Pedicures, Lasers, and Other Mycobacterial Adventures

Jason Stout, MD, MHS Division of Infectious Diseases Duke University Medical Center Disclosures-Funding

• NIH (grant) • CDC (contract) • UpToDate (card author) Pus-top problems

• 60 yr old woman with hypertension and osteoarthritis presents with progressive atypia of a nevus on the right thigh • Biopsy reveals melanoma, wide resection done • Noted some red papules around the wound and it never “sealed up” • 2 months later increased erythema and purulent drainage • Diagnosed with “spitting sutures” and prescribed amoxicillin/clavulanate • Two additional wound explorations and a steroid injection in the next 6 weeks, followed by a biopsy

Pus-top problems

• Culture grew abscessus, started on empiric clarithromycin, with ciprofloxacin added 10 days later • Resistance profile returns: • S to amikacin and tigecycline • I to cefoxitin • R to cipro, clarithromycin, doxycycline, imipenem, minocycline, moxifloxacin, and linezolid The Mycobacteria Family Tree

Mycobacteria

M. leprae M. complex Nontuberculous mycobacteria Over 190 species of NTM

Mycobacterium abscessus (Moore and Frerichs 1953) Kusunoki and Ezaki 1992, comb. nov. Mycobacterium kansasii Hauduroy 1955 (Approved Lists 1980), species. Mycobacterium agri (ex Tsukamura 1972) Tsukamura 1981, sp. nov., nom. rev. Mycobacterium komossense Kazda and Muller 1979 (Approved Lists 1980), species. Mycobacterium aichiense (ex Tsukamura 1973) Tsukamura 1981, sp. nov., nom. rev. Mycobacterium alvei Ausina et al. 1992, sp. nov. Mycobacterium kubicae Floyd et al. 2000, sp. nov. Mycobacterium aromaticivorans Hennessee et al. 2009, sp. nov. Mycobacterium lacus Turenne et al. 2002, sp. nov. Mycobacterium arosiense Bang et al. 2008, sp. nov. Mycobacterium lentiflavum Springer et al. 1996, sp. nov. Cloud et al. 2006, sp. nov. (Hansen 1880) Lehmann and Neumann 1896 (Approved Lists 1980), species. Weiszfeiler et al. 1971 (Approved Lists 1980), species. Mycobacterium aubagnense Adékambi et al. 2006, sp. nov. Mycobacterium lepraemurium Marchoux and Sorel 1912 (Approved Lists 1980), species. Tsukamura 1966 (Approved Lists 1980), species. Mycobacterium madagascariense Kazda et al. 1992, sp. nov. Mycobacterium austroafricanum Tsukamura et al. 1983, sp. nov. Mycobacterium mageritense Domenech et al. 1997, sp. nov. Mycobacterium avium Chester 1901 (Approved Lists 1980), species. Schroder and Juhlin 1977 (Approved Lists 1980), species. Mycobacterium avium subsp. avium Chester 1901, subsp. nov. Mycobacterium avium subsp. paratuberculosis (Bergey et al. 1923) Thorel et al. 1990, comb. nov. Aronson 1926 (Approved Lists 1980), species. Mycobacterium avium subsp. silvaticum Thorel et al. 1990, subsp. nov. Mycobacterium montefiorense Levi et al. 2003, sp. nov. Mycobacterium boenickei Schinsky et al. 2004, sp. nov. Mycobacterium moriokaense Tsukamura et al. 1986, sp. nov. Mycobacterium bohemicum Reischl et al. 1998, sp. nov. Mycobacterium mucogenicum Springer et al. 1995, sp. nov. Adékambi et al. 2006, sp. nov. Mycobacterium murale Vuorio et al. 1999, sp. nov. Mycobacterium botniense Torkko et al. 2000, sp. nov. Mycobacterium bouchedurhonense Ben Salah et al. 2009, sp. nov. Mycobacterium neoaurum Tsukamura 1972 (Approved Lists 1980), species. Mycobacterium branderi Koukila-Kähköläet al. 1995, sp. nov. Mycobacterium nebraskense Mohamed et al. 2004, sp. nov. Mycobacterium brisbanense Schinsky et al. 2004, sp. nov. Mycobacterium neworleansense Schinsky et al. 2004, sp. nov. Mycobacterium brumae Luquin et al. 1993, sp. nov. Mycobacterium nonchromogenicum Tsukamura 1965 (Approved Lists 1980), species. Mycobacterium canariasense Jiménez et al. 2004, sp. nov. (Aranaz et al. 1999) Aranaz et al. 2003, comb. nov. Mycobacterium novocastrense Shojaei et al. 1997, sp. nov. Mycobacterium celatum Butler et al. 1993, sp. nov. Mycobacterium obuense (ex Tsukamura and Mizuno 1971) Tsukamura and Mizuno 1981, sp. nov., nom. rev. corrig. Bergey et al. 1923 (Approved Lists 1980), species. Mycobacterium palustre Torkko et al. 2002, sp. nov. Mycobacterium chelonae subsp. abscessus corrig. (Moore and Frerichs 1953) Kubica et al. 1972 (Approved Lists 1980), subspecies. Mycobacterium parafortuitum Tsukamura et al. 1965 (Approved Lists 1980), species. Mycobacterium chelonae subsp. chelonae corrig. (Bergey et al. 1923) Kubica et al. 1972 (Approved Lists 1980), subspecies. Mycobacterium chimaera Tortoli et al. 2004, sp. nov. Mycobacterium parascrofulaceum Turenne et al. 2004, sp. nov. Mycobacterium chitae Tsukamura 1967 (Approved Lists 1980), species. Mycobacterium paratuberculosis Bergey et al. 1923 (Approved Lists 1980), species. Mycobacterium chlorophenolicum (Apajalahti et al. 1986) Briglia et al. 1994, comb. nov. Mycobacterium parmense Fanti et al. 2004, sp. nov. Mycobacterium chlorophenolicum (Apajalahti et al. 1986) Häggblomet al. 1994, comb. nov. (ex Bojalil et al. 1962) Kusunoki and Ezaki 1992, sp. nov., nom. rev. Mycobacterium chubuense (ex Tsukamura 1973) Tsukamura 1981, sp. nov., nom. rev. Mycobacterium confluentis Kirschner et al. 1992, sp. nov. Lehmann and Neumann 1899 (Approved Lists 1980), species. Mycobacterium conspicuum Springer et al. 1996, sp. nov. Cousins et al. 2003, sp. nov. Mycobacterium cookii Kazda et al. 1990, sp. nov. Mycobacterium porcinum Tsukamura et al. 1983, sp. nov. Mycobacterium cosmeticum Cooksey et al. 2004, sp. nov. Mycobacterium poriferae Padgitt and Moshier 1987, sp. nov. Mycobacterium diernhoferi (ex Bönicke and Juhasz 1965) Tsukamura et al. 1983, sp. nov., nom. rev. Mycobacterium psychrotolerans Trujillo et al. 2004, sp. nov. Mycobacterium doricum Tortoli et al. 2001, sp. nov. Mycobacterium duvalii Stanford and Gunthorpe 1971 (Approved Lists 1980), species. Mycobacterium pulveris Tsukamura et al. 1983, sp. nov. Mycobacterium elephantis Shojaei et al. 2000, sp. nov. Mycobacterium pyrenivorans Derz et al. 2004, sp. nov. Mycobacterium fallax Lévy-Frébault et al. 1983, sp. nov. Mycobacterium rhodesiae (ex Tsukamura et al. 1971) Tsukamura 1981, sp. nov., nom. rev. Mycobacterium farcinogenes Chamoiseau 1973 (Approved Lists 1980), species. Mycobacterium saskatchewanense Turenne et al. 2004, sp. nov. Mycobacterium flavescens Bojalil et al. 1962 (Approved Lists 1980), species. da Costa Cruz 1938 (Approved Lists 1980), species. Mycobacterium scrofulaceum Prissick and Masson 1956 (Approved Lists 1980), species. Mycobacterium fortuitum subsp. acetamidolyticumTsukamura et al. 1986, subsp. nov. Mycobacterium senegalense (Chamoiseau 1973) Chamoiseau 1979 (Approved Lists 1980), species. Mycobacterium fortuitum subsp. fortuitum da Costa Cruz 1938, subsp. nov. Mycobacterium septicum Schinsky et al. 2000, sp. nov. Mycobacterium frederiksbergense Willumsen et al. 2001, sp. nov. (ex Tsukamura et al. 1975) Tsukamura 1982, sp. nov., nom. rev. Mycobacterium gadium Casal and Calero 1974 (Approved Lists 1980), species. Mycobacterium gastri Wayne 1966 (Approved Lists 1980), species. Mycobacterium shottsii Rhodes et al. 2003, sp. nov. Mycobacterium genavense Böttger et al. 1993, sp. nov. Karassova et al. 1965 (Approved Lists 1980), species. Stanford and Gunthorpe 1971 (Approved Lists 1980), species. (Trevisan 1889) Lehmann and Neumann 1899 (Approved Lists 1980), species. Mycobacterium goodii Brown et al. 1999, sp. nov. Mycobacterium sphagni Kazda 1980, sp. nov. Mycobacterium gordonae Bojalil et al. 1962 (Approved Lists 1980), species. Mycobacterium haemophilum Sompolinsky et al. 1978 (Approved Lists 1980), species. Marks et al. 1972 (Approved Lists 1980), species. Mycobacterium hassiacum Schröder et al. 1997, sp. nov. Wayne 1966 (Approved Lists 1980), species. Mycobacterium heckeshornense Roth et al. 2001, sp. nov. Mycobacterium thermoresistibile Tsukamura 1966 (Approved Lists 1980), species. Mycobacterium heidelbergense Haas et al. 1998, sp. nov. Mycobacterium tokaiense (ex Tsukamura 1973) Tsukamura 1981, sp. nov., nom. rev. Mycobacterium hiberniae Kazda et al. 1993, sp. nov. Mycobacterium triplex Floyd et al. 1997, sp. nov. Mycobacterium hodleri Kleespies et al. 1996, sp. nov. Mycobacterium holsaticum Richter et al. 2002, sp. nov. Mycobacterium triviale Kubica 1970 (Approved Lists 1980), species. Mycobacterium houstonense Schinsky et al. 2004, sp. nov. Mycobacterium tusciae Tortoli et al. 1999, sp. nov. Mycobacterium immunogenum Wilson et al. 2001, sp. nov. MacCallum et al. 1950 (Approved Lists 1980), species. Mycobacterium interjectum Springer et al. 1995, sp. nov. Bönicke and Juhasz 1964 (Approved Lists 1980), species. Mycobacterium intermedium Meier et al. 1993, sp. nov. Mycobacterium intracellulare (Cuttino and McCabe 1949) Runyon 1965 (Approved Lists 1980), species. Mycobacterium vanbaalenii Khan et al. 2002, sp. nov. Brown et al. 1999, sp. nov. Mycobacterium xenopi Schwabacher 1959 (Approved Lists 1980), species.

http://www.bacterio.net/mycobacterium.html Commonly Encountered Species

• Mycobacterium marinum • Water exposure: aquariums, boating • Rapidly growing mycobacteria • Many different exposures • M. fortuitum • M. chelonae • M. abscessus • Don’t necessarily grow rapidly from human specimens

Philips RC et al, J Am Acad Derm 2019; 81: 730; Moreno G et al., Australas J Derm 2018; Why Is This Worth Discussing?

• Diagnostically challenging • Potentially disfiguring • Increasingly common! Cutaneous NTM Age Group 1980-1999 2000-2009 N (rate per N (rate per 100,000) 100,000) 0-39 7 (0.5) 6 (0.8) 40-59 5 (1.1) 11 (2.9) 60+ 2 (0.7) 9 (4.3)

Drage LA et al., Mayo Clin Proc 2013; 88: 38-45 Cutaneous NTM

• 87% were on extremities • 79% single lesions • 77% immunocompetent host • Predisposing factor: • 76% post-traumatic • 14% post cosmetic procedure • 10% post other surgery

Drage LA et al., Mayo Clin Proc 2013; 88: 38-45 Cutaneous NTM

• 50% rapid growers, 50% slow growers • 45% were M. marinum • 32% M. chelonae/abscessus • 16% M. fortuitum group • Wide variety of clinical presentations • 40% subcutaneous abscess • 28% cellulitis • 25% wound infection • 7% other

Drage LA et al., Mayo Clin Proc 2013; 88: 38-45 Cutaneous NTM

• 1/3 did not have granulomatous inflammation on pathology • Of those with treatment data, about half had surgery + abx, half had abx alone • 39% got monotherapy

Drage LA et al., Mayo Clin Proc 2013; 88: 38-45 Sore than meets the eye

• 42 yr old man with mixed connective tissue disease (RA/polymyositis overlap) presents with a red, tender skin lesion at the site of a muscle biopsy done 3 years ago • No systemic symptoms • On chronic abatacept, azathioprine, and prednisone Sore than meets the eye

• Lesion opens and drains a month later • Over next 4 months, 2 more lesions appear • Superficial swab of a draining lesion grows Bacillus cereus • One lesion opens up and ulcerates • Subsequent punch biopsy of lesion demonstrates AFB, culture grows MAC

Sore than meets the eye

• Treated for 6 months with resolution of skin lesions • 4 years later presented with malaise, right shoulder pain and swelling • Found to have right shoulder bursitis with osteomyelitis of the humerus, clavicle, and acromion • Went to OR for debridement, started on azithromycin, ethambutol, and IV amikacin • Did well until 11 mos later had swelling of the left shoulder with fluid collection on MRI • Rice bodies noted on surgical debridement, culture grew MAC • Doing well now after completion of 12 mos postop abx Tat’s a shame

• 32 yr old man presents with skin nodules about 3 weeks after getting a new tattoo

Falsey RR et al., Clin Inf Dis 2013; 57: e143 What’s My Line?

• 33 F with type 1 DM, history of multiple (15+ abdominal surgeries) with resultant short gut, on chronic total parenteral nutrition • Presented with about a month of subjective fevers and weight loss • Skin lesions then began to appear

Pedi-Regreti

• 21 year old woman presents with 6 weeks of progressive, painful red bumps on legs • No fever, chills, weight loss or other symptoms • No lesions above the knee • No unusual travel or other activities • Gets pedicures frequently, last 4 wks prior to onset of lesions

Winthrop, K. et al. N Engl J Med 2002;346:1366-1371 Risk Factors for Furunculosis Associated with the Nail Salon Identified as the Source of the Outbreak

Winthrop, K. L. et al. N Engl J Med 2002;346:1366-1371 Winthrop KL et al., NEJM 2002; 347: 1366 Endemic Pedicure-Associated NTM in North Carolina

Characteristic Number of cases (%) Female sex 39/40 (97.5%) White race 38/40 (95.0%) Mean age in years (range) 32.6 (13-53) Case definition Clinical 7/40 (17.5%) Culture-proven 33/40 (82.5%) Organism M. abscessus 18/33 (54.5%) M. fortuitum 2/33 (6.0%) M. bolletii 3/33 (9.0%) M. chelonae 1/33 (3.0%) M. chelonae/abscessus 7/33 (21.2%) M. massiliense/abscessus 1/33 (3.0%) Unknown species 1/33 (3.0%) Multiple lesions 30/40 (75.0%) Bilateral disease 22/39 (56.4%, 1 unknown)

Stout JE et al., Clin Inf Dis 2011; 53: 787 Pattern recognition

• 43 year old intellectually challenged man living in a group home admitted with “cellulitis” • Biopsy of a lesion subsequently grows M. chelonae • How did he get it?

Fraxel leads to Paxil

• 53 WF presents with confluent papules 10 days after fractionated CO2 laser resurfacing • Treated initially with corticosteroids, then low-grade fever developed, hospitalized Culton DA et al., Emerg Infect Dis 2013; 19: 365 What Does the Dermatologist Need to Know?

• Indolent, usually local infections in immunocompetent hosts • Cutaneous lesions often manifestations of disseminated disease in immunocompromised hosts • Must biopsy and get mycobacteria (AFB) cultures (swabs not sufficient) • Empiric treatment rarely a good idea • Rapid growers often resistant, phone a friend for help