Clinical efficacy of novel combinations of older beta-lactam and beta-lactamase inhibitors: Where are the evidences?

India is well known for the rampant growth of ESBLs that jeopardized the clinical utility of standalone betalactam. Pharmaceutical organizations fancied to rescue these beta-lactams by combining them with generic beta-lactamase inhibitors despite such combinations were never investigated in non-clinical or clinical studies. Lack of stringency in regulatory review practices allowed the market entry of these combinations. CSE 1034 (ceftriaxone, sulbactam and EDTA) and cefoperazone sulbactam are the most irrational antibiotics in clinical use. The effectiveness of such combinations relies on multiple factors such as relative beta-lactamase stability of the standalone beta-lactam, the inhibitory potency of the beta-lactamase inhibitor and more importantly the adequacy of the dose incorporated in the formulation. Unfortunately, none of the unconventional BL-BLI inhibitor combinations marketed in India has been subjected to such evaluations. Therefore, their therapeutic utility is uncertain. Besides questionable therapeutic utility, sub-optimal exposures would lead to the selection of resistant clones.