Ceftaroline fosamil: a brief clinical review.
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ABSTRACT:
SUBMITTER: Shirley DA
PROVIDER: S-EPMC4108109 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Ceftaroline is a novel cephalosporin recently approved in children for treatment of acute bacterial skin and soft tissue infections and community-acquired bacterial pneumonia (CABP) caused by methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae and other susceptible bacteria. With a favorable tolerability profile and efficacy proven in pediatric patients and excellent in vitro activity against resistant Gram-positive and Gram-negative bacteria, ceftaroline may serve as a therapeutic option for polymicrobial infections, CABP caused by penicillin- and ceftriaxone-resistant S. pneumoniae and resistant Gram-positive infections that fail first-line antimicrobial agents. However, limited data are available on tolerability in neonates and infants younger than 2 months of age, and on pharmacokinetic characteristics in children with chronic medical conditions and those with invasive, complicated infections. In this review, the microbiological profile of ceftaroline, its mechanism of action, and pharmacokinetic profile will be presented. Additionally, clinical evidence for use in pediatric patients and proposed place in therapy is discussed.
| S-EPMC5336419 | biostudies-other
Project description:BackgroundPneumonia is a relevant clinical and public health issue worldwide frequently associated with infections caused by Multi-Drug Resistant (MDR) pathogens. Ceftaroline fosamil is a promising new antibiotics with broad-spectrum bacterial activity. The aim of this systematic review and meta-analysis is to assess the efficacy and the effectiveness of ceftaroline fosamil in community-acquired (CAP), hospital-acquired (HAP), healthcare-associated (HCAP) and ventilator-associated (VAP) pneumonia.MethodsA systematic review and meta-analysis was carried out retrieving both experimental and observational studies.ResultsA total of 2364 records was found and 14 manuscripts were finally considered eligible. The pooled efficacy/effectiveness was 81.2% (I2: 1.2%) in all types of pneumonia. The pooled relative risk of clinical cure was 1.1 (I2: 0.0%). The success rate was higher than 70% for infections caused by S. pneumoniae and S. aureus, including MDR pathogens.ConclusionsCeftaroline fosamil showed a high efficacy/effectiveness in patients with any type of pneumonia with a good safety profile.
| S-EPMC6199731 | biostudies-literature
Project description:BACKGROUND:Osteomyelitis is often challenging to treat. This analysis examined the clinical experience of patients with gram-positive osteomyelitis treated with ceftaroline fosamil in the phase 4 Clinical Assessment Program and Teflaro® Utilization Registry (CAPTURE) study. METHODS:Data including patient demographics, past illnesses, risk factors, disease characteristics, antibiotic use, pathogens isolated, and clinical outcome were collected between September 2013 and February 2015 by review of randomly ordered patient charts from participating sites in the United States. Clinical success was defined as discontinuation of ceftaroline fosamil following clinical cure with no further need for antibiotics or clinical improvement with switch to another antibiotic treatment. RESULTS:A total of 150 patients with gram-positive osteomyelitis were treated with ceftaroline fosamil. Most patients (117/150; 78.0%) were treated with 600 mg ceftaroline fosamil per dose; 143/150 patients (95.3%) received a dose every 12 h. The majority (89/150 patients; 59.3%) had been previously diagnosed with diabetes mellitus or peripheral arterial disease. Osteomyelitis was associated with hardware in 32/150 patients (21.3%). Methicillin-resistant and methicillin-susceptible Staphylococcus aureus (MRSA; MSSA) were the most commonly isolated pathogens, observed in 93/150 (62.0%) and 21/150 (14.0%) patients, respectively. Clinical success with ceftaroline fosamil therapy was observed in 139/150 (92.7%) patients overall, 81/89 (91.0%) patients with diabetes or peripheral arterial disease, and 18/20 (90.0%) patients who had hardware implanted before ceftaroline fosamil therapy (none had hardware removed during therapy). Patients who received prior antibiotic therapy or ceftaroline fosamil as monotherapy experienced clinical success rates of 93.9% (107/114) and 91% (91/100), respectively. Among patients who received concurrent antibiotic therapy, the clinical success rate was 96.0% (48/50). Patients who were infected with MRSA or MSSA had clinical success rates of 92.5% (86/93) and 100% (21/21), respectively. A total of 2/150 (1.3%) patients discontinued ceftaroline fosamil therapy because of adverse events. CONCLUSIONS:Clinical success rates with ceftaroline fosamil were high in patients with gram-positive osteomyelitis, including those with diabetes or peripheral arterial disease and those with MRSA or MSSA.
| S-EPMC6385445 | biostudies-other
Project description:Ceftaroline has been approved for acute bacterial skin infections and community-acquired bacterial pneumonia. Limited clinical experience exists for use outside these indications. The objective of this study was to describe the outcomes of patients treated with ceftaroline for various infections. Retrospective analyses of patients receiving ceftaroline ?72 h from 2011 to 2013 were included. Clinical and microbiological outcomes were analyzed. Clinical success was defined as resolution of all signs and symptoms of infection with no further need for escalation while on ceftaroline treatment during hospitalization. A total of 527 patients received ceftaroline, and 67% were treated for off-label indications. Twenty-eight percent (148/527) of patients had bacteremia. Most patients (80%) were initiated on ceftaroline after receipt of another antimicrobial, with 48% citing disease progression as a reason for switching. The median duration of ceftaroline treatment was 6 days, with an interquartile range of 4 to 9 days. A total of 327 (62%) patients were culture positive, and the most prevalent pathogen was Staphylococcus aureus, with a frequency of 83% (271/327). Of these patients, 88.9% (241/271) were infected with methicillin-resistant S. aureus (MRSA). Clinically, 88% (426/484) achieved clinical success and hospital mortality was seen in 8% (40/527). While on ceftaroline, adverse events were experienced in 8% (41/527) of the patients and 9% (28/307) were readmitted within 30 days after discharge for the same infection. Patients treated with ceftaroline for both FDA-approved and off-label infections had favorable outcomes. Further research is necessary to further describe the role of ceftaroline in a variety of infections and its impact on patient outcomes.
| S-EPMC3993242 | biostudies-literature
Project description:Novel therapies for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) are needed in the setting of reduced antibiotic susceptibilities and therapeutic failure. Ceftaroline is a cephalosporin antibiotic with MRSA activity. Although not FDA approved for MRSA BSI, ceftaroline has generated much interest as a potential treatment option. However, detailed descriptions of its use in this setting remain limited. To address this, we conducted a retrospective, multicenter, observational study of adult patients with MRSA BSI treated with at least 72 h of ceftaroline from 2011 to 2015. Safety outcomes were examined in the overall cohort, while efficacy outcomes were examined among patients who had not cleared their BSI prior to ceftaroline initiation. Data were also stratified by ceftaroline monotherapy or combination therapy. Predictors of clinical failure on ceftaroline treatment were also sought. Overall, 211 patients were included in the safety population; Clostridium difficile infection, rash, and neutropenia occurred in 6 patients (2.8%), 7 patients (3.3%), and 3 patients (1.4%), respectively. Clinical success was observed in 86 (68.3%) of the 126 patients included in the efficacy population. The monotherapy and combination therapy subgroups had similar proportions of patients experiencing success (69.7 and 64.9%, respectively). The median BSI durations post-ceftaroline treatment were 2 days (interquartile range, 1 to 4 days) for monotherapy and 3 days (interquartile range, 1.5 to 5 days) for combination therapy. Higher acute physiology and chronic health evaluation II scores and comorbid malignancy independently predicted treatment failure. Ceftaroline appears effective for MRSA BSI as both monotherapy and combination therapy. However, comparative studies are needed to further delineate the role of ceftaroline in MRSA BSI treatment.
| S-EPMC5278749 | biostudies-literature
Project description:BackgroundCeftaroline fosamil is US Food and Drug Administration-approved for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia, but it is not known how ceftaroline is being used in real-world settings or how adverse effects (AEs) and mortality compare to clinical trials.ObjectiveThis study describes ceftaroline use, AEs, and mortality in US Veterans Health Administration (VHA) hospital patients.MethodsThis phase IV, population-based, epidemiologic study analyzed patients ≥18 years old who received one or more ceftaroline doses within 14 days of admission to 69 VHA hospitals in 41 US states/territories from 1 October 2010 to 30 September 2014. VHA repository data were linked using unique patient identifiers. Diagnoses and AEs were determined using ICD9-CM and CSS codes. Demographics, AEs within 30 days of therapy initiation, and all-cause in-hospital mortality were summarized using descriptive statistics.Results764 Patients met study criteria. Patients were 97% male and 56% White, with a median age of 61 years and a Charlson score of 6. Diagnoses included skin (40%), sepsis (30%), osteomyelitis (25%), diabetic foot (22%), pneumonia (16%), bacteremia (11%), endocarditis (6%), meningitis (2%), and device (2%) infections. Ceftaroline was used first-line (37%), second-line (56%), and third-line or greater (7%). Patients received ceftaroline a median of 3 days after hospital admission. All-cause in-hospital mortality rates were: overall (5%), skin (2%), sepsis (9%), osteomyelitis (3%), diabetic foot (1%), pneumonia (13%), bacteremia (6%), endocarditis (11%), meningitis (6%), and device (13%). Eosinophilia, leukopenia, leukocytosis, fibromyalgia, myalgia and myositis, and polymyalgia rates were <1% each.ConclusionsCeftaroline is used in VHA hospitals for various diagnoses. Mortality was low and comparable with rates from clinical trials. Additional studies comparing ceftaroline to other drugs used in similar situations are needed.
| S-EPMC5553123 | biostudies-literature
Project description:Ceftaroline fosamil (ceftaroline hereafter) is the latest addition to the armamentarium for the treatment of patients with community-acquired pneumonia (CAP). It is currently approved by the Food and Drug Administration (FDA) for community-acquired bacterial pneumonia (CABP), which is a recent FDA indication that centers on individuals with documented bacterial pneumonias that arise in the community setting. The purpose of this review is to summarize and discuss the major findings from the Phase III CAP clinical trials as well as the clinical experience with ceftaroline among patients with CAP in the "Ceftaroline Assessment Program and Teflaro(®) Utilization Registry" (CAPTURE). In its two Phase III CAP trials, ceftaroline was compared to ceftriaxone among adults with radiographically confirmed CAP requiring hospitalization who were classified as Pneumonia Outcomes Research Team (PORT) risk class III or IV. Among patients with CAP, clinical success at test of cure was 84.3% vs 77.7% (difference 6.6%, 95% confidence interval [CI]: 1.6-11.8%) in those treated with ceftaroline and ceftriaxone, respectively, across the two Phase III clinical trials. Among patients with a culture-confirmed CABP, day 4 response rates were numerically higher, albeit non-significant, among patients that received ceftaroline vs. ceftriaxone (69.5% for ceftaroline vs. 59.4% for ceftriaxone, difference 10.1%, 95% CI, -0.6% to 20.6%). The efficacy of ceftaroline is supported by real-world observational data from CAPTURE for patients with both CAP and CABP. In addition, the CAPTURE program afforded an opportunity to assess the outcomes of patients who were excluded or limited in the original Phase III trials in a non-comparative fashion. These underrepresented patient populations with CAP included: patients that received prior antibiotics, patients in the ICU, patients with severe renal dysfunction, and those with methicillin-resistant Staphylococcus aureus (MRSA) isolated from respiratory or blood culture. As CAPTURE is a retrospective, non-comparator convenience sample registry, all the findings need to be interpreted with caution.
| S-EPMC4269637 | biostudies-literature
Project description:AimsThe standard dose of ceftaroline fosamil for patients with normal renal function is 600 mg diluted in 250 ml by 60 min intravenous infusion every 12 h. This two part phase I trial (NCT01577589) assessed safety and local tolerability of multiple ceftaroline fosamil 50 ml and 250 ml infusions, and pharmacokinetics following single administrations of each infusion volume.MethodsPart A was a placebo-controlled, double-blind, multiple dose crossover study. Twenty-four healthy subjects were randomized to simultaneous, bilateral ceftaroline fosamil 600 mg and placebo infusions in each arm (50 ml then 250 ml or vice versa) every 12 h for 72 h, with a ≥ 4.5 day washout. Local tolerability was evaluated by the Visual Infusion Phlebitis scale, with scores ≥2 considered infusion site reactions (ISRs). Part B was an open label crossover study. Ten subjects were randomized to single 50 ml and 250 ml ceftaroline fosamil 600 mg infusions on days 1 and 3 (washout on day 2). Blood samples for pharmacokinetic analysis were taken over 24 h.ResultsIn part A, four subjects (16.7%) experienced ISRs, all of which were associated with placebo infusions. No ISRs were reported for either ceftaroline fosamil 50 ml or 250 ml. Plasma pharmacokinetics (ceftaroline fosamil, active ceftaroline and an inactive metabolite) were similar following single 50 ml and 250 ml infusions in part B.ConclusionsNo new safety concerns were identified for ceftaroline fosamil 600 mg 50 ml compared with 250 ml. These findings suggest infusion volumes down to 50 ml may be used in patients with fluid intake restrictions.
| S-EPMC4256619 | biostudies-literature
Project description:Ceftaroline fosamil (CPT-F) is currently approved for use for the treatment of complicated skin and soft tissue infections and community-acquired pneumonia at 600 mg twice daily (q12h), but other dosing regimens are under evaluation. To date, very limited data on the soft tissue pharmacokinetics (PK) of the active compound, ceftaroline (CPT), are available. CPT concentrations in the plasma, muscle, and subcutis of 12 male healthy volunteers were measured by microdialysis after single and repeated intravenous administration of 600 mg CPT-F q12h or three times daily (q8h) in two groups of 6 subjects each. Relevant PK and PK/pharmacodynamic (PD) parameters were calculated and compared between groups. In plasma, the area under the concentration-time curve (AUC) from 0 to 24 h for total CPT and the cumulative percentage of the dosing interval during which the free drug concentrations exceeded the MIC (fTMIC) for unbound CPT for the currently established threshold of 1 mg/liter were significantly higher in the group receiving CPT-F q8h. Exposure to free drug in soft tissues was higher in the group receiving CPT-F q8h, but high interindividual variability in relevant PK parameters was observed. The mean ratios of the AUC from time zero to the end of the dosing interval (AUC0-?) for free CPT in soft tissues and the AUC0-? for the calculated free fraction in plasma at steady state ranged from 0.66 to 0.75. Administration of CPT-F q8h led to higher levels of drug exposure in all investigated compartments. When MIC values above 1 mg/liter were assumed, the calculated fTMIC after dosing q12h was markedly lower than that after dosing q8h. The clinical implications of these differences are discussed in light of recently completed clinical phase III and PK/PD studies.
| S-EPMC4879389 | biostudies-literature
Project description:Pharmacokinetic-pharmacodynamic (PK-PD) analyses for efficacy using phase III trial data from patients treated with a ceftaroline fosamil dosing regimen of 600 mg intravenously (i.v.) every 12 h (q12h) for 5 to 7 days for community-acquired bacterial pneumonia (CABP) were conducted. High clinical and microbiological success rates (84.7 and 86.3%, respectively) and percentages of time during the dosing interval that free-drug steady-state concentrations remained above the MIC (f%T>MIC) (98.4% had f%T>MIC values of ?63.3) were observed among 124 microbiologically evaluable patients. As a result, significant PK-PD relationships could not be identified. These data provide support for the use of a ceftaroline fosamil dosing regimen of 600 mg i.v. q12h to treat patients with CABP.
| S-EPMC3837912 | biostudies-literature