International Journal of Antimicrobial Agents 43 (2014) 438–441
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International Journal of Antimicrobial Agents journal homepage: http://www.elsevier.com/locate/ijantimicag
Bacteraemia caused by Mycobacterium abscessus subsp. abscessus and M. abscessus subsp. bolletii: Clinical features and susceptibilities of the isolates Meng-Rui Lee a , Jen-Chung Ko a , Sheng-Kai Liang a , Shih-Wei Lee b , David Hung-Tsang Yen c , Po-Ren Hsueh d,e,∗ a
Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan Department of Internal Medicine, Taoyuan General Hospital, Taoyuan, Taiwan c Department of Emergency Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan d Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan e Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan b
a r t i c l e
i n f o
Article history: Received 30 October 2013 Accepted 7 February 2014 Keywords: Mycobacterium abscessus subsp. abscessus Mycobacterium abscessus subsp. bolletii Bacteraemia Tigecycline Clarithromycin
a b s t r a c t Mycobacterium abscessus complex (M. abscessus subsp. abscessus and M. abscessus subsp. bolletii) is an emerging pathogen causing various human infections. However, few studies have focused on M. abscessus complex bacteraemia with detailed species differentiation. The clinical characteristics of patients with bacteraemia due to M. abscessus complex treated at National Taiwan University Hospital from 2005–2012 were evaluated. Species identification was performed by molecular methods, and minimum inhibitory concentrations (MICs) were determined using a Sensititre RAPMYCO Panel Test for preserved M. abscessus complex isolates. During the study period, 15 patients with M. abscessus complex bacteraemia were found but only 14 isolates from 13 patients were preserved for analysis. One patient had two episodes of bacteraemia (one caused by M. abscessus subsp. bolletii and one by M .abscessus subsp. abscessus with a 9month interval). Of the remaining 12 patients, 9 patients had M. abscessus subsp. bolletii bacteraemia and 3 had M .abscessus subsp. abscessus bacteraemia. Patients were mainly middle-aged adults with various comorbidities. Steroid usage and malignancy (5/15) were the most common immunocompromised statuses, followed by diabetes mellitus (4/15). Surgical wound infection was the most common infection foci in all patients (5/15), particularly in M. abscessus subsp. bolletii bacteraemia patients. Clarithromycin and tigecycline exhibited good in vitro activities. Overall, the 14-day mortality was 20% (3/15). M. abscessus complex bacteraemia should be considered an emerging opportunistic infection in immunocompromised hosts. Clarithromycin and tigecycline have potent in vitro activities and are promising agents for treating infections due to M. abscessus complex. © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
1. Introduction Mycobacterium abscessus complex is an emerging pathogen worldwide and is notorious for its multidrug resistance and being a difficult-to-treat clinical disease [1]. Recently, geographic diversity in the prevalence of nontuberculous mycobacteria (NTM) has been reported, with rapidly growing mycobacteria becoming highly
∗ Corresponding author at: Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7 ChungShan South Road, Taipei 100, Taiwan. Tel.: +886 2 2312 3456x65355; fax: +886 2 2322 4263. E-mail address: [email protected] (P.-R. Hsueh).
prevalent in East Asia [2]. In Taiwan, M. abscessus complex has become the second most common NTM species isolated, second only to Mycobacterium avium complex, and the trend is still on the rise [3]. Two major types of infection caused by M. abscessus complex are pulmonary infection and skin and soft-tissue infection [1]. Three closely related Mycobacterium subsp., namely Mycobacterium massiliense, Mycobacterium bolletii and M. abscessus sensu stricto, have been differentiated from M. abscessus complex based on the erm(41), 23S rRNA and rpoB genes. Not until recently have M. massiliense and M. bolletii been proposed to be united and classified as M. abscessus subsp. bolletii [4]. Although mycobacterial bacteraemia is a rare disease, it carries significant mortality [5]. Bacteraemia caused by M. abscessus
http://dx.doi.org/10.1016/j.ijantimicag.2014.02.007 0924-8579/© 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
M.-R. Lee et al. / International Journal of Antimicrobial Agents 43 (2014) 438–441
complex constitutes only a small proportion of mycobacterial bacteraemia [5]. Few reports have described M. abscessus complex bacteraemia, which commonly develops in patients with immunocompromised status [5]. Even fewer studies, except case reports, have performed further species differentiation among M. abscessus complex bacteraemia [6,7]. This study was therefore initiated to describe the clinical characteristics, treatment and clinical outcome of M. abscessus complex bacteraemia. Differentiation between M. abscessus subsp. abscessus and M. abscessus subsp. bolletii was also performed.
2. Materials and methods 2.1. Subjects This study was conducted at National Taiwan University Hospital (NTUH), a 2900-bed tertiary care centre in northern Taiwan. The mycobacterial laboratory registry database covering the period January 2005 to May 2012 was searched to identify M. abscessus bacteraemia patients. A standardised case record form was used to collect demographic and clinical data, including age, sex, infection focus (portal of entry), underlying status, other sites of positive M. abscessus complex culture, and agents used for anti-NTM treatment. For steroid users, reasons for use, duration and dosage were recorded. Crude mortality was calculated on Days 14 and 30 after the bacteraemic episode as the main patient clinical outcome.
2.2. Isolation of M. abscessus complex from clinical specimens Preparation of different clinical specimens for culture of mycobacteria at NTUH Mycobacteriology Laboratory was reported previously and followed recommended guidelines [8]. Blood samples tested for mycobacteria were inoculated directly in BACTEC 9240 MYCO/F Lytic bottles (Becton Dickinson Microbiology Systems, Sparks, MD) and were incubated for 4 weeks as previously described [5]. NTM isolates were identified to species level using conventional biochemical methods as previously described [8]. Isolates of M. abscessus complex were further identified to subspecies level by erm(41) PCR and gene sequence analysis of rpoB and 23S rRNA [9]. The following primer pairs were used: ermF (5 -GAC CGG GGCCTT CTT CGT GAT-3 ) and ermR1 (5 -GAC TTC CCC GCA CCG ATT CC-3 ) for the whole erm(41) gene; rpoB F (5 -GGCAAGGTCACCCCGAAGGG3 ) and rpoB R (5 -AGCGGCTGCTGGGTGATCATC-3 ) for the rpoB gene; and 19 (5 -GTAGCGAAATTCCTTGTCGG-3 ) and 21 (5 TTCCCGCTTAGATGCTTTCAG-3 ) for the 23S rRNA gene [9].
2.3. Antimicrobial susceptibility Minimum inhibitory concentrations (MICs) of the identified M. abscessus complex isolates to 15 antimicrobial agents were determined using a Sensititre RAPMYCO Panel Test (TREK Diagnostic Systems, Magellan Biosciences, East Grinstead, UK). Agents included in the panel were amikacin, amoxicillin/clavulanic acid, cefepime, cefoxitin, ceftriaxone, ciprofloxacin, clarithromycin, doxycycline, imipenem, linezolid, minocycline, moxifloxacin, trimethoprim/sulfamethoxazole, tigecycline and tobramycin. The MICs of all agents tested were read on the fifth day after incubation, and those of clarithromycin were also read on extended incubation (14 days). MIC breakpoints indicating susceptible, intermediate or resistant isolates were interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines [10].
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3. Results During the period January 2005–May 2012, 15 patients with bacteraemia due to M. abscessus complex were treated at NTUH. Two isolates recovered from two patients were not preserved for further species identification. One 54-year-old female with chronic hepatitis C virus infection and previous pulmonary tuberculosis (TB) presented to the hospital with fever and lymphadenopathy over the bilateral cervical and periauricular area. The patient developed two episodes of M. abscessus complex bacteraemia (one caused by M. abscessus subsp. bolletii and the other due to M. abscessus subsp. abscessus within a 9-month interval). She received intravenous (i.v.) imipenem and amikacin during hospitalisation and oral clarithromycin plus minocycline or moxifloxacin treatment for 12 months and recovered well. Among the remaining 12 patients with M. abscessus complex singular bacteraemia in whom the isolates were preserved, 9 were confirmed to have M. abscessus subsp. bolletii and the other 3 patients were confirmed to have M. abscessus subsp. abscessus by erm(41) PCR and gene sequence analysis of rpoB and 23S rRNA. The details and summarised clinical characteristics of 15 patients with bacteraemia caused by M. abscessus complex are shown in Table 1. The 15 patients were mainly middle-aged adults (median age 54 years), and 3 patients were children. Primary bacteraemia was found in four patients (27%) and surgical wound infection was present in five patients (33%). Fourteen patients (93%) had healthcare-associated M. abscessus complex bacteraemia. Steroid usage (5/15; 33%) and malignancy (5/15; 33%) were the most common underlying immunocompromised statuses, followed by diabetes mellitus (4/15; 27%). All five patients receiving steroids received >10 mg of prednisolone equivalent corticosteroids for ≥2 months prior to M. abscessus complex bacteraemia. The reasons for steroid use were adrenal insufficiency in four patients and autoimmune disease in one patient. Clarithromycin in combination with imipenem and amikacin remained the most common treatment regimen used for M. abscessus complex bacteraemia. The mean duration of i.v. antimicrobial treatment was 27 days (range 4–57 days) for patients with M. abscessus subsp. bolletii infection and 7 days (range 2–15 days) for patients infected with M .abscessus subsp. abscessus. The mean duration of clarithromycin use was 85 days (range 7–210 days) among patients with M. abscessus subsp. bolletii infection and 120 days (range 18–221 days) among patients infected with M. abscessus subsp. abscessus. The number of patients classified by year of onset was two (13%) during 2005–2007, six (40%) during 2008–2010 and seven (47%) during 2011–2012. Among the nine patients with M. abscessus subsp. bolletii bacteraemia, two were infants. Wound infection (five post-surgical wound infection) was the most common infection focus (5/9; 56%). Among the three patients with M. abscessus subsp. abscessus bacteraemia, all had healthcare-associated bacteraemia and none was considered to be secondary to wound infection. The MICs of the 15 antimicrobial agents against the 14 M. abscessus complex isolates are shown in Table 2. Amoxicillin/clavulanic acid, cephalosporins, imipenem, tetracycline, fluoroquinolones and aminoglycosides had poor in vitro activities against all 14 isolates. Nine (90%) of the 10 M. abscessus subsp. bolletii isolates and all four of the M. abscessus subsp. abscessus isolates were susceptible to amikacin. Of the 14 M. abscessus complex isolates, 12 were inhibited by tigecycline at 1.0 mg/L and all 14 were inhibited by clarithromycin at 0.5 mg/L after 5 days of incubation. After prolonged incubation (14 days), two (20%) of the ten M. abscessus subsp. bolletii isolates had clarithromycin MICs (0.5 mg/L)
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Table 1 Clinical characteristics of 15 patients with bacteraemia caused by Mycobacterium abscessus complex treated at National Taiwan University Hospital from 2005 to 2012. M. abscessus subsp.
Age/sex
Underlying disease
Infection focus
Source
Treatment
Outcome
1 2 3 4 5 6 7 8 9 10a 11 12 13 14 15
bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii and abscessus abscessus abscessus abscessus N/A N/A
75 years/M 81 years/F 16 years/F 65 years/F 57 years/M 3 months/F 52 years/M 6 months/M 50 years/M 54 years/F 45 years/F 65 years/M 55 years/F 50 years/M 3 months/M
Diabetes mellitus, end-stage renal disease, steroid usage Diabetes mellitus, end-stage renal disease Heart transplantation, steroid usage Sjögren’s syndrome Diabetes mellitus, hepatocellular carcinoma, steroid usage, liver transplantation Down’s syndrome, congenital heart disease Pancreatic cancer, recent chemotherapy X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency Diabetes mellitus, ischaemic heart disease, steroid usage Hepatitis C virus infection Dermatomyositis, steroid usage Lung cancer Leukaemia, recent chemotherapy Nasopharyngeal cancer Hypoplastic left heart
Infective endocarditis Surgical wound Surgical wound Disseminated Surgical wound Surgical wound Surgical wound Primary Primary Disseminated Pneumonia Pneumonia Primary Catheter-related Primary
CA HA HA HA HA HA HA HA HA HA HA HA HA HA HA
IPM, MXF, CLR TIG, CIP IPM, AMK, LVX IPM, AMK, CLR, DOX IPM, AMK IPM, AMK, CLR, LNZ IPM, AMK, CLR, LVX IPM, AMK, CLR, LNZ IPM, CLR IPM, AMK, CLR, MIN, MXF IPM, LVX IPM, AMK, CLR, CIP IPM, AMK, CLR, MXF IPM, AMK, CLR, CIP Nil
Mortality (Day 7) Survived Survived Survived Survived Survived Survived Survived Survived Survived Mortality (Day 6) Survived Survived Survived Mortality (Day 6)
CA, community-acquired; HA, healthcare-associated; IPM, imipenem; MXF, moxifloxacin; CLR, clarithromycin; TIG, tigecycline; CIP, ciprofloxacin; AMK, amikacin; LVX, levofloxacin; DOX, doxycycline; LNZ, linezolid; MIN, minocycline; N/A, not available (isolate not preserved). a Patient 10 developed two episodes of M. abscessus complex bacteraemia, one caused by M. abscessus subsp. bolletii and the other due to M. abscessus subsp. abscessus.
Table 2 Antimicrobial susceptibilities of 14 isolates of Mycobacterium abscessus complex from 13 patients to 15 antimicrobial agents. Patient no.a
M. abscessus subspecies
MIC (mg/L) (susceptibility categoryb ) AMC
1 2 3 4 5 6 7 8 9 10d 10d 11 12 13
bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii abscessus abscessus abscessus abscessus
>64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32
FOX
CRO
FEP
IPM
CIP
MXF
64 (I) 32 (I) 32 (I) 64 (I) 32 (I) 64 (I) 64 (I) 32 (I) 32 (I) 64 (I) 128 (R) 32 (I) 64 (I) 64 (I)
>64 >64 >64 >64 >64 >64 >64 >64 >64 >64 >64 >64 >64 >64
>32 >32 >32 >32 >32 >32 >32 >32 >32 >32 32 >32 >32 >32
64 (R) 16 (R) 16 (R) 64 (R) 32 (R) 64 (R) 32 (R) 32 (R) 64 (R) 32 (R) 32 (R) 16 (R) 32 (R) 32 (R)
>4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R)
8 (R) >8 (R) >8 (R) >8 (R) >8 (R) >8 (R) >8 (R) >8 (R) >8 (R) >8 (R) 8 (R) 8 (R) 8 (R) >8 (R)
DOX
MIN
>16 (R) >16 (R) >16 (R) >16 (R) >16 (R) >16 (R) 16 (R) 16 (R) >16 (R) 16 (R) >16 (R) >16 (R) >16 (R) 16 (R)
>8 (R) >8 (R) >8 (R) >8 (R) 8 (R) 8 (R) 8 (R) 8 (R) 8 (R) 8 (R) >8 (R) >8 (R) >8 (R) 8 (R)
LZD
TOB
AMK
TIGc
16 (R) 8 (S) 16 (R) 16 (R) >32 (R) >32 (R) >32 (R) 32 (R) >32 (R) >32 (R) 8 (S) 16 (R) 16 (R) >32 (R)
>16 (R) 8 (R) 16 (R) 8 (R) 16 (R) >16 (R) 16 (R) >16 (R) >16 (R) 16 (R) 8 (R) 8 (R) 8 (R) >16 (R)
16 (S) 8 (S) 4 (S) 16 (S) 32 (I) 16 (S) 8 (S) 8 (S) 16 (S) 8 (S) 2 (S) 2 (S) 8 (S) 16 (S)
0.06 1 1 0.5 4 2 1 1 1 1 0.25 0.5 0.5 1
SXT >8/152 (R) >8/152 (R) >8/152 8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) 8/152 (R) >8/152 (R)
CLR (5-day/14-day) 0.06 (S)/0.12 (S) 0.06 (S)/0.5 (S) 0.5 (S)/0.5 (S) 0.06 (S)/0.5 (S) 0.25 (S)/0.5 (S) 0.25 (S)/0.5 (S) 0.25 (S)/1 (S) 0.25 (S)/0.5 (S) 0.5 (S)/0.5 (S) 0.12 (S)/0.25 (S) 0.25 (S)/0.25 (S) 0.12 (S)/0.5 (S) 0.5 (S)/>16 (R) 0.25 (S)/0.5 (S)
MIC, minimum inhibitory concentration; AMC, amoxicillin/clavulanic acid; FOX, cefoxitin; CRO, ceftriaxone; FEP, cefepime; IPM, imipenem; CIP, ciprofloxacin; MXF, moxifloxacin; DOX, doxycycline; MIN, minocycline; LZD, linezolid; TOB, tobramycin; AMK, amikacin; TIG, tigecycline; SXT, trimethoprim/sulfamethoxazole; CLR, clarithromycin; S, susceptible; I, intermediate; R, resistant. a See Table 1 for patient designation. b Susceptibility category criteria for each agent were according to the guidelines established by the Clinical and Laboratory Standards Institute (CLSI) [10]. c There are no CLSI breakpoints for tigecycline, therefore no susceptibility categories are shown. d These two isolates were obtained from one patient (No. 10) who developed two episodes of bacteraemia due to different M. abscessus complex species (one M. abscessus subsp. bolletii and one M. abscessus subsp. abscessus, with an interval of 9 months).
M.-R. Lee et al. / International Journal of Antimicrobial Agents 43 (2014) 438–441
Patient no.
M.-R. Lee et al. / International Journal of Antimicrobial Agents 43 (2014) 438–441
eight-fold higher than those (0.06 mg/L) by 5-day incubation. Only one (25%) of the four M. abscessus subsp. abscessus isolates had inducible clarithromycin resistance, with a MIC of 0.5 mg/L by 5-day incubation and >16 mg/L after 14-day incubation. 4. Discussion This study revealed that a great proportion of M. abscessus complex bacteraemia patients were due to M. abscessus subsp. bolletii. Only two cases of M. abscessus subsp. bolletii bacteraemia confirmed by hsp65 and rpoB genes and the 16S–23S rRNA internal transcribed spacer (ITS) region have been reported [6,7]. The first M. abscessus subsp. bolletii bacteraemia case report described a leukopenic kidney transplant patient with co-infection of pulmonary TB who had sudden death before identification of M. abscessus subsp. bolletii bacteraemia [7]. A more recent report described a chronic myelogenous leukaemia patient who had M. abscessus subsp. bolletii bacteraemia [6]. These two patients were both immunocompromised and M. abscessus subsp. bolletii was suspected as contributing to death in one patient. Rapidly growing mycobacteria bacteraemia is always considered to be related to catheter-related bloodstream infection [11]. However, in the current study only one case was attributed to catheter-related bacteraemia. M. abscessus subsp. bolletii has been reported in association with nosocomial infections, particularly resulting from surgical procedures [12]. It was also evident in the current study that M. abscessus subsp. bolletii was associated with surgical wound infections. The five patients with surgical wound infection had immunocompromised status in common, which can dispose vulnerable patients to the development of M. abscessus subsp. bolletii bacteraemia. Current American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines recommend the use of macrolidebased combination therapy with parenteral medications including amikacin, cefoxitin and imipenem [1]. Cefoxitin is not available in NTUH, and imipenem plus amikacin became the most common i.v. agents. No study has examined different treatment regimens for M. abscessus complex bacteraemia. Tigecycline is a novel antibiotic that has shown low MICs towards M. abscessus complex and is now being considered a promising agent [13]. However, particular caution should be paid to the use of the combination of tigecycline and amikacin owing to the potential antagonist effect of the two agents [14]. Instead, tigecycline plus clarithromycin exerts better synergistic activity against M. abscessus complex [14]. Use of tigecycline may be considered in bacteraemic M. abscessus complex patients, and further study is warranted to prove its efficacy. Amikacin is another agent that showed high susceptibility rates in this study. In a previous study testing M. abscessus complex isolates in Taiwan, a universal high susceptible rate to amikacin was found [15]. However, there are still concerns regarding amikacinassociated toxicity, especially in the setting of prolonged injection. The optimal treatment duration of antimicrobial therapy against M. abscessus complex bacteraemia still remains undetermined. One significant difference between M. abscessus subsp. abscessus and M. abscessus subsp. bolletii lies in their clarithromycin susceptibility [9]. Inducible clarithromycin resistance is frequently present in M. abscessus subsp. abscessus but not in M. abscessus subsp. bolletii [9]. In this study, inducible clarithromycin resistance was found in 25% of M. abscessus subsp. abscessus isolates but in none of the M. abscessus subsp. bolletii isolates. Although the limited case number and unstandardised treatment regimen prevented us from comparing the treatment response, there appeared to be a lower mortality rate in patients with singular bacteraemia due to M. abscessus subsp. bolletii compared with those with M. abscessus subsp. abscessus singular bacteraemia [14-day mortality, 11% (1/9) vs. 33% (1/3)].
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Compared with our previous study [5], there was a significant increase in the number of M. abscessus complex bacteraemia cases. There were seven new M. abscessus complex bacteraemia patients during January 2011–May 2012, which is a significant upward trend. The prolonged hospitalisation course among immunocompromised patients and the contribution of post-surgical infection together may contribute to the emerging M. abscessus complex bacteraemia. Whilst disease caused by NTM remains an emerging disease with increasing incidence, further studies and monitoring may be needed to elucidate the trend of M. abscessus complex bacteraemia. In conclusion, we describe 15 patients with M. abscessus complex bacteraemia and found these patients to be mainly middle-aged adults with underlying immunocompromised status and most with healthcare-associated bacteraemia. Surgical wound infections should be considered an important cause of M. abscessus subsp. bolletii bacteraemia. Clarithromycin and tigecycline exert low MICs. The incidence of M. abscessus complex bacteraemia appears to be increasing. Funding: No funding sources. Competing interests: None declared. Ethical approval: Not required. References [1] Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175: 367–416. [2] Hoefsloot W, van Ingen J, Andrejak C, Angeby K, Bauriaud R, Bemer P, et al. The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study. Eur Respir J 2013;42: 1604–13. [3] Lai CC, Tan CK, Chou CH, Hsu HL, Liao CH, Huang YT, et al. Increasing incidence of nontuberculous mycobacteria, Taiwan, 2000–2008. Emerg Infect Dis 2010;16:294–6. [4] 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;61:2311–13. [5] Tan CK, Lai CC, Liao CH, Chou CH, Hsu HL, Huang YT, et al. Mycobacterial bacteraemia in patients infected and not infected with human immunodeficiency virus, Taiwan. Clin Microbiol Infect 2010;16:627–30. [6] Hamamoto T, Yuki A, Naoi K, Kawakami S, Banba Y, Yamamura T, et al. Bacteremia due to Mycobacterium massiliense in a patient with chronic myelogenous leukemia: case report. Diagn Microbiol Infect Dis 2012;74: 183–5. [7] Tortoli E, Gabini R, Galanti I, Mariottini A. Lethal Mycobacterium massiliense sepsis, Italy. Emerg Infect Dis 2008;14:984–5. [8] Lee MR, Cheng A, Huang YT, Liu CY, Chung KP, Wang HC, et al. Performance assessment of the DR TBDR/NTM IVD kit for direct detection of Mycobacterium tuberculosis isolates, including rifampin-resistant isolates, and nontuberculous mycobacteria. J Clin Microbiol 2012;50:3398–401. [9] Kim HY, Kim BJ, Kook Y, Yun YJ, Shin JH, Kim BJ, et al. Mycobacterium massiliense is differentiated from Mycobacterium abscessus and Mycobacterium bolletii by erythromycin ribosome methyltransferase gene (erm) and clarithromycin susceptibility patterns. Microbiol Immunol 2010;54:347–53. [10] Clinical and Laboratory Standards Institute. Susceptibility testing of mycobacteria, nocardiae, and other aerobic actinomycetes; approved standard. 2nd ed. Document M24-A2 Wayne, PA: CLSI; 2011. [11] El Helou G, Hachem R, Viola GM, El Zakhem A, Chaftari AM, Jiang Y, et al. Management of rapidly growing mycobacterial bacteremia in cancer patients. Clin Infect Dis 2013;56:843–6. [12] Lee MR, Cheng A, Lee YC, Yang CY, Lai CC, Huang YT, et al. CNS infections caused by Mycobacterium abscessus complex: clinical features and antimicrobial susceptibilities of isolates. J Antimicrob Chemother 2012;67: 222–5. [13] Wallace Jr RJ, Brown-Elliott BA, Crist CJ, Mann L, Wilson RW. 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 2002;46:3164–7. [14] Huang CW, Chen JH, Hu ST, Huang WC, Lee YC, Huang CC, et al. Synergistic activities of tigecycline with clarithromycin or amikacin against rapidly growing mycobacteria in Taiwan. Int J Antimicrob Agents 2013;41:218–23. [15] Huang YC, Liu MF, Shen GH, Lin CF, Kao CC, Liu PY, et al. Clinical outcome of Mycobacterium abscessus infection and antimicrobial susceptibility testing. J Microbiol Immunol Infect 2010;43:401–6.
Contents lists available at ScienceDirect
International Journal of Antimicrobial Agents journal homepage: http://www.elsevier.com/locate/ijantimicag
Bacteraemia caused by Mycobacterium abscessus subsp. abscessus and M. abscessus subsp. bolletii: Clinical features and susceptibilities of the isolates Meng-Rui Lee a , Jen-Chung Ko a , Sheng-Kai Liang a , Shih-Wei Lee b , David Hung-Tsang Yen c , Po-Ren Hsueh d,e,∗ a
Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan Department of Internal Medicine, Taoyuan General Hospital, Taoyuan, Taiwan c Department of Emergency Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan d Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan e Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan b
a r t i c l e
i n f o
Article history: Received 30 October 2013 Accepted 7 February 2014 Keywords: Mycobacterium abscessus subsp. abscessus Mycobacterium abscessus subsp. bolletii Bacteraemia Tigecycline Clarithromycin
a b s t r a c t Mycobacterium abscessus complex (M. abscessus subsp. abscessus and M. abscessus subsp. bolletii) is an emerging pathogen causing various human infections. However, few studies have focused on M. abscessus complex bacteraemia with detailed species differentiation. The clinical characteristics of patients with bacteraemia due to M. abscessus complex treated at National Taiwan University Hospital from 2005–2012 were evaluated. Species identification was performed by molecular methods, and minimum inhibitory concentrations (MICs) were determined using a Sensititre RAPMYCO Panel Test for preserved M. abscessus complex isolates. During the study period, 15 patients with M. abscessus complex bacteraemia were found but only 14 isolates from 13 patients were preserved for analysis. One patient had two episodes of bacteraemia (one caused by M. abscessus subsp. bolletii and one by M .abscessus subsp. abscessus with a 9month interval). Of the remaining 12 patients, 9 patients had M. abscessus subsp. bolletii bacteraemia and 3 had M .abscessus subsp. abscessus bacteraemia. Patients were mainly middle-aged adults with various comorbidities. Steroid usage and malignancy (5/15) were the most common immunocompromised statuses, followed by diabetes mellitus (4/15). Surgical wound infection was the most common infection foci in all patients (5/15), particularly in M. abscessus subsp. bolletii bacteraemia patients. Clarithromycin and tigecycline exhibited good in vitro activities. Overall, the 14-day mortality was 20% (3/15). M. abscessus complex bacteraemia should be considered an emerging opportunistic infection in immunocompromised hosts. Clarithromycin and tigecycline have potent in vitro activities and are promising agents for treating infections due to M. abscessus complex. © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
1. Introduction Mycobacterium abscessus complex is an emerging pathogen worldwide and is notorious for its multidrug resistance and being a difficult-to-treat clinical disease [1]. Recently, geographic diversity in the prevalence of nontuberculous mycobacteria (NTM) has been reported, with rapidly growing mycobacteria becoming highly
∗ Corresponding author at: Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, No. 7 ChungShan South Road, Taipei 100, Taiwan. Tel.: +886 2 2312 3456x65355; fax: +886 2 2322 4263. E-mail address: [email protected] (P.-R. Hsueh).
prevalent in East Asia [2]. In Taiwan, M. abscessus complex has become the second most common NTM species isolated, second only to Mycobacterium avium complex, and the trend is still on the rise [3]. Two major types of infection caused by M. abscessus complex are pulmonary infection and skin and soft-tissue infection [1]. Three closely related Mycobacterium subsp., namely Mycobacterium massiliense, Mycobacterium bolletii and M. abscessus sensu stricto, have been differentiated from M. abscessus complex based on the erm(41), 23S rRNA and rpoB genes. Not until recently have M. massiliense and M. bolletii been proposed to be united and classified as M. abscessus subsp. bolletii [4]. Although mycobacterial bacteraemia is a rare disease, it carries significant mortality [5]. Bacteraemia caused by M. abscessus
http://dx.doi.org/10.1016/j.ijantimicag.2014.02.007 0924-8579/© 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
M.-R. Lee et al. / International Journal of Antimicrobial Agents 43 (2014) 438–441
complex constitutes only a small proportion of mycobacterial bacteraemia [5]. Few reports have described M. abscessus complex bacteraemia, which commonly develops in patients with immunocompromised status [5]. Even fewer studies, except case reports, have performed further species differentiation among M. abscessus complex bacteraemia [6,7]. This study was therefore initiated to describe the clinical characteristics, treatment and clinical outcome of M. abscessus complex bacteraemia. Differentiation between M. abscessus subsp. abscessus and M. abscessus subsp. bolletii was also performed.
2. Materials and methods 2.1. Subjects This study was conducted at National Taiwan University Hospital (NTUH), a 2900-bed tertiary care centre in northern Taiwan. The mycobacterial laboratory registry database covering the period January 2005 to May 2012 was searched to identify M. abscessus bacteraemia patients. A standardised case record form was used to collect demographic and clinical data, including age, sex, infection focus (portal of entry), underlying status, other sites of positive M. abscessus complex culture, and agents used for anti-NTM treatment. For steroid users, reasons for use, duration and dosage were recorded. Crude mortality was calculated on Days 14 and 30 after the bacteraemic episode as the main patient clinical outcome.
2.2. Isolation of M. abscessus complex from clinical specimens Preparation of different clinical specimens for culture of mycobacteria at NTUH Mycobacteriology Laboratory was reported previously and followed recommended guidelines [8]. Blood samples tested for mycobacteria were inoculated directly in BACTEC 9240 MYCO/F Lytic bottles (Becton Dickinson Microbiology Systems, Sparks, MD) and were incubated for 4 weeks as previously described [5]. NTM isolates were identified to species level using conventional biochemical methods as previously described [8]. Isolates of M. abscessus complex were further identified to subspecies level by erm(41) PCR and gene sequence analysis of rpoB and 23S rRNA [9]. The following primer pairs were used: ermF (5 -GAC CGG GGCCTT CTT CGT GAT-3 ) and ermR1 (5 -GAC TTC CCC GCA CCG ATT CC-3 ) for the whole erm(41) gene; rpoB F (5 -GGCAAGGTCACCCCGAAGGG3 ) and rpoB R (5 -AGCGGCTGCTGGGTGATCATC-3 ) for the rpoB gene; and 19 (5 -GTAGCGAAATTCCTTGTCGG-3 ) and 21 (5 TTCCCGCTTAGATGCTTTCAG-3 ) for the 23S rRNA gene [9].
2.3. Antimicrobial susceptibility Minimum inhibitory concentrations (MICs) of the identified M. abscessus complex isolates to 15 antimicrobial agents were determined using a Sensititre RAPMYCO Panel Test (TREK Diagnostic Systems, Magellan Biosciences, East Grinstead, UK). Agents included in the panel were amikacin, amoxicillin/clavulanic acid, cefepime, cefoxitin, ceftriaxone, ciprofloxacin, clarithromycin, doxycycline, imipenem, linezolid, minocycline, moxifloxacin, trimethoprim/sulfamethoxazole, tigecycline and tobramycin. The MICs of all agents tested were read on the fifth day after incubation, and those of clarithromycin were also read on extended incubation (14 days). MIC breakpoints indicating susceptible, intermediate or resistant isolates were interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines [10].
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3. Results During the period January 2005–May 2012, 15 patients with bacteraemia due to M. abscessus complex were treated at NTUH. Two isolates recovered from two patients were not preserved for further species identification. One 54-year-old female with chronic hepatitis C virus infection and previous pulmonary tuberculosis (TB) presented to the hospital with fever and lymphadenopathy over the bilateral cervical and periauricular area. The patient developed two episodes of M. abscessus complex bacteraemia (one caused by M. abscessus subsp. bolletii and the other due to M. abscessus subsp. abscessus within a 9-month interval). She received intravenous (i.v.) imipenem and amikacin during hospitalisation and oral clarithromycin plus minocycline or moxifloxacin treatment for 12 months and recovered well. Among the remaining 12 patients with M. abscessus complex singular bacteraemia in whom the isolates were preserved, 9 were confirmed to have M. abscessus subsp. bolletii and the other 3 patients were confirmed to have M. abscessus subsp. abscessus by erm(41) PCR and gene sequence analysis of rpoB and 23S rRNA. The details and summarised clinical characteristics of 15 patients with bacteraemia caused by M. abscessus complex are shown in Table 1. The 15 patients were mainly middle-aged adults (median age 54 years), and 3 patients were children. Primary bacteraemia was found in four patients (27%) and surgical wound infection was present in five patients (33%). Fourteen patients (93%) had healthcare-associated M. abscessus complex bacteraemia. Steroid usage (5/15; 33%) and malignancy (5/15; 33%) were the most common underlying immunocompromised statuses, followed by diabetes mellitus (4/15; 27%). All five patients receiving steroids received >10 mg of prednisolone equivalent corticosteroids for ≥2 months prior to M. abscessus complex bacteraemia. The reasons for steroid use were adrenal insufficiency in four patients and autoimmune disease in one patient. Clarithromycin in combination with imipenem and amikacin remained the most common treatment regimen used for M. abscessus complex bacteraemia. The mean duration of i.v. antimicrobial treatment was 27 days (range 4–57 days) for patients with M. abscessus subsp. bolletii infection and 7 days (range 2–15 days) for patients infected with M .abscessus subsp. abscessus. The mean duration of clarithromycin use was 85 days (range 7–210 days) among patients with M. abscessus subsp. bolletii infection and 120 days (range 18–221 days) among patients infected with M. abscessus subsp. abscessus. The number of patients classified by year of onset was two (13%) during 2005–2007, six (40%) during 2008–2010 and seven (47%) during 2011–2012. Among the nine patients with M. abscessus subsp. bolletii bacteraemia, two were infants. Wound infection (five post-surgical wound infection) was the most common infection focus (5/9; 56%). Among the three patients with M. abscessus subsp. abscessus bacteraemia, all had healthcare-associated bacteraemia and none was considered to be secondary to wound infection. The MICs of the 15 antimicrobial agents against the 14 M. abscessus complex isolates are shown in Table 2. Amoxicillin/clavulanic acid, cephalosporins, imipenem, tetracycline, fluoroquinolones and aminoglycosides had poor in vitro activities against all 14 isolates. Nine (90%) of the 10 M. abscessus subsp. bolletii isolates and all four of the M. abscessus subsp. abscessus isolates were susceptible to amikacin. Of the 14 M. abscessus complex isolates, 12 were inhibited by tigecycline at 1.0 mg/L and all 14 were inhibited by clarithromycin at 0.5 mg/L after 5 days of incubation. After prolonged incubation (14 days), two (20%) of the ten M. abscessus subsp. bolletii isolates had clarithromycin MICs (0.5 mg/L)
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Table 1 Clinical characteristics of 15 patients with bacteraemia caused by Mycobacterium abscessus complex treated at National Taiwan University Hospital from 2005 to 2012. M. abscessus subsp.
Age/sex
Underlying disease
Infection focus
Source
Treatment
Outcome
1 2 3 4 5 6 7 8 9 10a 11 12 13 14 15
bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii and abscessus abscessus abscessus abscessus N/A N/A
75 years/M 81 years/F 16 years/F 65 years/F 57 years/M 3 months/F 52 years/M 6 months/M 50 years/M 54 years/F 45 years/F 65 years/M 55 years/F 50 years/M 3 months/M
Diabetes mellitus, end-stage renal disease, steroid usage Diabetes mellitus, end-stage renal disease Heart transplantation, steroid usage Sjögren’s syndrome Diabetes mellitus, hepatocellular carcinoma, steroid usage, liver transplantation Down’s syndrome, congenital heart disease Pancreatic cancer, recent chemotherapy X-linked recessive anhidrotic ectodermal dysplasia with immunodeficiency Diabetes mellitus, ischaemic heart disease, steroid usage Hepatitis C virus infection Dermatomyositis, steroid usage Lung cancer Leukaemia, recent chemotherapy Nasopharyngeal cancer Hypoplastic left heart
Infective endocarditis Surgical wound Surgical wound Disseminated Surgical wound Surgical wound Surgical wound Primary Primary Disseminated Pneumonia Pneumonia Primary Catheter-related Primary
CA HA HA HA HA HA HA HA HA HA HA HA HA HA HA
IPM, MXF, CLR TIG, CIP IPM, AMK, LVX IPM, AMK, CLR, DOX IPM, AMK IPM, AMK, CLR, LNZ IPM, AMK, CLR, LVX IPM, AMK, CLR, LNZ IPM, CLR IPM, AMK, CLR, MIN, MXF IPM, LVX IPM, AMK, CLR, CIP IPM, AMK, CLR, MXF IPM, AMK, CLR, CIP Nil
Mortality (Day 7) Survived Survived Survived Survived Survived Survived Survived Survived Survived Mortality (Day 6) Survived Survived Survived Mortality (Day 6)
CA, community-acquired; HA, healthcare-associated; IPM, imipenem; MXF, moxifloxacin; CLR, clarithromycin; TIG, tigecycline; CIP, ciprofloxacin; AMK, amikacin; LVX, levofloxacin; DOX, doxycycline; LNZ, linezolid; MIN, minocycline; N/A, not available (isolate not preserved). a Patient 10 developed two episodes of M. abscessus complex bacteraemia, one caused by M. abscessus subsp. bolletii and the other due to M. abscessus subsp. abscessus.
Table 2 Antimicrobial susceptibilities of 14 isolates of Mycobacterium abscessus complex from 13 patients to 15 antimicrobial agents. Patient no.a
M. abscessus subspecies
MIC (mg/L) (susceptibility categoryb ) AMC
1 2 3 4 5 6 7 8 9 10d 10d 11 12 13
bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii bolletii abscessus abscessus abscessus abscessus
>64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32 >64/32
FOX
CRO
FEP
IPM
CIP
MXF
64 (I) 32 (I) 32 (I) 64 (I) 32 (I) 64 (I) 64 (I) 32 (I) 32 (I) 64 (I) 128 (R) 32 (I) 64 (I) 64 (I)
>64 >64 >64 >64 >64 >64 >64 >64 >64 >64 >64 >64 >64 >64
>32 >32 >32 >32 >32 >32 >32 >32 >32 >32 32 >32 >32 >32
64 (R) 16 (R) 16 (R) 64 (R) 32 (R) 64 (R) 32 (R) 32 (R) 64 (R) 32 (R) 32 (R) 16 (R) 32 (R) 32 (R)
>4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R) >4 (R)
8 (R) >8 (R) >8 (R) >8 (R) >8 (R) >8 (R) >8 (R) >8 (R) >8 (R) >8 (R) 8 (R) 8 (R) 8 (R) >8 (R)
DOX
MIN
>16 (R) >16 (R) >16 (R) >16 (R) >16 (R) >16 (R) 16 (R) 16 (R) >16 (R) 16 (R) >16 (R) >16 (R) >16 (R) 16 (R)
>8 (R) >8 (R) >8 (R) >8 (R) 8 (R) 8 (R) 8 (R) 8 (R) 8 (R) 8 (R) >8 (R) >8 (R) >8 (R) 8 (R)
LZD
TOB
AMK
TIGc
16 (R) 8 (S) 16 (R) 16 (R) >32 (R) >32 (R) >32 (R) 32 (R) >32 (R) >32 (R) 8 (S) 16 (R) 16 (R) >32 (R)
>16 (R) 8 (R) 16 (R) 8 (R) 16 (R) >16 (R) 16 (R) >16 (R) >16 (R) 16 (R) 8 (R) 8 (R) 8 (R) >16 (R)
16 (S) 8 (S) 4 (S) 16 (S) 32 (I) 16 (S) 8 (S) 8 (S) 16 (S) 8 (S) 2 (S) 2 (S) 8 (S) 16 (S)
0.06 1 1 0.5 4 2 1 1 1 1 0.25 0.5 0.5 1
SXT >8/152 (R) >8/152 (R) >8/152 8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) >8/152 (R) 8/152 (R) >8/152 (R)
CLR (5-day/14-day) 0.06 (S)/0.12 (S) 0.06 (S)/0.5 (S) 0.5 (S)/0.5 (S) 0.06 (S)/0.5 (S) 0.25 (S)/0.5 (S) 0.25 (S)/0.5 (S) 0.25 (S)/1 (S) 0.25 (S)/0.5 (S) 0.5 (S)/0.5 (S) 0.12 (S)/0.25 (S) 0.25 (S)/0.25 (S) 0.12 (S)/0.5 (S) 0.5 (S)/>16 (R) 0.25 (S)/0.5 (S)
MIC, minimum inhibitory concentration; AMC, amoxicillin/clavulanic acid; FOX, cefoxitin; CRO, ceftriaxone; FEP, cefepime; IPM, imipenem; CIP, ciprofloxacin; MXF, moxifloxacin; DOX, doxycycline; MIN, minocycline; LZD, linezolid; TOB, tobramycin; AMK, amikacin; TIG, tigecycline; SXT, trimethoprim/sulfamethoxazole; CLR, clarithromycin; S, susceptible; I, intermediate; R, resistant. a See Table 1 for patient designation. b Susceptibility category criteria for each agent were according to the guidelines established by the Clinical and Laboratory Standards Institute (CLSI) [10]. c There are no CLSI breakpoints for tigecycline, therefore no susceptibility categories are shown. d These two isolates were obtained from one patient (No. 10) who developed two episodes of bacteraemia due to different M. abscessus complex species (one M. abscessus subsp. bolletii and one M. abscessus subsp. abscessus, with an interval of 9 months).
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Patient no.
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eight-fold higher than those (0.06 mg/L) by 5-day incubation. Only one (25%) of the four M. abscessus subsp. abscessus isolates had inducible clarithromycin resistance, with a MIC of 0.5 mg/L by 5-day incubation and >16 mg/L after 14-day incubation. 4. Discussion This study revealed that a great proportion of M. abscessus complex bacteraemia patients were due to M. abscessus subsp. bolletii. Only two cases of M. abscessus subsp. bolletii bacteraemia confirmed by hsp65 and rpoB genes and the 16S–23S rRNA internal transcribed spacer (ITS) region have been reported [6,7]. The first M. abscessus subsp. bolletii bacteraemia case report described a leukopenic kidney transplant patient with co-infection of pulmonary TB who had sudden death before identification of M. abscessus subsp. bolletii bacteraemia [7]. A more recent report described a chronic myelogenous leukaemia patient who had M. abscessus subsp. bolletii bacteraemia [6]. These two patients were both immunocompromised and M. abscessus subsp. bolletii was suspected as contributing to death in one patient. Rapidly growing mycobacteria bacteraemia is always considered to be related to catheter-related bloodstream infection [11]. However, in the current study only one case was attributed to catheter-related bacteraemia. M. abscessus subsp. bolletii has been reported in association with nosocomial infections, particularly resulting from surgical procedures [12]. It was also evident in the current study that M. abscessus subsp. bolletii was associated with surgical wound infections. The five patients with surgical wound infection had immunocompromised status in common, which can dispose vulnerable patients to the development of M. abscessus subsp. bolletii bacteraemia. Current American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines recommend the use of macrolidebased combination therapy with parenteral medications including amikacin, cefoxitin and imipenem [1]. Cefoxitin is not available in NTUH, and imipenem plus amikacin became the most common i.v. agents. No study has examined different treatment regimens for M. abscessus complex bacteraemia. Tigecycline is a novel antibiotic that has shown low MICs towards M. abscessus complex and is now being considered a promising agent [13]. However, particular caution should be paid to the use of the combination of tigecycline and amikacin owing to the potential antagonist effect of the two agents [14]. Instead, tigecycline plus clarithromycin exerts better synergistic activity against M. abscessus complex [14]. Use of tigecycline may be considered in bacteraemic M. abscessus complex patients, and further study is warranted to prove its efficacy. Amikacin is another agent that showed high susceptibility rates in this study. In a previous study testing M. abscessus complex isolates in Taiwan, a universal high susceptible rate to amikacin was found [15]. However, there are still concerns regarding amikacinassociated toxicity, especially in the setting of prolonged injection. The optimal treatment duration of antimicrobial therapy against M. abscessus complex bacteraemia still remains undetermined. One significant difference between M. abscessus subsp. abscessus and M. abscessus subsp. bolletii lies in their clarithromycin susceptibility [9]. Inducible clarithromycin resistance is frequently present in M. abscessus subsp. abscessus but not in M. abscessus subsp. bolletii [9]. In this study, inducible clarithromycin resistance was found in 25% of M. abscessus subsp. abscessus isolates but in none of the M. abscessus subsp. bolletii isolates. Although the limited case number and unstandardised treatment regimen prevented us from comparing the treatment response, there appeared to be a lower mortality rate in patients with singular bacteraemia due to M. abscessus subsp. bolletii compared with those with M. abscessus subsp. abscessus singular bacteraemia [14-day mortality, 11% (1/9) vs. 33% (1/3)].
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Compared with our previous study [5], there was a significant increase in the number of M. abscessus complex bacteraemia cases. There were seven new M. abscessus complex bacteraemia patients during January 2011–May 2012, which is a significant upward trend. The prolonged hospitalisation course among immunocompromised patients and the contribution of post-surgical infection together may contribute to the emerging M. abscessus complex bacteraemia. Whilst disease caused by NTM remains an emerging disease with increasing incidence, further studies and monitoring may be needed to elucidate the trend of M. abscessus complex bacteraemia. In conclusion, we describe 15 patients with M. abscessus complex bacteraemia and found these patients to be mainly middle-aged adults with underlying immunocompromised status and most with healthcare-associated bacteraemia. Surgical wound infections should be considered an important cause of M. abscessus subsp. bolletii bacteraemia. Clarithromycin and tigecycline exert low MICs. The incidence of M. abscessus complex bacteraemia appears to be increasing. Funding: No funding sources. Competing interests: None declared. Ethical approval: Not required. References [1] Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175: 367–416. [2] Hoefsloot W, van Ingen J, Andrejak C, Angeby K, Bauriaud R, Bemer P, et al. The geographic diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET collaborative study. Eur Respir J 2013;42: 1604–13. [3] Lai CC, Tan CK, Chou CH, Hsu HL, Liao CH, Huang YT, et al. Increasing incidence of nontuberculous mycobacteria, Taiwan, 2000–2008. Emerg Infect Dis 2010;16:294–6. [4] 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;61:2311–13. [5] Tan CK, Lai CC, Liao CH, Chou CH, Hsu HL, Huang YT, et al. Mycobacterial bacteraemia in patients infected and not infected with human immunodeficiency virus, Taiwan. Clin Microbiol Infect 2010;16:627–30. [6] Hamamoto T, Yuki A, Naoi K, Kawakami S, Banba Y, Yamamura T, et al. Bacteremia due to Mycobacterium massiliense in a patient with chronic myelogenous leukemia: case report. Diagn Microbiol Infect Dis 2012;74: 183–5. [7] Tortoli E, Gabini R, Galanti I, Mariottini A. Lethal Mycobacterium massiliense sepsis, Italy. Emerg Infect Dis 2008;14:984–5. [8] Lee MR, Cheng A, Huang YT, Liu CY, Chung KP, Wang HC, et al. Performance assessment of the DR TBDR/NTM IVD kit for direct detection of Mycobacterium tuberculosis isolates, including rifampin-resistant isolates, and nontuberculous mycobacteria. J Clin Microbiol 2012;50:3398–401. [9] Kim HY, Kim BJ, Kook Y, Yun YJ, Shin JH, Kim BJ, et al. Mycobacterium massiliense is differentiated from Mycobacterium abscessus and Mycobacterium bolletii by erythromycin ribosome methyltransferase gene (erm) and clarithromycin susceptibility patterns. Microbiol Immunol 2010;54:347–53. [10] Clinical and Laboratory Standards Institute. Susceptibility testing of mycobacteria, nocardiae, and other aerobic actinomycetes; approved standard. 2nd ed. Document M24-A2 Wayne, PA: CLSI; 2011. [11] El Helou G, Hachem R, Viola GM, El Zakhem A, Chaftari AM, Jiang Y, et al. Management of rapidly growing mycobacterial bacteremia in cancer patients. Clin Infect Dis 2013;56:843–6. [12] Lee MR, Cheng A, Lee YC, Yang CY, Lai CC, Huang YT, et al. CNS infections caused by Mycobacterium abscessus complex: clinical features and antimicrobial susceptibilities of isolates. J Antimicrob Chemother 2012;67: 222–5. [13] Wallace Jr RJ, Brown-Elliott BA, Crist CJ, Mann L, Wilson RW. 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 2002;46:3164–7. [14] Huang CW, Chen JH, Hu ST, Huang WC, Lee YC, Huang CC, et al. Synergistic activities of tigecycline with clarithromycin or amikacin against rapidly growing mycobacteria in Taiwan. Int J Antimicrob Agents 2013;41:218–23. [15] Huang YC, Liu MF, Shen GH, Lin CF, Kao CC, Liu PY, et al. Clinical outcome of Mycobacterium abscessus infection and antimicrobial susceptibility testing. J Microbiol Immunol Infect 2010;43:401–6.
