Assessment of new β-lactam/β-lactamase inhibitors combinations against MDR Pseudomonas aeruginosa isolated from King Fahd Hospital of the University

Abstract

Resistance to antimicrobial agents among Gram-negative bacteria mostly among the nonfermentersand Enterobacteriaceae, is one of the most important public health worriesinternationally. Gram-negative bacteria infections are leading cause of mortality and morbidityglobally. The international spreading of antibiotic resistance has lately received much attention,especially after reports of the worldwide dissemination of multi-drug resistant. P. aeruginosa is aleading cause of nosocomial infections and accounts for nearly10% of all hospital-acquiredinfections. There are a lot of mechanisms involved in resistance such as target site modification,utilization of efflux pumps, the production of inactivating enzymes, and chromosomal mutations.The limitation in therapeutic options makes treatment of MDR P. aeruginosa very challenging.Adaptation and resistance to antibiotics allow P. aeruginosa to survive in other natural andartificial settings and surfaces in medical facilities. Due to the severity of P. aeruginosa infectionsand its resistance to wide range of antimicrobial agents, it is urgently important to find alternativeprevention and treatment strategies. In this current study we assessed the minimum inhibitoryconcentration of new combinations of new β-lactam antibiotics against a range of P. aeruginosastrains that are previously characterized to be of a multi-drug resistant phenotype. Carbapenemsare one of the best choices for curing infections affected by gram-negative bacteria resistant tomultiple drugs. In this study, we noticed a high resistance to all available antimicrobials, which isconsidered as a major threat that limits the therapy decisions. In this study carbapenem resistancewas high, indicated by elevated resistance to Imipenem (n = 37/56.1%) and to Meropenem (n =29/43.9%). The newly accepted agents offer significant activity againstMDR Pseudomonas infections. Out of 58 isolates 23 (39.65%) showed resistance toceftazidime/avibactam, whereas 35 (60.34%) were susceptible. The isolates showed 36.20%resistance to ceftolozane/tazobactam, however 63.79% were susceptible. The sequencing analysisof AmpD showed mutations in the nucleotide positions: 64, 290, 317, 318, 363, 388, 407, 439,445, 465, 472, 482, 483, 487, 488, 490, 503, 505, 513, 519, 575, 579, 582, and 611. According tothe results of this study 47 (71.21%) isolates out of 66 isolates found to have at least one of thebiofilm genes exoS, exoY, and ndvB. Biofilm genes-positive isolates constituted of 17 (36.17%)MDR isolates and 30 (63.82%) susceptible strains. The findings of this work will have an impacton treatment regimen developed to treat such hard-to-treat infections.