Ceftaroline fosamil for the treatment of Gram-positive endocarditis: CAPTURE study experience

Background

The clinical experience of ceftaroline fosamil (CPT-F) therapy for Gram-positive infective endocarditis is reported from CAPTURE, a retrospective study conducted in the USA.

Ceftaroline fosamil as first-line versus second-line treatment for acute bacterial skin and skin structure infections (ABSSSI) or community-acquired bacterial pneumonia (CABP)

The Clinical Assessment Program and Teflaro^® Utilization Registry (CAPTURE) is a multicenter registry study of acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP) patients treated with ceftaroline fosamil in the US. Data for this analysis were collected between August 2011 and February 2013 at US study centres by randomly ordered chart review. Clinical success rates among ABSSSI patients were >81% when ceftaroline fosamil was used as first- or second-line therapy, including monotherapy and concurrent therapy. Among CABP patients, clinical success rates were >77% among first-line and second-line patients and patients who received first-line concurrent therapy or second line monotherapy or concurrent therapy. For CABP patients treated with ceftaroline fosamil as first-line monotherapy, the clinical success rate was 70%. Ceftaroline fosamil is an effective treatment option for patients with ABSSSI or CABP with similar clinical success rates when used as first-line or second-line treatment.     

Ceftaroline fosamil and treatment of acute bacterial skin and skin structure infections: CAPTURE study experience

Abstract

The Clinical Assessment Program and TEFLARO Utilization Registry (CAPTURE) is a multicentre retrospective cohort study in the USA describing treatment of acute bacterial skin and skin structure infection (ABSSSI) with ceftaroline fosamil (CPT-F). Charts for review were chosen by random selection. Among 647 evaluable patients, 52% were obese, 46% had diabetes mellitus (DM), and 19% had peripheral vascular disease (PVD). Methicillin-resistant Staphylococcus aureus (MRSA) was recovered in 28% and methicillin-susceptible S. aureus (MSSA), 11%. Antibiotics were administered prior to CPT-F treatment in 80%, and concurrently in 39%. Clinical success overall was 85%; in patients with DM, 83%; with PVD, 76%; and in obese patients, 88%. Clinical success was ≧ 79% across all infection types; 81% for MRSA and 83% for MSSA; and 86% for ceftaroline monotherapy and 84% for concurrent therapy. These high clinical success rates support CPT-F as an effective treatment option for ABSSSI, including infections due to MRSA and patients with significant co-morbidities.     

Ceftaroline fosamil for the treatment of acute bacterial skin and skin structure infections

Skin infections have traditionally been classified by the US FDA as uncomplicated and complicated. In August 2010, the FDA released a new guidance document for the development of drugs to treat acute bacterial skin and skin structure infections (ABSSSI) and this was updated in 2013. Several new issues were addressed and henceforth skin infections in clinical trials were termed ABSSSI. In the USA, the annual prevalence of methicillin-resistant Staphylococcus aureus-related skin infections have continuously increased from 32.7% in 1998 to 53.8% in 2007. Ceftaroline fosamil is the only cephalosporin approved in the USA for monotherapy treatment of ABSSSI including infections caused by methicillin-resistant S. aureus. The efficacy of ceftaroline fosamil was shown in the CANVAS clinical trials. The CANVAS Day-3 analyses met an earlier, primary efficacy time point requested by the FDA. Ceftaroline has minimal drug–drug interactions, is well tolerated and possesses the safety profile associated with the cephalosporin class.     

Chlamydia/gonorrhea combo and HR HPV DNA testing in liquid-based pap

Residual material from liquid-based pap (LBP) test has been used for molecular testing of Human Papilloma Virus (HR HPV) DNA. LBP test specimens (1,025) were evaluated to determine how often residual material was insufficient to perform microbiological testing. The specimens were tested for Chlamydia trachomatis and Neisseria gonorrhea (CCGT) alone and in combination with HR HPV(CCGT + HR HPV), using PCR method and HYBRID CAPTURE 2, respectively. A minimum volume of 5 ml (CCGT: 0.5-1 ml, HPV: 4 ml) of residual material is required for both the tests. The residual material was measured at >5 ml, < or =5 ml, and 0.5 ml volumes and documented. Results were tabulated. The insufficient rate for cases submitted for CCGT was 0.2% and 7.6% for HR HPV, with a detection rate of 40.9% for HR HPV. Utilizing residual material from LBP test for microbiological testing, as well as DNA testing for HR HPV is a convenient, cost-effective means to enhance patient care.     

Are gadolinium contrast agents suitable for gadolinium neutron capture therapy?

Abstract

Objective: Gadolinium neutron capture therapy (GdNCT) is a potential treatment for malignant tumors based on two steps: (1) injection of a tumor-specific ¹⁵⁷Gd compound; (2) tumor irradiation with thermal neutrons. The GdNC reaction can induce cell death provided that Gd is proximate to DNA. Here, we studied the nuclear uptake of Gd by glioblastoma (GBM) tumor cells after treatment with two Gd compounds commonly used for magnetic resonance imaging, to evaluate their potential as GdNCT agents.

Methods: Using synchrotron X-ray spectromicroscopy, we analyzed the Gd distribution at the subcellular level in: (1) human cultured GBM cells exposed to Gd-DTPA or Gd-DOTA for 0–72hours; (2) intracerebrally implanted C6 glioma tumors in rats injected with one or two doses of Gd-DOTA, and (3) tumor samples from GBM patients injected with Gd-DTPA.

Results: In cell cultures, Gd-DTPA and Gd-DOTA were found in 84% and 56% of the cell nuclei, respectively. In rat tumors, Gd penetrated the nuclei of 47% and 85% of the tumor cells, after single and double injection of Gd-DOTA, respectively. In contrast, in human GBM tumors 6.1% of the cell nuclei contained Gd-DTPA.

Discussion: Efficacy of Gd-DTPA and Gd-DOTA as GdNCT agents is predicted to be low, due to the insufficient number of tumor cell nuclei incorporating Gd. Although multiple administration schedules in vivo might induce Gd penetration into more tumor cell nuclei, a search for new Gd compounds with higher nuclear affinity is warranted before planning GdNCT in animal models or clinical trials.     

Monoclonal antibody based capture ELISA/ELIFA for detection of Coxiella burnetii in clinical specimens

A CAPTURE ELISA/ELIFA system based on monoclonal capture and biotinylated monoclonal detection antibody is described. The assay is fast, highly specific and detects a minimum dose of 2500 Coxiella (C.) burnetii particles. In contrast to the sophisticated and cumbersome isolation procedures, even non-specialized laboratories could use this assay system for investigating clinical samples of different origin for C. burnetii within a short period of time.Corresponding author.     

Ceftaroline fosamil for treating skin and skin structure infections or community-acquired pneumonia in patients with renal insufficiency

The Clinical Assessment Program and Teflaro^® Utilization Registry (CAPTURE) is a multicenter retrospective study, conducted in the USA, describing the contemporary use of ceftaroline fosamil. Ceftaroline is primarily excreted by the kidneys and the dose should be reduced in patients with moderate to severe renal insufficiency. This article describes the clinical effectiveness of ceftaroline fosamil in the treatment of acute bacterial skin and skin structure infection (ABSSSI) or community-acquired bacterial pneumonia (CABP) patients with renal insufficiency. There were 985 ABSSSI patients and 344 CABP patients, of which 22 and 31%, respectively, had renal insufficiency. Ceftaroline fosamil was mostly administered to patients as second-line therapy. Overall clinical success was 78–91% among ABSSSI or CABP patients with renal insufficiency and, overall, >50% of patients were discharged to home. Ceftaroline fosamil is an effective treatment option for ABSSSI or CABP patients with renal insufficiency.     

Ceftaroline fosamil for the treatment of hospital-acquired pneumonia and ventilator-associated pneumonia

Objectives: Ceftaroline fosamil is a novel cephalosporin with bactericidal activity against common pathogens associated with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Ceftaroline is inactive against extended-spectrum β-lactamase-producing or AmpC-overexpressing Enterobacteriaceae and has limited activity against Pseudomonas aeruginosa. CAPTURE is a multicenter, retrospective study designed to collect information on contemporary clinical use of ceftaroline fosamil in the USA. Data on off-label use of ceftaroline fosamil for the treatment of patients with HAP/VAP between September 2013 and March 2014 are presented. Methods: Data were collected at participating study centers by randomized selection and review of patients’ charts, and included patients’ demographics, disease characteristics, pathogens isolated, antibiotic treatment and clinical outcomes. Patients receiving at least four consecutive doses of ceftaroline fosamil, with data available for determination of clinical cure, comprised the evaluable population. Clinical success was defined as either clinical cure with no further need for antibiotics treatment, or clinical improvement with a switch to another antibiotic. Results: A total of 40 patients were evaluated: 27 with HAP and 13 with VAP. Demographics for patients with HAP and VAP were similar (59% male, mean age of 63 years and 54% male, mean age of 58 years, respectively). The clinical success rates were 75% overall, 82% in patients with HAP and 62% in patients with VAP. Clinical success rates for patients with methicillin-resistant Staphylococcus aureus (MRSA) isolated were 58% in patients with HAP and 57% in patients with VAP. Ceftaroline fosamil was used as a second-line therapy in majority of patients (85%) with clinical success rates of 79% similar to the published literature. Conclusion: The CAPTURE study data support further evaluation of ceftaroline fosamil as an effective treatment option for HAP and VAP when a ceftaroline susceptible etiologic pathogen is identified, including MRSA, or as a concurrent therapy when resistant Gram-negative pathogens are suspected.