Mycobacterium Fortuitum 

Updated: Nov 29, 2018
Author: Joseph M Fritz, MD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD 

Overview

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.[1] 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.[2]

Epidemiology

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.[3] 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.[3] 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.

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, see eMedicineHealth's patient education article Bronchoscopy.

 

Presentation

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, as follows:

  • 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).[4]

  • Skin: Ulcerative skin lesions and/or subcutaneous nodules may be present. Deeper infections may lead to draining fistulas.[5, 6]

Causes

See the list below:

  • 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

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.

 

DDx

 

Workup

Laboratory Studies

According to American Thoracic Society criteria[7] , 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.

Polymerase chain reaction

A new multiplex polymerase chain reaction (PCR) test performed on the BD MAX System was shown to be sensitive and specific for M fortuitum complex.[8]

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.[9]

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

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.

Prevention

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

Long-Term Monitoring

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.

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.

Inpatient & Outpatient Medications

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).

 

Medication

Medication Summary

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.[10] 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.[11]

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.[12, 13] 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.[14]

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.[15, 16]

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.

Antibiotics

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.