Epidemiology
Risk Factors
General Comments
- In a Literature Review of >1,000 Cases, Approximately 64% of Nocardia Cases were Immunocompromised (Clin Microbiol Rev, 1994) [MEDLINE]
Defect in T-Cell Mediated Immunity
- General Comments
- Defect in T-Cell Mediated Immunity is Main Risk Factor for Nocardia Infection
- Clinical Types of Defects in T-Cell Mediated Immunity
- Corticosteroid Use (see Corticosteroids)
- Cushing Syndrome (see Cushing Syndrome)
- Diabetes Mellitus (see Diabetes Mellitus)
- Hematopoietic Cell Transplant (HSCT) (see Hematopoietic Cell Transplant)
- Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) (see Human Immunodeficiency Virus)
- Especially with CD4 Count is <100 Cells/mm3)
- Lymphoreticular Malignancy
- Malignancy
- Especially Following Chemotherapy and/or Glucocorticoid Therapy
- Solid Organ Transplant
- Liver Transplant (see Liver Transplant)
- In Organ Transplant Patients, History of Cytomegalovirus, Receipt of High-Dose Glucocorticoids, and High Calcineurin Inhibitor Levels were Indepednent Risk Factors for Nocardiosis (Clin Infect Dis, 2007)[MEDLINE]
- Renal Transplant (see Renal Transplant) (Transpl Infect Dis, 2011) [MEDLINE]
- In Organ Transplant Patients, History of Cytomegalovirus, Receipt of High-Dose Glucocorticoids, and High Calcineurin Inhibitor Levels were Indepednent Risk Factors for Nocardiosis (Clin Infect Dis, 2007)[MEDLINE]
- Liver Transplant (see Liver Transplant)
Granulocyte Defect
- General Comments
- Granulocyte Defect is a Lesser Risk Factor for Nocardiosis
- Chronic Granulomatous Disease (CGD) (see Chronic Granulomatous Disease)
- Patients with Chronic Granulomatous Disease are Susceptible to Specific Pathogens (Listed Below, with the Most Common Organisms Implicated in Chronic Granulomatous Disease Patients in North America) (J Pediatric Infect Dis Soc, 2018) [MEDLINE]
- Aspergillus (see Aspergillus)
- Burkholderia Cepacia Complex (see Burkholderia Cepacia Complex)
- Serratia Marcescens (see Serratia Marcescens)
- Nocardia (see Nocardiosis)
- Staphylococcus Aureus (see Staphylococcus Aureus)
- Patients with Chronic Granulomatous Disease are Susceptible to Specific Pathogens (Listed Below, with the Most Common Organisms Implicated in Chronic Granulomatous Disease Patients in North America) (J Pediatric Infect Dis Soc, 2018) [MEDLINE]
Immunoglobulin Defect
- General Comments
- Immunoglobulin Defect is a Lesser Risk Factor for Nocardiosis
Other
- Alcohol Abuse (see Ethanol) (Respirology, 2007) [MEDLINE]
- Risk Factor for Pulmonary Nocardiosis
- Chronic Lung Disease (Respirology, 2007) [MEDLINE]
- Risk Factor for Pulmonary Nocardiosis
- Clinical Types of Chronic Lung Disease
- Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)
- Pulmonary Alveolar Proteinosis (PAP) (see Pulmonary Alveolar Proteinosis)
Microbiology
Nocardia Species
- Nocardia Asteroides: accounts for 80% of Nocardiosis cases
- Nocardia Brasiliensis and Other Species (Nocardia Otitidiscaviarum, Nocardia Nova, Nocardia Farcinica, etc): account for 20% of Nocardiosis cases
Taxonomy
- Genus Nocardia is a Member of Family Actinomycetaceae (Colloquially Termed “Actinomycetes”) (see Actinomycetaceae)
- All of the Actinomycetes Organisms are Morphologically Similar and Exhibit Characteristic Filamentous Branching with Fragmentation into Bacillary or Coccoid Forms
Origin
- Nocardia Exists Ubiquitously in Nature as a Soil Contaminant
Features
- Gram-Positive, Beaded, Branching Filamentous Rod
- Nocardia Stains Weakly Acid-Fast
- Nocardia Requires Aerobic Growth Conditions: in contrast, Actinomyces requires anaerobic growth conditions (see Actinomycosis)
- Nocardia Can Be Grown on Standard Culture Medium (Blood Agar or Sabouraud’s): however, growth may not be apparent for 3-21 days
Physiology
- Portals of Nocardia Infection
- Respiratory Tract
- Skin
- Gastrointestinal Tract
- Local Extension
- Nocardia Extends from lung to Pleural Space (with or without Chest Wall Involvement) in 10% of Cases
- Comparison with Actinomyces (see Actinomycosis)
- Both Nocardiosis and Actinomycosis Occur in Healthy and Immunosuppressed Hosts
- Nocardia has Lesser Propensity for Sinus Tract Formation than Actinomyces
- Nocardia has Greater Propensity for Dissemination than Actinomyces
Clinical Manifestations
Pulmonary Manifestations
Segmental or Lobar Pneumonia (see Pneumonia)
- Epidemiology
- Symptoms May Be Present for Weeks Prior to Presentation
- Immunosuppressed Patients May Have Fulminant Presentation
- Diagnostic
- Sputum Gram Stain/Culture and Sensitivity (see Sputum Culture): although Nocardia frequently colonizes the respiratory tract, culturing the organism from sputum is highly predictive of infection
- Bronchoscopy (see Bronchoscopy)
- Useful to Obtain DIagnostic Specimens (and Rule Out Any Component of Endobronchial Disease)
- Clinical
- Fatigue (see Fatigue)
- Low-Grade Fever (see Fever)
- Night Sweats (see Night Sweats)
- Pleuritic Chest Pain (see Chest Pain)
- Productive Cough (see Cough)
- Weight Loss (see Weight Loss)
- Treatment
- Early Treatment May Prevent Cavitation and Dissemination
Solitary or Multiple Lung Nodules Which May Cavitate (see Lung Nodule or Mass and Cystic-Cavitary Lung Lesions)
- Diagnosis
- Chest X-Ray (CXR)/Chest Computed Tomography (CT) (see Chest X-Ray and Chest Computed Tomography): nodules may cavitate
Endobronchial Lesions (with/without Pneumonia)
- Epidemiology
- Diagnosis
- Bronchoscopy (see Bronchoscopy)
- Clinical
- XXXX
Lung Abscess (see Lung Abscess)
- Epidemiology
- Occurs in Some Cases
- Diagnosis
- Suppurative (Non-Granulomatous)
Interstitial Pneumonia/Miliary Infiltrates (see Interstitial Lung Disease)
- Epidemiology
- Interstitial Pneumonia Occurs in Some Cases
Pleural Effusion (see Pleural Effusion-Exudate)
- Epidemiology
- Pleural Effusion Occurs in 50% of Nocardia Cases (Almost Always in Association with Parenchymal Infiltrates)
- Diagnosis
- Pleural Fluid
- Appearance: ranges from serous fluid to frank pus
- Aerobic Culture: culture may be positive or negative (grows slowly, may take up to 3 weeks to grow out)
- Pleural Fluid
Disseminated Nocardiosis
General Comments
- Disseminated Nocardiosis is Defined as 2 Noncontiguous Anatomic Sites of Involvement Which May or May Not Include a Pulmonary Focus (Clin Infect Dis, 1996) [MEDLINE]
- Nocardia Can Disseminate from a Pulmonary or Cutaneous Focus to Almost Any Organ (Medicine-Baltimore, 1998) [MEDLINE] (Medicine-Baltimore, 2004) [MEDLINE]
- Although Dissemination is Presumed to Result from Hematogenous Spread, Identifying Nocardia in Blood Cultures is Uncommon Due, in Part, to the Fastidious Nature of the Organism (Medicine-Baltimore, 1998) [MEDLINE]
- To Maximize the Yield for Recovery of Nocardia, Blood Cultures Should Be Incubated for Approximately 4 wks
- In Cases Where the Original Focus of Nocardia Infection Cannot Be Ascertained, it is Presumed that Resolved Pulmonary or Cutaneous Disease was the Original Source
Cardiovascular Manifestations
- Endocarditis (see xxxx)
- Epidemiology
- Especially Associated with Prosthetic Heart Valves
- Epidemiology
Dermatologic Manifestations
- Clinical
- Subcutaneous Skin Abscess with/without Sinus Tract (see Skin Abscess)
- Diagnosis
- Suppurative (Non-Granulomatous)
- Diagnosis
- Subcutaneous Skin Abscess with/without Sinus Tract (see Skin Abscess)
Endocrinologic Manifestations
- Clinical
Gastrointestinal/Hepatic Manifestations
- Clinical
- Pancreatic Abscess
- Pyogenic Liver Abscess (see Pyogenic Liver Abscess)
- Retroperitoneal/Psoas Abscess (see Psoas Abscess) (Clin Microbiol Infect, 2003) [MEDLINE]
Hematologic Manifestations
- Clinical
- Splenic Abscess (see Splenic Abscess)
Infectious Manifestations
- Bacteremia (see Bacteremia)
- Epidemiology
- Nocardia Bacteremia Occurs Rarely (Int J Infect Dis, 2020) [MEDLINE]
- Blood Cultures are the Positive in Only 38% of Cases (Int J Infect Dis, 2020) [MEDLINE]
- In a Systematic Review of 138 Disseminated Nocardia Cases from 1999-2018, 81% of Patients were Immunocompromised (Int J Infect Dis, 2020) [MEDLINE]
- Corticosteroids (49% of Cases)
- Hematologic Malignancy (20% of Cases)
- Solid Organ Transplant (20% of Cases)
- Solid Organ Malignancy (19% of Cases)
- Hematopoietic Stem Cell Transplant (15% of Cases)
- Endovascular Device (29% of Cases)
- Nocardia Bacteremia Occurs Rarely (Int J Infect Dis, 2020) [MEDLINE]
- Diagnosis
- In a Literature Review of 36 Nocardia Bacteremia Cases, Approximately 30% of Cases Had Concomitant Bacteremia with Other Pathogens (Predominantly Gram-Negative Organisms) (Medicine-Baltimore, 1998) [MEDLINE]
- Clinical
- Pulmonary Infection is the Most Common Concurrent Site of Clinical Disease (67% of Cases) (Int J Infect Dis, 2020) [MEDLINE]
- The Clinical Presentation and Risk Factors for Disseminated Nocardiosis are Similar to in Both Bacteremic and Non-Bacteremic Cases
- The Only Unique Risk Factor for Nocardia Bacteremia is the Presence of an Endovascular Device (Medicine-Baltimore, 1998) [MEDLINE] (J Clin Pathol, 2004) [MEDLINE]
- In One Study, 10/17 Cases of Nocardia Bacteremia in Cancer Patients were Associated with the Presence of a Central Venous Catheter (Emerg Infect Dis, 2011) [MEDLINE]
- Prognosis
- Nocardia Bacteremia is Associated with a High Mortality Rate (Int J Infect Dis, 2020) [MEDLINE]
- Thirty-day all-cause mortality: 28%
- Overall All-Cause Mortality Rate: 40%
- Nocardia Bacteremia is Associated with a High Mortality Rate (Int J Infect Dis, 2020) [MEDLINE]
- Epidemiology
Neurologic Manifestations
- Clinical
- Brain Abscess (see Brain Abscess) (Neurochirurgie, 2022) [MEDLINE]
- Spinal Epidural (and Paravertebral) Abscess (see Spinal Epidural Abscess) (J Infect Chemother, 2005) [MEDLINE] (Medicine-Baltimore, 2018) [MEDLINE] (Indian J Pathol Microbiol, 2019) [MEDLINE]
Ophthalmologic Manifestations
- Clinical
- Keratitis (see Keratitis) (Cornea, 2007)[MEDLINE] (Am J Ophthalmol, 2007) [MEDLINE]
- Associated with Primary Infection Involving Direct Inoculation of Nocardia Organisms into the Eye
- Endophthalmitis (see Endophthalmitis) (Am J Ophthalmol, 2007) [MEDLINE]
- Associated with Primary Infection Involving Direct Inoculation of Nocardia Organisms into the Eye
- Nocardia Endophthalmitis Following Cataract Surgery is Associated with Poor Visual Outcomes
- Ocular Involvement
- Keratitis (see Keratitis) (Cornea, 2007)[MEDLINE] (Am J Ophthalmol, 2007) [MEDLINE]
Otolaryngologic
Renal Manifestations
- Clinical
- XXXXXXX
Reproductive Manifestations
- Clinical
- Prostatitis (see xxxx) (Transpl Infect Dis, 2003) [MEDLINE]
- Epididymitis/Orchitis/Testicular Abscess (see Epididymitis, Orchitis, and Testicular Abscess) (Urology, 2005)[MEDLINE]
Rheumatologic/Orthopedic Manifestations
- Clinical
- Osteomyelitis (Including the Vertebrae) (see Osteomyelitis) (Med J Malaysia, 2004) [MEDLINE] (Indian J Pathol Microbiol, 2019) [MEDLINE] (BMC Infect Dis, 2021) [MEDLINE]
- Septic Arthritis (see Septic Arthritis) Transplant Proc, 2004) [MEDLINE]
Other Manifestations
- Automatic Implantable Cardioverter-Defibrillator Pocket Infection (see Automatic Implantable Cardioverter-Defibrillator) (J Clin Microbiol, 2003) [MEDLINE] (J Interv Cardiol, 2003) [MEDLINE]
- Postoperative Mediastinitis (see xxxx) (J Infect Dis, 1998) [MEDLINE] (J Assoc Physicians India, 2003) [MEDLINE]
Prevention
Sulfamethoxazole-Trimethoprim (Bactrim, Septra) Prophylaxis (see Sulfamethoxazole-Trimethoprim)
- Daily Prophylaxis Decreases the Risk of Nocardiosis
- Intermittent Prophylaxis (2 DS Tablets Twice Per Week or 1 SS Tablet 3x Per Week) is Less Protective Against Nocardiosis
Treatment
Antibiotics
Treatment of Choice
- Sulfamethoxazole-Trimethoprim (Bactrim, Septra) (see Sulfamethoxazole-Trimethoprim)
- Administration: 5-10 mg/kg/day of trimethoprim component (or 25-50 mg/kg/day of sulfamethoxazole component)
- Sulfonamides are Bacteriostatic
- Good Central Nervous System Penetration
- Susceptibility Testing Should be Performed
- Nocardia Otitidiscaviarum is commonly resistant to Sulfamethoxazole-Trimethoprim
- Nocardia Nova and Nocardia Farcinica are occasionally resistant to Sulfamethoxazole-Trimethoprim
Alternative Antibiotics
- Amikacin (Amikin) (see Amikacin)
- Cephalosporins (see Cephalosporins)
- Cefotaxime (Claforan, Cefatam) (see Cefotaxime)
- Ceftriaxone (Rocephin) (see Ceftriaxone)
- Good Central Nervous System Penetration
- Carbapenems (see Carbapenems)
- Linezolid (Zyvox) (see Linezolid)
- Active Against Virtually All Known Nocardia Species
- Has Been Successfully Used to Treat Disseminated and Central Nervous System Nocardiosis
- Moxifloxacin (Avelox) (see Moxifloxacin)
- Fairly Active In Vitro Against Nocardia Astroides Complex
- Tetracyclines (see Tetracyclines)
- Minocycline (Minocin) (see Minocycline): has the best activity of the tetracyclines against Nocardia
- Tigecycline (Tygacil) (see Tigecycline)
- Has In Vitro Activity Against Most Nocardia Species
Combination Therapy
- General Comments
- Combination Therapy May Provide Enhanced Activity: recommended as initial therapy with de-escalation to a single agent (as dictated by clinical response)
- Imipenem + Cefotaxime
- Amikacin + Sulfamethoxazole-Trimethoprim
- Imipenem + Sulfamethoxazole-Trimethoprim
- Imipenem + Amikacin
Duration of Therapy
- Immunocompetent Patients with Isolated Pulmonary or Non-Central Nervous System Multifocal Nocardiosis: 6-12 mo
- Immunosuppressed Patients: ≥12 mo
Drainage of Abscesses/Empyema
- Required
Prognosis
- Mortality Rate: near 50% in those with CNS disease
- Mortality Rate: <10% in those with only pulmonary disease
References
Epidemiology
- Nocardia species: host-parasite relationships. Clin Microbiol Rev. 1994 Apr;7(2):213-64 [MEDLINE]
- Nocardiosis: review of clinical and laboratory experience. J Clin Microbiol. 2003;41(10):4497 [MEDLINE]
- Pulmonary nocardiosis: risk factors and outcomes. Respirology. 2007;12(3):394 [MEDLINE]
- Risk factors, clinical characteristics, and outcome of Nocardia infection in organ transplant recipients: a matched case-control study. Clin Infect Dis. 2007;44(10):1307 [MEDLINE]
- Nocardia species infections in a large county hospital in Miami: 6 years experience. J Infect. 2007;54(4):358 [MEDLINE]
- Nocardia infection in kidney transplant recipients: case report and analysis of 66 published cases. Transpl Infect Dis. 2011 Aug;13(4):385-91. doi: 10.1111/j.1399-3062.2011.00607.x [MEDLINE]
- Nocardiosis of the central nervous system: experience from a general hospital and review of 84 cases from the literature. Medicine (Baltimore). 2014;93(1):19 [MEDLINE]
- Considerations in the Diagnosis of Chronic Granulomatous Disease. J Pediatric Infect Dis Soc. 2018 May 9;7(suppl_1):S6-S11. doi: 10.1093/jpids/piy007 [MEDLINE]
Microbiology
- The medically important aerobic actinomycetes: epidemiology and microbiology. Clin Microbiol Rev. 1994;7(3):357 [MEDLINE]
Clinical Manifestations
- Endobronchial nocardiosis. Eur Respir J. 1994 Oct;7(10):1903-5. doi: 10.1183/09031936.94.07101903 [MEDLINE]
- Nocardia asteroides as a cause of sphenoidal sinusitis: case report. Clin Infect Dis. 1995;21(4):1041 [MEDLINE]
- Adrenal insufficiency, recurrent bacteremia, and disseminated abscesses caused by Nocardia asteroides in a patient with acquired immunodeficiency syndrome. Diagn Microbiol Infect Dis. 1996;24(1):47 [MEDLINE]
- Nocardiosis. Clin Infect Dis. 1996;22(6):891 [MEDLINE]
- Nocardia bacteremia. Report of 4 cases and review of the literature. Medicine (Baltimore). 1998;77(4):255 [MEDLINE]
- Nocardia farcinica sternotomy site infections in patients following open heart surgery. J Infect Dis. 1998;178(5):1539 [MEDLINE]
- Nocardia thyroiditis: unusual location of infection. J Clin Microbiol. 1999;37(7):2323 [MEDLINE]
- Nocardia asteroides mediastinitis complicating coronary artery bypass surgery. J Assoc Physicians India. 2003;51:1009 [MEDLINE]
- Implantable defibrillator pocket infection and bacteremia caused by Nocardia nova complex isolate. J Clin Microbiol. 2003;41(11):5325 [MEDLINE]
- Nocardia prostatitis in a small intestine transplant recipient. Transpl Infect Dis. 2003;5(2):94 [MEDLINE]
- Nocardia farcinica as the causative agent in a primary psoas abscess in a previously healthy cattle inspector. Clin Microbiol Infect. 2003;9(5):445 [MEDLINE]
- ICD nocardiosis. J Interv Cardiol. 2003;16(5):375 [MEDLINE]
- A case series and focused review of nocardiosis: clinical and microbiologic aspects. Medicine (Baltimore). 2004;83(5):300 [MEDLINE]
- Secular trends of nocardia infection over 15 years in a tertiary care hospital. J Clin Pathol. 2004;57(8):807 [MEDLINE]
- Septic arthritis caused by Nocardia asteroides in a renal transplant recipient. Transplant Proc. 2004;36(5):1415 [MEDLINE]
- Nocardia infection of the mastoid in an immunocompromised patient. Med J Malaysia. 2004;59(5):688 [MEDLINE]
- Nocardial epidural abscess of the thoracic spinal cord and review of the literature. J Infect Chemother. 2005;11(3):169 [MEDLINE]
- Epididymo-orchitis and testicular abscess due to Nocardia asteroides complex. Urology. 2005;65(3):591 [MEDLINE]
- Endobronchial pulmonary nocardiosis. Mt Sinai J Med. 2006 May;73(3):617-9 [MEDLINE]
- Nocardia keratitis: species, drug sensitivities, and clinical correlation. Cornea. 2007;26(3):255 [MEDLINE]
- Ocular nocardiosis: HSP65 gene sequencing for species identification of Nocardia spp. Am J Ophthalmol. 2007;144(4):570 [MEDLINE]
- Central venous catheter-associated Nocardia bacteremia in cancer patients. Emerg Infect Dis. 2011;17(9):1651 [MEDLINE]
- Nocardiosis: updates and clinical overview. Mayo Clin Proc. 2012 Apr;87(4):403-7. doi: 10.1016/j.mayocp.2011.11.016 [MEDLINE]
- Nocardial spinal epidural abscess with lumbar disc herniation: A case report and review of literature. Medicine (Baltimore). 2018;97(49):e13541 [MEDLINE]
- Disseminated Nocardia farcinica infection presenting as a paravertebral abscess in a patient with systemic lupus erythematosus. Indian J Pathol Microbiol. 2019;62(2):329 [MEDLINE]
- Nocardia bacteremia: A single-center retrospective review and a systematic review of the literature. Int J Infect Dis. 2020;92:197 [MEDLINE]
- Disseminated Nocardia farcinica involves the spinal cord: a case report and review of the literature. BMC Infect Dis. 2021 Dec 7;21(1):1224. doi: 10.1186/s12879-021-06905-y [MEDLINE]
- Nocardia farcinica cerebral abscess: A systematic review of treatment strategies . Neurochirurgie. 2022 Jan;68(1):94-101. doi: 10.1016/j.neuchi.2021.04.022 [MEDLINE]
Treatment
- Current treatment for nocardia infections. Expert Opin Pharmacother. 2013 Dec;14(17):2387-98. doi: 10.1517/14656566.2013.842553. Epub 2013 Oct 4 [MEDLINE]
- Experience with linezolid for the treatment of nocardiosis in organ transplant recipients. J Infect. 2015 Jan;70(1):44-51. doi: 10.1016/j.jinf.2014.08.010. Epub 2014 Aug 30 [MEDLINE]