scholarly journals Erratum to: In vitro activity of the novel β-lactamase inhibitor taniborbactam (VNRX-5133), in combination with cefepime or meropenem, against MDR Gram-negative bacterial isolates from China

2020 ◽  
Vol 75 (7) ◽  
pp. 2019-2019
Author(s):  
Xiaojuan Wang ◽  
Chunjiang Zhao ◽  
Qi Wang ◽  
Zhanwei Wang ◽  
Xinyue Liang ◽  
...  
2020 ◽  
Vol 75 (7) ◽  
pp. 1850-1858 ◽  
Author(s):  
Xiaojuan Wang ◽  
Chunjiang Zhao ◽  
Qi Wang ◽  
Zhanwei Wang ◽  
Xinyue Liang ◽  
...  

Abstract Objectives To evaluate in vitro activity of the novel β-lactamase boronate inhibitor taniborbactam (VNRX-5133) combined with cefepime or meropenem against 500 urinary Gram-negative bacilli. Methods Cefepime/taniborbactam and 14 comparators were tested by broth microdilution or agar dilution methods. A total of 450 Enterobacteriaceae and 50 Pseudomonas aeruginosa were selected from 2017 to 2019 based on different β-lactamase-producing or resistance phenotypes. For carbapenem-non-susceptible isolates, the modified carbapenem inactivation method (mCIM), EDTA-CIM (eCIM) and amplification of carbapenemase genes were performed. For NDM-producing isolates and those with cefepime/taniborbactam MICs >8 mg/L, the MICs of meropenem/taniborbactam and/or mutations in PBP3 were investigated. Results Taniborbactam improved cefepime activity with the same efficiency as avibactam improved ceftazidime activity against 66 KPC-2 producers, 30 non-carbapenemase-producing carbapenem-non-susceptible Enterobacteriaceae and 28 meropenem-susceptible P. aeruginosa. However, cefepime/taniborbactam exhibited more potent activity than ceftazidime/avibactam against 56 ESBL-producing, 61 AmpC-producing, 32 ESBL and AmpC co-producing, 87 NDM-producing and 21 MBL-producing Enterobacteriaceae predicted by phenotypic mCIM and eCIM, 82 Enterobacteriaceae that were susceptible to all tested β-lactams and 22 carbapenem-non-susceptible P. aeruginosa. A four-amino acid ‘INYR’ or ‘YRIN’ insertion, with or without a one/two-amino acid mutation in PBP3, may have caused cefepime/taniborbactam MICs >8 mg/L among 96.6% (28/29) of the NDM-5-producing Escherichia coli, which accounted for the majority of isolates with cefepime/taniborbactam MICs >8 mg/L (76.1%, 35/46). Conclusions Taniborbactam’s superior breadth of activity, when paired with cefepime or meropenem, suggests these β-lactam/β-lactamase inhibitor combinations could be promising candidates for treating urinary tract infections caused by ESBL and/or AmpC, KPC or NDM-producing Enterobacteriaceae or P. aeruginosa.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S628-S629
Author(s):  
Bahgat Gerges ◽  
Issam I Raad ◽  
Joel Rosenblatt ◽  
Samuel Shelbume ◽  
Randal Prince ◽  
...  

Abstract Background Fluoroquinolones have been used for infection prevention in patients with cancer (PWC). They are active against many Gram-negative bacilli (GNB) but are less active against Gram-positive organisms (GPO). Quinolone resistance is increasing and many institutions are using combination regimens for antimicrobial prophylaxis. We evaluated the in vitro activity of delafloxacin (DLX), a novel fluoroquinolone, and selected comparators against 560 bacterial isolates from PWC. Methods Isolates were from recent blood cultures. Susceptibility testing and time kill studies (TKS) were performed using CLSI approved methodology. Appropriate ATCC control strains were used. We calculated MIC50, MIC90, MIC ranges and percent susceptibility using FDA breakpoints when available. TKS were performed on 4 streptococcus mitis isolates at concentrations of MIC, 4x MIC, and 8x MIC. Results DLX was more active than ciprofloxacin (CIP) and levofloxacin (LEV) against methicillin-susceptible (MSSA), and resistant (MRSA) S. aureus, coagulase-negative staphylococci (CoNS), and viridans group streptococci (VGS), and had similar activity against beta-hemolytic streptococci. It also had low MICs for Bacillus species (SPP.), Listeria monocytogenes, Micrococcus spp., and Rothia spp. Overall GPO susceptibility was 73% to DLX, 42% to CIP, and 52% to LEV. The activity of DLX against Enterobacterales was similar to CIP and LEV. All 3 agents had moderate activity against Citrobacter spp., and non-MDR P. aeruginosa. Notably, all 3 quinolones had poor activity against E. coli, P. mirabilis, and MDR P. aeruginosa, all common pathogens in PWC. All 3 had low MICs for Acinetobacter spp. DLX and LEV achieved peak bactericidal activity at 6-8 h against all 4 VGS isolates (maximum activity at 8x MIC) but this was not always sustained at 24 h. Table 1. Percent Susceptibility of selected Gram-positive isolates to Delafloxacin, Ciprofloxacin and Levofloxacin Table 2. Percent Susceptibility of selected Gram-negative isolates to Delafloxacin, Ciprofloxacin and Levofloxacin Figure 1. Bactericidal Activity of DLX at 1x , 4x, and 8x MIC against VGS - Time Kill Study Conclusion DLX is more active than CIP and LEV against many GPO from PWC (including S. aureus and VGS), but like these agents there are significant gaps in its coverage against GNB. It is probably not suitable as a single agent for antimicrobial prophylaxis in high-risk PWC. The current practice of combining a quinolone with a beta-lactam probably still represents the best option in PWC who need prophylaxis. Disclosures Kenneth Rolston, MD, Tetraphase Pharmaceuticals (Grant/Research Support)


1999 ◽  
Vol 43 (12) ◽  
pp. 2996-2997 ◽  
Author(s):  
Peter C. Fuchs ◽  
Arthur L. Barry ◽  
Steven D. Brown

ABSTRACT SCH27899, an everninomicin antibiotic, was tested for its in vitro activity against 718 bacterial isolates representing 27 species. TheEnterobacteriaceae and nonenteric gram-negative bacilli were resistant to ≥8.0 μg/ml, but all others were inhibited by ≤1.0 μg/ml. When tested in combination with 17 other antimicrobial agents against 110 strains, SCH27899 demonstrated no significant antagonism or synergy. Consequently, combination therapy is not contraindicated.


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