Vaccination strategies to combat nosocomial infections

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Seasons 2013-14 to 2019-20. Source: National Centre for Epidemiology.<a class="elsevierStyleCrossRef" href="#bb0025">5</a> *CSHCI: confirmed severe hospitalised cases of influenza." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Josep Marès Bermúdez" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Josep Marès" "apellidos" => "Bermúdez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1576988722000759" "doi" => "10.1016/j.vacun.2022.08.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1576988722000759?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2445146023000183?idApp=UINPBA00004N" "url" => "/24451460/0000002400000001/v1_202302281528/S2445146023000183/v1_202302281528/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Vaccination strategies to combat nosocomial infections" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "60" "paginaFinal" => "67" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Rajesh Venkataraman, Umesh Yadav, Ravi Kurikempannadoddi Shivalingegowda, Yogendra Shrestha" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Rajesh" "apellidos" => "Venkataraman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "af0005" ] ] ] 1 => array:4 [ "nombre" => "Umesh" "apellidos" => "Yadav" "email" => array:1 [ 0 => "umesh1yadav1@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "af0010" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cr0005" ] ] ] 2 => array:3 [ "nombre" => "Ravi Kurikempannadoddi" "apellidos" => "Shivalingegowda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "af0015" ] ] ] 3 => array:3 [ "nombre" => "Yogendra" "apellidos" => "Shrestha" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "af0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of pharmacy practice, Sri Adichunchanagiri College of pharmacy, B. G. Nagara, 571448, Karnataka, India" "etiqueta" => "a" "identificador" => "af0005" ] 1 => array:3 [ "entidad" => "Department of Pharmacy Practice, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B. G. Nagara-571448, Nagamangala, Karnataka, India" "etiqueta" => "b" "identificador" => "af0010" ] 2 => array:3 [ "entidad" => "Department of otorhinolaryngology and head & neck surgery, Adichunchanagiri Institute of Medical Sciences, B. G. Nagara, 571448, Karnataka, India" "etiqueta" => "c" "identificador" => "af0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cr0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1986 "Ancho" => 2479 "Tamanyo" => 389307 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Flowchart showing the CDC list of Nosocomial Infections." ] ] ] "textoCompleto" => "IntroductionNosocomial Infections (NIs) is one of the most frequent localized or systemic adverse events in healthcare worldwide despite of progress in public health and hospital care. It can be caused by bacteria, viruses, parasites, and fungi that may be present in the air, surfaces, or equipment surrounding the health institutions and continue to develop in hospitalized patients. It may affects patients well-being, can transmit the infection to other patients and healthcare staffs, increasing the length of hospital stay and their treatment cost. NIs, also called Hospital Acquired Infections (HAIs) and healthcare associated infections (HCAI), are defined as infections which are not present or not incubating when the patient is hospitalized and are acquired during the hospital stay. It is usually defined as an infection that is identified at least 48–72 h following admission to hospital.<a class="elsevierStyleCrossRef" href="#bb0005">1</a>,<a class="elsevierStyleCrossRef" href="#bb0010">2</a>According to a 2011 systematic analysis by the World Health Organization (WHO), the prevalence of NIs is ranged from 3.6 to 12% in high-income countries, affecting about 6 million patients in the United States and Europe and in low and middle income countries it has reached 5.7 to 19.1%, which is around 2.5 times higher than in high-income countries.<a class="elsevierStyleCrossRef" href="#bb0015">3</a> NIs contributes significant burden of disease globally and can have extremely high levels of antimicrobial use and antimicrobial resistance (AMR). According to a recent projection, by 2050, cancer deaths would no longer be the leading cause of death, with AMR-related mortality increasing roughly 15-fold to 10 million deaths annually.<a class="elsevierStyleCrossRef" href="#bb0020">4</a>,<a class="elsevierStyleCrossRef" href="#bb0025">5</a> This could heighten the urgency of developing new antibiotics. Vaccines can help with the issue of AMR in a variety of ways. It can lower the incidence of resistance by lowering the need for antibiotic use, and it can lower the severity of antibiotic resistance by lowering the overall number of incidents. Therefore, the development of vaccinations that prophylactically prevent common NIs would be an alternative and possibly more successful way to control AMR and NIs.<a class="elsevierStyleCrossRef" href="#bb0030">6</a>,<a class="elsevierStyleCrossRef" href="#bb0035">7</a>This review will place its emphasis on the epidemiology of the most common nosocomial pathogens as well as vaccines approved or in development for its management.Materials and methodsThe literature search for this review was performed by searching bibliographic databases including; Google Scholar, and PubMed (using free downloads as the research did not have financial support).The search terms used were: “Strategies,” “Immunization,” “Vaccination,” “Antimicrobial Resistance,” “Nosocomial Infections,” and “Healthcare-Associated Infections” followed by snowballing references cited by critical articles. All types of peer-reviewed articles published in English were included. Articles for which the full text was not available and those not written in English were excluded. From the articles retrieved in the first round of search, additional references were identified by a manual search among the cited references.Target pathogens for vaccine-based approaches against nosocomial infectionsTetanus, Diphtheria, and Pertussis, as well as other bacteria like meningococci, pneumococci, and mycobacterium tuberculosis that cause serious illnesses and are widely transmitted among the population, have been the main targets of traditional vaccine development. In the former, disease occurs only when toxins are present, such as when Tetanus toxin invades wounds or when Corynebacteria and Bordetella species release Diphtheria and Pertussis toxins into the respiratory system. Because toxin-neutralizing antibodies are a mediator of protection and are generated by vaccination, can be measured in international units (the absolute correlate of protection).<a class="elsevierStyleCrossRef" href="#bb0040">8</a> The infections brought on by meningococci, pneumococci, and pneumoniae are also crucial to keep in mind. Human-to-human transmission of many infections occurs through droplets from nasal and respiratory secretions. Notably, humans are the primary source of transmission for many pathogens, making vaccination an effective strategy for protecting the community as a whole and slowing the spread of these illnesses. The clinicians emphasized the significance of the ESKAPE pathogens, such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, in the context of AMR.<a class="elsevierStyleCrossRef" href="#bb0045">9</a>,<a class="elsevierStyleCrossRef" href="#bb0050">10</a>This acronym describes the most frequently encountered pathogens in hospital-acquired bacterial infections ranging from ventilator-associated pneumonia, catheter associated urinary tract infection and sepsis to wound infections. However, other infections, including those brought on by Clostridium difficile, have seen a rise in frequency and rates of antibiotic resistance<a class="elsevierStyleCrossRef" href="#bb0055">11</a> and have been added to the list of nosocomial pathogens and possible bacterial targets for vaccine development. ESCAPE pathogens are the names given to them most often today (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae).The Center of Disease Control and Prevention (CDC) has listed out different Nosocomial Infections (<a href="https://www.cdc.gov/hai/organisms/organisms.html">https://www.cdc.gov/hai/organisms/organisms.html</a>), which are shown in the <a class="elsevierStyleCrossRef" href="#f0005">Fig. 1</a>, and also the global antibiotic resistance rates associated with major bacterial pathogens,<a class="elsevierStyleCrossRef" href="#bb0060">12</a> were shown in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>.<elsevierMultimedia ident="f0005"></elsevierMultimedia><elsevierMultimedia ident="t0005"></elsevierMultimedia>Vaccine against ESCAPE pathogensEnterococcus faeciumA member of the Enterococcus genus, Enterococcus faecium is a Gram-positive, gamma-hemolytic or non-hemolytic bacterium. It is one of the typical members of the gut flora and can lead to serious illness in the elderly or people who already have other medical conditions, such as people who have diabetes or chronic kidney failure. It is regarded as one of the major factors contributing to nosocomial infections.<a class="elsevierStyleCrossRef" href="#bb0065">13</a>,<a class="elsevierStyleCrossRef" href="#bb0070">14</a> Enterococcus can cause urinary tract infections (UTIs), pelvic and intraabdominal infections, bacteriemia, infective endocarditis, and infections of the nervous system. These are just a few of the illnesses that enterococcus can cause. Public health is severely challenged by the rapidly rising frequency of vancomycin-resistant enterococci (VRE) in general.<a class="elsevierStyleCrossRef" href="#bb0075">15</a> The United States has the greatest rates of vancomycin resistance; from 2009 to 2010. VRE was accountable for 35.5% of all enterococcal infections and 79.5% to 83.3% of Enterococcus faecium bloodstream infections.<a class="elsevierStyleCrossRef" href="#bb0080">16</a>,<a class="elsevierStyleCrossRef" href="#bb0085">17</a> The enterococcal antibiotic resistance genes could spread to other microorganisms, which is a concern for VRE because of the high mortality rate attributed to VRE infection.<a class="elsevierStyleCrossRef" href="#bb0065">13</a>,<a class="elsevierStyleCrossRef" href="#bb0080">16</a> The highest incidence of VRE due to nosocomial infections in Europe has been observed in southern European countries.<a class="elsevierStyleCrossRef" href="#bb0090">18</a> The development of novel treatments for Enterococcus faecium is thought to be of high importance according to the World Health Organization's 2017 issuance of a list of 12 antibiotic-resistant bacteria that pose the greatest risk to human health.<a class="elsevierStyleCrossRef" href="#bb0095">19</a> In order to better understand and treat VRE, investigation and the development of innovative medicines are key objectives.Targeting capsular polysaccharides (CPS), which are successfully employed in a number of other bacterial vaccines, is one approach for developing an enterococcus vaccine that is currently being investigated in preclinical studies. Preclinical research on CPS showed some effectiveness in reducing bacterial load, and some data indicates that serotype-C makes up the majority of pathogenic strains, raising the prospect of creating a CPS vaccine with broad immunologic protection.<a class="elsevierStyleCrossRef" href="#bb0100">20</a> An alternate technique is being investigated specifically to avoid catheter-associated infections such as urinary tract infections, blood stream infections, and so on by reducing biofilm formation.<a class="elsevierStyleCrossRef" href="#bb0105">21</a> More research is needed to develop a reliable vaccine to combat VRE and lower the AMR reservoir. VRE is frequently found in immune-compromised persons.<a class="elsevierStyleCrossRef" href="#bb0085">17</a> The invention of an enterococcal vaccination would assist patients with higher risk factors by extending their survival rate and shortening their duration of stay, lowering stress on the health-care system.<a class="elsevierStyleCrossRef" href="#bb0110">22</a>Probiotics are being suggested as a possible substrate for the synthesis of recombinant vaccines bearing cells of the immune system. In 2021, Yulia Desheva et al., developed and validated a live mucosal recombinant vaccine by incorporating genes expressing influenza virus neuraminidase (NA) of the N2 subtype into the DNA of the probiotic strain Enterococcus faecium L3. Researchers demonstrated NA expression in the pili of L3 and its immunization raised chance of survival by 34%. They indicated that oral dosing of probiotic vaccines developed by this technology could be beneficial for anti-viral protection in both humans and farm animals.<a class="elsevierStyleCrossRef" href="#bb0115">23</a>Staphylococcus aureusStaphylococcus aureus is gram-positive bacteria that is found in 30% of the general population<a class="elsevierStyleCrossRef" href="#bb0120">24</a> is a major cause of invasive disorders such bacteriemia, infected endocarditis, osteomyelitis, pneumonia, and a number of skin and soft tissue infections in both hospitals and the general community. More than 40% of nosocomial infections in patients who have undergone surgery are caused by surgical site infections (SSIs). Currently, between 300,000 and 500,000 cases are thought to occur annually in the United States.<a class="elsevierStyleCrossRef" href="#bb0125">25</a>,<a class="elsevierStyleCrossRef" href="#bb0130">26</a> Around one-fourth of pneumonia admissions worldwide are attributed to Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA) accounts for almost half of healthcare-associated pneumonia (HAP) or ventilator-associated pneumonia (VAP).<a class="elsevierStyleCrossRef" href="#bb0135">27</a> Bacterial resistance against B-lactams as well as other types of antibiotics can make infections more difficult to treat. MRSA infections are more difficult to treat than methicillin-sensitive variants, and they are attributed to longer hospital admissions, higher morbidity, and higher mortality rates.General infection management and the use of prophylactic antibiotics, such as the topical antimicrobial mupirocin, which targets Staphylococcus aureus, are preventive interventions against Staphylococcus aureus infection.<a class="elsevierStyleCrossRef" href="#bb0140">28</a> Pfizer's SA4Ag candidate, which consists of four antigens clumping factor A, a virulence factor that enables Staphylococcus aureus to bind to fibrinogen; the manganese transporter MntC; CP5; and CP8 is the only active advanced Staphylococcus aureus vaccine project at the moment. Phase 1 studies revealed quick production of functional antibodies that lasted for at least a year.<a class="elsevierStyleCrossRef" href="#bb0145">29</a> In the STRIVE trial (Staphylococcus aureus Surgical Inpatient Vaccine Effectiveness), a phase 2b placebo-controlled safety and efficacy study of SA4Ag in people undergoing elective spinal fusion surgery is now underway.<a class="elsevierStyleCrossRef" href="#bb0150">30</a>Clostridium difficileThe most common source of nosocomial infectious diarrhea in industrialized nations is Clostridium difficile, a gram-positive, anaerobic, spore-forming bacillus. It is the most often identified cause of infectious diarrhea in healthcare settings, accounting for 20–30% of episodes of diarrhea that appear following the administration of antibiotics and resulting in disturbance of the normal gut microbiota.<a class="elsevierStyleCrossRef" href="#bb0155">31</a> Around 2–7% of the overall population and 13–51% of hospital patients are carriers of Clostridium difficile. Adults over 65 who recently used antibiotics have the greatest chance of getting Clostridium difficile infections (CDIs).<a class="elsevierStyleCrossRef" href="#bb0160">32</a>,<a class="elsevierStyleCrossRef" href="#bb0165">33</a>Annually, there are 29,000 CDI-related deaths and over 500,000 new cases of CDI detected in the US alone. The CDC has identified Clostridium difficile as an urgent hazard due to the high incidence of CDIs and the quick emergence of outbreaks and antibiotic-resistant strains.<a class="elsevierStyleCrossRef" href="#bb0170">34</a> The occurrence of CDIs, as well as their pathogenicity and mortality, has increased dramatically over the last ten years.<a class="elsevierStyleCrossRef" href="#bb0175">35</a> These patterns have been linked to Clostridium difficile (BI/NAP1/027) epidemic strains, which exhibit increased pathogenicity.<a class="elsevierStyleCrossRef" href="#bb0180">36</a>,<a class="elsevierStyleCrossRef" href="#bb0185">37</a>The gut micro-biota plays a key role in CDI defense, and disruption of this ecosystem by antibiotic use causes substantial changes in the metabolic environment that support Clostridium difficile germination and growth (especially in the ratio of the primary and secondary bile acids and carbon sources). Whenever Clostridium difficile is vegetative, it generates the two exotoxins, toxin A and toxin B, which become its main virulence components. Binary toxin, a third toxin that is expressed by BI/NAP1/027 strains of Clostridium difficile, also seems to play a role in pathogenesis.<a class="elsevierStyleCrossRef" href="#bb0195">38</a>,<a class="elsevierStyleCrossRef" href="#bb0200">39</a> The provoking antibiotics must be withdrawn in order to treat CDI, and new antibiotics (vancomycin, metronidazole, or fidaxomicin) must be used in their place. Moreover, at least one relapse occurs in 20% of patients, and the likelihood of relapse rises with each succeeding episode.<a class="elsevierStyleCrossRef" href="#bb0205">40</a> Early preclinical investigations showed that antitoxin antibodies and active immunization using inactivated toxins (toxoids) may prevent animals from developing CDI.<a class="elsevierStyleCrossRef" href="#bb0210">41</a> This discovery finally resulted in the development of the non-antibiotic therapy bezlotoxumab, a monoclonal antibody towards TcdB that has been recently approved and which is intended to stop CDI relapse after the first infection.<a class="elsevierStyleCrossRef" href="#bb0215">42</a>The toxoid-based vaccine's clinical development was declared to come to an end due to the low probability that the phase 3 research (<a href="ctgov:NCT01887912">NCT01887912</a>) will achieve its main goal.<a class="elsevierStyleCrossRef" href="#bb0220">43</a> The combination of genetically altered as well as further detoxified TcdA and TcdB from Clostridium difficile, the main virulence factors generated by the organism, is the only vaccine now under research.<a class="elsevierStyleCrossRef" href="#bb0225">44</a> As a consequence of successful phase 1 and phase 2 studies (<a href="ctgov:NCT03090191">NCT03090191</a>), this vaccine has moved to phase 3 studies.<a class="elsevierStyleCrossRef" href="#bb0230">45</a>,<a class="elsevierStyleCrossRef" href="#bb0235">46</a> In March 2022, Pfizer released findings from the pivotal Phase 3 CLOVER trial (Clostridium difficile Vaccine Efficacy TRial), which assessed the efficacy of their Clostridium difficile vaccine candidate (PF-06425090) in preventing CDI. Even though the trial did not accomplish its pre-specified primary aim of prevention of primary CDI, initial assessments of 2 protocol-specified secondary endpoints demonstrated a highly favorable impact on lowering CDI severity and 100% vaccination effectiveness in decreasing medically treated CDI. The experimental vaccination was well tolerated and safe, according to safety reviews.<a class="elsevierStyleCrossRef" href="#bb0240">47</a>Acinetobacter baumanniiAcinetobacter are non-motile, Gram-negative coccobacilli which are most frequently found in sewage water, and soil. There are more than 50 distinct Acinetobacter species, the majority of which are not harmful. Generally, Acinobacter baumannii is regarded as an opportunistic pathogen that primarily affects hospitalized patients, those with impaired immune systems, and military personnel with war wounds, particularly in humid areas.<a class="elsevierStyleCrossRef" href="#bb0245">48</a> The peritoneal system, respiratory tract, and urinary tract are among of the organs and organ systems where Acinobacter baumannii pathogens are most common. Pneumonia, sepsis, skin and soft tissue infections, and meningitis are the most frequently infections associated with this pathogen.<a class="elsevierStyleCrossRef" href="#bb0250">49</a>According to research, Acinetobacter baumannii causes approximately 12% of all hospital-acquired infections worldwide.<a class="elsevierStyleCrossRef" href="#bb0255">50</a> One of the most typical clinical manifestations is pneumonia developed in patients undergoing respiratory support in an intensive care setting.<a class="elsevierStyleCrossRef" href="#bb0260">51</a> Because of the widespread use of antibiotic resistance, these pneumonia cases might be challenging to treat. According to a recent meta-analysis of 126 studies from 29 countries, multidrug-resistant Acinetobacter baumannii was found in 80% of ventilator- and hospital-acquired pneumonia patients.<a class="elsevierStyleCrossRef" href="#bb0265">52</a>Several vaccine antigens have already been investigated through preclinical trials, but there are still a lot of fundamental problems about proper antigen identification and beneficial immunological pathways.<a class="elsevierStyleCrossRef" href="#bb0270">53</a> The outer membrane protein 22 (Omp22) has been found to provide some prevention against the Acinetobacter baumannii threat in mice in research conducted using an outer membrane vesicle (OMV)-based vaccine.<a class="elsevierStyleCrossRef" href="#bb0275">54</a> Omp22 may be a viable strategy for an OMV-based human vaccine, but it's unclear given the insufficiency of several animal models for predicting human safeguards.<a class="elsevierStyleCrossRef" href="#bb0280">55</a>Pseudomonas aeruginosaPseudomonas aeruginosa is gram-negative comes under multi-drug resistant bacteria that affects immune-compromised individuals globally and causing fatal HAI.<a class="elsevierStyleCrossRef" href="#bb0285">56</a> It is a common environmental infection that prefers humid settings. In susceptible patients with altered or damaged epithelial barriers caused by cystic fibrosis, burn, wounds, and chemo-drugs, it can infiltrate in to the human mucosa.<a class="elsevierStyleCrossRef" href="#bb0290">57</a> With an estimated 51,000 Pseudomonas aeruginosa infections caused by medical care each year in the United States' hospitals. The blood stream infections are common, among infections associated with transplants and surgery, and urinary catheterization. Severe burns, cystic fibrosis, illnesses that impair immunity and other disorders that are more prevalent in hospital admissions are major risk factors for Pseudomonas infestations.<a class="elsevierStyleCrossRefs" href="#bb0295">58–60</a>Immunization is likely the most successful strategy to resolving the issues caused by Pseudomonas aeruginosa's multi-drug resistance. Although several Pseudomonas aeruginosa vaccines have entered clinical trials,<a class="elsevierStyleCrossRef" href="#bb0310">61</a> none has been authorized for use in humans. The translational fusion of the OMPs, OprF, and OprI recombinantly generated by Escherichia coli (IC43 vaccine) has been recently tested in a Phase II/III clinical study, but it was unable to trigger the necessary immune responses or lower the mortality.<a class="elsevierStyleCrossRef" href="#bb0315">62</a> A monoclonal antibody called MEDI3902 that works to prevent Pseudomonas aeruginosa infection has also advanced to phase 2 evaluations in patients receiving mechanical ventilation (<a href="ctgov:NCT02696902">NCT02696902</a>) as a result of promising preclinical evidence.<a class="elsevierStyleCrossRef" href="#bb0320">63</a>EnterobacteriaceaeEnterobacteriaceae is a broad genus of gram-negative bacteria that are inhabitants of the normal gut flora and can be a common source of NIs that are easily transmitted among patients. Perhaps the most well known pathogens are Escherichia coli, Klebsiella species, and Enterobacter species. Conventional antibiotics are not effective against Enterobacteriaceae, and carbapenems are only used as a last option.<a class="elsevierStyleCrossRef" href="#bb0325">64</a>,<a class="elsevierStyleCrossRef" href="#bb0330">65</a> The emergence of carbapenem-resistant Enterobacteriaceae is thus a considerable concern, especially given that fatality rates of up to 50% have been reported.<a class="elsevierStyleCrossRef" href="#bb0325">64</a>,<a class="elsevierStyleCrossRef" href="#bb0335">66</a> The WHO considers carbapenem-resistant Enterobacteriaceae to be a serious AMR concern.<a class="elsevierStyleCrossRef" href="#bb0340">67</a>Escherichia coli immunization approaches, such as live attenuated strains, entire inactivated strains, and subunit vaccines, are being researched to combat recurring UTIs. Through clinical studies, commonly available vaccines usually contain attenuated strains, such as Uromune® (a vaccine comprising strains from Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, and Proteus vulgaris) and Solco Urovac® (a vaccine containing 6 Escherichia coli strains along with strains from Proteus mirabilis, Klebsiella pneumoniae, Proteus morganii, and Escherichia faecalios) have shown little efficacy in clinical trials.<a class="elsevierStyleCrossRef" href="#bb0345">68</a>,<a class="elsevierStyleCrossRef" href="#bb0350">69</a> Considering these advancements, additional vaccination strategies are essential for the control of invasive Escherichia coli infection.Conclusion & future directionsIn spite of the widespread implementation of preventive strategies, Nosocomial infections continue to be a significant disease burden globally, and research has shown a high inflation of AMR in the past few years,<a class="elsevierStyleCrossRef" href="#bb0020">4</a>,<a class="elsevierStyleCrossRef" href="#bb0355">70</a> suggesting alternative solutions to control these infections are really important. However, for most of the pathogens involved in HAIs vaccines are not currently available and the development of effective vaccines for nosocomial pathogens remains challenging. Most approaches of vaccine development are directed against the surface component of pathogens (outer membrane protein, capsular polysaccharides, toxoid-based etc) and attenuated bacteria (probiotics).To deliver the greatest public-health advantages, efforts must be made to steadily improve vaccine coverage and also to finish study and licensing procedures for novel vaccines that address significant bacterial and viral pathogens for which vaccines previously did not exist. As a result, it is vital that vaccine research be promoted as a major global priority, with a special emphasis on the development of broadly protective vaccines targeting pathogens with high AMR rates.ContributionsRajesh Venkataraman and Ravi Kurikempannadoddi Shivalingegowda had conceptualization, supervision, visualization, and reviewing and editing. Umesh Yadav and Yogendra Shrestha did the conceptualization, search, data curation, and writing of the original draft.FundingThis study did not receive any particular funding." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1855526" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "as0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1613251" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1855525" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "as0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1613252" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "s0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "s0010" "titulo" => "Materials and methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "s0015" "titulo" => "Target pathogens for vaccine-based approaches against nosocomial infections" ] 1 => array:3 [ "identificador" => "s0020" "titulo" => "Vaccine against ESCAPE pathogens" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "s0025" "titulo" => "Enterococcus faecium" ] 1 => array:2 [ "identificador" => "s0030" "titulo" => "Staphylococcus aureus" ] 2 => array:2 [ "identificador" => "s0035" "titulo" => "Clostridium difficile" ] 3 => array:2 [ "identificador" => "s0040" "titulo" => "Acinetobacter baumannii" ] 4 => array:2 [ "identificador" => "s0045" "titulo" => "Pseudomonas aeruginosa" ] 5 => array:2 [ "identificador" => "s0050" "titulo" => "Enterobacteriaceae" ] ] ] ] ] 6 => array:2 [ "identificador" => "s0055" "titulo" => "Conclusion & future directions" ] 7 => array:2 [ "identificador" => "s0060" "titulo" => "Contributions" ] 8 => array:2 [ "identificador" => "s0065" "titulo" => "Funding" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-09-20" "fechaAceptado" => "2022-11-05" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1613251" "palabras" => array:4 [ 0 => "Nsocomial infections" 1 => "Vaccine" 2 => "Pathogens" 3 => "Antibiotic resistance" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1613252" "palabras" => array:4 [ 0 => "infecciones nosocomiales" 1 => "vacuna" 2 => "patógenos" 3 => "resistencia a antibióticos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "In spite of the widespread implementation of preventive strategies, nosocomial infections are one of the most frequent localized or systemic adverse events in healthcare worldwide despite of progress in public health and hospital care. The risk factors for these infections increased due to underlying health issues, immune-compromised individuals, increased age, and prolonged hospitalization of patients. Although a few novel antibiotics have recently been put into clinical practice, the exploration of alternative techniques to effectively battle nosocomial infections is urgently required to reduce the significant burden. Many common nosocomial pathogens have growing rates of antibiotic resistance, exacerbating the situation and emphasizing the need for preventative alternatives to antibiotic treatment, such as immunological strategies based on vaccine development or therapeutic antibodies, which may significantly enhance their control. This review will concentrate on the epidemiology of the most frequent nosocomial pathogens, as well as vaccines authorized or in development for the prevention of ESCAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae)." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Las infecciones nosocomiales constituyen uno de los eventos adversos localizados o sistémicos más frecuentes en la atención sanitaria a nivel mundial a pesar de los avances en salud pública y atención hospitalaria. Los factores de riesgo de estas infecciones aumentan debido a problemas de salud subyacentes, personas inmunocomprometidas, edad avanzada y hospitalización prolongada de los pacientes. Sin embargo, muchos patógenos nosocomiales comunes tienen tasas crecientes de resistencia a los antibióticos, lo que exacerba la situación y enfatiza la necesidad de alternativas preventivas al tratamiento con antibióticos, como las vacunas. En muchas circunstancias, las tasas de mortalidad relacionadas con las infecciones nosocomiales resistentes a los antibióticos son altas. Esta revisión pondrá énfasis en las infecciones nosocomiales junto con la patogenia y la enfermedad, los tratamientos disponibles y la revisión de las vacunas actualmente aprobadas o en preparación para el manejo de los patógenos ESCAPE (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa y Enterobacteriaceae)." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1986 "Ancho" => 2479 "Tamanyo" => 389307 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Flowchart showing the CDC list of Nosocomial Infections." ] ] 1 => array:8 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "The percentage of tested isolates that were resistant to each antibiotic class used for each infection is listed along with antibiotic resistance data from 2000 to 2014 for each pathogen. These medications target particular pathogens. Data for all pathogens were obtained from the Center for Disease Dynamics, Economics and Policy (https://resistancemap.cddep.org/). ND, no data provided." "tablatextoimagen" => array:1 [ 0 => array:1 [ "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"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pathogens</th><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="4" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Resistance rate (%)</th></tr><tr title="table-row"><th 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" scope="col" style="border-bottom: 2px solid black">United States \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">India \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">South Africa \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">UK \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Staphyloccus aureus \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–45 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–94 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–29 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Streptocococcus pneumoniae \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17–34 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7–8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acinetobacter baumannii \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6–49 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3–90 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–41 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pseudomonas aerugionasa \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–26 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–69 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–35 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3–14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Enterobacter spp. \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5–88 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3–100 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Klebsiella pneumonia \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8–22 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–80 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–68 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Escherichia coli \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1–55 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11–92 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–84 \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0–55 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Worldwide antibiotic resistance rates associated with major pathogens." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:70 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nosocomial infections and their control strategies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H.A. Khan" 1 => "A. Ahmad" 2 => "R. Mehboob" ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "APJTB" "fecha" => "2015" "volumen" => "5" "numero" => "7" "paginaInicial" => "509" "paginaFinal" => "514" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.apjtb.2015.05.001" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bb0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:1 [ "host" => array:2 [ 0 => array:1 [ "LibroEditado" => array:4 [ "editores" => "World Health Organization, G.Ducel, J.Fabry, L.Nicolle" "titulo" => "Prevention of hospital-acquired infections: a practical guide" "edicion" => "2nd. ed" "serieFecha" => "2002" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://apps.who.int/iris/handle/10665/67350" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bb0015" "etiqueta" => "3." 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Review article

Vaccination strategies to combat nosocomial infections

Rajesh Venkataramana, Umesh Yadavb,

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umesh1yadav1@gmail.com

Corresponding author.

, Ravi Kurikempannadoddi Shivalingegowdac, Yogendra Shresthab

a Department of pharmacy practice, Sri Adichunchanagiri College of pharmacy, B. G. Nagara, 571448, Karnataka, India

b Department of Pharmacy Practice, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B. G. Nagara-571448, Nagamangala, Karnataka, India

c Department of otorhinolaryngology and head & neck surgery, Adichunchanagiri Institute of Medical Sciences, B. G. Nagara, 571448, Karnataka, India

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Nosocomial Infections &#40;NIs&#41; is one of the most frequent localized or systemic adverse events in healthcare worldwide despite of progress in public health and hospital care&#46; It can be caused by bacteria&#44; viruses&#44; parasites&#44; and fungi that may be present in the air&#44; surfaces&#44; or equipment surrounding the health institutions and continue to develop in hospitalized patients&#46; It may affects patients well-being&#44; can transmit the infection to other patients and healthcare staffs&#44; increasing the length of hospital stay and their treatment cost&#46; NIs&#44; also called Hospital Acquired Infections &#40;HAIs&#41; and healthcare associated infections &#40;HCAI&#41;&#44; are defined as infections which are not present or not incubating when the patient is hospitalized and are acquired during the hospital stay&#46; It is usually defined as an infection that is identified at least 48&#8211;72&#8239;h following admission to hospital&#46;<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">According to a 2011 systematic analysis by the World Health Organization &#40;WHO&#41;&#44; the prevalence of NIs is ranged from 3&#46;6 to 12&#37; in high-income countries&#44; affecting about 6 million patients in the United States and Europe and in low and middle income countries it has reached 5&#46;7 to 19&#46;1&#37;&#44; which is around 2&#46;5 times higher than in high-income countries&#46;<a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> NIs contributes significant burden of disease globally and can have extremely high levels of antimicrobial use and antimicrobial resistance &#40;AMR&#41;&#46; According to a recent projection&#44; by 2050&#44; cancer deaths would no longer be the leading cause of death&#44; with AMR-related mortality increasing roughly 15-fold to 10 million deaths annually&#46;<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> This could heighten the urgency of developing new antibiotics&#46; Vaccines can help with the issue of AMR in a variety of ways&#46; It can lower the incidence of resistance by lowering the need for antibiotic use&#44; and it can lower the severity of antibiotic resistance by lowering the overall number of incidents&#46; Therefore&#44; the development of vaccinations that prophylactically prevent common NIs would be an alternative and possibly more successful way to control AMR and NIs&#46;<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">This review will place its emphasis on the epidemiology of the most common nosocomial pathogens as well as vaccines approved or in development for its management&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0030">Materials and methods</span><p id="p0020" class="elsevierStylePara elsevierViewall">The literature search for this review was performed by searching bibliographic databases including&#59; Google Scholar&#44; and PubMed &#40;using free downloads as the research did not have financial support&#41;&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">The search terms used were&#58; &#8220;Strategies&#44;&#8221; &#8220;Immunization&#44;&#8221; &#8220;Vaccination&#44;&#8221; &#8220;Antimicrobial Resistance&#44;&#8221; &#8220;Nosocomial Infections&#44;&#8221; and &#8220;Healthcare-Associated Infections&#8221; followed by snowballing references cited by critical articles&#46; All types of peer-reviewed articles published in English were included&#46; Articles for which the full text was not available and those not written in English were excluded&#46; From the articles retrieved in the first round of search&#44; additional references were identified by a manual search among the cited references&#46;</p><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Target pathogens for vaccine-based approaches against nosocomial infections</span><p id="p0030" class="elsevierStylePara elsevierViewall">Tetanus&#44; Diphtheria&#44; and Pertussis&#44; as well as other bacteria like meningococci&#44; pneumococci&#44; and <span class="elsevierStyleItalic">mycobacterium tuberculosis</span> that cause serious illnesses and are widely transmitted among the population&#44; have been the main targets of traditional vaccine development&#46; In the former&#44; disease occurs only when toxins are present&#44; such as when Tetanus toxin invades wounds or when Corynebacteria and Bordetella species release Diphtheria and Pertussis toxins into the respiratory system&#46; Because toxin-neutralizing antibodies are a mediator of protection and are generated by vaccination&#44; can be measured in international units &#40;the absolute correlate of protection&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> The infections brought on by meningococci&#44; pneumococci&#44; and pneumoniae are also crucial to keep in mind&#46; Human-to-human transmission of many infections occurs through droplets from nasal and respiratory secretions&#46; Notably&#44; humans are the primary source of transmission for many pathogens&#44; making vaccination an effective strategy for protecting the community as a whole and slowing the spread of these illnesses&#46; The clinicians emphasized the significance of the <span class="elsevierStyleItalic">ESKAPE</span> pathogens&#44; such as <span class="elsevierStyleItalic">Enterococcus faecium</span>&#44; <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; <span class="elsevierStyleItalic">Klebsiella pneumoniae</span>&#44; <span class="elsevierStyleItalic">Acinetobacter baumannii</span>&#44; <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#44; and Enterobacter species&#44; in the context of AMR&#46;<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a></p><p id="p0035" class="elsevierStylePara elsevierViewall">This acronym describes the most frequently encountered pathogens in hospital-acquired bacterial infections ranging from ventilator-associated pneumonia&#44; catheter associated urinary tract infection and sepsis to wound infections&#46; However&#44; other infections&#44; including those brought on by <span class="elsevierStyleItalic">Clostridium difficile</span>&#44; have seen a rise in frequency and rates of antibiotic resistance<a class="elsevierStyleCrossRef" href="#bb0055"><span class="elsevierStyleSup">11</span></a> and have been added to the list of nosocomial pathogens and possible bacterial targets for vaccine development&#46; <span class="elsevierStyleItalic">ESCAPE</span> pathogens are the names given to them most often today &#40;<span class="elsevierStyleItalic">Enterococcus faecium</span>&#44; <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; <span class="elsevierStyleItalic">Clostridium difficile</span>&#44; <span class="elsevierStyleItalic">Acinetobacter baumannii</span>&#44; <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#44; and Enterobacteriaceae&#41;&#46;</p><p id="p0040" class="elsevierStylePara elsevierViewall">The Center of Disease Control and Prevention &#40;CDC&#41; has listed out different Nosocomial Infections &#40;<a href="https://www.cdc.gov/hai/organisms/organisms.html">https&#58;&#47;&#47;www&#46;cdc&#46;gov&#47;hai&#47;organisms&#47;organisms&#46;html</a>&#41;&#44; which are shown in the <a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>&#44; and also the global antibiotic resistance rates associated with major bacterial pathogens&#44;<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a> were shown in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><elsevierMultimedia ident="t0005"></elsevierMultimedia></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">Vaccine against ESCAPE pathogens</span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Enterococcus faecium</span></span></span><p id="p0045" class="elsevierStylePara elsevierViewall">A member of the Enterococcus genus&#44; <span class="elsevierStyleItalic">Enterococcus faecium</span> is a Gram-positive&#44; gamma-hemolytic or non-hemolytic bacterium&#46; It is one of the typical members of the gut flora and can lead to serious illness in the elderly or people who already have other medical conditions&#44; such as people who have diabetes or chronic kidney failure&#46; It is regarded as one of the major factors contributing to nosocomial infections&#46;<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a> Enterococcus can cause urinary tract infections &#40;UTIs&#41;&#44; pelvic and intraabdominal infections&#44; bacteriemia&#44; infective endocarditis&#44; and infections of the nervous system&#46; These are just a few of the illnesses that enterococcus can cause&#46; Public health is severely challenged by the rapidly rising frequency of vancomycin-resistant enterococci &#40;VRE&#41; in general&#46;<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> The United States has the greatest rates of vancomycin resistance&#59; from 2009 to 2010&#46; VRE was accountable for 35&#46;5&#37; of all enterococcal infections and 79&#46;5&#37; to 83&#46;3&#37; of <span class="elsevierStyleItalic">Enterococcus faecium</span> bloodstream infections&#46;<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> The enterococcal antibiotic resistance genes could spread to other microorganisms&#44; which is a concern for VRE because of the high mortality rate attributed to VRE infection&#46;<a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> The highest incidence of VRE due to nosocomial infections in Europe has been observed in southern European countries&#46;<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a> The development of novel treatments for <span class="elsevierStyleItalic">Enterococcus faecium</span> is thought to be of high importance according to the World Health Organization&#39;s 2017 issuance of a list of 12 antibiotic-resistant bacteria that pose the greatest risk to human health&#46;<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a> In order to better understand and treat VRE&#44; investigation and the development of innovative medicines are key objectives&#46;</p><p id="p0050" class="elsevierStylePara elsevierViewall">Targeting capsular polysaccharides &#40;CPS&#41;&#44; which are successfully employed in a number of other bacterial vaccines&#44; is one approach for developing an enterococcus vaccine that is currently being investigated in preclinical studies&#46; Preclinical research on CPS showed some effectiveness in reducing bacterial load&#44; and some data indicates that serotype-C makes up the majority of pathogenic strains&#44; raising the prospect of creating a CPS vaccine with broad immunologic protection&#46;<a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a> An alternate technique is being investigated specifically to avoid catheter-associated infections such as urinary tract infections&#44; blood stream infections&#44; and so on by reducing biofilm formation&#46;<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> More research is needed to develop a reliable vaccine to combat VRE and lower the AMR reservoir&#46; VRE is frequently found in immune-compromised persons&#46;<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> The invention of an enterococcal vaccination would assist patients with higher risk factors by extending their survival rate and shortening their duration of stay&#44; lowering stress on the health-care system&#46;<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a></p><p id="p0055" class="elsevierStylePara elsevierViewall">Probiotics are being suggested as a possible substrate for the synthesis of recombinant vaccines bearing cells of the immune system&#46; In 2021&#44; Yulia Desheva et al&#46;&#44; developed and validated a live mucosal recombinant vaccine by incorporating genes expressing influenza virus neuraminidase &#40;NA&#41; of the N2 subtype into the DNA of the probiotic strain <span class="elsevierStyleItalic">Enterococcus faecium</span> L3&#46; Researchers demonstrated NA expression in the pili of L3 and its immunization raised chance of survival by 34&#37;&#46; They indicated that oral dosing of probiotic vaccines developed by this technology could be beneficial for anti-viral protection in both humans and farm animals&#46;<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a></p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Staphylococcus aureus</span></span></span><p id="p0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Staphylococcus aureus</span> is gram-positive bacteria that is found in 30&#37; of the general population<a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a> is a major cause of invasive disorders such bacteriemia&#44; infected endocarditis&#44; osteomyelitis&#44; pneumonia&#44; and a number of skin and soft tissue infections in both hospitals and the general community&#46; More than 40&#37; of nosocomial infections in patients who have undergone surgery are caused by surgical site infections &#40;SSIs&#41;&#46; Currently&#44; between 300&#44;000 and 500&#44;000 cases are thought to occur annually in the United States&#46;<a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> Around one-fourth of pneumonia admissions worldwide are attributed to <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; and methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> &#40;MRSA&#41; accounts for almost half of healthcare-associated pneumonia &#40;HAP&#41; or ventilator-associated pneumonia &#40;VAP&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a> Bacterial resistance against B-lactams as well as other types of antibiotics can make infections more difficult to treat&#46; MRSA infections are more difficult to treat than methicillin-sensitive variants&#44; and they are attributed to longer hospital admissions&#44; higher morbidity&#44; and higher mortality rates&#46;</p><p id="p0065" class="elsevierStylePara elsevierViewall">General infection management and the use of prophylactic antibiotics&#44; such as the topical antimicrobial mupirocin&#44; which targets <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; are preventive interventions against <span class="elsevierStyleItalic">Staphylococcus aureus</span> infection&#46;<a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a> Pfizer&#39;s SA4Ag candidate&#44; which consists of four antigens clumping factor A&#44; a virulence factor that enables <span class="elsevierStyleItalic">Staphylococcus aureus</span> to bind to fibrinogen&#59; the manganese transporter MntC&#59; CP5&#59; and CP8 is the only active advanced <span class="elsevierStyleItalic">Staphylococcus aureus</span> vaccine project at the moment&#46; Phase 1 studies revealed quick production of functional antibodies that lasted for at least a year&#46;<a class="elsevierStyleCrossRef" href="#bb0145"><span class="elsevierStyleSup">29</span></a> In the STRIVE trial &#40;<span class="elsevierStyleItalic">Staphylococcus aureus</span> Surgical Inpatient Vaccine Effectiveness&#41;&#44; a phase 2b placebo-controlled safety and efficacy study of SA4Ag in people undergoing elective spinal fusion surgery is now underway&#46;<a class="elsevierStyleCrossRef" href="#bb0150"><span class="elsevierStyleSup">30</span></a></p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0055"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Clostridium difficile</span></span></span><p id="p0070" class="elsevierStylePara elsevierViewall">The most common source of nosocomial infectious diarrhea in industrialized nations is <span class="elsevierStyleItalic">Clostridium difficile</span>&#44; a gram-positive&#44; anaerobic&#44; spore-forming bacillus&#46; It is the most often identified cause of infectious diarrhea in healthcare settings&#44; accounting for 20&#8211;30&#37; of episodes of diarrhea that appear following the administration of antibiotics and resulting in disturbance of the normal gut microbiota&#46;<a class="elsevierStyleCrossRef" href="#bb0155"><span class="elsevierStyleSup">31</span></a> Around 2&#8211;7&#37; of the overall population and 13&#8211;51&#37; of hospital patients are carriers of <span class="elsevierStyleItalic">Clostridium difficile</span>&#46; Adults over 65 who recently used antibiotics have the greatest chance of getting <span class="elsevierStyleItalic">Clostridium difficile</span> infections &#40;CDIs&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0160"><span class="elsevierStyleSup">32</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0165"><span class="elsevierStyleSup">33</span></a></p><p id="p0075" class="elsevierStylePara elsevierViewall">Annually&#44; there are 29&#44;000 CDI-related deaths and over 500&#44;000 new cases of CDI detected in the US alone&#46; The CDC has identified <span class="elsevierStyleItalic">Clostridium difficile</span> as an urgent hazard due to the high incidence of CDIs and the quick emergence of outbreaks and antibiotic-resistant strains&#46;<a class="elsevierStyleCrossRef" href="#bb0170"><span class="elsevierStyleSup">34</span></a> The occurrence of CDIs&#44; as well as their pathogenicity and mortality&#44; has increased dramatically over the last ten years&#46;<a class="elsevierStyleCrossRef" href="#bb0175"><span class="elsevierStyleSup">35</span></a> These patterns have been linked to <span class="elsevierStyleItalic">Clostridium difficile</span> &#40;BI&#47;NAP1&#47;027&#41; epidemic strains&#44; which exhibit increased pathogenicity&#46;<a class="elsevierStyleCrossRef" href="#bb0180"><span class="elsevierStyleSup">36</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0185"><span class="elsevierStyleSup">37</span></a></p><p id="p0080" class="elsevierStylePara elsevierViewall">The gut micro-biota plays a key role in CDI defense&#44; and disruption of this ecosystem by antibiotic use causes substantial changes in the metabolic environment that support <span class="elsevierStyleItalic">Clostridium difficile</span> germination and growth &#40;especially in the ratio of the primary and secondary bile acids and carbon sources&#41;&#46; Whenever <span class="elsevierStyleItalic">Clostridium difficile</span> is vegetative&#44; it generates the two exotoxins&#44; toxin A and toxin B&#44; which become its main virulence components&#46; Binary toxin&#44; a third toxin that is expressed by BI&#47;NAP1&#47;027 strains of <span class="elsevierStyleItalic">Clostridium difficile</span>&#44; also seems to play a role in pathogenesis&#46;<a class="elsevierStyleCrossRef" href="#bb0195"><span class="elsevierStyleSup">38</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0200"><span class="elsevierStyleSup">39</span></a> The provoking antibiotics must be withdrawn in order to treat CDI&#44; and new antibiotics &#40;vancomycin&#44; metronidazole&#44; or fidaxomicin&#41; must be used in their place&#46; Moreover&#44; at least one relapse occurs in 20&#37; of patients&#44; and the likelihood of relapse rises with each succeeding episode&#46;<a class="elsevierStyleCrossRef" href="#bb0205"><span class="elsevierStyleSup">40</span></a> Early preclinical investigations showed that antitoxin antibodies and active immunization using inactivated toxins &#40;toxoids&#41; may prevent animals from developing CDI&#46;<a class="elsevierStyleCrossRef" href="#bb0210"><span class="elsevierStyleSup">41</span></a> This discovery finally resulted in the development of the non-antibiotic therapy bezlotoxumab&#44; a monoclonal antibody towards TcdB that has been recently approved and which is intended to stop CDI relapse after the first infection&#46;<a class="elsevierStyleCrossRef" href="#bb0215"><span class="elsevierStyleSup">42</span></a></p><p id="p0085" class="elsevierStylePara elsevierViewall">The toxoid-based vaccine&#39;s clinical development was declared to come to an end due to the low probability that the phase 3 research &#40;<a href="ctgov:NCT01887912">NCT01887912</a>&#41; will achieve its main goal&#46;<a class="elsevierStyleCrossRef" href="#bb0220"><span class="elsevierStyleSup">43</span></a> The combination of genetically altered as well as further detoxified TcdA and TcdB from <span class="elsevierStyleItalic">Clostridium difficile</span>&#44; the main virulence factors generated by the organism&#44; is the only vaccine now under research&#46;<a class="elsevierStyleCrossRef" href="#bb0225"><span class="elsevierStyleSup">44</span></a> As a consequence of successful phase 1 and phase 2 studies &#40;<a href="ctgov:NCT03090191">NCT03090191</a>&#41;&#44; this vaccine has moved to phase 3 studies&#46;<a class="elsevierStyleCrossRef" href="#bb0230"><span class="elsevierStyleSup">45</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0235"><span class="elsevierStyleSup">46</span></a> In March 2022&#44; Pfizer released findings from the pivotal Phase 3 CLOVER trial &#40;<span class="elsevierStyleItalic">Clostridium difficile</span> Vaccine Efficacy TRial&#41;&#44; which assessed the efficacy of their <span class="elsevierStyleItalic">Clostridium difficile</span> vaccine candidate &#40;PF-06425090&#41; in preventing CDI&#46; Even though the trial did not accomplish its pre-specified primary aim of prevention of primary CDI&#44; initial assessments of 2 protocol-specified secondary endpoints demonstrated a highly favorable impact on lowering CDI severity and 100&#37; vaccination effectiveness in decreasing medically treated CDI&#46; The experimental vaccination was well tolerated and safe&#44; according to safety reviews&#46;<a class="elsevierStyleCrossRef" href="#bb0240"><span class="elsevierStyleSup">47</span></a></p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0060"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Acinetobacter baumannii</span></span></span><p id="p0090" class="elsevierStylePara elsevierViewall">Acinetobacter are non-motile&#44; Gram-negative coccobacilli which are most frequently found in sewage water&#44; and soil&#46; There are more than 50 distinct Acinetobacter species&#44; the majority of which are not harmful&#46; Generally&#44; Acinobacter baumannii is regarded as an opportunistic pathogen that primarily affects hospitalized patients&#44; those with impaired immune systems&#44; and military personnel with war wounds&#44; particularly in humid areas&#46;<a class="elsevierStyleCrossRef" href="#bb0245"><span class="elsevierStyleSup">48</span></a> The peritoneal system&#44; respiratory tract&#44; and urinary tract are among of the organs and organ systems where Acinobacter baumannii pathogens are most common&#46; Pneumonia&#44; sepsis&#44; skin and soft tissue infections&#44; and meningitis are the most frequently infections associated with this pathogen&#46;<a class="elsevierStyleCrossRef" href="#bb0250"><span class="elsevierStyleSup">49</span></a></p><p id="p0095" class="elsevierStylePara elsevierViewall">According to research&#44; <span class="elsevierStyleItalic">Acinetobacter baumannii</span> causes approximately 12&#37; of all hospital-acquired infections worldwide&#46;<a class="elsevierStyleCrossRef" href="#bb0255"><span class="elsevierStyleSup">50</span></a> One of the most typical clinical manifestations is pneumonia developed in patients undergoing respiratory support in an intensive care setting&#46;<a class="elsevierStyleCrossRef" href="#bb0260"><span class="elsevierStyleSup">51</span></a> Because of the widespread use of antibiotic resistance&#44; these pneumonia cases might be challenging to treat&#46; According to a recent meta-analysis of 126 studies from 29 countries&#44; multidrug-resistant <span class="elsevierStyleItalic">Acinetobacter baumannii</span> was found in 80&#37; of ventilator- and hospital-acquired pneumonia patients&#46;<a class="elsevierStyleCrossRef" href="#bb0265"><span class="elsevierStyleSup">52</span></a></p><p id="p0100" class="elsevierStylePara elsevierViewall">Several vaccine antigens have already been investigated through preclinical trials&#44; but there are still a lot of fundamental problems about proper antigen identification and beneficial immunological pathways&#46;<a class="elsevierStyleCrossRef" href="#bb0270"><span class="elsevierStyleSup">53</span></a> The outer membrane protein 22 &#40;Omp22&#41; has been found to provide some prevention against the <span class="elsevierStyleItalic">Acinetobacter baumannii</span> threat in mice in research conducted using an outer membrane vesicle &#40;OMV&#41;-based vaccine&#46;<a class="elsevierStyleCrossRef" href="#bb0275"><span class="elsevierStyleSup">54</span></a> Omp22 may be a viable strategy for an OMV-based human vaccine&#44; but it&#39;s unclear given the insufficiency of several animal models for predicting human safeguards&#46;<a class="elsevierStyleCrossRef" href="#bb0280"><span class="elsevierStyleSup">55</span></a></p></span><span id="s0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Pseudomonas aeruginosa</span></span></span><p id="p0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> is gram-negative comes under multi-drug resistant bacteria that affects immune-compromised individuals globally and causing fatal HAI&#46;<a class="elsevierStyleCrossRef" href="#bb0285"><span class="elsevierStyleSup">56</span></a> It is a common environmental infection that prefers humid settings&#46; In susceptible patients with altered or damaged epithelial barriers caused by cystic fibrosis&#44; burn&#44; wounds&#44; and chemo-drugs&#44; it can infiltrate in to the human mucosa&#46;<a class="elsevierStyleCrossRef" href="#bb0290"><span class="elsevierStyleSup">57</span></a> With an estimated 51&#44;000 <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> infections caused by medical care each year in the United States&#39; hospitals&#46; The blood stream infections are common&#44; among infections associated with transplants and surgery&#44; and urinary catheterization&#46; Severe burns&#44; cystic fibrosis&#44; illnesses that impair immunity and other disorders that are more prevalent in hospital admissions are major risk factors for Pseudomonas infestations&#46;<a class="elsevierStyleCrossRefs" href="#bb0295"><span class="elsevierStyleSup">58&#8211;60</span></a></p><p id="p0110" class="elsevierStylePara elsevierViewall">Immunization is likely the most successful strategy to resolving the issues caused by <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#39;s multi-drug resistance&#46; Although several <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> vaccines have entered clinical trials&#44;<a class="elsevierStyleCrossRef" href="#bb0310"><span class="elsevierStyleSup">61</span></a> none has been authorized for use in humans&#46; The translational fusion of the OMPs&#44; OprF&#44; and OprI recombinantly generated by <span class="elsevierStyleItalic">Escherichia coli</span> &#40;IC43 vaccine&#41; has been recently tested in a Phase II&#47;III clinical study&#44; but it was unable to trigger the necessary immune responses or lower the mortality&#46;<a class="elsevierStyleCrossRef" href="#bb0315"><span class="elsevierStyleSup">62</span></a> A monoclonal antibody called MEDI3902 that works to prevent <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> infection has also advanced to phase 2 evaluations in patients receiving mechanical ventilation &#40;<a href="ctgov:NCT02696902">NCT02696902</a>&#41; as a result of promising preclinical evidence&#46;<a class="elsevierStyleCrossRef" href="#bb0320"><span class="elsevierStyleSup">63</span></a></p></span><span id="s0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070"><span class="elsevierStyleItalic">Enterobacteriaceae</span></span><p id="p0115" class="elsevierStylePara elsevierViewall">Enterobacteriaceae is a broad genus of gram-negative bacteria that are inhabitants of the normal gut flora and can be a common source of NIs that are easily transmitted among patients&#46; Perhaps the most well known pathogens are <span class="elsevierStyleItalic">Escherichia coli</span>&#44; Klebsiella species&#44; and Enterobacter species&#46; Conventional antibiotics are not effective against Enterobacteriaceae&#44; and carbapenems are only used as a last option&#46;<a class="elsevierStyleCrossRef" href="#bb0325"><span class="elsevierStyleSup">64</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0330"><span class="elsevierStyleSup">65</span></a> The emergence of carbapenem-resistant Enterobacteriaceae is thus a considerable concern&#44; especially given that fatality rates of up to 50&#37; have been reported&#46;<a class="elsevierStyleCrossRef" href="#bb0325"><span class="elsevierStyleSup">64</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0335"><span class="elsevierStyleSup">66</span></a> The WHO considers carbapenem-resistant Enterobacteriaceae to be a serious AMR concern&#46;<a class="elsevierStyleCrossRef" href="#bb0340"><span class="elsevierStyleSup">67</span></a></p><p id="p0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Escherichia coli</span> immunization approaches&#44; such as live attenuated strains&#44; entire inactivated strains&#44; and subunit vaccines&#44; are being researched to combat recurring UTIs&#46; Through clinical studies&#44; commonly available vaccines usually contain attenuated strains&#44; such as Uromune&#174; &#40;a vaccine comprising strains from <span class="elsevierStyleItalic">Escherichia coli</span>&#44; <span class="elsevierStyleItalic">Klebsiella pneumoniae</span>&#44; <span class="elsevierStyleItalic">Enterococcus faecalis</span>&#44; and <span class="elsevierStyleItalic">Proteus vulgaris</span>&#41; and Solco Urovac&#174; &#40;a vaccine containing 6 <span class="elsevierStyleItalic">Escherichia coli</span> strains along with strains from <span class="elsevierStyleItalic">Proteus mirabilis</span>&#44; <span class="elsevierStyleItalic">Klebsiella pneumoniae</span>&#44; <span class="elsevierStyleItalic">Proteus morganii</span>&#44; and Escherichia faecalios&#41; have shown little efficacy in clinical trials&#46;<a class="elsevierStyleCrossRef" href="#bb0345"><span class="elsevierStyleSup">68</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0350"><span class="elsevierStyleSup">69</span></a> Considering these advancements&#44; additional vaccination strategies are essential for the control of invasive <span class="elsevierStyleItalic">Escherichia coli</span> infection&#46;</p></span></span></span><span id="s0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Conclusion &#38; future directions</span><p id="p0125" class="elsevierStylePara elsevierViewall">In spite of the widespread implementation of preventive strategies&#44; Nosocomial infections continue to be a significant disease burden globally&#44; and research has shown a high inflation of AMR in the past few years&#44;<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0355"><span class="elsevierStyleSup">70</span></a> suggesting alternative solutions to control these infections are really important&#46; However&#44; for most of the pathogens involved in HAIs vaccines are not currently available and the development of effective vaccines for <span class="elsevierStyleItalic">nosocomial pathogens</span> remains challenging&#46; Most approaches of vaccine development are directed against the surface component of pathogens &#40;outer membrane protein&#44; capsular polysaccharides&#44; toxoid-based etc&#41; and attenuated bacteria &#40;probiotics&#41;&#46;</p><p id="p0130" class="elsevierStylePara elsevierViewall">To deliver the greatest public-health advantages&#44; efforts must be made to steadily improve vaccine coverage and also to finish study and licensing procedures for novel vaccines that address significant bacterial and viral pathogens for which vaccines previously did not exist&#46; As a result&#44; it is vital that vaccine research be promoted as a major global priority&#44; with a special emphasis on the development of broadly protective vaccines targeting pathogens with high AMR rates&#46;</p></span><span id="s0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Contributions</span><p id="p0135" class="elsevierStylePara elsevierViewall">Rajesh Venkataraman and Ravi Kurikempannadoddi Shivalingegowda had conceptualization&#44; supervision&#44; visualization&#44; and reviewing and editing&#46; Umesh Yadav and Yogendra Shrestha did the conceptualization&#44; search&#44; data curation&#44; and writing of the original draft&#46;</p></span><span id="s0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Funding</span><p id="p0140" class="elsevierStylePara elsevierViewall">This study did not receive any particular funding&#46;</p></span></span>"
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          "titulo" => "Palabras clave"
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          "titulo" => "Introduction"
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          "titulo" => "Materials and methods"
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              "identificador" => "s0015"
              "titulo" => "Target pathogens for vaccine-based approaches against nosocomial infections"
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              "identificador" => "s0020"
              "titulo" => "Vaccine against ESCAPE pathogens"
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                  "identificador" => "s0025"
                  "titulo" => "Enterococcus faecium"
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                1 => array:2 [
                  "identificador" => "s0030"
                  "titulo" => "Staphylococcus aureus"
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                2 => array:2 [
                  "identificador" => "s0035"
                  "titulo" => "Clostridium difficile"
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                3 => array:2 [
                  "identificador" => "s0040"
                  "titulo" => "Acinetobacter baumannii"
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                  "titulo" => "Pseudomonas aeruginosa"
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                  "identificador" => "s0050"
                  "titulo" => "Enterobacteriaceae"
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          "identificador" => "s0055"
          "titulo" => "Conclusion &#38; future directions"
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          "titulo" => "Contributions"
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    "fechaRecibido" => "2022-09-20"
    "fechaAceptado" => "2022-11-05"
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            1 => "Vaccine"
            2 => "Pathogens"
            3 => "Antibiotic resistance"
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          "palabras" => array:4 [
            0 => "infecciones nosocomiales"
            1 => "vacuna"
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        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">In spite of the widespread implementation of preventive strategies&#44; nosocomial infections are one of the most frequent localized or systemic adverse events in healthcare worldwide despite of progress in public health and hospital care&#46; The risk factors for these infections increased due to underlying health issues&#44; immune-compromised individuals&#44; increased age&#44; and prolonged hospitalization of patients&#46; Although a few novel antibiotics have recently been put into clinical practice&#44; the exploration of alternative techniques to effectively battle nosocomial infections is urgently required to reduce the significant burden&#46; Many common nosocomial pathogens have growing rates of antibiotic resistance&#44; exacerbating the situation and emphasizing the need for preventative alternatives to antibiotic treatment&#44; such as immunological strategies based on vaccine development or therapeutic antibodies&#44; which may significantly enhance their control&#46; This review will concentrate on the epidemiology of the most frequent nosocomial pathogens&#44; as well as vaccines authorized or in development for the prevention of ESCAPE pathogens &#40;<span class="elsevierStyleItalic">Enterococcus faecium</span>&#44; <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; <span class="elsevierStyleItalic">Clostridium difficile</span>&#44; <span class="elsevierStyleItalic">Acinetobacter baumannii</span>&#44; <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#44; and Enterobacteriaceae&#41;&#46;</p></span>"
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        "resumen" => "<span id="as0010" class="elsevierStyleSection elsevierViewall"><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Las infecciones nosocomiales constituyen uno de los eventos adversos localizados o sist&#233;micos m&#225;s frecuentes en la atenci&#243;n sanitaria a nivel mundial a pesar de los avances en salud p&#250;blica y atenci&#243;n hospitalaria&#46; Los factores de riesgo de estas infecciones aumentan debido a problemas de salud subyacentes&#44; personas inmunocomprometidas&#44; edad avanzada y hospitalizaci&#243;n prolongada de los pacientes&#46; Sin embargo&#44; muchos pat&#243;genos nosocomiales comunes tienen tasas crecientes de resistencia a los antibi&#243;ticos&#44; lo que exacerba la situaci&#243;n y enfatiza la necesidad de alternativas preventivas al tratamiento con antibi&#243;ticos&#44; como las vacunas&#46; En muchas circunstancias&#44; las tasas de mortalidad relacionadas con las infecciones nosocomiales resistentes a los antibi&#243;ticos son altas&#46; Esta revisi&#243;n pondr&#225; &#233;nfasis en las infecciones nosocomiales junto con la patogenia y la enfermedad&#44; los tratamientos disponibles y la revisi&#243;n de las vacunas actualmente aprobadas o en preparaci&#243;n para el manejo de los pat&#243;genos ESCAPE &#40;<span class="elsevierStyleItalic">Enterococcus faecium</span>&#44; <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; <span class="elsevierStyleItalic">Clostridium difficile</span>&#44; <span class="elsevierStyleItalic">Acinetobacter baumannii</span>&#44; <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> y Enterobacteriaceae&#41;&#46;</p></span>"
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          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Flowchart showing the CDC list of Nosocomial Infections&#46;</p>"
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          "leyenda" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">The percentage of tested isolates that were resistant to each antibiotic class used for each infection is listed along with antibiotic resistance data from 2000 to 2014 for each pathogen&#46; These medications target particular pathogens&#46; Data for all pathogens were obtained from the Center for Disease Dynamics&#44; Economics and Policy &#40;<span class="elsevierStyleInterRef" id="ir0005" href="https://resistancemap.cddep.org/">https&#58;&#47;&#47;resistancemap&#46;cddep&#46;org&#47;</span>&#41;&#46; ND&#44; no data provided&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pathogens</th><th class="td-with-role" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Resistance rate &#40;&#37;&#41;</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">United States&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">India&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">South Africa&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">UK&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
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                  \t\t\t\t">Staphyloccus aureus&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">0&#8211;45&nbsp;\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="" valign="\n
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                  \t\t\t\t">2&#8211;94&nbsp;\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="" valign="\n
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                  \t\t\t\t">0&#8211;29&nbsp;\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="" valign="\n
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                  \t\t\t\t">0&#8211;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Streptocococcus pneumoniae&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">17&#8211;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">7&#8211;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Acinetobacter baumannii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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Article information

ISSN: 24451460
Original language: English

DOI:10.1016/j.vacune.2023.02.005

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