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.

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)

Update on the prevention and treatment of neonatal Carbapenem-resistant Klebsiella pneumoniae / 中国小儿急救医学

In recent years, the use of broad-spectrum antibiotics in clinical practice has led to an increase in the detection of Carbapenem-resistant Klebsiella pneumoniae(CrKP)in neonatal intensive care units.CrKP infection in newborns usually lacks specific clinical manifestations and can lead to bacteremia, meningitis and abdominal infections, which can be life-threatening.Combination of carbapenem antibiotics or newer drugs such as ceftazidime/avibactam, tigecycline and polymyxin are currently effective treatment options for CrKP infection in neonates.In addition to rational drug use, strict antimicrobial stewardship, hospital infection prevention and control measures are needed to reduce the colonisation and spread of CrKP in the neonatal ward.

Prognostic value of Pitt bacteremia score in patients with extensively drug-resistant Klebsiella pneumoniae bloodstream infection / 中华急诊医学杂志

Objective:To investigate the predictive value of Pitt bacteremia score (PBS) on 28-day mortality of patients with extensively drug-resistant Klebsiella pneumoniae (XDR-KP) bloodstream infection.Methods:A retrospective cohort study was conducted to analyze the clinical characteristics of patients with XDR-KP bloodstream infection admitted to the Emergency Intensive Care Unit of Nanjing Drum Tower Hospital from January, 2018, to December, 2021. The patients were divided into the survival and non-survival groups according to the 28-day survival. Multivariate logistic regression analysis was performed to determine the risk factors of 28-day mortality of the patients. Receiver operating curve (ROC) curve was drawn to analyze the predictive value of PBS in 28-day mortality of patients with XDR-KP bloodstream infection. The correlations between PBS, and acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure (SOFA) assessment were performed using Pearson correlation coefficient. The optimal cut-off value of PBS score was used as the boundary point to group the differences between APACHE II and SOFA scores in different groups. Kaplan-Meier method was used to analyze the prognosis of patients with XDR-KP bloodstream infection.Results:A total of 118 patients (82 males and 36 females) with XDR-KP bloodstream infection, aged (65.98±15.16) years, were included in this study. The 28-day mortality was 61.02%. The PBS was significant higher in the non-survival group than in the survival group [(5.68±1.86) vs. (2.48±1.02), P=0.011]. Multivariate logistic regression analysis showed that PBS ( OR=4.940, 95% CI: 2.720-8.968, P=0.008), APACHE II score ( OR=1.630, 95% CI: 1.361-1.952, P=0.010) and SOFA score ( OR=1.879, 95% CI: 1.451-2.422, P=0.009) were independently risk factors of 28-day mortality of patients with XDR-KP bloodstream infection. The area under the ROC curve of the PBS predicting 28-day mortality was 0.970 (95% CI: 0.945-0.995, P<0.001), and the optimal cut-of value was 3.5. In addition, PBS was significantly associated with APACHE II score ( r=0.916, P<0.001) and SOFA score ( r=0.829, P<0.001). Moreover, Kaplan-Meier analysis showed that the 28-day survival rate of patients with PBS <3.5 was significantly higher than that of patients with PBS >3.5 ( P=0.001). Conclusions:PBS is a significant, independent predictor of 28-day mortality in patients with XDR-KP bloodstream infection.

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.

Clinical observation of polymyxin B in the treatment of CRKP-BSI in patients with hematological malignancies / 中国药房

OBJECTIVE To analyze the efficacy and safety of polymyxin B in the treatment of carbapenem-resistant Klebsiella pneumoniae （CRKP）-bloodstream infection （BSI） in patients with hematologic malignancies. METHODS The medical records of patients with hematologic malignancies with CRKP-BSI who received polymyxin B for at least 3 days in our hospital from September 2019 to June 2021 were retrospectively analyzed. All patients were initially treated with a triple therapy namely polymyxin B+tigecycline+carbapenems for anti-infection therapy. RESULTS A total of 10 patients were enrolled as the study subjects. Eleven strains of CRKP were cultured in blood， including 10 strains of CRKP produced Klebsiella pneumoniae carbapenemase（KPC） and 1 strain of CRKP produced both KPC and metal-beta-lactamase； 9 strains were sensitive to colistin， 7 strains were sensitive to tigecycline， 5 strains were sensitive to amikacin and 2 strains were sensitive to compound sulfamethoxazole. All patients were accompanied by neutropenia， with an average duration of （14.1±6.4） days. They were all characterized by fever， chills and fatigue. After treatment， 6 patients were cured and discharged， 4 patients died of ineffective treatment of septic shock. No serious adverse events related to polymyxin B occurred in all patients. CONCLUSIONS Polymyxin B can be used as a therapeutic drug for CRKP-BSI in patients with hematological malignancies. No serious adverse event related to polymyxin B occurs during the treatment.

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.

Endoftalmitis endógena por Klebsiella pneumoniae: reporte de 2 casos y revisión de literatura referente a K. pneumoniae hipermucoviscosa e hipermucovirulenta / Endogenous Klebsiella pneumoniae endophthalmitis: report of 2 cases and literature review regarding hypermucoviscous and hypermucovirulent K. pneumoniae

Objetivo: Reportar dos casos de endoftalmitis endógena por Klebsiella pneumoniae hipermucoviscosa y revisar las características clínicas de esta entidad que ha aumentado su prevalencia en países occidentales. Observaciones: Dos pacientes fueron diagnosticados con endoftalmitis endógena por K. pneumoniae con confirmación microbiológica de un origen abdominal, uno de ellos por un absceso hepático y el otro por un absceso renal. Ambos pacientes fueron sometidos a vitrectomía precoz, y a antibióticos intravítreos/intravenosos, no obstante uno requirió evisceración y el otro presentó una agudeza visual de percepción de luz. Conclusiones e importancia: K. pneumoniae es la primera causa de endoftalmitis endógena en Asia oriental, pero es poco frecuente en los países occidentales. Sin embargo su prevalencia en esta última población parece estar aumentando en asociación con las variantes hipermucoviscosas e hipervirulentas de este microorganismo. La detección temprana y el tratamiento temprano de esta enfermedad son fundamentales para preservar la anatomía del ojo.

Objective: To report two cases of hypermucoviscous Klebsiella pneumoniae endogenous endophthalmitis and to review the clinical characteristics of this aggressive disease whose prevalence appears to be increasing in western countries. Observations: Two patients were diagnosed with K. pneumoniae endogenous endophthalmitis with microbiological confirmation of an abdominal source, one from a hepatic abscess and the other with a renal abscess. Both patients underwent early vitrectomy, and intravitreal/intravenous antibiotics, nonetheless one required evisceration and the other presented a postoperative visual acuity of light perception. Conclusions and importance: K. pneumoniae is the first cause of endogenous endophthalmitis in eastern Asia, but it is rare in western countries. Nevertheless, its prevalence in the latter population appears to be increasing in association with the hypermucoviscous and hypervirulent variants of this microorganism. The early detection and early management of this disease are pivotal to preserve the anatomy of the eye.

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.

Influences of notoginsenoside R1 on the injury of alveolar epithelial cells infected by Klebsiella pneumoniae by regulating JAK2STAT3 signaling pathway / 中国热带医学

@#Abstract: Objective　To investigate the influences of notoginsenoside R1 (NGR1) on cell injury and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway of alveolar epithelial cells infected by Klebsiella pneumoniae (Kp). Methods　A549 cells were grouped into five groups: control group (C group), infection group (Infect group), infection + low NGR1 group (Infect + L-NGR1 group), infection + high NGR1 group (Infect + H-NGR1 group), and infection+high NGR1+JAK2/STAT3 pathway inhibitor group (Infect+H-NGR1+SD-1029 group). Cell proliferation was measured using CCK8; ELISA kits were applied to detect the contents of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) in the culture medium; flow cytometry was applied to detect apoptosis; RT-qPCR was applied to detect the expressions of JAK2/STAT3; Western blot was applied to detect JAK2/STAT3 pathway, autophagy protein microtubule-associated protein 1 light chain 3 (LC3), autophagy-relatedgene5 (Atg5), autophagy-related gene (Atg) 6 (Beclin-1), apoptosis protein B-cell lymphoma 2 (Bcl-2), Bcl-2-accociated protein (Bax), cysteinyl aspartate specific proteinase (cleaved-caspase-3) proteins expression. Results　Compared with the C group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the mRNA relative expressions and protein phosphorylation levels of JAK2, STAT3 in the Infect group were obviously decreased (P<0.05); the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-caspase-3 were obviously increased (P<0.05). Compared with Infect group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the mRNA relative expressions and protein phosphorylation levels of JAK2, STAT3 in the Infect+L-NGR1 group and Infect+H-NGR1 group were obviously increased (P<0.05); the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-Caspase-3 were obviously decreased (P<0.05). Compared with Infect+H-NGR1 group, the 72 h cell viability, the protein levels of Bcl-2, LC3-II/I, Atg5, Beclin-1, the protein phosphorylation levels of JAK2, STAT3 in the Infect+H-NGR1+SD-1029 group were obviously decreased (P<0.05), and the contents of IL-1β, TNF-α, IFN-γ, apoptosis rate, the protein levels of Bax and cleaved-caspase-3 were obviously increased (P<0.05). Conclusions NGR1 can activate the JAK2/STAT3 signaling pathway, promote autophagy of alveolar epithelial cells, and inhibit Kp-induced inflammatory injury and apoptosis of alveolar epithelial cells.

Analysis of risk factors of multidrug-resistant organism infection in lung transplant recipients based on restricted cubic spline model / 器官移植

Objective To summarize current status of multidrug-resistant organism (MDRO) infection in lung transplant recipients and analyze the risk factors of MDRO infection. Methods Clinical data of 321 lung transplant recipients were retrospectively analyzed. According to the incidence of postoperative MDRO infection, they were divided into the MDRO group (n=122) and non-MDRO infection group (n=199). The incidence of MDRO infection in lung transplant recipients was summarized. The risk factors of MDRO infection in lung transplant recipients were analyzed by logistic regression model. The dose-response relationship between MDRO infection and time of ventilator use was determined by restricted cubic spline model. Results Among 321 lung transplant recipients, 122 cases developed MDRO infection, with an infection rate of 38.0%. Two hundred and twenty-nine strains of pathogenic bacteria were detected in the MDRO infection group, mainly Gram-negative bacteria (92.6%), and the top three strains were carbapenem-resistant acinetobacter baumannii (46.3%), carbapenem-resistant pseudomonas aeruginosa (22.3%) and carbapenem-resistant klebsiella pneumoniae (14.8%), respectively. MDRO infection mainly consisted of lower respiratory tract infection (61.5%), followed by ventilator-associated pneumonia (26.2%). Univariate analysis showed that the risk factors of MDRO infection in lung transplant recipients were single-lung transplantation, long-time postoperative use of extracorporeal membrane oxygenation (ECMO), long operation time, long-time urinary catheterization, long-time central venous catheterization and long-time ventilator use (all P < 0.05). Multivariate logistic regression analysis indicated that single-lung transplantation and long-time ventilator use were the independent risk factors for MDRO infection in lung transplant recipients (both P < 0.05). Results of restricted cubic spline model analysis showed that the risk of infection continued to increase with the prolongation of ventilator use time within 20 d. After 20 d, prolonging the time of ventilator use failed to increase the risk of infection, showing a plateau effect. Conclusions The MDRO infection rate tends to decline in lung transplant recipients year by year. Single-lung transplantation and long-time ventilator use are the independent risk factors for MDRO infection in lung transplant recipients.

Diagnosis and Treatment of Klebsiella Pneumoniae Combined with Enterobacter Cloacae in Lumbar Intervertebral Space Infection / 中山大学学报(医学科学版)

ObjectiveTo explore the clinical diagnosis and treatment of rare primary lumbar intervertebral space infection with Klebsiella pneumoniae and Enterobacter cloacae， and provide clinical experience for the diagnosis and treatment of this rare spinal infection. MethodsAn elderly male patient with low back pain and numbness in the left lower extremity for more than 7 months， which aggravated for more than 1 week， was diagnosed with lumbar disc herniation after laboratory and imaging examinations. After admission， the symptoms became acutely aggravated， and re-examination of lumbar enhanced MRI showed local enhancement at the posterior edge of the L3/4 intervertebral space. The VAS score was 9 points， and the lumbar JOA score was 6 points. A posterior lumbar interbody fusion of L3-L5 was performed， and L3/4 intervertebral disc specimens were collected during the operation for bacterial culture. ResultsBacterial culture results showed Klebsiella pneumoniae and Enterobacter cloacae infection. The patient was treated with sensitive antibiotics for 6 weeks after the operation， and the patient was cured during the follow-up of half a year after the operation. ConclusionFor middle-aged and elderly patients with clinical manifestations of acute severe low back pain or lower extremity pain， the possibility of spinal infection should be considered when routine laboratory and imaging examinations suggest lumbar degenerative diseases.

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.