Antibiotics Review _ __________________________________________________________________________
the drug loses its antimicrobial effect. Another example is the methylation of ribosomal ribonucleic acid (rRNA) that prevents the binding of macrolides. The effectiveness of trim- ethoprim/sulfamethoxazole, which acts through disruption of folate synthesis by the cell, may become diminished by the adaptive ability of some bacteria to utilize an alternate meta- bolic pathway, thereby avoiding the effects of trimethoprim [4]. These resistance mechanisms may be acquired through mutations in the genes that encode for the target or affected transport proteins. As the bacterial cells without the adap- tive mutations succumb to the action of the antibiotic, the subpopulation that has the adaptive mutation continues to replicate, replacing the original population with a resistant one. Bacterial resistance can be transferred from one bacterium to another, or from one bacterial species to related group, by means of plasmids or transposons that gain entry to the cell. These agents are small segments of DNA that are readily exchanged between bacteria. A plasmid that contains a gene for an adaptive mutation can be shared with many nearby bacteria, which may or may not be the same species. In this manner, resistance can quickly spread from species to species [5]. Many strategies have been used to circumvent the multiple mechanisms of resistance encountered in bacteria. Among these are addition of beta-lactamase inhibitors to extended- spectrum penicillins, alteration of cephalosporin side chains to produce new generations of the drug with broader activity, and combining drugs to enhance the antimicrobial effect (e.g., sulfamethoxazole with trimethoprim). In 2021, in response to perceived overuse of antibiotics, the American College of Physicians recommended limiting antibiotic courses to five to seven days for the some of the most common bacterial infec- tions, including durations of antibiotic therapy in patients with common bacterial infections, such as acute bronchitis, community-acquired pneumonia, urinary tract infection, and cellulitis [172].
In addition, new categories of antibiotics are being created to stay ahead of the rapid evolution of bacterial resistance. Linezolid and tedizolid, the only two FDA-approved drugs in the oxazolidinone category, are examples of this, with linezolid being the first of the two to be developed. Oxazolidinones are a unique category of drugs that prevent formation of the 70S protein synthesis complex in bacteria and may be useful in the treatment of vancomycin-resistant enterococci and MRSA [6; 7]. Nonetheless, development of resistance in bacteria is relentless. Considering the efficient means by which bacteria develop resistance, clinicians should avoid, where possible, practice pat- terns that contribute to the process. In 2002, the CDC issued a position paper outlining recommendations for minimizing nosocomial infection and the emergence of resistant organisms [8]. In this paper, the CDC recommended a multistep approach that included: preventing infection (by paying careful attention to the proper use of invasive medical devices); tailoring medi- cal treatment to fit the infection (by avoiding broad-spectrum antibiotics and prolonged treatment when possible); and pre- venting the transmission of resistant bacteria between patients (by emphasizing hand washing and implementing hospital infection control programs) [8]. Since issuance of the CDC’s position paper, the agency has taken many additional steps and implemented coordinated, strategic action plans to change the course of antibiotic resistance. This includes publication of The National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB), 2020–2025 [9]. The CARB builds on the first National Action Plan, released in 2015, and prioritizes infection prevention and control to slow the spread of resistant infections and reduce the need for antibiotic use. The CARB also integrates a “one health” approach, which recognizes the relationships between the health of humans, animals, plants, and the environment [9]. It has also been hypothesized that the response to severe acute respiratory syndrome coronavi- rus 2 (SARS-CoV-2) and associated COVID-19 illness might increase use of antibiotics and other antimicrobial medicines (both appropriate and inappropriate) to address primary or secondary infections, with the potential to further accelerate the emergence of antibiotic resistance despite the rate of the development of new antibiotics [9]. In 2022, the CARB Task Force issued a Year 5 Progress Report on combating antimicrobial-resistant bacteria, summarizing accomplishments achieved between 2015 and 2020. This report showed that substantial progress had been achieved for the following targeted bacteria: health care-associated C. difficile infection decreased by 36%; hospital-onset multidrug-resistant Pseudomonas aeruginosa decreased by 41%; and hospital-onset MRSA bloodstream infections decreased approximately 31.5% [173].
A meta-analysis published by the Cochrane Database of Systematic Reviews found high- certainty evidence that any professional or structural interventions are effective in increasing compliance with antibiotic policy and reducing duration of antibiotic
treatment in the hospital setting. (https://www.cochrane.org/CD003543/EPOC_ improving-how-physicians-working-hospital-settings- prescribe-antibiotics. Last accessed January 11, 2024.) Level of Evidence : Meta-analysis
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