Will it be a Survivor to Add Clavulanic Acid to Cephalosporins in Order to Overcome Resistance Problem?

Abstract

Background: Bacterial resistance is closely associated with the use of antimicrobial agents. Prolonged therapy with antibiotics can lead to the development of resistance in a microorganism that initially is sensitive to antibiotics, but later it can adapt gradually and develop resistance to antibiotics. Aims: We reviewed whether clavulanic acid plus cephalosporin combinations help to solve the resistance problem. Methods: We evaluated and reviewed this topic via “Antibiotic Resistance”, “Cephalosporin and β-Lactamase Inhibitor Combinations” and our suggestions. Results: Acquired resistance arises from: (1) mutations in cell genes (chromosomal mutation) leading to cross-resistance, (2) gene transfer from one microorganism to other by plasmids (conjugation or transformation), transposons (conjugation), integrons and bacteriophages (transduction). β-Lactamases hydrolyze nearly all β-lactams that have ester and amide bond, e.g., penicillins, cephalosporins, monobactams, andcarbapenems. Serine β-lactamases –  cephalosporinases, e.g. AmpC enzyme – are found in Enterobacter spp. and P. aeruginosa and penicillases in S. aureus. Amoxicillin-clavulanate resistance (MIC >16 microg/ml) in Escherichia coli is reported previously. Therefore, development of new drugs or combination is necessary for the antimicrobial resistance. To manage the Cephalosporin resistance, Cephalosporin and β-Lactamase Inhibitor Combinations, such as Ceftolozane/tazobactam or Ceftazidime/avibactam have been used. Conclusion: As resistance to cephalosporins have been increasing, cephalosporin + clavulonate combination will be another choice for managing the antibiotic resistance to the cephalosporins. Our suggestion is based on the success of the clavulonate combination of amoxicillin to manage the antibiotic resistance.