Mycobacterium Avium complex

For cavitary disease:

Clarithromycin 500-1000 mg po daily or azithromycin  250-500 mg po daily

AND

Rifampin 600 mg po daily (450 mg po daily if wt < 50 kg) (a)

AND

Ethambutol 15 mg/kg/day

For severe disease or previously treated, consider adding amikacin or streptomycin IV to the above three-drug regimen.

Alternatives to rifampin, as part of a multi-drug regimen:

· Levofloxacin

· Moxifloxacin

· Amikacin

· Streptomycin

· Rifabutin

In patients with mild disease and only nodular-bronchiectatic lung disease without cavitation, can consider  a two-drug regimen of a macrolide and ethambutol (Griffith, Askamit 2007))

Skin, soft tissue, and bone infections – 6-12 months

Pulmonary infections -  at least 12 months after negative sputum cultures

Surgical management if :

· Lymphadenitis

· Abscess formation

· Intolerance of drug therapy

· Retained foreign body

Surgical resection of focal pulmonary disease can be considered in centers with extensive experience and in conjunction with medical treatment.  Clinical evidence is limited to small series.

Macrolides are the cornerstone of MAC therapy, although  they should always be used with companion medications to prevent development of resistance.

Consider substitution of rifabutin (or alternative agent) for rifampin given potent drug interaction

 Mycobacterium kansasii

Rifampin 10 mg/kg/day (max 600 mg/day) (b,c)

AND

Ethambutol 15mg/kg/day

AND

 INH 5 mg/kg/day (max 300 mg/day) + pyridoxine 50 mg/day (d)

Rifampin 600 mg and ethambutol 25mg/kg and clarithromycin 500-1000 mg, all dosed three times weekly

Rifampin-resistant isolates:

3 of the following agents based on in vitro susceptibilities:

· Macrolide

· Moxifloxacin (e)

· Ethambutol

· ulfamethoxazole

· Streptomycin

IV streptomycin or amikacin, INH (900 mg daily), ethambutol (25mg/kg/day), and sulfamethazole (1 gm po tid) (Wallace, Dunbar 1994)

Agents with in vitro activity, but little clinical experience:

· Linezolid

Pulmonary infections – 12 months of negative sputum cultures.

Given the excellent response to medical treatment with rifamycin-based regimens, surgical management is generally not required.

Consider substitution of rifabutin, a macrolide, or moxifloxacin for rifampin as less potent drug interaction with immunosuppressants.

Mycobacterium fortuitum

2 of the following agents with in vitro activity based on susceptibility testing: (percentage of untreated isolates usually susceptible):

· Imipenem (100%)

· Amikacin (100%)

· Fluoroquinolone  (100%)

· ulfonamides(100%) (sulfamethoxazole or TMP/SMX)

· Clarithromycin (80%) (f)

· Doxycycline 100 mg po daily (50%)

· Cefoxitin (50%)

As part of multi-drug regimen:

·   Linezolid (g)

Skin and soft tissue infections – 4 months

Bone infections – 6 months

Pulmonary infections – at least 12 months of negative sputum cultures

Surgical management if :

· Extensive disease

· Abscess formation

· Intolerance of drug therapy

· Retained foreign body

Mycobacterium chelonae

A macrolide (e.g., Clarithromycin 1000 mg po daily)

AND

One other active agent based on in vitro susceptibility testing (percentage of untreated isolates usually susceptible):

· Tobramycin 5mg/kg per day in 2-3 divided doses (100%)

· Imipenem 1 g IV q 6 hrs (60%)[d]

· Amikacin (50%)

· Doxycycline (25%)

· Ciprofloxacin (20%)

As part of multi-drug regimen  (percentage of untreated isolates usually susceptible):

· Linezolid (90%)

· Tigecycline

Duration of treatment same as for mycobacterium fortuitum.

Surgical management same as for mycobacterium fortuitum.

 Mycobacterium abscessus

A macrolide (clarithromycin 1000 mg po daily or azithromycin 250-500 mg po daily)

AND

the following IV agents:

· Amikacin

and/or

· Cefoxitin 12g IV/day in divided doses or imipenem IV if cefoxitin unavailable.  In combination with amikacin until clinical stability or at least 2 wks of treatment.

For macrolide-resistant isolates, a combination of parenteral agents based on in vitro susceptibility testing.

Alternative second-line agents as part of multi-drug regimen:

· Linezolid

· Tigecycline

· Moxifloxacin

· Telithromycin

Efficacy of inhaled amikacin unknown, but could be considered in patients at high risk of renal failure on intravenous amikacin.

Skin and soft tissue infections – 4 months

Bone infections – 6 months

Pulmonary infections – no antibiotic regimens have been shown to reliably produce long-term sputum conversion. Several approaches reasonable.  Some advocate periodic antibiotics (macrolides and/or parenteral agents) either to control symptomatic disease flares or at regular intervals for disease suppression.

Surgical management for non-pulmonary infection if:

· Extensive disease

· Abscess formation

· Intolerance of drug therapy

· Retained foreign body

Surgical management of limited, focal pulmonary disease is the only predictably curative therapy.

 M. marinum

Multidrug regimen with at least two active agents:

· Rifampin (a)

· Rifabutin (a)

· Ethambutol

· Clarithromycin

· Sulfonamides

· Doxycycline  (intermediate susc)

· Minocycline  (intermediate susc)

1 – 2 months after resolution of symptoms, typically 3-4 months total duration

Surgical management if:

· Infection involving closed spaces of the hand

· Failure to respond to medical management

Rifampin or rifabutin should be avoided if other alternatives available

M. haemophilum

Optimal treatment regimens unkown, but should involve a multidrug regimen

Agents considered active in vitro:

· Amikacin

· Clarithromycin

· Ciprofloxacin

· Rifampin

· Rifabutin

Agents considered variably active:

· Doxycycline

· Sulfonamides

Optimal duration is unknown, but soft tissue infection should be treated at least a few months beyond resolution of symptoms.

Treatment duration for disseminated disease should generally be longer.