**1. General concepts**

#### **1.1. Global data**

The emergence of antibiotic and their use in clinical practice is one of the greatest achievements of Medicine. In the mid-twentieth century, its use became widespread, and it was thought that a rapid and definite eradication of infectious diseases was possible. However, the first resistant bacteria soon appeared, and antibiotic resistance has developed into a serious public health problem. It is estimated that up to 60% of nosocomial infections are caused by resistant germs both in Europe and in the United States. The Center for Disease Control and prevention (CDC)

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

in the United States has estimated that the problem of antibiotic resistance is responsible for 2 million infections and 23,000 deaths per year with a direct cost of 20 billion dollars, and losses of productivity equivalent to 33 billion dollars [1]; the European Center for Disease Control, ECDC, have estimated that accounts for 25,000 deaths and 1.5 billion € per year by infections by multiresistant bacteria (MRB) [2]. Some consequences of this problem are: increased cost of health care, increased rates of failure of antibiotic treatment and increased mortality. This is not a problem limited to certain regions or countries and resistance can spread quickly in our globalized world.

of certain antibiotics—such as penicillin-binding proteins, PBPs); alterations in the transmembrane passage (porins, mechanisms of uptake or active transport); enzyme production (betalactamases). The appearance of mutations in the genetic material of the bacteria or the transfer of resistance genes from other germs explains the transformation from sensible to resistant bacteria. The exposure to antibiotics induces the disappearance of a population sensitive, and

Current Status of Colonization and Infection by Multiresistant Bacteria in the Spanish Intensive…

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MRB are defined as those microorganisms resistant to three or more antibiotics, which must also have clinical relevance. The exception to this rule is methicillin-resistant *Staphylococcus aureus* (MRSA) and vancomycin-resistant enterococcus (VRE) cases, in which the resistance condition is given by only one antibiotic. The phenomenon of resistance constitutes a medical problem, since it becomes a difficulty for the treatment and also epidemiological relevance, given the possibility of transmission of the outbreak. The ESKAPE (*Enterococcus faecium*, *Staphylococcus aureus*, *Klebsiella pneumoniae*, *Pseudomonas aeruginosa* and Enterobacter especies) are a specific group of bacteria with clinical relevance, associated with health care, and with

*P. aeruginosa* (Pa) has a predilection for humid environments and usually contaminates aqueous solutions such as disinfectants or soaps, mechanical ventilation equipment, fiberoptic bronchoscopes, and so on. Resistance may appear in the course of an antibiotic treatment. Its main mechanism of resistance is the presence of extended-spectrum beta-lactamases (ESBL)

*Acinetobacter baumannii* (Ab) contaminates and endemically colonizes the hospital environment. It is capable of surviving and rapidly developing resistance to the main classes of antibiotics, more frequently in summer [7]. Some strains can survive to environmental drying form months, which facilitates transmission via contamination of fómites in the hospital. The health personnel is usually carrier of Gram-negative bacilli (GNB) (30%). Outbreaks have been described in relation to contaminated mechanical ventilation equipment and manual transmission. Infections have also been described in war wounds and in situations of natural disasters. Sixty-three percent of bacterial isolation from war wounds in Iraq and Afghanistan corresponded to this germ [8]. Infections tend to appear in patients with long stay in the ICU and health centers, dependent on mechanical ventilation, central catheter carriers, and with prior treatment with third-generation cephalosporins, fluorquinolones or carbapenemes. Although patients with Ab infection have high mortality, it is not clear whether mortality can be attributed to infection or to life-threatening conditions [9]. Several factors are associated with mortality: isolation in blood cultures, presence of signs of sepsis/septic shock, resistance to imipenem, longer stay in ICU, pneumonia and diabetes mellitus [10]. Cases of community acquisition have been described in situations of chronic obstructive pulmonary disease (COPD), diabetes, alcoholism and cancer [11]. It has great capacity to acquire and accumulate

and alterations in permeability (porin mutations and expulsion pumps).

the selection of resistant strains to the antibiotics that end up being predominant.

**1.4. Definition of MRB**

**1.5. Description of the MRB**

the capacity to develop antibiotic resistance [6].

### **1.2. Intensive care unit generalities**

Intensive care unit (ICU) accounts for less than 10% of total beds in most hospitals, but more than 20% of nosocomial infections are acquired in ICU [3]. Acquired in ICU infections pose significant morbidity, mortality and expense; they are the most frequent cause of death in non-cardiac ICUs and 40% of all ICU expenses [4]. In comparison with patients from other areas of the hospital, ICU patients have higher chronic comorbidity, more severe acute physiological deterioration and are relatively immunosuppressed [5]. Its management also implies a high degree of invasiveness, with use of intravascular catheter, contact with a large number of health personnel—predisposing to colonization and infection—and are subjected to an increased colonization pressure [5].

When a patient goes to the hospital today, he undergoes a more effective and complete care than in previous years. Advances in diagnostic and therapeutic methods mean improvements in care and may be accompanied by a greater number of associated complications. All these data are magnified in ICU; ICU patients are more vulnerable to develop infections during their stay and to become colonized/infected with MRB. Overcrowding in closed areas of these severely ill patients with multiple comorbidities and subjected to invasive devices are risk factors for the development of nosocomial infections.

There is a clear relationship between the appearance of resistance and the highest antibiotic consumption. Infections due to resistant germs/MRB have limited therapeutic options, so inadequate empirical treatments are prescribed, the start of the correct treatment is delayed and therapeutic failures increase. All this leads to longer ICU stay, costs and mortality, with worse prognosis of the patient.

The highest density of MRB is observed in ICU. The importance of adequate and early treatment is greater in critically ill patients; for all above, it is necessary to implement programs for the prevention and treatment of multiresistant bacteria MRB, both in the ICU and in the community—a great number of MRB can be related to inadequate or excessively prolonged treatments in the general ward or outside the hospital.

#### **1.3. Antibiotic resistance mechanisms**

The mechanisms related to the emergence of resistance are varied. Resistance can be intrinsic or acquired. the first occurs in certain germs that are not innately sensitive to certain antibiotics, by a special membrane structure or related to the mechanism of the antibiotic. There may be at the molecular level: modifications in the targets (nucleic acid, ribosomes, action points of certain antibiotics—such as penicillin-binding proteins, PBPs); alterations in the transmembrane passage (porins, mechanisms of uptake or active transport); enzyme production (betalactamases). The appearance of mutations in the genetic material of the bacteria or the transfer of resistance genes from other germs explains the transformation from sensible to resistant bacteria. The exposure to antibiotics induces the disappearance of a population sensitive, and the selection of resistant strains to the antibiotics that end up being predominant.
