CONTENTS
- Basics
- Epidemiology
- Clinical manifestations
- Radiology
- Laboratory evaluation
- Invasive diagnostic testing
- Differential diagnosis
- Treatment
- Questions & discussion
abbreviations used in the pulmonary section: 3
- ABPA: Allergic bronchopulmonary aspergillosis 📖
- AE-ILD: Acute exacerbation of ILD 📖
- AEP: Acute eosinophilic pneumonia 📖
- AFB: Acid Fast Bacilli
- AIP: Acute interstitial pneumonia (Hamman-Rich syndrome) 📖
- ANA: Antinuclear antibody 📖
- ANCA: Antineutrophil cytoplasmic antibodies 📖
- ARDS: Acute respiratory distress syndrome 📖
- ASS: Antisynthetase Syndrome 📖
- BAL: Bronchoalveolar lavage 📖
- BiPAP: Bilevel positive airway pressure 📖
- CEP: Chronic eosinophilic pneumonia 📖
- CF: Cystic fibrosis 📖
- COP: Cryptogenic organizing pneumonia 📖
- CPAP: Continuous positive airway pressure 📖
- CPFE: Combined pulmonary fibrosis and emphysema 📖
- CTD-ILD: Connective tissue disease associated interstitial lung disease 📖
- CTEPH: Chronic thromboembolic pulmonary hypertension 📖
- DAD: Diffuse alveolar damage 📖
- DAH: Diffuse alveolar hemorrhage 📖
- DIP: Desquamative interstitial pneumonia 📖
- DLCO: Diffusing capacity for carbon monoxide 📖
- DRESS: Drug reaction with eosinophilia and systemic symptoms 📖
- EGPA: Eosinophilic granulomatosis with polyangiitis 📖
- FEV1: Forced expiratory volume in 1 second 📖
- FVC: Forced vital capacity 📖
- GGO: Ground glass opacity 📖
- GLILD: Granulomatous and lymphocytic interstitial lung disease 📖
- HFNC: High flow nasal cannula 📖
- HP: Hypersensitivity pneumonitis 📖
- IPAF: Interstitial pneumonia with autoimmune features 📖
- IPF: Idiopathic pulmonary fibrosis 📖
- IVIG: Intravenous immunoglobulin 📖
- LAM: Lymphangioleiomyomatosis 📖
- LIP: Lymphocytic interstitial pneumonia 📖
- MAC: Mycobacterium Avium complex 📖
- MCTD: Mixed connective tissue disease 📖
- NIV: Noninvasive ventilation (including CPAP or BiPAP) 📖
- NSIP: Nonspecific interstitial pneumonia 📖
- NTM: Non-tuberculous mycobacteria 📖
- OP: Organizing pneumonia 📖
- PAP: Pulmonary alveolar proteinosis 📖
- PE: Pulmonary embolism 📖
- PFT: Pulmonary function test 📖
- PLCH: Pulmonary Langerhans Cell Histiocytosis 📖
- PPFE: Pleuroparenchymal fibroelastosis 📖
- PPF: Progressive pulmonary fibrosis 📖
- PVOD/PCH Pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis 📖
- RB-ILD: Respiratory bronchiolitis-associated interstitial lung disease 📖
- RP-ILD: Rapidly progressive interstitial lung disease 📖
- TNF: tumor necrosis factor
- UIP: Usual Interstitial Pneumonia 📖
- Actinomycosis is a chronic infection with a tendency to dissect across tissue planes, in a fashion which often mimics cancer. It is frequently misdiagnosed initially.
- Chronic mass-like lesions may occur near various mucous membranes (e.g., in the neck or pelvis).
- Culture may be difficult, since Actinomyces species are anaerobic. Consequently, diagnosis may depend on histopathological evaluation.
general epidemiology of actinomycosis
- Actinomyces species are part of the normal flora of the mouth, colon, bronchi, and vagina. Poor oral hygiene may increase oral carriage.
- Patients of any age may be affected.
- Infection is often promoted by violation of mucosal barriers, or superinfection of a foreign body or necrotic tissue. (32033657)
general epidemiology of thoracic actinomycosis
- 15% of Actinomyces infections involve the chest. (Fishman 2023)
- Thoracic actinomycosis is rare, affecting roughly one in 3 million people per year. (36801629)
- Males are more often affected, in a 3:1 ratio. (25045274)
risk factors for thoracic actinomycosis
- (1) Aspiration is considered the primary mechanism promoting thoracic actinomycosis. Risk factors may thus include: (Fishman 2023)
- Dental disease, poor dental hygiene.
- Risk factors for aspiration (e.g., alcoholism).
- (2) Disruption of normal lung anatomy:
- Bronchiectasis, chronic bronchitis.
- Foreign body or broncholith.
- Fibrosis due to prior tuberculosis or a similar granulomatous infection.
- Trauma, surgery.
- Actinomycosis doesn't seem to be substantially increased in patients with impaired cell-mediated immunity (e.g., HIV, chemotherapy, transplantation). (36801629)
parenchymal infection causes chronic pneumonia
- Pulmonary symptoms: (36801629)
- Chronic cough (90%).
- Sputum production (40%).
- Hemoptysis (40%).
- Chest pain (25%).
- Constitutional symptoms:
- Fever (30%).
- Malaise.
- Weight loss.
- Marked constitutional symptoms are a late feature that should suggest disseminated disease. (36801629)
- Actinomycosis will often mimic lung cancer or anaerobic pulmonary abscess. Thoracic actinomycosis is most frequently misdiagnosed as lung cancer. (36801629)
- Patients may improve transiently while on antibiotic therapy, but subsequently deteriorate off antibiotics. (Fishman 2023)
local extension from pneumonia
- Empyema may occur in 25% of patients.
- Osteomyelitis can occur.
- If seen, a fistulous tract is highly suggestive of actinomycosis.
- Less frequently:
- Pericarditis, pericardial effusion.
- Mediastinitis.
- Esophageal perforation.
- Vertebral involvement.
alternative presentation: pulmonary septic emboli
- Rarely, septic emboli may occur from a distal site (e.g., pelvic actinomycosis).
- Cavitation may occur.
parenchymal infection
- Chronic consolidation (e.g., segmental or lobar) or nodules may occur.
- Typically, there may be a central hypodensity within parenchymal consolidation (reflective of a necrotic abscess). (32145821) Rim enhancement may also be seen. (Rosado-de-Christensen 2022)
- Cavitation is frequent, sometimes involving multiple small cavities within a larger parenchymal lesion. (24428279)
- Distribution is often peripheral and involving the lower lung fields (a pattern consistent with aspiration). (32033657)
- Hilar or mediastinal lymphadenopathy may be seen in up to 50% of patients. (Kolditz 2013)
pleural effusion
- Effusion and/or pleural thickening occur in 15-50% of patients. (36801629)
- Empyema occurs in 9-15%. (36801629)
- Empyema necessitans: If extension to the chest wall is seen, this suggests actinomycosis (with a differential diagnosis discussed here: 📖)
violation of tissue planes
- May extend to involve the pleura and/or chest wall (e.g., osteomyelitis with rib erosion).
- Pericardial effusion may rarely be seen. (36801629)
- Cavity or mass may extend through an interlobar fissure. (Murray 2022
endobronchial actinomycosis
- Endobronchial actinomycosis may result from infection of a broncholith, bronchial stent, or foreign body (the broncholith may originally have formed due to a prior infection by tuberculosis or Histoplasma).
- Clinical consequences may include:
- (1) Airway obstruction
- (2) Post-obstructive pneumonia and/or localized bronchiectasis. (Fishman 2023)
- Overall, this process may mimic lung cancer. (Rosado-de-Christenson 2022)
basic properties of the bacteria
- Actinomyces are branching, filamentous gram-positive rods. They may be anaerobic or facultatively anaerobic.
- Actinomyces grow in branching filaments that resemble those of fungi.
- >30 species of Actinomyces have been identified. However, >70% of infections are caused by A. israelii and A. gerencseriae. (36801629)
bacterial culture is limited for several reasons
- (1) Culture takes a long time (up to 2-4 weeks).
- (2) Special stains and culture media are required (these must be ordered specifically).
- (3) Sensitivity of culture is often limited for several reasons:
- Actinomyces species are anaerobic, which may hinder recovering and growing them.
- Sputum or bronchiolar lavage specimens can be rendered sterile by a single dose of antibiotics (although the underlying infection persists). (Fishman 2023)
- Overgrowth of more rapidly growing bacteria may obscure Actinomyces.
- (4) Specificity is limited: Actinomyces species are part of the normal flora, so bronchoscopy or sputum revealing Actinomyces doesn't necessarily indicate infection.
- (5) Actinomycosis causes abscesses which are often polymicrobial, so culture may reveal a variety of unrelated organisms.
- 💡 In practice, culture confirmation of Actinomyces is obtained in only a minority of cases. (Kolditz 2013)
invasive diagnosis
- Diagnosis is generally made based on the microscopic identification of “sulfur granules” (masses of bacterial filaments).
- This usually requires a histologic biopsy, but collection of purulent material draining from a sinus tract may also be adequate.
bronchoscopy
- Bronchoscopy is frequently nondiagnostic, unless endobronchial disease is present (histologic exam of tissue may confirm the diagnosis; more on this below).
- Culture samples should ideally be obtained with a protected brush and delivered to the lab under anaerobic conditions. The laboratory must be alerted to the suspicion of possible Actinomyces. Culture is challenging for reasons discussed above.
- Cytology may reveal the presence of filamentous microorganisms. (32145821)
- Endobronchial involvement may rarely cause irregular granular thickening that resembles malignancy, with or without bronchial obstruction. (32145821) Purulent exudate may be present.
- Transbronchial biopsies are generally inadequate. (Murray 2022)
CT-guided core needle biopsy
- This may be useful to investigate peripheral lesions.
- Core needle biopsy can be diagnostic.
diseases which present similarly to actinomycosis:
- Lung abscess (especially anaerobic).
- Malignancy (e.g., lung cancer or lymphoma).
- ⚠️ Actinomycosis may coexist with malignancy. In some cases, necrotic malignancy may represent an initial nidus of superinfection with Actinomyces. Therefore, the presence of actinomycosis doesn't necessarily exclude the possibility of underlying malignancy.
- Tuberculosis.
- Nocardiosis.
- Fungal pneumonia:
- Histoplasmosis.
- Cryptococcus neoformans.
- GPA (granulomatosis with polyangiitis).
differential diagnosis of empyema necessitans: 📖
sorting out nocardiosis vs. actinomycosis
similarities:
- Similar appearance on Gram stain (filamentous gram-positive rods).
- May invade through tissue planes (e.g., leading to osteomyelitis).
Nocardia infection is suggested by:
- Immunocompromise is usually present (e.g., transplantation, steroid, HIV). 📖
- Nodular pulmonary infiltrates. 📖
- Metastatic infection, especially:
- CNS involvement, usually brain abscess(es). 📖
- Skin/soft tissue infections, often soft tissue abscess(es).
- Microbiology:
- Weakly positive on acid-fast staining. 📖
- Aerobic growth on blood agar or Sabouraud agar (unlike Actinomyces, which generally don't grow aerobically).
actinomycosis is suggested by:
- Epidemiologic risk factors:
- Aspiration (e.g., poor dental hygiene, alcoholism).
- Disruption of mucosal barriers (e.g., bronchiectasis, trauma/surgery).
- Sulfur granules suggest actinomycosis (yet they may occasionally be seen with Nocardia infection). (36801629)
antibiotic selection
- Preferred agents: (Kolditz 2013, 25045274)
- 🏆 Penicillin (all susceptible).
- 🏆 Amoxicillin/ampicillin (all susceptible).
- Doxycycline (most susceptible).
- Macrolides (most susceptible).
- Clindamycin (most susceptible).
- Probably effective:
- Piperacillin/tazobactam (most susceptible).
- Ceftriaxone (most susceptible). Cephalosporins overall seem to have reduced efficacy, as compared to penicillin.
- Imipenem/meropenem (most susceptible).
- Effective agents in vitro:
- Tigecycline (all susceptible)
- Linezolid (most susceptible)
- Ineffective agents in vitro:
- Quinolones.
- Vancomycin.
- Aztreonam.
- Aminoglycosides.
- Metronidazole.
- Trimethoprim-sulfamethoxazole. (36801629)
antibiotic-related issues
- Coverage of additional organisms? In some cases, Actinomyces may be one of several pathogenic organisms. Among patients with abscesses and polymicrobial culture results, treating solely the Actinomyces may be adequate (rather than trying to cover every organism cultured). However, ampicillin-sulbactam may also be utilized. (Fishman 2023)
- Oral vs IV antibiotic?
surgical debridement
- Debridement may be helpful therapeutically, for example: (36801629)
- Massive refractory hemoptysis.
- Excision of sinus tracts.
- Decompression of closed-space infections.
- Wide surgical excision isn't generally needed.
pleural effusion management
- Effusions may generally be managed based on the same rubric used for other types of bacterial pneumonia (in the absence of invasion of the chest wall).
- Empyema or complex parapneumonic effusion may require treatment similar to other bacterial empyemas (e.g., chest tube drainage and pleural thrombolytics).
endobronchial actinomycosis
- If a broncholith or foreign body is present, this may need to be removed.
- If removal is impossible, surgical resection may occasionally be warranted.
follow-up & treatment duration
- Radiographic improvement is expected within ~1-2 months of starting therapy. (32145821, Kolditz 2013) Occasional patients may have underlying malignancy, so serial imaging should be used to exclude this possibility.
- Treatment duration:
- Prolonged therapy may be needed for severe disease (e.g., ~2-6 weeks of intravenous therapy followed by 6-12 months of oral treatment). (Murray 2022) However, the duration of IV therapy may depend on clinical context and how well the selected antibiotic is orally absorbed.
- Premature discontinuation of therapy may lead to recurrence or local complications. (25045274)
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References
- 24428279 Heo SH, Shin SS, Kim JW, Lim HS, Seon HJ, Jung SI, Jeong YY, Kang HK. Imaging of actinomycosis in various organs: a comprehensive review. Radiographics. 2014 Jan-Feb;34(1):19-33. doi: 10.1148/rg.341135077 [PubMed]
- 24798841 Jones Q, Benamore R, Fryer E, Sykes A. A 50-year-old man with a cough and painful chest wall mass. Chest. 2014 May;145(5):1158-1161. doi: 10.1378/chest.13-2039 [PubMed]
- 25045274 Valour F, Sénéchal A, Dupieux C, Karsenty J, Lustig S, Breton P, Gleizal A, Boussel L, Laurent F, Braun E, Chidiac C, Ader F, Ferry T. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist. 2014 Jul 5;7:183-97. doi: 10.2147/IDR.S39601 [PubMed]
- 30121203 Scheifer C, Bor C, Debray MP, Chanson N, Chauveheid MP, Gombert B, Papo T, Sacré K. A 27-Year-Old Man With Multiple Cavitary Lung Lesions. Chest. 2019 Feb;155(2):e43-e46. doi: 10.1016/j.chest.2018.07.034 [PubMed]
- 32033657 Venkatnarayan K, Raj R, Krishnaswamy UM, Ramachandran P, Devaraj U, Crasta J, Aijaz T. A 51-Year-Old Woman With Pellets in the Sputum. Chest. 2020 Feb;157(2):e25-e29. doi: 10.1016/j.chest.2019.09.037 [PubMed]
- 32145821 Chew SY, Tan CS, Puan Y, Koh JMK. A 78-Year-Old Man With Recurrent Hemoptysis and Persistent Pulmonary Nodule. Chest. 2020 Mar;157(3):e79-e84. doi: 10.1016/j.chest.2019.10.046 [PubMed]
- 36088098 Cho K, Lichtenberger J, Diab K. A 57-Year-Old Man With a Large Left Pleural Effusion. Chest. 2022 Sep;162(3):e127-e131. doi: 10.1016/j.chest.2022.04.015 [PubMed]
- 36759118 Schluger B, Winston L, Juneja P, Stoner KC, Chandra S. A 25-Year-Old Patient With Chest Wall Erythema and Tenderness Who Was Ventilated Mechanically. Chest. 2023 Feb;163(2):e57-e61. doi: 10.1016/j.chest.2022.09.002 [PubMed]
- 36801629 Boot M, Archer J, Ali I. The diagnosis and management of pulmonary actinomycosis. J Infect Public Health. 2023 Apr;16(4):490-500. doi: 10.1016/j.jiph.2023.02.004 [PubMed]
Books:
- Martin Kolditz, Adelheid End. Actinomycosis of the lung and pleura. Eur Respir Monogr 2013; 61: 66-80
- Shah, P. L., Herth, F. J., Lee, G., & Criner, G. J. (2018). Essentials of Clinical pulmonology. In CRC Press eBooks. https://doi.org/10.1201/9781315113807
- Shepard, JO. (2019). Thoracic Imaging The Requisites (Requisites in Radiology) (3rd ed.). Elsevier.
- Walker C & Chung JH (2019). Muller’s Imaging of the Chest: Expert Radiology Series. Elsevier.
- Palange, P., & Rohde, G. (2019). ERS Handbook of Respiratory Medicine. European Respiratory Society.
- Rosado-De-Christenson, M. L., Facr, M. L. R. M., & Martínez-Jiménez, S. (2021). Diagnostic imaging: chest. Elsevier.
- Murray & Nadel: Broaddus, V. C., Ernst, J. D., MD, King, T. E., Jr, Lazarus, S. C., Sarmiento, K. F., Schnapp, L. M., Stapleton, R. D., & Gotway, M. B. (2021). Murray & Nadel’s Textbook of Respiratory Medicine, 2-Volume set. Elsevier.
- Fishman's: Grippi, M., Antin-Ozerkis, D. E., Cruz, C. D. S., Kotloff, R., Kotton, C. N., & Pack, A. (2023). Fishman’s Pulmonary Diseases and Disorders, Sixth Edition (6th ed.). McGraw Hill / Medical.