Staphylococcus schleiferi diabetic foot osteomyelitis and bacteraemia in an immunocompromised host

Abstract

Staphylococcus schleiferi is a Gram-positive coccus bacterium first discovered in 1988 that is typically associated with skin and ear infections in dogs, cats and birds. It is infrequently described as a human pathogen. There are, however, emerging reports of S. schleiferi infections in diverse clinical scenarios in humans, particularly in patients with weakened immune systems. S. schleiferi may be underrecognised due to limitations in routine microbiology diagnostic protocols and mislabelling as other Staphylococcus sp. We present a rare case of S. schleiferi diabetic foot osteomyelitis with subsequent bacteraemia in an immunocompromised host.

Background

Staphylococcus schleiferi is a Gram-positive coccus bacterium first described in 1988.¹ There are two subspecies: coagulase positive (subspecies schleiferi) and coagulase negative (subspecies coagulans).² Its numerous virulence factors include heat-stable nuclease, fibrinogen affinity factor, beta-hemolysin, protease, esterase, lipase and exoenzymes.³ It is also susceptible to novobiocin.¹ Typically associated with zoonotic pathogenicity, S. schleiferi is a causative agent of skin and ear infections in canines, with known isolation in cats and birds as well.^{4 5} There are a few reports of the microorganism cultured from human preaxillary skin flora during pacemaker evaluation.⁶ It remains unclear if carriage is transient or persistent.⁶

Literature noting S. schleiferi infections in humans is sparse. However, there are emerging reports of S. schleiferi being implicated in different clinical syndromes, including vertebral osteomyelitis, paediatric meningitis, endocarditis, pericardial effusions, surgical wound infections, bacteraemia, nosocomial urinary tract infections and iatrogenic bacteraemia from pacemaker insertion.^{3 6–11} Many of the documented infections involve animal contact as a potential source. In the case of paediatric meningitis, a child became ill after interacting with her family dog.⁷ The dog exhibited skin pustules and ear infections that later grew S. schleiferi after sampling.⁷ In another case, a patient developed endophthalmitis following cataract extraction after close contact with a dog harbouring the pathogen.¹² We describe a rare case of S. schleiferi infection presenting as diabetic foot osteomyelitis with subsequent bacteraemia in an immunocompromised host without known animal exposure.

Case presentation

A 75-year-old man presented with subacute left heel pain that started 3 days prior, accompanied by an enlarging foot ulcer of unknown duration. Medical history was notable for locally advanced rectal cancer, status-post low anterior resection with end colostomy and chemotherapy with one cycle of capecitabine 2 months prior to presentation. His medical history included diabetes mellitus type 2 and chronic urinary retention with an indwelling Foley catheter. He denied any other symptoms, including fevers, chills, malaise or recent trauma to his foot. Vital signs were stable on arrival, with blood pressure of 127/61 mm Hg, respiration rate of 18 breaths/min, heart rate of 111 beats/min, temperature of 36.5°C and room air oxygen saturation of 96%. Laboratory investigation showed a white cell count of 11.3×10⁹/L, neutrophil count of 10×10⁹/L, glucose of 469 mg/dL, creatinine of 0.80 mg/dL, sedimentation rate of 106 mm/hour, C reactive protein of 210 mg/L and haemoglobin A1c of >14.0%.

On admission, one set of blood cultures drawn from the right arm grew S. schleiferi and Enterococcus avium (Group D) with time to positivity of 15.1 hours. S. schleiferi was erroneously listed initially as S. epidermidis and was corrected 5 days later. The antibiotic sensitivities were not reported by the microbiology lab. E. avium (group D) was sensitive to ampicillin, gentamicin, linezolid, penicillin, streptomycin and vancomycin. The second set of initial blood cultures obtained from his left hand had no growth. X-ray of the left foot showed bony lucency with cortical discontinuity and irregularity along the posterior aspect of the calcaneous adjacent to the soft tissue ulceration, consistent with osteomyelitis (figure 1). MRI of the left foot showed osteomyelitis involving the posterior aspect of the calcaneus (figure 2).

Figure 1.

Ulceration in the patient’s left heel on the day of presentation.

Figure 2.

X-ray of the left foot with bony irregularity in the posterior calcaneus.

The patient underwent left calcanectomy 3 days after presentation. Aerobic bone culture grew + one S. schleiferi, +one Streptococcus mitis group, +one Proteus vulgaris group and two colonies of Corynebacterium striatum group. For antibiotic susceptibilities, S. schleiferi was pan-sensitive to cefazolin, clindamycin, erythromycin, gentamicin, linezolid, methicillin, oxacillin, penicillin-G, tetracycline, and vancomycin. P. vulgaris was sensitive to amikacin, cefazolin, cefepime, ceftriaxone, ciprofloxacin, ertapenem, gentamicin, imipenem and meropenem and was resistant to ampicillin. The sensitivities for the S. mitis group and C. striatum group were not resulted by the lab for unspecified reasons. Anaerobic bone culture grew +one anerobic Gram-positive cocci and +one anerobic Gram-negative bacilli without final speciation. Follow-up blood cultures the day after calcanectomy had no growth.

From recommendations of the infectious disease team, he was started on broad antibiotics postoperative day 1 for polymicrobial growth while awaiting antibiotic sensitivities. This included vancomycin (loading dose of 1500 mg and maintenance dose of 750 mg every 12 hours), cefepime 2000 mg every 8 hours and metronidazole 500 mg every 8 hours intravenously. On postoperative day 4, he was transitioned to piperacillin–tazobactam 4.5 g every 8 hours after antibiotic susceptibilities came back as shown above, with plan for 6 weeks of total antibiotics coverage.

Prior to discharge, he underwent an echocardiogram without evidence of vegetations. He was discharged to a skilled rehabilitation centre. After 2 weeks of piperacillin–tazobactam, he was de-escalated to ceftriaxone 2 g every 24 hours intravenously due to the rehabilitation centre’s inability to continue frequent dosing required for piperacillin–tazobactam. The patient continued with metronidazole 500 mg three times a day orally.

Outcome and follow-up

The patient completed a cumulative total of 6 weeks of antibiotics without detectable adverse side effects. He followed-up with infectious disease and orthopaedics clinic. He remained well without signs of active infection or recurrence of old symptoms after completion of his treatment. The patient is still alive today.

Discussion

S. schleiferi is an underrecognised bacterial species that is becoming more clinically relevant as a human pathogen with varied presentation. To our knowledge, this is the first documented case of S. schleiferi diabetic foot osteomyelitis with subsequent bacteraemia. While the bacteria is traditionally associated with animals, our case shows that it may be opportunistic in patients without known exposure. Our patient’s relative immunocompromised state from uncontrolled diabetes and recent chemotherapy likely increased his susceptibility for S. schleiferi infection. This is consistent with reports of similarly immunocompromised patients developing infections.^{3 13} In a study published in 2001 involving 28 patients with S. schleiferi infections, more than half of the patients exhibited some degree of immunosuppression.³ In addition, 22 of these cases were attributed as nosocomial infections.³

Given the ubiquitous nature of the Staphylococcus genus, careful screening for S. schleiferi should be incorporated into institutions’ clinical microbiology diagnostic protocols to enhance detection. Oftentimes it is not fully or correctly speciated. In our case, S. schleiferi was erroneously listed as S. epidermidis in an initial set of blood cultures that was then relabelled 5 days later. This may be problematic, as an isolated S. epidermidis growth is typically considered skin flora contamination and would not warrant antibiotic treatment. S. schleiferi also resembles S. aureus on blood agar with comparable colony morphology.^{2 10} S. schleiferi subsp schleiferi and S. aureus both produce heat-stable DNase and clumping factor.^{3 7 10} During coagulase testing, S. schleiferi subsp coagulans and S. aureus result positive.^{3 10} A method from which Staphylococcus sp can be distinguished involves PCR using primers for species-specific nuclease genes.^{9 11} Furthermore, S. schleiferi is becoming increasingly multidrug resistant. Numerous veterinary studies show that up to 24%–50% of isolates are now methicillin resistant.^{4 5} Piperacillin–tazobactam was chosen in this case based on antibiotic sensitivities to cover all of the pathogens that grew. A prolonged course of intravenous antibiotics for 6 weeks was selected as part of the standard treatment for osteomyelitis, as it takes up to 6 weeks for the debrided bone to be covered by vascularised soft tissue.

In conclusion, our case and literature review highlight S. schleiferi as an important human pathogen implicated in assorted clinical pathologies. Known risk factors appear to be canine exposure, immunosuppression and hospitalisation. Its prevalence is likely underrepresented due to difficulty distinguishing it from other Staphylococcus sp with standard microbiology diagnostic protocols. Given the bacteria’s association with human infections, any isolate of S. schleiferi should be treated as pathogenic.

Learning points.

• Traditionally associated with skin and ear infections in canines, Staphylococcus schleiferi is emerging as an important human pathogen.

• Based on the documented cases, risk factors include canine exposure, immunosuppression and hospitalisation.

• Its prevalence is likely underrepresented due to limitations in routine microbiology diagnostic protocols and common mislabelling as other Staphylococcus species.