrobial and other treatments implemented (type, route, duration). Where available, (either from follow-up appointments or communication records) response to treatment and outcomes were also recorded. Where no immediate follow-up was available, referring veterinarians were contacted and clinical follow-up information requested. This included information on presence/ absence of any clinical signs suggesting ongoing infection with SP or any events (morbidity/ mortality) potentially related to SP infection. Regardless of source of follow up, response to treatment was classified as either resolution (if all clinical signs relating to the site where the SP was isolated had resolved or where mild enough not to require veterinary care), resolution with potential recurrence (if clinical signs had resolved and recurred, but there was no repeat bacterial culture to confirm the involvement of SP ), improvement with ongoing signs, no improvement or non-available. Details on evidence for resolution, recurrence or ongoing infection (clinical signs, cytology, repeat culture, others) were also collated. Survival status (alive/ dead) at last follow up was recorded. In the event of death, specific information were collected to evaluate if the death was related (defined as death occurring because of damage to an organ infected with SP alone), possibly related (death occurring because of damage to an organ where SP was isolated alongside other pathogens or death occurring following complete resolution of SP infection with treatment but later infection of the same organ without later identification of the underlying pathogen), or unrelated to SP infection (death or euthanasia for reasons unrelated to the isolation of SP ). Data are presented as frequencies and percentages for qualitative variables and median ± range for quantitative variables. When relevant, relationship between categorical variables was examined using Fisher’s exact test. Statistical significance was defined as p < 0.05. Results Study population: A total of 90 microbiology reports from dogs and cats with SP isolates were identified out of 8357 cultures requests over the study period (90/8357, 1%). Eighty of those were from dogs, of which 38 were female (30 neutered and eight entire) and 42 were male (26 neutered and 16 entire). Median age was 7.4 years-old [range 0.3 – 14.2 years] and median body weight 17.8 kg [range 2.6 – 77.5 kg]. Forty dog breeds were represented: Labrador retriever (n = 8), cocker spaniel (n = 7), Border collie (n = 5), springer spaniel (n = 3), Cavalier King Charles spaniel (n = 3), French bulldog (n = 3), Lhasa Apso (n = 3), pug (n = 3), Boston terrier (n = 2), Chihuahua (n = 2), dalmatian (n = 2), golden retriever (n = 2), shih-tzu (n=2), West Highland white terrier (n = 2), Yorkshire terrier (n = 2), and one of each of the following breeds: basset-hound, beagle, bichon, boxer, Cairn terrier, dachshund, Doberman pinscher, flat-coat retriever, German shepherd dog, Havanese, Hungarian vizsla, husky, Italian spinone, lurcher, Newfoundland, papillon, podenco, poodle, rottweiler, Scottish terrier, shar-pei, Spanish water dog, Weimaraner and Welsh terrier; others were crossbreed dogs (n = 7). Of the ten cats in which SP was isolated, six were males and four females, all neutered. Their median age was 7.2 years [range 3.8 -17 years] with a median body weight of 5.1 kg [range 2.6 – 9.5 kg]. Four were domestic short hair, two Maine Coons and one of each of the following breeds: domestic long hair, Egyptian Mau, Norwegian forest and ragdoll. Origin of the samples : SP was most often isolated from the respiratory tract (33/90, 37%), specifically from bronchoalveolar lavage (BAL, n = 21), nasal biopsies (n = 4), nasal swabs (n = 4), endotracheal tubes (n = 3) and in sputum (n = 1). The second and third most common sites were urine (13/90, 14%, 11 free catch and two catheter samples) and skin (13/90, 14%, eight from surgical wounds, four from lip folds and one from a discharging lesion of nodular panniculitis). Three samples were isolated from the ear (two from the external canal and one from the middle ear) and four from miscellaneous sites (pleural effusion, abdominal effusion, gall bladder wall and vaginal discharge). The remaining samples were equally distributed (8/90, 9% each) amongst the oral cavity (two oral masses, two oral abscesses, three swabs from the soft palate and one from an intra-oral stick injury), corneal ulcers, and abscesses (two peri-orbital, two of the abdominal wall, and one of each of: falciform fat, anal gland, head, neck). Origin of the samples is summarized in Table 1. Characteristics of the isolates : Pure growths of S. paucimobilis were isolated from nine dogs (three BAL, three corneal ulcers, one urine, one surgical wound and from a gall bladder wall) with variable growth (Table 2). All other instances were mixed growths, primarily with other bacteria (80/90, 89%, 60 different strains detailed in Supplementary Table 1 and three non-identified ones), and in one case alongside an opportunistic fungus (1/90, Candida guilliermondii ). Among the 80 mixed bacterial growth, two also grew fungus ( Aspergillus fumigatus ). The bacteria most commonly identified alongside SP were Streptococcus spp. (n = 19), Escherichia coli (n = 18), Staphylococcus spp. (n = 15), Pseudomonas spp. (n = 10), Neisseria animaloris / zoodegmatis (n = 10), Pasteurella spp. (n = 9), Kocuria spp (n = 5) and Granulicatella spp (n = 5). Other bacteria were also identified sporadically (Supplementary Table 1) . Sensitivity testing : Sensitivity testing was only available for three isolates of SP (Table 3): from mixed growths from vaginal discharge, a nasal biopsy and urine. A total of 134 different bacterial isolates were recorded from the 80 mixed bacterial samples of which 43 had one or more antimicrobial resistance (43/134, 32%) (Supplementary Table 1). Treatment, response and outcomes Pure growth (n = 9) Of the nine dogs with pure SP growth, one did not receive specific antimicrobial treatment ( SP isolated in a BAL sample); the dog was alive 13 days after diagnosis with no further follow-up available. Eight dogs received antimicrobials (see Table 4); which included three with corneal ulcers successfully treated with topical ofloxacin, one with a urinary tract infection successfully treated with 7 days of amoxicillin and clavulanic acid (amoxi/clav), one with a skin infection which resolved after 6 days of amoxi/clav administration, but potentially recurred 5 months later; and one with cholecystitis treated with 10 days of amoxi/clav and 5 days of marbofloxacin. For the latter case no information on treatment response and outcome was available. Two cases were dogs with SP pneumonias, of which one was successfully treated with 42 days of amoxi/clav and marbofloxacin (repeat bacterial culture was negative for SP but positive for E. coli and Enterococcus faecium ). This dog was eventually euthanized for reasons unrelated to his initial pneumonia (decerebellate posture following general anesthesia presumed from either hepatic encephalopathy with secondary brain oedema or cerebrovascular event). The second dog with pneumonia had a partial response to four weeks of marbofloxacin with reported improvement of his cough but developed severe pneumonia within two weeks of discontinuing antimicrobials and was euthanized due to poor prognosis. This death was classified as possibly related to SP pneumonia. Mixed growth (n = 81) Without antimicrobials (n = 19) Nineteen animals (15 dogs and four cats) with SP isolates were treated with anti-inflammatory drugs (prednisolone n = 3, meloxicam n = 1), topical antiseptic (hypochlorous acid, n = 2), clotrimazole instillation for sinonasal aspergillosis (n = 1) or benign neglect (n = 12). Origin of the samples was respiratory tract (n = 10), free catch urine (n = 5), skin (n = 2), oral mass (n=1) and vaginal discharge (n=1). Response to treatment was available for 16/19 animals. Fourteen experienced a resolution of their clinical signs (including two cases with negative repeat bacterial culture and one with ongoing cough where repeat BAL documented resolution of SP and new infection with Mycoplasma spp.) and two had ongoing signs (intermittent vaginal discharge and lip fold dermatitis requiring surgery, respectively) but with no repeat bacteriology to confirm ongoing SP infection. Outcomes were documented for 18/19 cases with a median time of follow-up of 93 days [range 0 – 1957 days]. Nine animals died during the follow-up period, of which eight were deemed unrelated to SP infection and one was possibly related. The latter was a French Bulldog who developed pneumonia and profuse purulent nasal discharge shortly after surgery for brachycephalic obstruction airway syndrome and had a moderate mixed growth of SP and Pseudomonas aeruginosa from nasal swab. Despite tracheostomy and oxygen support, the dog continued to deteriorate (recurrent airway obstructions from mucus plugs, poor oxygenation despite high-flow oxygen supplementation) and was euthanized for presumed post-operative airway infection (rhinitis and possible pneumonia) with potential sepsis/ septicemia. Response to treatment was not established as death occurred within hours prior to antibiotic therapy. With antibiotics (n = 62) Most dogs and cats with documented mixed SP isolates were treated with antimicrobials (62/81, 77%) (Supplementary Table 2). The most commonly prescribed antimicrobial was amoxi/clav (38/62, 61%, median duration of 11 days [range 1 – 42 days]), either alone (30/38, 79%) or combined or followed by another antimicrobial (8/38, 21%). Administration was mainly per-os (36/38, 95%) but two dogs received injectable drugs. Fluoroquinolones were the second most frequent choice (12/62, 19%) either alone or in combination with other antimicrobials. Per-os fluoroquinolones were used in five cases, primarily for respiratory diseases (4/5) but also in one case of severe skin disease. Ocular topical medication (ofloxacin) was used for corneal ulcers (n = 4), and auricular topical marbofloxacin for three cases of ear infections. Other antimicrobials used are detailed in Supplementary Table 2. Information on response to treatment was available for 56/62 cases. Forty-eight (48/56, 86%) cases experienced a resolution of the infection based on clinical signs, with documented absence of SP on repeat bacterial culture in 8/48 (17%) and indirect findings supporting resolution in 7/48 (15%, four had normalization of their serum C-reactive protein and three had cytology showing absence of bacteria). One case required surgery (forelimb amputation for failure to heal) despite resolution of bacterial infection on cytology. Three cases (3/56, 5%) had a resolution of the clinical signs and potential recurrence (three dogs with cough that fully responded to antibiotic treatment but relapsed within weeks to months after discontinuation). Five cases (5/56, 9%) showed an improvement but had ongoing signs suggestive of persistent infection (B-lines on point-of-care ultrasound, nasal discharge, discharging oral mass, ongoing bacteria on cytology of the cornea and of the lip). The dog with corneal ulcer required enucleation before further effect of antimicrobial treatment could be assessed (concurrent glaucoma). Outcomes were documented for 61/62 cases, with a median time to outcome of 122 days [range 0 – 2046 days]. Twenty dogs and one cat died over the follow-up period, of which 18/21 (86%) were unrelated to SP . Three dogs were euthanized due to poor prognosis possibly relating to SP infection (3/61, 5%). All were diagnosed with severe bacterial pneumonia (mixed bacterial growth with E. coli, Kocuria rosea and Acinetobacter baumannii complex ; with Granulicatella elegans and E. coli and with E. coli alone, respectively). The first dog developed sepsis in the hospital and the second had concurrent megaesophagus. The last dog was euthanized 4 months after isolation of SP from a BAL. This dog was presumed successfully treated for SP with a 3-weeks course of doxycycline resulting in complete resolution of clinical signs. However, the dog was subsequently euthanized after re-presenting with bacterial pneumonia. In absence of repeat bacterial culture to document a different pathogen, his death was deemed possibly related to SP. Predisposing factors : Seventeen cases (17/90, 19%) were receiving concurrent medications that could cause immunosuppression at the time of identifying SP on bacterial culture. Eight were treated with oral prednisolone (dose range 0.5 – 2 mg/kg per day), four with chemotherapy (three with tyrosine kinase inhibitors and one with vinblastine), three received ciclosporin (two ocular topical, two oral at 5 mg/kg per day) and one was administered ocular tacrolimus. Two of these cases were left untreated (urine free catch sample and nasal biopsy), the other 15/17 cases received antibiotics. Response to treatment was documented in 14/17 and all experienced a resolution of their clinical signs, including the two cases not treated with antibiotics (urine culture was repeated on a cystocentesis sample and found negative suggesting environmental contamination, the nasal biopsy diagnosed lymphoma which was treated with radiation therapy). None of the deaths documented during follow up period (9/17) were related to SP . Seventy-one percent of cases (64/90) had at least one comorbidity that could predispose to the development of infection at the site where SP was isolated (Table 5). Only three of the cats had testing for feline retroviruses (feline leukemia virus, FeLV and feline immunodeficiency virus, FIV). Two were negative. The last cat was positive for FIV, but this was suspected to be a false positive due to vaccination and was therefore excluded from Table 5. Thirty-six animals had a history of previous (11/36, stopped 2 – 14 days prior to bacterial culture) or current antimicrobial treatment when SP was isolated (25/36, duration of the course ranged from 1 to 39 days). Six of those (6/36, 16%) were subsequently not treated with further antimicrobials (current antimicrobials stopped in 2/6, no antimicrobials restarted in 4/6), while 16/36 (44%) animals had the same antimicrobials they had already been given continued (median duration of treatment 8 days [range 1 – 42 days]) and 14/36 (39%) were treated with a different antimicrobial. Response to treatment and outcomes in relation to antibiotic treatment are summarized in Table 6. There was no significant difference between antibiotic naïve cases (39/46 resolution and 3/21 deaths related to SP ) compared to cases with recent or current antibiotic treatment (resolution of signs in 27/32 and death in 2/13, p = 0.96 and 0.93, respectively). Discussion The aim of this study was to report the occurrence of SP isolation from canine and feline samples and to describe the clinical manifestations, treatments and subsequent outcomes in these animals. This was based on the shift in perception of SP ’s pathogenic potential in human medicine: while it was previously considered a contamination or commensal, it is increasingly considered an emerging pathogen and associated with significant morbidity and mortality in people (1,6,7). To the authors’ knowledge, literature surrounding SP isolation or infection in dogs and cats is limited to studies documenting the presence of the bacteria on canine skin, in diseased joints and in the blood of sick patients with no information on its clinical relevance (28–31). Our retrospective analysis and case assessment suggests that identification of SP can be clinically significant, particularly when isolated from the respiratory tract, and associated with mortality in dogs and cats. In the described cohort of 90 dogs and cats, SP was indeed commonly isolated from the respiratory tract (nasal cavity and lower airways), which contrasts with human medicine where SP is mostly seen as bacteremia, caused by nosocomial infection (33,34). Over the study period only 166/8357 culture requests were blood cultures, none of which was positive for SP . This likely reflects the lack of consensus on the indication and value of blood cultures in the investigation of potential sepsis in companion animals, as well as the difficulties surrounding sampling (limited blood volumes due to patient size, tolerability of repeated sampling, regular false negative results) (35,36). Conversely, SP -associated pneumonias and empyema have been reported in people with a hypothesized origin from the oral flora (aspiration) (37). Bacteria commonly isolated from BAL samples in dogs and cats with aspiration pneumonia include: Escherichia coli , Klebsiella spp., Pasteurella spp., Streptococcus spp., Enterococcus spp., Pseudomonas spp. and Staphylococcus spp. (38–40). As these bacteria were commonly encountered alongside SP in samples from the respiratory tract, aspiration seems the most likely point of entry for SP in these cases. Other common sites where SP was identified (oral cavity, skin, urine) were not unexpected, as Sphingomonas spp . are ubiquitous environmental bacteria and part of the cutaneous flora of dogs (28). The clinical relevance of these isolates is difficult to ascertain. In people, positive cultures of superficial swabs are considered to represent colonization rather than infection, especially in the absence of concurrent systemic inflammatory response syndrome (SIRS) (33). The small animal cases included in this report were not assessed for SIRS criteria, but it seems unlikely that ulcerative keratitis or skin wounds would result in SIRS. This suggests that in many cases, SP isolation may be of minor clinical relevance. This is further supported by the largely positive clinical response documented in the small number of cases treated successfully without antibiotics. Three dogs had pure growths of SP from BAL samples. One was not treated (light growth) but follow-up is lacking. The other two dogs (with moderate growths) were treated with antimicrobials, which led to successful resolution of clinical signs in one dog, but only temporary improvement with subsequent persistent or recurrent pneumonia leading to euthanasia in the other. The retrospective nature of this study precludes any comments on the appropriateness of the chosen treatment regimen (4 weeks of amoxi/clav 20mg/kg per-os three times daily and marbofloxacin 5mg/kg per-os daily, and marbofloxacin sole therapy for 4 weeks at 2mg/kg per-os daily respectively) but human literature suggests that the combination of fluoroquinolones, carbapenem, and beta-lactam/beta-lactamase inhibitor are most effective to treat SP . Since the use of carbapenem and associated antimicrobials is strongly discouraged in veterinary species in the UK, a combination of fluoroquinolone with potentiated amoxicillin appears a sensible empirical choice to treat infections proven to be caused by SP (34), especially as antibiotic sensitivity testing is often not available. However, up to 27 and 25% of human SP isolates are resistant to potentiated amoxicillin and fluoroquinolones, respectively (29). In human medicine, sensitivity testing of SP isolates is recommended due to known resistance to colistin and poor sensitivity to beta lactam antibiotics, however no standardized clinical breakpoint exists for Sphingomonas spp. (1,41). As a result, microbiologists often resort to use breakpoints for “other non-Enterobacterales” species or might not offer routine sensitivity testing for these bacteria. In the 90 cases reported here, only three had sensitivity testing performed. As SP was formerly known as Pseudomonas paucimobilis (CDC group IIk-1) (33), and it shares the broad classification of being a non-fastidious non-fermenting gram-negative bacillus with Pseudomonas spp., established breakpoints for Pseudomonas spp. could potentially be applied to SP isolates, but their interpretation would require caution. Further studies are needed to establish specific breakpoints in human and veterinary medicine in order to best guide antibiotic choices. Most (up to 62%) SP infections in people occur in immunocompromised patients or patients with comorbidities (e.g. malignancy, diabetes mellitus and lung disease) (41). In the present animal cohort, the number of cases treated with immunosuppressive drugs was small and outcomes remained unchanged and overall good with or without antimicrobial treatment. In keeping with human medicine, most dogs and cats (71%) had at least one concurrent disease or recent general anesthesia, which can increase the risk of nosocomial infection (42). Dysbiosis is increasingly recognized as a risk factor for the development of infection and can occur secondary to many processes including chronic inflammation and antimicrobial use (43). Poorly justified use of antimicrobials is associated with development of bacterial resistance and SP is commonly multidrug resistant (1). However, recent or current use of antibiotics did not seem to significantly affect the outcome of dogs and cats in the present work. Regardless, strict adherence to the International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for antimicrobial administration in companion animals remains paramount (44). Overall morbidity in the presented cohort was low and, in most cases, not directly attributable to SP infection. Specifically, three dogs required surgery; one enucleation for glaucoma whose S. paucimobilis corneal infection and ulcerative keratitis could have resolved with medical treatment, one labioplasty for ongoing bacterial cheilitis based on cytology but without repeat culture to document ongoing involvement of SP and one forelimb amputation due to wound dehiscence on the elbow despite resolution of infection based on cytology which was probably attributable to the high tension area rather than SP . The main limitation of this study is the large number of cases in which SP was isolated as part of mixed bacterial growth, where other potentially more pathogenic bacterial species could have largely driven the clinical signs. This complicated the assessment of the pathogenicity of SP . However, five fatalities were possibly related to SP infections, one of which occurred in a dog with pure SP growth from a BAL sample. Although several weeks separated the documentation of SP in the lower airways and death, the dog only showed partial response to antimicrobials suggesting ongoing infection. Unfortunately, BAL sampling was not repeated on this occasion, hence the contribution of other pathogens cannot be excluded. Another dog with pneumonia showed pure growth of SP from the BAL sample which might indicate a role in respiratory tract infection. However, repeat BAL culture in this dog isolated only Mycoplasma spp . thus it cannot be excluded that SP represented an environmental contaminant or commensal overgrowth which inhibited the growth of more fastidious but more pathogenic bacteria (45). Resolution of the presence of SP was often assumed based on clinical improvement rather than demonstrated by repeat bacterial culture. Although regrettable, this is not unexpected in a retrospective analysis and largely explained by clinical decision making based on the lack of information regarding the relevance and the pathogenicity of SP isolation. Similarly, response to treatment, comorbidities and outcomes were based on medical records so we cannot exclude that significant morbidity, comorbidities or mortality were missed due to inappropriate record keeping. Conclusion S. paucimobilis was isolated from 1% of the samples from dogs and cats submitted for bacterial culture. While pure growth is rare, S. paucimobilis was commonly found in association with other bacteria. More studies with consistent antimicrobial sensitivity testing and prospective serial sampling are needed to better characterize the true pathogenicity of SP and to establish antimicrobial breakpoints. The most common site of isolation was the respiratory tract, and while overall mortality and morbidity was low, rare fatalities were documented in dogs with respiratory infections. Although SP likely represents an environmental contaminant or commensal in most cases, its isolation from the respiratory tract should be considered clinically significant, particularly in patients with comorbidities. Author Contributions: Perrine M. N. Henry: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation; Devon Russel: Investigation, Data curation; Gavin K. Paterson: Writing – Review & Editing; Silke Salavati Schmitz: Writing – Review & Editing; Alisdair M. Boag: Supervision, Writing – Review & Editing. Data availability statement: The data that supports the findings of this study are available on request from the corresponding author, [PMNH]. The data is not publicly available due to General Data Protection Regulation. Acknowledgements : N/A Conflict of interest : The authors have no conflict of interest to disclose. Ethic statement : Ethical approval for this study was obtained from our institutional veterinary ethical review committee (VERC 19.25). References : 1. Rohilla R, Raina D, Singh M, Pandita AK, Patwal S. Evaluation of Sphingomonas paucimobilis as an emerging nosocomial pathogen in a teaching hospital in Uttarakhand. Iran J Microbiol. 2021 Oct;13(5):617–23. 2. Holmes B, Owen RJ, Evans A, Malnick H, Willcox WR. Pseudomonas paucimobilis , a New Species Isolated from Human Clinical Specimens, the Hospital Environment, and Other Sources. Int J Syst Evol Microbiol. 1977;27(2):133–46. 3. Yabuuchi E, Yano I, Oyaizu H, Hashimoto Y, Ezaki T, Yamamoto H. Proposals of S phingomonas paucimobilis gen. nov. and comb. nov., Sphingomonas parapaucimobilis sp. nov., Sphingomonas yanoikuyae sp. nov., Sphingomonas adhaesiva sp. nov., Sphingomonas capsulata comb. nov., and two genospecies of the genus Sphingomonas . Microbiol Immunol. 1990;34(2):99–119. 4. Ryan MP, Adley CC. Sphingomonas paucimobilis : a persistent Gram-negative nosocomial infectious organism. J Hosp Infect. 2010 Jul 1;75(3):153–7. 5. El Beaino M, Fares J, Malek A, Hachem R. Sphingomonas paucimobilis -related bone and soft-tissue infections: A systematic review. Int J Infect Dis IJID Off Publ Int Soc Infect Dis. 2018 Dec;77:68–73. 6. Ionescu MI, Neagoe D Ștefan, Crăciun AM, Moldovan OT. The Gram-Negative Bacilli Isolated from Caves -Sphingomonas paucimobilis and Hafnia alvei and a Review of Their Involvement in Human Infections. Int J Environ Res Public Health. 2022 Feb 17;19(4):2324. 7. Alkhatib B, Veytsman E, Klumpp L, Hayes E. Sphingomonas paucimobilis Septic Shock in an Immunocompetent Patient. Cureus. 2022 Jul;14(7):e26720. 8. Vaz-Moreira I, Nunes OC, Manaia CM. Diversity and antibiotic resistance patterns of Sphingomonadaceae isolates from drinking water. Appl Environ Microbiol. 2011 Aug 15;77(16):5697–706. 9. Figueiredo CC, Monteiro HF, Cunha F, Bisinotto DZ, Ruiz AR, Duarte GA, et al. Shifts in uterine microbiome associated with pregnancy outcomes at first insemination and clinical cure in dairy cows with metritis. Sci Rep. 2024 May 24;14(1):11864. 10. Zhou G, Ye Z, Luo J, Zhang D, Thongda W, Xu Y, et al. Intestinal microbiota and gene expression alterations in leopard coral grouper ( Plectropomus leopardus ) under enteritis. Fish Shellfish Immunol. 2024 Jul;150:109644. 11. Wang F, Xu J, Wang Z, Cao J, Lu Y. Response signatures of intestinal microbiota and gene transcription of the pearl gentian grouper to Vibrio harveyi i nfection. Fish Shellfish Immunol. 2024 Jun;149:109590. 12. Zhu HJ, Qiang J, Tao YF, Ngoepe TK, Bao JW, Chen DJ, et al. Physiological and gut microbiome changes associated with low dietary protein level in genetically improved farmed tilapia ( Oreochromis niloticus ) determined by 16S rRNA sequence analysis. MicrobiologyOpen. 2020 May;9(5):e1000. 13. Abdel-Kafy ESM, Youssef SF, Magdy M, Ghoneim SS, Abdelatif HA, Deif-Allah RA, et al. Gut Microbiota, Intestinal Morphometric Characteristics, and Gene Expression in Relation to the Growth Performance of Chickens. Anim Open Access J MDPI. 2022 Dec 9;12(24):3474. 14. Zhang R, Zhong Z, Ma H, Lin L, Xie F, Mao S, et al. Mucosal Microbiota and Metabolome in the Ileum of Hu Sheep Offered a Low-Grain, Pelleted or Non-pelleted High-Grain Diet. Front Microbiol. 2021;12:718884. 15. Stalder GL, Pinior B, Zwirzitz B, Loncaric I, Jakupović D, Vetter SG, et al. Gut microbiota of the European Brown Hare ( Lepus europaeus ). Sci Rep. 2019 Feb 25;9(1):2738. 16. Zhang J, Shi K, Wang J, Zhang X, Zhao C, Du C, et al. Effects of respiratory disease on Kele piglets lung microbiome, assessed through 16S rRNA sequencing. Vet World. 2020 Sep;13(9):1970–81. 17. Bond SL, Timsit E, Workentine M, Alexander T, Léguillette R. Upper and lower respiratory tract microbiota in horses: bacterial communities associated with health and mild asthma (inflammatory airway disease) and effects of dexamethasone. BMC Microbiol. 2017 Aug 23;17(1):184. 18. McCann P, McFarland C, Megaw J, Siu-Ting K, Cantacessi C, Rinaldi G, et al. Assessing the microbiota of the snail intermediate host of trematodes, Galba truncatula . Parasit Vectors. 2024 Jan 23;17(1):31. 19. Santibáñez R, Lara F, Barros TM, Mardones E, Cuadra F, Thomson P. Ocular Microbiome in a Group of Clinically Healthy Horses. Anim Open Access J MDPI. 2022 Apr 7;12(8):943. 20. Di Ianni F, Dodi PL, Cabassi CS, Pelizzone I, Sala A, Cavirani S, et al. Conjunctival flora of clinically normal and diseased turtles and tortoises. BMC Vet Res. 2015 Apr 10;11:91. 21. Kilburn C, Rooks DJ, McCarthy AJ, Murray RD. Antimicrobial resistance in some gram-negative bacteria isolated from the bovine ejaculate. Reprod Domest Anim Zuchthyg. 2013 Jun;48(3):525–8. 22. Mocé ML, Esteve IC, Pérez-Fuentes S, Gómez EA, Mocé E. Microbiota in Goat Buck Ejaculates Differs Between Breeding and Non-breeding Seasons. Front Vet Sci. 2022;9:867671. 23. Silva MCO, Attademo FFL, Freire ACB, Sousa GP, Luna FO, Lima DCV, et al. Identification of bacteria in blood cultures from clinically ill captive Antillean manatees ( Trichechus manatus manatus ). J Zoo Wildl Med Off Publ Am Assoc Zoo Vet. 2017 Mar;48(1):13–7. 24. Glassman AR, Zachariah TT. Retrospective analysis of blood cultures and association with clinical findings and outcome in green sea turtles ( Chelonia Mydas ) at a Florida sea turtle rehabilitation facility, 2017-2020. J Zoo Wildl Med Off Publ Am Assoc Zoo Vet. 2024 Jan;54(4):766–75. 25. Khoo JJ, Chen F, Kho KL, Ahmad Shanizza AI, Lim FS, Tan KK, et al. Bacterial community in Haemaphysalis ticks of domesticated animals from the Orang Asli communities in Malaysia. Ticks Tick-Borne Dis. 2016 Jul;7(5):929–37. 26. Aljasham AT, Damra EM, Alkahtani NS, Alouffi A, Al Salem WS, Alshabanah AO, et al. Isolation, identification and antimicrobial susceptibility of the bacteria isolated from Hyalomma dromedarii infesting camels in Al-Jouf province, Saudi Arabia. Front Vet Sci. 2023;10:1227908. 27. Piccinini A, Ferri G, Olivastri A, Rossi F, Festino AR, Vergara A. Intradiaphragmatic abscesses in a wild boar ( Sus scrofa ): Inspective implications based on anatomopathological evidences. Ital J Food Saf. 2022 Aug 11;11(3):10346. 28. Harvey RG, Duclos D, Krumbeck J, Tang S. Quantification of the bacterial flora and its major constituents on the abdominal skin of clinically healthy dogs. Am J Vet Res. 2023 Sep 1;84(10):1–6. 29. Apostolopoulos N, Glaeser SP, Bagwe R, Janssen S, Mayer U, Ewers C, et al. Description and comparison of the skin and ear canal microbiota of non-allergic and allergic German shepherd dogs using next generation sequencing. PloS One. 2021;16(5):e0250695. 30. Davenport AC, Mascarelli PE, Maggi RG, Breitschwerdt EB. Phylogenetic diversity of bacteria isolated from sick dogs using the BAPGM enrichment culture platform. J Vet Intern Med. 2013;27(4):854–61. 31. Tuek-Um S, Yangtara S, Surachetpong W, Kaewmongkol S, Kaewmongkol G, Thengchaisri N. Bacterial DNA and osteoarthritis in dogs with patellar luxation and cranial cruciate ligament rupture. Vet World. 2023 Oct;16(10):2049–54. 32. VET06 | Methods for Antimicrobial Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria Isolated From Animals [Internet]. [cited 2025 Jun 26]. Available from: https://clsi.org/shop/standards/vet06/33. Toh HS, Tay HT, Kuar WK, Weng TC, Tang HJ, Tan CK. Risk factors associated with Sphingomonas paucimobilis infection. J Microbiol Immunol Infect. 2011 Aug 1;44(4):289–95. 34. Lin JN, Lai CH, Chen YH, Lin HL, Huang CK, Chen WF, et al. Sphingomonas paucimobilis bacteremia in humans: 16 case reports and a literature review. J Microbiol Immunol Infect Wei Mian Yu Gan Ran Za Zhi. 2010 Feb;43(1):35–42. 35. Neumann N, Solis SAF, Crawford S, Rogovskyy AS. Are multiple blood cultures advantageous for canine patients? J Vet Diagn Investig Off Publ Am Assoc Vet Lab Diagn Inc. 2023 May;35(3):332–5. 36. Saarenkari HK, Sharp CR, Smart L. Retrospective evaluation of the utility of blood cultures in dogs (2009–2018): 45 cases. J Vet Emerg Crit Care. 2022;32(1):141–5. 37. Kumar NR, Norwood BS. Sphingomonas Paucimobilis Pneumonia Complicated by Empyema in an Immunocompetent Patient: A Case Report and Concise Review of Literature. Cureus. 14(5):e24820. 38. Howard J, Reinero CR, Almond G, Vientos-Plotts A, Cohn LA, Grobman M. Bacterial infection in dogs with aspiration pneumonia at 2 tertiary referral practices. J Vet Intern Med. 2021 Nov;35(6):2763–71. 39. Cook S, Greensmith T, Humm K. Successful management of aspiration pneumopathy without antimicrobial agents: 14 dogs (2014-2021). J Small Anim Pract. 2021 Dec;62(12):1108–13. 40. Goggs RAN, Boag AK. Chapter 23 - Aspiration Pneumonitis and Pneumonia. In: Silverstein DC, Hopper K, editors. Small Animal Critical Care Medicine (Second Edition) [Internet]. St. Louis: W.B. Saunders; 2015 [cited 2025 Jun 26]. p. 127–33. Available from: https://www.sciencedirect.com/science/article/pii/B978145570306700023441. Laupland KB, Paterson DL, Stewart AG, Edwards F, Harris PNA. Sphingomonas paucimobilis bloodstream infection is a predominantly community-onset disease with significant lethality. Int J Infect Dis. 2022 Jun 1;119:172–7. 42. Layton R, Layton D, Beggs D, Fisher A, Mansell P, Stanger KJ. The impact of stress and anesthesia on animal models of infectious disease. Front Vet Sci. 2023 Feb 2;10:1086003. 43. Zeng MY, Inohara N, Nuñez G. Mechanisms of inflammation-driven bacterial dysbiosis in the gut. Mucosal Immunol. 2017 Jan;10(1):18–26. 44. Guidelines | ISCAID [Internet]. [cited 2025 Jul 25]. Available from: https://www.iscaid.org/guidelines45. Framst I, D Andrea C, Baquero M, Maboni G. Development of a long-read next generation sequencing workflow for improved characterization of fastidious respiratory mycoplasmas. Microbiol Read Engl. 2022 Nov;168(11). Tables: Table 1 : Breakdown of the origin of the samples of S. paucimobilis isolates per species (dog or cat). Respiratory tract 29 4 Urine 11 2 Skin 11 2 Oral sphere 7 1 Cornea 8 0 Abscesses 8 0 Ears 2 1 Miscellaneous 4 0 Table 2 : Summary of the characteristics of S. paucimobilis ’ isolates obtained from dogs and cats. Semi-quantitative assessment Heavy Moderate Light Enrichment required 1 2 3 3 20 25 36 0 Table 3: Sensitivity testing conducted on three separate S. paucimobilis isolates. Amikacin Sensitive (4) Sensitive (<2) Sensitive (<2) Gentamicin Sensitive (< 1) Sensitive (< 1) Sensitive (< 1) Tetracycline Sensitive (< 1) Sensitive (< 1) Intermediate (8) Enrofloxacin NA NA Sensitive (< 0.12) Marbofloxacin NA Sensitive (< 0.5) Sensitive (<0.5) Doxycycline NA Sensitive (16) Chloramphenicol Sensitive (4) Sensitive (4) Sensitive (<2) TMPS* NA Sensitive (< 20) Sensitive (< 20) * trimethoprim / sulfamethoxazole, NA: not available, Minimum inhibitory concentration, µg/ml, shown in brackets. Table 4: Summary of response to treatment and outcomes of dogs and cats with documented S. paucimobilis bacterial growth, subcategorized depending on the type of growth (pure, mixed) and whether antibiotics were administered or not. Pure growth 4 1 1 3 9 4 4 1 9 Without antibiotics 0 0 0 1 1 1 0 0 1 With antibiotics 4 1 1 2 8 3 4 (1/4 related) 1 8 Mixed growth 62 3 7 9 81 49 30 2 81 Without antibiotics 14 0 2 3 19 9 9 (1/9 possibly related) 1 19 With antibiotics 48 3 5 6 62 40 21 (3/21 possibly related) 1 62 Overall 66 4 8 12 90 53 34 (1/34 related, 4/34 possibly related) 3 90 Table 5 : Summary of comorbidities present in dogs and cats with S. paucimobilis identified on bacterial growth and subclassified by site of origin. Respiratory tract, n = 33 25, 76% Chronic bronchitis and/or rhinitis (n = 12, one of which had concurrent diabetes mellitus), gastrointestinal disease (n = 3, two of which had gastro-esophageal reflux and one megaesophagus), neoplasia (n = 4), recent general anesthesia (n = 2), brachycephalic obstructive airway syndrome, hyperparathyroidism, systemic lupus erythematosus and pneumocystis carinii. Urine, n = 13 12, 92% Neoplasia (n = 9, one of which had concurrent hypothyroidism), acute kidney injury, renal amyloidosis, benign prostatic hyperplasia Skin, n = 13 12, 92% Recent general anesthesia (n = 8, two of which were for neoplasia), atopic dermatitis (n = 3, one of which had concurrent ulcerative stomatitis), panniculitis Oral, n = 8 3, 38% Neoplasia (n = 2), recent general anesthesia Corneal ulcers, n = 8 6, 75% Keratoconjunctivitis sicca (n = 4, one of which had concurrent atopic dermatitis), glaucoma (n = 2) Abscesses, n = 8 2, 25% Recent general anesthesia, neoplasia Miscellaneous, n = 4 1, 25% Hyperadrenocorticism Ears, n = 3 3, 100% Chronic otitis, atopic dermatitis, inflammatory polyps Overall, n = 90 64, 71% Table 6 : Summary of documented responses to treatment and outcomes in cases with no prior antimicrobial use and in cases recently or currently treated with antimicrobials in which S. paucimobilis was isolated. No antimicrobial (n = 14) Antimicrobial (n = 40) No additional antimicrobial (n = 6) Same antimicrobial (n = 16) Different antimicrobial (n = 14) Response to treatment (n = 78) Resolution 10/11 Ongoing 1/11 Resolution 29/35 Ongoing 3/35 Resolution with possible recurrence 3/35 Resolution 5/5 Resolution 10/14 Ongoing 3/14 Resolution with possible recurrence 1/14 Resolution 12/13 Ongoing 1/13 Outcomes (n = 87) Five death (5/13) One possibly related (1/5) Sixteen death (16/39) Two possibly related (2/16) Four death (4/6) None related (0/4) Six death (6/16) One possibly related (1/6) Three death (3/13) One related (1/3) Appendices: Supplementary Table 1 (separate spreadsheet): Detailed etiology of the co-infections identified along with S. paucimobilis on bacterial culture of samples from 90 dogs and cats. Each co-infection is marked by a “X”. Bacteria with antibiotic resistance on sensitivity testing are in bold with purple-colored cells. Supplementary Table 2 : Detailed antibiotic treatments implemented for the management of infections and co-infections with S . paucimobilis and other bacteria in 70 cases. The numbers represent the duration of treatment in days. (X) signifies the antibiotic was administered for an unknown duration. The case numbers are the same as in Supplementary Table 1. Information & Authors Information Version history V1 Version 1 13 September 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords bacillus microbial interactions and pathogenesis respiratory infections Authors Affiliations Perrine Henry 0000-0003-1630-9080 [email protected] The University of Edinburgh Hospital for Small Animals View all articles by this author Devon Russell The University of Edinburgh Hospital for Small Animals View all articles by this author Gavin Paterson The University of Edinburgh Division of Pathology View all articles by this author Silke Salavati 0000-0003-1084-7013 The University of Edinburgh Hospital for Small Animals View all articles by this author Alisdair Boag 0000-0002-3819-1821 The University of Edinburgh Hospital for Small Animals View all articles by this author Metrics & Citations Metrics Article Usage 465 views 159 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Perrine Henry, Devon Russell, Gavin Paterson, et al. Clinical significance of identification of Sphingomonas paucimobilis on bacterial culture in companion dogs and cats.. 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