EVALUATION OF THE IN VITRO ACTIVITY OF CEFTAROLINE AND COMPARATORS AGAINST STREPTOCOCCUS PNEUMONIAE ISOLATES FROM THE UNITED STATES: RESULTS FROM 10 YEARS OF THE AWARE SURVEILLANCE PROGRAM (2011-2020)

Abstract

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Ceftaroline (CPT) is a broad-spectrum cephalosporin with activity against S. pneumoniae (SPN), including ceftriaxone-resistant and multidrug-resistant (MDR) strains. CPT fosamil is approved for clinical use in the United States (US) to treat community-acquired bacterial pneumonia (CABP). We evaluated trends in SPN antimicrobial susceptibility in US hospitals during 2011-2020. METHODS: 7,901 isolates were consecutively collected (1 per patient) from 28 medical centers and tested for susceptibility to CPT and comparator agents using CLSI broth microdilution methods. Resistant subgroups included isolates that were nonsusceptible (NS) to penicillin (PEN), ceftriaxone (CRO), amoxicillin-clavulanate (AMX-CLA), erythromycin (ERY), clindamycin (CLI), tetracycline (TET), and levofloxacin (LEV) as well as MDR (NS to ≥3 classes of agents) and extensively drug resistant (XDR; NS to ≥5 classes). Selected isolates were serotyped. 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 subgroups, including AMX-CLA-NS (8.9% at ≥4 mg/L), PEN-NS (6.2% at ≥4 mg/L), and CRO-NS (5.1% at ≥2 mg/L). CPT activity remained stable against all R subgroups each year. In general, susceptibility to PEN, CRO, AMX-CLA, CLI, trimethoprim-sulfamethoxazole, and tetracycline (TET) increased from 2011 to 2015 and remained relatively stable from 2016 to 2020. Similarly, MDR and XDR rates decreased from 2011 to 2015 and remained stable in 2016-2020. Susceptibility to ERY oscillated from 52.2% (2014) to 56.4% (2011) and LEV was very active during the study period (98.9-100.0%S). MDR rates varied from 23.7% in 2011 to 16.2% in 2020 (19.7% overall), and XDR rates varied from 13.3% in 2011 to 1.8% in 2019 (6.1% overall). Against MDR isolates (n=1,555), CPT (MIC50/90, 0.06/0.25 mg/L; 99.9%S), LEV (MIC50/90, 1/1 mg/L 98.1%S), linezolid (LZD; MIC50/90, 1/1 mg/L; 100.0%S), and vancomycin (VAN; MIC50/90, 0.25/0.5 mg/L, 100.0%S) were the most active agents. All XDR isolates were susceptible to CPT (MIC50/90, 0.12/0.25 mg/L), LZD (MIC50/90, 0.5/1 mg/L), and VAN (MIC50/90, 0.25/0.5 mg/L), and 97.5% were susceptible to TIG (MIC50/90, ≤0.03/0.06 mg/L). The CPT-NS isolate was isolated in 2014 and had multiple substitutions in the penicillin binding proteins (PBP), mainly PBP2x, when compared with reference sequences. The CPT-NS isolate also showed 31 amino acid alterations in MurM. CONCLUSIONS: CPT demonstrated potent and consistent (2010-2020) activity against SPN, including several resistant phenotypes and the less susceptible serotypes. SPN susceptibility to many antibiotics increased from 2011 to 2015 but remained stable in 2016-2020. CLINICAL IMPLICATIONS: Increases in susceptibility rates could be related to the anti-pneumococcal vaccine PVC-13 introduced in 2010. Continued surveillance is crucial since resistance clones not covered by the vaccine may expand. DISCLOSURES: my employer received research support relationship with AbbVie Please note: 2020-2022 Added 04/20/2021 by Cecilia Carvalhaes, source=Web Response, value=Grant/Research Support No relevant relationships by Mariana Castanheira, source=Web Response no disclosure on file for Rodrigo Mendes;Research Contractor relationship with Allergan Please note: $1001 - $5000 by Helio Sader, source=Web Response, value=Grant/Research Support Research Contractor relationship with AbbVIe (formerly Allergan) Please note: Ongoing Added 04/15/2021 by Helio Sader, source=Web Response, value=Grant/Research Supportemployer received grant/research support relationship with Allergan/ Abbvie Please note: 2020-2022 Added 04/20/2021 by Dee Shortridge, source=Web Response, value=Grant/Research Support No relevant relationships by Streit Streit, source=Web Response