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An in vitro study of ceftazidime and vancomycin concentrations in various fluid media: implications for use in
Alvin K H Kwok1, Mamie Hui, Chi Pui Pang
1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong, China.
Purpose:
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.
Insights
Ceftazidime precipitates in the vitreous at body temperature, impacting antibiotic levels for endophthalmitis treatment. Normal saline is a preferred preparation medium over BSS, though concentrations may remain insufficient for efficacy.
Area of Science:
- Ophthalmology
- Pharmacology
- Infectious Diseases
Background:
- Endophthalmitis requires effective antibiotic treatment.
- Intravitreal injections of vancomycin and ceftazidime are common treatment strategies.
- Antibiotic stability and concentration in the vitreous humor are critical for therapeutic success.
Purpose of the Study:
- To investigate the precipitation of vancomycin and ceftazidime mixtures using equilibrium dialysis.
- To determine the effect of precipitation on free antibiotic levels in the vitreous.
- To evaluate different preparation media for intravitreal antibiotic injections.
Main Methods:
- Equilibrium dialysis was employed to study antibiotic precipitation.
- High-performance liquid chromatography (HPLC) measured antibiotic concentrations.
- Normal saline (NS), balanced salt solution (BSS), and vitreous were used as dialysis media at 37°C and room temperature.
Main Results:
- Ceftazidime precipitated at 37°C in NS, BSS, and vitreous, both alone and with vancomycin.
- Precipitation was more extensive when ceftazidime was prepared in BSS compared to NS.
- After 168 hours, ceftazidime in NS showed 54% precipitation in vitreous compared to 88% in BSS; vancomycin precipitation was negligible.
Conclusions:
- Ceftazidime precipitates in the vitreous at body temperature, irrespective of vancomycin presence.
- Normal saline is a more suitable preparation medium than BSS to minimize ceftazidime precipitation.
- The resulting free ceftazidime concentrations may be sub-therapeutic for common endophthalmitis pathogens.