A novel chimeric vaccine containing multiple epitopes for simulating robust immune activation against Klebsiella pneumoniae.

BACKGROUND: Due to antibiotic resistance, the Klebsiella genus is linked to morbidity and death, necessitating the development of a universally protective vaccine against Klebsiella pathogens. METHODS: Core sequence analysis prioritized non-redundant host molecules and expected lipid bilayer peptides from fully sequenced Klebsiella genomes. These proteins were refined to identify epitopes, examining their immunogenicity, toxicity, solubility, and interaction with MHC alleles. Epitopes were linked to CPG ODN C274 via EAAAK, HEYGAEALERAG, and GGGS linkers to enhance immunological responses. The vaccine's tertiary structure was modelled and docked with MHC-I and MHC-II. RESULTS: Fifty-five proteins were recognized in the Vaxign collection as having remarkable features. Twenty-three proteins with potential pathogenicity were then identified. Eight options for vaccines emerged after the immunogenicity of proteins was examined. The best antigens were three proteins: MrkD, Iron-regulated lipid membrane polypeptides, and RmpA. These compounds were selected for their sensitivity. The structural protein sequences of K. pneumoniae were utilized to identify seven CTL epitopes, seven HTL epitopes, and seven LBL epitopes, respectively. The produced immunization displayed a stable contact with the receptors, based on molecular dynamic simulations lasting 250 nanoseconds. Intermolecular binding free energies also indicated the dominance of the van der Waals and electrostatic energies. CONCLUSION: In summary, the results of this study might help scientists develop a novel vaccine to prevent K. pneumoniae infections.

Patient-Derived Antibody Data Yields Development of Broadly Cross-Protective Monoclonal Antibody against ST258 Carbapenem-Resistant Klebsiella pneumoniae.

The most pressing challenge for the development of anti-capsular antibodies is maximizing coverage against the heterogenous capsular polysaccharide (CPS) of carbapenem-resistant Klebsiella pneumoniae (CR-Kp). So far, only CR-Kp with wzi154 CPS has been successfully targeted by antibodies. Here, we present murine antibody 24D11, which was developed by vaccinating mice with purified wzi50-type CPS. Cross-reactivity and protective efficacy of MAb 24D11 were confirmed against CR-Kp that express the 3 most prevalent CPS types (wzi29, wzi154, wzi50) using both in vitro and in vivo infection models. 24D11 induced complement-mediated and independent opsonophagocytosis in macrophages as well as killing of all CR-Kp strains in whole blood cells derived from healthy donors. In a murine intratracheal infection model, 24D11 reduced lung burden and dissemination of CR-Kp strains when administered 4 h pre- or postinfection. The protective efficacy of 24D11 remained effective in neutropenic mice. This is the first antibody which exhibits cross-protective efficacy against clade 1 and 2 ST258 CR-Kp strains. It overcomes a major barrier to successfully target wzi29, a major CPS expressed by ST258 CR-Kp. The finding that 24D11 also exhibits potent protective efficacy against wzi154 CR-Kp strains highlights its high potential as a lead agent for the development of broadly active immunotherapy. IMPORTANCE Here, we present in vitro and in vivo data for the wzi50 CPS-specific monoclonal antibody MAb 24D11, demonstrating its cross-protective efficacy against three prominent win types (wzi29, wzi154, and wzi50) of the carbapenem-resistant clonal group CG258. In a murine pulmonary infection model, MAb 24D11 reduced bacterial lung burden and dissemination to other organs even if administered 4 h postinfection. Its protective efficacy was also observed in neutropenic mice, which highlights its potential value in clinical settings where oncology patients with CG258 infections may also be neutropenic.

Vaccination induces rapid protection against bacterial pneumonia via training alveolar macrophage in mice.

Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell of Acinetobacter baumannii elicits rapid protection against broad A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.

Evaluation of riboflavin and ultraviolet light treatment against Klebsiella pneumoniae in whole blood-derived platelets: A pilot study.

BACKGROUND: Bacterial contamination of platelet concentrates (PCs) is the predominant cause of infectious transfusion reactions. The Pathogen Inactivation Mirasol system was implemented at the King Faisal Specialist Hospital (Saudi Arabia) to reduce the risk of transfusing contaminated PCs. This pilot study evaluated the effectiveness of Mirasol against Klebsiella pneumoniae, a pathogen associated with transfusion reactions, in whole blood-derived PCs. STUDY DESIGN AND METHODS: Whole blood (WB) units inoculated with one of six K. pneumoniae strains (five clinical isolates and ATCC-700603) at a concentration of 3-38 CFU/unit, were processed using the platelet-rich plasma (PRP) method. Each spiked PC was pooled with four unspiked units. The pooled PC was split into three Mirasol storage bags: an untreated unit (control), and two units treated with Mirasol at 26 and 32 h post-WB collection, respectively. PC samples obtained before and after Mirasol treatment were used for BacT/ALERT cultures and determination of bacteria quantification. Each experiment was repeated three independent times. RESULTS: Five strains were detected prior to PC treatment (24 h post-WB spiking), while one clinical isolate was not detected. Mirasol treatment after 26 h of WB collection resulted in complete inactivation of all K. pneumoniae strains. However, treatment 32 h post-WB collection resulted in the breakthrough of one clinical isolate in two of the three replicates with ~7.8 log10 CFU/unit detected on day 5 of PC storage. CONCLUSION: Delayed Mirasol treatment from 26 to 32 h post-WB collection, resulted in one breakthrough. These results highlight the importance of minimizing the time between WB collection and PI treatment.

Gérmenes aislados en pacientes ingresados en la terapia intensiva del Hospital Clínico Quirúrgico Provincial Dr. Joaquín Albarrán / Germs isolated from intensive care patients at Dr. Joaquín Albarrán Provincial Clinical Surgical Hospital

Introducción: Las infecciones asociadas a los cuidados sanitarios en los servicios de atención al paciente crítico se asocian a un alto riesgo de muerte y costos significativos. Objetivo: Identificar los gérmenes más frecuentes en los cultivos y su resistencia a los antimicrobianos en la terapia intensiva del Hospital Clínico Quirúrgico Provincial Dr. Joaquín Albarrán. Métodos: Se realizó un estudio descriptivo, retrospectivo, en la terapia intensiva del Hospital Clínico Quirúrgico Provincial Dr. Joaquín Albarrán, de enero del 2015 a diciembre del 2018, el universo estuvo constituido por 1847 cultivos realizados seleccionándose 654 en los que se obtuvo crecimiento; para el análisis estadístico se utilizó el SPSS 22.0. Resultados: De los gérmenes aislados, la Klebsiella spp fue la más frecuente (31 por ciento), seguida del Staphylococcus spp (24,5 por ciento) y de la E. coli (9,8 por ciento). En los esputos se mantuvo la Klebsiella spp (45,1 por ciento), en los hemocultivos el Staphylococcus spp (53,6 por ciento) y en los urocultivos la Candida (41,1 por ciento), seguida de la E. coli (27 por ciento). De los antimicrobianos usados en terapia para tratar la Klebsiella spp, la E. coli, el Acinetobacter y la pseudomona spp, el más recomendado es la colistina (0-25 por ciento de resistencia) y para el Staphylococcus spp, la vancomicina (1,8 por ciento). Conclusiones: Los gérmenes Gram negativos siguen siendo los más frecuentemente aislados en los cultivos de los pacientes hospitalizados en terapia, con un alto nivel de resistencia para la mayoría de los antibióticos(AU)

Introduction: Infections related to critical care settings are associated to high death risk and significant costs. Objective: Identify the germs most commonly found in cultures and their resistance to antimicrobials in the intensive care service of Dr. Joaquín Albarrán Provincial Clinical Surgical Hospital. Methods: A retrospective descriptive study was conducted at the intensive care service of Dr. Joaquín Albarrán Provincial Clinical Surgical Hospital from January 2015 to December 2018. The study universe was 1 847 cultures, from which 654 were selected in which growth was obtained. Data were processed with the statistical software SPPS 22.0. Results: Of the germs isolated, Klebsiella spp. were the most common (31 percent, followed by Staphylococcus spp. (24.5 percent) and E. coli (9.8 percent). Klebsiella spp. were frequent in sputum cultures (45.1 percent), Staphylococcus spp. in blood cultures (53.6 percent) and Candida in urine cultures (41.1 percent), followed by E. coli (27 percent). Among the antimicrobials used to treat Klebsiella spp., E. coli, Acinetobacter and Pseudomonas spp., the most recommended is colistin (0-25 percent resistance) and vancomycin for Staphylococcus spp. (1.8 percent). Conclusions: Gram-negative germs continue to be the most commonly isolated in cultures from intensive care patients, with a high level of resistance to most antibiotics(AU)

Early cytokine response to lethal challenge of Klebsiella pneumoniae averted the prognosis of pneumonia in FyuA immunized mice.

Klebsiella pneumoniae, a multi drug resistant nosocomial pathogen is associated with pneumonia and immunization gives a hope to fight its infections. A possible vaccine candidate is the conserved protein, yersiniabactin receptor FyuA. Its expression along with the siderophore yersiniabactin increases in bacteria under iron starving conditions prevailing in lungs. In this study, the potential of recombinant FyuA of K. pneumoniae has been evaluated against lung infection in BALB/c mice. Immunization generated both humoral and cell mediated response which conferred protection against the lethal dose of bacteria. Bacterial burden in lungs reduced by 6 log10 CFU/ml after 2nd day post infection as compared to control. Similarly, the levels of pro-inflammatory cytokines IL-17, TNF-α and IL-1ß were also reduced significantly; reduced tissue damage was evident from histopathology of lungs in immunized mice. These results indicate the protective role of FyuA which can be a potential vaccine candidate.

Benzothiazole-pyridone and benzothiazole-pyrazole clubbed emissive azo dyes and dyeing application on polyester fabric: UPF, biological, photophysical and fastness properties with correlative computational assessments.

Positional isomers of benzothiazole-pyridone and benzothiazole-pyrazole containing disperse azo dyes are reported. These heterocyclic azo dyes are decorated with 'separate ESIPT core' and show emission in seven solvents of different polarity. After application on polyester fabric, "very good to excellent" light and washing fastness properties were observed. Thermal stability of 'dyed fabric' was analysed by sublimation fastness test- and found 'very good to excellent' ratings at 210 °C. Ultraviolet Protection Factor (UPF) analysis of four 'dyed fabric' indicates the blocking 96-97% of UV radiation. Dyes were found effective on gram positive and negative bacteria by agar diffusion method and all the 'dyed fabrics' also showed more than 92% or 94% reduction of S. aureus or K. pneumoniae respectively by 'AATCC 100' method. Structures of the dyes were optimized using Density Functional Theory (DFT) to deduce stable tautomeric form. Calculated HOMO-LUMO gap is then compared with antibacterial activities. Electrophilicity index and lightfastness property were also compared and found to have very good correlation.

Successful Management of Unusual Multiple Gut Colonization With Extremely Drug-resistant Bacteria in an Infant Undergoing Hematopoietic Cell Transplantation.

Enterobacterales represent a serious threat to transplant patients due to their increase frequency of carbapenem resistance and wide spreading. We present a case of an infant with acute lymphoblastic leukemia undergoing hematopoietic stem cell transplantation. Before transplantation an unusual double colonization of the gastrointestinal tract with extremely resistant Escherichia coli and Klebsiella pneumoniae strains producing metallo-beta-lactamase was diagnosed. Respective epidemiologic management was implemented, based on the strict reverse isolation in patient-protective environment, and intensified antimicrobial surveillance. After granulocyte recovery, no extremely drug-resistant strains were found, and no case of isolation and/or transmission of carbapenem-resistant bacteria has been identified in the transplant center during the following 6 months.

Antimicrobial Stewardship Programs Are Required in a Department of Surgery: "How" Is the Question A Quasi-Experimental Study: Results after Three Years.

Objective: Our aim was to describe our antimicrobial stewardship program and the methodology based on the results in a surgical department. Methods: Our study was a quasi-experimental study conducted from January 1, 2009, through September 30, 2017. The site was the General and Digestive Surgery Department in a public primary referral center, the University Hospital of Getafe (Madrid, Spain). We implemented the antimicrobial stewardship program following a prospective audit and feedback model, with a surgeon incorporated into the manaagement group. We studied the deaths and 30-day re-admission rates, length of stay, prevalence of gram-negative bacilli, meropenem resistance, and days of treatment with meropenem. Results: After three years of the program, we recorded a significant decrease in Pseudomonas aeruginosa prevalence, a significant increase in Klebsiella pneumoniae prevalence, a decrease in meropenem resistance, and a reduction in meropenem days of treatment. Conclusions: Antimicrobial stewardship programs have a desirable effect on patients. In our experience, the program team should be led by a staff from the particular department. When human resources are limited, the sustainability, efficiency, and effectiveness of interventions are feasible only with adequate computer support. Finally, but no less important, the necessary feedback between the prescribers and the team must be based on an ad hoc method such as that provided by statistical control charts, a median chart in our study.

Frontline Science: Rev-Erbα links blue light with enhanced bacterial clearance and improved survival in murine Klebsiella pneumoniae pneumonia.

The wavelength of light is a critical determinant of light's capacity to entrain adaptive biological mechanisms, such as enhanced immune surveillance, that precede and prepare us for the active circadian day, a time when the risk of encountering pathogen is highest. Light rich in the shorter wavelength visible blue spectrum maximally entrains these circadian rhythms. We hypothesized that exposure to blue light during sepsis will augment immunity and improve outcome. Using a clinically relevant Klebsiella pneumoniae acute lower respiratory tract infection model, we show that blue spectrum light shifts autonomic tone toward parasympathetic predominance and enhances immune competence, as characterized by accelerated pathogen clearance that is accompanied by reduced alveolar neutrophil influx, inflammation, and improved survival. Blue light functioned through an optic-cholinergic pathway and expansion of splenic Ccr2+ monocytes to increase control of the infection and improve survival. The "keystone" mediating these effects is the circadian clock protein Rev-Erbα, and biochemical activation with Rev-Erbα agonist SR9009 enhanced mononuclear cell phagocytosis in vitro and recapitulated the enhanced pathogen elimination in vivo observed with blue light. These findings underscore the potential therapeutic value of blue light and modulating Rev-Erbα to enhance host immunity against infection.

Vaccine Protection against Multidrug-Resistant Klebsiella pneumoniae in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection.

Klebsiella pneumoniae is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by K. pneumoniae is often compounded by multidrug resistance-a potential problem for individuals with significant comorbidities or other risk factors for infection. A carbapenem-resistant K. pneumoniae strain classified as multilocus sequence type 258 (ST258) is widespread in the United States and is usually multidrug resistant. Thus, treatment of ST258 infections is often difficult. Inasmuch as new preventive and/or therapeutic measures are needed for treatment of such infections, we developed an ST258 pneumonia model in cynomolgus macaques and tested the ability of an ST258 capsule polysaccharide type 2 (CPS2) vaccine to moderate disease severity. Compared with sham-vaccinated animals, those vaccinated with ST258 CPS2 had significantly less disease as assessed by radiography 24 h after intrabronchial installation of 108 CFU of ST258. All macaques vaccinated with CPS2 ultimately developed ST258-specific antibodies that significantly enhanced serum bactericidal activity and killing of ST258 by macaque neutrophils ex vivo Consistent with a protective immune response to CPS2, transcripts encoding inflammatory mediators were increased in infected lung tissues obtained from CPS-vaccinated animals compared with control, sham-vaccinated macaques. Taken together, our data provide support for the idea that vaccination with ST258 CPS can be used to prevent or moderate infections caused by ST258. As with studies performed decades earlier, we propose that this prime-boost vaccination approach can be extended to include multiple capsule types.IMPORTANCE Multidrug-resistant bacteria continue to be a major problem worldwide, especially among individuals with significant comorbidities and other risk factors for infection. K. pneumoniae is among the leading causes of health care-associated infections, and the organism is often resistant to multiple classes of antibiotics. A carbapenem-resistant K. pneumoniae strain known as multilocus sequence type 258 (ST258) is the predominant carbapenem-resistant Enterobacteriaceae in the health care setting in the United States. Infections caused by ST258 are often difficult to treat and new prophylactic measures and therapeutic approaches are needed. To that end, we developed a lower respiratory tract infection model in cynomolgus macaques in which to test the ability of ST258 CPS to protect against severe ST258 infection.

Elimination of Klebsiella pneumoniae NDM from the air and selected surfaces in hospital using radiant catalytic ionization.

Due to increasing antibiotic resistance Klebsiella pneumoniae is a serious threat for the hospitalized patients. The aim of this study was the assessment of radiant catalytic ionization (RCI) efficacy on K. pneumoniae reduction in the air and on selected surfaces. Four K. pneumoniae NDM and ESBLs-producing strains were included in the study. Three types of surface were tested: cotton-polyester, terry and PVC. It was found that RCI significantly reduced the number of bacteria from all types of surface (terry: 0·56-1·22 log CFU m2 , cotton-polyester: 2·15-3·71 log CFU per m2 , PVC: 4·45-4·92 log CFU per m2 ) as well as from the air (1·80 log CFU per m3 ). The RCI technology may be a useful disinfection method in hospitals. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbial contamination of air and surfaces in hospitals play an important role in healthcare-associated infections. The aim was the assessment of Klebsiella pneumoniae elimination using radiant catalytic ionization (RCI). K. pneumoniae are aetiological agent of nosocomial infections, such as: pneumonia, infections of urinary tract, blood, e.t.c. The strains producing the New Delhi metallo-ß-lactamases are one of the greatest epidemiological threat. The use of RCI eliminate the tested bacteria from the hospital environment, but can also be effective in food processing plants or public facilities, ensuring the safety of people and products. This research is scarce in references and has a large innovation and application potential.

Microbial competition in environmental nosocomial reservoirs and diffusion capacity of OXA48-Klebsiella pneumoniae: potential impact on patients and possible control methods.

BACKGROUND: We have found clusters of Klebsiella pneumoniae with OXA48-carbepenemase cases in some hospital rooms, and decided to investigate whether bathroom siphons could be a reservoir for OXA48 bacteria, as occurs with K. oxytoca with other types of carbepenemases. METHODS: We evaluated the microbial competition between strains with OXA48 and VIM carbepenemases, in diluted nutrient-broth, on a slime germ-carrier. We compared the number of colonies at 5 and 10 days on the contaminated carriers with one or two strains. We evaluated the dissemination of K. pneumoniae with carbepenemase OXA48 or VIM from thumbs and index fingers of volunteers, to standard surfaces (20 glass germ-carrier by each volunteer). After, we counted the number of microorganisms on each carrier. Microbiological weekly studies of faecal microbiota of all patients were obtained in Traumatology and Oncology. Moreover, we studied samples of the sink in their rooms. PCR and MLST sequence-type was determined in all K. pneumoniae diagnosed from patients and sinks. RESULTS: A large possibility of diffusion from contaminated hands, which continue to transmit high numbers of microorganisms after more than 10 successive surface contacts, was highlighted; OXA bacteria were more persistent than VIM bacteria. Microbial competition studies showed that VIM bacteria are inhibited by OXA ones. These observations can explain the concentration of cases of K. pneumoniae OXA48 in some rooms in Traumatology and Oncology, producing a significant OR between rooms with OXA48-bacteria-contaminated siphons and other rooms (3.1 and 3.3 respectively). Risk was lowered after changing or disinfecting (heat plus chlorinated disinfectant) the contaminated siphons. Siphon colonization by VIM bacteria was not related with human infections by similar microorganisms. CONCLUSIONS: Bathroom siphons can be a reservoir for K. pneumoniae OXA48 and lead to outbreaks. Outbreaks can be controlled by replacement or heat plus chemical treatment of the sink-siphons.

Inhibition of nitric oxide production reverses diabetes-induced Kupffer cell activation and Klebsiella pneumonia liver translocation.

Klebsiella pneumoniae (KP) is the most common pathogen of pyogenic liver abscess in East and Southeast Asia and diabetes mellitus (DM) is a major risk factor. The effect and mechanism of diabetes on KP liver abscess was examined in streptozotocin-induced diabetic mice and Akita mice (C57BL/6J-Ins2Akita). KP translocation to liver and plasma alaine transaminase levels were increased and liver clearance of KP was decreased in DM mice. Diabetic mice exhibited overgrowth of Enterococcus as well as E.coli and decreased lactobacilli/bifidas growth in intestine, increased intestinal iNOS protein and nitrite levels in portal vein, and increased IL-1ß and TNF-α expression of Kupffer cells. Fructooligosaccharides (FOS) or dead L. salivarius (dLac) supplementation reversed diabetes-induced enteric dysbiosis, NO levels in portal vein, and KP translocation to liver. L-NAME treatment decreased intestinal iNOS protein expression as well as Kupffer cell activation and increased liver clearance of KP in DM mice. Dead E.coli (2×108 CFU/ml) feeding for one week induced iNOS and TLR4 expression of intestine in germ-free (GF) mice. Dead bacteria feeding induced IL-1ß and TNF-α expression of Kupffer cells in GF mice but not in GF TLR4-/- mice. In conclusion, balance of intestinal microflora is important for preventing intestinal iNOS expression, Kupffer cell activation, and KP liver translocation in diabetes. Reversal of diabetes-induced enteric dysbiosis with FOS or dead L. salivarius decreases diabetes-induced intestinal iNOS expression and KP liver translocation. Diabetes induces Kupffer cell activation and KP liver translocation through enteric dysbiosis and nitric oxide production.

Antibody-Based Immunotherapy To Treat and Prevent Infection with Hypervirulent Klebsiella pneumoniae.

Hypervirulent Klebsiella pneumoniae (hvKp) strains are predicted to become a major threat in Asia if antibiotic resistance continues to spread. Anticapsular antibodies (Abs) were developed because disseminated infections caused by hvKp are associated with significant morbidity and mortality, even with antibiotic-sensitive strains. K1-serotype polysaccharide capsules (K1-CPS) are expressed by the majority of hvKp strains. In this study, K1-CPS-specific IgG Abs were generated by conjugation of K1-CPS to immunogenic anthrax protective antigen (PA) protein. Opsonophagocytic efficacy was measured in vitro and in vivo by intravital microscopy in murine livers. In vivo protection was tested in murine models, including a novel model for dissemination in hvKp-colonized mice. Protective efficacy of monoclonal antibodies (MAbs) 4C5 (IgG1) and 19A10 (IgG3) was demonstrated both in murine sepsis and pulmonary infection. In hvKp-colonized mice, MAb treatment significantly decreased dissemination of hvKp from the gut to mesenteric lymph nodes and organs. Intravital microscopy confirmed efficient opsonophagocytosis and clearance of bacteria from the liver. In vitro studies demonstrate that MAbs work predominantly by promoting FcR-mediated phagocytosis but also indicate that MAbs enhance the release of neutrophil extracellular traps (NETs). In anticipation of increasing antibiotic resistance, we propose further development of these and other Klebsiella-specific MAbs for therapeutic use.

Characteristics of Surgical Site Infection Following Colorectal Surgery in a Tertiary Center: Extended-spectrum ß-Lactamase-producing Bacteria Culprits in Disease.

INTRODUCTION: Surgical site infection (SSI) is a well-known complication of colorectal surgery associated with increased morbidity and hospital stay. Antimicrobial prophylaxis can reduce the risk of SSI by as much as 75%. Extended-spectrum ß-lactamase (ESBL)-producing pathogens make the successful use of such prophylaxis a challenge and are a real threat to patient care following colorectal surgery. OBJECTIVE: The aim of this study is to report the common characteristics of SSIs after colorectal surgery and to highlight the prevalence, risk factors, and clinical relevance of ESBL infections among these patients in a tertiary center. MATERIALS AND METHODS: All patients who underwent bowel resection operation (ie, laparoscopy, laparotomy, or laparoscopic-assisted colectomy) for benign or malignant colorectal disease were identified retrospectively from the prospective database of the colorectal department in the authors' tertiary center from March 2015 to March 2016. RESULTS: There were 123 patients included in this study, of which 21% (n = 26) had a SSI. The microorganisms isolated in the surgical sites included Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, Proteus mirabilis, Morganella morganii, and Enterobacter cloacae. Thirty-eight percent of the wound infections grew ESBL-producing pathogens in their wound cultures and 62% grew non-ESBL microbes. CONCLUSIONS: More than one-third of the wound infections were due to ESBL-producing pathogens, which were resistant to the antibiotic prophylaxis given. Inappropriate antibiotic usage can delay postoperative recovery. High-risk patients for ESBL colonization may benefit from preoperative screening based on an established protocol. The cost effectiveness of an ESBL screening program needs to be further studied.

Normas 2017 de contención de infecciones por gérmenes productores de carbapenemasas del Hospital Nacional de Itauguá, Paraguay / 2017 regulations for the containment of carbapenemase-producing infections of the National Hospital of Itauguá, Paraguay

La carbapenemasa es una enzima producida por varias especies bacterianas, capaz de inactivar un grupo de antibióticos: los carbapenemes. El riesgo radica, además de la dificultad para el tratamiento de las infecciones resistentes a estos antibióticos, en su fácil diseminación entre especies bacterianas, entre pacientes y entre pacientes y contactos (familiares, personal de salud, etc.) Su sigla KPC se generalizó desde el primer caso se dio en la Klebsiella pneumoniae. Se publican Normas que tienen el objetivo de prevenir y controlar la colonización e infección de pacientes con gérmenes productores de carbapenemasa (tipo KPC-NDM etc.) en el Hospital Nacional.

Carbapenemase is an enzyme produced by several bacterial species, capable of inactivating a group of antibiotics: carbapenems. In addition to the difficulty in treating infections resistant to these antibiotics, the risk lies in their easy spread among bacterial species, between patients and between patients and contacts (family members, health personnel, etc.). Its initials KPC was generalized since the first case that occurred in Klebsiella pneumoniae. Guidelines that aim to prevent and control the colonization and infection of patients with carbape

[DISTRIBUTION OF BACTERIA OF THE KLEBSIELLA STRAIN IN WATER OBJECTS AND THEIR VALUE IN DEVELOPING OF THE WATER CAUSED ACUTE INTESTINAL INFECTIONS].

The wide circulation of Klebsiella bacteria in water ofwater objects of different climatic zones of Russia and various function is established. So bacteria of the Klebsiella strain are in superficial sources of the centralized water supply depending on extent of their biological and chemical pollution; underground waters at the unprotected water-bearing horizons; in drinking water at insufficiently effective system of its cleaning and disinfecting. Klebsiella circulating in water was shown to keep properties of pathogenicity and a virulence, possess resistance both to modern preparations and disinfecting agents (chlorine, an ultraviolet to radiation). Bacteria of the Klebsiella strain have high penetration in the water-bearing horizons. At strains of Klebsiella there is allocated considerable pathogenic potential (adhesive, invasive, phosphatase, lecithinase, DNA-ase, hemolytic activity) and genetic markers of pathogenicity of cnf-1. The etiologic role of bacteria of Klebsiella and an infecting (100, COE/dm3) dose emergence of acute intestinal infections (AII) is established. Detection of Klebsiella in water objects and especially in water of drinking appointment, in the absence of total coliform bacteria (TCB) contributes to the epidemic danger of water use.

The investigation of oxacillinase/metallo-beta-lactamase genes and clonal analysis in carbapenem-resistant Klebsiella pneumoniae.

Infections due to carbapenem-resistant Klebsiella pneumoniae represent a growing problem nationally. In our study, we aimed to examine carbapenem-resistant K. pneumoniae with multiple resistance isolated in the intensive care unit of our hospital. Isolates were investigated for the presence of oxacillinase and metallo-beta lactamase genes with a view to determining the clonal relationship between the strains intensely over a short period. Strain identification was completed with conventional methods and automated identification kit. OXA-58, OXA-23, OXA-51, OXA-24 and OXA-48 and metallo-beta lactamase genes IPM, VIM, SPM, SIM, GIM and NDM-1 were investigated with PCR. For clonal relationships of carbapenem-resistant strains, the PFGE experiment was performed. While all of these carbapenem-resistant strains were positive for OXA-48, the resistant genes NDM-1, VIM, KPC, IPM, SPM, GIM, SIM, OXA-23, OXA-24, OXA-58 and OXA-51 were not observed. When molecular typing results were investigated, PFGE determined clonal distribution of three pulsotypes. However, it was observed that the strains intensified in a single clone and this was assessed as the outbreak isolate. The results of this study showed the primary enzyme responsible for carbapenem resistance in K. pneumoniae strains in our hospital is still OXA-48. To prevent the spread of carbapenem-resistant K. pneumoniae isolates, with epidemic potential, national-level monitoring and effective infection control precautions should be enforced.

Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair.

Wound infection is a major clinical problem, yet understanding of bacterial host interactions in the skin remains limited. Microbe-derived molecules, known as pathogen-associated molecular patterns, are recognised in barrier tissues by pattern-recognition receptors. In particular, the pathogen-associated molecular pattern, lipopolysaccharide (LPS), a component of microbial cell walls and a specific ligand for Toll-like receptor 4, has been widely used to mimic systemic and local infection across a range of tissues. Here we administered LPS derived from Klebsiella pneumoniae, a species of bacteria that is emerging as a wound-associated pathogen, to full-thickness cutaneous wounds in C57/BL6 mice. Early in healing, LPS-treated wounds displayed increased local apoptosis and reduced proliferation. Subsequent healing progression was delayed with reduced re-epithelialisation, increased proliferation, a heightened inflammatory response and perturbed wound matrix deposition. Our group and others have previously demonstrated the beneficial effects of 17ß-estradiol treatment across a range of preclinical wound models. Here we asked whether oestrogen would effectively promote healing in our LPS bacterial infection model. Intriguingly, co-treatment with 17ß-estradiol was able to promote re-epithelialisation, dampen inflammation and induce collagen deposition in our LPS-delayed healing model. Collectively, these studies validate K. pneumoniae-derived LPS treatment as a simple yet effective model of bacterial wound infection, while providing the first indication that oestrogen could promote cutaneous healing in the presence of infection, further strengthening the case for its therapeutic use.