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Pseudomonas aeruginosa and some of the species of Enterobacteriaceae are Gram-negative hospital-acquired pathogens that are mostly difficult to treat. Carbapenem drugs are a group of β-lactams class that affect cell wall and are administered in the treatment of infections caused by these organisms. These organisms can be resistant to carbapenem drugs via mechanisms such as carbapenemase enzymes and multidrug efflux systems. Detection methods for carbapenem-resistant isolates are the modified Hodge test, Carba NP test, and PCR. This review will describe the current opinion in the treatment of multidrug-resistant and carbapenemase-producing Enterobacteriaceae and P. aeruginosa and suggest some available antibiotics to be administered in the treatment of infections involving these organisms. Based on carbapenem susceptibility patterns found in previous studies, some drugs such as antipseudomonal agents, colistin, or combined therapy have been suggested for carbapenemase-producing P. aeruginosa, and tigecycline, colistin, and fosfomycin have been suggested for carbapenemase-producing Enterobacteriaceae.