Activity Of Ceftaroline Research Articles

Evaluation of in vitro activity of ceftaroline, ceftobiprole and their combination with trimethoprim/sulfamethoxazole against MRSA isolates: a two center study

There is an increasing need for new synergistic antimicrobial combinations against multidrug-resistant bacteria. Our objective was to evaluate the activity of ceftaroline, ceftobiprole and their combination with trimethoprim/sulfamethoxazole against methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered at two centers in Turkey. Activities of ceftaroline and ceftobiprole were tested against 100 MRSA isolates using gradient diffusion method. Activities of ceftaroline and ceftobiprole in combination with trimethoprim/sulfamethoxazole against 20 selected isolates (including all isolates that were non-susceptible to ceftaroline or ceftobiprole, and randomly selected isolates) were investigated using MIC:MIC ratio method. Antimicrobial interactions were interpreted using the fractional inhibitory concentration (FIC) index. The MIC50/MIC90 values for ceftaroline and ceftobiprole were 0.75/1 and 1/1.5 mg/L, respectively. Ceftaroline and ceftobiprole susceptibility rates among 100 MRSA isolates were 94% and 96%, respectively. Ceftaroline, ceftobiprole and trimethoprim/sulfamethoxazole MICs of isolates were not increased when ceftaroline or ceftobiprole was combined with trimethoprim/sulfamethoxazole. Ceftobiprole- trimethoprim/sulfamethoxazole combination demonstrated additivity against 35%, whereas ceftaroline- trimethoprim/sulfamethoxazole combination demonstrated additivity against 10% of 20 MRSA isolates. The remaining interactions for MRSA isolates were indifference. Three (75%) of four ceftobiprole-resistant isolates became susceptible to ceftobiprole after adding trimethoprim/sulfamethoxazole. None of the ceftaroline non-susceptible isolates became susceptible to ceftaroline after adding trimethoprim/sulfamethoxazole. Ceftobiprole- trimethoprim/sulfamethoxazole combination may be a better treatment option than ceftaroline- trimethoprim/sulfamethoxazole combination for MRSA infections. Clinical studies are needed to confirm the results of our in vitro study.

In vitro Activity of Ceftaroline Against Isolates of Gram-Positive Bacteria from Patients with Bloodstream Infections Collected as a Part of ATLAS Between 2017 and 2020.

To assess the in vitro activity of ceftaroline and a panel of comparator agents against isolates of Gram-positive bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic streptococci, and coagulase-negative staphylococci (CoNS) from blood collected in Africa and Middle East (AfME), Asia Pacific (APAC), Europe, Latin America (LATAM), and North America from 2017 to 2020 as a part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Susceptibility and minimum inhibitory concentration were determined using broth microdilution for all antimicrobial agents by a central reference laboratory according to the Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Ceftaroline showed good activity (susceptibility ≥89.8%, MIC90 0.008-2 mg/L) against all Gram-positive isolates tested. All isolates of methicillin-susceptible S. aureus, penicillin-susceptible S. pneumoniae, S. agalactiae, S. dysgalactiae, and S. pyogenes were susceptible to ceftaroline (MIC90 0.008-0.25 mg/L). Ceftaroline susceptibility for MRSA isolates was 89.8% globally (MIC90 2 mg/L). Among the comparator agents, all isolates were susceptible to vancomycin, except S. epidermis (susceptibility, 99.9%). Among other agents, daptomycin, linezolid, and tigecycline showed potent activity (susceptibility ≥97.9%, MIC90 0.03-2 mg/L) against all isolates tested. Ceftaroline showed potent in vitro activity against global bloodstream isolates of Gram-positive bacteria collected between 2017 and 2020. Monitoring and surveillance of global as well as regional longitudinal trends of resistance rates among Gram-positive isolates causing bloodstream infections are important to limit the spread of AMR, establish stewardship measures, and manage and appropriately treat infections.

2127. In vitro Activities of Ceftaroline and Comparator Agents against Bacterial Pathogens Frequently Causing Community-Acquired Respiratory Tract Infections in Patients from a Global Population: ATLAS Surveillance Program 2018-2021

Abstract Background Community-acquired bacterial pneumonia (CABP) is a frequent cause of patient morbidity and mortality. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are frequent etiologic agents of CABP. Ceftaroline fosamil is a parenteral cephem approved treatment of patients with CABP caused by S. pneumoniae (including cases with concurrent bacteremia), methicillin-susceptible Staphylococcus aureus (MSSA), H. influenzae, and some species of Enterobacterales. In this study we report the in vitro activity of ceftaroline and comparators against isolates from community-acquired respiratory tract infections (CARTI) collected through a global surveillance program. Methods Clinically relevant, non-duplicate, isolates cultured from respiratory specimens by clinical laboratories in 54 countries in 2018-2021 were collected by the ATLAS Surveillance Program central laboratory (IHMA, Schaumburg, IL, USA). Community-acquired infections were defined as those from patients < 48 hours in hospital. In total, 7,886 isolates of S. pneumoniae, H. influenzae, M. catarrhalis, MSSA, and methicillin-resistant S. aureus (MRSA) were tested. The isolates (n/percent of total) originated from Asia/South Pacific (1,893/24.0%); Europe (4,283/54.3%); Latin America (671/8.5%); Middle East/Africa (659/8.4%); and North America (Canada only) (380/4.8%). Ceftaroline and comparator agent MICs were determined by CLSI M07 broth microdilution methodology. MICs were interpreted using 2023 CLSI M100 MIC breakpoints. Results The in vitro activity of ceftaroline and comparator agents is summarized in the table. Greater than 99% of S. pneumoniae and 100% of MSSA were susceptible to ceftaroline, including penicillin-nonsusceptible S. pneumoniae based on a dosage of 600 mg every 12h. Sixty-two (9.6%) MRSA were ceftaroline-susceptible-dose-dependent (MIC 2-4 µg/mL) based on a dosage of 600 mg every 8h administered over 2h, with the majority from (n) Thailand (9), S. Korea (7), and China (6). Four isolates, from S. Korea (2), China (1), and Ukraine (1) were resistant to CPT (MIC of ≥8 µg/mL). 99.6% of H. influenzae were susceptible to ceftaroline. Conclusion Ceftaroline demonstrated potent in vitro activity against current pathogens associated with CABP from a global collection. Disclosures Meredith Hackel, PhD, Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Gregory Stone, PhD, Pfizer: Stocks/Bonds Daniel F. Sahm, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation

In vitro activity of ceftaroline against bacterial isolates causing skin and soft tissue and respiratory tract infections collected in Latin American countries, ATLAS program 2016–2020

Objectives: Ceftaroline, a broad-spectrum cephalosporin has activity against Gram-positive and several Gram-negative bacteria (GNB). This study aimed to evaluate the antimicrobial activity of ceftaroline and comparators against isolates causing skin and soft tissue infections (SSTIs) and respiratory tract infections (RTIs) collected in Latin America (LATAM) in 2016-2020 as part of the Antimicrobial Testing Leadership and Surveillance program (ATLAS). Methods: Minimum inhibitory concentrations were determined using both Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Results: Ceftaroline demonstrated potent activity against methicillin-susceptible Staphylococcus aureus (CLSI/EUCAST: MIC90 0.25 mg/L; susceptibility 100%), whereas activity against methicillin-resistant S. aureus varied for SSTIs (MIC90 1 mg/L; susceptibility 92.5%) and RTIs isolates (MIC90 2 mg/L; susceptibility 72.9%) isolates. For Streptococcus pneumoniae, particularly penicillin-resistant isolates commonly causing respiratory infections, high ceftaroline activity (MIC90 0.25 mg/L; susceptibility 100%/98.4%) was noted. All isolates of β-hemolytic streptococci were susceptible to ceftaroline [S. agalactiae: MIC90 0.03 mg/L (SSTIs); MIC90 0.015 mg/L (RTIs); susceptibility 100%; S. pyogenes: MIC90 0.008 mg/L; susceptibility 100%). Ceftaroline was highly active against Haemophilus influenzae including β-lactamase positive isolates (MIC90 0.06 mg/L; susceptibility 100%/85.7%). Ceftaroline demonstrated high activity against non-ESBL-producing GNB (E. coli: MIC90 0.5 mg/L, susceptibility 91.9%; K. pneumoniae: MIC90 0.25 mg/L, susceptibility 95.1%; K. oxytoca, MIC90 0.5 mg/L; susceptibility 95.7%). Conclusion: Ceftaroline was active against the recent collection of bacterial pathogens commonly causing SSTIs and RTIs in LATAM. Local and regional surveillance of antimicrobial resistance patterns are crucial to understand evolving resistance and guide treatment management.

In Vitro Activity of Ceftaroline and Comparators against Bacterial Isolates Collected Globally from Patients with Skin and Soft Tissue Infections: ATLAS Program 2019-2020.

The objective of this study was to assess the in vitro activity of ceftaroline and a panel of comparator agents against isolates causing skin and soft tissue infections (SSTIs) collected in Africa/Middle East, Asia-Pacific, Europe, and Latin America from 2019-2020. Minimum inhibitory concentrations (MIC) were determined using European Committee on Antimicrobial Susceptibility Testing criteria. All the methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to ceftaroline. Across all regions, ceftaroline demonstrated potent activity against methicillin-resistant S. aureus (MRSA, susceptibility 89.5-93.7%) isolates. Susceptibility to vancomycin, daptomycin, linezolid, teicoplanin, trimethoprim sulfamethoxazole, and tigecycline was ≥94.1% in MSSA and MRSA isolates. Against β-hemolytic streptococci isolates, ceftaroline demonstrated very potent activity (MIC90 0.008-0.03 mg/L) across all regions. All β-hemolytic streptococci isolates were susceptible to linezolid, penicillin, and vancomycin (MIC90 0.06-2 mg/L). Among the extended-spectrum β-lactamases (ESBL)-negative Enterobacterales tested (E. coli, K. pneumoniae, and K. oxytoca), susceptibility to ceftaroline was high (88.2-98.6%) in all regions. All ESBL-negative Enterobacterales were susceptible to aztreonam. Potent activity was observed for amikacin, cefepime, and meropenem (94.1-100%) against these isolates. Overall, ceftaroline showed potent in vitro activity against isolates of pathogens causing SSTIs. Continuous surveillance of global and regional susceptibility patterns is needed to guide appropriate treatment options against these pathogens.

Evaluation of in vitro activity of ceftaroline against pathogens associated with community-acquired pneumonia: ATLAS program 2017–2019

Ceftaroline is an important therapeutic option for community-acquired pneumonia (CAP). Antimicrobial susceptibility to ceftaroline and other antimicrobial agents against Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilusinfluenzae isolates collected worldwide from identified respiratory tract sources is reported by age groups (0-18, 19-65, and >65years). Antimicrobial susceptibility of isolates, collected as part of the ATLAS program (2017-2019), was performed per EUCAST/CLSI guidelines. S. aureus (N=7103; methicillin-susceptible S. aureus [MSSA]=4203; methicillin-resistant S. aureus [MRSA]=2791), S. pneumoniae (N=4823; EUCAST/CLSI, penicillin-intermediate S. pneumoniae [PISP]=1408/870; penicillin-resistant S. pneumoniae [PRSP]=455/993), and H. influenzae (N=3850; β-lactamase [βL]-negative=3097; βL-positive=753) isolates were collected from respiratory tract specimens. Susceptibility to ceftaroline was 89.08%-97.83% for S. aureus, 99.95%-100% for MSSA, and 78.07%-92.74% for MRSA isolates across age groups; S. aureus as well as MRSA isolates derived from the 0-18 years age group demonstrated the highest susceptibility rates to ceftaroline. Susceptibility to ceftaroline was 98.25%-99.77% for S.pneumoniae, 99.74%-100% for PISP, and 86.23%-99.04% for PRSP isolates across age groups. Across all age groups, susceptibility to ceftaroline was 89.53%-99.70% for H.influenzae, 93.02%-100% for βL-negative, and 77.78%-98.35% for βL-positive isolates. Irrespective of age, susceptibility to ceftaroline was high among the majority of S. aureus, S. pneumoniae, and H. influenzae isolates collected in this study.

In vitro Activity of Ceftaroline Against an International Collection of Kingella kingae Isolates Recovered From Carriers and Invasive Infections.

Improvements in blood culture techniques and molecular-based diagnostics have led to increased recognition of Kingella kingae as an invasive human pathogen causing bacteremia, septic arthritis, osteomyelitis and endocarditis in young children. Serious disease and potentially life-threatening complications of infection due to K. kingae necessitate timely identification and appropriate antimicrobial therapy. Ceftaroline is a fifth-generation broad spectrum cephalosporin that possesses activity against Gram-negative and Gram-positive pathogens similar to third-generation cephalosporins, but also includes methicillin-resistant Staphylococcus aureus . This study reports the in vitro activity of ceftaroline and comparator agents against an international collection of K. kingae isolates. A collection of 308 K. kingae isolates was obtained primarily from children with bacteremia, endocarditis, osteoarticular infections or from asymptomatic pediatric carriers. Isolates were tested for antibiotic susceptibility using Clinical and Laboratory Standard Institute broth microdilution methodology and screened for β-lactamase production using a nitrocefin chromogenic test. Ceftaroline inhibited all K. kingae isolates at ≤0.06 mg/L (MIC 50/90 , 0.015/0.03 mg/L). Ceftaroline MICs were similar to results with ceftriaxone (MIC 50/90 , 0.015/0.015 mg/L), meropenem (MIC 50/90 , 0.015/0.015 mg/L) and ampicillin-sulbactam (MIC 50/90 , 0.06/0.06 mg/L). Ceftaroline MICs were slightly lower than MICs for cefuroxime and amoxicillin/clavulanate (MIC 50/90 , 0.06/0.12 mg/L). MICs were high for clindamycin (MIC 50/90 , 2/4 mg/L) and oxacillin (MIC 50/90 , 4/8 mg/L). Sixteen isolates (5.2%) yielded a positive nitrocefin test indicating production of β-lactamase; ceftaroline demonstrated equivalent MICs against β-lactamase - positive and β-lactamase - negative strains (MIC 50/90 , 0.015/0.3 mg/L). The potent activity of ceftaroline against this large international collection of K. kingae isolates supports further clinical evaluation in children.

1673. In vitro Activities of Ceftaroline and Comparator Agents against Bacterial Pathogens Frequently Causing Community-Acquired Respiratory Tract Infections in Patients from a Global Population: ATLAS Surveillance Program 2017-2020

Abstract Background Community-acquired bacterial pneumonia (CABP) is a frequent cause of patient morbidity and mortality. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are frequent etiologic agents of CABP. Ceftaroline fosamil is a parenteral cephem approved for treatment of patients with CABP caused by S. pneumoniae (including cases with concurrent bacteremia), methicillin-susceptible Staphylococcus aureus (MSSA), H. influenzae, and some species of Enterobacterales. In this study we report the in vitro activity of ceftaroline and comparators against isolates from community-acquired respiratory tract infections (CARTI) collected through a global surveillance program. Methods Clinically relevant, non-duplicate, isolates cultured from respiratory specimens by clinical laboratories in 54 countries in 2017-2020 were collected by the ATLAS Surveillance Program central laboratory (IHMA, Schaumburg, IL, USA). In total, 2,284 isolates of S. pneumoniae, H. influenzae, M. catarrhalis, MSSA, and methicillin-resistant S. aureus (MRSA) were tested. The isolates (n/percent of total) originated from Asia/South Pacific (579/25.4%); Europe (1281/56.1%); Latin America (298/13.0%); Middle East/Africa (55/2.4%); and North America (Canada only) (71/3.1%). Ceftaroline and comparator agent MICs were determined by CLSI M07 broth microdilution methodology. MICs were interpreted using 2022 CLSI M100 MIC breakpoints. Results Ceftaroline and comparator agent in vitro activities are summarized in the table. Greater than 98% of S. pneumoniae and >99% of MSSA were susceptible to ceftaroline, including penicillin-nonsusceptible S. pneumoniae based on a dosage of 600 mg every 12h. Fifty-eight (31.4%) MRSA were ceftaroline-susceptible-dose-dependent (MIC 2-4 µg/mL) based on a dosage of 600 mg every 8h administered over 2h, with the majority from (n) China (18), S. Korea (8), and Japan (8). Three isolates, all from China, were resistant to CPT (MIC of 8 µg/mL). 99.3% of H. influenzae were susceptible to ceftaroline. Conclusion Ceftaroline demonstrated potent in vitro activity against current pathogens associated with CABP from a global collection. Disclosures All Authors: No reported disclosures.

1522. Penicillin plus ceftaroline against Enterococcus faecalis blood isolates lacking ampicillin plus ceftriaxone activity

Abstract Background Enterococcus faecalis infective endocarditis standard of care treatment, ampicillin plus ceftriaxone, unfortunately has been unable to decrease mortality rates and additionally increases patient risk for vancomycin-resistant enterococci (VRE). Recent data also demonstrates decreased ampicillin plus ceftriaxone activity in E. faecalis isolates with an elevated penicillin MIC of 4 mcg/mL. Penicillin plus ceftaroline is a promising alternative but limited data is available to support. Methods Seven E. faecalis clinical blood isolates and one wild-type E. faecalis isolate (i.e., JH2-2) were tested against penicillin plus ceftaroline utilizing 24-hour in vitro time-kill assays. All isolates were penicillin susceptible with minimum inhibitory concentrations (MIC) of either 2 (n=4) or 4 (n=4) mcg/mL, and ceftaroline MICs ranged from 1 to 8 mcg/mL. Penicillin and ceftaroline were tested at subinhibitory concentrations (0.25x and 0.5xMIC) as monotherapy and in combination. Antibacterial activity was described as bactericidal or bacteriostatic, defined as a ≥ 3-log10 colony-forming units (CFU)/mL or < 3-log10 CFU/mL decrease from initial inoculum, respectively. Synergy was defined as a ≥ 2-log10 decrease in CFU/mL at 24 hours from the most active single agent. Results Penicillin and ceftaroline monotherapy did not demonstrate any antibacterial activity, except for ceftaroline 0.5xMIC where four isolates demonstrated bacteriostatic activity (Table 1). Penicillin plus ceftaroline was synergistic in all isolates except JH2-2 (penicillin MIC of 2 mcg/mL) due to the bacteriostatic activity of ceftaroline alone. Synergistic and bactericidal activity was also more frequently observed in isolates with a penicillin MIC of 4 mcg/mL with penicillin plus ceftaroline than ampicillin plus ceftriaxone. Conclusion Penicillin plus ceftaroline demonstrates synergistic activity against clinical E. faecalis blood isolates including isolates with a penicillin MIC of 4 mcg/mL, where ampicillin plus ceftriaxone less frequently demonstrated synergy. Further research is warranted to support utilization in patients with E. faecalis infective endocarditis. Disclosures Jaclyn A. Cusumano, PharmD, BCIDP, Shionogi: Advisor/Consultant.

Activities of Eravacycline, Tedizolid, Norvancomycin, Nemonoxacin, Ceftaroline, and Comparators against 1,871 Staphylococcus and 1,068 Enterococcus Species Isolates from China: Updated Report of the CHINET Study 2019.

To evaluate the in vitro activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus and Enterococcus species isolates were collected as part of the China Antimicrobial Surveillance Network (CHINET) in 2019 to provide susceptibility data for Staphylococcus spp. and Enterococcus spp. for their future development and application in clinical practice. Antimicrobial susceptibility testing was performed using the CLSI broth microdilution reference method. Eravacycline was highly active against Staphylococcus and Enterococcus species isolates, proved by the MIC50/90: 0.06/0.125, 0.06/0.25, 0.06/0.25, 0.06/0.25, 0.125/0.5, 0.125/0.25, and 0.03/0.06 mg/L for Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S. epidermidis, S. hominis, S. haemolyticus, Enterococcus faecalis, and E. faecium, respectively. S. aureus isolates tested were fully susceptible to tedizolid. Still, nonsusceptible isolates were found for E. faecalis (72/567 [12.7%]) and E. faecium (12/501 [2.4%]). Norvancomycin at 2 mg/L could inhibit 100% of Staphylococcus spp., while 1 mg/L of ceftaroline could inhibit 78.9% of MRSA and 99.9% of methicillin-susceptible S. aureus (MSSA) isolates. Additionally, nemonoxacin was also active against Staphylococcus and Enterococcus species isolates tested (shown by the following MIC90s and ranges, in milligrams per liter: 2 and ≤0.015 to 8 for MRSA, 0.25 and ≤0.015 to 4 for MSSA, 0.5 and ≤0.015 to 8 for S. epidermidis, and 4 and ≤0.015 to >32 for E. faecalis). In conclusion, both eravacycline and tedizolid were highly active against clinical isolates of Staphylococcus spp. and Enterococcus spp. recently collected across China. Nemonoxacin showed potent activity against Staphylococcus spp. and E. faecalis but limited activity against E. faecium. Norvancomycin and ceftaroline displayed highly potent activity against Staphylococcus spp. IMPORTANCE Antimicrobial resistance has become a severe threat to global public health. According to statistics, nearly 700,000 people die from bacterial infections worldwide (J. O'Neill, Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations, 2014; C. Y. Chin, K. A. Tipton, M. Farokhyfar, E. M. Burd, et al., Nat Microbiol 3:563-569, 2018, https://doi.org/10.1038/s41564-018-0151-5). The number of bacterial infections is expected to climb to 10 million by 2050, showing that bacterial resistance has become a significant problem that cannot be ignored. It is crucial to develop new antimicrobial agents to combat antimicrobial-resistant bacteria. In this study, we evaluated the in vitro activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus spp. and Enterococcus species isolates which were collected as part of CHINET in 2019. We believe that this study can provide susceptibility data for Staphylococcus spp. and Enterococcus spp. for their future development and application in clinical practice.

In vitro activity of ceftaroline, ceftazidime-avibactam, and comparators against Gram-positive and -negative organisms in China: the 2018 results from the ATLAS program

BackgroundData on antibiotic resistance is essential to adapt treatment strategies against the rapidly changing reality of antimicrobial resistance.ObjectiveTo study the in vitro activity of ceftaroline, ceftazidime-avibactam, and comparators against Gram-positive and Gram-negative bacteria collected from China in the year 2018.MethodsA total of 2301 clinical isolates were collected from 17 medical center laboratories in China, which participated in the ATLAS program in 2018. Antimicrobial susceptibilities were determined by the broth microdilution method at a central laboratory. Clinical and Laboratory Standards Institute (CLSI) breakpoints were used to interpret the results except for tigecycline, for which the US Food and Drug Administration (FDA) breakpoint were used.ResultsThe susceptibility rates of methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and β-hemolytic streptococcus to ceftaroline were 83.9%, 100%, and 100%, respectively. Escherichia coli, imipenem-susceptible (IMP-S) Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, IMP-S Enterobacter cloacae, Proteus mirabilis, Morganella morganii, Serratia marcescens and Pseudomonas aeruginosa had high susceptibility rates to ceftazidime-avibactam (95.8%, 100%, 97.7%, 94.5%, 100%, 90.2%, 96.0%, 97.5% and 90.7%, respectively). However, imipenem-resistant Escherichia coli and imipenem-resistant Pseudomonas aeruginosa demonstrated low susceptibility to ceftazidime-avibactam (33.3% and 75.8%, respectively). Against MRSA, methicillin-susceptible Staphylococcus aureus (MSSA), S. pneumoniae and β-hemolytic streptococci, the susceptibility rates of tigecycline were 93.5%, 99.2%, 100% and 100%, respectively. Levofloxacin also showed high in vitro activity against S. pneumoniae and β-hemolytic streptococci with a susceptibility rate of 100% and 98.4%. The susceptibility rate of E. faecalis to ampicillin was 100%. Among Gram-negative isolates, tigecycline and colistin showed good activity against E. coli, K. pneumoniae, imipenem-resistant E. cloacae, C. freundii and A. baumannii (susceptibility rates and intermediate susceptibility rates of 99.3% and 96.8%, 95.4% and 94.5%, 100% and 87.5%, 96.4% and 89.3%, MIC90 of 2 mg/L and 97.4%, respectively). E. coli and E. cloacae had high susceptibility rates to imipenem and meropenem (93.0% and 92.8%, 89.8% and 92.1%, respectively). M. morganii and P. mirabilis demonstrated meropenem and piperacillin-tazobactam susceptibility rates of 96.0% and 94.0%, 94.1% and 92.2%, respectively.ConclusionCeftaroline showed good activity among tested antimicrobial agents against Gram-positive species, while ceftazidime-avibactam had good activity against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Morganella morganii, Serratia marcescens and Pseudomonas aeruginosa excluding carbapenem-resistant isolates.

Update on the in vitro activity of ceftaroline against Staphylococcus aureus from United States (US) medical centers stratified by infection type (2018−2020)

Ceftaroline and comparators were tested against 9,268 Staphylococcus aureus isolates from 33 United States hospitals (2018−2020). Ceftaroline (MIC50/90, 0.25/1 mg/L) susceptibility ranged from 95.4% (pneumonia) to 98.5% (skin and skin structure) and was 97.2% overall. Ceftaroline retained potent and broad-spectrum activity against methicillin-resistant isolates, with a 93.4% overall susceptibility.

Antimicrobial Activity of Ceftaroline and Comparator Agents Against Ceftriaxone-Nonsusceptible Streptococcus pneumoniae from the United States (2008-2020).

We evaluated the activity of ceftaroline against clinical isolates of ceftriaxone-nonsusceptible Streptococcus pneumoniae from United States medical centers. Streptococcus pneumoniae isolates (n = 21,750) were consecutively collected from 201 medical centers in 2008-2020 and tested for susceptibility by broth microdilution method. Among these isolates, 1,419 (6.5%) were ceftriaxone-nonsusceptible (ceftriaxone minimum inhibitory concentration [MIC], ≥2 mg/L). Other resistant subgroups analyzed included multidrug-resistant (MDR; nonsusceptibility to ≥3 classes of agents; n = 4,454) and extensively drug-resistant (XDR; nonsusceptibility to ≥5 classes; n = 1,708) isolates. Ceftriaxone susceptibility increased from 89.0% (2008-2011) to 98.1% (2018-2020). Ceftaroline was active against 99.9% of ceftriaxone-nonsusceptible isolates (MIC50/90, 0.25/0.25 mg/L) and retained potent activity against MDR (n = 4,454; MIC50/90, 0.12/0.25 mg/L; >99.9% susceptible) and XDR (n = 1,708; MIC50/90, 0.25/0.25 mg/L; 100.0% susceptible) isolates. Only one isolate had a ceftaroline MIC ≥0.5 mg/L. In summary, ceftaroline demonstrated potent and consistent activity over time (2008-2020) against a large collection of S. pneumoniae from U.S. medical centers, including ceftriaxone-nonsusceptible, MDR, and XDR isolates.

Assessment of In vitro Activities of Ceftaroline, Ceftazidime/ avibactam and Colistin against different Gram Negative and Gram Positive Isolates

Assessment of In vitro Activities of Ceftaroline, Ceftazidime/ avibactam and Colistin against different Gram Negative and Gram Positive Isolates

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

BackgroundCeftaroline 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.MethodsFrom 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.ResultsThe 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 ConclusionCeftaroline 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)

1271. In vitro Activities of Ceftaroline and Comparator Agents Against Bacterial Pathogens Frequently Causing Community-Acquired Respiratory Tract Infections in Patients from a Global Population: ATLAS Surveillance Program 2016-2019

Abstract Background Community-acquired bacterial pneumonia (CABP) is a frequent cause of patient morbidity and mortality. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are frequent etiologic agents of CABP. Ceftaroline fosamil is a parenteral cephem approved for treatment of patients with CABP caused by S. pneumoniae (including cases with concurrent bacteremia), methicillin-susceptible Staphylococcus aureus (MSSA), H. influenzae, and some species of Enterobacterales. In this study we report the in vitro activity of ceftaroline and comparators against isolates from community-acquired respiratory tract infections (CARTI) collected through a global surveillance program. Methods Clinically relevant, non-duplicate, isolates cultured from respiratory specimens by clinical laboratories in 54 countries in 2016-2019 were collected by the ATLAS Surveillance Program central laboratory (IHMA, Schaumburg, IL, USA). In total, 2,636 isolates of S. pneumoniae, H. influenzae, M. catarrhalis, MSSA, and methicillin-resistant S. aureus (MRSA) were tested. The isolates (n/percent of total) originated from Asia/South Pacific (722/27.4%); Europe (1481/56.2%); Latin America (292/11.1%); Middle East/Africa (57/2.2%); and North America (Canada only) (84/3.2%). Ceftaroline and comparator agent MICs were determined by CLSI M07 broth microdilution methodology. MICs were interpreted using 2021 CLSI M100 MIC breakpoints. Results Ceftaroline and comparator agent in vitro activities are summarized in the table. Greater than 98% of S. pneumoniae and >99% of MSSA were susceptible to ceftaroline, including penicillin-nonsusceptible S. pneumoniae based on a dosage of 600 mg every 12h. Sixty-four (24.4%) MRSA were ceftaroline-susceptible-dose-dependent (MIC 2-4 µg/mL) based on a dosage of 600 mg every 8h administered over 2h, with the majority from (n) China (70), S. Korea (19), Japan (10), and Chile (8). Three isolates, all from China, were resistant to CPT (MIC of 8 µg/mL). 99.2% of H. influenzae were susceptible to ceftaroline. Results Table Conclusion Ceftaroline demonstrated potent in vitro activity against current pathogens associated with CABP from a global collection. 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)

1236. Update on the In Vitro Activity of Ceftaroline against Staphylococcus aureus from United States (US) Medical Centers Stratified by Infection Type (2018-2020)

1236. Update on the In Vitro Activity of Ceftaroline against Staphylococcus aureus from United States (US) Medical Centers Stratified by Infection Type (2018-2020)

1224. In vitro Activities of Ceftaroline and Comparator Agents against Gram-positive Bacterial Pathogens Causing Blood Stream Infections in a Global Population: ATLAS Surveillance Program 2012-2019

BackgroundTypical gram-positive organisms causing bloodstream infections (BSI) include Staphylococcus aureus (methicillin-susceptible [MSSA] and -nonsusceptible [MRSA]), coagulase negative staphylococci, Streptococcus pneumoniae and beta hemolytic streptococci. The parenteral cephem ceftaroline fosamil is approved for treatment of patients with community-acquired bacterial pneumonia caused by S. pneumoniae (including cases with concurrent bacteremia), MSSA, Haemophilus influenzae, and some species of Enterobacterales. Limited data have been published on the in vitro activity of ceftaroline against recent gram-positive clinical isolates known to be frequent bacterial causes of blood stream infections.MethodsStandard CLSI broth microdilution MIC determinations (M07) were performed with ceftaroline and comparator agents. MICs were interpreted using 2021 CLSI MIC breakpoints. Clinically relevant, non-duplicate, isolates cultured from blood by clinical laboratories in 2012-2019 were tested by the ATLAS (Antimicrobial Testing Leadership and Surveillance) program central laboratory (IHMA, Inc., Schaumburg, IL, USA). In total, 21,967 non-duplicate isolates of S. aureus, S. epidermidis, S. pneumoniae and beta hemolytic streptococci from BSI collected between 2012 and 2019 were tested. Isolates came from (n/%): Asia/South Pacific (2,970/13.5%), Europe (13,691/62.3%), Latin America (2,824/12.9%), MidEast/Africa (1,498/6.8%), and North America (Canada only) (984/4.5%).ResultsCeftaroline and comparator agent activities are summarized in the following table.Results Table ConclusionGreater than 99% of S. pneumoniae, beta-hemolytic streptococci and MSSA isolates included in a 2012-2019 collection of gram-positive blood stream pathogens were susceptible to ceftaroline. 90.8% of MRSA were susceptible, and 9.1% isolates categorized as susceptible-dose dependent (MIC, 2-4 µg/mL); four isolates (two from Thailand and one each from China and S. Korea) were resistant to ceftaroline (MIC >4 µg/mL). The ceftaroline MIC90 for S. epidermidis was 0.5 µg/mL, with 97.7% of MICs ≤1 µg/mL. Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with BSI.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)

Evaluation of the in vitro activity of ceftaroline, ceftazidime/avibactam and comparator antimicrobial agents against clinical isolates from paediatric patients in Kuwait: ATLAS data 2012-19.

To report antimicrobial resistance data for Gram-positive and Gram-negative pathogens isolated from paediatric patients in three hospitals in Kuwait during 2012-19. In vitro activity of antimicrobials against isolates from documented infections was determined using CLSI broth microdilution method and breakpoints at a central laboratory. Enterobacterales and Pseudomonas aeruginosa isolates were screened for β-lactamases using multiplex PCR assays. Phenotypic determination of resistance in Haemophilus influenzae and Gram-positive isolates was performed using standard methodologies. Among 515 Enterobacterales isolates, 29.3% were ESBL-positive; susceptibility was highest to amikacin, ceftazidime/avibactam and meropenem (≥97.4%), regardless of ESBL status. CTX-M-15 was identified in 87.1% of ESBL-positive Escherichia coli and 84.2% of ESBL-positive Klebsiella pneumoniae isolates. Of 111 P. aeruginosa isolates, 9.9% were MDR and 12.6% meropenem-resistant (MEM-R). Amikacin and ceftazidime/avibactam had the highest susceptibility rates in the overall group (≥92.8%), with reduced rates among MDR and MEM-R isolates. All 269 MRSA and 180 MSSA isolates were susceptible to daptomycin, linezolid, teicoplanin, tigecycline and vancomycin. All MSSA and 99.3% of MRSA were ceftaroline susceptible. All 168 pneumococcal isolates were susceptible to ceftaroline, linezolid, tigecycline and vancomycin. H. influenzae and Streptococcus pyogenes ceftaroline susceptibility rates were ≥93.3% and ≥95.6%. Most isolates of Enterobacterales (including resistant phenotypes) and P. aeruginosa from Kuwait during 2012-19 were susceptible to ceftazidime/avibactam. Ceftaroline was active against most Gram-positive isolates, including resistant phenotypes, and ESBL-negative Enterobacterales. These results indicate that novel antibiotics such as ceftazidime/avibactam and ceftaroline represent valuable treatment options for paediatric infections, including those caused by MDR organisms.

In vitro activity of ceftaroline and other antimicrobial agents against Gram positive bacterial isolates: Descriptive study from a university hospital

PurposeCeftaroline is a novel antibiotic approved by USA Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). It has potent in vitro activity against Staphylococci, including methicillin-resistant strains, whose incidence is increasing worldwide and they are often difficult to treat. The present study was done to investigate the susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MR-CoNS) to ceftaroline and other antimicrobial agents in patient samples and to evaluate clinical profile of these patients. MethodsAll consecutive, nonduplicate isolates of MRSA and MR-CoNS recovered from patient samples between June 2020 to December 2020 were included in the study. Species identification was done by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectromtery (MALDI-TOF-MS) (BioMérieux, France). Antimicrobial sensitivity of ceftaroline and other comparator antimicrobials was done as per the Clinical and Laboratory Standards Institute (CLSI, 2020). Statistical Package for the Social Sciences (IBM-SPSS) software (Version 25) was used for statistical study. ResultsTotal 134 clinical isolates of the study consisted of MR-CoNS (115 isolates; 85.8%) and MRSA (19 isolates; 14.2%).89.5% MRSA isolates were sensitive to ceftaroline. 44.3% and 32.2% MR-CoNS isolates had ceftaroline MIC ≤1 ​μg/ml and MIC ​= ​2–4 ​μg/ml respectively. ConclusionsCeftaroline exhibited potent in vitro activity against both MRSA and MR-CoNS in the study.