In Vitro Assessment of the Combination of Antibiotics against Some Integron-Harbouring Enterobacteriaceae from Environmental Sources

Abstract

One strategy for combating antimicrobial resistance in many infections is to combine antibacterial compounds to create combinations that outperform each molecule alone. In this study, we examine and study the inhibitory effect of combining two drugs belonging to different antibiotic classes to obtain a possible potentiating effect against some Enterobacteriaceae isolates harbouring integrons recovered from rivers and effluents of hospital and wastewater treatment plants in Eastern Cape Province, South Africa. These integrons could easily enable the isolates to acquire genes that confer additional resistance against conventional antibiotics. The minimum inhibitory concentration of the various antibiotics was determined using the broth microdilution, while the checkerboard method was used to determine the fractional inhibitory concentration indices (FICIs). A total of 26.3% (10/38) of the interactions were categorised as synergistic, while 73.7% (28/38) were indifferent. None of the combinations were antagonistic. The time–kill assays revealed all the synergistic interactions as bactericidal. Therefore, the combinations of gentamicin with tetracycline, ciprofloxacin, and ceftazidime against multidrug-resistant (MDR) Klebsiella pneumoniae, tetracycline–ceftazidime combination against MDR Escherichia coli, colistin combinations with ceftazidime and gentamicin, and tetracycline–gentamicin combinations against MDR Citrobacter freundii may be future therapeutic alternatives. Hence, the synergistic combinations reported in this study must be assessed further in vivo before their clinical applications.

Editorial: Antibiotics Special Issue on Pharmacokinetic/Pharmacodynamic Models of Antibiotics

“…The authors restricted analysis to strains possessing horizontal gene transfer elements to enrich organisms with mobile antibiotic resistance traits. Using checkerboard methodology [ 10 ], Fadare et al [ 11 ] identify combinations that demonstrated synergy and validated those preliminary findings in time–kill curves. Consistently, the simulated combinations outperformed single-agent therapy, resulting in sustained killing to the limit of detection.…”

Artificial intelligence-accelerated high-throughput screening of antibiotic combinations on a microfluidic combinatorial droplet system

“…The FIC indices for the combination of gentamicin/tetracycline, gentamicin/ chloramphenicol and gentamicin/cefepime were determined to be 0.60, 0.63 and 0.60, respectively, suggesting the additive effect of the pairwise antibiotics. In most cases, clinical combination therapy exploits synergistic alliances to achieve higher therapeutic efficacy than either monotherapy, 60 but additive combinations may also be selected for other reasons, like to decrease rates of resistance. 61 The above findings suggested that the AI-HTCDES could provide useful guidance in the clinical use of antibiotic combination therapy.…”

The key constituents underlying the combined toxicity of eight cosmetic contaminants towards Vibrio qinghaiensis

“…This accumulation is a cause for concern, as it has been linked not only to asthma in children but also to disturbances in endocrine secretion and an increased likelihood of carcinogenesis in the human body. [38][39][40] Nevertheless, the impact of BPA, BPS and TBEP on organisms at lower trophic levels in the environment remains uncertain, necessitating further research in this area.…”