In 1904 Guillemot first put weight to the theory that aspirated oropharyngeal organisms were responsible for cause of lung abscess[1]
In 1920-1930 Harold Neuhof, was the first thoracic surgeon to develop a valid and reliable therapeutic concept of new one-stage open drainage operation for surgery of acute pulmonary abscess.[2]
In 1938 first cutaneous drain of lung abscess was performed.[3]
In 1942 Brock added evidence in stating that aspirated contents gravitated to the dependents part of the lungs
In 1946,owing to the advent of antibiotics, and treatment of acute putrid lung abscess with penicillin showed good results and henceforth patients received antibiotics rather than surgical procedures[2]
Pathophysiology
Pathogenesis
Aspiration of anerobic bacteria from the oro-pharnynx, secondary to altered level of consciousness, absent gag reflex or inability to swallow is the primary pathogenesis in the development of lung abscess.
In healthy individuals, defense mechanisms cope up with the small amounts of aspirates with no effects, however, in conditions like alcoholism, diabetis mellitus, and immunocompromised state these defense mechanisms can be compromised leading to decreased activity of alveolar macrophages and mobility of leukocytes predisposing patients to developng abscess. [4].
In secondary lung abscess, abscess formation depends on the underlying lung disease and predisposing factors such as bronchial obstruction from benign or malignant intrabronchial lesions or extrinsic compression of bronchus (eg:middle lobe syndrome) results in distal abscess formation due to decrease oropharyngeal clearance due to decreased clearance mechanisms and favouring abscess formation.
Localization of the aspirate results in pneumonitis [5]
Inflammatory mediators along with bacterial toxins and proteolytic enzymes from neutrophils are released leading to rupture of small blood vessels resulting in the formation of colliquative necrosis [6]
Location of abscess
The right lung is more commonly affected than the left lung because is of it more angulation than the left bronchi.
The most common location is the posterior segment of the right apical lobe or apical segments of lower lobes of both the lungs.[7]
Lateral part of the posterior segment of upper lobe of the right lung is more commonly involved in alcoholics.
Genetics
Congenital diseases such as cystic fibrosis, vasculitis, pulmonary sequestration and bronchial cysts are associated with increased the risk of lung abscess in children.[8]
Gross Morphology
In acute lung abscess, the lesions are well circumscribed filled with necrotic debris and do not demonstrate well-defined borders with the surrounding lung parenchyma.[9]
In chronic long standing abscess, the lesions are irregular and filled with grayish thick debris.
Microscopic Findings
In acute lung abscess, neutrophilic granulocytes are demonstrated with dilated blood vessels and inflammatory edema.[9]
In chronic lung abscess, biopsy specimen demonstrates lymphocytes, plasma cells, and histiocytes around a layer of pyogenic membrane surounding the abscess cavity which is filled with pus.
Classification
Lung abscess can be classified into three types based on duration of symptoms, etiology and mode of spread as follows:
Based on duration of symptoms
Acute: If the duration of symptoms is less than 4-6 weeks before presenting to medical care.[10]
Chronic: If the symptoms persists for more than 6 weeks.
Based on Etiology
Primary: When the abscess develops after lung infection in previously healthy persons or in patients prone to aspiration [11]
Secondary: Abscess formation in patients due to complications of a co-existing lung disease such as post obstructive process (bronchial obstruction due to tumor , foreign body or enlarged lymphnodes) and systemic process resulting in decreased immune response like HIV, and patients on immunosuppressantss and corticosteroids.
Based on mode of spread
Bronchiogenic: Abscess formation is due to aspiration and inhalation.[10]
Aspiration of oropharyngeal secretions
Bronchial obstruction by tumor
Foreign body, congenital malformations, and enlarged lymph nodes
Hematogenic: Abscess formation due to dissemination of causative agents from other infected sites
Infective endocarditis
Abdominal sepsis
Septic thromboembolism
Risk Factors
Factors resulting in altered level of consciousness and decreased immune response play a key role in the development of lung abscess :
Lung abscess may be caused by either by a necrotizing infection of lung parenchyma or necrosis of an infarcted lung tissue and cavitation in the necrotic tissue by malignant lesions
Microbiology
About 90% of the lung abscess is caused by polymicrobial infection.[13][14]
Anaerobes are the predominant pathogens involved in primary lung abscess, followed by Streptococcus pneumoniae.
Klebsiella pneumoniae is the more commonly seen in alcoholics.[15]
Staphylococcus aureus is the most common pathogen responsible for lung abscess in children with cystic fibrosis.[16]
The following table elaborates the most common etiological pathogens responsible for lung abscess [17]
Klebsiella pneumoniae Heamophillus influenza type B Pseudomonas aeurongiosa Escherichia coli Legionella Pneumophilia Acinetobacter spp
Natural History, Prognosis and Complications
Natural History
Lung abscess is most commonly seen in the fourth decade of life in patients with risk factors or underlying other lung disorders.[18]
Clinical manifestations include fever, productive cough, pleuritic chest pain and occasional episodes of hemoptysis, typically developing 8-14 days after aspiration.
The progression of the abscess is dependent on two factors: immune status of the patient and antibiotic therapy.
In immunocompetent patients with adequate treatment abscess resolves forming a granulation tissue scar, without treatment the abscess progressively worsens and can result in septicemia, hemorrhage, and death.
Prognosis
The prognosis of lung abscess is good with appropriate antibiotic treatment with a high success rate. The outcomes depend on the other associated conditions underlying lung abscess. The mortality rate of lung abscess is as high as 75% in patients with underlying immunocompromised state and bronchial obstruction favoring poor prognosis
The following factors are considered to be associated with poor prognosis among patients.[19]
Large size cavities(>6cms)
Old age
Necrotizing pneumonia
Prolonged symptoms
Abscess due to aerobic bacteria and hospital acquired
Bronchial obstruction due to tumors or foreign body (secondary abscess)
Immuncompromised individuals
Complications
Without treatment, lung abscess can result in the following complications:
Patients with lung abscess can present with the history of following important findings.
Symptoms
Patients with lung abscess present with the following symptoms.
More common symptoms
Fever with chills,
Cough (initially non-productive and progress to productive)[22][23]
Pleuritic chest pain
Discolored, foul-smelling sputum is seen in anaerobic infections.
Rapid fever with rapid progression of symptoms is seen with aerobic bacteria and indulent and gradual progression in other causative agents.
Less common symptoms
Dyspnea
Weight Loss
Anemia and fatigue is more commonly seen in anaerobic infections
Clubbing of fingers.
Physical examination
The common physical examination findings in patients with lung abscess include:
General examination:
Respiratory distress
Fever with chills may be present
Poor oral hygiene with gingivitis, dental erosions or poor dentition.
Digital clubbing is seen in chronic lung abscess
Respiratory system
Dullness to percussion
Decreased breath sounds on the side of lung abscess
Bronchial breath sounds on auscultation
Inspiratory crackles
Localised crepitations
Laboratory findings
Diagnosis of lung abscess is made based on clinical symptoms, physical examination, radiographic studies and bacterial culture.
Microbial testing
To identify etiologic agent and to initiate appropriate antibiotic therapy
When patients present with typical symptoms of fever with chills, cough with purulent sputum for more than 2 weeks and with risk factors of aspiration it is appropriate to suspect anaerobes as a possible pathogen.[24]
Cultures of the sputum for anaerobic bacteria is not recommended because of its contamination by the normal flora in the oral cavity. The only cultures that can give a positive result for anaerobes is empyema
It is often difficult to get uncontaminated sputum specimens as both upper respiratory tract and lower respiratory tract along oral cavity is contaminated with various flora.
The only methods available for obtaining uncontaminated specimens are trans-tracheal aspirates (TTA), transthoracic needle aspirates (TTNA), culture of pleural fluid, or blood cultures are recommended before administration of empiric antibiotics
Sputum analysis and culture is recommended for finding out aerobic and other causative agents of lung abscess.The contamination of the sputum sample can be minimized by
Obtaining the sputum sample prior to antibiotic treatment.[25]
Rinsing the mouth prior to expectoration
NPO for one to two hours prior to expectoration
Inoculation of the culture media immediately after the specimen is obtained
Sputum Analysis
Acid Fast Stain
Culture on Sabourad's medium
Direct Microscopic Examination for sulphur granules
Gentain Voilet Stain
Aerobic Culture
Tuberculosis
Yeast and Fungi
Actinomyces and other mycelia of Fungi
Fusiform Bacteria and Spirochetes
Pyogenic organsims
Interpretation of sputum cultures in these cases must take into account the clinical features of the patient, concentrations of the different organisms found in the culture and Gram stain, and the antibiotics the patient has received.
Chest Xray
An irregularly shaped thick walled cavity with an air-fluid level is typically seen in lung abscess on chest xray. Lung abscess[26]
Lung abscesses as a result of aspiration most frequently occur in the posterior segments of the upper lobes or the superior segments of the lower lobes. [27][28]
The extent of the air-fluid level within a lung abscess is often the same in posteroanterior or lateral views.
Anaerobic infection may be suggested by cavitation within a dense segmental consolidation in the dependent lung zones.
Lung infection with a virulent organism results in more widespread tissue necrosis
Up to one-third of lung abscesses may be accompanied by an empyema.[29]
Repeat chest radiographs must be obtained to determine the response of antimicrobial therapy.
CT Scan
CT is helpful in differentiating the cavitation of abscess that cannot be clearly delineated on the chest radiograph from empyema and other cavitary lesions.[29]
On CT scan lung abscess is visualized as a rounded radiolucent lesion with a thick wall and ill-defined irregular margins, and is located within the parenchyma compared with loculated empyema, which may be difficult to distinguish on chest radiographs. [30]
Computed tomography (CT) lung is considered as the gold standard not only for the diagnosis of lung abscess but also for guiding therapeutic procedures such as trans-thoracic drainage of localized lung abscess .[31]
CT scan is very helpful in excluding endobronchial obstruction due to malignancy or foreign body and provides additional information about size and location of the abscess,
Ultrasound
Ultrasound has a minimal role in diagnosing lung abscess .
Lung abscess appears as a rounded hypoechoic lesion with an outer margin on ultrsound.
Lung abscesses which are peripheral and with pleural contact or included inside a lung consolidation are detectable using bedside lung ultrasonography.
Medical treatment
The mainstay of management for lung abscess is : hospital admission for chest drain and systemic antibiotics
Empiric treatment should be commenced after culture samples are obtained.
The choice of empiric antibiotics should be determined on the basis of the possible risk of multi-drug resistant causative bacteria, and culture results.
Clindamycin (600 mg i.v. every 8 hours followed by 150-300 mg every 6 hours p.o.) is considered the first-line drug of choice for anaerobic lung infections.[32][33]
With the emergence of resistance of anaerobic bacteria and microaerophilic Streptococci mostly to penicillin G and more rarely to clindamycin, due to β-lactamase production, β-lactam/β-lactamase inhibitor combinations (amoxicillin/clavulanate, ampicillin/sulbactam) presented as highly effective agents for community-acquired lung abscesses.[34][35]
This antimicrobial regimen provides adequate coverage against gram (+), gram (-) Enterobacteriaceae (e.g. Klebsiella pneumonia, Enterobacter) and anaerobic bacteria.[36]
A possible therapeutic alternative is the combination of a 2nd (cefuroxime, cefoxitin) or 3rd generation cephalosporin (ceftriaxone) with clindamycin or metronidazole.
Monotherapy with metronidazole should be avoided due to inadequate coverage for aerobic and microaerophilic Streptococci, such as Streptococcus milleri.[37]
Linezolid (initial i.v.administration 600 mg twice daily and subsequent oral administration after clinical improvement) is preferred in cases of lung abscess caused by MRSA.[38]
An alternative choice is vancomycin (15 mg/kg x2 i.v., with dose adapted according to optimal serum levels (15-20 mcg/ml) and renal function). Low daptomycin concentrations achieved in lung tissue renders daptomycin inadequate for lower respiratory infections.[39]
Clinical improvement is reflected in the subsidence of fever (within the first 3-4 days) and complete defervescence within 7-10 days.Persistent fever can be explained by treatment failure due to uncommon pathogens (multidrug resistant common bacteria, mycobacteria, fungi)or by the presence of an alternative diagnosis (e.g. endobronchial obstruction, vasculitis) that requires further diagnostic workup (e.g. bronchoscopy, transdermal or surgical lung biopsy).[40]
The duration of treatment with antibiotics is not well defined, according to many experts, the optimal duration of antimicrobial therapy is 3-6 weeks, whereas others take the timing of radiological response into consideration. [40]
In that case, the length of antibiotic treatment depends on complete radiological resolution or stabilization to a small residual lesion.
Treatment interval may then be prolonged to several months (more than 2),6 especially when the initial lesion is of large size (maximum diameter more than 6cm).
Medical Therapy for the management of Lung Abscess
Empiric Therapy
Clindamycin
Penicillin with betalactamase inhibitor
Non responsive to initial therapy and based on culture reports
MRSA: Linezolid or Vancomycin
Cephalosporin with clindamycin or metronidazole
Surgical Therapy
Indications
Abscess > 6 cm in diameter
If symptoms last more than 12 weeks with appropriate therapy
Surgical Options
Options for surgery includes: Chest tube drainage and surgical resection of the lung abscess with the surrounding lung tissue
Chest tube drainage
Percutaneous and endoscopic drainage techniques are considered as a first-line management, especially for patients who are not candidates for surgery [41]
Percutaneous drainage
Type of chest drain
Indications
Procedure
Complications
Advantages
Percutaneous thoracocentesis
It is the treatment of choice for patients who have failed to respond to antibiotic therapy .[42]
Patients who are unsuitable for surgical intervention (e.g. due to severe immunodeficiency or mechanical ventilation).
Lung abscesses with diameters greater than 4-8 cm
Performed under fluoroscopic, ultrasound or computed tomography guidance.(CT is generally preferred due to additional information provided about location, content and wall-thickness of the abscess.)
Two techniques of insertion of chest tube employed: Seldinger, and Trochar
Seldinger technique of insertion the tube is considered as it is safer and it permits greater control in the positioning of the drainage tube and is accompanied by fewer complications[43]
Chest tube drainage with trocar is highly effective surgical procedure and is recommended for thoracic surgeries
Drainage duration varies but a minimum of 4-5 weeks are required and is done according to radiographic findings.Chest tubes should not be flushed in order to avoid bronchogenic spread of the pus.[41]
The usage of intra-cavitary fibrinolytic agents (streptokinase, urokinaze) is not recommended, due to possibility of bronchopulmonary or bronchopleural fistula can occur.[44]
Technique related includes :advancing of the guidewire through the thicked-wall abscess may cause bending or rupture of the guidewire or the catheter.[45]
Hemothorax, hemoptysis, pyopneumothorax and fistula formation between the pleural cavity and the abscess resulting in empyema.
Less significant complications are those related to bending or leaking of the drainage catheter.
These techniques demonstrated benefits even in patients without contraindications to surgery. More specifically, cases of primary lung abscess that were treated by Yellin A et al during a 5-year period (1978-1982) underwent successful percutaneous drainage, without any complications or relapse after 2-5 years of monitoring.[46]
Percutaneous drainage of lung abscesses is characterized by high therapeutic effectiveness and preservation of functional lung tissue, it is a minimally invasive method with fewer complications and lower mortality rates (approximately 4%) in comparison to surgical management.[47]
In case of pleural space obliteration, with peripheral localization of lung abscess, it is possible to perform pneumostomy or cavernostomy-open drainage of abscess(Monaldi procedure) but it is limited due to it invasiveness.
Endoscopic thoracic drainage
Pateints with poor general condition,
Coagulopathies
For the abscesses with central locations in lungs.
A guidewire is inserted into the cavity through the working channel of a flexible bronchoscope.Once guidewire location has been ascertained by fluoroscopy, a 7 French pigtail catheter is advanced.
If infusion of contrast medium via the catheter confirms its proper positioning, the guidewire and bronchoscope are withdrawn and the catheter tip is stabilized at the nasal wall.
Subsequently, the cavity is flushed daily with normal saline solution through the catheter, along with antibiotic infusions (e.g. gentamicin or amphotericin in confirmed fungal infections).[48]
The catheter remains open for the rest of the day, thus ensuring the drainage of the abscess.
In a small number of patients with recurrent lung abscesses, endoscopic drainage was performed with the help of laser.[49]
The catheter is inserted through a bronchoscope and laser is used in order to perforate the wall of the abscess through the airway and to lead the catheter inside the cavity. The catheter is removed after 4-6 days with immediate improvement of clinical status and radiological imaging within the first 24 hours
Spillage of necrotic detritus in other parts of the lungs
Surgical Intervention
Surgery is considered in about 10% of the patients with unsuccessful medical therapy and thoracocentesis.
Rupture of abscess in the pleural cavity with pyopneumothorax/empyema.
Unsuccessfully treated lung abscess more than 6 weeks,
Suspicion of cancer,
Cavitary lesion larger than 6 cm,
Leukocytosis despite the use of antibiotics.
Surgical resection
The surgical approach is thoracotomy and the extent of surgical resection depends on the size of the underlying lesion. [50]
Lobectomy is the most common type of surgical resection. Segmentectomies are performed in smaller abscesses (<2 cm), whereas a pneumonectomy should be performed in the presence of multiple abscesses or gangrene. [51],[52]
Open surgical drainage is employed either by creating a pouch-like cavity communicating with the thoracic wall through limited rib resection in case of thoracotomy contraindication.
When sepsis cannot be controlled with conservative measures and in conditions that prohibit resection, debridement of the dead tissue is followed by immediate filling of the cavity with highly vascular tissue, or debridement and cavity fistulization into the pleural space followed by drainage by means of a chest tube is proposed.
When the chronic inflammatory process of pulmonary infection causes incomplete re-expansion of the remaining lobes, it is quite possible that a portion of the pleural space will remain empty. Some thoracic surgeons recommend filling that space with a large pedicled ipsilateral latissimus dorsi muscle flap or omentum.
In addition, bronchial stump reinforcement with a pedicled intercostal muscle flap or other highly vascular tissue may prevent the formation of a bronchopleural fistula.
Cross-contamination of contralateral lung is the main complication to be feared of during surgery. Placement of a double-lumen endotracheal tube, prone positioning of the patient and artificial obstruction of the main bronchus before removing the abscess are the usual measures for preventing cross-contamination.
Recently, a thoracoscopic technique (Video assisted thoracoscopic surgery: VATS) for abscess debridement and drainage has been effectively implemented in a small number of patients.53
Pulmunory nodules with cavities and infiltrates are a frequent manifestation on CXR.
Positive for P-ANCA
Biopsy of the tissue involved shows necrotizing granulomas [56]
Sarcoidosis
More common in African-American females.
Often asymptomatic except for enlarged lymph nodes.[58]
Associated with restrictive lung disease (interstitial fibrosis),
Erythema nodosum,
Lupus pernio (skin lesions on face resembling lupus),
Bell palsy,
Epithelioid granulomas containing microscopic Schaumann and asteroid bodies,
Uveitis,
Hypercalcemia
On chest Xray bilateral adenopathy and coarse reticular opacities are seen.
CT of the chest demonstrates extensive hilar and mediastinal adenopathy
Additional findings on CT include fibrosis (honeycomb, linear, or associated with bronchial distortion), pleural thickening, and ground-glass opacities.[59]
Exclusively afflicts smokers, with a peak age of onset of between 20 and 40 years.
Clinical presentation varies, but symptoms generally include months of drycough, fever, night sweats, and weight loss.
Thin-walled cystic cavities are the usual radiographic manifestation, observed in over 50% of patients by either plain chest radiography or computed tomography scans.[65]
For invasive aspergillosis; alcoholism, chronic obstructive pulmonary disease, collagen vascular disease, diabetes mellitus, low-dose corticosteroid use, malnutrition, pnemoconiosis for semi-invasive; and prior tuberculosis or other cavity causing disease for aspergilloma
Saprophytic fungi that grow on organic debris;
Potential environmental exposure for hospitalized high-risk patients
Effective measures for the primary prevention of lung abscess include:
Prevention of aspiration in high-risk individuals by providing proper attention towards airway protection, minimal sedation, and proper positioning of patients with elevation of the head in hospitalized patients.
Prophylactic antibiotics against certain pathogens in at-risk patients e.g.recipients of bone marrow or solid organ transplants or patients whose immune systems are significantly compromised by HIV infection must be given.
Improving oral hygiene and proper dental care in elderly and debilitated patients also helps in decreasing the risk of anaerobic lung abscess.
Intravenous penicillin G (10 to 20 million units daily in divided doses every four to six hours) for 4 to 6 weeks,
Nocardia .spp
TMP-SMX 15 mg/kg IV of the trimethoprim component per day in three or four divided doses
PLUS
Amikacin 7.5 mg/kg IV every 12 hours
Fungi
Amphotericin B 3-5mg/kg/day/IV
Parasite
Albendazole is dosed 10 to 15 mg/kg per day in two divided doses; the usual dose for adults is 400 mg twice daily.
one to three months may be appropriate, depending clinical factors; up to six months may be required.
† Risk factors for MRSA include:
Recent hospitalization, residence in a long-term care facility, recent antibiotic therapy, HIV infection, men who have sex with men, injection drug use, hemodialysis, incarceration, military service, sharing needles, razors, or other sharp objects, sharing sports equipment, diabetes, prolonged hospital stay, swine farming
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