DOI: 10.31662/jmaj.2021-0134
https://www.jmaj.jp/Short Communication

Therapeutic Drug Monitoring for Aminoglycosides: Not Yet Readily
Available in Japanese University Hospitals
Hideharu Hagiya, and Fumio Otsuka
Key Words:
aminoglycoside, antimicrobial resistance, gentamicin, tobramycin, amikacin, therapeutic drug monitoring
As leading hospitals, national and public university hospitals
have a mission to treat a large number of patients with intractable and/or critical diseases. Aminoglycosides broadly coverGram-negative glucose non-fermenters, such as Pseudomonas
aeruginosa and Acinetobacter species, by inhibiting the function of the ribosome 30S subunit (1). Thus, these agents are regarded as key drugs in the treatment of patients with sepsis, especially in cases of nosocomial onset and in those who havebeen isolated with antimicrobial-resistant pathogens (2), (3).
To ensure the safety and effectiveness of aminoglycosidetherapy, it is essential to maintain appropriate serum concentrations through therapeutic drug monitoring (TDM) (4). To
avoid renal and cochlear impairments, the trough level needs
to be kept reasonably low. To obtain clinical effectiveness, ahigh peak level should be achieved. Aminoglycosides are water-soluble drugs that generally penetrate the urinary tract, ascites, pleural fluid, and articular fluid. However, pharmacokinetically, they do not diffuse well into organ tissues, especiallythe lower respiratory tract, prostate, and biliary systems, andspread poorly within the central nervous system. Thus, a fineadjustment of serum concentrations is essential when administering aminoglycosides for infections of these organs. Aminoglycoside-resistant organisms may emerge as a consequenceof overexpression of the excretion pump and decreased binding to ribosomes by enzymatic modification (1). Thus, maintaining appropriate serum concentrations can also prevent theemergence of antimicrobial resistance (AMR). The purposeof this study was to understand the current availability of thein-house ability to measure aminoglycosides in national andpublic university hospitals in Japan.
In March 2021, we distributed a questionnaire to 43 national and public university hospitals in Japan, asking about
the status of TDM for aminoglycoside agents (gentamicin[GM], tobramycin [TOB], and amikacin [AMK]). For comparison, we also collected the measurement status of the fol-lowing four other antimicrobial drugs: vancomycin, teicoplanin, arbekacin, and voriconazole. Ethics committee approval
for the publication of the data was obtained from the Institutional Review Board of Okayama University Hospital (No.
2106-004). The need for informed consent was waived because detailed data on the individual institutions were anonymized.
A total of 30 institutions responded to the survey, ofwhich data from 27 institutions (62.8%), excluding one specialized dental hospital and two hospitals that have withdrawn
their participation in the data analysis, were included in theanalysis (Table 1). Serum concentrations of aminoglycosides
were measured in the clinical laboratory, pharmacy, or in bothat 10 (37.0%), 11 (40.7%), and 6 (22.2%) institutions, respectively. The number (proportion) of institutions with in-hospital assays of aminoglycoside agents were 15 (55.6%), 5 (18.5%),
and 3 (11.1%) for GM, TOB, and AMK, respectively. The
number (proportion) of institutions that outsourced serum
aminoglycoside testing was 12 (44.4%), 13 (48.1%), and 23(85.2%) for GM, TOB, and AMK, respectively. Several institutions did not offer even outsourced testing: 0 for GM, 9(33.3%) for TOB, and 1 (3.7%) for AMK, respectively. Of the
27 institutions, the number (percentage) of aminoglycosideagents tested in-hospital was 12 (44.4%), 9 (33.3%), 4 (14.8%),
and 2 (7.4%) for no agent, one agent, two agents, and threeagents, respectively.
By comparison, the availability of in-hospital monitoringof agents used to treat methicillin-resistant Staphylococcus aureus agents was 100% for vancomycin, 81.5% for teicoplanin,and 33.3% for arbekacin. Serum measurements of voriconazole were outsourced in about three-fourths of the institutions.
Our data revealed that TDM of aminoglycosides is still
not readily available at many national and public university
hospitals in Japan, although clinical guidelines recommend aDepartment of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Corresponding author: Hideharu Hagiya, hagiya@okayama-u.ac.jp
JMA J. 2022;5(1):127-129
Received: July 16, 2021 / Accepted: October 5, 2021 / Advance Publication: December 15, 2021 / Published: January 17, 2022
Copyright © Japan Medical Association127

DOI: 10.31662/jmaj.2021-0134
https://www.jmaj.jp/

JMA Journal: Volume 5, Issue 1

Table 1. Monitoring of Aminoglycosides and Other Antimicrobial Agents at 27 National and Public University Hospitals inJapan.
In-hospital

Outsourced

Not availablen(%)

n(%)

n(%)

1555.61244.400.0

Aminoglycosides
Gentamicin
Tobramycin

518.5

1348.1

933.3

Amikacin

311.1

2385.2

13.7

Vancomycin

27

100.0

00.0

00.0

Teicoplanin

2281.5

5

18.5

00.0

Arbekacin

933.3

1555.6

311.1

Voriconazole

829.6

1970.400.0

Other antimicrobials

fine adjustment of the drugs according to the TDM results (5), (6). The optimization of clinical indications, dosages,
and target concentrations of aminoglycosides has yet to be
fully established (7). However, aminoglycosides are the drugs ofchoice in frequently encountered clinical situations, such as
urinary tract infections, due to AMR organisms in outpatientsettings, and as both an empirical and definitive therapy forpatients in a state of shock.
In this age of AMR, promoting antimicrobial stewardshipand avoiding under-dosing of antimicrobials by means of
TDM is pivotal to prevent the emergence of AMR pathogens.
With the growing population of difficult-to-treat cases, practicing TDM-guided individualized treatment is required. Attainment of the pharmacokinetic/pharmacodynamic target isof great value in delivering appropriate drug doses, achieving ahigh treatment success rate, and improving the prognosis ofpatients without unnecessary adverse effects. To apply it fullyin clinical practice, TDM should be conducted at appropriate
intervals, without delay (4). Close collaboration between clinicians, microbiologists, and pharmacists is essential for the development of therapeutic strategies to manage fluctuating
drug levels by adjusting the dose of antimicrobial therapy.
Therefore, we believe that an in-house measurement systemshould be established in tertiary medical institutions such as
national and public university hospitals.

Author Contributions

All authors meet the ICMJE authorship criteria. HH was responsible for the study design, data analyses, and writing ofthe manuscript. FO supervised the study. All authors approved the final report.
Approval by Institutional Review Board (IRB)

The ethics committee approval for the publication of the data
was obtained from the Institutional Review Board of Okayama University Hospital (No. 2106-004). The need for informed consent was waived because detailed data on the individual institutions were anonymized.

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Conflicts of Interest

None

Acknowledgement

We would like to thank Editage (www.editage.jp) for assistingwith editing this manuscript.

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