Frontiers in Clinical Drug Research - Anti Infectives: Volume 2

Atta-ur-Rahman

• Éditeur: Bentham Science Publishers
• Année: 2016
• ISBN:
  9781681081533
• Sujet: Physical Sciences
• Sous-sujet: Clinical Chemistry

Frontiers in Clinical Drug Research – Anti infectives is an eBook series that brings updated reviews to readers interested in learning about advances in the development of pharmaceutical agents for the treatment of infectious diseases. The scope of the eBook series covers a range of topics including the chemistry, pharmacology, molecular biology and biochemistry of natural and synthetic drugs employed in the treatment of infectious diseases. Reviews in this series also include research on multi drug resistance and pre-clinical / clinical findings on novel antibiotics, vaccines, antifungal agents and antitubercular agents. Frontiers in Clinical Drug Research – Anti infectives is a valuable resource for pharmaceutical scientists and postgraduate students seeking updated and critically important information for developing clinical trials and devising research plans in the field of anti infective drug discovery and epidemiology.
The second volume of this series features reviews that cover a variety of topics including:
-Identification of nosocomial pathogens and antimicrobials using phenotypic techniques
-Topical antimicrobials
-Anti-infective drug safety
-Antimicrobial resistance
… and much more.

Identification of Nosocomial Pathogens and Antimicrobials Using Phenotypic Techniques

INTRODUCTION

Hospital-Acquired Infections

Nosocomial infections belong to the group of healthcare-associated infections (HAIs) [1] which are not only limited to hospitalization but also include all infections resulting from any interaction associated with the health care. The Council of the European Union considers HAIs as diseases that are “related to the presence of an infectious agent or its products in association with exposure to healthcare facilities or health care procedures or treatments” [2], with a lack of evidence that the infection was present or incubated at the time of entry of patient into the health care setting. Centers for Disease Control and Prevention define HAIs in a similar way [1].

The situation of HAIs is further complicated and aggravated by the increasing incidence of multidrug-resistant bacteria (MDRB) promoted by extensive use of antimicrobials during the last decades. The infections caused by MDRB contrary to those caused by susceptible bacteria are associated with significantly higher mortality, length of hospitalization, and health care costs [3, 4]. The European Centre for Disease Prevention and Control (ECDC) demonstrated that annually, HAIs involve 4.1 million patients in the European Union (EU) Member States and these infections directly result in approximately 37,000 deaths [2].

HAIs are caused by a wide variety of pathogens; namely Staphylococci, Enterococci, Pseudomonas aeruginosa, Klebsiella spp., Escherichia coli, etc. Especially, multiresistant strains of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and extended-spectrum lactamase producing gram-negative bacteria. These are very dangerous and their treatment is complicated [3, 5]. Also, certain fungal agents are commonly associated with HAIs, e.g., yeasts of Candida genus and aspergilli [6].

MRSA strains are considered as the most problematic nosocomial pathogens. These bacteria contain genes encoding penicillin-binding protein that differs from other penicillin-binding proteins in a way that its active site does not bind to methicillin or other β-lactam antibiotics [7]. Therefore, MRSA becomes resistant to the beta-lactam antibiotics, including those commonly used to treat ordinary staphylococcal infections. Only in the European Union, 171,200 of HAIs caused by MRSA were recognized in 2008 where 5,400 of extra deaths and 1,050,000 of extra days of hospitalization can be attributed to MRSA infections. The extra in-hospital costs attributable to MRSA were estimated to reach approximately 380 million EUR annually [8]. The development of antibiotic resistance of the gram-positive cocci such as staphylococci or enterococci to second-line antibiotics also complicates the treatment of diseases caused by these bacteria [9, 10].

Next to S. aureus, coagulase-negative staphylococci are other agents causing nosocomial infections. These infections are usually associated with indwelling medical devices, e.g., catheter-related sepsis [11]. The pathogenesis of these infections strongly depends on the ability of pathogens to form biofilms on artificial surfaces [12] because the growth in the biofilm form protects the bacterial cells from the attacks of the immune system as well as from the effect of antibiotics. Therefore, it is difficult to eradicate these focuses through a conservative therapy, which results in the chronic character of biofilm infections and in the poor response to the antibiotics [12, 13].

P. aeruginosa is one of the leading gram-negative organisms associated with nosocomial infections, especially in patients with compromised host defense mechanisms. P. aeruginosa typically infects the airways, urinary tract, burns, wounds, and also causes blood stream infections [3, 5]. These bacteria show inherent (natural) resistance to a number of antimicrobial agents [14]. P. aeruginosa also easily develops resistance to anti-pseudomonas drugs in a hospital environment. One of the most serious types of the resistance is based on the production of broad-spectrum beta-lactamases, which inhibit the activity of many β-lactam antibiotics, and carbapenemases providing the resistance to all beta-lactams including carbapenems [15]. Those strains that exhibit resistance to at least three unrelated classes of antibiotics, especially β-lactams, carbapenems, and aminoglycosides, are considered as MDRB [16].

Enterobacteria belong to the important nosocomial pathogens as well. Particularly, E. coli and Klebsiella sp., are leading etiological agents of nosocomial urinary tract infection [3]. In addition, these bacteria cause a number of other serious HAIs, e.g., pneumonia, bloodstream infections, and surgical wound site infections [3, 5]. These bacteria often produce extended-spectrum beta-lactamases or carbapenemases [17]. In addition, these strains frequently acquire co-resistance to many other classes of antibiotics in a hospital environment. The fact, that these bacteria show resistance to multiple antibiotics, increases the importance of the problem [18].

Fungal HAIs are less common than the bacterial HAIs, and they are restricted to immunocompromised patients. Difficult therapy and high mortality are characteristic for this type of infection [19]. The most common fungi causing HAIs are yeasts of the genus Candida of which Candida albicans is most prevalent. However, the increased incidence of other Candida species occurs in recent decades. Candida parapsilosis and Candida tropicalis are typically associated with the use of catheters or other indwelling medical devices, enabling a biofilm formation [20]. The highest mortality associated with Candida krusei and Candida glabrata, can be probably related to their resistance to azole antifungals [19, 20]. Aspergillus fumigatus represents an example of the filamentous fungi, which is the most common cause of HAIs. It is usually manifested in the form of pulmonary invasive aspergillosis [21].

Identification of the Etiological Agents of Nosocomial Infections

Early identification of the etiological agents of nosocomial infections improves antimicrobial use and ...