Stability of ciindamycin phosphate and ceftizoxime sodium, cefoxitin sodium, cefamandole nafate, or cefazoiin sodium in two intravenous solutions
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Design
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Stability study
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Objective
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To determine the stability and compatibility of clindamycin phosphate with four cephalosporins—ceftizoxime sodium, cefoxitin sodium, cefamandole nafate, and cefazolin sodium—in either 5% dextrose injection or 0.9% sodium chloride injection, and also to determine the stability of each cephalosporin alone
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Methods
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Sterile powder was reconstituted with either 5% dextrose or 0.9% sodium chloride injection and added to a 100-mL glass container, followed by agitation. Antibiotic concentration, pH, and visual appearance were assessed at mixing and at 1, 4, 8, 12, 24, and 48 hours, with all solutions stored at room temperature under fluorescent lighting.
High-performance liquid chromatography (HPLC) was used for antibiotic assays, with drug-specific assays separating the target antibiotic from others and breakdown products. Cefoxitin sodium samples were prepared by adding 200 μL of the test solution to 100 μL of internal standard (cefotaxime sodium 20 mg/mL), vortexing for 15 seconds, and injecting 2 μL onto a C18 reverse-phase column. Elution used a mobile phase of 14% acetonitrile in 0.02M KH2PO4 buffer (pH adjusted to 2.7 with H3PO4), with detection at 254 nm and a flow rate of 1.5 mL/min.
The initial antibiotic concentration was set at 100%, with subsequent concentrations expressed as a percentage of the initial concentration. The analysis involved comparing antibiotic concentrations at each sampling time with those at admixture, noting the time of a 10% or greater decrease in concentration.
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Duration
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48 hours
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Outcome Measures
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Stability of single antibiotic solutions, stability of clindamycin in combination with cefoxitin, stability of cefoxitin in combination with clindamycin |
Results
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Endpoint
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Mean % of initial concentration |
pH change over 48 hours
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Cefoxitin in D5W
1 hr
4 hr
8 hr
12 hr
24 hr
48 hr
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100.0 ± 0.3
101.5 ± 1.4
99.9 ± 2.1
96.9 ± 1.7
100.9 ± 0.8
94.0 ± 4.5
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4.6-6.6 |
Cefoxitin in NS
1 hr
4 hr
8 hr
12 hr
24 hr
48 hr
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101.2 ± 0.7
106.8 ± 0.7
100.8 ± 0.8
99.9 ± 1.7
103.7 ± 3.2
94.1 ± 0.06
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4.4-6.4 |
Stability of clindamycin in combination with cefoxitin
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Admixture |
Mean % of initial concentration |
pH change over 48 hours |
Clindamycin plus cefoxitin in D5W
1 hr
4 hr
8 hr
12 hr
24 hr
48 hr
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103.2 ± 0.0
100.7 ± 3.2
100.9 ± 3.9
100.7 ± 0.6
105.4 ±3.5
103.8 ± 0.4
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6.2-6.2 |
Clindamycin plus cefoxitin in NS
1 hr
4 hr
8 hr
12 hr
24 hr
48 hr
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104.7 ± 0.3
100.9 ± 0.2
101.7 ± 3.1
102.6 ± 1.3
104.3 ± 5.6
107.2 ± 0.3
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5.9-6.0 |
Stability of cefoxitin in combination with clindamycin
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Admixture |
Mean % of initial cefoxitin concentration |
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Cefoxitin and clindamycin in D5W
1 hr
4 hr
8 hr
12 hr
24 hr
48 hr
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99.5 ± 0.4
100.9 ± 0.7
98.5 ± 2.2
99.3 ± 0.9
98.2 ± 2.6
98.8 ± 1.2
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Cefoxitin and clindamycin in NS
1 hr
4 hr
8 hr
12 hr
24 hr
48 hr
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99.9 ± 4.3
97.6 ± 1.6
96.9 ± 3.3
94.7 ± 1.1
99.4 ± 1.7
92.8 ± 0.9
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D5W = 5% dextrose injection and NS = 0.9% sodium chloride injection
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Study Author Conclusions
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Clindamycin is stable for at least 48 hours when mixed with cefoxitin sodium, cefamandole nafate, or cefazolin sodium in either 5% dextrose or 0.9% sodium chloride injections and for at least 24 hours when mixed with ceftizoxime sodium in 0.9% sodium chloride injection. All of the cephalosporins tested are stable alone and in combination with clindamycin for at least 48 hours in the two fluids tested. Administration of clindamycin with any of these antibiotics in the same container could result in considerable cost savings for the hospital.
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InpharmD Researcher Critique
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The study had a relatively short observation period of 48 hours, a small sample size, and an absence of clinical outcome data. Additionally, the potential for interactions over longer durations was not assessed. Furthermore, the criteria used to define stability may not fully reflect clinical significance.
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