In Vitro Activity of Tigecycline Against Commonly Isolated Pathogens of Skin and Skin Structure Infections in Latin America: TEST 2011–2014

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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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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1437 ◽

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)

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