Antibiotics susceptibility and resistance

Smaill F Antibiotic susceptibility and resistance testing An overview. Can J Gastroenterol 2000 14 871-875. 

The oxazolidinones are a new class of synthetic antimicrobial agents. Produced in 1987, they were found to be active in vitro against antibiotic-susceptible and -resistant cocci and did not demonstrate cross-resistance with any other antibiotics. 

In conclusion, tryptic digestion of proteins and analysis of the resulting peptides by MALDI-TOF MS or LC-MS have proven to be a potent tool to elucidate mechanisms underlying bacterial resistance to antibiotics. Either proteins of interest or protein fractiorts such as outer membrane proteirrs can be analyzed, or the whole proteome of antibiotic-susceptible and -resistant strairrs can be compared. The proteins of interest or the differentially expressed proteirrs can be digested to... 

NE Allen, JN Hobbs Jr, TI Nicas. Inhibition of peptidoglycan biosynthesis in vancomycin-susceptible and -resistant bacteria by a semisynthetic glycopeptide antibiotic. Antimicrob Agents Chemother 40 2356-2362, 1996. 

Butaye P, Devriese LA, Haesebrouck F. Phenotypic distinction in Enterococcus faecium and Enterococcus faecalis strains between susceptibility and resistance to growthenhancing antibiotics. Antimicrob Agents Chemother... 

Diffusion tests are used to determine the susceptibility of microorganisms but have their limitations when equivocal results are obtained or in the case of prolonged serious infection, e.g., bacterial endocarditis, the elucidation of antibiotic action in relation to the pathogen needs to be more precise. Also the terms susceptible and resistant are open to interpretation. Thus, when in douht, a precise assessment is needed and involves determining the MIC of the antimicrobial compounds to the organisms using the 2-fold serial dilution method, which shown in Figure 11.2 [20,24]. 

The success of dibekacin prompted worldwide attention to the removal of selected OH groups in aminoglycoside antibiotics susceptible to modification by resistant bacteria, and the chemical deoxygenation procedure of D. H. R. Barton was found particularly useful. 

Acquired resistance. This occurs when bacteria which were previously susceptible become resistant, usually, but not always, after exposure to the antibiotic concerned. Intrirrsic resistance is always chromosomally mediated, whereas acquired resistance may occirr by mutations in the chromosome or by the acquisition of genes coding for resistance ftom an external source normally via a plasmid or transposon. Both types are clinically important and can result in treatment failure, although acquired resistance is more of a threat in the spread of antibiotic resistance (Russell Chopra 1996). 

For enterococci, it is imperative to determine species and antibiotic susceptibilities. If the organism is susceptible to penicillin and vancomycin, treatment may consist of high-dose penicillin G, ampicillin, or vancomycin plus gentamicin (see Table 71-6). Treatment length is usually 4 to 6 weeks, with the aminoglycoside used over the entire course. As resistance develops to penicillin, ampicillin and vancomycin remain treatment options. Once the isolate becomes resistant to ampicillin, vancomycin is considered the treatment of choice. 

Another important advance has been the application of PyMS with ANNs to discriminate between methicillin-resistant and methicillin-sensitive Staphylococcus aureusIn this study DFA and HCA showed that the major source of variation between the pyrolysis mass spectra of 15 methicillin-resistant (MRSA) and 22 methicillin-sensitive Staphylococcus aureus (MSSA) strains resulted from the phage group of the bacteria, rather than from their resistance or sensitivity to methicillin. By contrast, ANNs could recognize those aspects of the pyrolysis mass spectra that differentiated MRSA and MSSA strains. These results gave the first demonstration that the combination of PyMS with ANNs could provide a rapid and accurate antibiotic-susceptibility testing technique. 

In the case of /3-lactam antibiotics, the bacterial targets are the so-called PBPs. Modification of PBPs can result in a decreased affinity for /1-lactam antibiotics. In some cases the normal PBPs, through mutation, become less susceptible to acylation and inactivation by /3-lactam antibiotics. So, the target protein is unable to bind the antibiotic effectively, and hence resistance to a particular antibiotic is acquired [5]. Frequently, this difference consists of substitution of a single amino acid in the protein chain. In S. aureus, ac-... 

When bacteria are exposed to an antibiotic, only the cell with the resistant gene survives but it can then multiply, copying the resistant gene to its millions of progeny. This way, susceptible cells are obliterated and resistance becomes a stable feature of the bacterial population (Fig. 1). 

Walsh, S.E. et al., Development of bacterial resistance to several biocides and effects on antibiotic susceptibility. J. Hosp. Infect. 55, 98-107, 2003. 

For many antibiotics, the mechanism of antibiotic resistance can help establish the mechanism of action. Therefore, it may be instructive to determine the mechanism(s) of daptomycin resistance to see if it yields insights into the mechanism of action. The incidence of reduced susceptibility to daptomycin in clinical isolates is very low and resistant strains are usually associated with deep-seated infections in compromised patients.2,9,36,37... 

The component(s) of the mycobacterial cell wall responsible for conferring intrinsic resistance to antibiotics are not yet known with any certainty. However, it has been shown [91-93] that inhibitors of arabinogalactan synthesis increase mycobacterial sensitivity to antibiotics. When M. avium is treated with inhibitors of mycolic acid biosynthesis there are significant alterations in outer cell wall layers and the cells show an increased antibiotic susceptibility [93], Thus, arabinogalactan and mycolic acids are components of the wall associated with intrinsic resistance of mycobacteria to chemotherapeutic drugs and alteration of these structural building blocks leads to increased intracellular penetration of antibiotics [88,94,95],... 

Johnson AP, Warner M, HaUas G, Livermore DM. Susceptibility to quinupristin/dalfopristm and other antibiotics of vancomycin-resistant enterococci from the UK, 1997 to mid-1999. J Antimicrob Chemother 2000 46(l) 125-8. 

Pavia M, Nobile CG, Salpietro L, Angelillo IF. Vancomycin resistance and antibiotic susceptibility of enterococci in raw meat. J Food Prot 2000 63(7) 912-15. 

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