COVID-19 in patients with haematologic malignancies: Effect of RNAemia on clinical outcome in vaccinated patients.

OBJECTIVES: Patients with haematologic malignancies (HM) COVID-19 have more severe disease, with increased risk of mortality. Therefore, this study aimed to evaluate the effect of SARS-CoV-2 RNAemia and the specific humoral immune responses on the clinical outcomes of patients with HM and COVID-19. METHODS: Interferon-α/γ (IFN-α/IFN-γ) serum levels, neutralizing antibodies and RNAemia at COVID-19 diagnosis, and persistent RNAemia during the follow-up were evaluated. RESULTS: Overall, 63 (58.9%) out of 107 patients had RNAemia, which was persistent in 26 (41.3%) patients. RNAemia at diagnosis and persistent RNAemia were associated with the need for high-flow nasal oxygen therapy during admission. Persistent RNAemia, age >70 years, and CURB-65 score ≥2 in patients with pneumonia were associated with increased 90-day mortality (P = 0.009, P = 0.030 and P = 0.001, respectively). The 90-day overall survival was lower (P = 0.006) in patients with persistent RNAemia. In addition, dexamethasone administration was associated with a COVID-19 episode with persistent RNAemia. CONCLUSION: Our results suggest that in patients with HM, RNAemia at the time of COVID-19 diagnosis and during the follow-up can be used to stratify patients with HM according to their clinical evolution and to guide clinical decisions tailored to the specific needs of each patient.

Implications of Prenatal Exposure to Endocrine-Disrupting Chemicals in Offspring Development: A Narrative Review.

During the last decades, endocrine-disrupting chemicals (EDCs) have attracted the attention of the scientific community, as a result of a deepened understanding of their effects on human health. These compounds, which can reach populations through the food chain and a number of daily life products, are known to modify the activity of the endocrine system. Regarding vulnerable groups like pregnant mothers, the potential damage they can cause increases their importance, since it is the health of two lives that is at risk. EDCs can affect the gestation process, altering fetal development, and eventually inducing the appearance of many disorders in their childhood and/or adulthood. Because of this, several of these substances have been studied to clarify the influence of their prenatal exposure on the cognitive and psychomotor development of the newborn, together with the appearance of non-communicable diseases and other disorders. The most novel research on the subject has been gathered in this narrative review, with the aim of clarifying the current knowledge on the subject. EDCs have shown, through different studies involving both animal and human investigation, a detrimental effect on the development of children exposed to the during pregnancy, sometimes with sex-specific outcomes. However, some other studies have failed to find these associations, which highlights the need for deeper and more rigorous research, that will provide an even more solid foundation for the establishment of policies against the extended use of these chemicals.

Implications of two-component systems EnvZ/OmpR and BaeS/BaeR in in vitro temocillin resistance in Escherichia coli.

BACKGROUND: BaeS/BaeR is a two-component system of Escherichia coli that controls the expression of porins and efflux pumps. Its role in beta-lactam resistance is limited. OBJECTIVES: To study the role of baeS/baeR two-component system in temocillin resistance in E. coli. METHODS: E. coli strain BW25113 and single-gene deletion mutants related to two-component systems were collected from the KEIO collection. Double-gen deletion mutants were generated. Temocillin-resistant mutant frequencies were determined at 32 mg/L. E. coli BW25113 mutants were selected by selective pressure from serial passages. Biological costs were analysed by growth curves. Genomes of the generated mutants were sequenced. The expression level of the mdtA, mdtB, mdtC, acrD and tolC in the ΔbaeS mutant was determined by RT-PCR (with/without temocillin exposure). RESULTS: The frequency of temocillin mutants ranged from 2.12 × 10-8 to 4.51 × 10-8 in single-porin mutants. No mutants were recovered from E. coli BW25113 (>10-9). Selection of temocillin-resistant variants by serial passage yielded mutants up to 128 mg/L. Mutations were found in the baeS gene. Temocillin MICs ranged from 4 to 32 mg/L (highest MICs for ΔbaeS and ΔompR). The efflux pumps mdtA, mdtB, mdtC and acrD pumps were overexpressed 3-10-fold in the presence of temocillin in ΔbaeS compared to control. CONCLUSIONS: Mutations in the sensor histidine kinase, baeS, may be involved in temocillin resistance through the expression of the efflux pumps mdtABC and acrD. In addition, the low mutation rate may be a good predictor of temocillin activity.

Evaluation of temocillin efficacy against KPC-2-producing Klebsiella pneumoniae isolates in a hollow-fibre infection model.

BACKGROUND: Temocillin is an old antimicrobial that is resistant to hydrolysis by ESBLs but has variable activity against carbapenemase-producing Enterobacteriaceae. The current EUCAST susceptibility breakpoints for Enterobacterales are set at ≤16 mg/L (susceptible with increased exposure) based on a dose of 2 g q8h, but there is limited information on the efficacy of this dose against temocillin-susceptible carbapenemase-producing Klebsiella pneumoniae isolates. OBJECTIVES: To evaluate the efficacy of this dose using a hollow-fibre infection model (HFIM) against six KPC-2-producing clinical isolates of K. pneumoniae. METHODS: The isolates were characterized by WGS and temocillin susceptibility was determined using standard and high inoculum temocillin. Mutant frequencies were estimated and temocillin activity was tested in time-kill assays and in the HFIM. At standard conditions, three of the isolates were classified as susceptible (MIC ≤ 16 mg/L) and three as resistant (MIC > 16 mg/L). The HFIM was performed over 3 days to mimic human-like pharmacokinetics of 2 g q8h. Bacterial counts were performed by plating on Mueller-Hinton agar (MHA) and MHA containing 64 mg/L temocillin to detect resistant subpopulations. RESULTS: All isolates showed a reduction in bacterial population of at least 3 log cfu/mL within the first 8 h of simulated treatment in the hollow-fibre assay. Regrowth was observed for the three resistant isolates and one of the susceptible ones. The MIC value for these isolates was higher by at least two dilutions compared with their initial values. CONCLUSIONS: These data suggest that an optimized pharmacokinetic regimen may be of clinical interest for the treatment of KPC-2-producing K. pneumoniae susceptible to temocillin. These data showed activity of temocillin against KPC-2-producing K. pneumoniae susceptible to temocillin; however, a dose of 2g q8h administered over 30 min may be inadequate to prevent the emergence of resistant variants.

How quality of life is measured in studies of nutritional intervention: a systematic review.

BACKGROUND: Nutrition care can positively affect multiple aspects of patient's health; outcomes are commonly evaluated on the basis of their impact on a patient's (i) illness-specific conditions and (ii) health-related quality of life (HRQoL). Our systematic review examined how HRQoL was measured in studies of nutritional interventions. To help future researchers select appropriate Quality of Life Questionnaires (QoLQ), we identified commonly-used instruments and their uses across populations in different regions, of different ages, and with different diseases. METHODS: We searched EMCare, EMBASE, and Medline databases for studies that had HRQoL and nutrition intervention terms in the title, the abstract, or the MeSH term classifications "quality of life" and any of "nutrition therapy", "diet therapy", or "dietary supplements" and identified 1,113 studies for possible inclusion.We then reviewed titles, abstracts, and full texts to identify studies for final inclusion. RESULTS: Our review of titles, abstracts, and full texts resulted in the inclusion of 116 relevant studies in our final analysis. Our review identified 14 general and 25 disease-specific QoLQ. The most-used general QoLQ were the Short-Form 36-Item Health Survey (SF-36) in 27 studies and EuroQol 5-Dimension, (EQ-5D) in 26 studies. The European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC-QLQ), a cancer-specific QoLQ, was the most frequently used disease-specific QoLQ (28 studies). Disease-specific QoLQ were also identified for nutrition-related diseases such as diabetes, obesity, and dysphagia. Sixteen studies used multiple QoLQ, of which eight studies included both general and disease-specific measures of HRQoL. The most studied diseases were cancer (36 studies) and malnutrition (24 studies). There were few studies focused on specific age-group populations, with only 38 studies (33%) focused on adults 65 years and older and only 4 studies focused on pediatric patients. Regional variation in QoLQ use was observed, with EQ-5D used more frequently in Europe and SF-36 more commonly used in North America. CONCLUSIONS: Use of QoLQ to measure HRQoL is well established in the literature; both general and disease-specific instruments are now available for use. We advise further studies to examine potential benefits of using both general and disease-specific QoLQ to better understand the impact of nutritional interventions on HRQoL.

Interhospital Spread of blaVIM-1- and blaCTX-M-15-Producing K. pneumoniae ST15 on an IncR Plasmid in Southern Spain.

In 2014-2015, the main CTX-M-15- and OXA-48-producing clone in our region was ST15. Recently, K. pneumoniae ST15 isolates co-producing VIM-1 and CTX-M-15 were detected in several hospitals. The aim was to study the emergence and acquisition of this carbapenemase. Between 2017 and 2019, four hospitals submitted twenty-nine VIM-1- and CTX-M-15-producing K. pneumoniae ST15 isolates to our laboratory. Seven representatives of each XbaI PFGE pulsotype were sequenced using short- and long-read technologies. RAST, CGE databases, and Pathogenwatch were used for resistance determinants and capsule-type analysis. Plasmid comparison was performed with Easyfig2.1. Phylogenetic analysis included other contemporary ST15 isolates from Spain. The 29 isolates were clustered into seven different pulsotypes. The selected genomes, from three hospitals in two different provinces, were clustered together (fewer than 35 alleles) and differed by more than 100 alleles from other ST15 isolates obtained in the region. These seven isolates harbored one IncR plasmid (200-220 kb) with a common backbone and four regions flanked by IS26: one contained blaVIM-1, another contained blaCTX-M-15, the third contained blaOXA-1, and the fourth harbored heavy-metal-tolerance genes. The two initial plasmids, from two different centers, were identical, and rearrangement of four regions was observed in the five subsequent plasmids. Our findings showed the first intercenter dissemination of IncR plasmids carrying blaVIM-1, blaCTX-M-15, and metal-tolerance genes mediated by a new lineage of K. pneumoniae ST15. Two different capture events of the blaVIM-1 gene or different IS26-mediated plasmid rearrangements from a common ancestor may explain plasmid variations.

Outbreaks by Klebsiella oxytoca in neonatal intensive care units: Analysis of an outbreak in a tertiary hospital and systematic review.

OBJECTIVE: Klebsiella oxytoca can cause nosocomial infections, affecting vulnerable newborns. There are few studies describing nosocomial outbreaks in the neonatal intensive care units (NICU). In this study, a systematic review of the literature was carried out to know the main characteristics of these outbreaks and the evolution of one is described. METHODS: We conducted a systematic review in the Medline database up to July 2022, and present a descriptive study of an outbreak with 21 episodes in the NICU of a tertiary hospital, between September 2021 and January 2022. RESULTS: 9 articles met the inclusion criteria. The duration of outbreaks was found to be variable, of which 4 (44.4%) lasted for a year or more. Colonization (69%) was more frequent than infections (31%) and the mortality rate was 22.4%. In studies describing sources, the most frequent was the environmental origin (57.1%). In our outbreak there were 15 colonizations and 6 infections. The infections were mild conjunctivitis without sequelae. Molecular typing analysis made it possible to detect 4 different clusters. CONCLUSIONS: There is an important variability in the evolution and results of the published outbreaks, highlighting a greater number of colonized, use of PFGE (pulsed-field gel electrophoresis) techniques for molecular typing and implementation of control measures. Finally, we describe an outbreak in which 21 neonates were affected with mild infections, resolved without sequelae and whose control measures were effective.

Multidrug-resistant Enterobacterales responsible for septicaemia in a neonatal intensive care unit in Morocco.

OBJECTIVES: Neonatal sepsis caused by multidrug-resistant (MDR) bacteria has a high morbidity and mortality, especially in low- and middle-income countries. Here, the molecular mechanisms of multidrug resistance in bacteria responsible for neonatal sepsis were determined. METHODS: From July to December 2019, documented bacteraemia from 524 neonates hospitalised in a neonatal intensive care unit in Morocco were collected. Whole-genome sequencing was used to characterise the resistome; multi-locus sequence typing was used to investigate phylogeny. RESULTS: Among the 199 cases of documented bacteraemia, 40 (20%) and 20 (10%) were caused by MDR Klebsiella pneumoniae and Enterobacter hormaechei, respectively. Of these, 23 (38.5%) were early neonatal infections (≤3 days of life). Twelve different sequence types (STs) were observed among K. pneumoniae isolates, the most prevalent being ST1805 (n = 10) and ST307 (n = 8). Twenty-one K. pneumoniae isolates (53%) possessed the blaCTX-M-15 gene, six of which co-produced OXA-48; two, NDM-7; and two, OXA-48 and NDM-7. The blaOXA-48 gene was present in 11 K. pneumoniae isolates (27.5%); blaNDM-1, in 13 (32.5%); and blaNDM-7, in 4 (10.0%). Eighteen E. hormaechei isolates (90.0%) produced an extended-spectrum ß-lactamase (ESBL). Three were SHV-12 producers that co-produced CMY-4 and NDM-1, and 15 were CTXM-15 producers, of which 6 co-produced OXA-48. Twelve different STs belonging to three different E. hormaechei subspecies were observed, with one to four isolates. K. pneumoniae and E. hormaechei isolates belonging to the same ST had less than 20 single nucleotide polymorphism differences and were found throughout the study period, highlighting their endemic presence in the neonatal intensive care unit. CONCLUSION: Thirty percent of neonatal sepsis cases (23 early and 37 late) were caused by highly drug-resistant carbapenemase- and/or ESBL-producing Enterobacterales.

Red Blood Cells Protein Profile Is Modified in Breast Cancer Patients.

Metastasis is the primary cause of death for most breast cancer (BC) patients who succumb to the disease. During the hematogenous dissemination, circulating tumor cells interact with different blood components. Thus, there are microenvironmental and systemic processes contributing to cancer regulation. We have recently published that red blood cells (RBCs) that accompany circulating tumor cells have prognostic value in metastatic BC patients. RBC alterations are related to several diseases. Although the principal known role is gas transport, it has been recently assigned additional functions as regulatory cells on circulation. Hence, to explore their potential contribution to tumor progression, we characterized the proteomic composition of RBCs from 53 BC patients from stages I to III and IV, compared with 33 cancer-free controls. In this work, we observed that RBCs from BC patients showed a different proteomic profile compared to cancer-free controls and between different tumor stages. The differential proteins were mainly related to extracellular components, proteasome, and metabolism. Embryonic hemoglobins, not expected in adults' RBCs, were detected in BC patients. Besides, lysosome-associated membrane glycoprotein 2 emerge as a new RBCs marker with diagnostic and prognostic potential for metastatic BC patients. Seemingly, RBCs are acquiring modifications in their proteomic composition that probably represents the systemic cancer disease, conditioned by the tumor microenvironment.

Antimicrobial and Antibiofilm Effect of 4,4'-Dihydroxy-azobenzene against Clinically Resistant Staphylococci.

The spread of antibiotic resistance among human and animal pathogens is one of the more significant public health concerns. Moreover, the restrictions on the use of particular antibiotics can limit the options for the treatment of infections in veterinary clinical practice. In this context, searching for alternative antimicrobial substances is crucial nowadays. In this study, 4,4'-dihydroxy-azobenzene (DHAB) was tested for its potential in vitro as an antimicrobial agent against two relevant human and animal pathogens, namely Staphylococcus aureus and Staphylococcus pseudintermedius. The values of minimal inhibitory concentration (MIC) were 64 and 32 mg/L respectively, and they comparable to other azo compounds of probed antimicrobial activity. In addition, the minimal bactericidal concentrations (MCB) were 256 and 64 mg/L. The mechanism by which DHAB produces toxicity in staphylococci has been investigated. DHAB caused membrane damage as revealed by the increase in thiobarbituric acid reactive substances (TBARS) such as malondialdehyde. Furthermore, differential induction of the enzymes peroxidases and superoxide dismutase in S. aureus and S. pseudintermedius suggested their prevalent role in ROS-scavenging due to the oxidative burst induced by this compound in either species. In addition, this substance was able to inhibit the formation of biofilms by both bacteria as observed by colorimetric tests and scanning electron microscopy. In order to assess the relevance of DHAB against clinical strains of MRSA, 10 clinical isolates resistant to either methicillin or daptomycin were assayed; 80% of them gave values of CMI and CMB similar to those of the control S. aureus strain. Finally, cutaneous plasters containing a composite formed by an agar base supplemented with DHAB were designed. These plasters were able to inhibit in vitro the growth of S. aureus and S. pseudintermedius, particularly the later, and this suggests that this substance could be a promising candidate as an alternative to antibiotics in the treatment of animal skin infections, as it has been proven that the toxicity of this substance is very low particularly at a dermal level.

A genome-wide cell-free DNA methylation analysis identifies an episignature associated with metastatic luminal B breast cancer.

Breast cancers of the luminal B subtype are frequent tumors with high proliferation and poor prognosis. Epigenetic alterations have been found in breast tumors and in biological fluids. We aimed to profile the cell-free DNA (cfDNA) methylome of metastatic luminal B breast cancer (LBBC) patients using an epigenomic approach to discover potential noninvasive biomarkers. Plasma cfDNA was analyzed using the Infinium MethylationEpic array in a cohort of 14 women, including metastatic LBBC patients and nontumor controls. The methylation levels of cfDNA and tissue samples were validated with droplet digital PCR. The methylation and gene expression data of 582 primary luminal breast tumors and 79 nontumor tissues were obtained from The Cancer Genome Atlas (TCGA). We found an episignature of 1,467 differentially methylated CpGs that clearly identified patients with LBBC. Among the genes identified, the promoter hypermethylation of WNT1 was validated in cfDNA, showing an area under the ROC curve (AUC) of 0.86 for the noninvasive detection of metastatic LBBC. Both paired cfDNA and primary/metastatic breast tumor samples showed hypermethylation of WNT1. TCGA analysis revealed significant WNT1 hypermethylation in the primary tumors of luminal breast cancer patients, with a negative association between WNT1 methylation and gene expression. In this proof-of-principle study, we discovered an episignature associated with metastatic LBBC using a genome-wide cfDNA methylation approach. We also identified the promoter hypermethylation of WNT1 in cfDNA as a potential noninvasive biomarker for luminal breast cancer. Our results support the use of EPIC arrays to identify new epigenetic noninvasive biomarkers in breast cancer.

Effect of exposure to endocrine disrupting chemicals in obesity and neurodevelopment: The genetic and microbiota link.

Current evidence highlights the importance of the genetic component in obesity and neurodevelopmental disorders (attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID)), given that these diseases have reported an elevated heritability. Additionally, environmental stressors, such as endocrine disrupting chemicals (EDCs) have been classified as obesogens, neuroendocrine disruptors, and microbiota disrupting chemicals (MDCs). For this reason, the importance of this work lies in examining two possible biological mechanistic pathways linking obesity and neurodevelopmental/behavioural disorders: EDCs - gene and EDCs - microbiota interactions. First, we summarise the shared mechanisms of action of EDCs and the common genetic profile in the bidirectional link between obesity and neurodevelopment. In relation to interaction models, evidence from the reviewed studies reveals significant interactions between pesticides/heavy metals and gene polymorphisms of detoxifying and neurotransmission systems and metal homeostasis on cognitive development, ASD and ADHD symptomatology. Nonetheless, available literature about obesity is quite limited. Importantly, EDCs have been found to induce gut microbiota changes through gut-brain-microbiota axis conferring susceptibility to obesity and neurodevelopmental disorders. In view of the lack of studies assessing the impact of EDCs - gene interactions and EDCs - mediated dysbiosis jointly in obesity and neurodevelopment, we support considering genetics, EDCs exposure, and microbiota as interactive factors rather than individual contributors to the risk for developing obesity and neurodevelopmental disabilities at the same time.

Prevalence of the fimbrial operon mrkABCD, mrkA expression, biofilm formation and effect of biocides on biofilm formation in carbapenemase-producing Klebsiella pneumoniae isolates belonging or not belonging to high-risk clones.

BACKGROUND: The role of mrkA adhesin expression, biofilm production, biofilm viability and biocides in the biofilm of carbapenemase-producing Klebsiella pneumoniae isolates was investigated. METHODS: Seventeen isolates representing different sequence types and carbapenemases were investigated. mrkA expression was determined by real-time reverse transcription polymerase chain reaction. Biofilm production (25°C and 37°C, with and without humidity) was determined by the crystal violet assay. The effect of isopropanol, povidone-iodine, sodium hypochlorite, chlorhexidine digluconate, benzalkonium chloride, ethanol and triclosan on biofilm was determined. The effect of povidone-iodine on biofilm biomass and thickness was also determined by confocal laser scanning microscopy. RESULTS: mrkA expression ranged from 28.2 to 1.3 [high or intermediate level; 64% of high-risk (HR) clones] and from 21.5 to 1.3 (50% of non-HR clones). At 25°C, biofilm formation was observed in 41% of isolates (absence of humidity) and 35% of isolates (presence of humidity), whereas at 37°C, biofilm formation was observed in 76% of isolates with and without humidity. At 25°C, biofilm producers were more frequently observed in HR clones (45% with humidity and 55% without humidity) than non-HR clones (17% with and without humidity). Biofilm viability from day 21 was higher at 25°C than 37°C. The greatest decrease in biofilm formation was observed with povidone-iodine (29% decrease), which also decreased biofilm thickness. CONCLUSIONS: Biofilm formation in carbapenemase-producing K. pneumoniae is related to mrkA expression. Biofilm formation is affected by temperature (37°C>25°C), whereas humidity has little effect. Biofilm viability is affected by temperature (25°C>37°C). At 25°C, HR clones are more frequently biofilm producers than non-HR clones. Povidone-iodine can decrease biofilm production and biofilm thickness.

In vitro activity of six biocides against carbapenemase-producing Klebsiella pneumoniae and presence of genes encoding efflux pumps / Actividad in vitro de seis biocidas frente a Klebsiella pneumoniae productora de carbapenemasa y presencia de genes codificantes de bombas de expulsión

Introduction: Acquisition of reduced susceptibility to biocides may contribute to the dissemination of high-risk (HR) clones of carbapenemase-producing Klebsiella pneumoniae (CP-Kp). The aim of this study was (a) to determinate the activity of biocides against CP-Kp, and (b) to analyse the relationship between biocide activity and the presence of efflux pumps. Methods: The minimal inhibitory concentrations (MICs) of 6 biocides (sodium hypochlorite, chlorhexidine digluconate, benzalkonium chloride, povidone-iodine, ethanol and triclosan) were determined in triplicate at 25°C and 37°C in Mueller-Hinton broth (MHB) and M9 minimum medium, against 17 CP-Kp isolates representing different clones (HR and no-HR), sequence-types (STs) and carbapenemases. Efflux pumps genes were detected by whole genome sequencing (MiSeq). Results: Median MICs were slightly higher at 37°C than at 25°C (p≤0.05), except for benzalkonium chloride, triclosan and ethanol. MIC medians were much higher in MHB than in M9, except for triclosan. No significant differences were observed in the median MICs, regarding the type of clone, ST or carbapenemase; cepA, acrAB, kpnEF and oqxAB genes were detected in all isolates, whereas qacE and qacA were not detected; smvAR, and qacΔE genes were detected in 94% and 47% of isolates, respectively. Conclusions: Triclosan, chlorhexidine digluconate, benzalkonium chloride and ethanol were the most active biocides. The activity of some biocides is affected by temperature and growth media, suggesting that standardised procedures for biocide susceptibility testing based on MIC determination are required. This activity, in terms of MICs, are not related to the type of clone, ST, carbapenemase or the presence of the efflux pump genes.(AU)

Introducción: La adquisición de sensibilidad reducida a los biocidas puede contribuir a la diseminación de clones de alto riesgo (HR) de Klebsiella pneumoniae productor de carbapenemasa (Kp-PC). El objetivo de este trabajo fue: (a) determinar la actividad de varios biocidas frente a Kp-PC, y (b) analizar la relación de dicha actividad con la presencia de genes codificantes de bombas de expulsión. Métodos: Las concentraciones mínimas inhibitorias (CMI) de 6 biocidas (hipoclorito de sodio, digluconato de clorhexidina, cloruro de benzalconio, povidona yodada, etanol y triclosán) se determinaron por triplicado a 25 y 37°C, tanto en caldo Mueller-Hinton (MHB) como en medio mínimo M9, frente a 17 aislados de Kp-PC representativos de diferentes clones (HR y no HR), secuenciotipos (ST) y carbapenemasas. Los genes de bombas de expulsión se detectaron mediante secuenciación masiva del genoma completo (MiSeq). Resultados: Las medianas de las CMI fueron ligeramente superiores a 37°C que a 25°C, excepto para cloruro de benzalconio, etanol y triclosán. Las medianas de las CMI fueron considerablemente superiores en MHB que en M9, excepto para triclosán; cepA, acrAB, kpnEF y oqxAB se detectaron en todos los aislados, mientras que qacE y qacA no se detectaron; smvAR y qacΔE se detectaron en el 94% y en el 47% de los aislados, respectivamente. Conclusiones: La actividad de algunos biocidas se afecta por la temperatura y el medio de crecimiento. Esta actividad, en términos de CMI, no se relaciona con el tipo de clon, ST, carbapenemasa, ni con la presencia de genes que codifican bombas de expulsión.(AU)

Economic Impact of Reducing Reexcision Rates after Breast-Conserving Surgery in a Large, Integrated Health System.

BACKGROUND: Reexcision after breast-conserving surgery (BCS) is costly for patients, but few studies have captured the economic burden to a healthcare system. We quantified operating room (OR) charges as well as OR time and then modeled expected savings of a reexcision reduction initiative. METHODS: We performed a retrospective cohort review of all breast cancer patients with BCS between January 1, 2016 and December 31, 2020. Operating room charges of disposable supplies and implants as well as operative time were calculated. RESULTS: During the 5-year period, the 8804 patients who underwent BCS, 1628 (18.5%) required reexcision. The reexcision cohort was younger (61 vs. 64 years, p < 0.001), more likely to have ductal carcinoma in situ (DCIS) (23.7% vs. 15.2%, p < 0.001), and had larger tumors (T1+T2 73.2% vs. 83.1%, p < 0.001). Reexcision costs represented 39% of total costs, the cost per patient for surgery was fourfold higher for reexcision patients. Reexcision operations comprised 14% of total operating room (OR) time (1848 of 13,030 hours). The reexcision rate for 54 surgeons varied from 7.2-39.0% with 46% (n = 25) having a reexcision rate >20%. A model simulating reducing reexcision rates to 20% or below for all surgeons reduced the reexcision rate to 16.2% overall. Using per procedure data, the model predicted a decrease in reexcision operations by 18% (327 operations), OR costs by 14% ($287,534), and OR time by 11% (204 hours). CONCLUSIONS: Reexcision after BCS represents 39% of direct OR costs and 14% of OR time in our healthcare system. Modest improvements in surgeon reexcision rates may lead to significant economic and OR time savings.

In vitro activity of six biocides against carbapenemase-producing Klebsiella pneumoniae and presence of genes encoding efflux pumps.

INTRODUCTION: Acquisition of reduced susceptibility to biocides may contribute to the dissemination of high-risk (HR) clones of carbapenemase-producing Klebsiella pneumoniae (CP-Kp). The aim of this study was (a) to determinate the activity of biocides against CP-Kp, and (b) to analyse the relationship between biocide activity and the presence of efflux pumps. METHODS: The minimal inhibitory concentrations (MICs) of 6 biocides (sodium hypochlorite, chlorhexidine digluconate, benzalkonium chloride, povidone-iodine, ethanol and triclosan) were determined in triplicate at 25°C and 37°C in Mueller-Hinton broth (MHB) and M9 minimum medium, against 17 CP-Kp isolates representing different clones (HR and no-HR), sequence-types (STs) and carbapenemases. Efflux pumps genes were detected by whole genome sequencing (MiSeq). RESULTS: Median MICs were slightly higher at 37°C than at 25°C (p≤0.05), except for benzalkonium chloride, triclosan and ethanol. MIC medians were much higher in MHB than in M9, except for triclosan. No significant differences were observed in the median MICs, regarding the type of clone, ST or carbapenemase; cepA, acrAB, kpnEF and oqxAB genes were detected in all isolates, whereas qacE and qacA were not detected; smvAR, and qacΔE genes were detected in 94% and 47% of isolates, respectively. CONCLUSIONS: Triclosan, chlorhexidine digluconate, benzalkonium chloride and ethanol were the most active biocides. The activity of some biocides is affected by temperature and growth media, suggesting that standardised procedures for biocide susceptibility testing based on MIC determination are required. This activity, in terms of MICs, are not related to the type of clone, ST, carbapenemase or the presence of the efflux pump genes.