Effect of N-acetyl cysteine, rifampicin, and ozone on biofilm formation in pan-resistant Klebsiella pneumoniae: an experimental study

ABSTRACT BACKGROUND: To the best of our knowledge, this is the first study to evaluate the effectiveness of specific concentrations of antibiofilm agents, such as N-acetyl cysteine (NAC), rifampicin, and ozone, for the treatment of pan-resistant Klebsiella pneumoniae (PRKp). OBJECTIVES: We evaluated the effectiveness of antibiofilm agents, such as NAC, rifampicin, and ozone, on biofilm formation in PRKp at 2, 6, 24, and 72 h. DESIGN AND SETTING: This single-center experimental study was conducted on June 15, 2017, and July 15, 2018, at Istanbul Faculty of Medicine, Istanbul University, Turkey. METHODS: Biofilm formation and the efficacy of these agents on the biofilm layer were demonstrated using colony counting and laser-screened confocal microscopy. RESULTS: NAC at a final concentration of 2 μg/mL was administered to bacteria that formed biofilms (24 h), and no significant decrease was detected in the bacterial counts of all isolates (all P > 0.05). Rifampicin with a final concentration of 0.1 μg/mL was administered to bacteria that formed biofilm (24 h), and no significant decrease was detected in bacterial count (all P > 0.05). Notably, ozonated water of even 4.78 mg/L concentration for 72 h decreased the bacterial count by ≥ 2 log10. CONCLUSION: Different approaches are needed for treating PRKp isolates. We demonstrate that PRKp isolates can be successfully treated with higher concentrations of ozone.

Estenosis laringotraqueal recurrente asociada a Klebsiella pneumoniae subsp. rhinoscleromatis / Recurrent laryngotracheal stenosis associated with Klebsiella pneumoniae subsp. rhinoscleromatis

Introducción: Klebsiella rhinoscleromatis (KR) es una enterobacteria asociada con formación de granulomatosis crónica. Cuando este microorganismo afecta el tracto respiratorio se denomina escleroma, afectando principalmente la cavidad nasal; puede comprometer nasofaringe, laringe, tráquea y bronquios. Caso clínico: paciente femenina con antecedente de laringotraqueítis crónica con diagnóstico de estenosis traqueal y aislamiento en cultivos de Klebsiella pneumoniae ssp rhinoscleromatis multisensible, sin compromiso nasosinusal o extralaríngeo. Discusión: el escleroma puede afectar todo el tracto respiratorio y se deben tener presentes factores de riesgo asociados, como condiciones de hacinamiento, inmunosupresión y sexo femenino. El pilar del tratamiento es médico, basado en antibióticos; adicionalmente, se reserva manejo quirúrgico en la etapa esclerótica, donde hay ausencia del fenómeno inflamatorio. Conclusión: el escleroma es una patología rara con una evolución crónica y compromiso principalmente en cavidad nasal, que requiere alta sospecha diagnóstica para realizar manejo oportuno.

Introduction: Klebsiella rhinoscleromatis (KR) is an enterobacterium associated with the formation of chronic granulomatosis. When this microorganism affects the respiratory tract, it is called scleroma, the nasal cavity is the main one affected; additionally, it can involve nasopharynx, larynx, trachea, and bronchi. Clinical case: female patient with a history of chronic laryngotracheitis, with diagnosis of tra-cheal stenosis and isolation in cultures of multisensitive Klebsiella pneumoniae ssp rhinoscleromatis, without nasosinusal or extralaryngeal involvement. Discussion: scleroma can affect the entire respiratory tract, so associated risk factors should be taken into account, mainly overcrowding, immunosuppression, and female sex, in whom it is more common. The mainstay of treatment is medical, based on antibio-tics; additionally, surgical management is reserved for sclerotic stage, when there is no inflammatory phenomenon. Conclusion: scleroma is a rare pathology, with a chronic evolution, with involvement mainly in the nasal cavity, which requires a high diagnostic suspicion for its timely management.

Sepsis probada a Klebsiella oxytoca en un recién nacido

La sepsis neonatal constituye una de las principales causas de muertes neonatales en los países en desarrollo, con datos que estiman más de un millón de muertes en todo el mundo cada año. Se persigue presentar un caso, dada la infrecuencia de la sepsis neonatal tardía por Klebsiella oxytoca. Se trata de una paciente femenina, pretérmino y de bajo peso al nacer, que a los 17 días de vida comenzó con deterioro de su estado clínico dado por hipoactividad, palidez cutánea, succión morosa e incremento de la circunferencia abdominal, acompañados de disfunción hematológica severa dada por anemia, trombocitopenia y neutropenia, que requirió varias transfusiones con hemoderivados y terapéutica antimicrobiana combinada (primero con meronem y amikacina, luego con ciprofloxacina y vancomicina). Se trató también con antifúngicos, diuréticos, drogas vasoactivas, ventilación mecánica y eritropoyetina. Se interconsultó con Cardiología e Infectología pediátricas. Tuvo finalmente una evolución satisfactoria, con lactancia materna efectiva. El incremento de la sepsis en neonatos hospitalizados y la resistencia bacteriana son problemas de salud pública. Es importante reconocer los factores de riesgo para la sepsis en este grupo de pacientes, para su tratamiento oportuno.

Neonatal sepsis is one of the main causes of neonatal deaths in developing countries, with data estimating more than one million deaths around the world every year. The aim is to present case a case, given the infrequency of late neonatal sepsis by Klebsiella oxytoca. This is the case of a pre-term female patient, with low weight at birth, who at 17 days of birth began with deterioration of her clinical status due to hypo-activity, skin paleness, morose suction and increase in abdominal circumference, accompanied by severe hematological dysfunction given by anemia, thrombocytopenia and neutropenia, which required several transfusions with blood products and combined antimicrobial therapeutic (first with meronem and amikacin, then with ciprofloxacin and vancomycin). She was also treated antifungals, diuretics, vasoactive drugs, mechanical ventilation and erythropoietin. She was consulted with Pediatric Cardiology and Infectious diseases. Finally she had a satisfactory evolution, with effective maternal breastfeeding. Sepsis increase in hospitalized neonates and bacterial resistance are public health problems. It is important to recognize the risk factors for sepsis in this group of patients, for their timely treatment.

Construction of a risk prediction model for bloodstream infection induced by carbapenem-resistant Klebsiella pneumoniae / 中国药房

OBJECTIVE To construct a risk prediction model for bloodstream infection （BSI） induced by carbapenem-resistant Klebsiella pneumoniae （CRKP）. METHODS Retrospective analysis was conducted for clinical data from 253 patients with BSI induced by K. pneumoniae in the First Hospital of Qinhuangdao from January 2019 to June 2022. Patients admitted from January 2019 to December 2021 were selected as the model group （n＝223）， and patients admitted from January 2022 to June 2022 were selected as the validation group （n＝30）. The model group was divided into the CRKP subgroup （n＝56） and the carbapenem- sensitive K. pneumoniae （CSKP） subgroup （n＝167） based on whether CRKP was detected or not. The univariate and multivariate Logistic analyses were performed on basic information such as gender， age and comorbid underlying diseases in two subgroups of patients； independent risk factors were screened for CRKP-induced BSI， and a risk prediction model was constructed. The established model was verified with patients in the validation group as the target. RESULTS Admissioning to intensive care unit （ICU）， use of immunosuppressants， empirical use of carbapenems and empirical use of antibiotics against Gram-positive coccus were independent risk factors of CRKP-induced BSI （ORs were 3.749， 3.074， 2.909， 9.419， 95%CIs were 1.639-8.572， 1.292- 7.312， 1.180-7.717， 2.877-30.840， P＜0.05）. Based on this， a risk prediction model was established with a P value of 0.365. The AUC of the receiver operating characteristic （ROC） curve of the model was 0.848 [95%CI （0.779， 0.916）， P＜0.001]， and the critical score was 6.5. In the validation group， the overall accuracy of the prediction under the model was 86.67%， and the AUC of ROC curve was 0.926 [95%CI （0.809， 1.000]， P＜0.001]. CONCLUSIONS Admission to ICU， use of immunosuppressants， empirical use of carbapenems and empirical use of antibiotics against Gram-positive coccus are independent risk factors of CRKP- induced BSI. The CRKP-induced BSI risk prediction model based on the above factors has good prediction accuracy.

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.

Uso de ceftazidima-avibactam en una recién nacida prematura con infección urinaria bacteriémica por Klebsiella pneumoniae productora de carbapenemasa

Los recién nacidos tienen un alto riesgo de morbimortalidad asociada a infecciones durante su estancia en unidades de cuidado intensivo neonatal, a lo que se asocia un aumento progresivo de infecciones por microorganismos multi-resistentes que requiere el uso de nuevos antimicrobianos. Presentamos el caso de una recién nacida de pretérmino de 36 semanas que cursó con una infección del tracto urinario bacteriémica por Klebsiella pneumoniae productora de carbapenemasa tratada de forma efectiva con 14 días de cefazi- dima-avibactam, sin efectos adversos observados. Según nuestro conocimiento, este es el primer caso reportado en nuestro país del uso de este antimicrobiano en población neonatal. Se necesita más información sobre la eficacia y seguridad de ceftazidima-avibactam en este grupo de pacientes.

Neonates are high risk patients regarding morbimortality secondary to infections during their neonatal intensive care unit stay, which is associated to a progressive increase in the report of multidrug resistant organism infections, that require the use of new antimicrobial. We report the case of a 36-week preterm with an urinary tract infection with bacteriemia caused by carbapenemase- producing Klebsiella pneumoniae treated effectively with 14 day of ceftazidime-avibactam, without observed adverse effects. To our knowledge, this is the first case report in our country of the use of this antibiotic in neonatal population. More information is needed regarding efficacy and safety of ceftazidime-avibactam in this group of patients.

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)

Caracterización de la utilización de colistín en un hospital de alta complejidad

Resumen: El aumento de la resistencia y la escasez de nuevos antibacterianos ha requerido la reintroducción de antiguos antimicrobianos entre ellos colistín. Objetivo: Caracterizar la utilización de colistín durante el año 2017 en un hospital universitario, mediante la descripción de los pacientes, los tratamientos, la microbiología asociada y efectos adversos. Pacientes y Métodos: Trabajo observacional retrospectivo. Se revisaron los datos de todos los pacientes que recibieron colistín intravenoso (IV) por al menos 48 horas, durante el año 2017. Resultados: Se incluyeron 53 pacientes, equivalentes a 91 tratamientos. El foco respiratorio fue el principal (46,2%). El 68,1% de los tratamientos fue iniciado en la UCI. La mayoría de los pacientes tenía una hospitalización reciente (83,5%), y presentaban uso previo de antibacterianos (89%). Los dos patógenos mayoritariamente identificados fueron Pseudomonas aeruginosa y Klebsiella spp. El consumo promedio de colistín fue de 2,4 DDD/100 camas/día. El servicio que más consumió colistín fue la UCI, con 45,5 DDD/100 camas/día, usando generalmente la dosis de 3 MUI cada 8 horas IV y con una baja utilización de dosis de carga. Conclusión: Colistín corresponde a un antimicrobiano de uso restringido a infecciones sospechadas o confirmadas por agentes bacterianos multi resistentes. En esta serie, su uso inicial fue principalmente empírico, en pacientes con factores de riesgo para resistencia antibacteriana; se usó en forma asociada a otros antimicrobianos, siendo el foco principal el respiratorio.

Background: The increase in resistance and the shortage of new antibiotics has led to the reintroduction of old antimicrobials such as colistin. Aim: To evaluate the use of colistin during 2017 in a university hospital, through the characterization of patients and treatment, associated microbiology, response to treatment and adverse effects. Methods: Retrospective observational design. The data of all patients who received colistin for at least 48 hours during the year 2017 were reviewed. Results: 55 patients were included, equivalent to 144 treatments. The respiratory focus was the main one (57.9%). 64% of the treatments began in the ICU, while 7% in the ward. Most of the patients has a recent hospitalization (86.8%) and has previous use of antibiotics (90.4%). The two main pathogens identified were Pseudomonas aeruginosa and Klebsiella spp. In 87.1% of the cases with microbiological justifications for the use of colistin, a favorable response was obtained. The average consumption of colistin was 2.4 DDD/100 beds/day. The department that consumed the most colistin was the ICU, with 45,5 DDD/100 beds/day, generally using a dose of 3 MIU every 8 hours IV and with low use of loading doses. Conclusion: Colistin corresponds to an antibiotic whose use is restricted to infections suspected or confirmed by multi-resistant bacterial agents. Its initial use in this serie was mainly empirical, in patients with risk factors for antibiotics resistance, it was used in association with other antimicrobials, being the respiratory the main infectious focus.

Six-Year Surveillance of Acquired Bloodstream Infection in a Pediatric Intensive Care Unit in Israel

Objectives: We studied the profile of bloodstream infections (BSI) in the pediatric intensive care unit (PICU) and identified predictors of mortality. Methods: The study collected data from hospital records for children younger than 18-years who developed BSI during their PICU stay between 2014 and 2019. Results: In 114 patients, 136 PICU-acquired BSIs with 152 pathogens were documented. The incidence of BSI was 47.12/1000 PICU admissions and 7.95/1000 PICU hospital days. Gram-negative rods accounted for 75% of isolates, Gram-positive cocci accounted for 21.7% of isolates, and fungi accounted for 3.3% of isolated pathogens. ICU mortality was observed in 25 (21.9%) patients with a BSI compared to 94 (3.1%) patients without a BSI (P<0.001). Hemodynamic instability (P=0.014, OR 4.10, 95%CI 1.33-12.66), higher blood urea nitrogen (BUN) (P=0.044), and lower albumin levels (P=0.029) were associated with increased risk of ICU mortality. Conclusion: BSI in the PICU is associated with increased mortality. Early identification and management of risk factors independently associated with poor clinical outcomes in these patients should be aimed to ensure improved survival.

Evaluation of the combination treatments with intravenous fosfomycin for carbapenem-resistant Klebsiella pneumoniae

SUMMARY OBJECTIVE: The aim of this study was to evaluate the combination treatments with intravenous fosfomycin for carbapenem-resistant Klebsiella pneumoniae infections in a tertiary-care center. METHODS: Between December 24, 2018 and November 21, 2022, adult patients diagnosed with bloodstream infection or ventilator-associated pneumonia due to culture-confirmed carbapenem-resistant Klebsiella pneumoniae in the anesthesiology and reanimation intensive care units were investigated retrospectively. RESULTS: There were a total of 62 patients fulfilling the study inclusion criteria. No significant difference was recorded in 14- and 30-day mortality among different types of combination regimens such as fosfomycin plus one or two antibiotic combinations. Hypokalemia (OR:5.651, 95%CI 1.019-31.330, p=0.048) was found to be a significant risk factor for 14-day mortality, whereas SOFA score at the time of diagnosis (OR:1.497, 95%CI 1.103-2.032, p=0.010) and CVVHF treatment (OR:6.409, 95%CI 1.395-29.433, p=0.017) were associated with 30-day mortality in multivariate analysis. CONCLUSION: In our study, high mortality rates were found in patients with bloodstream infection or ventilator-associated pneumonia due to carbapenem-resistant Klebsiella pneumoniae, and no significant difference was recorded in 14- and 30-day mortality among different types of combination regimens such as fosfomycin plus one or two antibiotic combinations.

A case report of brain abscess caused by carbapenem-resistant Klebsiella pneumoniae

ABSTRACT The treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains is difficult due to the limited antimicrobial options and high mortality. There are many reports on intracranial infections caused by CR-Kp, but only a few on brain abscesses caused by CR-Kp. Here, we present a case of brain abscess caused by CR-Kp successfully treated with combined antibiotics. A 26-year-old male patient was admitted to our hospital due to high fever and headache. His past medical history includes a surgical intervention due to an acute subdural hematoma, performed at an external healthcare center. After the current diagnosis of cerebral abscess, he underwent two surgeries. During the procedure, multiple cerebral abscesses were drained and capsulotomies were performed under ultrasound guidance. The combination of meropenem and vancomycin was started. The contents of the abscesses were sent to the microbiology and pathology laboratory. On the 3 rd day of treatment, the medical team was informed that CR-Kp grew in an abscess culture. The patient's treatment was changed to meropenem + colistin + tigecycline. The patient developed electrolyte disturbances during the follow-up and this was considered an adverse effect of colistin. On the 41 st day of treatment, colistin was discontinued, fosfomycin was added, and meropenem and tigecycline were maintained. Treatment was discontinued on the 68 th day, when the patient was discharged. The general condition of the patient, who has been followed up for two years, is satisfactory. The treatment of CR-Kp infections should be individualized, and the pharmacokinetics and pharmacodynamics of antibiotics should be considered in each case.

Colistin resistance in Escherichia coli and Klebsiella pneumoniae in humans and backyard animals in Ecuador / Resistencia a la colistina de las bacterias Escherichia coli y Klebsiella pneumoniae en humanos y animales de granja en Ecuador / Resistência à colistina em Escherichia coli e Klebsiella pneumoniae em humanos e animais de quintal no Equador

ABSTRACT Objective. Colistin is an antibiotic of last resort for treating serious Gram-negative bacterial infections. However, the misuse of colistin, especially as an animal growth promoter, has contributed to increasing antimicrobial resistance, mediated mainly through plasmid transfer of the mcr-1 gene. This study assessed the prevalence of phenotypic and molecular colistin resistance in Escherichia coli and Klebsiella pneumoniae in Ecuador in healthy humans and their chickens and pigs. Methods. Fecal samples were collected from humans and their chickens and pigs in two rural coastal and Amazon regions between April and August 2020. Gram-negative bacteria were isolated and identified using conventional techniques. Phenotypic resistance was determined using the broth microdilution technique, and the mcr-1 gene was detected using conventional polymerase chain reaction. Results. A total of 438 fecal samples were obtained from 137 humans, 147 pigs and 154 chickens. The prevalence of E. coli isolates was 86.3% (378/438) and K. pneumoniae, 37.4% (164/438). Overall, the mcr-1 gene was found in 90% (340/378) of E. coli isolates, with higher prevalences found in isolates from coastal regions (96.5%, 191/198), humans (95.6%, 111/116) and chickens (91.8%, 123/134); for K. pneumoniae, the gene was found in 19.5% (32/164) of isolates, with equal distribution between regions and hosts. Only four isolates, two E. coli and two K. pneumoniae, showed phenotypic resistance: mcr-1 was present in both E. coli strains but absent in the K. pneumoniae strains. Conclusions. Despite a low prevalence of phenotypic resistance to colistin, the high prevalence of the mcr-1 gene in E. coli is of concern. Ecuador's ban on using colistin in animal husbandry must be enforced, and continual monitoring of the situation should be implemented.

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RESUMO Objetivo. A colistina é um antibiótico de último recurso para o tratamento de infecções graves por bactérias Gram-negativas. Entretanto, o uso indevido da colistina, principalmente como promotor de crescimento animal, tem contribuído para o aumento da resistência a antimicrobianos, principalmente por transferência horizontal do gene mcr-1 mediada por plasmídeos. Este estudo avaliou a prevalência de resistência fenotípica e molecular à colistina em Escherichia coli e Klebsiella pneumoniae no Equador em humanos hígidos e em galinhas e porcos por eles criados. Métodos. Entre abril e agosto de 2020, foram coletadas amostras de fezes de habitantes de duas regiões litorâneas e amazônicas do Equador e de galinhas e porcos por eles criados. Bactérias Gram-negativas foram isoladas e identificadas por meio de técnicas convencionais. A resistência fenotípica foi determinada pela técnica de microdiluição em caldo, e o gene mcr-1 foi detectado por reação em cadeia da polimerase convencional. Resultados. Foram obtidas 438 amostras fecais de 137 humanos, 147 suínos e 154 galinhas. A prevalência de isolados de E. coli foi de 86,3% (378/438), e de K. pneumoniae, 37,4% (164/438). Em geral, o gene mcr-1 foi encontrado em 90% (340/378) dos isolados de E. coli, com maiores prevalências encontradas em isolados de regiões litorâneas (96,5%, 191/198), humanos (95,6%, 111/116) e galinhas (91,8%, 123/134); para K. pneumoniae, o gene foi encontrado em 19,5% (32/164) dos isolados, com igual distribuição entre regiões e hospedeiros. Somente quatro isolados, dois de E. coli e dois de K. pneumoniae, demonstraram resistência fenotípica: o gene mcr-1 estava presente em ambas as cepas de E. coli, mas ausente nas de K. pneumoniae. Conclusões. Apesar da baixa prevalência de resistência fenotípica à colistina, a alta prevalência do gene mcr-1 em E. coli é preocupante. É preciso fiscalizar a proibição ao uso agropecuário de colistina no Equador e implementar o monitoramento contínuo da situação.

Virulence associated characteristics and drug resistance of Klebsiella pneumoniae isolated from patients living in Zhongjiang county of Sichuan province / 中国基层医药

Objective:To investigate the distribution characteristics of virulence-related phenotypes/genotype, capsular serotype, drug resistance phenotypes, and sequence typing (ST) of Klebsiella pneumoniae in patients living in Zhongjiang county, improve clinical understanding, and provide evidence for the prevention and control of bacterial drug resistance and clinical rational drug use. Methods:The data of 135 strains of Klebsiella pneumoniae isolated from patients who received treatment in Zhongjiang County People's Hospital from July to December 2019 were retrospectively analyzed. Bacterial identification and drug sensitivity testing were performed using the WalkAway-40Plus automated microbiology system. Strains with a high viscosity phenotype were identified using wire drawing experiments. Hypervirulence-associated capsular serotype and virulence genes were verified by polymerase chain reaction. ST of Klebsiella pneumoniae strain was identified using multilocus sequence typing. Results:Strains with a high viscosity phenotype were identified in 50.4% of the 135 strains. 54.1%, 54.8%, and 54.1% of the strains were positive for virulence genes iucA, iroN, rmpA. The proportion of strains with capsular Serotype K1 or K2 was 11.9% and 15.6%, respectively. A total of 65 kinds of ST were identified, with ST23 and ST37 being the most common, accounting for 11.1% and 6.7%, respectively. The resistance rate of the strains to 16 kinds of antibiotics was 0.0%-25.2%, and the resistance rate to Carbapenem antibiotics, Amikacin, and Tigecycline was less than 1%. The positive rate of virulence gene of strains with a high viscosity phenotype was significantly higher than that of strains without a high viscosity phenotype ( P < 0.001), and its resistance rate to Cephalosporin was significantly lower in strains with a high viscosity phenotype than that in strains without a high viscosity phenotype ( P < 0.001). Conclusion:Klebsiella pneumoniae in Zhongjiang County is characterized by "high virulence and low drug resistance". It is necessary to continuously monitor the changes in the virulence and drug resistance of Klebsiella pneumoniae in Zhongjiang County, Sichuan Province, and be alert to the rapid dissemination of highly virulent strains.

LASSO regression based risk prediction model establishment for Klebsiella pneumonia infection in patients with severe acute pancreatitis / 中华胰腺病杂志

Objective:To construct a risk prediction model for infection with Klebsiella pneumonia (KP) for patients with severe acute pancreatitis (SAP).Methods:Retrospective analysis was done on the clinical data of 109 SAP patients who were admitted to Shanghai General Hospital, between March 2016 and December 2021. Patients were classified into infection group ( n=25) and non-infection group ( n=84) based on the presence or absence of KP infection, and the clinical characteristics of the two groups were compared. The least absolute shrinkage and selection operator (LASSO) algorithm was used to reduce the dimension of the variables with statistical significance in univariate analysis. A nomogram prediction model was created by incorporating the optimized features from the LASSO regression model into the multivariate logistic regression analysis. Receiver operating characteristic curve (ROC) was drawn and the area under curve (AUC) was calculated; and consistency index (C-index) were used to assess the prediction model's diagnostic ability. Results:A total of 25 strains of KP were isolated from 109 patients with SAP, of which 21(84.0%) had multi-drug resistance. 20 risk factors (SOFA score, APACHEⅡ score, Ranson score, MCTSI score, mechanical ventilation time, fasting time, duration of indwelling of the peritoneal drainage tube, duration of deep vein indwelling, number of invasive procedures, without or with surgical intervention, without or with endoscopic retrograde cholangiopancreatography (ERCP), types of high-level antibiotics used, digestion disorders, abnormalities in blood coagulation, metabolic acidosis, pancreatic necrosis, intra-abdominal hemorrhage, intra-abdominal hypertension, length of ICU stay and total length of hospital stay) were found to be associated with KP infection in SAP patients by univariate analysis. The four variables (APACHEⅡ score, duration of indwelling of the peritoneal drainage tube, types of high-level antibiotics used, and total length of hospital stay) were extracted after reduced by LASSO regression. These four variables were found to be risk factors for KP infection in SAP patients by multiple logistic regression analysis (all P value <0.05). Nomogram prediction model for KP infection in SAP was established based on the four variables above. The verification results of the model showed that the C-index of the model was 0.939, and the AUC was 0.939 (95% CI 0.888-0.991), indicating that the nomogram model had relatively accurate prediction ability. Conclusions:This prediction model establishes integrated the basic clinical data of patients, which could facilitate the risk prediction for KP infection in patients with SAP and thus help to formulate better therapeutic plans for patients.

Clinical features of bacterial liver abscess in the context of coronavirus disease 2019 in Changchun， China / 临床肝胆病杂志

ObjectiveTo investigate the clinical and epidemiological features of patients with bacterial liver abscess during the outbreak of coronavirus disease 2019 （COVID－19） in Changchun， China. MethodsA retrospective analysis was performed for 37 411 patients who were discharged from The First Hospital of Jilin University from March 1 to June 30 in 2022， and finally 135 patients with bacterial liver abscess were included for analysis. Related clinical data were collected to summarize their clinical features， and these patients were compared with the patients with bacterial liver abscess in 2019－2021 in terms of disease onset and pathogen. The Kruskal－Wallis H test was used for comparison of continuous data between multiple groups， and the chi－square test was used for comparison of categorical data between multiple groups. ResultsThe patients with bacterial liver abscess accounted for 0.36% of the patients admitted to our hospital during the same period of time， which showed varying degrees of increase compared with the previous years （χ2=32.081， P<0.001）. The 135 patients with bacterial liver abscess had a mean hospital stay of 11 （6－18） days， which was longer than that in the previous years （H=9.223， P=0.026）. The patients with bacterial liver abscess had higher levels of white blood cell count and C－reactive protein （CRP） than the previous years （H=14.150 and 8.736， P=0.003 and 0.033）. Among the 135 patients， 69 （51.11%） received blood culture， and the results showed sterile growth （59.42%）， Klebsiella pneumoniae （30.43%）， Escherichia coli （4.35%）， Bacteroides fragilis （1.45%）， Enterococcus faecium （1.45%）， Staphylococcus epidermidis （1.45%）， and Klebsiella oxytoca （1.45%）. Among the 135 patients， 90 （66.67%） received pus culture， and the results showed Klebsiella pneumoniae （72.22%）， sterile growth （14.44%）， Escherichia coli （4.44%）， Enterococcus faecium （2.22%）， Pseudomonas aeruginosa （2.22%）， Acinetobacter baumannii （1.11%）， Klebsiella aerogenes （1.11%）， Klebsiella oxytoca （1.11%）， and Enterococcus casseliflavus （1.11%）. Of all 135 patients， 127 （94.07%） were improved and cured after anti－infective therapy and ultrasound－guided abscess puncture and drainage， and 3 patients （2.22%） died during hospitalization. ConclusionDuring the outbreak of COVID－19 in Changchun， there are increases in the number of patients with liver abscess in our hospital， the length of hospital stay， and the levels of white blood cell count and CRP， with Klebsiella pneumoniae as the main pathogen， and most patients are improved after treatment.

Epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae infection in adult inpatients / 公共卫生与预防医学

Objective To analyze the epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) in adult inpatients, and to provide a theoretical basis for the diagnosis and treatment of CRKP. Methods A total of 753 hospitalized patients with Klebsiella pneumoniae (KPN) infection in our hospital from 2017 to 2021 were selected as the investigation subjects. According to the sensitivity to carbapenem drugs, the patients were divided into carbapenem sensitive Klebsiella pneumoniae (CSKP) group (n=638) and CRKP group (n=115). The age, gender, department distribution, underlying diseases, length of hospital stay, use of antibiotics and other clinical data of all subjects were analyzed by self-made survey scale of our hospital. Univariate analysis and logistic regression analysis were used to analyze the risk factors of CRKP nosocomial infection in adult inpatients. Results Among of 753 KPN patients, 115 cases (15.27%) were detected with CRKP, including 87 males and 28 females. The detection rate of CRKP in different age groups was significantly different (P60 years was significantly higher than that in the age group of 41-60 years, 21-40 years, and 16-20 years (P2 value =0.725, P>0.05). CRKP strains were mainly isolated from oral and maxillofacial surgery (19.13%), infection department (15.65%), geriatric department (15.65%), and ICU (14.78%). The detection rate of CRKP in different pathogenic bacteria samples was different, including sputum (19.40%), urine (15.43%) and blood (12.58%), with statistically significant difference (P<0.05) The respiratory tract sputum specimens were all expectoration. There were significant differences in age, gender, use of carbapenems ≥7 days, invasive procedures, use of antibiotics ≥2 kinds, use of antibiotics ≥14 days, and use of enzyme inhibitors ≥7 days between the CSKP group and the CRKP group (P<0.05). Antimicrobial application time ≥14 days (OR=5.412), invasive operation (OR=6.431), and carbapenem use ≥7 days (OR=5.417) were the risk factors for CRKP nosocomial infection in adult inpatients (P<0.05). Conclusion Nosocomial infection of CRKP occurs mostly in elderly ICU patients. Intervention measures should be given to adult inpatients who have used antibiotics for ≥14 days, invasive procedures, and carbapenem antibiotics for ≥7 days, which can reduce the risk of CRKP infection in inpatients.

Advances in researches of polymyxin resistance mechanism in Klebsiella pneumoniae / 中华检验医学杂志

In recent years, the carbapenem-resistant Klebsiella pneumoniae (CRKP) continues to significantly threaten public health. The limited therapeutic options are increasingly challenging for clinicians to reintroduce the polymyxin as last-resort drug, with the results that polymyxin resistance is not scarce in settings. The polymyxin resistance mechanism is diversified, mainly the modification of the lipopolysaccharide (LPS). In addition to phoPQ, pmrAB, crrAB and mgrB on chromosome, plasmid-carried mcr gene have been found to mediate the LPS modification. The mgrB gene variation plays an important role in polymyxin resistance. Above all, the aim of the current review is to discuss the mechanism of polymyxin resistance mechanism in Klebsiella pneumoniae provide insights for preventing this phenomenon.

Comparison of the diagnostic effect on different machine learning predictive model of imipenem sensitivity of Klebsiella pneumoniae based on MALDI-TOF MS / 中华检验医学杂志

Objective:Machine learning is not only an important branch of artificial intelligence, but also supporting technologies for bioinformatics analysis. In the presence work, four machine-learning-predictive model for the drug-sensitivity of Klebsiella pneumoniae to imipenem were established based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and the diagnostic effect of these methods was exmained. Methods:A retrospective study was performed and the data of MALDI-TOF-MS and imipenem sensitivity of a total number of 684 cases Klebsiella pneumoniae isolated from clinical specimens in the laboratory of microbiology department of Tianjin Haihe Hospital from 2019 January to 2020 December were collected. The mass spectrometry and imipenem sensitivity data of 70 cases identified as imipenem-sensitive and 70 resistant cases were simple randomly selected to establish the training set model; whereas 30 cases of sensitive and 30 cases of resistant cases were randomly selected to establish the test set model. Mass spectral peak data were subjected to Orthogonal Partial least squares Discriminant Analysis (OPLS-DA). The training set data model was established by machine learning least absolute shrinkage and selection operator (LASSO) algorithm, Logistic Regression (LR) algorithm, Support vector machines (SVM) algorithm, neural network (NN) algorithm. The area under the curve (AUC) and confusion matrix of training set and test set model were calculated and selected by Grid search and 10-fold Cross-validation respectively, the accuracy of the prediction model was verified by test set confusion matrix. Results:The R2Y and Q2 of OPLS-DA were 0.546 3 and 0.017 8. The AUC of the best training set and test set models were 1.000 0 and 0.858 1, 1.000 0 and 0.820 1, 0.940 8 and 0.756 1, 1.000 0 and 0.697 2 evaluated by LASSO, LR, SVM and NN model respectively. The accuracy of the model were 99% (69/70), 100% (70/70), 91% (64/70) and 100% (70/70) for prediction of drug resistance, 100% (70/70), 100% (70/70), 90% (63/70) and 100% (70/70) for drug sensitivity prediction, the correct rate were 99% (139/140), 100% (140/140), 91% (127/140) and 100% (140/140) in training set, the test set showed that the accuracy were 93% (28/30), 87% (26/30), 60% (18/30) and 60% (18/30) for prediction of drug resistance, 100% (30/30), 80% (24/30), 93% (28/30) and 67% (20/30) for drug sensitivity prediction, the correct rate were 97% (58/60), 83% (50/60), 77% (46/60) and 63% (38/60) by LASSO, LR, SVM and NN model respectively.Conclusion:The LASSO prediction model of Klebsiella pneumoniae sensitivity to imipenem established in this study has a high accuracy rate and has potential clinical decision support ability.

Mechanism of polymyxin resistance related to lipopolysaccharide modification in carbapenem-resistant Klebsiella pneumoniae / 中华微生物学和免疫学杂志

Objective:To investigate the mechanism of polymyxin resistance related to lipopolysaccharide modification in carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods:Plasmid-mediated drug resistance genes in seven CRKP strains were detected by conjugation assay and mcr gene detection. The expression of polymyxin resistance-related genes was measured using quantitative real-time PCR. The complete genomes of CRKP strains were sequenced. Silver staining and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were performed to analyze the changes in lipopolysaccharide (LPS). Results:The seven CRKP strains were negative for mcr genes and the results of conjugation assay were also negative. Moreover, no mobile genetic elements related to drug resistance were detected. Compared with wild-type strain, all seven CRKP strains that were resistant to polymyxin showed increased expression of pmrA, pmrB and pmrC genes at the transcriptional level; six showed increased expression of phoP/ phoQ genes; three showed decreased expression of crrA/ crrB genes; four showed decreased expression of mgrB gene. The missense mutation sites in drug-resistant strains were mainly in KPHS_09430, KPHS_35900, KPHS_39520 and KPHS_52420. IS Kpn14 insertion sequence was detected in CRKP-6 strain. MALDI-TOF-MS reveals the modification of natural lipid A with L-Ara4N in CRKP LPS. Conclusions:LPS modification induced by chromosome-mediated mutation in the two-component regulatory system was the main molecular mechanism of polymyxin resistance in CRKP isolates in this study. Effects of the mutation in the two-component system on polymyxin resistance varied in different strains.