Tissue penetration of antimicrobials: Difference between revisions

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[[Category:Antimicrobials]]
  
[[Category:Antimicrobials]]

Revision as of 13:49, 7 March 2021

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 + – –
Polyenes liposomal amphotericin B – ±†
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

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
polyenes liposomal amphotericin B only detectable in inflamed eyes 4
echinocandins echinocandins very low penetration 4
micafungin excellent undetectable 34
Antivirals
acyclovir above IC
valacyclovir 20 to 30%, above IC in non-inflamed human eyes 5
ganciclovir close to IC
foscarnet 100% 10%, close to IC 6

References

  1. ^  Tomasz Jodlowski, Charles R Ashby, Sarath G Nath. Doxycycline for ESBL-E Cystitis. Clinical Infectious Diseases. 2020. doi:10.1093/cid/ciaa1898.
  2. 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.
  3. ^ nau2010pe 
  4. ^  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.
  5. 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.
  6. 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.
  7. ^  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.
  8. ^  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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