CASE REPORT
A 4-year old female with t (8,21) AML and central nervous system
involvement was treated with NOPHO-AML 2012 protocol. She developed
neutropenic fever 4 days after completed course 2 induction
chemotherapy, which persisted for 1 week despite multiple antimicrobials
and antifungals. She then complained of fluctuating right knee, hip and
ankle pain over 4 weeks (Fig. 1) . Clinical microbiologists and
orthopedic surgeons were consulted. Subsequent magnetic resonance
imaging (MRI) of right lower limb revealed multiple abscesses over right
groin and popliteal region with calcaneal osteomyelitis and subcutaneous
edema (Figs. 2A and 2B) . Ultrasound-guided aspiration and
biopsy yielded granulomas with surrounding suppurative inflammation(Fig. 2C) . Smear of joint fluid was positive for acid-fast
bacilli (AFB), while polymerase chain reaction (PCR) forMycobacterium tuberculosis (M. TB ) was negative. Child was
covered with intravenous (IV) daptomycin, meropenem, levofloxacin and
amikacin while awaiting identity and sensitivity testing of
mycobacteria. Calcaneal bone excision and debridement of right ankle
with incision and drainage (I&D) were then performed followed by
anti-mycobacterial chemotherapy with IV amikacin, oral clarithromycin,
oral levofloxacin, and oral ethambutol (stopped after 1 week after
revealing identity of NTM). Histology of excised os calcis bone
confirmed osteomyelitis, and culture of bone and pus grew M.
abscessus . Susceptibility testing of the M. abscessus isolate
was determined by broth microdilution method and results were
interpreted according to the Clinical and Laboratory Standards
Institute. The isolate was susceptible to amikacin and
trimethoprim-sulfamethoxazole, intermediate to cefoxitin, imipenem,
linezolid, and resistant to ciprofloxacin, doxycycline and moxifloxacin.
Antimicrobials were thus switched to oral trimethoprim-sulfamethoxazole
(with trimethoprim dosage 10mg/kg/day), oral clarithromycin, IV
imipenem-cilastatin (later switched to IV cefoxitin), IV amikacin and
thrice weekly interferon-gamma (IFN-γ). In retrospect, the child might
have sustained external injury to foot due to tight shoe according to
mother.
Initial clinical response was noted but patient developed another
abscess at right posterior thigh 12 days after the first operation as
confirmed with PET-CT (Fig. 2D) . Second operation was performed
3 weeks from first operation with I&D of right groin and popliteal
abscesses along with debridement of right ankle soft tissue achieved.
Pus from posterior thigh grew M. abscessus . Low dose chemotherapy
with oral thioguinine (6-TG) and IV with intrathecal cytarabine were
resumed when fever subsided for 48 hours, and was given for 4 weeks,
which led to worsening of infection necessitating third operation 4
weeks from second operation, involving sequestrectomy of right calcaneus
and insertion of antibiotic-infused cement (vancomycin, amikacin and
gentamycin). Child then developed drug-related rash and hepatitis with
highest alanine aminotransferase and aspartate aminotransferase above
1500IU/L. Rash subsided and liver function improved after stopping all
antimicrobials. Bedaquiline (100mg 3 days per week) and clofazimine
(50mg 2 days per week) were introduced as salvage therapy for NTM
infection 18 days from third operation. Antibiotic-infused cement was
kept 7 months before removal and bone graft insertion. Peri-operatively
patient was covered with 1-week course of IV amikacin and
imipenem-cilastatin. Intra-operative cultures did not yield any aerobic,
anaerobic bacteria, fungi or AFB. Histology showed granulomatous
inflammation with no evidence of AFB or fungi. Bone graft donor site and
right calcaneal wounds healed well with stitches removed on
post-operative day 11 and non-weight bearing for 6 weeks
post-operatively. Bedaquiline and clofazimine were continued for 4 more
weeks post-operatively then stopped. Total duration of usage was 8
months. Apart from mild prolongation of QTc from 450ms to 470ms during
initiation of medication, she did not suffer from any adverse effects.
Serial electrocardiograms and echocardiograms showed normal cardiac
anatomy and function. Serial audiograms also reported normal hearing
despite courses of prolonged amikacin. She was now 18 months from last
operation. Limb function was preserved with no problem in walking and
daily activities. For disease control, she had been followed up for 24
months since last chemotherapy given and remained in clinical and
hematological remission with regular monitoring by 4-weekly quantitative
PCR (qPCR) and 8-weekly marrow exam. Minimal residual disease (MRD) was
persistently negative <0.1%. No relapse so far for 2 years
now.