Unraveling resistance mechanisms in combination therapy: A comprehensive review of recent advances and future directions.

Antimicrobial resistance is a global health threat. Misuse and overuse of antimicrobials are the main drivers in developing drug-resistant bacteria. The emergence of the rapid global spread of multi-resistant bacteria requires urgent multisectoral action to generate novel treatment alternatives. Combination therapy offers the potential to exploit synergistic effects for enhanced antibacterial efficacy of drugs. Understanding the complex dynamics and kinetics of drug interactions in combination therapy is crucial. Therefore, this review outlines the current advances in antibiotic resistance's evolutionary and genetic dynamics in combination therapies-exposed bacteria. Moreover, we also discussed four pivotal future research areas to comprehend better the development of antibiotic resistance in bacteria treated with combination strategies.

Risk factors for acquiring BMR infections: Analytical study.

INTRODUCTION: In recent years, there has been a considerable increase in the prevalence of bacteria increasingly resistant to multiple families of antibiotics, which constitutes a major problem for public health. AIM: To determine the prevalence and different risk factors for the acquisition of multi-resistant bacteria. METHODS: This is an analytical and prospective study including patients hospitalized in the Batna University Hospital during the period from January 2023 to March 2023 presenting a documented infection with isolation of sensitive or multi-resistant strains. An operating sheet based on the different risk factors for acquiring multi-resistant bacteria has been established. RESULTS: We collected 250 patients. There are 160 men and 90 women with an average age of 44 years. Of all the strains that were identified, 100 isolates were multi-resistant bacteria. ESBL-producing Enterobacteriaceae are the most frequently isolated multi-resistant bacteria. Multivariate logistic regression analysis identified four risk factors that are significantly related to the risk of acquiring multi-resistant bacteria infection: prior antibiotic therapy [P = 0,029], use of invasive medical care [P = 0,024], the nosocomial origin of the infection [P = 0,036] and the use of public toilets [P = 0,015]. CONCLUSION: Our results clearly demonstrate that the inappropriate use of antibiotics, especially broad-spectrum antibiotics, and hand-held cross-transmission play a major role in the spread of multi-resistant bacteria in our hospital.

High Genetic Diversity in Third-Generation Cephalosporin-Resistant Escherichia coli in Wastewater Systems of Schleswig-Holstein.

The spread of multidrug-resistant bacteria from humans or livestock is a critical issue. However, the epidemiology of resistant pathogens across wastewater pathways is poorly understood. Therefore, we performed a detailed comparison of third-generation cephalosporin-resistant Escherichia coli (3GCREC) from wastewater treatment plants (WWTPs) to analyze dissemination pathways. A total of 172 3GCREC isolated from four WWTPs were characterized via whole genome sequencing. Clonal relatedness was determined using multi-locus sequence typing (MLST) and core genome MLST. Resistance genotypes and plasmid replicons were determined. A total of 68 MLST sequence types were observed with 28 closely related clusters. Resistance genes to eight antibiotic classes were detected. In fluoroquinolone-resistant isolates, resistance was associated with three-or-more point mutations in target genes. Typing revealed high genetic diversity with only a few clonal lineages present in all WWTPs. The distribution paths of individual lines could only be traced in exceptional cases with a lack of enrichment of certain lineages. Varying resistance genes and plasmids, as well as fluoroquinolone resistance-associated point mutations in individual isolates, further corroborated the high diversity of 3GCREC in WWTPs. In total, we observed high diversity of 3GCREC inside the tested WWTPs with proof of resistant strains being released into the environment even after treatment processes.

Mechanism of escape from the antibacterial activity of metal-based nanoparticles in clinically relevant bacteria: A systematic review.

The emergency of antibiotic-resistant bacteria in severe infections is increasing, especially in nosocomial environments. The ESKAPE group is of special importance in the groups of multi-resistant bacteria due to its high capacity to generate resistance to antibiotics and bactericides. Therefore, metal-based nanomaterials are an attractive alternative to combat them because they have been demonstrated to damage biomolecules in the bacterial cells. However, there is a concern about bacteria developing resistance to NPs and their harmful effects due to environmental accumulation. Therefore, this systematic review aims to report the clinically relevant bacteria that have developed resistance to the NPs. According to the results of this systematic review, various mechanisms to counteract the antimicrobial activity of various NP types have been proposed. These mechanisms can be grouped into the following categories: production of extracellular compounds, metal efflux pumps, ROS response, genetic changes, DNA repair, adaptative morphogenesis, and changes in the plasma membrane.

Diversity of Endophytic Fungi Isolated from the Bark of Ceiba pentandra (L.) Gaertn., (Bombacaceae) and Antibacterial Potential of Secalonic Acid A Produced by Diaporthe searlei EC 321.

The objective of this study was to study the diversity of endophytic fungi isolated from Ceiba pentandra and to isolate their bioactive chemical compounds. The methodology used during this study consisted in isolating endophytic fungi from the bark of C. pentandra on Potato Agar. The isolates obtained were identified on the basis of the ITS regions of their ribosomal DNA. Antibacterial screening of the mycelium of endophytic fungi isolated was evaluated against multidrug-resistant E. coli and S. aureus strains. This screening led to the selection of isolates EC 321 and EC 28 for their ability to effectively inhibit the growth of the bacterial strains tested. EC 321 was grown and fermented on rice medium. Secondary metabolites were extracted with ethyl acetate. From the crude extract, secalonic acid A was isolated and identified by chromatographic and NMR. The in vitro activity of secalonic acid A against the growth of multiresistant bacterial strains was evaluated. Secalonic acid A was active against all multidrug-resistant bacterial strains E. coli 942, E. coli 4814, S. aureus 931, S. aureus 934, S. aureus MRSA 1872 and K. pneumonia 815 with respective MICs of 18.75; 18.75; 18.75; 4.7; 37.5 and 37.5 µg/mL.

Long time persistence and evolution of carbapenemase-producing Enterobacterales in the wastewater of a tertiary care hospital in Germany.

BACKGROUND: Worldwide observations revealed increased frequencies of multi-resistant Enterobacterales and resistance genes in hospital wastewater compared to any other type of wastewater. Despite the description of clonal lineages possibly adapted to hospital wastewater, little is known about long term persistence as well as evolution of these lineages. METHODS: In this study, wastewater isolates of different Enterobacterales species from a tertiary care hospital were investigated with 2.5 years distance. Whole Genome Sequencing (WGS) and resistance gene identification were performed for E. coli, C. freundii, S. marcescens, K. pneumoniae, K. oxytoca, and E. cloacae isolates (n = 59), isolated in 2022 and compared with strains isolated from the same wastewater pipeline in 2019 (n = 240). RESULTS: Individual clonal lineages with highly related isolates could be identified in all species identified more than once in 2022 that appear to persist in the wastewater drainage. A common motif of all persistent clonal lineages was the carriage of mobile genetic elements encoding carbapenemase genes with hints for horizontal gene transfer in persistent clones in this environment observed over the 2.5-year period. Multiple plasmid replicons could be detected in both years. In 2022 isolates blaVIM-1 replaced blaOXA-48 as the most common carbapenemase gene compared to 2019. Interestingly, despite a similar abundance of carbapenemase genes (>80% of all isolates) at both time points genes encoding extended spectrum ß-lactamases decreased over time. CONCLUSIONS: This data indicates that hospital wastewater continuously releases genes encoding carbapenemases to the urban wastewater system. The evolution of the resident clones as well as the reasons for the selection advantage in this specific ecological niche needs to be further investigated in the future.

Description of Antimicrobial Resistance Patterns at the National Institute of Hygiene in Lome, Togo.

The monitoring of antimicrobial resistance has become a priority, mainly in developing countries, to control the emergence of multidrug-resistant bacterial strains. This study evaluated the antibiotic resistance profiles of bacteria isolated at the National Institute of Hygiene in Togo. The laboratory records from January 2013 to December 2015 were examined, which showed that a total of 33,147 samples had been analyzed. Among them, vaginal swabs and urine samples were predominant, amounting to 38.17% and 33.24%, respectively. In total, 3,497 Gram-positive and 1,970 Gram-negative bacterial strains were cultured. Enterobacteriaceae (57.6%), Staphylococcus spp. (21.1%), and Streptococcus spp. (10.5%) were primarily isolated. The records showed that over 3 years, Escherichia coli was resistant to piperacillin (79.66%, 75.1%, and 83%), trimethoprim/sulfamethoxazole (79.3%, 82%, and 82.8%), ticarcillin (89%, 89.7%, and 93%), and amoxicillin (94.1%, 94%, and 96.09%), whereas Staphylococcus aureus was resistant to penicillin G. Streptococcaceae isolates were resistant to trimethoprim/sulfamethoxazole (78.11-87.1%), tetracycline (82.2-91.16%), and norfloxacin (86.16-94.3%). Escherichia coli and S. aureus isolated from urine were more resistant to antibiotics than those isolated from vaginal swabs. There is a need to develop new strategies to fight the emergence of multi-resistant bacteria in Togo.

Multidrug resistant bacteria isolated from nosocomial infections at University Teaching Hospital of Point-G, Bamako, Mali.

An infection is said to be nosocomial or hospital if it is absent when the patient enters the hospital and it appears and develops at least 48 h late. The objective of this study was to determine the resistance phenotypes of bacteria isolated from nosocomial infections at the University Teaching Hospital of Point G. Urine, blood, pus, skin and bronchoalveolar fluid samples were taken in different units, and bacteria isolations were performed on usual selective media such as Drigalski Colombia agar supplemented with nalidixic acid and colistin and 5% sheep blood and chocolate agar. Identifications of bacteria such as Enterobacteriaceae, Pseudomonas and acinetobacter, and Staphylococci were done using API20E gallery, API20NE gallery and catalase/oxidase tests, and the Pastorex Staph kit respectively. The antimicrobial susceptibility testing was performed on Mueller-Hinton agar using the diffusion method. A total of 463 patients were inpatients for at least 48 h in the different units, and a nosocomial infection was notified in at least 57 patients (12.3%). A total of 65 episodes of nosocomial infections were observed in these 57 patients. Of the bacteria isolated, multidrug-resistant bacteria (MDR) represented 63.7% (n=36). These were extended-spectrum beta-lactamase (ESBL)-secreting Enterobacteriaceae (n=21), high-level cephalosporinase (n=13) and methicillin-resistant coagulase-negative Staphylococci (n=2). Despite this high number of multi-resistant bacteria isolated in this study; colistin and amikacin had very good activity on enterobacteriaceae. The results show the need to strengthen hygiene in the intensive care units in order to fight against nosocomial infections at the UTH of Point G.

Lipid nanoparticles based on natural matrices with activity against multidrug resistant bacterial species.

Lately, the bacterial multidrug resistance has been a reason to public health concerning around world. The development of new pharmacology therapies against infections caused by multidrug-resistant bacteria is urgent. In this work, we developed 10 NLC formulations composed of essential oils (EO), vegetable butter and surfactant. The formulations were evaluated for long-term and thermal cycling stability studies in terms of (particle size, polydispersion index and Zeta potential). In vitro antimicrobial assays were performed using disk diffusion test and by the determination of the minimum inhibitory concentration (MIC) performed with fresh and a year-old NLC. The most promising system and its excipients were structurally characterized through experimental methodologies (FTIR-ATR, DSC and FE-SEM). Finally, this same formulation was studied through nanotoxicity assays on the chicken embryo model, analyzing different parameters, as viability and weight changes of embryos and annexes. All the developed formulations presented long-term physicochemical and thermal stability. The formulation based on cinnamon EO presented in vitro activity against strains of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa isolated from humans and in vivo biocompatibility. Considering these promising results, such system is able to be further tested on in vivo efficacy assays.

High burden and diversity of carbapenemase-producing Enterobacterales observed in wastewater of a tertiary care hospital in Germany.

Hospitals are one of the main reservoirs of multi-resistant Enterobacterales (MRE). As MRE are resistant to the most frequently used antibiotics, therapy for patients with MRE infections is challenging. It has been previously described that MRE from hospital wastewater can pass into municipal wastewater and even surface water. In this study, we investigated the diversity and epidemiology of MRE in the wastewater of a large tertiary care hospital. Wastewater samples were collected for a four-day period and tested for the presence of Enterobacterales resistant to 3rd gen. cephalosporins. Representative isolates were further characterized by whole genome sequencing. In 120 ß-glucuronidase-producing isolates, 68 Escherichia coli and, interestingly, also 52 Citrobacter freundii were identified. In 120 ß-glucosidase-producing isolates 45 Serratia marcescens, 34 Klebsiella oxytoca, 32 Enterobacter cloacae and 9 Klebsiella pneumoniae were observed. For all species various MLST sequence types and different clusters of resistance genes were determined, showing a great diversity within the different Enterobacterales, further corroborated by clonal analysis performed by cgMLST. The most prominent clone was wastewater associated E. coli ST635, which accounted for 47.1% of all E. coli isolates. Interestingly, 45.6% of E. coli, 88.5% of C. freundii, 95.6% of S. marcescens, 91.2% of K. oxytoca, 96.9% of E. cloacae and 88.9% of K. pneumoniae isolates carried a carbapenemase gene, indicating a high burden with carbapenemase-producing Enterobacterales. Comparison with clinical isolates from the same hospital displayed few clonal matches. One wastewater isolate of K. pneumoniae was identified to be closely related compared to a clone that had been introduced into the hospital during an outbreak four years earlier. One E. coli isolate was identified as identical to an isolate from a patient, with inpatient stay during the sampling period. The data obtained in this study highlight the problem of antibiotic resistance of Enterobacterales in hospital wastewater. In particular, the clustered occurrence of carbapenemase genes is of great concern and underscores the problem of increasingly scarce antibiotic options against these bacteria.

Systematic Review of Plasmid AmpC Type Resistances in Escherichia coli and Klebsiella pneumoniae and Preliminary Proposal of a Simplified Screening Method for ampC.

Beta-lactamase (BL) production is a major public health problem. Although not the most frequent AmpC type, AmpC-BL is increasingly isolated, especially plasmid AmpC-BL (pAmpC-BL). The objective of this study was to review information published to date on pAmpC-BL in Escherichia coli and Klebsiella pneumoniae, and on the epidemiology and detection methods used by clinical microbiology laboratories, by performing a systematic review using the MEDLINE PubMed database. The predictive capacity of a screening method to detect AmpC-BL using disks with cloxacillin (CLX) was also evaluated by studying 102 Enterobacteriaceae clinical isolates grown in CHROMID ESBL medium with the addition of cefepime (FEP), cefoxitin (FOX), ertapenem (ETP), CLX, and oxacillin with CLX. The review, which included 149 publications, suggests that certain risk factors (prolonged hospitalization and previous use of cephalosporins) are associated with infections by pAmpC-BL-producing microorganisms. The worldwide prevalence has increased over the past 10 years, with a positivity rate ranging between 0.1 and 40%, although AmpC was only detected when sought in a targeted manner. CMY-2 type has been the most prevalent pAmpC-BL-producing microorganism. The most frequently used phenotypic method has been the double-disk synergy test (using CLX disks or phenyl-boronic acid and cefotaxime [CTX] and ceftazidime) and the disk method combined with these inhibitors. In regard to screening methods, a 1-µg oxacillin disk with CLX showed 88.9% sensitivity, 100% specificity, 100% positive predictive value (PPV), 98.9% negative predictive value (NPV), and 98.9% validity index (VI). This predictive capacity is reduced with the addition of extended-spectrum beta-lactamases, showing 62.5% sensitivity, 100% specificity, 100% PPV, 93.5% NPV, and 94.1% VI. In conclusion, there has been a worldwide increase in the number of isolates with pAmpC-BL, especially in Asia, with CMY-2 being the most frequently detected pAmpC-BL-producing type of microorganism. Reduction in its spread requires routine screening with a combination of phenotypic methods (with AmpC inhibitors) and genotypic methods (multiplex PCR). In conclusion, the proposed screening technique is an easy-to-apply and inexpensive test for the detection of AmpC-producing isolates in the routine screening of multidrug-resistant microorganisms.

High antimicrobial resistance in Salmonella spp. and Escherichia coli isolates from swine fecal samples submitted to a veterinary diagnostic laboratory in Colombia

Background: Commensal microflora such as Escherichia coli and Enterococcus spp. are representative indicators of antimicrobial resistance (AMR) as they are part of the normal intestinal microflora and can acquire and disseminate AMR to pathogenic or zoonotic bacteria like Salmonella spp. Objective: To investigate the state of AMR among E. coli and Salmonella spp., potential pathogens in humans, isolated from cecal contents of pigs submitted to a veterinary diagnostic laboratory in Colombia from 2016 to 2019. Methods: Susceptibility testing was conducted using the Kirby-Bauer disk diffusion method according to the Clinical and Laboratory Standards Institute guidelines for antimicrobial zone diameter breakpoints. An E. coli strain (ATCC 25922) was used as the quality control organism. Isolates showing resistance to three or more antimicrobial classes were classified as multidrug-resistant (MDR) as defined by a joint group of the European Centre for Disease prevention and Control and the Center for Disease Control and Prevention of the USA. Results: A total of 112 E. coli and 192 Salmonella spp. colonies were isolated from 557 samples received between 2016 and 2019. In order of decreasing frequency, E. coli was resistant to tetracycline (100%), sulfamethoxazol-trimethoprim (97.5%), amoxicillin (86.4%), enrofloxacin (82.6%), tylosin (82.1%), doxycycline (59%), neomycin (50%), ciprofloxacin (45.5%), ceftiofur (35%), gentamicin (30%), tilmicosin (29%), and fosfomycin (12.5%). When compared with E. coli, Salmonella spp. was generally resistant to the same agents with slightly less resistance (between 10-30%) to eight of the antimicrobials tested. Salmonella spp. showed <20% resistance to three antimicrobials, as follows: neomycin (17%), gentamicin (16%), and fosfomycin (14%). Multi-resistance occurred in 68.7% (77/112) of E. coli and 70.3% (135/192) of Salmonella spp. isolates. Resistance of Salmonella spp. was alarming to all the critically important antimicrobials tested: fluoroquinolones (enrofloxacin, ciprofloxacin), ceftiofur (third- generation cephalosporin), and macrolides (tylosin). Conclusions: According to our results, there is a high level of multi- drug resistance (MDR) in E. coli and Salmonella spp. It is necessary to implement a nationwide antimicrobial resistance monitoring program in Colombia, together with proper antimicrobial prescribing guidelines for pigs. The indiscriminate use of antimicrobial growth promoters by the swine industry is generating widespread bacterial resistance and should be discontinued.

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Antecedentes: Flora comensal como espécies de Escherichia coli e Enterococcus são tipicamente escolhidas como indicadores representativos de la resistência antimicrobiana (AMR), pois fazem parte da flora intestinal normal e podem adquirir e disseminar AMR a bactérias patogênicas ou zoonóticas como Salmonella spp. Objetivo: Investigar o estado da AMR entre E. coli e Salmonella spp. isolados do conteúdo cecal de porcos colombianos submetidos ao Laboratório de Diagnóstico Veterinário de 2016 a 2019, ambos sendo patógenos potenciais em humanos. Métodos: O teste de suscetibilidade foi conduzido usando o método de difusão em disco Kirby-Bauer de acordo com as diretrizes do Instituto de Padrões Clínicos e Laboratoriais para pontos de quebra de diâmetro da zona antimicrobiana. A cepa de E. coli (ATCC 25922) foi usada como organismo de controle de qualidade. Os isolados que apresentam resistência a três ou mais classes de antimicrobianos foram classificados como multirresistentes (MDR), conforme definido por um grupo conjunto do Centro Europeu para Prevenção e Controle de Doenças e Centro para Controle e Prevenção de Doenças dos EUA. Resultados: Um total de 112 E. coli e 192 Salmonella spp. foram isolados de 557 amostras submetidas entre 2016 e 2019. Em ordem decrescente de frequência, a resistência a E. coli foi: tetraciclina (100%), sulfametoxazol-trimetoprim (97,5%), amoxicilina (86,4%), enrofloxacina (82,6%), tilosina (82,1%), doxiciclina (59%), neomicina (50%), ciprofloxacina (45,5%), ceftiofur (35%), gentamicina (30%), tilmicosina (29%) e fosfomicina (12,5%). Quando comparada com E. coli, Salmonella spp. foi geralmente resistente aos mesmos agentes com resistência ligeiramente menor (entre 10-30%) a oito dos antimicrobianos. Apenas três antimicrobianos apresentaram resistência a Salmonella spp. abaixo de 20% da seguinte forma: neomicina (17%), gentamicina (16%) e fosfomicina (14%). Multi-resistência ocorreu em 68,7% (77/112) de E. coli e 70,3% (135/192) de Salmonella spp. isolados. Resistência de Salmonella spp. foi alarmante para todos os antimicrobianos criticamente importantes testados: fluoroquinolonas (enrofloxacina, ciprofloxacina), ceftiofur (cefalosporina de terceira geração) e macrolídeos (tilosina). Conclusões: Esses resultados indicam um alto nível de resistência a múltiplos medicamentos (MDR) e que um Programa Nacional de Monitoramento da Resistência Antimicrobiana é necessário para a Colômbia, juntamente com a implementação de diretrizes de prescrição de antimicrobianos para suínos. O uso indiscriminado de antimicrobianos para promoção de crescimento na indústria suína está claramente promovendo resistência generalizada e deve ser interrompido.

Impact of sink removal from intensive care unit rooms on the consumption of antibiotics and on results of Zero Resistance Project

IntroductionDue to the favourable impact of removing the sinks on isolations in bronchoaspirate samples of patients with mechanical ventilation, we now evaluate the impact on the consumption of antibiotics as well as on the results of the Zero Resistance Project (ZRP).Patients and methodsAll the patients admitted to the unit in a quasi-experimental before–after study with a pre-intervention period between 2014 and 2016 and a post-intervention period from 2016 to 2017, to evaluate antibiotic consumption in defined daily doses, and until 2018, to evaluate the ZRP indicators. The intervention was the removal of the sinks from the rooms of the ICU. We evaluated antibiotic consumption densities and their ratios, grouped as Enterobacteriaceae and non-fermenting gram-negative bacilli (NFGNB) according to their antibiograms; the absolute number of ‘antibiotic days’, ‘hospitalised days’, ‘isolation days’, and ‘multi-resistant bacteria (MRB) days’; as well as their incidence densities per 1000 hospitalised days and the ratio between the two years prior to and the two years after the intervention.ResultsPost-intervention antibiotic use was 1.61-fold (1.60–1.62) and 2.24-fold (2.10–2.37) lower for antibiotics used against Enterobacteriaceae and NFGNB, respectively. There were also reductions in the number of days of antibiotic use by 1.29-fold (1.22–1.36), number of MRB days by 1.84-fold (1.63–2.08), and number of patient isolation days by 1.51-fold (1.38–1.66).DiscussionThe results suggest that the intervention had a favourable impact on the consumption of antibiotics, as well as on the number of days on antibiotics, MRB, and isolation.

Occurrence of antibiotics and antibiotic-resistant bacteria (ARB) in the Nervión river.

The main hydrometeorological, microbiological and physico-chemical characteristics of the Nervión river were monitored during a year, including 10 antibiotics and the presence of bacteria resistant to these antibiotics among faecal coliforms (FC) and total aerobic bacteria at 22 °C (TAB22). The characteristics of the river water were variable without a clear seasonal component, strongly influenced by rainfall, with a good quality for drinking water production throughout the year according to the physico-chemical parameters. The antibiotic resistant bacteria isolated from the water of the Nervión river were especially resistant to ß-lactams and macrolide antibiotics, highlighting the absence of resistance to derivatives of tetracyclines among strains of TAB22. A third of the isolated strains were multi-resistant to antibiotics with a seasonal component in its presence, with multi-resistant FC more abundant during summer and multi-resistant TAB22 more abundant during winter. The presence of antibiotics in the waters of the Nervión river was not very significant, with total absence of ß-lactams, minocycline and ciprofloxacin. Erythromycin and clarithromycin can be considered ubiquitous with mean concentrations of 2.5 ± 2.3 ngL-1 and 5.7 ± 4.6 ngL-1 respectively, and the presence of sulfamethoxazole and trimethoprim was also noticeable with maximum concentrations of 78.3 ngL-1 for sulfamethoxazole. Dilution due to the increase of rainfall was observed for several analysed antibiotics, but without significant seasonal differences.

Impact of sink removal from intensive care unit rooms on the consumption of antibiotics and on results of Zero Resistance Project.

INTRODUCTION: Due to the favourable impact of removing the sinks on isolations in bronchoaspirate samples of patients with mechanical ventilation, we now evaluate the impact on the consumption of antibiotics as well as on the results of the Zero Resistance Project (ZRP). PATIENTS AND METHODS: All the patients admitted to the unit in a quasi-experimental before-after study with a pre-intervention period between 2014 and 2016 and a post-intervention period from 2016 to 2017, to evaluate antibiotic consumption in defined daily doses, and until 2018, to evaluate the ZRP indicators. The intervention was the removal of the sinks from the rooms of the ICU. We evaluated antibiotic consumption densities and their ratios, grouped as Enterobacteriaceae and non-fermenting gram-negative bacilli (NFGNB) according to their antibiograms; the absolute number of 'antibiotic days', 'hospitalised days', 'isolation days', and 'multi-resistant bacteria (MRB) days'; as well as their incidence densities per 1000 hospitalised days and the ratio between the two years prior to and the two years after the intervention. RESULTS: Post-intervention antibiotic use was 1.61-fold (1.60-1.62) and 2.24-fold (2.10-2.37) lower for antibiotics used against Enterobacteriaceae and NFGNB, respectively. There were also reductions in the number of days of antibiotic use by 1.29-fold (1.22-1.36), number of MRB days by 1.84-fold (1.63-2.08), and number of patient isolation days by 1.51-fold (1.38-1.66). DISCUSSION: The results suggest that the intervention had a favourable impact on the consumption of antibiotics, as well as on the number of days on antibiotics, MRB, and isolation.

The Kinocidin Interleukin-26 Shows Immediate Antimicrobial Effects Even to Multi-resistant Isolates.

The cationic proinflammatory cytokine Interleukin 26 (IL-26) shows antibacterial activity and inhibits the replication of cytomegalovirus and hepatitis C virus. This study evaluates the early microbicidal activities of IL-26 against major bacterial species including multi-resistant variants and Candida albicans. Recombinant IL-26 was bacterially expressed and studied for its microbicidal effects in culture. We show that IL-26 has strong 90% bactericidal activities against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, and Acinetobacter baumannii. Similarly, IL-26 sensitivity was also detectable in vancomycin-resistant Enterococcus species, methicillin-resistant S. aureus, and carbapenem-resistant A. baumannii clinical isolates. Additionally, a significant, albeit weak fungicidal effect against Candida albicans was observed. Activities against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were not detectable. The proinflammatory cytokine and kinocidin IL-26 shows strong bactericidal activities against A. baumannii and, almost selectively, against Gram-positive bacteria.

Infección nosocomial en Cuidados Intensivos del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas / Nosocomial infection in the Intensive Care Unit of the Teaching Clinic-Surgical Hospital Faustino Pérez Hernández, of Matanzas

RESUMEN Introducción: la diseminación de microorganismos multirresistentes en el hospital, constituye un importante problema epidemiológico y terapéutico que afecta especialmente a pacientes de la Unidad de Cuidados Intensivos. Objetivo: escribir el comportamiento de las infecciones nosocomiales y la resistencia antimicrobiana en la Unidad de Cuidados Intensivos. Materiales y métodos: se realizó un estudio de tipo descriptivo, observacional y prospectivo en la Unidad de Cuidados Intensivos del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, durante el primer semestre de 2020. El universo estuvo constituido por 102 pacientes que ingresaron en la Unidad de Cuidados Intensivos en el período estudiado, a los que se les realizó estudios microbiológicos. Las variables analizas fueron: causas de ingreso, edad, infecciones nosocomiales, neumonía en ventilados, gérmenes, resistencia antimicrobiana y mortalidad. Se expresaron en tablas y gráficos porcentuales. Resultados: el sexo masculino presentó mayor número de infección nosocomial respecto al femenino, en edades diferentes de la vida. La causa más frecuente de ingreso fue el politrauma. El sitio más común de infección nosocomial fue la vía respiratoria. Predominaron gérmenes como los bacilos gramnegativos fermentadores y las enterobacterias. Antibióticos como los inhibidores de las betalactamasas, otras penicilinas, quinolonas, cefalosporinas, aminoglucósidos y meropenen han adquirido un mayor porciento de resistencia. Conclusiones: la infección nosocomial por bacterias multirresistentes a los antibióticos estratégicos, es un problema dentro de la Unidad de Cuidados Intensivos asociado a la ventilación mecánica, que provoca una elevada mortalidad (AU).

ABSTRACT Introduction: the spread of multi-resistant microorganisms in the hospital is a major epidemiological and therapeutic problem that particularly affects critical patients admitted to the Intensive Care Unit. Objective: to describe the behavior of nosocomial infections and antimicrobial resistance in the Intensive Care Unit. Materials and Methods: a descriptive, observational and prospective study was carried out in the Intensive Care Unit of the Teaching Clinic-Surgical Hospital Faustino Pérez Hernández, during the first half of 2020. The universe was formed by 102 patients who entered the Intensive Care Unit during the studied period, to whom microbiological studies were carried out. The analyzed variables were the following: causes of admission, age, nosocomial infections, ventilator-associated pneumonia, germs, antimicrobial resistance and mortality. The results were expressed in tables and percentage charts. Results: Male sex showed the highest number of nosocomial infection compared to the female, at different ages of life. The most common cause of admission was polytrauma. The most common site of nosocomial infection was the airway. Germs like fermentative Gram-negative bacilli and enterobacteria predominated. Antibiotics such as beta-lactamase inhibitors, other kinds of penicillin, quinolones, cephalosporin, aminoglycosides and meropenen have acquired a higher percent of resistance. Conclusions: nosocomial infection caused by bacteria that have developed multi-resistance to strategic antibiotics is a problem within the Intensive Care Unit, associated to mechanical ventilation, and leads to high mortality (AU).

Assessment of actinobacteria use in the elimination of multidrug-resistant bacteria of Ibn Tofail hospital wastewater (Marrakesh, Morocco): a chemometric data analysis approach.

The efficiency of the treatment of hospital wastewater by actinobacteria was investigated using two chemometric data analysis methods. Six strains of multi-resistant bacteria isolated from Marrakesh hospital wastewater and four strains of antagonistic actinobacteria isolated from Moroccan marine environment were characterized by fatty acids released as methyl esters by thermochemolysis-GC/MS. The hierarchical cluster analysis (HCA) and the principal component analysis (PCA) were used to correlate fatty acids (FA) distributions within strains. HCA allowed to discriminate between bacteria and actinobacteria. A lower Euclidean distance is noted for bacteria. With PCA, linear and branched-chained FAs correlated with bacteria whereas mono unsaturated FAs correlated more specifically with Gram (-) bacteria. Terminally branched-chained FAs correlated most likely with actinobacteria. A co-culture of actinobacteria and bacteria monitored during 15 days demonstrated the efficiency of the biological treatment for 2 of the 4 studied actinobacteria. The effect is more important on Gram-negative bacteria. Antagonistic actinobacteria seem to be poorly efficient against Gram-positive bacteria.

Phytochemical Analysis, Antimicrobial and Antioxidant Properties of Thymus zygis L. and Thymus willdenowii Boiss. Essential Oils.

Essential oils (EOs) are chemical products produced by odoriferous glands from a variety of plants. These essential oils have many health benefits: antiseptic, anti-inflammatory and antimicrobial activities. So due to these medicinal properties, the present study was designed to analyze essential oils of Thymus zygis L. and Thymus willdenowii Boiss. for their chemical composition and biological activities. These two thyme species were collected from the region of Ifrane, Middle Atlas of Morocco. The EO was obtained by hydrodistillation, and the yields were 5.25% for T. zygis and 3.00% for T. willdenowii. The chemical composition of the EOs was analyzed by gas chromatography coupled with mass spectrometry (GC-MS), and the results showed that T. zygis EO is dominated by carvacrol (52.5%), o-cymene (23.14%), and thymol (9.68%), while the EO of T. willdenowii contains germacrene D (16.51%), carvacrol (16.19%), and geranyl acetate (8.35%) as major compounds. The antioxidant activity assessed by Diphenylpicrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays revealed that both EOs have excellent antioxidant activities; by DPPH it resulted in IC50 = 6.13 ± 0.11 for T. zygis and 6.78 ± 0.3 µg/mL for T. willdenowii, while the one by FRAP yielded EC50 = 2.46 ± 0.01 (T. zygis) and 5.17 ± 0.2 (T. willdenowii) µg/mL. The antimicrobial activity of the two essential oils was evaluated against six bacterial strains and five fungal strains by the disk diffusion method to determine the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC). The EOs revealed variable antimicrobial activities against the different tested microbial strains and showed strong antimicrobial activities, even against strains known as multi-resistant to antibiotics (Acinetobacter baumannii) at low concentrations (2 µL/mL). T. zygis EO showed the most powerful activity against all the studied bacteria, while that of T. willdenowii recorded moderate activity when tested against Shigella dysenteriae and Salmonella Typhi. With inhibition diameters that vary between 75 mm and 84 mm for concentrations of 2 µL/mL up to 12 µL/mL, S. aureus was shown to be the most sensitive to T. zygis EO. For the antifungal activity test, T. zygis EO showed the best inhibition diameters compared to T. willdenowii EO. These results showed that T. zygis EO has more powerful antioxidant and antimicrobial activities than T. willdenowii EO, therefore, we deduce that thyme EOs are excellent antioxidants, they have strong antimicrobial properties, and may in the future represent new sources of natural antiseptics that can be used in pharmaceutical and food industry.