Tissue penetration of antimicrobials: Difference between revisions
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+ | ==Summary== |
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{| class="wikitable" |
{| class="wikitable" |
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!Class |
!Class |
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Line 4: | Line 5: | ||
!Blood |
!Blood |
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!CNS |
!CNS |
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+ | !Vitreous |
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!Urine |
!Urine |
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!Prostate |
!Prostate |
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!Necrotic |
!Necrotic |
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|- |
|- |
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− | ! colspan=" |
+ | ! colspan="8" |Antibiotics: β-Lactams |
|- |
|- |
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− | | rowspan=" |
+ | | rowspan="3" |[[Penicillins]] |
|β-lactamase inhibitors |
|β-lactamase inhibitors |
||
+ | | style="text-align:center" | |
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+ | | style="text-align:center" |– |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | |- |
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+ | |[[ampicillin]] |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | + |
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+ | | style="text-align:center" |± |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" |– |
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+ | |- |
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+ | |[[piperacillin-tazobactam]] |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" |– |
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+ | | style="text-align:center" |– |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | +† |
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+ | | style="text-align:center" | |
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+ | |- |
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+ | | rowspan="6" |[[Cephalosporins]] |
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+ | |first-generation cephalosporins |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |– |
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+ | | style="text-align:center" |– |
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+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |– |
||
+ | |- |
||
+ | |second-generation cephalosporins |
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+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |– |
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+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | |- |
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+ | |third-generation cephalosporins |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" |± |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | +† |
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+ | | style="text-align:center" | |
||
+ | |- |
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+ | |[[ceftriaxone]] |
||
+ | | |
||
+ | | + |
||
| |
| |
||
− | | style="text-align:center" | – |
||
| |
| |
||
| |
| |
||
| |
| |
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|- |
|- |
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− | |[[ |
+ | |[[cefepime]] |
+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | + |
||
+ | |- |
||
+ | |[[ceftazidime]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
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+ | | style="text-align:center" |± |
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+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
||
+ | |- |
||
+ | | rowspan="2" |[[Cephamycins]] |
||
+ | |[[cephamycins]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | |- |
||
+ | |[[cefoxitin]] |
||
+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" |– |
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+ | |- |
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+ | | rowspan="2" |[[Carbapenems]] |
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+ | |[[imipenem]] |
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+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | + |
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+ | |- |
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+ | |[[meropenem]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
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+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | + |
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+ | |- |
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+ | ! colspan="8" |Antibiotics: Non-β-Lactams |
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+ | |- |
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+ | |[[Aminoglycosides]] |
||
+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" |– |
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+ | |- |
||
+ | |[[Chloramphenicol]] |
||
+ | |[[chloramphenicol]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
||
+ | |- |
||
+ | | rowspan="2" |[[Fluoroquinolones]] |
||
+ | |all |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |–? |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | + |
||
+ | |- |
||
+ | |[[moxifloxacin]] |
||
| |
| |
||
+ | | |
||
+ | | |
||
+ | |– |
||
+ | | |
||
+ | | |
||
+ | |- |
||
+ | |[[Fosfomycin]] |
||
+ | |[[fosfomycin]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
| style="text-align:center" | + |
| style="text-align:center" | + |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | |[[Lincosamides]] |
||
+ | |[[clindamycin]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
||
+ | |- |
||
+ | |[[Lipopeptides]] |
||
+ | |[[daptomycin]] |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" |– |
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+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
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+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | |[[Macrolides]] |
||
+ | |[[macrolides]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
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+ | | style="text-align:center" | + |
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+ | | style="text-align:center" | |
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+ | |- |
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+ | |[[Nitrofurans]] |
||
+ | |[[nitrofurantoin]] |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" |– |
||
+ | |- |
||
+ | |[[Nitroimidazoles]] |
||
+ | |[[metronidazole]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
||
+ | |- |
||
+ | |[[Oxazolidinones]] |
||
+ | |[[linezolid]] |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" |±‡ |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | |[[Rifamycins]] |
||
+ | |[[rifampin]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | |[[Sulfonamides]] |
||
+ | |[[trimethoprim-sulfamethoxazole]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | | rowspan="2" |[[Tetracyclines]] |
||
+ | |[[tetracyclines]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | |[[doxycycline]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |±<ref>Tomasz Jodlowski, Charles R Ashby, Sarath G Nath, Doxycycline for ESBL-E Cystitis, ''Clinical Infectious Diseases'', Volume 73, Issue 1, 1 July 2021, Pages e274–e275, https://doi.org/10.1093/cid/ciaa1898</ref> |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | + |
||
+ | |- |
||
+ | ! colspan="8" |Antivirals |
||
+ | |- |
||
| |
| |
||
+ | |[[acyclovir]] / [[valacyclovir]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
| |
| |
||
+ | |[[ganciclovir]] |
||
− | | style="text-align:center" | – |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
|- |
|- |
||
− | | rowspan="4" |Cephalosporins |
||
− | |first-generation cephalosporins |
||
| |
| |
||
+ | |[[foscarnet]] |
||
− | | style="text-align:center" | – |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | | style="text-align:center" | |
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+ | |- |
||
+ | ! 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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+ | | rowspan="3" |[[Azoles]] |
||
+ | |[[fluconazole]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" |± |
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+ | | style="text-align:center" | + |
||
+ | |- |
||
+ | |[[itraconazole]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |± |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | |[[voriconazole]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |± |
||
+ | | style="text-align:center" |± |
||
+ | | style="text-align:center" |± |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | | rowspan="3" |[[Echinocandins]] |
||
+ | |[[anidulafungin]] |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" |± |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" |± |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | |[[caspofungin]] |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" |± |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | |[[micafungin]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |± |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" |± |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | | rowspan="2" |[[Polyenes]] |
||
+ | |deoxycholate [[amphotericin B]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | |liposomal [[amphotericin B]] |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" |– |
||
+ | | style="text-align:center" |±† |
||
+ | | style="text-align:center" | + |
||
+ | | style="text-align:center" | |
||
+ | | style="text-align:center" | |
||
+ | |- |
||
+ | !Class |
||
+ | !Antimicrobial |
||
+ | !Blood |
||
+ | !CNS |
||
+ | !Vitreous |
||
+ | !Urine |
||
+ | !Prostate |
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+ | !Necrotic |
||
+ | |} |
||
+ | |||
+ | *† if inflammation present |
||
+ | *‡ very low levels, but likely enough for [[Enterococcus]] |
||
+ | |||
+ | ==Specific Tissues== |
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+ | |||
+ | === Central Nervous System === |
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+ | |||
+ | * Reviewed in [[CiteRef::nau2010pe]] |
||
+ | |||
+ | {| class="wikitable" |
||
+ | !Class |
||
+ | !Antimicrobial |
||
+ | !CSF Penetration (AUC) |
||
+ | !With Meningeal Inflammation |
||
+ | |- |
||
+ | ! colspan="4" |Antibiotics |
||
+ | |- |
||
+ | | rowspan="5" |[[penicillins]] |
||
+ | |overall |
||
+ | |2% |
||
+ | |2% |
||
+ | |- |
||
+ | |[[ampicillin]] |
||
| |
| |
||
| |
| |
||
− | | style="text-align:center" | – |
||
|- |
|- |
||
+ | |[[amoxicillin]] |
||
− | |second-generation cephalosporins |
||
| |
| |
||
+ | |6% |
||
− | | style="text-align:center" | – |
||
+ | |- |
||
+ | |[[cloxacillin]] |
||
+ | |0.87% |
||
| |
| |
||
+ | |- |
||
+ | |[[piperacillin]] |
||
+ | |3% |
||
+ | |32% |
||
+ | |- |
||
+ | | rowspan="3" |beta lactamase inhibitors |
||
+ | |overall |
||
+ | |7% |
||
+ | |10% |
||
+ | |- |
||
+ | |[[clavulanate]] |
||
+ | |4% |
||
+ | |8% |
||
+ | |- |
||
+ | |[[tazobactam]] |
||
+ | |11% |
||
| |
| |
||
+ | |- |
||
+ | | rowspan="4" |[[cephalosporins]] |
||
+ | |overall |
||
+ | |0.7 to 10% |
||
+ | |15% |
||
+ | |- |
||
+ | |[[cefotaxime]] |
||
+ | |12% |
||
+ | |4 to 17% |
||
+ | |- |
||
+ | |[[ceftriaxone]] |
||
+ | |0.7% |
||
| |
| |
||
|- |
|- |
||
− | |[[ |
+ | |[[ceftazidime]] |
+ | |0.6% |
||
| |
| |
||
+ | |- |
||
+ | | rowspan="3" |[[carbapenems]] |
||
+ | |overall |
||
+ | |20% |
||
+ | |30% |
||
+ | |- |
||
+ | |imipenem |
||
| |
| |
||
+ | |14% |
||
+ | |- |
||
+ | |meropenem |
||
+ | |5 to 25% |
||
+ | |39% |
||
+ | |- |
||
+ | |[[aminoglycosides]] |
||
+ | |overall |
||
+ | |20% |
||
| |
| |
||
+ | |- |
||
+ | | rowspan="4" |[[fluoroquinolones]] |
||
+ | |overall |
||
+ | |30 to 70% |
||
+ | |70 to 90% |
||
+ | |- |
||
+ | |[[ciprofloxacin]] |
||
+ | |24 to 43% |
||
+ | |92% |
||
+ | |- |
||
+ | |[[levofloxacin]] |
||
+ | |71% |
||
| |
| |
||
− | | style="text-align:center" | + |
||
|- |
|- |
||
− | |[[ |
+ | |[[moxifloxacin]] |
+ | |46% |
||
+ | |79% |
||
+ | |- |
||
+ | |[[chloramphenicol]] |
||
| |
| |
||
+ | |60 to 70% |
||
− | | style="text-align:center" | + |
||
+ | |60 to 70% |
||
+ | |- |
||
+ | |[[macrolides]] |
||
+ | |[[clarithromycin]] |
||
| |
| |
||
+ | |18% |
||
+ | |- |
||
+ | |[[tetracyclines]] |
||
+ | |[[doxycycline]] |
||
+ | |20% |
||
+ | |20% |
||
+ | |- |
||
+ | |[[fosfomycin]] |
||
+ | | |
||
+ | |18% |
||
| |
| |
||
− | | style="text-align:center" | + |
||
|- |
|- |
||
+ | |[[linezolid]] |
||
− | | rowspan="2" |Cephamycins |
||
+ | |90% |
||
− | |[[cephamycins]] |
||
| |
| |
||
− | | style="text-align:center" | – |
||
| |
| |
||
+ | |- |
||
+ | |[[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% |
||
+ | |- |
||
+ | ! colspan="4" |Antivirls |
||
+ | |- |
||
+ | | rowspan="2" |anti-herpes nucleoside analogues |
||
+ | |[[acyclovir]] |
||
+ | |31% |
||
| |
| |
||
− | | style="text-align:center" | – |
||
|- |
|- |
||
+ | |[[valacyclovir]] |
||
− | |Carbapenems |
||
+ | |19% |
||
− | |[[imipenem]] |
||
| |
| |
||
+ | |- |
||
+ | |[[foscarnet]] |
||
| |
| |
||
+ | |27 to 43% |
||
+ | |23 to 66% |
||
+ | |- |
||
+ | | rowspan="4" |HIV antiretrovirals |
||
+ | |[[abacavir]] |
||
+ | |35% |
||
| |
| |
||
+ | |- |
||
+ | |[[zidovudine]] |
||
+ | |75% |
||
| |
| |
||
− | | style="text-align:center" | + |
||
|- |
|- |
||
+ | |[[indinavir]] |
||
− | ! colspan="7" |Antibiotics: Non-β-Lactams |
||
+ | |6 to 15% |
||
+ | | |
||
|- |
|- |
||
+ | |[[lopinavir]] |
||
− | |Aminoglycosides |
||
+ | |29% |
||
| |
| |
||
+ | |- |
||
+ | ! colspan="4" |Antifungals |
||
+ | |- |
||
| |
| |
||
+ | |[[flucytosine]] |
||
| |
| |
||
+ | |74% |
||
+ | |- |
||
+ | | rowspan="2" |[[azoles]] |
||
+ | |[[fluconazole]] |
||
| |
| |
||
+ | |86% |
||
+ | |- |
||
+ | |[[voriconazole]] |
||
| |
| |
||
+ | |46% |
||
− | | style="text-align:center" | – |
||
|- |
|- |
||
+ | |[[polyenes]] |
||
− | |Chloramphenicol |
||
− | |[[ |
+ | |[[amphotericin B]] |
| |
| |
||
+ | |low |
||
+ | |- |
||
+ | ! colspan="4" |Antiparasitics |
||
+ | |- |
||
| |
| |
||
+ | |[[albendazole]] |
||
+ | |38 to 43% |
||
| |
| |
||
+ | |- |
||
+ | | |
||
+ | |[[praziquantel]] |
||
+ | |24% |
||
| |
| |
||
− | | style="text-align:center" | + |
||
|- |
|- |
||
− | |Fluoroquinolones |
||
| |
| |
||
+ | |[[sulfadiazine]] |
||
+ | |27 to 33% |
||
| |
| |
||
+ | |} |
||
− | | style="text-align:center" | –? |
||
+ | ===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 outcomes[[CiteRef::landersdorfer2009pe]] |
||
+ | |||
+ | ===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 inflammation[[CiteRef::brockhaus2019re]] |
||
+ | **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="wikitable" |
||
+ | !Class |
||
+ | !Antimicrobial |
||
+ | !Retinal Penetration |
||
+ | !Vitreal Penetration |
||
+ | !Ref |
||
+ | |- |
||
+ | ! colspan="5" |Antibiotics |
||
+ | |- |
||
+ | | rowspan="3" |[[penicillins]] |
||
+ | |[[ampicillin]] |
||
| |
| |
||
+ | |below MIC in non-inflamed rabbit eyes |
||
− | | style="text-align:center" | + |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
− | | style="text-align:center" | + |
||
|- |
|- |
||
+ | |[[amoxicillin]] |
||
− | |Lincosamides |
||
− | |[[clindamycin]] |
||
| |
| |
||
+ | |2% (below MIC) in non-inflamed rabbit eyes |
||
− | | style="text-align:center" | – |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
+ | |- |
||
+ | |[[piperacillin]] |
||
| |
| |
||
+ | |undetectable in inflamed human eyes |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
+ | |- |
||
+ | | rowspan="4" |[[cephalosporins]] |
||
+ | |[[cefazolin]] |
||
| |
| |
||
+ | |above MIC in inflamed rabbit eyes |
||
− | | style="text-align:center" | + |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
|- |
|- |
||
+ | |[[ceftriaxone]] |
||
− | |Macrolides |
||
− | |[[macrolides]] |
||
| |
| |
||
+ | |4% in non-inflamed human eyes |
||
− | | style="text-align:center" | – |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
+ | |- |
||
+ | |[[ceftazidime]] |
||
| |
| |
||
+ | |30% in inflamed rabbit eyes |
||
− | | style="text-align:center" | + |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
+ | |- |
||
+ | |[[cefipime]] |
||
| |
| |
||
+ | |8% in non-inflamed human eyes |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
|- |
|- |
||
+ | | rowspan="2" |[[carbapenems]] |
||
− | |Nitrofurans |
||
− | |[[ |
+ | |[[imipenem]] |
+ | | |
||
− | | style="text-align:center" | – |
||
+ | |8 to 10% in non-inflamed human eyes |
||
− | | style="text-align:center" | – |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
− | | style="text-align:center" | + |
||
− | | style="text-align:center" | – |
||
− | | style="text-align:center" | – |
||
|- |
|- |
||
+ | |[[meropenem]] |
||
− | |Nitroimidazoles |
||
− | |[[metronidazole]] |
||
| |
| |
||
+ | |30% in non-inflamed human eyes |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
+ | |- |
||
+ | |[[oxazolidinones]] |
||
+ | |[[linezolid]] |
||
| |
| |
||
+ | |30 to 80% in non-inflamed human eyes |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
+ | |- |
||
| |
| |
||
+ | |[[vancomycin]] |
||
| |
| |
||
+ | |above MIC in inflamed rabbit eyes |
||
− | | style="text-align:center" | + |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
|- |
|- |
||
− | |Rifamycins |
||
− | |[[rifampin]] |
||
| |
| |
||
+ | |[[daptomycin]] |
||
| |
| |
||
+ | |30% in inflamed human eyes |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
+ | |- |
||
+ | | rowspan="2" |[[aminoglycosides]] |
||
+ | |[[amikacin]] |
||
| |
| |
||
+ | |below MIC in inflamed rabbit eyes |
||
− | | style="text-align:center" | + |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
+ | |- |
||
+ | |[[gentamicin]] |
||
| |
| |
||
+ | |below MIC in inflamed rabbit eyes |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
|- |
|- |
||
+ | | rowspan="3" |[[fluoroquinolones]] |
||
− | |Sulfonamides |
||
− | |[[ |
+ | |[[ciprofloxacin]] |
| |
| |
||
+ | |below MIC in non-inflamed human eyes |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
+ | |- |
||
+ | |[[levofloxacin]] |
||
| |
| |
||
+ | |30% but below MIC in non-inflamed human eyes |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
+ | |- |
||
+ | |[[moxifloxacin]] |
||
| |
| |
||
+ | |10 to 40% and above MIC in non-inflamed human eyes |
||
− | | style="text-align:center" | – |
||
+ | |[[CiteRef::brockhaus2019re]] |
||
+ | |- |
||
+ | ! colspan="5" |Antifungals |
||
+ | |- |
||
+ | | rowspan="4" |[[azoles]] |
||
+ | |[[fluconazole]] |
||
+ | |40 to 50% |
||
+ | |40 to 50% |
||
+ | |[[CiteRef::suzuki2008oc]][[CiteRef::felton2014ti]] |
||
+ | |- |
||
+ | |[[itraconazole]] |
||
| |
| |
||
+ | |10% in inflamed eyes |
||
+ | |[[CiteRef::felton2014ti]] |
||
|- |
|- |
||
+ | |[[posaconazole]] |
||
− | | rowspan="2" |Tetracyclines |
||
− | |[[tetracyclines]] |
||
| |
| |
||
+ | |20% in inflamed eyes |
||
− | | style="text-align:center" | – |
||
+ | |[[CiteRef::felton2014ti]] |
||
+ | |- |
||
+ | |[[voriconazole]] |
||
| |
| |
||
+ | |40 to 100% |
||
− | | style="text-align:center" | + |
||
+ | |[[CiteRef::felton2014ti]] |
||
+ | |- |
||
+ | | |
||
+ | |[[flucytosine]] |
||
| |
| |
||
+ | |40 to 100% |
||
+ | |[[CiteRef::felton2014ti]] |
||
|- |
|- |
||
− | |[[ |
+ | |[[polyenes]] |
+ | |liposomal amphotericin B |
||
| |
| |
||
+ | |only detectable in inflamed eyes |
||
+ | |[[CiteRef::felton2014ti]] |
||
+ | |- |
||
+ | | rowspan="2" |[[echinocandins]] |
||
+ | |echinocandins |
||
| |
| |
||
+ | |very low penetration |
||
+ | |[[CiteRef::felton2014ti]] |
||
+ | |- |
||
+ | |[[micafungin]] |
||
+ | |excellent |
||
+ | |undetectable |
||
+ | |[[CiteRef::suzuki2008oc]][[CiteRef::felton2014ti]] |
||
+ | |- |
||
+ | ! colspan="5" |Antivirals |
||
+ | |- |
||
| |
| |
||
+ | |[[acyclovir]] |
||
+ | | |
||
+ | |above IC |
||
| |
| |
||
− | | style="text-align:center" | + |
||
|- |
|- |
||
+ | | |
||
− | ! colspan="7" |Antifungals |
||
+ | |[[valacyclovir]] |
||
+ | | |
||
+ | |20 to 30%, above IC in non-inflamed human eyes |
||
+ | |[[CiteRef::huynh2008vi]] |
||
|- |
|- |
||
− | |Azoles |
||
− | |[[fluconazole]] |
||
| |
| |
||
+ | |[[ganciclovir]] |
||
| |
| |
||
+ | |close to IC |
||
| |
| |
||
+ | |- |
||
| |
| |
||
+ | |[[foscarnet]] |
||
− | | style="text-align:center" | + |
||
+ | |100% |
||
+ | |10%, close to IC |
||
+ | |[[CiteRef::lópez-cortés2000in]] |
||
|} |
|} |
||
[[Category:Antimicrobials]] |
[[Category:Antimicrobials]] |
Revision as of 10:55, 1 November 2023
Summary
- † if inflammation present
- ‡ very low levels, but likely enough for Enterococcus
Specific Tissues
Central Nervous System
- Reviewed in 1
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 outcomes2
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 inflammation3
- 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 | 3 | |
amoxicillin | 2% (below MIC) in non-inflamed rabbit eyes | 3 | ||
piperacillin | undetectable in inflamed human eyes | 3 | ||
cephalosporins | cefazolin | above MIC in inflamed rabbit eyes | 3 | |
ceftriaxone | 4% in non-inflamed human eyes | 3 | ||
ceftazidime | 30% in inflamed rabbit eyes | 3 | ||
cefipime | 8% in non-inflamed human eyes | 3 | ||
carbapenems | imipenem | 8 to 10% in non-inflamed human eyes | 3 | |
meropenem | 30% in non-inflamed human eyes | 3 | ||
oxazolidinones | linezolid | 30 to 80% in non-inflamed human eyes | 3 | |
vancomycin | above MIC in inflamed rabbit eyes | 3 | ||
daptomycin | 30% in inflamed human eyes | 3 | ||
aminoglycosides | amikacin | below MIC in inflamed rabbit eyes | 3 | |
gentamicin | below MIC in inflamed rabbit eyes | 3 | ||
fluoroquinolones | ciprofloxacin | below MIC in non-inflamed human eyes | 3 | |
levofloxacin | 30% but below MIC in non-inflamed human eyes | 3 | ||
moxifloxacin | 10 to 40% and above MIC in non-inflamed human eyes | 3 | ||
Antifungals | ||||
azoles | fluconazole | 40 to 50% | 40 to 50% | 45 |
itraconazole | 10% in inflamed eyes | 5 | ||
posaconazole | 20% in inflamed eyes | 5 | ||
voriconazole | 40 to 100% | 5 | ||
flucytosine | 40 to 100% | 5 | ||
polyenes | liposomal amphotericin B | only detectable in inflamed eyes | 5 | |
echinocandins | echinocandins | very low penetration | 5 | |
micafungin | excellent | undetectable | 45 | |
Antivirals | ||||
acyclovir | above IC | |||
valacyclovir | 20 to 30%, above IC in non-inflamed human eyes | 6 | ||
ganciclovir | close to IC | |||
foscarnet | 100% | 10%, close to IC | 7 |
- ↑ Tomasz Jodlowski, Charles R Ashby, Sarath G Nath, Doxycycline for ESBL-E Cystitis, Clinical Infectious Diseases, Volume 73, Issue 1, 1 July 2021, Pages e274–e275, https://doi.org/10.1093/cid/ciaa1898
- ↑ 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: PMC3910906.
References
- ^ 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.
- 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.