Tissue penetration of antimicrobials

Summary

Class	Antimicrobial	Blood	CNS	Vitreous	Urine	Prostate	Necrotic
Antibiotics: β-Lactams
Penicillins	β-lactamase inhibitors		–
	ampicillin		+	±			–
	piperacillin-tazobactam			–		+†
Cephalosporins	first-generation cephalosporins		–	–			–
	second-generation cephalosporins		–
	third-generation cephalosporins			±		+†
	cefepime						+
	ceftazidime		+	±			+
Cephamycins	cephamycins		–
Cephamycins	cefoxitin						–
Carbapenems	imipenem						+
Carbapenems	meropenem		+	+			+
Antibiotics: Non-β-Lactams
Aminoglycosides							–
Chloramphenicol	chloramphenicol						+
Fluoroquinolones			–?			+	+
Fosfomycin	fosfomycin					+
Lincosamides	clindamycin		–				+
Lipopeptides	daptomycin	+	–		+
Macrolides	macrolides		–			+
Nitrofurans	nitrofurantoin	–	–		+	–	–
Nitroimidazoles	metronidazole						+
Oxazolidinones	linezolid	+	+	+
Rifamycins	rifampin					+
Sulfonamides	trimethoprim-sulfamethoxazole					+
Tetracyclines	tetracyclines		–			+
Tetracyclines	doxycycline					+	+
Antivirals
	acyclovir / valacyclovir			+
	ganciclovir			+
	foscarnet
Antifungals
Azoles	fluconazole			+			+
Echinocandins		+		–	–
Polyenes	liposomal amphotericin B		–	±†
Class	Antimicrobial	Blood	CNS	Vitreous	Urine	Prostate	Necrotic

Poorly penetrated by most antibiotics
Penetration is higher with a high concentration gradient, high lipid solubility, low degree of ionization, high dissociation constant, low protein binding, and small molecular size
Fluoroquinolones are the mainstay of therapy, though there is increasing resistance
TMP-SMX often used, though conflicting data about its penetration into the prostate
Minocycline, doxycycline, and macrolides achieve high levels in the prostate but are rarely indicated for the causative organisms
Third-generation cephalosporins and carbapenems can be used
Piperacillin, aztreonam, imipenem, and some aminoglycosides are likely useful

Essentially all antibiotics achieve similar bone-to-serum levels, with the exception of oral β-lactams which nevertheless have no worse outcomes1

Ocular compartments include anterior and posterior
- Anterior includes aqeous humour, and is best accessed using topical medications
- Posterior includes vitreous humour, retina, and choroid, and is best accessed using intravitreal or systemic medications
Penetration of systemic antimicrobials into retina and vitreous is poor (~0 to 2%), but is better with inflammation2
- Preferred agents for vitreal penetration include meropenem, linezolid, and moxifloxacin
- Agents that are likely effective, especially when inflammation is present, include vancomycin, cefazolin, ceftriaxone, ceftazidime, imipenem, and trimethoprim-sulfamethoxazole, and possible daptomycin and rifampin
- Agents that do not reach adequate levels include ciprofloxacin, levofloxacin, aminoglycosides, aminopenicillins, piperacillin, cefepime, and clarithromycin

Class	Antimicrobial	Retinal Penetration	Vitreal Penetration	Ref
Antibiotics
penicillins	ampicillin		below MIC in non-inflamed rabbit eyes	2
	amoxicillin		2% (below MIC) in non-inflamed rabbit eyes	2
	piperacillin		undetectable in inflamed human eyes	2
cephalosporins	cefazolin		above MIC in inflamed rabbit eyes	2
	ceftriaxone		4% in non-inflamed human eyes	2
	ceftazidime		30% in inflamed rabbit eyes	2
	cefipime		8% in non-inflamed human eyes	2
carbapenems	imipenem		8 to 10% in non-inflamed human eyes	2
carbapenems	meropenem		30% in non-inflamed human eyes	2
oxazolidinones	linezolid		30 to 80% in non-inflamed human eyes	2
	vancomycin		above MIC in inflamed rabbit eyes	2
	daptomycin		30% in inflamed human eyes	2
aminoglycosides	amikacin		below MIC in inflamed rabbit eyes	2
aminoglycosides	gentamicin		below MIC in inflamed rabbit eyes	2
fluoroquinolones	ciprofloxacin		below MIC in non-inflamed human eyes	2
	levofloxacin		30% but below MIC in non-inflamed human eyes	2
	moxifloxacin		10 to 40% and above MIC in non-inflamed human eyes	2
Antifungals
azoles	fluconazole	40 to 50%	40 to 50%	34
	itraconazole		10% in inflamed eyes	4
	posaconazole		20% in inflamed eyes	4
	voriconazole		40 to 100%	4
	flucytosine		40 to 100%	4
polyenes	liposomal amphotericin B		only detectable in inflamed eyes	4
echinocandins	echinocandins		very low penetration	4
echinocandins	micafungin	excellent	undetectable	34

^ Cornelia B. Landersdorfer, Jürgen B. Bulitta, Martina Kinzig, Ulrike Holzgrabe, Fritz Sörgel. Penetration of Antibacterials into Bone. Clinical Pharmacokinetics. 2009;48(2):89-124. doi:10.2165/00003088-200948020-00002.
a b c d e f g h i j k l m n o p q r L. Brockhaus, D. Goldblum, L. Eggenschwiler, S. Zimmerli, C. Marzolini. Revisiting systemic treatment of bacterial endophthalmitis: a review of intravitreal penetration of systemic antibiotics. Clinical Microbiology and Infection. 2019;25(11):1364-1369. doi:10.1016/j.cmi.2019.01.017.
a b Takashi Suzuki, Toshihiko Uno, Guangming Chen, Yuichi Ohashi. Ocular distribution of intravenously administered micafungin in rabbits. Journal of Infection and Chemotherapy. 2008;14(3):204-207. doi:10.1007/s10156-008-0612-5.
a b c d e f g h Timothy Felton, Peter F. Troke, William W. Hope. Tissue Penetration of Antifungal Agents. Clinical Microbiology Reviews. 2014;27(1):68-88. doi:10.1128/cmr.00046-13.