Cefditoren and Ceftriaxone Enhance Complement-Mediated Immunity in the Presence of Specific Antibodies against Antibiotic-Resistant Pneumococcal Strains

Abstract

BackgroundSpecific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health.Methodology/Principal FindingsFlow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae.Conclusions/SignificanceUsing cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections.

Improving the Lethal Effect of Cpl-7, a Pneumococcal Phage Lysozyme with Broad Bactericidal Activity, by Inverting the Net Charge of Its Cell Wall-Binding Module

“…S5 in the supplemental material). The latter strain is resistant to tetracycline, erythromycin, chloramphenicol, and amoxicillin, among other antibiotics (36). These results demonstrated that the Cpl-1, Cpl-7, and Cpl-7S lysozymes did not display the same bacteriolytic properties when acting from the outside of live cells, in spite of having rather similar specific activities.…”

Cefdinir for Recent-Onset Pediatric Neuropsychiatric Disorders: A Pilot Randomized Trial

“…In addition to their antibacterial activity, this group of antibiotics has immunomodulatory effects, an attribute that may help explain its potential therapeutic effects (Ramos-Sevillano et al 2012). Interestingly, other cephalosporins, such as ceftriaxone, have been shown to exhibit antidepressant properties, via increasing glutamate uptake in a mouse model of depression (Mineur et al 2007;Thone-Reineke et al 2008).…”

Efficacy and safety of cefditoren pivoxil for exacerbations of chronic obstructive pulmonary disease: A prospective multicenter interventional study

“…negative ampicillin-resistant strains, which are among the most common causes of community-acquired pneumonia and chronic respiratory tract infection [32]. Furthermore, cefditoren pivoxil enhances complement-mediated immunity in the presence of specific antibodies against S. pneumoniae [33]. Its preferable pharmacological data and efficacy in the treatment of communityacquired pneumonia have also been reported with the high doses used in this study [34].…”