Fifth-generation Cephalosporin Research Articles

Real-World Experience of Ceftobiprole for Community- and Hospital-Acquired Pneumonia from a Stewardship Perspective.

Ceftobiprole is a fifth-generation cephalosporin approved by European and American regulatory agencies for the treatment of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). Ceftobiprole administration is useful in severe CAP as well as HAP where the potential is to save other β-lactams including carbapenems or linezolid/vancomycin in clinical practice. The aim of this study was to report the real-world evidence of ceftobiprole in patients with CAP and HAP in a single center. In this retrospective study, we included 159 patients with CAP or HAP: 105 (66%) had CAP and 54 (34%) had HAP. The median age was 70 years (IQR 60-77), the median Charlson Comorbidity Index was 5 (IQR 3-7.5) and baseline INCREMENT ESBL score was 8 (IQR 6-11). Ceftobiprole was mostly given as a combination treatment (77%) or as a carbapenem-sparing strategy (44%). There were no differences in mortality between shorter and longer duration of treatment (<7 days compared with ≥7 days (HR 1.02, C.I. 0.58-1.77, p = 0.93) or between first-line (HR 1.00, C.I. 0.46-2.17, p = 0.989) and second-line therapy. Ceftobiprole use in CAP or HAP in the real world is effective as a first- and second-line treatment as well as a carbapenem-sparing strategy. Further studies are needed to explore the full potential of ceftobiprole, including its real-world use in antimicrobial stewardship programs.

Computational Study of Antimicrobial Peptides for Promising Therapeutic Applications Against Methicillin-resistant Staphylococcus Aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a causative agent for multiple drug-resistant diseases and is a prime health concern. Currently, antibiotics like vancomycin, daptomycin, fluoroquinolones, linezolid, fifth-generation cephalosporin and others are available in the market for the treatment of MRSA infection. With the increasing prevalence of drug-resistant cases, researchers are actively investigating alternative strategies to combat MRSA, including the exploration of peptide therapeutics. This study employed computational methods to prospect for potential Antimicrobial Peptides (AMPs). A total of One hundred and fifty antimicrobial peptides were explored based on physicochemical properties. The results showed that Clavanin B was the most appropriate candidate. Molecular Docking and Molecular Dynamics Simulation results showed the protein-peptide interaction of the MRSA target proteins, Penicillin Binding Protein 2a and Panton-Valentine Leukocidin Toxin, with the Antimicrobial Peptide Clavanin B. Currently, the antimicrobial peptide database highlights Clavanin B's role as an anti-HIV peptide. Moreover, this investigation proposes Clavanin B as a viable repurposed drug for treating MRSA, underscoring its potential deployment in the management of MRSA infections.

Ceftaroline fosamil – fifth-generation cephalosporin with anti-MRSA activity in the treatment of severe infections in pediatric practice

Сeftaroline fosamil is a fifth-generation cephalosporin and a unique β-lactam and the only currently registered in the Russian Federation cephalosporin with activity against MRSA. Сeftaroline is approved for use in pediatric practice for the treatment of children with community-acquired pneumonia and complicated skin and soft tissue infections, including cases of patients with concomitant bacteremia. The place of ceftaroline in the treatment of severe and life-threatening infections in children is primarily due to its high activity against the key causative agents of community-acquired pneumonia and skin and soft tissue infections (first of all, S. pneumoniae and S. aureus, including MRSA), bactericidal mechanism of action, creation of effective concentrations and penetration into the infection’s site, low potential for resistance development, proven significant development of clinical effect, high clinical efficacy in these infections and favorable tolerability and safety profile. The review presents the results of the program of clinical evaluation of ceftaroline in children, analyzes current data on etiology and antimicrobial resistance of the key pathogens of community-acquired pneumonia and skin and soft tissue infections in the Russian Federation, defines the place of ceftaroline in clinical recommendations in children, and characterizes the patient’s profile to whom the prescription of ceftaroline in hospital is indicated.

Ceftobiprole medocaril: clinical and pharmacological characteristics and possibilities of clinical use

Ceftobiprole medocaril is a fifth-generation cephalosporin (anti-MRSA cephem) with a broad spectrum of antibacterial activity. Ceftobiprole is active against gram-positive bacteria, including strains resistant to other beta-lactams, such as methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae, as well as gram-negative bacteria such as Pseudomonas aeruginosa. The purpose of this review is to consider the mechanism of action and safety profile of ceftobiprole, as well as to summarize the results of clinical studies of the drug. Possible areas of clinical use of ceftobiprole for infections of the skin and soft tissues, complicated staphylococcal bacteremia, infective endocarditis, as well as communityacquired and nosocomial pneumonia are given. Summarizing the available information, ceftobiprole can be considered as the most important antibacterial drug for the treatment of severe pneumonia not associated with mechanical ventilation, skin and soft tissue infections, as well as a part of combination antimicrobial therapy for infective endocarditis.

Population Pharmacokinetic and Pharmacodynamic Analysis for Maximizing the Effectiveness of Ceftobiprole in the Treatment of Severe Methicillin-Resistant Staphylococcal Infections.

Ceftobiprole is a fifth-generation cephalosporin used for different Gram-positive bacterial infections. A population pharmacokinetic analysis was conducted in real-life clinical patients to assess the adequacy of current dosages. Population pharmacokinetics was conducted using non-linear mixed effect modeling. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) of free trough or steady-state concentration over MIC (fCtrough/MIC or fCss/MIC) ≥ 1 or ≥4 associated with both the standard and intensified dosing regimens adjusted for renal function. Cumulative fraction of response (CFR) against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were also calculated. A total of 132 patients with 503 concentrations were included. Most of them (107/132, 81.1%) had hospital- or community-acquired pneumonia, endocarditis, and bacteremia. A three-compartment model adequately fitted ceftobiprole concentration-time data. Estimated glomerular filtration rate significantly affected drug clearance. Monte Carlo simulations showed that the optimal target of fCtrough/MIC or fCss/MIC ≥ 4 is achieved only with the use of the standard dosages administered by continuous infusion (CI) against MRSA infections in patients with preserved renal function. Intensified dosages administered by CI are needed in patients with impaired renal function and/or augmented renal clearance against MRSA and in patients with preserved renal functions against MRSE.

Evaluation of In-Vitro Activity of Ceftaroline Against Methicillin-Resistant Staphylococcus aureus Clinical Isolates.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital and community-acquired infections. Fewer drugs, such as vancomycin, teicoplanin, and daptomycin, are effective against it, but they come with high toxicity. Fifth-generation cephalosporins like ceftaroline and second-generation cefuroxime are effective against MRSA. Limited studies are available on ceftaroline resistance in the literature. This study was undertaken to determine ceftaroline resistance in MRSA in a tertiary care hospital in Eastern India. A cross-sectional, hospital-based study was carried out with MRSA isolates obtained from various clinical samples of patients. Identification of the isolates to the species level was performed by an automated Vitek system, and selected samples were genotypically confirmed by detecting the mecA gene via real-time PCR. Out of a total of 334 Staphylococcus aureus isolates examined in this study, the prevalence of MRSA was seen in 59.3% (198/334), and methicillin-sensitive Staphylococcus aureus was in 40.7% (136/334). Of the total 198 MRSA isolates, ceftaroline intermediate MRSA was seen in 8.6% (17/198), and ceftaroline sensitive MRSA was in 91.4% (181/198), respectively. Among the 17 ceftaroline intermediate MRSA isolates, 88.2% (15/17) showed aminimum inhibitory concentration (MIC) of 2 µg/ml, and 11.8% (2/17) showed an MIC of 3 µg/ml. All the remaining 91.4% (181/198) isolates were sensitive to ceftaroline and showed an MIC ≤1 µg/ml. Real-time PCR confirmed the presence of the mecA gene in MRSA isolates. In this present study, not a single isolate was resistant to ceftaroline, suggesting that it, being a safer drug, can be used in place of glycopeptides such as vancomycin or teicoplanin and linezolid, where resistance has already been detected. The rational use of ceftaroline could be useful in clinical settings, and further studies will confirm the findings.

Ceft-to-Ceft Study: Real-Life Experience with Ceftaroline and Ceftobiprole in Treatment of the Principal Infectious Syndromes in a Spanish Multicenter Hospital Cohort.

To compare the real-life effectiveness and safety of ceftaroline fosamil (ceftaroline-F) and ceftobiprole medocaril (ceftobiprole-M) for infections in hospitalized patients. This comparative, observational, retrospective, and multicenter Spanish study included patients receiving outpatient parenteral antimicrobial therapy (OPAT) and hospitalized patients treated for at least 48 h with ceftaroline-F or ceftobiprole-M between their first incorporation in the clinical protocol of each hospital and 31 July 2022. Ceftaroline-F was administered to 227 patients and ceftobiprole-M to 212. In comparison to the latter, ceftaroline-F-treated participants were younger (63.02 vs. 66.40 years, OR 1.1; 95%CI: 1.001-1.05) and had higher rates of septic shock (OR 0.27; 95%CI: 0.09-0.81) and higher frequencies of targeted (57.7 vs. 29.7%; OR: 0.35; 95%CI: 0.18-0.69) and combined (89.0 vs. 45.8%, OR: 0.13; 95%CI: 0.06-0.28) therapies that were second line or more (82.4% vs. 64.6%%; OR 0.35; 95%CI: 0.18-0.69), and higher rates of infections due to Gram-positive cocci (92.7 vs. 64.7%, p = 0.001), bacteremia (51.9 vs. 21.7%, p = 0.001), infective endocarditis (24.2 vs. 2.4%, p = 0.0001), and mechanical ventilation-associated pneumonia (8.8 vs. 2.4%, p = 0.0001). Ceftobiprole-M was more frequently administered against polymicrobial infections (38.1 vs. 14.0%, p = 0.001), those produced by Gram-negative bacilli (19.7 vs. 6.0%, p = 0.0001), nosocomial pneumonia (33 vs. 10.6%, p = 0.0001), and skin and soft-tissue infections (25.4 vs. 10.1%, p = 0.0001). Patients treated with ceftaroline-F had a longer hospital stay (36 (IQR: 19-60) vs. 19.50 (IQR: 12-30.75, p = 0.0001) days), with no difference in infection-related mortality at 14 (13.2 vs. 8.0%, p = 0.078) or 28 (4.8 vs. 3.3%, p = 0.415) days or in dropout rate for adverse effects (2.2 vs. 0.9%; p = 1). The fifth-generation cephalosporins, ceftaroline-F and ceftobiprole-M, are safe and effective in real life, with no difference between them in health outcomes.

Unraveling the mechanism of ceftaroline-induced allosteric regulation in penicillin-binding protein 2a: insights for novel antibiotic development against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) acquires high-level resistance against β-lactam antibiotics by expressing penicillin-binding protein 2a (PBP2a). PBP2a is a cell wall-synthesizing protein whose closed active site exhibits a reduced binding affinity toward β-lactam antibiotics. Ceftaroline (CFT), a fifth-generation cephalosporin, can effectively inhibit the PBP2a activity by binding to an allosteric site to trigger the active site opening, allowing a second CFT to access the active site. However, the essential mechanism behind the allosteric behavior of PBP2a remains unclear. Herein, computational simulations are employed to elucidate how CFT allosterically regulates the conformation and dynamics of the active site of PBP2a. While CFT stabilizes the allosteric domain surrounding it, it simultaneously enhances the dynamics of the catalytic domain. Specifically, the study successfully captured the opening process of the active pocket in the allosteric CFT-bound systems and discovered that CFT alters the potential signal-propagating pathways from the allosteric site to the active site. These findings reveal the implied mechanism of the CFT-mediated allostery in PBP2a and provide new insights into dual-site drug design or combination therapy against MRSA targeting PBP2a.

Impact of an Inpatient Allergy Guideline on β-Lactam and Alternative Antibiotic Use.

A guideline identifying when inpatients with penicillin or cephalosporin antibiotic allergy labels (PCAAL) can receive β-lactam antibiotics increased β-lactam receipt at a large northeastern US health care system. To report outcomes of implementing a similar guideline and electronic order set (OS) at an independent academic health care system. Penicillin/cephalosporin receipt (percentage of inpatients receiving full doses) and alternative antibiotic use (days of therapy per 1000 patient-days [DOT/1000PD]) were compared over 3 periods before (February 1, 2017, to January 31, 2018) and after guideline implementation (February 1, 2018, to January 31, 2019), and after OS implementation (February 1, 2019, to January 31, 2020) among inpatients with PCAAL admitted on medical services with access to guideline/OS and education (Medical-PCAAL, n= 8721), surgical services with access to guideline/OS without education (Surgical-PCAAL, n= 5069), and obstetrics/gynecology services without interventions (Ob/Gyn-PCAAL, n= 798) and inpatients without PCAAL admitted on the same services (Medical-No-PCAAL, n= 50,840; Surgical-No-PCAAL, n= 29,845; Ob/Gyn-No-PCAAL, n= 6109). χ2 tests were used to compare categorical variables, and analysis of variance was used to compare continuous and interrupted time series analyses (ITSA) to investigate the guideline/OS implementation effect on penicillin/cephalosporin receipt. In the Medical-PCAAL group, penicillin/cephalosporin receipt increased (58%-68%, P < .001), specifically for cefazolin (8%-11%, P= .02) and third- to fifth-generation cephalosporins (43%-48%, P= .04), and aztreonam use decreased (12 DOT/1000PD, P= .03). In the Medical-No-PCAAL group, penicillin/cephalosporin receipt increased (88%-90%, P= .004), specifically for penicillin (40%-44%, P < .001), without changes in aztreonam use. Significant changes were not observed in these outcomes on surgical or obstetrics/gynecology services. Per ITSA, guideline/OS implementation was associated with increased penicillin/cephalosporin receipt in the Medical-PCAAL group only. Guideline and OS implementation was associated with improved antibiotic stewardship on inpatient services that also received allergy education.

Cefto Real-Life Study: Real-World Data on the Use of Ceftobiprole in a Multicenter Spanish Cohort.

Ceftobiprole is a fifth-generation cephalosporin that has been approved in Europe solely for the treatment of community-acquired and nosocomial pneumonia. The objective was to analyze the use of ceftobiprole medocaril (Cefto-M) in Spanish clinical practice in patients with infections in hospital or outpatient parenteral antimicrobial therapy (OPAT). This retrospective, observational, multicenter study included patients treated from 1 September 2021 to 31 December 2022. A total of 249 individuals were enrolled, aged 66.6 ± 15.4 years, of whom 59.4% were male with a Charlson index of four (IQR 2-6), 13.7% had COVID-19, and 4.8% were in an intensive care unit (ICU). The most frequent type of infection was respiratory (55.8%), followed by skin and soft tissue infection (21.7%). Cefto-M was administered to 67.9% of the patients as an empirical treatment, in which was administered as monotherapy for 7 days (5-10) in 53.8% of cases. The infection-related mortality was 11.2%. The highest mortality rates were identified for ventilator-associated pneumonia (40%) and infections due to methicillin-resistant Staphylococus aureus (20.8%) and Pseudomonas aeruginosa (16.1%). The mortality-related factors were age (OR: 1.1, 95%CI (1.04-1.16)), ICU admission (OR: 42.02, 95%CI (4.49-393.4)), and sepsis/septic shock (OR: 2.94, 95%CI (1.01-8.54)). In real life, Cefto-M is a safe antibiotic, comprising only half of prescriptions for respiratory infections, that is mainly administered as rescue therapy in pluripathological patients with severe infectious diseases.

Ceftobiprole medocaril for the treatment of pneumonia

ABSTRACT Introduction Ceftobiprole, a fifth-generation cephalosporin, exhibits a broad-spectrum activity against common pathogens causing pneumonia, including multidrug-resistant organisms (MDROs), such as penicillin-resistant S. pneumoniae (PRSP) and methicillin-resistant Staphylococcus aureus (MRSA) and non-extended-spectrum β -lactamase (non-ESBL) producing Enterobacterales strains. Therefore, ceftobiprole should be considered as a potential alternative for the empirical treatment of pneumonia in patients with high risk for MDROs. Area covered In this review, we discussed the role of ceftobiprole in the treatment of patients with pneumonia. Expert opinion Ceftobiprole has several advantages in the treatment of pneumonia. First, ceftobiprole exerts its bactericidal activity by inhibiting transpeptidases, especially showing strong affinities to penicillin-binding protein (PBP) 2a, PBP2× and PBP3. Second, its plasma protein binding is minimal, allowing it to penetrate lung tissue and achieve high concentrations in epithelial lung fluid. Third, ceftobiprole exhibits potent in vitro activity against a wide range of susceptible pathogens, including S. aureus, S. pneumoniae, Viridans streptococci, H. influenzae, M. catarrhalis, Enterobacterales, and particularly, MRSA and P. aeruginosa. Finally, several randomized controlled trials have demonstrated the clinical efficacy and safety of ceftobiprole in the treatment of pediatric and adult patients with community-acquired pneumonia and hospital-acquired pneumonia (excluding ventilator-associated pneumonia).

A Review on Ceftaroline in the Treatment of Community Acquired Bacterial Pneumonia

Ceftaroline fosamil (ceftaroline) is approved by the United States Food and Drug Administration (FDA) for the treatment of community-acquired pneumonia (CAP). It is a fifth-generation cephalosporin having broad-spectrum efficacy against gram-positive bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP), as well as a variety of common gram-negative pathogens. Ceftaroline can bind to penicillin-binding protein (PBP)2a, an MRSA-specific PBP with minimal affinity for the majority of other β-lactam antibiotics. The drug is often given intravenously in doses of 600 mg every 12 hours for 5-7 days. Only a parenteral formulation of ceftaroline is commercially available, and the prodrug, ceftaroline fosamil, is rapidly and completely hydrolysed after intravenous administration. Ceftaroline was found to be noninferior to comparator agents in Phase II and Phase III clinical studies, with good clinical cure rates in the treatment of CAP. Ceftaroline is well tolerated, which is consistent with the cephalosporin class's safety and tolerability profile. In this review, we will evaluate the microbiological properties, pharmacological features, efficacy, safety, and tolerability of ceftaroline in the treatment of CAP. Keywords: Ceftaroline, MRSA, CAP, efficacy.

Infections in Acute Pancreatitis: Organisms, Resistance-Patterns and Effect on Mortality.

Acute pancreatitis (AP) is a common gastrointestinal disease in which infection is a serious complication. Understanding its bacterial spectrum and antibiotic resistance is of great significance for treatment. This retrospective study analyzed the Medical Information Mart for Intensive Care database with the aim of identifying the distribution characteristics of pathogenic bacteria in AP patients. First, 2089 AP patients were classified and analyzed statistically according to culture results. Second, the bacterial profile, antibiotic resistance, and antibiotic-use data of positive culture group were analyzed. Third, logistic regression analysis was used to identify the rick factors of culture results, and culture results correlations with mortality. This study included 1486 patients in negative culture group, 603 patients in positive cultures. Enterococcus spp. (71%), Enterococcus faecium (61%), and Staphylococcus aureus coagulase-positive (54%) exhibited the highest proportions of drug resistance. Logistic regression revealed five factors related to positive culture (the number of antibiotics, length of stay in hospital, length of stay in intensive care unit, mechanical ventilation, and parenteral nutrition) and four factors related to distribution of multidrug-resistant bacterial infection (age, hemoglobin, length of stay in hospital, and duration on antibiotics). This study found that enteric bacteria were the most common source of infection (26.7%). Carbapenems, penicillins containing enzyme inhibitors, fifth-generation cephalosporins, oxazolidinones, and some of the aminoglycoside antibiotics had high sensitivity, which can guide the use of clinical empiric antibiotics. Positive culture was an independent risk factor for in-hospital all-cause mortality of AP patients.

Antimicrobial activity of ceftobiprole and comparator agents when tested against gram-positive and -negative organisms collected across China (2016–2018)

BackgroundCeftobiprole is a fifth-generation cephalosporin which has been reported to have broad antibacterial spectrum when tested against bacteria collected from other countries except China. This study evaluated the in vitro activity of ceftobiprole in comparison with other comparators against clinically significant isolates collected across from China.ResultsSusceptibility testing of ceftobiprole and comparators against 1163 clinically isolated Gram-positive and Gram-negative bacteria was performed with broth micro dilution method following the CLSI guidelines. All 110 S. aureus were susceptible to ceftobiprole with MIC50/90 of 1/2 mg/L for MRSA and 0.5/1 mg/L for MSSA. For Coagulase-negative staphylococci (CNS), MIC50/90 of ceftobiprole for MRCNS and MSCNS was 1/2 mg/L and 0.25/0.5 mg/L. Ceftobiprole demonstrated good potency against E. faecalis (MIC50/90 of 0.5/1 mg/L) but limited activity against E. faecium (MIC50/90 of > 32/ > 32 mg/L). Ceftobiprole demonstrated potent activity against all 39 β-hemolytic Streptococcus spp. with MIC50/90 ≤ 0.015/ ≤ 0.015–2 mg/L and 110 of PSSP with 98.2% susceptibility. Ceftobiprole inhibited all isolates of H. influenzae and M. catarrhalis at ≤ 1 mg/L. 91.8% and 98.2% of the ESBL-negative E. coli and K. pneumoniae were susceptible to ceftobiprole, but most of the ESBL-positive or carbapenem-resistant strains were also resistant to ceftobiprole. Ceftobiprole inhibited 84.2% of carbapenem-susceptible P. aeruginosa and 94.1% of carbapenem-susceptible A. baumannii at ≤ 8 mg/L, but only 52.6% of carbapenem-resistant P. aeruginosa and 5.3% of carbapenem-resistant A. baumannii.ConclusionCeftobiprole demonstrated good in vitro activity against a broad range of clinically relevant contemporary Gram-positive and Gram-negative bacterial isolates.

An Observational Study of MDR Hospital-Acquired Infections and Antibiotic Use during COVID-19 Pandemic: A Call for Antimicrobial Stewardship Programs.

The pandemic caused by the COVID-19 virus has required major adjustments to healthcare systems, especially to infection control and antimicrobial stewardship. The objective of this study was to describe the incidence of multidrug-resistant (MDR) hospital-acquired infections (HAIs) and antibiotic consumption during the three waves of COVID-19 and to compare it to the period before the outbreak at Molinette Hospital, located in the City of Health and Sciences, a 1200-bed teaching hospital with surgical, medical, and intensive care units. We demonstrated an increase in MDR infections: particularly in K. pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp), A. baumannii, and MRSA. Fluoroquinolone use showed a significant increasing trend in the pre-COVID period but saw a significant reduction in the COVID period. The use of fourth- and fifth-generation cephalosporins and piperacillin–tazobactam increased at the beginning of the COVID period. Our findings support the need for restoring stewardship and infection control practices, specifically source control, hygiene, and management of invasive devices. In addition, our data reveal the need for improved microbiological diagnosis to guide appropriate treatment and prompt infection control during pandemics. Despite the infection control practices in place during the COVID-19 pandemic, invasive procedures in critically ill patients and poor source control still increase the risk of HAIs caused by MDR organisms.

Incidence and risk factors for mortality in patients treated with combined ceftaroline for Gram-positive infective endocarditis.

Ceftaroline is a fifth-generation cephalosporin and represents an alternative in the treatment of infective endocarditis (IE). The main objective of this study was to describe the incidence of in-hospital and 42-day mortality in patients with IE treated with ceftaroline. An observational retrospective study included adult patients with IE admitted during a 3.5-year period (January 2018-June 2021) and treated with ceftaroline in a single center. All cases were definite or possible IE according to the modified Duke criteria. Seventy cases were analyzed. The mean age was 67.35 ± 16.62 (16-89) and 39 (55.7%) were males. The mean number of days of treatment with ceftaroline was 21.26 ± 16.17 (1-75). Overall mortality at 42days was 30%, 20.7% in the first line, and 36.6% in rescue therapy. Predictors of 42days-mortality were increased Charlson comorbidity index (CCI) (OR of 1.7 per 1 point increment, 95% CI 1.2-2.4, P 0.001), presence of methicillin-resistance (OR 6.8, 95% CI 1.3-36.8, P 0.026) and evidence of septic shock (OR 8.6 95% CI 1.7-44.2, P 0.01). Predictors of 42days of therapeutic failure were the increase in the CCI (OR of 1.6 per 1 point increment, 95% CI 1.3-2.1, P 0.000) and septic shock (OR 4.5 95% CI 1.1-18 P 0.036). Adverse effects were described in 6/70 (8.6%) of the patients, precipitating in 4/70 (5.7%) the definitive withdrawal of the antibiotic. The incidence of in-hospital and 42day-mortality of IE patients treated with ceftaroline remains similar to literature data. Increased CCI, septic shock, and methicillin resistance are associated with poor prognosis.

Ceftaroline in severe community-acquired pneumonia.

Severe community-acquired pneumonia (SCAP) is associated with high mortality. Factor such as early adequate antibiotic therapy, delay in intensive care unit (ICU) care and pneumonia caused by resistant pathogens are associated with worse outcomes in SCAP patients. Ceftaroline is a fifth-generation cephalosporin with bactericidal activity against Gram-positive pathogens (including methicillin-resistant Staphylococcus aureus [MRSA] and multidrug-resistant Streptococcus pneumoniae) and common Gram-negative organisms. The efficacy and safety for the treatment of pneumonia was evaluated in three randomized control trials were ceftaroline demonstrated superiority against ceftriaxone for the treatment of pneumonia in hospitalized patients with Pneumonia Severity Index (PSI) III – IV.

Ceftaroline.

Community-acquired pneumonia (CAP) is one of the leading causes of admission to emergency departments. Ceftaroline is a fifth-generation cephalosporin with a potent In vitro activity against Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus, the three most important pathogens causing CAP. Three randomized and double-blind clinical trials compared the efficacy of ceftaro-line versus ceftriaxone in patients with CAP and the results of each trial and a meta-analysis, concluded the superiority of ceftaroline in terms of clinical success. In particular, the major difference was observed among patients with CAP caused by S. aureus. Accordingly, ceftaroline has been included as a first-line option in the recent clinical guidelines for the management of CAP.

Ceftobiprole: a clinical view.

Ceftobiprole is a broad-spectrum, fifth-generation cephalosporin currently approved for community-acquired and non-ventilator-associated hospital-acquired pneumonia. High bactericidal and anti-biofilm activity has been exhibited in in vitro and animal models. This, together with its synergism with other antibiotics against gram-positive bacteria, makes it an ideal candidate for treatment of complex infections, such as those associated with devices or infective endocarditis. More clinical data are needed to achieve drug positioning.

Characterization and Clonal Diffusion of Ceftaroline Non-Susceptible MRSA in Two Hospitals in Central Italy.

Background: Ceftaroline represents a novel fifth-generation cephalosporin to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Ceftaroline susceptibility of 239 MRSA isolates was assessed by disk diffusion and a MIC test strip following both EUCAST and CLSI guidelines. Non-susceptible isolates were epidemiologically characterized by pulsed-field gel electrophoresis, spa typing, and multilocus sequence typing, and further investigated by PCR and whole genome sequencing to detect penicillin-binding protein (PBP) mutations as well as antibiotic resistance and virulence genes. Results: Fourteen isolates out of two hundred and thirty-nine (5.8%) were non-susceptible to ceftaroline (MIC > 1 mg/L), with differences between the EUCAST and CLSI interpretations. The characterized isolates belonged to seven different pulsotypes and three different clones (ST228/CC5-t041-SCCmecI, ST22/CC22-t18014-SCCmecIV, and ST22/CC22-t022-SCCmecIV), confirming a clonal diffusion of ceftaroline non-susceptible strains. Mutations in PBPs involved PBP2a for ST228-t041-SCCmecI strains and all the other PBPs for ST22-t18014-SCCmecIV and ST22-t022-SCCmecIV clones. All isolates harbored antibiotic resistance and virulence genes with a clonal distribution. Conclusion: Our study demonstrated that ceftaroline non-susceptibile isolates belonged not only to ST228 strains (the most widespread clone in Italy) but also to ST22, confirming the increasing role of these clones in hospital infections.