European Respiratory Society
Complex Pleuropulmonary Infections

Pleuropulmonary infections are among the major causes of morbidity and mortality worldwide. This issue of the European Respiratory Monograph considers pleuropulmonary infections from both medical and surgical angles. It features chapters written by well-known experts in the fields of respiratory medicine and thoracic surgery, with particular focus on antibiotic prophylaxis prior to thoracic surgical procedures, the medical and surgical treatment of tuberculosis, fungal infections, abscesses and empyema of the lung, bronchiectasis, hydatid disease, mediastinitis, post-operative infection and complications, and much more.

  • European Respiratory Society Monographs
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  2. Page vii
  3. Page ix
  4. Page 1
    Correspondence: N. Roche, Pneumologie, Groupe Hospitalier Cochin-Broca Hôtel-Dieu, AP-HP, Site Val de Grâce, Hôpital d’Instruction des Armées du Val de Grâce, 74 boulevard de Port-Royal, 75230 Paris cedex 05, France. Email:

    Post-operative pneumoniae are a major source of post-operative morbidity and mortality in patients undergoing lung resection surgery. Empyema is another severe complication, most frequently related to bronchopleural fistula, although empyema without fistula exists in pneumonectomy patients. Risk factors for infectious post-operative complications include smoking history, underlying chronic obstructive pulmonary disease, other comorbidities including lung cancer, impaired nutritional status and extra-thoracic chronic diseases. The extent of resection and peri-operative care also play a role, as well as the presence of pre-existing airway colonisation. The most frequent pathogens are Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus and Gram-negative pathogens. Altogether, the relatively small number of randomised controlled trials available provides convincing evidence supporting the use of antibiotic prophylaxis in patients undergoing lung surgery. The evidence is strong for prevention of wound infection, but more limited for empyema and post-operative pneumonia. First- and second- generation cephalosporins have been the most extensively used prophylactic antibiotics. Amoxicillin–clavulanate has also been shown to be effective. The optimal duration of prophylactic antibiotic treatment has not been extensively studied. Similarly, how antibiotic prophylaxis could be tailored to specific populations or risk factors is currently unknown.

  5. Page 11
    Correspondence: G.B. Migliori, World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Via Roncaccio 16, 21049 Tradate, Italy. Email:

    Tuberculosis (TB) remains among the leading causes of death among treatable infectious diseases. Treatment of pulmonary TB has progressed enormously from the initial monotherapy options offered in the 1940s. However, while a standard 6-month course of chemotherapy has proved to be extremely effective in treating drug-susceptible TB cases, the appearance of drug-resistant TB has complicated the management of pulmonary TB. Rapid drug susceptibility testing is strongly advised in order to avoid inadequate treatment at the time of TB diagnosis, and the regimen prescribed should include at least four potentially active drugs and have an increased duration of treatment. Drug–drug interactions between anti-TB and anti-HIV drugs also increase poor treatment outcome rates and the occurrence of adverse events. However, therapeutic drug monitoring can be used as a diagnostic tool to assess the dosing, through evaluation of blood concentrations. Despite the growing problem of drug resistance, hope is generated by the growing evidence that old drugs may still be useful and that new effective and well-tolerated drugs are now available. Today, patients can benefit from novel drugs and regimens, but it is necessary to administer them carefully to avoid the real risk of losing their effectiveness in a time shorter than that necessary to develop them.

  6. Page 20
    Correspondence: P. Yablonski, Ligovsky Ave 4, 191036, St Petersburg, Russia. Email:

    Before the introduction of antituberculous drugs, collapse therapy was the dominant surgical treatment for cavitating lung tuberculosis (TB). Today, there is a wide range of indications for surgery in different geographical regions. Most frequently, surgical procedures are indicated for cavernous lesions and tuberculomas in 91.6% of patients, haemoptysis in 58% of patients, and in all patients with multidrug-resistant (MDR) TB. Currently, indications for surgery can be summarised as follows: 1) operations with diagnostic purpose, if it is not possible to rule out TB by other diagnostic methods; 2) elimination of the source of Mycobacterium tuberculosis in patients with cavities persisting under chemotherapy (MDR-TB or destroyed lung); 3) tuberculous pleural empyema; and 4) sequelae of past TB. This overview highlights current controversies in different groups of indications in order to facilitate an optimal therapeutic approach in these patients.

  7. Page 37
    Correspondence: M. Bassetti, Infectious Diseases Division, Santa Maria Misericordia University Hospital, Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy. Email:

    Invasive fungal infections have increased worldwide and represent a threat for immunocompromised patients, including those who are HIV infected, recipients of solid organ and stem cell transplants, and patients receiving immunosuppressive therapies. High mortality rates and difficulties in early diagnosis characterise pulmonary fungal infections. In this chapter, invasive pulmonary aspergillosis, cryptococcosis and Pneumocystis jirovecii pneumonia have been reviewed, focusing on clinical aspects and therapeutic management. Although new compounds have become available in recent years (e.g. amphotericin B lipid formulations, third-generation azoles and echinocandins), new diagnostic tools and careful therapeutic management are mandatory to ensure an early appropriate targeted treatment, which is the key to a successful conservative approach in respiratory fungal infections.

  8. Page 50
    Correspondence: G. Massard, Service de Chirurgie Thoracique, Hôpitaux Universitaires de Strasbourg, F-67091 Strasbourg, France. Email:

    Thoracic aspergillosis covers a large spectrum of diseases, with several potential surgical implications.

    Traditional aspergillomas arise in pre-existing parenchymal cavities or bronchiectasis. There are two clinical variants, defined by clinical presentation, radiological findings and post-operative outcome, referred to as simple and complex aspergilloma. Semi-invasive aspergillosis has an acute onset with lobar pneumonia; subsequently, the lung excavates and a mycetoma appears.

    Surgical intervention for invasive aspergillosis may be discussed either to prevent fatal haemoptysis or to resect residual mycotic sequestra. Since the advent of contemporary antifungal drugs, such operations are seldom required.

    Pleural aspergillosis is a variant of empyema and needs to be treated as such.

    Invasive bronchial aspergillosis in lung transplant recipients and parietal aspergillosis in drug addicts have been reported as case reports.

    Whatever the presentation, treatment should be defined on a multidisciplinary basis.

  9. Page 58
    Correspondence: A. End, Dept of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18–20, A-1090 Vienna, Austria. Email:

    Invasive pulmonary aspergillosis (IPA) is encountered in immunocompromised or neutropenic patients presenting with a high mortality rate. A high index of suspicion is necessary in patients with risk factors such as haematopoietic stem cell transplantation and solid organ transplantation. Radiological imaging is the cornerstone in diagnosing IPA. Modern antifungal therapy with voriconazole and liposomal amphotericin B plays a major role. In selected patients, surgery may be necessary to prevent massive haemoptysis or to prevent re-infection during subsequent chemotherapy. Parenchyma-sparing surgery with open wedge resections or thoracoscopic procedures is recommended, whereas pneumonectomy has a high mortality and is only indicated in emergency situations. In carefully selected patients and with excellent interdisciplinary management, surgery can be performed with low operative morbidity and with a beneficial effect on disease control and survival. Prognosis of IPA is strongly influenced by the underlying disease.

  10. Page 66
    Correspondence: M. Kolditz, Dept of Pulmonology, University Hospital Carl Gustav Carus, Fetscherstr. 74, 01307 Dresden, Germany. Email:

    Pulmonary actinomycosis is a rare and slowly progressing bacterial lung infection. Actinomyces are commensal bacteria of the oropharynx. Risk factors for pulmonary infection include aspiration and poor dental hygiene; it is not necessarily associated with an immunosuppressed state. Radiological and clinical appearances are nonspecific and mimic a variety of other lung diseases including cancer. Diagnosis requires microbiological isolation of the bacteria from an infected specimen or histopathological evidence of sulfur granules, usually obtained after bronchoscopic, transthoracic or surgical biopsy. Long-term and high-dose antibiotic treatment is essential to achieve high clinical cure rates and good prognosis. Penicillin remains the drug of choice; doxycycline, macrolides and clindamycin have been used successfully as alternatives. Duration of antibiotic treatment should be individualised according to the resolution of symptoms and radiological lesions. Surgical treatment is reserved for patients developing complications, such as massive haemoptysis or empyema, and for those in whom a medical diagnosis cannot be established.

  11. Page 81
    Correspondence: K. Athanassiadi, Konstantinoupoleosstr. 34A, 15562 Holargos, Athens, Greece. Email:

    Lung abscess is a necrotising lung infection characterised by a pus-filled cavitary lesion and is potentially life threatening since it is often complicated to manage and difficult to treat. Lung abscess was a devastating disease in the pre-antibiotic era, when one-third of the patients died, another one-third recovered and the remainder developed debilitating illnesses, such as recurrent abscesses, chronic empyema, bronchiectasis or other consequences of chronic pyogenic infections. In the early post-antibiotic period, sulfonamides did not improve the outcome of patients with lung abscess until the penicillins and tetracyclines were available. Although resectional surgery was often considered a treatment option in the past, the role of surgery has greatly diminished over time because most patients with uncomplicated lung abscess eventually respond to prolonged antibiotic therapy.

  12. Page 90
    Correspondence: D. Subotic, Clinic for Thoracic Surgery, Clinical Center of Serbia, University of Belgrade School of Medicine, Belgrade, Serbia. Email:

    The role of surgery for the treatment of the localised form of bronchiectasis has changed with the development of more effective antibiotics and conservative treatment options, such as embolisation or effective novel anti-inflammatory treatment approaches in subjects with cystic fibrosis (CF) and non-CF bronchiectasis, as suggested recently. However, surgery is the only option for a potential cure for certain patients with bronchiectasis. Complete resection of bronchiectasis should be intended with the preservation of as much lung function as possible. Incomplete resection is often used for the palliative treatment of life-threatening symptoms, e.g. major haemoptysis.

    The usual clinical problems in patients undergoing surgery for bronchiectasis are bilateral bronchiectasis, haemoptysis and previous pleural empyema. The outcome for surgical treatment is good, with a low operative mortality and morbidity rate; however, higher than reported for non-infectious pathology. Complications of surgery usually range between 10% and 25% and largely consist of a prolonged air leak, bleeding, empyema and/or respiratory failure. In most series, lobectomy is the commonest type of resection with a rate of approximately 60%. Video-assisted thoracoscopic surgery for pulmonary resection has become an established alternative approach to conventional open surgery for selected patients.

    The educational aim of this chapter is to provide a comprehensive overview of the possible solutions to the most frequent practical problems encountered by patients who have a localised form of bronchiectasis and are being considered for surgical treatment.

  13. Page 107
    Correspondence: D. Petrov, Thoracic Surgery Division, Saint Sophia University Hospital for Pulmonary Diseases, 19 Ivan Geshov Str., 1431 Sofia, Bulgaria. Email:

    Pulmonary echinococcosis is the most severe form of helminthic zoonosis, which has significant medical, social and economical impact. Surgery is the primary mode of treatment. The diversity of the hydatid pathological process offers various treatment tactics and approaches (especially in the bilateral and associated forms), which must be individually tailored in each and every case. Organ-preserving extirpation techniques, by open surgery or video-assisted thoracoscopic surgery, are the methods of choice. Anatomical resections are justified only when a certain anatomical structure is completely destroyed by a giant cyst or several uncomplicated cysts, as well as in complicated echinococcosis with irreversible changes in the adjacent lung parenchyma. The incidence rates of morbidity and mortality are low. Post-operative chemoprevention is indicated only in cases of intra-operative dissemination and suspicion of residual cysts. Chemotherapy alone is an alternative for patients with multiple, single intact cysts or relapses, and for those who can not tolerate surgery.

  14. Page 122
    Correspondence: S. Elia, General Thoracic Surgery, Policlinico Tor Vergata University, Viale Oxford, 81, I-00133 Rome, Italy. Email:

    The term mediastinitis refers to inflammation of the tissues located in the mediastinal space. Many aetiological factors contribute to acute and chronic infection of the mediastinum. Although long recognised as a complication of certain infectious diseases, most cases of acute mediastinitis follow oesophageal perforation and open chest surgery. Less common causes include tracheal, bronchial perforation or direct infection from adjacent tissues. Acute mediastinitis is a life-threatening condition that is almost always a complication of other clinical problems. Chronic fibrosing mediastinitis is a slow deposition of thick fibrous tissue encasing any of the mediastinal structures, most commonly secondary to tuberculosis, histoplasmosis, other fungal infections, cancer or sarcoidosis. Descending necrotising mediastinitis is the most dreaded and lethal form of mediastinitis originating from oropharyngeal infection that extends through the deep neck planes to the mediastinum. The clinical spectrum ranges from the subacute to the fulminate critically ill patient, and therefore early diagnosis and prompt aggressive medical and surgical treatment are required to prevent death.

  15. Page 141
    Correspondence: M. Gonzalez, Thoracic Surgery Division, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon, 1011 Lausanne, Switzerland. Email:

    Pleural empyema has been classified into three different stages in order to facilitate the establishment of treatment guidelines. The treatment, which may range from conservative measures to more aggressive surgical management, depends on the chronicity of the empyema, the underlying disease and the condition of the patient. In this chapter, we review the different surgical options, with emphasis on the thoracoscopic management, which are now routinely performed for early-stage empyema. For advanced empyema, decortication is mandatory to prevent pulmonary restriction. Thoracoplasty or thoracostomy are reserved for special kinds of empyema.

  16. Page 153
    Correspondence: J.M.H. Hendriks, Dept of Thoracic and Vascular Surgery, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium. Email:

    Parapneumonic effusion and pleural empyema in children are more frequently encountered in the age group >2 years. This is explained by routine vaccination with the pneumococcal conjugated vaccine for Streptococcus pneumoniae in children aged <2 years. In every child treated for a lower respiratory tract infection, a complicated pneumonia should be suspected in case of clinical changes. Differential diagnosis and treatment are based on radiographic assessment with ultrasonography and computed tomographic scan of the chest, and biochemical and microbiological analysis of the pleural fluid. For early cases of parapneumonic effusion, drainage with a small drain (≤16 French) is advised. In the case of loculation or a pleural peel, thoracoscopic surgery is indicated. For more severe cases, a thoracotomy or a conservative treatment with surgery in a second stage is advised, especially for lung abscesses. Intrapleural fibrinolysis has shown contradictory results, but a recent prospective trial showed great promise for the combination of fibrinolysis and DNAse for stage 1 and 2 complicated pneumonia.

  17. Page 162
    Correspondence: D. Subotic, Clinic for Thoracic Surgery, Clinical Center of Serbia, University of Belgrade School of Medicine, Belgrade, Serbia. Email:

    There are two forms of infection that may precede a lung resection: 1) lung infection without previous pleural empyema; and 2) pleural empyema preceding a lung resection. The first form refers mainly to the operation of cavitating tumours with or without clinical signs of infection. Although some studies detailing protected brush and lung tissue biopsies confirmed colonisation with one or more potential pathogens in 41% patients, no major practical benefit from performing biopsies was observed, as the post-operative infection rate was low (12%) and without correlation with bronchial colonisation. Current imaging techniques are unreliable in differentiating in situ infection from necrosis in cavitating lung tumours. Furthermore, a severe and putrid infection within a tumour may be not clinically evident before surgery. The association between empyema and malignant disease reached 22% in 1994, with 80% of malignancies representing a lung cancer. Mortality for empyema associated with malignant disease is 60–80%. In these patients, surgery is possible only after full control of infection and pleural space obliteration is achieved.

  18. Page 171
    Correspondence: E. Canalis, Hospital Universitari Joan XXIII, C/ Doctor Mallafré Guasch 4, 43007 Tarragona, Spain. Email:

    Irrespective of the extent of resection, post-operative pleural infection is a dominant cause of operative morbidity and mortality. Two major causes of infection are prolonged air leak and bronchopleural fistula (BPF) after pneumonectomy. Prolonged air leaks occur in around 33% of patients after a lobectomy. As this inevitably leads to pleural empyema, the treatment goal is to obliterate the pleural space. If empyema occurs, chest tube aspiration will obliterate the pleural space after 7–14 days, unless a BPF exists. Prevention of the air leak can be achieved by an appropriate technique or by the use of sealants. After pneumonectomy, pleural empyema and BPF are associated in up to 80% of patients and mortality is high (total of 10–20%; up to 50% mortality with BPF). Chest tube aspiration may lead to a stable condition with a chronic small-sized fistula that can be tolerated for years. Definitive treatment includes wide opening of the pleural cavity with muscle transposition for fistula closure. Fistulae may be closed through a trans-sternal trans-pericardial approach as well.