Johns Hopkins Antibiotic (ABX) Guide

Mycobacterium abscessus

Paul Auwaerter, M.D.

MICROBIOLOGY

  • Human pathogen, occasional environmental contaminant. Present in water, sewerage, vegetation.
  • Considered among the most pathogenic and chemotherapy-resistant of rapid-growing mycobacterium.
  • Formerly part of "M. chelonae-complex", but important to distinguish from M. chelonae as antimycobacterial therapy more difficult with M. abscessus senso strictu.
    • Subset of M. abscessus may be M. massiliense or now M. abscessus subspecies bolletii, importance is lack of inducible macrolide resistance or erm gene[Leao, 2011].
  • Occasionally confused with Corynebacterium spp. (described as diphtheroid growing in broth systems).

CLINICAL[Top]

  • Southeastern US (Texas-Florida) considered endemic, but reported throughout U.S.
  • Community-acquired and health-care-associated disease.
  • Relatively antibiotic resistant.
  • Diagnosis by AFB culture +/- compatible histopathology and stains.
  • ATS criteria for pulmonary disease: the minimum evaluation of suspected of nontuberculous mycobacterial (NTM) lung disease and criteria below (all three):
    • Chest radiograph or, in the absence of cavitation, chest high-resolution computed tomography (HRCT) scan with compatible lung disease.
    • Three or more sputum specimens for acid-fast bacilli (AFB) analysis.
      • Microbiologic criteria: positive culture results from at least two separate expectorated sputum samples or at least one bronchial wash or lavage, or transbronchial or other lung biopsy with mycobacterial histopathologic features (granulomatous inflammation or AFB) and positive culture for NTM or biopsy showing mycobacterial histopathologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washings that are culture positive for NTM.
    • Exclusion of other disorders, such as tuberculosis (TB).
    • Clinical, radiographic, and microbiologic criteria are equally important and all must be met to make a diagnosis of NTM lung disease. ATS states that criteria apply to symptomatic patients with radiographic opacities, nodular or cavitary, or an HRCT scan that shows multifocal bronchiectasis with multiple small nodules. These criteria fit best with Mycobacterium avium complex (MAC), M. kansasii, and M. abscessus (there is not enough known about most other NTM to be certain that these diagnostic criteria are universally applicable for all NTM respiratory pathogens).
  • Patients who are suspected of having NTM lung disease but who do not meet the diagnostic criteria should be followed until the diagnosis is firmly established or excluded.

SITES OF INFECTION[Top]

  • Pulmonary disease (most common): risk factors bronchiectasis, cystic fibrosis, gastroesophageal disorders; older women without apparent underlying pulmonary disease or immunosuppression.
  • Health-care-associated disease: surgical wound infections (mammoplasty, facial plastic surgery, cardiac surgery), post-injection abscesses.
  • Cutaneous: post-traumatic wound infections after break in skin followed by contact w/ contaminated soil or water, localized (cellulitis/abscess) or may develop sporotrichoid appearance of ascending lymphadenitis
  • Lymphadenitis: rare
  • Disseminated disease (mostly immunosuppressed w/ corticosteroids): rare, usually presents w/ multiple draining erythematous cutaneous nodules.
  • Bacteremia/endocarditis: described in hemodialysis patients.

TREATMENT[Top]

Pulmonary or serious extrapulmonary disease

  • In vitro data has not yielded effective regimen for treating pulmonary disease. May not achieve sputum culture negativity even with 12 mos of therapy. Lung disease should be considered a chronic, incurable infection.
  • Susceptibility testing should guide therapy in case of macrolide-resistance. Goal is to limit progression and control symptoms.
  • Combination therapy always recommended:
    • Clarithromycin 500 mg PO twice-daily plus amikacin (15 mg/kg/d IV) plus either cefoxitin (2 grams q 4 hr IV) or imipenem (1 gram q 6 hr) IV.
    • Duration: combination therapy w/ injectable agents + clarithromycin at least 2-4 months but duration often limited by adverse effects
    • Maintenance: once with good effect with combination therapy consider switch to oral clarithromycin 500mg PO twice daily or 1000mg XR once daily OR oral azithromycin 250mg PO once daily ("suppressive treatment") indefinitely.
  • Other agents: little good data to guide on selection or use in combination.
    • Tigecycline 100mg IV load then 50mg IV q12h. Little reported clinical data but may be in vitro susceptible and could be substituted as one of the injectables. Often poorly tolerated due to GI distress.
    • Linezolid 600 mg q12h PO is potentially useful oral agent (combined with clarithromycin) in pts in whom parental tx not tolerated or feasible; no clinical studies to guide this practice, and long-term risks exist (neuropathy, optic neuritis, cytopenias). Some use 600mg once daily to reduce risk of toxicities.
    • Clofazimine: may have in vitro activity, little clinical experience regarding use in M. abscessus, although long track records in leprosy.
  • For refractory or macrolide-resistant pulmonary disease consider periodic 1-2 week courses of parenteral agents as tolerated.
  • Treatment duration: 6 months for extrapulmonary, at least 12 months for pulmonary (see above).
  • Often not considered a medically curable condition, but rather that antibiotics contain the infection from spreading.
  • Not infrequently, sputum remains culture positive while on drug therapy (with clarithromycin for example) and the isolate remains reported as susceptible to macrolides in vitro.
  • Surgery, if feasible, is only known predictably curative strategy.

Selected Drug Comments

Azithromycin

Alternative to clarithromycin that is probably as effective. Published studies have used at least 500 mg daily, but this dose was associated with high incidence of GI intolerance, and hearing loss with prolonged use. Recommend 500 mg daily for 1 day, then 250 mg once-daily.

Clarithromycin

Cornerstone of current therapy for M. abscessus. Monotherapy is usually effective if disease is localized/limited. For pulmonary disease and serious extrapulmonary disease, combine with other agents (as listed above) especially during initial treatment phase when organism burden high, in order to prevent acquired clarithromycin resistance.

Clofazimine

Drug has in vitro activity in one report[Shen, 2010]. As with all NTMs, in vitro results may not correlate with clinical efficacy. No good data exist in this regard.

Ertapenem

Although imipenem is a routine recommendation, organisms are not routinely susceptible to either ertapenem or meropenem--so do NOT use.

Imipenem/cilastatin

Routinely used drug for M. abscessus. Cannot substitute ertapenem or meropenem as these drugs are not routinely susceptible!

Linezolid

Limited clinical experience but encouraging. Potential for long-term toxicities must be balanced however.

Meropenem

Although imipenem is a routine recommendation, organisms are not routinely susceptible to either ertapenem or meropenem--so do NOT use.

Metronidazole

One study suggests in vitro activity in large screening study[Chopra, 2011]. Clinical experience reported: zero.

Moxifloxacin

Fluoroquinolone resistance in vitro often high (90-95%+), but drug often used by some clinicians in combination. Unclear if in vitro resistance meaningful with this organism.

Tigecycline

In vitro activity, clinical utility undefined but may be substituted as one of the two injectable drugs commonly used. Used most commonly as a salvage drug, it is often poorly tolerated by this patient population.

Drug

Recommendation

OTHER INFORMATION[Top]

  • Drug toxicities or intolerance often force choices or cessation of therapy.
  • Of rapidly growing mycobacteria, M. abscessus is most virulent respiratory pathogen. Pulmonary disease is often incurable medically, and careful consideration should be weighed as whether surgery can render a cure (consider referral to center with significant experience).
  • Clinical significance of a positive culture should be carefully evaluated (see ATS diagnostic criteria).
  • Drug susceptibility testing should be used to guide antibiotic therapy but importance is unclear. Clarithromycin resistance does predict treatment failure. M. abscessus is resistant to first-line tuberculosis drugs (isoniazid, rifampin, pyrazinamide, ethambutol).
  • Almost all isolates resistant to tetracycline, doxycycline, ciprofloxacin. 5-10% of isolates susceptible to gatifloxacin and moxifloxacin. Despite this, one report cites improvement with regimen often incorporating ciprofloxacin, doxycycline and macrolide[Jeon, 2009].
  • Cluster of pts with M. abscessus infection after cosmetic injections by nonmedical practitioners in New York City area in 2002.

Basis for recommendation[Top]

  • Griffith DE et al: An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 175:367, 2007 Feb. 15  [PMID:17277290]

    Comment: Guideline reviews evaluation and treatment recommendations presented in this module.
    Rating: Basis for recommendation

References[Top]

  1. Leao SC et al: Proposal that Mycobacterium massiliense and Mycobacterium bolletii be united and reclassified as Mycobacterium abscessus subsp. bolletii comb. nov., designation of Mycobacterium abscessus subsp. abscessus subsp. nov. and emended description of Mycobacterium abscessus. Int J Syst Evol Microbiol 61:2311, 2011   [PMID:21037035]

    Comment: Taxonomy shift proposed based on sequencing data showing that a subset of M. abscessus organisms likely represent Mycobacterium massiliense that is proposed to be called now Mycobacterium abscessus subsp. bolletii

  2. Chopra S et al: Identification of antimicrobial activity among FDA-approved drugs for combating Mycobacterium abscessus and Mycobacterium chelonae. J Antimicrob Chemother 66:1533, 2011   [PMID:21486854]

    Comment: Metronidazole MICs were extremely low < 0.015 against M. abscessus. Clinical evidence to date is nil.

  3. Jarand J et al: Clinical and microbiologic outcomes in patients receiving treatment for Mycobacterium abscessus pulmonary disease. Clin Infect Dis 52:565, 2011 March 1  [PMID:21292659]

    Comment: Important study of 107 patients showed improved response compared to older studies based on use of multiple drug combinations including macrolides (azithromycin, clarithromycin) + parenteral agents (mostly amikacin or cefoxitin), and surgery. Despite this, 29% remained culture positive, 16% died but 48% appeared to have durable microbiological cure.
    Rating: Important

  4. Griffith DE: The talking Mycobacterium abscessus blues. Clin Infect Dis 52:572, 2011 March 1  [PMID:21292660]

    Comment: Author reflects on how this infection was rarely cured, to more recent studies showing improved outcomes using combination therapy +/- surgery. Expert with significant experience who nicely frames much of the contentious in vitro data that seems little predictive of clinical outcomes.

  5. Shen GH et al: High efficacy of clofazimine and its synergistic effect with amikacin against rapidly growing mycobacteria. Int J Antimicrob Agents 35:400, 2010   [PMID:20138481]

    Comment: In vitro studies suggest that clofazimine is highly effective and synergy documented with amikacin. Cycloserine and dapsone show no activity against M. abscessus.
    Rating: Important

  6. Nash KA, Brown-Elliott BA, Wallace RJ: A novel gene, erm(41), confers inducible macrolide resistance to clinical isolates of Mycobacterium abscessus but is absent from Mycobacterium chelonae. Antimicrob Agents Chemother 53:1367, 2009   [PMID:19171799]

    Comment: Discovery of inducible macrolide resistance by novel erm gene may help partly explain poor responses seen in this infection. Standard methods reveal isolates to be susceptible to clarithromycin, but 7/10 isolates found to have MICs > 32 μg/ml under incubation in macrolide-containing media.
    Rating: Important

  7. Cremades R et al: Mycobacterium abscessus from respiratory isolates: activities of drug combinations. J Infect Chemother 15:46, 2009   [PMID:19280301]

    Comment: In vitro study of only a few strains suggest clarithromycin as most active and then linezolid. FQ + rifabutin + clarithromycin suggested as possibly useful combination.

  8. Jeon K et al: Antibiotic treatment of Mycobacterium abscessus lung disease: a retrospective analysis of 65 patients. Am J Respir Crit Care Med 180:896, 2009 Nov. 1  [PMID:19661243]

    Comment: Large series from South Korea looking at 188 patients over an eight year period, of whom 65/86 patients given early/aggressive antibiotic therapy completed 12+ month course. Initial therapy was 4wks of parenterals (amikacin + cefoxitin) + orals (clarithromycin, ciprofloxacin, doxycycline). Some patients had imipenem substituted. Total course was planned as 24mos or 12mos post sputum conversion. By 6mos, 72% of pts had negative sputum. Relapse occurred in 19%, such that only 58% were sputum negative at the conclusion of the study. In vitro resistance to clarithromycin was identified as important to contributing to treatment failure by multiple logistic regression (p=0.004). Overall, unclear if in vitro testing other than for the macrolide is important (e.g., all isolates were resistant to ciprofloxacin) and patients have high rates of treatment failure despite this multi-drug regimen. Surgery played a role likely in improved outcomes, and severity of disease may be less than other reported series.
    Rating: Important

  9. Appelgren P et al: Late-onset posttraumatic skin and soft-tissue infections caused by rapid-growing mycobacteria in tsunami survivors. Clin Infect Dis 47:e11, 2008 July 15  [PMID:18549312]

    Comment: Of fifteen patients with NTMs, Mycobacterium abscessus (in 7), Mycobacterium fortuitum (6), Mycobacterium peregrinum and Mycobacterium mageritense (1 each) developed between 20-105d post-tsunami. Authors emphasize the need for repeated cultures to secure diagnosis especially with negative standard bacteria cultures.

  10. Shu CC et al: Nontuberculous mycobacteria pulmonary infection in medical intensive care unit: the incidence, patient characteristics, and clinical significance. Intensive Care Med 34:2194, 2008   [PMID:18648768]

    Comment: Study from Taiwan examined >5300 ICU pts with over half undergoing respiratory mycobacterial cultures. 169 pts (5.8%) had AFB identified with nearly half then receiving anti-NTM treatment. A higher mortality was associated in patients with NTM than those who were culture negative, but this retrospective examination precludes making a strong statement. M. abscessus (16.6%) was third in frequency of isolation, after MAI (38.3%) and M. chelonae(19.4%).

  11. Miyasaka T et al: In vitro efficacy of imipenem in combination with six antimicrobial agents against Mycobacterium abscessus. Int J Antimicrob Agents 30:255, 2007   [PMID:17616451]

    Comment: In vitro synergy testing suggest that improved activity was witnessed when imipenem was combined with clarithromycin, minocycline, levofloxacin and moxifloxacin.
    Rating: Important

  12. Han XY, Dé I, Jacobson KL: Rapidly growing mycobacteria: clinical and microbiologic studies of 115 cases. Am J Clin Pathol 128:612, 2007   [PMID:17875513]

    Comment: Series of rapid grower nontubercular mycobacterial infections. 32/43 reported M. abscessus infections were from respiratory sources.
    Rating: Important

  13. Song JY et al: An outbreak of post-acupuncture cutaneous infection due to Mycobacterium abscessus. BMC Infect Dis 6:, 2006   [PMID:16412228]

    Comment: Large outbreak following use of contaminated acupuncture needles.

  14. Fox LP et al: Mycobacterium abscessus cellulitis and multifocal abscesses of the breasts in a transsexual from illicit intramammary injections of silicone. J Am Acad Dermatol 50:450, 2004   [PMID:14988690]

    Comment: Report of a cluster of M. abscessus infections after injections for cosmetic purposes by nonmedical practitioners in New York City in 2002.

  15. Olivier KN et al: Nontuberculous mycobacteria. I: multicenter prevalence study in cystic fibrosis. Am J Respir Crit Care Med 167:828, 2003 March 15  [PMID:12433668]

    Comment: Prospective, cross-sectional study of the prevalence of NTM and clinical features of patients at 21 U.S. centers. Overall NTM prevalence in sputum 13%, with M. avium complex (72% of NTM isolates) and M. abscessus (16%) most common. Molecular typing revealed that almost all patients within each center had unique NTM strains -- evidence against person to person or nosocomial acquisition.

  16. Wallace RJ 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 46:3164, 2002   [PMID:12234839]

    Comment: In vitro activity seen in M. abscessus-chelonae group, but not with slow growers such as M. marinum or M. kansasii . As of 2008 there has been no published clinical experience with this compound, although often used as last resort drug given need for parenteral route and side effects.
    Rating: Important

  17. Bange FC et al: Lack of transmission of mycobacterium abscessus among patients with cystic fibrosis attending a single clinic. Clin Infect Dis 32:1648, 2001 June 1  [PMID:11340540]

    Comment: Among 214 CF patients attending a single clinic, 5 had respiratory cultures positive for M. abscessus. Molecular typing demonstrated that each patient had a unique strain, suggesting that the bacterium was not spread person-to-person within that health care setting, and that it may not be necessary to segregate patients with CF who are infected with M. abscessus.

  18. Wallace RJ et al: Activities of linezolid against rapidly growing mycobacteria. Antimicrob Agents Chemother 45:764, 2001   [PMID:11181357]

    Comment: Approximately 50% of 98 M. abscessus isolates studied were inhibited by linezolid at 16 ug/ml (a drug concentration achievable in serum after oral doses of 600 mg twice-daily)

  19. Villanueva A et al: Report on an outbreak of postinjection abscesses due to Mycobacterium abscessus, including management with surgery and clarithromycin therapy and comparison of strains by random amplified polymorphic DNA polymerase chain reaction. Clin Infect Dis 24:1147, 1997   [PMID:9195073]

    Comment: Report of the largest outbreak of M. abscessus post-injection abscesses in an alternative medicine clinic, in which 205 of 350 patients (59%) developed cellulitis or localized cutaneous abscesses.

  20. Fauroux B et al: Mycobacterial lung disease in cystic fibrosis: a prospective study. Pediatr Infect Dis J 16:354, 1997   [PMID:9109135]

    Comment: CF patients with M. abscessus pulmonary disease are at risk for development of disseminated disease following lung transplantation.

  21. Griffith DE, Girard WM, Wallace RJ: Clinical features of pulmonary disease caused by rapidly growing mycobacteria. An analysis of 154 patients. Am Rev Respir Dis 147:1271, 1993   [PMID:8484642]

    Comment: "Cure" (permanent sputum conversion and complete resolution of symptoms) of M. abscessus pulmonary disease is rare with medical therapy alone. Surgical resection is a useful adjunct in patients with localized disease who are able to tolerate surgery.
    Rating: Important

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Mycobacterium abscessus
Last updated: November 18, 2011
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