Impact of ward pharmacist-led antimicrobial stewardship in intensive care units

Figures & data

Figure 1. Monitoring sheet by organ system in the intensive care unit, and examples of descriptions (partial excerpt). This sheet was created to enable systematic evaluation of drug therapy by organs. It allows for the checking of antimicrobial drug type and dose, bacterial detection, and inflammatory markers related to infection. By sharing monitoring points for each patient among ICU pharmacists, early AS can be implemented. ICU: Intensive care unit, WBC: White blood cell, CRP: C-reactive protein, PCT: Procalcitonin, CD: Clostridioides difficile, VCM: Vancomycin, TDM: Therapeutic Drug Monitoring, TAZ/PIPC: Tazobactam/Piperacillin, MCFG: Micafungin, MRSA: methicillin‐resistant Staphylococcus aureus, F-FLCZ: Fosfluconazole.

Table 1. Characteristics of patients admitted to the ICU.

	Control period	Introduction period	P-value
Patients admitted	2583	2540	–
Sex, male (ratio)^a	1559 (60.4%)	1485 (58.5%)	.168
Age, median (min–max)^b	68 (0–106)	68 (0–96)	.183
Patients using antimicrobial drugs^a	1957	1927	.713
Total length of ICU admission^b	9955	9970	.843
Number of surgeries^a	2102	2095	.932
Mean length of ICU stay^b	4.99	4.84	.485

^a χ² test was used.

^b Mann–Whitney U test was used.

ICU: intensive care unit.

Table 2. Number of patients undergoing AS and the number of AS implementations.

		Control period	Introduction period	P-value
Number of patients undergoing AS (excluding repetitions)^a	TDM^a	102	118	.219
	Non-TDM^a	19	116	<.001
Total number of AS implementations^a	TDM^a	322 (90.4)	514 (95.7)	<.001
	Non-TDM^a	20 (75.0)	193 (78.8)	<.001
Mean number of AS cases per patient^b	TDM^b	3.41	4.38	.498
	Non-TDM^b	1.05	1.66	.020
Days required from ICU admission to AS implementation^b	TDM^b	7.87	5.54	.021
	Non-TDM^b	15.35	7.34	.075

Numerical values in brackets indicated proposal acceptance rate (%). ^a χ² test was used. ^b Mann–Whitney U test was used.

AS, antimicrobial stewardship; ICU, intensive care unit; TDM, therapeutic drug monitoring.

Table 3. Types of AS.

Proposal content		Control period	Introduction period	P-value
TDM	Initial design	9 (2.8%)	35 (6.8%)	<.001^a
	Dose reduction	112 (34.8%)	187 (36.4%)	<.001^a
	Dose increase	94 (29.2%)	133 (25.9%)	.005^a
	Drug change/discontinuation	6 (1.9%)	8 (1.6%)	.573 ^a
	Continuation (no change)	101 (31.4%)	151 (29.4%)	<.001 ^a
	Total	322 (100.0%)	514 (100.0%)	<.001 ^a
Non-TDM	Dose reduction	5 (25.0%)	49 (25.4%)	<.001 ^a
	Dose increase	7 (35.0%)	39 (20.2%)	<.001 ^a
	Antimicrobial drug change	6 (30.0%)	37 (19.2%)	<.001 ^a
	Antimicrobial drug addition	0 (0.0%)	13 (6.7%)	- ^c
	Antimicrobial drug discontinuation	0 (0.0%)	24 (12.4%)	- ^c
	Administration method	2 (10.0%)	20 (10.4%)	<.001 ^b
	Test addition	0 (0.0%)	8 (4.1%)	- ^c
	Others	0 (0.0%)	3 (1.6%)	- ^c
	Total	20 (100.0%)	193 (100.0%)	<.001 ^a

^a χ² test was used.

^b Fisher’s exact test was used.

^c The analysis could not be performed because the frequency is 0.

AS, antimicrobial stewardship; TDM, therapeutic drug monitoring.

Table 4. AUD and DOT of antimicrobial drugs by class.

	AUD			DOT
	Control period	Introduction period	P-value	Control period	Introduction period	P-value
Penicillin	5.07 ± 2.17	6.92 ± 2.00	.052	9.88 ± 3.36	11.64 ± 2.46	.242
Anti-P. aeruginosa Penicillin	10.67 ± 2.35	12.90 ± 3.57	.028	17.19 ± 3.80	20.68 ± 5.12	.052
First-generation cephems	7.41 ± 1.16	9.15 ± 2.81	.219	16.64 ± 3.17	17.41 ± 2.13	.713
Second-generation cephems	4.56 ± 1.22	5.04 ± 1.39	.291	8.63 ± 1.95	9.01 ± 1.79	.630
Third-generation cephems	4.66 ± 2.35	3.99 ± 1.53	.410	5.32 ± 2.39	4.64 ± 1.73	.378
Fourth-generation cephems	2.14 ± 1.41	2.58 ± 1.61	.443	3.19 ± 1.57	3.80 ± 2.09	.514
Carbapenems	7.97 ± 2.46	6.39 ± 2.56	.219	13.54 ± 3.83	10.63 ± 3.31	.068
Monobactams	0.06 ± 0.16	0.72 ± 1.03	.008	0.07 ± 0.19	1.12 ± 1.38	.007
Aminoglycosides	0.59 ± 0.42	0.79 ± 0.90	.843	1.76 ± 1.00	1.61 ± 1.14	.590
Macrolides	0.65 ± 0.53	0.49 ± 0.50	.478	0.65 ± 0.53	0.49 ± 0.50	.478
Tetracyclines	1.07 ± 1.15	0.94 ± 1.22	.713	1.41 ± 1.72	1.06 ± 1.33	.630
Quinolones	3.76 ± 2.50	3.02 ± 2.82	.291	3.79 ± 2.26	2.90 ± 2.32	.291
Glycopeptides	4.32 ± 1.60	5.98 ± 2.52	.101	7.28 ± 1.96	10.38 ± 2.97	.010
Lincosamides	0.60 ± 0.46	1.30 ± 1.29	.266	1.19 ± 0.75	1.74 ± 1.54	.551
Others	4.30 ± 2.18	6.69 ± 2.02	.020	4.52 ± 2.17	6.32 ± 2.33	.078
Antifungal drugs	3.89 ± 1.66	7.16 ± 3.46	.033	3.63 ± 1.29	6.37 ± 2.94	.012
Total	61.71 ± 9.63	74.06 ± 9.82	.017	98.68 ± 11.09	109.80 ± 11.09	.014

Expressed as mean ± standard deviations. Mann–Whitney U test was used.

AUD, antimicrobial use density; DOT, days of therapy.

Table 5. AUD and DOT of broad-spectrum antimicrobial drugs.

Broad-spectrum antimicrobial drug	Control period	Introduction period	P-value
AUD	24.53 ± 5.71	24.88 ± 5.61	.887
AUD ratio (%)	42.4	37.2	–
DOT	37.70 ± 7.21	38.01 ± 6.66	.887
DOT ratio (%)	39.7	36.7	–

Anti-Pseudomonas aeruginosa penicillin, fourth-generation cephems, carbapenems, and quinolones were defined as broad-spectrum antimicrobial drugs, and the ratio was calculated by excluding antifungal drugs.

Expressed as mean ± standard deviations. Mann–Whitney U test was used.

AUD, antimicrobial use density; DOT, days of therapy.

Table 6. Bacterial test implementation and resistant bacteria detection.

		Control period	Introduction period	P-value
Specimen submissions		3181	2977	–
Patients submitting specimens		647	588	.086^a
Total blood culture submissions		1187	1257	–
Patients submitting blood culture		320	317	.939^a
MRSA	Resistant bacteria detected^c	26 (48)	13 (39)	–
	Detection rate (‰)	2.61	1.30	.042^a
ESBL-producing bacteria	Resistant bacteria detected^c	8 (13)	6 (21)	–
	Detection rate (‰)	0.80	0.60	.614^a
Dual-drug-resistant Pseudomonas aeruginosa	Resistant bacteria detected^c	5 (7)	7 (8)	–
	Detection rate (‰)	0.50	0.70	.544^a
Multidrug-resistant P. aeruginosa (MDRP)	Resistant bacteria detected^c	0 (0)	2 (2)	–
	Detection rate (‰)	0.00	0.20	.246^b

MRSA, methicillin-resistant Staphylococcus aureus; ESBL, extended-spectrum β-lactamase; MDRP, multidrug-resistant Pseudomonas aeruginosa; CD, Clostridioides difficile.

^c Number of detections after the third day of admission is shown, and the total number of detections including brought-ins is shown in (). Detection rate of resistant bacteria was measured on the third day and after admission.

^a χ² test was used.

^b Fisher’s exact test was used.

Table 7. Detection of CD toxins.

	Early control period	Late control period	Early introduction period	Late introduction period	P-value
Tests (positive cases)	90 (8)	95 (5)	129 (5)	92 (2)	–
Detection rate (‰)^a	1.64	0.98	1.02	0.39	.060^b

^a The detection rate of CD toxins was calculated as the detection (positive) rate per 1000 bed days.

^b Fisher’s exact test was performed Early Control Period versus Late Introduction Period.

CD, Clostridioides difficile.

Table 8. Thirty-day mortality.

	Early control period	Late control period	Early introduction period	Late introduction period	P-value
30-day Mortality (%)	4.82	5.41	4.43	3.93	.074^a

^a χ² test was used. Late control period vs. late introduction period.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [S.A], upon reasonable request.