An in vitro study of ceftazidime and vancomycin concentrations in various fluid media: implications for use in treating endophthalmitis.
OBJECTIVE
To investigate the precipitation process of a mixture of vancomycin and ceftazidime by equilibrium dialysis and determine its subsequent effect on the level of free antibiotics for treatment of endophthalmitis.


METHODS
Concentrations of vancomycin and ceftazidime in an equilibrium dialysis chamber were measured during the equilibrium process by high-performance liquid chromatography. Normal saline (NS), balanced salt solution (BSS), and vitreous were used separately as the medium of dialysis.


RESULTS
Precipitation of ceftazidime occurred at 37 degrees C but not at room temperature and did not affect the pH of the medium. It formed precipitate on its own or when mixed with vancomycin in all the three media of NS, BSS, and vitreous. More precipitation was formed if ceftazidime was initially prepared in BSS than in NS. After 168 hours in the dialysis chambers, ceftazidime prepared in NS precipitated to 54% of that in vitreous, compared with 88% if prepared in BSS. At 48 hours, ceftazidime prepared in NS decreased from an initial concentration of 137.5 to 73.4 microg/mL in vitreous medium and to 6.3 microg/mL if prepared in BSS. Precipitation of vancomycin was negligible.


CONCLUSIONS
Based on this in vitro investigation, ceftazidime precipitates in vitreous at body temperature, regardless of the presence of vancomycin. NS is preferred to BSS as a preparation medium for antibiotics for intravitreal injection, because the extent of ceftazidime precipitation is less. However, due to precipitation, the concentration of free ceftazidime in vitreous may not be sufficiently high for antibacterial activity against most common organisms.
Kwok
Alvin K H
AK
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong, China.
Hui
Mamie
M
Pang
Chi Pui
CP
Chan
Raphael C Y
RC
Cheung
Siu Wai
SW
Yip
Cynthia M S
CM
Lam
Dennis S C
DS
Cheng
Augustine F B
AF
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D001831:Body Temperature; D002442:Ceftazidime / Q000737:chemistry / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000737:chemistry / Q000493:pharmacokinetics*; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D015314:Dialysis Solutions; D004338:Drug Combinations; D004355:Drug Stability; D009877:Endophthalmitis / Q000188:drug therapy* / Q000382:microbiology; D015818:Eye Infections, Bacterial / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009883:Ophthalmic Solutions; D014640:Vancomycin / Q000737:chemistry / Q000493:pharmacokinetics*; D014822:Vitreous Body / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D015314:Dialysis Solutions; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D014640:Vancomycin; D002442:Ceftazidime