Antibiotics Review _ __________________________________________________________________________
Retapamulin is used for the topical treatment of impetigo. A small amount is applied to the affected area twice per day for five days [6]. Possible side effects include eczema, application site reactions, diarrhea, headache, and nasopharyngitis. Lefamulin is approved for the treatment of community- acquired bacterial pneumonia [6; 167]. The usual dose is 600 mg every 12 hours for oral administration or 150 mg every 12 hours for IV use [6]. Treatment is generally at least five days; patients should be afebrile for ≥48 hours and clinically stable prior to discontinuation. The most common adverse reactions include diarrhea, nausea, injection site reactions, elevated liver enzymes, and vomiting [167]. It is contraindicated in patients with certain arrhythmias or who are prescribed drugs to pro- long QT intervals. INVESTIGATIONAL ANTIBIOTICS FOR DRUG-RESISTANT MICRO-ORGANISMS Researchers continue to explore new methods and the search for drugs to aid in the prevention of antibiotic resistance. Progress has been made in recent years, with two new anti- biotics void of cross-resistance with existing antibiotics being discovered through soil sample screening: teixobactin and pseudouridimycin. Teixobactin, a cyclic depsipeptide antibiotic, works by binding to a highly conserved motif of lipid II (precursor of peptidogly- can) and lipid III (precursor of cell wall teichoic acid), inhibit- ing bacterial cell wall biosynthesis [168; 169]. Teixobactin has been shown effective at treating an array of gram-positive patho- gens, including MRSA, vancomycin-resistant Enterococcus , and Mycobacterium tuberculosis , with no known cross-resistance to other antibiotics [168; 169]. With reports in 2016 of efficient syntheses of two teixobactin analogues, this class of drugs may be part of the solution to bacteria resistant to currently available antibiotics [168; 169]. Pseudouridimycin, a nucleoside-analog inhibitor, acts by inhibiting bacterial RNA polymerase, an enzyme responsible for bacterial RNA synthesis, through a binding site. The structure is similar to rifampin, an antitubercular agent that inhibits the enzyme; however, the mechanism of action does differ so as not to cause a cross-reaction with rifampin [170; 171]. Pseudouridimycin has been shown effective for a broad spectrum of drug-sensitive and drug-resistant bacteria.
Researchers are currently attempting to conduct synthesis of these two new classes of drugs with varying, but promising, suc- cess. Although it may take several years for these or other new antibiotics with no cross-resistance to be developed, promising progress is continuing, and researchers estimate that, once approved, resistance to these novel drugs could take decades, rather than years, to develop [168; 169; 170; 171]. CONCLUSION Antibiotics are commonly used drugs that have diverse actions, side effects, and toxicities. The large number of antibiotics available makes it challenging to understand the important characteristics of each antimicrobial class, including clini- cal indications, spectrum of activity, dosage, and toxicities. Knowing the general characteristics by antibiotic class and having experience with one or two key agents within each class improves recall and facilitates the selection of the most appropriate antibiotic for a given bacterial infection. An understanding of the mode of action, spectrum of activ- ity, and potential toxicity enables the practitioner to tailor a therapeutic regimen specific to the infectious etiology and of appropriate duration. This in turn lessens the likelihood devel- oping microbial resistances and reduces risk of adverse effects. It is important to remember that the indications given by the FDA are guidelines. Many antibiotics are used for off-label pur- poses, and occasionally in doses that differ from those recom- mended for the usual indications. This may be necessary when faced with managing severe and life-threatening infections or for special populations, such as premature infants, neonates, and the elderly. Before using a specific agent, one should always consider carefully reviewing the detailed information (package insert) provided by the manufacturer.
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