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    "titulo" => "Bacterial resistance unrelated to antibiotic use&#58; The perfect excuse&#63;"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Guidelines&#44; recommendations and stewardship programmes<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1&#8211;3</span></a> propose limiting antimicrobial exposure in humans as the core intervention to combat bacterial resistance&#46; Specifically&#44; it is expected that the risk of development of bacterial resistance to antibiotics will be reduced by shortening therapy and prophylaxis&#44; as well as avoiding indications like colonization or non-bacterial infections&#46; The underlying concept of these proposals is that direct contact of antimicrobials with the patient&#39;s flora provides a survival benefit to intrinsically resistant microorganisms by eliminating those that are susceptible and&#47;or directly induces mechanisms of resistance&#46; A multitude of more or less radical experiences limiting antimicrobial drug exposure<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> &#40;see also references 1&#8211;11 and 25&#8211;34 in &#193;lvarez-Lerma<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a>&#41; support that this strategy is associated with reduction&#44; whereas increases are followed by worsening rates of resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a> In discrepancy with these experiences and the accepted dogma&#44; however&#44; &#193;lvarez-Lerma et al&#46; report in this issue of <span class="elsevierStyleItalic">Medicina Intensiva</span> that consumption of several antipseudomonal antibiotics and their respective resistance in <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> are statistically unrelated&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a> The authors review ten years of the 3-monthly&#44; April to June&#44; Spanish National Nosocomial ICU-acquired Infection Surveillance Study &#40;ENVIN-HELICS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> A data base of 187&#46;100 critically ill patients&#44; 11&#46;652 &#40;6&#46;2&#37;&#41; of whom developed device-associated infection&#44; 2&#46;095 &#40;13&#46;6&#37;&#41; caused by <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; provides susceptibility data and consumption in days of antipseudomonal drug treatment over the 10-year study period&#46; The author&#39;s analyses show that significant reductions in consumption of aminoglycosides&#44; ceftazidime&#44; cefepime&#44; quinolones and carbapenems parallel significant increases in resistance of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> isolates to piperacillin-tazobactam&#44; imipenem&#44; meropenem&#44; ceftazidime and cefepime&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Potential causes of this lack of association&#44; as the authors correctly point out in their discussion&#44; are that some bacterial reservoirs remain unaffected by reductions in antibiotic administration in the intensive care unit&#46; A high percentage of patients being admitted to a given unit who have been or are currently on broad-spectrum antibiotics and carry or are infected with resistant bacteria may influence the efficacy of the combat against antimicrobial resistance of that unit&#44; more so&#44; if these are not detected at admission and barrier precautions are not implemented immediately&#46; Secondly&#44; the control of inanimate reservoirs of resistant bacteria is a formidable challenge in some units located in old buildings with contaminated tap water&#44; sinks&#44; and taps&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Other factors worth mentioning&#44; that may contribute to a lack of association of antibiotic consumption and resistance rates&#44; but are difficult to evaluate in retrospective analyses&#44; are prescription behaviour of non-antipseudomonal antibiotics&#44; both for therapy and prophylaxis&#44; as well as for infections other than those captured in ENVIN-HELICS&#46; Tracheobronchitis&#44; for example&#44; is currently a frequent and important indication for antibiotic administration in intubated patients&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> with 61&#37; caused by multidrug resistant bacteria and <span class="elsevierStyleItalic">P&#46; aeruginosa</span> being the most frequent cause&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The ratio of resistant to susceptible <span class="elsevierStyleItalic">Pseudomonas</span> strains may have shifted from the years 2006 to 2016 in Spanish ICUs by reductions of susceptible strains in the denominator&#46; This effect&#44; admittedly&#44; remains to be confirmed&#44; and would require assessment of the protective or risk-increasing effects of the individual components of the Spanish National infection prevention and resistance bundles&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">2&#44;9&#8211;11</span></a> which were implemented in early 2009&#44; as well as the synergistic combination of individual measures when applied in bundles&#46; Of note is&#44; that the above mentioned recommendations include direct antimicrobial interventions like the use of chlorhexidine for skin infection&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">2&#44;9</span></a> administration of topical antibiotics for selective decontamination of the digestive tract intubated patients<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a> and a short course of intravenous antibiotics for the prevention of primary endogenous pneumonia&#46; In fact&#44; &#193;lvarez-Lerma et al&#46; show that <span class="elsevierStyleItalic">Pseudomonas</span> isolates slightly decrease from 217 to 199 over the study period&#44; while the patient sample increases from 12&#44;000 to 24&#44;000 over the study period&#46; In other words&#44; prevention bundles may have reduced ICU-acquired infection rates&#44; with a greater impact on infections caused by the more susceptible flora&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Finally&#44; antibiotic diversity or heterogeneity has been associated with reductions in bacterial resistance&#44; meaning that overuse of certain classes of drugs with the same mechanism of action&#44; the opposite circumstance to diversity&#44; should be avoided&#46; Ideally&#44; a similar percentage of exposure to the different antibiotic classes&#44; i&#46;e&#46; 20&#37; of patients&#44; if 5 different groups are used&#44; should be receiving beta-lactams&#44; quinolones&#44; tetracyclines&#44; beta-lactam with beta-lactam inhibitor &#40;BL-BLI&#41;&#44; including the novel BL-BLI&#44; and fosfomycin&#44; in a given ICU&#46; This concept is antagonistic to antibiotic cycling&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">12</span></a> has been shown to be associated with lower resistance rates when compared to cycling<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">13</span></a> and has been proposed to reverse resistance in <span class="elsevierStyleItalic">P&#46; aeruginosa</span> in a situation of homogeneity due to overuse of carbapenems&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">6&#44;14</span></a> Table 2 in &#193;lvarez-Lerma et al&#46;&#8217;s manuscript&#44; in fact&#44; shows marked homogeneity or lack of diversity&#44; with noticeable preponderance of beta-lactam antibiotic use&#44; ranging from 53 to 83&#37; treatment days over the 10-year study period&#44; with carbapenems being the choice in 1 of 3 patients&#46; Achieving diversity is challenging&#44; because randomized clinical trials-based decision algorithms are needed to support each antibiotic drug choice&#44; but requires future studies to avoid the current overuse of carbapenems&#44; i&#46;e&#46; as a carbapenem-sparing strategy&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In summary&#44; &#193;lvarez-Lerma&#39;s study results strongly suggest that other infection control and antibiotic policy factors influence resistances rates and should be considered when generating strategic plans to combat bacterial resistance&#46; Rather than providing a waiver for the continued effort of reducing antibiotic exposure&#44; they should be interpreted as an indication of the need to expand our efforts and incorporate additional measures to increase efficacy in tackling the problem of bacterial resistance&#46;</p></span>"
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Editorial
Bacterial resistance unrelated to antibiotic use: The perfect excuse?
La resistencia bacteriana no está relacionada con el consumo de antibióticos: ¿la excusa perfecta?
M. Sánchez-García
Critical Care Department, Hospital Clínico San Carlos, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Guidelines&#44; recommendations and stewardship programmes<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1&#8211;3</span></a> propose limiting antimicrobial exposure in humans as the core intervention to combat bacterial resistance&#46; Specifically&#44; it is expected that the risk of development of bacterial resistance to antibiotics will be reduced by shortening therapy and prophylaxis&#44; as well as avoiding indications like colonization or non-bacterial infections&#46; The underlying concept of these proposals is that direct contact of antimicrobials with the patient&#39;s flora provides a survival benefit to intrinsically resistant microorganisms by eliminating those that are susceptible and&#47;or directly induces mechanisms of resistance&#46; A multitude of more or less radical experiences limiting antimicrobial drug exposure<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a> &#40;see also references 1&#8211;11 and 25&#8211;34 in &#193;lvarez-Lerma<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a>&#41; support that this strategy is associated with reduction&#44; whereas increases are followed by worsening rates of resistance&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">6</span></a> In discrepancy with these experiences and the accepted dogma&#44; however&#44; &#193;lvarez-Lerma et al&#46; report in this issue of <span class="elsevierStyleItalic">Medicina Intensiva</span> that consumption of several antipseudomonal antibiotics and their respective resistance in <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> are statistically unrelated&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">5</span></a> The authors review ten years of the 3-monthly&#44; April to June&#44; Spanish National Nosocomial ICU-acquired Infection Surveillance Study &#40;ENVIN-HELICS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> A data base of 187&#46;100 critically ill patients&#44; 11&#46;652 &#40;6&#46;2&#37;&#41; of whom developed device-associated infection&#44; 2&#46;095 &#40;13&#46;6&#37;&#41; caused by <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; provides susceptibility data and consumption in days of antipseudomonal drug treatment over the 10-year study period&#46; The author&#39;s analyses show that significant reductions in consumption of aminoglycosides&#44; ceftazidime&#44; cefepime&#44; quinolones and carbapenems parallel significant increases in resistance of <span class="elsevierStyleItalic">P&#46; aeruginosa</span> isolates to piperacillin-tazobactam&#44; imipenem&#44; meropenem&#44; ceftazidime and cefepime&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Potential causes of this lack of association&#44; as the authors correctly point out in their discussion&#44; are that some bacterial reservoirs remain unaffected by reductions in antibiotic administration in the intensive care unit&#46; A high percentage of patients being admitted to a given unit who have been or are currently on broad-spectrum antibiotics and carry or are infected with resistant bacteria may influence the efficacy of the combat against antimicrobial resistance of that unit&#44; more so&#44; if these are not detected at admission and barrier precautions are not implemented immediately&#46; Secondly&#44; the control of inanimate reservoirs of resistant bacteria is a formidable challenge in some units located in old buildings with contaminated tap water&#44; sinks&#44; and taps&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Other factors worth mentioning&#44; that may contribute to a lack of association of antibiotic consumption and resistance rates&#44; but are difficult to evaluate in retrospective analyses&#44; are prescription behaviour of non-antipseudomonal antibiotics&#44; both for therapy and prophylaxis&#44; as well as for infections other than those captured in ENVIN-HELICS&#46; Tracheobronchitis&#44; for example&#44; is currently a frequent and important indication for antibiotic administration in intubated patients&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">8</span></a> with 61&#37; caused by multidrug resistant bacteria and <span class="elsevierStyleItalic">P&#46; aeruginosa</span> being the most frequent cause&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The ratio of resistant to susceptible <span class="elsevierStyleItalic">Pseudomonas</span> strains may have shifted from the years 2006 to 2016 in Spanish ICUs by reductions of susceptible strains in the denominator&#46; This effect&#44; admittedly&#44; remains to be confirmed&#44; and would require assessment of the protective or risk-increasing effects of the individual components of the Spanish National infection prevention and resistance bundles&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">2&#44;9&#8211;11</span></a> which were implemented in early 2009&#44; as well as the synergistic combination of individual measures when applied in bundles&#46; Of note is&#44; that the above mentioned recommendations include direct antimicrobial interventions like the use of chlorhexidine for skin infection&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">2&#44;9</span></a> administration of topical antibiotics for selective decontamination of the digestive tract intubated patients<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a> and a short course of intravenous antibiotics for the prevention of primary endogenous pneumonia&#46; In fact&#44; &#193;lvarez-Lerma et al&#46; show that <span class="elsevierStyleItalic">Pseudomonas</span> isolates slightly decrease from 217 to 199 over the study period&#44; while the patient sample increases from 12&#44;000 to 24&#44;000 over the study period&#46; In other words&#44; prevention bundles may have reduced ICU-acquired infection rates&#44; with a greater impact on infections caused by the more susceptible flora&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Finally&#44; antibiotic diversity or heterogeneity has been associated with reductions in bacterial resistance&#44; meaning that overuse of certain classes of drugs with the same mechanism of action&#44; the opposite circumstance to diversity&#44; should be avoided&#46; Ideally&#44; a similar percentage of exposure to the different antibiotic classes&#44; i&#46;e&#46; 20&#37; of patients&#44; if 5 different groups are used&#44; should be receiving beta-lactams&#44; quinolones&#44; tetracyclines&#44; beta-lactam with beta-lactam inhibitor &#40;BL-BLI&#41;&#44; including the novel BL-BLI&#44; and fosfomycin&#44; in a given ICU&#46; This concept is antagonistic to antibiotic cycling&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">12</span></a> has been shown to be associated with lower resistance rates when compared to cycling<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">13</span></a> and has been proposed to reverse resistance in <span class="elsevierStyleItalic">P&#46; aeruginosa</span> in a situation of homogeneity due to overuse of carbapenems&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">6&#44;14</span></a> Table 2 in &#193;lvarez-Lerma et al&#46;&#8217;s manuscript&#44; in fact&#44; shows marked homogeneity or lack of diversity&#44; with noticeable preponderance of beta-lactam antibiotic use&#44; ranging from 53 to 83&#37; treatment days over the 10-year study period&#44; with carbapenems being the choice in 1 of 3 patients&#46; Achieving diversity is challenging&#44; because randomized clinical trials-based decision algorithms are needed to support each antibiotic drug choice&#44; but requires future studies to avoid the current overuse of carbapenems&#44; i&#46;e&#46; as a carbapenem-sparing strategy&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In summary&#44; &#193;lvarez-Lerma&#39;s study results strongly suggest that other infection control and antibiotic policy factors influence resistances rates and should be considered when generating strategic plans to combat bacterial resistance&#46; Rather than providing a waiver for the continued effort of reducing antibiotic exposure&#44; they should be interpreted as an indication of the need to expand our efforts and incorporate additional measures to increase efficacy in tackling the problem of bacterial resistance&#46;</p></span>"
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