Atypical mycobacterial infections in dermatology
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Atypical mycobacterial infections in dermatology
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Atypical mycobacterial infections in dermatology
- 1. Atypical Mycobacterial infections in dermatology Dr Sanjay Singh AIIMS
- 2. Cutaneous Atypical Mycobacterial Infection Infections caused by Mycobacteria other than M tuberculosis and M leprae Now called as non –Tuberculous Mycobacteria Atypical mycobacteria are found in many environmental areas, such as wet soil, tap water, house dust, water, dairy products, cold-blooded animals, vegetation, and human feces Accidentally transmitted by inhalation, ingestion, or percutaneous penetration and can cause disease in the skin, lungs, lymph nodes, and skeletal and genitourinary systems
- 3. Diagnosis easily missed on ZN staining and culture Most common NTM causing Human disease is MAC
- 5. Mycobacterium Marinum (Mycobacterium Balnei or Mycobacterium Platypoecilus) Usually causes disease in fish Normally found in salt water, fresh water, or brackish water sources, such as swimming pools, rivers, lakes, oceans, and aquariums Cause human disease by penetration through impaired skin barrier : Traumas, such as abrasions and puncture wounds It is not transmittable from person to person Swimming pool granuloma or Fish tank granuloma
- 6. Mycobacterial marinum infection in Fish
- 7. Risk factors • Trauma • A fish-related job or home aquarium • Patients on TNF-α inhibitors e.g Etanercept and Infliximab
- 8. Clinical features Incubation period : 2 weeks Sites : – Extremities – Fingers most common : fish tank finger – back of hands – Elbows and knees of swimmers.
- 9. Morphological variants • Nodule • Pustule • Ulcer or abscess • Verrucous plaque • Sporotrichoid form : 20% cases
- 14. Diagnosis: culture on Lowenstein-Jensen medium at 37ºC became positive after 3 weeks, PCR 16s rRNA + Amikacin 750 mg daily and clarithromycin 500 mg twice daily x 6weeks
- 15. 1. Superficial infection : Usually solitary and frequently undergo central ulceration 2. Granulomatous 3. Deep : Tendons, bones, joints, and bursae Infection with the organism does not lead to immunity and thus reinfection with M marinum is possible.
- 16. Histopathology Mixed infiltrate including lymphocytes, neutrophils, and histiocytes, is seen Granulomatous inflammatory infiltrate mimicking tuberculoid granuloma, sarcoid-like granuloma, or rheumatoid-like nodules may be noted.
- 17. CULTURE • Sample: Tissue biopsy • Culture media – Solid media: Lowenstein Jensen medium – Liquid media: Mycobacterial growth indicator tube media • Temperature for optimal growth: 30 – 32 °c • Colonies – smooth, shiny and creamy coloured – turns yellow on exposure to light (Photochromogenic)
- 18. M marinum histopathology Courtesy: Weedons
- 19. TREATMENT Clinical types Treatment Type 1 (limited 1- 3lesions) Minocycline 100mg bd , clarithromycin 500mg bd, doxycycline 100mg bd, Cotrimoxazole 800mg BD Monotherapy effective Type 2 Rifampicin 600mg/day + ethambutol 15 -25mg/k/day. Rifampicin + minocycline ± surgical excision. Type 3 Type 4 Duration of treatment Atleast 2 months after definite clinical resolution
- 20. Q. Which of the following drug show primary resistance to M marinum infection (a) Rcin (b) INH (c) Ethambutol (d) Streptomycin Ans : INH & Steptomycin
- 21. RAPID GROWERS
- 22. RAPID GROWERS • Show visible growth on solid laboratory media • within 7 days • Consist of • Non-pigmented • Pigmented species • There are 5 groups of rapid growers
- 23. CLASSIFICATION RGM GROUP SPECIES M fortuitum M fortuitum M peregrinum , M senegalense M chelonae abscessus M chelonae M abscessus M smegmatis M smegmatis , M goodii , M wolinskyi M mucogenicum M mucogenicum M aubagnense Recently described 5th group M flavescens ,M vaccae M phlei, M thermoresistible
- 24. M fortuitum, chelonae and abscessus • They are ubiquitously distributed in nature. • They have been recovered from soil, dust, water, milk and even from saliva and tap water. • They are extremely hardy. • M. fortuitum group can grow at 45°C • M. chelonae/abscessus group • Resist the activity of organomercurials, chlorine • 2% concentrations of formaldehyde
- 25. Outbreaks :: jet injectors, hemodialysis, peritoneal dialysis, contaminated gentian violet skin-marking solution, catheters, prosthetic valves, surgical site infections, nail salons, skin resurfacing with CO2 laser, and contaminated injection solutions.
- 26. BASIC DIFFERENCES M fortuitum • Accounts for • 60% of community acquired localized cutaneous infection by rapid growers. • This includes cases of • Post trauma • Post-surgical wound infections • Catheter infections M chelonae/abscessus • Account for • 95% of disseminated cutaneous infections caused by rapid growers • Commonly causes • Chronic lung disease
- 27. Skin and soft tissue infections due to rapidly growing mycobacteria: comparison of clinical features, treatment, and susceptibility. Uslan DZ, Kowalski TJ, Wengenack NL, Virk A, Wilson JW. Arch Dermatol. 2006;142(10):1287. ●M. fortuitum infections were more likely to present as a single lesion (89%) ●M. chelonae and M. abscessus were more likely to present as multiple lesions (62%) ●Patients with multiple lesions were more likely to be immunosuppressed (67%)
- 28. M. fortuitum • Cutaneous lesions occur in 3 clinical settings • Post surgical • Disseminated disease in immunocompromised • Primary cutaneous infection
- 30. Growth on L-J media
- 31. Surgical Site Infections Due to Rapidly Growing Mycobacteria in Puducherry, India 19 patients Clarithromycin, linezolid, and amikacin :: 100% isolates were susceptible Ciprofloxacin :: 82% susceptible Rifampicin :: 58% susceptible Tobramycin :: 30%susceptible
- 32. Periocular atypical mycobacterial infections. Chang WJ et al. Ophthalmology 1999 Jan;106(1):86-90 • Six patients • 4: fortuitum 2: chelonae Risk factors • Immunosuppression • Nasolacrimal duct obstruction • Presence of a foreign body • h/o of recent surgery.
- 34. Disseminated folliculitis by Mycobacterium fortuitum in an immunocompetent woman An Bras Dermatol. 2013 Jan-Feb;88(1):102-4.
- 35. Mycobacterium chelonae • M. chelonae is named after • Sea turtle, Chelona corticata • M. chelonae is classified into three subspecies • M. chelonae chelonei • M. chelonae abscessus • Unnamed subspecies known as M.chelonae like organism (MCLO).
- 36. Incubation 4-6weeks ImmunocompromisedImmunocompetent Infection with M chelonae Disseminated diseaseLocalised abscess/cellulitis
- 37. Causes nosocomial skin and soft tissue infections following • Contaminated injections • Cosmetic surgical procedures • Laparoscopic surgery.
- 38. Chronic cutaneous disease caused by the rapid growers Mycobacterium fortuitum and chelonae Palwade P et al. Br J Dermatol.2006 Apr;154(4):774-5 Amikacin 500 mg OD + Oral Tmp-Smx 160 / 800 mg BD : 21 days Oral clarithromycin 500 mg BD, ciprofloxacin 500 mg + Tmp-Smx 160 / 800 mg BD : 8 months
- 39. Extensive infection of face by mycobacterium chelonae: An unusual presentation Indian J Dermatol. 2014 Sep;59(5):495-7.
- 41. M chelonae complicating hidradenitis suppurutiva Patnaik S et al. Disseminated Mycobacterium chelonae infection: Complicating a case of hidradenitis suppurativa Indian Dermatol Online J 2013 Oct;4(4):336-9
- 42. M chelonae complicating hidradenitis suppurutiva Zn staining LJ media
- 43. Diagnosis and Management of Atypical Mycobacterial Infection after Laparoscopic Surgery Indian J Surg. 2010 Dec; 72(6): 438–442. 19 patients : Laparoscopic cholecystectomy Rounded erythematous swellings at the port sites with mild to moderate pain along with tenderness 1 Month treatment with Clarithromycin and Ciprofloxacin (500 mg each, twice daily) x 28 days 7 patient with persistent local nodules : 500mg Amikacin I/L
- 44. Disseminated M. chelonae infection DISSEMINATED CUTANEOUS MYCOBACTERIUM CHELONAE INFECTION Kane C et al
- 45. M abscessus • Infection: Morphological variants • Asymptomatic • Tender erythematous violaceous nodules and plaques, • Cellulitis • Abscesses • Ulcer • Sinus with serosanguinous discharge
- 46. Mycobacterium chelonae Abscesses Associated with Biomesotherapy, Australia, 2008 Mihaela Ivan et al. Emerg Infect Dis. 2013 Sep
- 47. Successfully treated Mycobacterium abscessus mastitis: A rare cause of breast masses. Yasar K et al. Indian J Med Microbiol 2011;29:425-7.
- 48. Postoperative sinus formation due to M abscessus : case report Haider m et al . Indian J Tuberc 2013;60:177-179
- 49. CLUES FOR SUSPECTING RAPID GROWING MYCOBACTERIAL INFECTION • Chronic cutaneous infection • Pus discharging nodules • Healing with puckered scars • Absence of granules in pus • No response to • Short course of antibiotics • ATT • Past h/o of post injection abscess
- 50. Rapid growers(RGM) identification • IDSA (Infectious Disease Society of America) recommendation • Identification of RGM isolates • To the species level • Not merely as groups such as the M. chelonae abscessus group
- 51. LABORATORY DIAGNOSIS FOR RAPID GROWERS • Collection and transport of specimens • Most sensitive: Tissue biopsy • COLLECT IN STERILE NORMAL SALINE • Refrigeration of specimens : 4 °C • Culture • Solid media: Lowenstein Jensen media • Liquid media: Mycobacterium growth indicator tube
- 52. PRE REQUISITES FOR SENDING CULTURE • Make sure patient is not on any antibiotics • Macrolides , Quinolone, ATT • Adequate tissue biopsy sample • Send in sterile normal saline
- 53. CULTURE TECHNIQUES • All specimens for mycobacterial culture • inoculated on both solid and liquid media. • Recommended solid media • Lowenstein Jensen agar • Middlebrook 7H10 or 7H11 media • Liquid /Broth culture media • Mycobacteria Growth Indicator Tube (MGIT) • Optimal incubation temperature • 28-30 °C and 35-37 °C.
- 54. • Culture ++ on MGIT MEDIA • Subculture done on L-J media • Microscopy : Zn staining. • Identification of AFB • SPECIES IDENTIFICATION • Biochemical tests • PCR • DRUG SUSCEPTIBILITY TESTING • Culture : negative, if no growth • L-J media: 8 weeks • MGIT media: 7 weeks
- 55. TECHNIQUES FOR SPECIES IDENTIFICATION • Nitrate reductase • Utilization of carbohydrates ( mannitol, inositol ). • Accurate identification of the commonly encountered species Biochemical tests Species Arylsulfatase activity at 3days M fortuitum, M chelonae ++ M smegmatis -ve Yellow Pigment production at 3days M smegmatis ++ M goodii ++ Iron uptake, Tolerance to 5% Nacl. M fortuitum + M chelonae -
- 56. PCR 16s rRNA • 16S ribosomal RNA (rRNA) gene sequence analysis • Considered a Gold standard PCR technique • For identification for all bacteria • Widely recognized as • Rapid and accurate method of identifying known mycobacteria
- 57. Susceptibility testing for RGM • Recommended • Drugs tested • Macrolides • Quinolones • Tetracyclines • Imipenem • Gold standard technique for drug susceptibility testing • Microbroth dilution
- 58. Treatment: Recommended drugs M. fortuitum • Amikacin • Cefotaxime • Ciprofloxacin • Imipenem M. chelonae/abscessus • Amikacin • Clarithromycin • Erythromycin • Doxycycline • Linezolid Alternative drugs: Ethambutol, Cotrimoxazole and Amoxicillin-clavulinic acid Combination of at least 2 drugs to be used (with at least 1 parenteral agent) Duration: no standard guidelines Usually 2months after clinical resolution
- 59. PREVENTION OF HEALTH CARE ASSOCIATED NTM (IDSA GUIDELINES) • Patients with Intravenous catheters: avoid contact/ contamination with tap water • Fibreoptic endoscopes • Avoid tap water in automated endoscopic washing machine • Proper sterilisation technique • Local injections : Avoid benzalkonium chloride as a skin disinfectant • It allows growth of M abscessus • Proper sterilization techniques for surgical instruments and surgical site
- 60. M peregrinum
- 61. M smegmatis
- 62. M avium intracellulare • Chronic pulmonary infection: most common form • Skin lesions • multiple nodules • ulcerated nodules • abscesses • painless nodules and plaques • Sprotrichoid spread
- 63. M avium intracellulare Mimicing lupus vulgaris
- 64. MAC IN HIV SETTING • Most common manifestation : Mycobacteraemia • skin lesions • Clue to the presence of disseminated infection. • Infection occur late in HIV disease • most frequently in patients whose CD4+< 50 cells/mm3
- 65. M scrofulaceum • Cervical lymphadenitis in children • (In India: M tuberculosis usual suspect). • Subcutaneous abscesses. • Disseminated infection in immunocompromised
- 66. TREATMENT • Lymphadenectomy treatment of choice • Clarithromycin + Rifabutin for 12weeks
- 67. SUMMARY • M marinum • Inflammatory nodulo-plaques in exposed site solitary or in sporotrichoid distribution. • M ulcerans • Exposed site, rapidly progressive painless ulcer with necrotic slough • Not reported in India
- 68. • Rapid growers • Commonly suspected in our clinical setting • Risk factors: • Injections • Surgery • Trauma • Presenting as chronic nodules and discharging sinuses. • Multiple biopsies: Culture and PCR • Treatment according to drug susceptibility testing. SUMMARY
- 69. CLUES FOR SUSPECTING RAPID GROWING MYCOBACTERIAL INFECTION • Chronic cutaneous infection • Pus discharging nodules • Healing with puckered scars • Absence of granules in pus • No response to • Short course of antibiotics • ATT • Past h/o of post injection abscess
- 70. Thank You
Notas do Editor
- Culture The organism is isolated from the lesion, as well as from the patient’s aquarium and infected fish. The required temperature for optimal growth is 30 – 32 ° C, and this explains why it almost exclusively infects the cooler extremities and is confined to superficial structures, rarely achieving systemic distribution. Colonies are smooth, shiny and creamy coloured, turning yellow under exposure to light (Photochromogenic).
- Courtesy: weedons
- In limited superficial cutaneous infections (Type I), the second-generation tetracycline minocycline (100 mg bd.), clarithromycin 500 mg bd. and the ‘older’, doxycycline (100 mg bd.) and trimethoprim-sulfamethoxazole (800 mg bd.), each as monotherapy, are considered effective treatment options. In immunocompromised individuals or in cases of severe cutaneous infections (Type II or III) with nodules, abscesses and/or sporotrichoid distribution pattern, a combination of rifampicin 600 mg/day and ethambutol 15 – 25 mg/kg/day seems to be the most consistently recommended regimen. In limited or severe cutaneous infections (Type I – III), surgical treatment may be required if the infection has not been controlled by chemotherapy. Deeper infections (Type III) may require prolonged systemic treatment and surgical debridement. However, the selection of cases and the time of surgical intervention require good judgment. In disseminated infection or bacteraemia (Type IV), combined (antimicrobial plus antimycobacterial) intravenous therapy of three drugs may be required.
- The RGM are generally defined as nontuberculous species of mycobacteria that show visible growth on solid laboratory media within 7 days. The species of RGM capable of producing disease in humans consist of nonpigmented and pigmented species
- Cutaneous lesions caused by Mfortuitum may occur in three clinical settings; a) post surgical, most commonly reported in sternotomy wounds, b) as a manifestation of disseminated disease, usually occurring in immunocompromised host with signs and symptoms of a systemic infection, and c) primary cutaneous infections (non surgical). The last type usually occurs as a localized infection in an otherwise healthy individual, with a history of trauma 1-2 months before developing symptoms at the involved site. When dissemination occurs, usually the primary source is unknown. Morphologically, the patients may present with abscesses, ulcers, draining sinus tracts, cellulitis or tender erythematous nodules. Occasionally the lesions may be multiple and tend to be distributed along the course of the afferent lymphatics, simulating the lesions of sporotrichosis, often referred to as 'sporotrichoid mycobacteriosis. All the three cases presented here could be included in this category.
- Periocular atypical mycobacterial infections
- The growth was subcultured on MacConkey’s culture medium, which grew similar colonies within 5 days suggestive of rapidly growing mycobacteria. Species identification and antibiotic sensitivity testing could not be done due to lack of facilities, and the growth was identified as M. fortuitum and chelonae complex. Before the confirmation of diagnosis she had received intramuscular injections of amikacin 500 mg once daily and oral trimethoprim–sulfamethoxazole 160 / 800 mg twice daily for 14 days. The same treatment was continued for the next 7 day Then the regimen was changed to a combination of oral clarith- romycin 500 mg, ciprofloxacin 500 mg and trimethoprim–sulfa- methoxazole 160 / 800 mg twice daily for 8 months. During this period there was progressive improvement: no new lesions appeared and the active lesions healed (Fig. 1b). Skin ultrasonography was repeated after 4 months of the lesion-free period, which showed a reduction in thickness of the dermis, with uniform normal hyperechoeic dermis (dermal thickness 1Æ6mm). Culture of a punch biopsy taken from a healed nodule did not yield growth of AFB. One year after stopping treatment there was no evidence of disease activity.
- Ivan M, Dancer C, Koehler AP, Hobby M, Lease C. Mycobacterium chelonae abscesses associated with biomesotherapy, Australia, 2008. Emerg Infect Dis [Internet]. 2013 Sep An outbreak of skin abscesses occurred in Adelaide, Australia, in association with biomesotherapy, an alternative therapy practice. Mycobacterium chelonae was identified in 8 patient and 3 environmental samples. Our findings show M. chelonae infection can be associated with alternative therapies when infection-control breaches occur. Tighter regulations of alternative therapy practices are needed.
- 38-year-old HIV negative woman with a 3-year history of bilaterally fibrocystic disease and breast abscess presented with a change in characteristics in her right breast abscess in last 2 months. Her right breast mass got bigger with associated pain, redness and haemorrhagic discharge from a fistula. Non-specific mastitis was the initial diagnosis 1 year ago and was unresponsive to antimicrobial agents. The patient had undergone aspiration for drainageCombination therapy with clarithromycin, linezolid and amikacin was effective and full recovery was obtained for this patient without surgical debridement following abscess aspiration in the present report. Since breast lesions of this patient disappeared at the end of the second month, the therapy was completed in 4 months. During the follow-up period, there was no relapse or any other problem suggesting treatment failureAmikacin 1g/day + Clarithromycin 500mg bd ± Linezolid 600mg bd Duration : Till 2months after clinical resolution.
- A 40-year-old immuno-competent female underwent laproscopic cholecystectomy for acute cholecystitis. The operation was uneventful. Three weeks later, she developed port site granuloma with persistent seropurulent discharge (Figure 1). Empirical oral antibiotics were started but provided no relief. In view of no response to antibiotic therapy, the wound was explored three months post-surgery and a biopsy was taken. Histopathological examination of the biopsy reported an acute on chronic non-specific inflammation but bacterial. PCR for mycobacteria came out to be negative. Rapid mycobacterial culture yielded Mycobacteria other than Tuberculosis (MOTT) on BacT/Alert MB 3D automatic culture system on two separate occasions. The isolates were identified by Hains test to be Mycobacterium abscessus. Mycobacterium abscessus was sensitive to Amikacin, Clarithromycin and Linezolid. ATT was stopped and patient started on i/v Amikacin for one month along with Clarithromycin, after which Clarithromycin alone was continued. The discharging sinuses improved and healed completely by the end of six months of Clarithromycin therapy.
- Infectious Disease Society of America
- Tissue biopsy specimen should not be wrapped in gauze or diluted in liquid material. If only a little amount of tissue is available, it may be immersed in a small amount of sterile normal saline (not formalin) to avoid excessive drying
- Iron uptake by fortuitum not chelonae species. All members of the M. chelonae abscessus group and the M. fortuitum group show strong arylsulfatase activity at 3 days whereas the M. smegmatis group does not. The latter group is the only pigment producing group. Approximately 95% of M. smegmatis and 80% of M. goodii isolates develop a late yellow pigment after 7–10 days. iron uptake, nitrate reductase, tolerance to 5% NaCl, and utilization of the carbohydrates mannitol, inositol, and citrate. The utilization of carbohydrates has allowed more accurate identification of the commonly encountered species and discrimination of some not all newly described species
- Infectious Disease Society of America most widely used sequence for PCR-based identification of the RGM and is highly accurate for the M. fortuitum group, the M. chelonae abscessus group, and the M. smegmatis group.
- Amikacin, kanamycin, tobramycin, imipenem, doxycycline, clarithromycin, azithromycin, trimethoprim-sulphamethoxazole amoxicillin-clavulanic acid, cefoxitin, ciprofloxacin ,gatifloxacin, moxifloxacin, and linezolid.
- Clarithromycin and azithromycin are the only oral agents reliably active Amikacin most active of the parenteral agents. Others: Cefoxitin or Imipenem For serious skin, soft tissue and bone Infection Combination of 2 drugs (Atleast 1 parentral ) minimum of 4 months
- Presence of tetracycline-resistant genetic determinants in 50% M. fortuitum strains usually susceptible to Amikacin, Ciprofloxacin Sulfonamides, cefoxitin and imipenem. For serious skin, bone and soft tissue infection Minimum of 4 months therapy with at least two agents
- An 83-year-old Japanese man presented with a 2-month history of symptomatic nodules o the left hand. He was not in an immunocompromised condition and reported no causal events. A biopsy specimen demonstrated granulomatous tissue with mixed cell infiltration consisting of neutrophils, histiocytes, lymphocytes, and multinuclear giant cells. No bacillus was detected by PAS, acid-fast stain, immunofluorescent stain or polymerase chain reaction analysis. The isolate was found to be a rapidly growing mycobacterium after 4 weeks of incubation at 25°C on an Ogawa egg slant. Mycobacterium peregrinum was isolated by DNADNA hybridization 16S rRNA gene sequence, and by its production of 3-day arylsulfatase. The patient received 200 mg oral minocycline for 28 weeks. The lesion disappeared after 10 weeks of this treatment.
- are of variable appearance and include multiple nodules, ulcerated nodules abscesses, painless nodules and plaques resembling lepromatous leprosy or lupus vulgaris, and also lesions resembling prurigo nodularis
- Mimics lupus vulgaris