Treatment of osteomyelitis due to nontuberculous mycobacteria in adults
- Shannon Kasperbauer, MD
Shannon Kasperbauer, MD
- Assistant Professor of Medicine
- National Jewish Health
- Charles L Daley, MD
Charles L Daley, MD
- Professor of Medicine
- National Jewish Health
Nontuberculous mycobacteria (NTM) are a vast group of organisms that are widespread in the environment (table 1). They have been isolated from numerous environmental sources, including water and soil. NTM can cause a broad range of infections that vary depending on the NTM species and on the host’s immune status. In immunocompetent individuals, disease can present as chronic pneumonia, lymphadenitis, or skin, soft tissue, and/or bone infection. Immunocompromised individuals can also present with any of these findings, but disease in such patients may also manifest as disseminated infection. Unfortunately, NTM are seldom considered as a possible etiology in infections of the soft tissues and/or bones; therefore, delays in diagnosis and treatment are common.
The treatment of osteomyelitis due to NTM will be reviewed here. The epidemiology, clinical manifestations, and diagnosis of NTM osteomyelitis is discussed separately. (See "Epidemiology, clinical manifestations, and diagnosis of osteomyelitis due to nontuberculous mycobacteria".)
Other NTM infections and the management of osteomyelitis due to bacteria and Mycobacterium tuberculosis are reviewed elsewhere. (See "Epidemiology of nontuberculous mycobacterial infections" and "Microbiology of nontuberculous mycobacteria" and "Overview of nontuberculous mycobacteria (excluding MAC) in HIV-infected patients" and "Mycobacterium avium complex (MAC) infections in HIV-infected patients" and "Treatment of Mycobacterium avium complex lung infection" and "Rapidly growing mycobacterial infections: Mycobacteria abscessus, chelonae, and fortuitum" and "Overview of osteomyelitis in adults" and "Hematogenous osteomyelitis in adults" and "Vertebral osteomyelitis and discitis in adults" and "Treatment and prevention of osteomyelitis following trauma in adults" and "Hematogenous osteomyelitis in children: Management" and "Skeletal tuberculosis".)
Osteomyelitis caused by nontuberculous mycobacteria (NTM) requires combination antimycobacterial therapy, often in conjunction with surgery. Concomitant immunosuppression should be minimized whenever possible. There are no randomized controlled trials or comparative observational studies that have evaluated the efficacy of treatment for NTM osteomyelitis. Thus, treatment recommendations are based upon case reports and small retrospective reviews, as well as on in vitro susceptibility patterns.
Unlike isolation of M. tuberculosis, isolation of an NTM species does not necessarily dictate initiation of therapy. Because NTM can be isolated as a result of contamination of a clinical specimen and because the pathogenicity of the various NTM species varies substantially, clinicians must determine the clinical significance of any isolate and whether treatment is indicated . In addition, the results of in vitro susceptibility testing for many NTM do not correlate with clinical response, and therefore the clinician should use these data with an appreciation for the limitations of such testing.
- Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007; 175:367.
- Stone MS, Wallace RJ Jr, Swenson JM, et al. Agar disk elution method for susceptibility testing of Mycobacterium marinum and Mycobacterium fortuitum complex to sulfonamides and antibiotics. Antimicrob Agents Chemother 1983; 24:486.
- Swenson JM, Wallace RJ Jr, Silcox VA, Thornsberry C. Antimicrobial susceptibility of five subgroups of Mycobacterium fortuitum and Mycobacterium chelonae. Antimicrob Agents Chemother 1985; 28:807.
- Brown BA, Wallace RJ Jr, Onyi GO, et al. Activities of four macrolides, including clarithromycin, against Mycobacterium fortuitum, Mycobacterium chelonae, and M. chelonae-like organisms. Antimicrob Agents Chemother 1992; 36:180.
- Wallace RJ Jr, Brown BA, Onyi GO. Susceptibilities of Mycobacterium fortuitum biovar. fortuitum and the two subgroups of Mycobacterium chelonae to imipenem, cefmetazole, cefoxitin, and amoxicillin-clavulanic acid. Antimicrob Agents Chemother 1991; 35:773.
- Nash KA, Zhang Y, Brown-Elliott BA, Wallace RJ Jr. Molecular basis of intrinsic macrolide resistance in clinical isolates of Mycobacterium fortuitum. J Antimicrob Chemother 2005; 55:170.
- 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 1985; 152:500.
- Wallace RJ Jr, Brown BA, Onyi GO. Skin, soft tissue, and bone infections due to Mycobacterium chelonae chelonae: importance of prior corticosteroid therapy, frequency of disseminated infections, and resistance to oral antimicrobials other than clarithromycin. J Infect Dis 1992; 166:405.
- Wallace RJ Jr, Brown-Elliott BA, Ward SC, et al. Activities of linezolid against rapidly growing mycobacteria. Antimicrob Agents Chemother 2001; 45:764.
- Adékambi T, Reynaud-Gaubert M, Greub G, et al. Amoebal coculture of "Mycobacterium massiliense" sp. nov. from the sputum of a patient with hemoptoic pneumonia. J Clin Microbiol 2004; 42:5493.
- Adékambi T, Berger P, Raoult D, Drancourt M. rpoB gene sequence-based characterization of emerging non-tuberculous mycobacteria with descriptions of Mycobacterium bolletii sp. nov., Mycobacterium phocaicum sp. nov. and Mycobacterium aubagnense sp. nov. Int J Syst Evol Microbiol 2006; 56:133.
- Leao SC, Tortoli E, Euzéby JP, Garcia MJ. 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 2011; 61:2311.
- Nash KA, Brown-Elliott BA, Wallace RJ Jr. A novel gene, erm(41), confers inducible macrolide resistance to clinical isolates of Mycobacterium abscessus but is absent from Mycobacterium chelonae. Antimicrob Agents Chemother 2009; 53:1367.
- Choi GE, Shin SJ, Won CJ, et al. Macrolide treatment for Mycobacterium abscessus and Mycobacterium massiliense infection and inducible resistance. Am J Respir Crit Care Med 2012; 186:917.
- Jarand J, Levin A, Zhang L, et al. Clinical and microbiologic outcomes in patients receiving treatment for Mycobacterium abscessus pulmonary disease. Clin Infect Dis 2011; 52:565.
- Jeon K, Kwon OJ, Lee NY, et al. Antibiotic treatment of Mycobacterium abscessus lung disease: a retrospective analysis of 65 patients. Am J Respir Crit Care Med 2009; 180:896.
- Wallace RJ Jr, Nash DR, Tsukamura M, et al. Human disease due to Mycobacterium smegmatis. J Infect Dis 1988; 158:52.
- Wallace RJ Jr, Bedsole G, Sumter G, et al. Activities of ciprofloxacin and ofloxacin against rapidly growing mycobacteria with demonstration of acquired resistance following single-drug therapy. Antimicrob Agents Chemother 1990; 34:65.
- Bernard L, Vincent V, Lortholary O, et al. Mycobacterium kansasii septic arthritis: French retrospective study of 5 years and review. Clin Infect Dis 1999; 29:1455.
- Yano T, Okuda S, Kato K, et al. Mycobacterium kansasii osteomyelitis in a patient with AIDS on highly active antiretroviral therapy. Intern Med 2004; 43:1084.
- Tsai CW, Wang JT, Tsai CC, Yeh KH. Disseminated Mycobacterium kansasii infection in an HIV-negative patient presenting with mimicking multiple bone metastases. Diagn Microbiol Infect Dis 2006; 54:211.
- Williams B, Neth O, Shingadia D, et al. Mycobacterium kansasii causing septic arthritis and osteomyelitis in a child. Pediatr Infect Dis J 2010; 29:88.
- Pezzia W, Raleigh JW, Bailey MC, et al. Treatment of pulmonary disease due to Mycobacterium kansasii: recent experience with rifampin. Rev Infect Dis 1981; 3:1035.
- Ahn CH, Lowell JR, Ahn SS, et al. Chemotherapy for pulmonary disease due to Mycobacterium kansasii: efficacies of some individual drugs. Rev Infect Dis 1981; 3:1028.
- Ahn CH, Lowell JR, Ahn SS, et al. Short-course chemotherapy for pulmonary disease caused by Mycobacterium kansasii. Am Rev Respir Dis 1983; 128:1048.
- Banks J, Hunter AM, Campbell IA, et al. Pulmonary infection with Mycobacterium kansasii in Wales, 1970-9: review of treatment and response. Thorax 1983; 38:271.
- Elsayed S, Read R. Mycobacterium haemophilum osteomyelitis: case report and review of the literature. BMC Infect Dis 2006; 6:70.
- Shah MK, Sebti A, Kiehn TE, et al. Mycobacterium haemophilum in immunocompromised patients. Clin Infect Dis 2001; 33:330.
- Bernard EM, Edwards FF, Kiehn TE, et al. Activities of antimicrobial agents against clinical isolates of Mycobacterium haemophilum. Antimicrob Agents Chemother 1993; 37:2323.
- McBride ME, Rudolph AH, Tschen JA, et al. Diagnostic and therapeutic considerations for cutaneous Mycobacterium haemophilum infections. Arch Dermatol 1991; 127:276.
- Aubry A, Chosidow O, Caumes E, et al. Sixty-three cases of Mycobacterium marinum infection: clinical features, treatment, and antibiotic susceptibility of causative isolates. Arch Intern Med 2002; 162:1746.
- Etuaful S, Carbonnelle B, Grosset J, et al. Efficacy of the combination rifampin-streptomycin in preventing growth of Mycobacterium ulcerans in early lesions of Buruli ulcer in humans. Antimicrob Agents Chemother 2005; 49:3182.
- World Health Organization. Buruli ulcer (Mycobacterium ulcerans infection). http://www.who.int/buruli/en/ (Accessed on June 13, 2012).
- Petitjean G, Fluckiger U, Schären S, Laifer G. Vertebral osteomyelitis caused by non-tuberculous mycobacteria. Clin Microbiol Infect 2004; 10:951.
- Marr MA, Algozzine GJ. Use of bone cement containing tobramycin sulfate. Clin Pharm 1983; 2:401.
- Klekamp J, Dawson JM, Haas DW, et al. The use of vancomycin and tobramycin in acrylic bone cement: biomechanical effects and elution kinetics for use in joint arthroplasty. J Arthroplasty 1999; 14:339.
- Hanssen AD, Spangehl MJ. Practical applications of antibiotic-loaded bone cement for treatment of infected joint replacements. Clin Orthop Relat Res 2004; :79.
- González Della Valle A, Bostrom M, Brause B, et al. Effective bactericidal activity of tobramycin and vancomycin eluted from acrylic bone cement. Acta Orthop Scand 2001; 72:237.
- Scott CP, Higham PA, Dumbleton JH. Effectiveness of bone cement containing tobramycin. An in vitro susceptibility study of 99 organisms found in infected joint arthroplasty. J Bone Joint Surg Br 1999; 81:440.
- Nelson CL, Griffin FM, Harrison BH, Cooper RE. In vitro elution characteristics of commercially and noncommercially prepared antibiotic PMMA beads. Clin Orthop Relat Res 1992; :303.
- Adams K, Couch L, Cierny G, et al. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res 1992; :244.
- Seeley SK, Seeley JV, Telehowski P, et al. Volume and surface area study of tobramycin-polymethylmethacrylate beads. Clin Orthop Relat Res 2004; :298.
- Evans RP. Successful treatment of total hip and knee infection with articulating antibiotic components: a modified treatment method. Clin Orthop Relat Res 2004; :37.
- Greene N, Holtom PD, Warren CA, et al. In vitro elution of tobramycin and vancomycin polymethylmethacrylate beads and spacers from Simplex and Palacos. Am J Orthop (Belle Mead NJ) 1998; 27:201.
- Kuechle DK, Landon GC, Musher DM, Noble PC. Elution of vancomycin, daptomycin, and amikacin from acrylic bone cement. Clin Orthop Relat Res 1991; :302.
- Masri BA, Duncan CP, Jewesson P, et al. Streptomycin-loaded bone cement in the treatment of tuberculous osteomyelitis: an adjunct to conventional therapy. Can J Surg 1995; 38:64.
- Kerens B, Gans EH, Pilot P, et al. [Atypical tuberculous osteomyelitis of the humeral shaft caused by Mycobacterium avium]. Ned Tijdschr Geneeskd 2006; 150:1728.
- Pring M, Eckhoff DG. Mycobacterium chelonae infection following a total knee arthroplasty. J Arthroplasty 1996; 11:115.
- Curtis JM, Sternhagen V, Batts D. Acute renal failure after placement of tobramycin-impregnated bone cement in an infected total knee arthroplasty. Pharmacotherapy 2005; 25:876.
- Patrick BN, Rivey MP, Allington DR. Acute renal failure associated with vancomycin- and tobramycin-laden cement in total hip arthroplasty. Ann Pharmacother 2006; 40:2037.
- GENERAL APPROACH
- SUSCEPTIBILITY TESTING
- ANTIMYCOBACTERIAL THERAPY
- Rapidly growing mycobacteria
- - M. fortuitum complex
- - M. chelonae
- - M. abscessus
- - M. smegmatis
- Slowly growing mycobacteria
- - M. avium complex
- - M. kansasii
- - M. haemophilum
- - M. marinum
- - M. ulcerans
- - Other species
- Duration of therapy
- Monitoring during therapy
- Adverse effects
- Drug interactions
- MANAGING POOR TREATMENT RESPONSES
- SUMMARY AND RECOMMENDATIONS