Clinical Microbiology Perspective of Empyema caused by Streptococcus constellatus in Malignancy Patient: A Case Report

Article history: Received 7 February 2021 Received in revised form 27 May 2021 Accepted 28 May 2021 Available online 31 May 202


INTRODUCTION
Streptococcus constellatus (SC) is a grampositive, facultative anaerobic bacterium related to Streptococcus anginosus and Streptococcus intermedius. In general, these bacteria were included as Streptococcus anginosus group (SAG), formerly known as Streptococcus milleri group. They are commensal bacteria in respiratory, digestive, and reproductive tract. 1 Nevertheless, recent evidence shows that they are also pathogenic and may cause infections. The incidence rate has reportedly increased continuously in the past two decades. 2 They are associated with abdominal, central nervous system, and pleuropulmonary infections. 1,3 SC empyema is a clinical entity that is described in the scientific literature in very few studies and with few patients, especially in Indonesia. This is a rare case report of Empyema caused by SC in patient with malignancy

CASE
A 45 -year-old man with no underlying diseases who was admitted to the emergency room of public hospital with respiratory insufficiency on November 11 th 2020. The symptom was followed with general weakness. There was no history of loss of appetite, loss of weight, and night sweats two days before on November 9 th 2020.
In the first three months, his symptoms began with non-productive cough, with no fever or other symptoms. Fifteen days before being admitted to Dr.
Soetomo General Hospital, he went to a secondary referral hospital due to suffering pain in the chest and dyspnea. A total of 1,500 ml of yellowish purulent fluid was removed. He was hospitalized for 3 days. After being discharged, he was referred to Puskesmas (primary health center/PHC) and was diagnosed as lung tuberculosis. He started consuming fixed dose combination of oral anti tuberculosis drugs (4FDC ATD) consisted of rifampicin, ethambutol, isoniazid, pyrazinamide for 10 days, but then he terminated the ATD due to vomitting.
Physical examination during the admission found asymmetrically thorax movement was decreasing on the right hemithorax. During palpation, fremitus was detected in half inferior of the right hemithorax, dullness in lower half of right hemithorax, pulmonary auscultation with diminished of respiratory sounds, and detected rhonchi on lower half of right hemithorax. The physical examination on November 13 th 2020 revealed rhonchi was not detected on lower half of right hemithorax.
The infection marker results taken from complete blood tests on November 9 th 2020 and November 12 nd 2020 were increased while on November 16 th 2020 and November 19 th 2020 were within normal range, listed in Table 1  with GeneXpert of pleural fluid was negative.
The yellowish fluid of about 50 ml was removed using water seal drainage to relieve the shortness of breath. Codein pills and antibiotics were given to the patient. Ampicillin-sulbactam 1.5 gram every 6 hours and metronidazole 500 mg every 8 hours were delivered to the patient for 10 days. After 10 days of antibiotics, the patient was discharged on November 20 th with no difficulty in breathing, no fever, no pain in chest tube insertion site, and no cough. than healthy patients. 3 These bacteria can rarely cause pyogenic infections, such as abcess, empyema, arthritis, and intra-abdominal infections. 4 Among pyogenic infections, empyema was third common manifestation after intra abdominal abscess and soft tissue abscess. 5 The possible explanation of increased pathogenicity of these bacteria is cell surface adhesins, exotoxin production, evasion of phagocytosis, as well as synergism with anaerobic of polymicrobial infections. 6 A molcular study detected multiple of pathogenicity factors in S. anginosus. 7 Culture is a gold standard and most common technique used for isolating S. constellatus. However, the turn around time of culture usually takes 3-5 days.
This would cause treatment delay. Multiplex PCR method for detection of six streptococci species has been developed. This technique gives rapid, simple, and reliable result for identification of these bacteria. 8 Therefore, multiplex PCR can be used for identification and survaillance of these bacteria, along with culturebased method.
We reported a case in which SC caused an empyema in an immunocompromised patient. The initial presentation was non chronic non-productive cough increasing into shortness of breath with an empyema.
The removal of purulent drainage and intravenous antibiotics improved the patient's symptoms.
Empyema is most commonly referred to pusfilled pockets which develop in the pleural space.
Empyema is a serious condition that requires treatment. 2,9,10 In this case, empyema in the patient Previous study showed colonized SAG directly induced noninvasive infections and caused invasive infections after entering normal sterile sites in the body including pleura. 2 SAG can enter pleura through blood or lymph (hematogenous) or per continuitatem from lungs to pleura. 10 The underlying disease such as malignancy could cause a certain degree of immunosuppression which made SC easier to enter pleural space. Therefore, infection caused by SAG should be considered in clinical diagnosis and treatmentrelated infections.
Generally, the prognosis of infection caused by SC is relatively less severe, sufficiently treated with simple drainage and intravenous antibiotics, had a shorter hospital stay, and lower than 30-day mortality rate compared to other SAG species. 2,12 Those reports were similar to the patient in this case which clinically and laboratory improved after being hospitalized for 10 days and was treated with water seal drainage and intravenous combined antibiotics. Clinically, the patient's symptoms such as difficulty in breathing, cough, and weakness were decreasing after 2 days and were resolved after 10 days of therapy. This result was supported with physical examination that rhonchi on lower half of right hemithorax was not detected on 2 nd day of antibiotics.
Furthermore, the blood infection markers were decreasing on the 1 st day of antibiotics (November 12 th 2020) and returned to normal range in 5 th day of antibiotics (November 16 th 2020).
However, a report in the UK reported a patient with empyema caused by SC that required extensive decortication and prolonged hospital admission. 12 Therefore, the pathogenic potential of commensal bacteria such as SCshould not be underestimated especially in patients with immunocompromised.
The antibiotic course is usually long, with mean duration of up to 34 days and most SAG isolates seem to be sensitive to penicillin and cefotaxime. 13 Those data were similar to SC isolates in this case which are sensitive to penicillin. Some reports indicate that patients infected by SAG can be co-infected by other agents including an-aerobes. Thus, ampicillin-sulbactam and metronidazole were added at the beginning of the treatment.

CONCLUSION
As an opportunistic pathogen, SC was found to produce an empyema infection in patient with malignancy. Although it was a rare case infection caused by SC, it should be considered in clinical diagnosis and treatment of related infections After being treated with antibiotics and water seal drainage, the patient had a good outcom.