Abstract
We often come across difficult to treat infections—even after administering appropriate antibiotics according to the minimal inhibitory concentration of the causative bacteria. Antibiotic tolerance has recently started to garner attention as a crucial mechanism of refractory infections. However, few studies have reported the correlation between clinical outcomes and antibiotic tolerance. This study aims to clarify the effect of antibiotic tolerance on clinical outcomes of respiratory tract infection caused by Pseudomonas aeuginosa (P. aeruginosa). We examined a total of 63 strains isolated from sputum samples of different patients and conducted a retrospective survey with the medical records of 37 patients with imipenem-sensitive P. aeruginosa infections. Among them, we selected 15 patients with respiratory infections, and they were divided into high-tolerance minimal bactericidal concentration for adherent bacteria (MBCAD)/minimal inhibitory concentration for adherent bacteria (MICAD) ≥ 32 (n = 9) group and low-tolerance MBCAD/MICAD ≤ 16 (n = 6) group for further investigations. The findings indicated that the high-tolerance group consisted of many cases requiring hospitalization. Chest computed tomography findings showed that the disease was more extensive in the high-tolerance group compared to the low-tolerance group. Regarding the bacterial phenotypic characterization, the high-tolerance group significantly upregulated the production of the virulence factors compared to the low-tolerance group. Our study provided evidence that carbapenem tolerance level is a potent prognostic marker of P. aeruginosa infections, and carbapenem tolerance could be a potential target for new antimicrobial agents to inhibit the progression of persistent P. aeruginosa infections.
Highlights
Pseudomonas aeruginosa has become an important cause of infection, especially in immunocompromised patients [1,2]
We focused on 37 sensitive strains to investigate antibiotic tolerance
We investigated the correlation between carbapenem tolerance and clinical features using isolates of P. aeruginosa obtained from sputum samples of patients
Summary
Pseudomonas aeruginosa has become an important cause of infection, especially in immunocompromised patients [1,2]. Pseudomonas infections are complicated and can be severe and life-threatening. P. aeruginosa is a cause of chronic respiratory tract infections [3]. The minimum bactericidal concentration (MBC) denotes the minimum concentration required to kill 99.9% of the bacteria, whereas. MIC is the lowest concentration of antibacterial agent that inhibits the growth. Treatment can be unsuccessful despite the selection of antibacterial agents on the basis of MIC, which could be because of antibiotic tolerance. In cases of antibiotic tolerance, wherein MIC and MBC get apart, complete elimination of the bacteria is not achieved despite suppressing bacterial growth
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