Resistant strain

Development of Resistance. One of the principal disadvantages of sulfonamide therapy is the emergence of dmg-resistant strains of bacteria. Resistance develops by several mechanisms overproduction of PABA (38) altered permeabiUty of the organisms to sulfonamides (39) and reduced affinity of dihydropteroate synthetase for sulfonamides while the affinity for PABA is retained (40). Sulfonamides also show cross-resistance to other sulfonamides but not to other antibacterials. In plasmodia, resistance may occur by means of a bypass mechanism in which the organisms can use preformed foHc acid (41). 

Florfenicol iahibited 91% of the 399 bacterial isolates at a concentration of 12.5 )J.g/mL (31). At the same concentration, chloramphenicol and thiamphenicol iahibited only 70% and 24% of the isolates, respectively. Other work has also confirmed the superior activity of fiorfenicol against chloramphenicol-resistant strains (32—35). More recendy it has been shown that fiorfenicol is active against E. coli strains that produce type I, II, or III CAT enzymes (36). 

The efficacy of florfenicol in vivo was determined by measuring the dose required to obtain values for protection from infection in 50% of the animals (PD q) against 10 chloramphenicol-resistant strains and two chloramphenicol-sensitive isolates. Florfenicol, chloramphenicol, and thiamphenicol were evaluated concurrendy against each strain. Against sensitive Enterobacter 50 subcutaneous and oral routes were similar for dorfenicol and... 

The production of elfamycins is described in the references cited in Table 1. Fermentation yield improvements with aurodox (1, R = CH ) proved difficult because of feedback inhibition (48). Aurodox-resistant strains (49), however, responded positively to conventional mutagenic methods leading to yield increases from 0.4 to 2.5 g/L (50). Scale-up of efrotomycin (7, R = CH ) fermentations were found to be particularly sensitive to small changes in sterilization conditions of the oil-containing medium used (51). 

Preventive medicine through vaccination continues to be the most cost-effective pubHc health practice, even with the drastic advance in modern medicine. Mass vaccination programs have eradicated smallpox from the earth. The World Health Organization (WHO) has a major campaign underway to eradicate poHo by the year 2000. The development of vaccines has saved millions of Hves and prevented many more from suffering. However, there are stiU many diseases without effective vaccines, such as malaria. With the recent emergence of antibiotic-resistance strains and exotic vimses, an effective vaccine development program becomes a top priority of pubHc health poHcy. 

C QHyN O SNa, as a potentially useful P-lactamase inhibitor capable of potentiating the activity of a number of clinically important P-lactam antibiotics against resistant strains (153). 

Clavulanic acid has only weak antibacterial activity, but is a potent irreversible inhibitor for many clinically important P-lactamases (10—14,57,58) including penases, and Richmond-Sykes types 11, 111, IV, V, VI ([Bacteroides). Type I Cephases are poorly inhibited. Clavulanic acid synergizes the activity of many penicillins and cephalosporins against resistant strains. The chemistry (59—63), microbiology (64,65), stmcture activity relationships (10,13,60—62,66), biosynthesis (67—69), and mechanism of action (6,26,27,67) have been reviewed. 

Resistance to Tetracyclines. The tetracyclines stiU provide inexpensive and effective treatment for several microbial infections, but the emergence of acquired resistance to this class of antibiotic has limited their clinical usehilness. Studies to define the molecular basis of resistance are underway so that derivatives having improved antibacterial spectra and less susceptibiUty to bacterial resistance may be developed. Tetracyclines are antibiotics of choice for relatively few human infections encountered in daily clinical practice (104), largely as a result of the emergence of acquired tetracycline-resistance among clinically important bacteria (88,105,106). Acquired resistance occurs when resistant strains emerge from previously sensitive bacterial populations by acquisition of resistance genes which usually reside in plasmids and/or transposons (88,106,107). Furthermore, resistance deterrninants contained in transposons spread to, and become estabUshed in, diverse bacterial species (106). 

Flucytosine-resistant strains can develop very rapidly. These mutants may have a disturbed 5-FC-metabohsm, or a compensatory mechanism for the disturbed nucleic acid functions. No cytosine permease was found in a resistant Cyptococcus neoformans strain, whereas cytosine deaminase was absent in resistant C. albicans strains. A deficiency of uridine monophosphate pyrophosphorylase occurs frequently in resistant C. albicans strains (1). 

Malaria affects an estimated 270 million people and causes 2—3 million deaths annually, approximately one million of which occur in children under the age of five. While primarily an affliction of the tropics and subtropics, it has occurred as far north as the Arctic Circle. The disease essentially has been eradicated in most temperate-zone countries, but some 1100 cases of malaria in U.S. citizens returning from abroad were reported to the Centers for Disease Control during 1990. Malaria is seen today in Southeast Asia, Africa, and Central and South America. It is on the increase in Afghanistan, Brazil, China, India, Mexico, the Philippines, Sri Lanka, Thailand, and Vietnam. Escalation of the disease is because of the discontinued use of the insecticide DDT which effectively kills mosquito larvae, but has been found to be toxic to Hvestock and wildlife. Also, chloroquine (6), a reUable dmg for the prophylaxis and treatment of falcipamm malaria, is ineffective in many parts of the world because of the spread of dmg-resistant strains. 

Plasmodium vivax, responsible for the most prevalent form of malaria (benign tertian), has an incubation period of 8—27 days (14 average). A variety seen in northern and northeastern Europe has an incubation period as long as 8—10 months. The disease can cause splenic mpture and anemia. Relapses (renewed manifestations of erythrocytic infection) can occur with this type of malaria. Overall, P. vivax is stiU susceptible to chloroquine however, resistant strains have been reported from Papua New Guinea and parts of Indonesia. Plasmodium malariae the cause of quartan malaria, has an incubation period of 15—30 days and its asexual cycle is 72 hours. This mildest form of malaria can cause nephritis in addition to the usual symptoms. It is a nonrelapsing type of malaria but the ted blood ceU infection can last for many years. No resistance to chloroquine by this plasmodium has been reported. Plasmodium ovale responsible for ovale tertian malaria, has an incubation period of 9—17 days (15 average). Relapses can occur in people infected with this plasmodium. No chloroquine resistance has been reported for this parasite. 

Quinacrine (49) is an acridine that was used extensively from the mid-1920s to the end of World War 11. It acts much like chloroquine and is reasonably effective. Because it causes the skin to turn yellow and, in high doses, causes yellow vision, the dmg is no longer in use as an antimalarial. Pyronaridine (77), a 1-azaacridine developed in China, appears to be effective against mefloquine-resistant, but not entirely against chloroquine-resistant, strains of P falciparum. 

In its simplest form, the Wheatstone bridge is used on D.C. for the measurement of an unknown resistance in terms of three known resistors. Its accuracy depends on that of the known units and the sensitivity of the detector. It is also used for sensing the changes which occur in the output from resistance strain-gauge detectors. The latter instruments can be made portable and can detect variations of less than 0.05 per cent. 

Bactericides are substances that destroy bacteria, and they can be used in various ways. They may be incorporated into the soluble-oil concentrate, either at concentrations suitable to protect the oil in storage, or at levels sufficient to provide a persistent bactericidal effect on the emulsion in service. The cost of providing sufficient bactericide to cover the use of the soluble oil at a high dilution might prove prohibitive. Continued use of the same bactericide may produce resistant strains of bacteria. 

Closely related to the penicillins are the cephalosporins, a group of /3-lactam antibiotics that contain an unsaturated six-membered, sulfur-containing ring. Cephalexin, marketed under the trade name Keflex, is an example. Cephalosporins generally have much greater antibacterial activity than penicillins, particularly against resistant strains of bacteria. 

There are different techniques to evaluate the quantitative stress level in prototype and production products. They can predict potential problems. Included is the use of electrical resistance strain gauges bonded on the surface of the product. This popular method identifies external and internal stresses. Their various configurations are made to identify stresses in different directions. This technique has been extensively used for over a half century on very small to very large products such as toys to airplanes. There is the optical strain measurement system that is based on the principles of optical interference. It uses Moire, laser, or holographic interferometry (2,3,20). 

Because the natural penicillins have been used for many years, drug-resistant strains of microorganisms have developed, making the natural penicillins less effective than some of the newer antibiotics in treating a broad range of infections. Bacterial resistance has occurred within tire penicillins. Bacterial resistance is the ability of bacteria to produce substances that inactivate or destroy the penicillin. One example of bacterial resistance is tiie ability of certain bacteria to produce penicillinase, an enzyme that inactivates penicillin. The penicillinase-resistant penicillins were developed to combat this problem. 

Promoting Optimal Response to Therapy The results of a culture and sensitivity test take several days because time must be allowed for the bacteria to grow on the culture media However, infections are treated as soon as possible In a few instances, the primary health care provider may determine that a penicillin is the treatment of choice until the results of the culture and sensitivity tests are known. In many instances, the primary health care provider selects a broad-spectrum antibiotic (ie, an antibiotic that is effective against many types or strains of bacteria) for initial treatment because of the many penicillin-resistant strains of microorganisms. 

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