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		–
	cefoxitin						–
Carbapenems	imipenem						+
	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		–			+
	doxycycline					+	+
Antivirals
	acyclovir / valacyclovir			+
	ganciclovir			+
	foscarnet
Antifungals
Azoles	fluconazole			+			+
Echinocandins		+		–	–
Class	Antimicrobial	Blood	CNS	Vitreous	Urine	Prostate	Necrotic

• † if inflammation present

Specific Tissues

Prostate

• 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

Bone

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

Eye

• 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
	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
	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
	liposomal amphotericin B		only detectable in inflamed eyes	4
echinocandins	echinocandins		very low penetration	4
	micafungin	excellent	undetectable	34