In the Journals

Clofazimine safe, well-tolerated alternative for M. abscessus infection

Clofazimine was a safe and well-tolerated part of a multidrug regimen used to treat children with odontogenic Mycobacterium abscessus infection that was caused during an outbreak at a dental facility, according to study results published in the Journal of the Pediatric Infectious Diseases Society.

M. abscessus is a very difficult infection to treat due to many factors, including antimicrobial resistance and adverse effects from the treatment medications,” Felice C. Adler-Shohet, MD, FAAP, director of outpatient services for the department of infectious diseases at the Children’s Hospital of Orange County, California, told Infectious Diseases in Children. “In addition, this infection seems to be increasing in incidence. Our results show that clofazimine offers one more possible antimicrobial agent as part of our armamentarium to help fight this infection in children.”

Adler-Shohet and colleagues administered clofazimine (CFZ) — an oral antibiotic approved for treating leprosy that is thought to work by interfering with cell metabolism, they wrote — during an outbreak of severe odontogenic mycobacterial infections. All patients underwent a pulpotomy at the same dental practice with a contaminated water system between January 2016 and September 2016.

A total of 1,099 patients were considered at-risk, and 71 total cases were identified. Of 65 patients treated at the Children’s Hospital of Orange County, 27 were diagnosed with confirmed or probable mycobacterial jaw osteomyelitis that required surgical debridement and antimicrobial therapy. Culture samples from 14 patients with infection grew M. abscessus subspecies abscessus, which can cause chronic pneumonia in patients with an underlying pulmonary pathology such as cystic fibrosis, according to the researchers.

The researchers initially administered first-line drugs to the patients, but the minimum inhibitory concentration (MIC) revealed intermediate susceptibility to these agents. According to the MIC levels, the organisms were more susceptible to CFZ (0.5 µg/mL or less) than to imipenem (8 µg/mL), amikacin (8 µg/mL), cefoxitin (32 µg/mL) or the presumed inducible macrolide resistance from azithromycin. CFZ was added to the first-line regimen at a mean of 29.7 days after the start of therapy, they wrote. Most of the children who received CFZ were young, Hispanic and previously healthy.

The researchers used in vitro testing and found synergy of CFZ with amikacin. The amikacin MIC decreased from 8 µg/mL to 2 µg/mL with the addition of CFZ, they wrote. CFZ therapy lasted for a mean of 105.6 days. Skin dryness/discoloration and gastrointestinal symptoms were common adverse events associated with CFZ therapy but were not severe enough to warrant discontinuation of therapy.

“By offering these children CFZ, we were able to stop their beta-lactam antibiotic, an intravenous medication that was given three times a day,” Adler-Shohet said. “This had been a huge burden for the parent/caretaker and caused many side effects. Ultimately, it was very gratifying and very appreciated by the patients and their families to be able to stop this medication in favor of a safe and well-tolerated oral therapy.”

Although the researchers concluded that CFZ therapy was safe and well-tolerated, they noted that they cannot draw firm conclusions on the efficacy of the regimen, particularly for infections caused by other clones. – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.

Clofazimine was a safe and well-tolerated part of a multidrug regimen used to treat children with odontogenic Mycobacterium abscessus infection that was caused during an outbreak at a dental facility, according to study results published in the Journal of the Pediatric Infectious Diseases Society.

M. abscessus is a very difficult infection to treat due to many factors, including antimicrobial resistance and adverse effects from the treatment medications,” Felice C. Adler-Shohet, MD, FAAP, director of outpatient services for the department of infectious diseases at the Children’s Hospital of Orange County, California, told Infectious Diseases in Children. “In addition, this infection seems to be increasing in incidence. Our results show that clofazimine offers one more possible antimicrobial agent as part of our armamentarium to help fight this infection in children.”

Adler-Shohet and colleagues administered clofazimine (CFZ) — an oral antibiotic approved for treating leprosy that is thought to work by interfering with cell metabolism, they wrote — during an outbreak of severe odontogenic mycobacterial infections. All patients underwent a pulpotomy at the same dental practice with a contaminated water system between January 2016 and September 2016.

A total of 1,099 patients were considered at-risk, and 71 total cases were identified. Of 65 patients treated at the Children’s Hospital of Orange County, 27 were diagnosed with confirmed or probable mycobacterial jaw osteomyelitis that required surgical debridement and antimicrobial therapy. Culture samples from 14 patients with infection grew M. abscessus subspecies abscessus, which can cause chronic pneumonia in patients with an underlying pulmonary pathology such as cystic fibrosis, according to the researchers.

The researchers initially administered first-line drugs to the patients, but the minimum inhibitory concentration (MIC) revealed intermediate susceptibility to these agents. According to the MIC levels, the organisms were more susceptible to CFZ (0.5 µg/mL or less) than to imipenem (8 µg/mL), amikacin (8 µg/mL), cefoxitin (32 µg/mL) or the presumed inducible macrolide resistance from azithromycin. CFZ was added to the first-line regimen at a mean of 29.7 days after the start of therapy, they wrote. Most of the children who received CFZ were young, Hispanic and previously healthy.

The researchers used in vitro testing and found synergy of CFZ with amikacin. The amikacin MIC decreased from 8 µg/mL to 2 µg/mL with the addition of CFZ, they wrote. CFZ therapy lasted for a mean of 105.6 days. Skin dryness/discoloration and gastrointestinal symptoms were common adverse events associated with CFZ therapy but were not severe enough to warrant discontinuation of therapy.

“By offering these children CFZ, we were able to stop their beta-lactam antibiotic, an intravenous medication that was given three times a day,” Adler-Shohet said. “This had been a huge burden for the parent/caretaker and caused many side effects. Ultimately, it was very gratifying and very appreciated by the patients and their families to be able to stop this medication in favor of a safe and well-tolerated oral therapy.”

Although the researchers concluded that CFZ therapy was safe and well-tolerated, they noted that they cannot draw firm conclusions on the efficacy of the regimen, particularly for infections caused by other clones. – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.