Tissue penetration of antimicrobials: Difference between revisions

Latest revision as of 17:51, 19 September 2024

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		–
Cephamycins	cefoxitin						–
Carbapenems	imipenem						+
Carbapenems	meropenem		+	+			+
Antibiotics: Non-β-Lactams
Aminoglycosides							–
Chloramphenicol	chloramphenicol						+
Fluoroquinolones	all		–?			+	+
Fluoroquinolones	moxifloxacin				–
Fosfomycin	fosfomycin					+
Lincosamides	clindamycin		–				+
Lipopeptides	daptomycin	+	–		+
Macrolides	macrolides		–			+
Nitrofurans	nitrofurantoin	–	–	–	+	–	–
Nitroimidazoles	metronidazole						+
Oxazolidinones	linezolid	+	+	+	±‡
Rifamycins	rifampin					+
Sulfonamides	trimethoprim-sulfamethoxazole					+
Tetracyclines	tetracyclines		–			+
Tetracyclines	doxycycline				±1	+	+
Antivirals
	acyclovir / valacyclovir			+
	ganciclovir			+
	foscarnet
Antifungals2
Azoles	fluconazole		+	+	+	±	+
	itraconazole		±	–	+	–
	voriconazole		±	±	±
Echinocandins	anidulafungin	+	±	–	±
	caspofungin	+	–	–	±
	micafungin		±	–	±
Polyenes	deoxycholate amphotericin B			–	+
Polyenes	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%
anti-herpes nucleoside analogues	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%
azoles	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
carbapenems	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
aminoglycosides	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
echinocandins	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

References

^ Tomasz Jodlowski, Charles R Ashby, Sarath G Nath. Doxycycline for ESBL-E Cystitis. Clinical Infectious Diseases. 2020. doi:10.1093/cid/ciaa1898.
a b c d e f g h i 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.
^ nau2010pe
^ 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.
^ Tony H. Huynh, Mark W. Johnson, Grant M. Comer, Douglas N. Fish. Vitreous Penetration of Orally Administered Valacyclovir. American Journal of Ophthalmology. 2008;145(4):682-686. doi:10.1016/j.ajo.2007.11.016.
^ Luis F. López-Cortés, R. Ruiz-Valderas, M. J. Lucero-Muñoz, E. Cordero, M. T. Pastor-Ramos, J. Marquez. Intravitreal, Retinal, and Central Nervous System Foscarnet Concentrations after Rapid Intravenous Administration to Rabbits. Antimicrobial Agents and Chemotherapy. 2000;44(3):756-759. doi:10.1128/aac.44.3.756-759.2000.

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+! colspan="8" |Antifungals[[CiteRef::felton2014ti]]
-! colspan="8" |Antifungals<ref>Felton T, Troke PF, Hope WW. Tissue penetration of antifungal agents. Clin Microbiol Rev. 2014 Jan;27(1):68-88. doi: 10.1128/CMR.00046-13. PMID: 24396137; PMCID: [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910906/ PMC3910906].</ref>
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