scholarly journals 681. In vitro Activity of the β-Lactamase Inhibitor QPX7728 in Combination with Several β-Lactams Against Acinetobacter baumannii (AB) and Pseudomonas aeruginosa (PSA)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S310-S311 ◽  
Author(s):  
Olga Lomovskaya ◽  
Jill Lindley ◽  
Debora Rubio-Aparicio ◽  
Kirk J Nelson ◽  
Mariana Castanheira
Keyword(s):  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Microdilution Method ◽  
Carbapenem Resistant ◽  
Broth Microdilution Method ◽  
Data Representative ◽  
Lactamase Inhibitor

Abstract Background QPX7728 (QPX) is a novel broad-spectrum boron-containing inhibitor of serine- and metallo-β-lactamases (MBLs). We evaluated the in vitro activity of QPX combined with several β-lactams against carbapenem-resistant AB (CRAB) and PSA clinical isolates with varying β-lactam resistance mechanisms. Methods A total of 503 CRAB (meropenem [MEM] MIC ≥8 µg/mL) and 762 PSA clinical isolates were tested by the reference broth microdilution method against β-lactams alone and combined with QPX (4 µg/mL and 8 µg/mL). PSA isolates were selected to represent the normal distribution of MEM, ceftazidime–avibactam (CAZ-AVI), and ceftolozane-tazobactam (TOL-TAZ) resistance according to 2017 surveillance data (representative panel). Additionally, 262 PSA isolates that were either nonsusceptible (NS) to MEM (MIC, ≥4 µg/mL) or to TOL-TAZ (MIC, ≥8 µg/mL), or resistant (R) to CAZ-AVI (MIC, ≥16 µg/mL) (challenge panel) were also tested. Within this 262 strain challenge set, 56 strains carried MBLs and the majority also had nonfunctional OprD. Results Against CRAB, QPX at 4 and 8 µg/mL increased the potency of all β-lactams tested. MEM-QPX was the most potent combination (table) displaying MIC50/MIC90 at 1/8 and 0.5/4 µg/mL with QPX at fixed 4 and 8 µg/mL, respectively. Susceptibility (S) to MEM was restored in >95% of strains. Against the 500 PSA from the representative panel, S for all QPX combinations was >90%. For the challenge panel, TOL-QPX and piperacillin (PIP)-QPX were the most potent combinations, restoring S in 76–77% of strains. TOL-QPX and MEM-QPX or cefepime (FEP)-QPX restored the MIC values to S rates when applying the CLSI breakpoint for the compound alone (comparison purposes only) in ~90% and ~75% of non-MBL-producing strains, respectively, vs. 60–70% for TOL-TAZ and CAZ-AVI. PIP-QPX reduce the MIC values to S values for PIP-TAZ in ~60% of MBL-producing strains vs. 20–30% and 3–7% for other QPX combinations and non-QPX tested combinations, respectively. Conclusion Combinations of QPX with various β-lactam antibiotics displayed potent activity against CRAB and resistant PSA isolates and warrant further investigation. Disclosures All authors: No reported disclosures.

scholarly journals In Vitro Activity of Eravacycline in Combination with Colistin Against Carbapenem-Resistant A. baumannii Isolates

2019 ◽  
Author(s):  
H. Selcuk Ozger ◽  
Tugba Cuhadar ◽  
Serap Suzuk Yildiz ◽  
Zehra Demirbas Gulmez ◽  
Murat Dizbay ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Vitro Activity ◽  
Synergistic Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Similar Activity ◽  
Microdilution Method ◽  
Carbapenem Resistant ◽  
Broth Microdilution Method

AbstractThe synergistic activity of eravacycline in combination with colistin on carbapenem-resistant A.baumannii (CRAB) isolates was evaluated in this study. Minimum inhibitory concentrations (MICs) of eravacycline and colistin were determined by the broth microdilution method. MICs values ranged between 1 to 4 mg and 0,5 to 128 mg/L for eravacycline and colistin, respectively. In-vitro synergy between eravacycline and colistin was evaluated by using the chequerboard methodology. Synergistic activity was found in 10 % of the strains, and additive effect in 20 %. No antagonism was detected. Similar activity was also observed in colistin resistant CRAB isolates. The result of this study indicates that eravacycline and colistin combination may be a potential therapeutic option for the treatment of CRAB related infections.

scholarly journals In vitro activity of thiamphenicol against Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes clinical isolates

2021 ◽  
Vol 23 (1) ◽  
pp. 92-99
Author(s):  
Nataly V. Ivanchik ◽  
Мarina V. Sukhorukova ◽  
Аida N. Chagaryan ◽  
Ivan V. Trushin ◽  
Andrey V. Dekhnich ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Haemophilus Influenzae ◽  
Streptococcus Pyogenes ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Clinical Breakpoints

Objective. To determine in vitro activity of thiamphenicol and other clinically available antimicrobials against clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus pyogenes. Materials and Methods. We included in the study 875 clinical isolates from 20 Russian cities during 2018–2019. Among tested strains, 126 were H. influenzae, 389 – S. pneumoniae, 360 – S. pyogenes. Antimicrobial susceptibility testing was performed using broth microdilution method according to ISO 20776-1:2006. AST results were interpreted according to EUCAST v.11.0 clinical breakpoints. Results. The minimum inhibitory concentrations (MICs) of thiamphenicol did not exceed 2 mg/L for 94.4% of H. influenzae strains (MIC50 and MIC90 were 0.5 and 1 mg/L, respectively). Thiamphenicol was active against 76.9% of ampicillin-resistant H. influenzae strains (MIC of thiamphenicol < 2 mg/L). The MIC of thiamphenicol was in the range of 0.06–2 mg/L for 96.7% of S. pneumoniae strains (MIC50 and MIC90 were 0.5 and 2 mg/L, respectively). The MIC of thiamphenicol for 90.6% of S. pneumoniae strains with reduced susceptibility to penicillin (MIC of penicillin > 0.06 mg/L) did not exceed 2 mg/L. A total of 88.1% of S. pneumoniae strains resistant to erythromycin were highly susceptible to thiamphenicol (MIC < 2 mg/L). The MIC of thiamphenicol did not exceed 8 mg/L for 96.1% of S. pyogenes strains (MIC50 and MIC90 were 2 and 4 mg/L, respectively). Conclusions. Thiamphenicol was characterized by relatively high in vitro activity, comparable to that of chloramphenicol, against tested strains of H. influenzae, S. pneumoniae and S. pyogenes, including S. pneumoniae isolates with reduced susceptibility to penicillin.

scholarly journals In vitro activity of rifabutin against 293 contemporary carbapenem-resistant Acinetobacter baumannii clinical isolates and characterization of rifabutin mode of action and resistance mechanisms

2020 ◽  
Vol 75 (12) ◽  
pp. 3552-3562
Author(s):  
Vincent Trebosc ◽  
Birgit Schellhorn ◽  
Julian Schill ◽  
Valentina Lucchini ◽  
Jacqueline Bühler ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Mode Of Action ◽  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Oral Drug ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
The Usa

Abstract Background Rifabutin, an oral drug approved to treat Mycobacterium avium infections, demonstrated potent activity against Acinetobacter baumannii in nutrient-limited medium enabled by rifabutin cellular uptake through the siderophore receptor FhuE. Objectives To determine rifabutin in vitro activity and resistance mechanisms in a large panel of A. baumannii isolates. Methods Two hundred and ninety-three carbapenem-resistant A. baumannii clinical isolates collected from Europe, the USA and Asia during 2017–19 were used for MIC determination. Sequencing/genotyping of fhuE, rpoB and arr-2 genes in isolates with elevated rifabutin MIC combined with genetic engineering and gene expression quantification was used to characterize rifabutin’s mode of action and resistance mechanisms. Results Rifabutin showed excellent activity on the strain panel, with an MIC50/90 of 0.008/1 mg/L, and was superior to all other antibiotics tested, including colistin, tigecycline and cefiderocol (MIC90 of 8 mg/L). Rifabutin remained active on resistant subpopulations, including strains resistant to the siderophore–drug conjugate cefiderocol (MIC90 of 2 mg/L, n = 23). At least two independent resistance mechanisms were required to abolish rifabutin activity, which is in line with the dose-dependent mutational resistance frequency reaching 10−9 at rifabutin concentrations at or above 2 mg/L. Conclusions This study demonstrated the potent activity of rifabutin against carbapenem-resistant A. baumannii. We propose that FhuE-mediated active uptake of rifabutin enables activity against rifampicin-resistant isolates. To achieve clinically meaningful strain coverage and to avoid rapid resistance development, rifabutin concentrations ≥2 mg/L are required, something rifabutin oral formulations cannot deliver.

scholarly journals 1279. In Vitro Activity of Nacubactam (OP0595) Alone and in Combination with β-Lactams against β-Lactamase-Producing Enterobacterales Isolated in Japan

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S655-S655
Author(s):  
Yu Nagira ◽  
Keiko Yamada ◽  
Hayato Okade ◽  
Nami Senju ◽  
Yuko Tsutsumi ◽  
...  
Keyword(s):  
Enzyme Stability ◽  
Antimicrobial Effect ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Microdilution Method ◽  
Class D ◽  
Broth Microdilution Method ◽  
Time Kill ◽  
Lactamase Inhibitor

Abstract Background Nacubactam (NAC) is a novel serine β-lactamase inhibitor in clinical development, and inhibits Ambler class A, class C, and some class D β-lactamases. In addition, it has penicillin-binding protein (PBP) 2-dependent antibacterial activity and an ‘enhancer’ effect when combined with β-lactams bound to PBP3. This study assessed the in vitro activity of NAC alone and in combination with β-lactams against IMP-type metallo-β-lactamase-producing and ESBL-producing Enterobacterales isolated in Japan. Methods The MICs for the clinical isolates in Japan were determined and time kill studies were performed. IMP and ESBL genes were detected by PCR. The MICs were determined by broth microdilution method following CLSI methodology. β-lactams and NAC were tested as a ratio of 1:1. Time kill profiles were also studied according to CLSI methodology. Results The MIC50/MIC90s of NAC alone against 112 IMP-producing Enterobacterales and 154 ESBL-producing Enterobacterales were 2/ &gt;32 and 2/8 mg/L, respectively. Regarding the MICs of cefepime (FEP)/NAC and aztreonam (ATM)/NAC against IMP-producing isolates, the MIC90s were 2 and 1 mg/L and the MIC ranges were 0.06 - 32 and 0.06 - 4 mg/L, respectively. The MIC90s of FEP/NAC and ATM/NAC against ESBL-producing isolates were 0.5 and 1 mg/L. These MIC90s of β-lactam/NAC against IMP-producing and ESBL-producing isolates were significantly lower than those of β-lactam alone (&gt;128 mg/L). The highest MIC of ATM/NAC against IMP-producing isolates was lower than that of FEP/NAC. In addition, bactericidal activities of β-lactam/NAC were observed at the lower concentration of β-lactam compared to that of β-lactam alone. Conclusion NAC in combination with β-lactams showed excellent in vitro activities against not only ESBL-producing Enterobacterales but also IMP-producing Enterobacterales isolated in Japan. ATM/NAC tended to show higher antimicrobial effect against IMP-producing isolates by the enzyme stability of ATM. These results support the complex activities of NAC which works as a β-lactamase inhibitor, an antibacterial agent and also an enhancer when combined with β-lactams. Furthermore, these will be useful for selecting a partner β-lactam for NAC. Disclosures Yu Nagira, MS, Meiji Seika Pharma Co., Ltd. (Employee) Keiko Yamada, BS, Meiji Seika Pharma Co., Ltd. (Employee) Hayato Okade, Ph.D, Meiji Seika Pharma Co., Ltd. (Employee) Nami Senju, BS, Meiji Seika Pharma Co., Ltd. (Employee) Yuko Tsutsumi, MS, Meiji Seika Pharma Co., Ltd. (Employee) Yuji Tabata, Ph.D, Meiji Seika Pharma Co., Ltd. (Employee)

scholarly journals 1044. In vitro Activity of Tebipenem Against Relevant Clinical Isolates in the Presence of Pulmonary Surfactant

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S614-S614
Author(s):  
S J Ryan Arends ◽  
Abby L Klauer ◽  
Nicole Cotroneo ◽  
Ian A Critchley ◽  
Rodrigo E Mendes
Keyword(s):  
Pulmonary Surfactant ◽  
Positive Control ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Tract Infections ◽  
Research Grant

Abstract Background Tebipenem (TBP) is an orally administered broad-spectrum carbapenem antibiotic under development for the treatment of acute pyelonephritis and complicated urinary tract infections. This study evaluated the effect of bovine pulmonary surfactant (BPS) on the in vitro activity of TBP and ertapenem (ETP) against a recent collection of clinical isolates. Methods A total of 10 isolates recovered from patients with infections in 2018 were tested for antimicrobial susceptibility to TBP and ETP in the absence or presence of 1%, 5%, or 10% BPS (Infasurf; ONY Biotech). These isolates included the following species: C. freundii, E. cloacae, E. coli, H. influenzae, H. parainfluenzae, K. pneumoniae, methicillin-susceptible S. aureus, M. catarrhalis, S. pneumoniae, and S. pyogenes. Isolates were tested with the appropriate broth microdilution method for each organism as specified by CLSI. For most organisms, MICs were determined in cation-adjusted Mueller-Hinton broth (CAMHB). CAMHB was supplemented with 2.5-5% lysed horse blood for streptococci and Haemophilus Test Medium broth for Haemophilus spp. Daptomycin (DAP) was tested against S. aureus ATCC 29213 as a positive control. Results All isolates displayed TBP MIC values ranging from ≤0.004 to 0.06 mg/L in media without BPS. There were no observed MIC increases &gt;2-fold in the presence of BPS. 4 of the 10 isolates displayed slightly higher (≥4-fold) ETP than TBP MIC values. The ETP MIC values ranged from 0.015-0.25 mg/L in media without BPS. Similarly, there were no observed instances of a &gt;2-fold shift toward lower potency in the presence of BPS. For both TBP and ETP, MIC endpoint values were easily determined, except for in the case of the 2 Haemophilus strains growing in the presence of 5% or 10% BPS. For these conditions, resazurin was added to establish an MIC value. The MIC values found with this method did not differ from the MIC values found in either HTM media or HTM media with 1% BPS. As expected, the addition of BPS shifted DAP S. aureus MIC values to &gt;8 mg/L for all 3 BPS concentrations. Conclusion TBP displayed potent activity against all isolates tested, as all observed MIC values were ≤0.06 mg/L. The addition of BPS to the testing medium did not affect the in vitro MIC values of TBP or ETP against these species. Disclosures S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Abby L. Klauer, n/a, Cidara Therapeutics, Inc. (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Nicole Cotroneo, Spero Therapeutics (Employee, Shareholder) Ian A. Critchley, Ph.D., Spero Therapeutics (Employee, Shareholder) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)

scholarly journals 1280. In-Vitro Activity of Cefiderocol, Imipenem/Relebactam, & Ceftazidime/Avibactam in Ceftolozane/Tazobactam Resistant Strains of Multidrug Resistant Pseudomonas aeruginosa

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S655-S655
Author(s):  
Daniel Navas ◽  
Angela Charles ◽  
Amy Carr ◽  
Jose Alexander
Keyword(s):  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Resistance Testing ◽  
Clinical Samples ◽  
In Vitro Activity ◽  
Carbapenemase Gene ◽  
Resistant Strains

Abstract Background The activity of imipenem/relebactam (I/R), ceftazidime/avibactam (CZA) and cefiderocol (FDC) were evaluated against clinical isolates of multidrug resistant (MDR) strains of P. aeruginosa which was resistant to ceftolozane/tazobactam (C/T). The recent increase of MDR P. aeruginosa strains isolated from clinical samples has prompted research and development of new antimicrobials that can withstand its multiple resistance mechanisms. C/T is an effective option for treatment of MDR P. aeruginosa in our facility with only 10% of resistance in MDR strains, but the emergence of resistance may occur due to the presence of a carbapenemase gene or an ampC mutation. Methods Antimicrobial susceptibility testing for C/T Etest® (bioMérieux, Inc.) were performed on all MDR strains initially screened by the VITEK2® (bioMérieux, Inc.). 10% (n=20) of all MDR isolates were resistant to C/T by the CLSI 2019 breakpoints. These resistant isolates were tested for presence of a carbapenemase gene using the GeneXpert CARBA-R (Cepheid®) PCR and against CZA Etest® (bioMérieux, Inc.) I/R gradient strips (Liofilchem®) and FDC broth microdilution (Thermo Scientific™ Sensititre™). Results A total of 20 clinical isolates of MDR P. aeruginosa resistant to C/T were tested following standardized CLSI protocols and techniques. All 20 isolates were screened for the presence of a carbapenemase gene (blaVIM, blaNDM, blaKPC, blaOXA-48, blaIMP). A blaVIM gene was detected in 6 (30%) out of 20 isolates. FDC demonstrated the greatest activity with 85% (n=17) of susceptible isolates (CLSI MIC &lt;4µg/dL). CZA (CLSI MIC &lt;8µg/dL) and I/R (FDA MIC &lt;2µg/dL) showed 15% (n=3) and 10% (n=2) of susceptible isolates respectively. FDC was active against all 6 blaVIM isolates, where all 6 strains were resistant to CZA and I/R as expected. 3 isolates tested non-susceptible against FDC; additional characterization was not performed at this time. Conclusion Based on these results, FDC demonstrated the greatest in-vitro activity against C/T resistant strains of MDR P. aeruginosa. FDC also demonstrated activity against all 6 MDR P. aeruginosa carrying blaVIM gene. FDC is a strong option to consider on MDR P. aeruginosa strains based on a resistance testing algorithm and a cost/effective protocol. Disclosures All Authors: No reported disclosures

scholarly journals 1366. In Vitro and In Vivo Activity of Cefiderocol against Stenotrophomonas maltophilia Clinical Isolates

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S418-S418 ◽  
Author(s):  
Akinobu Ito ◽  
Merime Ota ◽  
Rio Nakamura ◽  
Masakatsu Tsuji ◽  
Takafumi Sato ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Systemic Infection ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Infection Model ◽  
In Vitro Activity ◽  
In Vivo Efficacy ◽  
Broth Microdilution Method

Abstract Background Cefiderocol (S-649266, CFDC) is a novel siderophore cephalosporin against Gram-negatives, including carbapenem (CR)-resistant strains. Its spectrum includes both the Enterobacteriaceae but also nonfermenters, including Stenotrophomonas maltophilia—an opportunistic pathogen with intrinsic resistance to carbapenem antibiotics. In this study, in vitro activity and in vivo efficacy of CFDC and comparators against S. maltophilia were determined. Methods MICs of CFDC and comparators (trimethoprim/sulfamethoxazole (TMP/SMX), minocycline (MINO), tigecycline (TGC), ciprofloxacin (CPFX), cefepime (CFPM), meropenem (MEPM), and colistin (CL)) were determined by broth microdilution method as recommended by CLSI. The MIC against CFDC was determined using iron-depleted cation-adjusted Mueller–Hinton broth. In vivo efficacy of CFDC, CFPM, ceftazidime–avibactam (CAZ/AVI), MEPM, and CL was evaluated using neutropenic murine systemic infection model caused by strain SR21970. The 50% effective doses (ED50s) were calculated by the logit method using the survival number at each dose 7 days after infection. Results MIC90 of CFDC and comparators against the 216 clinical isolates from global countries collected in SIDERO-CR 2014/2016 study are shown in the table. CFDC, TMP/SMX, MINO, and TGC showed good activity with MIC90 of 0.5, 0.25/4.75, 1, and 2 µg/mL, respectively. CFDC, MINO, and TGC inhibited growth of all tested strains at ≤1, ≤4, and ≤8 µg/mL although two strains showed resistance to TMP/SMX. MICs of CFPM, CAZ/AVI, MEPM, and CL were ≥32 µg/mL. The ED50 of CFDC against S. maltophilia SR21970 with MIC of 0.125 mg/mL was 1.17 mg/kg/dose. Conversely, MICs of CFPM, CAZ/AVI, MEPM/CS, and CL against SR21970 were 32 μg/mL or higher, and ED50s were &gt;100 mg/kg/dose, showing that CFDC had potent in vivo efficacy against S. maltophilia strain which was resistant to other antibiotics. Conclusion CFDC showed potent in vitro activity against S. maltophilia, including TMP/SMX-resistant isolates. CFDC also showed potent in vivo efficacy reflecting in vitro activity against S. maltophilia in murine systemic infection model. Disclosures A. Ito, Shionogi & Co., Ltd.: Employee, Salary. M. Ota, Shionogi & Co., Ltd.: Employee, Salary. R. Nakamura, Shionogi & Co., Ltd.: Employee, Salary. M. Tsuji, Shionogi & Co., Ltd.: Employee, Salary. T. Sato, Shionogi & Co., Ltd.: Employee, Salary. Y. Yamano, Shionogi & Co., Ltd.: Employee, Salary.

scholarly journals 598. In Vitro Activity of Aztreonam in Combination with Ceftazidime–Avibactam, Amoxicillin–Clavulanate, and Piperacillin–Tazobactam vs. NDM-Producing Escherichia coli and Klebsiella pneumoniae Clinical Isolates

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S281-S281
Author(s):  
Andrew Walkty ◽  
James Karlowsky
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Disk Diffusion ◽  
In Vitro Activity ◽  
Zone Diameter ◽  
Amoxicillin Clavulanate ◽  
Lactamase Inhibitor

Abstract Background There are limited options available for the treatment of infections caused by Enterobacteriaceae that produce an NDM metallo-β-lactamase. The purpose of this study was to compare the in vitro activity of aztreonam in combination with three different β-lactam/β-lactamase inhibitors (ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin–tazobactam) vs. NDM-positive Enterobacteriaceae clinical isolates. Methods Seven Escherichia coli and three Klebsiella pneumoniae clinical isolates (all NDM-positive by PCR) were included in this study. The in vitro activities of ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin–tazobactam, and aztreonam were determined by disk diffusion as described by CLSI. For synergy testing, disks containing a β-lactamase inhibitor (ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin tazobactam) were applied to Mueller–Hinton agar plates inoculated with the test organisms, and the plates were incubated for 1 hour. The disks were then removed and aztreonam disks were dropped on the previous disk sites. The plates were then incubated as per standard CLSI recommendations for disk diffusion testing. Results All ten isolates demonstrated phenotypic resistance to aztreonam, amoxicillin-clavulanate, and piperacillin–tazobactam, and eight were resistant to ceftazidime–avibactam (CLSI breakpoints). The zone diameter observed for aztreonam in combination with ceftazidime–avibactam was greater than for either antimicrobial on its own for nine isolates. Seven isolates (70%) had susceptibility to aztreonam restored (zone diameter ≥21 mm) in the presence of avibactam. Aztreonam in combination with amoxicillin-clavulanate demonstrated in increase in zone diameter for all isolates relative to the zone for each antimicrobial alone, but only two (20%) had aztreonam susceptibility restored. Aztreonam susceptibility was not restored for any of the isolates in combination with piperacillin–tazobactam. Conclusion Of the three β-lactam/β-lactamase inhibitor-aztreonam combinations evaluated, ceftazidime–avibactam plus aztreonam demonstrated the greatest in vitro activity vs. NDM-producing Enterobacteriaceae. Disclosures All authors: No reported disclosures.

In vitro activity of a novel antibacterial agent, levonadifloxacin, against clinical isolates collected in a prospective, multicentre surveillance study in India during 2016–18

2019 ◽  
Vol 75 (3) ◽  
pp. 600-608 ◽  
Author(s):  
Boppe Appalaraju ◽  
Sujata Baveja ◽  
Shrikala Baliga ◽  
Suchitra Shenoy ◽  
Renu Bhardwaj ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Tertiary Care ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Surveillance Study ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
In Vitro Activity ◽  
Broth Microdilution Method

Abstract Background Levonadifloxacin is a novel antibiotic belonging to the benzoquinolizine subclass of fluoroquinolones with potent activity against MRSA and quinolone-resistant Staphylococcus aureus. IV levonadifloxacin and its oral prodrug alalevonadifloxacin have recently been approved in India for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) including diabetic foot infections. Objectives To investigate the in vitro activity of levonadifloxacin against contemporary clinical isolates collected from multiple tertiary care hospitals across India in the Antimicrobial Susceptibility Profiling of Indian Resistotypes (ASPIRE) surveillance study. Methods A total of 1376 clinical isolates, consisting of staphylococci (n = 677), streptococci (n = 178), Enterobacterales (n = 320), Pseudomonas aeruginosa (n = 140) and Acinetobacter baumannii (n = 61), collected (2016–18) from 16 tertiary hospitals located across 12 states in India, were included in the study. The MICs of levonadifloxacin and comparator antibiotics were determined using the reference agar dilution method and broth microdilution method. Results Levonadifloxacin exhibited potent activity against MSSA (MIC50/90: 0.5/1 mg/L), MRSA (MIC50/90: 0.5/1 mg/L) and levofloxacin-resistant S. aureus (MIC50/90: 1/1 mg/L) isolates. Similarly, potent activity of levonadifloxacin was also observed against CoNS including MDR isolates (MIC50/90: 1/2 mg/L). Against Streptococcus pneumoniae, levonadifloxacin (MIC50/90: 0.5/0.5 mg/L) showed superior activity compared with levofloxacin (MIC50/90: 1/2 mg/L). Among levofloxacin-susceptible Enterobacterales, 80.6% of isolates were inhibited at ≤2 mg/L levonadifloxacin. Conclusions Levonadifloxacin displayed potent activity against contemporary MRSA and fluoroquinolone-resistant staphylococcal isolates, thus offering a valuable IV as well as an oral therapeutic option for the treatment of ABSSSIs. Furthermore, levonadifloxacin exhibited a broad-spectrum activity profile as evident from its activity against streptococci and levofloxacin-susceptible Gram-negative isolates.

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