Background

Bordetella trematum is an infrequent gram-negative coccobacillus [1], typically related to tissue infections. Related information is scarce due to the low frequency of isolates [2]. As laboratories gain greater access to technologies for accurate and specific bacterial identification, rare microorganisms can arise. It is essential to understand the clinical significance of these unusual findings and the need for treatment. We reviewed the published case reports and will be discussing a new one here.

Case presentation

A 74-year-old female patient attended the vascular surgery outpatient clinic and was referred to the hospital for revascularization of the distal arteries. She had necrotic ulcers in both legs, worse in the right. She reported pain, signs of local infection and myiasis on the lateral side of the ankle, tendon exposure, edema, and dry skin, but no signs of acute ischemia. Her underlying diseases were difficult to control: systemic arterial hypertension for 20 years; type II diabetes mellitus (DM) for 13 years; hypothyroidism; a stroke 6 years ago, chronic renal failure class IV; peripheral arterial occlusive disease, and postmenopausal osteoporosis. The patient referred to previous angioplasty performed 1 year earlier on the lower right leg due to peripheral arterial occlusive disease. Upon hospital admission, several sites of infection other than skin and soft tissue were discarded. Laboratory tests showed a normal leukocyte count and reactive C protein of 3.98 mg/dL (reference value: < 0.30 mg/dL). Empiric treatment with piperacillin-tazobactam (4.5 g IV 6/6 h) was initiated, which was prescribed for 5 days.

Two days after admission, surgical debridement was performed. Limb amputation was discussed, but rejected by the patient and family members. During the surgery, a fragment of the ulcer tissue was collected and sent to the hospital’s microbiology laboratory. In the staining procedure, a few gram-positive cocci and gram-negative bacilli were observed. The specimen was submitted for enrichment in the brain-heart infusion broth for 24 h/37 °C and later seeded in 5% sheep blood agar and MacConkey agar, incubated for 37 °C, and presented growth after 24 h. VITEK 2 system (bioMérieux, Marcy l’Etoile, France) identified Enterococcus faecalis, Stenotrophomonas maltophilia, and B. trematum. The isolate was subsequently identified as B. trematum, using VITEK MS (bioMérieux, Marcy l’Etoile, France) and confirmed by 16S rRNA gene sequencing with Illumina MiSeq (Illumina, San Diego, CA, USA). The oxidase test was negative. MICs were determined by Sensititre gram-negative MIC plate (Thermo Scientific, Waltham, MA, USA) (Table 1).

Table 1 Case reports associated with Bordetella trematum
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After surgery, the intubated patient was transferred to the ICU, using vasoactive drugs through a central venous catheter. Three days later, she presented a worsening clinical condition. Oxacillin-resistant Staphylococcus hominis was isolated from a blood culture drawn through a peripheral vein. Piperacillin-tazoctam was replaced by meropenem (500 mg IV 24/24 h) and vancomycin (1 g IV 24/24 h), prescribed for 14 days. Four days later, levofloxacin (750 mg IV 24/24 h) was added for 24 days aiming at S. maltophilia isolated from the ulcer tissue.

The necrotic ulcers evolved without further complication and the patient’s clinical condition improved, leading to temporary withdrawal of the vasoactive drugs and extubation. However, the patient’s general condition and kidney function worsened, probably due to the severity of her underlying diseases, and she died from sepsis of cutaneous origin 58 days after hospital admission. Autopsy was not performed. Figure 1 shows a timeline of the events.

Fig. 1
figure 1

A timeline of the main events of the patient’s illness

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Discussion and conclusions

B. trematum was described in 1996, isolated from human wounds and ear infections [1]. Information about its reservoir, life cycle and pathogenesis remain unknown. Regarding virulence, little is known [5]. Typically associated with tissue infections in diabetic patients, and generally occurs in polymicrobial infections, which further complicates its clinical interpretation [2]. In our case, where E. faecalis and S. maltophilia were isolated with B. trematum in the ulcer, the role of B. trematum in the patient’s prognosis became unclear. However, as this microorganism was previously reported as a causative agent of bloodstream infection [4, 6, 8], its interpretation and implication in disease was challenging and required integration of clinical, epidemiological, and microbiological issues.

When first described, B. trematum presented the following phenotypic characteristics: non-glucose metabolizer, grown on MacConkey agar, motile, with variable nitrate reduction, catalase and citrate positive, urease, oxidase and lysine decarboxylase negative [1]. Methodologies such as MALDI-TOF MS and VITEK 2 system were efficient in identifying B. trematum. However, there are reports that demonstrate problems regarding microorganism misidentification by API 20 NE (bioMérieux, Marcy l’Etoile, France), due to the absence of B. trematum in its identification database [2]. In another case, also using API 20 NE, B. trematum was misidentified as Achromobacter denitrificans/Bordetella bronchiseptica. This may have occurred because the nitrate reduction test was variable, and the oxidase test reagent was different from the one used by other researchers [7]. In some cases, the confirmation of the microorganism identification was carried out by 16S rRNA gene sequencing [3,4,5, 7, 8]. In our case, the isolate was correctly identified by the VITEK 2 system and MALDI-TOF MS and confirmed by 16S rRNA gene sequencing. Even with credible identification by using routine laboratory instruments, the available literature only reports a few cases, as summarized in Table 1.

There is no standardized methodology by the Clinical Laboratory Standard Institute (CLSI) or the European Committee on Antimicrobial Susceptibility Testing that performs an antimicrobial susceptibility test, specifically for B. trematum. Some authors have used the CLSI manual as an interbreeding source [2, 5,6,7,8], cited as the MIC interpretative standards for other Non-Enterobacteriaceae and MIC interpretative standards for Enterobacteriaceae, along with the use of antibiotics such as ampicillin and cephalothin.

Analyzing antimicrobial susceptibility tests performed by other authors (Table 1), B. trematum has always shown sensitivity to piperacillin-tazobactam, which was initially used as an empirical therapy. Indeed, for this antimicrobial, we obtained the same MIC (≤ 8/4 μg/mL) as reported by Saksena et al. (2015), which may have been a contributing factor to the favorable outcome of the surgical wound. Cefotaxime showed MIC 32 μg/mL in other studies [2, 7], as it is considered to be an intermediate resistant. The MIC in our study (8 μg/mL) was lower than that described by other authors. However, it is not possible to define whether this MIC represents susceptibility. The problems with MIC interpretation are probably due to lack of in vitro/in vivo susceptibility correlation or breakpoints [6].

Since B. trematum infection/colonization occurs primarily in wounds, debridement is essential for treatment, because it removes pathogens from nonviable tissues and reduces recurrence of the infection. Debridement associated with the correct use of antibiotics can lead to a favorable outcome [5]. However, there were no further cultures to determine whether B. trematum was actually eradicated.

The pathogenicity of this microorganism is not well-established, so it is unclear what the contribution of B. trematum was to the patient’s infection and outcome. Despite being a rare finding, B. trematum is typically associated with clinical manifestations of disorders that predispose to the development of ulcers that can become infected by microorganisms. The combination of antibiotic therapy and surgical debridement plays a key role in the cure, preventing systemic infections. Monitoring the appearance of new cases of B. trematum is essential, as it could be an emerging microorganism. Isolating and defining the clinical relevance of unusual bacteria facilitates an overall perspective towards the development of new diagnostic tools and allows for assessment of proper antimicrobial therapy.