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In vitro comparison of ampicillin-chloramphenicol and ampicillin-cefotaxime against 284 Haemophilus isolates
Abstract:
Since November 1982 at the Sainte-Justine Hospital in Montreal, ampicillin and cefotaxime were used in association as initial treatment (greater than or equal to 48 h) for childhood bacterial meningitis. In this report is described the in vitro interaction of the new regimen in comparison with that of the previous ampicillin-chloramphenicol combination against 284 Haemophilus isolates. Among the 156 ampicillin-susceptible, beta-lactamase-negative isolates, synergy was detected in 13 with ampicillin-cefotaxime, and antagonism was detected in only 1; in contrast, synergy was found in only 2 strains with ampicillin-chloramphenicol, and antagonism was found in 15. These differences were statistically significant (P less than 0.01). Such significant differences were not observed among the 128 ampicillin-resistant, beta-lactamase-positive Haemophilus isolates. The synergy of ampicillin-cefotaxime did not contribute to a decrease of the MIC of cefotaxime for 90% of isolates tested, whereas the antagonism of ampicillin-chloramphenicol did not contribute to increase the MIC of ampicillin for 90% of isolates tested.
Insights
The ampicillin-cefotaxime combination showed greater synergy against susceptible bacterial meningitis strains than ampicillin-chloramphenicol. This new regimen offers improved in vitro interaction for treating childhood bacterial meningitis.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Childhood bacterial meningitis treatment has evolved.
- Ampicillin and chloramphenicol was a previous standard treatment.
- Ampicillin and cefotaxime is a newer treatment regimen.
Purpose of the Study:
- To compare the in vitro interaction of ampicillin-cefotaxime with ampicillin-chloramphenicol.
- To evaluate the efficacy against Haemophilus isolates.
Main Methods:
- In vitro susceptibility testing was performed.
- 284 Haemophilus isolates were analyzed.
- Synergy and antagonism were assessed for both drug combinations.
Main Results:
- Ampicillin-cefotaxime demonstrated significantly higher synergy (13/156) and lower antagonism (1/156) against ampicillin-susceptible, beta-lactamase-negative isolates compared to ampicillin-chloramphenicol (synergy 2/156, antagonism 15/156).
- No significant differences in interaction were observed for ampicillin-resistant, beta-lactamase-positive isolates.
- Neither combination significantly altered the minimum inhibitory concentration (MIC) of the primary drug for 90% of isolates.
Conclusions:
- The ampicillin-cefotaxime combination exhibits superior in vitro synergy against susceptible Haemophilus isolates compared to ampicillin-chloramphenicol.
- The findings support the use of ampicillin-cefotaxime as an effective initial treatment for childhood bacterial meningitis.
- Further clinical studies are warranted to confirm these in vitro observations.