Tissue penetration of antimicrobials
From IDWiki
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 | + | |||||
| 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 | – | + | ||||
| doxycycline | + | + | |||||
| Antivirals | |||||||
| acyclovir / valacyclovir | + | ||||||
| ganciclovir | + | ||||||
| foscarnet | |||||||
| Antifungals | |||||||
| Azoles | fluconazole | + | |||||
| Echinocandins | + | – | |||||
| Class | Antimicrobial | Blood | CNS | 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
- In general, linezolid, ceftazidime, meropenem, and moxifloxacin appear to reliably reach adequate intravitreal levels to be used routinely, and likely vancomycin as well
| 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 |
| 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 |
| 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 |
References
- ^ 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.
- a b c d e f g h 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.
- ^ 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.
