Antimicrobial spectrum of activity

Empirical therapy should be based on patient- and antimicrobial-specific factors such as the anatomic location of the infection, the likely pathogens associated with the presentation, the potential for adverse effects, and the antimicrobial spectrum of activity. 

Most initial antimicrobial therapy is empirical because cultures usually have not had sufficient time to identify a pathogen. Empirical therapy should be based on patient- and antimicrobial-specific factors such as the anatomic location of the infection, the likely pathogens associated with the presentation, the potential for adverse effects in a given patient, and the antimicrobial spectrum of activity. Prompt initiation of appropriate therapy is paramount in hospitalized patients who are critically ill. Patients who receive initial antimicrobial therapy that provides coverage against the causative pathogen survive at twice the rate of patients who do not receive adequate therapy initially.8... 

Empirical selection of antimicrobial spectrum of activity should be related to the severity of the illness. Generally, acutely ill patients may require broader-spectrum antimicrobial coverage, whereas less ill patients may be managed initially with narrow-spectrum therapy. While a detailed description of antimicrobial pathogen- specific spectrum of activity is beyond the scope of this chapter, this information can be obtained readily from a number of sources.9,10... 

Antimicrobial Spectrum of Activity Minimum Inhibitory Concentration Study... 

Challenge Microorganisms. The antimicrobial spectrum of activity of the test products must be broad, versus 25 ATCC strains of 20 species of bacteria and 2 species of yeasts listed in 333.470(a)(l)(ii) of the TFM, plus 25 fresh clinical isolates of these same species of bacteria and yeasts. The challenge microorganisms include members of normal flora in humans, common environmental contaminants, or systemic pathogens. 

The generally accepted structure-activity relationships developed in the early work in the quinolone series held that the N-1 substituent needed to be small and aliphatic. This picture was upset in a dramatic way with the discovery of the excellent potency and antimicrobial spectrum of difloxacin (45) and its congeners in which the substituent on N-1 is an aromatic ring. The synthe-... 

Select empirical antimicrobial therapy based on spectrum-of-activity considerations that provide a measured response proportional to the severity of illness. Provide a rationale for why a measured response in antimicrobial selection is appropriate. 

Drug-specific considerations in antimicrobial selection include the spectrum of activity, effects on nontargeted microbial flora, appropriate dose, pharmacokinetic and pharmacodynamic properties, adverse-effect and drug-interaction profile, and cost. 

Spectrum of activity A qualitative term that describes the number of different bacterial species that are susceptible to an antimicrobial regimen. Generally, broad-spectrum activity refers to regimens that possess activity against many bacterial species, whereas narrow-spectrum therapy refers to activity against a few bacterial species. 

Among pharmaceuticals, antibiotics have become of special concern in recent years. The reason is that these substances are continuously being introduced into the environment and may spread and maintain bacterial resistance in the different compartments. Sulfonamides are very commonly used antimicrobials in humans but mainly in veterinary medicine, due to their broad spectrum of activity and low cost, being the second most widely used veterinary antibiotic in the EU. Their occurrence has been reported in all kinds of water matrices their high excretion rates (after their intake by humans of livestock) and high water solubility make them very ubiquitous and persistent pollutants in the environment. 

Increasing the coverage of antimicrobial therapy is generally necessary in mixed infections where multiple organisms are likely to be present, such as intraabdominal and female pelvic infections in which a variety of aerobic and anaerobic bacteria may produce disease. Another clinical situation in which increased spectrum of activity is desirable is with nosocomial infection. 

The aminoacyl side chain of this drug, which is analogous to that of ceftazidime, is responsible for the high activity with respect to Gram-negative aerobic bacteria. The spectrum of use of aztreonam is very similar to the antimicrobial spectrum of aminoglycosides, and in the majority of cases it is a potential replacement. 

The penicillins are a large group of bactericidal compounds. They can be subdivided and classified by their chemical structure and spectrum of activity. The structure common to all penicillins is a (3-lactam ring fused with a thiazolidine nucleus (Fig. 45.1).The antimicrobial activity of penicillin resides in the (3-lactam ring. Splitting of the (3-lactam ring by either acid hydrolysis or (3-lactamases results in the formation of penicilloic acid, a product without antibiotic activity. Addition of various side chains (R) to the basic penicillin molecule... 

Topical antibiotics may be considered to be advantageous over their systemic counterparts because they deliver a higher concentration of medication directly to the desired area and are less frequently implicated in causing bacterial resistance. An ideal topical antimicrobial has a broad spectrum of activity, persistent antibacterial effects, and minimal toxicity or incidence of allergy. 

Many antimicrobial products that were formerly used with textiles are now strictly regulated because of their toxicity and potential for environmental damage. Products such as copper naphthenate, copper-8-quinolinate, and numerous organo mercury compounds fall into this category. Other materials that still have limited use in specialised areas include tributyl tin oxide (deleted in many countries. Fig. 15.1a), dichlorophene (Fig. 15.1b) and 3-iodopropynylbutyl carbamate (Fig. 15.1c). These products typically show a very broad spectrum of activity against bacteria and fungi, but suffer from application and durability problems. 

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