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.     

Current and future treatment options for community-associated MRSA infection

Introduction: Community-associated MRSA (CA-MRSA) represents a global epidemic which beautifully encapsulates the fascinating ability of bacterial organisms to adapt quickly on an evolutionary basis to the extreme selective pressure of antibiotic exposure. In stark contrast to Healthcare-associated MRSA (HA-MRSA), it has become apparent that CA-MRSA is less straight forward of a challenge in terms of controlling its transmission, and has forced clinicians to adjust empiric management of clinical syndromes such as skin and soft tissue infection (SSTI) as well as pneumonia.

Areas covered: This review details the history and epidemiology of CA-MRSA, while covering both current and future treatment options that are and may be available to clinicians. The authors reviewed both historic and more recent literature on this ever-evolving topic.

Expert opinion: While development of new anti-MRSA agents should be encouraged, the importance of antimicrobial stewardship in the battle to stay ahead of the curve with regards to the ongoing control of the MRSA epidemic should be emphasised.     

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.     

Antimicrobial activity of ceftaroline combined with avibactam tested against bacterial organisms isolated from acute bacterial skin and skin structure infections in United States medical centers (2010–2012)

Ceftaroline-avibactam and comparator agents were tested against clinical isolates collected at 174 medical centers from patients with acute bacterial skin and skin structure infection (ABSSSI) in the United States (USA) during 2010–2012. Isolates were processed at the medical centers and forwarded to a central laboratory for confirmatory identification and susceptibility testing using reference methods. Ceftaroline-avibactam was highly active against methicillin-susceptible (MIC_50/90, 0.25/0.25 μg/mL) and methicillin-resistant Staphylococcus aureus (MRSA; MIC_50/90, 0.5/1 μg/mL). Vancomycin, tigecycline, daptomycin, and linezolid were also active (>99.9% susceptible) against MRSA (51.4% of S. aureus), but activity against MRSA was decreased for erythromycin, levofloxacin, and clindamycin (10.8, 40.3, and 81.9% susceptible, respectively). β-Hemolytic streptococci were highly susceptible to β-lactam antimicrobials, including ceftaroline-avibactam (MIC_50/90, ≤0.03/≤0.03 μg/mL). Ceftaroline-avibactam was very active against Escherichia coli and Klebsiella pneumoniae (MIC_50/90, 0.03/0.06 and 0.06/0.25 μg/mL, respectively) including extended-spectrum β-lactamase (ESBL) screen–positive phenotypes (MIC_50/90, 0.06/0.12 and 0.12/1 μg/mL, respectively). Susceptibility of ESBL screen–positive E. coli and K. pneumoniae was 100.0/97.9% for tigecycline and 99.2/56.1% for meropenem, respectively. Susceptibility to other agents for ESBL screen–positive E. coli and K. pneumoniae was decreased. Ceftaroline-avibactam exhibited a broad-spectrum of in vitro activity against isolates from patients in the USA with ABSSSI including MRSA, β-hemolytic streptococci, E. coli, and K. pneumoniae as well as ESBL screen–positive phenotype isolates and merits further study in clinical indications where these resistant organisms may be a concern.     

Transitions of care in the management of acute bacterial skin and skin structure infections: a paradigm shift

Acute bacterial skin and skin structure infections (ABSSSI) have evolved over a relatively short period of time to become one of the most challenging medical problems encountered in clinical practice. Notably the high incidence of methicillin-resistant S. aureus (MRSA) across the continuum of care has coincided with increased outpatient failures and higher rates of hospital admissions for parental antibiotic therapy. Consequently the management of ABSSSI constitutes a tremendous burden to the healthcare system in terms of cost of care and consumption of institutional and clinical resources.

This perspective piece discusses current and new approaches to the management of ABSSSI in a hospital setting and the need for a multifaceted approach. Treatment strategies for the management through the utilization of observation units (OU), Outpatient Parental Antibiotic Therapy (OPAT), and newly developed antibiotics for the use against skin infections caused by Gram-positive bacteria will be discussed in the context of ABSSSI.     

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.     

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.     

抗革兰阳性耐药菌的新型头孢菌素类抗生素头孢洛林酯

头孢洛林酯是新型注射给药的广谱头孢菌素类抗生素,对革兰阳性菌,包括耐甲氧西林金黄色葡萄球菌(MRSA)和多药耐药肺炎链球菌(MDRSP)以及常见革兰阴性菌具有杀菌活性。2010年10月29日,美国FDA批准其用于治疗成人社区获得性细菌肺炎(CABP)和急性细菌皮肤和皮肤结构感染(ABSSSI),包括MRSA的感染。文中对其抗菌活性、药动学/药效学、临床疗效、不良反应等做一综述。