Bacteria antibiotic resistance: New challenges and opportunities for implant-associated orthopedic infections

Abstract

There has been a dramatic increase in the emergence of antibiotic-resistant bacterial strains, which has made antibiotic choices for infection control increasingly limited and more expensive. In the U.S. alone, antibiotic-resistant bacteria cause at least 2 million infections and 23,000 deaths a year resulting in a $55-70 billion per year economic impact. Antibiotics are critical to the success of surgical procedures including orthopedic prosthetic surgeries, and antibiotic resistance is occurring in nearly all bacteria that infect people, including the most common bacteria that cause orthopedic infections, such as Staphylococcus aureus (S. aureus). Most clinical cases of orthopedic surgeries have shown that patients infected with antibiotic-resistant bacteria, such as methicillin-resistant S. aureus (MRSA), are associated with increased morbidity and mortality. This paper reviews the severity of antibiotic resistance at the global scale, the consequences of antibiotic resistance, and the pathways bacteria used to develop antibiotic resistance. It highlights the opportunities and challenges in limiting antibiotic resistance through approaches like the development of novel, non-drug approaches to reduce bacteria functions related to orthopedic implant-associated infections. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:22-32, 2018.

Keywords: S. aureus; antibiotic alternative; antibiotic resistance; infection; multidrug resistance; orthopedic implant.

Fig. 1

Timeline showing the time between the introduction of an antibacterial and the development of clinically significant resistance. Reprinted with permission from .

Fig. 2

(A) Intrinsic mechanisms of resistance. The figure shows an overview of intrinsic resistance mechanisms. The example shown is of β-lactam antibiotics targeting a penicillin-binding protein (PBP). Antibiotic A can enter the cell via a membrane-spanning porin protein, reach its target and inhibit peptidoglycan synthesis. Antibiotic B can also enter the cell via a porin, but unlike Antibiotic A, it is efficiently removed by efflux. Antibiotic C cannot cross the outer membrane and so is unable to access the target PBP. Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Microbiology, copyright (2015). (B) The four resistance acquisition pathways, the four main mechanisms of resistance, and the five main targets for antibiotics. Reprinted with permission from .

Fig. 3

Major factors that contribute to the emergence, spread, and persistence of antibiotic resistance in orthopaedic implant-associated infections.