QPX7728 is a novel β-lactamase inhibitor (BLI) that belongs to a class of cyclic boronates. The first member of this class, vaborbactam, is a BLI in the recently approved Vabomere (meropenem-vaborbactam). In this paper we provide the overview of the biochemical, structural and microbiological studies that were recently conducted with QPX7728. We show that QPX7728 is an ultra-broad-spectrum β-lactamase inhibitor with the broadest spectrum of inhibition reported to date in a single BLI molecule; in addition to potent inhibition of clinically important serine β-lactamases, including Class A and D carbapenemases from Enterobacterales and notably, diverse Class D carbapenemases from Acinetobacter, it also inhibits many metallo β-lactamases. Importantly, it is minimally affected by general intrinsic resistance mechanisms such as efflux and porin mutations that impede entry of drugs into gram-negative bacteria. QPX7728 combinations with several intravenous (IV) β-lactam antibiotics shows broad coverage of Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa, including strains that are resistant to other IV β-lactam-BLI combinations, e.g., ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam and imipenem-relebactam that were recently approved for clinical use. Based on studies with P. aeruginosa, different partner β-lactams in combination with QPX7728 may be optimal for the coverage of susceptible organisms. This provides microbiological justification for a stand-alone BLI product for co-administration with different β-lactams. QPX7728 can also be delivered orally; thus, its ultra-broad β-lactamase inhibition spectrum and other features could be also applied to oral QPX7728-based combination products. Clinical development of QPX7728 has been initiated.
To review the susceptibility of bacterial isolates to ceftazidime and vancomycin isolated from patients with endophthalmitis. Microbiology records of patients with endophthalmitis between June 2010 and May 2013 were reviewed. Vitreous and AC fluids obtained from patients with endophthalmitis were subjected to direct microscopy examination and culture. Antibiotic susceptibility of the isolates was performed by Kirby Bauer disk diffusion method. Resistant to ceftazidime in Gram negative bacteria (GNB) by disk diffusion method is confirmed by minimum inhibitory concentration using E test. Culture was positive for bacteria/Fungi in 224/356 patients (62.9 %). Out of 224 patients, 191 (85.2 %) patients showed bacterial growth and 33 (14.0 %) showed fungal growth. Mixed bacterial infection was seen in five patients. Among the GNB, 23/123 (18 %) of the isolates were resistant to ceftazidime, and all the Gram positive bacteria 73/73 (100 %) were susceptible to vancomycin. Sixteen of 123 (13 %) GNB were resistant to amikacin. Although there is an increase in resistance to ceftazidime compared to amikacin in GNB, amikacin intravitreal injection is associated with macular toxicity and no single antibiotic has full coverage for all GNB. Combination of vancomycin and ceftazidime empiric therapy can be continued in patients with suspected endophthalmitis and treatment is modified based on clinical response and susceptibility results.
We describe two cases with epiretinal membrane (ERM) from uncontrolled gliosis seen after multilayered inverted internal limiting membrane (ILM) flap technique for full thickness macular hole (FTMH). Two patients with FTMH who had undergone surgery with inverted ILM flap technique were examined by serial optical coherence tomography scans to evaluate the course of multilayered ILM flaps seen as foveal hyperreflective lesions postoperatively. We observed excessive uncontrolled gliosis over these hyperreflective ILM flaps with ERM formation, along with worsening metamorphopsia and best-corrected visual acuity. Case 1 underwent a repeat surgery for ERM. We report excessive uncontrolled gliosis as a rare complication of multilayered inverted ILM flap technique for FTMH.
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Ophthalmic Surg Lasers Imaging Retina
. 2021;52:663–665.]
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