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 >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 >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 >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 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 Cefepime-Zidebactam (WCK 5222) Activity Tested against Gram-negative Organisms Causing Bloodstream Infections Worldwide

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S374-S375 ◽  
Author(s):  
Helio S Sader ◽  
Mariana Castanheira ◽  
Jennifer M Streit ◽  
Leonard R Duncan ◽  
Robert K Flamm
Keyword(s):  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Asia Pacific ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Research Grant

Abstract Background Zidebactam (ZID), a bicyclo-acyl hydrazide, is a β-lactam enhancer with a dual mechanism of action involving selective and high binding affinity to Gram-negative (GN) PBP2 and β-lactamase inhibition. We evaluated the in vitro activity of cefepime (FEP) combined with ZID against GN organisms causing bloodstream infections (BSI) in hospitals worldwide. Methods A total of 2,094 isolates from 105 medical centers were evaluated. Isolates were collected from Europe (1,050), USA (331), Latin America (LA; 200) and the Asia-Pacific region (AP; 393) in 2015, and China (120) in 2013 by the SENTRY Program. Susceptibility (S) testing was performed by reference broth microdilution method against FEP-ZID (1:1 ratio) and comparators. The collection included 1,809 Enterobacteriaceae (ENT), 170 P. aeruginosa (PSA) and 115 Acinetobacter spp. (ASP). Results FEP-ZID was very active against ENT (MIC50/90 of ≤0.03/0.12 μg/mL) with 99.9 and 100.0% of isolates inhibited at ≤4/4 and ≤8/8 μg/mL, respectively, and retained potent activity against carbapenem-resistant (CRE; n = 44; MIC50/90, 1/4 μg/mL), multidrug-resistant (MDR), and extensively drug-resistant (XDR) isolates (Table). Amikacin (AMK; MIC50/90, 2/4 μg/mL; 97.7% S) was also very active against ENT, and colistin (COL; MIC50/90, 0.12/>8 μg/mL) inhibited only 87.3% of isolates at ≤2 μg/mL. FEP-ZID was highly active against PSA, including isolates resistant to other antipseudomonal β-lactams, MDR (MIC50/90, 4/8 μg/mL) and XDR (MIC50/90, 4/8 μg/mL) isolates. Among the comparators, COL (MIC50/90 of ≤0.5/1 μg/mL; 100.0% S) and AMK (MIC50/90, 4/16 μg/mL; 91.2% S) were the most active agents against PSA. FEP-ZID (MIC50/90, 16/32 μg/mL) was 4-fold more active than FEP against ASP. Conclusion FEP-ZID (WCK 5222) exhibited potent in vitro activity against a large worldwide collection of GN isolates from BSI, including MDR and XDR isolates. These results support further clinical development of WCK 5222 for treating BSI. Disclosures H. S. Sader, Wockhardt Bio Ag: Research Contractor, Research grant; M. Castanheira, Wockhardt Bio Ag: Research Contractor, Research grant; J. M. Streit, Wockhardt Bio Ag: Research Contractor, Research grant; L. R. Duncan, Wockhardt Bio Ag: Research Contractor, Research grant; R. K. Flamm, Wock: Research Contractor, Research support

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 1054. Activity of a Anti-staphylococcal Lysin, LSVT-1701: In vitro Susceptibility of Staphylococcus aureus and Coagulase-Negative Staphylococci (CoNS) Global Clinical Isolates (2002 to 2019)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S618-S619
Author(s):  
David Huang ◽  
Helio S Sader ◽  
Paul R Rhomberg ◽  
Katyna Borroto-Esoda ◽  
Eric Gaukel
Keyword(s):  
The United States ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Asia Pacific ◽  
In Vitro Activity ◽  
Coagulase Negative Staphylococci ◽  
Medical Centers ◽  
Broth Microdilution Method ◽  
Research Grant

Abstract Background LSVT-1701, formerly SAL200, is a novel, recombinantly-produced, bacteriophage-encoded lysin that specifically targets staphylococci via cell wall enzymatic hydrolysis. We reported the in vitro activity of LSVT-1701 against clinical isolates of S. aureus and coagulase-negative staphylococci (CoNS) collected worldwide. Methods LSVT-1701 and comparators were tested against 415 S. aureus (n=315) and CoNS (n=100) clinical isolates expressing various resistance phenotypes. The isolates were collected in 2002-2019 from medical centers located in the United States (50 medical centers; 174 isolates; 41.9% overall), Europe (37 medical centers; 140 isolates; 33.7% overall), Asia-Pacific region (15 medical centers; 55 isolates; 13.3% overall), and Latin America (12 medical centers; 46 isolates; 11.1% overall). These isolates originated mostly from the year 2019 (n=323).The isolates were susceptibility tested by the CLSI broth microdilution method. MIC interpretations were based on CLSI and EUCAST criteria where available. Results LSVT-1701 was highly active against S. aureus and CoNS isolates with MIC90 values of 2 mg/L for all S. aureus, methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and CoNS (Table). The highest LSVT-1701 MIC values were 4 and 8 mg/L among S. aureus and CoNS, respectively. LSVT-1701 retained potent activity against S. aureus isolates showing resistance or decreased susceptibility to oxacillin, vancomycin, teicoplanin, telavancin, linezolid, daptomycin, ceftaroline, or lefamulin; MIC50 values ranged from 0.5 to 1 mg/L and MIC90 values ranged from 1 to 4 mg/L among S. aureus resistant subsets. Summary of LSVT-1701 activity against S. aureus, CoNS and resistant subsets Conclusion LSVT-1701 demonstrated potent in vitro activity against contemporary clinical isolates of S. aureus and CoNS collected from medical centers worldwide and against resistant S. aureus isolates with uncommon resistance phenotypes. The results of this study support further clinical development of LSVT-1701 to treat staphylococcal infections. Disclosures David Huang, MD, PhD, Lysovant (Consultant) Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support, Contract no. HHSO100201600002C)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) Paul R Rhomberg, Cidara Therapeutics, Inc. (Research Grant or Support)Pfizer, Inc. (Research Grant or Support) Katyna Borroto-Esoda, PhD, Lysovant (Consultant) Eric Gaukel, BS, Lysovant (Employee)

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.

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.

scholarly journals In vitro activity of a new echinocandin, LY303366, compared with those of amphotericin B and fluconazole against clinical yeast isolates.

1997 ◽  
Vol 41 (5) ◽  
pp. 1156-1157 ◽  
Author(s):  
O Uzun ◽  
S Kocagöz ◽  
Y Cetinkaya ◽  
S Arikan ◽  
S Unal
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method

The in vitro activity of LY303366, a new echinocandin derivative, was evaluated with 191 yeast isolates by a broth microdilution method. The MICs at which 50% of the isolates were inhibited were 0.125 microg/ml for Candida albicans and C. tropicalis, 0.25 microg/ml for C. krusei, C. kefyr, and C. glabrata, and 2.0 microg/ml for C. parapsilosis.

scholarly journals In vitro activity of the trinem sanfetrinem (GV104326) against gram-positive organisms.

1996 ◽  
Vol 40 (9) ◽  
pp. 2142-2146 ◽  
Author(s):  
K V Singh ◽  
T M Coque ◽  
B E Murray
Keyword(s):  
Staphylococcus Aureus ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Gentamicin Resistance ◽  
High Level

The in vitro activity of the trinem sanfetrinem (formerly GV104326) (GV) was compared with that of vancomycin, ampicillin, and/or nafcillin against 287 gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and multiresistant enterococci, by the agar and microbroth dilution methods. GV demonstrated 2 to 16 times more activity than ampicillin and nafcillin against the majority of these organisms. The MIC range of GV was 16 to 64 micrograms/ml for 19 Enterococcus faecium strains that were highly resistant to ampicillin (ampicillin MIC range, 64 to 512 micrograms/ml) and vancomycin resistant and 0.25 to 32 micrograms/ml for resistant Rhodococcus spp. Similar activities (+/-1 dilution) were observed by either the agar or the broth microdilution method. GV demonstrated bactericidal activity against a beta-lactamase-producing Enterococcus faecalis strain and against two methicillin-susceptible Staphylococcus aureus strains in 10(5)-CFU/ml inocula. Synergy between GV and gentamicin was observed against an E. faecalis strain that lacked high-level gentamicin resistance. The activity of GV suggests this compound warrants further study.

scholarly journals In Vitro Activity of Meropenem-Vaborbactam against Clinical Isolates of KPC-Positive Enterobacteriaceae

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Meredith A. Hackel ◽  
Olga Lomovskaya ◽  
Michael N. Dudley ◽  
James A. Karlowsky ◽  
Daniel F. Sahm
Keyword(s):  
Clinical Isolates ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Content Type ◽  
Class A ◽  
Microdilution Method ◽  
Fixed Concentration ◽  
Broth Microdilution Method ◽  
The U.S

ABSTRACT Vaborbactam (formerly RPX7009) is a novel inhibitor of serine β-lactamases, including Ambler class A carbapenemases, such as KPCs. The current study evaluated the in vitro activity of the combination agent meropenem-vaborbactam against a global collection of 991 isolates of KPC-positive Enterobacteriaceae collected in 2014 and 2015 using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method. The MIC90 of meropenem (when tested with a fixed concentration of 8 μg/ml of vaborbactam) for isolates of KPC-positive Enterobacteriaceae was 1 μg/ml, and MIC values ranged from ≤0.03 to >32 μg/ml; 99.0% (981/991) of isolates had meropenem-vaborbactam MICs of ≤4 μg/ml, the U.S. FDA-approved MIC breakpoint for susceptibility to meropenem-vaborbactam (Vabomere). Vaborbactam lowered the meropenem MIC50 from 32 to 0.06 μg/ml and the MIC90 from >32 to 1 μg/ml. There were no differences in the activity of meropenem-vaborbactam when the isolates were stratified by KPC variant type. We conclude that meropenem-vaborbactam demonstrates potent in vitro activity against a worldwide collection of clinical isolates of KPC-positive Enterobacteriaceae collected in 2014 and 2015.

Sign in / Sign up

Export Citation Format

Share Document