Challenge of Cupriavidus gilardii infection in an immunocompromised child: a case report

Introduction

Cupriavidus gilardii, which has a complex taxonomic history, is a Gram-negative, aerobic, motile and oxidase-positive bacterium (1). The bacterium often colonizes environments such as contaminated water sources, heavy metal-polluted soils and plants, and is closely related to severe human infections and even fatal cases, especially in immunocompromised patients (2). Clinically, C. gilardii has been isolated from diverse samples, including blood, throat swabs, fecal materials, abscesses, wound secretions, and bronchoalveolar lavage fluid (3-9). Its virulence intensity is significantly correlated with the number of virulence factors that it carries (2).

C. gilardii is recognized as a potentially lethal opportunistic pathogen. Its complex intrinsic resistance profile poses a significant challenge to clinical diagnosis and treatment. Among the seven reported cases, antimicrobial regimens varied significantly, and susceptibility profiles of the isolates showed marked heterogeneity (Tables S1,S2) (3-9). In this study, we report the diagnostic and therapeutic process of a case involving a young boy with leukemia who developed a C. gilardii infection. We present this case in accordance with the CARE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-592/rc).

Case presentation

A 4-year-old boy, 15.5 kg, was diagnosed with acute lymphoblastic leukemia and received reinduction chemotherapy with cyclophosphamide, cytarabine (Ara-C), mercaptopurine (CAM) chemotherapy according to the SCCCG-ALL-2023 protocol. Approximately six and a half months later, he developed agranulocytosis with recurrent high fever (up to 39.5 ℃), severe sepsis, and respiratory distress. Blood culture performed at the referring hospital identified Ralstonia mannitolilytica, which was sensitive to levofloxacin. Although levofloxacin was adopted based on this susceptibility, the patient’s condition worsened and was transferred to our hospital for further treatment.

On admission, the child presented with extremely severe myelosuppression, with a total white blood cell (WBC) count of only 0.02 G/L, an uncalculated neutrophil count and a high sensitivity C-reactive protein (HSCRP) of 234.63 mg/L. The patient appeared to be in poor general condition with an exacerbated systemic inflammatory response. We subsequently referred to the laboratory results from the previous hospital and treated the patient with multiple antibiotics, including vancomycin, piperacillin-tazobactam, imipenem, sulfonamide, levofloxacin and gentamicin. On hospital day (HD) 2, blood cultures revealed a rare growth of C. gilardii, and a chest computed tomography (CT) scan suggested C. gilardii pneumonia. On HD8, peripheral blood metagenomic next-generation sequencing (mNGS) reconfirmed the positivity for C. gilardii (sequence reads 160).

On HD9, there was no improvement in the patient’s body temperature or inflammatory marker levels, and a chest CT scan revealed expansion of the solid lung lesions. Given the ineffectiveness of empirical antibiotic therapy and persistent sepsis, the child was transferred to the pediatric intensive care unit (PICU) on HD9. On the basis of the drug susceptibility report and literature review, we modified the antibiotic regimen to ceftazidime-avibactam (CAZ-AVI) (1 g q8h) in combination with tigecycline (10 mg q8h) under the guidance of a multidisciplinary team. Two weeks later, the child experienced no adverse reactions, and was able to reduce fever spontaneously, and the abdominal pain disappeared. The total WBC count rebounded to 3.10 G/L, the HSCRP dropped to 26.96 mg/L (Figure 1), and the blood culture was negative 3 consecutive times on HD12, HD14, and HD18. Repeat mNGS testing on HD15 showed a reduction in the number of sequence reads of C. gilardii to 7, and a follow-up CT scan showed partial resolution of the bilateral pulmonary lesions compared with the previous ones. Unfortunately, the child died of sudden pulmonary hemorrhage on HD26. All procedures performed in this case were in accordance with the ethical standards of the Ethics Committee of Zhujiang Hospital (approval No. 2025-KY-429) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s parent for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Figure 1 Changes in inflammatory markers and granulocyte markers during hospitalization. HSCRP, high-sensitivity C-reactive protein; IL-6, interleukin-6; Neut#, absolute neutrophil count; WBC, white blood cell count.

Microbiological analysis

The isolated bacteria were cultured on Columbia blood agar plates at 35 ℃ for 24 hours. Colonies that were gray-white, circular, raised, opaque, and well-defined were observed. The strain was identified as C. gilardii via the VITEK mass spectrometry system with a confidence level of 99.9%. The child’s blood mNGS analysis revealed 160 sequences of C. gilardii in the sample (Figure 2).

Figure 2 Relevant information of C. gilardii. (A) Colony morphology of C. gilardii; (B) ceftriaxone sensitivity test (MIC: 1 µg/mL); (C) ceftazidime-avibactam sensitivity test (MIC: 8 µg/mL); (D) imipenem sensitivity test (MIC: >32 µg/mL); (E) meropenem sensitivity test (MIC: >32 µg/mL); (F) ceftazidime sensitivity test (MIC: 24 µg/mL); (G) mNGS results on hospital day 8. MIC, minimum inhibitory concentration; mNGS, metagenomic next-generation sequencing.

Discussion

Infections caused by C. gilardii are extremely rare, with only seven cases identified in our literature. Notably, all reported pediatric patients were immunocompromised and had a history of invasive procedures. This finding highlights the need for clinicians to remain highly vigilant regarding potential infectious risks when performing invasive procedures. However, the specific source of the C. gilardii infection in the present case remains undetermined and requires further investigation.

There are currently no standardized therapeutic strategies for C. gilardii infection, primarily because of its complex antimicrobial resistance profiles (2). Zhao et al. reported that this pathogen carries nine resistance determinants, including five efflux pump system genes (MuxB/C, MexB/D, and cecoB), three intrinsic resistance genes [OXA-837, AAC(3)-IVb, and ANT(3")-Ib] and the colistin resistance gene MCR-5.1. Notably, there are significant differences in the treatment regimens and clinical prognoses of C. gilardii infected patients reported in different studies, accompanied by marked differences in susceptibility to β-lactam antibiotics. These observations correlate with the high genomic and phenotypic heterogeneity of the species. In this case, although the child received multiple rounds of antibiotics, the pathogen still showed a broadly resistant phenotype, which may be linked to the decreased effectiveness of antimicrobial drugs against bacterial infections due to neutropenia (10). Currently, there is no uniform international treatment consensus for C. gilardii infection, which makes the selection of antibiotics somewhat blind.

This case represents a breakthrough as the first successful implementation of CAZ-AVI in managing pediatric C. gilardii sepsis. CAZ-AVI is a novel antibiotic composed of a third-generation cephalosporin and a β-lactamase inhibitor. Ceftazidime exerts its bactericidal effect by inhibiting the synthesis of bacterial cell wall products, whereas avibactam inhibits various β-lactamases, including KPC enzymes and some OXA enzymes. This combination significantly enhances the antibacterial activity of ceftazidime against drug-resistant pathogens, offering a dual mechanism to combat multidrug-resistant Gram-negative bacteria (11). CAZ-AVI has excellent safety and low resistance rates, with no major adverse events reported to date. Studies have indicated that CAZ-AVI is an important therapeutic option for treating multidrug-resistant bacterial infections in critically ill pediatric patients, and it has been found to be well tolerated (12). This innovative decision was guided by two critical considerations: (I) previous multidrug therapeutic failure and local antimicrobial susceptibility testing revealing C. gilardii carbapenem resistance, which strongly suggests that β-lactamase is a likely primary cause of resistance; (II) established adult evidence demonstrating the efficacy of CAZ-AVI against refractory Gram-negative infections. Therefore, we adopted a combination regimen of CAZ-AVI and tigecycline. After a week of treatment, CAZ-AVI effectively eradicated C. gilardii and alleviated lung damage. However, this report is based on a single pediatric case, and detailed immune function evaluation was also not available for this patient, limiting generalizability. Long-term outcomes and molecular mechanisms of antimicrobial resistance were not assessed. Further pediatric cases and studies are needed to guide evidence-based diagnosis and treatment.

Conclusions

This case highlights the effectiveness of CAZ-AVI in treating C. gilardii infection, particularly when conventional therapies fail. This study provides valuable evidence for the management of rare, multidrug-resistant Gram-negative infections in pediatric patients. However, challenges persist in clinical management, so comprehensive investigations are necessary to characterize its pathogen dynamics and explain its resistance pathways.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-592/rc

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-592/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-592/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this case were in accordance with the ethical standards of the Ethics Committee of Zhujiang Hospital (approval No. 2025-KY-429) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s parent for publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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