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\begin{document}

\title{Laryngitis after inhalation of liposomal amikacin}



\author[1]{Atsuho Morita}%
\author[2]{Ho Namkoong}%
\author[2]{Makoto Hosoya}%
\author[2]{Naoki  Hasegawa}%
\affil[1]{Keio University School of Medicine Department of Internal Medicine}%
\affil[2]{Keio University School of Medicine Graduate School of Medicine}%


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  \date{May 24, 2024}


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\begin{abstract}
A 56-year-old female with pulmonary Mycobacterium avium complex disease
started to inhale of liposomal amikacin. One month later, she developed
hoarseness and was diagnosed with laryngitis. The laryngitis healed
immediately after discontinuing the treatment, and no recurrence
occurred even after resuming intermittent inhalation.%
\end{abstract}%



\sloppy


Laryngitis after inhalation of liposomal amikacin

Atsuho Morita M.D.\textsuperscript{1}, Ho Namkoong M.D., Ph.D.
MPH\textsuperscript{2}, Makoto Hosoya M.D., Ph.D. \textsuperscript{3},
and Naoki Hasegawa M.D., Ph.D. \textsuperscript{2}

\textsuperscript{1} Division of Pulmonary Medicine, Department of
Medicine, Keio University School of Medicine, Tokyo, Japan.

\textsuperscript{2} Department of Infectious Diseases, Keio University
School of Medicine, Tokyo, Japan.

\textsuperscript{3} Department of Otorhinolaryngology, Head and Neck
Surgery, Keio University School of Medicine, Tokyo, Japan.

\textbf{Corresponding author:}

Ho Namkoong, M.D., Ph.D., MPH

Department of Infectious Diseases, Keio University School of Medicine,
35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan

\textbf{Keywords}

Laryngitis; hoarseness; amikacin liposomal inhalation suspension
(ALIS);\emph{Mycobacterium avium} complex (MAC);

Written informed consent was obtained from the patient to publish this
report in accordance with the journal's patient consent policy.



\textbf{ABSTRACT}

A 56-year-old female with pulmonary \emph{Mycobacterium avium} complex
disease started to inhale of liposomal amikacin. One month later, she
developed hoarseness and was diagnosed with laryngitis. The laryngitis
healed immediately after discontinuing the treatment, and no recurrence
occurred even after resuming intermittent inhalation.

(43 words)

\textbf{KEY CLINICAL MESSAGE}

Inhalation of liposomal amikacin may cause laryngitis and associated
hoarseness, although rapid improvement can be expected by discontinuing
treatment. The intermittent inhalation may be effective in resume
without recurrence.

(29 words)

\textbf{CASE DESCRIPTION}

A 56-year-old female patient had been on medication for
macrolide-resistant pulmonary \emph{Mycobacterium avium} complex
disease, and had persistently had positive sputum cultures. Because the
minimal inhibitory concentration (MIC) of amikacin was sensitive at
4\selectlanguage{greek}μ\selectlanguage{english}g/ml, She started amikacin liposomal inhalation suspension (ALIS) in
combination with rifampicin and ethambutol. Thereafter, the amount of
bacteria in the sputum smear gradually decreased, the cough and sputum
were under control. However, hoarseness appeared one month after
treatment initiation. Fiberoptic laryngoscopy showed redness and
swelling of both vocal cords, indicating laryngitis (Figure 1, black
arrow). ALIS therapy was discontinued, and hoarseness improved within a
few days. After two weeks, the treatment was resumed and administered
every other day. There was no recurrence of hoarseness until five weeks
after the resumption, at which point laryngitis had healed (Figure 2,
white arrow). There was no laryngeal edema consistently.

It has been reported that dysphonia occurs in 46.6\% of patients
subjected to daily ALIS (1), but can improve with a temporary reduction
in ALIS inhalation frequency (2). In the present case, the vocal cord
morphologically returned to normal after seven weeks of dose reduction.
This report suggests that, in case hoarseness appears, intermittent
inhalation could permit healing while continuing treatment.

(199 words)

\textbf{Acknowledgments}

This study was supported by AMED (21fk0108621h0001) and JSPS
Grant-in-Aid for Young Scientists (21K15667).

\textbf{Ethics statement}

This paper was written after obtaining informed consent, and the
procedures followed were in accordance with the Declaration of Helsinki.

\textbf{Conflict of interests}

The authors state that they have no conflict of interest.

\textbf{Data availability}

The data will not be shared with patient confidentiality.

\textbf{REFERENCES}

1 Griffith DE, Eagle G, Thomson R, et al. Amikacin Liposome Inhalation
Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium
avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study. Am
J Respir Crit Care Med 198(12): 1559-1569, 2018.

2 Swenson C, Lapinel NC, Ali J. Clinical Management of Respiratory
Adverse Events Associated With Amikacin Liposome Inhalation Suspension:
Results From a Patient Survey. Open Forum Infect Dis 7(4): ofaa079,
2020.

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