A Review of the Resistance Mechanisms for β-Lactams, Macrolides and Fluoroquinolones among Streptococcus pneumoniae

Abstract

Streptococcus pneumoniae (S. pneumoniae) is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of S. pneumoniae as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like β-lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of S. pneumoniae infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in S. pneumoniae against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes β-lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of S. pneumoniae may aid researchers in developing a more efficacious antibiotic in future endeavors.

Keywords: AMR; antimicrobial resistance; bacterial infections; community-acquired pneumonia (CAP); fluoroquinolones.

Figure 1

Pathogenesis and immunopathogenesis of pneumonia by S. pneumoniae. The host can become infected by the pathogen in a number of ways, such as through aspiration, direct inoculation, breathing in, and hematogenous or contiguous spread from a nearby focus. Once the pathogen reaches the alveoli, it multiplies and evokes a host response.

Figure 2

Mechanism of action and resistance mechanism of β-lactams. There are few resistance mechanisms that involve mutation of penicillin-binding proteins, non-pbp genes, and destruction by beta-lactamase.

Figure 3

How antibiotic resistance moves directly from germ to germ. Resistance traits are transmissible from generation to generation. They can be transmitted directly between bacteria via mobile genetic components like plasmids, transposons, and phages. The genetic component works by transduction, conjugation, and transformation.

Figure 4

How bacteria fight back against antimicrobials. Antibiotics combat bacteria. However, bacteria adapt and discover new ways to survive. Their defensive strategies are known as resistance mechanisms.

Figure 5

Mechanism of action and resistance mechanism of macrolides. Mutations of penicillin-binding proteins and active efflux pumps are involved in the resistance mechanisms of macrolides among S. pneumoniae.

Figure 6

Mechanisms of action and resistance for fluoroquinolones. Mutations in the gyrA, parC, and parE genes, as well as efflux and acquisition of plasmid-encoded genes, are involved in the resistance mechanisms of fluoroquinolone among S. pneumoniae.