Bloodstream infection caused by Cupriavidus gilardii in a systemic lupus erythematosus patient with invasive pulmonary aspergillosis

Introduction

Systemic lupus erythematosus (SLE) is the most common form of autoimmune disease which is vulnerable to funguses and bacteria (1). Microorganism colonized in respiratory tract and lung is a leading cause of pneumonia when glucocorticoid and immunosuppressor are prescribed (2). Aspergillus isolated in SLE patients from sputum culture is not uncommon and Cupriavidus gilardii is also occasionally isolated from the sputum sample. However, it is difficult to identify Cupriavidus gilardii accurately and the clinical significance of the pathogen is uncertain. In addition, bloodstream infection (BSI) caused by Cupriavidus gilardii due to invasive pulmonary aspergillosis (IPA) has never been reported in the literature.

Case presentation

A 52-year-old female was admitted to our intensive care unit (ICU) with cough, hemoptysis and fever for about one month from the rescue room. Her medical history included SLE for three years which was treated with daily oral prednisone 40 mg. On physical examination, she appeared cyanotic with fever up to 39.2 °C and moist rale could be clearly heard on the lower lobe of both sides. Chest X-ray images after intubation showed the cloudiness on both sides (Figure 1). Respiratory failure was managed with protective mechanical ventilation (tidal volume 360 mL, plateau pressure 25 cmH₂O and positive end-expiratory pressure 15 cmH₂O) (3). Laboratory evaluation at the time of ICU admission revealed negative blood cultures and normal procalcitonin (0.08 ng/mL). However, the level of galactomannan (GM) reached up to 2.54 µg/L.

Figure 1 Plain chest X-ray after intubation showing the cloudiness on both sides caused by aspergillosis.

Bronchoscopy was performed through the endotracheal intubation. Hyperemia and bleeding can be detected with pseudomembrane formation around tracheal (Figure 2). Aspergillus fumigatus was isolated from the culture of bronchoalveolar lavage fluid (BALF) sample (Figure 3A,B,C) and the level of GM in BALF sample was 4.33 µg/L which was well above the normal range. Therefore, IPA was probably diagnosed and voriconazole was initiated (intravenous medication, 200 mg q12 h). Another bacteria was also isolated from the BALF sample, which appeared as very small colonies on 5% sheep blood agar after incubation at 24 h in normal atmosphere at 35 °C (Figure 3A). However, the strain could not be identified by Vitek 2 (BioMérieux, Inc) through biochemical testing.

Figure 2 Bronchoscopy image. Hyperemia and bleeding can be detected with pseudomembrane formation around tracheal (branches of left principal bronchus).

Figure 3 Bacterial morphological exam. (A) Aspergillus (yellow arrow) and Cupriavidus gilardii (green arrow) can be detected in blood nutrition agar plates (Bronchoalveolar Lavage Fluid sample); (B) Aspergillus hyphae can be detected in bronchoalveolar lavage fluid sample (Gram staining, 100×); (C) Aspergillus fumigatus can be detected in bronchoalveolar lavage fluid sample (lactate gossypol blue staining, 400×); (D) Cupriavidus gilardii can be detected in blood sample (Gram staining, 1,000×).

Hemoptysis was still heavily and the patient became febrile to 40.1 °C the next week with chills. The concentration of procalcitonin in serum reached to 46.2 ng/mL and one gram-negative bacteria was isolated from the culture of blood (Figure 3D) which could not be identified by Vitek 2 again. Matrix assisted desorption ionization time of flight mass spectrometry (MALDI-TOF MS, bioMérieux Inc., Durham, NC, USA) was performed and Cupriavidus gilardii was identified (with concordance 97%, Figure 4). Further identification was performed by 16S rRNA gene sequencing which revealed the same result.

Figure 4 MALDI-TOF MS analysis.

Antimicrobial susceptibility testing was performed and the breakpoints (susceptible, intermediate, or resistant) was determined according to Pseudomonas aeruginosa M100-S27 provided by the Clinical and Laboratory Standards Institute (CLSI) standards. Minimal inhibitory concentrations (MICs) of antibiotics were identical in blood and BALF sample. Ciprofloxacin was prescribed (intravenous medication, 400 mg q8 h) according to the results of antimicrobial susceptibility test (Table 1). However, the culture of blood was still positive three days after antibiotics prescription and the concentration of PCT did not reduce. One week later, she still developed a more serious condition and was maintained on vasopressor support but ultimately succumbed to multiorgan failure and died after two weeks.

Table 1 Antimicrobial agent susceptibilities of Cupriavidus gilardii
Full table

Discussion

Cupriavidus gilardii is a nonfermenting gram-negative bacillus which can be isolated from contaminated soils or plants (4). This sort of bacteria can also be identified as a rare colonizer in upper respiratory tract and seldom cause infection. Furthermore, clinical materials about Cupriavidus gilardii were not well documented due to difficulty in accurately identifying the species. However, this organism may represent an emerging pathogen in immunocompromised patients due to its innate antimicrobial resistance and its ability to acquire new resistances as it colonizes in human host (5). Therefore, more and more attention should be paid to this bacteria, especially in patients with immunosuppression.

IPA is often develops in severely immunocompromised patients when glucocorticoid and immunosuppressor are prescribed in those with asymptomatic aspergillosis colonization (6). Lung tissue and capillary were impaired by hyphae during the progress of IPA which could demonstrate on histology. Pulmonary vascular invasion is involved in the pathogenesis in hosts and is responsible for the higher frequency of dissemination to other organs such as eyes, liver and skin (7). Sometimes, colonization bacteria may circulated through the bloodstream by the damaged vessels and cause BSI like our patient.

Timely, appropriate treatment of infection depends on rapid, specific identification of causative microorganisms. Traditionally, microbial identification involves morphologic characterization by microscopy and staining, growth in culture, phenotypic and metabolic characterization by biochemical tests. Up to now, it was reported that difficulty still remained in correctly classifying Cupriavidus gilardii by biochemical (5). Gene sequencing like nanopore, 16S rRNA and next generation sequencing (NGS) are methods for identifying rare bacteria species with high precision up to now. However, complicated operation and high cost restrict their usage especially in the species-level discrimination. The technology of MALDI-TOF MS develops rapidly in the last decade which leads to the routine use in a part of clinical microbiology laboratory. Rare pathogens are identified via ribosomal proteins compare. Therefore, a considerable number of organism is needed in the process of MALDI-TOF MS (8,9).

A review of literature for characteristics in cases of infection caused by Cupriavidus gilardii is summarized as below (Table 2). Only three cases (10-12) were reported.

Table 2 Review of literature
Full table

In summary, pulmonary vascular invasion is involved in the pathogenesis in hosts of IPA which can induce BSI by some rare pathogens like Cupriavidus gilardii. Identification of this strain is difficult using typical methods such as biochemical testing which may delay the initiation of treatment and lead to poor prognosis. MALDI-TOF MS might be a better choice in rare bacteria identification which is accurate, rapid with cost-saving.

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

Informed Consent: Written informed consent was obtained from the family members of the patient for publication of this manuscript.

References

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