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			±		+†
	ceftriaxone		+
	cefepime						+
	ceftazidime		+	±			+
Cephamycins	cephamycins		–
	cefoxitin						–
Carbapenems	imipenem						+
	meropenem		+	+			+
Antibiotics: Non-β-Lactams
Aminoglycosides							–
Chloramphenicol	chloramphenicol						+
Fluoroquinolones	all		–?			+	+
	moxifloxacin				–
Fosfomycin	fosfomycin					+
Lincosamides	clindamycin		–				+
Lipopeptides	daptomycin	+	–		+
Macrolides	macrolides		–			+
Nitrofurans	nitrofurantoin	–	–	–	+	–	–
Nitroimidazoles	metronidazole						+
Oxazolidinones	linezolid	+	+	+	±‡
Rifamycins	rifampin					+
Sulfonamides	trimethoprim-sulfamethoxazole					+
Tetracyclines	tetracyclines		–			+
	doxycycline				±1	+	+
Antivirals
	acyclovir / valacyclovir			+
	ganciclovir			+
	foscarnet
Antifungals2
Azoles	fluconazole		+	+	+	±	+
	itraconazole		±	–	+	–
	voriconazole		±	±	±
Echinocandins	anidulafungin	+	±	–	±
	caspofungin	+	–	–	±
	micafungin		±	–	±
Polyenes	deoxycholate amphotericin B			–	+
	liposomal amphotericin B		–	±†	+
Class	Antimicrobial	Blood	CNS	Vitreous	Urine	Prostate	Necrotic

• † if inflammation present
• ‡ very low levels, but likely enough for Enterococcus

Specific Tissues

Central Nervous System

• Reviewed in 3

Class	Antimicrobial	CSF Penetration (AUC)	With Meningeal Inflammation
Antibiotics
penicillins	overall	2%	2%
	ampicillin
	amoxicillin		6%
	cloxacillin	0.87%
	piperacillin	3%	32%
beta lactamase inhibitors	overall	7%	10%
	clavulanate	4%	8%
	tazobactam	11%
cephalosporins	overall	0.7 to 10%	15%
	cefotaxime	12%	4 to 17%
	ceftriaxone	0.7%
	ceftazidime	0.6%
carbapenems	overall	20%	30%
	imipenem		14%
	meropenem	5 to 25%	39%
aminoglycosides	overall	20%
fluoroquinolones	overall	30 to 70%	70 to 90%
	ciprofloxacin	24 to 43%	92%
	levofloxacin	71%
	moxifloxacin	46%	79%
chloramphenicol		60 to 70%	60 to 70%
macrolides	clarithromycin		18%
tetracyclines	doxycycline	20%	20%
fosfomycin		18%
linezolid	90%
metronidazole			87%
rifamycins	rifampin	22%
trimethoprim-sulfamethoxazole	trimethoprim	18%	42 to 51%
	sulfamethoxazole	12%	24 to 30%
glycopeptides	vancomycin	14 to 18%	30%
antituberculosis medications	isoniazid		86%
Antivirls
anti-herpes nucleoside analogues	acyclovir	31%
	valacyclovir	19%
foscarnet		27 to 43%	23 to 66%
HIV antiretrovirals	abacavir	35%
	zidovudine	75%
	indinavir	6 to 15%
	lopinavir	29%
Antifungals
	flucytosine		74%
azoles	fluconazole		86%
	voriconazole		46%
polyenes	amphotericin B		low
Antiparasitics
	albendazole	38 to 43%
	praziquantel	24%
	sulfadiazine	27 to 33%

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 outcomes4

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 inflammation5
  • 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	5
	amoxicillin		2% (below MIC) in non-inflamed rabbit eyes	5
	piperacillin		undetectable in inflamed human eyes	5
cephalosporins	cefazolin		above MIC in inflamed rabbit eyes	5
	ceftriaxone		4% in non-inflamed human eyes	5
	ceftazidime		30% in inflamed rabbit eyes	5
	cefipime		8% in non-inflamed human eyes	5
carbapenems	imipenem		8 to 10% in non-inflamed human eyes	5
	meropenem		30% in non-inflamed human eyes	5
oxazolidinones	linezolid		30 to 80% in non-inflamed human eyes	5
	vancomycin		above MIC in inflamed rabbit eyes	5
	daptomycin		30% in inflamed human eyes	5
aminoglycosides	amikacin		below MIC in inflamed rabbit eyes	5
	gentamicin		below MIC in inflamed rabbit eyes	5
fluoroquinolones	ciprofloxacin		below MIC in non-inflamed human eyes	5
	levofloxacin		30% but below MIC in non-inflamed human eyes	5
	moxifloxacin		10 to 40% and above MIC in non-inflamed human eyes	5
Antifungals
azoles	fluconazole	40 to 50%	40 to 50%	62
	itraconazole		10% in inflamed eyes	2
	posaconazole		20% in inflamed eyes	2
	voriconazole		40 to 100%	2
	flucytosine		40 to 100%	2
polyenes	liposomal amphotericin B		only detectable in inflamed eyes	2
echinocandins	echinocandins		very low penetration	2
	micafungin	excellent	undetectable	62
Antivirals
	acyclovir		above IC
	valacyclovir		20 to 30%, above IC in non-inflamed human eyes	7
	ganciclovir		close to IC
	foscarnet	100%	10%, close to IC	8