Safety and effectiveness of fifth generation cephalosporins for the treatment of methicillin-resistant staphylococcus aureus bloodstream infections: a narrative review exploring past, present, and future.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) is a major issue in healthcare, since it is often associated with endocarditis or deep site foci. Relevant morbidity and mortality associated with MRSA-BSIs forced the development of new antibiotic strategies; in particular, this review will focus the attention on fifth-generation cephalosporins (ceftaroline/ceftobiprole), that are the only ß-lactams active against MRSA. AREAS COVERED: The review discusses the available randomized controlled trials and real-world observational studies conducted on safety and effectiveness of ceftaroline/ceftobiprole for the treatment of MRSA-BSIs. Finally, a proposal of MRSA-BSI treatment flowchart, based on fifth-generation cephalosporins, is described. EXPERT OPINION: The use of anti-MRSA cephalosporins is an acceptable choice either in monotherapy or combination therapy for the treatment of MRSA-BSIs due to their relevant effectiveness and safety. Particularly, their use may be advisable in combination therapy in case of severe infections (including endocarditis or persistent bacteriemia) or in monotherapy in subjects at higher risk of drugs-induced toxicity with older regimens. On the contrary, caution should be taken in case of suspected/ascertained central nervous system infections due to inconsistent data regarding penetration of these drugs in cerebrospinal fluid and brain tissues.

Increase in invasive group A streptococcal infections in Milan, Italy: a genomic and clinical characterization.

Background: Group A Streptococcus (GAS) causes multiple clinical manifestations, including invasive (iGAS) or even life-threatening (severe-iGAS) infections. After the drop in cases during COVID-19 pandemic, in 2022 a sharp increase of GAS was reported globally. Methods: GAS strains collected in 09/2022-03/2023 in two university hospitals in Milan, Italy were retrospectively analyzed. Clinical/epidemiological data were combined with whole-genome sequencing to: (i) define resistome/virulome, (ii) identify putative transmission chains, (iii) explore associations between emm-types and clinical severity. Results: Twenty-eight isolates were available, 19/28 (67.9%) from adults and 9/28 (32.1%) from pediatric population. The criteria for iGAS were met by 19/28 cases (67.9%), of which 11/19 (39.3%) met the further criteria for severe-iGAS. Pediatric cases were mainly non-invasive infections (8/9, 88.9%), adult cases were iGAS and severe-iGAS in 18/19 (94.7%) and 10/19 (52.6%), respectively. Thirteen emm-types were detected, the most prevalent being emm1 and emm12 (6/28 strains each, 21.4%). Single nucleotide polymorphism (SNP) analysis of emm1.0 and emm12.0 strains revealed pairwise SNP distance always >10, inconsistent with unique transmission chains. Emm12.0-type, found to almost exclusively carry virulence factors speH and speI, was mainly detected in children and in no-iGAS infections (55.6 vs. 5.3%, p = 0.007 and 66.7 vs. 0.0%, p < 0.001, respectively), while emm1.0-type was mainly detected in severe-iGAS (0.0 vs. 45.5%, p = 0.045). Conclusions: This study showed that multiple emm-types contributed to a 2022/2023 GAS infection increase in two hospitals in Milan, with no evidence of direct transmission chains. Specific emm-types could be associated with disease severity or invasiveness. Overall, these results support the integration of classical epidemiological studies with genomic investigation to appropriately manage severe infections and improve surveillance.