Resistencia bacteriana a antibióticos en ambientes acuáticos: origen e implicaciones para la salud pública

El alarmante incremento de la resistencia bacteriana a los antibióticos a nivel global ha dilucidado otras fuentes diferentes al hospital y la comunidad, donde el agua ha cobrado gran importancia. El ambiente acuático constituye la fuente y el hábitat natural de un gran número de microorganismos, incluyendo bacterias resistentes a antibióticos; así mismo, se considera uno de los principales receptores de antimicrobianos, bacterias resistentes y genes de resistencia a antibióticos provenientes de las actividades humanas. La contaminación del agua con estos contaminantes emergentes tiene implicaciones serias para la salud humana, relacionadas con la diseminación de la resistencia bacteriana y la emergencia de nuevos mecanismos de resistencia. En esta revisión se brinda una descripción global del papel de los ambientes acuáticos en el problema de la resistencia bacteriana, las principales fuentes de contaminación, además del impacto para la salud pública. Ante este panorama, se establece la necesidad de abordar la problemática de la resistencia bacteriana desde la perspectiva de "una salud", donde a la vigilancia tradicional, enfocada a nivel humano y veterinario, se articule la vigilancia epidemiológica ambiental, principalmente basada en aguas residuales.

The alarming increase in bacterial resistance to antibiotics globally has diluted sources other than the hospital and community, where water has taken on great importance. The aquatic environment is the source and natural habitat of a large number of microorganisms, including antibiotic-resistant bacteria, as well as being considered one of the main receptors for antimicrobials, resistant bacteria and antibiotic resistance genes from human activities. Contamination of water with these emerging contaminants has serious implications for human health related to the spread of bacterial resistance and the emergence of new resistance mechanisms. This review provides a global description of the role of aquatic environments in the problem of bacterial resistance, the main sources of contamination, as well as the impact on Public Health. In this context, the need arises to address the problem of bacterial resistance from the perspective of "one health", where traditional surveillance, focused at the human and veterinary level, is articulated with environmental epidemiological surveillance, mainly in wastewater.

O incremento alarmante da resistência bacteriana aos antibióticos no nível global tem revelado outras fontes diferentes do hospital e da comunidade, em que a água tem ganho grande importância. O ambiente aquático constitui a fonte e o hábitat natural de um grande número de microrganismos, incluindo bactérias resistentes a antibióticos; é considerado, também, um dos principais receptores de antimicrobianos, bactérias resistentes e genes de resistência a antibióticos provindos das atividades humanas. A poluição da água com esses poluentes emergentes tem sérias implicações para a saúde humana, relacionadas com a disseminação da resistência bacteriana e a emergência de novos mecanismos de resistência. Nesta revisão oferece-se uma descrição global do papel dos ambientes aquáticos na situação problemática da resistência bacteriana, as principais fontes de poluição, além do impacto para a saúde pública. Diante desse panorama, determina-se a necessidade de abordar a problemática da resistência bacteriana desde a perspectiva de "uma saúde" em que a vigilância tradicional, focada nos níveis humano e veterinário, esteja articulada com a vigilância epidemiológica ambiental, principalmente baseada em águas residuais.

Clinical Analysis of Colistin Sulfate in the Treatment of Hematonosis Infected by Multidrug-Resistant Gram-Negative Bacteria / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of colistin sulfate in the treatment of hematonosis patients infected by multidrug-resistant (MDR) gram-negative bacteria (GNB), and discuss the possible factors that affect the efficacy of colistin sulfate.@*METHODS@#The clinical data of 85 hematologic patients infected with MDR GNB in the Soochow Hopes Hematonosis Hospital from April 2022 to November 2022 were collected and divided into clinically effective group with 71 cases and ineffective group with 14 cases according to the therapeutic efficacy of colistin sulfate. The age, gender, type of hematologic disease, status of hematopoietic stem cell transplantation, infection sites, type of pathogen, timing of administration, daily dose and duration of colistin sulfate, and combination with other antibacterial agents of patients in two groups were compared. Logistic regression was used to analyze on the meaningful variables to study the influencing factors of colistin sulfate. The adverse reactions of colistin sulfate were also evaluated.@*RESULTS@#There were no significant differences in age, gender, type of hematologic disease, hematopoietic stem cell transplantation status, infection sites and pathogen type between the effective group and the ineffective group (P>0.05). Compared with the medication time more than 7 days, meropenem used within 7 days in the clinical effective group, and timely replacement with colistin sulfate could obtain better efficacy, the difference was statistically significant (P=0.018). The duration of tigacycline before colistin sulfate did not affect the efficacy, and there was no significant difference in efficacy between the effective and ineffective groups. The therapeutic effect of colistin sulfate at daily dose of 500 000 U q8h was better than that of 500 000 U q12h, the difference was statistically significant (P=0.035). The time of colistin sulfate use in the clinically effective group was longer than that in the ineffective group, which had a statistical difference (P=0.003). Compared with the clinical ineffective group, the efficacy of combination regimens with colistin sulfate was better than that of colistin sulfate monotherapy, and the difference was statistically significant (P=0.013). Multivariate logistic regression analysis was performed on the indicators with statistical differences in the two groups of patients, which suggested that the use time of colistin sulfate (B: 2.358; OR: 10.573; CI: 1.567-71.361; P=0.015) and the combination of colistin sulfate (B: 1.720; OR: 5.586; CI: 1.210-25.787; P=0.028) were influential factors in the efficacy of colistin sulfate. During the treatment, the incidence of nephrotoxicity, hepatotoxicity and peripheral neurotoxicity were 5.9%, 1.2% and 1.2%, respectively.@*CONCLUSION@#The use of colistin sulfate improves the clinical efficacy of MDR GNB infections in hematological patients, and the timing of colistin sulfate administration and the combination of drugs are independent factors affecting its clinical efficacy, and the safety during treatment is high.

Potential of natural products containing 3-acyl tetramic acid as antibacterial precursors / 药学学报

The natural products containing 3-acyl tetramic acid units have a large number of complex and diverse structures, showing a variety of biological activities such as antibacterial, antiviral, anti-tumor and so on, especially antibacterial activity which are regarded as a potential reservoir of new antibiotics. In this paper, the antibacterial activities of various natural products containing 3-acyl tetramic acids and the new research hotspots and directions are reviewed.

Analysis of drug resistance and its influencing factors in different infection sites of patients / 中国热带医学

@#Abstract： Objective　To analyze the characteristics and corresponding drug resistance of pathogenic bacterial spectrum in eight major infection sites of hospitalized patients, and to provide epidemiological data for the rational selection of antibiotics in clinical practice. Methods　A total of 396 bacterial strains isolated from clinical specimens of hospitalized patients in member institutions of the Hainan Provincial Bacterial Resistance Monitoring Network from September 1, 2020, to September 30, 2022, were included in this study. Data were screened and filtered from the database of MH120 Microbial Identification and Drug Sensitivity Analysis System based on the technical scheme of the National Bacterial Drug Resistance Surveillance Network and Science and Technology Basic Resources Investigation Project research plan in 2020. The testing data were integrated, summarized, and analyzed using EXCEL and WHONET 5.6 software, and statistical analysis was conducted using SPSS 26.0 software. Results　Among of 396 strains of bacteria, 78 (19.7%) were isolated from respiratory tract specimens, 74 (18.7%) from urinary tract specimens, 72 (18.2%) from blood specimens, 54 (13.6%) from abdominal cavity specimens, 48 (12.1%) from skin and soft tissue specimens 48 strains (12.1%), 30 (7.6%) from reproductive tract specimens, 22 (5.6%) from central nervous system specimens, 18 (4.5%) from digestive tract specimens. Gram-negative bacteria accounted for 69.4% of the isolates, while gram-positive bacteria accounted for 30.6%. The top five gram-negative bacteria isolated were Klebsiella pneumoniae (14.9%), Escherichia coli (14.4%), Pseudomonas aeruginosa (10.4%), Acinetobacter baumannii (5.3%), and Salmonella species (4.5%). The top five gram-positive bacteria were Staphylococcus aureus (11.1%), Streptococcus agalactis (7.8%), Enterococcus faecalis (3.0%), Enterococcus faecium (2.8%), and Streptococcus suis (1.8%). Respiratory failure and bloodstream infection were independent influencing factors of treatment response (P<0.01). The resistance rate of Escherichia coli to ampicillin was 81.4%, and the resistance rate of Staphylococcus aureus to gentamicin and levofloxacin were both below 7%. Conclusions　The pathogen spectra vary with different infection sites of patients, and rational selection of antibiotics based on drug susceptibility testing is crucial to shorten the treatment time of patients and avoid the unnecessary emergence of drug-resistant strains caused by drug abuse.

Analysis of drug resistance and risk factors of multi drug resistant bacteria in bloodstream infection / 中国热带医学

@#Abstract: Objective To analyze the antimicrobial resistance rate and risk factors of multi drug resistant organisms (MDRO) in bloodstream infection for rational treatment. Methods　A total of 696 cases of bloodstream infections of Staphylococcus aureus, Enterococcus, Enterobacteriaceae (excluding Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter in our hospital from 2017 to 2021 were selected, and 711 pathogenic strains were isolated from their whole blood samples. The antimicrobial resistance rates of various multi drug resistant strains were analyzed and the risk factors of MDRO infection were analyzed. Results　696 non repeated cases were screened out from 13 187 whole blood culture specimens, with a positive rate of 5.3%, and a total of 711 blood influenza pathogens were detected, among them, 350 strains of MDRO were detected with a detection rate of 49.23% (350/711). Among the pathogenic bacteria of bloodstream infection, Escherichia coli was the most, with 277 strains accounting for 38.96% (277/711), of which 201 strains were MDRO, accounting for 57.43% (201/350); followed by Klebsiella pneumoniae and Staphylococcus aureus, with 155 strains accounting for 21.80% (155/711) and 89 strains accounting for 12.52% (89/711), among which 43 strains of Klebsiella pneumoniae MDRO accounted for 12.29% (43/350) and 38 strains of Staphylococcus aureus MDRO accounted for 10.86% (38/350). The change trend of the three pathogens during 2017-2021 was not obvious. The drug sensitivity test showed that Escherichia coli and Klebsiella pneumoniae were highly resistant to cephalosporins and fluoroquinolones, and the drug resistance rate of aminoglycosides was relatively low. They had almost no resistance to cephalosporins and carbapenems. Staphylococcus aureus has a high resistance rate to lincomycin and macrolides, but no resistance to oxazolidinone, glycopeptides and glycylcyclins. There were 350 cases of MDRO infection and 361 cases of non MDRO infection. Univariate analysis showed that the age, sex, cardiovascular and cerebrovascular history, renal insufficiency, lung disease, hypoalbuminemia, hepatobiliary disease, electrolyte disorder and anemia of the patients had no statistical significance in MDRO infection (P>0.05); diabetes, urinary tract infection, surgical operation and burn were the influencing factors of MDRO (P<0.05). According to logistic analysis, diabetes, urinary tract infection, surgical operation and burn were the risk factors of MDRO infection (P<0.05). Conclusion　The infection of MDRO in patients with bloodstream infection is serious, and early prevention and control should be paid attention to, and the principle of graded use of antibiotics should be strictly observed, and the rational application should be carried out to actively and effectively control the production of MDRO.

Analysis of Nosocomial Infection in a Cancer Hospital from 2019 to 2021 / 中山大学学报(医学科学版)

ObjectiveTo understand the situation of nosocomial infection in cancer hospitals and its changing trend， so as to provide a basis for adjusting the focus of nosocomial infection prevention and control in cancer hospitals. MethodsData of nosocomial infection quality control indices of Sun Yat-sen University Cancer Center from 2019 to 2021 were obtained through the nosocomial infection monitoring system， and the changes of these indices across the three years were analyzed by Chi-square test and Cochran-Armitage trend test. ResultsFrom 2019 to 2021， the incidence rates of nosocomial infection in this hospital were 0.80%， 0.78% and 0.57%， which decreased significantly year by year （P<0.001）. Among them， surgical site and respiratory system infection were more common， accounting for 35.75% and 31.08%， respectively. Gram-negative bacteria and fungi were the main pathogens. The incidence rate of multidrug-resistant bacteria in hospital increased year by year， from 0.08‰ to 0.14‰ （P<0.001）， among which methicillin-resistant staphylococcus aureus， carbapenem-resistant Enterobacter and bacteria producing ultra-broad spectrum β-lactamase （ESBLs） bacteria increased significantly. The incidence rates of three-tube associated infections were no different across 3 years （P>0.05）， which were still at high levels. ConclusionFrom 2019 to 2021， the prevention and control of nonsocomial infection in the cancer hospital has been improved overall. Meanwhile， the infections of respiratory system and surgical sites， ESBLs related multidrug-resistant bacteria and three-tube are weak links in cancer specialized hospitals， which need to be emphasized and improved.

Antibacterial and bacteriostatic potential of coelomic fluid and body paste of Pheretima posthuma (Vaillant, 1868) (Clitellata, Megascolecidae) against ampicillin resistant clinical bacterial isolates / Potencial antibacteriano e bacteriostático do fluido celômico e pasta corporal de Pheretima posthuma (Vaillant, 1868) (Clitellata, Megascolecidae) contra isolados bacterianos clínicos resistentes à ampicilina

Pheretima posthuma (Vaillant, 1868), a native earthworm of Pakistan and Southeast Asia, has wide utilization in vermicomposting and bioremediation process. In this study, P. posthuma coelomic fluid (PCF) and body paste (PBP) was evaluated as antibacterial agent against ampicillin (AMP) resistant five Gram positive and four Gram negative clinical isolates. The antibacterial effect of different doses (i.e. 25-100 µg/ml) of PCF and PBP along with AMP and azithromycin (AZM) (negative and positive controls, respectively) were observed through disc diffusion and micro-dilution methods. All nine clinical isolates were noticed as AMP resistant and AZM sensitive. Antibacterial effects of PCF and PBP were dose dependent and zone of inhibitions (ZI) against all clinical isolates were between 23.4 ± 0.92 to 0 ± 00 mm. The sensitivity profile of PCF and PBP against clinical isolates was noticed as 44.44 and 55.56%, respectively. Both PCF and PBP showed bacteriostatic (BTS) action against S. aureus, S. pyogenes, K. pneumonia, N. gonorrhoeae. Moreover, the cumulative BTS potential of PCF and PBP against all isolates was 66.67 and 55.56%, respectively. The MICs of PCF and PBP were ranged from 50-200 µg/ml against selected isolates. The bacterial growth curves indicated that PCF and PBP inhibited the growth of all isolates at their specific MIC concentrations. However, PBP has better antibacterial potential compared to PCF against selected isolates. Therefore, it is concluded that both PCF and PBP of P. posthuma possess antibacterial and BTS potential against ampicillin resistant clinical isolates. This organism might be considered as a second choice of antibacterial agents and can further be utilized in pharmaceutical industries for novel drug manufacturing by prospecting bioactive potential agents.

Pheretima posthuma (Vaillant, 1868), uma minhoca nativa do Paquistão e sudeste da Ásia, tem ampla utilização em processos de vermicompostagem e biorremediação. Neste estudo, o fluido celômico de P. posthuma (PCF) e a pasta corporal (PBP) foram avaliados como agente antibacteriano contra cinco isolados clínicos Gram-positivos e quatro Gram-negativos resistentes à ampicilina (AMP). O efeito antibacteriano de diferentes doses (ou seja, 25-100 µg / ml) de PCF e PBP juntamente com AMP e azitromicina (AZM) (controles negativo e positivo, respectivamente) foi observado por meio de métodos de difusão em disco e microdiluição. Todos os nove isolados clínicos foram notados como resistentes a AMP e sensíveis a AZM. Os efeitos antibacterianos de PCF e PBP foram dependentes da dose e a zona de inibição (ZI) contra todos os isolados clínicos foi entre 23,4 ± 0,92 a 0 ± 00 mm. O perfil de sensibilidade do PCF e PBP contra isolados clínicos foi observado como 44,44% e 55,56%, respectivamente. Tanto o PCF quanto o PBP mostraram ação bacteriostática (BTS) contra S. aureus, S. pyogenes, K. pneumonia, N. gonorrhoeae. Além disso, o potencial BTS cumulativo de PCF e PBP contra todos os isolados foi de 66,67% e 55,56%, respectivamente. Os MICs de PCF e PBP variaram de 50-200 µg / ml contra isolados selecionados. As curvas de crescimento bacteriano indicaram que o PCF e o PBP inibiram o crescimento de todos os isolados em suas concentrações específicas de MIC. No entanto, PBP tem melhor potencial antibacteriano em comparação com PCF contra isolados selecionados. Portanto, conclui-se que tanto o PCF quanto o PBP de P. posthuma possuem potencial antibacteriano e BTS contra isolados clínicos resistentes à ampicilina. Esse organismo pode ser considerado como uma segunda escolha de agentes antibacterianos e pode ainda ser utilizado nas indústrias farmacêuticas para a fabricação de novos medicamentos por meio da prospecção de agentes com potencial bioativo.

Antibacterial and bacteriostatic potential of coelomic fluid and body paste of Pheretima posthuma (Vaillant, 1868) (Clitellata, Megascolecidae) against ampicillin resistant clinical bacterial isolates

Abstract Pheretima posthuma (Vaillant, 1868), a native earthworm of Pakistan and Southeast Asia, has wide utilization in vermicomposting and bioremediation process. In this study, P. posthuma coelomic fluid (PCF) and body paste (PBP) was evaluated as antibacterial agent against ampicillin (AMP) resistant five Gram positive and four Gram negative clinical isolates. The antibacterial effect of different doses (i.e. 25-100 µg/ml) of PCF and PBP along with AMP and azithromycin (AZM) (negative and positive controls, respectively) were observed through disc diffusion and micro-dilution methods. All nine clinical isolates were noticed as AMP resistant and AZM sensitive. Antibacterial effects of PCF and PBP were dose dependent and zone of inhibitions (ZI) against all clinical isolates were between 23.4 ± 0.92 to 0 ± 00 mm. The sensitivity profile of PCF and PBP against clinical isolates was noticed as 44.44 and 55.56%, respectively. Both PCF and PBP showed bacteriostatic (BTS) action against S. aureus, S. pyogenes, K. pneumonia, N. gonorrhoeae. Moreover, the cumulative BTS potential of PCF and PBP against all isolates was 66.67 and 55.56%, respectively. The MICs of PCF and PBP were ranged from 50-200 µg/ml against selected isolates. The bacterial growth curves indicated that PCF and PBP inhibited the growth of all isolates at their specific MIC concentrations. However, PBP has better antibacterial potential compared to PCF against selected isolates. Therefore, it is concluded that both PCF and PBP of P. posthuma possess antibacterial and BTS potential against ampicillin resistant clinical isolates. This organism might be considered as a second choice of antibacterial agents and can further be utilized in pharmaceutical industries for novel drug manufacturing by prospecting bioactive potential agents.

Resumo Pheretima posthuma (Vaillant, 1868), uma minhoca nativa do Paquistão e sudeste da Ásia, tem ampla utilização em processos de vermicompostagem e biorremediação. Neste estudo, o fluido celômico de P. posthuma (PCF) e a pasta corporal (PBP) foram avaliados como agente antibacteriano contra cinco isolados clínicos Gram-positivos e quatro Gram-negativos resistentes à ampicilina (AMP). O efeito antibacteriano de diferentes doses (ou seja, 25-100 µg / ml) de PCF e PBP juntamente com AMP e azitromicina (AZM) (controles negativo e positivo, respectivamente) foi observado por meio de métodos de difusão em disco e microdiluição. Todos os nove isolados clínicos foram notados como resistentes a AMP e sensíveis a AZM. Os efeitos antibacterianos de PCF e PBP foram dependentes da dose e a zona de inibição (ZI) contra todos os isolados clínicos foi entre 23,4 ± 0,92 a 0 ± 00 mm. O perfil de sensibilidade do PCF e PBP contra isolados clínicos foi observado como 44,44% e 55,56%, respectivamente. Tanto o PCF quanto o PBP mostraram ação bacteriostática (BTS) contra S. aureus, S. pyogenes, K. pneumonia, N. gonorrhoeae. Além disso, o potencial BTS cumulativo de PCF e PBP contra todos os isolados foi de 66,67% e 55,56%, respectivamente. Os MICs de PCF e PBP variaram de 50-200 µg / ml contra isolados selecionados. As curvas de crescimento bacteriano indicaram que o PCF e o PBP inibiram o crescimento de todos os isolados em suas concentrações específicas de MIC. No entanto, PBP tem melhor potencial antibacteriano em comparação com PCF contra isolados selecionados. Portanto, conclui-se que tanto o PCF quanto o PBP de P. posthuma possuem potencial antibacteriano e BTS contra isolados clínicos resistentes à ampicilina. Esse organismo pode ser considerado como uma segunda escolha de agentes antibacterianos e pode ainda ser utilizado nas indústrias farmacêuticas para a fabricação de novos medicamentos por meio da prospecção de agentes com potencial bioativo.

Antibacterial and bacteriostatic potential of coelomic fluid and body paste of Pheretima posthuma (Vaillant, 1868) (Clitellata, Megascolecidae) against ampicillin resistant clinical bacterial isolates / Potencial antibacteriano e bacteriostático do fluido celômico e pasta corporal de Pheretima posthuma (Vaillant, 1868) (Clitellata, Megascolecidae) contra isolados bacterianos clínicos resistentes à ampicilina

Abstract Pheretima posthuma (Vaillant, 1868), a native earthworm of Pakistan and Southeast Asia, has wide utilization in vermicomposting and bioremediation process. In this study, P. posthuma coelomic fluid (PCF) and body paste (PBP) was evaluated as antibacterial agent against ampicillin (AMP) resistant five Gram positive and four Gram negative clinical isolates. The antibacterial effect of different doses (i.e. 25-100 µg/ml) of PCF and PBP along with AMP and azithromycin (AZM) (negative and positive controls, respectively) were observed through disc diffusion and micro-dilution methods. All nine clinical isolates were noticed as AMP resistant and AZM sensitive. Antibacterial effects of PCF and PBP were dose dependent and zone of inhibitions (ZI) against all clinical isolates were between 23.4 ± 0.92 to 0 ± 00 mm. The sensitivity profile of PCF and PBP against clinical isolates was noticed as 44.44 and 55.56%, respectively. Both PCF and PBP showed bacteriostatic (BTS) action against S. aureus, S. pyogenes, K. pneumonia, N. gonorrhoeae. Moreover, the cumulative BTS potential of PCF and PBP against all isolates was 66.67 and 55.56%, respectively. The MICs of PCF and PBP were ranged from 50-200 µg/ml against selected isolates. The bacterial growth curves indicated that PCF and PBP inhibited the growth of all isolates at their specific MIC concentrations. However, PBP has better antibacterial potential compared to PCF against selected isolates. Therefore, it is concluded that both PCF and PBP of P. posthuma possess antibacterial and BTS potential against ampicillin resistant clinical isolates. This organism might be considered as a second choice of antibacterial agents and can further be utilized in pharmaceutical industries for novel drug manufacturing by prospecting bioactive potential agents.

Resumo Pheretima posthuma (Vaillant, 1868), uma minhoca nativa do Paquistão e sudeste da Ásia, tem ampla utilização em processos de vermicompostagem e biorremediação. Neste estudo, o fluido celômico de P. posthuma (PCF) e a pasta corporal (PBP) foram avaliados como agente antibacteriano contra cinco isolados clínicos Gram-positivos e quatro Gram-negativos resistentes à ampicilina (AMP). O efeito antibacteriano de diferentes doses (ou seja, 25-100 µg / ml) de PCF e PBP juntamente com AMP e azitromicina (AZM) (controles negativo e positivo, respectivamente) foi observado por meio de métodos de difusão em disco e microdiluição. Todos os nove isolados clínicos foram notados como resistentes a AMP e sensíveis a AZM. Os efeitos antibacterianos de PCF e PBP foram dependentes da dose e a zona de inibição (ZI) contra todos os isolados clínicos foi entre 23,4 ± 0,92 a 0 ± 00 mm. O perfil de sensibilidade do PCF e PBP contra isolados clínicos foi observado como 44,44% e 55,56%, respectivamente. Tanto o PCF quanto o PBP mostraram ação bacteriostática (BTS) contra S. aureus, S. pyogenes, K. pneumonia, N. gonorrhoeae. Além disso, o potencial BTS cumulativo de PCF e PBP contra todos os isolados foi de 66,67% e 55,56%, respectivamente. Os MICs de PCF e PBP variaram de 50-200 µg / ml contra isolados selecionados. As curvas de crescimento bacteriano indicaram que o PCF e o PBP inibiram o crescimento de todos os isolados em suas concentrações específicas de MIC. No entanto, PBP tem melhor potencial antibacteriano em comparação com PCF contra isolados selecionados. Portanto, conclui-se que tanto o PCF quanto o PBP de P. posthuma possuem potencial antibacteriano e BTS contra isolados clínicos resistentes à ampicilina. Esse organismo pode ser considerado como uma segunda escolha de agentes antibacterianos e pode ainda ser utilizado nas indústrias farmacêuticas para a fabricação de novos medicamentos por meio da prospecção de agentes com potencial bioativo.

Investigation of Factors Affecting the Success Rate of Third-Line Therapy against Helicobacter pylori Infection / 医薬品情報学

Objective: The success rate of third-line treatment for Helicobacter pylori (H. pylori) infection has been reported to depend on the use of antibacterial agents, potassium-competitive acid blockers, and proton pump inhibitors. However, there is insufficient information on the success rate of H. pylori treatment due to the differences in the clinically used drugs. Here, the factors influencing the success rate of third-line treatment for H. pylori infection was investigated.Methods: Patients aged 20 years or older, who had received third-line treatment for H. pylori infection from January 2013 to December 2021 at the Kameda Medical Center were included. The exclusion criteria were as follows: patients with unknown treatment results and discontinuation of treatment. The primary endpoint was treatment success rate, based on the differences in the treatment regimen and drug choice, which was retroactively investigated from medical records. Confounding factors were adjusted by multivariate logistic regression analysis.Results: Treatment regimens containing sitafloxacin resulted in higher treatment success rates (p<0.05). Multivariate logistic regression analysis showed that the administration of sitafloxacin was the only statistically significant factor influencing treatment success. However, vonoprazan also tended to influence treatment success.Conclusion: Treatment with sitafloxacin and vonoprazan increases the success rate of third-line treatment against H. pylori infection.

Variación de la susceptibilidad a antimicrobianos en aislados clínicos de Klebsiella pneumoniae y Escherichia coli de pacientes hospitalizados / Variation of antimicrobial susceptibility in clinical isolates of Klebsiella pneumoniae and Escherichia coli in inpatients

Introducción: La presencia de enterobacterias multirresistentes en los hospitales es cada vez más frecuente. Objetivos: Describir la variación de la susceptibilidad a los antimicrobianos en aislados de Klebsiella pneumoniae y Escherichia coli e identificar la frecuencia de aislados multirresistentes. Métodos: Estudio descriptivo retrospectivo realizado entre el 1 de enero de 2018 y 31 de diciembre de 2021. Se estudió la susceptibilidad a los antimicrobianos por el método de difusión de discos Bauer-Kirby a 220 aislados (111 de K. pneumoniae y 109 de E. coli) obtenidos de muestras clínicas (sangre, lesiones de piel, catéteres vasculares, secreciones traqueobronquiales y de herida quirúrgica) de pacientes hospitalizados en el Hospital Clínico-Quirúrgico Docente Aleida Fernández Chardiet, provincia Mayabeque, Cuba. Resultados: Durante los 4 años de estudio, en los aislados de K. pneumoniae la resistencia mostró tendencia a crecer en el tiempo para todos los antimicrobianos probados, excepto para amoxicilina/ácido clavulánico con tendencia a decrecer de -3,34. La diferencia porcentual de la resistencia del año 2021 con respecto al 2018 fue mayor para meropenem, cloranfenicol y amikacina (108,3 %, 70,2 % y 70,2 %, respectivamente). Aun así, los datos mostraron significación estadística para los antibióticos cefepima, aztreonam y meropenem (p ≤ 0,05). En cuanto a los aislados de E. coli, la resistencia mostró tendencia a decrecer en ocho de los antimicrobianos investigados, pero el cloranfenicol y amikacina evidenciaron una tendencia al incremento de 3,65 y 4,83, respectivamente. La diferencia porcentual entre los años extremos del estudio en nueve antimicrobianos mostró valores inferiores al 50,0 %. Los datos evidenciaron significación estadística (p ≤ 0,05) para cefotaxima y ampicilina/sulbactam. Conclusiones: Hubo variación en la susceptibilidad a los antimicrobianos en los aislados de K. pneumoniae y E. coli durante los 4 años del estudio. Además, se observó una alta prevalencia de aislados multirresistentes.

Introduction: The presence of multidrug resistant enterobacteria in hospitals is increasingly frequent. Objectives: To describe the variation of the antimicrobial susceptibility pattern of Klebsiella pneumoniae and Escherichia coli isolates obtained from clinical samples of patients who were hospitalized and to identify the frequency of multidrug resistant isolates. Methods: A retrospective and descriptive study was performed between January 1, 2018 and December 31, 2021. The antimicrobial susceptibility was analyzed using the Bauer- Kirby disc diffusion method of 220 isolates (111 K. pneumoniae and 109 E. coli) obtained from clinical samples (blood, skin lesions, vascular catheters and tracheobronchial and surgical wound secretions) of patients hospitalized at the Hospital teaching surgical - clinic Aleida Fernández Chardiet, located in the province of Mayabeque, Cuba. Results: In the K. pneumoniae isolates during the four years of the study, resistance showed a tendency to increase over time, for all antibiotic tested, except for amoxicillin / ácid clavulánic, which showed a tendency to decrease from 3.34. The percentage difference of the resistance between the year 2021 in relation to 2018 were greater for meropenem, chloramphenicol and amikacin (108.3%, 70,2% y 70.2% respectively). Even so, the data provided evidence that showed statistical significance for the antibiotics cefepime, aztreonam y meropenem (p ≤ 0,05). Regarding the E. coli isolates, resistance showed a tendency to decrease over the course of the four years of the study in eight of the investigated antibiotics. chloramphenicol and amikacin showed an increasing trend of 3.65 y 4.83 respectively. The percentage difference between the extreme years of the study in nine antimicrobials showed values lower than 50.0%. The data provide elements to suggest the presence of statistical significance (p ≤ 0.05) for cefotaxim y ampicilin/sulbactam. Finally, 83.87% of K. pneumoniae isolates and 80.73% of E. coli isolates were multidrug resistant. Conclusions: There was variation in the susceptibility to antibiotic in the K. pneumoniae and E. coli isolates during the four years of the study. In addition, a high prevalence of multiresistant isolates was observed.

Evaluating bacterial resistance to antimicrobials in isolated bacteria from food contact surfaces / Evaluación de la resistencia bacteriana a los antimicrobianos en bactérias aisladas de superficies en contacto con alimentos / Avaliação da resistência bacteriana a antimicrobianos em bactérias isoladas de superfícies em contacto com alimentos

ABSTRACT Bacteria isolated from food contact surfaces, can transfer resistance factors when exposed to pressure exerted by inappropriate use of antimicrobial agents. This study aimed to evaluate bacterial resistance against antibiotics and disinfectants commonly used (NaOCl and CH3COOH) in bacteria isolated from food contact surfaces. Additionally, using PCR, the presence of tetracycline resistance genes was evaluated. Results showed that 47% of the isolates exhibit resistance against more than one antibiotic, being Tetracycline the antibiotic that most isolates were resistant to (35.3%). A PCR analysis found that the tet M gene is the most frequent of the genes tested. Likewise, it was evidenced that although NaOCl is effective as a surface disinfectant, Aerococcus urinae and Kocuria kristinae isolates could resist up to 10 min of exposure. Likewise, all isolates were resistant to CH3COOH, demonstrating the low inhibitory capacity of this disinfectant. Finally, the observed correlation between resistance to antibiotics and resistance to disinfectants is confirmed. An important factor that should be studied since the generalized use of disinfectants can increase the spectrum of antibiotic resistance.

RESUMEN Bacterias aisladas de superficies en contacto con alimentos pueden transferir factores de resistencia cuando se exponen a presiones ejercidas por el uso inadecuado de agentes antimicrobianos. En este estudio se evaluó la resistencia bacteriana frente a antibióticos y desinfectantes de uso común (NaOCl y CH3COOH) en bacterias aisladas de superficies en contacto con alimentos. Adicionalmente, mediante la PCR se evaluó la presencia de genes de resistencia a la Tetraciclina. Los resultados mostraron que el 47% de los aislados presentaron resistencia a más de un antibiótico, siendo la Tetraciclina al que la mayoría de los aislamientos fueron resistentes (35,3%). El análisis de PCR encontró que el gen tet M fue el más frecuente. Además, se evidenció que, si bien el NaOCl es efectivo como desinfectante de superficies, Aerococcus urinae y Kocuria kristinae pudieron resistir hasta 10 minutos de exposición. Igualmente, todos los aislados fueron resistentes a CH3COOH, demostrando la baja capacidad inhibitoria de este desinfectante. Finalmente, se confirma una correlación entre la resistencia a antibióticos y desinfectantes. Un factor importante que conviene estudiar ya que el uso generalizado de desinfectantes podría incrementar el espectro de resistencia a los antibióticos.

RESUMO Bactérias isoladas de superfícies em contacto com alimentos podem transferir factores de resistência quando expostas a tensões exercidas pela utilização inadequada de agentes antimicrobianos. Neste estudo, foi avaliada a resistência bacteriana aos antibióticos e desinfectantes comummente utilizados (NaOCl e CH3COOOH) em bactérias isoladas de superfícies em contacto com alimentos. Além disso, a presença de genes de resistência à tetraciclina foi avaliada por PCR. Os resultados mostraram que 47% dos isolados mostraram resistência a mais do que um antibiótico, sendo a Tetraciclina a que a maioria dos isolados era resistente (35,3%). A análise PCR constatou que o gene tet M era o mais frequente. Além disso, era evidente que, embora NaOCl seja eficaz como desinfectante de superficie, Aerococcus urinae e Kocuria kristinae foram capazes de resistir até l0 minutos de exposição. Da mesma forma, todos os isolados eram resistentes ao CH3COOH, demonstrando a baixa capacidade inibitória deste desinfectante. Finalmente, é confirmada uma correlação entre a resistência aos antibióticos e a resistência aos desinfectantes. Este é um factor importante que deve ser estudado uma vez que a utilização generalizada de desinfectantes poderia aumentar o espectro da resistência aos antibióticos.

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.

está disponible en el texto completo

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.

Riesgo de infección en pacientes oncológicos colonizados por bacterias productoras de p-lactamasas de espectro extendido y enterobacterias productoras de carbapenemasas / Risk of infection in cancer patients colonized by extended expectrum p-lactamases and carbapenem producing Enterobacteriaceae

INTRODUCCIÓN: La prevalencia de microorganismos multirresistentes es un problema de salud pública que continúa creciendo a lo largo del mundo. Existe una población principalmente susceptible de ser colonizada y posteriormente infectarse, son los pacientes oncológicos. OBJETIVO: Identificar las características clínicas y patológicas de los pacientes oncológicos y su relación con la infección con microorganismos productores de BLEE y EPC. PACIENTES Y MÉTODOS: Se condujo un estudio retrospectivo y de carácter analítico entre el primero de enero de 2019 y el 30 de junio de 2020 en tres unidades hemato-oncológicas. RESULTADOS: Incluyó a 3.315 pacientes, de los cuales 217 (6,5%) se encontraban colonizados por microorganismos productores de BLEE y EPC; de éstos, 106/217 (48,8%) presentaron al menos un episodio de infección. El microorganismo más frecuentemente aislado fue Klebsiella pneumoniae, en 29/106 (27,4%). De los infectados, 18/106 (17%) presentaron infección por el mismo microorganismo colonizador. La mucositis (p = 0,002), edad mayor a 65 años (p = 0,041), hipoalbuminemia (p < 0,01), neutropenia (p < 0,01) y la presencia dispositivos invasivos (p < 0,01) demostraron una relación con el desarrollo de infección. CONCLUSIÓN: La presencia de hipoalbuminemia (OR 3,3, IC 1,5-7,1, p < 0,01), dispositivos invasivos (OR 5,8, IC 3.0-11,4, p < 0,01) y neutropenia (OR 4,1, IC 1,5-11,4, p < 0,01) predicen el desarrollo de infecciones.

BACKGROUND: The prevalence of multi-resistant microorganisms is a public health problem that continues to grow globally. There is a population that is mainly susceptible to being colonized and subsequently infected, and these are cancer patients. AIM: To identify the clinical and pathological characteristics of cancer patients and their relationship with infection with ESBL and CPE producing microorganisms. METHODS: A retrospective and analytical study was conducted between January 1, 2019 and June 30, 2020 in three hematooncological units. RESULTS: We included 3315 patients of which 217 (6.5%) were colonized by microorganisms producing ESBL and CPE. Of these, 106/217 (48.8%) had at least one episode of infection. The most frequently isolated microorganism was Klebsiella pneumoniae 29/106 (27.4%). Of those infected, 18/106 (17%) presented infection by the same colonizing microorganism. Mucositis (p = 0.002), age over 65 years (p = 0.041), hypoalbuminemia (p < 0.01), neutropenia (p < 0.01) and the presence of invasive devices (p < 0.01) demonstrated a relationship with development of infection. The presence of hypoalbuminemia (OR 3.3, CI 1.5-7.1, P < 0.01), invasive devices (OR 5.8, CI 3.0-11.4, p < 0.01) and neutropenia (OR 4.1, CI 1.5-11.4, p < 0.01) predict the development of infections.

Diversity of antibiotic resistance genes in raw water from drinking water source in Shanghai / 上海预防医学

ObjectiveTo determine the distribution of various antibiotic resistance genes （ARGs） in raw water from drinking water source， and to explore the correlation between the ARGs and common carbapenem-resistant and multidrug-resistant bacteria isolated from drinking water source， so as to provide scientific evidence for improving the safety of urban drinking water. MethodsA total of 30 raw water samples were collected from a major drinking water source in Shanghai in 2020. Bacterial strains were selectively cultured on Columbia blood agar medium containing 1 μg·μL-1 meropenem， and then identified by MALDI-TOF-MS mass spectrometry system. Minimum inhibitory concentration （MIC） of the strains was detected by broth microdilution method. The water samples were filtered through a 0.45 μm filter membrane and diversity of ARGs was determined by using high-throughput metagenomic sequencing. ResultsA total of 64 strains of carbapenem-resistant bacteria were isolated from the water samples， including Stenotrophomonas maltophilia， Enterococcus faecium， Pseudomonas aeruginosa， Acinetobacter baumannii and Klebsiella pneumoniae， which were resistant to a variety of common antibiotics. Using metagenomic sequencing，1 244 ARGs were identified. The relative average abundance of the top 100 ARGs accounted for 96.1%， and that of the multidrug-resistant ARGs accounted for 63.41%. Furthermore， the multidrug-resistant ARGs were mainly adeJ， mexT， adeC， oprM， mexF， mdfA， mexB， mdtK， adeK， etc. Using Spearman's correlation， five multidrug-resistant bacteria isolated from the drinking water source were significantly associated with the ARGs. ConclusionRelative abundance of multidrug-resistant ARGs is high in raw water from main drinking water source. The five isolated carbapenem-resistant and multidrug-resistant bacteria are significantly correlated with the ARGs. It warrants strengthening the rational and standardized application of antibiotics to protect water resources and ensure the safety of drinking water.

Multi-drug resistant bacteria infection and clinical outcome of diabetic foot: An update / 中华内分泌代谢杂志

With multi-drug-resistant bacteria being more prevalent over years, diabetic foot complicated with multi-drug-resistant bacteria infection emerges as a significant challenge for clinicians and patients. Diabetic foot is predisposed to multi-drug resistant bacterial infection. Growing body of evidence shows that ulcer type, ulcer grade, ulcer area, history of antibiotics treatment, previous hospitalization history, osteomyelitis, and proliferative retinopathy are risk factors. Among multi-drug-resistant bacteria, methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing bacteria are the most common strains. Infection with multiple drug-resistant bacteria contributes to the amputation rate and mortality in patients with diabetic foot ulcers. The aim of this review is to give an update on multi-drug resistant bacteria infection and clinical outcome of diabetic foot, with a goal to improve clinical awareness and management.

Preliminary investigation of multiple antibiotic-resistant bacteria isolated from blood cockles (Anadara granosa) and green lipped mussel (Perna viridis)

Aims@#Bivalve molluscs are filter feeders that tend to accumulate and concentrate any suspended particles or bacteria from the water environment. Although they have been proven to accumulate heavy metals, investigation on the presence of antibiotic-resistant bacteria is still lacking. Therefore, this study examines the occurrence of antibiotic-resistant bacteria isolated from bivalve shellfish, namely, blood cockles (Anadara granosa) and green-lipped mussel (Perna viridis) purchased from markets in Johor, Malaysia.@*Methodology and results@#Samples purchased were homogenized and then diluted. Viable cell count and bacterial isolation were performed using diluted samples followed by an antibiotic susceptibility test (ampicillin, ciprofloxacin and tetracycline) conducted on the pure isolates. The total viable count of bacterial colonies for cockle and mussel samples ranged from 1.1 × 107 to 4.4 × 109 CFU/mL and 1.2 × 109 to 4.3 × 109 CFU/mL. The numbers of colonies isolated from respective bivalves were 11 and 6. Generally, cockles isolates revealed higher resistance towards all three antibiotics at or above the Clinical and Laboratory Standard Institute (CLSI) threshold value. Meanwhile, mussel isolates showed full susceptibility to any ciprofloxacin concentration and tetracycline but exhibited resistance to ampicillin at a concentration exceeding the CLSI value. The number of drug resistance isolates in cockle and mussel samples decreased with increasing antibiotic concentration. The maximum number of antibiotics the mussel isolates were resistant to was two, whereas cockle isolates achieved three.@*Conclusion, significance and impact of study@#The outcome of this study concludes that some isolates from cockle and mussel samples can resist antibiotic concentration above the CLSI threshold value. Resistance of more than the CLSI threshold level revealed that these isolates could pose significant health risks especially when the bivalves are ingested raw or undercooked.

Multi-department cooperation in prevention and control of multi-drug-resistant bacteria nosocomial infectionata hospital / 公共卫生与预防医学

Objective To explore the role of multi-department cooperation in the prevention and control of nosocomial infection of multi-drug-resistant bacteria(MDRO). Methods Theretrospective analysis was conducted on 1 478 inpatients before the implementation of multi-department cooperative management (January 2019 to December 2019). The implementation of multi-department cooperative management began in January 2020, including :(1) the establishment of multi-department cooperative management organization system; (2) Establish a three-level MANAGEMENT network of MDRO; (3) Multidisciplinary joint training; (4) Clinical departments shall be equipped with clinical pharmacists; (5) The hospital infection monitoring system was used to conduct real-time monitoring on the submission of microbial samples, the detection rate of MDRO, the changes of drug-resistant bacteria and the use of antibiotics; (6) Led by the department of hospital pathology and medical Service, regular joint ward rounds should be conducted in the departments and key departments with high DETECTION rate of MDRO; (7) PDCA cycle mode was adopted for quality control of all links of nosocomial infection prevention and control measures; After the implementation of multi-department cooperative management (January 2020 to December 2020), all the hospitalized patients in 1849 cases were detected and counted, and the incidence of nosocomial infection, the detection rate of MDRO, the compliance rate of hand hygiene, the implementation rate of contact isolation, and the specimen inspection rate of therapeutic use of antibiotics and the reasonable utilization rate of antibiotics were compared before and after the implementation. Results The incidence of nosocomial infection and the detection rate of MDRO were significantly lower after the implementation of multi-department cooperative management than before (χ2=46.611, χ2=16.814, P 2 = 25.357, χ2=29.227, P2=25.576, χ2=33.624, P<0.05). Conclusion The practice of multi-department cooperative management brings into full play the advantages of interdisciplinary complementarity, improves the ability of medical staff to implement the prevention and control measures for MDRO, and can effectively reduce the incidence of nosocomial infection in MDRO.

Antibióticos e bactérias multirresistentes em esgoto e águas superficiais receptoras: riscos da propagação de genes codificadores de ESBL, de carbapenemases e de tolerância aos metais no contexto da saúde única / Antibiotics and multidrug-resistant bacteria in sewage and receiving surface waters: risks of spreading genes encoding ESBL, carbapenemases and metal tolerance in the context of one health

Os antibióticos estão compreendidos entre as classes de medicamentos de maior sucesso na medicina, pelo tratamento de infecções bacterianas e consequentemente aumento na expectativa de vida da população. No entanto, seu uso exacerbado desde a sua descoberta promoveram a inserção de antibióticos no ambiente, bem como dispersão global de bactérias resistentes. Como medida à escassez de novos antibióticos, os metais têm sido considerados como potenciais agentes antimicrobianos, no entanto mecanismos de tolerância vêm sendo relatados, mas com distribuição epidemiológica desconhecida. Nesse sentido, os objetivos do presente trabalho foi de avaliar a ocorrência de antibióticos, de bactérias resistentes e de determinantes de resistência aos antibióticos e de tolerância à metais em amostras de esgoto hospitalar, sanitário e água superficial, no contexto da Saúde Única. No total, 10 antibióticos de diferentes classes foram avaliados em sistema de cromatografia líquida de ultra performance acoplado à espectrometria de massas (UPLC-MS) e bactérias resistentes foram isoladas e quantificadas a partir de meios cromogênicos seletivos para bactérias produtoras de ESBL e de carbapenemases. Os isolados obtidos foram submetidos ao teste de susceptibilidade aos antibióticos, bem como à detecção de genes de resistência aos antibióticos e de tolerância à metais, por Reação em Cadeia da Polimerase (PCR). Os antibióticos amoxicilina e ampicilina foram encontrados em altas concentrações, variando entre 131,5 e 1896,29 ng L-1 e entre 366,35 e 1113,07 ng L-1 , respectivamente. Os antibióticos ciprofloxacina, sulfametoxazol e tetraciclina também foram detectados. O porcentual de remoção dos antibióticos no efluente tratado consiste de 53,43% para amoxicilina, 16,88% para ampicilina, 95,6% para sulfametoxazol e de 65,5% para tetraciclina. O perfil das concentrações de bactérias fenotipicamente produtoras de ESBL e de carbapenemases foram semelhantes, sendo de maior ocorrência no esgoto hospitalar. Deve-se destacar que o sistema municipal de tratamento de esgoto não apresentou eficiência na remoção dessas bactérias e altas concentrações foram detectadas no efluente tratado (ESBL: 3.80E+08, KPC: 6.17E+08 UFC/100mL). Foi possível verificar que as concentrações de bactérias resistentes à jusante da ETE foram maiores em relação às concentrações de bactérias à montante, evidenciando um possível impacto do lançamento do efluente tratado no corpo hídrico. Com relação ao fenótipo de resistência, os isolados apresentaram resistência majoritariamente aos antibióticos ß-lactâmicos, seguido por antibióticos da classe das quinolonas. Foi calculado o índice de resistência à múltiplos antibióticos (MAR Index), onde verificou-se que todos os pontos de amostragem configuraram como fontes de alto risco para resistência bacteriana. Quanto à detecção molecular de genes de resistência aos antibióticos, verificou-se que 51% dos isolados (n = 55/108) carreavam o gene codificador de carbapenemase blaKPC e 33% dos isolados (n =36/108) abrigavam o gene codificador de ESBL blaCTX-M dos grupos 1 ou 8. Em menores porcentagens foram detectados os genes blaGES (2,8%), blaNDM (1,9%) e blaVIM (0,9%), sendo esses dois últimos genes codificadores de carbapenemases do tipo metallo-ß-lactamase que são considerados pouco frequentes. Com relação aos genes de tolerância à metais, genes que conferem tolerância à prata, ao cobre e ao mercúrio foram detectados respectivamente em 52%, 50% e 28% dos isolados. Uma correlação forte foi verificada na coexistência entre os genes de tolerância à prata (silA) e de tolerância ao cobre (pcoD) (r = 0,85). Os resultados apontam para a disseminação de bactérias resistentes aos antibióticos nas matrizes avaliadas, com predominância de genes codificadores de carbapenemases. Em termos de saúde pública, os dados levantados apontam para uma emergência sanitária, em que medidas de mitigação precisam ser urgentemente aderidas. Nesse sentido, e em consonância com a abordagem de Saúde Única, propõe-se a necessidade de tratamento do efluente hospitalar, bem como adição de tratamento terciário na ETE. A colaboração integrada entre os setores da saúde pública, veterinária e ambiental são fundamentais para frear essa "pandemia silenciosa"

Antibiotics are among the most successful classes of drugs in medicine, by treating bacterial infections and consequently increasing the life expectancy of the population. However, their exacerbated use since their discovery has promoted the insertion of antibiotics into the environment, as well as global dispersion of resistant bacteria. As a measure to the scarcity of new antibiotics, metals have been considered as potential antimicrobial agents, however, tolerance mechanisms have been reported, but with unknown epidemiological distribution. In this sense, the objectives of the present work were to evaluate the occurrence of antibiotics, resistant bacteria, and determinants of antibiotic resistance and metal tolerance in samples of hospital wastewater, urban wastewater, and surface water, in the context of One Health. In total, 10 antibiotics of different classes were evaluated in ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) and resistant bacteria were quantified and isolated from chromogenic media selective for bacteria producing ESBL and carbapenemases. The isolates obtained were subjected to antibiotic susceptibility testing, as well as detection of antibiotic resistance and metal tolerance genes by Polymerase Chain Reaction (PCR). The antibiotics amoxicillin and ampicillin were found in high concentrations, ranging between 131.5 and 1896.29 ng L-1 and between 366.35 and 1113.07 ng L-1 , respectively. The antibiotics ciprofloxacin, sulfamethoxazole, and tetracycline were also detected. The removal percentage of the antibiotics in the treated effluent consists of 53.43% for amoxicillin, 16.88% for ampicillin, 95.6% for sulfamethoxazole, and 65.5% for tetracycline. The concentration profiles of phenotypically ESBL- and carbapenemase-producing bacteria were similar, with higher occurrence in hospital wastewater. It should be noted that the municipal sewage treatment system did not show efficiency in removing these bacteria and high concentrations were detected in the treated effluent (ESBL: 3.80E+08, KPC: 6.17E+08 CFU/100mL). It was possible to verify that the concentrations of resistant bacteria downstream of the WWTP were higher in relation to the concentrations of bacteria upstream, showing a possible impact of the discharge of the treated effluent into the water body. Regarding the resistance phenotype, the isolates showed resistance mostly to ß-lactam antibiotics, followed by quinolone class antibiotics. The multiple antibiotic resistance index (MAR Index) was calculated, where it was verified that all sampling points configured as high-risk sources for bacterial resistance. Regarding the molecular detection of antibiotic resistance genes, it was found that 51% of isolates (n = 55/108) carried the carbapenemase encoding gene blaKPC and 33% of isolates (n =36/108) harbored the ESBL encoding gene blaCTX-M from groups 1 or 8. In smaller percentages, blaGES (2.8%), blaNDM (1.9%) and blaVIM (0.9%) genes were detected, these last two genes encoding carbapenemases of the metallo-ß-lactamase type that are considered infrequent. Regarding metal tolerance genes, genes conferring tolerance to silver, copper and mercury were detected in 52%, 50% and 28% of isolates, respectively. A strong correlation was verified in the coexistence between silver tolerance (silA) and copper tolerance (pcoD) genes (r = 0.85). The results point to the spread of antibiotic-resistant bacteria in the evaluated matrices, with a predominance of genes encoding carbapenemases. In terms of public health, the data raised point to a health emergency, in which mitigation measures need to be urgently adhered to. In this sense, and in line with the One Health approach, the need for treatment of the hospital effluent is proposed, as well as the addition of tertiary treatment in the WWTP. The integrated collaboration between the public health, veterinary, and environmental sectors are fundamental to curb this "silent pandemic"

Genótipos e Fenótipos de Resistência a Metais Pesados e Agrotóxicos em Patógenos de Alto Risco em Saúde Única / Genotypes and Phenotypes of Resistance to Heavy Metals and Pesticides in High-Risk Pathogens in Single Health

As atividades industriais e de agronegócio, embora necessárias para o desenvolvimento da sociedade, tem causado sérios problemas ambientais devido à eliminação inadequada de seus efluentes, sendo o tratamento destes um dos assuntos mais importantes em relação ao controle de poluição. Os microrganismos podem ser utilizados como biomarcadores de contaminação, portanto, o conhecimento de mecanismos associados à resistência e a capacidade de imobilização e biotransformação de poluentes é um fator importante para a identificação de linhagens adaptadas, que podem ser eficientes no tratamento e na recuperação de áreas contaminadas. O objetivo do presente projeto foi avaliar o perfil de tolerância de patógenos bacterianos de alto risco em saúde única, aos metais pesados (mercúrio, prata, telúrio e arsênio) e ao agrotóxico glifosato; identificando o resistoma associado. A correlação fenótipo-genótipo foi avaliada em isolados de Klebsiella pneumoniae (n= 35), Escherichia coli (n=46), e Salmonella spp. (n=19), determinando a CIM pelo método de microdiluição, e analisando as respectivas sequências genômicas. Entre os isolados de K. pneumoniae, 32 cepas apresentaram CIM elevadas (64- 512µg/mL) para o metal prata, dos quais 20 carregam o operon silPABCRSE responsável por conferir resistência. Uma cepa de K. pneumoniae carregando genes terABCE apresentou uma CIM de 64 µg/mL para telúrio. Seis cepas de E. coli apresentaram uma CIM >32 µg/mL para telúrio, sendo que 3 cepas carregam os genes tehA/B. Outras 6 cepas de E. coli apresentaram CIM para prata de 256-512 µg/mL, mas só duas carregaram genes silPFCE. Duas cepas de Salmonella apresentaram CIM 64-128 µg/mL para telúrio, e carregam genes tehA/B e terABCDEF. Em relação ao arsênio, 24 cepas de E. coli apresentaram uma CIM ≥ 512 µg/mL, e destas, 12 cepas carregam os genes arsRBC. Salmonella spp., que carregam o gene merR apresentaram CIMs de 8-16 µg/mL para mercúrio. Não foi possível correlacionar a presença do operon phnC-P (sugerido como responsável pela tolerância ao glifosato) com CIMs elevadas para este composto. Os resultados obtidos suportam a hipóteses que a exposição de bactérias de origem humana, animal e ambiental, aos metais pesados pode estar contribuindo para a seleção de linhagens tolerantes, sendo que a tolerância à prata mediada pelo operon silPABCRSE em K. pneumoniae foi predominante no grupo clonal CG258, característica com potencial de biomarcador que pode ser utilizado para monitorar o impacto do uso deste metal nas diferentes atividades humanas. Neste trabalho foi possível padronizar a técnica de PCR com os genes do operon sil de interesse

Industrial and agribusiness activities have caused serious environmental problems due to the inadequate disposal of their effluents, the treatment of which being one of the most important issues in relation to pollution control. Microorganisms can be used as biomarkers of contamination, therefore the knowledge of mechanisms associated with resistance and the immobilization and biotransformation capacity of pollutants can be an important factor for the identification of adapted strains, efficient in the treatment and recovery of contaminated areas. The aim of this study was to evaluate the tolerance profile of critical priority bacterial pathogens relevant in One Health, to heavy metals (mercury, silver, tellurium, and arsenic) and to the pesticide glyphosate, identifying the associated resistome. The phenotype-genotype correlation was evaluated in antibiotic-resistant isolates of Klebsiella pneumoniae (n= 35), Escherichia coli (n= 46), and Salmonella spp. (n= 19), by MIC determination using the microdilution method, and by analysis of their respective genomic sequences. Among the isolates of K. pneumoniae, 32 strains showed elevated MIC (64-512 µg/mL) for silver metal, of which 20 carried the silPABCRSE operon responsible for conferring resistance. A strain of K. pneumoniae carrying terrace genes showed a MIC of 64 µg/mL for tellurium. Six strains of E. coli showed an MIC> 32 µg/mL for tellurium, with 3 strains carrying the Thea/B genes. Other 6 strainsof E. coli showed MIC for silver of 256-512 µg/mL, but only two carried silPFCE genes. Two strains of Salmonella showed MIC 64-128 µg/mL for tellurium and carried the/B and terABCDEF genes. In relation to arsenic, 24 strains of E. coli had a MIC 512 µg/mL, and of these, 12 strains carried the arsRBC genes. Salmonella spp., which carriedthe mer gene, had MICs of 8-16 µg/mL for mercury. It was not possible to correlate thepresence of the phonic-P operon (suggested as responsible for glyphosate tolerance) with elevated MICs for this compound. The silver tolerance mediated by the operon sil was a predominant feature in K. pneumoniae strains belonging to the clonal group CG258, suggesting a intrinsic property that has contributed to the persistence and wide dissemination of CG258 within a One Health context, which could be as a biomarkerto monitor the impact of the use of silver compounds and silver-based biomaterial on different human activities. In this work it was possible to standardize the PCR technique with the genes of the sil operon of interest