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.

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.

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%

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.

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

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

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

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

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

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

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

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.

Programmed cell death induced by Klebsiella pneumoniae infection / 中华微生物学和免疫学杂志

Klebsiella pneumoniae can cause a variety of infectious diseases, especially in immunocompromised population. The emergence of multidrug-resistant hypervirulent Klebsiella pneumoniae has greatly limited the choice of treatment for Klebsiella pneumoniae infection, and the exploration of new treatment strategies is imminent. In the process of infection, there is a complex interaction between the programmed cell death of host cells and the invasion of Klebsiella pneumoniae. This paper mainly reviewed the research progress in several mechanisms of programmed cell death such as pyroptosis, apoptosis, necroptosis and autophagy caused by Klebsiella pneumoniae.

Dissemination mechanism of blaKPC-2 among carbapenem-resistant Klebsiella pneumoniae strains / 中华微生物学和免疫学杂志

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is highly prevalent and poses a great health challenge due to the lack of effective treatments. Klebsiella pneumoniae carbapenemase-2 (KPC-2), encoded by blaKPC-2 gene, is one of the major contributors to carbapenem resistance in CRKP. In China and other Asian regions, Tn1721 and plasmid IncFⅡ are the main vectors for blaKPC-2 transfer between Kpn ST11 strains, which lack clustered regularly interspaced short palindromic repeats (CRISPR) and restriction-modification (R-M) systems. The structure of transposons has a significant impact on the transposition frequency of blaKPC-2, which may be related to the different transposition patterns of transposons. The prevalence advantage of blaKPC-2 in Kpn ST11 strains is highly associated with the immune deficiency in Kpn ST11. By acquiring a re-engineered CRISPR-Cas3 system via conjugation, the high-risk IncFⅡ plasmid can be successfully cleaved and ST11 CRKP can regain antibiotic sensitivity, which provides a promising approach for clinical treatment and prevention of CRKP.

Clinical analysis of 12 cases of invasive Klebsiella pneumoniae liver abscess syndrome / 中华全科医师杂志

Objective:To analyze the clinical features of patients with invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS). Methods:The clinical data of 12 patients diagnosed as IKLAS in Zhuzhou Central Hospital from January 2020 to January 2023 were retrospectively analyzed.Results:Among 12 patients there were 6 males and 6 females with an mean age of 65.3±12.2 years (49-90). Nine patients were complicated with type 2 diabetes. The main clinical manifestations were fever ( n=9), chill ( n=6), shiver ( n=4), nausea and vomiting ( n=2), upper abdominal pain ( n=2), fatigue and anepithymia ( n=2), cough and expectoration ( n=1), disturbance of consciousness ( n=1) and hemoptysis ( n=1). The leukocyte count was increased in 8 cases, lymphocyte count decreased in 10 cases, and platelets count decreased in 3 cases. C-reactive protein and procalcitonin levels were elevated, while serum albumin levels were lowered in all patients. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased in 7 cases each. Liver abscess was located in the right lobe in 8 cases, in the left lobe in 1 cases, and in both lobes in 3 cases. There were 7 patients with single abscess, and 5 patients with multiple abscesses. The etiology was confirmed by liver pus culture ( n=10) and blood culture ( n=5), respectively. The main sites of invasion were lung and blood stream ( n=10 and n=5, respectively). The majority of Klebsiella pneumoniae isolates were antibiotic sensitive strains and the overall drug resistance rate was relatively low. All patients were given antibiotics, and 10 of them also received liver abscess puncture drainage. After treatment, 11 patients were discharged, and 1 died of septic shock. Conclusions:Patients with IKLAS exhibit diverse clinical symptoms, most patients are complicated with diabetes, and the main sites of invasion are in the lungs and blood stream. Timely diagnosis, active screening of extrahepatic infection sites, effective drainage of abscess and appropriate antibiotic treatment can improve the survival of patients.

Clinical outcomes after treatment for NDM-producing Klebsiella pneumoniae infection after kidney transplantation / 中华器官移植杂志

Objective:To explore the clinical efficacy of ceftazidime/avibactam(CZA)plus aztreonam(ATM)for New Delhi metallo-β-lactamase(NDM)carbapenem-resistant Klebsiella pneumoniae(CRKP)infection after kidney transplantation.Methods:Clinical data are retrospectively reviewed for 11 RT recipients infected with NDM metallo-β-lactamase CRKP admitted into First Affiliated Hospital of Xi 'an Jiaotong University and Affiliated Renji Hospital of Shanghai Jiao Tong University from November 2018 to December 2019.Based upon treatment protocol, they are divided into two groups of ceftazidime/avibactam plus aztreonam(CZA-ATM, 5 cases)and other effective antibiotics(OAA, 6 cases).Age, gender, infection type, drug resistance gene, changes in body temperature and leucocyte count, treatment course and prognosis are summarized.Results:A total of 11 patients with NDM-producing CRKP infection after RT are recruited.There are seven males and four females with an age range of(19~66)(38.9±14.4)years.There are mixed pulmonary and urinary tract infections(3 cases), urinary tract infection(2 cases), pulmonary infection(1 case)and perirenal infection(5 cases).All isolates harbore NDM carbapenemase gene, 5 isolates carry Klebsiella pneumoniae carbapenemase(KPC)gene and 1 isolate contained both imipenemase metallo-β-lactamase(IMP)and verona integron-encoded metallo-β-lactamase(VIM)gene concurrently.Ceftazidime-avibactam plus aztreonam(CZA-ATM)is prescribed in five patients while the remainders receive OAA.No adverse reactions occurred in individuals on CZA-ATM and 2 cases on OAA have adverse reactions with a poor appetite and diarrhea.After 30-day infection, the curative cases of CZA-ATM and OAAs groups reach 4 and 5 respectively.No death occurred in neither groups at Day 30.And 90-day mortality is 0 and 1 respectively.Conclusions:For RT patients infected with NDM-producing CRKP, CZA-ATM combination therapy may be another effective treatment.

Risk factors of carbapenem-resistant Klebsiella pneumoniae infection in ICU patients and construction of a prediction model for infection / 中华临床感染病杂志

Objective:To analyze the risk factors of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection in intensive care unit (ICU) patients and to construct a prediction model for infection. Methods:The clinical data of 204 patients with Klebsiella pneumoniae infection admitted in ICU of Jining First Hospital during January 2020 to December 2022 were retrospectively analyzed. Patients admitted during January 2020 to December 2021 were selected as model set ( n=150), and patients admitted during January to December 2022 were selected as validation set ( n=54). In model set, there were 59 cases infected with CRKP (CRKP group) and 91 cases infected with carbapenem-sensitive Klebsiella pneumonia (CSKP group). The risk factor of CRKP infection in ICU patients were analyzed with multivariate Logistic regression, based on which an infection prediction model was constructed. The predictive value of the model was evaluated by ROC, and verified in the validation group. Results:Multivariate Logistic regression analysis showed that empirical use of beta-lactam antibiotics( OR=6.985, 95 % CI 1.658-29.423, P=0.008), central vein catheterization( OR=7.486, 95 % CI 2.776-20.186, P<0.001)and tracheal intubation/incision( OR=10.695, 95 % CI 2.701-42.351, P=0.001)were risk factors for CRKP infection in ICU patients. The regression equation for predicting the risk of infection was -4.851+ empirical use of beta-lactam antibiotics×1.944+ central vein catheterization×2.013+ tracheal intubation/incision×2.370. The area under the ROC curve (AUC) of the model for predicting infection in the model group was 0.905, with sensitivity and specificity of 79.7% and 90.1%, respectively. The AUC of the model for predicting infection in validation group was 0.881, with sensitivity and specificity of 84.2% and 85.7%, respectively. Conclusion:The constructed infection prediction model in the study can effectively predict CRKP infection in ICU patients.

Risk factors of mortality in Klebsiella pneumoniae bloodstream infection and construction of a prediction model for prognosis of patients / 中华临床感染病杂志

Objective:To explore the risk factors of mortality in patients with Klebsiella pneumoniae bloodstream infection, and to construct a predictive model. Methods:The clinical data of 234 patients with Klebsiella pneumoniae bloodstream infection admitted in the First Hospital of Qinhuangdao from January 2020 to December 2022 were retrospectively analyzed, including 202 cases admitted during January 2020 to June 2022 (model set), and 32 cases admitted during July to December 2022 (validation set). There were 64 cases died (fatal group) and 138 cases survived (survival group) within 28 d after admission in model set. Multivariate Logistic regression was used to analyze the risk factors of death in patients with Klebsiella pneumoniae bloodstream infection and a mortality prediction model was constructed. The constructed model was applied in validation set, and the consistency between predicted mortality and real mortality was analyzed. Results:Multivariate Logistic regression analysis showed that male sex ( OR=2.598, 95% CI 1.179-5.725, P=0.018), age≥65 years ( OR=4.420, 95% CI 2.029-9.627, P<0.001), admitted to intensive care unit (ICU) ( OR=10.299, 95% CI 4.752-22.321, P<0.001), and the empirical use of quinolones antibiotics ( OR=4.288, 95% CI 1.127-16.317, P=0.033) were independent risk factors for 28-day mortality in Klebsiella pneumoniae bloodstream infection patients. The regression equation for predicting the risk of death was -3.469+ male × 0.955+ age ≥ 65 years × 1.486+ admitted to ICU × 2.332+ empirical use of quinolone antibiotics × 1.456. The area under the ROC curve (AUC) for predicting death in the model set was 0.831, with sensitivity and specificity of 71.9% and 80.4%, respectively. The AUC for predicting death in the validation set was 0.881, with sensitivity and specificity of 91.7% and 75.0%, respectively. Conclusion:The constructed mortality prediction model in the study has good application value for the prognosis of patients with Klebsiella pneumoniae bloodstream infection.

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.

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.