1223. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales from ICU and Non-ICU Wards Collected in Latin America and Globally as part of the ATLAS Surveillance Program 2017-2019

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with activity against Enterobacterales producing class A, C and some class D β-lactamases. Resistance caused by these β-lactamases is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales isolates from patients in ICU and non-ICU wards. Methods Non-duplicate clinical isolates were collected in 2017-2019 from patients in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC >1 µg/ml, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with aztreonam or ceftazidime MIC >1 µg/ml. Results The activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global Enterobacterales were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI, which inhibited >96% of isolates from both ward types. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 62.3% and 65.6% of ICU and non-ICU isolates, respectively, and 36.3% and 33.2%, respectively, carried metallo-β-lactamases (MBLs). CAZ-AVI inhibited >97% of MEM-NS MBL-negative isolates collected globally. Antimicrobial activity against all Enterobacterales from both ICU and non-ICU wards in Latin America (LA) was generally similar to the global average. Among MEM-NS isolates, antimicrobial activity of CAZ-AVI was >10 percentage points higher in LA than the global average among isolates from both ward types, at least partly because of a lower proportion of MBL-positive isolates in this subset (24.4% and 22.0% in ICU and non-ICUs, respectively). CAZ-AVI inhibited >98% of MEM-NS MBL-negative isolates from LA. Results Table Conclusion CAZ-AVI provides a valuable treatment option for infections caused by Enterobacterales that do not carry MBLs, including those from patients in ICU wards, where antimicrobial resistance is typically higher. 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)

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1570. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales from ICU and Non-ICU Wards Collected in Latin America and Globally as part of the ATLAS Surveillance Program 2017-2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1750 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S784-S784

Author(s):

Sibylle Lob ◽

Krystyna Kazmierczak ◽

Greg Stone ◽

Daniel F Sahm

Keyword(s):

Antimicrobial Activity ◽

Latin America ◽

Vitro Activity ◽

Asia Pacific ◽

Surveillance Program ◽

In Vitro Activity ◽

Independent Contractor ◽

Global Average ◽

Valuable Treatment

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with activity against Enterobacterales producing class A, C and some class D β-lactamases. Resistance caused by these β-lactamases is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales isolates from patients in ICU and non-ICU wards. Methods Non-duplicate clinical isolates were collected in 2017-2018 from patients in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2020 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC >1 µg/ml, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with aztreonam or ceftazidime MIC >1 µg/ml. Results The activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global Enterobacterales were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI, which inhibited ≥97% of isolates from both ward types. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 66.5% and 68.1% of ICU and non-ICU isolates, respectively (of which 31.8% and 30.8%, respectively, carried metallo-β-lactamases [MBLs]). CAZ-AVI inhibited >97% of MEM-NS MBL-negative isolates collected globally. Antimicrobial activity against all Enterobacterales from both ICU and non-ICU wards in Latin America (LA) was generally similar to the global average. Among MEM-NS isolates, antimicrobial activity of CAZ-AVI and TGC was higher in LA than the global average among isolates from both ward types, at least partly because of a lower proportion of MBL-positive isolates in this subset (15.8% and 17.9% in ICU and non-ICUs, respectively). CAZ-AVI inhibited 100% of MEM-NS MBL-negative isolates from LA. Table Conclusion CAZ-AVI provides a valuable treatment option for infections caused by Enterobacterales that do not carry MBLs, including those among patients in ICU wards, where antimicrobial resistance is typically higher. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Krystyna Kazmierczak, 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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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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1749 ◽

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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1568. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa Collected < 48 Hours and ≥48 Hours Post-Admission from Pediatric Patients, ATLAS Surveillance Program 2015-2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1748 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S783-S783

Author(s):

Krystyna Kazmierczak ◽

Greg Stone ◽

Daniel F Sahm

Keyword(s):

Pseudomonas Aeruginosa ◽

Pediatric Patients ◽

Therapeutic Option ◽

Vitro Activity ◽

Asia Pacific ◽

Surveillance Program ◽

In Vitro Activity ◽

Independent Contractor ◽

Infection Types

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 presumed community-acquired (CA; cultured < 48 h after hospital admission) and hospital-acquired (HA; cultured ≥48 h post-admission) isolates collected from pediatric patients as part of the ATLAS surveillance program. Methods 6023 non-duplicate isolates were collected in 50 countries in Europe (n=3122), Latin America (n=1220), Middle East/Africa (n=1007), and Asia/Pacific (excluding China; n=674) from patients (newborn to 17 y) with lower respiratory tract (LRTI; n=1641), urinary tract (UTI; n=1595), skin and soft tissue (SSTI; n=1027), intra-abdominal (IAI; n=949), and bloodstream (BSI; n=811) infections. 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 CAZ or aztreonam MICs ≥2 µg/mL (Escherichia coli, Klebsiella spp., Proteus mirabilis) or meropenem MICs ≥2 µg/mL (all Ent species) or ≥4 µg/mL (Psa) were screened for β-lactamase genes. Results The in vitro activity of CAZ-AVI exceeded that of meropenem and other tested β-lactams against Ent (98.5% susceptible (S)) and Psa (93.1% S) collected globally from pediatric patients (Table). Percentages of susceptibility to CAZ-AVI ranged from 96.8-99.3% among CA Ent from different infection types and were reduced 0.4-1.0% among HA isolates from SSTI, IAI and BSI. Susceptibility to CAZ-AVI was also similar (92.7-95.4% S) among CA Psa from different infection types and was reduced 0.1-4.4% among HA isolates. For both Ent and Psa, the lowest percentages of susceptibility to the tested β-lactams were observed among isolates from BSI, which included a higher proportion of isolates carrying extended-spectrum β-lactamases and/or carbapenemases than isolates from other infection types. Table Conclusion CAZ-AVI could provide a valuable therapeutic option for treatment of CA and HA infections caused by Ent and Psa in pediatric patients. Disclosures Krystyna Kazmierczak, 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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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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1436 ◽

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)

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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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.748 ◽

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.

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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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1751 ◽

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)

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1567. In Vitro Activity of Aztreonam-Avibactam and Comparator Agents Against Multidrug-Resistant Enterobacterales Collected Globally as Part of the ATLAS Surveillance Program, 2016-2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1747 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S783-S783

Author(s):

Krystyna Kazmierczak ◽

Francis Arhin ◽

Greg Stone ◽

Daniel F Sahm

Keyword(s):

Multidrug Resistant ◽

Vitro Activity ◽

Asia Pacific ◽

Multiple Drug ◽

Surveillance Program ◽

Drug Resistant ◽

In Vitro Activity ◽

Independent Contractor ◽

Drug Classes

Abstract Background Avibactam (AVI) is a serine-β-lactamase inhibitor in development with aztreonam (ATM) for treatment of infections caused by drug-resistant Enterobacterales (Ent), especially carbapenem-resistant isolates co-producing serine- and metallo-β-lactamases (MBL), which are often resistant to agents from multiple drug classes. This study evaluated the in vitro activity of ATM-AVI and comparators against Ent collected globally as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Methods 44,671 non-duplicate clinical isolates were collected in 2016-2018 in 52 countries in Europe, Asia/Pacific (excluding China and India), Middle East/Africa, and Latin America. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2020 and FDA (tigecycline) breakpoints. ATM-AVI was tested at a fixed concentration of 4 µg/mL AVI. Drug-resistant phenotypes were defined as: multidrug resistant (MDR), resistant (R) to ≥3 of 7 sentinel agents (amikacin [AMK], ATM, cefepime [FEP], colistin [CST], levofloxacin [LVX], meropenem [MEM], piperacillin-tazobactam [TZP]); extensively drug resistant (XDR), susceptible to ≤2 sentinel agents; and pandrug resistant (PDR), non-susceptible to all sentinel agents. Isolates with MEM MIC >1 µg/mL were screened for β-lactamase genes by PCR and sequencing. Results 14.9%, 4.3%, 3.7%, 1.3%, and 0.3% of Ent collected globally were MDR, XDR, MEM-R, MBL-positive, and PDR, respectively. ATM-AVI tested with MIC90 values of 0.12 µg/mL against all Ent and 0.5 µg/mL against subsets of resistant isolates (Table). On the regional level, similar values were observed against all (MIC90, 0.12 µg/mL) and resistant isolates (MIC90, 0.25-1 µg/mL) (not shown). The tested comparators, excluding TGC, showed percentages of susceptibility < 90% against regional and global subsets of resistant isolates. 99.97% (44658 of 44671) Ent, including all MBL-positive and PDR isolates, were inhibited by ≤8 µg/mL of ATM-AVI. Table Conclusion Based on MIC90 values, ATM-AVI demonstrated potent in vitro activity against resistant and MBL-positive subsets of Ent collected globally. ATM-AVI could be an effective therapy for difficult-to-treat infections caused by drug-resistant Ent. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Francis Arhin, PhD, Pfizer, Inc. (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)

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1252. In Vitro Activity of Aztreonam-Avibactam and Comparator Agents Against Enterobacterales from Patients with Bloodstream Infections collected during the ATLAS Global Surveillance Program, 2015-2019

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1444 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S715-S715

Author(s):

Sibylle Lob ◽

Krystyna Kazmierczak ◽

Francis Arhin ◽

Daniel F Sahm

Keyword(s):

Treatment Options ◽

Mainland China ◽

Bloodstream Infections ◽

Vitro Activity ◽

Asia Pacific ◽

Surveillance Program ◽

Drug Resistant ◽

In Vitro Activity ◽

Independent Contractor

Abstract Background Treatment options for β-lactamase-producing Enterobacterales are limited, particularly for infections caused by metallo-β-lactamase (MBL)-producing strains. The β-lactam/non-β-lactam β-lactamase inhibitor combination aztreonam-avibactam (ATM-AVI) is active in vitro against Enterobacterales isolates carrying MBLs, including those co-producing β-lactamases of Class A, C, and some class D enzymes. This study evaluated the in vitro activity of ATM-AVI and comparators against Enterobacterales isolates collected in 2015-2019 from patients with bloodstream infections (BSI) as part of the ATLAS program. Methods Non-duplicate clinical isolates were collected in 53 countries in Europe, Latin America, Asia/Pacific (excluding mainland China and India), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. ATM-AVI was tested at a fixed concentration of 4 µg/mL AVI. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin, aztreonam, cefepime, colistin, levofloxacin, meropenem, and piperacillin-tazobactam. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis phenotypically positive for ESBL activity (2015) or with aztreonam or ceftazidime MIC >1 µg/mL (2016-2019). Results ATM-AVI was active in vitro against Enterobacterales isolates from BSI (MIC90, 0.12 µg/mL), with 99.97% of isolates inhibited by ≤8 µg/mL of ATM-AVI, including 100% of isolates that produced MBLs. ATM-AVI tested with MIC90 values of 0.5 µg/mL against subsets of cefepime-nonsusceptible (NS), meropenem-NS, amikacin-NS, colistin-resistant, and MBL-positive Enterobacterales (Table). The tested β-lactam comparators showed susceptibility of < 79% against these subsets of resistant isolates. Results Table Conclusion Based on MIC90 values, ATM-AVI was the most potent agent tested against drug-resistant and MBL-positive subsets of Enterobacterales collected from BSI. The promising in vitro activity of ATM-AVI warrants further development of this combination for treatment of BSI caused by drug-resistant Enterobacterales. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Francis Arhin, PhD, Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

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1263. 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, 2017-2019

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1455 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S720-S720

Author(s):

Sibylle Lob ◽

Meredith Hackel ◽

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 ◽

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 2017-2019. Methods A total of 48193 Eba and 15376 Pae non-duplicate clinically significant isolates, including 9224 Eba and 1808 Pae isolated from bloodstream infections, were collected in 53 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 0.4-3.4% 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, 0.5-4 µg/ml, 91.7-97.4% S). Reduced activity against MEM-NS Eba was attributable to carriage of class B metallo-β-lactamases (MBLs) as 98.1% 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, 89.7% S). Activity was reduced against CAZ-NS and MEM-NS subsets (55.9-63.0% S), which included isolates carrying MBLs, but exceeded the activity of CAZ against MEM-NS and MEM against CAZ-NS by 26-28 percentage points. Amikacin was the only tested comparator that demonstrated comparable activity against Pae bloodstream isolates. Results Table Conclusion CAZ-AVI provides a valuable therapeutic option for treating bloodstream infections caused by MBL-negative Eba and Pae isolates. 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)

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1264. In Vitro Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa Collected < 48 Hours and ≥48 Hours Post-Admission from Pediatric Patients, ATLAS Surveillance Program 2016-2019

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1456 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S720-S721

Author(s):

Krystyna Kazmierczak ◽

Sibylle Lob ◽

Gregory Stone ◽

Daniel F Sahm

Keyword(s):

Pseudomonas Aeruginosa ◽

Pediatric Patients ◽

Therapeutic Option ◽

Vitro Activity ◽

Asia Pacific ◽

Surveillance Program ◽

In Vitro Activity ◽

Independent Contractor ◽

Infection Types

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 presumed community-acquired (CA; cultured < 48 h after hospital admission) and hospital-acquired (HA; cultured ≥48 h post-admission) isolates collected from pediatric patients as part of the ATLAS surveillance program. Methods 6654 non-duplicate isolates were collected in 52 countries in Europe (n=3423), Latin America (n=1323), Middle East/Africa (n=1177), and Asia/Pacific (excluding China; n=731) from patients (newborn to 17 y) with lower respiratory tract (LRTI; n=1687), urinary tract (UTI; n=1631), bloodstream (BSI; n=1149), skin and soft tissue (SSTI; n=1122), and intra-abdominal (IAI; n=981) infections. Susceptibility testing was performed by CLSI broth microdilution and values were interpreted using CLSI 2021 breakpoints. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Isolates with CAZ or aztreonam MICs ≥2 µg/mL (Escherichia coli, Klebsiella spp., Proteus mirabilis) or meropenem MICs ≥2 µg/mL (all Ent species) or ≥4 µg/mL (Psa) were screened for β-lactamase genes. Results The in vitro activity of CAZ-AVI exceeded that of meropenem and other tested β-lactams against Ent (97.8% susceptible (S)) and Psa (92.1% S) collected globally from pediatric patients (Table). Percentages of susceptibility to CAZ-AVI ranged from 95.4-99.2% among CA Ent from different infection types and were reduced 0.6-1.3% among HA isolates from LRTI, UTI, SSTI, and IAI. Susceptibility to CAZ-AVI was also similar (92.6-95.8% S) among CA Psa from different infection types and was reduced 1.2-7.0% among HA isolates. Larger differences in susceptibility were typically seen for the tested comparator β-lactams. For Ent, the lowest percentages of susceptibility to the tested β-lactams were observed among isolates from BSI, while the pattern was less clear for Psa. Results Table Conclusion CAZ-AVI could provide a valuable therapeutic option for treatment of CA and HA infections caused by Ent and Psa in pediatric patients. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Sibylle Lob, PhD, 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)

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