Drug-resistant bacterial infections

Thus, mersacidin represents a promising antibiotic candidate with the potential of treating multi-drug resistant bacterial infections. 

The recent increase in resistant bacterial infections has created a critical need to develop novel antibacterial drugs that elude existing mechanisms of resistance. For this reason, many researchers worldwide have been interested in the search and evaluation of novel lead antibacterial compounds. Because the experimental tests (based on trial and error screening especially pharmacological and toxicological tests) are usually expensive and time consuming, the... 

The true chemotherapeutic significance of this phenomenon is not defined at the moment but it requires careful scrutiny since it involves so many drugs and so many organisms (Coli, Salmonella, Klebsiella, Shigella, Vibrio). Perhaps, by means of this new look at a bacterially old process, we will now be able to devise a cure for this "infectious disease" of bacteria which will be effective in vivo and will finally enable us to deal with the important problem of bacterial resistance (cf. a clinical study9 of atebrin in combination therapy of multi-drug-resistant urinary infections). 

Deeper bacterial infections of the skin include folliculitis, erysipelas, cellulitis, and necrotizing fasciitis. Since streptococcal and staphylococcal species also are the most common causes of deep cutaneous infections, penicilUns (especially ji-lactarruise-resistant ji-lactams), and cephalosporins are the systemic antibiotics used most frequently in their treatment (see Chapter 44). A growing concern is the increased incidence of skin and soft tissue infections with hospital- and community-acquired methicillin-resistant S. aureus (MRSA) and drug-resistant pneumococci. Infection with community-acquired MRSA often is susceptible to trimethoprim—sulfamethoxazole. 

Meropenem, a promising agent for combating resistant bacterial infections, is marketed as a powder blend of the crystalline drug and sodium carbonate. NMR spectra recorded for solution and solid state showed [51] that the carbonate in the formulation was the cause of a chemical modification of meropenem in solution. The C CPMAS spectrum of the reconstituted formulation showed the signal of bicarbonate at 159 ppm and a broader one, centered at 164 ppm of meropenem-C02 adduct. It is interesting that such a carbon dioxide adduct could be observed in the solid state, obtained after lyophilization. 

The emergence of microbial pathogens that are resistant to multiple classes of available antimicrobial agents is becoming a major worldwide pubhc health concern. These multidrug resistant bacteria are ubiquitous in both hospital and community settings [ 120]. The majority of these strains have been found to carry multiple drug resistance factors. At present, the only effective treatment for multiply resistant bacterial infections is vancomycin. Unfortunately,... 

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. 

Streptococcus pneumoniae is the most common bacterial cause of community-acquired respiratory tract infections. S. pneumoniae causes approximately 3000 cases of meningitis, 50,000 cases of bacteremia, 500,000 cases of pneumonia, and over 1 million cases of otitis media each year. The increasing prevalence of drug-resistant S. pneumoniae has highlighted the need to prevent infection through vaccination. Both licensed pneumococcal vaccines are highly effective in preventing disease from the common S. pneumoniae serotypes that cause human disease. 

Much information on the mechanism of action and cross-resistance of purine analogues has been obtained in bacteria, some of which are quite sensitive to certain of these compounds in vitro. There is a great deal of variation in response of the various bacteria to a particular agent and of a particular bacterium to the various cytotoxic purine analogues. Some, if not most, of these differences are probably due to differences in the anabolism of the various compounds. Despite the fact that certain purine analogues have quite a spectrum of antibacterial activity in vitro, none has been useful in the treatment of bacterial infections in vivo because their toxicity is not selective—the metabolic events whose blockade is responsible for their antibacterial activity are also blocked in mammalian cells and thus inhibition of bacterial growth can only be attained at the cost of prohibitive host toxicity. In contrast, the sulpha drugs and antibiotics such as penicillin act on metabolic events peculiar to bacteria. 

Since 1969, the Food and Drug Administration s Center for Veterinary Medicine (formerly the Bureau of Veterinary Medicine) has had cause for concern that the subtherapeutic use of antibiotics in animal feeds may cause bacteria in animals to become resistant to antibiotics. This resistance to antibiotics is said by many knowledgeable scientists to be transferred to bacteria in humans, thus making these antibiotics ineffective in treating human bacterial infections due to compromise of therapy. For this reason, FDA proposed in 1977 to withdraw the use of penicillin in animal feed and restrict the use of the tetracyclines (chlortetracycline and oxytetracycline) to certain uses in animal feed. This talk will focus on FDA s efforts to finalize its review of the issue and present an update on the current status of the 1977 proposals. 

Resistance Prescribing tigecycline in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. 

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