Original article
Extended-spectrum beta-lactamases in urinary tract infections caused by Enterobacteria: Understanding and guidelines for action
Betalactamasas de espectro extendido en las infecciones del tracto urinario causadas por enterobacterias: aproximación a su conocimiento y pautas de actuación
A. García-Telloa,
, H. Gimbernata, C. Redondoa, D.M. Aranab, J. Cachob, J.C. Anguloa
Corresponding author
a Servicio de Urología, Hospital Universitario de Getafe, Departamento Clínico, Facultad de Ciencias Biomédicas, Universidad Europea de Madrid, Madrid, Spain
b Servicio de Microbiología, Hospital Universitario de Getafe, Departamento Clínico, Facultad de Ciencias Biomédicas, Universidad Europea de Madrid, Madrid, Spain
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"apellidos" => "Angulo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Urología, Hospital Universitario de Getafe, Departamento Clínico, Facultad de Ciencias Biomédicas, Universidad Europea de Madrid, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Microbiología, Hospital Universitario de Getafe, Departamento Clínico, Facultad de Ciencias Biomédicas, Universidad Europea de Madrid, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Betalactamasas de espectro extendido en las infecciones del tracto urinario causadas por enterobacterias: aproximación a su conocimiento y pautas de actuación" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1900 "Ancho" => 2238 "Tamanyo" => 290319 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Protocol for choosing empiric therapy for suspected ESBL-producing pathogens.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Beta-lactamases are bacterial enzymes encoded in chromosomes or plasmids that protect microorganisms from the lethal effects of beta-lactam antibiotics by hydrolyzing the beta-lactam ring. Its production is the most important mechanism of resistance to these antibiotics, especially in Gram-negative bacteria. The first plasmid-mediated beta-lactamases in gram-negative bacteria (TEM-1, SHV-1) were described in the 1960s.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The extended-spectrum beta-lactamases (ESBLs) are a group of these enzymes, encoded on plasmids, which are characterized by having hydrolytic capacity against beta-lactam antibiotics of the oximino group. They confer, thus, resistance to penicillins, cephalosporins of first, second, and third generation and aztreonam. They are inhibited in vitro by beta-lactamase inhibitors such as clavulanic acid or tazobactam. They are often found in enterobacteria, mainly <span class="elsevierStyleItalic">Klebsiella</span> sp. and <span class="elsevierStyleItalic">Escherichia coli</span>. The presence of ESBL was also associated with a high proportion of resistance to other non-beta-lactam antibiotics, such as fluoroquinolones, aminoglycosides, or cotrimoxazole.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The first ESBL-producing strain appeared in 1983 in Germany.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Since then, various outbreaks have been published in Europe, the USA, and Asia. The incidence of strains producing these enzymes has possibly been undervalued in many countries. In Spain, the first ESBL-producing microorganisms were described in 1988.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> As in the rest of Europe, the incidence of infections caused by these pathogens has increased in recent decades and its epidemiology is changing. Until recently, these were considered an exclusively nosocomial problem, with disease outbreaks, but in recent clinical studies, a high percentage of gram-negative bacteremia of the community was caused by ESBL-producing enterobacteriaceae.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Urinary tract infections are a major cause of bacterial infection both in hospitalized patients and in the community, and beta-lactam antibiotics have been widely used to treat these infections. The emergence of gram-negative bacteria producing extended-spectrum beta-lactamases complicates therapy by severely limiting the treatment options. In addition, antibiotics are usually empirically indicated before obtaining laboratory results. There are studies that show that inadequate antibiotic treatment is a predictor of mortality in patients with bacteremia of urinary origin.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–8</span></a> For this reason, it is extremely important to start an appropriate therapy as soon as possible. It is essential to understand the microorganisms that more often cause these infections in our environment and their patterns of sensitivity and antimicrobial resistance, to carry out proper treatment.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Definition of extended-spectrum beta-lactamases</span><p id="par0020" class="elsevierStylePara elsevierViewall">The continuous description of new beta-lactamases has created problems in their classification and nomenclature. Currently, more than 890 enzymes are known. They are usually classified according to 2 general schemes. The Ambler molecular classification, proposed in 1980,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> divides beta-lactamases into 4 main groups (A, B, C, and D) based on their proteic homology.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The functional classification was proposed by Bush in 1989 based on the affinity of the enzymes through different substrates and their sensitivity to the inhibitory action through clavulanic acid. This classification was revised in 1995 by Bush et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and updated again in 2010. It describes 4 major groups and numerous subgroups. Due to their interest and clinical implications, it is worth stressing the following betalactamases:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0025" class="elsevierStylePara elsevierViewall">Extended-spectrum beta-lactamases (groups 2be, 2ber, and 2de of the classification by Bush and Jacoby): TEM, SHV, CTX-M, and OXA-type enzymes.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0030" class="elsevierStylePara elsevierViewall">Beta-lactamases resistant to the inhibitors (group 2br): TEM and SHV-type enzymes.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0035" class="elsevierStylePara elsevierViewall">AmpC-type beta-lactamases (group 1): LAT, MIR, CMY, and FOX-type enzymes.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0040" class="elsevierStylePara elsevierViewall">Carbapenemases (2f, 2df, and 3 groups) VIM, IMP, IMI, KPC, NDM, and OXA-type.</p></li></ul></p><p id="par0045" class="elsevierStylePara elsevierViewall">Extended-spectrum betalactamases are defined as beta-lactamases capable of conferring bacterial resistance to penicillins, cephalosporins (including extended-spectrum), and monobactams (aztreonam) by means of hydrolysis of these antibiotics and that are inhibited by beta-lactamase inhibitors such as clavulanic acid or tazobactam. They cannot hydrolyze cephamycins (cefoxitin) or carbapenems (imipenem, meropenem, ertapenem). The genes that encode them are found in mobile elements that facilitate its spread and often show co-resistance with other antibacterials such as aminoglycosides, cotrimoxazole, and quinolones.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Most belong to the Ambler molecular class A. These include TEM and SHV, derived from beta-lactamases with a lower spectrum of hydrolysis, the CTX-M family, from chromosomal beta-lactamases from the Kluyvera gender, and other less prevalent such as PER, VEB, BES, GES, TLA, and SFO, all of them included in the functional group 2be by Bush and Jacoby. They also belong to class A, subgroup 2ber, TEM complex mutant beta-lactamases (CMT). Some enzymes of the OXA family (class D Ambler and functional group 2de) are also extended-spectrum beta-lactamases. Since its initial description, over 300 different ESBLs have been identified, most of them belonging to the TEM, SHV, and CTX-M families.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The predominant ESBLs in Europe were initially those of SHV type, but from 2000, the CTX-M type has become the most prevalent in most of the world, especially in certain countries of Europe and South America.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> The enzymes of this group confer a high activity against cefotaxime and ceftazidime. They are not limited to nosocomial infection, but they have a significant potential to expand beyond the hospital environment, and thus they represent a real public health problem. In Spain, the most common types are CTX-M9 and M14.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Detection of extended-spectrum beta-lactamases</span><p id="par0055" class="elsevierStylePara elsevierViewall">The clinical microbiology laboratory is the first step in the health system that should alert about the presence of bacterial resistance mechanisms of clinical relevance. ESBL detection methods are divided into 2 groups: phenotypic methods that use non-molecular techniques and detect the ability of ESBLs enzymes to hydrolyze different cephalosporins and genotypic methods that use molecular techniques to detect the genes responsible for the production of the above mentioned ESBLs. Phenotypic methods are more widely used because they are simpler and possibly more cost-effective, while genotypic ones are usually performed in specialized or reference laboratories. The former are crucial for proper treatment of patients, but the latter provide essential information in order to prevent and control infectious diseases.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The United States Clinical and Laboratory Standards Institute (CLSI) and the United Kingdom Health Protection Agency (HPA) have published guidelines for detection of ESBL production in enterobacteriaceae, particularly <span class="elsevierStyleItalic">E. coli</span>, <span class="elsevierStyleItalic">Klebsiella</span> sp., and <span class="elsevierStyleItalic">Proteus</span> sp.; the UK guideline includes other species such as <span class="elsevierStyleItalic">Salmonella</span> sp.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,16</span></a> Both recommend performing a screening test for the potential ESBL production and a second confirmatory test if the first proved positive. When the microdilution technique is used, the screening is performed with 8<span class="elsevierStyleHsp" style=""></span>mg/l (CLSI) or 1<span class="elsevierStyleHsp" style=""></span>mg/l (HPA) of cefpodoxime or 1<span class="elsevierStyleHsp" style=""></span>mg/l cefotaxime, ceftazidime, ceftriaxone, or aztreonam. The presence of ESBL is suspected when the minimum inhibitory concentration (MIC) is increased compared to the expectations. When the disk diffusion technique is used, it is suspected when the inhibition halos decrease. The confirmatory test is done with cefotaxime and ceftazidime in combination with clavulanic at concentrations of 4<span class="elsevierStyleHsp" style=""></span>mg/l. In samples with ESBL, the MIC of ceftazidime or cefotaxime should be reduced in the presence of clavulanate. A decrease greater than or equal to 8 times the MIC of one or 2 antimicrobials in the presence of the inhibitor indicates the presence of ESBL. In the centers that use the technique of double-disk synergy greater than or equal to 5<span class="elsevierStyleHsp" style=""></span>mm in the diameter of the inhibition zone between the discs of each antimicrobial agent, with or without clavulanate, it is interpreted as positive test (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). With a correct implementation of the recommendations of these guidelines, the sensitivity and specificity to detect ESBL in <span class="elsevierStyleItalic">E. coli</span>, <span class="elsevierStyleItalic">Klebsiella</span> sp., and <span class="elsevierStyleItalic">Proteus</span> sp. are very high, above 94 and 98%, respectively.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Phenotypic detection in other bacteria is controversial, because the effect of the clavulanic acid is not always present in other species such as <span class="elsevierStyleItalic">Enterobacter</span> or <span class="elsevierStyleItalic">Citrobacter</span>. Detection by means of genotypic techniques is quite complex, and it is further complicated due to the increase in the number of subtypes within each family of ESBL. Therefore, it is often limited to reference laboratories and in the context of studies of molecular follow-up.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Risk factors for colonization and infection by extended-spectrum beta-lactamase producers</span><p id="par0070" class="elsevierStylePara elsevierViewall">We have conducted numerous case-control studies with the intention of determining the risk factors associated with colonization and infection by these pathogens. Although the analysis of the results of these studies is sometimes controversial because of differences in study populations, selection of cases, selection of controls, and sample size, some general conclusions can be drawn. There is high risk of infection or colonization by ESBL-producing pathogens in patients with prolonged hospital stay or that required invasive devices for long period of time (urinary catheter, endotracheal tube, central pathway). The hospital stay until the appearance of an isolated ESBL producer range from 11 to 67 depending on the series.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,18</span></a> Other factors that have been postulated in some studies in isolation include the presence of nasogastric tube, gastrostomy, or jejunostomy, arterial pathways, administration of parenteral nutrition, recent surgery (especially if it is urgent abdominal surgery), hemodialysis, bedsores, or poor nutritional status.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Advanced age and diagnosis of diabetes mellitus have also emerged as potential factors,<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> like traveling to endemic areas.</p><p id="par0075" class="elsevierStylePara elsevierViewall">The use of antibiotics in previous months has also been identified as a possible risk factor, with a wide range of variations depending on the studies: third-generation cephalosporins, aztreonam, quinolones, trimethoprim-sulfamethoxazole, aminoglycosides, and metronidazole.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> There is evidence at the same time of the association between infections due to isolated ESBL producers and the previous stay in care residences.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In these centers, the frequent use of antibiotic treatments is usual and patients may have other associated risk factors such as ulcers, urinary catheters, or recent hospitalization. Many of them also have urinary or fecal incontinence, thereby exposing other residents to risk of contamination.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Prevention strategies</span><p id="par0080" class="elsevierStylePara elsevierViewall">The main target that prevention programs should be focused on is nosocomial infection, which can occur in an epidemic or endemic manner. When it comes to clonal proliferation of a single strain, the transmission has occurred horizontally, but if it is not the same clone, it may mean that there has been a selection due to antibiotic use.</p><p id="par0085" class="elsevierStylePara elsevierViewall">The environment and potential vectors for infection must be disinfected, because contamination was found in gels used for ultrasounds, bronchoscopes, pressure cuffs, glass thermometers, and even in soaps, wedges, and baby baths. Several studies reveal that the hands of the healthcare personnel are an important transfer factor in horizontal contamination,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> so that proper hand hygiene (washing with chlorhexidine or alcohol solutions) is a simple but very effective measure to reduce the time transmission.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Many patients may act as a reservoir, especially those with colonization by ESBL-producing organisms without clinical manifestation of infection. In certain cases, especially when an outbreak occurs in a hospital or unit, identification of these patients and decolonization may be necessary. Oropharyngeal and rectal sampling with swab is required to perform isolation of the carrier patients. There have also been reports of colonization in wounds or ulcers. Finally, to control endemic infection it is important to implement a restrictive policy on the use of antibiotics, based primarily on avoiding the use of cephalosporins and quinolones.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Treatment recommendations</span><p id="par0095" class="elsevierStylePara elsevierViewall">The choice of appropriate treatment becomes complicated when we are facing ESBL-producing pathogens, among other factors, because many of these bacteria associate resistance to different antibiotics, as with quinolone resistance in CTX-M-producing strains.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> In addition, the plasmids that encode beta-lactam resistance often carry resistance genes to cotrimoxazole and aminoglycosides. In most cases, treatment should be started empirically and there are 48<span class="elsevierStyleHsp" style=""></span>h until the results of the cultures and the antibiogram are received. The delay or failure in starting appropriate therapy affects seriously increased morbidity and even mortality in severe infection.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> It is therefore essential to individualize the treatment of choice for each individual case based on a knowledge of the susceptibility patterns of each country, each city, and each hospital.</p><p id="par0100" class="elsevierStylePara elsevierViewall">There is another peculiarity which makes treatment of these infections difficult: clinical efficacy of a particular antibiotic does not always correspond to expectations for its in vitro activity. This fact is known as inoculum effect, which means that the MICs of antimicrobials can increase from 10 to 100 times simply because the bacterial load is large, and it was described for cephalosporins, piperacillin–tazobactam, and less in quinolones.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Other drugs such as cephamycins are not recommended because of the risk of developing resistance during treatment, due to the modification of membrane proteins (porins) which results in decreased permeability.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In summary, the use of cephalosporins must be avoided. In the case of the fourth-generation ones, their use is not recommended in severe infections, as they are very sensitive to the inoculum effect. In the case of using them, they should be administered at high doses and associated with another antimicrobial agent. Piperacillin–tazobactam is not recommended because of the high rate of resistance in many geographic areas and because it is also very sensitive to the inoculum effect. Cephamycins are a bad option due to the above mentioned, and aminoglycosides, cotrimoxazole, and quinolones should be restricted due to the high rate of co-resistance. On other agents such as temocillin and tigecycline, there are still not enough data available.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Thus, pending further evidence from randomized clinical trials, the treatment of choice for severe infections by gram-negative bacteria producing ESBL is carbapenems. However, its indiscriminate use should be avoided, since it is almost the only effective therapy against this type of microorganisms. In cases that they cannot be used because of intolerance or resistance, there is no specific treatment recommendation, although it is advisable to associate multiple antimicrobials. In the uncomplicated lower urinary tract infection, fosfomycin and nitrofurantoin seem to be the best therapeutic alternatives, because they both have good activity against ESBL. The use of nitrofurantoin is controversial because it requires longer treatment cycles, which makes therapeutic adherence difficult and may have toxic effects.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The failure of empirical treatment involves high morbidity and mortality and increased hospital costs, so we believe that therapeutic decisions should be based on knowledge of the local distribution of pathogens and their resistance patterns. In our environment, we proposed to define the patterns of susceptibility and antimicrobial resistance for this type of infections, in order to develop a treatment protocol. Positive urine cultures for ESBL-producing enterobacteria were analyzed in hospitalized patients or in those who had come to the emergency department from January to December 2013. Only one episode per patient was included, and in the case of having several urine cultures, the first one was selected. 92 patients were detected with a urine culture positive for ESBL-producing enterobacteriaceae, 69 (75%) <span class="elsevierStyleItalic">E. coli</span>, 20 (21.7%) <span class="elsevierStyleItalic">Klebsiella</span> sp., one (1.1%) <span class="elsevierStyleItalic">Enterobacter</span>, and 2 (2.2%) other pathogens. A total of 84.8% were resistant to ciprofloxacin, 69.7% to cotrimoxazole, 62% to amoxicillin–clavulanate, 37% to gentamicin, 31.5% to fosfomycin, and 10.9% and to nitrofurantoin. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the distribution of resistance depending on the pathogen. Only in 33% of the cases empirical treatment was adequate, and considered the administration of at least one antimicrobial with in vitro activity against the organism. No patient died of the infection. Taking these data into account, a protocol to facilitate the choice of treatment in patients with suspected infection with ESBL-producing microorganisms has been developed (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusions</span><p id="par0120" class="elsevierStylePara elsevierViewall">ESBLs are enzymes with hydrolytic ability against beta-lactam antibiotics, which confers resistance to penicillins, cephalosporins, and aztreonam. In vitro are inhibited by beta-lactamase inhibitors. They are often found in enterobacteriaceae, mainly in <span class="elsevierStyleItalic">Klebsiella</span> sp. and <span class="elsevierStyleItalic">Escherichia coli</span>, and they are associated to a high proportion of resistance to other antibiotics such as fluoroquinolones, aminoglycosides, or cotrimoxazole. Phenotypic methods are the most widely used for its detection, with high sensitivity and specificity if the expert recommendations for application are followed. Genotypic methods are carried out in specialized laboratories and provide essential information in order to prevent and control. Prevention strategies should focus on nosocomial infection, but it should not be forgotten that the epidemiology of these infections is changing and occurrence of these pathogens in community-acquired infections is becoming more and more frequent. The failure of empirical treatment involves high morbidity and mortality, so that therapeutic decisions should be based on knowledge of the local distribution of pathogens and their resistance patterns. The treatment of choice for severe infections due to ESBL-producing gram-negative bacteria is the carbapenems, so its indiscriminate use should be avoided.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:2 [ "identificador" => "xres385830" "titulo" => array:6 [ 0 => "Abstract" 1 => "Context" 2 => "Objective" 3 => "Acquisition of evidence" 4 => "Summary of the evidence" 5 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec364589" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres385829" "titulo" => array:6 [ 0 => "Resumen" 1 => "Contexto" 2 => "Objetivo" 3 => "Adquisición de evidencia" 4 => "Síntesis de evidencia" 5 => "Conclusión" ] ] 3 => array:2 [ "identificador" => "xpalclavsec364588" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Definition of extended-spectrum beta-lactamases" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Detection of extended-spectrum beta-lactamases" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Risk factors for colonization and infection by extended-spectrum beta-lactamase producers" ] 8 => array:2 [ "identificador" => "sec0020" "titulo" => "Prevention strategies" ] 9 => array:2 [ "identificador" => "sec0025" "titulo" => "Treatment recommendations" ] 10 => array:2 [ "identificador" => "sec0030" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-05-09" "fechaAceptado" => "2014-05-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec364589" "palabras" => array:4 [ 0 => "Extended-spectrum beta-lactamases" 1 => "Urinary tract infection" 2 => "Antibiotic resistance" 3 => "Carbapenems" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec364588" "palabras" => array:4 [ 0 => "Betalactamasas de espectro extendido" 1 => "Infección del tracto urinario" 2 => "Resistencia antibiótica" 3 => "Carbapenémicos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Context</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Beta-lactamases are bacterial enzymes that protect microorganisms from the lethal effects of β-lactam antibiotics. The production of beta-lactamases is the most important mechanism of resistance to these antibiotics, especially in Gram-negative bacteria.</p> <span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Review the magnitude of the problem of extended-spectrum beta-lactamases (ESBLs) in the urological setting and present the fundamental action guidelines on the issue, the main risk factors and the prevention strategies.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Acquisition of evidence</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A structured search strategy for patient, problem, intervention, comparison and result was conducted in the PubMed-Medline database to identify the most relevant studies related to the management of patients with urinary tract infection by ESBL-producing microorganisms. We also present a caseload analysis of our center on this issue.</p> <span class="elsevierStyleSectionTitle" id="sect0025">Summary of the evidence</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">ESBLs are found in Enterobacteria, mainly <span class="elsevierStyleItalic">Klebsiella</span> sp. and <span class="elsevierStyleItalic">Escherichia coli</span> and are characterized by their hydrolytic ability compared with beta-lactam antibiotics, which entails resistance to penicillin, cephalosporin and aztreonam. They are also associated with resistance to other antibiotics. There is a high risk of infection and colonization by ESBL producers in patients with prolonged hospital stays or who required invasive devices. The prior use of antibiotics and stays in residential care are also risk factors. Prevention programs should focus on preventing nosocomial infection. It is essential that a restrictive policy on the use of antibiotics be implemented. The therapy of choice for severe infections is focused on carbapenems, although their indiscriminate use should be avoided. In uncomplicated lower urinary tract infections, fosfomycin and nitrofurantoin are the best treatment alternatives.</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">ESBL-producing strains constitute a true global health problem. Prevention strategies should focus on nosocomial infection. We should not forget, however, that the appearance of these pathogens in community-acquired infections is increasingly frequent. Therapeutic decisions should be based on an understanding of the local distribution of microorganisms and their resistance patterns.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0040">Contexto</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Las betalactamasas son enzimas bacterianas que protegen a los microorganismos de los efectos letales de los antibióticos β-lactámicos. Su producción es el mecanismo más importante de resistencia a estos antibióticos, especialmente en bacterias gramnegativas.</p> <span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Revisar la magnitud del problema de las betalactamasas de espectro extendido (BLEE) en el ámbito urológico y presentar las pautas de actuación fundamentales al respecto, los principales factores de riesgo y las estrategias de prevención.</p> <span class="elsevierStyleSectionTitle" id="sect0050">Adquisición de evidencia</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se lleva a cabo una estrategia de búsqueda estructurada tipo paciente, problema, intervención, comparación y resultado en PubMed-Medline identificando los estudios más relevantes relacionados con el manejo de pacientes con infección urinaria por microorganismos productores de BLEE. Se presenta también análisis de la casuística de nuestro centro en esta misma problemática.</p> <span class="elsevierStyleSectionTitle" id="sect0055">Síntesis de evidencia</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Las BLEE se encuentran en enterobacterias, fundamentalmente <span class="elsevierStyleItalic">Klebsiella</span> sp. y <span class="elsevierStyleItalic">Escherichia coli</span> y se caracterizan por tener capacidad hidrolítica frente a los antibióticos betalactámicos, lo que implica resistencia frente a penicilinas, cefalosporinas y aztreonam. También se asocian a resistencia a otros antibióticos. Existe alto riesgo de infección o colonización por productores de BLEE en pacientes con estancia hospitalaria prolongada o que han precisado dispositivos invasivos. El uso previo de antibióticos y la estancia en residencia de cuidados son también elementos de riesgo. Los programas de prevención deben centrarse en evitar la infección nosocomial. Resulta fundamental implantar una política restrictiva en el uso de antibióticos. La terapia de elección en infecciones graves se centra en carbapenémicos, aunque debe evitarse su uso indiscriminado. En la infección de tracto urinario bajo no complicada fosfomicina y nitrofurantoína son las mejores alternativas terapéuticas.</p> <span class="elsevierStyleSectionTitle" id="sect0060">Conclusión</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Las cepas productoras de BLEE constituyen un verdadero problema de salud a nivel mundial. Las estrategias de prevención deben centrarse en la infección nosocomial, pero no debe olvidarse que cada vez es más frecuente la aparición de estos patógenos en infecciones comunitarias. Las decisiones terapéuticas deben basarse en el conocimiento de la distribución local de los microorganismos y sus patrones de resistencia.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: García-Tello A, Gimbernat H, Redondo C, Arana DM, Cacho J, Angulo JC. Betalactamasas de espectro extendido en las infecciones del tracto urinario causadas por enterobacterias: aproximación a su conocimiento y pautas de actuación. Actas Urol Esp. 2014;38:678–684.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 738 "Ancho" => 1500 "Tamanyo" => 186886 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Technique of positive double disk synergy to detect ESBL producing germs: difference equal to or greater than 5<span class="elsevierStyleHsp" style=""></span>mm in the diameter of the inhibition zone between the discs of each antimicrobial agent (cefotaxime and ceftazidime in different plate) with or without clavulanate (10<span class="elsevierStyleHsp" style=""></span>μg).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1900 "Ancho" => 2238 "Tamanyo" => 290319 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Protocol for choosing empiric therapy for suspected ESBL-producing pathogens.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Ciprofloxacin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Gentamicin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Amoxicillin-clavulanate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Fosfomycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Nitrofurantoin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Cotrimazole \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Escherichia coli</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23.2% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73.9% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Klebsiela</span> sp. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">80% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab591284.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Patterns of antibiotic resistance in patients hospitalized or seen in the emergency room from January to December 2013 at the University Hospital of Getafe, Madrid, Spain.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Penicillinase synthesis controlled by infectious R factors in <span class="elsevierStyleItalic">Enterobacteriaceae</span>" "autores" => array:1 [ 0 => array:2 [ "etal" => 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 May | 1 | 2 | 3 |
| 2018 February | 14 | 0 | 14 |
| 2018 January | 31 | 1 | 32 |
| 2017 December | 9 | 2 | 11 |
| 2017 November | 29 | 1 | 30 |
| 2017 October | 19 | 5 | 24 |
| 2017 September | 21 | 6 | 27 |
| 2017 August | 21 | 7 | 28 |
| 2017 July | 23 | 3 | 26 |
| 2017 June | 19 | 5 | 24 |
| 2017 May | 24 | 5 | 29 |
| 2017 April | 25 | 10 | 35 |
| 2017 March | 13 | 65 | 78 |
| 2017 February | 21 | 6 | 27 |
| 2017 January | 6 | 2 | 8 |
| 2016 December | 16 | 6 | 22 |
| 2015 October | 0 | 1 | 1 |
| 2015 July | 0 | 1 | 1 |
| 2015 January | 1 | 1 | 2 |
| 2014 December | 1 | 0 | 1 |
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