Management of Pleural Infection

Pulm Ther (2021) 7:59–74 https://doi.org/10.1007/s41030-020-00140-7 REVIEW Management of Pleural Infection Anand Sundaralingam . Radhika Banka . Najib M. Rahman Received: August 29, 2020 / Accepted: November 16, 2020 / Published online: December 9, 2020 Ó The Author(s) 2020 ABSTRACT Pleural infection is a millennia-spanning condition that has proved challenging to treat over many years. Fourteen percent of cases of pneumonia are reported to present with a pleural effusion on chest X-ray (CXR), which rises to 44% on ultrasound but many will resolve with prompt antibiotic therapy. To guide treatment, parapneumonic effusions have been separated into distinct categories according to their biochemical, microbiological and radiological characteristics. There is wide variation in causative organisms according to geographical location and healthcare setting. Positive cultures are only obtained in 56% of cases; therefore, empirical antibiotics should provide Grampositive, Gram-negative and anaerobic cover whilst providing adequate pleural penetrance. With the advent of next-generation sequencing techniques, yields are expected to improve. A. Sundaralingam (&)
R. Banka
N. M. Rahman Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK e-mail: N. M. Rahman Oxford Respiratory Trials Unit, University of Oxford, Oxford, UK N. M. Rahman Oxford NIHR Biomedical Research Centre, Oxford, UK Complicated parapneumonic effusions and empyema necessitate prompt tube thoracostomy. It is reported that 16–27% treated in this way will fail on this therapy and require some form of escalation. The now seminal Multicentre Intrapleural Sepsis Trials (MIST) demonstrated the use of combination fibrinolysin and DNase as more effective in the treatment of empyema compared to either agent alone or placebo, and success rates of 90% are reported with this technique. The focus is now on dose adjustments according to the patient’s specific ‘fibrinolytic potential’, in order to deliver personalised therapy. Surgery has remained a cornerstone in the management of pleural infection and is certainly required in late-stage manifestations of the disease. However, its role in early-stage disease and optimal patient selection is being re-explored. A number of adjunct and exploratory therapies are also discussed in this review, including the use of local anaesthetic thoracoscopy, indwelling pleural catheters, intrapleural antibiotics, pleural irrigation and steroid therapy. Keywords: Chest drain; Effusion; Empyema; Intrapleural enzyme therapy; Intrapleural fibrinolytic therapy; Parapneumonic; Pleural infection; Management Pulm Ther (2021) 7:59–74 60 Key Summary Points Parapneumonic effusions are separated into distinct categories according to their biochemical, microbiological and radiological characteristics. It is increasingly recognised there exists heterogeneity within these groups, and there is a paucity of evidence for the optimal first-line intervention, in the form of head-to-head comparator trials. The causative organism varies widely according to geographical location and healthcare setting, and positive cultures are achieved in only 56% of cases. This is expected to increase with next-generation sequencing techniques. Whilst 16–27% of cases managed with tube thoracostomy are expected to require escalation of therapies, treatment success rates of 90% are now reported in the literature with intrapleural enzyme therapy (IET). Future directions will look at delivering personalised therapies according to individual patients’ ‘fibrinolytic potential’ and targeting upstream biochemical pathways. DIGITAL FEATURES This article is published with digital features, including a summary slide, to facilitate understanding of the article. To view digital features for this article go to https://doi.org/10.6084/ m9.figshare.13227905. INTRODUCTION Pleural infection is a disease that has plagued both the ancient and modern world [1, 2]. It has been studied and described by the great and the good, but has afflicted them in equal measure. Sir William Osler (1849–1919), hailed as the father of modern medicine, opted for surgical management of his empyema only to succumb to his illness, whilst ironically, the eminent French surgeon Guillaume Dupuytren (1777–1835) opted for conservative measures and eventually met the same fate [3–5]. That we still grapple with some of the same issues our forefathers did serves as a source of both comfort and frustration. Many advances have been made in the management of pleural infection, and in this review, we aim to summarise the evidence to date and outline best practice in the management of empyema in adults. It is important to note that empyema in children is a distinctively different condition from that in adults, and management recommendations for adults do not necessarily apply to children and vice versa. DEFINITION ‘Pleural infection’ is a stepwise progressive condition, classified into stages, and whilst there is some variation in the classification system between different international guidelines, the principles are largely similar. This is summarised in Table 1 and incorporates pertinent features from each of these guidelines. Traditionally, it is the presence of pus within the pleural space that earns pleural infection the title of ‘empyema’; however, in the literature, the terms pleural infection, complicated parapneumonic effusion (CPPE) and empyema are used fairly interchangeably, and in clinical practice their management is identical. It should be borne in mind that pleural fluid biomarkers are simply tests and, like any other, have varying sensitivity, specificity and likelihood ratios. They are not infallible and must be interpreted within the context of the overall clinical picture. Whilst novel pleural fluid markers have been proposed, their discussion is beyond the scope of this review [9–14]. Pulm Ther (2021) 7:59–74 61 Table 1 The varying stages of development of pleural infection [6–8] Stage Stage I Pleural fluid characteristics Radiological characteristics pH [ 7.30 Simple exudate ‘uncomplicated parapneumonic effusion’ (UPPE) Free-flowing effusion Glucose [ 60 mg/ dL (or [ 3.3 mmol/ L) Stage II pH \ 7.20 Fibrinopurulent ‘Complicated parapneumonic effusion’ (CPPE) Echogenic effusion Glucose \ 35 mg/ dL Tendency (or \ 2.2 mmol/ towards L) septations and LDH [ 1000 IU/ loculations L Neutrophilic Positive microbiology (gram stain/culture) Presence of pus = ‘empyema’ Stage III As above Organising Visceral pleural thickening Trapped lung ANTIMICROBIALS The cornerstones of treatment in pleural infection is prompt evacuation of the infected collection from the pleural space and initiation of antimicrobial therapy [6]. Antimicrobial therapy should be guided by specific pathogen susceptibility. The bacteriology implicated in pleural infection is distinct from that of pneumonia and serves as further (...truncated)