Tissue penetration of antimicrobials: Difference between revisions

Revision as of 11:20, 6 March 2021

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						+
Antibiotics: Non-β-Lactams
Aminoglycosides							–
Chloramphenicol	chloramphenicol						+
Fluoroquinolones			–?			+	+
Fosfomycin	fosfomycin					+
Lincosamides	clindamycin		–				+
Lipopeptides	daptomycin	+	–		+
Macrolides	macrolides		–			+
Nitrofurans	nitrofurantoin	–	–		+	–	–
Nitroimidazoles	metronidazole						+
Rifamycins	rifampin					+
Sulfonamides	trimethoprim-sulfamethoxazole					+
Tetracyclines	tetracyclines		–			+
Tetracyclines	doxycycline					+	+
Antivirals
	acyclovir / valacyclovir			+
	ganciclovir			+
	foscarnet
Antifungals
Azoles	fluconazole						+
Echinocandins		+			–
Class	Antimicrobial	Blood	CNS		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	Vitreal Penetration
penicillins	ampicillin	below MIC in non-inflamed rabbit eyes
	amoxicillin	2% (below MIC) in non-inflamed rabbit eyes
	piperacillin	undetectable in inflamed human eyes
cephalosporins	cefazolin	above MIC in inflamed rabbit eyes
	ceftriaxone	4% in non-inflamed human eyes
	ceftazidime	30% in inflamed rabbit eyes
	cefipime	8% in non-inflamed human eyes
carbapenems	imipenem	8 to 10% in non-inflamed human eyes
carbapenems	meropenem	30% in non-inflamed human eyes
oxazolidinones	linezolid	30 to 80% in non-inflamed human eyes
	vancomycin	above MIC in inflamed rabbit eyes
	daptomycin	30% in inflamed human eyes
aminoglycosides	amikacin	below MIC in inflamed rabbit eyes
aminoglycosides	gentamicin	below MIC in inflamed rabbit eyes
fluoroquinolones	ciprofloxacin	below MIC in non-inflamed human eyes
	levofloxacin	30% but below MIC in non-inflamed human eyes
	moxifloxacin	10 to 40% and above MIC in non-inflamed human eyes

^ 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.
^ 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.

@@ Line 305: / Line 305: @@
 **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 inflammation[[CiteRef::brockhaus2019re]]
+**Preferred agents for vitreal penetration include [[meropenem]], [[linezolid]], and [[moxifloxacin]]
-*In general, linezolid, ceftazidime, meropenem, and moxifloxacin appear to reliably reach adequate intravitreal levels to be used routinely, and likely vancomycin as well
+**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="wikitable"