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
4.
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
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.
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)
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
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
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.
33.
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).
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.
40.
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
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
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
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
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
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.
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