AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Mycobacterium fortuitum is a nontuberculous mycobacterium (NTM), a grouping that encompasses all mycobacteria outside of the Mycobacterium tuberculosis complex. M fortuitum is classified in the Runyon group IV, rapidly growing mycobacteria. It has been found in natural and processed water sources, as well as in sewage and dirt. Distribution is probably worldwide.

Pathophysiology

M fortuitum infection can cause various clinical syndromes. It is an uncommon cause of NTM lung disease. Local cutaneous disease, osteomyelitis, joint infections, and ocular disease (eg, keratitis, corneal ulcers) may occur after trauma. M fortuitum infection is a rare cause of isolated lymphadenitis. Disseminated disease, usually with disseminated skin lesions and soft tissue lesions, occurs almost exclusively in the setting of severe immunosuppression, especially AIDS. Endocarditis has been documented.

Surgical-site infections due to M fortuitum infection are well-documented, especially in association with cardiothoracic surgery. The source is frequently contamination of the wound, directly or indirectly, with colonized tap water. Other nosocomial infections with this organism include infections of implanted devices (eg, catheters) and injection-site abscesses. Pseudo-outbreaks have been associated with contaminated endoscopes. Recent outbreaks have also been described in immunocompetent hosts after use of contaminated whirlpool footbaths in nail salons.¹

Frequency

United States

NTM infections are not required to be reported; therefore, exact estimates of disease prevalence and incidence are impossible to determine. The most recent estimates come from voluntary reports tracked by the Centers for Disease Control and Prevention (CDC). From 1993-1996, 4.65-5.99 cases per million persons were reported to the CDC.² Sputum was the most frequently reported site, but this may represent a bias in the sites most likely to be cultured for mycobacteria.

Most cases are reported from the southeast United States, including Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, Tennessee, Virginia, and West Virginia, and the south-central United States, including Arkansas, Kansas, Louisiana, Missouri, Oklahoma, and Texas. Because all cases were likely not reported and some positive culture results may not represent disease, which is perhaps especially true of positive sputum culture results, these numbers may significantly overestimate or underestimate true disease incidence. However, they suggest the general order of magnitude of the situation. An increased appreciation of these organisms as true pathogens may be the reason NTM infection rates are perceived to be increasing, even excluding Mycobacterium avium complex (MAC) infections in persons with AIDS.

International

The World Health Organization does not track NTM infections. Incidence and prevalence undoubtedly vary greatly by locale.

Mortality/Morbidity

• Mortality due to localized M fortuitum infection is rare. Death may result from extensive pulmonary or disseminated disease in patients who are immunocompromised.
• Morbidity depends largely on the site of the infection. Localized skin lesions may eventually heal without therapy or surgical intervention. At other sites, chronic infection is the rule.

Race

No clear racial predilection exists.

Sex

No sexual predominance is known; however, from 1993-1996, more cases reported to the CDC were involved men than did women.² Whether this represents a true sex-based preference or reflects a bias in testing and reporting is unclear.

Age

In general, no known age predominance exists. Lung disease in a younger patient (<50 y) strongly suggests a primary underlying lung disorder. Isolated lymphadenitis primarily occurs in children.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients with skin disease may develop a nonhealing but nonspreading wound or skin ulcer.
• Patients with lung disease may develop a chronic cough.
• Pulmonary and disseminated disease cause easy fatigability, occasional fever, night sweats, and weight loss. These symptoms are less common with M fortuitum infection than with tuberculosis.

Physical

No findings are pathognomonic of M fortuitum infection. Physical findings depend on the infection site.

• Eye: Keratitis or corneal ulcers may be present.
• Lungs: Rales or rhonchi may be present.
• Heart: Valvular murmur with endocarditis may be present.
• Abdomen: Diffuse tenderness with peritonitis may be present (eg, a patient undergoing peritoneal dialysis).
• Skin: Ulcerative skin lesions and/or subcutaneous nodules may be present. Deeper infections may lead to draining fistulas.

Causes

• Trauma or injection - Skin lesions, subcutaneous lesions, ocular lesions, and osteomyelitis
• Immunosuppression - Disseminated disease, especially in patients with AIDS or in those who use corticosteroids
• Lung disease – Bronchiectasis

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Bacterial osteomyelitis
Contaminant/pseudoinfection
Colonization
Cutaneous vasculitis
Fusarium species infection
Phaeohyphomycosis
Prototheca species infection
Pseudallescheria boydii infection

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

According to American Thoracic Society criteria³, diagnosis of lung disease requires (1) pulmonary symptoms with consistent radiographic features, (2) exclusion of other diagnoses, especially tuberculosis, and (3) appropriate microbiological findings.

• Sputum smear for acid-fast bacilli and culture for mycobacteria
• • Microbiological findings to satisfy ATS diagnostic criteria include the following (at least one must apply):
  • • Positive culture from at least 2 separate sputum samples
    • Positive culture from bronchial wash or lavage
    • Biopsy specimen with appropriate histopathologic features and a positive culture from an associated bronchial wash or biopsy culture
  • Induced sputum samples may be substituted for expectorated sputum samples but, data establishing the effectiveness of this technique are lacking.
  • A single positive isolate may represent a contaminant or persistent or transient colonizer without pathogenicity.
• Swab culture for acid-fast bacilli
• • Notifying the microbiology laboratory personnel that a NTM is suspected may help ensure appropriate processing of specimens. Most laboratories use liquid media (eg, BACTEC) for mycobacterial cultures.
  • Swab specimens are less optimal than cultures obtained via aspiration. Consider contacting laboratory personnel for proper procedures regarding adequate specimen collection to increase the yield and significance of cultures.
  • Interpret the result with caution because a single positive culture, especially of a superficial lesion, may represent a contaminant.
• Additional testing if M fortuitum infection is discovered
• • An HIV test may be warranted, especially if disseminated disease is diagnosed without an obvious underlying condition.
  • Sweat chloride and/or genetic screening for cystic fibrosis may be warranted if a lung infection is found in a relatively young patient (<50 y). Most patients with cystic fibrosis also have a history of recurrent lung infections, although milder disease is being recognized more frequently.

Imaging Studies

• Chest radiography
• • Perform chest radiography if pulmonary symptoms are present.
  • Normal chest radiographic findings with a single positive culture suggest that the organism is a contaminant or a transient colonizer and is not clinically significant. However, in the presence of chronic persistent pulmonary symptoms or repeatedly positive culture results, additional testing may be necessary.
• Chest CT scanning
• • If the patient has significant respiratory symptoms or repeatedly positive cultures for the same organism with a lack of cavitary disease on chest radiography, high-resolution CT scanning is indicated.
  • Typical CT scan findings include bronchiectasis or diffuse small nodules; these are often not revealed by routine chest radiography.
  • If the chest radiographic findings are abnormal, chest CT scanning may be performed to obtain better definition of the abnormalities present. Lymphadenopathy may also be detected. This study is not necessary in every case but should be strongly considered. 
• CT scanning of the abdomen and pelvis: This study may be indicated to detect local abscesses or lymphadenopathy, including retroperitoneal abscesses or lymph nodes, in patients with disseminated disease, localizing signs or symptoms, or a history of injections in those locations.
• Bone imaging, MRI, and nuclear imaging: These studies may be helpful in detecting osteomyelitis or joint disease if suspected, especially in patients with a history of penetrating trauma.

Other Tests

• Erythrocyte sedimentation rate, C-reactive protein, and other inflammatory markers may be useful if mycobacterial disease is suspected. However, these tests are nonspecific, and their precise role in aiding diagnosis and follow-up care is currently not well-defined.

Procedures

• Lung procedures
• • Perform bronchoscopy with bronchial washes and/or bronchoalveolar lavage, ideally in conjunction with transbronchial biopsy, for acid-fast bacilli (AFB) smear, culture, and histology. Because the diagnosis is usually uncertain at this stage, bacterial and fungal cultures are often sent as well.
  • Open or thorascopic lung biopsy may be considered if suspicion is high but diagnostic criteria have not been met. Send specimens for fungal and AFB cultures, as well as histology.
  • A biopsy specimen culture positive for M fortuitum is considered diagnostic. A positive AFB smear result correlates with an increased number of organisms and further supports the diagnosis.
  • The presence of either AFB or granulomas in a lung biopsy specimen or a transbronchial biopsy specimen along with even a single positive culture result of sputum or bronchial wash (even in low numbers) is considered diagnostic.
• Skin tests
• • Perform a biopsy for localized or disseminated skin lesions. Send specimens for mycobacterial and fungal cultures, as well as histology.
  • PPD testing with nontuberculous mycobacterial specific antigens is non-specific and general not indicated.  These tests are not commercially available.
• Aspiration biopsy
• • Perform an aspiration biopsy of a localized abscess for culture.
  • Perform a fine-needle aspiration biopsy or a surgical excision of lymph nodes for histology and culture.

Histologic Findings

Histologic findings may reveal acute inflammation, microabscesses, granulomatous inflammation, or granulomas (with or without caseation). These findings may be mixed. Special stains for AFB may reveal organisms.

Staging

The disease may be limited or disseminated (2 noncontiguous organs) or in the blood (mycobacteremia).

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Local wound care for cutaneous lesions is always appropriate. Small lesions may improve with local care and antibiotics without surgical intervention.
• In vitro susceptibilities may not correlate with in vivo activities. Before considering major surgery, a course of at least 2 drugs may be useful, even with resistant organisms.

Surgical Care

• Surgical debridement of cutaneous or subcutaneous lesions, especially if the lesions are extensive, is usually required for cure.
• Surgical debridement of ocular and bone lesions is almost always required.
• Surgical excision of pulmonary lesions may be considered if response to therapy is lacking or if the organism is relatively resistant to antibiotics.
• Surgical excision of lymphadenitis is the therapy of choice and is usually curative.
• If the infection involves an implanted device, removal of the device is usually necessary for cure.

Consultations

• Obtain consultation with an infectious diseases specialist for diagnostic and therapeutic guidance.
• Obtain consultation with a pulmonologist for lung lesions, for possible bronchoscopy, and for therapeutic guidance.
• Obtain consultation with a surgeon for debridement and/or biopsy. Indwelling catheter placement may also be necessary if long-term antibiotics are to be administered.
• Obtain consultation with a dermatologist for possible biopsy of cutaneous lesions.
• If local expertise in NTM infections is not available, consider obtaining expert advice from a national center, such as the National Jewish Medical and Research Center in Denver, Colo, or a regional medical school, such as the Mycobacterial Disease Clinic at The University of Texas Health Center at Tyler.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

Drug Category: Antibiotics

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.

Drug Name	Cefoxitin (Mefoxin)
Description	Usually used with amikacin for severe pulmonary or disseminated disease.
Adult Dose	2 g IV q4h or 3 g IV q6h for serious disease; lower doses may be considered for less serious disease or after 2 wk of therapy
Pediatric Dose	<3 months: Not established >3 months: 80-160 mg/kg/d IV in divided equal doses q4h or q6h; not to exceed 12 g/d
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase effects of cefoxitin; coadministration with aminoglycosides or furosemide may increase nephrotoxicity (closely monitor renal function)
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	May cause allergic reaction in patients who are penicillin sensitive; adjust dose for impaired renal function; may cause eosinophilia, leukopenia, or elevated AST; bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged use or repeated treatment

Drug Name	Imipenem/cilastatin (Primaxin)
Description	Usually used with amikacin for severe pulmonary or disseminated disease.
Adult Dose	500 mg IV q6h to 1g IV q6-8h
Pediatric Dose	<3 months: Not established >3 months: 15-25 mg/kg IV q6h; each dose not to exceed 500 mg (not to exceed 2 g/d)
Contraindications	Documented hypersensitivity
Interactions	Coadministration with cyclosporine may increase CNS adverse effects of both agents; coadministration with ganciclovir may result in generalized seizures
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	May cause seizures, especially in elderly age, renal dysfunction, and preexisting seizure disorders; adjust dose for impaired renal function; avoid use in children <12 y with CNS infections

Drug Name	TMP-SMZ; cotrimoxazole (Septra, Bactrim)
Description	Use alone or in combinations. Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.
Adult Dose	1 DS tab (160 mg TMP/800 mg SMZ) bid to 2 DS tab tid
Pediatric Dose	<2 months: Not recommended > 2 months: 6-10 mg/kg (of TMP component) PO/IV divided q12h
Contraindications	Documented hypersensitivity; megaloblastic anemia due to 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 in elderly patients; 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	Discontinue at first appearance of rash or sign of adverse reaction; obtain CBC counts frequently; 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, administer 5-15 mg/d leucovorin); caution in folate deficiency (eg, chronic alcoholism, elderly age, current anticonvulsant therapy, malabsorption syndrome); hemolysis may occur in G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation

Drug Name	Ciprofloxacin (Cipro)
Description	Use alone or in combinations. Inhibits bacterial DNA synthesis and, consequently, growth.
Adult Dose	400 mg IV q12h or 500 mg PO q12h
Pediatric Dose	<18 years: Not currently approved for use; although sometimes used in these patients for acute infections, long-term use required for therapy of Mycobacterium chelonei would likely be problematic
Contraindications	Documented hypersensitivity; avoid in CNS or seizure disorders
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; may increase toxicity of theophylline, caffeine, cyclosporine, anticoagulants (monitor PT), and digoxin (monitor digoxin levels)
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	Adjust dose for impaired renal function; discontinue upon any evidence of tendonitis; monitor glucose with antidiabetic agents; in prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); superinfections may occur with prolonged or repeated antibiotic therapy

Drug Name	Tigecycline (Tygacil)
Description	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.
Adult Dose	Infuse each dose over 30-60 min 100 mg IV once, then 50 mg IV q12h Severe hepatic impairment (ie, Child Pugh class C): 100 mg IV once, then 25 mg IV q12h
Pediatric Dose	<18 years: Not established >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Coadministration decreases warfarin clearance and increases warfarin Cmax and AUC (monitor aPTT and INR); coadministration of antibiotics with oral contraceptives may decrease contraceptive effect
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	Should be considered only in patients with limited other options given lack of clinical data Caution in severe hepatic impairment (reduce dose); may adversely effect tooth development; may permit clostridia overgrowth, resulting in antibiotic-associated colitis; may have adverse effects similar to those of tetracyclines (eg, photosensitivity, pseudotumor cerebri, pancreatitis, antianabolic action)

Drug Name	Levofloxacin (Levaquin)
Description	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.
Adult Dose	500-750 mg/d PO/IV (1000 mg/d or 500 mg bid dosing can be considered for more severe disease)
Pediatric Dose	<18 years: Not currently approved for use; although sometimes used in these patients for acute infections, long-term use required for treatment of M chelonei infection may be problematic
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 1-2 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations
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	Adjust dose for impaired renal function; superinfections may occur with prolonged or repeated antibiotic therapy

Drug Name	Doxycycline (Vibramycin, Doryx)
Description	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.
Adult Dose	100 mg PO qd/bid
Pediatric Dose	<8 years: Not recommended >8 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Bioavailability is decreased slightly with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Photosensitivity may rarely occur with prolonged exposure to sunlight or tanning equipment

Drug Name	Clarithromycin (Biaxin)
Description	Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Use alone or in combinations.
Adult Dose	500 mg PO bid
Pediatric Dose	7.5 mg/kg PO bid, not to exceed 500 mg bid
Contraindications	Documented hypersensitivity; concurrent use of drugs that increase QT interval
Interactions	Toxicity increases with coadministration of fluconazole, astemizole, and pimozide; effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, and HMG CoA-reductase inhibitors; serious cardiac arrhythmias may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels 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	Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; administer one half dose or increase dosing interval if CrCl <30 mL/min; superinfections may occur with prolonged or repeated antibiotic therapies

Drug Name	Azithromycin (Zithromax)
Description	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.
Adult Dose	500-600 mg/d PO
Pediatric Dose	<6 months: Not established >6 months: 10 mg/kg/d PO; not to exceed 500-600 mg/d
Contraindications	Documented hypersensitivity; hepatic impairment; do not administer with drugs that prolong QT interval
Interactions	May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function or prolonged QT intervals; caution in hospitalized, geriatric, or debilitated patients

Drug Name	Ofloxacin ophthalmic (Ocuflox)
Description	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.
Adult Dose	1-2 gtt in affected eye q2-4h for first 2 d; then qid
Pediatric Dose	<2 years: Not recommended >2 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
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	Expected to work on sensitive strains, but no case reports of actual use in Medline

Drug Name	Ciprofloxacin ophthalmic (Ciloxan)
Description	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.
Adult Dose	1-2 gtt in the eye(s) q2h while awake for 2 d and 1-2 gtt q4h while awake
Pediatric Dose	<1 year: Not recommended >1 year: Administer as in adults
Contraindications	Documented hypersensitivity; avoid coadministration with steroid combinations after uncomplicated removal of a foreign body from cornea
Interactions	None reported
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	A white crystalline precipitate located in superficial portion of corneal defect may occur (onset starts in 1-7 d); precipitate is usually cleared within 2 wk and does not adversely affect clinical course or outcome; do not use in ocular infections that may become systemic; superinfections may occur with prolonged or repeated antibiotic therapy

Drug Name	Moxifloxacin (Avelox)
Description	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.
Adult Dose	400 mg PO/IV qd
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity; known QT prolongation; concurrent administration of drugs that cause QT prolongation
Interactions	Antacids and electrolyte supplements reduce absorption; loop diuretics, probenecid, and cimetidine increase serum levels; NSAIDs enhance CNS stimulating effect May increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT); ferrous sulfate decreases bioavailability (administer moxifloxacin 4 h prior or 8 h following ferrous sulfate); coadministration with drugs that prolong QTc interval (quinidine, procainamide, amiodarone, sotalol, erythromycin, tricyclic antidepressants) increase risk of life-threatening arrhythmia
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	In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); superinfections may occur with prolonged or repeated antibiotic therapy; fluoroquinolones have induced seizures in CNS disorders and caused tendinitis or tendon rupture

Drug Name	Linezolid (Zyvox)
Description	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.
Adult Dose	400-600 mg PO/IV q12h
Pediatric Dose	Preterm neonate <7 days: 10 mg/kg PO/IV q12h Term neonates through 12 years: 10 mg/kg PO/IV q8h >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	May cause hypertension when used concomitantly with adrenergic agents including pseudoephedrine, sympathomimetic agents, and 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 or pseudomembranous colitis inhibitors
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	Has mild MAOI properties and has potential to have same interactions as other MAOIs; caution in uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism and in 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 CBC); unnecessary use may lead to development of resistance to drug; may cause peripheral or optic neuropathy

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Many, if not most, patients do not require inpatient care. The duration of inpatient care is dictated by the time needed to recover from any procedures performed.

Further Outpatient Care

• The frequency of outpatient visits is determined by the extent of the disease and whether the patient is receiving oral or intravenous therapy.
• • Initially, at least monthly follow-up care for adverse effects is reasonable.
  • More frequent visits may be necessary for patients with central catheters to evaluate for line infections.
• Outpatients taking aminoglycoside therapy should undergo periodic (at least weekly) assessment of renal function and, possibly, antibiotic levels.
• Monthly sputum cultures may be useful in patients with pulmonary disease to demonstrate the efficacy of the treatment plan.

In/Out Patient Meds

• Administer antibiotics daily (see Medication).
• Infrequent dosing (eg, 2-3 times/wk, as for tuberculosis) has not been evaluated and is not recommended.

Transfer

• Patients who require intravenous antibiotic therapy but who are unable to receive home intravenous therapy need to be placed in a facility capable of administering antibiotics.
• Patients with refractory disease may require a referral to a specialty center (usually as an outpatient rather than as an inpatient transfer).

Deterrence/Prevention

• No specific deterrence methods are available. M fortuitum is a ubiquitous organism.

Complications

• Severe lung disease or disseminated disease may cause death.
• Skin lesions and subsequent debridement may be disfiguring.
• Antibiotic monotherapy may lead to drug resistance.

Prognosis

• With debridement and antibiotic therapy, prognosis is very good for most sites of infection.
• Lung disease may be difficult or impossible to eradicate. Chronic suppression of the infection and slowing of the progression of lung disease may be the only achievable goal in this setting.
• Cure of infected implants that cannot be removed may be impossible.

Patient Education

• Educate patients about the importance of compliance with multiple drug regimens to avoid development of antibiotic resistance.
• Patients may confuse the disease with tuberculosis and need to be reassured that they are not contagious to others.
• For excellent patient education resources, visit eMedicine's Procedures Center. Also, see eMedicine's patient education article Bronchoscopy.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• No specific pitfalls are documented. Potential problem areas include the following:
• • Failure to consider the diagnosis in patients with chronic infection is possible.
  • Because M fortuitum may be a contaminant, consider the possibility of pseudoinfection in any patient with a culture positive for M fortuitum before committing the patient to an extended course of treatment. This is especially true of sputum samples and cultures from other nonsterile sites (eg, a swab culture of an ulcer base).
  • Because disease by this organism can be indolent, a culture positive for M fortuitum should prompt a careful evaluation to exclude unrecognized disease.

Special Concerns

• If the M fortuitum infection is believed to be nosocomial, notify hospital infection control. Finding even a single case of nosocomial NTM warrants an evaluation.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Winthrop KL, Abrams M, Yakrus M, Schwartz I, Ely J, Gillies D, et al. An outbreak of mycobacterial furunculosis associated with footbaths at a nail salon. N Engl J Med. May 2 2002;346(18):1366-71. [Medline].
2. CDC. Nontuberculous mycobacteria reported to the Public Health Laboratory Information System by State Public Health Laboratories United States, 1993-1996. [Full Text].
3. ATS. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Medical Section of the American Lung Association. Am J Respir Crit Care Med. Aug 1997;156(2 Pt 2):S1-25. [Medline].
4. Wallace RJ, Swenson JM, Silcox VA, Bullen MG. Treatment of nonpulmonary infections due to Mycobacterium fortuitum and Mycobacterium chelonei on the basis of in vitro susceptibilities. J Infect Dis. Sep 1985;152(3):500-14. [Medline].
5. Heifets LB. Antimycobacterial drugs. Semin Respir Infect. Jun 1994;9(2):84-103. [Medline].
6. Brown-Elliott BA, Wallace RJ, Crist CJ. Comparison of in vitro activities of gatifloxacin and ciprofloxacin against four taxa of rapidly growing mycobacteria. Antimicrob Agents Chemother. Oct 2002;46(10):3283-5. [Medline].
7. Wallace RJ, Brown-Elliott BA, Crist CJ. Comparison of the in vitro activity of the glycylcycline tigecycline (formerly GAR-936) with those of tetracycline, minocycline, and doxycycline against isolates of nontuberculous mycobacteria. Antimicrob Agents Chemother. Oct 2002;46(10):3164-7. [Medline].
8. ATS/IDSA: Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et al. An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases. Am J Respir Crit Care Med. February 2007;175:367-416. [Medline].
9. Griffith DE, Wallace RJ. New developments in the treatment of nontuberculous mycobacterial (NTM) disease. Semin Respir Infect. Dec 1996;11(4):301-10. [Medline].
10. Kyle SD, Porter WM. Mycobacterium chelonae infection successfully treated with oral clarithromycin and linezolid. Br J Dermatol. Nov 2004;151(5):1101. [Medline].
11. Wagner D, Young LS. Nontuberculous mycobacterial infections: a clinical review. Infection. Oct 2004;32(5):257-70. [Medline].
12. Wallace RJ, Brown-Elliott BA, Ward SC. Activities of linezolid against rapidly growing mycobacteria. Antimicrob Agents Chemother. Mar 2001;45(3):764-7. [Medline].

Article Last Updated: Dec 3, 2007