Yokenella regensburgei: Infection in an immunocompetent patient

INTRODUCTION

Yokenella regensburgei is a rarely encountered Gram-negative bacillus within the order Enterobacteriales. Since its initial description in the mid-1980s, the organism has been infrequently isolated from human clinical specimens, and its pathogenic role has remained incompletely characterised.^[1] In routine diagnostic laboratories, particularly those relying on conventional phenotypic methods, Y. regensburgei may be overlooked or misidentified because of its close biochemical similarity to other members of the Enterobacter ales, most notably Hafnia alvei.

Environmental studies have identified Y. regensburgei in a range of non-human reservoirs, including insects, reptiles, raw vegetables, and water sources. Human infections attributed to this organism have been reported only sporadically and have predominantly involved individuals with underlying immunosuppression or chronic systemic disease. Documented clinical presentations include bloodstream infection, urinary tract infection, soft tissue infection, and rare invasive manifestations such as necrotising fasciitis.^[2] Reports of infection in immunocompetent hosts remain exceptional, contributing to limited clinical awareness of its pathogenic potential in this population.

Accurate identification of Y. regensburgei continues to pose a diagnostic challenge in settings where automated identification systems are unavailable. Increasing adoption of mass spectrometry-based techniques, such as matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS), has improved recognition of uncommon Enterobacterales, suggesting that earlier reliance on biochemical methods may have contributed to underreporting. In India, only a small number of confirmed cases have been documented, including reports of systemic and urinary tract infection identified using automated methods.^[3]

The present report describes a case of chronic wound infection caused by Y. regensburgei in an immunocompetent adult, highlighting the organism’s pathogenic potential outside the context of overt immunosuppression and underscoring the importance of accurate laboratory identification for appropriate antimicrobial management.

CASE REPORT

A 52-year-old male farmer from rural Jodhpur, Rajasthan, India, presented to the emergency department of the All-India Institute of Medical Sciences, Jodhpur, on 10^th June 2023 with complaints of weakness involving the right upper and lower limbs. The patient did not report any associated focal neurological symptoms. Neurological examination revealed hypotonia with right-sided paraplegia. No additional focal neurological deficits were identified at the time of presentation. General physical examination revealed the presence of a non-healing ulcer over the left great toe. In view of the presenting neurological complaints, the patient was initially admitted under the Department of Neurology for further evaluation and management.

A detailed history revealed that the patient had sustained a thorn-prick injury to the left great toe approximately one month prior to presentation while working on his farm. He reported that the wound had failed to heal since the injury and was associated with moderate pain. The patient initially sought treatment at a local clinic, where wound debridement was performed. However, no antimicrobial therapy was prescribed following the procedure. Despite this intervention, the wound showed no clinical improvement and progressively increased in size, with darkening of the surrounding tissue over time. The patient had no known history of hypertension, diabetes mellitus, or other systemic illnesses. There was no history of previous surgical interventions. He has been a chronic smoker for the past 20 years.

A 3×3 cm local inspection of the ulcer showed elevated margins and a core area of induration. There was no noticeable discharge. Tenderness was present on palpation and had a grey colour base, indicating a non-healing ulcer. The entire investigational workup was done for the patient for his primary complaints. Complete blood count (total leucocyte count 7800/mm³), liver function test and kidney function test were within normal limits. Although the lipid profile revealed a total cholesterol of 195 mg/dL, triglycerides of 283 mg/dL and an low-density lipoprotein/high-density lipoprotein ratio of 4.3. In view of his neurological complaints, a computed tomography (CT) scan revealed a cardiovascular accident (CVA) of the left cerebellar region, and the patient was treated for the same, showing a significant improvement in power and tone of the affected muscles. Further radiological investigations were performed. CT angiography revealed atherosclerosis and non-opacification of the common iliac artery, proximal 2/3rd of the left external iliac artery and distal 1/3rd of the bilateral proximal tibial artery. CT thorax and abdomen (contrast) revealed occlusion of the left common iliac, external and internal iliac arteries. An arterial doppler of the lower limb revealed peripheral vascular disease. X-ray of the affected foot showed tissue erosion [Figures 1 and 2]. The patient was diagnosed with a case of peripheral vascular disease with CVA. The patient was shifted to the cardio-thoracic and vascular surgery (CTVS) department for further management of the disease.

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Figure 1:

Radiographic findings of soft tissue erosion in the left foot (Anterio-posterior (AP) view).

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Figure 2:

Radiographic findings of soft tissue erosion in the left foot (Oblique view).

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A punch biopsy specimen obtained from the base of the non-healing ulcer was submitted to the microbiology laboratory for aerobic bacterial, fungal, and mycobacterial cultures. Direct Gram staining of the tissue demonstrated occasional pus cells along with a small number of Gram-negative bacilli. Fungal and mycobacterial cultures yielded no growth.

For aerobic bacterial culture, the biopsy specimen was initially inoculated into enrichment broth and subsequently subcultured onto 5% sheep blood agar, MacConkey agar, and chocolate agar. All cultures were incubated aerobically at 37 °C. After overnight incubation, the growth of a single colony morphotype was observed. Colonies on blood agar [Figure 3] were non-haemolytic, small, moist, and convex with smooth margins, while chocolate agar showed comparable growth. On MacConkey agar, the organism produced non-lactose-fermenting colonies [Figure 4].

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Figure 3:

Colony morphology of Y. regensburgei on 5% sheep blood agar.

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Figure 4:

Non-lactose-fermenting colonies of Y. regensburgei on MacConkey agar.

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The isolate was found to be catalase-positive and oxidase-negative. Microscopic examination revealed short, uniformly staining Gram-negative bacilli, and motility was demonstrated by hanging drop preparation. Definitive identification was achieved using MALDI-TOF MS, with phenotypic confirmation performed using a panel of conventional biochemical tests, all of which were concordant with the automated identification.

Antimicrobial susceptibility testing was performed by the disk diffusion method, and results were interpreted in accordance with contemporary standard guidelines. The isolate demonstrated susceptibility to cefepime, ceftriaxone, gentamicin, cotrimoxazole, tigecycline, levofloxacin, and meropenem, while showing intrinsic resistance to colistin. To establish the clinical significance of the isolate, a repeat biopsy specimen was obtained prior to initiation of antimicrobial therapy, which again yielded isolation of Y. regensburgei.

The treating physician was promptly informed of the microbiological identification, following which targeted antimicrobial therapy was initiated, as the patient had not received any prior systemic antibiotics. The patient was started on oral levofloxacin 750 mg once daily for a duration of seven days. In addition, regular wound care was advised, along with local application of neomycin ointment twice daily for 14 days after discharge. The patient was discharged on 18 June 2023 with clinical evidence of healing of the ulcer. He was also advised to follow up with the Cardiothoracic and Vascular Surgery department for planned surgical intervention as part of the management of his underlying vascular disease. The patient returned for follow-up on 10 July 2023, at which time the ulcer had healed completely [Figures 5 and 6].

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Figures 5:

Clinical appearance of the completely healed ulcer at follow-up.

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Figure 6:

Clinical appearance of the completely healed ulcer at follow-up.

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DISCUSSION

Y. regensburgei has traditionally been regarded as an opportunistic organism with limited relevance to human disease. Although sporadic reports of human infection have appeared since its original description by Kosako and colleagues ^[1], the organism continues to be more commonly associated with environmental and non-human reservoirs, including insects, reptiles, vegetables, and water sources. This apparent rarity in clinical practice is likely influenced by diagnostic limitations rather than true absence, particularly in laboratories that rely predominantly on conventional biochemical identification methods. On the basis of biochemical characteristics, Y. regensburgei closely resembles Hafnia alvei, which likely contributes to its underrecognition and underreporting in clinical settings.

To date, only a small number of well-documented human infections caused by Y. regensburgei have been reported in the literature. Most reported cases involve opportunistic infections in immunocompromised hosts, including septicaemia in individuals with HIV infection, brain abscess in patients with lymphoma, necrotising fasciitis in an immunocompromised patient, and diabetic foot infection in a renal transplant recipient with chronic kidney disease.^[2] Clinical presentations have ranged from urinary tract infection and bacteraemia to more severe manifestations such as necrotising soft tissue infection. In contrast, reports involving immunocompetent individuals remain exceedingly uncommon. Overall, human infection with this organism remains rare. In contrast, a case of sepsis associated with infectious diarrhoea was reported in 2017 from Greece in an immunocompetent male patient, highlighting the organism’s potential pathogenicity even in the absence of overt immunosuppression. ^[4] Within the Indian context, confirmed reports of Y. regensburgei infection are particularly limited. Previously published cases include presentations mimicking enteric fever and urinary tract infection, both of which were identified using automated diagnostic systems.^[2,5] Given that many microbiology laboratories in low- and middle-income settings continue to depend on phenotypic methods, infections due to Y. regensburgei may be misidentified as other members of the Enterobacterales, most commonly Hafnia alvei. This diagnostic challenge likely contributes to underreporting and underestimation of the organism’s clinical significance. Reporting an increasing number of such cases will aid in improving recognition of this uncommon pathogen and contribute to a better understanding of its clinical spectrum and pathophysiology.

In the present case, a thorn-prick injury sustained during agricultural work appears to have served as the portal of entry, with subsequent development of a chronic wound infection. Repeated isolation of the organism from biopsy tissue, in conjunction with clear clinical improvement following targeted antimicrobial therapy, supports its role as a true pathogen rather than a coloniser or contaminant. Despite persistence of symptoms for over one month, the patient showed rapid clinical improvement following a seven-day course of levofloxacin. The prompt therapeutic response, along with repeated isolation of the organism, supports the clinical relevance and pathogenic role of the isolated strain in this case. Fluoroquinolones have previously demonstrated effectiveness in the treatment of Y. regensburgei infections. Similar favourable outcomes have been reported in earlier case reports, including those by Abbott and Janda (1994) ^[6] and Fajardo et al. (2005) ^[7], further supporting the choice of therapy.

From a biochemical standpoint, Y. regensburgei is a motile organism that ferments mannitol, glucose, arabinose, rhamnose, maltose, xylose, and trehalose, while failing to ferment lactose, sucrose, dulcitol, adonitol, inositol, or sorbitol. It produces a positive methyl red reaction and demonstrates delayed gas production during carbohydrate fermentation, along with delayed citrate utilisation. The organism also decarboxylates the amino acid ornithine. Owing to its metabolic profile, Y. regensburgei may be misidentified unless carefully differentiated. It can be distinguished from Hafnia alvei based on methyl red positivity, citrate utilisation, and lack of inositol and sorbitol fermentation. Differentiation from Enterobacter species relies on methyl red positivity and absence of lysine decarboxylation, while separation from Serratia species is aided by methyl red testing, malonate utilisation, arabinose fermentation, gelatine liquefaction, and DNase testing.^[8,9] With respect to antimicrobial susceptibility, Y. regensburgei has demonstrated intrinsic resistance to colistin, azithromycin, and certain β-lactam antibiotics.^[10] The organism is known to express inducible β-lactamases and possesses ampC genes, comparable to the chromosomal ampC enzymes found in Enterobacter and Citrobacter species, as reported by Stock et al. in 2004.^[11] Consequently, the organism exhibits natural resistance to cefoxitin and first-and second-generation cephalosporins.

CONCLUSION

This case underscores the emerging clinical relevance of Y. regensburgei as a true pathogen capable of causing chronic wound infections even in immunocompetent hosts, particularly following environmental inoculation such as thorn-prick injuries in agricultural settings. The repeated isolation of the organism from biopsy tissue, coupled with a clear clinical response to targeted antimicrobial therapy, establishes its pathogenic role rather than colonisation or contamination. From a diagnostic standpoint, this report highlights the limitations of conventional biochemical methods, where Y. regensburgei may be misidentified as Hafnia alvei, and reinforces the value of automated identification systems such as MALDI-TOF MS in accurately detecting rare Enterobacteriaceae. Clinically, awareness of its intrinsic resistance patterns, including resistance to colistin and early-generation cephalosporins, is essential to guide appropriate therapy and avoid treatment failure. Increased recognition and reporting of such infections will enhance understanding of the organism’s epidemiology, antimicrobial susceptibility trends, and clinical spectrum, ultimately aiding timely diagnosis and optimised patient management.