Infection Imitating Lymphocutaneous Sporotrichosis During

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Clinical microbiological case: infection mon. Skin and subcutaneous involvement is the imitating lymphocutaneous sporotrichosis most common early manifestation. M. fortuitum during pregnancy in a healthy woman from the [3], M. chelonae [4,5] and M. abscessus [6] are the south-eastern USA three main species of RGM associated with A. Safdar human infection. In individuals with intact immunity, cutaneous infections due to RGM are observed after traumatic implantation, fol- Please refer to the article on page 221 of this issue lowing reconstructive surgery [7,8], or, rarely, to view the questions to which these answers as abscesses at the site of intramuscular or refer. subcutaneous injections [9–11]. A case of disseminated M. fortuitum skin abscesses has been described in a woman during pregnancy [12], CLINICAL OUTCOME and as in this patient, progressive RGM infection during pregnancy probably resulted from The patient was given several empirical courses of physiologic suppression of adaptive cellular antibiotics, with no response. Further laboratory immune responce promoting immunologic tol- studies indicated: negative serology for HIV-I and erance during pregnancy. HIV-II; antinuclear antibodies <1 : 40; normal 2. Skin infections commonly present as localized complement levels (C3, 151 mg/dL; C4, 31 mg/ nodules, papules, and/or pustules [13,14]. M. dL); rheumatoid factor <25 IU/mL; angiotensin- fortuitum has also been associated with inflam- I-converting enzyme 23 U/L; thyroid-stimulating mation of the panniculus, which is the subcu- hormone 2.62 micro-IU/mL; free thyroxin (T-4) taneous tissue consisting of fibrocytes, fibrous 1.2 hg/dL; and normal serum globulin electro- trabeculae, fat cells, and blood vessels, leading phoresis. to the clinical syndrome of ‘panniculitis’ [15]. In Within 10 days of incubation, rapidly growing rare instances, despite apparently intact cellular mycobacteria (RGM) were isolated and identified immunity, cutaneous infections may become by standard methods [1] from skin biopsy sam- widespread [14]. ples. Treatment with clarithromycin (500 mg twice 3. The lymphocutaneous syndrome is character- daily) and ciprofloxacin (500 mg twice daily) was ized by an initial lesion that extends along the commenced. DNA sequencing was performed, proximal course of the area of lymph drainage, and the isolate was confirmed as being genetically and presents clinically as contiguous subcuta- most closely related to Mycobacterium fortuitum. neous nodules and lymphangitis [16]. Several The antimicrobial susceptibility profile (MIC, bacterial, fungal, mycobacterial, parasitic and mg/L) was determined by a standard microdilu- viral pathogens may progress in this manner. tion method [2]: amikacin 0.25, cefoxitine 8.0, The sporotrichoid manifestation is similar to the ciprofloxacin 0.06, clarithromycin 2.0, doxycycline lymphocutaneous syndrome, except that skin 0.12, erythromycin 0.25, imipenem 0.25, tobramy- and subcutaneous tissue between the involved cin 0.5, and trimethoprim–sulfamethoxazole 0.12. areas is frequently normal, and signs of lym- Twelve months after oral antibiotic therapy, the phangitis are often subclinical. Pathogens patient’s lesions resolved completely, leaving thin- associated with a sporotrichoid presentation walled scars at the sites of infection. include Sporothrix schenckii, Nocardia brasiliensis, Leishmania spp., M. leprae, M. marinum, and RGM, especially M. chelonae [4,5]. Infrequent DIAGNOSIS opportunistic fungi such as Scedosporium apios- Sporotrichoid lymphocutaneous infection due to permum [17] and Paecilomyces spp. [18] may lead M. fortuitum complex during pregnancy. to skin lesions resembling cutaneous sporotrichosis. In contrast, in the case presented, a paradoxical spread along the distal lymphatic DISCUSSION distribution was seen as M. fortuitum complex 1. Cutaneous infections due to mycobacteria other infection progressed caudally along the right than Mycobacterium tuberculosis are not uncom- lower leg, causing three distinct lesions with

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normal interlesional skin and subcutaneous linezolid in a patient with progressive clarithro- tissue (Figure 1). mycin-resistant RGM infection [28] provides 4. Clinical features of M. fortuitum infections may another possible treatment option for refractory be misinterpreted. In a recent report of 11 cases. A regimen of two active antimicrobial patients, two-thirds (64%) were misdiagnosed agents is considered optimal for the treatment initially, and, like the case presented, inap- of M. fortuitum infection [21], and in the case propriate empirical antimicrobial therapy was presented, prolonged therapy with clarithro- initiated [19]. Early diagnostic biopsy and mycin and ciprofloxacin resulted in a complete mycobacterial cultures of tissue samples remain and durable response. the mainstay of establishing a correct diagnosis [3]. Histopathologic features of RGM infections can be distinct [20,21], and characteristic REFERENCES dimorphic (acute and chronic) inflammation 1. Nolte FS, Metchock B. Mycobacterium. In: Murray or mixed suppurative reaction (granulocytes PR, Baron EJ, Pfaller MA, Tenover FC, Yolken RH, and lymphocytes) may be present along with eds. Manual of clinical microbiology. Washington, DC: tissue necrosis, which includes granulocytic ASM Press, 1995; 400–37. microabscesses and/or non-necrotizing granu- 2. Swenson JM, Thornsberry C, Silcox VA. Rapidly lomatous reactions [19–21]. growing mycobacteria: testing of susceptibility 5. Infections due to non-M. tuberculosis mycobac- to 34 antimicrobial agents by broth microdilution. teria, especially the RGM, are in general diffi- Antimicrob Agents Chemother 1982; 22: 186–92. 3. Escalonilla P, Esteban J, Soriano ML et al.Cu- cult to treat and do not respond to traditional taneous manifestations of infections by nontubercu- anti-M. tuberculosis therapy. As with other lous mycobacteria. Clin Exp Dermatol 1998; 23: 214–21. mycobacterial infections, RGM are usually trea- 4. Demitsu T, Nagato H, Inoue T et al. Cutaneous ted with multidrug regimens in order to reduce Mycobacterium chelonae infection with bilateral the emergence of drug-resistant organisms. sporotrichoid involvement. Int J Dermatol 2001; 40: This approach may change in future if a single, 597–9. highly active antimicrobial agent becomes 5. Greer KE, Gross GP, Martensen SH. Sporotrichoid available [22]. Several antimicrobial agents cutaneous infection due to Mycobacterium chelonei. are active against the RGM [2]; a recent in vitro Arch Dermatol 1979; 115: 738–9. 6. Fitzgerald DA, Smith AG, Lees A et al. Cutaneous antimicrobial susceptibility analysis showed infection with Mycobacterium abscessus. Br J Dermatol that amikacin [23], azithromycin [24], cefoxitine 1995; 132: 800–4. [25], ciprofloxacin [22,25], clarithromycin 7. Wallace RJ Jr, Brown BA, Griffith DE. Nosocomial [24,25], doxycycline [25], imipenem [25] and outbreaks/pseudo-outbreaks caused by nontuber- trimethoprim–sulfamethoxazole [25] remain culous mycobacteria. Annu Rev Microbiol 1998; 52: active against M. fortuitum. Similarly, no in vitro 453–90. antimicrobial resistance was seen in the myco- 8. Murillo J, Torres J, Bofill L et al. Skin and wound bacteria isolated from this patient. Fluoroqui- infection by rapidly growing mycobacteria: an nolones are bactericidal against most strains of unexpected complication of liposuction and lipos- culpture. The Venezuelan Collaborative Infectious M. fortuitum, and relative bactericidal indices and Tropical Diseases Study Group. Arch Dermatol for moxifloxacin (1.8), ciprofloxacin (0.5), spar- 2000; 136: 1347–52. floxacin (0.2) and ofloxacin (0.2) suggest that 9. Toth EL, Boychuk LR, Kirkland PA. Recurrent moxifloxacin and ciprofloxacin, in that order, infection of continuous subcutaneous insulin infu- are the most bactericidal fluorinated quinolones sion sites with Mycobacterium fortuitum. Diabetic [26]. Aminoglycosides are bacteriostatic against Care 1998; 18: 1284–5. M. fortuitum, amikacin and neomycin being the 10. Nagore E, Ramos P, Botella-Estrada R, Ramos- most active in this group [27]. Topical applica- Niguez JA, Sanmartin O, Castejon P. Cutane- tion of neomycin-based preparations in patients ous infection with Mycobacterium fortuitum after localized microinjections (mesotherapy) treated with recalcitrant cutaneous M. fortuitum infec- successfully with triple drug regimen. Acta Derma- tion has been recommended, but must be used tovenerelogica 2001; 81: 291–3. with caution until clinical validation of topical 11. O’Brien DP, Rawluk DJ. Iatrogenic Mycobacterium antimicrobial therapy in this setting becomes infection after an epidural injection. Spine 1999; 24: available. A report of successful treatment with 1257–9.

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12. Katayama I, Nishioka K, Nishiyama S. Mycobacter- 21. Safdar A, Bains M, Polsky B. Clinical microbiological ium fortuitum infection presenting as widespread case: refractory chest wall infection following recon- cutaneous abscess in a pregnant woman. Int J structive surgery in a patient with relapsed lung Dermatol 1990; 29: 383–4. cancer. Clin Microbiol Infect 2001; 7(563–4): 577–9. 13. Silvestre Salvador JF, Betlloch MI, Alfanso R, 22. Alangaden GJ, Lerner SA. The clinical use of Ramon RL, Morell AM, Navas J. Disseminated skin fluoroquinolones for the treatment of mycobacterial infection due to Mycobacterium fortuitum in an disease. Clin Infect Dis 1997; 25: 1213–21. immunocompetent patient. J Eur Acad Dermatol 23. Hernanadez AM, Arias A, Felipe A, Alvarez R, Venereol 1998; 11: 158–61. Sierra A. Determination of the in vitro susceptibility 14. Passeron T, Desruelles F, Fosse T et al. Dissemi- of 220 Mycobacterium fortuitum isolates to ten nated papulopustular eruption due to Mycobacter- antimicrobial agents. J Chemother 1995; 7: 503–8. ium fortuitum in an immunocompetent patient. Clin 24. Tartaglione T. Treatment of nontuberculous myco- Infect Dis 1999; 28: 924–5. bacterial infections: role of clarithromycin and 15. Retief CR, Tharp MD. Mycobacterium fortuitum azithromycin. Clin Ther 1997; 19: 626–38. panniculitis in a steroid-dependent asthmatic pa- 25. Woods GL, Bergmann JS, Witebsky FG et al. tient. J Am Acad Dermatol 1998; 39: 650–3. Multisite reproducibility of results obtained by the 16. Smego RA, Castiglia M, Asperilla MO. Lymphocu- broth microdilution methods for susceptibility taneous syndrome. Medicine 1999; 78: 38–63. testing of Mycobacterium abscessus, Mycobacterium 17. Canet JJ, Pagerols X, Sanchez C, Vives P, Garau J. chelonae, and Mycobacterium fortuitum. J Clin Micro- Lymphocutaneous syndrome due to Scedosporium biol 1999; 37: 1676–82. apiospermum. Clin Microbiol Infect Dis 2001; 7: 648–52. 26. Gillespie SH, Morrissey I, Everett D. A comparison 18. Leigheb G, Mossini A, Boggio P, Gattoni M, of the bactericidal activity of quinolone antibiotics Bornacina G, Griffanti P. Sporotrichosis-like lesions in a Mycobacterium fortuitum model. J Med Microbiol caused by a Paecilomyces genus fungus. Int J 2001; 50: 565–70. Dermatol 1994; 33: 275–6. 27. Ho YI, Chan CY, Cheng AF. In-vitro activity of 19. Smith MB, Schnadig VJ, Boyars MC, Woods GL. aminoglycoside-aminocyclitols against mycobacter- Clinical and pathologic features of Mycobacterium ia. J Antimicrob Chemother 1997; 40: 27–32. fortuitum infections. An emerging pathogen in pa- 28. Brown-Elliott BA, Wallace RJ Jr, Blinkhorn R, Crist tients with AIDS. Am J Clin Pathol 2001; 116: 225–32. CJ, Mann LB. Successful treatment of disseminated 20. Wolinsky E. Nontuberculous mycobacteria and as- Mycobacterium chelonae infection with linezolid. Clin sociated disease. Am Rev Respir Dis 1979; 119: 107–59. Infect Dis 2001; 33: 1433–4.

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