___________________________________________________________________________ Antibiotics Review
INTRODUCTION The number of antibiotic agents available is remarkable, and new agents are added regularly. This course is intended as an overview of the general characteristics of the major antibiotic classes, emphasizing mechanism of action, pharmacokinetics, and potential toxicities, with a brief discussion of the individ- ual member agents and their clinical indications. The purpose of this course is to enlarge clinical perspective and enhance the understanding and confidence required for the selection of appropriate therapy of bacterial infections. The goal is to improve efficacy and safety while limiting the risk for selection and transmission of antimicrobial-resistant pathogens. Given the large array of available antimicrobial agents, the scope of this course is confined to the eight major classes of antibiotics commonly employed for acute bacterial infection: the penicillins, cephalosporins, carbapenems, aminoglycosides, quinolones, macrolides, sulfonamides, and tetracyclines. A brief discussion of vancomycin, daptomycin, and newer gly- copeptide analogues available for treatment of multi-resistant Staphylococcus aureus (MRSA) and enterococcal species is included. For the purposes of the course, it is impractical to list or describe all the possible adverse effects, recommended uses, and off-label uses of the antibiotics discussed. Before using any antimicrobial, it is important to review the manufacturer’s package insert and dosing recommendations for the drug.
According to the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America, the infusion of bezlotoxumab should be performed while a patient is receiving standard-of-care antibiotics and has
been shown to be effective in preventing recurrent C. difficile infection if administered at any time before ending antibacterial treatment (https://academic.oup.com/cid/article/73/5/ e1029/6298219. Last accessed January 11, 2024.) Strength of Recommendation : Expert Opinion/ Consensus Statement
ANTIBIOTIC RESISTANCE Repeated exposure to an antibiotic may lead to the emergence of selective subpopulations of the same or related bacteria now resistant to the therapeutic agent. The Centers for Disease Control and Prevention (CDC) note that approximately 2.8 million people become infected with bacteria that are resistant to antibiotics, and approximately 35,000 people die annually because of these infections [2]. When C. difficile colitis, not typically resistant but associated with antimicrobial use, is added to these, the U.S. toll of all threats exceeds 3 million infections and 48,000 deaths [2]. Mechanisms of microbial resistance include altered cellular permeability (leading to greatly diminished intracellular concentration of the drug), increased efflux of the antibiotic from the cell, and elaboration of deactivating enzymes that alter the antibiotic’s interaction at binding sites within the cell wall or cytoplasm [3]. Decreased cell membrane permeability is an important mecha- nism of bacterial resistance to beta-lactams, quinolones, and vancomycin. Microbial resistance to tetracyclines and quino- lones is often mediated by increased efflux of the antibiotic from the cell. Enzymatic deactivation by beta-lactamases is the common mechanism of resistance to penicillins and cephalo- sporins. Resistance to aminoglycosides may result from altered cytoplasmic membrane transport (influx) or from intracellular enzymes (e.g., phosphotransferases and acetyltransferases) that deactivate the drug. There are various mechanisms by which the interaction of an antibiotic with its binding site may be altered or bypassed, resulting in loss of antimicrobial activity. One such example, affecting the target site for quinolone activity, is an acquired structural alteration of deoxyribonucleic acid (DNA) gyrase, an enzyme essential for bacterial DNA synthesis. As a result, quinolones are no longer able to bind to the enzyme and
GENERAL CHARACTERISTICS OF ANTIBIOTICS
There are some characteristics that all antibiotics share. All antibiotics can elicit allergic responses, although some are more allergenic than others. Allergic reactions can range from mild, annoying rashes to life-threatening reactions such as anaphylaxis and the Stevens-Johnson syndrome. In some cases, there is a cross-sensitivity between agents in different classes. In addition, all antibiotics exert some impact on normal body flora as well as pathogens, in some cases leading to the emergence of Candida species and pathogenic bacteria such as Clostridioides difficile . Overgrowth of C. difficile within intestinal flora is often a serious complication of antimicrobial therapy that can produce symptoms ranging from mild diar- rhea to severe, life-threatening pseudomembranous colitis [1]. Most cases resolve with supportive care and discontinuation of the offending antibiotic, but many require treatment. Fur- thermore, C. difficile colitis can develop days or weeks after the primary antimicrobial has been discontinued. A high degree of suspicion and judicious use of laboratory testing are the keys to recognizing and managing these complications.
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