scholarly journals The Utility of Rapid Microbiological and Molecular Techniques in Optimizing Antimicrobial Therapy

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Edward H. Eiland ◽  
Nicholas Beyda ◽  
Jian Han ◽  
William Lindgren ◽  
Randy Ward ◽  
...  
Author(s):  
D. L. Taylor

Cells function through the complex temporal and spatial interplay of ions, metabolites, macromolecules and macromolecular assemblies. Biochemical approaches allow the investigator to define the components and the solution chemical reactions that might be involved in cellular functions. Static structural methods can yield information concerning the 2- and 3-D organization of known and unknown cellular constituents. Genetic and molecular techniques are powerful approaches that can alter specific functions through the manipulation of gene products and thus identify necessary components and sequences of molecular events. However, full knowledge of the mechanism of particular cell functions will require direct measurement of the interplay of cellular constituents. Therefore, there has been a need to develop methods that can yield chemical and molecular information in time and space in living cells, while allowing the integration of information from biochemical, molecular and genetic approaches at the cellular level.


1996 ◽  
Vol 75 (06) ◽  
pp. 959-964 ◽  
Author(s):  
I M Nesbitt ◽  
A C Goodeve ◽  
A M Guilliatt ◽  
M Makris ◽  
F E Preston ◽  
...  

Summaryvon Willebrand factor (vWF) is a multimeric glycoprotein found in plasma non covalently linked to factor VIII (FVIII). Type 2N von Willebrand disease (vWD) is caused by a mutation in the vWF gene that results in vWF with a normal multimeric pattern, but with reduced binding to FVIII.We have utilised methods for the phenotypic and genotypic detection of type 2N vWD. The binding of FVIII to vWF in 69 patients, 36 with type 1 vWD, 32 with mild haemophilia A and one possible haemophilia A carrier with low FVIII levels was studied. Of these, six were found to have reduced binding (five type 1 vWD, one possible haemophilia A carrier), DNA was extracted from these patients and exons 18-23 of the vWF gene encoding the FVIII binding region of vWF were analysed. After direct sequencing and chemical cleavage mismatch detection, a Thr28Met mutation was detected in two unrelated individuals, one of whom appears to be a compound heterozygote for the mutation and a null allele. No mutations were found in the region of the vWF gene encoding the FVIII binding region of vWF in the other four patients


2020 ◽  
Vol 65 (9-10) ◽  
pp. 64-70
Author(s):  
V. B. Beloborodov ◽  
I. A. Kovalev ◽  
G. V. Sapronov

Progredient growth of morbidity and mortality of patients with community-acquired pneumonia (CAP) requires optimization of treatment including antibacterial therapy. Implementation of molecular-genetic methods of diagnostics of viral and viral-bacterial infections in clinical practice has significantly augmented the conception of etiology of community-acquired pneumonia. Seasonal fluctuation of CAP prevalence corresponds with growth of morbidity of acute respiratory infections and influenza which contribute to the etiological structure of CAP by increasing the risk of infection caused by staphylococci. The synergy between influenza A virus and S.aureus has been shown; it is associated with an increase of virus replication in the presence of specific staphylococcal proteases and the ability of viruses to increase adhesion of S.aureusin the respiratory tract, to decrease phagocytosis of S.aureus by macrophages/neutrophils and production of antimicrobial peptides, as well as to increase the probability of secondary bacterial co-infection. Therefore, the most important requirement for the empiric therapy agents of CAP is high streptococcal and staphylococcal activity. According to the current guidelines on antimicrobial therapy of severe CAP, antipneumococcic cephalosporins, macrolides, and fluoroquinolones are the basic treatment agents, but none of them have the combined high antistaphylococcal and antipneumococcal activity inherent in ceftaroline. The advantages of ceftaroline over ceftriaxone and levofloxacin in terms of the probability of reaching target concentrations for clinically relevant pharmacokinetic/pharmacodynamic parameters are shown. Meta-analysis of randomized clinical trials showed the higher clinical efficacy of ceftaroline in comparison to ceftriaxone with similar adverse event rate. Summarized analysis of antibiotic susceptibility data, pharmacokinetic/pharmacodynamic and clinical data, as well as negative epidemiological trends confirms the necessity of optimization of antimicrobial therapy of CAP for implementation of ceftaroline advantages against pneumococci and staphylococci in comparison to other β-lactams. Therefore, empiric treatment with ceftaroline is the most rational option for the therapy of CAP in critically ill patients during the season of respiratory viral infection.


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