scholarly journals 789. Susceptibility of Phenotypic Subsets of Pseudomonas aeruginosa Isolates to Cefiderocol and Comparator Agents from SIDERO-WT 2014-2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S491-S491
Author(s):  
Sean Nguyen ◽  
David Fam ◽  
Daniel F Sahm ◽  
Meredith Hackel ◽  
Roger Echols ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Surveillance Program ◽  
National Surveillance ◽  
In Vitro Activity ◽  
Central Laboratory ◽  
High Susceptibility ◽  
Independent Contractor ◽  
Fixed Concentration ◽  
Sources Of Infection

Abstract Background Multidrug-resistant (MDR) phenotypes are frequently observed among P. aeruginosa (PsA) isolated from hospitalized patients. This study describes the in vitro activities of cefiderocol (CFDC) and comparator agents against various non-susceptible (NS) phenotypic subsets of MDR PsA isolates from the SIDERO-WT multi-national surveillance program. Methods Clinical PsA isolates were collected from North America (NA) and Europe in 2014-2019 and tested for susceptibility at a central laboratory. MICs (μg/ml) were determined for CFDC, ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), colistin, cefepime, meropenem (MEM), and ciprofloxacin by broth microdilution according to CLSI guidelines. Aztreonam-avibactam (avibactam fixed concentration of 4 µg/ml) and imipenem/relebactam (I/R) were only tested during SIDERO-WT Year 5 (i.e. 2019). Susceptibility was interpreted according to current FDA and 2021 CLSI breakpoints. Results The different phenotypic subsets and susceptibility of tested compounds are shown in the table. Among 7700 PsA isolates, 47.7% and 23% were from respiratory and gastrointestinal sources of infection. CFDC inhibited 97.5% and 99.9% of all PsA at its FDA-S and CLSI-S MIC breakpoint of ≤1 and ≤4, respectively. CFDC had the lowest MIC90 of all tested agents and >99% S at an MIC ≤4 for all phenotypic subsets. At a MIC ≤1, CFDC displayed high susceptibility rates against all subsets including ≥88% S against CZA-NS, C/T-NS, I/R-NS, and MEM+I/R-NS isolates. Against MDR subsets, comparator agents consistently demonstrated lower activity than CFDC; 88% of MEM+C/T-NS and MEM+CZA-NS isolates had a CFDC MIC≤1 while 15.6% and 20.3% were S to I/R, respectively. 86% of MEM+CZA+C/T-NS and 80.4% CZA+C/T+I/R-NS isolates were S to CFDC. CFDC inhibited 98.1% and 99.4% of PsA isolates from NA (n = 3548) at a MIC of ≤1 and ≤4, respectively. In NA isolates that were MEM+C/T-NS; 85.7% of PsA isolates had a MIC ≤1 to CFDC and 33.3% and 28.6% were S to CZA and I/R, respectively. MEM: Meropenem; NS: Non-susceptible; CZA: Ceftazidime/avibactam; C/T: Ceftolozane/tazobactam; I/R: Imipenem/relebactam Conclusion CFDC demonstrated potent in vitro activity against a variety of phenotypic subsets of MDR P. aeruginosa isolates as compared to agents that are commonly used to treat MDR PsA infections including strains NS to other agents. These data support the use of CFDC as an important treatment option for MDR PsA. Disclosures Sean Nguyen, PharmD, Shionogi Inc (Employee) David Fam, PharmD, Shionogi (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Roger Echols, MD, Shionogi (Consultant) Yoshinori Yamano, PhD, Shionogi (Employee)

scholarly journals 1372. In Vitro Activity of Novel Ceftazidime–Avibactam and Aztreonam–Avibactam Combinations Against Carbapenem-Nonsusceptible Enterobacteriaceae Isolates by Phenotype Collected in Latin America From 2014 to 2017 as Part of the INFORM Surveillance Program

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S420-S420
Author(s):  
Krystyna Kazmierczak ◽  
Boudewijn De Jonge ◽  
Gregory G Stone ◽  
Dan Sahm
Keyword(s):  
Latin America ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Class A ◽  
Fixed Concentration ◽  
Clinically Significant

Abstract Background Carbapenem-nonsusceptible Enterobacteriaceae (CRE) are often multidrug-resistant and infections caused by these organisms are associated with increased morbidity and mortality. The combination of avibactam (AVI), a non-β-lactam/β-lactamase inhibitor of Class A, C, and some D serine β-lactamases, with ceftazidime (CAZ) and aztreonam (ATM) is being developed to treat infections caused by CRE. CAZ-AVI reveals potent in vitro activity against CRE, except those producing metallo-β-lactamases (MBLs), whereas ATM-AVI inhibits growth of both MBL-positive and MBL-negative CRE. We evaluated the in vitro activity of CAZ-AVI and ATM-AVI against Enterobacteriaceae isolates nonsusceptible to meropenem (MEM-NS) collected in 2014–2017 in Latin America through the INFORM global surveillance program. Methods Nonduplicate clinically significant isolates were collected from 29 hospital laboratories located in Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela. Susceptibility testing was performed by CLSI broth microdilution. AVI was tested at a fixed concentration of 4 µg/mL in combination with CAZ and ATM. MEM-NS Eba (MIC >1 µg/mL) were screened for the presence of β-lactamase genes by PCR and sequencing. Results Five hundred fifty-seven MEM-NS isolates were identified (440 Klebsiella pneumoniae and 117 isolates of 13 other species). Of these, 441 (79.2%) carried carbapenemases (Cpase) (KPC only, n = 383; MBL only, n = 48; OXA-48-like only, n = 5; KPC and OXA-48-like, n = 2; MBL and GES, n = 2; MBL and KPC, n = 1). CAZ-AVI showed potent in vitro activity against Cpase-positive MBL-negative and Cpase-negative Eba and against all MEM-NS Eba, but was not active against MBL-positive Eba. 100% of MEM-NS Eba were inhibited by ≤8 µg/mL of ATM-AVI. Conclusion CAZ-AVI and ATM-AVI displayed potent in vitro activity against MEM-NS Eba collected in LA. These agents could serve as promising options for treatment of infections caused by CRE. Disclosures K. Kazmierczak, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. B. De Jonge, AstraZeneca: Shareholder, Dividends. Pfizer Inc: Employee, Salary. G. G. Stone, Pfizer Inc.: Employee, Salary. AstraZeneca: Former Employee and Shareholder, Salary. D. Sahm, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary.

scholarly journals 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

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)

scholarly journals Evaluation of In Vitro Activity of Ceftaroline Tested against Streptococcus pneumoniae Isolates from United States Hospitals: Results from 7 Years of the AWARE Surveillance Program (2010–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S378-S378
Author(s):  
Michael A Pfaller ◽  
Rodrigo E Mendes ◽  
Leonard R Duncan ◽  
Robert K Flamm ◽  
Helio S Sader
Keyword(s):  
United States ◽  
The United States ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Amoxicillin Clavulanate ◽  
Infection Types ◽  
Research Grant

Abstract Background Ceftaroline (CPT) is a broad-spectrum cephalosporin with activity against S. pneumoniae (SPN), including multidrug-resistant (MDR) strains. CPT fosamil is approved for clinical use in the United States (US) to treat community-acquired bacterial pneumonia (CABP). The AWARE Program monitors the in vitro activity of CPT against clinical bacteria from various infection types. We evaluated the activity of CPT against isolated SPN clinical isolates from US hospitals collected in 2010 through 2016. Methods A total of 8,768 isolates were consecutively collected (1 per patient) from 47 medical centers in 2010–2016 and tested for susceptibility (S) to CPT and comparator agents using CLSI broth microdilution methods. Resistant subgroups included isolates that were nonsusceptible (NS) to penicillin (PCN), ceftriaxone (CRO), amoxicillin-clavulanate (AMC), erythromycin (ERY), clindamycin (CM), and levofloxacin (LEV) as well as MDR (NS to ≥3 classes of agents) and extensively drug resistant (XDR; NS to ≥5 classes). Results CPT inhibited 99.99% of SPN isolates at ≤0.5 mg/L (only 1 isolate had a CPT MIC of 1 mg/L) and remained active against all SPN-resistant (R) subgroups, including PCN-NS (8.7% at ≥4 mg/L), CRO-NS (6.9% at ≥2 mg/L), MDR (21.7%), and XDR (8.4%) strains. CPT activity remained stable against all R subgroups each year. MDR and XDR frequency decreased from 25.0% and 14.1% in 2011 to 17.8% and 3.2% in 2015, respectively; and S to PCN, CRO, AMC, CM, trimethoprim-sulfamethoxazole (TMX), and tetracycline (TET) increased in the same period (Table). The CPT-NS isolate had multiple substitutions in the penicillin binding proteins (PBP), mainly PBP2x, when compared with reference sequences, and showed 31 amino acid alterations in MurM. For MDR isolates, CPT (99.9%S), tigecycline (99.9%S), linezolid (100.0%S), and vancomycin (100.0%S) were the most active agents. Conclusion CPT demonstrated potent and consistent (2010–2016) activity against SPN, including several R phenotypes and the less S serotypes. SPN S to many antibiotics increased from 2011 to 2015, but remained stable in 2015–2016. Increases in S rates could be related to the anti-pneumococcal vaccine PVC-13 introduced in 2010. Disclosures M. A. Pfaller, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; L. R. Duncan, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant; H. S. Sader, Allergan: Research Contractor, Research grant

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)

scholarly journals 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

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)

scholarly journals 1265. In Vitro Activity of Aztreonam-Avibactam against Klebsiella pneumoniae Isolates Analyzed by Epidemic Lineage and Hypervirulence Factors Collected in China as Part of the ATLAS Global Surveillance Study in 2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S721-S721
Author(s):  
Mark Estabrook ◽  
Krystyna Kazmierczak ◽  
Francis Arhin ◽  
Daniel F Sahm
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Surveillance Study ◽  
In Vitro Activity ◽  
Independent Contractor ◽  
Illumina Hiseq ◽  
Carbapenem Resistant ◽  
Class D

Abstract Background Hypervirulent Klebsiella pneumoniae (hvKp), unlike classical K. pneumoniae (cKp), are often responsible for community-acquired infections in otherwise healthy individuals. The acquisition of hypervirulence genes by sequence type 11 (ST11) carbapenem-resistant (CR) Kp endemic in Asia is a grave threat. Aztreonam-avibactam (ATM-AVI) is a monobactam combined with a β-lactamase inhibitor for the treatment of infections caused by Enterobacterales isolates that carry Class A, B, C and some Class D β-lactamases. Methods 487 K. pneumoniae isolates were collected from 17 sites in China in 2019 as a part of the ATLAS global surveillance study. 220 isolates with MICs >1 µg/ml to meropenem (MEM), ceftazidime or ATM were selected for whole genome sequencing (Illumina Hiseq 2x150 bp reads). Analyses were carried out using the CLC Genomics Workbench (Qiagen). Presence of the aerobactin synthesis locus differentiated hvKp and cKp. Antimicrobial susceptibility was determined by CLSI broth microdilution. Results Of the 487 isolates, MIC90 values for ATM-AVI (0.5 µg/ml; Table) were lower than those for any comparator tested, with only two isolates testing with MIC >4 µg/ml. Of the isolates sequenced, 82/220 (37.3%) were ST11. 53/82 (64.6%) of these ST11 isolates were hvKp (ATM-AVI, MIC90 1 µg/ml; range, 0.25-4 µg/ml) and showed percentages of susceptibility < 90% to three last-line agents (0% MEM-susceptible (S); 18.9% amikacin (AMK)-S; 88.7% tigecycline (TGC)-S). Isolates of other STs (Non-ST11) were less frequently identified as hvKp (24/138, 17.4%) and more Non-ST-11 hvKp and cKp alike were S to MEM and AMK relative to isolates of ST11 (75.0-86.8% MEM-S; 83.3-96.5% AMK-S). Likewise, the ATM-AVI MIC90 value (0.25 µg/ml) was 4-fold lower for Non-ST11 isolates. Results Table Conclusion CR ST11 hvKp represented at least 10.9% of the collected Kp isolates. ATM-AVI retained potent in vitro activity against these isolates which displayed resistance to a range of last-line agents. CST and TGC also displayed some activity but are limited in utility due to nephrotoxicity and poor accumulation in blood, respectively. The spread of virulence factors leading to the complicated clinical presentation of hvKp infection into multidrug-resistant lineages warrants continued surveillance. Disclosures Mark Estabrook, 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)

scholarly journals 1245. In Vitro Activities of Ceftaroline and Comparator Agents Against Bacterial Pathogens Collected from Patients with Skin and Skin Structure Infections: ATLAS Global Surveillance Program 2012-2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S711-S711
Author(s):  
Meredith Hackel ◽  
Gregory Stone ◽  
Daniel F Sahm
Keyword(s):  
Klebsiella Oxytoca ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Bacterial Isolates ◽  
Independent Contractor ◽  
Ceftaroline Fosamil ◽  
Skin Structure ◽  
Dose Dependent

Abstract Background Ceftaroline fosamil, the prodrug of ceftaroline, is a parenteral cephem approved for the treatment of patients with skin and skin structure infections (SSSIs) caused by Staphylococcus aureus (both methicillin-susceptible [MSSA] and methicillin-resistant [MRSA] isolates), β-hemolytic streptococci (Streptococcus pyogenes, S. agalactiae, S. dysgalactiae), and select species of Enterobacterales (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca). The current study is part of the ATLAS (Antimicrobial Testing Leadership and Surveillance) program and evaluated the current activities of ceftaroline and comparator agents against commonly encountered bacterial isolates associated with SSSIs. Methods From 2012 to 2019 the ATLAS program received 124,694 bacterial isolates that had been cultured by 493 clinical laboratories in 71 countries from samples of patients diagnosed with SSSIs. All isolates were transported to IHMA, (Schaumburg, IL, USA) where their identities were confirmed using MALDI-TOF mass spectrometry and antimicrobial susceptibility testing performed following standardized CLSI broth microdilution methodology (M07). Percent susceptibilities were determined using 2021 CLSI MIC breakpoints. Phenotypic extended-spectrum β-lactamase (ESBL) screening and confirmatory testing were performed using the CLSI M100 method. Results The in vitro activity of ceftaroline is summarized in the following table. Overall, >99.9% of MSSA and 92.8% of MRSA from SSSI were susceptible to ceftaroline (MIC ≤1 µg/ml); 7.1% of MRSA isolates were ceftaroline-susceptible dose-dependent (MIC 2-4 µg/ml) with greatest proportion being from Chile (53.3% of 392 isolates), S. Korea (29.3% of 321 isolates), and China (24.7% of 652 isolates). Twelve ceftaroline-resistant MRSA were observed, consisting of 11 of 109 isolates from Thailand (10.1%) and 1 of 161 from China (0.6%). All S. pyogenes and 88.0% of ESBL-negative Enterobacterales were susceptible to ceftaroline. Results Table Conclusion Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with SSSIs. Disclosures 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 1565. In Vitro Activities of Ceftaroline and Comparator Agents against Bacterial Pathogens Collected from Patients with Skin and Skin Structure Infections: ATLAS Global Surveillance Program 2012-2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S782-S782
Author(s):  
Meredith Hackel ◽  
Greg Stone ◽  
Daniel F Sahm
Keyword(s):  
Klebsiella Oxytoca ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Bacterial Isolates ◽  
Independent Contractor ◽  
Ceftaroline Fosamil ◽  
Skin Structure ◽  
Dose Dependent

Abstract Background Ceftaroline fosamil, the prodrug of ceftaroline, is a parenteral cephem approved for the treatment of patients with skin and skin structure infections (SSSIs) caused by Staphylococcus aureus (both methicillin-susceptible [MSSA] and methicillin-resistant [MRSA] isolates), β-hemolytic streptococci (Streptococcus pyogenes, Streptococcus agalactiae), and select species of Enterobacterales (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca). The current study is part of the ATLAS (Antimicrobial Testing Leadership and Surveillance) program and evaluated the current activities of ceftaroline and comparator agents against commonly encountered bacterial isolates associated with SSSIs. Methods From 2012 to 2018 the ATLAS program received 90,119 bacterial isolates that had been cultured by 370 clinical laboratories in 56 countries from samples of patients diagnosed with SSSIs. All isolates were transported to IHMA, Inc., (Schaumburg, IL, USA) where their identities were confirmed using MALDI-TOF mass spectrometry and antimicrobial susceptibility testing performed following standardized CLSI broth microdilution methodology (M07). Percent susceptibilities were determined using 2020 CLSI MIC breakpoints. Phenotypic ESBL screening and confirmatory testing were performed using the CLSI M100 method. Results The in vitro activity of ceftaroline is summarized in the following table. Overall, 100% of MSSA and 93.8% of MRSA from SSSI were susceptible to ceftaroline (MIC ≤1 µg/ml); 6.2% of MRSA isolates were ceftaroline -susceptible dose-dependent (MIC 2-4 µg/ml) with greatest proportion being from Chile (57.1% of 1,669 isolates), Thailand (36.5% of 2,318 isolates), and S. Korea (29.3% of 1,231 isolates). No ceftaroline-resistant MRSA were observed. All S. pyogenes and 88.5% of ESBL-negative Enterobacterales were also susceptible to ceftaroline. Table Conclusion Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with SSSIs. Disclosures 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 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

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 &lt; 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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