Tissue penetration of antimicrobials: Difference between revisions
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|[[meropenem]] |
|[[meropenem]] |
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! colspan="8" |Antibiotics: Non-Ξ²-Lactams |
! colspan="8" |Antibiotics: Non-Ξ²-Lactams |
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|[[Lipopeptides]] |
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|[[daptomycin]] |
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|[[Macrolides]] |
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|[[Oxazolidinones]] |
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|[[linezolid]] |
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|[[Rifamycins]] |
|[[Rifamycins]] |
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|[[acyclovir]] / [[valacyclovir]] |
|[[acyclovir]] / [[valacyclovir]] |
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! colspan="8" |Antifungals |
! colspan="8" |Antifungals |
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|[[Polyenes]] |
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|liposomal [[amphotericin B]] |
|liposomal [[amphotericin B]] |
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Revision as of 17:52, 7 March 2021
Summary
| Class | Antimicrobial | Blood | CNS | Vitreous | Urine | Prostate | Necrotic |
|---|---|---|---|---|---|---|---|
| Antibiotics: Ξ²-Lactams | |||||||
| Penicillins | Ξ²-lactamase inhibitors | β | |||||
| ampicillin | + | Β± | β | ||||
| piperacillin-tazobactam | β | +β | |||||
| Cephalosporins | first-generation cephalosporins | β | β | β | |||
| second-generation cephalosporins | β | ||||||
| third-generation cephalosporins | Β± | +β | |||||
| cefepime | + | ||||||
| ceftazidime | + | Β± | + | ||||
| Cephamycins | cephamycins | β | |||||
| cefoxitin | β | ||||||
| Carbapenems | imipenem | + | |||||
| meropenem | + | + | + | ||||
| Antibiotics: Non-Ξ²-Lactams | |||||||
| Aminoglycosides | β | ||||||
| Chloramphenicol | chloramphenicol | + | |||||
| Fluoroquinolones | β? | + | + | ||||
| Fosfomycin | fosfomycin | + | |||||
| Lincosamides | clindamycin | β | + | ||||
| Lipopeptides | daptomycin | + | β | + | |||
| Macrolides | macrolides | β | + | ||||
| Nitrofurans | nitrofurantoin | β | β | + | β | β | |
| Nitroimidazoles | metronidazole | + | |||||
| Oxazolidinones | linezolid | + | + | + | |||
| Rifamycins | rifampin | + | |||||
| Sulfonamides | trimethoprim-sulfamethoxazole | + | |||||
| Tetracyclines | tetracyclines | β | + | ||||
| doxycycline | + | + | |||||
| Antivirals | |||||||
| acyclovir / valacyclovir | + | ||||||
| ganciclovir | + | ||||||
| foscarnet | |||||||
| Antifungals | |||||||
| Azoles | fluconazole | + | + | ||||
| Echinocandins | + | β | β | ||||
| Polyenes | liposomal amphotericin B | β | Β±β | ||||
| Class | Antimicrobial | Blood | CNS | Vitreous | Urine | Prostate | Necrotic |
- β 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 Ξ²-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
- 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 | 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
- ^ Cornelia B. Landersdorfer, JΓΌrgen B. Bulitta, Martina Kinzig, Ulrike Holzgrabe, Fritz SΓΆrgel. 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. LΓ³pez-CortΓ©s, R. Ruiz-Valderas, M. J. Lucero-MuΓ±oz, 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.
