Editorial
The challenge of multiresistant microorganisms
El reto de los microorganismos multirresistentes
Servicio de Medicina Intensiva, Hospital Universitario y Politécnico la Fe, Valencia, Spain
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Beside her, the family doctor watched, unable to stop the disease from progressing. Many years later, in the early 1940s, the beginning of large-scale use of penicillin greatly reduced the impotence of physicians and the mortality associated with bacterial infections. Since then, many bacteria have been identified and many antibiotics have been discovered and marketed. At the same time, and as if in competition, strains of bacteria that have mutated towards antibiotic resistance have been naturally selected. In fact, the first resistance of <span class="elsevierStyleItalic">Staphylococcus aureus</span> to penicillin was detected one year after the drug was marketed. In the case of methicillin it took 3 years of use before the first resistant strain was detected. None of the subsequently developed antibiotics has escaped the emergence of antibiotic resistant strains of <span class="elsevierStyleItalic">S. aureus</span>.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This is therefore a phenomenon inherent to the use of antibiotics and to which we must adapt. However, when the magnitude of the phenomenon reaches a quantitative and/or qualitative intensity that exceeds the production and distribution of the new molecules, adaptation is not feasible and the physician’s position reverts to that of Fields in his painting.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The number of infections caused by microorganisms that are not susceptible to antimicrobial agents (even though they were in the past) is growing exponentially.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> This includes multi-resistant bacteria, i.e., resistant to at least 3 antibiotic families.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The consequences are obvious: either there are no effective antimicrobial agents available, or they are not necessarily the ones that were empirically chosen. More than 20,000 patients in the US and more than 25,000 in Europe die each year from infection caused by multi-resistant microorganisms.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Moreover, the mortality of an infection caused by a multidrug-resistant strain can be up to twice as high as that observed for the same infection caused by a standard strain.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> And it is precisely the choice of an inappropriate antimicrobial that has the greatest impact on mortality.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The most important consideration is that, unlike other factors such as age or comorbidity, the presence of multidrug resistance and the choice of empiric antibiotic are elements over which we have control. Our interventions can be managed through actions aimed at reducing the selection and dissemination of multidrug-resistant strains or through the application of tools that allow us to predict the presence of multidrug-resistant strains and thus modulate the empirical choice of treatment in the particular patient.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The management of antimicrobial resistance requires a holistic approach in which all aspects involved are addressed.</p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Antimicrobial policy:</span> assessment of antibiotic use in hospital or primary care repeatedly shows unjustified overuse and involvement in the selection of multi-resistant strains. Antimicrobial stewardship (AMS) programmes are the key element in safely reducing unnecessary antimicrobial use.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a> Efforts must now focus on the generalisation of its implementation and the involvement of society.</p><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Research and development</span>: investment in the development of new antibiotics and alternative treatments is essential to stay ahead of the evolution of resistant strains.</p><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Epidemiological surveillance systems</span>: accurate acquisition of information and monitoring of the various indicators are essential for the detection of problems and the evaluation of the effectiveness of interventions.</p><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Nosocomial infection control:</span> the action of nosocomial infection control teams should be one of the main factual powers in hospitals, both in the specific prevention of the different infections and in the implementation of global and specific measures to prevent the cross transmission of microorganisms. As demonstrated in the SARS-CoV-2 pandemic, transmission control (use of masks, hand washing and isolation of cases) is essential to control epidemiological outbreaks.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">“One health” concept:</span> recognising the interconnection of human, animal and environmental health is essential to address the spread of resistant bacteria. All of these measures require the cooperation of individuals and must be led by political institutions and health administrations.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The global or ecological challenge coexists with the specific challenge of appropriate treatment of the patient affected by an infection caused by a multidrug-resistant microorganism. In the infected patient, antibiotic treatment, together with control of the focus and supportive care, is one of the main pillars of treatment. Once the responsible microorganism has been identified and characterised, it seems relatively straightforward to choose a drug from among those available that suits the microbiological and clinical findings. However, all clinicians are aware of the need to get the antimicrobial right at an early stage, and this means making an appropriate choice on an empirical basis, i.e., without delaying until the microbiological information is complete. Various clinical, microbiological and epidemiological tools have been used in the search for a predictor of multidrug resistance, but none has been able to achieve an accuracy that would completely rule out the overuse of broad-spectrum antimicrobials or a therapeutic deficit.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> So many elements are involved that the application of artificial intelligence seems to be a potential future option.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In both the empirical and targeted approaches, one of the biggest challenges for clinicians is the positioning of new molecules that cover today’s most complex resistance mechanisms and represent significant healthcare costs. Clearly a delay in administering these new molecules when they are indicated will mean a significant loss of the potential benefit they would bring, but overuse could mean the selection of new resistant strains in addition to the associated economic cost. In this complex equation, multi-resistance and the option to use new molecules brings a new example of health inequity. Multidrug resistance is a global problem although with clear geographical differences, but its epidemiological intervention and above all the treatment of the specific patient entails an economic cost that is difficult for lower income countries to bear.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The adaptation of the microorganism and the selection of antimicrobial resistant strains is a natural and evolutionary phenomenon. However, in recent times this selection has soared, reaching rates that are difficult to assume in some regions. The increase in antimicrobial use in healthcare and non-healthcare settings has followed a parallel and probably causal course. The control of the epidemiological situation and the appropriate treatment of patients are two challenges that we are currently facing and will probably continue to face to a greater or lesser extent in the future. However, interventions of greater or lesser magnitude have been shown to be able to mitigate and control the problem, suggesting the need for individual and institutional commitment to the problem of multidrug resistance.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical considerations</span><p id="par0055" class="elsevierStylePara elsevierViewall">None.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0060" class="elsevierStylePara elsevierViewall">None.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical considerations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:12 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> therapy: past, present, and future" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.A. 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