eMedicine Specialties > Infectious Diseases > Mycobacterial Infections

Mycobacterium Kansasii

Janak Koirala, MD, MPH, FACP, Associate Professor, Department of Internal Medicine, Division of Infectious Diseases, Southern Illinois University School of Medicine

Updated: Mar 18, 2009

Introduction

Background

Mycobacterium kansasii is an acid-fast bacillus (AFB) that is readily recognized based on its characteristic photochromogenicity, which produces a yellow pigment when exposed to light. In 1953, Buhler and Pollack first described the bacterium. Under light microscopy, M kansasii appears relatively long, thick, and cross-barred.

The most common presentation of M kansasii infection is a chronic pulmonary infection that resembles pulmonary tuberculosis. However, it may also infect other organs. M kansasii infection is the second-most-common nontuberculous opportunistic mycobacterial infection associated with AIDS, surpassed only by Mycobacterium avium complex (MAC) infection. For this reason, the incidence of M kansasii infection has increased because of the HIV/AIDS epidemic.

Pathophysiology

Unlike other nontuberculous mycobacteria (NTM), M kansasii is not readily isolated from environmental sources. However, it has been isolated from a small percentage of specimens obtained from water supplies in areas with high endemicity. Most likely, M kansasii is acquired via either aspiration or local inoculation from the environment. Little evidence exists of person-to-person transmission. Molecular characterization of M kansasii shows that it is a homogeneous group of organisms. Five genotypes, or subtypes, are described. Types I and II are common clinical isolates, while the remaining types (III, IV, V) are recovered from environmental samples only. Type I probably is the most prevalent M kansasii isolate from human sources worldwide.

M kansasii infection of the lung causes a pulmonary disease similar to tuberculosis. Its histopathologic appearance is similar to that of tuberculosis and may include acute suppuration, nonnecrotic tubercles, or caseation. In persons with AIDS or in patients with other forms of immunocompromise, many of its characteristic histologic features may be absent.

After skin inoculation, M kansasii can cause local disease of the skin and subcutaneous tissue. It may spread from the local site and cause lymphadenitis, infection of a distant organ, or disseminated disease.

Frequency

United States

The prevalence of M kansasii, an unusual pathogen in the pre-AIDS era, has increased with the HIV pandemic. M kansasii is the second-most-common cause of NTM disease in patients with AIDS. M kansasii infection has typically been described as a disease of urban dwellers and of patients with high incomes and better standards of living. One study of 3 northern California counties found that M kansasii infection was more common in census tracts with a lower income (median income <$32,000). However, this study consisted of a large proportion of patients with HIV infection.¹

M kansasii infection occurs throughout the United States, with the highest incidence in the Midwest and the Southwest. The study mentioned above, which was performed in northern California, estimated an overall incidence of 2.4 cases per 100,000 adults per year in the general population, 115 cases per 100,000 persons with HIV infection per year, and 647 cases per 100,000 persons with AIDS per year. This incidence of M kansasii infection is much higher than that determined by a national laboratory surveillance during 1982-1983, which estimated a prevalence of 0.3 cases per 100,000 persons.

International

M kansasii infection has been reported in most areas of the world. The incidence appears to be relatively high in England and Wales and among South African gold miners.² In the United Kingdom, it has been reported as the most common cause of NTM lung infection in patients without HIV infection.³

An increasing incidence of NTM infections, including M kansasii, has been reported in other countries, including Israel, Korea, Portugal, France, and Japan.

Mortality/Morbidity

The likelihood of mortality associated with M kansasii infection depends on various factors, including the presence of comorbid diseases, treatment compliance, rifampicin use, and extent of infection. One US center's experience, which included 302 patients over more than a 50-year period (1952-1995), showed a mortality rate of 11%, but this included both immunocompromised and nonimmunocompromised patients.⁴

• A retrospective study of South African gold miners treated for M kansasii infection reported mortality rates of 2% in those without HIV infection and 9% in patients with HIV infection.²
• Untreated pulmonary M kansasii disease progresses and can lead to death in more than 50% of infected individuals.

Race

M kansasii infection has no reported racial predilection.

Sex

M kansasii infection is more common men, with a male-to-female ratio of 3:1.

Age

• M kansasii infection is more common in the older population and is rare in children.
• The age predilection shifts in conjunction with age predilections of HIV infection.

Clinical

History

In most cases, M kansasii causes lung disease that is clinically indistinguishable from tuberculosis. Symptoms may be less severe and more chronic than Mycobacterium tuberculosis infection. Asymptomatic M kansasii infection occurs in a small proportion (16%) of affected patients.⁴

• Healthy host
  • The most common symptoms of pulmonary M kansasii infection include cough (91%), sputum production (85%), weight loss (53%), breathlessness (51%), chest pain (34%), hemoptysis (32%), and fever or sweats (17%).⁵
  • Cutaneous M kansasii infection resembles sporotrichosis secondary to local lymphatic spread. Cutaneous lesions may include nodules, pustules, verrucous lesions, erythematous plaques, abscesses, and ulcers.
• Immunocompromised host
  • M kansasii infection manifests late in the course of HIV disease. The lung is the organ most commonly involved. Commonly reported symptoms include fever, chills, night sweats, productive or nonproductive cough, weight loss, fatigue, dyspnea, and chest pain.
  • Almost 20% of patients with HIV infection who develop M kansasii infection eventually develop disseminated disease.
  • M kansasii meningitis similar to M tuberculosis meningitis has been reported in patients infected with HIV and may carry a higher mortality rate despite appropriate antibiotic therapy.
  • M kansasii bacteremia, pericarditis with cardiac tamponade, oral ulcers, chronic sinusitis, osteomyelitis, and scalp abscess have been reported in patients with AIDS.
  • Disseminated M kansasii infection has also been reported in other immunocompromised hosts (eg, patients with myelodysplastic syndrome, patients on hemodialysis).
  • Cutaneous M kansasii infections in immunocompromised hosts usually have atypical clinical features (eg, cellulitis, seroma). These features, along with atypical histology (eg, absence of granuloma), may delay diagnosis.

Physical

• Common physical findings of M kansasii infection include the following:
  • Fever
  • Pulmonary crackles and wheezing
  • Lymphadenopathy
• Analysis of a series of 49 patients coinfected with HIV showed the following physical findings at the time of initial isolation of M kansasii:⁶
  • Pulmonary disease
    • Fever (45%)
    • Lung crackles (40%)
    • Lymphadenopathy (25%)
    • Wheezes (20%)
    • Hepatosplenomegaly (5%)
  • Disseminated disease
    • Fever (60%)
    • Hepatosplenomegaly (40%)
    • Lung crackles (25%)
    • Lymphadenopathy (10%)
    • Cutaneous lesions (10%)
    • Wheezes (5%)
• Patients with cutaneous M kansasii infection may develop nodules, pustules, verrucous lesions, erythematous plaques, abscesses, or ulcers.
• Other signs depend on the site of infection or dissemination.

Causes

Immunocompromised patients, including patients with HIV/AIDS, are at a high risk for M kansasii infection.

• Predisposing conditions for M kansasii infection include pulmonary conditions resulting from pneumoconioses (especially silicosis, gold mining, and coal mining), healed chronic infections (eg, tuberculosis, mycosis, chronic obstructive pulmonary disease, bronchiectasis), heavy smoking, and chronic obstructive pulmonary disease.
• Other risk factors include cancer, diabetes mellitus, long-term steroid use, alcoholism, peptic ulcer disease, coronary artery disease, and prior pneumonia.

Differential Diagnoses

Other Problems to Be Considered

Mycobacterium scrofulaceum infection
Bacterial cellulitis

Workup

Laboratory Studies

• Diagnosis of M kansasii infection requires isolation of the organism. Unlike other nontuberculous mycobacteria (NTM), M kansasii is believed to rarely represent colonization or an environmental contaminant.
• Initially, evaluate at least 3 sputum samples by AFB staining and mycobacterial cultures. Bacteriologic examination may include AFB stain and culture of specimens (eg, bronchoalveolar lavage, aspirates from sterile sites, tissues).
• Blood culture may be useful to detect M kansasii bacteremia and to establish a diagnosis of disseminated infection. Approximately 10% of patients with HIV infection who are also infected with M kansasii have blood cultures positive for M kansasii.
• Nucleic acid probes and polymerase chain reaction (PCR) are useful for early identification of growing M kansasii colonies. They are highly sensitive and specific, providing species identification using a culture directly from BACTEC broth within 2-4 hours.
• Susceptibility testing: The Clinical and Laboratory Standards Institute (CLSI) recommends that all initial isolates of M kansasii be tested only for rifampin susceptibility.⁷ Rifampin-susceptible isolates are also susceptible to rifabutin. If the isolate is resistant to rifampin, further susceptibility to rifabutin, isoniazid, streptomycin, clarithromycin, amikacin, ethambutol, trimethoprim-sulfamethoxazole, ciprofloxacin, moxifloxacin, and gatifloxacin should be determined. Rifampin-resistant isolates should be sent to an experienced reference laboratory for further testing.⁸ Ciprofloxacin susceptibility results mirror those of susceptibility for both ofloxacin and levofloxacin.
• Interpretation of isoniazid susceptibility may be confusing because most M kansasii organisms show resistance to IN isoniazid H at 1 mcg/mL but are susceptible at 5 mcg/mL. The latter reflects a better correlation with in vivo isoniazid activity.
• The currently available skin test is not helpful in establishing diagnosis.

Imaging Studies

• Approximately 90% of patients with M kansasii disease have cavitary infiltrates on chest radiography. Among patients without cavitary lung lesions, clinical symptoms and high-resolution computed tomography (HRCT) scanning are important adjuncts in defining the presence of lung disease.
  
  

  

  Chest radiograph in a patient with Mycobacterium kansasii pulmonary infection shows left lower lung infiltrates.

  
  
  

  

  Chest CT scan in a patient with Mycobacterium kansasii pulmonary infection (see Image 1).

  
  
  

  

  Chest radiograph in a patient with classic right upper lobe cavitary lung disease secondary to Mycobacterium kansasii infection (see Image 4 for CT thorax in the same patient). Courtesy of Raj Sreedhar, MD, SIU School of Medicine, Springfield, IL.

  
  
  

  

  CT thorax of a patient with classic right upper lobe cavitary lung disease secondary to Mycobacterium kansasii infection (see Image 3 for the chest radiograph in the same patient). Courtesy of Raj Sreedhar, MD, SIU School of Medicine, Springfield, IL.

  
  
• The characteristic radiological feature of M kansasii pulmonary infection has been described as a right-sided, apical or subapical, thin-walled cavitary infiltrate.⁴ In a separate study, which included only patients without HIV infection, a comparison of chest radiography findings in patients with M kansasii infection with those in patients with tuberculosis showed that M kansasii infection occurred more frequently as unilateral, right-sided infiltrates. Cavities were observed in both cases, whereas pleural effusions and air space shadowing involving multiple bronchopulmonary segments were less common in M kansasii infection.³
• Analysis of chest radiographs in a series of 16 patients infected with HIV and M kansasii pulmonary infection showed the following abnormalities (in decreasing order of frequency):
  1. Alveolar opacities
  2. Cavity
  3. Thoracic lymphadenopathy
  4. Pleural effusions
  5. Interstitial opacities

Other Tests

• Baseline laboratory workup for M kansasii infection should include complete blood cell count (CBC), renal profile, and liver profile.
• Patients with M kansasii infection should be counseled about HIV infection and tested for HIV infection.
• Perform a complete HIV evaluation if the patient tests positive for HIV. This evaluation should include CD4 counts and HIV viral load.

Procedures

• Bronchoscopy, tissue biopsy, thoracentesis, or pericardiocentesis may be needed to recover the pathogen and establish diagnosis. In some cases, transthoracic needle aspiration or open-lung biopsy may be necessary.
• Bone marrow and liver biopsies may be useful in establishing disseminated M kansasii infection.
• Needle aspiration or biopsy of a skin lesion (eg, nodule) may be useful for establishing M kansasii skin infections.

Histologic Findings

The variable histopathologic findings of M kansasii disease may include acute suppuration, nonnecrotic tubercles, or caseation. In general, the findings are similar to tuberculosis.

Examination of lung tissue and lymph nodes usually shows caseating granulomas. Skin lesions may show granulomas with areas of necrosis or foci of acute and chronic inflammation without well-formed granulomas. Other tissues may show caseating or noncaseating granulomas.

AFB are commonly seen in tissues from lungs and lymph nodes. They are found less commonly in tissues from other sites.

In patients with AIDS or other immunocompromised states, many of the histologic characteristics usually associated with M kansasii infection may be absent. Cytologic and histologic material may show a wide range of inflammatory reactions, including granulomas with and without necrosis, neutrophilic abscesses, spindle-cell proliferation, and focal granular eosinophilic necrosis.⁹

Diagnostic Criteria Based on American Thoracic Society/Infectious Disease Society of America Guidelines

In 1997, the American Thoracic Society (ATS) established diagnostic criteria for NTM lung disease, regardless of the host's HIV status.¹⁰ These guidelines were revised and approved by the American Thoracic Society and Infectious Disease Society of America (IDSA) in 2007.

M kansasii is considered a highly pathogenic mycobacterium, and many experts advise that M kansasii isolated from lungs or elsewhere almost always warrants treatment, especially in patients with HIV/AIDS and in other immunocompromised groups. The authors of the ATS/IDSA guidelines also acknowledge and suggest that the treatment decisions for M kansasii should be made carefully, even if some specimens are not positive for M kansasii or if multiple specimens are not available, and they recommend expert consultation in the decision-making process.

The general diagnostic criteria for all NTM pulmonary infections based on 2007 ATS/IDSA guidelines are summarized below.¹¹

Clinical criteria

Both of the following clinical criteria are required to establish a diagnosis of NTM lung disease:

• Pulmonary symptoms, nodular or cavitary opacities on chest radiography, or a HRCT scan that shows multifocal bronchiectasis with multiple small nodules
• Appropriate exclusion of other diagnoses

Microbiologic criteria

One of the following microbiologic criteria is required for diagnosis of NTM lung disease:

• Positive culture results from at least 2 separate expectorated sputum samples (If these culture results are nondiagnostic, consider repeat sputum AFB smears and cultures.)
• Positive culture result from at least one bronchial wash or lavage
• Transbronchial or other lung biopsy sample with mycobacterial histopathologic features (granulomatous inflammation or AFB) and positive culture for NTM; alternatively, a biopsy sample showing mycobacterial histopathologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washings that are culture-positive for NTM

The ATS/IDSA guideline also recommends the followings for diagnosis:

• Expert consultation should be obtained when NTM that are either infrequently encountered or that usually represent environmental contamination are recovered.
• Patients with suspected NTM lung disease but who do not meet the diagnostic criteria should be observed until the diagnosis is firmly established or excluded.
• A diagnosis of NTM lung disease does not automatically necessitate the institution of therapy, which is a decision based on potential risks and benefits of therapy in individual patients.

Treatment

Medical Care

In general, M kansasii shows good in vitro susceptibility to rifampin, rifabutin, ethambutol, ethionamide, amikacin, streptomycin, clarithromycin, sulfamethoxazole, and ciprofloxacin. Rifampin-resistant strains are usually cross-resistant to rifabutin and, therefore, need separate susceptibility testing. In vitro susceptibility of isoniazid should be interpreted carefully, as it does not correlate with clinical outcome. In patients with no prior exposure to isoniazid, the drug is useful in the treatment of M kansasii infection, regardless of poor susceptibility results. Isoniazid susceptibility testing in laboratories is performed at lower concentrations (0.2 or 1 mcg/mL), which were designed for M tuberculosis, whereas M kansasii susceptibility requires a higher concentration (5 mcg/mL) . Pyrazinamide should not be used to treat M kansasii infection.

Patients in whom M kansasii infection is diagnosed should be treated with at least 3 drugs. The initial drug regimen should include rifampin, which has been shown to yield low failure rates (1.1%) and low long-term relapse rates (<1%).¹² Rifampin is the cornerstone of treatment for M kansasii infection.

The 2007 ATS/IDSA guidelines for nontuberculous mycobacterial (NTM) infections recommend the following regimens for treatment of M kansasii infection:¹¹

• First-line regimen: This consists of rifampin (10 mg/kg/day; maximum, 600 mg) plus ethambutol (15 mg/kg/day) plus isoniazid (5 mg/kg/day; maximum 300 mg) plus pyridoxine (50 mg/day), with the treatment duration continuing until sputum culture results are negative for 12 months.
• Alternative regimen: In patients with rifampin-resistant M kansasii disease, a 3-drug regimen should be used based on in vitro susceptibilities. These 3 drugs should include clarithromycin or azithromycin, moxifloxacin, ethambutol, sulfamethoxazole, or streptomycin.

Patients with M kansasii pulmonary infection should be closely monitored with routine clinical examinations and regular sputum for AFB smears and cultures for mycobacteria during the treatment period. The antimycobacterials can be stopped after AFB sputum results are negative for at least 12 months.

Patients with extrapulmonary and disseminated M kansasii infections should be treated in a similar manner to those with pulmonary disease.

Surgical Care

Surgical treatment is unnecessary in M kansasii infection, as it responds very well to antimycobacterial therapy.

Consultations

• Infectious disease specialist, especially in patients who are co-infected with HIV
• Pulmonologist if bronchoscopy with bronchoalveolar lavage and transbronchial biopsies are needed
• Dermatologist if skin is involved and biopsy is desired
• Thoracic surgeon if open-lung biopsy is necessary (rare)

Diet

A dietitian should evaluate malnourished patients.

Activity

Activity is not limited in patients with M kansasii infection and should be performed as tolerated.

Medication

The 2007 ATS/IDSA guideline for the treatment of M kansasii pulmonary disease recommends a regimen containing rifampin (600 mg), ethambutol (15 mg/kg) and isoniazid (300 mg) with pyridoxine (50 mg) daily for a total duration that includes at least 12 months of negative sputum culture results.

Patients with severe M kansasii infections and disseminated infections should also be treated with 3-drug regimens similar to that instituted for pulmonary infection . Rifampin should not be used concurrently with HIV protease inhibitors or nonnucleoside reverse transcriptase inhibitors (NNRTIs) because rifampin significantly enhances their metabolism. Rifabutin at a lower dose (150 mg/d) should be substituted for rifampin in patients receiving protease inhibitors.

Patients who are infected with rifampin-resistant M kansasii or who are intolerant to rifampin should be treated with a 3-drug regimen based on susceptibility results. For example, rifampin-resistant M kansasii can be treated with a combination of clarithromycin or azithromycin and moxifloxacin with ethambutol or sulfamethoxazole.

Most M kansasii isolates are pyrazinamide-resistant in vitro. Pyrazinamide is unacceptable as an alternative drug for M kansasii infection.

Other agents with useful activity against M kansasii include fluoroquinolones (moxifloxacin, sparfloxacin), aminoglycosides (streptomycin, amikacin), sulfamethoxazole, and linezolid.¹³

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Rifampin (Rifadin, Rimactane)

Considered the most important drug. Inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Cross-resistance may occur. Treat for 6-9 mo or until 6 mo have elapsed from conversion to sputum culture negativity.

Dosing

Adult

10 mg/kg/d PO/IV

Pediatric

10-20 mg/kg/d PO/IV

Interactions

Induces microsomal enzymes, which may decrease effects of acetaminophen, PO anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, PO contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with INH may result in higher rate of hepatotoxicity than with either agent alone (discontinue 1 or both agents if alterations in LFT results occur)

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

Obtain CBCs and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur

Isoniazid (INH, Laniazid)

Best combination of effectiveness, low cost, and minor adverse effects. First-line drug unless known resistance or another contraindication is present. Therapeutic regimens of <6 mo demonstrate unacceptably high relapse rate.
Coadministration of pyridoxine is recommended if peripheral neuropathies secondary to INH therapy develop. Prophylactic doses of 6-50 mg of pyridoxine daily are recommended.

Dosing

Adult

5-10 mg/kg/d PO; usual dose 300 mg/d

Pediatric

5-10 mg/kg/d PO

Interactions

Higher incidence of INH-related hepatitis can occur with alcohol ingestion on daily basis; aluminum salts may decrease INH serum levels (administer 1-2 h before taking aluminum salts); may increase anticoagulant effects with coadministration; may inhibit metabolic clearance of benzodiazepines; carbamazepine toxicity or INH hepatotoxicity may result from concurrent use (monitor carbamazepine concentrations, liver function); coadministration with cycloserine may increase CNS adverse effects (eg, dizziness); acute behavioral and coordination changes may occur with coadministration of disulfiram; coadministration with rifampin after halothane anesthesia may result in hepatotoxicity and hepatic encephalopathy; may inhibit hepatic microsomal enzymes and increase toxicity of hydantoin

Contraindications

Documented hypersensitivity; previous INH-associated hepatic injury or other severe adverse reactions

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

Caution in renal and hepatic impairment because severe or fatal hepatitis may develop; hepatotoxicity is increased in patients with preexisting alcoholic liver disease, pregnancy, and when used in combination with acetaminophen; periodic ophthalmologic examinations during INH therapy are recommended, even when visual symptoms do not occur; pyridoxine (10-50 mg/d) is recommended for prevention of peripheral neuropathy (especially in patients with poor nutrition, alcoholism, diabetes mellitus, uremia, and children with low milk or meat intake)

Ethambutol (Myambutol)

Impairs cell metabolism by inhibiting synthesis of 1 or more metabolites, which in turn, causes cell death. No cross-resistance demonstrated.
Mycobacterial resistance is frequent with previous therapy. Use in combination with second-line drugs that have not been administered previously.
Administer q24h until permanent bacteriologic conversion and maximal clinical improvement are observed. Absorption is not significantly altered by food.

Dosing

Adult

15 mg/kg/d PO; not to exceed 2.5 g/d

Pediatric

<12 years: Not recommended, but has been used in tuberculosis with a small chance of ocular toxicity ( <5%)
>12 years: Administer as in adults

Interactions

Aluminum salts may delay and reduce absorption (administer several h before or after EMB dose)

Contraindications

Documented hypersensitivity; optic neuritis (unless clinically indicated)

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Use only in children in whom visual acuity can be monitored; reduce dose in impaired renal function; has visual adverse effects that are reversible if promptly discontinued

Rifabutin (Mycobutin)

Ansamycin antibiotic derived from rifamycin S. Inhibits DNA-dependent RNA polymerase, preventing chain initiation, in susceptible strains of Escherichia coli and Bacillus subtilis but not in mammalian cells. If GI upset occurs, administer dose bid with food.

Dosing

Adult

300 mg PO qd

Pediatric

5 mg/kg PO qd

Interactions

Inducer of hepatic microsomal enzymes leading to reduction in plasma concentrations of many drugs, including barbiturates, chloramphenicol, corticosteroids, cyclosporine, digoxin, fluconazole, itraconazole, ketoconazole, methadone, PO anticoagulants, PO contraceptives, quinidine, halothane, theophylline, and verapamil; microsomal enzyme inhibitors (eg, fluconazole, protease inhibitors, clarithromycin) increase plasma rifabutin concentrations; in patients infected with HIV who are on protease inhibitors, rifabutin (150 mg/d) should be used as alternative for rifampin; has less effect than rifampin on metabolism of protease inhibitors

Contraindications

Documented hypersensitivity; WBC <1000/µL; platelet count <50,000/µL

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with liver impairment; perform hematologic studies periodically because of association with neutropenia and, more rarely, thrombocytopenia

Clarithromycin (Biaxin)

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

Dosing

Adult

500 mg PO bid or 1 g PO qd if Biaxin XL

Pediatric

7.5 mg/kg PO bid

Interactions

Toxicity increases with coadministration of fluconazole and pimozide; clarithromycin 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 arrhythmia may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmia and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents

Contraindications

Documented hypersensitivity; coadministration of pimozide

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 half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

Streptomycin

Recommended by some experts during the initial phase, especially with positive sputum smear results and positive blood cultures. For treatment of susceptible mycobacterial infections.
Use in combination with other antituberculous drugs (eg, INH, EMB, rifampin).

Dosing

Adult

15 mg/kg (usually 1 g) IM, 3-5 doses/wk

Pediatric

20-40 mg/kg/d IM for 7-14 d or until patient is afebrile for 5-7 d; not to exceed 0.75-1 g/d

Interactions

Nephrotoxicity may be increased with aminoglycosides, amphotericin B, and loop diuretics

Contraindications

Documented hypersensitivity; non–dialysis-dependent renal insufficiency

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Narrow therapeutic index; not intended for long-term therapy; caution in renal failure (patient not taking dialysis); caution with myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission

Amikacin (Amikin)

Occasionally necessary during initial treatment phase, especially with positive sputum smear results. Irreversibly binds to 30S subunit of bacterial ribosomes. Blocks recognition step in protein synthesis. Causes growth inhibition. Use patient's IBW for dosage calculation.

Dosing

Adult

500-1000 mg IV, 3-5 doses/wk

Pediatric

Administer as in adults

Interactions

Coadministration with other aminoglycosides and amphotericin B increases nephrotoxicity; enhances effects of neuromuscular blocking agents; causes respiratory depression; irreversible hearing loss may occur with coadministration of loop diuretics

Contraindications

Documented hypersensitivity; renal insufficiency

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Not intended for long-term therapy; caution in patients with renal failure (patient not taking dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission

Moxifloxacin (Avelox)

Inhibits bacterial DNA synthesis and growth. Activity is similar to that of ciprofloxacin and levofloxacin.

Dosing

Adult

400 mg PO/IV qd for 10 d

Pediatric

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

Interactions

Antacids, 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; known QT prolongation, concurrent administration of drugs that cause QT prolongation

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, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); superinfections may occur with prolonged or repeated antibiotic therapy; fluoroquinolones have induced seizures in CNS disorders and caused tendinitis or tendon rupture

Follow-up

Further Inpatient Care

• Isolation is not required in patients with M kansasii infection.

Further Outpatient Care

• Monitor patient care clinically and with chest radiography to assess response to therapy and clinical improvement. Induced sputum sample collection at regular intervals for AFB stain and culture are useful.
• Monitor patients for drug toxicity, including periodic monitoring for the following:
  • Visual acuity, visual symptoms, and color vision in patients receiving ethambutol
  • Uveitis due to rifabutin, indicated by eye pain, decreased visual acuity, and anterior chamber fluid level
  • Liver enzymes for hepatotoxicity caused by drugs such as isoniazid, rifampin, rifabutin, and clarithromycin
  • Monitoring and education of patients to avoid drug interactions (The macrolides [clarithromycin, azithromycin] increase levels of many drugs metabolized in the liver, while rifampin and rifabutin decrease levels of other drugs metabolized in the liver.)

Transfer

• In treatment-resistant cases, consulting the National Jewish Hospital Medical and Research Center in Denver, Colo; the Centers for Disease Control and Prevention in Atlanta, Ga; or other local experts may be useful.

Deterrence/Prevention

• General HIV prevention recommendations

Prognosis

• Untreated M kansasii infection persists in sputum and progresses both clinically and radiographically.
• Before rifampin was available, treatment success rates with antimycobacterial drugs were disappointing when compared to tuberculosis. With the advent of rifampin, 4-month sputum conversion rates with rifampin-containing regimens were 100% in 180 patients from 3 studies. Researchers report that long-term relapse rates in patients on these regimens are less than 1%.
• In patients infected with HIV, predictors of survival include higher CD4 counts, antiretroviral therapy, negative smear microscopy results, and adequate treatment for M kansasii infection.¹⁴

Patient Education

• Explain the adverse effects of any medications used for treatment.
  • Visual problems may occur with administration of ethambutol.
  • Rifampin reduces the efficacy of oral contraceptives.
• For excellent patient education resources, visit eMedicine's Lung and Airway Center and Procedures Center. Also, see eMedicine's patient education articles Tuberculosis and Bronchoscopy.

Miscellaneous

Medicolegal Pitfalls

• Ethambutol may cause optic neuritis. Monthly monitoring may be useful.
• Medications may cause liver failure. Advise patients to contact their physicians if they experience jaundice, abdominal pain, or discomfort.
• Rifampin reduces the efficacy of medications such as oral contraceptives, antiretroviral drugs, and warfarin (Coumadin).
• Macrolides (clarithromycin and azithromycin) increase serum levels of certain drugs metabolized in the liver (eg, statins), leading to potential toxicity.

Special Concerns

• Aminoglycosides are contraindicated in pregnancy.
• Rifampin, ethambutol, and isoniazid are considered safe in pregnancy; termination is unnecessary.

Multimedia

Media file 1: Chest radiograph in a patient with Mycobacterium kansasii pulmonary infection shows left lower lung infiltrates.

Media file 2: Chest CT scan in a patient with Mycobacterium kansasii pulmonary infection (see Image 1).

Media file 3: Chest radiograph in a patient with classic right upper lobe cavitary lung disease secondary to Mycobacterium kansasii infection (see Image 4 for CT thorax in the same patient). Courtesy of Raj Sreedhar, MD, SIU School of Medicine, Springfield, IL.

Media file 4: CT thorax of a patient with classic right upper lobe cavitary lung disease secondary to Mycobacterium kansasii infection (see Image 3 for the chest radiograph in the same patient). Courtesy of Raj Sreedhar, MD, SIU School of Medicine, Springfield, IL.

References

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2. Corbett EL, Churchyard GJ, Hay M. The impact of HIV infection on Mycobacterium kansasii disease in South African gold miners. Am J Respir Crit Care Med. Jul 1999;160(1):10-4. [Medline].

3. Evans AJ, Crisp AJ, Hubbard RB. Pulmonary Mycobacterium kansasii infection: comparison of radiological appearances with pulmonary tuberculosis. Thorax. Dec 1996;51(12):1243-7. [Medline].

4. Maliwan N, Zvetina JR. Clinical features and follow up of 302 patients with Mycobacterium kansasii pulmonary infection: a 50 year experience. Postgrad Med J. 2005;81:530-33. [Medline].

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7. National Committee for Clinical Laboratory Standards. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standard. M24-A. Wayne, PA: National Committee for Clinical Laboratory Standards; 2003.

8. Woods GL. Susceptibility testing for mycobacteria. Clin Infect Dis. 2000;31:1209-1. [Medline].

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10. 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].

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Keywords

Mycobacterium kansasii, M kansasii, acid-fast bacillus, AFB, nontuberculous mycobacterial infection, NTM infection, AIDS, Mycobacterium avium complex, MAC, M kansasii chronic pulmonary disease, pulmonary tuberculosis, cutaneous M kansasii infection, M kansasii nodule, M kansasii pustule, M kansasii verrucous lesion, M kansasii erythematous plaque, M kansasii abscess, M kansasii ulcer, M kansasii bacteremia, M kansasii pericarditis, M kansasii oral ulcer, chronic M kansasii sinusitis, M kansasii osteomyelitis, M kansasii scalp abscess

Contributor Information and Disclosures

Author

Janak Koirala, MD, MPH, FACP, Associate Professor, Department of Internal Medicine, Division of Infectious Diseases, Southern Illinois University School of Medicine
Janak Koirala, MD, MPH, FACP is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, International Society for Infectious Diseases, and International Society of Travel Medicine
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: Nothing to disclose.

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.

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