You are in: eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease NocardiosisArticle Last Updated: Dec 7, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Nicholas John Bennett, MBBCh, PhD, Staff Physician, Department of Pediatrics, State University of New York Upstate Medical University Nicholas John Bennett is a member of the following medical societies: American Academy of Pediatrics Coauthor(s): Joseph Domachowske, MD, Associate Professor, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University; Rosemary Johann-Liang, MD, Medical Officer, Infectious Diseases and Pediatrics, Division of Special Pathogens and Immunological Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration Editors: Gary J Noel, MD, Department of Pediatrics, Clinical Associate Professor, Weill Medical College of Cornell University; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Joseph Domachowske, MD, Associate Professor, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University; Robert W Tolan Jr, MD, Chief of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine; Russell W Steele, MD, Professor and Vice Chairman, Department of Pediatrics, Head, Division of Infectious Diseases, Louisiana State University Health Sciences Center Author and Editor Disclosure Synonyms and related keywords: nocardiosis, Nocardia, Nocardiaceae, Nocardia asteroides, Nocardia brasiliensis, Nocardia pseudobrasiliensis, Nocardia otitidis-caviarum, Nocardia caviae, Nocardia farcinica, Nocardia nova, Nocardia transvalensis, Nocardia carnea, Nocardia elegans, Nocardia paucivorans, Nocardia puris, Nocardia takedensis, chronic mycetoma, Nocardia abscessus, Nocardia africana, pneumonia, Nocardia ignorata, Nocardia cyriacigeorgica, cutaneous abscess, lymphocutaneous abscess, chronic granulomatous disease, human immunodeficiency virus, HIV, pulmonary alveolar proteinosis, tuberculosis, interleukin 12 deficiency, systemic lupus erythematosus, sepsis, subcutaneous abscesses, cervical adenitis, mycetoma, septic arthritis, anorexia, lymphoreticular neoplasms, respiratory distress, respiratory failure, bronchopneumonia, lobar pneumonia, necrotizing pneumonia, cerebral abscess, peritonitis, hematogenous endophthalmitis, sinusitis, aortitis, endocarditis, mediastinitis INTRODUCTIONSection 2 of 10
  BackgroundNocardia are weakly gram-positive, filamentous bacteria found worldwide in soils. Human disease from this microbe was first described by Eppinger in 1890, after bovine disease was described by Nocard in 1888. Pathogenic Nocardia are members of the family Nocardiaceae, the aerobic actinomycetes. Nocardia asteroides is the principal cause of systemic nocardiosis in the United States. Nocardia pseudobrasiliensis, Nocardia otitidis-caviarum (formerly Nocardia caviae), Nocardia farcinica, Nocardia nova, and Nocardia transvalensis have also been rarely associated with human systemic disease. Two newly described species have been associated with disease in humans: Nocardia abscessus, from soft-tissue abscesses,2 and Nocardia africana, from respiratory secretions of patients with pneumonia in the Sudan.3 Most recently, Nocardia ignorata, a new agent of human nocardiosis, was isolated from respiratory specimens in Europe and soil samples from Kuwait.4 Case reports of Nocardia cyriacigeorgica occurring in the United States have been published, with several infections being retrospectively identified from stored samples. Disseminated and fulminant disease mainly occurs in immunocompromised hosts (among persons with deficient cell-mediated immunity) with underlying illnesses, such as chronic granulomatous disease or human immunodeficiency virus (HIV) infection, and in children undergoing cytotoxic chemotherapy, bone marrow transplantation, or prolonged glucocorticoid treatment. PathophysiologyIntroduction of N asteroides via the respiratory tract results in pulmonary lesions that most often manifest as multiple abscesses. Nocardia abscesses are characteristically confluent, with little evidence of encapsulation, which probably accounts for the ready dissemination from the initial pulmonary focus. This organism also evades the host's bactericidal mechanisms. Host neutrophil mobilization can inhibit Nocardia but does not kill them. Cell-mediated immunity triggered by activated macrophages and the induction of a T-cell population capable of direct lymphocyte-mediated cytotoxicity are necessary to kill Nocardia. Infection progresses after the initial inhibition by neutrophils unless antimicrobial therapy or cytotoxic lymphocytes take over. Nocardia exhibit specific organ tropisms. Log-phase cells of Nocardia, which contain specific cell wall mycolic acids, are more virulent and may influence the ability of nocardiae to localize in certain tissues, such as the brain. Nocardial metastasis manifests as multiple abscesses without granules in different organs. In patients with poor neutrophil activity or impaired cell-mediated immunity, fulminant pulmonary or systemic nocardiosis is an uncommon but opportunistic infection. It is curable but has a high mortality rate (exceeding 50% in some reports), probably because of delayed diagnosis and treatment. A high index of suspicion, followed by aggressive diagnosis and treatment, is necessary for optimal results. FrequencyUnited StatesNocardiosis is sporadic and person-to-person spread is not well documented. Rare outbreaks have been associated with contamination of the hospital environment. Incidence estimates vary in immunocompromised populations. In patients who undergo renal transplant, the incidence rate is 0-20%. In patients who undergo bone marrow transplant, the incidence rate is 0.3%, and in patients with systemic lupus erythematosus, the incidence rate is 2.8%. InternationalNocardiosis occurs sporadically worldwide. Mortality/MorbidityDeath occurs from sepsis, overwhelming pneumonia, or brain abscess, rather than the untreated underlying disease. Mortality is increased in patients with acute infection and in those with disseminated disease involving 2 or more contiguous organs or the CNS. Mortality is also increased in patients taking corticosteroids or antineoplastic agents. RaceNo racial predilection is known. AgeNo age predilection is recognized. CLINICALSection 3 of 10
History
Physical
Causes
DIFFERENTIALSSection 4 of 10
Actinomycosis Aspergillosis Tuberculosis
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| Drug Name | Trimethoprim-sulfamethoxazole (Bactrim, Septra) |
|---|---|
| Description | Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Doses are based on the trimethoprim component. |
| Adult Dose | 160 mg (trimethoprim) and 800 mg (sulfamethoxazole) PO bid (ie, 1 double-strength tab PO bid) for 6 mo Immunocompromise: Duration of treatment lifelong if patient has AIDS |
| Pediatric Dose | <6 weeks: Not recommended >6 weeks: 15-20 mg/kg/d IV divided q6-8h; initial IV then PO for a total of 6-12 wk (lymphocutaneous disease) Disseminated: Continue at least 3 mo after clinical cure is achieved; usually up to 1 y, especially with CNS involvement |
| Contraindications | Documented hypersensitivity; megaloblastic anemia caused by folate deficiency |
| Interactions | May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly persons; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Avoid in pregnancy near term (risk of kernicterus in newborn); discontinue at first appearance of rash or sign of adverse reaction; frequently obtain CBC counts; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, chronic alcoholics, elderly persons, those receiving anticonvulsant therapy, or those with malabsorption syndrome); hemolysis may occur in individuals with G-6-PD deficiency; patients with AIDS may not tolerate or respond; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation |
| Drug Name | Imipenem and cilastatin (Primaxin) |
|---|---|
| Description | Therapy with this alternative agent often is used in combination with amikacin. For CNS nocardiosis, consider the related drug, meropenem, instead. |
| Adult Dose | 250-500 mg IV q6h; not to exceed 3-4 g/d |
| Pediatric Dose | 60 mg/kg/d IV divided q6-8h; not to exceed 4 g/d for 6-12 wk (lymphocutaneous disease) Disseminated: Continue at least 3 mo after clinical cure is achieved; usually up to 1 y |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration with ganciclovir may result in generalized seizures; coadministration with cyclosporine, may increase CNS effects of both agents |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Give slowly via IV over 30-60 min; pruritus, urticaria, GI symptoms, seizures, dizziness, hypotension, elevated LFT findings, and blood dyscrasias can occur; adjust dose in renal insufficiency; nausea associated with infusion can be improved by slowing the infusion rate |
| Drug Name | Amikacin (Amikin) |
|---|---|
| Description | Used in conjunction with trimethoprim-sulfamethoxazole or imipenem-cilastatin. Peak therapeutic levels are 20-30 mg/L, and trough levels are 5-10 mg/L. |
| Adult Dose | 15 mg/kg/d IV/IM divided bid/tid; not to exceed 1.5 g/d regardless of higher BW |
| Pediatric Dose | 15-22.5 mg/kg/d IV/IM divided q8h |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration with other aminoglycosides, penicillins, cephalosporins, and amphotericin B increases nephrotoxicity; enhances effects of neuromuscular blocking agents; causes respiratory depression; irreversible hearing loss may occur with coadministration of loop diuretics |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Not intended for long-term therapy; caution in patients with renal failure (not on dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission |
| Drug Name | Minocycline (Dynacin, Minocin) |
|---|---|
| Description | Another alternative drug both in PO and IV formulations for prolonged treatment. However, it is not recommended in children <8 y. |
| Adult Dose | 200 mg PO bid for 6 mo |
| Pediatric Dose | <8 years: Not recommended >8 years: Loading dose: 4 mg/kg/dose PO/IV then, 2 mg/kg/dose q12h; not to exceed 400 mg/d for 6-12 wk (lymphocutaneous) Disseminated: Continue at least 3 mo after clinical cure is achieved; usually up to 1 y |
| Contraindications | Documented hypersensitivity; severe hepatic dysfunction |
| Interactions | Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines |
| Drug Name | Amoxicillin and clavulanate (Augmentin) |
|---|---|
| Description | Aminopenicillin with a beta-lactamase inhibitor. Doses are based on the amoxicillin component. This drug is used as a follow-up treatment PO agent for prolonged therapy following IV treatment with imipenem or meropenem/amikacin. (See trimethoprim-sulfamethoxazole for suggested treatment duration.) |
| Adult Dose | 500 mg q12h PO or 250 mg PO q8h |
| Pediatric Dose | <40 kg: 20-40 mg/kg/d PO divided bid >40 kg: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration with warfarin or heparin, increases risk of bleeding |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | GI upset, rash, diarrhea may occur |
| Drug Name | Ampicillin (Marcillin, Omnipen) |
|---|---|
| Description | Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take PO medication. |
| Adult Dose | 0.5-1 g IV q6h |
| Pediatric Dose | 200-400 mg/kg/d IV divided q6h |
| Contraindications | Documented hypersensitivity |
| Interactions | Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of PO contraceptives |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction |
| Drug Name | Meropenem (Merrem IV) |
|---|---|
| Description | Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. Effective against most gram-positive and gram-negative bacteria. Has slightly increased activity against gram-negative bacteria and slightly decreased activity against staphylococci and streptococci compared to imipenem. Not recommended for children. |
| Adult Dose | 1-2 g IV q8h |
| Pediatric Dose | 60 mg/kg/d IV divided q8h Meningitis: 120 mg/kg/d IV divided q8h |
| Contraindications | Documented hypersensitivity |
| Interactions | Probenecid may inhibit renal excretion of meropenem, increasing meropenem levels |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Pseudomembranous colitis and thrombocytopenia may occur, requiring immediate discontinuation of medication |
| Drug Name | Doxycycline (Bio-Tab, Doryx, Vibramycin) |
|---|---|
| Description | Inhibits protein synthesis and thus bacterial growth by binding to 30S and, possibly, 50S ribosomal subunits of susceptible bacteria. |
| Adult Dose | 200 mg PO/IV on day 1, then 100-200 mg PO/IV qd |
| Pediatric Dose | <8 years: Not recommended >8 years: 2-4 mg/kg/d PO/IV qd |
| Contraindications | Documented hypersensitivity; severe hepatic dysfunction |
| Interactions | Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines |
| Drug Name | Sulfadiazine (Microsulfon) |
|---|---|
| Description | Exerts bacteriostatic action by competitive antagonism of para-aminobenzoic acid (PABA). Microorganisms that require exogenous folic acid and do not synthesize folic acid are not susceptible to the action of sulfonamides. |
| Adult Dose | Loading dose: 2-4 g PO once Maintenance: 2-4 g/d PO divided q3-6h |
| Pediatric Dose | 120-150 mg/kg/d PO divided q6h |
| Contraindications | Documented hypersensitivity |
| Interactions | Increases effect of PO anticoagulants and PO hypoglycemic agents; sulfadiazine effects are decreased when concurrently administered with PABA or PABA metabolites of drugs such as proparacaine, tetracaine, sunscreens, and procaine |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Pregnancy category D near term (risk of kernicterus in newborn); caution in impaired renal, hepatic function, or G-6-PD deficiency; dose should be adjusted in renal insufficiency |
| Drug Name | Linezolid (Zyvox) |
|---|---|
| Description | A synthetic antibiotic of the oxazolidinone class, which prevents the formation of functional 70S initiation complex. This is essential for the bacterial protein translation process. Although it seems to be bacteriostatic against Nocardia (as it is with most bacteria except pneumococci), it does seem to be a very effective therapy even as a monotherapy. |
| Adult Dose | 400-600 mg PO/IV q12h for 10-28 days |
| Pediatric Dose | Preterm neonate <7 days: 10 mg/kg PO/IV q12h Term neonates-12 years: 10 mg/kg PO/IV q8h >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Has mild MAOI properties and has potential to have same interactions as other MAOIs; caution with tyramine-containing foods and compounds; may cause hypertension when used concomitantly with adrenergic agents including pseudoephedrine, sympathomimetic agents, vasopressor or dopaminergic agents (reduce dose of dopamine or epinephrine if concurrent use required); serotonin syndrome may occur if used concomitantly with serotonergic agents including tricyclic antidepressants, meperidine, dextromethorphan, trazodone, venlafaxine, and selective serotonin reuptake; may cause myelosuppression (monitor blood counts when on chronic therapy) or pseudomembranous colitis |
| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus |
| Precautions | Caution in uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism, and patients who are at increased risk for bleeding, have preexisting thrombocytopenia, receive concomitant medications that may decrease platelet count or function, or who may require >2 wk of therapy (monitor platelet counts); unnecessary use may lead to development of resistance to drug; may cause peripheral or optic neuropathy. |
Article Last Updated: Dec 7, 2007
