International Survey of Antibiotic Dosing and Monitoring in Adult Intensive Care Units

Paul G. Williams; Alexis Tabah; Menino Osbert Cotta; Indy Sandaradura; Salmaan Kanji; Marc H. Scheetz; Sahand Imani; Muhammed Elhadi; Sónia Luque-Pardos; Natalie Schellack; Cristina Sanches; Jean-Francois Timsit; Jiao Xie; Andras Farkas; Kathryn Wilks; Jason A. Roberts

Disclosures

Crit Care. 2023;27(241)

Abstract and Introduction

Abstract

Background: In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time.

Methods: A cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing, administration and monitoring of vancomycin, piperacillin/tazobactam, meropenem and aminoglycosides.

Results:A total of 538 respondents (71% physicians and 29% pharmacists) from 409 hospitals in 45 countries completed the survey. Vancomycin was mostly administered as an intermittent infusion, and loading doses were used by 74% of respondents with 25 mg/kg and 20 mg/kg the most favoured doses for intermittent and continuous infusions, respectively. Piperacillin/tazobactam and meropenem were most frequently administered as an extended infusion (42% and 51%, respectively). Therapeutic drug monitoring was undertaken by 90%, 82%, 43%, and 39% of respondents for vancomycin, aminoglycosides, piperacillin/tazobactam, and meropenem, respectively, and was more frequently performed in high-income countries. Respondents rarely used dosing software to guide therapy in clinical practice and was most frequently used with vancomycin (11%).

Abstract and Introduction
Background
Methods
Results
Discussion
Conclusions
References

Table 1. Respondent demographics
Characteristic	n (%)
Position (n = 534)
Physicians	377 (71)
Physician in training (ICU)	69 (13)
Physician in training (ID)	31 (6)
Specialist in intensive care medicine	187 (35)
Specialist in infectious diseases	30 (6)
Other	59 (11)
Pharmacists	153 (29)
ICU pharmacist	96 (18)
ID pharmacist	20 (4)
AMS pharmacist	28 (5)
Other	9 (2)
Others	4 (1)
Experience in ICU (n = 533)
< 5 years	258 (48)
5–10 years	131 (25)
> 10 years	144 (27)
Type of hospital (n = 529)
General	188 (36)
Rural	13 (2)
University	199 (38)
University affiliated	123 (23)
Other	6 (1)
ICU type (n = 528)
Cardiac	9 (2)
Medical	99 (19)
Medical-surgical	342 (65)
Surgical	48 (9)
Other	30 (6)
Open or closed ICU (n* = 532)
Closed	339 (64)
Open	193 (37)
Access to either national or institutional guidelines for antibiotic dosing? (n = 534)
Yes	407 (76)
No	127 (24)
Access to guidelines for TDM application, interpretation and dose adjustment? (n = 534)
Yes	260 (49)
No	274 (51)

ICU, intensive care unit; ID, infectious diseases; TDM, therapeutic drug monitoring; n, number; %, percentage
*An open ICU allows any physician to admit patients, while a closed ICU is managed by intensivists

Table 2. TDM utilization according to antibiotic
Characteristic	Target	n (%)
Vancomycin TDM
PK/PD target II (n = 380)	AUC/MIC target 400–600 mg·h/L	80 (21)
	Trough target	300 (79)
	10–15 mg/L	36 (9)
	12–18 mg/L	31 (8)
	15–20 mg/L	183 (48)
	20–25 mg/L	40 (11)
	Other	10 (3)
PK/PD target CI (n = 69)	AUC/MIC target 400–600 mg·h/L	9 (13)
	Css target	60 (87)
	20–25 mg/L	45 (65)
	15–20 mg/L	11 (16)
	Other	4 (6)
Piperacillin/tazobactam TDM
PK/PD target (n = 258)	100% fT > 4xMIC	59 (23)
	100% fT > MIC	92 (36)
	50% fT > 4xMIC	46 (18)
	50% fT > MIC	33 (13)
	AUC/MIC	11 (4)
	Unsure or other	17 (7)
Meropenem TDM
PK/PD target (n = 204)	100% fT > 4xMIC	52 (25)
	100% fT > MIC	57 (28)
	50% fT > 4xMIC	27 (13)
	50% fT > MIC	29 (14)
	AUC/MIC	9 (4)
	Unsure or other	18 (9)
Aminoglycoside TDM
PK-PD target (n = 385)	100% fT > MIC	24 (6)
	AUC/MIC	65 (17)
	CMax/MIC	166 (43)
	Unsure	130 (34)
1^st TDM sample (n = 387)	Peak	144 (37)
	Trough	205 (53)
	Other	41 (11)
Peak and trough sample taken? (n = 144)	Yes	108 (75)
	No	36 (25)

TDM, therapeutic drug monitoring; PK, pharmacokinetics; PD, pharmacodynamics; II, intermittent infusion; AUC, area under the curve; MIC, minimum inhibitory concentration; CI, continuous infusion; EI, extended infusion; Css, concentration at steady state; fT, free time; CMax, concentration maximum; n, number; %, percentage

Table 3. Dose adjustment method according to antibiotics
Survey question	Response	n (%)
Vancomycin doses are generally adjusted by: (select all that apply) (n = 535)	Clinical judgement of treating physician	307 (57)
	Linear adjustment following TDM	167 (31)
	Dosing software	60 (11)
	Dosing guideline	178 (33)
	Other	25 (5)
Beta-lactam doses are generally adjusted by: (select all that apply) (n = 506)	Clinical judgement of treating physician	290 (57)
	Product information	159 (31)
	TDM	74 (15)
	Dosing software	15 (3)
	Dosing guideline	129 (25)
	Pharmacist recommendation	156 (31)
	ID/AMS recommendation	123 (24)
	Other	24 (5)
Aminoglycoside doses are generally adjusted by: (select all that apply) (n = 497)	Clinical judgement of treating physician	256 (52)
	Product information	102 (21)
	TDM	178 (36)
	Dosing software	38 (8)
	Dosing guideline	91 (18)
	Pharmacist recommendation	194 (39)
	ID/AMS recommendation	107 (22)
If the peak concentration is below your target, do you: (select all that apply) (n = 325)	Increase the next daily dose	179 (55)
	Leave the daily dose unchanged	19 (6)
	Administer a supplementary dose	38 (12)
	Use dosing software to guide therapy	45 (14)
	Unsure	62 (19)
If the trough concentration is above your target, do you: (select all that apply) (n = 362)	Leave the daily dose unchanged	44 (12)
	Decrease the next daily dose	137 (38)
	Delay next dose until the trough is below the target concentration	78 (22)
	Extend the dosing frequency	120 (33)
	Use dosing software to guide therapy	43 (12)

TDM, therapeutic drug monitoring; ID, infectious diseases; AMS, antimicrobial stewardship; n, number; %, percentage

Authors and Disclosures

Paul G. Williams^1,2*, Alexis Tabah^1,3,4, Menino Osbert Cotta¹, Indy Sandaradura^5–7, Salmaan Kanji⁸, Marc H. Scheetz⁹, Sahand Imani¹⁰, Muhammed Elhadi¹¹, Sónia Luque-Pardos^12–14, Natalie Schellack¹⁵, Cristina Sanches¹⁶, Jean-Francois Timsit^17,18, Jiao Xie¹⁹, Andras Farkas^20,21, Kathryn Wilks^22,23 and Jason A. Roberts^1,24–26, National Coordinators on behalf of the European Society of Intensive Care Medicine (ESICM) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Critically Ill Patients [ESGCIP]

¹Faculty of Medicine, University of Queensland Centre for Clinical Research (UQCCR), The University of Queensland, Brisbane, QLD 4029, Australia. ²Pharmacy Department, Sunshine Coast University Hospital, Birtinya, QLD, Australia. ³Intensive Care Unit, Redcliffe Hospital, Redcliffe, QLD, Australia. ⁴Queensland University of Technology, Brisbane, QLD, Australia. ⁵Sydney Medical School, University of Sydney, Sydney, NSW, Australia. ⁶Centre for Infectious Diseases and Microbiology, Westmead Hospital, Sydney, NSW, Australia. ⁷Institute for Clinical Pathology and Medical Research, New South Wales Health Pathology, Sydney, NSW, Australia. ⁸The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, ON, Canada. ⁹Pharmacometric Center of Excellence, Departments of Pharmacy Practice and Pharmacology, College of Pharmacy, Midwestern University, Downers Grove, IL, USA. ¹⁰Nepean Blue Mountains Local Health District, Nepean Hospital, Sydney, NSW, Australia. ¹¹Faculty of Medicine, University of Tripoli, Tripoli, Libya. ¹²Pharmacy Department, Parc de Salut Mar, Barcelona, Spain. ¹³Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d'Investigacions Mediques (IMIM), Barcelona, Spain. ¹⁴CIBER of Pharmacy, Saint Clare's Infectious Diseases (CIBERINFEC CB21/13/0002) Institute of Health Carlos III, Madrid, Spain. ¹⁵Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa. ¹⁶Campus Centro Oeste Dona Lindu, Federal University of Sao João del Rei, Divinópolis, Minas Gerais, Brasil. ¹⁷Assistance Publique Hôpitaux de Paris – Bichat hospital Medical and infectious diseases ICU (MI2), 75018 Paris, France. ¹⁸IAME U 1137 Université Paris-Cité Site Bichat, 75018 Paris, France. ¹⁹Department of Pharmacy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. ²⁰Optimum Dosing Strategies, Bloomingdale, NJ, USA. ²¹Department of Pharmacy, Saint Clare's Health, Denville, NJ, USA. ²²Infectious Diseases Department, Sunshine Coast University Hospital, Birtinya, QLD, Australia. ²³School of Public Health, The University of Queensland, Brisbane, QLD, Australia. ²⁴Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. ²⁵Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. ²⁶Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.

*Correspondence:
Paul G. Williams paul.williams3@uqconnect.edu.au

Author contributions
PW designed the survey, sought societal endorsement, led and coordinated distribution of the survey, analyzed the data, and wrote the manuscript. AT, MC, and JAR contributed to the conception, design, analysis and writing of the manuscript. All other authors contributed to the design of survey, distributed the survey via their national networks, and provided manuscript feedback. All authors read and approved the final manuscript.

Competing interests
The authors declare that they have no competing interests.