. 2022 Aug 12;10:53. doi: 10.1038/s41413-022-00227-8

Table 3.

Overview of cell wall disruptors tested against intracellular S. aureus

Antibiotic Class	Antibiotic	Bone: plasma ratio	Bone concentration	Intra- to extracellular ratio	MIC at ca pH5 (μg·mL⁻¹ or mg·L⁻¹)	MIC at ca pH7 (μg·mL⁻¹ or mg·L⁻¹)	Intracellular effectivity against S. aureus	Model tested
Antibiotic Class	Antibiotic	Bone: plasma ratio	Bone concentration	Intra- to extracellular ratio	MIC at ca pH5 (μg·mL⁻¹ or mg·L⁻¹)	MIC at ca pH7 (μg·mL⁻¹ or mg·L⁻¹)	Intracellular effectivity against S. aureus	bone cell	Other cells	In vivo
Beta-lactam antibiotics	Oxacillin	0.1¹⁰⁷ 0.11⁴⁰ 0.17⁵³	4 μg·mL⁻¹ ⁴¹ 10 μg·mL⁻¹ ⁵³	4.0⁷⁴	<0.015–0.062 5⁴³ 0.06⁷⁴ 0.016 MSSA, 0.023 MRSA¹⁵³	0.125 SCV & 0.5 WT¹⁷ 0.094⁵³ <0.015–0.062 5⁴³ 0.125⁷⁴ 0.25 MSSA, > 256 MRSA¹⁵³	SCV 1-log, more effective against the WT¹⁷ 4-log (dose depending), SCV emergence reduction⁵³ 2-log, time depending⁷⁴ <1-log¹⁵³	MG63^53,153	THP-1^17,74
	Cefatroline	0.19⁵³	4 μg·mL⁻¹⁵³		0.006 MSSA, 0.008 MRSA¹⁵³	0.19⁵³ 0.125 MSSA, 0.25 MRSA¹⁵³	2-log, SCV induction⁵³ <1-log, similar MRSA/MSSA¹⁵³	MG63^53,153
	Cefuroxime	0.04–0.55⁴⁰					<1-log immediately, no effect after 7d⁵⁵	pHOBs⁵⁵		C57BL/6 mice⁵⁵
	Cefazolin	0.75–0.37¹⁰⁷ 0.18⁴⁰	3–30 μg·g⁻¹ ¹⁰⁷ 4.2 μg·mL⁻¹⁴¹		0.03–0.125⁴³	0.062 50–0.5⁴³	No effect^58,141	UMR106⁵⁸ MC3T3¹⁴¹
	Flucloxacillin		89.5 μg·mL⁻¹⁴¹				<1-log immediately, no effect after 7d⁵⁵	pHOBs⁵⁵
	Ampicillin	0.17–0.33¹⁰⁷ 0.11–0.71⁴⁰	12–20 μg·g⁻¹ ¹⁰⁷	1.0⁷⁴	0.03¹⁵⁰ 0.03⁷⁴	0.06⁷⁴ 0.07¹⁵⁰	1-log⁷⁴ No effect (1 h)¹⁴¹ 1-log, time depending less dose depending¹⁵⁰	MC3T3¹⁴¹	THP-1^74,150
	Dicloxacillin		3.8 μg·mL⁻¹ ⁴¹				ns (ca log1) decrease of bacteria, but can be increased by adding efflux inhibitors (piperine or cyanide m-chlorophenyl hydrazone)¹⁵²	Saos-2¹⁵²
	Nafcillin			2.6⁷⁴	0.06⁷⁴	0.25⁷⁴	1-log⁷⁴		THP-1⁷⁴
	Penicillin V			1.2⁷⁴	<0.015⁷⁴	0.06⁷⁴	1-log⁷⁴		THP-1⁷⁴
	Penicillin G						<0.1-log¹⁵⁷		A594¹⁵⁷
	Ertapenem	0.13–0.19⁴⁰			0.06¹⁵⁰	0.11¹⁵⁰	1-log, time depending less dose depending¹⁵⁰		THP-1¹⁵⁰
	Meropenem				0.06¹⁵⁰	0.15¹⁵⁰	1-log, time depending less dose depending¹⁵⁰		THP-1¹⁵⁰
Glycopeptides	Vancomycin	0.05–0.21¹⁰⁷ 0.05–0.97⁴⁰ 0.21⁵³	1.1–3.6 μg·mL⁻¹¹⁰⁷ 3.8–4.5 μg·mL⁻¹ ⁴¹ 6 μg·mL⁻¹ ⁵³	6.3⁷⁴	1 SCV & 0.5 WT¹²⁵ 0.125–1⁴³ 1⁷⁴	0.5 SCV & WT¹⁷ 1.5⁵³ 1 SCV & 0.5 WT¹²⁵ 0.25–2⁴³ 1⁷⁴ 2³¹	SCV, in beginning growth, max 1-log, WT much more effective¹⁷ Ns effect^141,162,164 Max 1-log^{31,125,144,152,166} immediately & after 7d⁵⁵ 1-log dose and time dependent⁷⁴ Ns bacterial growth⁵³ 2-log¹⁶³	MG63^53,144 pHOBs⁵⁵ MC3T3¹⁴¹ Saos-2¹⁵²	THP-1^{17,74,125,163} A594¹⁶⁶ J774¹⁶² RAW264.7^164,166	Sprague-Dawley rats³¹ Kunming mice¹⁶⁶
	Oritavancin		27–65 μg·mL⁻¹ ⁴¹	148⁷⁴ 336–344⁷⁵ (highest by far)	0.25^74,75 0.125 SCV & 0.25–1 WT¹²⁵	0.015 SCV & 0.03 WT¹⁷ 0.07⁷⁴ 0.25⁷⁵ 0.03–0.06¹²⁵	3-log against SCV (best drug of 13)¹⁷ 3-log strongly time & dose dependent⁷⁴ 4-log dose depending¹²⁵ 3.5-log all phenotypes⁷⁵		THP-1^17,74,125 J774⁷⁵
	Teicoplanin	0.5–0.85⁴⁰ 0.21⁵³	3 μg·mL⁻¹ ⁵³	7.4⁷⁴	0.0625–2⁴³ 1⁷⁴	0.25–0.5⁴³ 1.5⁵³ 1⁷⁴	3-4-log⁵³ <1-log⁷⁴	MG63⁵³	THP-1⁷⁴
	Telavancin					0.125 all phenotypes¹⁷	<1-log SCV, WT better¹⁷		THP-1¹⁷
Fosfomycin		0.25¹⁰⁷ 0.13–0.45⁴⁰ 0.35⁵³	16-96 μg·g⁻¹¹⁰⁷ 4 μg·mL⁻¹ ⁵³		1–16⁴³	2⁵³ 0.25–8⁴³	3-log no dose depending⁵³ Immediately effective not after 7d⁵⁵	MG63⁵³ pHOBs⁵⁵
Lipopeptides	Daptomycin	0.07¹⁰⁷ 0.24⁵³	5 μg·g⁻¹¹⁰⁷ 5 μg·mL⁻¹⁵³		0.5 SCV & WT¹²⁵ 0.75 MSSA, 0.19 MRSA¹⁵³ 4⁴³	0.125 SCV & WT¹⁷ 0.19⁵³ 0.5–2 WT, 0.25–0.5 SCV¹²⁵ 0.064 MSSA, 0.19 MRSA¹⁵³ 1–2⁴³	SCV 1-log, WT better¹⁷ Ns/ bacterial growth^43,53,153 2-log¹²⁵ <1-log immediately, after 7d ns⁵⁵ <1-log¹⁷⁸	MG63^{43,53,153,178} pHOBs⁵⁵	THP-1^17,125	C57BL/6 mice¹⁷⁸