Pleural Infections

Pleural Infections

References:

1) Davies HE, Davies RJO, Davies CWH

Management of pleural infection in adults: British Thoracic Society pleural disease guideline 2010

Thorax 2010;65:ii41-ii53

2) Lehtomäki A, Nevalainen R, Ukkonen M, Nieminen J, Laurikka J, Khan J. Trends in the incidence, etiology, treatment, and outcomes of pleural infections in adults over a decade in a Finnish University Hospital. Scand J Surg. 2020;109(2):127–132. doi:10.1177/1457496919832146

3) Nayak R, Brogly SB, Lajkosz K, Lougheed MD, Petsikas D. Two decades of thoracic empyema in Ontario, Canada. Chest. 2020;157(5):1114–1116. doi:10.1016/j.chest.2019.11.040

4) Grijalva CG, Zhu Y, Nuorti JP, Griffin MR. Emergence of parapneumonic empyema in the USA. Thorax. 2011;66(8):663–668. doi:10.1136/thx.2010.156406

5) Bobbio A, Bouam S, Frenkiel J, et al. Epidemiology and prognostic factors of pleural empyema. Thorax. 2021:thoraxjnl-2020-215267. doi:10.1136/thoraxjnl-2020-215267

6) Gupta I, Eid SM, Gillaspie EA, Broderick S, Shafiq M. Epidemiologic Trends in Pleural Infection. A Nationwide Analysis. Annals ATS. 2021;18(3):452–459. doi:10.1513/AnnalsATS.202001-075OC

7)Brims F, Popowicz N, Rosenstengel A, et al. Bacteriology and clinical outcomes of patients with culture-positive pleural infection in Western Australia: a 6-year analysis: empyema in Western Australia 2006–2011. Respirology. 2019;24(2):171–178. doi:10.1111/resp.13395

8) Pleural infection: past, present, and future directions

John P Corcoran, John M Wrightson, Elizabeth Belcher, Malcolm M DeCamp, David Feller-Kopman, Najib M Rahman

9) Hassan M, Cargill T, Harriss E, et al. The microbiology of pleural infection in adults: a systematic review. Eur Respir J 2019; 54: 1900542

10) Hassan M, Patel S, Sadaka AS, Bedawi EO, Corcoran JP, Porcel JM. Recent Insights into the Management of Pleural Infection. Int J Gen Med. 2021;14:3415-3429

11) Meyer CN, Armbruster K, Kemp M, et al. Pleural infection: a retrospective study of clinical outcome and the correlation to known etiology, co-morbidity and treatment factors. BMC Pulm Med. 2018;18(1):160. doi:10.1186/s12890-018-0726-1

2-5

Incidence

Stage Three

Lehtomaki et al.

- Finland

- Two cohorts (2000-2008 & 2012-2016)

- Incidence increased 4.4-9.9/100,000

Nayak et al.

- Canada

- 1996-2015. 9,306 patients

- Incidence increased 2.9-6.7/100,000

Bobbio et al.

- France

- 2013-2017. 25,512 patients

- 7.15-7.75/100,000

Grijalva et al.

- USA

- 1996-2008

- Hospitalisations incr 3.04 - 5.98/1000,000

Overview:

- The what: What is a pleural infection?

- The who: brief epidemiology

- The why: Commonest causes

- The how: Pathogenesis

- The treatments

- Fibroblast proliferation occurs along established fibrin matrix

- Dense inelastic septations and collagenous thickening within and around pleural cavity

- Walls off residual infection but also affects lung compliance

6

There's always one

Gupta et al

- USA

- 2005-2015. 150,000 patients

- Decrease in hospitalisations 5.4 -> 4.1/100,000

- Decrease in LoS 13.2 -> 11.2

- Decrease in mortality 4.2% -> 2.6%

- Decrease in cost

Stage Two

The Who

Why is it important?

Management

8

The How

- Although the incidence is relatively low, it's getting more common

- Depending on where you're looking, incidence has doubled so far this century

- It's expensive

- Average LoS is 14-17 days

- Mortality and morbidity are an issue and appropriate management makes a significant impact on this

1. General measures - Timely abx therapy, adequate nutrition, and thromboprophylaxis

2. Antibiotic therapy - Empirical abx choices governed by local guidelines. Both aerobic and anaerobic cover is required

3. ICC - Multicentre RCT data suggests smaller-bore (<14F) not associated with increased mortality or CTS increase.

4. Intrapleural Enzyme Therapy

5. Surgical intervention

1. Transpleural from adjacent consolidated lung

2. Visceral pleural defects or fistulae

3. Haematogenous spread (bacteriaemia)

4. Penetrating injury

5. Spread from mediastinum

6. Transdiaphragmatic spread

As bacteria multiply various changes occur in pleural space which results in classic

biochemical findings. IL-6, IL-8, TNFa,

VEGF, MCP, PAI involved

IET

Surgery

- Preventing progression from fibropurulent stage to organising stage is important

- MIST-2 RCT in 2011 showed the combination of an intrapleural plasminogen activator (tPA) and deoxyribonuclease (DNase) augmented drainage, with an improvement in radiographic appearance, and a decrease in LoS and surgical referrals

- Utilised when final organising stage of infection is apparent/medical management has failed

Encompasses VATS, and thoracotomy & drainage

- VATS favoured due to minimally invasive nature, decreased hospital LoS and reduced mortality

- Aim of both is debridement and evacuation of infected material

More extensive decortication is required where there is a thick pleural peel

- ~ 10% of parapneumonic effusions become complex due to co-infection of the pleural space

Stage One: Initial formation of effusion thought to be due to increased permeability of visceral pleural membranes. Sterile

Stage Two: Bacterial invasions and growth. Fibrin deposition that coats visceral and parietal pleural surfaces

Stage Three: Purulent fluid/empyema in context of bacterial and leucocytic cell death and lysis

- Age - Average age in UK, Australia, Canada and USA is 58-63yr

- Co-morbidities

- Immunosuppression

- Alcohol excess and dependance

- Malignancy (especially in post procedure infections)

- IVDU

8,10,11

Outcomes

- Prompt diagnosis and initiation of appropriate therapies is paramount

- Average LoS 14-17 days

- Mortality ranges from 10-30%

- Age, CCI >3, alcohol excess,

lung resection all associated

with higher mortality

- Meyer et al. 2018

- 437 patients Denmark

- Higher 90 day, disease severity and ICU admission was observed in sub-group with broad spectrum abx

Stage One

1

The What

Simple parapneumonic effusion: sterile exudate

Complicated paraneumonic effusion: fibrinopurulent but not overtly purulent collection with pH <7.20, glucose <2.2mmol/L, and LDH >1000IU/L

Empyema: add in some frank pus

-Inflammation of the underlying parenchyma

- Promotion of neutrophil migration together with release of pro-inflammatory cytokies (IL-6, IL-8, TNFa) result in development of intercellular gaps and accumulation of excess pleural fluid

8,9

The Culprits

Hassan et al.

- Systematic review of papers 2000-2018

- Geophraphical sub-group analysis

- Whole data set results:

o Staph Aureus 20.7%

o Viridans streptococci group (18.7%)

o Pseudomonas spp. (17.6%)

o Enterobacteriacacae group (11.9%)

o Step Pneumoniae (10.8%)

o Klebsiella spp. (10.7%)

o Acinetobacter (5%)

o Coag negative staph (4.5%)

2,6-8

The Why

- Pneumonia: Most common cause

- Oesophageal rupture

- Cirrhosis-associated empyema -

Different micro (Enterococcus,

salmonella, clostridium perfinges)

- Trauma

- Procedural complication

- Malignancy

The Bottom Line

- Incidence is increasing

- Associated with poor clinical outcome with up to 20% mortality

- Process by which bacteria enter pleural space is poorly understood

- Micro profile suggest not as simple as just pneumonia for cause

- There's a large number od cases that will not have positive micro

- Intrapleura tPA and DNase has been shown to significantly improve drainage and secondary outcome measures

- Surgery remains key treatment, but patient selection

and timing not well sefined

Diagnosis

- Index of suspicion

- Is there a parapneumonic effusion? Is the patient getting worse despite antibiotics? -> Diagnostic tap

- Gram stain and culture (or pus) make diagnosis straightforward, however up to half are micro negative

- Which is why pH, glucose and LDH are used