ppi-0903 and Respiratory-Tract-Infections

Ceftaroline, with a unique activity against methicillin-resistant Staphylococcus aureus (MRSA), was not launched in Taiwan before 2019. The in vitro susceptibility data of ceftaroline against important Taiwanese pathogens are lacking.. The in vitro susceptibility of ceftaroline against important pathogens collected from 2012 through 2018 were extracted from the Antimicrobial Testing Leadership and Surveillance program. Broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) to ceftaroline against all isolates.. From the pharmacodynamic perspectives, the ceftaroline dosage of 600 mg as a 2-h intravenous infusion every 8 h is effective against all S. aureus and other Gram-positive isolates regardless of acquisition sites in Taiwan. Before ceftaroline is prescribed in treatment of the patient with Gram-negative infection, a cautious evaluation about patient's healthcare-associated factor is warranted.

Topics: Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Haemophilus; Humans; Klebsiella pneumoniae; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Respiratory Tract Infections; Soft Tissue Infections; Staphylococcus aureus; Taiwan

To 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.. Pathogens 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.. All 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.. Ceftaroline-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.

Topics: Africa; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Humans; Microbial Sensitivity Tests; Middle East; Respiratory Tract Infections

Data on ceftaroline (CPT) susceptibility amongst clinical isolates of meticillin-resistant Staphylococcus aureus (MRSA, n=1284) and phenotypic non-extended-spectrum β-lactamase-producing (non-ESBL-P) Klebsiella pneumoniae (n=466), obtained from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme from 2012 to 2018, and selected MRSA isolates from patients with bloodstream infections (BSIs) (n=95) from the Surveillance of Multicentre Antimicrobial Resistance in Taiwan (SMART) programme from 2018 to 2019 were analysed. The minimum inhibitory concentrations (MICs) of ATLAS isolates were determined using the broth microdilution method, whereas the MICs of SMART BSI-MRSA isolates were determined using the Etest and MicroScan system. The pharmacokinetic profiles and pharmacodynamic parameters of CPT were applied to explore the optimal dosage against infections caused by Taiwanese MRSA and K. pneumoniae isolates. Approximately 7.1% of ATLAS MRSA isolates were susceptible-dose dependent (S-DD) to CPT, and 19.7% of the non-ESBL-P K. pneumoniae isolates were not susceptible to CPT. Amongst the ATLAS MRSA isolates, the S-DD rates to CPT amongst isolates causing lower respiratory tract infections were 11.9% and 8.5% for isolates from intensive care units (ICUs) and general wards (GWs), and those causing skin and soft tissue infections (SSTIs) were 20% and 5.3% for isolates from ICUs and GWs, respectively (P=0.015). Of the SSTI MRSA isolates from GWs, 22.7% displayed vancomycin MICs >1 mg/L. Amongst 95 SMART BSI MRSA isolates, 28 (46.7%) isolates exhibited lower CPT MICs by the Etest compared with 60 isolates with CPT MICs of 1-2 mg/L by the MicroScan system. CPT 600 mg as a 2-h intravenous infusion every 8 h is suggested for treatment of infections caused by MRSA and phenotypic non-ESBL-P K. pneumoniae in Taiwan.

Topics: Anti-Bacterial Agents; beta-Lactamases; Ceftaroline; Cephalosporins; Drug Resistance, Bacterial; Humans; Klebsiella pneumoniae; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Respiratory Tract Infections; Skin Diseases, Bacterial; Soft Tissue Infections; Taiwan

Ceftaroline fosamil has recently received US Food and Drug Administration approval for treatment of acute bacterial skin/skin structure infections (SSSIs), including those caused by methicillin-resistant Staphylococcus aureus and community-acquired bacterial pneumonia for pediatric patients ≥2 months old. We evaluated the potency and spectrum of ceftaroline and comparators when tested against community-acquired respiratory tract infection (CARTI) and SSSI pathogens from pediatric patients. A total of 3141 consecutive, unique pediatric patient isolates of clinical significance (1460 CARTI and 1681 SSSI isolates) were collected from 29 US medical centers and tested for susceptibility to ceftaroline and comparators by broth microdilution methods. The organism collection included Streptococcus pneumoniae (n = 754), Haemophilus influenzae (487), S. aureus (1399), β-hemolytic streptococci (214), Enterobacteriaceae (112), Pseudomonas aeruginosa (58), Klebsiella spp. (39), Escherichia coli (26) and miscellaneous other bacteria (52). Susceptibility results were analyzed according to patient age as follows: ≤1, 2-5, 6-12 and 13-17 years old. Overall, 99%-100% of Gram-positive isolates and H. influenzae were susceptible to ceftaroline according to Clinical and Laboratory Standards Institute clinical breakpoint criteria. Ceftaroline exhibited potent in vitro activity against bacterial pathogens from CARTI and SSSI recently (2012-2014) collected from pediatric patients in US medical centers. Ceftaroline was particularly active against methicillin-resistant S. aureus from SSSI ([minimum inhibitory concentration for 50% and 90% of isolates (MIC50/90,)] and ceftriaxone-nonsusceptible isolates of S. pneumoniae from CARTI (MIC50/90, 0.25/0.5 μg/mL; 98.3% susceptible).

Topics: Adolescent; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Child; Child, Preschool; Community-Acquired Infections; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Haemophilus influenzae; Hospitals; Humans; Infant; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Respiratory Tract Infections; Retrospective Studies; Skin Diseases, Bacterial; Staphylococcal Infections; Streptococcus pneumoniae; United States

The objective of this report was to document antimicrobial susceptibility testing surveillance data for ceftaroline and comparative agents from the AWARE (Assessing Worldwide Antimicrobial Resistance Evaluation) global surveillance program for bacterial pathogens causing skin and soft tissue and respiratory tract infections in African and Middle Eastern countries from 2012 through 2014. Pathogen identities were confirmed by MALDI-TOF and antimicrobial susceptibility testing performed by CLSI broth microdilution methodology in a central laboratory. All methicillin-susceptible Staphylococcus aureus (MSSA) (n= 923; MIC90, 0.25 μg/mL) and 91.8% of methicillin-resistant S. aureus (MRSA) (n= 1161; MIC90, 1 μg/mL) tested were susceptible to ceftaroline. The maximum ceftaroline MIC observed for isolates of MRSA was 2 μg/mL. All Streptococcus pyogenes (n= 174; MIC90, 0.008 μg/mL), Streptococcus agalactiae (n= 44; MIC90, 0.015 μg/mL), Streptococcus pneumoniae (n= 351; MIC90, 0.25 μg/mL), and Haemophilus influenzae (n= 84; MIC90, ≤0.015 μg/mL) were susceptible to ceftaroline. Rates of susceptibility to ceftaroline among ESBL-negative Escherichia coli (n= 338), Klebsiella pneumoniae (n= 241), and Klebsiella oxytoca (n= 97) were 89.1% (MIC90, 1 μg/mL), 94.2% (MIC90, 0.5 μg/mL), and 99.0% (MIC90, 0.5 μg/mL), respectively.

Topics: Africa; Anti-Bacterial Agents; Bacteria; Ceftaroline; Cephalosporins; Epidemiological Monitoring; Humans; Microbial Sensitivity Tests; Middle East; Respiratory Tract Infections; Skin Diseases, Bacterial; Soft Tissue Infections; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

A total of 4533 isolates from community-acquired respiratory tract infections (CARTIs) and 8446 from skin and skin structure infections (SSSIs) were consecutively collected in 149 US medical centers in 2013. Strains were susceptibility tested by broth microdilution method against ceftaroline and numerous comparators. Ceftaroline (MIC(50/90), ≤0.015/0.12 μg/mL) was more potent than ceftriaxone (MIC(50/90), ≤0.06/1 μg/mL) against Streptococcus pneumoniae and highly active against ceftriaxone-nonsusceptible strains (n=201; MIC(90), 0.25 μg/mL). Ceftaroline was also very active against Haemophilus influenzae (MIC(50/90), 0.008/0.015 μg/mL), methicillin-susceptible (MIC(50/90), 0.25/0.25 μg/mL) and methicillin-resistant Staphylococcus aureus (MIC(50/90), 1/1 μg/mL), and β-hemolytic streptococci (highest MIC, 0.03 μg/mL). Ceftaroline exhibited good activity against non-extended-spectrum β-lactamase (ESBL) phenotype isolates of Klebsiella spp. and Escherichia coli (96.7% susceptible and MIC(90) of 0.25 μg/mL for both) but limited activity against ESBL phenotype isolates. In summary, ceftaroline exhibited potent in vitro activity against a large collection of bacterial isolates causing CARTI and SSSI in US medical centers.

Topics: Academic Medical Centers; Anti-Bacterial Agents; Bacteria; Ceftaroline; Cephalosporins; Microbial Sensitivity Tests; Respiratory Tract Infections; Skin Diseases, Bacterial; United States

The aim of this study was to investigate the effectiveness of ceftaroline against agents frequently isolated from respiratory tract and wound infections.. The study included a total of 250 strains isolated from various clinical specimens, among which were Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysagalactiae, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catharralis. The bacteria were identified using the matrix-assisted laser desorption/ionization time-of-flight method and conventional methods. The bacteria's antibiotic susceptibility was tested using appropriate broth microdilution. Mueller-Hinton broth with 4% lysed horse blood, Haemophilus test medium broth, and Mueller-Hinton broth were used. Ceftaroline fosamil results at the minimum inhibitory concentration (MIC) were evaluated using Clinical and Laboratory Standards Institute (CLSI) criteria. For quality assurance, E. coli ATCC 35218, S. aureus ATCC 29213, S. aureus ATCC 43300, S. pneumoniae ATCC 49619, H. influenzae ATCC 49766, H. influenzae ATCC 10211, and H. influenzae ATCC 49247 standard strains were used.. According to CLSI criteria, resistance was not detected in any strains. Due to the absence of CLSI criteria for M. catharralis, the susceptibility state for this bacterium was not evaluated. The various strains' MIC50-MIC90 values were as follows: for S. pyogenes, 0.015-0.06; for S. agalactiae, 0.03-0.125; for S. dysagalactiae, 0.03-0.06; for S. pneumoniae, 0.06-0.125; for H. influenzae, 0.015-0.125; and for M. catharralis, 0.5-1.. The results indicate that ceftaroline is quite effective against bacteria that are frequently isolated from respiratory tract and wound infections.

Topics: Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Moraxella catarrhalis; Respiratory Tract Infections; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Streptococcus; Wound Infection

The Assessing Worldwide Antimicrobial Resistance Evaluation Program monitors the activity of ceftaroline and comparator agents tested against pathogens causing either respiratory or skin and soft tissue infections. A total of 7733 isolates from patients in 80 medical centers across the United States (USA) identified as respiratory tract pathogens by the infection type and/or specimen site recorded by the submitting laboratory during 2009-2011 were evaluated. There were 3360 isolates of Streptococcus pneumoniae, 1799 Haemophilus influenzae, 1087 Staphylococcus aureus, 678 Moraxella catarrhalis, 459 Klebsiella pneumoniae, 223 Escherichia coli, and 127 Klebsiella oxytoca. Annual penicillin resistance among S. pneumoniae ranged from 21.9 to 24.3%. All S. pneumoniae strains were inhibited at a ceftaroline MIC of ≤0.5 μg/mL with 100.0% of isolates categorized as susceptible. Ceftaroline was 16-fold more active than ceftriaxone and 32-fold more active than amoxicillin-clavulanate against penicillin-resistant pneumococci. Only 49.8% of the penicillin-resistant isolates were susceptible to ceftriaxone. There were a total of 1087 S. aureus (48.9% methicillin-resistant S. aureus [MRSA]) isolates, and the yearly MRSA rate ranged from 47.9 to 49.7%. The ceftaroline MIC50/90 for S. aureus was at 0.25/1 μg/mL; 98.2% susceptible and no resistant strains (≥4 μg/mL). Ceftaroline activity against methicillin-susceptible S. aureus (MSSA) isolates (MIC50 and MIC90, 0.25 and 0.25 μg/mL, respectively; 100% susceptible) was 2- to 4-fold greater than for MRSA (MIC50/90, 0.5/1 μg/mL; 96.2% susceptible). The ceftriaxone MIC90 for MSSA was 4 μg/mL. Ceftaroline was active against H. influenzae (MIC50/90 ≤0.015/0.03 μg/mL; 100.0% susceptible) and against M. catarrhalis (MIC50/90, 0.06/0.12 μg/mL). Ceftaroline was active against non-extended spectrum β-lactamase (ESBL) phenotype strains of Enterobacteriaceae but not against ESBL-positive phenotype strains. In summary, ceftaroline was highly active against a large collection of bacterial pathogens isolated from patients with respiratory tract infections in the USA during 2009 through 2011.

Topics: Academic Medical Centers; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Ceftaroline; Cephalosporins; Child; Child, Preschool; Female; Hospitals; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Middle Aged; Respiratory Tract Infections; United States; Young Adult

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a cephalosporin with in vitro bactericidal activity against resistant Gram-positive organisms including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant strains of Streptococcus pneumoniae, and common Gram-negative organisms, including wild-type Enterobacteriaceae. We evaluated the in vitro activity of ceftaroline and selected comparator agents against bacterial isolates collected from patients with skin and soft tissue infections (SSTI) and community-acquired respiratory tract infections (CARTI) in the Asia-Pacific region and South Africa. A total of 2351 isolates, 1100 from SSTI and 1251 from CARTI, were collected from 25 medical centers distributed across 8 countries as part of the 2010 AWARE ceftaroline surveillance program and tested for susceptibility by reference broth microdilution methods. Ceftaroline was very active against S. aureus (MIC50/90, 0.25/1 μg/mL; 93.4% susceptible), including MRSA (MIC50/90, 1/2 μg/mL; 80.6% susceptible). Against β-hemolytic streptococci, ceftaroline demonstrated greater activity (MIC90, 0.015 μg/mL) than penicillin (MIC90, 0.06 μg/mL). Ceftaroline was also highly active against viridans group streptococci (MIC90, 0.12 μg/mL). Similarly to ceftriaxone, ceftaroline activity against Escherichia coli (MIC50/90, >32/>32 μg/mL) and Klebsiella spp. (MIC50/90, 0.12/>32 μg/mL) was compromised by the high prevalence of isolates with an ESBL phenotype in the region, particularly in China. Ceftaroline was the most potent β-lactam tested against S. pneumoniae (MIC50/90 of 0.015/0.25 μg/mL; 99.8% susceptible by Clinical and Laboratory Standards Institute [CLSI] criteria), and it was also highly potent against Haemophilus influenzae (MIC50/90, ≤ 0.008/0.03 μg/mL; 100% susceptible by CLSI criteria). Ceftaroline was also active against H. parainfluenzae (MIC50/90, ≤ 0.008/0.015 μg/mL) and Moraxella catarrhalis (MIC50/90, 0.06/0.12 μg/mL). In summary, ceftaroline showed potent in vitro activity against a large collection of bacterial isolates (2351) associated with SSTI and CARTI from the Asia-Pacific region and South Africa.

Topics: Anti-Bacterial Agents; Asia; Ceftaroline; Cephalosporins; Community-Acquired Infections; Haemophilus influenzae; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Moraxella catarrhalis; Respiratory Tract Infections; Skin Diseases, Bacterial; Soft Tissue Infections; South Africa; Staphylococcus aureus; Streptococcus pneumoniae

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a novel cephalosporin exhibiting in vitro bactericidal activity against Gram-positive organisms, including Streptococcus pneumoniae and methicillin-susceptible and -resistant Staphylococcus aureus, as well as common Gram-negative organisms. The objective of this study was to determine the spectrum and potency of ceftaroline against recent leading pathogens causing community-acquired respiratory tract infections (CARTI) isolated in Europe. A total of 1563 isolates from the 2010 Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) Program were identified as CARTI pathogens by the infection type and/or specimen type recorded by the participating laboratory. Isolates were collected from patients in 52 medical centers located in 19 European countries (including Israel and Turkey). Susceptibility testing for ceftaroline and commonly used antimicrobials was performed by Clinical and Laboratory Standards Institute (CLSI) broth microdilution methodology. Susceptibility interpretations for comparators were as published in CLSI and the European Committee on Antimicrobial Susceptibility Testing guidelines, and for ceftaroline US-FDA breakpoints were also applied. Ceftaroline was very active overall against 799 S. pneumoniae (MIC(50/90,) ≤ 0.008/0.12 μg/mL) and inhibited 100.0% of all isolates at a MIC ≤ 0.5 μg/mL. Ceftaroline was very potent against penicillin-resistant (CLSI oral penicillin V breakpoints) and -intermediate S. pneumoniae (MIC(50/90), 0.12/0.25 and 0.03/0.12 μg/mL, respectively), but potency was lower than observed against penicillin-susceptible isolates (MIC(50/90), ≤ 0.008/≤ 0.008 μg/mL). Ceftaroline was also very active (MIC(50/90), ≤ 0.008/0.015 μg/mL) against 515 Haemophilus influenzae, including β-lactamase-producing strains (MIC(50/90), 0.015/0.06 μg/mL). Ceftaroline also demonstrated good activity against 205 Moraxella catarrhalis isolates (MIC(50/90), 0.06/0.12 μg/mL). This study demonstrated the potent in vitro activity of ceftaroline against contemporary pathogens isolated from patients with documented CARTI from Europe. These data suggest that ceftaroline fosamil has an acceptable in vitro spectrum and potency against CARTI pathogens.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Ceftaroline; Cephalosporins; Community-Acquired Infections; Europe; Humans; Microbial Sensitivity Tests; Respiratory Tract Infections