Lung penetration and pneumococcal target binding of antibiotics in lower respiratory tract infection.

OBJECTIVES

To achieve the therapeutic effects, antibiotics must penetrate rapidly into infection sites and bind to targets. This study reviewed updated knowledge on the ability of antibiotics to penetrate into the lung, their physicochemical properties influencing the pulmonary penetration and their ability to bind to targets on pneumococci.

METHODS

A search strategy was developed using PubMED, Web of Science, and ChEMBL. Data on serum protein binding, drug concentration, target binding ability, drug transporters, lung penetration, physicochemical properties of antibiotics in low respiratory tract infection (LRTI) were collected.

RESULTS

It was seen that infection site-to-serum concentration ratios of most antibiotics are >1 at different time points except for ceftriaxone, clindamycin and vancomycin. Most agents have proper physicochemical properties that facilitate antibiotic penetration. In antimicrobial-resistant Streptococcus pneumoniae, the binding affinity of antibiotics to targets mostly decreases compared to that in susceptible strains. The data on binding affinity of linezolid, clindamycin and vancomycin were insufficient. The higher drug concentration at the infection sites compared to that in the blood can be associated with inflammation conditions. Little evidence showed the effect of drug transporters on the clinical efficacy of antibiotics against LRTI.

CONCLUSIONS

Data on antibiotic penetration into the lung in LRTI patients and binding affinity of antibiotics for pneumococcal targets are still limited. Further studies are required to clarify the associations of the lung penetration and target binding ability of antibitotics with therapeutic efficacy to help propose the right antibiotics for LRTI.