## DISCUSSION

These results point to an important level of cost avoidance of the TDM performed by pharmacists on the selected antibiotics. It is also important to point out that the percentage of TDM performed for gentamicin and amikacin was significantly lower than vancomycin. One of the major limitations of this study is the usage of other cohort and case studies to define the probabilities of occurrence of the adverse events. In the future, it would be best to use real-world data from our center, as it could provide more accurate estimates in our setting.

## CONCLUSIONS

Measuring the economic benefit of interventions by health professionals remains a challenge, largely because of the availability of data, selecting the appropriate variables and models, or the difficulty of translating avoided costs into direct savings. In this study, it is possible to frame the benefit of therapeutic monitoring in a cost matrix adjusted to the setting of a Portuguese hospital. We also construct a probability matrix based on the currently available studies. Future research should try to quantify and assess these phenomena and values, through robust studies, within the Portuguese reality.

We conclude that TDM is highly cost-avoidant. Furthermore, the implementation costs of TDM by the pharmaceutical services are clearly lower than the benefit achieved. In future studies, it will be important to measure the translation of this cost avoidance into direct savings, use this methodology in other settings, and populate the probability matrix with real-world evidence from local centers.

## References

References
1.
Kang
J,
Lee
M.
Overview of therapeutic drug monitoring
.
Korean J Intern Med
.
2009
;
24
:
1
.
2.
Gross
A.
Best practice in therapeutic drug monitoring
.
Br J Clin Pharmacol
.
1998
;
46
:
95
99
.
3.
Monteiro
J,
Hahn
S,
Gonçalves
J,
Fresco
P.
Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations
.
Pharmacol Res Perspect
.
2018
;
6
:
e00420
.
4.
Ibrahim
M,
Abdelrahim
H,
Ab Rahman A. Cost evaluation of therapeutic drug monitoring of gentamicin at a teaching hospital in Malaysia
.
.
2014
;
12
:
372
.
5.
Imamura
C.
Therapeutic drug monitoring of monoclonal antibodies: applicability based on their pharmacokinetic properties
.
Drug Metab Pharmacokinet
.
2019
;
34
:
14
18
.
6.
Morawska
K,
Goirand
F,
Marceau
L,
et al.
5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer
.
Oncotarget
.
2018
;
9
:
11559
11571
.
7.
Nesbit
T,
Shermock
K,
Bobek
M,
et al.
Implementation and pharmacoeconomic analysis of a clinical staff pharmacist practice model
.
Am J Health-Syst Pharm
.
2001
;
58
:
784
790
.
8.
Regulamentos e as Tabelas de Preços das Instituições e Serviços Integrados no Serviço Nacional de Saúde (SNS)
.
2018; Portaria n.° 254/2018.
9.
Bamgbola
O.
Review of vancomycin-induced renal toxicity: an update
.
Ther Adv Endocrinol Metab
.
2016
;
7
:
136
147
.
10.
Forouzesh
A,
Moise
P,
Sakoulas
G.
Vancomycin ototoxicity: a reevaluation in an era of increasing doses
.
Antimicrob Agents Chemother
.
2008
;
53
:
483
486
.
11.
Bakke
V,
Sporsem
H,
Von der Lippe
E,
et al.
Vancomycin levels are frequently subtherapeutic in critically ill patients: a prospective observational study
.
Acta Anaesthesiol Scand
.
2017
;
61
:
627
635
.
12.
Selby
N,
Shaw
S,
Woodier
N,
Fluck
R,
Kolhe
N.
Gentamicin-associated acute kidney injury
.
QJM
.
2009
;
102
:
873
880
.
13.
Xie
J,
A,
Schacht
J.
New developments in aminoglycoside therapy and ototoxicity
.
Hear Res
.
2011
;
281
:
28
37
.
14.
Saunders
N,
D,
Lynn
W.
A prospective laboratory-based audit of gentamicin use and therapeutic monitoring
.
J Antimicrob Chemother
.
1995
;
36
:
729
736
.
15.
Jenkins
A,
Thomson
A,
Brown
N,
et al.
Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review
.
J Antimicrob Chemother
.
2016
;
71
:
2754
2759
.
16.
Duszynska
W,
Taccone
F,
Hurkacz
M,
Kowalska-Krochmal
B,
Wiela-Hojeńska
A,
Kübler
A.
Therapeutic drug monitoring of amikacin in septic patients
.
Crit Care
.
2013
;
17
:
R165
.

## Competing Interests

Source of Support: None. Conflict of Interest: None.