No Amikacin, No Problem: a Successful Treatment Approach for Pediatric Otomastoiditis Due to Amikacin-Resistant Mycobacterium abscessus

Pediatric otomastoiditis due to Mycobacterium abscessus can be a devastating infection that presents multiple treatment challenges. Van Wijk et al. report the use of a structured approach with a standardized regimen of intravenous (i.v.), topical, and oral antibiotics and surgical intervention for four pediatric patients with multidrug-resistant Mycobacterium abscessus otomastoiditis. Despite treatment-related adverse events, all four patients achieved sustained cure with this approach.

ABSTRACT

Pediatric otomastoiditis due to Mycobacterium abscessus can be a devastating infection that presents multiple treatment challenges. Van Wijk et al. report the use of a structured approach with a standardized regimen of intravenous (i.v.), topical, and oral antibiotics and surgical intervention for four pediatric patients with multidrug-resistant Mycobacterium abscessus otomastoiditis. Despite treatment-related adverse events, all four patients achieved sustained cure with this approach. This case series provides a framework for managing drug-resistant Mycobacterium abscessus otomastoiditis.

TEXT

Mycobacterium abscessus constitutes a complex of rapidly growing nontuberculous mycobacteria (NTM), which have emerged as pathogens that can be difficult to treat due to both innate and acquired drug resistance (1). While human disease from M. abscessus most commonly presents as a chronic pulmonary infection in the setting of structural lung disease, such as cystic fibrosis, bronchiectasis, or chronic obstructive pulmonary disease (COPD), extrapulmonary infections also occur. Otomastoiditis typically occurs due to infections with Pseudomonas aeruginosa, Staphylococcus aureus, or enteric Gram-negative bacilli; however, it can also be caused by NTM (2–4). Pediatric otomastoiditis due to M. abscessus has been previously noted to be a particular clinical management challenge (2–4), often necessitating surgery in addition to prolonged multidrug antibiotic regimens. To date, there are no standard guidelines for the management of NTM otomastoiditis. Prior case series on NTM otomastoiditis describe diverse treatment approaches for antibiotic regimen composition, variable multidrug course lengths, and inconsistent use of surgical interventions (3, 4).

In this issue of Antimicrobial Agents and Chemotherapy, van Wijk et al. (5) report their application of a standardized, structured treatment protocol on the management of drug-resistant M. abscessus otomastoiditis in four pediatric cases. The authors employed a standardized multidrug antibiotic approach comprising an initial 3-month intensive phase with imipenem-cilastatin (both topical and intravenous), tigecycline (both topical and intravenous), azithromycin (oral), and clofazimine (oral) paired with tympanoplasty and surgical debridement. An oral continuation phase with azithromycin and clofazimine was subsequently administered for an additional 3 to 6 months. Ultimately, all four patients were able to achieve sustained cure of their drug-resistant M. abscessus otomastoiditis.

While the high efficacy of this regimen was observed, all four patients experienced treatment-related adverse events. Unsurprisingly, the most poorly tolerated drug of the regimen was tigecycline, which led to significant nausea and vomiting. Aggressive treatment of nausea with antiemetics such as granisetron or metoclopramide did not completely control symptoms, and tigecycline therapy was interrupted in three of the four patients. Other adverse events included hepatotoxicity and drug rash, among others.

Despite the limited number of included cases, it is noteworthy that this standardized regimen yielded treatment success of drug-resistant M. abscessus otomastoiditis in all four cases. In the setting of pulmonary M. abscessus infection, there is good correlation between in vitro susceptibility to macrolides and amikacin and improved clinical outcomes (6, 7). With respect to drug susceptibility profiling of the M. abscessus isolates described by Wijk et al., all four cases were amikacin resistant, and three out of four were clarithromycin resistant. The largest prior case series of NTM otomastoiditis (4) reported a 92% cure for 12 cases of M. abscessus infections in Sweden. However, the included cases were 83% (10/12) clarithromycin susceptible, and 66% (8/12) were amikacin susceptible, which may predict a more favorable outcome.

Due to the multipronged intervention and combination of antibiotics, it is difficult to identify the key components of the studied multidrug regimen that were responsible for the observed clinical successes. Additionally, it is unknown whether different and better-tolerated antibiotics, shorter antibiotic course lengths, different routes of administration (e.g., additional topical rather than intravenous [i.v.] antibiotics), or altered timing of surgery could achieve the same degree of treatment efficacy for this infection. In 2018, the FDA approved omadacycline, a novel tetracycline for use against bacterial acute skin and soft tissue infections and community-acquired pneumonia. In comparison to tigecycline, omadacycline has fewer gastrointestinal toxicities and is orally bioavailable, obviating the need for i.v. administration. As omadacycline has been recently shown to exhibit excellent in vitro susceptibility against drug-resistant M. abscessus (8), it is potentially an attractive substitute for tigecycline, which was responsible for a significant amount of the observed treatment-related toxicities reported in van Wijk et al. (5).

This case series provides an optimistic outlook for treatment of pediatric drug-resistant M. abscessus otomastoiditis. Ultimately, further study is needed in a larger cohort of patients to better assess the efficacy of this regimen and identify the critical aspects that were responsible for treatment efficacy. We hope the success reported with this standardized approach will promote further studies to define optimal management strategies for drug-resistant M. abscessus otomastoiditis.

The views expressed in this article do not necessarily reflect the views of the journal or of ASM.