Tissue penetration of antimicrobials: Difference between revisions

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==Summary==
 
{| class="wikitable"
  
{| class="wikitable"
 
!Class
  
!Class
Line 4: Line 5:
 
!Blood
  
!Blood
 
!CNS
  
!CNS
  +
!Vitreous
 
!Urine
  
!Urine
  +
!Prostate
 
!Necrotic
  
!Necrotic
 
|-
  
|-
−
! colspan="6" |Antibiotics
 +
! colspan="8" |Antibiotics: β-Lactams
 
|-
  
|-
−
| rowspan="2" |Penicillins
 +
| rowspan="3" |[[Penicillins]]
 
|β-lactamase inhibitors
  
|β-lactamase inhibitors
  +
| style="text-align:center" |
  +
| style="text-align:center" |–
  +
| style="text-align:center" |
  +
| style="text-align:center" |
  +
| style="text-align:center" |
  +
| style="text-align:center" |
  +
|-
  +
|[[ampicillin]]
  +
| style="text-align:center" |
  +
| style="text-align:center" | +
  +
| style="text-align:center" |±
  +
| style="text-align:center" |
  +
| style="text-align:center" |
  +
| style="text-align:center" |–
  +
|-
  +
|[[piperacillin-tazobactam]]
  +
| 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="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" |–
  +
|-
  +
|second-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" |
  +
|-
  +
|third-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" |
  +
|-
  +
|[[ceftriaxone]]
  +
|
  +
| +
  +
|
 
|
  
|
−
|NO
  
 
|
  
|
 
|
  
|
 
|-
  
|-
−
|[[ampicillin]]
 +
|[[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" |
  +
| style="text-align:center" |
  +
|-
  +
|[[cefoxitin]]
  +
| 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" |[[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" | +
  +
|-
  +
|[[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
  +
|-
  +
|[[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="3" |Cephalosporins
  
  +
|[[fosfomycin]]
−
|first- and second-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" |±<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]]
−
|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" |
 
|-
  
|-
−
|[[cefepime]]
  
 
|
  
|
  +
|[[foscarnet]]
  +
| 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<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>
  +
|-
  +
| 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]]
 
|
  
|
 
|
  
|
−
|YES
 +
|-
  +
|[[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%
  +
|
 
|-
  
|-
 
|[[ceftazidime]]
  
|[[ceftazidime]]
  +
|0.6%
 
|
  
|
−
|YES
 +
|-
  +
| rowspan="3" |[[carbapenems]]
  +
|overall
  +
|20%
  +
|30%
  +
|-
  +
|imipenem
 
|
  
|
−
|YES
 +
|14%
 
|-
  
|-
  +
|meropenem
−
| rowspan="2" |Cephamycins
  
  +
|5 to 25%
−
|[[cephamycins]]
  
  +
|39%
  +
|-
  +
|[[aminoglycosides]]
  +
|overall
  +
|20%
 
|
  
|
−
|NO
 +
|-
  +
| 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%
 
|-
  
|-
−
|[[cefoxitin]]
 +
|[[macrolides]]
  +
|[[clarithromycin]]
 
|
  
|
  +
|18%
  +
|-
  +
|[[tetracyclines]]
  +
|[[doxycycline]]
  +
|20%
  +
|20%
  +
|-
  +
|[[fosfomycin]]
 
|
  
|
  +
|18%
 
|
  
|
−
|NO
  
 
|-
  
|-
  +
|[[linezolid]]
−
|Carbapenems
  
  +
|90%
−
|[[imipenem]]
  
 
|
  
|
 
|
  
|
  +
|-
  +
|[[metronidazole]]
 
|
  
|
−
|YES
 +
|
  +
|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]]
  
 
|
  
|
−
|NO
 +
|-
  +
|[[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
  
−
|[[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 10:55, 1 November 2023

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 ± +†
ceftriaxone +
cefepime +
ceftazidime + ± +
Cephamycins cephamycins –
cefoxitin –
Carbapenems imipenem +
meropenem + + +
Antibiotics: Non-β-Lactams
Aminoglycosides –
Chloramphenicol chloramphenicol +
Fluoroquinolones all –? + +
moxifloxacin –
Fosfomycin fosfomycin +
Lincosamides clindamycin – +
Lipopeptides daptomycin + – +
Macrolides macrolides – +
Nitrofurans nitrofurantoin – – – + – –
Nitroimidazoles metronidazole +
Oxazolidinones linezolid + + + ±‡
Rifamycins rifampin +
Sulfonamides trimethoprim-sulfamethoxazole +
Tetracyclines tetracyclines – +
doxycycline ±[1] + +
Antivirals
acyclovir / valacyclovir +
ganciclovir +
foscarnet
Antifungals[2]
Azoles fluconazole + + + ± +
itraconazole ± – + –
voriconazole ± ± ±
Echinocandins anidulafungin + ± – ±
caspofungin + – – ±
micafungin ± – ±
Polyenes deoxycholate amphotericin B – +
liposomal amphotericin B – ±† +
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 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

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
  1. ↑ 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
  2. ↑ 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

  1. ^  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.
  2. 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.
  3. 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.
  4. a b c d e f g h  T. Felton, P. F. Troke, W. W. Hope. Tissue Penetration of Antifungal Agents. Clinical Microbiology Reviews. 2014;27(1):68-88. doi:10.1128/cmr.00046-13.

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