422 • CID 2010:51 (15 August) • IMMUNOCOMPROMISED HOSTS
I M M U N O C O M P R O M I S E D H O S T SI N V I T E D A R T I C L E
David R. Snydman, Section Editor
Rapidly Growing Mycobacteria Infection in Patients
Gil Redelman-Sidi and Kent A. Sepkowitz
Memorial Sloan-Kettering Cancer Center, New York, New York
and immunocompromised hosts. The risk factors and outcomes of RGM infection in patients with cancer have not been clearly
Data were derived from 2 distinct sources. Demographic and clinical data were collected for all patients with cancer
at Memorial Sloan-Kettering Cancer Center with a culture positive for RGM from January 1999 through December 2008. We
also reviewed the literature for studies describing RGM infection in patients with cancer.
During the 10-year period, 28 patients with cancer at Memorial Sloan-Kettering Cancer Center had cultures positive
for RGM. Most cases occurred in patients with solid tumors and were confined to the lung. A review of the literature identified
313 additional patients with cancer and RGM infection. Combining our series data with cases from the literature, we defined 3
distinct syndromes: pulmonary disease, which occurred in 158 patients (47%); bloodstream infection, occurring in 151 patients
(45%); and disseminated infection involving at least 1 end organ, affecting 26 persons (8%). The syndromes differed by age of
onset, underlying cancer, main RGM species, and outcome. Persons with bloodstream infection typically were young and had an
excellent outcome; those with disseminated infection were older, had pronounced immunosuppression, and had a very poor
RGM infections in patients with cancer comprise 3 distinct disorders with different risk factors, predominant
mycobacterial species, and prognoses. In turn, the approach to management, including number and duration of antimycobacterial
drugs, may be fundamentally different for various patients with cancer who receive a diagnosis of RGM infection.
Rapidly growing mycobacteria (RGM) havebeenassociatedwithvariousclinicalsyndromesinimmunocompetent
Rapidly growing mycobacteria (RGM) were defined by Runyon
as mycobacteria that form colonies in subcultures in ?7 days
[1, 2]. They are ubiquitous in nature and can be found in soil,
bioaerosols, and water. Several strains have intrinsic resistance
to many antibiotics, which complicates treatment .
RGM infections have emerged in 2 different clinical settings.
Disease is described in apparently normal hosts who have an
invasive procedure that introduces the organism [4–10]. Ad-
ditionally, cases are found in hosts with either abnormal anat-
omy, such as bronchiectasis, or profound dysfunction of im-
mune response, such as occurs after some cancer therapies or
organ transplant [3, 11]. RGM infection is rare in human im-
munodeficiency virus (HIV)-infected patients, although they
are predisposed to infection with other nontuberculous my-
Received 2 February 2010; accepted 6 May 2010; electronically published 8 July 2010.
Reprints or correspondence: Gil Redelman-Sidi, Infectious Disease Service, Dept of
Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065
Clinical Infectious Diseases2010;51(4):422–434
? 2010 by the Infectious Diseases Society of America. All rights reserved.
cobacteria, particularly Mycobacterium avium-intracellulare
Although RGM infection has been described in patients with
cancer, the specific factors that predispose patients to infection
remain unclear. To better understand these factors, we analyzed
the clinical features of all patients with positive cultures for
RGM in our institution during a 10-year period and reviewed
the literature for all additional cases of RGM infection in pa-
tients with cancer.
MATERIAL AND METHODS
Study setting and patients.
Center (MSKCC) is a 432-bed comprehensive cancer center.
We retrospectively reviewed medical records of all patients with
a positive culture for RGM from January 1999 through De-
cember 2008. Patients with RGM but without cancer were ex-
cluded. We divided cases into pulmonary, bloodstream/cathe-
ter-related, disseminated, or other on the basis of the source
of the isolate. The MSKCC Institutional ReviewBoardreviewed
the study and granted a Health Insurance Portability and Ac-
countability Act waiver of authorization.
Positive respiratory specimens were categorized as definitive,
by guest on October 14, 2011
IMMUNOCOMPROMISED HOSTS • CID 2010:51 (15 August) • 423
probable, possible infection, or contaminant on the basis of the
American Thoracic Society and the Infectious Diseases Society
of America criteria . Catheter-related cases were defined
according to published guidelines for evaluation of catheter-
related infections . Disseminated infection was defined ac-
cording to an article published elsewhere  and included
patients with at least 1 of the following characteristics: (1)
multiple cutaneous abscesses, (2) visceral involvement with or
without skin manifestations,or(3)positiveblood/bonemarrow
culture and clinical evidence of deep infection.
Blood cultures were performed
using the BACTEC Plus aerobic/F bottles and Mycobacteria
Growth Indicator tubes (BD Diagnostic Systems). Recom-
mended volumes of blood per bottle were 8–10 mL for adults
and 4–5 mL for children. Culture bottles were incubated for 5
days at 37?C. Indicator tubes were incubated for 42 days at
37?C. Positive cultures were grown on 7H11 and blood agar
At MSKCC, deep respiratory specimens, such as bronchoal-
veolar washings, tracheal aspirates, and specimens of lung tis-
sue, are commonly cultured for mycobacteria. Specimens from
other sites, such as sputum, skin/soft tissue, and stool, were
cultured for mycobacteria at the discretion of the clinician.
These practices did not change throughout the study period.
Cultures for mycobacteria followed standard techniques and
were incubated for 6 weeks. Sterile specimens were inoculated
directly into media. Nonsterile specimens were first decontam-
inated by treatment with 4% sodium hydroxide for 15 min.
All mycobacterial strains were sent to the Mayo Clinic for
identification through sequencing analysis of the 16S ribosomal
RNA gene .
We searched MEDLINE for English lan-
guage articles published since 1980 with the following search
terms: RGM, rapidly-growing, rapid-grower, nontuberculous,
chelonae, chelonei, abscessus, fortuitum, smegmatis, neoau-
rum, aurum, mucogenicum, oncologic, cancer,lymphoma,leu-
kemia, myeloma, transplant, transplantation, and hematologic.
Additional articles were obtained by checking references from
selected studies and from review articles. We excluded 6 cases
from 3 studies [16–18] in which dissemination was suspected
but not proven. All of these had positive blood cultures with
concurrent undiagnosed pulmonary nodules which resolved
with routine empiric antimicrobialtreatment.Onlystudieswith
a description of the demographic and/or clinical aspects of the
cases were included. Abstracts not published as full papers were
excluded. We extracted the following data from the selected
papers: age, sex, RGM species, underlying cancer, additional
underlying conditions, presence of central venous catheter
(CVC), presence of neutropenia or lymphopenia, use of che-
motherapy or corticosteroids, treatment, and outcome.
for univariate comparisons when appropriate. In all analyses,
a P value of !.05 was considered to indicate statistical signif-
icance. All probabilities were 2-tailed.
The student’s T test and x2tests were used
Cases at MSKCC
Demographic and clinical features of cases at MSKCC.
During the 10-year period, there were 1913 positive mycobac-
terial cultures at MSKCC. Of these, 130 cultures from 39 pa-
tients grew RGM, including 28 with an underlying history of
cancer (Table 1) and 11 without. The mean rate of RGM in-
fection was 2.9 cases per 100,000 patient-days. In comparison,
rates of Staphylococcus aureus, Escherichia coli, and Candida
species bloodstream infections at MSKCC during the same pe-
riod were 77, 90, and 31 cases per 100,000 patient-days, re-
Of the 28 patients with cancer, 17 (61%) were female and
11 (39%) were male. Twenty-one were adults, and 7 were pe-
diatric patients. One patient had 2 different RGM species iso-
lated in cultures during the time period, comprising 29 strains
overall. Isolated species (Table 2) included Mycobacterium ab-
scessus (13 patients), Mycobacterium fortuitum (9 patients),My-
cobacterium mucogenicum (3 patients), Mycobacterium smeg-
matis, and Mycobacterium neoaurum. All isolates from blood
cultures grew in standard aerobic blood culture bottles. All
isolates from other sources grew in mycobacterial cultures.
The median age of adult patients was 62 years (range, 31–
86 years). Ten were male, and 11 were female. Four (19%) had
a history of hematologic malignancy,including2hematopoietic
stem cell transplant (HSCT) recipients, and 17 (81%) had a
history of a solid tumor. Of the 22 isolates, 13 (59%) arose
from respiratory samples. Four (18%) were collectedfromskin/
soft-tissue samples, and 1 (5%) was collected from a CVC
culture. One patient had positiveculturesfromrespiratorysam-
ples, blood culture, and skin lesions.
Two patients were HIV infected; the first was a 58-year-old
man with HIV infection (CD4 count, 180 cells/mm3) and lym-
phoma who developed CVC infection with M. mucogenicum;
the second was a 48-year-old man with HIV infection (CD4
count, 23 cells/mm3) and Kaposi sarcoma with M. fortuitum
in a stool specimen.
For pediatric patients, the median age was 5 years (range,
1–9 years). Five had neuroblastoma, 1 had Wilms tumor, and
1 had osteosarcoma. Three had undergone autologous HSCT.
The source of isolates was CVC in 6 cases and wound culture
in 1. The proportion of CVC-relatedinfectionswassignificantly
higher among pediatric patients than adults (85% vs 5%; P !
Overall, 13 patients (46%) received chemotherapy in the 3
months preceding the isolation of RGM. Of these, 7 were pe-
by guest on October 14, 2011
IMMUNOCOMPROMISED HOSTS • CID 2010:51 (15 August) • 433
caused by rapidly growing mycobacteria in patients with cancer. Chest
20. JacobsonK, GarciaR, LibshitzH,etal.Clinicalandradiologicalfeatures
of pulmonary disease caused by rapidly growingmycobacteriaincancer
patients. Eur J Clin Microbiol Infect Dis 1998;17(9):615–621.
21. Mohite U, Das M, Saikia T, et al. Mycobacterial pulmonary infection
post allogeneic bone marrow transplantation. Leuk Lymphoma 2001;
22. Au WY, Cheng VC, Ho PL, et al. Nontuberculous mycobacterial in-
fections in Chinese hematopoietic stem cell transplantation recipients.
Bone Marrow Transplant 2003;32(7):709–714.
23. Han XY, De I, Jacobson KL. Rapidly growing mycobacteria: clinical
and microbiologic studies of 115 cases. Am J Clin Pathol 2007;128(4):
24. Peres E, Khaled Y, Krijanovski OI, et al. Mycobacterium chelonae nec-
rotizing pneumonia after allogeneic hematopoietic stemcelltransplant:
report of clinical response to treatment with tigecycline. Transpl Infect
25. Svirbely JR, Buesching WJ, Ayers LW, Baker PB, Britton AJ. Mycobac-
terium fortuitum infection of a Hickman catheter site. Am J Clin Pathol
26. Davison MB, McCormack JG, Blacklock ZM, Dawson DJ, Tilse MH,
Crimmins FB. Bacteremia caused by Mycobacterium neoaurum. J Clin
27. Engler HD, Hass A, Hodes DS, Bottone EJ. Mycobacterium chelonei
infection of a Broviac catheter insertion site. Eur JClinMicrobiolInfect
28. Raad, II, Vartivarian S, Khan A, Bodey GP. Catheter-related infections
caused by the Mycobacterium fortuitum complex: 15 cases and review.
Rev Infect Dis 1991;13(6):1120–1125.
29. Hoy JF, Rolston KV, Hopfer RL, Bodey GP. Mycobacterium fortuitum
bacteremia in patients with cancer and long-term venous catheters.
Am J Med 1987;83(2):213–217.
30. Holland DJ, Chen SC, Chew WW, Gilbert GL. Mycobacterium neoau-
rum infection of a Hickman catheter in an immunosuppressed patient.
Clin Infect Dis 1994;18(6):1002–1003.
31. Moreno A, Llanos M, Gonzalez A, Batista N. Mycobacterium fortuitum
bacteremia in an immunocompromised patient with a long-term ve-
nous catheter. Eur J Clin Microbiol Infect Dis 1996;15(5):423–424.
32. Rodgers GL, Mortensen JE, Blecker-Shelly D, Fisher MC, Long SS. Two
case reports and review of vascular catheter-associated bacteremia
caused by nontuberculous Mycobacterium species. Pediatr Infect Dis J
33. Roy V, Weisdorf D. Mycobacterial infections following bone marrow
transplantation: a 20 year retrospective review. Bone Marrow Trans-
34. Graham JC, Tweddle DA, Jenkins DR, Pollitt C, Pedler SJ. Non-tu-
berculous mycobacterial infection in children with cancer. Eur J Clin
Microbiol Infect Dis 1998;17(6):394–397.
35. Levendoglu-Tugal O, Munoz J, Brudnicki A, Fevzi Ozkaynak M, San-
doval C, Jayabose S. Infections due to nontuberculous mycobacteria
in children with leukemia. Clin Infect Dis 1998;27(5):1227–1230.
36. Skiest DJ, Levi ME. Catheter-related bacteremia due to Mycobacterium
smegmatis. South Med J 1998;91(1):36–37.
37. Hogg GG, Schinsky MF, McNeil MM, Lasker BA, Silcox VA, Brown
JM. Central line sepsis in a child due to a previously unidentified
mycobacterium. J Clin Microbiol 1999;37(4):1193–1196.
38. Schinsky MF, McNeil MM, Whitney AM, et al. Mycobacterium septicum
sp. nov., a new rapidly growing species associated with catheter-related
bacteraemia. Int J Syst Evol Microbiol 2000;50(Pt 2):575–581.
39. Gaviria JM, Garcia PJ, Garrido SM, Corey L, Boeckh M. Nontuber-
culous mycobacterial infections in hematopoietic stem cell transplant
recipients: characteristics of respiratory and catheter-related infections.
Biol Blood Marrow Transplant 2000;6(4):361–369.
40. McCracken D, Flanagan P, Hill D, Hosein I. Cluster of cases of My-
cobacterium chelonae bacteraemia. Eur J Clin Microbiol Infect Dis
41. Woo PC, Tsoi HW, Leung KW, et al. Identification of Mycobacterium
neoaurum isolated from a neutropenic patient with catheter-related
bacteremia by 16S rRNA sequencing. J Clin Microbiol 2000;38(9):
42. Suara R, WhitlockJ,SpearmanP.Mycobacteriafortuitumcentralvenous
catheter-related bacteremia in an infant with renal sarcoma. Pediatr
Hematol Oncol 2001;18(5):363–365.
43. Hong T, Butler WR, Hollis F, et al. Characterization of a novel rapidly
growing Mycobacterium species associated with sepsis. J Clin Microbiol
44. Koranyi KI, Ranalli MA. Mycobacterium aurum bacteremia in an im-
munocompromised child. Pediatr Infect Dis J 2003;22(12):1108–1109.
45. Kiska DL, Turenne CY, Dubansky AS, Domachowske JB. First case
report of catheter-related bacteremia due to “Mycobacterium lacticola”.
J Clin Microbiol 2004;42(6):2855–2857.
46. Kline S, Cameron S, Streifel A, et al. An outbreak of bacteremias
associated with Mycobacterium mucogenicum in a hospitalwatersupply.
Infect Control Hosp Epidemiol 2004;25(12):1042–1049.
47. Lee SA, Raad, II, Adachi JA, Han XY. Catheter-related bloodstream
infection caused by Mycobacterium brumae. J Clin Microbiol 2004;
48. Reilly AF, McGowan KL. Atypical mycobacterial infections in children
with cancer. Pediatr Blood Cancer 2004;43(6):698–702.
49. Oh WS, Ko KS, Song JH, et al. Catheter-associated bacteremia by
Mycobacterium senegalense in Korea. BMC Infect Dis 2005;5:107.
50. Unni M, Jesudason MV, Rao S, George B. Mycobacterium fortuitum
bacteraemia in an immunocompromised patient. Indian J Med Mi-
51. Fleming GA, Frangoul H, Dermody TS, Halasa N. A cord blood trans-
plant recipient with Mycobacterium mucogenicum central venous cath-
eter infection after infusion of tap water. Pediatr Infect Dis J 2006;
52. Nicholson O, Feja K, LaRussa P, et al. Nontuberculous mycobacterial
infections in pediatric hematopoietic stem cell transplant recipients:
case report and review of the literature. Pediatr Infect Dis J2006;25(3):
53. Washer LL, Riddell Jt, Rider J, Chenoweth CE. Mycobacterium neoau-
rum bloodstream infection: report of 4 cases and review of the liter-
ature. Clin Infect Dis 2007;45(2):e10–e13.
54. Cooksey RC, Jhung MA, YakrusMA,etal.Multiphasicapproachreveals
genetic diversity of environmental and patient isolates of Mycobacte-
rium mucogenicum and Mycobacterium phocaicum associated with an
outbreak of bacteremias at a Texas hospital. Appl Environ Microbiol
55. Livni G, Yaniv I, Samra Z, et al. Outbreak of Mycobacterium muco-
genicum bacteraemia due to contaminated water supply in a paediatric
haematology-oncology department. J Hosp Infect2008;70(3):253–258.
56. Marshall C, Samuel J, Galloway A, Pedler S. Mycobacterium mucogen-
icum from the Hickman line of an immunocompromised patient. J
Clin Pathol 2008;61(1):140–141.
57. Landau W, Feczko J, Kaplan RL.Radiometricdetectionofmycobacteria
in routine blood cultures. J Clin Microbiol 1980;12(3):477–478.
58. Pottage JC Jr, Harris AA, Trenholme GM, Levin S, Kaplan RL, Feczko
JM. Disseminated Mycobacterium chelonei infection: a report of two
cases. Am Rev Respir Dis 1982;126(4):720–722.
59. Righter J, Hart GD, Howes M. Mycobacterium chelonei: report of a
case of septicemia and review of the literature. Diagn Microbiol Infect
60. Wallace RJ Jr, Swenson JM, Silcox VA, Good RC, Tschen JA, Stone
MS. Spectrum of disease due to rapidly growing mycobacteria. Rev
Infect Dis 1983;5(4):657–679.
61. Carpenter JL, Troxell M, Wallace RJ Jr. Disseminated disease due to
Mycobacterium chelonei treated with amikacin and cefoxitin: absence
of killing with either agent and possible role of granulocytes in clinical
response. Arch Intern Med 1984;144(10):2063–2065.
62. Bennett C, Vardiman J, Golomb H. Disseminated atypical mycobac-
by guest on October 14, 2011
434 • CID 2010:51 (15 August) • IMMUNOCOMPROMISED HOSTS
terial infection in patients with hairy cell leukemia. Am J Med 1986;
63. Lazo-de-la-Vega SA, Pezzarossi HE, Ponce-de-LeonS,SifuentesJ,Ruiz-
Palacios GM. Cutaneous manifestation of disseminated infection by
Mycobacterium fortuitum biovariant “third group”. J Am Acad Der-
matol 1987;16(5 Pt 1):1058–1060.
64. Wallace RJ Jr, Tanner D, Brennan PJ, Brown BA. Clinical trial of cla-
rithromycin for cutaneous (disseminated) infection due to Mycobac-
terium chelonae. Ann Intern Med 1993;119(6):482–486.
65. Vogels MT, Tjan-Heijnen VC, Alkemade JA, Beex LV, Muytjens HL.
Cutaneous infection due to Mycobacterium abscessus: a case report.
Acta Derm Venereol 1997;77(3):222–224.
66. Mueller PS, Edson RS. Disseminated Mycobacteriumabscessusinfection
manifesting as fever of unknown origin and intra-abdominal lym-
phadenitis: case report and literature review. Diagn Microbiol Infect
67. Robinson H, Smith S. Mycobacterium fortuitum infection in a patient
with chronic lymphocytic leukaemia. Br J Haematol 2004;127(2):126.
68. Chen YC, Jou R, Huang WL, et al. BacteremiacausedbyMycobacterium
wolinskyi. Emerg Infect Dis 2008;14(11):1818–1819.
69. Kusunoki S, Ezaki T. Proposal of Mycobacterium peregrinum sp. nov.,
nom. rev., and elevation of Mycobacterium chelonae subsp. abscessus
(Kubica et al.) to species status: Mycobacterium abscessus comb. nov.
Int J Syst Bacteriol 1992;42(2):240–245.
70. Griffith DE, Girard WM, Wallace RJ Jr. Clinical features of pulmonary
disease caused by rapidly growing mycobacteria: an analysis of 154
patients. Am Rev Respir Dis 1993;147(5):1271–1278.
71. Rosenzweig SD, Holland SM. Defects in the interferon-gamma and
interleukin-12 pathways. Immunol Rev 2005;203:38–47.
72. Agheli A, Tehranirad M, Cofsky R. An unusual presentation of My-
cobacterium fortuitum: massive isolated empyemainapatientwithHIV.
73. Benwill J, Babineaux M, Sarria JC. Pulmonary Mycobacterium abscessus
in an AIDS Patient. Am J Med Sci 2010;339(5):495–496.
74. Butt AA. Cervical adenitis due to Mycobacterium fortuitum in patients
with acquired immunodeficiency syndrome. Am J Med Sci 1998;
75. Butt AA, Janney A. Arthritis due to mycobacterium fortuitum. Scand
J Infect Dis 1998;30(5):525–527.
76. Eichmann A, Huszar A, Bon A. Mycobacterium chelonae infection of
lymph nodes in an HIV-infected patient. Dermatology 1993;187(4):
77. Ersoz G, Kaya A, Cayan S, et al. Urinary Mycobacterium fortuitum
infection in an HIV-infected patient. AIDS 2000;14(17):2802–2803.
78. Khatter S, Singh UB, Arora J, Rana T, Seth P. Mycobacterial infections
in human immuno-deficiency virus seropositive patients: role of non-
tuberculous mycobacteria. Indian J Tuberc 2008;55(1):28–33.
79. Lambert GW, Baddour LM. Right middle lobe syndrome caused by
Mycobacterium fortuitum in a patient with human immunodeficiency
virus infection. South Med J 1992;85(7):767–769.
80. Phowthongkum P, Prasanthai V, Udomsantisook N, Suankratay C.
Rapidly growing mycobacteria in King Chulalongkorn Memorial Hos-
pital and review of the literature in Thailand. J Med Assoc Thai
81. Rodriguez-Barradas MC, Clarridge J, Darouiche R. Disseminated My-
cobacterium fortuitum disease in an AIDS patient. Am J Med 1992;
82. Sack JB. Disseminated infection due to Mycobacterium fortuitum in a
patient with AIDS. Rev Infect Dis 1990;12(5):961–963.
83. Sakai T, Kobayashi C, Shinohara M. Mycobacterium peregrinum infec-
tion in a patient with AIDS. Intern Med 2005;44(3):266–269.
84. Saritsiri S, Udomsantisook N, Suankratay C. Nontuberculous myco-
bacterial infections in King Chulalongkorn Memorial Hospital. J Med
Assoc Thai 2006;89(12):2035–2046.
85. Smith MB, Schnadig VJ, Boyars MC, Woods GL. Clinical and path-
ologic features of Mycobacterium fortuitum infections: an emerging
pathogen in patients with AIDS. Am J Clin Pathol 2001;116(2):
86. Sungkanuparph S, Sathapatayavongs B, PracharktamR. Infectionswith
rapidly growing mycobacteria: report of 20 cases. Int J Infect Dis
87. Brady MT, Marcon MJ, Maddux H. Broviac catheter-related infection
due to Mycobacterium fortuitum in a patient with acquired immu-
nodeficiency syndrome. Pediatr Infect Dis J 1987;6(5):492–494.
by guest on October 14, 2011