Mycobacterium Mucogenicum Group Infections: a Review

REVIEW 10.1111/j.1469-0691.2009.03028.x

Mycobacterium mucogenicum group infections: a review

T. Ade´kambi Division of Infectious Diseases, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA

Abstract

It has become apparent that Mycobacterium mucogenicum isolates recovered from clinical samples are more diverse than was previously realized and include an increasing number of emerging pathogens, as depicted by multilocus sequence analysis. Most clinically signiﬁcant cases of those organisms involved catheter-related infections. They are susceptible to most antimicrobial agents, but like other rapidly growing mycobacteria, they are resistant to ﬁrst-line antituberculous agents. A review of the cases of M. mucogenicum complex infection in the literature is addressed here, as well as two additional cases of the closely related species Mycobacterium aubagnense.

Keywords: Infections, Mycobacterium mucogenicum, prevention, review, treatment, water Clin Microbiol Infect 2009; 15: 911–918

Corresponding author and reprint requests: T. Ade´kambi, Division of Infectious Diseases, Emory Vaccine Center, Emory Univer- sity School of Medicine, 952 Gatewood Rd, Atlanta, GA 30322, USA E-mail: [email protected]

Several studies have isolated M. mucogenicum-like strains Introduction from clinical samples [14,15] which suggested that the M. mucogenicum group is more diverse than was previously Based on multilocus sequence analysis, the Mycobacterium mu- realized. M. aubagnense and M. phocaicum were recently dis- cogenicum group comprises M. mucogenicum, Mycobacterium criminated among the M. mucogenicum group; it is possible aubagnense and Mycobacterium phocaicum [1,2]. This group of that the clinical spectrum of infection due to M. aubagnense organisms was first named Mycobacterium chelonae-like and M. phocaicum overlapped with that of infection due to organism in 1982 and was reported as the etiologic agent in a M. mucogenicum as described in previous reports. peritonitis outbreak involving two peritoneal dialysis units [3]. I therefore describe two additional cases of M. aubagn- Springer et al. [4] proposed the name M. mucogenicum for this ense infection and review the previously published cases of group of organisms, reflecting the highly mucoid character of M. mucogenicum. the isolates. While the 16S rRNA gene sequence of the M. aubagnense type strain differed from that of the M. muco- Infection with M. mucogenicum genicum type strain by 14 base pairs, M. phocaicum shared 100% similarity [2]. The ecological niche of the M. mucogen- cum group is unknown but this species seems ubiquitous and Mycobacterium mucogenicum isolates are associated with a contaminated water is a likely source of nosocomial infections wide spectrum of clinical disease in both immunocompetent [5–7]. Members of this group are present in both public and and immunosuppressed individuals. They are also commonly hospital water systems, where their persistence in biofilms implicated in outbreaks of infection resulting from contami- and amoeba is enabled by their ability to tolerate disinfec- nated hospital equipment and water sources. tants, chlorination and extreme temperatures [6–11]. How- ever, the epidemiology of infection due to rapidly growing Catheter-related infections mycobacteria (RGM) in nine public hospitals in Spain recently Mycobacterium mucogenicum was originally discovered in two showed that M. mucogenicum isolates were clinically not outbreaks of peritonitis in 1976 and 1978 in 5/22 (18%) and significant [12]. Recently, chili sauces sold by street venders 5/8 (63%) patients, respectively, undergoing intermittent in Mexico have been identified as a potential source of chronic peritoneal dialysis [3]. Seven sporadic cases of M. mu- M. mucogenicum infection [13]. cogenicum peritonitis were further diagnosed in the same two

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases 912 Clinical Microbiology and Infection, Volume 15 Number 10, October 2009 CMI

centres. Investigations suggested that ineffective disinfection acyclovir, fluconazole and amoxicillin for post-transplantation of the equipment followed by colonization of the machines prophylaxis. The fact that M. mucogenicum isolates are suscep- with M. mucogenicum was responsible for the outbreaks [3]. tible to antibiotics, including amoxicillin and amoxicillin-clavul- In 1985, Bolan et al. [16] described a mycobacterial out- anic acid [2], may explain why this patient remained apyretic. break in a hemodialysis centre in Louisiana, USA. Among 26 Most reports have described infections in neutropenic and isolates, 25 were identified as M. abscessus and one as non-neutropenic cancer patients. Only one patient died, pre- M. mucogenicum. The single factor common to all patients sumably from the disseminated rhadomyosarcoma (Table 1). was exposure to hemodialyzers (artificial kidneys) that had been treated with a formaldehyde concentration that was Central nervous system diseases below effective levels for these RGM species [16]. Central nervous system (CNS) diseases involving M. mucogeni- Catheter-related infections are the most clinically signifi- cum are rare but serious. Both immunosuppressed and immu- cant cases of M. mucogenicum infection [17]. These infections nocompetent patients may develop CNS diseases. Among 87 can be local or systemic. In one study, M. mucogenicum was reported cases of M. mucogenicum isolates, only two cases responsible for 23/44 (52%) bloodstream and catheter- without clinical data have been mentioned; both occurred in related infections in patients who had a primary diagnosis of AIDS patients. For one of the two patients, multiple cerebro- cancer and a consecutive diagnosis of M. abscessus 6/44 spinal fluid samples were AFB smear positive for an unrelated (14%) and M. fortuitum 6/44 (14%) infection [14]. reason 3 weeks prior to lumbar puncture [17]. This organism In contrast, in a study by Gaviria et al., [18], M. mucogeni- has also been reported to have caused two fatal cases of menin- cum was responsible for 2/23 (9%) of catheter-related infec- gitis in immunocompetent patients. It is unlikely that M. muco- tions in haematopoietic stem cell transplant recipients while genicum meningitis was nosocomial. In one case, this organism M. abscessus accounted for 10/23 (43%), M. fortuitum for 6/23 was the aetiological agent of cerebral thrombophlebitis [21]. (26%) and Mycobacterium chelonae for 5/23 (22%). Contamina- tion of the catheter during bathing, where catheters were Respiratory infection exposed to shower (poured) water, was found to be the In 1993, Wallace et al. [17] evaluated 87 sporadic isolates of route of infection due to M. mucogenicum in an outbreak of M. mucogenicum. Among these isolates, 54 (62%) were iso- bactaeremia among five bone marrow transplant patients and lated from the respiratory tract and only two (4%), both one oncology patient at a tertiary-care hospital in Minnesota from AIDS patients, were clinically significant. Infections [6] and in five paediatric haematology-oncology patients in caused by the remaining 33 non-respiratory tract isolates Israel, four of whom had fever and one had signs of an exit- included post-traumatic wound infections and catheter- site infection [7]. Suboptimal water chlorination may also con- related sepsis. Recovery of M. mucogenicum from skin, tribute to the latter outbreak [7]. A cord blood transplant wound or blood cultures was most often associated with recipient who developed a central venous catheter (CVC) clinical disease. In contrast, a single positive sputum culture infection after the patient herself had flushed her catheter was almost never clinically significant. with tap water was also reported [19]. Hawkins et al. [20] The frequent presence of this organism in tap water, conducted a retrospective single-centre review of RGM cath- including ice machines [22], may contribute to the transient eter-related blood stream infections. RGMs isolated from colonization or contamination of sputum samples [17]. blood cultures of six patients included M. mucogenicum Han et al. [14] reported that, among 28 cases of definite (n = 2), M. fortuitum (n = 2), Mycobacterium neoaurum (n =1) and probable respiratory tract infections, M. mucogenicum and Mycobacterium septicum (n = 1). In a later study, an accounted for 11% (three cases) whereas M. abscessus M. mucogenicum cluster represented an increasing trend in accounted for 64% (18 cases) and M. fortuitum for 14% (four catheter-related blood stream infections rather than an out- cases). The rare isolation of M. mucogenicum from respira- break, given the distinct susceptibility patterns and the lack of tory specimens could also be due, in part, to pre-treatment obvious epidemiological links [20]. Review of the literature with mucolytics and sodium hydroxide and the addition of revealed ten well documented cases of catheter-related infec- antibiotics to the culture medium which might inactivate this tion (Table 1). Most commonly, long-term central indwelling organism more than other RGMs because of its mucoid cell catheters, e.g. a Hickman catheter, port-a-cath and peripheral surface and low resistance to antibiotics [14]. inserted central catheters, are incriminated. Anticancer chemotherapy often requires the use of indwelling CVCs. Fever Skin and soft tissue infection was the most common clinical symptom in cases of M. muco- RGM cause post-traumatic skin infections. Recently, a skin genicum bactaeremia, except in the case of a patient receiving infection due to M. mucogenicum in a patient treated with

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 911–918 CMI

TABLE 1. Clinical features of ten patients with catheter–related infection caused by M. mucogenicum

Case 1 2 3 4 5 6 7 8 9 10

Sex (age) M (!5) M (3) M (5) F (5) M (17.5) M (33) F (42) F (6) M (16) F (23) Underlying disease ALL, Burkitt ALL Rhadomyosarcoma Neuroblastoma Aplastic anaemia ALL, HSCT, Gastric cancer, Cord blood transplant Lymphoblastic Ear surgery, myringoplasty, lymphoma graft failure chemotherapy for myelodysplastic leukaemia perforated otitis media, syndrome chronic otorrhea, cervical lymph node, Munchausen syndrome ora Compilation Journal Catheter type Hickman PAC Hickman Hickman Hickman PAC, PICC PICC Hickman Hickman N/A Catheter days 14 150 30 14 45 180 90 74 30 26 (from insertion) Clinical symptoms None Fever Fever Redness and Fever Fever Fever None Fever Fever tenderness in exit site White blood count Normal Normal Normal Neutropenia Lymphopenia Unknown Neutropenia Unknown Neutropenia Polyclonal hypergammaglobulinemia and lymphopenia

ª Time to bacterial 6 3 NA 5 7 2–5 2–5 6 6 N/A 09Erpa oit fCiia irbooyadIfciu Diseases, Infectious and Microbiology Clinical of Society European 2009

growth (days) Ade No. of positive 151 1 1 8 3 2 4 2

blood cultures ´ kambi Source Blood Blood Blood Blood Blood Blood Blood Blood Blood Blood + cervical node biopsy Context Outbreak Outbreak Outbreak Outbreak Outbreak Increasing trend Increasing trend Exposure to tap water Exposure Multiple infection to tap water and surgical wounds

Identiﬁcation methods hsp65 + RAPD hsp65 + RAPD hsp65 + RAPD hsp65 + RAPD hsp65 + RAPD 16S rRNA 16S rRNA Unknown 16S rRNA 16S rRNA, hsp65 mucogenicum Mycobacterium Antibiotic treatment AMK CLA + CIP None CLA + CIP CLA AMK then LEV then TMP/SMX AMK + CEF + CLA then MER then MER + RIF LEV + CLA then AMK + CLA AMK + CIP + MER + TEICO + then RIF + MOX CLA then CIP + CLA GEN + ACY Therapy duration Unknown Unknown 0 Unknown Unknown 24 8 8 5 12 (weeks) Line removal Yes Yes No Yes Yes Yes Yes Yes Yes Yes Recovered Yes Yes Died Yes Yes Yes Yes Yes Yes No Reference [7] [7] [7] [7] [7] [20] [20] [19] [33] [31]

ALL, acute lymphoblastic leukaemia; HSCT, hematopoietic stem cell transplant; PAC, port-a-corth; PICC, peripheral inserted central catheter; ACY, acyclovir; AMK, amikacin; CEF, cefepime; CIP, ciproﬂoxacin; CLA, clarithromycin; GEN, gentamicin; LEV, levaquin; MER, meropenem; MOX, moxiﬂoxacin; RIF, rifampin; TMP/SMX, trimethoprim–sulfamethoxazole; TEC, teicoplanin. ru infections group ª CMI 09TeAuthor The 2009 , 15 911–918 , 913 914 Clinical Microbiology and Infection, Volume 15 Number 10, October 2009 CMI

the TNF-a antagonist etanercept, who had not had a preced- ing soft tissue injury, was reported [23]. A 61-year-old woman presented with a 3-month history of recurring asymptomatic bumps on her legs. These lesions would periodically ulcerate and drain a cloudy, yellow exudate. The patient suffered from rheumatoid arthritis, managed with low-dose prednisone and etanercept. The patient reported feeling well. She excluded any exposure to whirlpool foot- baths, though she did frequently have pedicures in a nail salon. The patient did not recall any previous leg injury. Examination revealed several firm, erythematous papules on her legs, as well as several deeper dermal to subcutaneous nodules near her ankles. Several of the lesions had overlying FIG. 2. Erythematous nodules in the side and posterior faces of the erosion. No inguinal adenopathy was noted. An incisional right lower member [24]. biopsy was performed from a deep nodule near her ankle. The conventional bacteriological and mycological cultures Histological examination of this lesion showed necrotizing, of the exudates were negative. Then, it was decided to per- granulomatous inflammation with mycobacteria identified on form two punch biopsies and one of the nodules was used an acid fast stain. Additionally, a culture grew M. mucogeni- for microbiological and anatomo-pathological studies. In the cum. Her therapy entailed both discontinuation of the eta- derma, the histological inspection showed inflammatory infil- nercept and initiation of systemic antimicrobials. Based on trates with polymorphonuclear leucocytes and a tendency of the identified susceptibilities of the isolates of M. mucogeni- suppurative granuloma formation (Figs 3 and 4). cum, treatment with clarithromycin 500 mg BID and minocy- The Ziehl–Neelsen, Fite-Faraco, periodic acid Schiff (PAS) cline 100 mg BID was initiated. Continuous treatment with and PAS-diastase stainings were negative. The culture on these medications is planned for 6 months and further Lo¨wenstein medium at 30C showed creamy, non-pigmented follow-up is pending. colonies of AFB, identified as M. mucogenicum. The patient was Another case of skin infection involved an 11-year-old treated with clarithromycin, in doses of 500 mg each 12 h for female who presented with erythematous nodules which felt 5 months. The lesions evolved favourably but small plaque of warm and were painful (some of them were confluent), with atrophic aspect and off-white peri-lesional halo remained [24]. central ulceration and purulent exudation, located in the side and posterior faces of both lower members (Figs 1 and 2). She did not present with fever or any other systemic clinical sign. Infection with M. aubagnense As for antecedents, she referred to a wound in the popliteal cavity after an accidental fall into a pool which evolved later We initially described M. aubagnense without clinical data [2]. into an abscess; the remainder of the lesions appeared after Here, I report two cases related to these isolates in two depilation with cold wax. patients from a hospital in Marseille, France. The first patient

FIG. 1. Erythematous nodules in the side and posterior faces of the FIG. 3. Histological findings in the derma: inflammatory infiltrates left lower member [24]. with polymorphonuclear leucocytes [24].

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 911–918 CMI Ade´kambi Mycobacterium mucogenicum group infections 915

ogy patients with bloodstream infection in a Texas hospital using rpoB gene sequencing. A multiphasic approach showed later that one of the isolates matched an environmental isolate from a swab of a hand shower in the patient’s room [5]. This outbreak was the first of a catheter-associated bacteraemia caused by M. phocaicum and the first report of a clinical isolate from a US hospital, although their identification may overlap with that of M. mucogenicum in previous reports. This organism has also been isolated from respiratory secre- tions [2] and from the therapy pool water in a hospital in Marseille [25]. An investigation which was undertaken to FIG. 4. Histological findings in the derma: tendency of suppurative determine the Mycobacterium species responsible for the his- granuloma formation. tological changes consistent with mycobacteriosis observed during routine screening of zebrafish at a research facility was a 55-year-old man with a history of tobacco abuse (one revealed the presence of M. phocaicum in the tank or tubing pack/day) who was admitted with hemoptysis and bilateral surface biofilms but not in the zebrafish [26]. Furthermore, fibrosis lesion suggestive of pulmonary tuberculosis. Comput- M. phocaicum represented 18% of amoeba-associated myco- erized tomography revealed thickening of left pleura and non- bacterial species in three cooling towers located in the systematized opacity of the right lung. Microscopic observa- centre of Paris, France [27]. tion of the bloody mucoid bronchial aspirate lavage after Ziehl–Neelsen staining disclosed epithelial cells and numerous Miscellaneous Diseases polymorphonuclear leucocytes but no AFB. Cultures of the bronchial aspirate lavage and two further sputum specimens revealed the presence of the same isolate, identified as an The case of a rapidly progressive granulomatous hepatitis organism closely related to M. mucogenicum. This organism was caused by M. mucogenicum was reported in a 51 year-old man, later identified as M. aubagnense. On the basis of susceptibility a retired anthracite coal miner. Significant in his social profile data obtained for this isolate, a regime including clarithromycin was a history of tobacco abuse (90 packs/year) and remote plus amikacin was prescribed and proved to be well tolerated alcohol use. Significant in his medical history were hypothy- by the patient. The bacteriological results (two additional spu- roidism, arthritis and a questionable diagnosis of coal worker’s tum specimens were negative for AFB by smear and culture) pneumoconiosis. The patient died because of multi-organ fail- were conclusive and the clinical response was favourable. ure secondary to gram-negative sepsis. Autopsy liver cultures The second patient was a 91-year-old woman who under- revealed the presence of M. mucogenicum colonies [28]. went hip prosthesis revision because of suspected sepsis M. mucogenicum was recently identified in a surgically- (with fever at 39C). An X-ray revealed bone lyses with resected, formalin-fixed, paraffin-embedded specimen from necrosis and pathological fracture. Microbiological investiga- one of 11 patients with Crohn’s disease. Mycobacterium tuber- tions of the joint fluid collected at the time of surgery culosis was identified in two cases; Mycobacterium avium revealed the presence of an organism closely related to subsp. paratuberculosis was not identified in any. The patient M. mucogenicum, whereas Gram staining revealed no bacteria. infected with M. mucogenicum was a 22-year old man who Colonies were formed in pure culture after 4-day inoculation presented with abdominal pain, vomiting and tarry stool. He onto Middelbrook 7H10 and 5% sheep-blood agar at 37Cin had undergone ileal resection for a perforation at the distal a5%CO2 atmosphere. The organism was later identified as ileum; the postoperative complications included functional M. aubagnense. Amikacin and imipenem therapy was success- bowel disturbance and constipation [29]. ful and the patient’s condition improved without much pain The scope of disease caused by M. mucogenicum could and she was referred for rehabilitation. include disseminated infection. This organism was found to be responsible for bacteraemia in a patient with cirrhosis. No localizing signs of infection were present, although the Infection with M. phocaicum patient had a CVC in situ for haemodialysis. The patient died as a result of hepatic and renal failure [30]. M. phocaicum which is undistinguishable from M. mucogenicum A case of M. mucogenicum sepsis in an immunocompetent using 16S rRNA [2] was identified in two hospitalized oncol- woman with Munchausen syndrome with multiple abscesses

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 911–918 916 Clinical Microbiology and Infection, Volume 15 Number 10, October 2009 CMI

has been reported. M. mucogenicuum was isolated from the identity with M. mucogenicum and 98.8% and 96% hsp65 blood 12 days after insertion of a CVC and 42 days after the sequence identity [2]. These methods allowed the differentia- cervical node biopsy [31]. tion between M. mucogenicum species and ‘diphteroid spe- Vargas et al. [32] reported M. mucogenicum to be the cause cies’ [33]. of disseminated infection in a patient with idiopathic CD4+ T lymphocytopenia with prolonged fever of unknown origin. Treatment of Infections due to the The patient had no relevant history of disease or exposure. M. mucogenicum Complex

Identification of M. mucogenicum Complex Overall, M. mucogenicum complex isolates were the most Species susceptible RGM species. They are susceptible to most antimicrobial agents but, like other RGM, they are resistant to Occasionally, interpretation of the Gram stain of a positive first-line antituberculous agents (isoniazid, rifampin, pyrazina- blood culture can be difficult; if there is a low bacterial load, mide…) [2,4,35]. Han et al. [14] reported that 100% (25/25) no organisms can be seen [33]. M. mucogenicum isolates of M. mucogenicum isolates were susceptible to amikacin, appear as Gram-positive bacteria on Gram stain and on cefoxitin, clarithromycin, imipenem and trimethoprim–sulfa- sheep blood and chocolate agar. methoxazole. In addition 88% (22/25) of isolates were sus- Based on the positive catalase reaction, the isolate can be ceptible to ciprofloxacin, and c. 50% were susceptible to easily misidentified as Corynebacterium or Nocardia species doxycycline and minocycline. M. aubagnense and M. phocai- [33,34]. Also, Gram stain of wound drainage often reveals cum isolates were also found to be susceptible to those anti- leucocytes with no visible organisms. Acid-fast stains are biotics (Table 2). M. mucogenicum complex isolates were also often positive. M. mucogenicum complex organisms can be susceptible to amoxicillin, amoxicillin-clavulanate, erythromy- cultivated in Lowenstein-agar or even routine culture media. cin, azithromycin, ofloxacin, sparfloxacin, gatifloxacin, levo- Evidence of growth usually occurs within 3–7 days of inocu- floxacin, moxifloxacin and linezolid [2,20,21,31] according to lation at 28 to 37C but not at 42C [4]. In most clinical lab- the Clinical and Laboratory Standards Institute (CLSI) guide- oratories, species identification of the M. mucogenicum lines formerly NCCLS [38]. Despite the availability of these complex relies upon the phenotypic characteristics deter- in vitro data, the management of M. mucogenicum catheter- mined by limited biochemical testing [35]. M. mucogenicum related infection is largely based on clinical experience. isolates were found to be inconsistent, independent of the Timely intravascular catheter removal and initiation of appro- carbon utilization tests for reliable identification [36]. Species priate antibiotic therapy are required to achieve successful identification based on 16S rRNA, rpoB and hsp65 is the outcomes. An aminoglycoside combined with a macrolide most rapid and accurate method [2,37]. While the 16S and/or a quinolone is the most common empirical regimen rRNA gene sequence of the M. aubagnense type strain dif- [35]. The choice of antimicrobial therapy may ultimately be fered from the M. mucogenicum type strain by 14 base pairs, guided by antimicrobial susceptibility testing. The optimal M. phocaicum shared 100% identity. Furthermore, rpoB and duration of antimicrobial therapy for M. mucogenicum cathe- hsp65 gene sequences contribute to unambiguously distin- ter-related infection is unknown. The duration of parenteral guishing among those organisms. M. aubagnense and M. phoc- therapy is usually 2–4 weeks, followed by oral therapy for aicum shared, respectively, 95.5% and 90.1% rpoB sequence 4–6 weeks.

TABLE 2. Antimicrobial suscept- M. mucogenicum M. mucogenicum –like M. aubagnense M. phocaicum ibility of M. mucogenicum complex (n = 25) (n =1) (n =2) (n =4) species isolates Amikacin 100% S 100% S 100% S 100% S Cefoxitin 100% S 100% I 100% S 100% S Ciproﬂoxacin 88%S, 12% I 100% S 100% S 100% S Clarithromycin 100% S 100% S 100% S 100% S Imipenem 100% S 100% S 100% S 100% S TMP-SMZ 100% S 100% S 100% S 100% I Doxycycline 67% S, 11% NT 100% S 100% S I, 22% R Minocycline 45% S, 10% 100% S 100% S 100% S I, 45% R Reference [14] [14] [2] [2]

S, susceptible; I, intermediately susceptible; R, Resistant; TMP-SMZ, trimethoprim-sulfamethoxazole; NT, not tested.

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 911–918 CMI Ade´kambi Mycobacterium mucogenicum group infections 917

Prevention of Infections due to the no adverse clinical consequences were observed with the M. mucogenicum Complex patients to whom the contaminated PBSC products were given. Substituting reusable ice trays for an ice machine resolved the outbreak [15]. Recently, chili sauces sold by Catheter-related infections are the most clinically significant street venders in Mexico have been identified as a potential cases of M. mucogenicum infection [17]. The CDC guidelines source of M. mucogenicum infection [13]. recommend covering intravenous catheters during bathing to prevent opportunistic infections [38]. Bathing or showering can wet CVCs at the distal IV catheter cap connections and Conclusions at the catheter entry to the chest. It is especially important to educate all direct care providers, patients and family Opportunistic M. mucogenicum complex species in water may members concerning the risks of water contamination of contaminate chemical devices and equipment and provide a CVCs during bathing and the methods to use during bathing mechanism for bacterial invasion into the bloodstream. to minimize water contact indwelling. Several immunosuppressed patients are at risk of significant The efficacy of this policy has been shown since no fur- morbidity and mortality from exposure to these health-care ther cases of M. mucogenicum catheter–related infection environmental pathogens. Although, according to common were observed after an outbreak [6,7]. Water samples view, the extensive descriptive detail required for taxonomic should be collected periodically and sent to the reference investigations of M. mucogenicum complex organisms is not laboratory for microorganism control. Also, logbooks should necessary for routine diagnostic laboratories, it is important be maintained for measurement of free chlorine concentra- to identify the individual species because they can cause dif- tion because low levels of chlorine in the water supply may ferent diseases, they can have different susceptibility patterns be associated with high levels of growth of M. mucogenicum for certain drugs, and they have obvious epidemiological in tap water, posing a great risk to immunosuppressed links. Consideration should be given to M. mucogenicum com- patients who have been exposed to this water while bathing plex isolates as a possible cause of infection in the case of with unprotected CVCs and IV catheters. positive blood cultures from immunocompromised patients.

Ecological Niche Acknowledgement

Mycobacterium mucogenicum complex species are present in We thank M Drancourt for expert reviewing of the manu- both public and hospital water systems. In a study of 113 script. mycobacterial isolates from tap water from various geographi- cal sites, the most frequently occurring (41%) nontuberculous mycobacterium was M. mucogenicum [22]. This study under- Transparency Declaration scored the potential threat of these ubiquitous organisms. M. mucogenicum complex species have been found in various The author has no conﬂict of interest. aquatic environments around the world, including cooling towers, pools and drinking water [22,25,27]. M. mucogenicum complex species can form bioﬁlms and replicate within proto- References zoan hosts such as A. polyphaga which allow them to tolerate disinfectants, chlorination and extreme temperatures [6–11]. 1. Ade´kambi T, Drancourt M. Dissection of phylogenetic relationships This organism was found in shower water and in the air of a among 19 rapidly growing Mycobacterium species by 16S rRNA, stem cell transplant unit in relative high numbers during the hsp65, sodA, recA and rpoB gene sequencing. Int J Syst Evol Microbiol 2004; 54: 2095–2105. summer but not during the winter [40]. M. mucogenicum were 2. Ade´kambi T, Berger P, Raoult D, Drancourt M. rpob gene sequence- detected in a dental unit waterline before and after treatment based characterization of emerging non-tuberculous mycobacteria with an intermittent use, iodine-containing waterline cleaner with descriptions of Mycobacterium bolletii sp. nov., Mycobacterium phocaicum sp. nov. and Mycobacterium aubagnense sp. nov. Int J Syst [41]. Recently, a closely related species of M. mucogenicum Evol Microbiol 2006; 56: 133–143. was isolated from 6/45 units of peripheral blood stem cell 3. Band JD, Ward JI, Fraser DW et al. Peritonitis due to a Mycobacte- products (PBSC). The source of the contamination was traced rium chelonei-like organism associated with intermittent chronic peri- to ice cubes used in processing the PBSC products. However, toneal dialysis. J Infect Dis 1982; 145: 9–17.

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 911–918 918 Clinical Microbiology and Infection, Volume 15 Number 10, October 2009 CMI

4. Springer B, Bo¨ttger EC, Kirschner P, Wallace RJ Jr. Phylogeny of the 22. Covert TC, Rodgers MR, Reyes AL, Stelma GN Jr. Occurrence of Mycobacterium chelonae-like organism based on partial sequencing of nontuberculous mycobacteria in environmental samples. Appl Environ the 16S rRNA gene and proposal of Mycobacterium mucogenicum sp. Microbiol 1999; 65: 2492–2496. nov. Int J Syst Bacteriol 1995; 45: 262–267. 23. Shehan JM, Sarma DP. Mycobacterium mucogenicum: report of a 5. Cooksey RC, Jhung MA, Yakrus MA et al. Multiphasic approach skin infection associated with etanercept. Dermatol Online J 2008; reveals genetic diversity of environmental and patient isolates of 14: 5. Mycobacterium mucogenicum and Mycobacterium phocaicum associated 24. Go´mez-Moyano E, Del Boz Gonza´lez J, Bermu´dez-Ruiz P, Sanz- with an outbreak of bacteremias at a Texas hospital. Appl Environ Trelles A. Furuncle-like lesions by Mycobacterium mucogenicum in a Microbiol 2008; 74: 2480–2487. immunocompetent patient. Med Clin (Barc) 2009; 132: 370. 6. Kline S, Cameron S, Streifel A et al. An outbreak of bacteremias 25. Ben Salah I, Ade´kambi T, Drancourt M. Mycobacterium phocaicum in associated with Mycobacterium mucogenicum in a hospital water sup- therapy pool water. Int J Hyg Environ Health 2009; 212: 439–444. ply. Infect Control Hosp Epidemiol 2004; 25: 1042–1049. 26. Whipps CM, Matthews JL, Kent ML. Distribution and genetic charac- 7. Livni G, Yaniv I, Samra Z et al. Outbreak of Mycobacterium mucogeni- terization of Mycobacterium chelonae in laboratory zebrafish Danio cum bacteraemia due to contaminated water supply in a paediatric rerio. Dis Aquat Organ 2008; 82: 45–54. haematology-oncology department. J Hosp Infect 2008; 70: 253–258. 27. Pagnier I, Merchat M, Raoult D, La Scola B. Emerging Mycobacteria 8. Wallace RJ Jr, Brown BA, Griffith DE. Nosocomial outbreaks/pseudo- spp. In cooling towers. Emerg Infect Dis 2009; 15: 121–122. outbreaks caused by nontuberculous mycobacteria. Annu Rev Microbiol 28. Goldblatt MR, Ribes JA. Mycobacterium mucogenicum isolated from a 1998; 52: 453–490. patient with granulomatous hepatitis. Arch Pathol Lab Med 2002; 126: 9. Ade´kambi T, Ben Salah S, Khlif M, Raoult D, Drancourt M. Survival 73–75. of environmental mycobacteria in Acanthamoeba polyphaga. Appl Envi- 29. Tzen CY, Wu TY, Tzen CY. Detection of mycobacteria in Crohn’s ron Microbiol 2006; 72: 5974–5981. disease by a broad spectrum polymerase chain reaction. J Formos 10. Simo˜es LC, Simo˜es M, Vieira MJ. Biofilm interactions between distinct Med Assoc 2006; 105: 290–298. bacterial genera isolated from drinking water. Appl Environ Microbiol 30. Paterson DL, Singh N, Gayowski T, Marino IR. Mycobacterium muco- 2007; 73: 6192–6200. genicum bacteremia in a patient with cirrhosis. J Clin Gastroenterol 11. Thomas V, Loret JF, Jousset M, Greub G. Biodiversity of amoebae 1998; 27: 346–347. and amoebae-resisting bacteria in a drinking water treatment plant. 31. Fonteyn N, Wauters G, Vandercam B et al. Mycobacterium mucogeni- Environ Microbiol 2008; 10: 2728–2745. cum sepsis in an immunocompetent patient. J Infect 2006; 53: e143– 12. Esteban J, Martıń-de-Hijas NZ, Fernandez AI, Fernandez-Roblas R, Ga- e146. dea I; Madrid Study Group of Mycobacteria. Epidemiology of infections 32. Vargas J, Gamboa C, Negrin D et al. Disseminated Mycobacterium mu- due to nonpigmented rapidly growing mycobacteria diagnosed in an cogenicum infection in a patient with idiopathic CD4+ T lymphocy- urban area. Eur J Clin Microbiol Infect Dis 2008; 27: 951–957. topenia manifesting as fever of unknown origin. Clin Infect Dis 2005; 13. Cerna-Corte´s JF, Estrada-Garcıá T, Gonza´lez-y-Merchand JA. Isolation 41: 759–760. of Mycobacterium mucogenicum from street-vended chili sauces: a 33. Marshall C, Samuel J, Galloway A, Pedler S. Mycobacterium mucogeni- potential source of human infection. J Food Prot 2009; 72: 182–184. cum from the Hickman line of an immunocompromised patient. J Clin 14. Han XY, De´ I, Jacobson KL. Rapidly growing mycobacteria: clinical Pathol 2008; 61: 140–141. and microbiologic studies of 115 cases. Am J Clin Pathol 2007; 128: 34. Rodgers GL, Mortensen JE, Blecker-Shelly D, Fisher MC, Long SS. 612–621. Two case reports and review of vascular catheter-associated bactere- 15. Kassis I, Oren I, Davidson S et al. Contamination of peripheral mia caused by nontuberculous Mycobacterium species. Pediatr Infect hematopoeitic stem cell products with a Mycobacterium mucogenicum- Dis J 1996; 15: 260–264. related pathogen. Infect Control Hosp Epidemiol 2007; 28: 755–757. 35. Brown-Elliott BA, Wallace RJ Jr. Clinical and taxonomic status of 16. Bolan G, Reingold AL, Carson LA et al. Infections with Mycobacterium pathogenic nonpigmented or late-pigmenting rapidly growing myco- chelonei in patients receiving dialysis and using processed hemodialyz- bacteria. Clin Microbiol Rev 2002; 15: 716–746. ers. J Infect Dis 1985; 152: 1013–1019. 36. Conville PS, Witebsky FG. Lack of usefulness of carbon utilization 17. Wallace RJ Jr, Silcox VA, Tsukamura M et al. Clinical significance, bio- tests for identification of Mycobacterium mucogenicum. J Clin Microbiol chemical features, and susceptibility patterns of sporadic isolates of 2001; 39: 2725–2728. the Mycobacterium chelonae-like organism. J Clin Microbiol 1993; 31: 37. Ade´kambi T, Colson P, Drancourt M. rpoB-based identification of 3231–3239. nonpigmented and late-pigmenting rapidly growing mycobacteria. 18. Gaviria JM, Garcia PJ, Garrido SM, Corey L, Boeckh M. Nontubercu- J Clin Microbiol 2003; 41: 5699–5708. lous mycobacterial infections in hematopoietic stem cell transplant 38. National Committee for Clinical Laboratory Standards (NCCLS). recipients: characteristics of respiratory and catheter-related infec- Susceptibility testing of Mycobacteria, Nocardia and other aerobic tions. Biol Blood Marrow Transplant 2000; 6: 361–369. actinomycetes. Approved standard M24-A, Wayne (PA); The 19. Fleming GA, Frangoul H, Dermody TS, Halasa N. A cord blood Committee; 2003. transplant recipient with Mycobacterium mucogenicum central venous 39. Centers for Disease Control, Prevention; Infectious Disease Society catheter infection after infusion of tap water. Pediatr Infect Dis J 2006; of America; American Society of Blood, Marrow Transplantation. 25: 567–569. Guidelines for preventing opportunistic infections among hematopoi- 20. Hawkins C, Qi C, Warren J, Stosor V. Catheter-related bloodstream etic stem cell transplant recipients. MMWR Recomm Rep 2000; 10: infections caused by rapidly growing nontuberculous mycobacteria: a 1–125, CE1-7. case series including rare species. Diagn Microbiol Infect Dis 2008; 61: 40. Perkins SD, Mayfield J, Fraser V, Angenent LT. Potential Pathogenic 187–191. Bacteria in Shower Water and Air of a Stem Cell Transplant Unit. 21. Ade´kambi T, Foucault C, La Scola B, Drancourt M. Report of two Appl Environ Microbiol 2009; 75: 5363–5372. fatal cases of Mycobacterium mucogenicum central nervous system 41. Porteous NB, Redding SW, Jorgensen JH. Isolation of non-tuberculo- infection in immunocompetent patients. J Clin Microbiol 2006; 44: sis mycobacteria in treated dental unit waterlines. Oral Surg Oral Med 837–840. Oral Pathol Oral Radiol Endod 2004; 98: 40–44.

ª2009 The Author Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 15, 911–918