1582. In Vitro Activity of Ceftolozane/Tazobactam against Enterobacterales and Pseudomonas aeruginosa Isolates from Geriatric Patients in the Asia/Pacific region – SMART 2016-2018

Abstract Background Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for complicated urinary tract and intraabdominal infections, and hospital-acquired and ventilator-associated bacterial pneumonia. We evaluated the activity of C/T against isolates collected from patients ≥65 years old as part of the SMART surveillance program in Asia/Pacific. Methods In 2016-2018, 49 clinical laboratories in Australia, Hong Kong, Malaysia, New Zealand, Philippines, Singapore, Korea, Taiwan, Thailand, and Vietnam each collected up to 250 consecutive gram-negative pathogens per year. Susceptibility was determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) Enterobacterales (ENT) and P. aeruginosa (PA) isolates were screened by PCR and sequenced for genes encoding β-lactamases (except ENT from 1 site in Taiwan). Results 2082 PA (68.3% lower respiratory tract, 12.7% intraabdominal, 15.1% urinary tract, and 3.0% bloodstream infection isolates) and 8181 ENT isolates (29.8%, 27.8%, 32.5%, and 9.2%, respectively) were collected from patients ≥65 years old. In vitro susceptibility of PA and ENT stratified by length of hospital stay at time of specimen collection (LOS) is shown (Table). C/T maintained activity against 75.5% of 518 P/T-NS, 67.9% of 395 cefepime-NS, and 71.6% of 377 meropenem-NS PA isolates. Among 136 C/T-NS PA isolates, 44.9% carried metallo-β-lactamases (MBL), 0.7% KPC, 1.5% GES carbapenemases, 5.9% only ESBL, and in 47.1% no acquired β-lactamases were detected. Among 878 characterized C/T-NS ENT, 14.1% carried MBL, 5.2% KPC, 3.3% OXA-48-like carbapenemases, and 53.5% AmpC and/or ESBL; no acquired β-lactamases were detected in 23.8% of isolates, of which 89.5% were species with intrinsic AmpC. Table Conclusion Susceptibility of PA and ENT to all studied agents was lower for isolates collected ≥48 than < 48 hours post-admission. C/T was active against >92% of PA in both strata, 7-29 percentage points higher than the studied comparators except amikacin, and against >84% of ENT, 4-30% higher than the comparators except meropenem and amikacin. C/T is a potential new treatment option for older patients with infections caused by ENT and PA in Asia/Pacific. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Yivonne Khoo, PhD, Merck, Sharp & Dohme, Malaysia (Employee) Kanchan Balwani, MBBS, MS, Merck, Sharp & Dohme, Hong Kong (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

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1583. In Vitro Activity of Imipenem/Relebactam against Klebsiella pneumoniae and Pseudomonas aeruginosa from Patients in ICUs in the Asia/Pacific region – SMART 2015-2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1763 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S789-S789

Author(s):

Sibylle Lob ◽

Meredith Hackel ◽

Wei-Ting Chen ◽

Yivonne Khoo ◽

Kanchan Balwani ◽

...

Keyword(s):

Hong Kong ◽

Urinary Tract ◽

Antimicrobial Susceptibility ◽

Bloodstream Infections ◽

Asia Pacific ◽

Surveillance Program ◽

Independent Contractor ◽

Icu Patients ◽

Tract Infections

Abstract Background Relebactam (REL) is an inhibitor of class A and C β-lactamases approved in the USA in combination with imipenem (IMI) and cilastatin for the treatment of complicated intraabdominal and urinary tract infections. Elevated antimicrobial resistance rates have been reported in ICUs. Using isolates collected in Asia/Pacific for the SMART surveillance program, we evaluated the activity of IMI/REL and comparators against K. pneumoniae (KP) and P. aeruginosa (PA) from ICU patients. Methods In 2015-2018, 51 clinical laboratories in Australia, Hong Kong, Malaysia, New Zealand, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam each collected up to 250 consecutive aerobic gram-negative pathogens per year. Susceptibility was determined using CLSI broth microdilution and CLSI and FDA (IMI/REL) breakpoints. IMI-nonsusceptible KP and PA were screened for β-lactamase genes. Results Analyzing only the 6322 isolates from ICU patients, the 3 most common species collected were KP (21.4%), E. coli (20.5%), and PA (19.7%). Tables 1 and 2 show % susceptible and % MBL- and/or OXA-48-like-positive for the most common Enterobacterales species (KP; 70.6% from lower respiratory tract, 17.6% from intraabdominal, 7.1% from urinary tract, and 4.1% from bloodstream infections) and the most common non-Enterobacterales species (PA; 83.6%, 9.9%, 4.3%, and 1.9%, respectively). % IMI/REL-susceptible ranged from 66-79% in Thailand and Vietnam (where 13-36% of isolates carried MBL and/or OXA-48-like carbapenemases, which REL does not inhibit) to ≥95% in 6 countries (0-3% MBL- and/or OXA-48-like-positive). Among 103 IMI/REL-nonsusceptible KP isolates, 66.0% carried MBL, 20.4% OXA-48-like carbapenemases, 2.9% KPC, 2.9% acquired AmpC and/or ESBL, and in 7.8% no acquired β-lactamases were detected. Among 145 IMI/REL- nonsusceptible PA, 54.5% carried MBL, 1.4% GES carbapenemases, 4.1% only ESBL, and 40.0% no acquired β-lactamases. Table 1. Antimicrobial susceptibility of K. pneumoniae collected from ICU patients Table 2. Antimicrobial susceptibility of P. aeruginosa collected from ICU patients Conclusion IMI/REL was active against 92% of KP and 88% of PA from ICU patients in Asia/Pacific overall, with higher activity in countries with lower prevalence of MBL or OXA-48-like carbapenemases. IMI/REL provides a potential treatment option for ICU patients in Asia/Pacific with infections caused by KP and PA. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Yivonne Khoo, PhD, Merck, Sharp & Dohme, Malaysia (Employee) Kanchan Balwani, MBBS, MS, Merck, Sharp & Dohme, Hong Kong (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

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1225. In Vitro Activity of Aztreonam-Avibactam and Comparator Agents Against Enterobacterales Collected from Geriatric Patients in ICU and non-ICU wards, ATLAS Surveillance Program 2016-2019

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1417 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S702-S702

Author(s):

Sibylle Lob ◽

Krystyna Kazmierczak ◽

Francis Arhin ◽

Daniel F Sahm

Keyword(s):

Geriatric Patients ◽

Therapeutic Option ◽

Mainland China ◽

Asia Pacific ◽

Surveillance Program ◽

Independent Contractor ◽

Doubling Dilution ◽

Infection Types ◽

Resistance Rates

Abstract Background Elevated resistance rates have been reported in ICUs. Aztreonam (ATM) combined with avibactam (AVI) is being developed for use against drug-resistant Enterobacterales (Ebact), including metallo-β-lactamase (MBL)-positive isolates. We examined the activity of ATM-AVI and comparators against Ebact isolates collected from geriatric patients in ICU and non-ICU wards as part of the ATLAS surveillance program. Methods 23754 non-duplicate Ebact isolates were collected in 53 countries in Asia/Pacific (excluding mainland China and India), Europe, Latin America, and Middle East/Africa from patients ≥65 years with lower respiratory tract (LRTI), urinary tract (UTI), skin and soft tissue (SSTI), intra-abdominal (IAI), and bloodstream (BSI) infections. Susceptibility testing was performed by CLSI broth microdilution and values interpreted using CLSI 2021 breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC >1 µg/mL. Results Susceptibility of the studied comparator agents was generally slightly lower among Ebact from BSI than other infection types (Table). Susceptibility was also generally lower among Ebact from ICU than non-ICU wards by up to 10 percentage points, and MIC90 values were up to 32-fold higher. ATM-AVI MIC90 values were within one doubling-dilution across all studied strata (0.12-0.25 µg/mL), were comparable to or lower than for meropenem in all strata, and were 2 to ≥9 dilutions lower than all other tested comparators. MBL-positive Ebact were found in 1.5% of LRTI (n=91), 1.2% of UTI (n=70), 1.1% of SSTI (n=52), 1.3% of BSI (n=49), and 0.7% of IAI isolates (n=22). MBL-positive rates were higher among ICU (1.7%, n=101) than non-ICU isolates (1.0%, n=183). ATM-AVI MIC90 values were 0.5 µg/mL against MBL-positive isolates from all ward and infection types except SSTI (MIC90 0.25 µg/mL) and BSI (MIC90 1 µg/mL), 2-4 dilutions lower than tigecycline and at least 5-10 dilutions lower than the other comparators. Results Table Conclusion ATM-AVI could provide a valuable therapeutic option for treatment of infections caused by Ebact in patients ≥65 years old in both ICU and non-ICU wards. 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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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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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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In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Asia-Pacific Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02569-17 ◽

2018 ◽

Vol 62 (7) ◽

Cited By ~ 13

Author(s):

James A. Karlowsky ◽

Krystyna M. Kazmierczak ◽

Samuel K. Bouchillon ◽

Boudewijn L. M. de Jonge ◽

Gregory G. Stone ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Hong Kong ◽

Multidrug Resistant ◽

Clinical Isolates ◽

Asia Pacific ◽

Surveillance Program ◽

Asia Pacific Region ◽

Content Type ◽

Medical Centers

ABSTRACT The in vitro activities of ceftazidime-avibactam and comparators against 9,149 isolates of Enterobacteriaceae and 2,038 isolates of Pseudomonas aeruginosa collected by 42 medical centers in nine countries in the Asia-Pacific region from 2012 to 2015 were determined as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. Antimicrobial susceptibility testing was conducted by Clinical and Laboratory Standards Institute (CLSI) broth microdilution, and isolate subset analysis was performed on the basis of the resistant phenotypes and β-lactamase content. Ceftazidime-avibactam demonstrated potent in vitro activity (MIC, ≤8 μg/ml) against all Enterobacteriaceae tested (99.0% susceptible) and was the most active against isolates that were metallo-β-lactamase (MBL) negative (99.8% susceptible). Against P. aeruginosa , 92.6% of all isolates and 96.1% of MBL-negative isolates were susceptible to ceftazidime-avibactam (MIC, ≤8 μg/ml). The rates of susceptibility to ceftazidime-avibactam ranged from 97.0% (Philippines) to 100% (Hong Kong, South Korea) for Enterobacteriaceae and from 83.1% (Thailand) to 100% (Hong Kong) among P. aeruginosa isolates, with lower susceptibilities being observed in countries where MBLs were more frequently encountered (Philippines, Thailand). Ceftazidime-avibactam inhibited 97.2 to 100% of Enterobacteriaceae isolates, per country, that carried serine β-lactamases, including extended-spectrum β-lactamases, AmpC cephalosporinases, and carbapenemases (KPC, GES, OXA-48-like). It also inhibited 91.3% of P. aeruginosa isolates that were carbapenem nonsusceptible in which no acquired β-lactamase was detected. Among MBL-negative Enterobacteriaceae isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 96.1, 87.7, 100, and 98.8% of isolates, respectively, and among MBL-negative P. aeruginosa isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 79.6, 83.6, 83.3, and 68.2% of isolates, respectively. Overall, clinical isolates of Enterobacteriaceae and P. aeruginosa collected in nine Asia-Pacific countries from 2012 to 2015 were highly susceptible to ceftazidime-avibactam.

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1588. Activity of Imipenem/Relebactam Against Clinical Isolates of P. aeruginosa and K. pneumoniae Collected in Asia/Pacific Countries – SMART 2016-2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1768 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S791-S791

Author(s):

Sibylle Lob ◽

Krystyna Kazmierczak ◽

Wei-Ting Chen ◽

Tsz Kin Khan ◽

Katherine Young ◽

...

Keyword(s):

Urinary Tract ◽

Urinary Tract Infections ◽

Bloodstream Infections ◽

Clinical Isolates ◽

Asia Pacific ◽

Surveillance Program ◽

Independent Contractor ◽

The Usa ◽

Infection Source ◽

Tract Infections

Abstract Background Relebactam (REL) inhibits class A and C β-lactamases and was approved in the USA in combination with imipenem (IMI) and cilastatin for the treatment of complicated intraabdominal and urinary tract infections. We evaluated the activity of IMI/REL against clinical isolates collected in Asia/Pacific as part of the global SMART surveillance program. Methods In 2016-2018, 56 clinical laboratories each collected up to 250 consecutive, aerobic and facultative gram-negative pathogens from various infection sources per year. Susceptibility was determined using CLSI broth microdilution and CLSI breakpoints. IMI-nonsusceptible isolates (except from India) were screened for β-lactamase genes. Results Among 5501 K. pneumoniae and 4362 P. aeruginosa isolates, 46.6% and 65.3%, respectively, were collected from patients with lower respiratory tract infections, 25.6% and 17.1% from intraabdominal infections, 19.9% and 13.9% from urinary tract infections, and 7.2 and 2.9% from bloodstream infections. No infection source was specified for 0.7% of isolates from either species. 90.7% of collected K. pneumoniae isolates were IMI/REL-susceptible, ranging from 56.8% in India and ~80% in Thailand and Vietnam (~16% MBL-positive) to ≥97% in 7 countries (0-2% MBL-positive). 28.6% (202/707) of IMI-nonsusceptible K. pneumoniae were IMI/REL-susceptible. Of the 425 molecularly characterized IMI-nonsusceptible K. pneumoniae, 187 (44.0%) were MBL/OXA-48-like negative and 83.4% of these (156/187) were IMI/REL-susceptible; 82 isolates (19.3%) were KPC-positive and 91.5% of these (75/82) were IMI/REL-susceptible. The table shows percent susceptible and percent MBL-positive among all collected P. aeruginosa isolates. 74.3% of IMI-nonsusceptible P. aeruginosa (n=1236) were IMI/REL-susceptible. Table Conclusion IMI/REL was active against 91% of K. pneumoniae and 89% of P. aeruginosa isolates collected in Asia/Pacific overall, with higher activity in countries with lower MBL-positive rates. IMI/REL promises to be an important treatment option for IMI-nonsusceptible MBL-negative isolates, including KPC-producing K. pneumoniae. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Tsz Kin Khan, PhD, Merck, Sharp & Dohme, Hong Kong (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) 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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1594. Antimicrobial Resistance Monitoring through the ATLAS Global Surveillance Program 2012-2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1774 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S793-S794

Author(s):

Meredith Hackel ◽

Daniel F Sahm ◽

Michael Dowzicky

Keyword(s):

Antimicrobial Resistance ◽

Antimicrobial Agents ◽

Multiple Infection ◽

Surveillance Program ◽

Good Activity ◽

Independent Contractor ◽

Gram Positive ◽

In Vitro Susceptibility ◽

Gram Negative

Abstract Background Antimicrobial resistance is an increasingly serious threat to global public health. The Antimicrobial Testing Leadership and Surveillance (ATLAS) program has provided reliable, global, regional and local in vitro susceptibility data, including mechanisms of resistance, since 2004. In this analysis, data from the ATLAS program are used to measure the in vitro activity of several key gram-negative/gram-positive agents against major global pathogens. Methods A total of 251,837 gram-negative and 132,363 gram-positive non-duplicate, clinical isolates were collected from multiple infection sources from 743 unique sites in 74 countries during 2012-2018 in the ATLAS program. Identification was confirmed to the species level using MALDI-TOF spectrometry. Only one clinically relevant causative isolate per patient was accepted into the study. MICs were determined by broth microdilution following CLSI guidelines and interpreted using 2020 CLSI breakpoints. Phenotypic ESBL screening and confirmatory testing were performed using the CLSI M100 method. Results The in vitro activities of selected antimicrobial agents are provided in the table below. Based on percent susceptibility, ceftazidime-avibactam, amikacin, tigecycline, meropenem, and ceftolozane-tazobactam were the most active agents against most gram-negative isolates. The CRE rate among Enterobacterales isolates was 3.2%, with tigecycline and ceftazidime-avibactam the most active among this resistant subgroup. Ceftazidime-avibactam, ceftolozane-tazobactam, and amikacin were the most active agents against Pseudomonas aeruginosa. Ceftaroline, linezolid, tigecycline and vancomycin all showed good activity against gram-positive isolates. Table Conclusion Ceftazidime-avibactam, ceftolozane-tazobactam, tigecycline, meropenem, and amikacin all showed good activity against a global collection of Enterobacterales. Ceftaroline, tigecycline, linezolid and vancomycin all exhibited excellent activity against gram-positive isolates. Continued monitoring of susceptibility patterns among common pathogens will provide useful information for determining treatment strategies. Disclosures Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor) Michael Dowzicky, MS, M.T. A.S.C.P., Pfizer, Inc. (Employee)

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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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