Octenidine Dihydrochloride – Antimicrobial Activity, Adaptation and Clinical Application

Tomasz M. Karpiński; Marzena Korbecka-Paczkowska; Agnieszka Zeidler; Wojciech Grzywna

doi:10.2478/am-2025-0014

Figures & Tables

Mode of action of octenidine dihydrochloride. Created using the BioRender.com.

Antibiofilm activity of octenidine dihydrochloride_

Microorganism	Tested concentrations (μg/mL)	Time of action	% of biofilm reduction	Type of antibiofilm study	Reference
E. faecium	15.7-31.3	24 h	100	mature biofilm reduction	(Dydak et al. 2021)
S. epidermidis	15.7-125	24 h	100		(Dydak et al. 2021)
S. aureus	62.5	24 h	100		(Dydak et al. 2021)
	~50	24 h	100		(Krasowski et al. 2021)
	1000	24 h	~85%		(Rembe et al. 2020)
MRSA	1000	3 days	80%		(Davis et al. 2017)
A. baumannii	7.8-250	24 h	100		(Dydak et al. 2021)
E. coli	250	3 days	100	biofilm formation inhibition	(Loose et al. 2021)
E. coli	125-500	24 h	100	mature biofilm reduction	(Dydak et al. 2021)
E. cloacae	250-500	24 h	100		(Dydak et al. 2021)
K. pneumoniae	62.5-500	24 h	100		(Dydak et al. 2021)
P. mirabilis	250	24 h	100	biofilm formation inhibition	(Loose et al. 2021)
P. aeruginosa	500	24 h	100	biofilm formation inhibition	(Loose et al. 2021)
	250 to >500	24 h	100	mature biofilm reduction	(Dydak et al. 2021)
	~180	24 h	100		(Krasowski et al. 2021)
	1000	24 h	~100		(Rembe et al. 2020)
C. albicans	500	24 h	47 ± 11		(Korbecka-Paczkowska and Karpiński 2024)
	1000	24 h	51 ± 13		(Korbecka-Paczkowska and Karpiński 2024)
	15.7-31.3	24 h	100		(Dydak et al. 2021)
	~60	24 h	100		(Krasowski et al. 2021)

Minimal inhibitory concentrations (MIC) of octenidine against bacteria and fungi using microdilution method_

Microorganisms	Range of MICs (μg/mL)	Methodological remarks (medium type, colony counts, incubation time, and temperature)	References
Gram-positive bacteria
Clostridium perfringens	1	MHB, 10⁵ cfu/mL, 24-48 h, 36°C	(Koburger et al. 2010)
Enterococcus faecalis	4	MHB, 10⁵ cfu/mL, 24-48 h, 36°C	(Koburger et al. 2010)
Enterococcus faecalis	3.125-6.25	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
E. faecium	0.49-1.95	TSB, 10⁵ cfu/mL, 24 h, 37°C	(Dydak et al. 2021)
E. faecium	3.125-6.25	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
E. hirae	0.6-10	TSB, 10⁸-10⁹ cfu/mL, 24-72 h, no data	(Schug et al. 2022)
Staphylococcus aureus	2	MHB, 10⁵ cfu/mL, 24-48 h, 36°C	(Koburger et al. 2010)
	0.49-0.98	TSB, 10⁵ cfu/mL, 24 h, 37°C	(Dydak et al. 2021)
	2-4	SCS, 1.5-5×10⁵cfu/mL, 48 h, 37°C	(Denkel et al. 2022)
	0.9	MHB, 10⁵ cfu/mL, 24 h, 37°C	(Krasowski et al. 2021)
	0.3-5	TSB, 10⁸-10⁹ cfu/mL, 24-72 h, no data	(Schug et al. 2022)
	3.125-6.25	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Methicillin-resistant S. aureus (MRSA)	1	MHB, 10⁵ cfu/mL, 24-48 h, 36°C	(Koburger et al. 2010)
Methicillin-resistant S. aureus (MRSA)	1-4	MHB, 5×10⁵ cfu/mL, 24-48 h, 37°C	(Dittmann et al. 2019)
S. epidermidis	0.49-7.8	TSB, 10⁵ cfu/mL, 24 h, 37°C	(Dydak et al. 2021)
Coagulase-negative staphylococci	2-4	SCS, 1.5-5×10⁵cfu/mL, 48 h, 37°C	(Denkel et al. 2022)
Streptococcus pneumoniae	8-32	MHB, 10⁵ cfu/mL, 24-48 h, 36°C	(Koburger et al. 2010)
S. pyogenes	3.125-6.25	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Gram-negative bacteria
Acinetobacter baumannii	0.25-3.9	TSB, 10⁵ cfu/mL, 24 h, 37°C	(Dydak et al. 2021)
Enterobacter cloacae	3.9	TSB, 10⁵ cfu/mL, 24 h, 37°C	(Dydak et al. 2021)
Enterobacter cloacae	6.25	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Escherichia coli	2	MHB, 10⁵ cfu/mL, 24-48 h, 36°C	(Koburger et al. 2010)
	1.95-3.9	TSB, 10⁵ cfu/mL, 24 h, 37°C	(Dydak et al. 2021)
	2-4	SCS, 1.5-5×10⁵cfu/mL, 48 h, 37°C	(Denkel et al. 2022)
	1.95-3.9	MHB or artificial urine, 10⁵-10⁶ cfu/mL, 20 ± 2 h, 37°C	(Loose et al. 2021)
	1-4	MHB, 10⁶ cfu/mL, 20 ± 2 h, 37°C	(da Silva et al. 2023)
	0.6-20	TSB, 10⁸-10⁹ cfu/mL, 24-72 h, no data	(Schug et al. 2022)
	3.125-6.25	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Haemophilus influenzae	1	MHB 10⁵ cfu/mL, 24-48 h, 36°C	(Koburger et al. 2010)
Klebsiella spp.	2-4	SCS, 1.5-5×10⁵cfu/mL, 48 h, 37°C	(Denkel et al. 2022)
K. pneumoniae	1.95-7.8	TSB, 10⁵ cfu/mL, 24 h, 37°C	(Dydak et al. 2021)
K. pneumoniae	3.125-6.25	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Proteus mirabilis	1.95-3.9	MHB or artificial urine, 10⁵-10⁶ cfu/mL, 20 ± 2 h, 37°C	(Loose et al. 2021)
Proteus mirabilis	3.125-6.25	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Pseudomonas aeruginosa	2-8	MHB, 10⁵ cfu/mL, 24-48 h, 36°C	(Koburger et al. 2010)
	3.9-15.7	TSB, 10⁵ cfu/mL, 24 h, 37°C	(Dydak et al. 2021)
	8-32	SCS, 1.5-5×10⁵cfu/mL, 48 h, 37°C	(Denkel et al. 2022)
	2.25±0.95	MHB, 10⁵ cfu/mL, 24 h, 37°C	(Krasowski et al. 2021)
	3.9-7.8	MHB or artificial urine, 10⁵-10⁶ cfu/mL, 20 ± 2 h, 37°C	(Loose et al. 2021)
	3.91-15.63	TSB, 10⁵ cfu/mL, 24 h, 36°C	(Karpiński, et al. 2025b)
	1.25-80	TSB, 10⁸-10⁹ cfu/mL, 24-72 h, no data	(Schug et al. 2022)
	3.125-12.5	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Salmonella enterica	6.25	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Shigella flexneri	6.25-12.5	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Yersinia enterocolitica	6.25	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Fungi
Ascophera apis	0.78-3.125	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Candida albicans	1	MHB, 10⁵ cfu/mL, 24-48 h, 36°C	(Koburger et al. 2010)
	0.49-0.98	TSB, 10⁵ cfu/mL, 24 h, 37°C	(Dydak et al. 2021)
	0.45	RPMI with 2% glucose, 10⁵ cfu/mL, 24 h, 37°C	(Krasowski et al. 2021)
	0.5 ± 0.25 and 0.9 ± 0.4	TSB, 10⁶ cfu/mL, 24 h, 36°C	(Korbecka-Paczkowska and Karpiński 2024)
	1.95-3.91	Sabouraud broth, 10⁶ cfu/mL, 24 h, 36°C	(Karpiński et al. 2024)
	0.78-1.56	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
C. auris	3.125	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
C. glabrata	0.78-3.125	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
C. tropicalis	0.78-1.56	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Cryptococcus neoformans	3.125	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)
Rhodotorula mucilaginosa	3.125	TSB, 10⁵ cfu/mL, 24-48 h, 37°C	(Karpiński, et al. 2025a)

Results of studies on the development of microorganism adaptation to OCT_

Microorganism	Initial MIC (before adaptation) (μg/mL)	MIC after adaptation (μg/mL)	Fold increase in adaptation relative to initial MIC	Reference	Karpinski Adaptation Index (KAI)	Risk of clinical resistance to OCT
S. aureus	2	4.5	× 2.25	(Karpiński 2024)	0.009	Very low
S. epidermidis	0.2	0.49	× 2.45	(Nicolae Dopcea et al. 2020)	0.00098	Very low
Citrobacter spp.	2	2	× 1	(Garratt et al. 2021)	0.004	Very low
Enterobacter spp.	4	4-8	× 1-2	(Garratt et al. 2021)	0.008-0.016	Very low
P. mirabilis	2	128	× 64	(Pelling et al. 2024)	0.256	Moderate
P. mirabilis	8	16	× 2	(Tagliaferri et al. 2024)	0.032	Very low
P. aeruginosa	7.8–15.6	50-75	× 3.2–12.8	(Karpiński, et al. 2025b)	0.12	Low
	4	32-64	× 8-16	(Garratt et al. 2021)	0.064-0.128	Very low/Low
	32	256	× 8	(Tagliaferri et al. 2024)	0.512	Moderate
	4-8	32-128	× 4-32	(Shepherd et al. 2018)	0.064-0.256	Very low/Moderate
C. albicans	1.95-3.9	7.5-10	× 1.9-5.1	(Karpiński et al. 2024)	0.019	Very low

Octenidine Dihydrochloride – Antimicrobial Activity, Adaptation and Clinical Application

Figures & Tables

Figure 1.

Antibiofilm activity of octenidine dihydrochloride_

Minimal inhibitory concentrations (MIC) of octenidine against bacteria and fungi using microdilution method_

Results of studies on the development of microorganism adaptation to OCT_

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