Limited treatment options exist to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria possessing broad-spectrum β-lactamases. The design of novel β-lactamase inhibitors is of paramount importance. Here, three novel diazabicyclooctanes (DBOs), WCK 5153, zidebactam (WCK 5107), and WCK 4234 (compounds 1-3, respectively), were synthesized and biochemically characterized against clinically important bacteria. Compound 3 inhibited class A, C, and D β-lactamases with unprecedented k/ K values against OXA carbapenemases. Compounds 1 and 2 acylated class A and C β-lactamses rapidly but not the tested OXAs. Compounds 1-3 formed highly stable acyl-complexes as demonstrated by mass spectrometry. Crystallography revealed that 1-3 complexed with KPC-2 adopted a "chair conformation" with the sulfate occupying the carboxylate binding region. The cefepime-2 and meropenem-3 combinations were effective in murine peritonitis and neutropenic lung infection models caused by MDR Acinetobacter baumannii. Compounds 1-3 are novel β-lactamase inhibitors that demonstate potent cross-class inhibition, and clinical studies targeting MDR infections are warranted.

In adults, lichen planus (LP) is relatively more common than in children. Among 222 cases of LP, there were 25 (11.2%) children in our study. The majority of the cases were females in the age group of 8-14; the youngest child was 3 years old. Papular and linear types of LP were common in children. There was no familial history of LP in any of the cases. The patients with classic LP lesions responded well to dapsone therapy. This study supports the suggestion of Ramsay and Hurley that childhood LP is more common in the tropics.

Multidrug-resistant (MDR) Acinetobacter spp. poses a significant therapeutic challenge in part due to the presence of chromosomally encoded β-lactamases, including class C Acinetobacter-derived cephalosporinases (ADC) and class D oxacillinases (OXA), as well as plasmid-mediated class A β-lactamases. Importantly, OXA-like β-lactamases represent a gap in the spectrum of inhibition by recently approved β-lactamase inhibitors such as avibactam and vaborbactam. ETX2514 is a novel, rationally designed, diazabicyclooctenone inhibitor that effectively targets class A, C, and D β-lactamases. We show that addition of ETX2514 significantly increased the susceptibility of clinical Acinetobacter baumannii isolates to sulbactam. AdeB and AdeJ were identified to be key efflux constituents for ETX2514 in A. baumannii. The combination of sulbactam and ETX2514 was efficacious against A. baumannii carrying blaTEM-1, blaADC-82, blaOXA-23, and blaOXA-66 in a neutropenic murine thigh infection model. We also show that, in vitro, ETX2514 inhibited ADC-7 (k2/Ki 1.0 ± 0.1 × 106 M−1 s−1) and OXA-58 (k2/Ki 2.5 ± 0.3 × 105 M−1 s−1). Cocrystallization of ETX2514 with OXA-24/40 revealed hydrogen bonding interactions between ETX2514 and residues R261, S219, and S128 of OXA-24/40 in addition to a chloride ion occupied in the active site. Further, the C3 methyl group of ETX2514 shifts the position of M223. In conclusion, the sulbactam-ETX2514 combination possesses a broadened inhibitory range to include class D β-lactamases as well as class A and C β-lactamases and is a promising therapeutic candidate for infections caused by MDR Acinetobacter spp. IMPORTANCE The number and diversity of β-lactamases are steadily increasing. The emergence of β-lactamases that hydrolyze carbapenems poses a significant threat to our antibiotic armamentarium. The explosion of OXA enzymes that are carbapenem hydrolyzers is a major challenge (carbapenem-hydrolyzing class D [CHD]). An urgent need exists to discover β-lactamase inhibitors with class D activity. The sulbactam-ETX2514 combination demonstrates the potential to become a treatment regimen of choice for Acinetobacter spp. producing class D β-lactamases.

Fish protein hydrolysates were prepared from Catla catla using different proteases viz. alcalase, bromelain, flavorzyme and protamex and designated as HA (alcalase), HB (bromelain), HF (flavorzyme) and HP (protamex), respectively. HB was found to have higher 2, 2 diphynyl‐1‐picrylhydrazyl (DPPH) free radical‐scavenging activity followed by HF, HP and HA. HB had higher ferric‐reducing power followed by HP, HF and HA. Linoleic acid peroxidation inhibition of HA, HB, HF and HP were 54 ± 4.75, 50 ± 2.60, 49 ± 3.00 and 36 ± 6.15%, respectively. Higher emulsion stability index and foaming capacity were recorded for HB. The emulsion activity index was higher in HP (52.76 ± 1.27 m2/g). The foaming stability was found to be good in HF. Practical Application The properties of fish protein hydrolysates from Catla catla using different enzymes have been studied. The protein hydrolysates prepared from C. catla can be used as antioxidant and functional ingredient in the processed food products. Among four different enzymes used, bromelain was effective in obtaining the protein hydrolysate with desired antioxidant and functional properties. The potential to use bromelain for hydrolysate preparation is high considering the abundance of pineapples in southern India.