New β-Lactam–β-Lactamase Inhibitor Combinations

Yahav, Dafna; Giske, Christian G.; Grāmatniece, Alise; Abodakpi, Henrietta; Tam, Vincent H.; Leibovici, Leonard

doi:10.1128/cmr.00115-20

Cited by 321 publications

(300 citation statements)

References 297 publications

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“…Among them three inhibitors are now approved or in phase 3, avibactam (belonging to diazibyciclooctanone DBO), relebactam (DBO), and vaborbactam (boronic acid derivative) ( 182 ). Avibactam, formerly NXL-104, in combination with ceftazidime, proved its efficacy against class A, C, and some class D but not against class B β-lactamases ( 183 ). Among rare carbapenemases, avibactam demonstrated efficacy against CTX-M-33-, GES-5-, SME-2-producing isolates ( 42 , 184 ).…”

Section: β-Lactamase Inhibitors and Rare Carbapenemasesmentioning

confidence: 99%

“…However, this combination has limited activity against class B (NDM-, VIM-, or IMP-producing isolates) and class D (OXA-48-like-producing isolates) ( 191 ). Relebactam demonstrated inhibition toward KPC-, SHV-, CTX-M-,TEM-, or class C-β-lactamases but exhibited moderate inhibition against OXA-48-like ( 183 ). However, it has been observed that, despite activity against class A carbapenemases such as KPC, relebactam does not inhibit SME-4 enzyme ( 192 ).…”

Section: β-Lactamase Inhibitors and Rare Carbapenemasesmentioning

confidence: 99%

“…A GES-20-producing K. pneumoniae resistant to imipenem-relebactam was also reported ( 193 ). Cefepime-enmetaozactam, formerly AAI101, demonstrated activity against ESBLs- or AMPc-producing isolates but limited activity toward KPC- and VIM-producing isolates ( 183 ). No data regarding its activity against minor carbapenemase is available.…”

Section: β-Lactamase Inhibitors and Rare Carbapenemasesmentioning

confidence: 99%

“…Zidebactam (formerly WCK 5107) exhibited activity against class A and B carbapenemases and moderate inhibition activity OXA-23/-40/-58-producing A. baumannii ( 194 ). Noticeably, zidebactam also inhibits PBP2 and thus possess intrinsic antibacterial activity ( 183 ). Among minor carbapenemases, cefepime/zidebactam demonstrated activity against a GES-18-producing isolate ( 194 ).…”

Section: β-Lactamase Inhibitors and Rare Carbapenemasesmentioning

confidence: 99%

“…Among minor carbapenemases, cefepime/zidebactam demonstrated activity against a GES-18-producing isolate ( 194 ). Nacubactam, formerly FPI-1465, demonstrated in vitro inihibition against class A, C, and some class D β-lactamases ( 183 ). As observed for zidebactam, Nacubactam demonstrated affinity to PBP2 and thus also exhibited activity toward MBL-producing isolates ( 188 ).…”

Section: β-Lactamase Inhibitors and Rare Carbapenemasesmentioning

confidence: 99%

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Genetic Diversity, Biochemical Properties, and Detection Methods of Minor Carbapenemases in Enterobacterales

et al. 2021

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Gram-negative bacteria, especially Enterobacterales, have emerged as major players in antimicrobial resistance worldwide. Resistance may affect all major classes of anti-gram-negative agents, becoming multidrug resistant or even pan-drug resistant. Currently, β-lactamase-mediated resistance does not spare even the most powerful β-lactams (carbapenems), whose activity is challenged by carbapenemases. The dissemination of carbapenemases-encoding genes among Enterobacterales is a matter of concern, given the importance of carbapenems to treat nosocomial infections. Based on their amino acid sequences, carbapenemases are grouped into three major classes. Classes A and D use an active-site serine to catalyze hydrolysis, while class B (MBLs) require one or two zinc ions for their activity. The most important and clinically relevant carbapenemases are KPC, IMP/VIM/NDM, and OXA-48. However, several carbapenemases belonging to the different classes are less frequently detected. They correspond to class A (SME-, Nmc-A/IMI-, SFC-, GES-, BIC-like…), to class B (GIM, TMB, LMB…), class C (CMY-10 and ACT-28), and to class D (OXA-372). This review will address the genetic diversity, biochemical properties, and detection methods of minor acquired carbapenemases in Enterobacterales.

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Section: β-Lactamase Inhibitors and Rare Carbapenemasesmentioning

confidence: 99%

Section: β-Lactamase Inhibitors and Rare Carbapenemasesmentioning

confidence: 99%

Section: β-Lactamase Inhibitors and Rare Carbapenemasesmentioning

confidence: 99%

Section: β-Lactamase Inhibitors and Rare Carbapenemasesmentioning

confidence: 99%

Section: β-Lactamase Inhibitors and Rare Carbapenemasesmentioning

confidence: 99%

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Genetic Diversity, Biochemical Properties, and Detection Methods of Minor Carbapenemases in Enterobacterales

et al. 2021

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Clinical characteristics and pathogen analysis of bronchoalveolar lavage fluid in elderly patients with community‐acquired pneumonia

Guo

Zhang

Zhu

et al. 2023

Immunity Inflam & Disease

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Objective To analyze the clinical characteristics and bronchoalveolar lavage fluid pathogens in elderly patients with community‐acquired pneumonia (CAP). Methods This was a retrospective observational epidemiological study using that elderly cases diagnosed with community‐acquired pneumonia receiving treatment at the Affiliated Hospital of North China University of Technology, Tangshan Hongci Hospital and Tangshan Fengnan District Hospital of Traditional Chinese Medicine. A total of 92 cases were divided into two groups according to age. There were 44 patients over 75‐year‐old and 48 patients between 65 and 74‐year‐old. Results Compared with the elderly 65 to 74‐year‐old, the elderly over 75‐year‐old with diabetes are more likely to suffer from CAP (35.42% vs. 63.64%, p = 0.007) and are more likely to have mixed infections (6.25% vs. 22.73%, p = 0.023) or larger lesions (45.83% vs. 68.18%, p = 0.031). Their hospital stays will also be extended (39.58% vs. 63.64%, p = 0.020), and the albumin level (37.51 ± 8.92 vs. 30.93 ± 6.58, p = 0.000), the neutrophils level (9.09(6.26–10.63) vs. 7.18(5.35–9.17),p = 0.026) is significantly lower and the d‐dimer (505.42 ± 197.12 vs. 611.82 ± 195.85, p = 0.011), PCT (0.08 ± 0.04 vs. 0.12 ± 0.07, p = 0.001) levels are significantly higher. Conclusion The clinical symptoms and signs of elderly CAP patients are not so typical, and the infection is more serious. Attention should therefore be paid to elderly patients. Hypoalbuminemia and high d‐dimer can predict the prognosis of patients.

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Re‐Imagining Drug Discovery using Mass Spectrometry

Cooks

Feng

Huang

et al. 2023

Israel Journal of Chemistry

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It is argued that each of the three key steps in drug discovery, (i) reaction screening to find successful routes to desired drug candidates, (ii) scale up of the synthesis to produce amounts adequate for testing, and (iii) bioactivity assessment of the candidate compounds, can all be performed using mass spectrometry (MS) in a sequential fashion. The particular ionization method of choice, desorption electrospray ionization (DESI), is both an analytical technique and a procedure for small‐scale synthesis. It is also highly compatible with automation, providing for high throughput in both synthesis and analysis. Moreover, because accelerated reactions take place in the secondary DESI microdroplets generated from individual reaction mixtures, this allows either online analysis by MS or collection of the synthetic products by droplet deposition. DESI also has the unique advantage, amongst spray‐based MS ionization methods, that complex buffered biological solutions can be analyzed directly, without concern for capillary blockage. Here, all these capabilities are illustrated, the unique chemistry at droplet interfaces is presented, and the possible future implementation of DESI‐MS based drug discovery is discussed.

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New β-Lactam–β-Lactamase Inhibitor Combinations

Cited by 321 publications

References 297 publications

Genetic Diversity, Biochemical Properties, and Detection Methods of Minor Carbapenemases in Enterobacterales

Genetic Diversity, Biochemical Properties, and Detection Methods of Minor Carbapenemases in Enterobacterales

Clinical characteristics and pathogen analysis of bronchoalveolar lavage fluid in elderly patients with community‐acquired pneumonia

Re‐Imagining Drug Discovery using Mass Spectrometry

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