eMedicine Specialties > Infectious Diseases > Mycobacterial Infections

Mycobacterium Chelonae

F Matthew Kuhlmann, MD, Fellow, Division of Infectious Diseases, Washington University School of Medicine
Keith F Woeltje, MD, PhD, Associate Professor, Department of Internal Medicine, Division of Infectious Diseases, Washington University School of Medicine

Updated: Aug 26, 2009

Introduction

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

Scanning electron micrograph of Mycobacterium chelonae. Courtesy of the CDC and Janice Haney Carr.

Scanning electron micrograph of Mycobacterium chelonae. Courtesy of the CDC and Janice Haney Carr.

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 M chelonae infections 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

M chelonae infection has no clear racial predilection.

Sex

M chelonae infection has no known sexual preference; approximately equal numbers of cases in men and in women were reported to the CDC from 1993-1996.⁸

Age

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

Clinical

History

• Patients with M chelonae skin disease may have a nonhealing but nonspreading wound or skin ulcer.
• Patients with M chelonae 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
  
  

  

  Cutaneous lesions from Mycobacterium abscessus. Courtesy of K. Galil, US Centers for Disease Control and Prevention.

  
  
• 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

Differential Diagnoses

Other Problems to Be Considered

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

Workup

Laboratory Studies

According to American Thoracic Society (ATS) criteria,^11,2 diagnosis of M chelonae 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 significance12
• 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.
• ChestCT 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

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 abscessus13
• 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

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 carbapenem.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.

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.

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. Frequently used as a component of oral therapy.

Dosing

Adult

500 mg PO bid

Pediatric

7.5 mg/kg PO bid; not to exceed 500 mg bid; not approved in children <20 months

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

Contraindications

Documented hypersensitivity to macrolides; concurrent use of drugs that increase QT interval

Precautions

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

Azithromycin (Zithromax)

Use alone or in combinations.

Dosing

Adult

500-600 mg/d PO

Pediatric

<6 months: Not established
>6 months: 10 mg/kg/d PO; not to exceed 500-600 mg/d
>16 years: Adult dosage

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

Contraindications

Documented hypersensitivity to macrolides; concurrent use of drugs that prolong QT interval

Precautions

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

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.

Dosing

Adult

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

Administer as in adults

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

Contraindications

Documented hypersensitivity; impaired vestibular dysfunction

Precautions

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

Tobramycin (AKTob, Tobrex)

Has activity against most isolates of M chelonae. Usually used with clarithromycin for severe pulmonary or disseminated disease.

Dosing

Adult

3 mg/kg/d IV/IM divided tid
Infrequent dosing regimens (eg, once daily) are also likely to work

Pediatric

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)

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)

Contraindications

Documented hypersensitivity; coadministration with cidofovir

Precautions

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

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.

Dosing

Adult

400 mg/d PO/IV

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

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

Contraindications

Documented hypersensitivity

Precautions

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

Ciprofloxacin (Cipro)

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

Dosing

Adult

500 mg PO q12h or 400 mg IV q12h

Pediatric

<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

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

Contraindications

Documented hypersensitivity; avoid in CNS/seizure disorders; current use of tizanidine

Precautions

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

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.

Dosing

Adult

1-2 gtt in the eye(s) q2h while awake for 2 d and 1-2 gtt q4h while awake

Pediatric

<1 year: Not recommended
>1 year: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; coadministration with steroid combinations after uncomplicated removal of a foreign body from cornea

Precautions

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

Levofloxacin (Levaquin)

Probably fluoroquinolone of choice.

Dosing

Adult

500-750 mg/d PO/IV (1000 mg or bid use can be considered with more severe disease)

Pediatric

<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

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

Contraindications

Documented hypersensitivity

Precautions

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

Linezolid (Zyvox)

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.

Dosing

Adult

400-600 mg PO/IV q12h

Pediatric

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

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

Contraindications

Documented hypersensitivity

Precautions

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)

Imipenem/cilastatin (Primaxin)

Usually used with amikacin for severe pulmonary or disseminated disease.

Dosing

Adult

500 mg to 1 g IV q6h

Pediatric

>3 months: 15-25 mg/kg IV q6h, each dose not to exceed 500 mg (not to exceed 2 g/d)

Interactions

Coadministration with cyclosporine may increase CNS adverse effects of both agents; coadministration with ganciclovir may result in generalized seizures

Contraindications

Documented hypersensitivity

Precautions

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

Doxycycline (Bio-Tab, Doryx, Vibramycin)

Because sensitivity to doxycycline is variable, usually not part of initial empiric regimen.

Dosing

Adult

100 mg PO qd/bid

Pediatric

<8 years: Not recommended
>8 years: Administer as in adults

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

Contraindications

Documented hypersensitivity; severe hepatic dysfunction; children <8 y

Precautions

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

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.

Dosing

Adult

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

<18 years: Not established
>18 years: Administer as in adults

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

Contraindications

Documented hypersensitivity

Precautions

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

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.

Inpatient & Outpatient Medications

• 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

Medicolegal 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

Media file 1: Cutaneous lesions from Mycobacterium abscessus. Courtesy of K. Galil, US Centers for Disease Control and Prevention.

Media file 2: Scanning electron micrograph of Mycobacterium chelonae. Courtesy of the CDC and Janice Haney Carr.

Media file 3: Scanning electron micrograph of Mycobacterium chelonae. Courtesy of the CDC and Janice Haney Carr.

References

1. Simmon KE, Pounder JI, Greene JN, Walsh F, Anderson CM, Cohen S. Identification of an emerging pathogen, Mycobacterium massiliense, by rpoB sequencing of clinical isolates collected in the United States. J Clin Microbiol. Jun 2007;45(6):1978-80. [Medline].

2. [Guideline] Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. Feb 15 2007;175(4):367-416. [Medline].

3. Hadjiliadis D, Adlakha A, Prakash UB. Rapidly growing mycobacterial lung infection in association with esophageal disorders. Mayo Clin Proc. Jan 1999;74(1):45-51. [Medline].

4. Sañudo A, Vallejo F, Sierra M, Hoyos JG, Yepes S, Wolff JC. Nontuberculous mycobacteria infection after mesotherapy: preliminary report of 15 cases. Int J Dermatol. Jun 2007;46(6):649-53. [Medline].

5. Centers for Disease Control and Prevention. Mycobacterium chelonae infections associated with face lifts--New Jersey, 2002-2003. MMWR Morb Mortal Wkly Rep. Mar 12 2004;53(9):192-4. [Medline].

6. Vijayaraghavan R, Chandrashekhar R, Sujatha Y, Belagavi CS. Hospital outbreak of atypical mycobacterial infection of port sites after laparoscopic surgery. J Hosp Infect. Dec 2006;64(4):344-7. [Medline].

7. Chetchotisakd P, Kiertiburanakul S, Mootsikapun P, Assanasen S, Chaiwarith R, Anunnatsiri S. Disseminated nontuberculous mycobacterial infection in patients who are not infected with HIV in Thailand. Clin Infect Dis. Aug 15 2007;45(4):421-7. [Medline].

8. Centers for Disease Control and Prevention. Nontuberculous Mycobacteria Reported to the Public Health Laboratory Information System by State Public Health Laboratories United States, 1993-1996. [Full Text].

9. Marras TK, Daley CL. Epidemiology of human pulmonary infection with nontuberculous mycobacteria. Clin Chest Med. Sep 2002;23(3):553-67. [Medline].

10. Uslan DZ, Kowalski TJ, Wengenack NL, Virk A, Wilson JW. Skin and soft tissue infections due to rapidly growing mycobacteria: comparison of clinical features, treatment, and susceptibility. Arch Dermatol. Oct 2006;142(10):1287-92. [Medline].

11. American Thoracic Society. 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].

12. Esteban J, Fernández Roblas R, García Cía JI, Zamora N, Ortiz A. Clinical significance and epidemiology of non-pigmented rapidly growing mycobacteria in a university hospital. J Infect. Feb 2007;54(2):135-45. [Medline].

13. Fonseca MT, Fonseca MM, Bicalho R, Hadad DJ. Mycobacterium chelonae synovitis. Pediatr Infect Dis J. Nov 2006;25(11):1086. [Medline].

14. Tebas P, Sultan F, Wallace RJ Jr, Fraser V. Rapid development of resistance to clarithromycin following monotherapy for disseminated Mycobacterium chelonae infection in a heart transplant patient. Clin Infect Dis. Feb 1995;20(2):443-4. [Medline].

15. Wallace RJ Jr, Tanner D, Brennan PJ, Brown BA. Clinical trial of clarithromycin for cutaneous (disseminated) infection due to Mycobacterium chelonae. Ann Intern Med. Sep 15 1993;119(6):482-6. [Medline].

16. Wallace RJ Jr, 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].

17. Heifets LB. Antimycobacterial drugs. Semin Respir Infect. Jun 1994;9(2):84-103. [Medline].

18. Brown-Elliott BA, Wallace RJ, Crist CJ, et al. 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].

19. Woods GL, Bergmann JS, Witebsky FG, Fahle GA, Wanger A, Boulet B. Multisite reproducibility of results obtained by the broth microdilution method for susceptibility testing of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum. J Clin Microbiol. Jun 1999;37(6):1676-82. [Medline].

20. Brown-Elliott BA, Wallace RJ, Blinkhorn R, et al. Successful treatment of disseminated Mycobacterium chelonae infection with linezolid. Clin Infect Dis. Oct 15 2001;33(8):1433-4. [Medline].

21. Wallace RJ Jr, Brown-Elliott BA, Ward SC, et al. Activities of linezolid against rapidly growing mycobacteria. Antimicrob Agents Chemother. Mar 2001;45(3):764-7. [Medline].

22. Wallace RJ, Brown-Elliott BA, Crist CJ, et al. 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].

23. Hyon JY, Joo MJ, Hose S, Sinha D, Dick JD, O'Brien TP. Comparative efficacy of topical gatifloxacin with ciprofloxacin, amikacin, and clarithromycin in the treatment of experimental Mycobacterium chelonae keratitis. Arch Ophthalmol. Aug 2004;122(8):1166-9. [Medline].

24. Holland SM. Nontuberculous mycobacteria. Am J Med Sci. Jan 2001;321(1):49-55. [Medline].

25. Griffith DE, Wallace RJ. New developments in the treatment of nontuberculous mycobacterial (NTM) disease. Semin Respir Infect. Dec 1996;11(4):301-10. [Medline].

26. Iseman MD, Marras TK. The importance of nontuberculous mycobacterial lung disease. Am J Respir Crit Care Med. Nov 15 2008;178(10):999-1000. [Medline].

27. Kim RD, Greenberg DE, Ehrmantraut ME, Guide SV, Ding L, Shea Y, et al. Pulmonary nontuberculous mycobacterial disease: prospective study of a distinct preexisting syndrome. Am J Respir Crit Care Med. Nov 15 2008;178(10):1066-74. [Medline].

28. Kyle SD, Porter WM. Mycobacterium chelonae infection successfully treated with oral clarithromycin and linezolid. Br J Dermatol. Nov 2004;151(5):1101. [Medline].

29. Mitchell JD, Bishop A, Cafaro A, Weyant MJ, Pomerantz M. Anatomic lung resection for nontuberculous mycobacterial disease. Ann Thorac Surg. Jun 2008;85(6):1887-92; discussion 1892-3. [Medline].

30. Parrish SC, Myers J, Lazarus A. Nontuberculous mycobacterial pulmonary infections in Non-HIV patients. Postgrad Med. Nov 2008;120(4):78-86. [Medline].

31. Tabarsi P, Baghaei P, Farnia P, Mansouri N, Chitsaz E, Sheikholeslam F, et al. Nontuberculous mycobacteria among patients who are suspected for multidrug-resistant tuberculosis-need for earlier identification of nontuberculosis mycobacteria. Am J Med Sci. Mar 2009;337(3):182-4. [Medline].

32. U.S. Food and Drug Administration. Available at http://www.fda.gov/cder/drug/infopage/linezolid/default.htm.

33. van Ingen J, Boeree MJ, de Lange WC, Dekhuijzen PN, van Soolingen D. Impact of new American Thoracic Society diagnostic criteria on management of nontuberculous mycobacterial infection. Am J Respir Crit Care Med. Aug 15 2007;176(4):418; author reply 419. [Medline].

34. Wagner D, Young LS. Nontuberculous mycobacterial infections: a clinical review. Infection. Oct 2004;32(5):257-70. [Medline].

Keywords

Mycobacterium chelonei, M chelonei, M chelonae, Mycobacterium chelonae, Mycobacterium abscessus, M abscessus, nontuberculous mycobacterium, nontuberculous mycobacteria, mycobacterium other than tuberculosis, MOTT, Mycobacterium tuberculosis, mycobacterial cutaneous infection, NTM, NTM lung disease, AIDS, HIV, Runyon classification, Runyon's classification, Runyon classification group IV, Runyon group IV, rapidly growing mycobacteria, osteomyelitis, keratitis, corneal ulcers

Contributor Information and Disclosures

Author

F Matthew Kuhlmann, MD, Fellow, Division of Infectious Diseases, Washington University School of Medicine
F Matthew Kuhlmann, MD is a member of the following medical societies: American Medical Association and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Keith F Woeltje, MD, PhD, Associate Professor, Department of Internal Medicine, Division of Infectious Diseases, Washington University School of Medicine
Keith F Woeltje, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Medical Informatics Association, Infectious Diseases Society of America, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

Medical Editor

Klaus-Dieter Lessnau, MD, FCCP, Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital
Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Artificial Internal Organs, American Thoracic Society, Physicians for Social Responsibility, and Society of Critical Care Medicine
Disclosure: sepracor Ownership interest None

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Aaron Glatt, MD, Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, New Island Hospital
Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Clinical trials

Study of Mycobacterial Infections

Serum Inflammatory Marker in Patients With Diagnosis of Nontuberculous Mycobacterial Pulmonary Infection

Mycobacterial and Opportunistic Infections in HIV-Negative Thai and Taiwanese Patients Associated With Autoantibodies to Interferon-gamma

Genetic Disorders of Mucociliary Clearance in Nontuberculous Mycobacterial Lung Disease

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