ppi-0903 and Bacterial-Infections

Antibiotic resistance is an increasingly growing health problem worldwide, so it is imperative to look for new, more effective antibiotics. Ceftaroline has a broad spectrum of activity against clinically relevant Grampositive strains, including methicillin-resistant Staphylococcus aureus and resistant Streptococcus pneumoniae strains, as well as Gram-negative pathogens implicated in skin and soft tissue infections or community-acquired pneumonia; it is therefore a potential therapeutic option. We conducted a systematic review to assess whether ceftaroline was safer and more effective than comparators.. A comprehensive bibliographic search was done to identify experimental clinical trials that compared the safety and effectiveness of ceftaroline to a comparator in the pediatric population. The rate of therapeutic failure was used to determine the effectiveness, while the presence of any adverse event was considered for safety.. Three studies were identified: two in community-acquired pneumonia and one in skin and soft tissue infections. No study showed a difference in the risk for therapeutic failure, relative risk (RR): 0.97 (0.54-1.73), or safety criterion, RR: 0.79 (0.51-1.23).. The available evidence suggests that ceftaroline may be a valid therapeutic option for the management of skin and soft tissue infections or community-acquired pneumonia in pediatric patients. No studies with a high-quality of evidence were observed in other types of infections or in patients admitted to the critical care unit.. Introducción. La resistencia a los antibióticos plantea un problema de salud mundial cada vez mayor, por lo que la búsqueda de nuevos y más efectivos antibióticos es prioritaria. La ceftarolina tiene un amplio espectro de actividad contra cepas Gram-positivas clínicamente relevantes, que incluyen el Staphylococcus aureus meticilino resistente y cepas de Streptococcus pneumoniae resistentes, así como algunos patógenos Gram-negativos implicados en infecciones de piel y tejidos blandos o en la neumonía adquirida en la comunidad; es una potencial opción terapéutica. Se realizó una revisión sistemática que evaluó si la ceftarolina era más efectiva y segura que los comparadores. Material y métodos. Se realizó una búsqueda bibliográfica exhaustiva para identificar estudios clínicos experimentales que compararan la seguridad y eficacia de la ceftarolina con un comparador en la población pediátrica. El criterio de evaluación de eficacia fue la tasa de fracaso terapéutico y, para seguridad, la presencia de cualquier efecto adverso. Resultados. Se identificaron tres estudios, 2 de neumonía adquirida en la comunidad y uno de infecciones de piel y tejidos blandos. En ninguno, se detectó diferencia en el riesgo de fracaso terapéutico, RR 0,97 (0,54-1,73), ni en el criterio de seguridad, RR 0,79 (0,51-1,23). Conclusiones. La evidencia disponible sugiere que la ceftarolina podría ser una opción terapéutica válida en el tratamiento de las infecciones de piel y tejidos blandos o neumonía adquirida en la comunidad en pacientes pediátricos. No se encontraron trabajos de alta calidad de evidencia en otro tipo de infecciones o en pacientes admitidos en la Unidad de Cuidados Críticos.

Topics: Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Child; Drug Resistance, Bacterial; Humans; Treatment Outcome

The development of resistance to antibiotics has been ignored for a long time. But nowadays, increasing resistance is an important topic. For a decade no new antibiotics had been developed and it is not possible to quickly close this gap of new resistance and no new drugs. This work presents six new antibiotics (ceftaroline, ceftobiprole, solithromycin, tedizolid, ceftolozane/tazobactam, ceftazidime/avibactam). In part, only expert opinions are given due to lack of study results.The two 5th generation cephalosporins ceftaroline and ceftobiprole have beside their equivalent efficacy to ceftriaxone (ceftaroline) and cefipim (ceftobiprole) high activity against MRSA. The fluoroketolide solithromycin should help against macrolide-resistant pathogens and has been shown to be noninferior to the fluorochinolones. The oxazolidinone tedizolid is effective against linezolid-resistant MRSA. The two cephalosporins ceftolozane/tazobactam and ceftazidime/avibactam are not only effective against gram-negative pathogens, but they have a very broad spectrum. Due to the efficacy against extended-spectrum β‑lactamases, they can relieve the selection pressure of the carbapenems. We benefit from all new antibiotics which can take the selection pressure from other often used antibiotics. The increasing number of resistant gram-negative pathogens worldwide is alarming. Thus, focusing on the development of new drugs is extremely important.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Infections; Ceftaroline; Ceftazidime; Cephalosporins; Clinical Trials as Topic; Drug Approval; Drug Combinations; Drug Resistance, Multiple, Bacterial; Ephedrine; Humans; Macrolides; Methicillin-Resistant Staphylococcus aureus; Organophosphates; Oxazoles; Penicillanic Acid; Phenobarbital; Staphylococcal Infections; Tazobactam; Theophylline; Triazoles

Antimicrobial drug-resistance continues to force adaptation in our clinical practice. We explore new evidence regarding adjunctive antibiotic therapy for skin and soft tissue abscesses as well as duration of therapy for intra-abdominal abscesses. As new evidence refines optimal practice, it is essential to support clinicians in adopting practice patterns concordant with evidence-based guidelines. We review a simple approach that can 'nudge' clinicians towards concordant practices. Finally, the use of novel antimicrobials will play an increasingly important role in contemporary therapy. We review five new antimicrobials recently FDA-approved for use in drug-resistant infections: dalbavancin, oritavancin, ceftaroline, ceftolozane-tazobactam, and ceftazidime-avibactam.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Drug Administration Schedule; Drug Approval; Drug Combinations; Drug Resistance, Microbial; Glycopeptides; Humans; Lipoglycopeptides; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Soft Tissue Infections; Teicoplanin; United States; United States Food and Drug Administration

Septic arthritis is a rheumatologic emergency as joint destruction occurs rapidly and can lead to significant morbidity and mortality. Accurate diagnosis can be particularly challenging in patients with underlying inflammatory joint disease. This review outlines the risk factors for septic arthritis and summarizes the causative bacterial organisms. We highlight advances in antibiotic management with a focus on new drugs for methicillin-resistant Staphylococcus aureus (MRSA) and discuss the use of adjunctive therapies for treatment of septic arthritis in adults.

Topics: Acetamides; Anti-Bacterial Agents; Arthritis, Infectious; Bacterial Infections; Ceftaroline; Cephalosporins; Daptomycin; Drug Therapy, Combination; Humans; Immunologic Factors; Linezolid; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Risk Factors; Staphylococcal Infections; Treatment Outcome; Virginiamycin

Ceftaroline fosamil is a cephalosporin antibacterial approved by the US Food and Drug Administration (FDA) for use in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). After intravenous administration, ceftaroline fosamil is rapidly converted to its bioactive metabolite, ceftaroline. Ceftaroline has broad-spectrum in vitro activity against Gram-positive and Gram-negative bacteria, including contemporary resistant Gram-positive phenotypes, such as methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae. Because of its unique spectrum of activity, the Clinical and Laboratory Standards Institute (CLSI) designated ceftaroline as a member of a new subclass of β-lactam antimicrobials, cephalosporins with anti-MRSA activity. The activity of ceftaroline against S. aureus extends to heteroresistant vancomycin-intermediate, vancomycin-intermediate, vancomycin-resistant and daptomycin-nonsusceptible isolates. Ceftaroline has low minimum inhibitory concentrations (MICs) for all tested species of streptococci, and has potent activity against S. pneumoniae isolates with varying degrees of penicillin resistance. The activity of ceftaroline is limited against Enterococcus faecalis and Enterococcus faecium and against anaerobes such as Bacteroides fragilis. The in vitro activity of ceftaroline includes many Gram-negative pathogens, but does not extend to bacteria that produce extended-spectrum β-lactamases, class B metallo-β-lactamases or AmpC cephalosporinases, or to most nonfermentative Gram-negative bacilli. Ceftaroline fosamil has been studied for the treatment of complicated skin and skin structure infections (cSSSI) and community-acquired pneumonia (CAP) in phase III randomized, double-blind, international, multicentre noninferiority clinical trials. Two identical trials (CANVAS 1 and CANVAS 2) compared the efficacy of ceftaroline fosamil with that of vancomycin plus aztreonam in 1378 adults with cSSSI. Results demonstrated that ceftaroline was noninferior to vancomycin plus aztreonam, with 91.6% in the ceftaroline fosamil group (pooled analysis) achieving clinical response compared with 92.7% in the vancomycin plus aztreonam group (difference -1.1%, 95% CI -4.2, 2.0). An additional analysis evaluated clinical cure in a subgroup of patients who met the FDA guidance definition of ABSSSI at treatment day 3. Clinical response, defined as cessation o

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Clinical Trials as Topic; Community-Acquired Infections; Double-Blind Method; Humans; Pneumonia, Bacterial; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial

The pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of ceftaroline are reviewed.. Ceftaroline, a new broad- spectrum antibiotic, is approved for the treatment of complicated skin and skin structure infections (cSSSIs) and community- acquired pneumonia (CAP). This β-lactam antibiotic has extended activity against gram-positive organisms and has activity against common gram-negative organisms. The drug's spectrum of activity includes both methicillin-resistant Staphylococcus aureus and multidrug-resistant Streptococcus pneumoniae. However, its activity against extended-spectrum β-lactamase-producing bacteria is limited. These bacteria, particularly those that express AmpC β-lactamase, greatly reduce the activity of ceftaroline. The prodrug of ceftaroline (ceftaroline fosamil) is rapidly converted to its active form (ceftaroline) in plasma. This dose-linear drug has been found to be pharmacodynamically best correlated with the percentage of time that free drug concentrations remain above the minimum inhibitory concentration. Ceftaroline's safety profile is similar to that of the other cephalosporins, with minimal adverse drug reactions, most of which are considered mild. Currently available pharmacokinetic, animal, and clinical studies have found that ceftaroline has reasonable efficacy and tolerability but have also revealed that dosing regimen modifications may be needed in patients with moderate-to-severe renal impairment. The recommended dosage of ceftaroline for the treatment of cSSSIs and CAP is 600 mg infused intravenously over 60 minutes every 12 hours. The recommended duration of therapy is 5-14 and 5-7 days for cSSSIs and CAP, respectively. Additional Phase III studies are currently underway.. Ceftaroline is a new broad-spectrum cephalosporin indicated for the treatment of cSSSIs and CAP caused by susceptible gram-positive and gram-negative organisms.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Drug Resistance, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests

Ceftaroline fosamil, the prodrug form of ceftaroline, is a novel broad-spectrum parenteral cephalosporin that exhibits antibacterial activity against typical respiratory pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and common Gram-negative pathogens. In particular, ceftaroline has activity against resistant Gram-positive cocci, including penicillin- and multidrug-resistant S. pneumoniae, as well as methicillin-resistant S. aureus. The activity of ceftaroline against these phenotypes is attributed to its ability to bind to modified penicillin-binding proteins with high affinity when compared with other β-lactams. The activity of ceftaroline is not compromised by the ability of H. influenzae to produce β-lactamase. Ceftaroline fosamil was compared with ceftriaxone for safety and efficacy in two randomized, double-blinded, controlled Phase III clinical trials for the treatment of community-acquired pneumonia (CAP). Microbiological assessments at baseline included respiratory specimen cultures, blood cultures, urinary antigen testing and atypical pathogen serology testing. By-subject and by-pathogen microbiological outcomes were assessed in the microbiologically evaluable population at the test-of-cure visit. The favourable microbiological response rates by subject for ceftaroline were 87.0% compared with 81.0% for ceftriaxone. The by-pathogen microbiological response rates of ceftaroline and ceftriaxone were 87.3% and 72.9% for S. pneumoniae, 83.3% and 85.0% for H. influenzae and 76.0% and 70.4% for S. aureus, respectively. Key baseline pathogens such as S. pneumoniae, H. influenzae and methicillin-susceptible S. aureus were susceptible to ceftaroline, with MIC(90)s of 0.03, 0.03 and 0.25 mg/L, respectively, supporting its utility as a promising new agent for treatment of CAP.

Topics: Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Ceftriaxone; Cephalosporins; Community-Acquired Infections; Double-Blind Method; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Treatment Outcome

Ceftaroline fosamil is a new extended-spectrum cephalosporin with activity against drug-resistant Grampositive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae. At the same time, its Gramnegative spectrum of coverage includes common respiratory pathogens such as Haemophilus influenzae and Moraxella catarrhalis, as well as wild-type Enterobacteriaceae. In vivo efficacy for the treatment of experimental endocarditis, pneumonia, myositis and osteomyelitis has been demonstrated in animal models, while efficacy in the treatment of complicated skin and soft tissue infections and community-acquired pneumonia has been demonstrated in phase II and III clinical trials in humans. The drug is well tolerated and has a low rate of reported adverse events. The dose of ceftaroline fosamil used is 600 mg i.v. every 12 h for patients with normal renal function or mild renal dysfunction. In patients with moderate renal dysfunction, it has been suggested that ceftaroline fosamil be dosed at 400 mg i.v. over 60 min every 12 h. Ceftaroline fosamil is still under review by the U.S. FDA, and when approved, will be one of the first commercially available β-lactams with the ability to treat infections due to MRSA and other drug-resistant Gram-positive pathogens.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests

Ceftaroline fosamil, the prodrug form of ceftaroline, is a novel broad-spectrum parenteral cephalosporin that exhibits antibacterial activity against typical respiratory pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and common Gram-negative pathogens. In particular, ceftaroline has activity against resistant Gram-positive cocci, including penicillin- and multidrug-resistant S. pneumoniae, as well as methicillin-resistant S. aureus. The activity of ceftaroline against these phenotypes is attributed to its ability to bind to modified penicillin-binding proteins with high affinity when compared with other β-lactams. The activity of ceftaroline is not compromised by the ability of H. influenzae to produce β-lactamase. Ceftaroline fosamil was compared with ceftriaxone for safety and efficacy in two randomized, double-blinded, controlled Phase III clinical trials for the treatment of community-acquired pneumonia (CAP). Microbiological assessments at baseline included respiratory specimen cultures, blood cultures, urinary antigen testing and atypical pathogen serology testing. By-subject and by-pathogen microbiological outcomes were assessed in the microbiologically evaluable population at the test-of-cure visit. The favourable microbiological response rates by subject for ceftaroline were 87.0% compared with 81.0% for ceftriaxone. The by-pathogen microbiological response rates of ceftaroline and ceftriaxone were 87.3% and 72.9% for S. pneumoniae, 83.3% and 85.0% for H. influenzae and 76.0% and 70.4% for S. aureus, respectively. Key baseline pathogens such as S. pneumoniae, H. influenzae and methicillin-susceptible S. aureus were susceptible to ceftaroline, with MIC(90)s of 0.03, 0.03 and 0.25 mg/L, respectively, supporting its utility as a promising new agent for treatment of CAP.

Topics: Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Ceftriaxone; Cephalosporins; Community-Acquired Infections; Double-Blind Method; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Treatment Outcome

Topics: Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Daptomycin; Humans; Methicillin; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Neoplasms; Staphylococcal Infections; Vancomycin

A total of 84,704 isolates were collected from 191 medical centers in 2009 to 2013 and tested for susceptibility to ceftaroline and comparator agents by broth microdilution methods. Ceftaroline inhibited all Staphylococcus aureus isolates at ≤2 μg/ml and was very active against methicillin-resistant strains (MIC at which 90% of the isolates tested are inhibited [MIC90], 1 μg/ml; 97.6% susceptible). Among Streptococcus pneumoniae isolates, the highest ceftaroline MIC was 0.5 μg/ml, and ceftaroline activity against the most common Enterobacteriaceae species (MIC50, 0.12 μg/ml; 78.9% susceptible) was similar to that of ceftriaxone (MIC50, ≤0.25 μg/ml; 86.8% susceptible).

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Ceftaroline; Ceftriaxone; Cephalosporins; Enterobacteriaceae; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Staphylococcus aureus; Streptococcus pneumoniae; 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 is a new parenteral cephalosporin agent with excellent activity against methicillin-sensitive (MSSA) and resistant strains of Staphylococcus aureus (MRSA). Critically ill surgical patients are susceptible to infection, often by multi-drug-resistant pathogens. The activity of ceftaroline against such pathogens has not been described.. Three hundred thirty-five consecutive microbial isolates were collected from surgical wounds or abscesses, respiratory, urine, and blood cultures from patients in the surgical intensive care unit (SICU) of a major tertiary medical center. Using Clinical and Laboratory Standards Institute (CLSI) standard methodology and published breakpoints, all aerobic, facultative anaerobic isolates were tested against ceftaroline and selected comparative antimicrobial agents.. All staphylococcal isolates were susceptible to ceftaroline at a breakpoint of ≤1.0 mcg/mL. In addition, ceftaroline exhibited excellent activity against all streptococcal clinical isolates and non-ESBL-producing strains of Enterobacteriaceae (93.5%) recovered from SICU patients. Ceftaroline was inactive against ESBL-producing Enterobacteriaceae, Pseudomonas aeruginosa, vancomycin-resistant enterococci, and selective gram-negative anaerobic bacteria.. At present, ceftaroline is the only cephalosporin agent that is active against community and healthcare-associated MRSA. Further studies are needed to validate the benefit of this novel broad-spectrum anti-infective agent for the treatment of susceptible serious infections in the SICU patient population.

Topics: Anti-Infective Agents; Bacteria; Bacterial Infections; Ceftaroline; Cephalosporins; Critical Care; Humans; Microbial Sensitivity Tests; Prevalence

Topics: Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Drug Approval; Drug Industry; Drug Resistance, Bacterial; Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Translational Research, Biomedical

Ceftaroline, the bio-active form of parenterally administered ceftaroline fosamil, is a unique broad-spectrum cephalosporin with in vitro and in vivo activity against methicillin-resistant Staphylococcus aureus and was approved for clinical use by the United States Food and Drug Administration in October 2010. In over a year since ceftaroline fosamil approval, no widely used commercial susceptibility test system has added this new compound to its product, therefore requiring use of alternative agar diffusion methods for clinical microbiology laboratories that want to test clinical isolates for ceftaroline susceptibility. An alternative strategy of applying a surrogate β-lactam class marker agent was assessed here, using results from 14,902 organisms (2008-2010) sampled in the USA. Very high and acceptable accuracy (≥ 99.75%) was observed for predicting ceftaroline susceptibility as follows: 1) use of imipenem or meropenem minimum inhibitory concentrations (MICs) at ≤ 8 μg/mL (susceptible and intermediate categories) when testing S. aureus; 2) use of ceftriaxone MIC at ≤ 2 μg/mL (susceptible and intermediate categories) when testing Streptococcus pneumoniae as well as other streptococci (S. pyogenes and S. agalactiae); and 3) use of ceftriaxone, or cefepime, or ceftazidime at ≤ 2 μg/mL (susceptible category) when testing Haemophilus influenzae. Only when testing indicated Enterobacteriaceae species using ceftriaxone susceptibility results did the ceftaroline-nonsusceptible errors increase (4.11%). These presented analyses offer a validated surrogate marker strategy for ceftaroline susceptibility testing, pending development and validation by the commonly used automated systems and agar diffusion commercial methods.

Topics: Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; United States

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

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Clostridioides difficile; Drug Resistance, Multiple, Bacterial; Enterocolitis, Pseudomembranous; Fidaxomicin; Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections; Streptococcal Infections; Streptococcus pneumoniae; Streptococcus pyogenes

Topics: Anti-Bacterial Agents; Bacterial Infections; Ceftaroline; Cephalosporins; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests

The in vitro activities of ceftaroline, a novel, parenteral, broad-spectrum cephalosporin, and four comparator antimicrobials were determined against anaerobic bacteria. Against Gram-positive strains, the activity of ceftaroline was similar to that of amoxicillin-clavulanate and four to eight times greater than that of ceftriaxone. Against Gram-negative organisms, ceftaroline showed good activity against beta-lactamase-negative strains but not against the members of the Bacteroides fragilis group. Ceftaroline showed potent activity against a broad spectrum of anaerobes encountered in respiratory, skin, and soft tissue infections.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Bacteroides fragilis; Ceftaroline; Ceftriaxone; Cephalosporins; Drug Resistance, Bacterial; Gram-Negative Aerobic Bacteria; Gram-Positive Bacteria; Humans; In Vitro Techniques; Microbial Sensitivity Tests