scholarly journals 706. In Vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against MDR Enterobacteriaceae and Pseudomonas aeruginosa Collected in Latin America During the ATLAS Global Surveillance Program 2016–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S318-S319
Author(s):  
Sibylle Lob ◽  
Krystyna Kazmierczak ◽  
Gregory Stone ◽  
Daniel F Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Latin America ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Effective Treatment Option ◽  
Class D ◽  
Inhibitor Combination ◽  
In Vitro Data

Abstract Background Ceftazidime–avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination that can inhibit class A, C and some class D β-lactamases. Resistance caused by these β-lactamases often results in multidrug-resistance (MDR). This study evaluated the in vitro activity of CAZ-AVI and comparators against MDR Enterobacteriaceae and Pseudomonas aeruginosa isolates collected from patients in Latin America. Methods Nonduplicate clinical isolates were collected in 2016–2017 in 6 countries in Latin America. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2019 and FDA (tigecycline) breakpoints. MDR was defined as nonsusceptible (NS) (intermediate or resistant) to ≥3 of 7 sentinel drugs: amikacin, aztreonam, cefepime, levofloxacin, colistin, meropenem, and piperacillin–tazobactam. Results The activity of CAZ-AVI and comparators against all isolates and MDR subsets is shown in the table. MDR rates ranged from 28.4% among E. cloacae to 41.5% among K. pneumoniae. CAZ-AVI was active against >97% of Enterobacteriaceae isolates and maintained activity against >92% of MDR isolates of the examined species. No other tested drug consistently exceeded this activity. Among P. aeruginosa, CAZ-AVI was active against 87% of all isolates and 63% of MDR isolates; only colistin was more active. The two most common MDR phenotypes among Enterobacteriaceae were (1) NS to aztreonam, cefepime, and levofloxacin (n = 580, 41% of all MDR Enterobacteriaceae; 100% susceptible to CAZ-AVI) and (2) NS to aztreonam, cefepime, levofloxacin, and piperacillin–tazobactam (n = 301, 21% of all MDR isolates; 99.7% susceptible to CAZ-AVI). The two most common MDR phenotypes among P. aeruginosa were (1) NS to all sentinel drugs except colistin (n = 154, 33% of all MDR isolates; 30.5% susceptible to CAZ-AVI) and (2) NS to all drugs except colistin and amikacin (n = 97, 21% of all MDR isolates; 70.1% susceptible to CAZ-AVI). Conclusion These in vitro data suggest that CAZ-AVI can be an effective treatment option for infections caused by MDR Enterobacteriaceae and P. aeruginosa collected in Latin America. Disclosures All authors: No reported disclosures.

scholarly journals 1244. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against MDR Enterobacterales and Pseudomonas aeruginosa Collected in Latin America During the ATLAS Global Surveillance Program 2018-2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S711-S711
Author(s):  
Sibylle Lob ◽  
Meredith Hackel ◽  
Gregory Stone ◽  
Daniel F Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Latin America ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Effective Treatment Option ◽  
Independent Contractor ◽  
Class D ◽  
In Vitro Data

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination that can inhibit class A, C, and some class D β-lactamases. Resistance caused by these β-lactamases often results in multidrug-resistance (MDR). This study evaluated the in vitro activity of CAZ-AVI and comparators against MDR Enterobacterales and Pseudomonas aeruginosa isolates collected from patients in Latin America. Methods Non-duplicate clinical isolates were collected in 2018-2019 in 10 countries in Latin America. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin (AMK), aztreonam (ATM), cefepime (FEP), colistin (CST), levofloxacin (LVX), meropenem (MEM), and piperacillin-tazobactam (TZP). Results The activity of CAZ-AVI and comparators against all isolates and MDR subsets is shown in the table. MDR rates for the studied species ranged from 16.3% among E. cloacae to 35.7% among K. pneumoniae. CAZ-AVI was active against 98% of Enterobacterales isolates and maintained activity against 74-98% of MDR isolates of the examined Enterobacterales species. Only tigecycline showed higher activity. Among P. aeruginosa, CAZ-AVI was active against 87% of all isolates and 47% of MDR isolates; no other studied drug was more active. The three most common MDR phenotypes among Enterobacterales were 1) R to ATM, FEP, and LVX (n=544, 44.8% of all MDR Enterobacterales; 100% susceptible (S) to CAZ-AVI), 2) R to ATM, FEP, LVX, and TZP (n=150, 12.4% of all MDR Enterobacterales; 99.3% S to CAZ-AVI), and 3) R to all sentinel drugs except AMK and CST (n=145, 11.9% of all MDR isolates; 78.6% S to CAZ-AVI). The three most common MDR phenotypes among P. aeruginosa were 1) R to all sentinel drugs except CST (n=85, 19.7% of all MDR isolates; 24.7% S to CAZ-AVI), 2) R to all sentinel drugs except AMK and CST (n=42, 9.7% of all MDR isolates; 66.7% S to CAZ-AVI), and 3) R to AMK, LVX, and MEM (n=37, 8.6% of all MDR isolates; 24.3% S to CAZ-AVI). Conclusion These in vitro data suggest that CAZ-AVI can be an effective treatment option for infections caused by MDR Enterobacterales and P. aeruginosa collected in Latin America. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

scholarly journals 1571. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against MDR Enterobacterales and Pseudomonas aeruginosa Collected in Latin America During the ATLAS Global Surveillance Program 2017-2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S784-S785
Author(s):  
Krystyna Kazmierczak ◽  
Sibylle Lob ◽  
Greg Stone ◽  
Daniel F Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Latin America ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Effective Treatment Option ◽  
Independent Contractor ◽  
Class D ◽  
In Vitro Data

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination that can inhibit class A, C and some class D β-lactamases. Resistance caused by these β-lactamases often results in multidrug-resistance (MDR). This study evaluated the in vitro activity of CAZ-AVI and comparators against MDR Enterobacterales and Pseudomonas aeruginosa isolates collected from patients in Latin America. Methods Non-duplicate clinical isolates were collected in 2017-2018 in 10 countries in Latin America. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2020 and FDA (tigecycline) breakpoints. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin (AMK), aztreonam (ATM), cefepime (FEP), colistin (CST), levofloxacin (LVX), meropenem (MEM), and piperacillin-tazobactam (TZP). Results The activity of CAZ-AVI and comparators against all isolates and MDR subsets is shown in the table. MDR rates for the studied species ranged from 17.6% among E. cloacae to 31.0% among K. pneumoniae. CAZ-AVI was active against 99% of Enterobacterales isolates and maintained activity against 85-99% of MDR isolates of the examined species. Only tigecycline showed comparable or higher activity. Among P. aeruginosa, CAZ-AVI was active against 86% of all isolates and 45% of MDR isolates; no other studied drug was more active. The three most common MDR phenotypes among Enterobacterales were 1) R to ATM, FEP, and LVX (n=538, 50% of all MDR Enterobacterales; 100% susceptible (S) to CAZ-AVI), 2) R to all sentinel drugs except AMK and CST (n=112, 10% of all MDR isolates; 88% S to CAZ-AVI), and 3) R to ATM, FEP, LVX, and TZP (n=111, 10% of all MDR Enterobacterales; 100% S to CAZ-AVI). The three most common MDR phenotypes among P. aeruginosa were 1) R to all sentinel drugs except CST (n=70, 22% of all MDR isolates; 20% S to CAZ-AVI), 2) R to AMK, LVX, and MEM (n=33, 10% of all MDR isolates; 33% S to CAZ-AVI), and 3) R to all sentinel drugs except AMK and CST (n=30, 9% of all MDR isolates; 70% S to CAZ-AVI). Table Conclusion These in vitro data suggest that CAZ-AVI can be an effective treatment option for infections caused by MDR Enterobacterales and P. aeruginosa collected in Latin America. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

scholarly journals 680. In vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Pseudomonas aeruginosa from ICU and Non-ICU Wards Collected in Latin America and Globally as Part of the ATLAS Surveillance Program 2016–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S310-S310
Author(s):  
Sibylle Lob ◽  
Krystyna Kazmierczak ◽  
Gregory Stone ◽  
Daniel F Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Latin America ◽  
Resistance Mechanisms ◽  
Vitro Activity ◽  
Asia Pacific ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Class B ◽  
Additional Resistance

Abstract Background Ceftazidime–avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination that can inhibit class A, C and some class D β-lactamases but not class B metallo-β-lactamases (MBLs). Antimicrobial resistance due to these β-lactamases and other mechanisms is increasing and is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Pseudomonas aeruginosa isolates from patients in ICU and non-ICU wards. Methods Nonduplicate clinical isolates were collected in 2016–2017 in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2019 breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC >2 µg/mL. Results The activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global P. aeruginosa were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI (89% and 92% susceptible, respectively) and for amikacin and colistin. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 72% and 70% of isolates, respectively, of which 18.4% and 18.7% were MBL-positive. CAZ AVI inhibited >83% of MEM-NS MBL-negative isolates globally. In Latin America (LA), CAZ-AVI was active against 87% of isolates from both ward types. Susceptibility rates were generally lower than the global average, especially among MEM-NS isolates and isolates from non-ICU wards. The proportion of MBL-positive isolates in the MEM-NS subset was only slightly higher in LA than globally (19.2% and 19.5% in ICU and non-ICU wards, respectively), suggesting the presence of additional resistance mechanisms. Only colistin exceeded the activity of CAZ-AVI against isolates collected globally and in LA. Conclusion CAZ-AVI showed potent antimicrobial activity, second only to that of colistin, against P. aeruginosa isolates from both ICU and non-ICU wards, with >88% of isolates collected globally testing as susceptible. Activity was in part compromised by MBLs, although additional resistance mechanisms may also be responsible. Disclosures All authors: No reported disclosures.

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

scholarly journals 1580. In Vitro Activity of Ceftazidime-Avibactam Against Enterobacterales and Pseudomonas aeruginosa Collected in Latin America as part of the ATLAS Global Surveillance Program, 2017-2019

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S788-S788
Author(s):  
Krystyna Kazmierczak ◽  
Maria Lavinea Valente ◽  
Elkin Lemos ◽  
Monique Baudrit ◽  
Alvaro Quintana ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Latin America ◽  
Costa Rica ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Independent Contractor

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with in vitro activity against Enterobacterales (Ent) and Pseudomonas aeruginosa (Psa) carrying Class A, C and some Class D β-lactamases. We examined the in vitro activity of CAZ-AVI and comparators against isolates collected in Latin America (LA) as part of the ATLAS surveillance program. Methods Non-duplicate isolates of Ent (n=8416) and Psa (n=2521) were collected in 10 countries in Central America (CAC; Costa Rica, Dominican Republic, Guatemala, Panama [2018-2019 only]) and South America (SA; Argentina, Brazil, Chile, Colombia, Mexico, Venezuela [2017-2019]). Susceptibility testing was performed by CLSI broth microdilution and values were interpreted using CLSI 2020 breakpoints. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Isolates with meropenem (MEM) MICs ≥2 µg/mL (Ent) or ≥4 µg/mL (Psa) were screened for β-lactamase genes. Results CAZ-AVI demonstrated potent in vitro activity against Ent collected in LA overall and in the CAC and SA subregions (95-99% susceptible (S)) that was comparable to or exceeded the activity of comparators including MEM, amikacin (AMK) and tigecycline (TGC) (Table). CAZ-AVI retained good activity against MEM non-susceptible (NS) Ent collected in SA (82% S; 6.9% of collected isolates) but activity was reduced against MEM-NS Ent from CAC (10% S; 5.7% of collected isolates), which included a high proportion of isolates carrying NDM-type metallo-β-lactamases (MBL). Among Psa, CAZ-AVI showed greater activity than the tested comparators against both all (86-92% S) and MEM-NS (61-66% S) isolates collected in LA overall and in the two subregions. Table Conclusion CAZ-AVI showed potent in vitro activity against Ent and Psa collected from patients in the CAC and SA subregions of LA. Activity was also good against MEM-NS isolates from SA but was reduced against MEM-NS Ent from CAC that included a high proportion of MBL-positive isolates. The regional and country prevalence of different carbapenem-resistance mechanisms must be considered when evaluating treatment options; however, CAZ-AVI could provide a valuable therapeutic option for treatment of infections caused by Ent and Psa in LA. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Maria Lavinea Valente, MD, Pfizer Brazil (Employee) Elkin Lemos, MD, PhD, Pfizer Columbia (Employee) Monique Baudrit, MD, MSc, Pfizer Costa Rica (Employee) Alvaro Quintana, MD MSc, Pfizer, Inc. (Employee) Paurus Irani, MD, Pfizer United Kingdom (Employee) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

scholarly journals In Vitro Activity of Ceftolozane-Tazobactam vs. Antimicrobial Non-Susceptible Pseudomonas aeruginosa Clinical Isolates Obtained from Across Canada as Part of the CANWARD Study, 2008–2016

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S372-S372
Author(s):  
Andrew Walkty ◽  
Heather J Adam ◽  
Melanie Baxter ◽  
Philippe Lagace-Wiens ◽  
James Karlowsky ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Research Support ◽  
Research Relationship ◽  
Inhibitor Combination ◽  
Patient Infection

Abstract Background Ceftolozane-tazobactam (C/T) is a novel β-lactam β-lactamase inhibitor combination with a broad spectrum of activity that includes Pseudomonas aeruginosa. The purpose of this study was to evaluate the in vitro activity of C/T and relevant comparators vs. a large collection of antimicrobial non-susceptible (NS) P. aeruginosa clinical isolates obtained from patients across Canada (CANWARD, 2008–2016). Methods From January 2008 to December 2016, inclusive, 12 to 15 sentinel hospitals across Canada submitted clinical isolates from patients attending ERs, medical and surgical wards, hospital clinics, and ICUs (CANWARD). Each center was asked to annually submit clinical isolates (consecutive, one per patient/infection site) from blood, respiratory, urine, and wound infections. Susceptibility testing was performed using broth microdilution as described by CLSI. Multidrug-resistant (MDR) P. aeruginosa were defined as isolates that tested NS to at least one antimicrobial from ≥3 classes. Extensively drug-resistant (XDR) P. aeruginosa were defined as isolates that tested NS to at least one antimicrobial from ≥5 classes. Results 3229 P. aeruginosa isolates were obtained as a part of CANWARD. The in vitro activity of C/T and relevant comparators is presented below. Conclusion C/T demonstrated excellent in vitro activity vs. antimicrobial NS P. aeruginosa clinical isolates, including MDR, XDR, and meropenem NS subsets. It may prove useful in the treatment of infections caused by these organisms. Disclosures D. Hoban, Abbott: Research relationship, Research support Achaogen: Research relationship, Research support Astellas: Research relationship, Research support Merck Canada: Research relationship, Research support Merck USA: Research relationship, Research support Paratek Pharma: Research relationship, Research support Pharmascience: Research relationship, Research support Sunovion: Research relationship, Research support Tetraphase: Research relationship, Research support The Medicines Co.: Research relationship, Research support Zoetis: Research relationship, Research support; G. Zhanel, Achaogen: Research relationship, Research support Astellas: Research relationship, Research support Merck Canada: Research relationship, Research support Merck USA: Research relationship, Research support Paratek Pharma: Research relationship, Research support Pharmascience: Research relationship, Research support Sunovion: Research relationship, Research support Tetraphase: Research relationship, Research support The Medicines Co.: Research relationship, Research support Zoetis: Research relationship, Research support

scholarly journals 693. In Vitro Activity of Ceftazidime–Avibactam and Comparator Agents Against Enterobacteriaceae and Pseudomonas aeruginosa Collected From Patients with Bloodstream Infections as Part of the ATLAS Global Surveillance Program, 2014–2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S314-S314
Author(s):  
Krystyna Kazmierczak ◽  
Gregory Stone ◽  
Daniel F Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Therapeutic Option ◽  
Bloodstream Infections ◽  
The United States ◽  
Vitro Activity ◽  
Asia Pacific ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Susceptibility Data

Abstract Background Avibactam (AVI) is a β-lactamase inhibitor with potent inhibitory activity against Class A, Class C, and some Class D serine β-lactamases. The combination of ceftazidime (CAZ) with AVI has been approved in Europe and in the United States for several indications. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacteriaceae (Eba) and Pseudomonas aeruginosa (Pae) isolates collected from patients with bloodstream infections as part of the ATLAS surveillance program in 2014–2017. Methods A total of 53416 Eba and 15050 Pae nonduplicate clinically significant isolates, including 5155 Eba and 845 Pae isolated from bloodstream infections, were collected by 167 hospital laboratories in 36 countries in Europe, Latin America, Asia/Pacific (excluding China), and the Middle East/Africa region. Susceptibility testing was performed by CLSI broth microdilution. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Meropenem-nonsusceptible (MEM-NS) Eba and Pae isolates were screened for the presence of β-lactamase genes. Results Susceptibility data are shown in the Table. Percentages of susceptibility (% S) to the tested agents were 0.2–2.8% lower among Eba and Pae from bloodstream infections compared with isolates from combined sources in most cases. CAZ-AVI showed potent in vitro activity against all Eba bloodstream isolates and subsets of CAZ-NS and colistin-resistant (CST-R) isolates (MIC90, 0.5–2 µg/mL, 96.0–100% S). Reduced activity against MEM-NS Eba was attributable to carriage of class B metallo-β-lactamases (MBLs) because all MEM-NS MBL-negative isolates were susceptible to CAZ-AVI. CAZ-AVI also showed good in vitro activity against the majority of Pae bloodstream isolates (MIC90, 16 µg/mL, 89.5% S). Activity was reduced against CAZ-NS, MEM-NS and CST-R subsets (53.7–85.0% S), which included isolates carrying MBLs, but exceeded the activity of CAZ and MEM against these subsets by 15–65%. CST and amikacin were the only tested comparators that demonstrated comparable or greater activity against Pae bloodstream isolates. Conclusion CAZ-AVI provides a valuable therapeutic option for treating bloodstream infections caused by MBL-negative Eba and Pae isolates. Disclosures All authors: No reported disclosures.

scholarly journals 521. Comparative In Vitro Activity of Meropenem/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S251-S251 ◽  
Author(s):  
Twisha S Patel ◽  
Keith S Kaye ◽  
Jay Krishnan ◽  
Vince Marshall ◽  
John Mills ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Real World ◽  
Carbapenem Resistance ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Limited Data ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Inhibitor Combination

Abstract Background Meropenem/vaborbactam (MV) is a carbapenem and boronic acid–based β-lactamase inhibitor combination product with potent in vitro activity against Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. As carbapenem resistance in Pseudomonas aeruginosa (PSA) is primarily driven by porin mutations, efflux pumps, or infrequently by metallo-β-lactamases, vaborbactam is not expected to improve the in vitro activity of meropenem (MEM) against this pathogen. However, limited data currently exists assessing the comparative in vitro activity of MEM and MV. The purpose of this study was to compare the in vitro activity of MV and MEM against a large real-world sample of clinical isolates of PSA where both MV and MEM are routinely tested on all isolates. Methods All cultures from patient infections with PSA from May 2018 to February 2019 at Michigan Medicine were included. Minimum inhibitory concentrations (MICs) were determined using TREK broth microdilution panels and isolates were considered susceptible to MV if the MIC was ≤4 mg/L and MEM if the MIC was ≤2 mg/L. Results A total of 2,967 isolates of PSA from clinical specimens were included. 80.5% of isolates were susceptible to MEM (MIC50 ≤1 mg/L and MIC90 8 mg/L, range ≤1 to >32 mg/L) at a breakpoint of ≤2 mg/L and 86.3% at a breakpoint of ≤4 mg/L; whereas 90.8% of isolates were susceptible to MV (MIC50 ≤1 mg/L and MIC90 4 mg/L, range ≤1 to >8 mg/L). Of those displaying MEM MIC >2 mg/L, 53% (n = 308) were susceptible to MV. Of those displaying MEM MIC >4 mg/L, 33.7% (n = 137) were susceptible to MV. Although the majority of MIC discordances in MEM-R/MV-S isolates were 1–2 doubling dilutions, 52 (38%) isolates had their meropenem MIC decreased ≥3 doubling dilutions by the addition of vaborbactam suggesting significant inhibitory activity (Table 1). Conclusion We found a surprising number of PSA isolates with discordant MV and MEM susceptibility at Michigan Medicine. Further exploration of mechanisms of meropenem resistance in these isolates is warranted. Disclosures All authors: No reported disclosures.

scholarly journals 1569. In Vitro Activity of Ceftazidime-avibactam and Comparator Agents against Enterobacterales and Pseudomonas aeruginosa Collected from Patients with Bloodstream Infections as Part of the ATLAS Global Surveillance Program, 2015-2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S783-S784
Author(s):  
Krystyna Kazmierczak ◽  
Sibylle Lob ◽  
Greg Stone ◽  
Daniel F Sahm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Therapeutic Option ◽  
Bloodstream Infections ◽  
The United States ◽  
Vitro Activity ◽  
Asia Pacific ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Independent Contractor

Abstract Background Avibactam (AVI) is a β-lactamase inhibitor with potent inhibitory activity against Class A, Class C, and some Class D serine β-lactamases. The combination of ceftazidime (CAZ) with AVI has been approved in Europe and in the United States for several indications. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales (Eba) and Pseudomonas aeruginosa (Pae) isolates collected from patients with bloodstream infections as part of the ATLAS surveillance program in 2015-2018. Methods A total of 57048 Eba and 15813 Pae non-duplicate clinically significant isolates, including 7720 Eba and 1286 Pae isolated from bloodstream infections, were collected in 52 countries in Europe, Latin America, Asia/Pacific (excluding mainland China), and the Middle East/Africa region. Susceptibility testing was performed by CLSI broth microdilution. CAZ-AVI was tested at a fixed concentration of 4 µg/ml AVI. Meropenem-nonsusceptible (MEM-NS) Eba and Pae isolates were screened for the presence of β-lactamase genes. Results Susceptibility data are shown in the Table. Percentages of susceptibility (% S) to the tested agents were 0.3-2.9% lower among Eba and Pae from bloodstream infections compared to isolates from combined sources in most cases. CAZ-AVI showed potent in vitro activity against all Eba bloodstream isolates and the CAZ-NS subset (MIC90, 0.5-2 µg/ml, 93.4-98.1% S). Reduced activity against MEM-NS Eba was attributable to carriage of class B metallo-β-lactamases (MBLs) because 99% of MEM-NS MBL-negative isolates were susceptible to CAZ-AVI. None of the tested comparators exceeded the activity of CAZ-AVI. CAZ-AVI also showed good in vitro activity against the majority of Pae bloodstream isolates (MIC90, 16 µg/ml, 89.4% S). Activity was reduced against CAZ-NS and MEM-NS subsets (54.2-63.8% S), which included isolates carrying MBLs, but exceeded the activity of CAZ and MEM against these subsets by 26-31 percentage points. Amikacin was the only tested comparator that demonstrated comparable activity against Pae bloodstream isolates. Table Conclusion CAZ-AVI provides a valuable therapeutic option for treating bloodstream infections caused by MBL-negative Eba and Pae isolates. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

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