Selected Antimicrobials

The half-life of vancomycin following intraocular injection is long, and ranges from 25.5 to 56 hours (14,15). Removal of the lens dramatically decreases the half-life to 9.8 hours (14). In inflamed eyes the half-life is slightly longer in the phakic eye and is slightly shorter in a model of infection (14,15). 

In two studies, samples were obtained from the vitreous cavity after intraocular injection. Ferencz (43) identified a range of 25-182 pg 44-72 hours after injection. Gan (44) identified average levels of 10.3 pg/mL three days after injection. Rough estimates indicate this is consistent with the half-life of 24 hours as suggested by data in the rabbit (44). 

Betalactam antibiotics resemble penicillin with the exception of replacement of a five-member thiazolidine ring. Various modifications of these antimicrobials have been made to alter their penetration, pharmacokinetics, and range of efficacy. 

The mechanisms of action of betalactams are complex. Betalactams are bactericidal and are known to inactivate specific targets on the inner aspects of bacterial cell membranes, thus making them inactive. Betalactams are time-dependent antimicrobials that have been successively developed into four generations. The first-generation 

Clearance of first-generation cephalosporins after intravitreal injection suggests a posterior clearance route (23). Newer agents may be removed by the anterior route or by the combined posterior and anterior route (30). In phakic eyes, the half-life of cefazolin in the monkey and the rabbit is 6.5 7 hours (22,45). The half-life is decreased by inflammation, presumably by interference with active transport across posterior structures. In studies of third-generation agents (ceftizoxime and ceftriaxone), there was increased drug half-lives in infected rabbit eyes as compared to controls (30). Ceftazadime has a half-life of 13.8 20 hours in the rabbit, but the half-life is dramatically lowered by removal of the lens and vitreous (46). 

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Studies to elucidate the mode of bacteriostatic property of xanthostatin (XS), a novel depsipeptide antibiotic with an A/-acetylglydne side chain and selective antimicrobial activity against Xanthomonas spp., were carried ont by Kim and coworkers [80]. Two biotransformed XSs were isolated by the treatment of XS with the cell... 

Evaluate and apply at least six major drug-specific considerations when selecting antimicrobial therapy. 

Guidelines suggest that if an operation exceeds two half-lives of the selected antimicrobial, then another dose should be administered.1 Repeat dosing has been shown to lower rates of SSI. For example, cefazolin has a half-life of about 2 hours, thus... 

When selecting antimicrobial regimens, local susceptibility data should be considered whenever possible rather than information published by other institutions or national compilations. 

Tegos GP, Demidova TN, Arcila-Lopez D, Lee H, Wharton T, Gali H, Flamblin MR (2005) Cationic fullerenes are effective and selective antimicrobial photosensitizers. Chem. Biol. 12 1127-1135. 

Table 51-6 Cerebrospinal Fluid (CSF) Penetration of Selected Antimicrobials.

Gerhard Domagk, German pathologist and Nobel prize winner, observed the antibacterial property of a prototypical sulfonamide (Prontosil) that is considered to be the first selective antimicrobial agent... 

Folate analogs such as trimethoprim have potent antibacterial and antiprotozoal activity. Trimethoprim binds lO -fold less tightly to mammalian dihydrofolate reductase than it does to reductases of susceptible microorganisms. Small differences in the active-site clefts of these enzymes account for its highly selective antimicrobial action. The combination of trimethoprim and sulfamethoxazole (an inhibitor of folate synthesis) is widely used to treat infections. 

Akers MJ. Considerations in selecting antimicrobial preservative agents for parenteral product development. Pharm Technol 1984 8(5) 36-40, 43, 44, 46. 

Nanavaty J, Mortensen J E, Shryock T R 1998 The effects of environmental conditions on the in vitro activity of selected antimicrobial agents against Escherichia coli. Current Microbiology 36 212-215... 

Efflux-related multidrug resistance (MDR) is a significant means by which bacteria can evade the effects of selected antimicrobial agents. Two geometric stereoisomers of flupentixol, with intrinsic antimicrobial... 

Knowledge of the mechanisms of action of antimicrobial agents is required for understanding resistance acquired through chromosomal mutation and selection, and forms the basis of selecting antimicrobials for concurrent use, either as combination preparations or separately. 

Infectious diseases pharmacists typically practice in a hospital setting that allows them to devote all their time to managing antimicrobial therapy. All aspects of infectious diseases pharmacotherapy, including interventions on antimicrobial selection, antimicrobial dosing, and intravenous-to-oral conversion are the responsibility of the infectious diseases pharmacist. In addition, the pharmacist is usually responsible for analyzing new antimicrobials for formulary inclusion, medication use evaluations, and antimicrobial restriction or therapeutic interchange policies. 

TABLE 103—2. Suggested Therapeutic Serum Concentrations for Selected Antimicrobial Agents... 

The syntheses of benzophenanthridine bases were also studied (132, 771-776). Much interest was shown in the synthesis of the alkaloids of this group, particularly after their antitumor activity in mouse leukemia L-1210 (LE) and P-388 (PS) as well as some selected antimicrobial activities had been established (776). On photocyclization, protopine, tetrahydroprotober-berine, and 13-methyltetrahydroprotoberberine yielded sanguinarine via anhydroprotopine (114) (680, 681, 777, 778) (Schemes 33 and 40). 

Substituted 2-acylamino-IbPs (e.g., 677) are claimed to be a new class of antiinflammatory agents (77USP4059584). Selective antimicrobial, antiseptic and disinfectant action was found in 2-guanidyl-IbP and IcP 678 connected by polymethylene chains (83USP4395552). 

Table 3.2 Antibacterial activity and selectivity (antimicrobial template shown directly below) ...

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