Medication Summary
General treatment guidelines for nocardiosis are hindered by (1) lack of controlled clinical trials of therapy; (2) difficult, and, in the past, poorly standardized in vitro susceptibility testing leading to widely disparate reports of in vitro antimicrobial susceptibility [41, 42] ; (3) lack of firm data on the correlation of in vitro susceptibility with in vivo therapeutic efficacy; and (4) the changing taxonomy of Nocardia species. Various species of Nocarida have different antimicrobial susceptibility patterns, N. farcinica has high rates of resistnace to numeous antibiotics. Therapy should guided by in vitro susceptibility testing at a specialized laboratory experienced at testing Nocardia strains.
Sulfonamides have long been the first-line antimicrobial therapy for nocardiosis. Among the sulfonamides, sulfadiazine is generally preferred because of its CNS and CSF penetration. Although not convincingly demonstrated superior, trimethoprim-sulfamethoxazole (TMP-SMX) is considered the therapy of choice by most authorities. Divided doses of 5-10 mg/kg/d of the trimethoprim (TMP) component should be administered in mild-moderate pulmonary infections in immunocompetent patients. Divided dosing of 10-15 mg/kg of the TMP component should be required in immunocompromised patients with mild-moderate pulmonary infecton and with CNS ifnection. Patients with sulfa allergy should be densensitized if possible. Dosing of trimethoprim-sulmamethoxazole requires adjustment with renal insufficiency.
Additional parenteral therapies include carbapenems (imipenem or meropenem, but not ertapenem), third-generation cephalosporins (cefotaxime or ceftriaxone), and amikacin, alone or in combination. Imipenem plus amikacin may be the preferred regimen in sulfonamide-allergic individuals. Linezolid in vitro activity and in vivo efficacy has been reported. [43] Tigecycline also has reported activity in vitro. [1]
For most serious Nocardia infections, combination therapy has been recommended with at least IV agents. [1] Combination therapy should be continued until clinical improvement occurs and confirmation of in vitro drug susceptibility has been acquired. Typically 3-6 weeks of induction therapy with IV antibiotics are necessary for severe infeciton until patients can be switched to oral antibiotic therapy.
Oral antibiotic therapies include minocycline, amoxicillin/clavulanate and linezolid. These may be used initially in mild-to-moderately severe disease or as sequential therapy after an induction course of parenteral therapy. Modern fluoroquinolones often have demonstrable in vitro activity against Nocardia species but have failed therapeutically. Clarithromycin may have activity against Nocardia nova. Guidance regarding which oral antibiotics to are effective depends of susceptibility testing.
Duration of treatment is generally prolonged to minimize risk of disease relapse. Immunocompetent patients with non-CNS nocardiosis may be successfully treated with 3-6 months of antimicrobial therapy. All immunosuppressed patients and those with CNS disease should receive 12 months of therapy or longer if escalation of immunosuppression takes place (such as graft or organ rejections). For patients on chronic steroid or cytotoxic therapy, prolonged maintenance of anti-nocardial therapy may be indicated. Appropriate clinical monitoring should be conducted during protracted antimicrobial therapy. [1]
Antibiotics
Class Summary
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Sulfadiazine (Microsulfon)
Exerts its bacteriostatic action by competitive antagonism of paraaminobenzoic acid (PABA). Microorganisms that require exogenous folic acid and do not synthesize folic acid are not susceptible to the action of sulfonamides. In difficult cases, may be important to document peak serum levels (2 h after PO dose are 100-150 mg/L).
Trimethoprim-sulfamethoxazole (Bactrim, Septra)
Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.
Meropenem (Merrem IV)
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 organisms and slightly decreased activity against staphylococci and streptococci compared to imipenem.
Cefotaxime (Claforan)
Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms. Arrests bacterial cell wall synthesis, which in turn inhibits bacterial growth.
Ceftriaxone (Rocephin)
Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.
Amikacin (Amikin)
For gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin. Effective against Pseudomonas aeruginosa.
Irreversibly binds to 30S subunit of bacterial ribosomes and blocks recognition step in protein synthesis, which causes growth inhibition. Use patient's IBW for dosage calculation.
Minocycline (Minocin)
Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma.
Amoxicillin and clavulanate (Augmentin)
Drug combination treats bacteria resistant to beta-lactam antibiotics. In children >3 mo, base dosing protocol on amoxicillin content. Because of different amoxicillin/clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg.
Linezolid (Zyvox)
Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. Used as alternative in patients allergic to vancomycin and for treatment of vancomycin-resistant enterococci.
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High-power microscopic appearance of Nocardia. Image courtesy of CDC.
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Photomicrograph of tissue biopsy stained with Gomori methenamine silver demonstrating acute inflammatory response and organisms compatible with Nocardia.
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Plain chest radiograph in a patient with nocardiosis. Image courtesy of Applied Radiology, Anderson Publishing, LTD.
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Chest CT scan in a patient with pleuropulmonary nocardiosis. Image courtesy of Applied Radiology, Anderson Publishing, LTD.
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Brain CT scan in a patient with nocardial brain abscess. Image courtesy of Applied Radiology, Anderson Publishing, LTD.
