scholarly journals 692. In Vitro Antibacterial Activity of Cefiderocol Against a Multi-national Collection of Carbapenem-Nonsusceptible Gram-Negative Bacteria From Respiratory Infections: SIDERO-WT-2014–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S313-S314
Author(s):  
Sonia N Rao ◽  
Sean T Nguyen ◽  
Melinda M Soriano ◽  
Jennifer M Hayes ◽  
Meredith M Hackel ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Respiratory Infections ◽  
Active Agent ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Mueller Hinton ◽  
In Vitro Antibacterial Activity

Abstract Background Cefiderocol (CFDC) is a new siderophore cephalosporin with potent in vitro activity against a broad range of Gram-negative (GN) pathogens, including carbapenem-nonsusceptible (Carb-NS) strains. We evaluated the in vitro activity of CFDC and comparator agents against recent clinical Carb-NS GN respiratory isolates collected from North America and Europe as part of the multi-national SIDERO-WT surveillance program. Methods A total of 2831 Carb-NS GN respiratory isolates collected from 2014 to 2017 were tested centrally (IHMA, Inc., Schaumburg, IL). Minimum inhibitory concentrations (MIC) were determined for CFDC, cefepime (FEP), ceftazidime–avibactam (CZA), ceftolozane-tazobactam (C/T), ciprofloxacin (CIP), colistin (CST), and meropenem (MEM) by broth microdilution and interpreted according to the 2018 CLSI guidelines. CFDC MICs were tested in iron-depleted cation-adjusted Mueller–Hinton broth, and interpreted according to the 2018 CLSI provisional breakpoints. Carb-NS strains were defined as MEM MIC of ≥2 µg/mL for Enterobacteriaceae (ENB) and of ≥4 µg/mL for nonfermenters (NF). Results CFDC exhibited predictable in vitro activity against 2807 clinically relevant Carb-NS GN isolates (214 ENB, 1086 A. baumannii complex, 693 P. aeruginosa, 794 S. maltophilia, and 20 Burkholderia cepacia) isolated from respiratory infections. CFDC was the most active agent against Carb-NS ENB with 97.7% susceptibility followed by 78.0% CZA, 59.4% CST, and 16.4% CIP. Against Carb-NS A. baumannii complex, CFDC demonstrated 94% susceptibility vs. 83.7% for CST. CFDC was the most active agent against Carb-NS P. aeruginosa with 99.9% susceptibility followed by 97.8% CST, 77.6% C/T, and 77.5% CZA. 99.7% of S. maltophilia and 100% of B. cepacia isolates had CFDC MICs of ≤4 µg/mL. The MIC90s of tested compounds for clinically relevant pathogens are shown in the table. Conclusion In a multinational collection of Carb-NS GN respiratory isolates, CFDC demonstrated potent in vitro activity with MIC90 of ≤4 µg/mL for all clinically relevant ENB and NF. These findings suggest that CFDC can be a potential option for the treatment of respiratory infections caused by Carb-NS ENB, A. baumannii complex, P. aeruginosa, S. maltophilia, and B. cepacia. Disclosures All authors: No reported disclosures.

scholarly journals Collective assessment of antimicrobial susceptibility among the most common Gram-negative respiratory pathogens driving therapy in the ICU

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Pamela A Moise ◽  
Marcela Gonzalez ◽  
Irina Alekseeva ◽  
Diego Lopez ◽  
Brune Akrich ◽  
...  
Keyword(s):  
Respiratory Infections ◽  
Vitro Activity ◽  
Surveillance Program ◽  
Antibiotic Prescribing ◽  
Respiratory Pathogens ◽  
In Vitro Activity ◽  
First Line ◽  
Icu Patients ◽  
Gram Negative

Abstract Objectives To describe the pathogen predominance and to evaluate the probability of covering the most common Gram-negative pathogens collectively in both empirical and early adjustment prescribing scenarios in ICU patients with respiratory infections. Methods Data were collected from an international cohort of hospitals as part of the SMART Surveillance Program (2018). Susceptibility testing (mg/L) was performed by broth microdilution methods. Results 7171 Gram-negative respiratory isolates from adult ICU patients across 209 hospitals from 56 different countries were studied. Overall, the most common ICU respiratory pathogens isolated were Pseudomonas aeruginosa (25%), Klebsiella pneumoniae (18%), Acinetobacter baumannii (14%), and Escherichia coli (11%), with inter-regional differences among these pathogens. Among Enterobacterales, 36% were ESBL positive. When the collective susceptibility profile of this set of pathogens (P. aeruginosa plus Enterobacterales; comprising 78% of all organisms isolated) was performed, ceftolozane/tazobactam (84%), followed by meropenem (81%), provided the most reliable in vitro activity in the empirical prescribing scenario compared with other β-lactam antibiotics. P. aeruginosa co-resistance was common among first-line β-lactam antibiotics. If P. aeruginosa was non-susceptible to piperacillin/tazobactam, less than one-third were susceptible to meropenem or ceftazidime. In contrast, ceftolozane/tazobactam offered in vitro coverage in over two-thirds of these resistant pathogens. Conclusions Ceftolozane/tazobactam demonstrated high cumulative susceptibility levels and in vitro activity in both empirical and adjustment antibiotic prescribing scenarios. High frequency of co-resistance undermines reliable coverage for Gram-negative pathogens already resistant to first-line agents. Ceftolozane/tazobactam would offer additional coverage in this setting.

scholarly journals 1375. In vitro Activity of Cefiderocol and Comparator Agents against Gram-Negative Isolates from Cancer Patients

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S421-S422 ◽  
Author(s):  
Kenneth V I Rolston ◽  
Bahgat Gerges ◽  
Issam Raad ◽  
Samuel L Aitken ◽  
Ruth Reitzel ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Active Agent ◽  
Vitro Activity ◽  
Significant Activity ◽  
In Vitro Activity ◽  
Research Support ◽  
Gram Negative ◽  
E Coli ◽  
Research Grant

Abstract Background Gram-negative bacilli (GNB) are now the predominant cause of bacterial infection in cancer patients (CP). Many GNB are problematic because they have become resistant to commonly used antibiotics. Cefiderocol (CFDC), a novel siderophore cephalosporin, is active against a wide spectrum of GNB. We evaluated its in vitro activity and that of eleven comparator agents against GNB isolated from CP. Methods A total of 341 recent GNB blood isolates from CP were tested using CLSI approved methods for MIC determination by broth microdilution. Comparator agents were amikacin (A), aztreonam (AZ), ceftazidime (CZ), ceftazidime/avibactam (CAV), cefepime (CEF), ciprofloxacin (CIP), colistin (CL), meropenem (MR), ceftolozane/tazobactam (C/T), tigecycline (TG), and trimethoprim/sulfamethoxazole (T/S). Results CFDC MIC90s as mg/L were: S. maltophilia [50 isolates] 0.25, E. coli (ESBL−) [50 isolates] 0.5, E. coli (ESBL+) [51 isolates] 2.0, K. pneumoniae (ESBL− and +) [60 isolates] 0.5; K. pneumoniae (CRE) [22 isolates] 2.0; P. aeruginosa (MDR) [32 isolates] 1.0; E. cloacae [27 isolates] 4.0; Achromobacter spp. [15 isolates] 0.12. CFDC inhibited P. agglomerans, Burkholderia spp., Sphingomonas spp., Ochrobactrum spp. at ≤1 mg/L [23 total isolates] and Elizabethkingia spp. and R. radiobacter at ≤8 mg/L [11 total isolates]. Among comparator agents, only T/S had consistent activity against S. maltophilia. For E. coli (ESBL− and +) MR, TG, CAV, CL were most active. For K. pneumoniae (ESBL–and +) MR, CAV were most active. For K. pneumoniae (CRE) and P. aeruginosa (MDR), none of the comparators had significant activity. For E. cloacae, MR, A, CAV, TG were most active. Among the uncommon organisms, MR and TG had the greatest activity. Conclusion Although susceptibility breakpoints have yet to be determined, CFDC has significant activity (≤4 mg/L) against most problematic Gram-negative organisms causing infections in CP based on available pharmacokinetic/pharmacodynamic data. In particular, its activity against S. maltophilia was superior to the comparators. Also, it was the most active agent against P. aeruginosa (MDR) and K. pneumoniae (CRE). Based on our results, CFDC warrants clinical evaluation for the treatment of blood stream infections caused by GNB in CP. Disclosures K. V. I. Rolston, Merck: Investigator, Research grant; JMI Laboratories: Investigator, Research grant; Shionogi (Japan): Investigator, Research grant. B. Gerges, Shionogi: Collaborator, Research support. S. L. Aitken, Shionogi: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Medicines Co: Scientific Advisor, Consulting fee; Achaogen: Scientific Advisor, Consulting fee; Zavante: Scientific Advisor, Consulting fee; R. Prince, Shionogi: Investigator, Research support. Merck: Investigator, Research support.

scholarly journals 1349. Global Surveillance of Cefiderocol Against Gram-Negative Clinical Strains Collected in North America: SIDERO-WT-2015

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S413-S413 ◽  
Author(s):  
Masakatsu Tsuji ◽  
Meredith Hackel ◽  
Roger Echols ◽  
Yoshinori Yamano ◽  
Dan Sahm
Keyword(s):  
North America ◽  
Burkholderia Cepacia ◽  
Dose Range ◽  
The United States ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Wide Range

Abstract Background Cefiderocol (CFDC) is a novel parenteral siderophore cephalosporin with potent activity against a wide range of Gram-negative pathogens, including carbapenem-resistant strains. Additionally, a recently conducted in vivo murine-based study has demonstrated an incremental exposure-response profile over a dose range without the appearance of adaptive resistance. In this study, we evaluated the in vitro activity of CFDC and comparator agents against clinical isolates collected in 2015–2016 from North America from SIDERO-WT-2015 surveillance study. Methods A total of 3,602 isolates (2,470 Enterobacteriaceae, 223 A. baumannii, 85 Acinetobacter spp., 619 P. aeruginosa, 165 S. maltophilia and 17 Burkholderia cepacia, and 23 Burkholderia spp.) collected from the United States and Canada in 2015–2016 were tested. MICs were determined for CFDC, cefepime (FEP), ceftazidime–avibactam (CZA), ceftolozane–tazobactam (C/T), ciprofloxacin (CIP), colistin (CST), and meropenem (MEM) by broth microdilution and interpreted according to CLSI guidelines. As recommended by CLSI, cefiderocol was tested in iron-depleted cation-adjusted Mueller–Hinton broth (ID-CAMHB). Carbapenem nonsusceptible (Carb-NS) strains were defined as MEM MIC ≥2 µg/mL for Enterobacteriaceae, and ≥4 µg/mL for nonfermenters. Results CFDC exhibited potent in vitro activity against 3,602 strains of Gram-negative bacteria with an overall MIC90 of 0.5 mg/mL. As shown in the following table, MIC90 of CFDC against P. aeruginosa, A. baumannii, S. maltophilia, and Enterobacteriaceae including the subset of Carb-NS isolates were 0.5, 2, 0.5 and 0.5 mg/mL, respectively. At 4 mg/mL, CFDC inhibited the growth of 99.6% of the isolates while 18.1%, 12.6%, and 13.8% showed resistance to CZA, C/T, and CST, respectively. Conclusion CFDC demonstrated potent in vitro activity against the teat isolates collected from North America with greater than 99.6% of isolates having MIC values ≤4 mg/mL, including Carb-NS isolates of A. baumannii, P. aeruginosa, and Enterobacteriaceae. These findings indicate that this agent has high potential for treating infections caused by these problematic organisms. Disclosures M. Tsuji, Shionogi & Co., Ltd.: Employee, Salary. M. Hackel, IHMA, Inc.: Employee, Salary. Y. Yamano, Shionogi & Co., Ltd.: Employee, Salary. D. Sahm, IHMA, Inc.: Employee, Salary.

scholarly journals 1595. Comparative In Vitro Activity of Imipenem–Relebactam Against Drug-Resistant Gram-Negative Isolates from Pediatric Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S582-S582
Author(s):  
Dithi Banerjee ◽  
Christopher J Harrison ◽  
Morgan Pence ◽  
Rangaraj Selvarangan
Keyword(s):  
Klebsiella Oxytoca ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Mueller Hinton ◽  
Thermo Fisher Scientific ◽  
Spectrum Activity ◽  
Fisher Scientific

Abstract Background Drug resistance in Gram-negative bacteria is of particular concern in children. Relebactam, a novel diazabicyclooctane inhibitor, coupled with imipenem has broad-spectrum activity against β-lactamase producing organisms. Here, we compare the in vitro activity of imipenem-relebactam to 10 standard comparator drugs against resistant Gram-negative isolates from two US pediatric hospitals. Methods We tested 100 isolates (50 per site) from pediatric clinical specimens tested during 2015–2017. All isolates were extended-spectrum cephalosporin-resistant (ESC-R); more than half were multidrug resistant (67%). Selected ESC-R isolates included Escherichia coli (90), Klebsiella pneumoniae (8), Klebsiella oxytoca (1), and Enterobacter cloacae (1) that were resistant or intermediate to ≥1 cephalosporins and/or aztreonam. A 0.5 McFarland suspension was prepared from colonies grown on blood agar plates (Thermo Scientific) at 35 ± 1°C for 18–24 hours. A final inoculum of 5 × 105 CFU/mL was prepared in Mueller–Hinton broth. Sensititre plates (Thermo Fisher Scientific) containing graded concentrations of imipenem/relebactam and 10 comparator drugs were inoculated and incubated at 35 ± 1°C for 18–24 hours. The minimum inhibitory concentration (MIC) was determined using the Sensititre Vizion system (Thermo Fisher Scientific) and endpoints were interpreted using CLSI (2019) breakpoint criteria, with the exception of colistin (EUCAST 2019). Results Selected ESC-R isolates had high rates of resistance to cephalosporins (64%–97%), aztreonam (80%), and levofloxacin (61%). All isolates were susceptible to imipenem/relebactam, imipenem and meropenem (MIC, ≤1 μg/mL for all). The imipenem/relebactam MIC50 (0.06 μg/mL) and MIC90 (0.12 μg/mL) values for ESC-R isolates were within one dilution of MICs of imipenem alone (0.12 μg/mL and 0.25 μg/mL). Among the comparators, colistin, amikacin, and piperacillin/tazobactam demonstrated comparable activities with 100%, 99%, and 94% susceptibilities, respectively. Conclusion Meropenem, imipenem alone and in combination with relebactam exhibited 100% susceptibilities against ESC-R Enterobacteriaceae isolated from pediatric specimens, demonstrating the high potency of carbapenems. Disclosures All authors: No reported disclosures.

scholarly journals In Vitro Activity of HSR-903, a New Oral Quinolone, against Bacteria Causing Respiratory Infections

1999 ◽  
Vol 43 (7) ◽  
pp. 1767-1768 ◽  
Author(s):  
Akira Watanabe ◽  
Yutaka Tokue ◽  
Hiroshi Takahashi ◽  
Tohru Kikuchi ◽  
Takao Kobayashi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Respiratory Infections ◽  
The Other ◽  
Vitro Activity ◽  
Respiratory Pathogens ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Resistant Strains

ABSTRACT The in vitro activity of HSR-903, an oral quinolone, against 196 recent clinical isolates of respiratory pathogens was evaluated. HSR-903 was 2 to 32 times more active than ofloxacin, ciprofloxacin, and sparfloxacin against Staphylococcus aureus, including methicillin-resistant strains, and Streptococcus pneumoniaeand was at least as active as the other quinolones against gram-negative pathogens.

scholarly journals Analysis of Oritavancin Activity against Gram-Positive Clinical Isolates Responsible for Bacterial Endocarditis in United States and European Hospitals (2008–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S369-S369 ◽  
Author(s):  
Michael A Pfaller ◽  
Helio S Sader ◽  
Dee Shortridge ◽  
Robert K Flamm ◽  
Rodrigo E Mendes
Keyword(s):  
United States ◽  
Active Agent ◽  
Bacterial Endocarditis ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Research Grant

Abstract Background Oritavancin (ORI) has documented in vitro activity against gram-positive (GP) isolates. This study analyzed ORI tested against organisms causing endocarditis in United States (US) and European (EU) sites. Methods A total of 424 organisms recovered from patients with a diagnosis of bacterial endocarditis at US and EU sites during the SENTRY Antimicrobial Surveillance Program (2008–2016) were included (see Table). Isolates were identified by standard biochemical algorithms and MALDI-TOF. Susceptibility (S) testing was performed by CLSI methods, and MICs were interpreted per CLSI and/or EUCAST criteria. Results Among the 424 isolates, 212 (50.0%) were S. aureus (SA; 31.6% methicillin-resistant [MRSA]), 47 (11.1%) were coagulase-negative staphylococci (CoNS), 81 (19.1%) were E. faecalis (EFC), 21 (5.0%) were E. faecium (EFM), 24 (5.7%) were BHS, and 39 (9.2%) were viridans group streptococci (VGS). ORI had similar MIC90 values (0.06 µg/mL) against SA and CoNS, inhibiting 98.8% of these isolates at ≤0.12 µg/mL. ORI MIC50 values were 8- to 32-fold lower than those for vancomycin (VAN), daptomycin (DAP), and ceftaroline (CPT) against staphylococci. ORI showed MICs against EFM (MIC50/90, 0.008/0.03 µg/mL) that were 2-fold lower than against EFC (MIC50/90, 0.015/0.03 µg/mL; 97.5%S against all or 100%S against indicated VAN-S isolates). ORI inhibited 98.0% of all enterococci, including VAN-resistant isolates at ≤0.12 µg/mL. VAN, DAP, ampicillin (MIC50/90, ≤1/2 µg/mL), and linezolid (LZD) (MIC50/90, 1/2 µg/mL) were similarly active against EFC, while DAP and LZD had coverage (100.0%S) against EFM. Overall, BHS were highly S to all agents tested, except for erythromycin (70.8%S) and tetracycline (43.5%S). ORI was the most active agent (MIC90, 0.12 µg/mL) tested against VGS. Conclusion ORI showed potent in vitro activity against isolates recovered from patients with endocarditis in US and EU sites. The data presented here warrant further investigations to determine whether ORI has a role for treating endocarditis. Disclosures M. A. Pfaller, The Medicines Company: Research Contractor, Research grant; H. S. Sader, The Medicines Company: Research Contractor, Research grant; D. Shortridge, The Medicines Company: Research Contractor, Research grant; R. K. Flamm, The Medicines Company: Research Contractor, Research grant; R. E. Mendes, The Medicines Company: Research Contractor, Research grant

scholarly journals In vitro Activity of Cefiderocol Against Gram-Negative Clinical Isolates Collected from Urinary Track Source: SIDERO-WT-2014/SIDERO-WT-2015

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S375-S376 ◽  
Author(s):  
Masakatsu Tsuji ◽  
Meredith Hackel ◽  
Roger Echols ◽  
Yoshinori Yamano ◽  
Dan Sahm
Keyword(s):  
Vitro Activity ◽  
Clinical Isolates ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Mueller Hinton ◽  
The Usa ◽  
Fermenting Bacteria

Abstract Background The global rise of carbapenem resistant Gram-negative bacteria such as carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant non-fermenting bacteria is alarming and become threats to patient as only a few drugs remain active (e.g. colistin). Cefiderocol (S-649266) is a novel parenteral siderophore cephalosporin with potent activity against a wide variety of Gram-negative pathogens including carbapenem-resistant strains. This study evaluated the in vitro activity of cefiderocol and comparator agents against clinical isolates collected from urinary track source from North America. Methods A total of 3,323 Enterobacteriaceae, 263 Acinetobacter spp, 509 Pseudomonas aeruginosa, and 38 Stenotrophomonas maltophilia collected from the USA and Canada in 2014–2016 were tested. MIC was determined for cefiderocol, cefepime (FEP), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), ciprofloxacin (CIP), colistin (CST), and meropenem (MEM) by broth microdilution and interpreted according to CLSI 2016 guidelines. All testing was done at IHMA, Inc. As recommended by CLSI, cefiderocol was tested in iron-depleted cation-adjusted Mueller Hinton broth. Based upon CLSI breakpoints, carbapenem-non-susceptible (CarbNS) strains were defined as follows: MEM: MIC ≥2 µg/mL for Enterobacteriaceae, ≥4 µg/mL for non-fermenters. Quality control testing was performed on each day of testing by using E. coli ATCC25922 and P. aeruginosa ATCC27853. Results Cefiderocol exhibited in vitro activity against 4,133 strains of Gram-negative bacteria with an overall MIC90 of 0.5 µg/mL. At 4 µg/mL cefiderocol inhibited the growth of 99.9% of the all isolates. MIC90 of cefiderocol against CarbNS Enterobacteriaceae was 4 µg/mL although MIC90 of other comparators were >64 or >8 (CST) µg/mL. The cefiderocol MIC90value was 1 µg/mL for CarbNS non-fermeneters. Conclusion Cefiderocol demonstrated potent in vitro activity against Enterobacteriaceae, A. baumannii, P. aeruginosa, and S. maltophilia isolates collected from a UTI source, with greater than 99.9% of isolates having MIC values ≤4 µg/mL. These findings indicate that this agent has high potential for treating cUTI infections caused by these problematic organisms, including isolates resistant to colistin. Disclosures M. Tsuji, Shionogi & Co.: Employee, Salary; M. Hackel, IHMA: Employee, Salary; R. Echols, Shionogi & CO., LTD: Consultant, Consulting fee; Y. Yamano, Shionogi & Co.: Employee, Salary

scholarly journals Activity of Ceftazidime–Avibactam Against Respiratory Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Latin America as Part of the INFORM Global Surveillance Program, 2014–2016

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S379-S379
Author(s):  
Krystyna Kazmierczak ◽  
Mark Estabrook ◽  
Gregory G Stone ◽  
Dan Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Latin America ◽  
Respiratory Infections ◽  
Capital Gains ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Drug Classes ◽  
Tract Infections

Abstract Background The β-lactam/non-β-lactam β-lactamase inhibitor combination ceftazidime-avibactam (CAZ-AVI) is active in vitro against isolates producing class A, C, and some class D β-lactamases, including extended-spectrum β-lactamases, stably derepressed AmpC, and serine carbapenemases. This study evaluated the in vitro activity of CAZ-AVI and comparators against respiratory isolates of Enterobacteriaceae (Eba) and Pseudomonas aeruginosa (Pae) collected in Latin America from 2014–2016 as part of the INFORM surveillance program. Methods Non-duplicate isolates from hospitalized patients with lower respiratory tract infections were collected from 24 medical centers in Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela. Susceptibility (S) testing was performed by broth microdilution and interpreted using CLSI breakpoints except for CAZ-AVI (U.S. FDA) and colistin (EUCAST; Ebaonly). AVI was tested at a fixed concentration of 4 µg/mL with doubling dilutions of CAZ. Multidrug resistance (MDR) phenotype was defined as resistant by CLSI breakpoints to sentinel agents from ≥3 drug classes. Isolates were screened for β-lactamase genes by PCR and sequencing. Results CAZ-AVI showed potent in vitro activity against Eba isolates (MIC90, 0.5 µg/mL; 99.3% S) and against CAZ-non-susceptible (CAZ-NS), colistin-resistant (CST-R) and MDR subsets (>93% S). CAZ-AVI activity against meropenem-non-susceptible (MEM-NS) Eba (89.7% S) was reduced due to production of metallo-β-lactamases (MBL); MEM-NS MBL-negative isolates were 100% S. CAZ-AVI showed greater in vitro activity against Pae isolates (MIC90, 32 µg/mL; 85.4% S) than CAZ (69.2% S) or MEM (59.9% S). CAZ-AVI activity against CAZ-NS, CST-R, MEM-NS, MEM-NS MBL-negative, and MDR Paeisolates (50.4–92.6% S) also exceeded that of CAZ and MEM against these resistant subsets. Conclusion CAZ-AVI is a potential treatment option for respiratory infections in Latin America that are caused by Eba and Pae resistant to commonly used and last-in-line agents. Funding: This study was sponsored by AstraZeneca. The AstraZeneca product ceftazidime-avibactam was acquired by Pfizer in December 2016. Disclosures G. G. Stone, Pfizer: Employee, Salary AstraZeneca: Shareholder, Capital Gains

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