Ceftriaxone is one of the most important beta-lactams suggested for the treatment of severe and non-severe community-acquired pneumonia in the guidelines [1], [2], [3]. There have been some longitudinal studies for antimicrobial susceptibility testing of isolates of Streptococcus pneumoniae in some countries [4], [5], [6], [7], [8]. Due to the relatively low and stable non-susceptibility rates for ceftriaxone in S. pneumoniae isolates, most of these studies focused on penicillin non-susceptibility and macrolide resistance [9].

The occurrence of pneumococci with cefotaxime/ceftriaxone resistance (MICs of ≥4 mg/L) is infrequent worldwide, according to a previous study [9]. Resistance to ceftriaxone in S. pneumoniae comes from specific serotypes and amino acid alterations in the penicillin-binding protein 2B [10]. Although 1 study in the US did not show higher mortality in patients with pneumococcal bloodstream infection with isolates with cefotaxime MICs ≥2.0 mg/L than susceptible isolates [11], ceftriaxone non-susceptibility was found to be linked to increased mortality in patients aged ≥5 y with pneumococcal meningitis [12]. Another study of non-meningeal S. pneumoniae bacteraemia in Korea found that ceftriaxone non-susceptibility (ceftriaxone minimum inhibitory concentrations (MICs) of ≥2 mg/L) was an independent risk factor for 30-d mortality [13]. In an invasive pneumococcal disease cohort, the ceftriaxone resistance (non-meningitis criteria) of the isolate was the major independent risk factor associated with inappropriate therapy [14]. Additionally, in an in vitro pharmacokinetic/pharmacodynamic model of ceftriaxone-resistant pneumococci, ceftriaxone was unable to sustain bactericidal activity [15].

In the United States, there was a trend of a gradual decrease in ceftriaxone resistance from 1998 to 2009, and ceftriaxone had an 11% non-susceptibility rate, including a 2.1% resistance rate in 2008–2010 [16]. Surveillance data in Spain and South Africa during a similar period prior to 2015 showed ceftriaxone/cefotaxime resistance rates below 5% [5,17]. However, some reports from Asia later indicated the presence of a certain percentage of ceftriaxone-non-susceptible pneumococci, including the emergence of resistant strains [7,14,[18], [19], [20]]. These findings suggest that non-susceptibility in pneumococci may exhibit geographic variations. To ensure that empirical treatment guidelines for community-acquired pneumonia are suitable for the local setting, it is crucial to closely observe S. pneumoniae resistance patterns in various countries. The Antimicrobial Testing Leadership and Surveillance (ATLAS) database, which combines 3 surveillance programs (TEST, AWARE, INFORM), is available as a seamlessly searchable and user-friendly website and mobile application. This comprehensive resource provides rapid access to vital resistance information for anyone interested in antimicrobial data. To gain a better understanding of global changes in non-susceptibility rates for third-generation cephalosporins in S. pneumoniae after 2016, we conducted a study using the ATLAS database to assess longitudinal changes in ceftriaxone non-susceptibility rates in different geographic regions worldwide.