Tissue penetration of antimicrobials
From IDWiki
Summary
- † 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% | |
| 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% | |
| 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 | |
| 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 | |
| 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 | |
| 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
- ^ 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.
