Ralstonia is a Gram-negative non-fermentative bacterium widespread in nature, and includes four species, Ralstonia pickettii, Ralstonia solanacearum, Ralstonia mannitolilytica, and Ralstonia insidiosa, which were proposed in 2003. Ralstonia is mainly found in the external water environment, including municipal and medical water purification systems. This bacterium has low toxicity and is a conditional pathogen. It has been reported in recent years that infections due to Ralstonia are increasing. Previous studies have shown that most cases of infection are caused by Ralstonia pickettii, a few by Ralstonia mannitolilytica, and infections caused by Ralstonia insidiosa are rare.

A 2-year-old Chinese child suffered from intermittent fever and cough for 20 d and was admitted to hospital with bronchial pneumonia. Bronchoscopy and alveolar lavage fluid culture confirmed Ralstonia insidiosa pneumonia. The infection was well controlled after treatment with meropenem and azithromycin.

Ralstonia infections are increasing, and we report a rare case of Ralstonia insidiosa infection in a child. Clinicians should be vigilant about Ralstonia infections.

Ralstonia is a non-fermentative species widespread in nature, it is a Gram-negative bacterium, which was first isolated in 1973 and incorporated into Burkholderia (Burkholderia pickettii and Burkholderia solanacearum). The genus Ralstonia was named separately in 1995 by Yabuuchi et al[1], and it includes Ralstonia pickettii, Ralstonia solanacearum, Ralstonia mannitolilytica, and Ralstonia insidiosa, which were newly introduced in 2003[2]. Ralstonia reproduces in wet conditions and can survive long-term in harsh environments, mainly in external water environments, including municipal water and medical water purification systems[3,4]. Previous reports indicated that the bacterium was less virulent and was an opportunistic pathogen. However, human infections with Ralstonia without exposure to a contaminated solution are rare, thus the bacterium was not considered a major pathogen[5].

However, the incidence of Ralstonia infection is increasing in recent years. Previous studies have shown that most cases of infection are caused by Ralstonia pickettii, and a few by Ralstonia mannitolilytica; these pathogens can cause bloodstream infections, pneumonia, prostatitis, and many other diseases[6]. Ralstonia pickettii, has been isolated from various clinical specimens, such as sputum, blood, infected wounds, urine, ears, nasal swabs, and cerebrospinal fluid[5].

Ralstonia insidiosa is a new species proposed in 2003[7], which is closest to Ralstonia pickettii, and it has been reported to be isolated from the respiratory tract of patients with cystic fibrosis. In addition, Ralstonia insidiosa has been detected in water distribution and laboratory-purified water systems[8]. However, due to the low incidence of this bacterium infection and insufficient clinical awareness, reports of Ralstonia insidiosa infection are infrequent.

The patient was eventually diagnosed with Ralstonia insidiosa pneumonia.

The patient was started on conventional empirical medication with amoxicillin sodium-clavulanate potassium 30 mg/kg 3 times daily and adenosine monophosphate 5 mg/kg once a day. On the third day of admission, the child had increased fever and was given meropenem 20 mg/kg 3 times daily and immunoglobulin 1 g/kg once a day intravenously. Subsequently, meropenem 20 mg/kg was administered 3 times daily combined with azithromycin 10 mg/kg once a day. Based on the timeline of the onset of the infection, a chart of the child’s fever trend (Figure 2) and WBC count (Figure 3) was prepared for comparison.

Open in New Tab   Full Size Figure   Download Figure

Figure 2 The body temperature in the figure is the highest daily body temperature of the child.

Open in New Tab   Full Size Figure   Download Figure

Figure 3 A chart of the child’s fever trend and white blood cell count. The usual white blood cell count range is (4.0-10.0) × 10⁹ according to the “National Clinical Laboratory Operating Procedures” compiled by the Department of Medical Administration, Ministry of Health, China.

The child has been followed up, and no disease recurrence has been observed. A pulmonary CT performed 42 d after discharge on March 21, 2019, showed texture enhancement in both lungs. The lower lobe of the right lung showed patchy and cord-like high-density opacities with blurred edges (Figure 1C).

With regard to Ralstonia infections, a review of previous literature showed that the majority of cases were nosocomial infections, with evidence that Ralstonia enters the hospital environment primarily through a contaminated water supply system[9]. Infections are primarily caused by contaminated solutions, including blood products, sterile water, saline, respiratory therapeutic fluids[10-13], and that the most common infected items are blood collection tubes, dialysis machines, and nebulizers, which may eventually lead to different diseases such as bacteremia, sepsis, respiratory infections, and pneumonia[14], with human infections unrelated to contaminated solutions being rare. Infections occur predominantly in weak or immunosuppressed individuals, mainly in the elderly or neonates who are immunocompromised.

The child in the present report was admitted to hospital with intermittent fever and cough for 20 d, with no history of surgery or invasive procedures which excluded contact with medical devices such as ventilators and dialysis machines. The child had a long course of the disease and received antibiotics for 19 d before admission to the hospital (exact dose was unknown). After admission, we ruled out febrile illnesses such as tuberculosis, infectious mononucleosis, Kawasaki disease, rheumatic fever, and epidemic hemorrhagic fever. Physical and chemical examinations showed lower values of immunoglobulin A, complement C3, and serum T3 and T4, suggesting that the child was immunocompromised. On admission, CT showed a patchy dense shadow in the lower lobe of the right lung. A blood culture was tested on the next day after admission, and the result was negative on the 7^th d. This also made the diagnosis difficult. The child was initially considered to have lobar pneumonia and was given amoxicillin sodium-clavulanate potassium, immunoglobulin, and meropenem as empirical treatment against infection. The child’s condition did not improve, and a second CT scan showed a significant increase in the hyperdense shadow in the lower lobe of the right lung and a small amount of pleural effusion. The child was also tested for fungal-D glucan, which was higher than 162 mg/L. This also led us to consider the possibility of specific flora infectious pneumonia and fungal pneumonia at the time of diagnosis. As fungal pneumonia does not have characteristic imaging, bronchoalveolar lavage is used for diagnosis[15]. During follow-up, the child underwent bronchoscopy, and an alveolar lavage fluid culture was performed, which eventually confirmed the diagnosis of Ralstonia insidiosa infection based on the lavage fluid culture results.

Reliable therapeutic data on Ralstonia insidiosa infection are lacking. Studies related to drug resistance in Ralstonia insidiosa have shown that this bacterium is highly resistant to the aminoglycoside gentamicin and the β-lactam antibiotic aztreonam, with different drug resistance to ticarcillin-clavulanic acid mixtures[16]. Studies by Ryan and Adley[16] have shown that most Ralstonia strains are sensitive to carbapenem antibiotics. All isolates were sensitive to quinolones (ciprofloxacin and ofloxacin), tetracyclines (tetracycline and minocycline), cephalosporins (cefotaxime and ceftazidime), folate pathway inhibitors (meperidine/sulfamethoxazole) and uropipexicillin broad-spectrum-lactam antibiotics (piperacillin)[17]. Our patient, after 3 d of anti-infective treatment with azithromycin 10 mg/kg once daily combined with meropenem 20 mg/kg three times daily prior to the diagnosis of Ralstonia insidiosa infection, showed a significant reduction in fever and a significant improvement in clinical signs. Therefore, this regimen was continued for 4 d after diagnosis and the infection eventually improved and was controlled.

Ralstonia infections are becoming increasingly common in clinical practice. The reasons for this may be associated with the massive clinical use and partial misuse of antibiotics, the insidious nature of the bacterium, which is easily overlooked in the early stages of infection, and its multi-drug resistance, which makes the infection difficult to control. Our report presents a rare case of childhood Ralstonia insidiosa pneumonia. Clinicians should be vigilant about Ralstonia infections, especially in immunocompromised patients and those with a history of invasive procedures such as ventilators and dialysis machines.

We would like to thank the patient and his family members for their contributions to this report.