Penetration of cefuroxime into chronically inflamed sinus mucosa.
OBJECTIVE
Despite its seeming relevance, limited information exists about antibiotic sinus tissue penetration and how it is affected by inflammation. Thus the reason for the present investigation.


METHODS
A randomized, open, multiple-dose, pharmacological study, employing cefuroxime axetil, an approved oral antimicrobial for the treatment of acute bacterial rhinosinusitis, was developed.


METHODS
Twenty subjects, selected for surgery because of chronic rhinosinusitis, were randomly allocated to receive either a short (3-8 d) or a long (9-14 d) preoperative treatment regime with 500 mg cefuroxime axetil BID, the last dosage being taken 3 to 4 hours before surgery. At the operation, tissue samples were collected at specific sinonasal sites for both pharmacological determination of antibiotic levels and histopathological assessment of the degree of inflammation. The blood levels of the drug were simultaneously assayed.


RESULTS
Cefuroxime kinetic behavior on chronically inflamed mucosa was shown to be, for the most part, dependent on the blood levels, regardless of the inflammatory state. Distribution was even throughout the different sinus cavities, and the tissue levels were still, 3 to 4 hours after dosing, above the reported minimum inhibitory concentration (MIC) values for some of the most prevalent sinus pathogens. The extended treatment course did not seem to add any extra histopathological or pharmacological benefit.


CONCLUSIONS
Cefuroxime penetrates adequately and uniformly into chronically inflamed sinus mucosa, apparently unaffected by the degree of inflammation, in a way not dissimilar to its pharmacokinetic behavior in the normal state. Persistent MIC levels for common pathogens still warrant antimicrobial efficacy for a significant period of time after dosing.
Dinis
P B
PB
Department of Otorhinolaryngology, Hospital de Pulido Valente, Lisbon, Portugal.
Monteiro
M C
MC
Lobato
R
R
Martins
M L
ML
Gomes
A
A
D000328:Adult; D000368:Aged; D002444:Cefuroxime / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism*; D012220:Rhinitis / Q000378:metabolism*; D012852:Sinusitis / Q000378:metabolism*; D014018:Tissue Distribution
D002511:Cephalosporins; D002444:Cefuroxime; C040738:cefuroxime axetil