Tissue penetration of antimicrobials: Difference between revisions
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==Summary== |
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{| class="wikitable" |
{| class="wikitable" |
||
!Class |
!Class |
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| Line 4: | Line 5: | ||
!Blood |
!Blood |
||
!CNS |
!CNS |
||
!Vitreous |
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!Urine |
!Urine |
||
!Prostate |
|||
!Necrotic |
!Necrotic |
||
|- |
|- |
||
! colspan=" |
! colspan="8" |Antibiotics: β-Lactams |
||
|- |
|- |
||
| rowspan=" |
| rowspan="3" |[[Penicillins]] |
||
|β-lactamase inhibitors |
|β-lactamase inhibitors |
||
| 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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| style="text-align:center" | |
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| style="text-align:center" | |
|||
|- |
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|[[ampicillin]] |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | + |
|||
| style="text-align:center" |± |
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| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" |– |
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|- |
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|[[piperacillin-tazobactam]] |
|||
| 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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| style="text-align:center" | |
|||
|- |
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| rowspan="6" |[[Cephalosporins]] |
|||
|first-generation cephalosporins |
|||
| style="text-align:center" | |
|||
| style="text-align:center" |– |
|||
| style="text-align:center" |– |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" |– |
|||
|- |
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|second-generation cephalosporins |
|||
| 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" | |
|||
| style="text-align:center" | |
|||
|- |
|||
|third-generation cephalosporins |
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| style="text-align:center" | |
|||
| 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" | |
|||
|- |
|||
|[[ceftriaxone]] |
|||
| |
|||
| + |
|||
| |
|||
| |
| |
||
|NO |
|||
| |
| |
||
| |
| |
||
|- |
|- |
||
|[[ |
|[[cefepime]] |
||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | + |
|||
|- |
|||
|[[ceftazidime]] |
|||
| 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" |[[Cephamycins]] |
|||
|[[cephamycins]] |
|||
| 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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|- |
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|[[cefoxitin]] |
|||
| 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" | |
|||
| style="text-align:center" |– |
|||
|- |
|||
| rowspan="2" |[[Carbapenems]] |
|||
|[[imipenem]] |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | + |
|||
|- |
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|[[meropenem]] |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | + |
|||
| style="text-align:center" | + |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | + |
|||
|- |
|||
! colspan="8" |Antibiotics: Non-β-Lactams |
|||
|- |
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|[[Aminoglycosides]] |
|||
| 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" |– |
|||
|- |
|||
|[[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" |–? |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | + |
|||
| style="text-align:center" | + |
|||
|- |
|||
|[[moxifloxacin]] |
|||
| |
|||
| |
|||
| |
|||
|– |
|||
| |
| |
||
|YES |
|||
| |
| |
||
|NO |
|||
|- |
|- |
||
|[[Fosfomycin]] |
|||
| rowspan="4" |Cephalosporins |
|||
|[[fosfomycin]] |
|||
|first-generation cephalosporins |
|||
| 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" |– |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | + |
|||
| 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" | |
|||
| style="text-align:center" | + |
|||
| style="text-align:center" | |
|||
|- |
|||
|[[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" | |
|||
| 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" |±[[CiteRef::jodlowski2020do]] |
|||
| style="text-align:center" | + |
|||
| style="text-align:center" | + |
|||
|- |
|||
! colspan="8" |Antivirals |
|||
|- |
|||
| |
| |
||
|[[acyclovir]] / [[valacyclovir]] |
|||
|NO |
|||
| 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]] |
|||
|NO |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | + |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
|- |
|- |
||
|second-generation cephalosporins |
|||
| |
| |
||
|[[foscarnet]] |
|||
|NO |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | |
|||
|- |
|||
! colspan="8" |Antifungals[[CiteRef::felton2014ti]] |
|||
|- |
|||
| rowspan="3" |[[Azoles]] |
|||
|[[fluconazole]] |
|||
| style="text-align:center" | |
|||
| style="text-align:center" | + |
|||
| style="text-align:center" | + |
|||
| style="text-align:center" | + |
|||
| style="text-align:center" |± |
|||
| 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 |
|||
!Necrotic |
|||
|} |
|||
*† if inflammation present |
|||
*‡ very low levels, but likely enough for [[Enterococcus]] |
|||
==Specific Tissues== |
|||
=== Central Nervous System === |
|||
* Reviewed in [[CiteRef::nau2010pe]] |
|||
{| class="wikitable" |
|||
!Class |
|||
!Antimicrobial |
|||
!CSF Penetration (AUC) |
|||
!With Meningeal Inflammation |
|||
|- |
|||
! colspan="4" |Antibiotics |
|||
|- |
|||
| rowspan="5" |[[penicillins]] |
|||
|overall |
|||
|2% |
|||
|2% |
|||
|- |
|||
|[[ampicillin]] |
|||
| |
| |
||
| |
| |
||
|- |
|- |
||
|[[ |
|[[amoxicillin]] |
||
| |
| |
||
|6% |
|||
|- |
|||
|[[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% |
|||
| |
| |
||
|YES |
|||
|- |
|- |
||
|[[ceftazidime]] |
|[[ceftazidime]] |
||
|0.6% |
|||
| |
| |
||
| |
|- |
||
| rowspan="3" |[[carbapenems]] |
|||
|overall |
|||
|20% |
|||
|30% |
|||
|- |
|||
|imipenem |
|||
| |
| |
||
| |
|14% |
||
|- |
|- |
||
|meropenem |
|||
| rowspan="2" |Cephamycins |
|||
|5 to 25% |
|||
|[[cephamycins]] |
|||
|39% |
|||
|- |
|||
|[[aminoglycosides]] |
|||
|overall |
|||
|20% |
|||
| |
| |
||
| |
|- |
||
| rowspan="4" |[[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% |
|||
| |
| |
||
|NO |
|||
|- |
|- |
||
|[[linezolid]] |
|||
|Carbapenems |
|||
|90% |
|||
|[[imipenem]] |
|||
| |
| |
||
| |
|||
|- |
|||
|[[metronidazole]] |
|||
| |
| |
||
| |
| |
||
| |
|87% |
||
|- |
|- |
||
|[[rifamycins]] |
|||
|Aminoglycosides |
|||
|[[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% |
|||
| |
| |
||
|NO |
|||
|- |
|- |
||
|[[valacyclovir]] |
|||
|Fluoroquinolones |
|||
|19% |
|||
| |
| |
||
|- |
|||
|[[foscarnet]] |
|||
| |
| |
||
|27 to 43% |
|||
|NO? |
|||
|23 to 66% |
|||
|- |
|||
| rowspan="4" |HIV antiretrovirals |
|||
|[[abacavir]] |
|||
|35% |
|||
| |
| |
||
|YES |
|||
|- |
|- |
||
|[[zidovudine]] |
|||
|Lincosamides |
|||
|75% |
|||
|[[clindamycin]] |
|||
| |
| |
||
| |
|- |
||
|[[indinavir]] |
|||
|6 to 15% |
|||
| |
| |
||
|YES |
|||
|- |
|- |
||
|[[lopinavir]] |
|||
|Macrolides |
|||
|29% |
|||
| |
| |
||
|- |
|||
! colspan="4" |Antifungals |
|||
|- |
|||
| |
| |
||
|[[flucytosine]] |
|||
|NO |
|||
| |
| |
||
|74% |
|||
|- |
|||
| rowspan="2" |[[azoles]] |
|||
|[[fluconazole]] |
|||
| |
| |
||
|86% |
|||
|- |
|- |
||
|[[voriconazole]] |
|||
|Nitroimidazoles |
|||
|[[metronidazole]] |
|||
| |
| |
||
|46% |
|||
|- |
|||
|[[polyenes]] |
|||
|[[amphotericin B]] |
|||
| |
| |
||
|low |
|||
|- |
|||
! colspan="4" |Antiparasitics |
|||
|- |
|||
| |
|||
|[[albendazole]] |
|||
|38 to 43% |
|||
| |
| |
||
|YES |
|||
|- |
|- |
||
| rowspan="2" |Tetracyclines |
|||
|[[tetracyclines]] |
|||
| |
| |
||
|[[praziquantel]] |
|||
|NO |
|||
|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 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 |
|||
|[[doxycycline]] |
|||
|- |
|||
| rowspan="3" |[[penicillins]] |
|||
|[[ampicillin]] |
|||
| |
| |
||
|below MIC in non-inflamed rabbit eyes |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|||
|[[amoxicillin]] |
|||
| |
| |
||
|2% (below MIC) in non-inflamed rabbit eyes |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|||
|[[piperacillin]] |
|||
| |
| |
||
|undetectable in inflamed human eyes |
|||
|YES |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|- |
||
| rowspan="4" |[[cephalosporins]] |
|||
|Chloramphenicol |
|||
|[[ |
|[[cefazolin]] |
||
| |
| |
||
|above MIC in inflamed rabbit eyes |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|||
|[[ceftriaxone]] |
|||
| |
| |
||
|4% in non-inflamed human eyes |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|||
|[[ceftazidime]] |
|||
| |
| |
||
|30% in inflamed rabbit eyes |
|||
|YES |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|- |
||
|[[cefipime]] |
|||
! colspan="6" |Antifungals |
|||
| |
|||
|8% in non-inflamed human eyes |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|- |
||
| rowspan="2" |[[carbapenems]] |
|||
|Azoles |
|||
|[[imipenem]] |
|||
| |
|||
|8 to 10% in non-inflamed human eyes |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|||
|[[meropenem]] |
|||
| |
|||
|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 |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|||
| |
|||
|[[daptomycin]] |
|||
| |
|||
|30% in inflamed human eyes |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|||
| rowspan="2" |[[aminoglycosides]] |
|||
|[[amikacin]] |
|||
| |
|||
|below MIC in inflamed rabbit eyes |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|||
|[[gentamicin]] |
|||
| |
|||
|below MIC in inflamed rabbit eyes |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|||
| rowspan="3" |[[fluoroquinolones]] |
|||
|[[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 |
|||
|[[CiteRef::brockhaus2019re]] |
|||
|- |
|||
! colspan="5" |Antifungals |
|||
|- |
|||
| rowspan="4" |[[azoles]] |
|||
|[[fluconazole]] |
|[[fluconazole]] |
||
|40 to 50% |
|||
|40 to 50% |
|||
|[[CiteRef::suzuki2008oc]][[CiteRef::felton2014ti]] |
|||
|- |
|||
|[[itraconazole]] |
|||
| |
| |
||
|10% in inflamed eyes |
|||
|[[CiteRef::felton2014ti]] |
|||
|- |
|||
|[[posaconazole]] |
|||
| |
| |
||
|20% in inflamed eyes |
|||
|[[CiteRef::felton2014ti]] |
|||
|- |
|||
|[[voriconazole]] |
|||
| |
|||
|40 to 100% |
|||
|[[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 |
|||
| |
|||
|- |
|||
| |
|||
|[[valacyclovir]] |
|||
| |
|||
|20 to 30%, above IC in non-inflamed human eyes |
|||
|[[CiteRef::huynh2008vi]] |
|||
|- |
|||
| |
|||
|[[ganciclovir]] |
|||
| |
|||
|close to IC |
|||
| |
|||
|- |
|||
| |
| |
||
|[[foscarnet]] |
|||
|YES |
|||
|100% |
|||
|10%, close to IC |
|||
|[[CiteRef::lópez-cortés2000in]] |
|||
|} |
|} |
||
[[Category:Antimicrobials]] |
[[Category:Antimicrobials]] |
||
Latest revision as of 17:51, 19 September 2024
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
- ^ Tomasz Jodlowski, Charles R Ashby, Sarath G Nath. Doxycycline for ESBL-E Cystitis. Clinical Infectious Diseases. 2020. doi:10.1093/cid/ciaa1898.
- 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.
- ^ 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.
- ^ 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.
