Current Pharmaceutical Design - Volume 19, Issue 2, 2013

Early after the introduction of the first (narrow spectrum) penicillins into clinical use, penicillinase-producing staphylococci replaced (worldwide) the previously susceptible microorganisms. Similarly, the extensive use of broad-spectrum, orally administered β- lactams (like ampicillin, amoxicillin or cefalexin) provided a favorable scenario for the selection of gram-negative microorganisms producing broad spectrum β-lactamases al Read More

Treatment of serious P. aeruginosa infections becomes more challenging with each passing year. As this pathogen acquires more transferrable resistance mechanisms and continues to rapidly adapt and emerge resistant during the course of antimicrobial therapy, we face the growing threat of pan-resistance. This review has focused on those mechanisms that directly impact the future of β-lactam antibiotics, including the pro Read More

Acinetobacter spp. are Gram-negative bacteria that have become one of the most difficult pathogens to treat. The species A. baumannii, largely unknown 30 years ago, has risen to prominence particularly because of its ability to cause infections in immunocompromised patients. It is now a predominant pathogen in many hospitals as it has acquired resistance genes to virtually all antibiotics capable of treating Gram-negativ Read More

Although β-lactams remain a cornerstone of veterinary therapeutics, only a restricted number are actually approved for use in food-producing livestock in comparison to companion animals and wildlife. Nevertheless, both registered and off-label use of third and fourth-generation cephalosporins in livestock may have influenced the emergence of plasmid-encoded AmpC β-lactamases (pAmpC) (mainly CMY-2) and C Read More

Pathogens that produce extended spectrum β-lactamases (ESBLs), plasmid-mediated AmpC β-lactamases, and carbapenemases may appear falsely susceptible to β-lactam antibiotics in the laboratory. Infected patients may be treated with inappropriate antibiotics if laboratories do not perform accurate tests to detect these resistance mechanisms. Furthermore the resistant pathogens may spread undetected to amplify Read More

Escherichia coli remains one of the most frequent causes of nosocomial and community-acquired bacterial infections including urinary tract infections, enteric infections, and systemic infections in humans. Extra-intestinal pathogenic E. coli or ExPEC had emerged during the 2000s as an important player in the resistance to antibiotics, especially to the cephalosporins and fluoroquinolones. Most importantly among ExPEC, i Read More

Although reports of antimalarial drug resistance emerged as early as 1910 from South America, the first event that really had a major impact on malaria control and drug development was the emergence of chloroquine resistance in the 2nd half of the 20th century. The appearance of resistance to chloroquine has marked the onset of a race between the development of ever new generations of antimalarial drugs and t Read More

The malaria parasite has been allowed to get perilously close to winning the upper hand in the race between new drugs and resistance development. Today, just one class of drugs is left to avoid a public health disaster of global proportions, the artemisinins, and even they are showing signs of a possible impending failure. Rational approaches to overcoming antimalarial drug resistance are difficult for several re Read More

Drug development often seeks to find “magic bullets” which target microbiologic proteins while not affecting host proteins. Paul Ehrlich tested methylene blue as an antimalarial but this dye was not superior to quinine. Many successful antimalarial therapies are “magic shotguns” which target many Plasmodium pathways with little interference in host metabolism. Two malaria drug classes, the 8- aminoquinolines and the Read More

The most common treatments for infectious diseases target the invading pathogen. The efficacy of such an approach may, however, be countered by the possibility of the development of resistance to a pharmacophore, through mutation(s) in pathogen molecules required for activity. Given the fact that pathogens exploit host factors in order to grow in an otherwise hostile environment, one possible way to circumvent the emerg Read More

Antimalarial drugs have in the past fallen prey to resistance and this problem is likely to continue in the future. One approach to developing drugs that might be less prone to resistance might be to target the disease rather than the parasite itself. The rationale for this idea, which has been somewhat developed in antibacterial chemotherapy, is that drugs that can alleviate disease pathogenesis while not compromising the s Read More