A case of pulmonary Serratia marcescens granuloma radiologically mimicking metastatic malignancy and tuberculosis infection

Background

Serratia marcescens is a gram-negative bacillus, which is ubiquitous in soil and water. S. marcescens was first described by an Italian pharmacist called Bartolomeo Bizio in 1823. At the time this organism was regarded as innocuous and non-pathogenic, indeed it had been used as a tracer organism in medical experiments and also as a biological warfare test agent in the past. The first case of S. marcescens colonisation in the human respiratory tract was published over a hundred years ago. In 1913, S. marcescens was isolated from the sputum of a patient with chronic cough. The first case of pneumonia caused by S. marcescens was reported in 1936. ¹ It is now well established that S. marcescens is an opportunistic pathogen, capable of causing both community-acquired infections and nosocomial infections resulting in significant morbidity and mortality.^2,3

S. marcescens has been implicated as an aetiological agent in a wade spectrum of infections, such as pneumonia, ⁴ lung abscess, ⁵ empyema, ⁶ urinary tract infection, ⁷ wound infection, ⁸ endocarditis, ⁹ septicaemia, ¹⁰ ocular infections, ¹¹ septic arthritis, ¹² osteomyelitis, ¹³ peritonitis, ¹⁴ meningitis ¹⁵ and cerebral abscess. ¹⁶ However, granuloma formation by S. marcescens is rare and only a handful of cases of Serratia granulomas have been reported. Also S. marcescens infections commonly occur in immunocompromised patients.^17–19 Other risk factors for S. marcescens infection include: indwelling medical devices, ¹⁰ use of antibiotics,^6,20 corticosteroids use, ¹⁰ use of illicit intravenous drugs, ⁹ chronic debilitating illnesses, ¹⁰ extremes of age ¹⁷ and lengthy hospital admission. ²⁰ We are reporting a case of pulmonary Serratia granuloma radiologically mimicking metastatic malignancy and tuberculosis infection in an immunocompetent patient.

Case presentation

A 57-year-old female life-long smoker was admitted to our hospital with shortness of breath and productive cough. Her background included chronic obstructive pulmonary disease, alcohol excess, congestive cardiac failure and cannabis smoking. A chest X-ray and computed tomographic (CT) pulmonary angiogram on admission showed only minor inflammatory changes together with some emphysematous changes (Figure 1a and b). The initial sputum, blood, stool and urine cultures did not grow any clinically significant organism. The urinary antigens for atypical pneumonia were negative. The patient was treated with corticosteroids, nebulised bronchodilators and meropenem for community-acquired pneumonia OPEN IN VIEWER

Within 48 h of admission the patient’s condition deteriorated and she developed type 2 respiratory failure needing non-invasive ventilation in the intensive care unit (ICU). During her ICU admission the patient required a central venous catheter, arterial catheter and urinary catheter. The patient stayed in the hospital for a month before she was discharged home.

A chest x-ray in the follow-up chest clinic, six weeks after her discharge demonstrated multiple ‘cannon ball’–like opacities bilaterally (Figure 2a). At this point her productive cough remained but she was otherwise well. She was admitted from clinic for further investigations and treatment. OPEN IN VIEWER

The patient’s sputum culture grew S. marcescens, sensitive to piperacillin/tazobactam. There was no growth of acid-fast bacilli in her sputum. A staging CT scan of her thorax, abdomen and pelvis revealed multiple large soft tissue masses throughout both lungs and enlarged mediastinal lymph nodes, which were not present on the previous CT scan (Figure 2b and c). Bronchial washings, brushing and biopsy found no malignant cell but evidence of acute inflammation was demonstrated and the samples grew S. marcescens. Following a two-week course of intravenous piperacillin/tazobactam no further S. marcescens was grown in her sputum.

A third thoracic CT scan was then carried out to assess treatment response, which showed development of a cavitation in one of the soft tissue masses in the right upper lobe (Figure 2d and e). At this stage malignancy remained a very real differential and a CT-guided lung biopsy was performed. The findings were consistent with necrotic granulomatous changes rather than malignancy – necrotic debris and cores of fibrous connective tissue were seen, within which there were epithelioid histiocytes forming granulomas, scattered lymphocytes and haemosiderin (Figure 2f).

In this case the ‘cannon ball’ lesions developed over a relatively short ten-week period in between the first two CT scans. The presence of S. marcescens in both sputum and bronchial washings, a rapid onset of disease and the absence of malignant cell in her histology samples suggested that the cause for these widespread lesions in her lungs and mediastinal lymphadenopathy was likely to be S. marcescens infection.

Other differentials were thoroughly investigated thus: Stains for fungal organisms and acid-fast bacilli were negative and the culture of the histology sample did not grow any organism. There was no histological evidence of vasculitis and in addition, her serum autoantibodies for vasculitis were also negative. A transoesophageal echocardiogram ruled out infective endocarditis. There was no evidence of immunosuppression; blood tests were negative for HIV infection, hepatitis or immunoglobulin deficiency.

Discussion

In this case, the patient was probably inoculated with S. marcescens during her first admission when she was in ICU. A survey of ICU-acquired infections in European countries by the European Centre for Disease Prevention and Control in 2011 revealed that 3.4% of ICU-acquired pneumonia cases and 2.1% of ICU-acquired blood steam infections were caused by Serratia species. ²¹ Over the years the ICU-acquired Serratia infections rates in the UK are falling.^21,22 However, ICU-acquired Serratia infection rates in the UK are still higher than in many European countries.^21,22 In 2011 Serratia species were responsible for 4.2% of ICU-acquired pneumonia cases and 4.4% of ICU-acquired blood steam infections in the UK. ²¹

In this case the portal of entry for S. marcescens was unclear. The pattern of disease in the chest indicates haematogenous spread of the infecting organism. S. marcescens is capable of producing virulence factors, such as fimbriae for adherence and biofilms, which allow the organism to colonise the indwelling medical devices and protect it from antibiotics and the host’s immune system. ¹ Although the patient required central venous catheter, arterial catheter and urinary catheter during her admission in ICU, Serratia was not isolated from any of the cultures including blood, urine, central venous catheter tip or the arterial catheter tip.

S. marcescens infections typically occur in adults with immunocompromise or debilitating illness.^10,18,19 In this case the patient had multiple comorbidities. However, she did not have any specific immunodeficiency disorder. The patient had a history of alcohol excess, which is associated with poor nutritional status and immunodeficiency. ²³ During her stay in ICU the patient was treated with corticosteroids which may have predisposed her to S. marcescens infection. ¹⁰ Other important risk factors for this infection are use of antibiotics and lengthy hospital admissions, both present here.^10,20

The treatment of S. marcescens infection can be challenging due to its antibiotic resistance. ²⁴ Despite a two-week course of piperacillin/tazobactam there was no significant radiological improvement and in fact the last thoracic CT scan after treatment with antibiotic revealed a cavity formation in the right upper lobe.

Cavity formation with S. marcescens pneumonia is uncommon.^4,25 The pathologic pattern of Serratia pneumonia depends on the host’s immune system; in neutropenic patients Serratia infection in lungs leads to diffuse neutropenic pneumonitis, whereas, in non-neutropenic patients Serratia causes acute necrotising bronchopneumonia. ²⁵ The patient in this case was not neutropenic. Unlike in this case, Serratia pneumonia in non-neutropenic patients usually appears as patchy consolidation, typically bilateral and most extensive in the lower lobes. ²⁵

Goldstein et al. ²⁵ reported that microabscesses were present in around 50% of the cases of Serratia pneumonia in non-neutropenic patients, whereas cavities were infrequent and usually associated with infected pulmonary intracts from pulmonary embolisms. Goldstein et al. also observed that the alveolar exudates in non-neutropenic patients with Serratia pneumonia contained polymorphonuclear leukocytes and macrophages, fibrin and various degrees of haemorrhage. Macrophages organised into granulomas were not reported to be a feature of Serratia pneumonia by Goldstein and his colleagues.

Our literature review revealed only a few cases of Serratia granuloma: three cases of Serratia granuloma formation in the skin,^26–28 one case of granulomatous osteomyelitis ²⁹ and one case of perinephric soft tissue granuloma. ³⁰ We are reporting a unique case of pulmonary granuloma formation by S. marcescens in a patient with no history of specific immunodeficiency disorder. The radiological appearance of this infection was similar to metastatic malignancy or tuberculosis infection.

Conclusion

There have been a few reported cases of Serratia granulomas in the literature, but to our knowledge there has not been any report of pulmonary Serratia marcescens granuloma in an immunocompetent adult.