Nocardiosis Medication

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. Trimethoprim-sulfamethoxazole (TMP-SMX) is considered by most an acceptable alternative to sulfadiazine. The addition of trimethoprim has not been shown convincingly to enhance the efficacy of sulfonamide. Therefore, this drug must be dosed to provide a dose of sulfamethoxazole equivalent to that given with sulfadiazine alone. TMP-SMX may be the preferred therapy when parenteral therapy is required because it is generally the only available parenteral sulfonamide agent.

In patients who are unable to take sulfonamides, therapy may be guided by in vitro susceptibility testing, although such testing for Nocardia species is difficult technically, poorly standardized, and not fully correlated with in vivo results of therapy. No data exist from comparative clinical trials to guide the choice among alternative therapies.

Table. In Vitro Susceptibility Data^[1] (Open Table in a new window)

A 10-year retrospective evaluation determined that the most commonly antimicrobial-resistant Nocardia species were N nova (28%), N brasiliensis (14%), and N farcinica (14%).^[18] Of the 765 isolates reviewed, 61% demonstrated resistance to SMX, and 42% demonstrated resistance to TMP-SMX.

Alternative parenteral therapies include the carbapenem meropenem, third-generation cephalosporins (cefotaxime or ceftriaxone), and amikacin, alone or in combination. Meropenem plus amikacin may be the preferred regimen. Linezolid efficacy has been reported in a single case of nocardiosis.^[19]

Alternative oral therapies include minocycline and amoxicillin/clavulanate. 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.

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.