Mycobacterium Fortuitum Medication

Prolonged antibiotic therapy is generally required for M fortuitum infection. Intravenous therapy is preferred for serious illness or disseminated disease, at least initially.

Although numerous reports have documented cases of successful therapy with one drug (eg, clarithromycin), reports also describe resistance to treatment. Therefore, antibiotic therapy with 2 drugs is preferable in most patients. Test initial isolates for antibiotic sensitivity to guide therapy because the sensitivity of individual isolates can vary considerably.^[4] Susceptibility testing does not guarantee clinical success as correlations of susceptibility testing and clinical response have not been assessed.

In many patients, the disease has been long-standing, and no urgency in initiating therapy is indicated. In this setting, waiting for the results of sensitivity testing before beginning treatment provides much greater certainty in the choice of an antibiotic regimen. First-line antituberculous drugs (eg, isoniazid, rifampin, pyrazinamide) have no role in the treatment of M fortuitum infection .^[5]

Amikacin is the aminoglycoside preferred for treatment of M fortuitum infection, and almost all isolates are susceptible. Both cefoxitin and imipenem have been used successfully, but susceptibility is variable. Some fluoroquinolones have very good activity. Ciprofloxacin and levofloxacin have both been used successfully. Moxifloxacin is largely untested clinically but has good in vitro activity and would be expected to work.^[6] Doxycycline has activity against roughly one half of isolates. This organism may possess an inducible erythromycin methylase erm gene. Thus, the use of erythromycin should be avoided. This gene may also confer resistance to other macrolides despite minimum inhibitory concentration (MIC) levels that are considered susceptible. These agents may be active against M fortuitum, but they should be used with caution.

Sulfamethoxazole has activity against M fortuitum. Conflicting data exist regarding whether trimethoprim, which has no activity alone, adds activity to sulfamethoxazole. The trimethoprim-sulfamethoxazole fixed-dose combination is a readily available form of the sulfa drug, and the combination has been used successfully, even as monotherapy. In vitro, more than 90% of isolates of M fortuitum were susceptible to linezolid; however, little clinical experience exists with its use specifically for this organism. Linezolid has been used successfully for other rapidly growing mycobacteria, so it is a reasonable consideration in patients whose organism is resistant to other antimicrobials. Tigecycline has also shown good in vitro results, but no clinical data exist on its use; it should be considered only in the absence of other options.^[7]

Topical amikacin and ciprofloxacin have been used successfully for ocular disease, both alone and in combination with parenteral or oral antibiotics. Topical ofloxacin is expected to be effective.

No standard duration of therapy has been reported. Treatment usually lasts for months, and courses that are 6 months or more are not unusual. Drugs should be administered at least long enough to allow for a complete resolution of clinically apparent lesions. How much additional therapy is needed to prevent relapse is unclear. Some experts obtain monthly sputum cultures in patients with NTM pulmonary disease and treat for at least a year after the last positive sputum culture result.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Deferring therapy until sensitivity results are available may be prudent.

Amikacin (Amikin)

Irreversibly binds to 30S subunit of bacterial ribosomes; blocks recognition step in protein synthesis; causes growth inhibition. Use patient's IBW for dosage calculation. Often used with cefoxitin or imipenem for severe pulmonary or disseminated disease.

Cefoxitin (Mefoxin)

Usually used with amikacin for severe pulmonary or disseminated disease.

Imipenem/cilastatin (Primaxin)

Usually used with amikacin for severe pulmonary or disseminated disease.

TMP-SMZ; cotrimoxazole (Septra, Bactrim)

Use alone or in combinations. Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Ciprofloxacin (Cipro)

Use alone or in combinations. Inhibits bacterial DNA synthesis and, consequently, growth.

Tigecycline (Tygacil)

Good in vitro activity but no documented clinical use. A glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. Inhibits bacterial protein translation by binding to 30S ribosomal subunit and blocks entry of amino-acyl tRNA molecules in ribosome A site.

Levofloxacin (Levaquin)

Used alone or in combination. Second-generation quinolone. Acts by interfering with DNA gyrase in bacterial cells. Bactericidal. Highly active against gram-negative and gram-positive organisms, including Pseudomonas aeruginosa. Probably fluoroquinolone of choice.

Doxycycline (Vibramycin, Doryx)

Because doxycycline has activity against approximately one third of isolates, generally not used as part of initial empiric regimen. Use should be guided by sensitivity data.

Clarithromycin (Biaxin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Use alone or in combinations.

Azithromycin (Zithromax)

Use alone or in combinations. Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected. Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues. Treats mild-to-moderate microbial infections.

Plasma concentrations are very low, but tissue concentrations are much higher, giving it value in treating intracellular organisms. Has a long tissue half-life.

Ofloxacin ophthalmic (Ocuflox)

For use with or without systemic antibiotics (either oral or parenteral). Pyridine carboxylic acid derivative with broad-spectrum bactericidal effect. Inhibits bacterial growth by inhibiting DNA gyrase. Indicated for superficial ocular infections of the conjunctiva or cornea caused by strains susceptible to ofloxacin.

Ciprofloxacin ophthalmic (Ciloxan)

For use with or without systemic antibiotics (either oral or parenteral). Inhibits bacterial growth by inhibiting DNA gyrase. Indicated for superficial ocular infections of the conjunctiva or cornea caused by strains susceptible to ciprofloxacin.

Moxifloxacin (Avelox)

Good in vitro activity but no documented clinical use.

Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

Linezolid (Zyvox)

Good in vitro activity. No documented use in M fortuitum infections but has been used successfully against other rapidly growing mycobacteria.

Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process.