Caracterización de aislamientos de Klebsiella pneumoniae doble productores de carbapenemasas en un hospital universitario / Phenotypic and genotypic characterization of double carbapenemase producing Klebsiella pneumoniaeisolates in a University Hospital

La emergencia de aislamientos de Klebsiella pneumoniaedoble productores de carbapenemasas (KPC y NDM) es una de las consecuencias de la pandemia causada por SARS-CoV-2 que ha causado un impacto significativo en las tasas de resistencia a los antimicrobianos en las infecciones intrahospitalarias por esta enterobacteria. Estos aislamientos representan un desafío para los servicios de salud, por su detección y caracterización y posterior tratamiento. En este trabajo se describen los aislamientos portadores de KPC y NDM recuperados durante 2022 aislados de distintas muestras clínicas de pacientes internados en un hospital universitario de la Ciudad de Buenos Aires, se los caracteriza fenotípicamente y genotípicamente como portadores de ambas carbapenemasas y se destaca la excelente actividad in vitro de la combinación ceftazidima-avibactam y aztreonam en el tratamiento de estas infecciones en donde las alternativas terapéuticas estarían limitadas a antibióticos no ß-lactámicos con porcentajes de resistencia que superan el 70%

The emergence of double-carbapenemase (KPC and NDM) producing Klebsiella pneumoniae isolates is one of the consequences derived from the SARS CoV-2 pandemic, which has caused significant impact on the antimicrobial resistance rates in hospital acquired infections. These isolates represent a real challenge for Health Services due to their difficult detection and characterization and subsequent treatment. In the present work we describe the double carbapenemase producing isolates recovered during the year 2022 from clinical samples belonging to hospitalized patients at a University Hospital in Buenos Aires city, we report their phenotypic and genotypic characterization and the excellent "in vitro" activity of the ceftazidime-avibactam-aztreonam combination in the treatment of infections in which the therapeutical options are restricted to non ß- lactamic antimicrobials which hold resistance rates higher than 70%

Respuesta de procalcitonina ante co-infección e infección secundaria por bacterias multirresistentes en pacientes COVID -19 / Procalcitonin response in co-infection and secondary infection by multidrug resistant bacteria in COVID -19 patients

INTRODUCCIÓN. La procalcitonina, es un biomarcador que puede usarse como apoyo diagnóstico en infecciones bacterianas y la monitorización del tratamiento antibiótico, sobre todo en pacientes con sepsis. De ahí que, fue utilizado durante la pandemia COVID-19 OBJETIVO. Determinar los valores de procalcitonina en pacientes con COVID-19 y definir una p osible correlación entre su incremento y vinculación en coinfección o infección secundaria por Klebsiella pneumoniae y Pseudomonas aeruginosa con multidrogo resistencia y resistencia extendida a los antibióticos. MATERIALES Y MÉTODOS. Estudio retrospectivo observacional, descriptivo transversal, realizado del 1 de mayo al 31 de octubre del 2020 en el Hospital de Especialidades Carlos Andrade Marín sobre 7028 pacientes adultos, hospitalizados, con diagnóstico de COVID-19, y resultados de procalcitonina, cuyas muestras de secreción traqueal y/o hemocultivo presentaron desarrollo de Klebsiella pneumoniae y Pseudomonas aeruginosa. Su análisis estadístico fue desarrollado mediante la prueba Chi Cuadrado de Pearson. RESULTADOS. Se recibieron 861 muestras de hemocultivo y 391 de secreción traqueal, obteniéndose: 32% aislamientos de Klebsiella pneumoniae y Pseudomonas aeruginosa multidrogo y extremadamente resistente. Entre los pacientes COVID-19 que fallecieron, 34,4% mostraron incrementos de procalcitonina. Al contrario, entre los pacientes que sobrevivieron sólo en 8,8% se observó incrementos de procalcitonina evidenciándose un vínculo entre el incremento de procalcitonina y mortalidad. CONCLUSIONES. No existe diferencia en relación al incremento en los valores de procalcitonina en pacientes COVID-19 con co-infección o infección secundaria por Klebsiella pneumoniae y Pseudomonas aeruginosa multidrogo y extremadamente resistente y los valores de procalcitonina en pacientes con coinfección e infección secundaria con otro tipo de aislamientos bacterianos.

INTRODUCTION. Procalcitonin is a biomarker that can be used as a diagnostic support in bacterial infections and the monitoring of antibiotic treatment, especially in patients with sepsis. Hence, it was used during the COVID-19 pandemic OBJECTIVE. To determine the values of procalcitonin in patients with COVID-19 and to define a possible correlation between its increase and linkage in co-infection or secondary infection by Klebsiella pneumoniae and Pseudomonas aeruginosa with multidrug resistance and extended resistance to antibiotics. MATERIALS AND METHODS. Retrospective observational, descriptive cross-sectional study, conducted from May 1 to October 31, 2020 at the Hospital de Especialidades Carlos Andrade Marín on 7028 adult patients, hospitalized, with diagnosis of COVID-19, and procalcitonin results, whose tracheal secretion and/or blood culture samples presented development of Klebsiella pneumoniae and Pseudomonas aeruginosa. Their statistical analysis was developed using Pearson's Chi-squared test. RESULTS. We received 861 blood culture and 391 tracheal secretion samples, obtaining: 32% isolates of Klebsiella pneumoniae and multidrug-resistant and extremely resistant Pseudomonas aeruginosa. Among the COVID-19 patients who died, 34.4% showed increased procalcitonin levels. On the contrary, among patients who survived, only 8.8% showed increased procalcitonin levels, showing a link between increased procalcitonin levels and mortality. CONCLUSIONS. There is no difference in relation to the increase in procalcitonin values in COVID-19 patients with co-infection or secondary infection by Klebsiella pneumoniae and multidrug-resistant and extremely resistant Pseudomonas aeruginosa and procalcitonin values in patients with co-infection and secondary infection with other types of bacterial isolates.

High-risk clones of ESBL-producing Klebsiella pneumoniae colonizing ICU patients in Natal, northeastern Brazil / Clones de alto risco de Klebsiella pneumoniae produtores de ESBL colonizando pacientes de UTI em Natal, Nordeste do Brasil / Clones de alto riesgo de Klebsiella pneumoniae productores de BLEE que colonizan pacientes de UCI en Natal, noreste de Brasil

Background and objectives: colonization by extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae in Intensive Care Unit (ICU) patients is considered a risk factor for infections, and poses as a source of spreading these strains in hospital facilities. This study aimed to perform the genetic characterization of ESBL-producing K. pneumoniae isolates recovered from surveillance swabs in an ICU in northeastern Brazil. Methods: the isolates were recovered between 2018-2019 from the nasal, axillary, and rectal sites of 24 patients admitted to the ICU. Bacterial identification was performed by traditional biochemical tests. Antimicrobial susceptibility was assessed by disk diffusion, and ESBL phenotype was detected by double-disc synergy test. Polymerase chain reaction (PCR) for blaCTX-M, blaSHV, and blaTEM genes, PFGE, and MLST were carried out in representative isolates. Results: a total of 27 isolates were recovered from 18 patients (75%). The ESBL production was detected in 85% of isolates. Resistance to ciprofloxacin, sulfamethoxazole/trimethoprim and most of the ß-lactams tested was recurrent, except for carbapenems. The blaSHV, blaTEM, and blaCTX-M genes were found in high frequency, and the CTX-M-(1, 2 and 9) groups were identified. Seven sequence types (ST11, ST14, ST17, ST395, ST709, ST855, and ST3827) were described, most of them considered high-risk. Conclusion: these findings emphasize the potential threat of well-established high-risk clones in an ICU, and highlight the importance of monitoring these clones to prevent infections.(AU)

Justificativa e objetivos: a colonização por Klebsiella pneumoniae produtora de ß-lactamase de espectro estendido (ESBL) em pacientes de Unidade de Terapia Intensiva (UTI) é considerada um fator de risco para infecções, e representa uma fonte de disseminação dessas cepas em instalações hospitalares. Este estudo objetivou realizar a caracterização genética de isolados de K. pneumoniae produtores de ESBL recuperados de swabs de vigilância em uma UTI no Nordeste do Brasil. Métodos: os isolados foram recuperados entre 2018-2019 dos sítios nasal, axilar e retal de 24 pacientes internados na UTI. A identificação bacteriana foi realizada por testes bioquímicos tradicionais. A suscetibilidade antimicrobiana foi avaliada por disco-difusão, e o fenótipo ESBL foi detectado pelo teste de sinergia de duplo-disco. Polymerase chain reaction (PCR) para os genes blaCTX-M, blaSHV e blaTEM, PFGE e MLST foram realizados em isolados representativos. Resultados: foram recuperados 27 isolados de 18 pacientes (75%). A produção de ESBL foi detectada em 85% dos isolados. A resistência à ciprofloxacina, sulfametoxazol/trimetoprima e à maioria dos ß-lactâmicos testados foi recorrente, exceto para os carbapenêmicos. Os genes blaSHV, blaTEM e blaCTX-M foram encontrados em alta frequência, e os grupos CTX-M-(1, 2 e 9) foram identificados. Sete sequence types (ST11, ST14, ST17, ST395, ST709, ST855 e ST3827) foram descritos, a maioria deles considerados de alto risco. Conclusão: esses achados enfatizam a ameaça potencial de clones de alto risco bem estabelecidos em uma UTI, e destacam a importância do monitoramento desses clones para prevenir infecções.(AU)

Justificación y objetivos: la colonización por Klebsiella pneumoniae productora de ß-lactamasas de espectro extendido (BLEE) en pacientes de Unidades de Cuidados Intensivos (UCI) se considera un factor de riesgo para infecciones, y se presenta como una fuente de propagación de estas cepas en instalaciones hospitalarias. Este estudio tuvo como objetivo realizar la caracterización genética de aislamientos de K. pneumoniae productores de BLEE recuperados de hisopos de vigilancia en una UCI en el noreste de Brasil. Métodos: los aislamientos se recuperaron entre 2018-2019 de sitios nasales, axilares y rectales de 24 pacientes ingresados en la UCI. La identificación bacteriana se realizó mediante pruebas bioquímicas tradicionales. La susceptibilidad antimicrobiana se evaluó mediante difusión en disco, y el fenotipo BLEE se detectó mediante la prueba de sinergia de doble-disco. La polymerase chain reaction (PCR) para los genes blaCTX-M, blaSHV y blaTEM, PFGE y MLST se llevaron a cabo en aislamientos representativos. Resultados: se recuperaron 27 aislamientos de 18 pacientes (75%). La producción de ESBL se detectó en 85% de los aislamientos. La resistencia a ciprofloxacino, sulfametoxazol/trimetoprima y a la mayoría de los ß-lactámicos evaluados fue recurrente, excepto a los carbapenémicos. Los genes blaSHV, blaTEM y blaCTX-M se encontraron en alta frecuencia, y se identificaron los grupos CTX-M-(1, 2 y 9). Se describieron siete sequence types (ST11, ST14, ST17, ST395, ST709, ST855 y ST3827), la mayoría consideradas de alto riesgo. Conclusión: estos hallazgos enfatizan la amenaza potencial de los clones de alto riesgo bien establecidos en una UCI, y resaltan la importancia de monitorear estos clones para prevenir infecciones.(AU)

Atividade in vitro de extratos e frações de Copernicia prunifera (Arecaceae) contra bactérias de importância clínica em saúde pública / In vitro activity of extracts and fractions of Copernicia prunifera (Arecaceae) against bacteria of clinical importance in public health / Actividad in vitro de extractos y fracciones de Copernicia prunifera (Arecaceae) frente a bacterias de importancia clínica en salud pública

Introdução: O aumento contínuo da resistência bacteriana aos antibióticos convencionais é um problema de importância global. Encontrar produtos como alternativas terapêuticas naturais é essencial. As plantas medicinais possuem uma composição química muito rica, que podem ser estruturalmente otimizadas e processadas em novos antimicrobianos. Objetivo: Avaliar o potencial antibacteriano frente a microrganismos humanos potencialmente patogênicos do extrato etanólico e frações de Copernicia prunifera. Metodologia: A triagem fitoquímica de plantas foi realizada usando métodos de precipitação e coloração e a atividade antibacteriana utilizando o método de difusão em disco e microdiluição em caldo contra cepas padronizadas de Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa e Staphylococcus aureus. Resultados: A triagem fitoquímica revela a presença de taninos, flavonoides, esteroides, triterpernóides, saponinas e alcaloides. Os extratos etanólico e frações da casca do caule e folhas tiveram atividade inibitória contra S. aureus e K. pneumonie com zona de inibição que variou de 7,0±1,73 a 9,33±0,58 mm pelo método de difusão em disco. Pelo método de microdiluição em caldo os extratos foram satisfatórios somente contra K. pneumoniae (CIM = 125 a 1000 µg/mL) S. aureus, P. aeruginosa e E. coli se mostraram resistentes aos testes (CIM > 1000 µg/mL). Conclusão: Esses resultados fornecem uma base para futuras investigações em modelos in vivo, para que os compostos de C. prunifera possam ser aplicados no desenvolvimento de novos agentes antimicrobianos contra K. pneumoniae.

Introduction: The continuous increase in bacterial resistance to conventional antibiotics is a problem of global importance. Finding products as natural therapeutic alternatives is essential. Medicinal plants have a very rich chemical composition, which can be structurally optimized and processed into novel antimicrobials. Objective: To evaluate the antibacterial potential against potentially pathogenic human microorganisms of the ethanolic extract and fractions of Copernicia prunifera. Methodology: Phytochemical screening of plants was performed using precipitation and staining methods and antibacterial activity using the disk diffusion and broth microdilution method against standardized strains of Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Results: Phytochemical screening reveals the presence of tannins, flavonoids, steroids, triterpernoids, saponins and alkaloids. The ethanolic extracts and fractions of stem bark and leaves had inhibitory activity against S. aureus and K. pneumonie with zone of inhibition ranging from 7.0±1.73 to 9.33±0.58 mm by disc diffusion method. By broth microdilution method the extracts were satisfactory only against K. pneumoniae (MIC = 125 to 1000 µg/mL) S. aureus, P. aeruginosa and E. coli were resistant to the tests (MIC > 1000 µg/mL). Conclusion: These results provide a basis for further investigation in in vivo models, so that compounds from C. prunifera can be applied in the development of new antimicrobial agents against K. pneumoniae.

Introducción: El continuo aumento de la resistencia bacteriana a los antibióticos convencionales es un problema de importancia mundial. Es esencial encontrar productos como alternativas terapéuticas naturales. Las plantas medicinales tienen una composición química muy rica, que puede optimizarse estructuralmente y transformarse en nuevos antimicrobianos. Objetivo: Evaluar el potencial antibacteriano frente a microorganismos humanos potencialmente patógenos del extracto etanólico y fracciones de Copernicia prunifera. Metodología: Se realizó el cribado fitoquímico de las plantas mediante los métodos de precipitación y tinción y la actividad antibacteriana mediante el método de difusión en disco y microdilución en caldo frente a cepas estandarizadas de Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa y Staphylococcus aureus. Resultados: El cribado fitoquímico revela la presencia de taninos, flavonoides, esteroides, triterpernoides, saponinas y alcaloides. Los extractos etanólicos y las fracciones de la corteza del tallo y las hojas presentaron actividad inhibitoria contra S. aureus y K. pneumonie con una zona de inhibición que osciló entre 7,0±1,73 y 9,33±0,58 mm por el método de difusión en disco. Por el método de microdilución en caldo, los extractos sólo fueron satisfactorios frente a K. pneumoniae (CMI = 125 a 1000 µg/mL). S. aureus, P. aeruginosa y E. coli fueron resistentes a las pruebas (CMI > 1000 µg/mL). Conclusiones: Estos resultados proporcionan una base para futuras investigaciones en modelos in vivo, de modo que los compuestos de C. prunifera puedan aplicarse en el desarrollo de nuevos agentes antimicrobianos contra K. pneumoniae.

Facteurs pronostiques des pneumopathies acquises sous ventilation mécanique en réanimation polyvalente du CHU d'Angre (RCI) / Prognostic factors for pneumopathy acquired under mechanical ventilation in multi-purpose resuscitation at the Angre CHU (RCI)

Objectifs : Identifier les facteurs de mauvais pronostic des pneumopathies acquises sous ventilation mécanique(PAVM) afin d'améliorer leur prise en charge.Patients et methode : Etude prospective, descriptive et analytique portant sur les patients admis en réanimation du CHU d'Angré du 1er novembre 2019 au 31 juillet 2021 et ayant présenté une PAVM.Resultats : Nous avons colligé 43 patients sur 625 admissions soit 6,88%. L'âge moyen était de 49,06 ans. Le sex ratio était de 0,38. Le principal motif d'admission était le coma avec 88,37%. L'HTA et le diabète étaient les principaux antécédents .Les PAVM précoces représentaient 53,49%. Le Klebsiella pneumoniae était le principal germe. Les patients intubés à l'admission représentaient 79,07%. La durée moyenne de ventilation était de 26,95 jours et la durée moyenne d'hospitalisation était de 30,8140 jours. Une antibiothérapie probabiliste a été réalisée chez 75,76% des patients. La mortalité était de 76,74%. Les facteurs de mortalité étaient une durée de ventilation mécanique supérieure à 15 jours et l'âge supérieur à 50 ans.Conclusion :La mortalité secondaire au PAVM demeure élevée. L'identification des deux facteurs pronostiques devrait améliorer la prise en charge ultérieure de tous nouveaux cas

Objectives: To identify the factors of poor prognosis of ventilator-associated lung disease (VAP) in order to improve their management. Patients and method: Prospective, descriptive and analytical study of patients admitted to intensive care at the Angré University Hospital from November 1, 2019 to July 31, 2021 and having presented VAP.Results: We collected 43 patients out of 625 admissions, i.e. 6.88%. The average age was 49.06 years. The sex ratio was 0.38. The main reason for admission was coma with 88.37%. Hypertension and diabetes were the main antecedents. Early VAP accounted for 53.49%. Klebsiella pneumoniae was the main germ. Patients intubated on admission accounted for 79.07%. The average duration of ventilation was 26.95 days and the average duration of hospitalization was 30.8140 days. Probabilistic antibiotic therapy was performed in 75.76% of patients. Mortality was 76.74%. The mortality factors were duration of mechanical ventilation greater than 15 days and age greater than 50 years.Conclusion:Secondary mortality from VAP remains high. The identification of the two prognostic factors should improve the subsequent management of all new cases.

Clinical Outcome and Risk Factors of Treatment Failure of Peritoneal Dialysis Associated Peritonitis Caused by Klebsiella Pneumoniae:A Multicenter Study / 中国医学科学院学报

Objective To investigate the treatment outcomes,prognosis,and risk factors of treatment failure of peritoneal dialysis associated peritonitis (PDAP) caused by Klebsiella pneumoniae,and thus provide clinical evidence for the prevention and treatment of this disease. Methods The clinical data of PDAP patients at four peritoneal dialysis centers from January 1,2014 to December 31,2019 were collected retrospectively.The treatment outcomes and prognosis were compared between the patients with PDAP caused by Klebsiella.pneumoniae and that caused by Escherichia coli.Kaplan-Meier method was employed to establish the survival curve of technical failure,and multivariate Logistic regression to analyze the risk factors of the treatment failure of PADP caused by Klebsiella pneumoniae. Results In the 4 peritoneal dialysis centers,1034 cases of PDAP occurred in 586 patients from 2014 to 2019,including 21 cases caused by Klebsiella pneumoniae and 98 cases caused by Escherichia coli.The incidence of Klebsiella pneumoniae caused PDAP was 0.0048 times per patient per year on average,ranging from 0.0024 to 0.0124 times per patient per year during 2014-2019.According to the Kaplan-Meier survival curve,the technical failure rate of Klebsiella pneumoniae caused PDAP was higher than that of Escherichia coli caused PDAP (P=0.022).The multivariate Logistic regression model showed that long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP (OR=1.082,95%CI=1.011-1.158,P=0.023).Klebsiella pneumoniae was highly sensitive to amikacin,meropenem,imipenem,piperacillin,and cefotetan,and it was highly resistant to ampicillin (81.82%),cefazolin (53.33%),tetracycline (50.00%),cefotaxime (43.75%),and chloramphenicol (42.86%). Conclusion The PDAP caused by Klebsiella pneumoniae had worse prognosis than that caused by Escherichia coli,and long-term dialysis was an independent risk factor for the treatment failure of Klebsiella pneumoniae caused PDAP.

Evaluation of antibacterial activity of vitamin C against human bacterial pathogens / Avaliação da atividade antibacteriana da vitamina C contra patógenos bacterianos humanos

Now a day’s multidrug resistance phenomenon has become the main cause for concern and there has been an inadequate achievement in the development of novel antibiotics to treat the bacterial infections. Therefore, there is an unmet need to search for novel adjuvant. Vitamin C is one such promising adjuvant. The present study was aimed to elucidate the antibacterial effect of vitamin C at various temperatures (4°C, 37°C and 50°C) and pH (3, 8, and 11), against Gram-positive and Gram-negative bacteria at various concentrations (5-20 mg/ml) through agar well diffusion method. Growth inhibition of all bacterial strains by vitamin C was concentration-dependent. Vitamin C significantly inhibited the growth of Gram-positive bacteria: Bacillus licheniformis (25.3 ± 0.9 mm), Staphylococcus aureus (22.0 ± 0.6 mm), Bacillus subtilis (19.3 ± 0.3 mm) and Gram-negative bacteria: Proteus mirabilis (27.67 ± 0.882 mm), Klebsiella pneumoniae (21.33±0.9 mm), Pseudomonas aeruginosa (18.0 ± 1.5 mm) and Escherichia coli (18.3 ± 0.3 mm). The stability of vitamin C was observed at various pH values and various temperatures. Vitamin C showed significant antibacterial activity at acidic pH against all bacterial strains. Vitamin C remained the stable at different temperatures. It was concluded that vitamin C is an effective and safe antibacterial agent that can be used in the future as an adjunct treatment option to combat infections in humans.

Agora, a resistência antimicrobiana de um dia em patógenos aos antibióticos tornou-se a principal causa de preocupação e houve uma realização inadequada no desenvolvimento de novos antibióticos para tratar infecções bacterianas. Portanto, há uma necessidade de pesquisar um novo adjuvante, e a vitamina C é um desses adjuvantes promissores. O objetivo do presente estudo foi elucidar o efeito antibacteriano da vitamina C em diferentes temperaturas (4 °C, 37 °C e 50 °C) e pH (3, 8 e 11), contra Gram-positivos e Gram-cepas bacterianas negativas em várias concentrações (5-20 mg / ml) através do método de difusão em ágar bem. A inibição do crescimento de todas as cepas bacterianas pela vitamina C era dependente da concentração. A vitamina C inibiu significativamente o crescimento de bactérias Gram-positivas: Bacillus licheniformis (25,3 ± 0,9 mm), Staphylococcus aureus (22,0 ± 0,6 mm), Bacillus subtilis (19,3 ± 0,3 mm) e bactérias Gram- negativas: Proteus mirabilis (27,7 ± 0,9 mm), Klebsiella pneumoniae (21,3 ± 0,9 mm), Pseudomonas aeruginosa (18,0 ± 1,5 mm) e Escherichia coli (18,3 ± 0,3 mm). A estabilidade da vitamina C foi observada em vários valores de pH e várias temperaturas. A vitamina C mostrou atividade antibacteriana significativa em pH ácido contra todas as cepas bacterianas. A estabilidade da vitamina C permaneceu nas mesmas diferentes temperaturas (4 °C, 37 °C e 50 °C). Concluímos que a vitamina C é um agente antibacteriano eficaz e seguro que pode ser usado no futuro como uma opção de tratamento auxiliar para combater infecções em humanos, pois pode apoiar o sistema imunológico diretamente.

UhpTE350Q mutation along with the presence of fosA6/5 genes in the genome probably contributes to inherent fosfomycin resistance of Klebsiella pneumoniae / 南方医科大学学报

OBJECTIVE@#To investigate the molecular mechanism underlying inherent fosfomycin resistance of Klebsiella pneumoniae (K. pneumoniae).@*METHODS@#The draft genomic sequences of 14 clinical hypervirulent/hypermucoviscous K. pneumoniae (HvKP/ HmKP) isolates were obtained using the next-generation sequencing technology. The genomic sequences were analyzed using the Resistance Gene Identifier (RGI) software for predicting the resistome based on homology and SNP models in the Comprehensive Antibiotic Resistance Database (CARD) and for identification of the presence of phosphomycin resistancerelated genes uhpt and fosA and their mutations in the bacterial genomes. The results were verified by analyzing a total of 521 full-length genomic sequences of K. pneumonia strains obtained from GenBank.@*RESULTS@#All the 14 clinical isolates of HvKP/ HmKP carried hexose phosphate transporter (UhpT) gene mutation, in which the glutamic acid was mutated to glutamine at 350aa (UhpTE350Q mutation); the presence of fosA6 gene was detected in 12 (85.71%) of the isolates and fosA5 gene was detected in the other 2 (14.29%) isolates. Analysis of the genomic sequences of 521 K. pneumonia strains from GenBank showed that 508 (97.50%) strains carried UhpTE350Q mutation, 439 (84.26%) strains harbored fosA6, and 80 (15.36%) strains harbored fosA5; 507 (97.31%) strains were found to have both UhpTE350Q mutation and fosA6/5 genes in the genome. Only 12 (2.30%) strains carried fosA6/5 genes without UhpTE350Q mutation; 1 (0.19%) strain had only UhpTE350Q mutation without fosA6/5 genes, and another strain contained neither UhpTE350Q mutation nor fosA6/5 genes.@*CONCLUSION@#UhpTE350Q mutation with the presence of fosA6/5 genes are ubiquitous in K. pneumonia genomes, indicating a possible intrinsic mechanism of fosfomycin resistance in the bacterium to limit the use of fosfomycin against infections caused by K. pneumoniae, especially the multi-resistant HvKP/HmKP strains.

Pathogenic characterization of Klebsiella pneumoniae resistant to carbapenems and polymyxin / 中华预防医学杂志

Objective: Analysis and investigation of pathogenic characteristics of polymyxin-and carbapenem-resistant Klebsiella pneumoniae (PR-CRKP). Methods: A total of 23 PR-CRKP strains isolated from clinical specimens from the General Hospital of Southern Theater Command from March 2019 to July 2021 were retrospectively collected, Whole-genome sequencing was performed on 23 PR-CRKP strains, resistance genes were identified by comparison of the CARD and the ResFinder database, high-resolution typing of PR-CRKP strains was analyzed by core genomic multilocus sequencing (cgMLST) and single nucleotide polymorphism (SNP); polymyxin resistance genes were determined by PCR and sequencing. Results: All PR-CRKP strains were KPC-2 producing ST11 types. cgMLST results showed that the evolutionary distance between the PR-CRKP strains and Klebsiella pneumoniae in mainland China was 66.44 on average, which is more closely related than foreign strains; the 23 PR-CRKP strains were divided into 3 main subclusters based on SNP phylogenetic trees, with some aggregation among Clade 2-1 in the isolation department and date. The two-component negative regulatory gene mgrB has seven mutation types including point mutations, different insertion fragments and different insertion positions. Conclusion: The close affinity of PR-CRKP strains indicate the possibility of nosocomial clonal transmission and the need to strengthen surveillance of PR-CRKP strains to prevent epidemic transmission of PR-CRKP.

Clinical distribution and drug resistance characteristics of carbapenem-resistant Klebsiella pneumoniae / 中华预防医学杂志

To explore the clinical distribution and drug resistance characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP), in order to provide reference for the prevention and treatment of CRKP infection. Retrospective analysis was performed on 510 clinical isolates of CRKP from January 2017 to December 2021, and strain identification and drug sensitivity tests were conducted by MALDI-TOF mass spectrometer and VITEK-2 Compact microbial drug sensitivity analyzer. The carbapenemase phenotype of CRKP strain was detected by carbapenemase inhibitor enhancement test. The CRKP strain was further categorized by immunochromogenic method and polymerase chain reaction (PCR) was used for gene detection. The results showed that 302 strains (59.2%) were derived from sputum, 127 strains (24.9%) from urine and 47 strains (9.2%) from blood. 231 (45.3%) were mainly distributed in intensive care, followed by 108 (21.2%) in respiratory medicine and 79 (15.5%) in neurosurgery. Drug susceptibility test result shows that the resistant rate of tigecycline increased from 1.0% in 2017 to 10.1% in 2021, the difference was statistically significant (χ2=14.444,P<0.05). The results of carbapenemase inhibitor enhancement test showed that 461 carbapenemase strains (90.4%) of 510 CRKP strains, including 450 serinase strains (88.2%), 9 metalloenzyme strains (1.8%), and 2 strains (0.4%) produced both serine and metalloenzyme. 49 strains (9.6%) did not produce enzymes. Further typing by immunochromogenic assay showed that 461 CRKP strains were KPC 450 (97.6%) and IMP 2 (0.4%). 7 NDM (1.5%); 2 strains of KPC+NDM (0.4%); PCR results were as follows: 450 strains of blaKPC (97.6%), 2 strains of blaIMP (0.4%), 7 strains of blaNDM (1.5%), and 2 strains of blaKPC+NDM (0.4%). In conclusion, CRKP strains mainly originated from sputum specimens and distributed in intensive care department, and the drug resistance characteristics were mainly KPC type in carbapenemase production. Clinical microbiology laboratory should strengthen the monitoring of CRKP strains, so as to provide reference for preventing CRKP infection and reducing the production of bacterial drug resistance.

Regularity of ventilator-associated pneumonia induced by three common pathogens / 中华危重病急救医学

OBJECTIVE@#To investigate the incidence and infection regularity of ventilator-associated pneumonia (VAP) in patients undergoing tracheal intubation and to provide reference for the prevention and treatment of VAP infection in the future.@*METHODS@#A retrospective study was conducted to collect the microbial data of airway secretion cultures from 72 patients with endotracheal intubation admitted to the emergency ward of Shanghai Fifth People's Hospital from May 2020 to February 2021, and the species of microorganisms and intubation time were statistically analyzed.@*RESULTS@#Among 72 patients with endotracheal intubation, males were more than females (58.33% vs. 41.67%); Patients over 60 years old accounted for 90.28%; pneumonia was the main primary disease, accounting for 58.33%. Pathogenic tests showed that: (1) 72 patients were infected with Acinetobacter baumannii (AB), Klebsiella pneumoniae (KP), and Pseudomonas aeruginosa (PA) 48 hours after intubation, 51.39% (37/72), 27.78% (20/72), and 26.39% (19/72), respectively. The infection rate of AB was significantly higher than that of KP and PA. Within 48 hours of intubation, the infection rates of AB, KP, and PA were 20.83% (15/72), 13.89% (10/72), and 4.17% (3/72), respectively. Of the 42 patients with primary pneumonia, 61.90% (26/42) were infected with one or more of the three pathogenic bacteria AB, KP, and PA 48 hours after intubation, indicating a change in the etiology of the pathogenic bacteria, with the main pathogenic bacteria transitioning from other pathogenic bacteria to AB, KP, and PA. (2) AB, KP, and PA were prone to cause late onset VAP (i.e., intubation ≥ 5 days). Respectively, among VAP patients infected with AB, late onset VAP accounted for 59.46% (22/37). Among patients infected with KP, 75.00% (15/20) had late onset VAP. Among patients infected with PA, late onset VAP accounted for 94.74% (18/19), indicating a higher proportion of late onset VAP caused by PA and KP. (3) Infection was closely related to intubation time, and the pipeline can be replaced according to the peak period of infection. AB and KP infections peaked within 4 days after intubation, reaching 57.69% (30/52) and 50.00% (15/30), respectively. It is recommended to replace the tubes or undergo sensitive antimicrobial therapy around 3-4 days after starting the machine. The proportion of PA infection after 7 days of intubation was 72.73% (16/22), and it was considered to replace the pipeline after 7 days. (4) Most of the three pathogenic bacteria, AB, KP, and PA were carbapenem resistant pathogens with multiple drug resistance. Except for PA, the infection rate of carbapenem resistant bacteria (CRAB, CRKP) was significantly higher than that of non-carbapenem resistant bacteria (AB, KP), accounting for 86.54% (45/52) and 66.67% (20/30) of the corresponding infection cases, respectively, while CRPA only accounts for 18.18% (4/22).@*CONCLUSIONS@#The main differences in VAP infection caused by AB, KP, and PA pathogens are infection time, infection probability, and carbapenem resistance. Targeted prevention and treatment measures can be implemented for patients with intubation.

Genes involucrados con resistencia antimicrobiana en hospitales del Ecuador / Genes involved with antimicrobial resistance in Ecuadorian hospitals

INTRODUCCIÓN. La resistencia a los antimicrobianos es un problema de salud pública actual asociado con alta mortalidad, hospitalización prolongada, alternativas terapéuticas reducidas, mayores costos económicos y la posibilidad de brotes hospitalarios. OBJETIVO. Describir los principales genes involucrados con resistencia antimicrobiana en hospitales del Ecuador. MATERIALES Y MÉTODOS. Se realizó una descripción retrospectiva no experimental, de artículos indexados relacionados con resistencia antimicrobiana en hospitales del Ecuador, con evidencia desde el año 2009 al 2022. La revisión de bibliografías se llevó a cabo en bases de datos como Pubmed, Science Direct y Google Scholar. RESULTADOS. De un grupo original de 77 artículos, se seleccionaron 33 documentos. En Ecuador, varios estudios han descrito los mecanismos moleculares involucrados en la resistencia bacteriana. Sin embargo, en bacterias menos comunes, falta investigación sobre los genes asociados. CONCLUSIONES. Las principales bacterias multirresistentes descritas en Ecuador son Klebsiella pneumoniae, Escherichia coli y Acinetobacter baumanni, las cuales presentan genes involucrados en la producción de carbapenemasas (blaKPC, blaNDM, blaOXA-48). Estas bacterias presentan altos niveles de resistencia a los antibióticos y son objeto de vigilancia epidemiológica por parte del sistema nacional de salud. A nivel local, otras bacterias presentan mecanismos de resistencia a los carbapenémicos (Pseudomonas aeruginosa, Enterobacter sp., Serratia marcescens, Citrobacter sp.), pero no existen descripciones detalladas del genotipo, sus características microbiológicas o la clínica del paciente. El conocimiento de las tasas de resistencia a los antimicrobianos en los diferentes hospitales, la implementación de un plan de administración de antibióticos, el uso correcto de los equipos de protección personal, el aislamiento de las personas con infecciones multirresistentes, así como el trabajo colaborativo entre las diferentes áreas del hospital, son esenciales para reducir la propagación de estos patógenos.

INTRODUCTION. Antimicrobial resistance is a current public health problem associated with high mortality, prolonged hospitalization, reduced therapeutic alternatives, increased economic costs, and the potential for hospital outbreaks. OBJECTIVE. To describe the main genes involved with antimicrobial resistance in hospitals in Ecuador. MATERIALS AND METHODS. A retrospective non-experimental description of indexed articles related to antimicrobial resistance in hospitals in Ecuador was carried out, with evidence from 2009 to 2022. The review of bibliographies was carried out in databases such as Pubmed, Science Direct and Google Scholar. RESULTS. From an original group of 77 articles, 33 papers were selected. In Ecuador, several studies have described the molecular mechanisms involved in bacterial resistance. However, in less common bacteria, research on the associated genes is lacking. CONCLUSIONS. The main multidrug-resistant bacteria described in Ecuador are Klebsiella pneumoniae, Escherichia coli and Acinetobacter baumanni, which present genes involved in the production of carbapenemases (blaKPC, blaNDM, blaOXA-48). These bacteria present high levels of antibiotic resistance and are subject to epidemiological surveillance by the national health system. Locally, other bacteria present mechanisms of resistance to carbapenemics (Pseudomonas aeruginosa, Enterobacter sp., Serratia marcescens, Citrobacter sp.), but there are no detailed descriptions of the genotype, their microbiological characteristics or the patient's clinic. Knowledge of antimicrobial resistance rates in different hospitals, the implementation of an antibiotic stewardship plan, the correct use of personal protective equipment, the isolation of individuals with multidrug-resistant infections, as well as collaborative work between different areas of the hospital, are essential to reduce the spread of these pathogens.

Eficacia de la terapia con aminoglicósidos en infectados por Klelsiella pneumoniae resis-tente a carbapenémicos / Efficacy of aminoglycoside therapy in patients infected with Carbapenem-Resistant Klel-siella pneumoniae

El tratamiento de infecciones por bacterias resistentes a determinados grupos farmacológicos resulta un tema de alto interés para la ciencia. Así, la investigación tuvo el propósito de sistema-tizar la información acerca de la eficacia de los aminoglicósidos en pacientes infectados por Klebsiella pneumoniae resiste a carbapenémicos; para lo que se hizo una revisión sistemática siguiendo el protocolo PRISMA. Las fuentes se ubicaron a partir de una pesquisa se hizo en las bases de datos: PubMed, MEDLINE y SCOPUS; quedando seleccionados 11 artículos que cumplieron con los requisitos establecidos. Se observó un predominio de los artículos provenientes de los Estados Unidos de América (4/11) y Brasil (3/11). La población global fue de 3778 pacientes entre las 11 investigaciones incluidas. El uso de aminoglicósidos resultó más eficaz que otros grupos farmacológicos en la mejoría en el estado clínico, reflejando menores valores de mortalidad en pacientes hospitalizados por la infección en cuestión.

The treatment of infections by bacteria resistant to certain pharmacological groups is a topic of great interest for science. Thus, the research had the purpose of systematizing the information about the efficacy of aminoglycosides in patients infected by Carbapenem-Resistant Klebsiella pneumoniae. This systematic review was carried out following the PRISMA protocol. The sour-ces were located from a search made in the databases: PubMed, MEDLINE, and SCOPUS; 11 articles were selected that met the established requirements. A predominance of articles from the United States of America (4/11) and Brazil (3/11) was observed. The overall population was 3,778 patients among the 11 studies included. The use of aminoglycosides was more effective than other pharmacological groups in improving clinical status, reflecting lower mortality values in patients hospitalized for the infection in question

Complicaciones por accesos venosos centrales en pacientes adultos / Complications due to central venous access in adult patients

Los accesos venosos centrales son técnicas de uso regular en el ámbito hospitalario, es por ello que la investigación tiene como Objetivo: Establecer la incidencia de complicaciones asociadas a la colocación de accesos venosos centrales en pacientes atendidos en el Hospital Militar Universitario "Dr. Carlos Arvelo". Métodos: estudio prospectivo, de selección intencional de pacientes en el ámbito hospitalario que presenten complicaciones asociadas a la canalización de accesos venosos centrales; a los cuales se les aplicó un cuestionario donde se registraron, además de datos demográficos y clínicos, los resultados del funcionamiento del acceso venoso central. Al séptimo día se retiró o se recambió el acceso venoso central y se tomó muestra para cultivo y antibiograma de la punta de catéter. Los datos fueron tabulados, analizados en gráficos y tablas. Resultados: Uno de los principales hallazgos fueron las complicaciones infecciosas en un 65.93 % y producto de complicaciones mecánicas un 34.05 % del grupo de estudio. Las complicaciones infecciosas fueron atribuibles en su mayoría a Staphylococcus aureus (27,39 %), Pseudomona sp (21,91 %), Stenotrophomonas maltophilia (16,44%), Burkholderia cepacia (10,95 %) y Klebsiella pneumonia (5,48 %). En cuanto al porcentaje de éxito de las intervenciones se encontró que el promedio de intentos fue de 5 con una desviación estándar de ± 3 intentos y una duración promedio menor a 30 minutos en 90 de los casos representando el 76,27 % y duración mayor de 30 minutos en 28 casos representando 23,7 %. Conclusiones: Los accesos venosos yugulares internos fueron los procedimientos más frecuentes seguido de los accesos subclavios, sin predilección de lateralidad alguna. Al revisar los hallazgos se puede evidenciar que la punción arterial se convierte en la complicación mecánica más frecuente produciendo hematomas y equimosis con un alto porcentaje de intentos superiores a 30 minutos o un número de intentos mayores a tres, así como las complicaciones infecciosas generadas por el Staphylococcus aureus y sin que dichas complicaciones se encontraran asociadas al tipo de abordaje estudiado, tiempo de intervención u otros factores de carácter demográfico(AU)

Central venous accesses are a technique of regular use in the hospital environment, that is why the objective of this research is: to establish the incidence of complications treated at the University Military Hospital "Dr. Carlos Arvelo". Methods: prospective study, of intentional selection of patients in the hospital setting who present complications associated to the cannulation of central venous accesses; to whom a questionnaire was applied where, in addition to demographic and clinical data, the results of the central venous access operation were registered. On the seventh day, the central venous access was removed or replaced and a sample was taken for culture and antibiogram of the catheter tip. Data were tabulated, analyzed in graphs and tables. Results: One of the main findings was infectious complications in 65.93 % and mechanical complications in 34.05 % of the study group. Infectious complications were mostly attributable to Staphylococcus aureus (27.39 %), Pseudomona sp (21.91 %), Stenotrophomonas maltophilia (16.44 %), Burkholderia cepacia (10.95 %) and Klebsiella pneumonia (5.48 %). Regarding the percentage of success of the interventions, it was found that the average number of attempts was 5 with a standard deviation of ± 3 attempts and an average duration of less than 30 minutes in 90 of the cases representing 76.27 % and duration greater than 30 minutes in 28 cases representing 23.7 %. Conclusions: Internal jugular venous accesses were the most frequent procedures followed by subclavian accesses, with no predilection for laterality. When reviewing the findings, it can be evidenced that arterial puncture becomes the most frequent mechanical complication producing hematomas and ecchymosis with a high percentage of attempts longer than 30 minutes or a number of attempts longer than three, as well as infectious complications generated by Staphylococcus aureus and without these complications being associated to the type of approach studied, time of intervention or other demographic factors(AU)

Resistencia a colistina en aislados de Klebsiella pneumoniae resistente a carbapenémicos en un hospital pediátrico de Corrientes / Colistin resistance in carbapenem-resistant Klebsiella pneumoniae isolates from a pediatric hospital from Corrientes, Argentina

INTRODUCCIÓN: Existe un incremento de las infecciones por Klebsiella pneumoniae resistente a carbapenémicos (KPRC) en la población pediátrica y los datos epidemiológicos son limitados. OBJETIVOS: Conocer la frecuencia de KPRC en pacientes pediátricos, determinar la actividad in vitro de colistina y detectar el gen mcr-1 en dichos aislados. MATERIALES Y MÉTODOS: Se estudiaron 220 aislados de K. pneumoniae en un hospital pediátrico durante los años 2018 y 2019. La susceptibilidad antimicrobiana se determinó por microdilución en caldo según CLSI y EUCAST. Los genes blaKPC, blaNDM, blaIMP, blaVIM, blaOXA-48 y mcr-1 se analizaron mediante reacción de polimerasa en cadena (RPC). RESULTADOS: El 9,5% (n: 21) de los aislados fueron caracterizados como KPRC, donde se observó una resistencia a colistina de 47,6% (10/21) con valores de CIM50 de 2 μg/mL y CIM90 de > 4 μg/mL. En todos los aislados de KPRC se caracterizó el gen blaKPC y no se detectó el gen mcr-1. El perfil de resistencia observado en otros antimicrobianos fue el siguiente: gentamicina 100% (n: 21), ciprofloxacina 100% (n: 21), cotrimoxazol 100% (n: 21) y amikacina 19% (n: 4). Se observó 100% de sensibilidad a tigeciclina y ceftazidima/avibactam. CONCLUSIÓN: Este estudio demuestra un valor significativo de la resistencia a colistina en comparación a ceftazidima/avibactam y tigeciclina.

BACKGROUND: There is an increase of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in the pediatric population and epidemiological data are limited. Aim: To calculate the frequency of CRKP in pediatric patients, to determine the in vitro activity of colistin and to detect the presence of mcr-1 gene in said isolates. METHODS: 220 isolates of K. pneumoniae were studied in a pediatric hospital between January 2018 and December 2019. Antimicrobial susceptibility was determined by microdilution in broth according to guidelines of CLSI and EUCAST. The genes blaKPC, blaNDM, blaIMP, blaVIM, blaOXA-48 and mcr-1 were detected by polymerase chain reaction (PCR). RESULTS: 9.5% (n: 21) of the isolates were characterized as CRKP, where was observed a resistance to colistin of 47.6% (10/21) with values of MIC50 of 2 μg/mL and MIC90 of ≥ 4 μg/mL. In 100% of CRKP strains the blaKPC gene was detected and the mcr-1 gene was not found. The resistance profile to other antimicrobials was as follow: gentamicin 100% (n: 21), trimethoprim/sulfamethoxazole 100% (n: 21), ciprofloxacin 100% (n: 21), amikacin 19% (n: 4). All of the isolates were sensitive to ceftazidime/avibactam and tigecycline. CONCLUSION: This study demonstrates a significant value of resistance to colistin in pediatric patients compared to other last line antimicrobial such as ceftazidime/avibactam and tigecycline.

Occurrence of blaKPC gene in clinical isolates of Pseudomonas aeruginosa from Brazil

Pseudomonas aeruginosa is one of the main microorganisms causing healthcarerelated infections. The rise of carbapenem-resistant P. aeruginosa (CRPA) strains has become a serious public health problem. Dissemination of the enzyme Klebsiella pneumoniae carbapenemase (KPC) encoded by the blaKPC gene cause the inactivation of ß-lactam antibiotics being one of the mechanisms involved in this resistance. Given the above, the objective of this review was to evaluate the occurrence of the blaKPC gene in clinical isolates of P. aeruginosa in Brazil. For this, the online databases used were: Lilacs, SciELO and PubMed. The search for articles included articles published from 2012 to 2020, using the following keywords: blaKPC (KPC), Pseudomonas aeruginosa, and Brazil (in Portuguese and English). Initially, 30 publications eligible for inclusion in this review were identified. After the first analysis, two articles were excluded due to duplication. Subsequently, titles and abstracts were evaluated, 15 articles were excluded because they did not fit the theme, and 13 articles that met the inclusion criteria were read in full. In these studies, the presence of the blaKPC gene was investigated in 566 clinical isolates of P. aeruginosa in Brazil, with 86 (15.2%) positive samples found. Pernambuco was the state with the highest number of articles and positive samples, respectively, 38.5% (5/13), and 65.1% (56/86). This study reinforces the need to investigate the occurrence of this gene in all regions of the country in CRPA, aiming to understand how its dissemination occurs and to promote prevention and therapeutic strategies.

Características clinicoepidemiológicas de pacientes con infecciones intrahospitalarias en un servicio de medicina interna de Santiago de Cuba / Clinical-epidemiological characteristics of patients with hospital acquired infections in a service of internal medicine from Santiago de Cuba

Introducción: La infección nosocomial o intrahospitalaria constituye un importante problema de salud en todos los hospitales del orbe. Objetivo: Describir las características clínicas y epidemiológicas de pacientes con infecciones intrahospitalarias. Métodos: Se realizó un estudio descriptivo y transversal de 57 pacientes con infecciones intrahospitalarias, ingresados en el Servicio de Medicina Interna del Hospital Provincial Docente Clínico-Quirúrgico Saturnino Lora de Santiago de Cuba, de octubre a diciembre de 2019, para lo cual se analizaron las variables edad, enfermedades asociadas, factores predisponentes, tipo de infección y gérmenes aislados. Resultados: En la serie sobresalieron el grupo etario de 60-69 años y la hipertensión arterial como enfermedad crónica concomitante (26,0 %). Entre los factores predisponentes resultó más frecuente el tabaquismo (32,8 %) y el tipo de infección preponderante fue la bronconeumonía bacteriana (47,0 %), cuyo germen causal en la mayoría de los casos (35,1 %) fue la Klebsiella pneumoniae. Conclusiones: Las infecciones intrahospitalarias aquejaron principalmente a pacientes de edad avanzada con enfermedades crónicas asociadas, como la diabetes mellitus y la hipertensión arterial. Cabe destacar la importancia de conocer la flora microbiana existente en el servicio donde se adquiere la infección, a fin de lograr tanto la prevención como el diagnóstico oportuno y el tratamiento adecuado.

Introduction: The cross or hospital infections constitute an important health problem in all the hospitals of the world. Objective: To describe the clinical and epidemiological characteristics of patients with hospital infections. Methods: A descriptive and cross-sectional study of 57 patients with hospital acquired infections was carried out. They were admitted to the Internal Medicine Service of Saturnino Lora Clinical-surgical Teaching Provincial Hospital of Santiago de Cuba, from October to December, 2019, for which the variables age, associated diseases, predisposing factors, type of infection and isolated germs were analyzed. Results: In the series the 60-69 years age group and hypertension as concomitant chronic disease (26.0 %) were notable. Among the predisposing factors nicotine addiction (32.8 %) was more frequent and the preponderant type of infection was the bacterial bronchopneumonia (47.0 %) whose causal germ in most of the cases (35.1 %) was the Klebsiella pneumoniae. Conclusions: The hospital acquired infections mainly afflicted patients of advanced age with associated chronic diseases, as diabetes mellitus and hypertension. It is necessary to highlight the importance of knowing the existent microbial flora in the service where the infection is acquired, in order to achieve boththe prevention, the opportune diagnosis and the appropriate treatment.

Characterization of the health-care-associated urinary tract infections at the Hospital das Clínicas de Ribeirão Preto, São Paulo, Brazil / Caracterização das infecções do trato urinário relacionadas à assistência médica no Hospital de Ribeirão Preto - SP

Urinary tract infections (UTIs) are the most common health-care-associated infections (HCAIs) and one of the top-ranking microbial infections. In the community, about 80% of UTIs are caused by uropathogenic Escherichia coli (UPEC), but there is a high variability of etiological agents involved in hospital-acquired UTIs. With this context in mind, the current study aimed to evaluate the prevalence of the main etiological agents responsible for UTIs and their susceptibility profile at the Hospital das Clínicas de Ribeirão Preto, a high complexity reference hospital in the Southeast region of Brazil. This retrospective and descriptive study analyzed all positive inpatient cultures [100,000 colony-forming unit (CFU)/mL] from November 2016 to April 2017. The most prevalent microorganism was Kleb-siella pneumoniae (23 isolates), equivalent to 37.7% of positive urocultures. The second most prevalent agent was UPEC, with 19 isolates (31.1%). The risk factors evaluated in these inpatients showed that 17.5% underwent a uro-logical procedure on admission, 31.6% were using a urinary catheter; 26.2% were using immunosuppressive drugs during the period in which the clinical diagnosis was made. Our results demonstrate the prevalence of UTI causes in the hospital context and the main risk factors for them and will be pretty helpful in guiding empirical treatment in severe UTIs inside the hospital as well as reflect on the actual need and time duration of invasive procedures in the hospital environmen (AU)

As infecções do trato urinário (IU) são a terceira causa principal de infecções associadas ao ambiente hospitalar, logo após as infecções pulmonares e da corrente sanguínea. Na comunidade, cerca de 80% das IU são causadas por E. coli, mas há uma alta variabilidade de agentes etiológicos envolvidos nas IU hospitalares. Este estudo visa avaliar a prevalência dos principais agentes etiológicos e perfil de suscetibilidade envolvidos em IU em um am-biente hospitalar de referência de alta complexidade no sul do Brasil. Este é um estudo retrospectivo e descritivo que analisou todas as culturas positivas (100.000 ufc/ml) de pacientes nas enfermarias de um hospital terciário no período entre novembro de 2016 a abril de 2017. O microorganismo mais prevalente foi Klebsiella pneumoniae (23 isolados), o que equivale a 37,7% das uroculturas. O segundo agente mais prevalente foi Escherichia coli, com 19 isolados (31,1%). Os fatores de risco avaliados nestes pacientes mostraram que 17,5% foram submetidos a um procedimento urológico na admissão, 31,6% estavam usando um cateter urinário; 26,2% estavam usando drogas imunossupressoras no período em que o diagnóstico clínico foi feito. Nossos resultados demonstram uma mudança importante na prevalência das causas de IU no contexto hospitalar e os principais fatores de risco para elas e serão bastante úteis para orientar o tratamento empírico em IU grave dentro do hospital, bem como refletir sobre a real necessidade e a duração dos procedimentos invasivos no ambiente hospitalar (AU)

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.

Caracterização molecular e fenotípica de Klebsiella spp. produtoras de NDM / Molecular and phenotypic characterization of Klebsiella spp. NDM producers

O perfil de resistência, que algumas das espécies do complexo Klebsiella pneumoniae podem expressar, representa uma grande ameaça à saúde humana, particularmente quando resistentes aos carbapenêmicos, que são amplamente utilizados no tratamento de infecções graves em pacientes hospitalizados. O principal mecanismo de resistência aos carbapenêmicos é a produção de carbapenemases, particularmente dos tipos KPC e NDM. Um dos compostos desenvolvidos para o tratamento de infecções causadas por cepas produtoras de KPC é a combinação ceftazidimaavibactam (CAZ-AVI), mas que não tem atividade inibitória sobre metalo-betalactamases, a exemplo das NDMs. Os objetivos deste trabalho foram determinar a frequência das espécies do complexo K. pneumoniae e da coprodução de KPC, avaliar a clonalidade dos isolados, a sensibilidade ao aztreonam-avibactam (ATM-AVI), o desempenho do disco de meropenem (MEM) com inibidores para detecção de coprodução de NDM e KPC e desenvolver um teste de triagem para prever a sensibilidade ao ATM-AVI. Um total de 113 isolados do complexo K. pneumoniae produtoras de NDM ou coprodutoras de NDM e KPC, provenientes da coleção de bactérias do Grupo Fleury, coletadas períodos pré e pós início do uso de CAZ-AVI no Brasil, foram utilizadas neste estudo. A identificação da espécie e a presença dos genes blaNDM e blaKPC foi confirmada por PCR multiplex. A clonalidade dos isolados foi avaliada por eletroforese em campos pulsados (PFGE) após clivagem com XbaI. A produção de carbapenemases foi confirmada utilizando-se o teste Blue Carba. O desempenho dos discos de meropenem e CAZ-AVI contendo um ou mais inibidores de carbapenemases foi comparado com o teste molecular. A pré-difusão combinada foi realizada pré-incubando-se o ágar não inoculado com disco de CAZ-AVI, e a seguir aplicando-se o inóculo bacteriano e um disco de ATM após remover o disco de CAZ-AVI. Após incubação, os halos foram aferidos e correlacionados com a concentração inibitória mínima para ATM-AVI. As CIMs para ATM e ATM-AVI foram determinadas segundo o EUCAST. A identificação das espécies por PCR evidenciou as seguintes frequências: K. pneumoniae 75,2% (n=85); K. quasipneumoniae 16,8% (n=19), e K. variicola 8% (n=9). Uma fração de 12,4% (n=14) dos isolados apresentaram os genes blaNDM e blaKPC e 87,6% (n=99) apenas blaNDM. A análise dos perfis de PFGE de K. pneumoniae evidenciou a presença de cinco grupos clonais predominantes. Isolados do principal grupo clonal Ap (n=15) foram detectados nas cidades de São Paulo e Porto Alegre durante todo o período analisado. O grupo clonal Lp foi detectado nas cidades de São Paulo e Recife em 2019. Os dois principais grupos clonais no período pré-CAZ-AVI continham maior número de isolados do que aqueles no período de uso do CAZ-AVI. Os perfis de PFGE de K. quasipneumoniae evidenciaram quatro grupos clonais predominantes, e presentes apenas no estado de São Paulo, com persistência do grupo clonal Aq desde 2017. Quanto à K. variicola, foram observados dois grupos clonais predominantes Av e Bv, o primeiro presente apenas em São Paulo desde 2018 e o segundo em Porto Alegre apenas em 2019. Calculando-se a diferença entre os diâmetros de halo do disco MEM contendo EDTA e ácido fenilborônico (AFB) e o maior dos halos obtidos para MEM com EDTA ou AFB, observou-se que todos os isolados com coexpressão de KPC e NDM apresentaram diferença ≥ 5 mm. Uma fração de 42,3% dos isolados positivos apenas para blaNDM apresentaram sensibilidade para ATM (CIM ≤ 4 mg/L). Todos os isolados testados apresentaram CIM para ATM-AVI ≤ 1/4 mg/L, sendo a CIM90 0,125/4 mg/l. No teste de pré-difusão combinada, o menor diâmetro de halo obtido foi de 23 mm. A espécie predominante na amostragem foi K. pneumoniae. A disseminação clonal, observada neste estudo, contrasta com a diversidade clonal descrita em outros locais do mundo para produtores de NDM, exceto Grécia e China. Considerando os pontos de corte atuais para ATM, é provável que haja resposta clínica adequada no uso de ATM-AVI no tratamento de infecções causadas por isolados produtores de NDM e coprodutores de KPC e NDM. Utilizando-se o valor de corte de ≤ 5 mm para a diferença entre halos de inibição, de MEM com AFB e EDTA e o segundo maior halo com inibidor, a sensibilidade foi de 100% e a especificidade foi de 96,1,0%. O método de pré-difusão com CAZ-AVI e ATM é um método simples e o diâmetro ≥ 23 mm tem excelente correlação com a CIM para ATM-AVI ≤ 1/4 mg/L

The resistance profile, which some species of the Klebsiella pneumoniae complex may express, represent a great threat to human health, particularly when resistant to carbapenems, which are widely used in the treatment of severe infections in hospitalized patients. The main mechanism of resistance to carbapenems is the production of carbapenemases, particularly KPCs and NDMs. One of the compounds developed for the treatment of infections caused by KPC-producing strains is the combination ceftazidime-avibactam (CAZ-AVI), but which has no inhibitory activity on metallobetalactamases, as is the case for NDMs. The objectives of this work were to determine the frequency of K. pneumoniae complex species and KPC co-production, evaluate the clonality of isolates, the susceptibility to aztreonam-avibactam (ATM-AVI), the performance of meropenem (MEM) disks with inhibitors for detecting NDM co-production and KPC and develop a screening test to predict sensitivity to ATM-AVI. A total of 113 NDM-producing or NDM and KPC co-producing K. pneumoniae complexes, from the Fleury Group's bacteria collection, collected in the pre- and post-starting periods of CAZ-AVI use in Brazil, were used in this study. Species identification and the presence of the blaNDM and blaKPC genes were confirmed by multiplex PCR. The clonality of the isolates was evaluated by pulsed field electrophoresis (PFGE) after cleavage with XbaI. Carbapenemase production was confirmed using the Blue Carba test. The performance of MEM and CAZ-AVI disks containing one or more carbapenemase inhibitors was compared with the molecular test. Combined pre-diffusion was performed by preincubating the uninoculated agar with a CAZ-AVI disk, and then applying the bacterial inoculum and na ATM disk after removal of the CAZ-AVI disk. After incubation, halos were measured and correlated with the minimum inhibitory concentration (MIC) for ATM-AVI. ATM and ATM-AVI MICs were determined according to EUCAST. The identification of species by PCR evidenced the following frequencies: K. pneumoniae 75.2% (n=85); K. quasipneumoniae 16.8% (n=19), and K. variicola 8% (n=9). A fraction of 12.4% (n=14) of the isolates had the blaNDM and blaKPC genes and 87.6% (n=99) had only blaNDM. The analysis of the PFGE profiles of K. pneumoniae evidenced the presence of five predominant clonal groups. Isolates from the main clonal group Ap (n=16) were detected in the cities of São Paulo and Porto Alegre throughout the analyzed period. The clonal group Lp was detected in the cities of São Paulo and Recife 2019. The PFGE profiles of K. quasipneumoniae showed four predominant clonal groups, present only in the state of São Paulo, with persistence of the clonal group Aq since 2017. As for K. variicola, two predominant clonal groups Av and Bv were observed, the first present only in São Paulo since 2018 and the second in Porto Alegre only in 2019. Calculating the difference between the inhibition zone diameters of the MEM disk containing EDTA and phenylboronic acid (AFB) and the largest of the inhibition zone diameters obtained for MEM with EDTA or AFB, it was observed that all isolates with co-expression of KPC and NDM showed a difference 5 ≥mm. A fraction of 42.3% of isolates positive only for blaNDM showed sensitivity to ATM (MIC ≤ 4 mg/L). All tested isolates presented MIC for ATM-AVI ≤ 1/4 mg/L, being the MIC90 0.125/4 mg/l. In the combined pre-diffusion test, the smallest inhibition zone diameter obtained was 23 mm. The predominant species in the sample was K. pneumoniae, but a significant fraction of the other species in the complex was also observed in the sample. The clonal spread observed in this study contrasts with the clonal diversity described elsewhere in the world for NDM-producing isolates, except Greece and China. Considering the current cut-off points for ATM, it is likely that there is an adequate clinical response in the use of ATM-AVI in infections caused by NDM-producing and KPC-NDM co-producing isolates in Brazil. Using the cutoff value of 5 mm for the difference between inhibition zones, of MEM with AFB and EDTA and the second largest zone of MEM with inhibitor, the sensitivity was 100% and the specificity was 96.1%. The pre-diffusion method with CAZ-AVI and ATM is a simple method and the diameter ≥ 23 mm has excellent correlation with the MIC for ATM-AVI ≤ 1/4 mg/L