ppi-0903 and Meningitis

Ceftaroline fosamil is a fifth-generation cephalosporin with anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. It has been approved by the EMA and FDA for the treatment of adults and children with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). However, ceftaroline fosamil has a broad spectrum of activity, and a good safety and tolerability profile, so is frequently used off-label. The aim of this systematic review was to summarize the safety and efficacy of off-label use of ceftaroline. The review was conducted according to PRISMA guidelines. MEDLINE, EMBASE and CENTRAL databases (2010-2018) were searched using as the main term ceftaroline fosamil and its synonyms in combination with names of infectious diseases of interest. A total of 21 studies with 1901 patients were included: the most common off-label indications for ceftaroline use were bacteremia (n=595), endocarditis (n=171), osteoarticular infections (n=368), hospital-acquired pneumonia (n=115) and meningitis (n=23). The most common reasons for off-label use were persistent or recurrent infection after standard treatment or non-susceptibility to vancomycin and daptomycin. Clinical success was evaluated in 933 patients, and 724 (77%) of these reached this positive outcome. Incidence of adverse events (AEs) was reported in 11 studies. In 83 (9%) cases there were AEs related to the use of ceftaroline; the most common reported AEs were nausea, vomiting, diarrhea, rash and neutropenia. The review results show that ceftaroline may be used in clinical settings other than those currently approved; however, the use of ceftaroline in these contexts deserves further investigation.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftaroline; Cephalosporins; Community-Acquired Infections; Cross Infection; Endocarditis, Bacterial; Healthcare-Associated Pneumonia; Humans; Meningitis; Off-Label Use

The aim of this study was to compare the antibacterial activity of ceftaroline versus vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) meningitis in an experimental rabbit meningitis model.. The antibacterial activity of ceftaroline was compared with vancomycin in the treatment of meningitis induced by MRSA strain ATCC 43300 in an experimental rabbit meningitis model. Quantitative cerebrospinal fluid (CSF) cultures were performed at the beginning of antibiotic treatment and 24h and 73h after the first antibiotic dose. Furthermore, in vitro time-kill data were investigated at 0, 2, 4, 6, 8, 12 and 24h in sterile human serum.. The difference between the control group versus both treatment groups was significant when comparing the decrease in colony counts in CSF both at 24h and 73h after the first antibiotic dose (P<0.05). At the end of the experiment, there was a significant difference in survival between both the ceftaroline-treated group and the vancomycin-treated group versus the control group, but not between the two treatment groups.. These results suggest that the antibacterial activity of both ceftaroline and vancomycin are similar in the treatment of MRSA meningitis in an experimental rabbit meningitis model.

Topics: Animals; Ceftaroline; Cephalosporins; Meningitis; Methicillin-Resistant Staphylococcus aureus; Rabbits; Staphylococcal Infections; Vancomycin

Ceftaroline is a new cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae, as well as common Gram-negative organisms. This study tested the prodrug, ceftaroline fosamil, against a penicillin-sensitive and a penicillin-resistant strain of S. pneumoniae in an experimental rabbit meningitis model. The penetration of ceftaroline into inflamed meninges was approximately 14%. Ceftaroline fosamil was slightly superior to ceftriaxone against the penicillin-sensitive strain and significantly superior to the combination of ceftriaxone and vancomycin against the penicillin-resistant strain.

Topics: Animals; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Meningitis; Penicillin Resistance; Penicillins; Rabbits; Streptococcus pneumoniae