A team led by Dr. Jordi Vila, director of the Antibiotic Resistance Initiative at ISGlobal, has investigated the in vivo evolution of resistance mechanisms in Pseudomonas aeruginosa strains isolated from patients admitted to an intensive care unit. The results, published in the journal Antimicrobial Chemotherapy, point to the gradual acquisition of resistance phenotypes and identify certain antibiotics as drivers of multidrug resistance development.
The number of hospital acquired infections is increasing worldwide, particularly among patients admitted to intensive care units. The opportunistic bacteria P. aeruginosa is the second most frequently isolated microorganism and many strains display high rates of resistance to most antibiotics. Such resistance mechanisms include mutations in genes or changes in their expression levels that allow the bacteria to "pump-out" the drug, block its entrance, or inhibit its action.
By analyzing clinical isolates of P. aeroginosa obtained from ICU patients, the authors investigated the relationship between drug resistance, molecular mechanisms and previous exposure to antimicrobial agents. The results, obtained by comparing paired isolates obtained from the same patient, suggest the need for several resistance mechanisms to reach the ‘resistance breakpoint' beyond which susceptibility to antimicrobial drugs is lost.
"Importantly", explains Dr. Vila, "we could identify certain drugs (e.g. meropenem) that favor the appearance of multidrug resistance, as well as ceftazidime, that has a higher impact on resistance selection than piperacillin/tazobactam. In contrast, no resistance was detected for amikacin, making it a good option to use together with piperacillin/tazobactam for the treatment of this particular patient population."
Solé M, Fàbrega A, Cobos-Trigueros N, Zamorano L, Ferrer-Navarro M, Ballesté-Delpierre C, Reustle A, Castro P, Nicolás JM, Oliver A, Martínez JA, Vila J. In vivo evolution of resistance of Pseudomonas aeruginosa strains isolated from patients admitted to an intensive care unit: mechanisms of resistance and antimicrobial exposure. J Antimicrob Chemother. 2015. Aug 9. pii: dkv228. [Epub ahead of print]