Here's an excerpt of the article written by H. Nikaido titled "Multidrug Resistance in Bacteria" from the NIH:
The discovery of penicillin in 1928 was followed by the discovery and commercial production of many other antibiotics. We now take for granted that any infectious disease is curable by antibiotic therapy. Antibiotics are manufactured at an estimated scale of about 100,000 tons annually worldwide, and their use had a profound impact on the life of bacteria on earth. More strains of pathogens have become antibiotic resistant, and some have become resistant to many antibiotics and chemotherapeutic agents, the phenomenon of multidrug resistance.
Indeed, some strains have become resistant to practically all of the commonly available agents. A notorious case is the methicillin-resistant Staphylococcus aureus (MRSA), which is resistant not only to methicillin (which was developed to fight against penicillinase-producing S. aureus) but usually also to aminoglycosides, macrolides, tetracycline, chloramphenicol, and lincosamides. Such strains are also resistant to disinfectants, and MRSA can act as a major source of hospital-acquired infections. An old antibiotic, vancomycin, was resurrected for treatment of MRSA infections. However, transferable resistance to vancomycin is now quite common in Enterococcus and found its way finally to MRSA in 2002, although such strains are still rare (1).
An even more serious threat may be the emergence of gram-negative pathogens that are resistant to essentially all of the available agents (2). Research had time to react against the threat by MRSA. Thus, there are newly developed agents that are active against vancomycin-resistant MRSA, such as linezolid and quinupristin/dalfopristin. However, the emergence of “pan-resistant” gram-negative strains, notably those belonging to Pseudomonas aeruginosa and Acinetobacter baumanii, occurred more recently, after most major pharmaceutical companies stopped the development of new antibacterial agents. Hence, there are almost no agents that could be used against these strains, in which an outer membrane barrier of low permeability and an array of efficient multidrug efflux pumps are combined with multitudes of specific resistance mechanisms.
Multidrug resistance in bacteria occurs by the accumulation, on resistance (R) plasmids or transposons, of genes, with each coding for resistance to a specific agent, and/or by the action of multidrug efflux pumps, each of which can pump out more than one drug type.
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