Ceftriaxone and methicillin-susceptible staphylococcus aureus: a perspective from pharmacokinetics/pharmacodynamics studies

ABSTRACT

Introduction: Usage of ceftriaxone-based therapy to treat Methicillin-Susceptible Staphylococcus aureus (MSSA) infections is a controversial issue, from in vitro to clinical studies.

Area covered: We conducted a literature review using PubMed of articles with ceftriaxone pharmacokinetics parameters and built a probability of target attainment (PTA) based on PK values from stable conditions (non-critically-ill patients) with goals of fT>55%, fT>75%, and fT>100%. Ceftriaxone’s minimal inhibitory concentration from 31 MSSA strains (0.25–64 mg/L) was used to build the cumulative fraction response (CFR). The isolates were clinically relevant from blood, bronchoalveolar lavage, and soft tissue biopsy.

Expert opinion: The results from controversies about using ceftriaxone for MSSA infections have been commonly addressed in the literature. However, variables such as (i) pharmacokinetic profile, (ii) pharmacodynamic target, (iii) site of infection, and (iv) MIC distributions may influence divergences. From this pharmacokinetics-pharmacodynamics perspective, ceftriaxone may be a reasonable option for MSSA infections when the MIC50 and MIC90 were 4 mg/L and 8 mg/L. CFR analysis demonstrated that ceftriaxone 1 g q24 h could be used if bacteriostasis is the aim (fT>55%), while 1 g q12h should be used for bactericidal effects (fT>75% or fT>100%). These dosing regimens should be considered in other clinical trials.

KEYWORDS:

• Ceftriaxone
• staphylococcus aureus
• pharmacodynamics
• pharmacokinetics

Article highlights

• Ceftriaxone-based therapy to MSSA infections is controversial issue. Anti-staphylococcal standard options are costly to poor- and middle-income countries, and OPAT services are not suitable for more than two times daily infusion.

• After reviewing literature, non-critically ill patients demonstrated ceftriaxone VD, CL, and half-life of 10.04L±1.22 L, 1.16±0.47 L/h, and 7.4±1.13h, respectively.

• MSSA ceftriaxone MIC₅₀ and MIC₉₀ founds were 4 mg/L and 8mg/L, respectively.

• CFR analysis demonstrated that ceftriaxone 1g q24h may be used if bacteriostasis is aimed (fT>55%), while 1g q12h should be used for bactericidal effects (fT>75% or fT>100%).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author’s contributions

Joao Paulo Telles: Study design, literature review, writing draft, final review

Rodrigo Cuiabano Paes Leme: Literature review, writing draft

Michel Leandro Campos: Study design, statistical analysis, final review

Carmen Ito: Microbiological analysis, statistical analysis

Larissa Bail: Microbiological analysis, writing draft

Keite da Silva Nogueira: Microbiological analysis, writing draft

Felipe Francisco Tuon: Study design, microbiological analysis, final review

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This paper was not funded.