Antibiotics Within the Same Class May Not Be Ideal in Combination Therapy for Bloodstream Infections

Results of a study that assessed the potential efficacy of antibiotic combinations for the treatment of Escherichia coli bloodstream infections found no synergistic effects on isolates. These findings were published in EBioMedicine.

Clinical E coli strains isolated from positive blood cultures from patients treated at the intensive care units of hospitals affiliated with Uppsala University Hospital in Sweden between 2014 and 2017 were used in this study. A total of 500 E coli isolates were tested with 4 pairwise combinations of 2 b-lactam antibiotics (ampicillin [AMP] and cefotaxime [CTX]) with 2 aminoglycosides (gentamicin [GEN] and tobramycin [TOB]). The efficacy of each treatment combination was quantified using the Fractional Inhibitory index (FICi).

Of the 500 isolates, 254 (50.8%) were susceptible to all 4 antibiotics.

Among the susceptible strains, no GEN combination was synergistic (FICi <0.5). For the AMP-GEN combination, 3.14% had additive to synergistic effects (0.5<FICi<1), 95% had additive to antagonistic effects (1<FICi<4), and 1.97% had antagonistic effects (FICi>4). For the CTX-GEN combination, 0.78% were additive to synergistic, 98.03% were additive to antagonistic, and 1.18% were antagonistic.

Similar to the GEN combinations, no TOB combination was synergistic. For the AMB-TOB and CTX-TOB combinations, 6.69% and 10.62% were additive to synergistic, 92.51% and 89.37% were additive to antagonistic, and 0.78% and 0.0% were antagonistic, respectively.

In a principal component analysis, 78% of the variance in the data was explained. This analysis indicated that both TOB and GEN combinations tended to cluster, indicating a potential correlation of effects. In a Spearmen correlation analysis, AMP-GEN and CTX-GEN were 61% correlated (P <.001) and CTX-TOB and AMP-TOB were 46% correlated (P <.001).

Using a time kill assay with a subset of isolates, the antibiotic combinations generally had decreased kill rates compared with the theoretical additive combination of the antibiotics. In 3 of 5 cases, antibiotics did not prevent bacterial resurgence after 24 hours.

This study was limited by not evaluating isolate-stratified mechanisms of resistance.

These data indicated that antibiotic combinations of b-lactam and aminoglycosides may not be a suitable empirical treatment for E coli bloodstream infections, as no combination exhibited a synergistic interaction among the 254 susceptible isolates.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Fatsis-Kavalopoulos N, Roelofs L, Andersson DI. Potential risks of treating bacterial infections with a combination of b-lactam and aminoglycoside antibiotics: A systemic quantification of antibiotic interactions in E. coli blood stream infection isolates. EBioMedicine. 2022;78:103979. doi:10.1016/j.ebiom.2022.103979