Spectrum of Activity

She of Action Antibiotic Process Interrupted Type of Activity 

Cell membnoe AnqAiotflricin B Membrane funcUon Fungicidal 

SOS subunit Aminoglycoskles Protein isyiithesis and fidelity Bactericidal 

Nucleic acids Actinomycm DNA and mRNA synlliesis Panctdal 

Antibacterial agents may be classified according to the class of target microorganism. Accordingly, antibacterial agents that inhibit only bacteria are described as narrower medium-spectrum, whereas those that also inhibit mycoplasma, rickettsia, and chlamydia (so-called atypical bacteria) are described as broad-spectrum. The spectrum of activity of common antibacterial drugs is shown in Table 1.1. 

TABLE 1.1 Spectrum of Activity of Common Antibacterial Drugs 

Notation Presence or absence of activity against certain protozoa is indicated by plus or minus sign (+/—). 

Source Reference 2. Reprinted with permission of John Wiley Sons, Inc. Copyright 2006, Blackwell Pubhshing. 

Water fleas, acute (48 h), EC50, Daphnia magna 1.8 mg L  

growth inhibition (72 h), ErCso, Sdenastrum capricomutum 4.3 mg L  

Fluopicolide has been tested successfully on the crops and pathogens shown in Table 19.4. 

Fluopicolide is being developed worldwide, in combination with other fungicides, for use in a wide variety of crops. The first commercial launches of fluopicolide are in co-formulation with fosetyl-Al for use in vines, to be marketed as Profiler , and with propamocarb-HCl for use in potatoes and vegetables, under the trade name Infinito . 

---

The industry is increasingly acknowledging the value of oontractors and service companies in improving their individual core capabilities through alliances, i.e. a joint venture for a particular project or a number of projects. A lead contractor e.g. a drilling company may form alliances with a number of sub contractors to be able to cover a wider spectrum of activities e.g. completions, workovers and well interventions. 

The pseudo-barbiturate , 2-methyl-3-o-tolylquinazolin-4(3H)-one (methaqualone, Revonal 1017) has an even wider spectrum of activities than do the barbiturates proper it appears to be quite widely used as- a sedative, hypnotic, anticonvulsant, antispasmodic and local anaesthetic agent (63MI21301, b-75MI21301>. 

One of the most popular orally active penicillins in present clinical use is amoxicillin (12). Its oral effectiveness and broad spectrum of activity against common pathogens as well as its better absorption than its closest precedent competitor, ampicillin (14), largely accounts for this. Higher blood and tissue levels of antibiotics is another means of dealing with resistance. In an attempt to achieve yet further improvements in oral bioavailability and hence blood and ti.ssue levels of amoxicillin, the prodmg fumoxicillin (13) is prepared from amoxicillin (12) by treatment with furfural [3]. The imine moiety is less basic than the primary amine so that the isoelectric point of fumoxicillin is more on the acid side than is that of amoxicillin. 

Class C Serine p-lactamases AmpC enzymes of coti, Shigella spp., Enterobacterspp., C. freundii, M. morganii, Providencia spp. and Serratia spp. cephalos-porinases with wide spectrum of activity CMY, LAT, BIL, MOX, ACC, FOX and DHA types. All genes are ampC genes that have been mobilized by transfer to plasmid DNA. 

The natural penicillins also have a fairly narrow spectrum of activity, which means that they are effective against only a few strains of bacteria Newer penicillins have been developed to combat this problem. These penicillins are a result of chemical treatment of a biologic precursor to penicillin. Because of their chemical modifications, they are more slowly excreted... 

The above-described structures are the main representatives of the family of nitrogen ligands, which cover a wide spectrum of activity and efficiency for catalytic C - C bond formations. To a lesser extent, amines or imines, associated with copper salts, and metalloporphyrins led to good catalysts for cyclo-propanation. Interestingly, sulfinylimine ligands, with the chirality provided solely by the sulfoxide moieties, have been also used as copper-chelates for the asymmetric Diels-Alder reaction. Amide derivatives (or pyridylamides) also proved their efficiency for the Tsuji-Trost reaction. 

In cephalosporins suseeptible to / -lactamases, opening of the y8-lactam ring occurs with concomitant loss of the substituent at (except in cephalexin, where represents H see Fig. 5.4). This is followed by fragmentation of the molecule. Provided that they are not inaetivated by "-laetamases, the cephalosporins generally have a broad spectrum of activity, although there may be a wide variation. Haemophilus influenzae, for example, is partieularly suseeptible to eefuroxime see also Table 5.2. 

Teicoplanin is a naturally occurring complex of five closely related tetracyclic molecules. Its mode of action and spectrum of activity are essentially similar to vancomycin, although it might be less active a inst some strains of coagulase-negative staphylococci. Teicoplanin can be administered by intramuscular injection. 

Over 10000 quinolone antibacterial agents have now been synthesized. Nalidixic acid is regarded as the progenitor of the new quinolones. It has been used for several years as a clinically important drug in the treatment of urinary tract infections. Since its clinical introduction, other 4-quinolone antibacterials have been synthesized, some of which show considerably greater antibacterial potency. Furthermore, this means that many types of bacteria not susceptible to nahdixic acid therapy m be sensihve to the newer derivahves. The most important development was the introduction of a fluorine substituent at C-6, which led to a considerable increase in potency and spectrum of activity compared with nalidixic add. These second-generation quinolones are known as fluoroquinolones, examples of which are ciprofloxacin and norfloxacin (Fig. 5.19). 

Table 9.1 Spectrum of activity of some antibacterial antibiotics ... 

AGAC-modifying enzymes are active outside the cytoplasmic membrane, in the periplasmic space in Gram-negative bacteria and extracellularly in Gram-positives. Table 9.4 summarizes some of the enzymes involved in AGAC resistance and their spectrum of activity. 

Chloroform (CHCI3) has a narrow spectrum of activity. It has been used extensively as a preservative in pharmaceuticals since the last century though recently has had limitations placed on its use. Marked reductions in concentration may occur through volatilization from products resulting in the possibility of microbial growth. 

As already mentioned before a complete family of pectin lyases is present in A. niger. With all the genes sequenced and individually expressed, sometimes via promoter gene fusions (see below), the way is open to characterize the full spectrum of activities as outlined in the intro-... 

It is often difficult to narrow the spectrum of activity of the antibiotic choice since the infections are usually polymicrobial. As such, patients may receive long courses of broad-spectrum antibiotics such as imipenem/cilastatin and... 

The antibiotic of choice for group B streptococcal disease is penicillin G, although ampicillin is an alternative.43 No resistance to either agent has been reported, and their narrow spectrum of activity makes them ideal choices.43 Resistance has developed with the use of alternative choices for penicillin-allergic patients. A treatment algorithm for group B Streptococcus is shown in Fig. 44—3, and dosing recommendations are shown in Table 44-5. 

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. 

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. 

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. 

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... 

Spectrum of activity and effects on nontargeted flora Dosing... 

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... 

---