Pleural infection: a closer look at the etiopathogenesis, microbiology and role of antibiotics

Abstract

BACKGROUND: Pleural infection is a condition that continues to pose a significant challenge to respiratory physicians. We hypothesise that the main barriers to progress include a limited understanding of the pathogenesis, microbiology and role of antibiotics in the pleural space. DATA SOURCE: PubMed was searched for articles related to adult pleural infection using the terms 'pleural infection', 'empyema' and 'parapneumonic'. The search focused on developments in the last ten years, with any older citations only used to display context or lack of progress. Tuberculous pleural infection was excluded. RESULTS: We summarise our latest understanding of the pathogenesis of pleural infection, including recent advances in diagnostics and biomarkers. We discuss our understanding of the pleural microbiome, which differs inherently to that of the lung, and rationalise the current use of antibiotics in treating this condition. 2 Pneumonia vs Pleural Infection 2.1 The pathogenesis of pneumonia Pneumonia can be defined as an infectious process resulting from the invasion and overgrowth of microorganisms in lung parenchyma, breakdown of host defences and provocation of intra-alveolar exudates[8]. The causes can be divided into intrinsic and extrinsic factors. Extrinsic factors include exposure to a causative agent, pulmonary irritants or direct injury. Intrinsic factors are related to the host relating to loss of upper airway reflexes, which allows aspiration of contents and microorganisms from the upper airways into the lung. Underlying disease, loss of mechanical respiratory defences with the use of sedatives, tracheal intubation, and antibiotic treatment are all determinant factors for change in the normal flora of the upper respiratory tract. Once these bacteria find their way to down to the lung parenchyma , a combination of factors may lead to bacterial pneumonia. These include virulence of infecting organism, status of local defences and overall health of the patient. Susceptibility to infection is usually increased in patients of advanced age, or those with chronic disease, due to impairment of the immune response. Dysfunction of defence mechanisms, such as is seen in smokers, patients with chronic obstructive pulmonary disease and tumours, can also lead to greater susceptibility. 2.2 The evolution of the parapneumonic effusion 2.2.1 The exudative phase The interval between aspiration of organisms and the development of pneumonia varies from a few days up to one week. Pneumonia typically begins in dependent lobes at the periphery of the lung, and if untreated, spreads centripetally towards the hilum. If left untreated for the subsequent 2-5 days, a 'simple' parapneumonic effusion will develop and this is known as the "exudative" phase[9]. The development of the initial effusion is due to increased permeability of the pleural membranes in response to inflammation in the underlying lung parenchyma, which is thought to result in transfer of the interstitial fluid across the visceral pleura. Indirect clinical evidence sugg...

Management of Pleural Infection

“…Though an oversimplification, it is proposed that IPFT acts to disrupt the fibrin-rich adhesions via the activation of plasminogen and may have something of a lavage effect by stimulating pleural fluid production, whilst DNase reduces pleural fluid viscosity through the breakdown of extracellular DNA and biofilm formation. It is their synergistic action that results in better drainage and resolution of pleural infection [66,[76][77][78][79][80][81]. These findings build on the earlier work by Tillet and Sherry but also go some way in confirming other proofof-concept studies [61,64,82,83].…”

“…Intrapleural antibiotic therapy has often been proposed as a way of overcoming the poor pleural penetrance seen with a number of antibiotic classes. A recent review found little evidence to support the routine use of these therapies in post-pneumonic pleural infection, although there is more evidence for its use in post-pneumonectomy infections [80]. A number of antibiotic-eluting drainage catheters are now commercially available, and a recent study was able to demonstrate sustained release of bactericidal concentrations of penicillin within the pleural space compared to an intravenous regime in healthy rabbits [123].…”

Advances in pleural infection and malignancy

“…Antibiotic choice should be dictated by local prescribing policies and often empirically with adequate aerobic and anaerobic cover unless culture results are available. The role of antibiotics in pleural infection has been recently reviewed [24]. The duration of course and timing of the switch from intravenous to oral has not been evaluated in randomised clinical trials, but generally should be governed by clinical response and experts would advocate a total of 4 weeks of antibiotic therapy.…”

Pleural infection: moving from treatment to prevention

“…Studies of antibiotic penetration in human pleural fluid are lacking and based on small numbers [43]. As recently reviewed, animal model data would suggest that most antibiotics exceed the minimum inhibitory concentration (MIC) for the bacteria for which it would normally be used [45]. The notable exception is gentamicin and therefore guidelines recommend against the use of aminoglycosides in pleural infection [27].…”

“…The current recommendation is that the switch from intravenous to oral therapy be guided by cessation of pyrexia, clinical improvement and resolution of inflammatory markers, aiming for a total duration of 4 weeks as a minimum [27]. As recently reviewed, there is currently no role for intrapleural antibiotics in the routine treatment of pleural infection [45].…”