Rapid Cavitary Pneumonia and Reversible Hepatic Injury in Burkholderia pseudomallei ST271 Infection

Introduction

Burkholderia pseudomallei is a gram-negative bacterium that causes melioidosis, a disease endemic to tropical and subtropical regions [1]. It is known for its diverse clinical presentations, which range from mild localized infections to life-threatening septicemia [2]. Infection with B. pseudomallei may present as either acute or chronic disease, with a broad clinical spectrum influenced by host factors and disease course [3]. Although pneumonia is the most common clinical manifestation, systemic dissemination to internal organs – particularly the spleen, prostate, liver, and kidneys – is clinically significant in severe cases with hematogenous spread [4].

The clinical heterogeneity of melioidosis makes its diagnosis and management particularly challenging worldwide. In China, ST46, ST50, ST55, ST58, and ST70 represent the dominant B. pseudomallei sequence types (STs); other STs lack systematic surveillance and clinical profiling [5,6]. This report describes a previously healthy 50-year-old male construction worker who exhibited fever, hemoptysis, and cavitary pneumonia due to infection with B. pseudomallei ST271, along with associated reversible hepatic injury.

Case Report

A 50-year-old male construction worker from Haikou, China, was admitted to the hospital in mid-2024 after experiencing intermittent fever and a persistent cough for 2 weeks. His temperature reached 39°C; this was accompanied by chest pain and expectoration of blood-tinged sputum. The patient had been treated with cefixime and celecoxib at a local clinic without improvement. He had a 5-year smoking history, did not misuse alcohol, and had no other underlying diseases or clinically significant medical history.

On admission, the patient had a body temperature of 39.8°C, blood pressure of 101/68 mmHg, pulse of 102 beats per minute, and respiratory rate of 21 breaths per minute. Blood tests revealed strongly elevated systemic inflammatory markers, including a C-reactive protein level of 125.6 mg/L (reference: <5 mg/L) and erythrocyte sedimentation rate of 54 mm/h (reference: <15 mm/h). White blood cell count was normal (8.92×109/L; reference: 4–10×109L) and neutrophils were modestly increased (72.2%; reference: 50–70%). Acute hepatic injury was evident from substantially elevated liver enzymes: alanine aminotransferase 329 U/L (reference: 9–50 U/L), aspartate aminotransferase 134 U/L (reference: 15–40 U/L), and gamma-glutamyl transferase 284 U/L (reference: 10–60 U/L). Chest computed tomography (CT) showed a large right upper-lobe mass with thick-walled cavitation, suggestive of a lung abscess (Figure 1A).

Initial microbiological investigations revealed negative results for Mycoplasma pneumoniae antibodies, influenza A and B viruses, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Serological tests for hepatitis A, hepatitis B, hepatitis C, human immunodeficiency virus, and syphilis also yielded negative results. Furthermore, the immunocolloid gold assay for Mycobacterium tuberculosis IgG antibodies and the sputum acid-fast bacilli test both showed negative findings.

Bronchoalveolar lavage was performed 2 days after admission; the sample was analyzed by metagenomic sequencing and conventional culture. Five days after admission, metagenomic sequencing identified B. pseudomallei with 21 reads (SRA accession number SRR32060362). Bacterial cultures demonstrated that the isolate grew well on Luria-Bertani agar; it formed circular, dry, smooth colonies with a grayish-white to pale yellow appearance after 48 hours of incubation (Figure 2A). On Burkholderia cepacia selective agar, the isolate formed circular, convex, gray to white metallic colonies with a yellow color change in the agar (Figure 2B). Gram staining revealed gram-negative bacilli with a characteristic bipolar “safety-pin” appearance (Figure 2C). Antibiotic susceptibility testing indicated sensitivity to imipenem, trimethoprim-sulfamethoxazole, and ceftazidime. Using our previously described method [7], the isolate could be lysed by bacteriophage vB_BpP_HN01 at a titer of 106 plaque-forming units (PFU)/mL (Figure 2D).

Whole-genome sequencing of the isolate showed that its genome (GenBank accession number GCA_046524095.1) was 7 050 744 bp in size, with a G+C content of 68.19%. The strain exhibited a 94.4% digital DNA-DNA hybridization value and 99.5% average nucleotide identity with the reference B. pseudomallei strain (RefSeq accession number GCF_000959285.1). These values exceed the threshold for bacterial species delineation [8,9], confirming its classification within this species. After whole-genome sequencing, submission to the pubMLST database identified the isolate as B. pseudomallei ST271 [10].

Upon admission, the patient was treated empirically with moxifloxacin (0.4 g once daily, intravenous) and glutathione (1.2 g daily, intravenous) for hepatic protection – glutathione acts as an antioxidant and supports hepatocellular detoxification. However, his fever and cough persisted without noticeable improvement during subsequent days. Five days after admission, contrast-enhanced chest CT revealed extensive consolidation and cavitation in the right upper lobe, along with multiple enlarged mediastinal lymph nodes (Figure 1B). During bronchoscopy, a substantial amount of white purulent secretion was observed in the right upper lobe (Figure 1C).

Following identification of B. pseudomallei ST271, and 5 days after admission, the antibiotic regimen was adjusted to intravenous ceftazidime (2.0 g every 8 hours). The patient’s fever resolved within 48 hours, and his cough substantially improved by day 5. Follow-up liver function tests demonstrated complete normalization of previously elevated enzymes, confirming resolution of hepatitis. The patient experienced no complications during hospitalization and was discharged 12 days after admission with a prescription for oral trimethoprim-sulfamethoxazole (960 mg every 12 hours) as extended outpatient therapy. One month after admission, follow-up chest CT demonstrated considerable improvement in the lung abscess and consolidation (Figure 1D). Two months after admission, follow-up CT revealed further absorption of inflammatory exudates and consolidation, along with clinically significant regression of hilar and mediastinal lymph nodes (Figure 1E). The patient is currently in good condition and will continue to be followed for 6 months.

Discussion

B. pseudomallei is a highly virulent pathogen that can invade multiple organ systems, often leading to abscess formation in various tissues [2]. Clinical outcomes are influenced by host factors and bacterial characteristics. In endemic regions such as Hainan, melioidosis remains an important public health concern. According to the international B. pseudomallei MLST database (https://pubmlst.org/bpseudomallei/, search date: January 6, 2025), only 10 of 7295 isolates (0.14%) belong to ST271, including 9 clinical isolates from Malaysia and 1 from China. Consistent with these database records, the limited number of published clinical reports indicates that ST271 infections have been predominantly documented in Malaysia and southern China [11,12]. The scarcity of data concerning this ST underscores the need for further research to elucidate its clinical significance and geographic distribution. Our report adds to the limited clinical literature regarding B. pseudomallei ST271 and illustrates how early molecular diagnosis can influence clinical outcomes in severe melioidosis.

In the present case, the ST271 strain demonstrated multi-organ involvement, with rapid progression to a cavitary lung abscess and concurrent hepatic injury. Pneumonia represents the initial presentation in approximately half of melioidosis cases; dissemination can extend to internal organs such as the spleen, prostate, liver, and kidneys, thereby complicating diagnosis and management [4]. Hepatic involvement may manifest as abnormal liver function tests, jaundice, or focal abscesses, and in some cases as hepatitis-like biochemical abnormalities without a discrete abscess [13]. Despite severe radiologic findings, our patient exhibited a strongly elevated C-reactive protein level along with a normal leukocyte count. This dissociation between systemic inflammation and leukocyte response may reflect a unique host-pathogen interaction, as previously suggested [14]. Notably, follow-up liver function test results were completely normalized after treatment, indicating toxin-mediated hepatocellular damage rather than irreversible necrosis.

Melioidosis often presents with nonspecific symptoms, making it difficult to differentiate from other respiratory infections [15]. Early identification of B. pseudomallei is essential for effective treatment. Although culture remains the diagnostic gold standard, it often requires several days and may delay targeted therapy, particularly in settings with limited clinical suspicion or diagnostic resources [16]. In contrast, metagenomic sequencing provides a rapid and accurate alternative. In the present case, sequencing enabled prompt identification of the pathogen, guiding the transition from ineffective empirical therapy to targeted treatment and thus directly contributing to the patient’s favorable clinical outcome.

Treatment of melioidosis typically requires prolonged antibiotic therapy due to the high relapse rate [17]. The combination of ceftazidime and trimethoprim-sulfamethoxazole has proven effective in treating B. pseudomallei infections [2]. Our patient responded well to intravenous ceftazidime followed by oral trimethoprim-sulfamethoxazole. This regimen facilitated complete resolution of the lung abscess and hepatic injury; no relapse has been observed during follow-up to date.

In addition to conventional antibiotic therapy, our laboratory performed preliminary in vitro bacteriophage testing on the isolated strain, which revealed promising inhibitory activity against the pathogen. A growing body of research indicates that phage therapy represents a potentially effective adjunctive therapeutic strategy for intractable bacterial diseases, particularly those caused by multidrug-resistant pathogens [18,19]. Our recent study demonstrated that N4-like bacteriophages from Hainan exhibit activity against clinical B. pseudomallei strains and show therapeutic potential in experimental models [20]. Those findings support the biological plausibility of phage susceptibility in the present ST271 isolate and warrant further investigation.

Conclusions

The ST271 strain of B. pseudomallei poses a clinical challenge due to its rapid and aggressive progression in pulmonary and hepatic systems, even among immunocompetent hosts. This case demonstrates the importance of early diagnosis, particularly in endemic regions such as Hainan, along with the utility of metagenomic sequencing in identifying rare pathogens. Timely, targeted antibiotic therapy can lead to favorable outcomes. Ongoing research into novel treatment modalities, such as bacteriophage therapy, holds promise for the future.