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Nocardiosis

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Nocardiosis

BASICS

DESCRIPTION

Initial Tests (lab, imaging)

Consider early infectious disease consult for suspected or confirmed nocardiosis. ‚

Surgical or interventionist consultation may be needed to drain abscesses for laboratory specimen analysis and therapeutic drainage for larger abscesses and in individuals not responding to therapy (2)[B]. ‚

Admission Criteria/Initial Stabilization

Supportive care for nocardiosis may require IV fluids in the hospitalized patient. ‚

Recovery after a variable period of convalescence; activity may be increased as patients improve. ‚

Patients on high-dose sulfonamide therapy should have a serial CBC, up to every other week or as indicated; other assessments (kidney, liver) are based on patient comorbidities and response to therapy. ‚

11 Welsh ‚ O, Vera-Cabrera ‚ L, Salinas-Carmona ‚ MC. Current treatment for nocardia infections. Expert Opin Pharmacother. 2013;14(17):2387 " “2398.22 Wilson ‚ JW. Nocardiosis: updates and clinical overview. Mayo Clin Proc. 2012;87(4):403 " “407.33 Shen ‚ Q, Zhou ‚ H, Li ‚ H, et al. Linezolid combined with trimethoprim-sulfamethoxazole therapy for the treatment of disseminated nocardiosis. J Med Microbiol. 2011;60(Pt 7):1043 " “1045.

  • A rare infectious disease caused by Nocardia sp. bacteria
  • No pathognomonic presentation
  • Nocardiosis can be acute, subacute, or chronic, and involve multiple systems:Pulmonary (>70% overall, 39% only lung)Disseminated: ≥2 sites (32% overall)Cutaneous (~8%)CNS (20% overall, 44% of disseminated, 9% brain only)
  • Patients are typically immunocompromised or have chronic pulmonary or systemic disease.
  • Less commonly, Nocardia can infect the eye, heart valves, bone, and any other organ system.
  • Pulmonary (>70% overall, 39% only lung)
  • Disseminated: ≥2 sites (32% overall)
  • Cutaneous (~8%)
  • CNS (20% overall, 44% of disseminated, 9% brain only)

EPIDEMIOLOGY

  • Overall: 0.4/100,000 cases/person-years
  • >60% are immunocompromised.
  • All ages are susceptible; mean age at diagnosis is in 4th decade of life.
  • Male > female (3:1)
  • ~500 to 1,000 clinically evident cases/year in United States; not a reportable disease
  • HIV/AIDS: 53/100,000 cases/person-years
  • Bone marrow transplant recipients: 128/100,000 cases/person-years
  • Solid-organ transplant recipients: 1,122/100,000 cases/person-years

ETIOLOGY AND PATHOPHYSIOLOGY

  • Nocardia sp. are aerobic gram-positive branching rods found worldwide in soil, decaying plants, fresh and salt water.
  • >80 species, >30 cause human disease.
  • Nocardia asteroides complex causes the majority of symptomatic infections and includes Nocardia abscessus, Nocardia cyriacigeorgica, Nocardia farcinica and Nocardia nova.
  • Nocardia enters through inhalation (e.g., contaminated dust), traumatic skin inoculation and ingestion.
  • Nocardiosis of the skin has four patterns: primary cutaneous, lymphocutaneous, cutaneous secondary to disseminated spread, and mycetoma.
  • Pulmonary, CNS, and other organ system infection with Nocardia is typically suppurative, often leading to abscess formation.
  • Incubation period: days to weeks
  • Pathologic Nocardia sp. have several intrinsic means of overcoming host immune responses.

RISK FACTORS

  • Most cases occur in immunocompromised hosts, particularly those with impaired cell-mediated immunity. Other chronic diseases (e.g., DM, COPD) may predispose individuals to nocardiosis.
  • Farm workers and other immunocompetent individuals may develop pulmonary, cutaneous, and disseminated disease after appropriate exposure.
  • Nocardiosis can be severe and fatal in immunocompromised patients; immunologically normal people rarely develop severe disease.
  • Immunocompromised children are also at risk.

COMMONLY ASSOCIATED CONDITIONS

  • Chronic pulmonary disease
  • Hematologic and other malignancies
  • Bone marrow and solid-organ transplantation
  • Chronic corticosteroid therapy
  • Autoimmune diseases
  • Tumor necrosis factor therapy
  • Kidney failure
  • Cirrhosis and alcoholism
  • Hypogammaglobulinemia
  • HIV/AIDS
  • Diabetes mellitus
  • TB and other granulomatous disease

DIAGNOSIS

HISTORY

  • Diagnosis requires a high index of clinical suspicion
  • Symptoms vary by site of infection. Pulmonary CNS and cutaneous symptoms are most frequently infected:Headache, anorexia, weight loss, pleuritic chest pain, dyspnea, malaise, cough, confusion, painNocardiosis produces suppurative necrosis and abscess formation at sites of infectionDisseminated disease may involve any organ (with corresponding symptoms): CNS, pulmonary, and skin are the most commonly involved.
  • Headache, anorexia, weight loss, pleuritic chest pain, dyspnea, malaise, cough, confusion, pain
  • Nocardiosis produces suppurative necrosis and abscess formation at sites of infection
  • Disseminated disease may involve any organ (with corresponding symptoms): CNS, pulmonary, and skin are the most commonly involved.

PHYSICAL EXAM

  • Pulmonary nocardiosisFeverHemoptysisTachypneaRales
  • CNS nocardiosisCan be clinically silent in the immunocompetentFeverMeningismusSeizuresFocal neurologic signs
  • Primary cutaneous nocardiosisUlcerationsCellulitisSkin nodulesAbscesses
  • Lymphocutaneous nocardiosisSpread of primary cutaneous nocardiosis to include regional lymphangitis
  • Nocardial mycetomaPainless nodule at inoculation siteMay become large complex inflammatory noduleLocal induration
  • Cutaneous nocardiosis from disseminated spreadIdentical to primary cutaneous and/or lymphocutaneous infections
  • Disseminated nocardiosisTwo noncontiguous sites of infectionSymptoms corresponding to those sites (e.g., pulmonary, CNS, eye, bone, etc.)
  • Unusual Nocardia infections and presentations:Keratoconjunctivitis associated with contact lenses, penetrating eye injury or surgeryPeritonitis in patients on peritoneal dialysisPericarditis and cardiac tamponadeHematogenous endophthalmitisProsthetic joint infectionsNatural/prosthetic valve endocarditisMale genitourinary tractIntravascular access device related infections
  • Fever
  • Hemoptysis
  • Tachypnea
  • Rales
  • Can be clinically silent in the immunocompetent
  • Fever
  • Meningismus
  • Seizures
  • Focal neurologic signs
  • Ulcerations
  • Cellulitis
  • Skin nodules
  • Abscesses
  • Spread of primary cutaneous nocardiosis to include regional lymphangitis
  • Painless nodule at inoculation site
  • May become large complex inflammatory nodule
  • Local induration
  • Identical to primary cutaneous and/or lymphocutaneous infections
  • Two noncontiguous sites of infection
  • Symptoms corresponding to those sites (e.g., pulmonary, CNS, eye, bone, etc.)
  • Keratoconjunctivitis associated with contact lenses, penetrating eye injury or surgery
  • Peritonitis in patients on peritoneal dialysis
  • Pericarditis and cardiac tamponade
  • Hematogenous endophthalmitis
  • Prosthetic joint infections
  • Natural/prosthetic valve endocarditis
  • Male genitourinary tract
  • Intravascular access device related infections

DIFFERENTIAL DIAGNOSIS

  • Pulmonary nocardiosisOther symptomatic pulmonary infections: bacterial (typical or atypical pneumonias), mycobacterial (e.g., TB), fungal (e.g., Aspergillus)Malignancy, primary or metastatic
  • CNS nocardiosisOther symptomatic CNS infections: bacterial abscesses-meningitis, fungal (e.g., Coccidioides), parasitic (e.g., cysticercosis)Malignancy, primary or metastatic
  • Cutaneous nocardiosisMultiple skin infections can mirror Nocardia: fungal (e.g., Sporothrix), several non-TB mycobacteria, bacterial (e.g., Francisella tularensis), parasitic (e.g., Leishmania)Can be clinically insignificant and overlooked
  • Disseminated nocardiosisInfectious processes and malignancies that can impact multiple organ systems
  • Other symptomatic pulmonary infections: bacterial (typical or atypical pneumonias), mycobacterial (e.g., TB), fungal (e.g., Aspergillus)
  • Malignancy, primary or metastatic
  • Other symptomatic CNS infections: bacterial abscesses-meningitis, fungal (e.g., Coccidioides), parasitic (e.g., cysticercosis)
  • Malignancy, primary or metastatic
  • Multiple skin infections can mirror Nocardia: fungal (e.g., Sporothrix), several non-TB mycobacteria, bacterial (e.g., Francisella tularensis), parasitic (e.g., Leishmania)
  • Can be clinically insignificant and overlooked
  • Infectious processes and malignancies that can impact multiple organ systems
  • Microscopic examination of purulent fluid, with Gram stain showing fine, filamentous, branching gram-positive rods (similar to Actinomyces); same appearance on modified partial acid-fast staining (Actinomyces do not acid-fast stain)
  • Culture, speciation, and sensitivity help guide therapy.
  • Notify laboratory if suspicious for nocardiosis because Nocardia grows very slowly (2 to 3 weeks) and may require use of selective media.
  • Blood cultures for patients with endovascular devices; maintain specimens 2 to 4 weeks. Alert lab and culture under appropriate conditions.
  • RadiographyCXR findings include pulmonary or mediastinal masses, nodules, cavities, infiltrates, pleural effusions.MRI or CT if CNS symptoms, in all immunocompromised patients, and in immunocompetent people with pulmonary or disseminated infections
  • CXR findings include pulmonary or mediastinal masses, nodules, cavities, infiltrates, pleural effusions.
  • MRI or CT if CNS symptoms, in all immunocompromised patients, and in immunocompetent people with pulmonary or disseminated infections
  • Consult a reference laboratory, including the CDC 's Special Bacteriology Reference Laboratory (SBRL), 1-800-CDC-INFO (232-4636).
  • US or MRI may be required to assess extent of complex mycetomas, abscesses, and focal-disseminated infections.
  • Invasive procedures may be required for specimen analysis, to improve culture yield, for speciation and antibiotic sensitivity.
  • Polymerase chain reaction (PCR) offers rapid, accurate Nocardia testing but is only available in select labs.

TREATMENT

GENERAL MEASURES

  • Consider infectious disease consultation.
  • Modify treatment based on sensitivity results.

MEDICATION

  • CNS/disseminated nocardiosis (1,2)[B]Trimethoprim-sulfamethoxazole 15 mg/kg/day TMP IV divided in 2 to 4 doses; plus,Imipenem 500 mg IV q6h; ‚ ±,Amikacin 7.5 mg/kg IV q12hAfter bacterial sensitivity results and/or 3 to 6 weeks of improvement, may change to oral therapy for immunocompetent patients: trimethoprim-sulfamethoxazole 10mg/kg/day of trimethoprim component in 2 to 3 divided doses or minocycline 100 to 200 mg PO BID and/or amoxicillin-clavulanate 500 mg PO TID or 875 mg PO BID; total duration 3 to 6 months and at least 1 month beyond resolutionFor immunocompromised patients, two drug therapy for 12 months and at least 1 month beyond resolution, including one sulfa-based antibiotic; consideration for lifelong suppressive therapy with trimethoprim-sulfamethoxazole
  • Pulmonary (only) nocardiosis (1,2)[B]Trimethoprim-sulfamethoxazole 15 mg/kg/day TMP IV divided in 2 to 4 doses; plus,Imipenem 500 mg IV q6hAfter bacterial antibiotic sensitivity results and/or 3 to 6 weeks of improvement, may change to oral for immunocompetent patients trimethoprim-sulfamethoxazole 10 mg/kg/day in 2 to 3 divided doses or minocycline 100 to 200 mg PO BID or amoxicillin-clavulanate 500 mg PO TID or 875 mg PO BID; total duration 3 to 6 months and at least 1 month beyond resolutionFor immunocompromised patients, two drug therapy for 6 to 12 months and at least 1 month beyond resolution, including one sulfa-based antibiotic
  • For treatment of CNS, pulmonary, and disseminated nocardiosis trimethoprim-sulfamethoxazole or sulfadiazine are the mainstay of treatment with a recommended sulfonamide level at 100 to 150 Ž ¼g/mL 2 hours after dosing; many experts recommend desensitization therapy if allergic to sulfa (1,2)[B].
  • Cutaneous (only) nocardiosisTrimethoprim-sulfamethoxazole 5 to 10 mg/kg/day TMP component IV or PO divided in 2 to 4 doses; total duration 3 months and at least 1 month beyond resolution; for immunocompromised, 6 months with at least 1 month beyond resolution (1,2)[B]
  • Empiric therapy for acutely ill patients should be ceftriaxone 2 g IV q12h or meropenem 1 to 2 g IV q8h + amikacin 7.5 to 15 mg/kg IV q12h, with an IV sulfonamide considered in critically or acutely ill patients (1,2)[B].
  • Trimethoprim-sulfamethoxazole 15 mg/kg/day TMP IV divided in 2 to 4 doses; plus,
  • Imipenem 500 mg IV q6h; ‚ ±,
  • Amikacin 7.5 mg/kg IV q12h
  • After bacterial sensitivity results and/or 3 to 6 weeks of improvement, may change to oral therapy for immunocompetent patients: trimethoprim-sulfamethoxazole 10mg/kg/day of trimethoprim component in 2 to 3 divided doses or minocycline 100 to 200 mg PO BID and/or amoxicillin-clavulanate 500 mg PO TID or 875 mg PO BID; total duration 3 to 6 months and at least 1 month beyond resolution
  • For immunocompromised patients, two drug therapy for 12 months and at least 1 month beyond resolution, including one sulfa-based antibiotic; consideration for lifelong suppressive therapy with trimethoprim-sulfamethoxazole
  • Trimethoprim-sulfamethoxazole 15 mg/kg/day TMP IV divided in 2 to 4 doses; plus,
  • Imipenem 500 mg IV q6h
  • After bacterial antibiotic sensitivity results and/or 3 to 6 weeks of improvement, may change to oral for immunocompetent patients trimethoprim-sulfamethoxazole 10 mg/kg/day in 2 to 3 divided doses or minocycline 100 to 200 mg PO BID or amoxicillin-clavulanate 500 mg PO TID or 875 mg PO BID; total duration 3 to 6 months and at least 1 month beyond resolution
  • For immunocompromised patients, two drug therapy for 6 to 12 months and at least 1 month beyond resolution, including one sulfa-based antibiotic
  • Trimethoprim-sulfamethoxazole 5 to 10 mg/kg/day TMP component IV or PO divided in 2 to 4 doses; total duration 3 months and at least 1 month beyond resolution; for immunocompromised, 6 months with at least 1 month beyond resolution (1,2)[B]
  • CNS/disseminated nocardiosis (1,2 and 3)[B]Linezolid 600 mg IV or PO q12h; plusMeropenem 1 to 2 g IV q8hAlternate for trimethoprim-sulfamethoxazole " “allergic: amikacin + imipenem 500 mg IV q6h or meropenem 1 to 2 g IV q8h or ceftriaxone 2 g IV q12h or cefotaxime 2 g IV q8h
  • Pulmonary nocardiosis (1,2 and 3)[B]Alternate for trimethoprim-sulfamethoxazole " “allergic: amikacin + imipenem or meropenem or ceftriaxone or cefotaximeAlternate linezolid; + meropenem
  • Cutaneous nocardiosis (1,2 and 3)[B])Sulfisoxazole 2 g PO BID, or minocycline 100 to 200 mg PO BID; total duration 3 months and at least 1 month beyond resolution; for immunocompromised, 6 months and at least 1 month beyond resolution; linezolid may be considered as an alternative.
  • Linezolid 600 mg IV or PO q12h; plus
  • Meropenem 1 to 2 g IV q8h
  • Alternate for trimethoprim-sulfamethoxazole " “allergic: amikacin + imipenem 500 mg IV q6h or meropenem 1 to 2 g IV q8h or ceftriaxone 2 g IV q12h or cefotaxime 2 g IV q8h
  • Alternate for trimethoprim-sulfamethoxazole " “allergic: amikacin + imipenem or meropenem or ceftriaxone or cefotaxime
  • Alternate linezolid; + meropenem
  • Sulfisoxazole 2 g PO BID, or minocycline 100 to 200 mg PO BID; total duration 3 months and at least 1 month beyond resolution; for immunocompromised, 6 months and at least 1 month beyond resolution; linezolid may be considered as an alternative.

ISSUES FOR REFERRAL

SURGERY/OTHER PROCEDURES

INPATIENT CONSIDERATIONS

  • Patients with symptomatic nocardiosis are often immunocompromised and require hospitalization.
  • Patients with a mild to moderate presentation may not require hospitalization, especially if immunocompetent.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

DIET

PATIENT EDUCATION

  • Not a contagious disease
  • Patients may need long-term antibiotic therapy to treat nocardiosis and reduce the likelihood of relapse.
  • Educate patients about adverse medication reactions.

PROGNOSIS

  • Overall mortality is 7 " “44%.
  • Approximately 10% of cases with uncomplicated pneumonia are fatal.
  • The case fatality rate increases with overwhelming infection, disseminated disease, or brain abscess.

COMPLICATIONS

  • Organ system deficits from the lasting effects of suppuration, tissue destruction, and mass effect
  • Adverse reactions from long-term antimicrobial therapy

REFERENCES

ADDITIONAL READING

  • Bargehr ‚ J, Flors ‚ L, Leiva-Salinas ‚ C, et al. Nocardiosis in solid-organ transplant recipients: spectrum of imaging findings. Clin Radiol. 2013;68(5):e266 " “e271.
  • Brown-Elliott ‚ BA, Brown ‚ JM, Conville ‚ PS, et al. Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev. 2006;19(2):259 " “282.
  • Corti ‚ ME, Villafa ƒ ±e-Fioti ‚ MF. Nocardiosis: a review. Int J Infect Dis. 2003;7(4):243 " “250.
  • Filice ‚ GA. Nocardiosis in persons with human immunodeficiency virus infection, transplant recipients, and large, geographically defined populations. J Lab Clin Med. 2005;145(3):156 " “162.
  • Mei-Zahav ‚ M, Livnat ‚ G, Bentur ‚ L, et al. The spectrum of nocardia lung disease in cystic fibrosis. Pediatr Infect Dis J. 2015:34(8):909 " “911.
  • Saubolle ‚ MA, Sussland ‚ D. Nocardiosis: review of clinical and laboratory experience. J Clin Microbiol. 2003;41(10):4497 " “4501.

CODES

ICD10

  • A43.9 Nocardiosis, unspecified
  • A43.0 Pulmonary nocardiosis
  • A43.1 Cutaneous nocardiosis
  • A43.8 Other forms of nocardiosis

ICD9

  • 039.9 Actinomycotic infection of unspecified site
  • 039.1 Pulmonary actinomycotic infection
  • 039.0 Cutaneous actinomycotic infection
  • 039.8 Actinomycotic infection of other specified sites

SNOMED

  • Nocardiosis (disorder)
  • Pulmonary nocardiosis (disorder)
  • Cutaneous nocardiosis
  • Disseminated nocardiosis (disorder)

CLINICAL PEARLS

  • The diagnosis of nocardiosis requires a high degree of clinical suspicion. Nocardiosis lacks a pathognomonic appearance and may present in a variety of ways.
  • Immunocompromised patients have more severe manifestations of disease.
  • Nocardiosis can progress and relapse despite appropriate therapy.
  • Microscopic examination of purulent fluid should include Gram stain and modified partial acid-fast staining for preliminary diagnosis and to guide treatment.
  • Treatment is based on location of disease and results of culture and sensitivity. Prolonged antibiotic therapy is typically required.