A Rare Case of Empyema Due to Cutibacterium acnes in the Setting of COVID-19

Abstract

Introduction: Cutibacterium acnes is a Gram-positive anaerobic rod that is part of the normal skin flora, as well as the oral cavity, genitourinary and gastrointestinal tracts. When detected, it is usually considered contaminant; but it is infrequently responsible for invasive infections, mainly neurosurgical and joint infections. It is rarely found as a pathogen responsible for lung infections or empyema. Case report: We present a unique case of C. acnes empyema following severe COVID-19, making this the first documented case of empyema due to this bacterium following COVID-19. The microorganism was identified by 16S rRNA gene sequencing. The patient was treated with a combination of antibiotics and surgical intervention. Conclusions: This case demonstrates the potential severity of C. acnes empyema. Further studies are needed to establish management guidance.

Introduction

Cutibacterium acnes is an anaerobic Gram-positive, facultative, pleomorphic diphtheroid-like bacterium. It is a non-spore-forming bacillus that colonizes the skin, the oropharynx and the gastrointestinal tract [1]. It is infrequently isolated as a pathogen from sterile body fluids and responsible for invasive infections [2]. The most common human infections reported and known are those of orthopedic implant-associated infections (mainly after shoulder arthroplasty) and post-neurosurgical infections [3].

Invasive infections due to C. acnes usually have a delayed presentation and an indolent nature as patients usually have a prolonged duration of symptoms before presenting, have normal white blood cell count and rarely report having a fever as a symptom. C. acnes can be difficult to isolate due to its slow growth and anaerobic requirements [2]. It is susceptible to a wide range of antibiotics including beta-lactams, quinolones, and clindamycin; however, resistance to other antibiotics is progressively increasing [4].

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is known to cause coronavirus disease 2019 (COVID-19). It has wide variety of respiratory manifestations, from self-limited upper respiratory tract infection to severe acute respiratory distress syndrome (ARDS). The incidence of empyema in COVID-19 has not been well studied [5].

The purpose of this presentation is to increase awareness of C. acnes as a cause of pleural empyema.

Case report

A 19-year-old man with no known comorbidities presented to the emergency department for evaluation of right-sided chest pain of 3 days duration, associated with dyspnea.

The patient had been recently admitted to the hospital, one month prior to this admission, with complains of shortness of breath, cough, diarrhea, loss of taste and smell. These symptoms had started two weeks back. He had complained of progressive dyspnea which had prompted him to present to the emergency room where he was found to have severe COVID-19 with bilateral pneumonia. He was unvaccinated against COVID-19. He had high O₂ requirements on AirVo-HFNC 60 L/min flow and 75% FiO2 saturating 98%. He had to be admitted to the ICU. Given the fact that his symptoms had started 2 weeks prior to presenting to the hospital, he was out of window for remdesivir. He was treated with tocilizumab and dexamethasone. His chest CT at that time showed pulmonary embolism bilaterally without right heart strain and he was started on anticoagulants. On day 2 of his ICU stay, his oxygen requirements improved and had was on AirVo-HFNC 40 L/min flow and 51% FiO2 saturating 97%. Blood and sputum cultures remained negative as well as urine Legionella antigen. He subsequently improved clinically, stayed in the ICU for 3 days then he was transferred to the floor where he continued to be on dexamethasone and anticoagulants as well as O₂ supplementation. His total hospital stay lasted for 5 days. He was able to be weaned off O₂ before discharge home.

Three weeks after discharge, he presented again with complaints of shortness of breath and right-sided chest pain that had started 3 days prior. He also reported some fatigue. He denied any nausea, vomiting, diarrhea or urinary symptoms. He denied any fever or chills. He had no recent travel or sick contacts.

Physical examination revealed a young man in no distress who was looking ill. He was febrile with a temperature of 39.4 °C (102.9 °F), tachycardic with a heart rate of 113 beats/min, and tachypneic with a respiratory rate of 36 breaths/min, but otherwise, he was hemodynamically stable with a normal blood pressure of 125/71 mmHg. His mucous membranes were dry. His neck was supple with no lymphadenopathy. His lung exam revealed diminished breath sounds in the lower lobes bilaterally mainly on the right side, without wheezing. His skin exam did not show any rash or lesions. His heart exam did not reveal any murmurs, and his abdominal exam was unremarkable.

Initial laboratory findings showed a white blood cell count of 11.4/μL, mild anemia with a hemoglobin level of 12 gm/dL, thrombocytosis with a platelet count of 513000/μL, normal ALT/AST and bilirubin levels. Renal function and electrolyte levels were normal. Chest X-ray (CXR) showed a right-sided pleural effusion with loculations as well as some atelectasis at the left lateral pulmonary base (Figure 1), and computed tomography of the chest revealed a large loculated right pleural effusion with moderate partial atelectasis of the right lung base and some fibrotic changes on the left side (Figure 2).

Blood culture was obtained on admission and remained negative. The patient was initially started on broad spectrum antibiotics including vancomycin and cefepime. He underwent a diagnostic thoracentesis, 6 CC of fluid were aspirated and sent for analysis, and were consistent with empyema, showing lactate dehydrogenase (LDH) 895 U/L, and nucleated cell count 7,390/mm³ with 74% neutrophils. A chest tube thoracostomy was performed and intrapleural fibrinolysis was started. A repeat chest CT showed persistent loculations, therefore, the patient underwent video-assisted thoracic surgery (VATS) on day 5 of hospitalization with complete decortication of the right pleural space. Operating room (OR) specimens were obtained in maximum conditions of sterility, sent for cultures that also remained negative (Gram stain showed moderate amount of polymorphonuclear neutrophils (PMNs) but no organisms were seen).

The patient’s clinical status significantly improved. His leukocytosis also resolved. Repeat CXR the day after decortication showed improved aeration of the lungs with some atelectasis and small pleural effusion on the right side. He was switched to oral antibiotics including doxycycline and amoxicillin/clavulanic acid on day 7 of hospitalization and was discharged in stable condition with plans to complete a total of 4 weeks of therapy. Fluid culture from the initial thoracentesis as well as from OR samples remained negative after 7 days (media used for culture include blood agar, chocolate Agar, MacConkey Agar and anaerobic media). Bacterial DNA detection by PCR was requested (OR specimens were sent to University of Washington) and results came back in 2 weeks revealing C. acnes. As the culture remained negative, no antimicrobial susceptibility testing was performed.

The patient followed up after completing his antibiotics course. He had a repeat chest X-ray that showed significant improvement of the right lung with minimal atelectasis of the right lung base. Another CXR obtained 3 months after discharge showed complete resolution of the changes seen previously, without any airspace disease of persistent effusion.

To date, six months after the completion of antibiotics, the patient remains afebrile and doing well with no evidence of infection recurrence.

Discussion

C. acnes (more commonly referred to as P. acnes) can be responsible for many invasive infections including prosthetic joint infections, cardiovascular device-related infections, cerebrovascular devices and many others, including empyema [6]. Many times, a mixture of aerobic and anaerobic bacteria can be found in pleuropulmonary infections, and anaerobes are relatively frequent pathogens isolated in pleural empyema fluid cultures [7], however, C. acnes is rarely found as the only organism responsible for empyema.

SARS-CoV-2 can cause many complications. The incidence of empyema in the setting of COVID-19 has not been well studied [6]. Bacterial coinfections carry higher morbidity and mortality. A previous report showed that the most common pathogens causing respiratory coinfections in patients hospitalized with COVID-19 were Staphylococcus aureus and Haemophilus influenzae [8].

Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) has demonstrated its usefulness for the easier identification of anaerobic bacteria. It is a fast and highly-reliable tool due to the little amount of bacteria required and its accuracy. 16S rRNA gene sequencing is a polymerase chain reaction (PCR) method that is used to identify poorly isolated and nonculturable bacteria, and is considered gold standard for the identification of bacteria including anaerobes [9]. In our patient, as there was no growth on the plate, MALDI-TOF MS could not be performed, and 16s rRNA gene sequencing was helpful in identifying the pathogen responsible for our patient’s empyema. To our knowledge, this is the first case in the literature of empyema due to C. acnes after severe COVID-19.

Guidelines for the management of empyema in COVID-19 have not yet been established. It usually requires a combination of antibiotics and surgical intervention [10].

Regarding antibiotic treatment, C. acnes is highly susceptible in vitro to many antibiotics such as beta-lactams, clindamycin, vancomycin and quinolones. Susceptibility testing is advised as antibiotic resistance for C. acnes is on the rise [3].

Conclusions

This case report highlights C. acnes as a possible cause of pleural infection. Although rare, it can however play an important role in invasive infection. It should not be considered a contaminant if isolated from a sterile sample as it may require further investigations. Where appropriate, extended microbiology culture or PCR testing should be requested for bacterial identification to assist with diagnosis and treatment plan.