First case report of concurrent infection with Cupriavidus gilardii and Yarrowia lipolytica following esophageal stenosis resection and anastomosis in a newborn

Abstract

Background

Cupriavidus gilardii and Yarrowia lipolytica are recognized as opportunistic pathogens with a low incidence of human infections. Notably, cases involving concurrent infection by these two pathogens have not been previously documented in the literature.

Case presentation

We present a case of a 1-month-old male neonate who developed concurrent infection with C. gilardii and Y. lipolytica following surgical resection and anastomosis for congenital esophageal stenosis. The patient developed a postoperative pulmonary infection and subsequent microbiological culture of thoracic drainage fluid confirmed the presence of both C. gilardii and Y. lipolytica. Based on the results of antimicrobial susceptibility testing (AST), the neonate was treated with a combined antimicrobial regimen comprising cefoperazone/sulbactam and fluconazole, and resulting in full clinical and microbiological recovery.

Conclusion

To the best of our knowledge, this is the first reported case of a human co-infected with C. gilardii and Y. lipolytica. The clinical course of this case underscores the indispensable role of microbiological laboratory diagnostics in facilitating accurate diagnosis and informing targeted therapeutic strategies. Timely identification and confirmation of pathogen, combined with in vitro AST, can provide active guidance for anti-infective therapy. For immunocompromised patients, high-risk factors predisposing to nosocomial infections such as intubation should be eliminated as soon as possible. Such systematic approaches are essential to avert significant therapeutic delays, prevent clinical deterioration, and avoid futile treatments attributable to unidentified or misidentified pathogens.

Clinical trial number

Not applicable.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12879-026-13515-z.

Background

Cupriavidus gilardii is an aerobic, Gram-negative, glucose-nonfermenting rod bacteria and can be isolated from plants [1] and soil contaminated with heavy metals [2]. As an opportunistic pathogen, C. gilardii can be occasionally isolated from cerebrospinal fluid, bone marrow and wounds. So far, there are only nine reported clinical infections of C. gilardii [3–10], including one case reported under Ralstonia gilardii [11]. Yarrowia lipolytica is a strictly aerobic yeast that is widely distributed in various environments. It can be isolated from refrigerated meat products, petroleum products and soil [12]. It also resides in the oral cavity, lungs, and intestines of healthy individuals [13]. Although Y. lipolytica is generally regarded as a non-pathogenic or low-virulence organism, it has been increasingly recognized as a cause of opportunistic infections, particularly catheter-related bloodstream infections in immunocompromised or critically ill patients [13–15]. Despite their distinct biological classifications, infections caused by either organism-especially in neonates-remain exceptionally rare. To our knowledge, this represents the first reported case of co-infection with both species. Here, we present the first documented case of a neonate with concurrent C. gilardii and Y. lipolytica infection following esophageal stenosis resection and anastomosis. This report aims to enhance clinical awareness of such rare polymicrobial infections and to provide diagnostic and therapeutic insights for clinicians encountering similar scenarios.

Case presentation

A 1-month-old baby boy was admitted to the hospital on October 7, 2020 for surgical correction of congenital esophageal stenosis (CES). Physical examination revealed a lethargic appearance, severe malnutrition leading to compromised immunity, and bilateral coarse breath sounds with no rales in both lungs. Laboratory examination revealed a white blood cell (WBC) count of 14.42 × 10⁹/L (reference range 15.0–20.0 × 10⁹/L) and a hypersensitive C-reactive protein (hsCRP) level of 1.03 mg/L (reference range 0–10.0 mg/L). Upper gastrointestinal contrast showed thickening of the middle and lower esophageal wall with luminal narrowing. Chest computed tomography (CT) indicated bilateral pulmonary inflammation, particularly in the right upper lobe (Fig. 1). After admission, the patient was given cefoperazone/sulbactam (SCF, 0.5 g, via intravenous (IV) infusion) for anti-infection treatment, budesonide suspension (0.2 mg/inhalation) and ambroxol (5 mg via IV infusion) for expectorant treatment. On hospital day 3 (HD 3), the pneumonia symptoms basically disappeared after treatment, meeting the criteria for surgical intervention. On HD 7, laparoscopic resection and anastomosis of the esophageal stenosis segment were performed under general anesthesia. A stenosis approximately 1 cm in length was observed in the esophagus, located approximately 2 cm proximal to the cardia. An 8-French gastric tube was inserted and the esophageal stenosis segment was resected in a high-anterior and low-posterior position. The esophageal stump was repaired using end-to-end anastomosis with 4.0 absorbable sutures. A 10-French drainage tube was placed at the mediastinal anastomosis site, and an 18-French drainage tube was placed below the diaphragm for drainage. Anti-infective treatment with SCF (0.1 g/kg via IV infusion q12h) was continued. On HD 8, The infant was afebrile but dyspneic. Laboratory investigations revealed leukocytosis (WBC 20.11 × 10⁹/L) and markedly elevated hs-CRP (84.0 mg/L). Chest and abdominal CT scans revealed left-sided pneumothorax, requiring closed thoracic drainage and continued anti-infective treatment (Fig. 1). Consequently, the antibiotic regimen was escalated to meropenem (MEM, 50 mg, via IV infusion q8h). The abdominal drainage tube was removed on HD 15, with no obvious signs of redness, swelling, or purulent discharge at the incision site. On HD 16, the infant continued to have fever with a peak temperature of 38.3℃, WBC count of 33.40 × 10⁹/L, and hs-CRP of 77.15 mg/L. On HD 17, the closed thoracic drainage system drained pale yellow fluid, and Gram stain of the fluid revealed a small number of short Gram-negative bacilli and fungal spores (Fig. 2). On HD 21, C. gilardii and Y. lipolytica were cultured. Drug susceptibility testing showed that C. gilardii was resistant to MEM, so sensitive SCF (80 mg/kg via IV infusion q8h) was resumed, and fluconazole (FCZ 30 mg po qd) was administered based on the in vitro AST results on HD 22. The infant’s body temperature gradually returned to normal, and inflammation was significantly reduced. Follow-up microbiological testing on HD 35 showed negative cultures for C. gilardii and Y. lipolytica. The infant was discharged on December 9, 2020. Follow-up examination on December 27, 2020 showed normal development and good healing of the surgical site.

Fig. 1.

Chest CT images of the pediatric patient. A: The lung markings throughout both lungs were increased, disordered, and blurred. Several patchy opacities with ill-defined margins were observed in the upper lobe of the right lung and the lower lobes of both lungs. B: Pleural effusion and pneumothorax were present in the left thoracic cavity, accompanied by left lung atelectasis. Several patchy opacities were also noted in the right lower lobe

Fig. 2.

Gram staining and colony culture of the specimen. A: Gram staining of the specimen demonstrated numerous Gram-negative short bacilli and a few Gram-positive Candida spores (Gram stain, ×1000). B: Colonies were smooth, moist, grayish-white, and non-hemolytic, with a diameter of approximately 0.5 mm (BAP, 35 ℃, 48 h). C: Colonies were milky white and moist, with a diameter of approximately 8 mm (SDA, 27 ℃, 48 h)

Laboratory examinations

On HD 17, a pale yellow fluid was drained from the closed thoracic drainage system and immediately sent to the clinical laboratory for examination. The specimen was inoculated onto blood agar plates (BAP) and incubated at 37℃ in an environment with 5% carbon dioxide. Fungal cultures were conducted on Sabouraud Dextrose Agar (SDA) at 28℃. After 48 h of incubation, smooth, moist, gray-white non-hemolytic colonies with a diameter of approximately 0.5 mm were observed on the BAP (Fig. 2). The isolate was identified as C. gilardii using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS; Bruker Daltonics GmbH Microflex LT/SH, USA). This identification was further confirmed throµgh 16 S rRNA sequencing. In vitro AST was performed according to the CLSI document M100-S29 (2019), showing that C. gilardii was resistant to MEM and susceptible to SCF(Table 1). Fungal culture results indicated yeast-like growth (Fig. 2), which was identified as Y. lipolytica via both mass spectrometry and 26 S rDNA sequencing. In vitro AST was performed using the YeastOne Susceptibility Panel from Thermo Fisher Scientific according to CLSI M27-Ed4(2017), and it was found that the minimum inhibitory concentration (MIC) of FCZ against the isolate was 2 µg/mL(Table 2). The 16 S rRNA sequence of C. gilardii and 26 S rDNA sequence of Y. lipolytica have been deposited in GenBank(Accession number: PX830042, PX850829 respectively).

Table 1.

Antimicrobial susceptibilities testing of Cupriavidus gilardii

Antibacterial drµgs	SCF	LEV	MEM	IPM	CAZ	CRO	FEP	TOB	CN	CIP
MIC(µg/mL)	4	1	32	16	16	4	≦ 1	≧ 16	≧ 16	≥ 4
sensitivity	S	S	R	R	I	S	S	R	R	R

Cefperazone-Sulbactam: SCF, Levofloxacin: LEV, Meropenem: MEM, Imipenem: IPM, Ceftazidime: CAZ,

Ceftriaxone: CRO, Cefepime: FEP, Tobramycin: TOB, Gentamicin: GN, Ciprofloxacin: CIP

S: susceptible; I: intermediate; R: resistant.According to M100-S29 (2019)

MIC, minimum inhibitory concentration (µg/mL)

Table 2.

The MIC of Antifungal agents against Yarrowia lipolytica

Antifungal agents	AMB	VCZ	FCZ	ICZ	CAS	5-FC	MFG	POS	ANF
MIC(µg/mL)	0.125	0.03	2	0.125	0.25	64	0.03	0.06	0.03

Amphotericin B: AMB, Voriconazole: VCZ, Fluconazole: FCZ, Itraconazole: ICZ, Caspofungin: CAS, 5-fluorocytosine:5-FC, Micafungin: MFG, Posaconazole: POS, Anidulafungin: ANF. According to CLSI M27-Ed4 (2017)

Discussion and conclusions

The diagnosis was challenging due to the rarity of concurrent C. gilardii and Y. lipolytica infection and the difficulty in distinguishing colonization from pathogenic infection. However, based on the concordance between Gram-stained smear microscopy and culture results, the favorable response to antibacterial combined antifungal therapy, and considering the rarity of these organisms as colonizers, a diagnosis of co-infection with C. gilardii and Y. lipolytica was ultimately established in this immunocompromised infant.

Being a rare opportunistic pathogen, C. gilardii has had a complicated taxonomic history. Initially, Coenye et al. classified it under the genus Ralstonia and proposed the name Ralstonia gilardii sp. nov. in 1999 [16], subsequently renamed Wautersia gilardii by Mario Vaneechoutte et al. in 2004 [17], but was finally given its current name in the same year [18]. Considered as an opportunistic bacterium with low pathogenicity, C. gilardii rarely causes infections. To date, including former names such as R. gilardii, a total of 9 articles have reported 12 cases of infection.The infection mechanism of C. gilardii remains unclear, it can cause infections in both immunocompromised [3, 4, 7, 11] and immunocompetent individuals [5, 6, 8]. Invasive procedures may be the cause of infection in immunocompetent individuals. The patient with C. gilardii infection reported by Kobayashi had a pacemaker implanted, and the surgical incision became infected and did not heal. After the pacemaker and leads were removed, the patient’s condition improved with drug treatment [5]. The use of corticosteroid drugs may be a potential cause of infection in immunocompetent individuals, as corticosteroids can suppress T cell-mediated immune responses and impair the patient’s immune response to microbial infections. Fang et al. reported a patient who recovered from COVID-19 following glucocorticoid treatment but developed progressive dyspnea three days later. Marked lymphopenia was observed (lymphocytes: 2.8% of leukocytes; T cells: 53.88%). C. gilardii was isolated from both bronchoalveolar lavage fluid and peripheral blood. Despite intravenous imipenem/cilastatin and trimethoprim-sulfamethoxazole, the patient died [8]. In another study involving four cases of C. gilardii infection, the values of CD4⁺/CD8⁺ T cells and CD19⁺ B cells were lower in the two patients who died than in the two survivors [19]. Currently, the standardized treatment regimen for C. gilardii infection remains unclear. Among the 12 previously reported infected patients, six succumbed to the infection and six recovered. C. gilardii is a Gram-negative bacillus, it exhibits high resistance to carbapenem and aminoglycosides, but susceptible to cephalosporins and quinolones. Zhao et al. discovered nine antimicrobial resistance genes, including five genes encoding efflux pump systems (MuxC/B, MexB/D, and ceoB), three intrinsic resistance genes (OXA-837, AAC(3)-IVb, and ANT(3”)-Ib), and the colistin resistance gene MCR-5.1. The MexB/D and OXA-837 genes may mediate resistance to meropenem, and all five C. gilardii strains in the study were highly resistant to meropenem [19]. Therefore, identifying the pathogen and selecting sensitive antimicrobial agents was crucial for the recovery of this patient. Y. lipolytica belongs to hemiascomycetes, within the class Saccharomyces. It rarely causes human infection, and the first reported case was a bloodstream infection reported by Wehrspann and Fullbrandt in 1985 [20]. Trabelsi et al. reported 55 cases of nosocomial infection caused by Y. lipolytica in intensive care, and most of these patients were intubated, with central venous intubation being an important risk factor for Y. lipolytica infection. Of the 55 enrolled patients, 37 underwent catheter removal, and 43 were administered intravenous antifungal therapy. Among these treated patients, 13 received combined FCZ and amphotericin B(AMB), 12 had FCZ monotherapy, and 17 received AMB alone. Of the 43 patients who received antifungal treatment, 20 died; of the 12 patients who did not receive antifungal treatment, 8 died [21]. Removal or replacement of intubation is key to treatment and can be combined with systemic antifungal agents [21, 22].

The infant reported in this case was born with esophageal stenosis, which led to severe malnutrition and compromised immunity. Additionally, the presence of a drainage tube in the body further predisposed the infant to infections. Preoperative empirical SCF therapy achieved initial control of the pneumonia. However, postoperative infection worsening prompted escalation to MEM, which proved ineffective. Guided by AST, a rechallenge with SCF was unsuccessful because of a concurrent Y. lipolytica infection. The addition of FCZ then led to a gradual clinical improvement. A 21 - day combined antimicrobial treatment course, customized according to the clinical response and follow - up cultures, ensured complete eradication of the pathogen and the patient’s full recovery. Successful management of this rare infection relies on prompt and comprehensive microbiological identification, timely administration of sensitive antimicrobial agents guided by laboratory testing, and aggressive removal of risk factors associated with intubation-related infections. Regrettably, while the two pathogens were identified and basic antimicrobial susceptibility testing was completed in this case, deeper mechanistic investigations such as whole-genome sequencing and virulence factor analysis could not be performed due to limitations in clinical laboratory resources. These studies would have helped to further elucidate the pathogenic mechanisms and inform the optimization of treatment regimens.

There has been no previous report of humans being simultaneously infected with these two pathogens, and this is the first documented case.

The parents were satisfied with the treatment outcome, written informed consent was obtained from the patient’s parents for publication of this case report.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

C. gilardii

Cupriavidus gilardii

Y. lipolytica

Yarrowia lipolytica

CES

Congenital esophageal stenosis

WBC

White blood cell

hsCRP

Hypersensitive C-reactive protein

CT

Computed tomography

SCF

Cefoperazone/sulbactam

HD

Hospital day

cm

Centimeter

MEM

Meropenem

FCZ

Fluconazole

BAP

Blood agar plates

SDA

Sabouraud Dextrose Agar

MIC

Minimum inhibitory concentration

Author contributions

M.L. performed the research, extracted the data, and formed the final table. S.S. designed the study, prepared the manuscript. J.G. performed the culture, staining, mass spectrometry analysis. Y. W. helped with manuscript preparation, and advised the overall process scientifcally. All authors reviewed the manuscript.

Funding

The study has no funding support, the data was obtained from clinical work.

Data availability

Data is provided within the manuscript or supplementary information files.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent for the publication of this case report was obtained from the patient’s legal guardians.

Competing interests

The authors declare no competing interests.