Heteroresistance of Pseudomonas aeruginosa to penicillins

Abstract:

[Background] Pseudomonas aeruginosa (PA) is a common opportunistic pathogen in clinical practice, and its heteroresistance often leads to failure of clinical treatment. [Objective] To study the heteroresistance of PA to penicillins, and to provide a basis for the treatment of related clinical infections. [Methods] We collected 50 clinical isolates of PA and investigated their heteroresistance characteristics by using disk diffusion method (Kirby-Bauer (K-B) test), population analysis profile (PAP), growth assay and passage stability test. [Results] According to the preliminary screening results obtained with K-B test, 52%, 52%, and 54% of the PA isolates had heteroresistance to piperacillin (PIP), piperacillin/tazobactam (TZP) and ticarcillin/clavulanic acid (TIM), respectively. Thirteen (26%) strains were confirmed to have heteroresistance by PAP. Eight heteroresistant strains were randomly selected, and the frequency of resistant subpopulations ranged from 7.3×10⁻⁷ to 1.2×10⁻⁵. Without antibiotic pressure, the heteroresistant strains PAS92 and PAS57 and their three subpopulations on the plates with the highest PIP concentration showed no statistical difference in growth rate (P>0.05), while the growth of the subpopulations in the inhibition zone of PAS92 was faster than that of PAS92 within 8–12 h (P=0.002 2<0.01). The subpopulations with different levels of resistance in the inhibition zone and those with high levels of resistance selected from the plates with the highest PIP concentration in PAP were subcultured without antibiotic pressure. Only one of the subpopulations was found to be unstable and returned to the sensitivity level of the original strain, while the others had good stability of resistance. [Conclusion] In this study, PA isolates show low heteroresistance ratio while high frequency of resistant subpopulations to penicillins. Besides, they have high heteroresistance to PIP, and most of the resistant subpopulations had good passage stability. Therefore, when using this type of antibiotics, attention should be paid to the occurrence of heteroresistance to prevent the emergence of strains with higher drug-resistance from causing treatment failure.