Activity Of Ceftaroline Research Articles

In vitro activity of ceftaroline and comparators against bacterial isolates collected globally from patients with skin infections

This study reports the antimicrobial activities of ceftaroline and comparators against bacterial isolates from patients with skin and skin-structure infections (2015-2018). A central laboratory performed antimicrobial susceptibility testing according to CLSI broth microdilution methodology. EUCAST breakpoints were used. Isolates were collected in Europe (14 408 isolates; 53.9%), Asia/South Pacific (SP) (5317; 19.9%), Latin America (4268; 16.0%) and Africa/Middle East (ME) (2753; 10.3%). In all regions, all 7950 methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to ceftaroline and vancomycin; susceptibility to daptomycin, linezolid, teicoplanin and tigecycline was ≥99.6%. Susceptibility of all 9174 methicillin-resistant S. aureus (MRSA) isolates to daptomycin, linezolid, teicoplanin, tigecycline and vancomycin was ≥97.7%, with 90.8-96.5% susceptible to ceftaroline. The ceftaroline MIC90 was 0.008 mg/L against Streptococcus pyogenes, 0.015-0.03 mg/L against Streptococcus agalactiae and 0.008-0.015 mg/L against Streptococcus dysgalactiae. All β-haemolytic streptococci were susceptible to vancomycin. Susceptibility of extended-spectrum β-lactamase (ESBL)-negative Escherichia coli to ceftaroline ranged from 67.0% in Asia/SP to 91.0% in Africa/ME; susceptibility to amikacin, meropenem and tigecycline was ≥96.7% in all regions. Susceptibility of ESBL-negative Klebsiella pneumoniae to ceftaroline ranged from 78.4% in Europe to 83.2% in Africa/ME, and among ESBL-negative Klebsiella oxytoca was 76.3% in Asia/SP and 89.0-93.5% in other regions. Among ESBL-negative K. pneumoniae and ESBL-negative K. oxytoca, susceptibility was highest to amikacin (93.7-96.4% and 95.7-100%, respectively) and meropenem (89.7-97.4% and 98.3-100%, respectively). Ceftaroline was active against the Gram-positive isolates collected. Susceptibility of ESBL-negative Gram-negative isolates showed regional variations.

Ceftaroline In-vitro Activity against Methicillin Resistant Staphylococcal Isolates in a Rural Tertiary Healthcare Centre

Introduction: The emergence of Methicillin Resistant (MR) staphylococcal infections had led to fewer therapeutic options. Ceftaroline fosamil is the only cephalosporin approved by United States of America (USA) Food and Drug Administration (FDA) till now which has activity against MR staphylococcal isolates. Until now, studies on in-vitro activity of ceftaroline are limited. Aim: To know the susceptibility pattern of Methicillin Resistant Staphylococcus aureus (MRSA) and Methicillin Resistant Coagulase Negative Staphylococci (MRCoNS) against ceftaroline in a rural tertiary health care centre. Materials and Methods: The present cross-sectional study was conducted in a tertiary care hospital in rural part of Karnataka between two months (July and August 2019). A total of 50 consecutive, non repetitive clinical isolates of MRSA and MRCoNS were obtained. Antibiotic susceptibility testing was done according to Clinical and Laboratory Standards Institute (CLSI) guidelines. The Minimum Inhibitory Concentration (MIC) of ceftaroline was detected using E-strips (Biomerieux). The CLSI breakpoints applied for the interpretation of ceftaroline MIC- Sensitive: ≤1 μg/mL; Susceptible Dose Dependent (SDD): 2-4 μg/ mL and resistant ≥8 μg/mL). Staphylococcus aureus American Type Culture Collection (ATCC) 29213 was used as a quality control. Statistical analysis was done using microsoft excel. Percentages were used in this study to analyse variables. Results: Out of 50 MR staphylococcal isolates, 10 (20%) were MRSA and 40 (80%) were MRCoNS. Of the MR staphylococcal isolates tested, 49 (98%) were sensitive to ceftaroline. The MIC 50 and MIC 90 for the 50 MR staphylococci was 0.25 μg/mL and 1 μg/mL, respectively. Conclusion: Ceftaroline demonstrated a potent in-vitro activity against MR staphylococci. So it can be used as an effective drug in the treatment of such infections.

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

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, 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.MethodsFrom 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.ResultsThe 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 ConclusionCeftaroline 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)

1566. In vitro Activities of Ceftaroline and Comparator Agents against Gram-positive Bacterial Pathogens Causing Blood Stream Infections in a Global Population: ATLAS Surveillance Program 2012-2018

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 2020 CLSI MIC breakpoints. Clinically relevant, non-duplicate, isolates cultured from blood by clinical laboratories in 2012-2018 were tested by the ATLAS (Antimicrobial Testing Leadership and Surveillance) program central laboratory (IHMA, Inc., Schaumburg, IL, USA). In total, 10,998 non-duplicate isolates of S. aureus, S. epidermidis, S. pneumoniae and beta hemolytic streptococci from BSI collected between 2012 and 2018 were tested. Isolates came from (n/%): Asia/South Pacific (1,739/15.8%), Europe (5,448/49.5%), Latin America (1,805/16.4%), MidEast/Africa (861/7.8%), and North America (1,145/10.4%).ResultsCeftaroline and comparator agent activities are summarized in the following table.Table ConclusionGreater than 98% of S. pneumoniae, S. epidermidis, beta-hemolytic streptococci and MSSA isolates included in a 2012-2018 collection of gram-positive blood stream pathogens were susceptible to ceftaroline. 91.4% of MRSA were susceptible, and 8.6% isolates categorized as susceptible-dose dependent (MIC, 2-4 ug/mL); two isolates (one each from Thailand and S. Korea) were resistant to ceftaroline (MIC >4 ug/mL). Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with BSI.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)

In vitro activity of ceftaroline against bacterial pathogens isolated from patients with skin and soft tissue and respiratory tract infections in the Middle East and Africa: AWARE global surveillance programme 2015–2018

ObjectivesTo report antimicrobial susceptibility testing surveillance data for ceftaroline and comparative agents from the AWARE global surveillance programme for bacterial pathogens causing skin and soft tissue infections (SSTIs) and lower respiratory infections (RTIs) in Middle East and African countries from 2015 to 2018. MethodsPathogens were identified by MALDI-TOF/MS. Antimicrobial susceptibility testing was performed using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. MICs were interpreted by both CLSI (M100, 2020) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) (v 10.0, 2020) breakpoints. ResultsAll MSSA (n = 1125) and 93.9% of MRSA (n = 1235) were susceptible to ceftaroline (MIC ≤ 1 μg/mL, CLSI and EUCAST). The maximum ceftaroline MIC observed for MRSA was 2 μg/mL; no ceftaroline-resistant MRSA were identified among SSTI (CLSI and EUCAST) and RTI (CLSI) isolates. All isolates of β-haemolytic Streptococcus (n = 324), and penicillin-susceptible (PSSP) and -intermediate Streptococcus pneumoniae (PISP; n = 369) were susceptible to ceftaroline. Rates of susceptibility to ceftaroline for penicillin-resistant S. pneumoniae (penicillin MIC ≥ 2 μg/mL; n = 175), and β-lactamase-negative (BLNHI; n = 224) and β-lactamase-positive Haemophilus influenzae (n = 49) were 99.4%, 98.7%, and 98.0% (CLSI) and 92.6%, 98.2%, and 83.7% (EUCAST), respectively. Rates of susceptibility to ceftaroline for ESBL-negative Escherichia coli (n = 442), Klebsiella pneumoniae (n = 381), and Klebsiella oxytoca (n = 103) were 92.1%, 93.2%, and 96.1%, respectively. ConclusionCeftaroline-resistant isolates of MRSA causing SSTIs were not identified in Middle East and African countries in 2015–2018 using recently revised CLSI (in 2019) or EUCAST (in 2018) breakpoint criteria. Common bacterial pathogens causing SSTIs (Staphylococcus aureus, β-haemolytic Streptococcus) and lower RTIs (PSSP, PISP, BLNHI) demonstrated no resistance or low levels of resistance (0–1.8%) to ceftaroline.

Prevalence and molecular epidemiology of ceftaroline non-susceptible methicillin-resistant Staphylococcus aureus isolates, first clinical report from Iran.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major pathogens in Iran with a high prevalence and a high level of antibiotic resistance. Ceftaroline is a fifth generation cephalosporin binding and inhibiting penicillin binding protein (PBP2a). In the present study, 228 clinical MRSA isolates were collected from four cities of Iran and their susceptibility to ceftaroline was evaluated by E-test and the disk diffusion method. Our results showed a high susceptibility rate (97.3%) to ceftaroline in MRSA strains from Iran. Six isolates were found to be ceftaroline non-susceptible (CPT-NS) with Minimum inhibitory concentration (MIC) ≥2 µg/mL. All CPT-NS isolates were isolated from blood and tracheal aspirate and belonged to SCCmec type III as well as agr type I and were all susceptible to vancomycin. Out of six isolates, three, two and one belonged to spa type t030, t4864, and t969, respectively. Vancomycin, quinupristin/dalfopristin, linezolid, chloramphenicol, and tigecycline were the most active agents against CPT-NS isolates. Due to the broad-spectrum activity and low toxicity of ceftaroline as well as the increased rate of vancomycin resistance among MRSA strains in recent years, ceftaroline can be considered as a novel approach to treat MRSA-induced infections.

Ceftaroline activity against Staphylococcus aureus isolated from patients with infective endocarditis, worldwide (2010–2019)

ObjectiveTo evaluate the antimicrobial activity of ceftaroline against Staphylococcus aureus isolated from patients with infective endocarditis (IE). Methods23,833 S. aureus isolates were collected consecutively from patients with bloodstream infections (BSI) from 2010 to 2019, via the SENTRY Antimicrobial Surveillance Program, including 396 isolates from patients with a diagnosis of IE. Isolates were collected from 340 medical centers worldwide and susceptibility tested by reference broth microdilution in a monitoring laboratory. ResultsThe oxacillin resistance (MRSA) rate was 29.0% among IE isolates, and was higher in North America (40.3%) than in Europe (25.4%) or the Latin America/Asia-Pacific region (LATAM-APAC; 18.6%). Ceftaroline was active against 95.2% of IE isolates (MIC50/90, 0.25/1 mg/L), with ceftaroline susceptibility higher in North America (99.2%) and LATAM-APAC (98.3%) than in Europe (92.0%). Among MRSA isolates from IE (n = 115; MIC50/90, 1/2 mg/L), ceftaroline susceptibility was 98.0% in North America, 90.9% in LATAM-APAC, and 68.5% in Europe. Among BSI isolates, MRSA rates were 43.6% in North America and 25.6% in Europe, while ceftaroline susceptibility rates were 98.1% in North America and 95.4% in Europe. ConclusionsCeftaroline demonstrated potent in vitro activity against a large collection of S. aureus isolates recovered from patients with BSI, including IE.

Comparative In Vitro Activities of Ceftaroline and Tedizolid against Clinical Strains of Staphylococcus aureus and Enterococcus: Results from the China Antimicrobial Surveillance Network (CHINET) in 2018.

The in vitro activities of ceftaroline and tedizolid were compared against Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium clinical isolates collected from the China Antimicrobial Surveillance Network. Ceftaroline demonstrated potent activity against S. aureus isolates (MIC50/90, ≤0.25/1 mg/liter). Tedizolid was also highly active against S. aureus (MIC50/90, 0.25/0.5 mg/liter) and Enterococcus (MIC50/90, 0.5/0.5 mg/liter) isolates. Our results support the clinical usefulness of ceftaroline and tedizolid in treating Gram-positive infections.

ANTIMICROBIAL ACTIVITY OF CEFTAROLINE AGAINST STAPHYLOCOCCUS AUREUS ISOLATED FROM PATIENTS WITH INFECTIVE ENDOCARDITIS WORLDWIDE (2010-2019)

SESSION TITLE: Chest Infections Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Ceftaroline is approved by the United States (US) Food and Drug Administration for community-acquired bacterial pneumonia and skin and skin-structure infections, including cases with concurrent bacteremia, and has demonstrated efficacy in cases of infective endocarditis (IE). We evaluated the antimicrobial activity of ceftaroline against S. aureus isolated from patients with IE. METHODS: 23,834 S. aureus isolates were collected consecutively from patients with bloodstream infections (BSI) from 2010 to 2019 via the SENTRY Antimicrobial Surveillance Program, including 396 isolates patients with a diagnosis of IE. IE isolates were collected from 19 medical centers in the US (n=124), 34 in Europe (EUR; n=213), and 22 in other geographic regions (n=59) and were tested for susceptibility against ceftaroline and comparators by reference broth microdilution method in a monitoring laboratory (JMI Laboratories). RESULTS: Among IE isolates, the overall oxacillin resistance (MRSA) rate was 29.0%, but this rate was higher in the US (40.3%) than EUR (25.4%) and other regions (18.6%). Ceftaroline was active against 95.2% of IE isolates (MIC50/90, 0.25/1 mg/L) and ceftaroline susceptibility was higher in the US (99.2%) and other regions (98.3%) than EUR (92.0%). Among oxacillin-susceptible (MSSA) isolates, the highest ceftaroline MIC value was 0.5 mg/L (94.7% inhibited at ≤0.25 mg/L). Among MRSA isolates from IE (n=115; MIC50/90, 1/2 mg/L), ceftaroline susceptibility was 98.0% in the US and 68.5% in EUR (90.9% in other regions; n=11). The highest ceftaroline MIC was only 2 mg/L and all ceftaroline-nonsusceptible isolates were categorized as susceptible dose dependent or intermediate (0.0% resistant). Dalbavancin (MIC50/90, ≤0.03/0.06 mg/L), daptomycin (MIC50/90, 0.25/0.5 mg/L), linezolid (MIC50/90, 1/2 mg/L), teicoplanin (MIC50/90, ≤2/≤2 mg/L), tigecycline (MIC50/90, 0.06/0.12 mg/L), and vancomycin (MIC50/90, 1/1 mg/L) exhibited complete activity (100.0% susceptible) against S. aureus from IE. Among all BSI S. aureus isolates (n=23,834), MRSA rates were 43.6% in the US and 25.6% in EUR, and ceftaroline susceptibility rates were 98.1% in the US and 95.4% in EUR. CONCLUSIONS: Ceftaroline exhibited potent in vitro activity against a large collection of S. aureus isolates recovered from patients with IE. Ceftaroline was particularly active against MRSA-causing BSI and IE in US medical centers. These results support further investigations to determine the role of ceftaroline in the treatment of IE. CLINICAL IMPLICATIONS: These results support further investigations to determine the role of ceftaroline in the treatment of IE. DISCLOSURES: No relevant relationships by Cecilia Carvalhaes, source=Web Response no disclosure on file for Rodrigo Mendes; Research Contractor relationship with Allergan Please note: $1001 - $5000 Added 03/11/2020 by Helio Sader, source=Web Response, value=Grant/Research Support no disclosure on file for Streit Streit

Activity of ceftaroline versus ceftobiprole against staphylococci and pneumococci in the UK and Ireland: analysis of BSAC surveillance data.

Ceftaroline and ceftobiprole inhibit most MRSA and MDR pneumococci. Few direct comparisons of their activity have been published, but in several years (2008, 2013, 2017 and 2018) both were tested in parallel in the BSAC Resistance Surveillance Programme, giving paired results. These are reviewed. Isolates included were bloodstream Staphylococcus aureus [n = 1884 (MRSA, n = 234)], bloodstream CoNS (n = 813; 574 methicillin resistant), and bloodstream (n = 852) and respiratory (n = 670) Streptococcus pneumoniae. MICs were determined by BSAC agar dilution and reviewed against EUCAST breakpoints; S. aureus breakpoints were assumed for CoNS. Ceftaroline MICs were mostly 2-fold lower than those of ceftobiprole, but, for all groups, MICs of both agents were strongly inter-related. Methicillin-susceptible staphylococci were universally susceptible to both agents; all MRSA were susceptible to ceftobiprole, whereas 10/234 had intermediate/high-dose susceptibility to ceftaroline. Among methicillin-resistant CoNS, 88% were susceptible to both agents, but reduced ceftaroline susceptibility and ceftobiprole resistance were frequent (65%) among methicillin-resistant Staphylococcus haemolyticus. One S. pneumoniae was resistant to both ceftaroline (MIC 0.5 mg/L) and ceftobiprole (MIC 1 mg/L) and seven others were only resistant to ceftobiprole (MIC 1 mg/L); seven of these eight pneumococci belonged to serotype 19A or 19F. No time trend in susceptibility was seen for either cephalosporin. Ceftaroline and ceftobiprole have similarly good activity against staphylococci and pneumococci. Therapeutic choices between these agents should be predicated on other differentiating factors, including licensed indications, clinical experience and need for Gram-negative coverage.

In vitro activity of ceftaroline and ceftobiprole against clinical isolates of Gram-positive bacteria from infective endocarditis: are these drugs potential options for the initial management of this disease?

The in vitro activity of ceftaroline and ceftobiprole was assessed against 77 Gram-positive bacterial isolates recovered from patients diagnosed with infective endocarditis (IE). Our data confirm that these drugs are highly in vitro active against the most common agents of IE including methicillin-resistant Staphylococcus aureus, methicillin-resistant coagulase-negative staphylococci, and Streptococcus spp., with no significant differences between them. Also, ceftaroline and ceftobiprole have demonstrated a good activity against Enterococcus faecalis (MIC90 0.75 μg/mL and 0.5 μg/mL, respectively). The spectrum of these drugs together with the in vitro and in vivo data on them related with IE published in the scientific literature places them as potential options for the initial management of this disease.

Ceftaroline versus vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in an experimental MRSA meningitis model

ObjectivesThe aim of this study was to compare the antibacterial activity of ceftaroline versus vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) meningitis in an experimental rabbit meningitis model. MethodsThe antibacterial activity of ceftaroline was compared with vancomycin in the treatment of meningitis induced by MRSA strain ATCC 43300 in an experimental rabbit meningitis model. Quantitative cerebrospinal fluid (CSF) cultures were performed at the beginning of antibiotic treatment and 24h and 73h after the first antibiotic dose. Furthermore, in vitro time–kill data were investigated at 0, 2, 4, 6, 8, 12 and 24h in sterile human serum. ResultsThe difference between the control group versus both treatment groups was significant when comparing the decrease in colony counts in CSF both at 24h and 73h after the first antibiotic dose (P<0.05). At the end of the experiment, there was a significant difference in survival between both the ceftaroline-treated group and the vancomycin-treated group versus the control group, but not between the two treatment groups. ConclusionThese results suggest that the antibacterial activity of both ceftaroline and vancomycin are similar in the treatment of MRSA meningitis in an experimental rabbit meningitis model.

In Vitro Activity of Ceftaroline, Linezolid, and Tigecycline against Staphylococcus aureus and Streptococcus pneumoniae by Infection Site in the Africa/Middle East Region, 2014-17

In Vitro Activity of Ceftaroline, Linezolid, and Tigecycline against Staphylococcus aureus and Streptococcus pneumoniae by Infection Site in the Africa/Middle East Region, 2014-17

In vitro activity of ceftaroline in combination with other antimicrobials active against Staphylococcus spp.

IntroductionWe evaluated the in vitro activity of the combination of ceftaroline with daptomycin, linezolid and vancomycin against methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus (CNS). Material and methodsWe analysed 70 staphylococcal strains (31 S. aureus and 39 CNS) with the Etest using the MIC:MIC ratio method and calculation of fractional inhibitory concentration indexes. ResultsThe combination of ceftaroline with daptomycin showed an additive effect (53.2%) and synergy (6.6%) against methicillin-susceptible S. aureus, and an additive effect (81.2%) against methicillin-resistant S. aureus (MRSA). This combination also showed an additive effect against 33% of linezolid-susceptible CNS and was not synergistic against linezolid-resistant CNS. The combination of ceftaroline with vancomycin was synergistic (87%) and ceftaroline with linezolid was additive (37%) against MRSA. ConclusionsThe combinations of ceftaroline with daptomycin, vancomycin or linezolid showed additive and/or synergistic effects against methicillin-resistant Staphylococcus.

1588. Delafloxacin Activity Against Staphylococcus aureus with Reduced Susceptibility or Resistance to Methicillin, Vancomycin, Daptomycin, or Linezolid

BackgroundDelafloxacin is a recently approved anionic fluoroquinolone antibiotic with broad-spectrum activity against Gram-positive and Gram-negative organisms. The drug has been approved for patients with acute bacterial skin and skin structure infections including those caused by methicillin-resistant S. aureus. There is limited data available against methicillin-resistant S. aureus blood isolates (MRSABI), vancomycin intermediate strains (VISA), vancomycin-resistant strains (VRSA), daptomycin non-susceptible strains (DNSSA) and linezolid-resistant S. aureus (LRSA).MethodsAntimicrobial activity of delafloxacin, levofloxacin, vancomycin, daptomycin, ceftaroline, and linezolid was determined against recent (2016–2018) MRSABI (110), VRSA (15), VISA (35), DNSSA (40), and LRSA (6). Broth microdilution testing using Mueller–Hinton broth was used to determine minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) according to CLSI guidelines. FDA breakpoints were used to determine delafloxacin susceptibility, and CLSI breakpoints were used for all other antibiotics.ResultsAntimicrobial MIC90 expressed in mg/L and (% susceptible) MRSABI VISA VRSA DNSSA Delafloxacin1 (68)1 (40)4 (7)1 (38)Levofloxacin>16 (38)>16 (9)> 16 (0)>16 (15)Vancomycin1 (99)8 (0)>64 (0)8 (35)Daptomycin1 (96)4 (26)1 (100)4 (0)Ceftaroline1 (99)1 (100)1 (100)1 (100)Linezolid2 (100)2 (100)2 (100)2 (100)None of the LRSA were susceptible to delafloxacin or levofloxacin. All strains that were susceptible to the antimicrobial agents above had an MBC that was the same as the MIC or one dilution greater except for linezolid which demonstrated an MBC that was more than eight-fold greater than the MIC. For MRSABI isolates with a levofloxacin MIC ≥ 8 mg/L (55/110) suggesting multiple mutations in the quinolone-resistant determining region, the delafloxacin MIC90 was 1 mg/L with a 36.4% susceptibility rate.ConclusionDelafloxacin demonstrates superior activity to levofloxacin against recent MRSA blood isolates, VISA, VRSA, and DNSSA.Disclosures All authors: No reported disclosures.

Activity of ceftaroline against pathogens associated with community-acquired pneumonia collected as part of the AWARE surveillance program, 2015–2016

We report Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) program data for ceftaroline and comparators against isolates collected from identified lower respiratory tract sources in 2015 and 2016. MICs and susceptibility were determined using CLSI broth microdilution methodology and EUCAST breakpoints. Ceftaroline susceptibility among penicillin-resistant Streptococcus pneumoniae (MIC≥4 mg/L [nonmeningitis breakpoint]) ranged from 77.4% (Asia, 72/93) to 100% (Oceania, 16/16; Latin America, 15/15). Among MRSA, ceftaroline susceptibility ranged from 72.3% (Asia, 553/765) to 100% (Oceania, 39/39). Among β-lactamase–positive Haemophilus influenzae, ceftaroline susceptibility ranged from 69.2% (Asia, 36/52) to 100% (Oceania, 19/19). Susceptibility to ceftaroline against non–ESBL-producing Klebsiella pneumoniae was between 91.4% (Europe, 659/721) and 100% (Oceania, 55/55) and for Escherichia coli between 85.7% (Africa/Middle East, 42/49) and 92.1% (Oceania, 35/38). Ceftaroline is not active against ESBL producers. In this study, susceptibility to ceftaroline was high among the S. pneumoniae, Staphylococcus aureus, β-lactamase–negative H. influenzae, and ESBL-negative K. pneumoniae and E. coli collected.

2376. In Vitro Activities of Ceftaroline and Comparator Agents Against Bacterial Pathogens Collected From Patients With Skin and Skin Structure Infections in Latin America: AWARE Surveillance Program 2017

BackgroundThe parenteral cephem ceftaroline (CPT) fosamil is 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 Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca). Limited data have been published on the in vitro activity of CPT against recent clinical isolates cultured from patients with SSSIs in Latin America (LA).MethodsStandard CLSI broth microdilution MIC determinations (M07) were performed with CPT and comparator agents. MICs were interpreted using current CLSI M100 MIC breakpoints. Clinically relevant, non-duplicate, isolates cultured from patients with SSSIs in 6 countries in LA in 2017 were tested by the AWARE Surveillance Program central laboratory (IHMA). In total, 1,435 non-duplicate isolates of MSSA, MRSA, β-hemolytic streptococci, and Enterobacteriaceae were tested: Argentina (n = 349/24.3% of all isolates tested), Brazil (114/7.9%), Chile (153/10.7%), Columbia (175/12.2%), Mexico (339/23.6%), and Venezuela (305/21.3%).ResultsCPT activity is summarized in the following table.CPT MIC Breakpoints (µg/mL)CPT MIC (µg/mL)CPT MIC InterpretationBacteria n S | I | RMIC50MIC90% S% I% RMSSA354≤1 | 2 | ≥40.250.510000MRSA389≤1 | 2 | ≥40.5195.14.90β-Hemolytic streptococcia130≤0.5 | − | −0.0080.015100−−Enterobacteriaceae, All562≤0.5 | 1 | ≥20.5>12855.33.940.8 Enterobacteriaceae, ESBL screen-negative358≤0.5 | 1 | ≥20.12186.65.97.5 a S. pyogenes (n = 90), S. agalactiae (n = 26), and S. dysgalactiae (n = 14).ConclusionOverall, 100% of MSSA and 95.1% of MRSA from LA were susceptible to CPT (MIC ≤1 µg/mL); 19 isolates of MRSA were CPT-intermediate (MIC 2 µg/mL) with 17 of the 19 isolates being from Chile; no CPT-resistant MRSA were observed. All β-hemolytic streptococci and 86.6% of ESBL-negative Enterobacteriaceae were also susceptible to CPT. CPT continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with SSSIs for patients in LA.Disclosures M. Hackel, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. J. Karlowsky, IHMA, Inc.: Consultant, Consulting fee. D. Sahm, Pfizer Inc.: Consultant, Consulting fee. IHMA, Inc.: Employee, Salary. G. G. Stone, Pfizer Inc.: Employee, Salary. AstraZeneca: Former Employee and Shareholder, Salary.

In vitro activity of ceftaroline and ceftobiprole against methicillin-resistant Staphylococcus aureus with decreased susceptibility to vancomycin isolated in paediatric patients

Minimal inhibitory concentrations (MIC, mg/l) of ceftaroline and ceftobiprole were evaluated over 70 methicillin-resistant Staphylococcus aureus (MRSA) strains with vancomycin MIC ≥1 isolated in a paediatric hospital. The proportion of non-wild-type strains (MIC > epidemiological cut off) was 18% for ceftobiprole and 64% for ceftaroline. Only 1.4% of strains was resistant to ceftobiprole, and none to ceftaroline. These results are worrisome, since show the presence of non-negligible proportions of MRSA strains with high MIC values for ceftaroline and ceftobiprole in a setting where both drugs were never used.

Antimicrobial activity of ceftaroline and comparator agents tested against organisms isolated from patients with community-acquired bacterial pneumonia in Europe, Asia, and Latin America

ObjectiveTo evaluate the potency and spectrum of ceftaroline and comparator agents tested against contemporary bacteria isolated from patients with community-acquired bacterial pneumonia (CABP) in Europe (EUR), Asia-Pacific (APAC), and Latin America (LATAM). MethodsA total of 4321 bacterial isolates were collected consecutively by the SENTRY Antimicrobial Surveillance Program in 2015–2017 from 65 medical centers located in Western Europe (W-EUR; 21 centers in 10 nations), Eastern Europe and the Mediterranean region (E-EUR; 15 centers in 11 nations), APAC (18 centers in nine nations), and LATAM (11 centers in nine nations). Isolates were collected from lower respiratory tract specimens, and an isolate obtained from an outpatient or earlier than 48h after hospitalization was considered community-acquired. Organisms were tested for susceptibility by reference broth microdilution methods in a central laboratory. ResultsAmong Streptococcus pneumoniae (n=1736), 99.9% of isolates were ceftaroline-susceptible (MIC50/90, 0.008/0.12mg/l), and ceftriaxone susceptibility (≤1mg/l) ranged from 97.4% in W-EUR to 85.3% in the APAC region. Ceftaroline was also active against Haemophilus influenzae (n=1172; MIC50/90, 0.008/0.03mg/l; 99.8%/93.9% susceptible per CLSI/EUCAST criteria) and Staphylococcus aureus (n=777; MIC50/90, 0.25/1mg/l; 97.4% susceptible). Oxacillin resistance ranged from 31.9% in the APAC region to 15.0% in E-EUR. Ceftaroline also demonstrated potent activity against Moraxella catarrhalis (n=613; MIC50/90, 0.06/0.25mg/l) and Haemophilus parainfluenzae (n=23; MIC50/90, 0.015/0.03mg/l). ConclusionsSusceptibility rates varied widely by geographic region. Ceftaroline was active against the vast majority of bacterial organisms isolated from patients with CABP.

In vitro activity of ceftaroline against clinical Staphylococcus aureus isolates collected during a national survey conducted in Belgian hospitals

OBJECTIVES The aim of this study was to estimate the in vitro activity of ceftaroline against clinical Staphylococcus aureus isolates collected during national surveillance in Belgian acute-care hospitals. Ceftaroline-resistant isolates were further investigated for their resistance mechanisms. METHODS From October 2013 to March 2014, 155 laboratories of Belgian acute-care hospitals were invited to send to the National Reference Centre-Staphylococcus aureus (Belgium) up to five non-duplicate S. aureus including three MRSA and two MSSA from hospitalized patients. Isolates were analysed by spa typing, SCCmec typing (for MRSA) and PCR for detection of 16S-mecA-nuc and 16S-mecC. MICs of oxacillin, cefoxitin and ceftaroline were determined by the broth microdilution method. The nucleotide sequences of mecA, native pbp and gdpP genes of isolates with reduced susceptibility to ceftaroline were analysed for the presence of mutations responsible for amino acid substitutions. RESULTS Ninety-nine percent of isolates, including MRSA (n = 284) and MSSA (n = 131), were susceptible to ceftaroline. Only four MRSA isolates showed resistance to ceftaroline (MIC = 2 mg/L). These four isolates belonged to lineages CC5 (n = 1), CC22 (n = 2) and CC8 (n = 1). Two isolates (CC22 and CC8) carried mutations in mecA, as well as in other pbp genes. The remaining isolates carried mutations in native pbp genes or in gdpP. CONCLUSIONS This is the first Belgian in vitro survey on ceftaroline activity against S. aureus. This antibiotic showed excellent activity against MRSA and MSSA, and only a few MRSA isolates with resistance were found. Reduced susceptibility to ceftaroline seems a complex phenomenon due to the accumulation of mutations in genes involved in β-lactam tolerance.