Case of the Month

A 32-year-old man presented to the casualty department of a district hospital in April 2021 with a history of coughing, progressive dyspnoea, decreased effort tolerance, fever, and general weakness. The symptoms started approximately one week prior. He was diagnosed with HIV in 2018 and was started on first line antiretroviral treatment (fixed dose combination of tenofovir, emtricitibine and efavirenz) at the time of diagnosis, but interrupted treatment towards the end of 2019. He reported no previous history of tuberculosis (TB) nor any close contacts with TB. On examination he was cachexic, with generalized lymphadenopathy and palmar pallor. He was not cyanosed and saturated at 92% on room air. He had a tachycardia of approximately 120 beats per minute and a blood pressure of 95/56 mmHg. On auscultation, decreased air entry in the left lung and bilateral basal crepitations were noted. There was dullness to percussion over the lower costal margin of his back on the left side. The chest X-ray demonstrated a large left sided pleural effusion. The lung fields were clear on the right. A thoracentesis was performed, and pus was aspirated from the pleural space. The pus was submitted to the laboratory for microscopy, culture, and susceptibility testing (MCS), GeneXpert MTB/Rif Ultra (Cepheid, Sunnyvale, California, United States) and TB MC&S. Blood was also taken for laboratory investigations (Table 1 below). No blood culture or sputum specimens were collected. An intercostal drain was inserted and drained approximately 1.5 L of pus. The patient was initiated on amoxicillin-clavulanate 1.2g intravenously to be given 12 hourly, and arrangements were made to refer the patient to a tertiary hospital for further management. Unfortunately, the patient deteriorated suddenly and despite attempts at resuscitation, demised later the same day.

On microscopy of the pus specimen numerous (3+) Gram-positive cocci and a high number (2+) of neutrophils were observed. The specimen was cultured onto 5% sheep blood agar (SBA) and MacConkey agar and incubated in ambient air overnight, as well as onto 10% SBA that was incubated anaerobically for 48-hours. On SBA a pure growth of large white glistening colonies with a narrow zone of beta haemolysis was observed. The same organism grew on the anaerobic plate. Poor growth of the same organism was observed on the MacConkey agar. The colonies were catalase negative. A Streptex assay (Thermo Fisher Scientific, Remel, Lenexa, KS, USA) was performed that typed the isolate as Streptococcus Group B. The isolate’s identity was confirmed on the VITEK® 2 system (bioMerieux, Marcy l’Etoile, France) as Streptococcus agalactiae. The isolate was susceptible to all antibiotics tested using the VITEK® 2 ST03 panel including: penicillin, ceftriaxone, erythromycin, clindamycin, vancomycin, and linezolid. The TB workup of the specimen including the GeneXpert MTB/Rif Ultra, the auramine stain for acid fast bacilli and 42-day culture (BD BACTEC MGIT, Becton, Dickinson and Company, Franklin Lakes, New Jersey, United States) were all negative.

Discussion

Empyema, commonly defined as the presence of a bacterial infection or pus in the pleural space, is a serious infection with high morbidity and mortality (15-20%) [1]. With the introduction of antibiotics, the mortality rate has decreased from 60% to less than 10% in developed countries [1,2]. Predisposing conditions include bacterial pneumonia, surgery, trauma, oesophageal perforation, thoracentesis, subdiaphragmatic infection, spontaneous pneumothorax, and septicaemia [2]. In the past the predominant cause was assumed to be bacterial pneumonia in which bacteria breach the visceral pleura to establish an infected parapneumonic effusion [1]. However, differences between the typical bacteriology of pneumonia and empyema have been highlighted, with many patients with empyema having no evidence of an underlying pneumonia [1-5]. Such observations suggest that pleural empyema and pneumonia should, in some cases, be considered separate conditions, [1] and that the mechanisms and sources of bacterial invasion of the pleural cavity are poorly understood [1-3]. Dyrhovden et al. (2019) used polymerase chain reaction (PCR) of the 16S rRNA and rpoB gene to identify bacteria from pleural fluid obtained from 64 patients aged 18 years and above from Haukeland University Hospital, Bergen, Norway who presented with pleural empyema [1]. They found that among samples from patients with an empyema of uncertain aetiology the organisms isolated reflected that of an oesophageal rupture and correlated with that seen on oral-origin subdural empyemas. Of the isolates, Streptococcus intermedius and Fusobacterium nucleatum alone or in combination were found in 96% of the isolates tested and Parvimonas micra and Eubacterium brachy were present in 30% of samples from an empyema of uncertain aetiology [1]. Among isolates that had a certain cause, monomicrobial infections caused by Streptococcus pneumoniae (8), Staphylococcus aureus (5), Pseudomonas aeruginosa (2), Streptococcus pyogenes (1), Escherichia coli (1), Klebsiella pneumoniae (1) were the most common causes of empyema [1]. In the South African setting of high TB and HIV prevalence, and given the patient’s HIV status, one would suspect TB to be one of the leading causes of empyema in this patient. Interestingly, the patient presented here did not culture any of the aforementioned organisms and instead cultured a pure growth of S. agalactiae. In the past this organism used to be more prevalent, but the incidence has drastically declined since the introduction of pasteurization [3]. In recent times S. agalactiae is mainly associated with colonization of the female genital tract and serious neonatal infections such as meningitis [2]. It is still occasionally associated with purulent infections such as septic arthritis and central nervous system infections [3,4]. To the best of the authors’ knowledge, only four previous cases of pleural empyema in adult patients caused by S. agalactiae have been reported in the literature [2-5]. All were complicated by dissection of the infection beyond the pleural space into the soft tissue of the chest wall, a condition known as empyema necessitans. This condition, unlike a typical pleural empyema, requires surgical intervention by means of incision and drainage as opposed to the standard management which consists of intercostal drain insertion. Antibiotics are also required to treat both conditions [2-5]. Like the case presented, in none of the previously reported cases was there a clear source from which the S. agalactiae originated established [2-5]. This demonstrates our incomplete understanding of the pathogenesis of this type of pleural empyema. Unlike our case, the patients in the previous reports all survived [2-5]. Advanced age, diabetes mellitus, chronic kidney disease, malignancy and immunosuppressive conditions predispose to severe infections by S. agalactiae [2]. Specifically advanced age, diabetes mellitus and an elevated C-reactive protein (CRP) have been identified as risk factors for increased mortality in patients with invasive S. agalactiae infections [2-4]. Of these risk factors the case presented only had a massively raised CRP.