Resistance to Antibacterial Drugs

Bacterial resistance can occur because of several mechanisms.28,76 Certain bacterial strains may be able to enzymatically destroy the antibacterial drug. The best example is the beta-lactamase enzyme that is found in bacteria that are resistant to beta-lactam drugs (penicillins and cephalosporins).54,86 As previously discussed, bacteria containing this enzyme can destroy certain penicillin and cephalosporin drugs, thus rendering the drug ineffective against these strains. 

Bacillus Common Disease(s) Primary Agent(s) Alternative Agent(s) 

Bacillus anthracis Anthrax pneumonia Ciprofloxacin or doxycycline plus a penicillin another [alternative] agent Clarithromycin clindamycin chloramphenicol imipenem rifampin vancomycin 

Clostridium difficile Antibiotic-associated colitis Metronidazole Vancomycin 

Clostridium perfringens Gas gangrene Penicillin G clindamycin Cefazolin clindamycin doxycycline metronidazole imipenem 

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The second general mechanism to cause resistance to antibacterial agents is to prevent the drug from reaching its target site. This is either achieved by altered rates of entry (reduced uptake) or by the active removal of the dtug (active efflux) [4]. 

There are four general properties for a good antibacterial agent. It must be selective. Eliminating all species of bacteria from the body may leave the patient prone to superinfection. It should kill bacteria rather than just prevent their multiplication it should be bactericidal rather than bacteriostatic. Bacteria should not develop resistance to the drug. Lastly,... 

Davies D. 2003. Understanding biofihn resistance to antibacterial agents. Nature Rev Drug Discov 2 114-122. 

Davies, D. (2003). Understanding biofilm resistance to antibacterial agents. Nat. Rev. Drug Discov. 2,114-122. 

Over 80 years since the discovery of penicillin [1], the (3-lactam motif continues to have a great importance in the pharmaceutical and biochemical sciences [2]. Their historically widespread role as antibacterial agoits has come under increased pressure due to recent discoveries of bacterial strains resistant to current drugs [3]. This challenge, coupled with their use in emerging nonantibacterial therapeutic areas, such as serine protease inhibitors [4], makes the development of novel (3-lactam based scaffolds a valuable endeavor. 

Although reaction-diffusion limitation and the presence of nutritionally restricted phenotypes are obviously important determinants of biofilm drug resistance, neither, either separately or in combination, provides a complete explanation of the phenomena. Cells on the periphery of the biofilm, subject to nutrient fluxes similar to planktonic organisms would succumb to antibacterial concentrations that are effective against the planktonic cells. Cell-death at the periphery would lead to increased nutrient availability for deeper-lying cells. These would, in turn, grow faster and adopt a more susceptible... 

Due to the frequent difficulty of doing cultures before giving an antibacterial drug, topical treatment often requires the use of broad-spectrum antibiotics. However, the selection of resistant strains, especially via the use of broad-spectrum antimicrobials with marked systemic dif-... 

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