AUTHOR AND EDITOR INFORMATION

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
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INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
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• Follow-up
• Miscellaneous
• Multimedia
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Background

Mycobacterium chelonae and Mycobacterium abscessus are nontuberculous mycobacteria (NTM), a grouping that encompasses all mycobacteria outside of the Mycobacterium tuberculosis complex. They are classified in the Runyon group IV, rapidly growing mycobacteria. They have been found in natural and processed water sources, as well as in sewage, and are especially common in tap water. Distribution is probably worldwide.

M abscessus was previously classified as a subspecies of M chelonae. For this reason, determining which species is actually involved in an infection is often difficult, especially in older reports. Further identification of newer species such as Mycobacterium massiliense and Mycobacterium bolletii may further complicate future taxonomy.¹ Prior reviews have dealt with both M abscessus and M chelonae infection; however, this review focuses solely on infections due to M chelonae.

These organisms are difficult to treat once true infection (versus colonization) is diagnosed and documented.

Of note, most information regarding diagnosis and treatment of M chelonae infection is derived from case reviews and expert opinion. Definitive statements regarding diagnosis and treatment are often lacking.²

Pathophysiology

M chelonae causes various clinical syndromes, including lung disease, local cutaneous disease, osteomyelitis, joint infections, and ocular disease (eg, keratitis or corneal ulcers). With the exception of lung disease, these syndromes commonly develop after trauma. M chelonae is a rare cause of isolated lymphadenitis. Endocarditis has also been documented. Disseminated disease, usually with disseminated skin and soft tissue lesions, occurs almost exclusively in the setting of immunosuppression, especially AIDS. Esophageal disorders may place patients at increased risk for pulmonary disease due to rapidly growing mycobacteria.³

Surgical-site infections due to M chelonae are well documented, especially in association with cardiothoracic surgery and augmentation mammoplasty. Alternative practices such as mesotherapy have been associated with skin infections.⁴ Frequently, the source is contamination of the wound, directly or indirectly, with colonized tap water; however, nosocomial infections have also been associated with contaminated gentian violet used for skin marking in plastic surgery.⁵ Other nosocomial infections with this organism include infections of implanted devices (eg, catheters) and injection-site abscesses. A recent hospital outbreak in India was associated with the water used to rinse endoscopes for laparoscopic surgery, resulting in 145 infections in 35 patients. Pseudo-outbreaks have been associated with contaminated endoscopes.⁶ No human-to-human transmission has been documented.

In patients without HIV infection, cell-mediated immune defects may be responsible for dissemination of NTM, as many patients have concomitant reactive skin diseases.⁷

Frequency

United States

Reporting of NTM infections is not required; therefore, exact estimates of disease prevalence and incidence are impossible to determine. The most recent estimates come from voluntary reports tracked by the US Centers for Disease Control and Prevention (CDC). From 1993-1996, 0-0.27 cases of M abscessus infection per million population were reported to the CDC. For M chelonae infection, the rate was 0.93-2.64 cases per million population.⁸ Sputum was the most frequently reported site for both organisms, but this may represent a bias in the sites most likely to be cultured for mycobacteria.

One half of the reports of M abscessus infection came from mountainous regions of the western United States, including Arizona, Colorado, Idaho, Montana, Nevada, New Mexico, Utah, and Wyoming. Almost all the cases of M chelonae infection were reported from the north-central United States, including Illinois, Indiana, Iowa, Michigan, Minnesota, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin; the south-central United States, including Arkansas, Kansas, Louisiana, Missouri, Oklahoma, and Texas; and the southeast United States, including Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, Tennessee, Virginia, and West Virginia.

Because all cases were likely not reported and some positive cultures may not represent disease, which is especially true of positive sputum cultures, these numbers may significantly overestimate or underestimate true disease incidence. However, they suggest the general order of magnitude of the situation. The increased recognition of M abscessus and M chelonae as true pathogens may be one reason why NTM infection rates are perceived to be increasing, even excluding Mycobacterium avium complex (MAC) infections in patients with AIDS.

International

The World Health Organization does not track NTM infections. Incidence and prevalence undoubtedly vary greatly by locale. For an extensive review of the international epidemiology of pulmonary nontuberculous mycobacteria, please see the review article by Marras and Daley.⁹ A recent study suggests that the incidence in Thailand may be increasing.⁷

Mortality/Morbidity

• Mortality from localized M chelonae infection is rare. Death may result from extensive pulmonary or disseminated disease.
• Morbidity largely depends on the site of infection. Localized skin lesions may eventually heal without therapy or surgical intervention. At other sites, chronic infection is common.

Race

No clear racial predilection exists.

Sex

No sexual preference is known; however, approximately equal numbers of cases in men and in women were reported to the CDC from 1993-1996.⁸

Age

In general, no known age preference 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 11  

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• Workup
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• Follow-up
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History

• Patients with skin disease may have a nonhealing but nonspreading wound or skin ulcer.
• Patients with lung disease may have a chronic cough.
• Easy fatigability, occasional fever, night sweats, and weight loss occur with pulmonary or disseminated disease, although less commonly than with tuberculosis.

Physical

No physical examination findings are pathognomonic for M chelonae infection. Findings depend on infection site.

• Skin: Ulcerative lesions and/or subcutaneous nodules may be present. Deep infection may lead to draining fistulas. In contrast with Mycobacterium fortuitum infection, the skin lesions caused by M chelonae infection tend to be multiple and tend to occur in older patients and individuals receiving immunosuppressive drugs.¹⁰
• Eye: Corneal ulcers or keratitis 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, similar to that associated with peritoneal dialysis.

Causes

• Trauma or injection - Skin lesions, subcutaneous lesions, ocular lesions, and osteomyelitis
• Disseminated disease - Immunosuppression, especially AIDS or corticosteroid use
• Lung disease - Achalasia and bronchiectasis

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

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

WORKUP

Section 5 of 11  

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Lab Studies

According to American Thoracic Society (ATS) criteria^{11, 2}, diagnosis of lung disease requires (1) pulmonary symptoms with consistent radiographic features (see Imaging Studies), (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 2 separate sputum samples
    • One positive culture from bronchial wash or lavage
    • A 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 a persistent or transient colonizer without pathogenicity.
• Swab culture for acid-fast bacillus  
• • Notifying the microbiology laboratory personnel that an 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 or an "innocent bystander." In one study from Spain, 13 of 24 isolates of M chelonae were deemed of questionable clinical significance.¹²
• Additional testing if M chelonae or M abscessus 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 lung infection is found in a relatively young patient (<50 y).
  • A purified protein derivative (of tuberculin) (PPD) test should be considered to assist in ruling out tuberculosis.
• Susceptibility testing should be performed on all isolates to guide treatment. General susceptibility results reported in the new ATS guidelines are as follows:² 
• • Tobramycin - 100%
  • Clarithromycin - 100%
  • Linezolid - 90%
  • Imipenem - 60%
  • Amikacin - 50%
  • Clofazimine and doxycycline - 25%
  • Ciprofloxacin - 20%

Imaging Studies

• Chest radiography
• • Perform chest radiography if pulmonary symptoms are present. Typical findings are bilateral patchy nodular or cavitary opacities (15% are cavitary) with an upper lobe predominance.
  • 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 likely 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, including retroperitoneal abscesses, in 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 suspected osteomyelitis or joint disease, especially in patients with a history of penetrating trauma.
  • Gallium scanning may be useful to screen for supradiaphragmatic lymphadenopathy (intrathoracic or axillary).

Other Tests

• Erythrocyte sedimentation rate or C-reactive protein assessments may be useful to differentiate colonizer and pathogen, but these are nonspecific tests and the results must be carefully evaluated within the clinical context of the patient.

Procedures

• Lung procedures
• • Perform bronchoscopy with bronchial washes for acid-fast bacillus (AFB) culture, ideally with transbronchial biopsy, for culture and histology. A bronchioloalveolar lavage may also be useful. Because the diagnosis is usually uncertain at this stage, fungal cultures are typically 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 culture positive for M chelonae or M abscessus is considered diagnostic.
  • The presence of either AFB or granulomas in a lung biopsy or a transbronchial biopsy specimen along with even a single positive culture 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 AFB and fungal cultures, as well as histology.
  • PPD testing with nontuberculous mycobacterial specific antigens is nonspecific and generally not indicated. These tests are not commercially available.
• Aspiration biopsy
• • Perform an aspiration biopsy of a localized abscess for culture; this method is preferred over culture via swab of draining abscess fluid.
  • Perform a fine-needle aspiration biopsy of a lymphadenitis 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 tissue stains for AFB may reveal organisms.

Staging

Contamination, colonization, and localized and disseminated disease are present.

TREATMENT

Section 6 of 11  

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Medical Care

Local wound care for cutaneous lesions is always appropriate. With local care and antibiotics, small lesions may improve without surgical intervention.

Surgical Care

• Surgical debridement of cutaneous or subcutaneous lesions, especially if the lesions are extensive, is usually required for cure.
• Surgical excision combined with local wound care may be sufficient for cure as evidenced in one pediatric case and inference from infections due to M abscessus.¹³
• Surgical debridement of ocular and bone lesions is almost always required.
• If the infection involves an implanted device, removal of the device is almost always necessary for cure.
• Consider surgical excision of pulmonary lesions only if the 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.

Consultations

• Obtain a consultation with an infectious diseases specialist for diagnostic and therapeutic guidance.
• Obtain a consultation with a pulmonologist for lung lesions, possible bronchoscopy, and therapeutic guidance.
• Obtain a consultation with a dermatologist for possible biopsy of cutaneous lesions.
• Obtain a consultation with a surgeon for debridement and/or biopsy. Indwelling catheter placement may also be necessary if long-term antibiotics are to be administered.
• 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 11  

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Prolonged antibiotic therapy is generally required for M abscessus infections and should be considered for M chelonae infections. For serious disease due to M chelonae, a minimum of 4 months of combination therapy is required, usually with clarithromycin and an additional agent. If osteomyelitis is present, therapy should be extended to a minimum of 6 months.²

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.¹⁴ In fact, only one clinical trial has assessed monotherapy against M chelonae; clarithromycin was used in the trial, and one patient’s infection relapsed with a resistant strain.¹⁵ Test all initial isolates for antibiotic sensitivity to guide therapy because the sensitivity patterns between given isolates can vary considerably.¹⁶ Susceptibility testing does not guarantee clinical success, as correlations of susceptibility testing and clinical response have not been assessed. M chelonae tends to be more antibiotic resistant than M fortuitum.

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 chelonae infection.¹⁷

Amikacin is the preferred aminoglycoside for treating rapidly growing mycobacteria; however, tobramycin remains the most active aminoglycoside against M chelonae. M chelonae is universally resistant to cefoxitin. Imipenem also has activity against M chelonae and is the preferred carbepenem.² Ciprofloxacin and levofloxacin have activity against these organisms. Of these, ciprofloxacin has been reported most often, but levofloxacin has the better in vitro activity. Moxifloxacin also has good in vitro activity.¹⁸ Clarithromycin and azithromycin have both been used successfully and are more active than erythromycin, which should no longer be considered.

Doxycycline has activity against some isolates. Sulfamethoxazole has limited activity against M chelonae.¹⁹ Linezolid has good in vitro activity against M chelonae and has been used successfully alone and in combination to treat infections with this organism.^{20, 21} Tigecycline has good in vitro activity against both M chelonae and M fortuitum, but no clinical data exist on its use; tigecycline should be considered only in the absence of other options.²²

Topical amikacin and ciprofloxacin have been reported as useful for ocular disease. Topical quinolones may also be effective. For keratitis, fourth-generation quinolones may have increased penetration over older preparations for topical application. Additionally, they may provide some synergy with amikacin or clarithromycin.²³

Treatment with immunomodulatory agents such as interleukin (IL)–12 or interferon (IFN)–γ may be of benefit in refractory disease but should be performed only in consultation with a specialist.²⁴

No standard duration of therapy is reported. Treatment usually lasts for many months, and courses that are 6 months or longer are not unusual. Administer drugs for a duration 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.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. In some patients, waiting for sensitivity information rather than starting empiric therapy may be prudent.

Drug Name	Azithromycin (Zithromax)
Description	Use alone or in combinations.
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 >16 years: Adult dosage
Contraindications	Documented hypersensitivity to macrolides; concurrent use of 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	Amikacin (Amikin)
Description	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.
Adult Dose	5-7.5 mg/kg IV q12h (average 400 mg IV q12h) in patients with normal renal function; aim for a trough <5 mcg/mL to minimize risk of toxicity; aim for peaks near 20 mcg/mL
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; impaired vestibular dysfunction
Interactions	Enhances effects of neuromuscular blockers; high concentrations of penicillin/cephalosporin may decrease effect; amphotericin, loop diuretics, vancomycin, enflurane, and methoxyflurane increase toxicity; coadministration with amphotericin B increases nephrotoxicity; may cause respiratory depression
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Adjust dose in renal function; monitor renal function at least weekly; in patients with obesity, base initial dose on average of actual and IBW; avoid other nephrotoxic and ototoxic drugs if possible; not intended for long-term therapy; caution in renal failure (patient not on dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission

Drug Name	Tobramycin (AKTob, Tobrex)
Description	Has activity against most isolates of M chelonae. Usually used with clarithromycin for severe pulmonary or disseminated disease.
Adult Dose	3 mg/kg/d IV/IM divided tid Infrequent dosing regimens (eg, once daily) are also likely to work
Pediatric Dose	6-7.5 mg/kg/d IV/IM divided tid/qid (2-2.5 mg/kg q8h or 1.5-1.9 mg/kg q6h)
Contraindications	Documented hypersensitivity; coadministration with cidofovir
Interactions	Increases effects of neuromuscular blockers; potentiates effect of extended spectrum penicillins; concurrent administration with amphotericin B, cephalosporins, and loop diuretics increases risk of nephrotoxicity (avoid additional nephrotoxins)
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Caution in renal impairment, preexisting auditory or vestibular impairment, and neuromuscular disorders; aminoglycosides are associated with nephrotoxicity and ototoxicity; age >65 y or <1 mo

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/d PO/IV
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Antacids and electrolyte supplements reduce absorption; loop diuretics, probenecid, 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, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); superinfections may occur with prolonged or repeated antibiotic therapy; fluoroquinolones have induced seizures in patients with CNS disorders and have caused tendinitis or tendon rupture, known Q-T prolongation, concurrent administration of drugs that cause Q-T prolongation

Drug Name	Ciprofloxacin (Cipro)
Description	Inhibits bacterial DNA synthesis and, consequently, growth. Use alone or in combinations.
Adult Dose	500 mg PO q12h or 400 mg IV q12h
Pediatric Dose	<18 years: Not currently approved for use in mycobacterial infections; although sometimes used in these patients for acute infections, long-term use required for treatment of M chelonei infection is likely problematic
Contraindications	Documented hypersensitivity; avoid in CNS/seizure disorders; current use of tizanidine
Interactions	May increase levels of cyclosporine, theophylline, and caffeine; antacids and other metal cations decrease absorption; NSAIDs increase CNS adverse effects; coadministration with warfarin increases INR; may cause hyperglycemia or hypoglycemia with insulin/oral hypoglycemic therapy; 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	In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

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; 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	Do not use in ocular infections that may become systemic; superinfections may occur with prolonged or repeated antibiotic therapy

Drug Name	Levofloxacin (Levaquin)
Description	Probably fluoroquinolone of choice.
Adult Dose	500-750 mg/d PO/IV (1000 mg or bid use can be considered with more severe disease)
Pediatric Dose	<18 years: Not currently approved in mycobacterial infections; 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
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 in renal function impairment

Drug Name	Linezolid (Zyvox)
Description	Has been used alone and in combination for the treatment of M chelonae infection. Ninety percent of isolates of M chelonae are susceptible in vitro to linezolid. 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 to children aged 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, or 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 patients with uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism and 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 count); unnecessary use may lead to drug resistance; may cause peripheral or optic neuropathy In March 2007, the FDA issued an alert that linezolid may increase the risk of mortality in patients with infections due to organisms other than gram-positive bacteria (as of this writing, these findings are under further review)

Drug Name	Imipenem/cilastatin (Primaxin)
Description	Usually used with amikacin for severe pulmonary or disseminated disease.
Adult Dose	500 mg to 1 g IV q6h
Pediatric Dose	>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; may cause hepatitis and blood dyscrasias

Drug Name	Doxycycline (Bio-Tab, Doryx, Vibramycin)
Description	Because sensitivity to doxycycline is variable, usually not part of initial empiric regimen.
Adult Dose	100 mg PO qd/bid
Pediatric Dose	<8 years: Not recommended >8 years: Administer as in adults
Contraindications	Documented hypersensitivity; severe hepatic dysfunction; children <8 y
Interactions	Bioavailability is slightly decreased with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; decreased levels with CYP3A4 inducers; may increase effects of CYP3A4 substrates
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	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	D - Fetal risk shown in humans; use only 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 tetracyclines (eg, photosensitivity, pseudotumor cerebri, pancreatitis, antianabolic action)

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• 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, its sequelae, 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. Peak levels are not necessary, and trough levels may be useful to document a nontoxic range.
• Monthly sputum cultures may be useful in patients with pulmonary disease to determine the efficacy of therapy.

In/Out Patient Meds

• Administer antibiotics daily (see Medication). Infrequent dosing (eg, 2-3 times per week, 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 chelonae and M abscessus are ubiquitous organisms.
• Isolation is not indicated.
• Patients with disease due to nontuberculous mycobacteria should be considered for treatment prior to starting anti-TNF alpha agents.

Complications

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

Prognosis

• With debridement and antibiotic therapy, the prognosis is very good for most infection. Prognosis is worse if the patient is immunocompromised.
• 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 goals in this setting.
• Cure of infected implants that cannot be removed may be impossible.
• Toxicities due to prolonged antibiotic use may develop.

Patient Education

• Educate patients on the importance of adherence with multiple drug regimens to avoid the development of antibiotic resistance.
• Patients may confuse this disease with tuberculosis. Reassure patients that they are not contagious to others.
• Discuss possible medication adverse effects with most patients to increase the chance of early diagnosis.
• • Restrict sports activities for patients receiving quinolones to avoid Achilles tendon ruptures (rare).
  • Advise patients to prevent pregnancy during therapy.
• For excellent patient education resources, visit eMedicine's Procedures Center. Also, see eMedicine's patient education article Bronchoscopy.

MISCELLANEOUS

Section 9 of 11  

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

Medical/Legal Pitfalls

• No specific pitfalls are documented. The following are potential problems:
• • Failure to consider the diagnosis in patients with chronic infection is possible.
  • Because M chelonae or M abscessus may be contaminants, consider the possibility of pseudoinfection in any patient with a positive culture before committing the patient to an extended course of treatment. This is especially true of sputum samples and cultures from other nonsterile sources (eg, a swab culture of a wound).
  • Because disease caused by these organisms can be indolent, a culture positive for M chelonae or M abscessus should prompt a careful evaluation to exclude unrecognized disease.
  • Before starting medications such as amikacin, documenting whether the patient is pregnant may be useful. Documenting counseling about potential medication adverse effects may also be useful.

Special Concerns

• If an M chelonae or an M abscessus infection is believed to be nosocomial, notify hospital infection control. Finding even a single case of nosocomial NTM may warrant an investigation.

MULTIMEDIA

Section 10 of 11  

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

Media file 1:  Cutaneous lesions from Mycobacterium abscessus. Courtesy of K. Galil, US Centers for Disease Control and Prevention.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

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

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Article Last Updated: Nov 21, 2007