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.

Sensibilidad disminuida a los antibóticos Beta-Lactamicos en estreptococos Beta-Hemolíticos / Decreased sensitivity to beta-lactam antibiotics in beta-hemolytic streptococci

Últimamente, se están detectando mutaciones en las proteínas ligadoras de penicilina (PBP) de los estreptococos beta-hemolíticos que corresponden a sitios que en Streptococcus pneumoniae han determinado sensibilidad disminuida a los antibióticos beta-lactámicos. Primero, se describieron cepas con sensibilidad intermedia a penicilina en Streptococcus agalactiae (estreptococos del grupo B), luego en Streptococcus dysgalactiae subsp. equisimilis (mayormente grupos C y G) y, más recientemente, cepas con sensibilidad disminuida a aminopenicilinas y cefalosporinas de tercera generación en Streptococcus pyogenes (grupo A). El costo biológico de estas modificaciones nos permite pensar que los niveles de resistencia no han de ser tan elevados como para comprometer por ahora la efectividad clínica de los beta-lactámicos (AU)

Recently, mutations in penicillin-binding proteins (PBPs) of beta-hemolytic streptococci have been detected corresponding to sites that in Streptococcus pneumoniae have been determined to have decreased sensitivity to beta-lactam antibiotics. First, strains with intermediate sensitivity to penicillin were described in Streptococcus agalactiae (group B streptococci), subsequently in Streptococcus dysgalactiae subsp. equisimilis (mainly groups C and G) and, more recently, strains with decreased sensitivity to third-generation aminopenicillins and cephalosporins were found in Streptococcus pyogenes (group A). The biological cost of these modifications suggests that, for now, resistance levels are not high enough to compromise the clinical effectiveness of beta-lactams (AU)

Escherichia coli y Klebsiella pneumoniae productoras de betalactamasas de espectro extendido en un hospital de La Habana

RESUMEN Introducción: En microorganismos gramnegativos la producción de enzimas betalactamasas es el mecanismo más común de resistencia. Las de espectro extendido constituyen un grupo importante por su capacidad de inactivar las cefalosporinas de tercera y cuarta generación y el aztreonam. Su detección es vital para indicar el tratamiento óptimo y las medidas de aislamiento que eviten la dispersión de los microorganismos que las portan. Objetivos: Determinar la incidencia y principales características de los aislados de Escherichiacoli y Klebsiellapneumoniae productores de betalactamasas de espectro extendido en muestras no urogenitales. Métodos: Estudio transversal realizado en el hospital "Salvador Allende" durante el año 2017. Se determinó la frecuencia de Escherichia coli y Klebsiella pneumoniae productoras de betalactamasas de espectro extendido, su procedencia según servicio del hospital, tipo de muestra clínica, y su sensibilidad antimicrobiana. La identificación de betalactamasas de espectro extendido se hizo por el método de doble disco de Jarlier. Resultados: Fueron productores de betalactamasas de espectro extendido 46 y 50 % de aislados de Escherichia coli y Klebsiella pneumoniae, respectivamente. La mayoría provenían de muestras de las salas del Instituto de Angiología, el antimicrobiano con mayor efectividad fue el meropenem, la sensibilidad al resto de los antimicrobianos estuvo por debajo de 80 % y no hubo aislados sensibles a las cefalosporinas de tercera generación. Conclusiones: Se demuestra una alta incidencia de aislados de Escherichia coli y Klebsiella pneumoniae productores de betalactamasas de espectro extendido en el Hospital "Salvador Allende" de La Habana, más marcada en las salas del Instituto de Angiología y en muestras de piel.

ABSTRACT Introduction: Beta-lactamase production is the most common resistance mechanism in gram-negative microorganisms. Extended-spectrum beta-lactamases are an important group of enzymes capable of inactivating third- and fourth-generation cephalosporins and aztreonam. Their detection is important to indicate the optimum treatment as well as isolation measures aimed at preventing the spread of carrier microorganisms. Objectives: Determine the incidence and main characteristics of isolates of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae from non-urogenital samples. Methods: A cross-sectional study was conducted at Salvador Allende hospital during the year 2017. Determination was made of the frequency of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae, their origin by hospital service, the type of clinical sample and their antimicrobial sensitivity. Identification of extended-spectrum beta-lactamases was based on the Jarlier double disc method. Results: Of the total Escherichia coli and Klebsiella pneumoniae isolates studied, 46% and 50%, respectively, were extended-spectrum beta-lactamase producers. Most had been obtained from samples taken in wards of the Institute of Angiology; the most effective antimicrobial was meropenem; sensitivity to the remaining antimicrobials was below 80%; no isolates were sensitive to third-generation cephalosporins. Conclusions: A high incidence was found of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolates at Salvador Allende Hospital in Havana, more noticeably in Institute of Angiology wards and skin samples.

Prevalencia de Escherichia coli, productora de BLEE en pacientes ambulatorios de la ciudad de Cuenca / Prevalence of Escherichia coli, ESBL producer in outpatients of the city of Cuenca

Se analizó un total de 274 muestras de orina de pacientes ambulatorios que acudieron a los centros de salud 1, 2 y 3 de la ciudad de Cuenca durante el periodo comprendido entre mayo y junio del año 2013, con el fin de obtener al menos 100 muestras de orina con presencia de Escherichia coli. Se recuperaron 103 cepas de Escherichia coli y se continuó el estudio con la identificación de la producción de Betalactamasas de Espectro Extendido (BLEE), mediante la técnica descrita en el manual CLSI. Se realizaron las pruebas presuntivas y confirmatorias, aplicando el método convencional de difusión en agar, en placas de agar Mueller-Hinton, con un inóculo Mac Farland 0,5 y ensayando los discos de antimicrobiano. Para la prueba presuntiva se emplearon los discos de aztreonam, cefotaxime, ceftazidime y ceftriaxona; para la prueba confirmatoria se utilizaron los discos de ceftazidime y cefotaxime en combinación con ácido clavulánico; la producción de BLEE se determinó mediante la diferencia del diámetro de los halos según se indica en la técnica. Los resultados mostraron que de 103 cepas de E. coli se recuperaron siete (6,8 %) cepas productoras de BLEE y si se considera que la población con la que se trabajó fue de pacientes ambulatorios resulta muy importante la realización de los métodos de identificación de BLEE como apoyo para la correcta terapia antimicrobiana, previniendo de esta manera la diseminación de cepas de E. coli productoras de BLEE.

A total of 274 urine samples were analyzed from outpatients presenting to Health Centers 1, 2 and 3 of the city of Cuenca during the period between May and June 2013, with the purpose to get at least 100 samples positive urine with Escherichia coli. Were retrieved 103 strains of Escherichia coli and the study was continued with the identification of the production of Extended Spectrum Beta Lactamases (ESBL), using the technique described in the CLSI manual. Were performed presumptive and confirmatory tests, applying the conventional method of agar diffusion plates in Mueller-Hinton agar, with a 0.5 McFarland inoculum and tested antimicrobial discs. For the presumptive test was used discs aztreonam, cefotaxime, ceftazidime and ceftriaxone, for the confirmatory test were used discs of ceftazidime and cefotaxime in combination with clavulanic acid. ESBL production was determined by the difference in the diameter of the halos as indicated in the technique. The results showed that of 103 strains of E. coli recovered seven (6,8 %) ESBL producing strains, when considering that the population which was worked was of outpatient, is very important the implementation of identification methods as ESBL for correct support of antimicrobial therapy, preventing this way the spread of strains of E. coli ESBL producing.

Actividad comparativa in vitro de doripenem y otros carbapenemicos frente a pseudomonas aeruginosa aisladas en el laboratorio de microbiología del hospital Vargas de Caracas / Comparative in vitro activity of dorypenem and other carbapenems in pseudomonas aeruginosa isolates on Vargas Caracas Hospital´s Microbiology

Los ensayos de cuantificación de ARN plasmáticos de VIH-1 son importantes para el control de pacientes infectados, así como el monitoreo de la respuesta a la terapia antirretroviral. Por lo tanto, los ensayos comerciales empleados para este propósito deben presentar buena correlación entre si, para dar lugar al manejo terapéutico apropiado. El objetivo del estudio consistió en correlacionar los resultados obtenidos mediante el ensayo de amplificación de señal (bDNA) y PCR en tiempo real (RT-PCR), ambas casas comerciales aprobadas por la FDA y con diferente diana de detección del VIH-1. La validación se realizó con 180 muestras clínicas de pacientes referidos al INHRR. Los resultados fueron comparados con la subpoblación de linfocitos TCD4+ determinados mediante citometría de flujo. El análisis estadístico se realizó empleando el coeficiente de regresión lineal de Pearson (R2) y el valor de contraste de hipótesis con una significancia del 95 %, usando el programa SPSS Statistics v10.0. Se observó una buena correlación entre los ensayos (R2=0.961, p<0.05), siendo la RTPCR más sensible. Las diferencias cuantitativas de carga viral entre las técnicas ensayadas fue menor de 0.5 log10 copias/ml para el 89% de las muestras, y >1 log10 copias/ml solo en dos pacientes, no indicando necesariamente cambio terapéutico. Adicionalmente, se encontró una correlación inversa entre los linfocitos TCD4+ y carga viral del VIH-1 medida por bDNA (R2= 0.20, p<0.05) y RT-PCR (R2= 0.15, p<0.05). Los ensayos evaluados mostraron que ambas técnicas puedes ser empleadas indistintamente para el control de los pacientes VIH positivo.

The assay for quantification of plasma HIV-1 RNA are important for the control of patients infected, as well as the monitoring of the response to antiretroviral therapy. Therefore, the commercial assays used for this purpose must submit good correlation between to give place to the appropriate therapeutic management. In this study, we correlate the results obtained through the testing of signal amplification (bDNA) and real-time PCR (RT-PCR), two comercial technical approved by the FDA and with different targets of detection HIV-1. The validation was carried out with 180 clinical samples of patients referred to the INHRR. The results were compared with the subpopulation of lymphocytes TCD4+ determined by flow cytometry. The statistical analysis was performed using the program SPSS Statistics v10. It was observed good correlation between the tests studied (R2=0.961, p<0.05), with RT-PCR more sensitive. The quantitative differences in viral load between the techniques tested was less than 0.5 log10 copies/ml for the 89% of the samples, and >1 log10 copies/ml in only two patients. Additionally, it was found an inverse correlation between lymphocytes TCD4+ and viral load of HIV-1, measured by bDNA (R2= 0.20, p<0.05) and RT-PCR (R2= 0.15, p<0.05). Therefore, these assays can be employed for the patient control HIV.

Prevalence of extended spectrum beta-lactamase producing uropathogens and their antibiotic resistance profile in patients visiting a tertiary care hospital in central India: Implications on empiric therapy.

Context: Antimicrobial resistance showed by different uropathogens is one of the barricades that might hinder a successful treatment. Detection of extended spectrum beta-lactamase (ESBL) production among uropathogens is an important marker of endemicity. Aims: The present prospective study was done to identify the trends of uropathogens, to find the prevalence of ESBL isolates and to study the antibiotic resistance profile of the ESBL and non-ESBL uropathogenic isolates. Materials and Methods: This study was conducted in the Department of Microbiology of a teaching tertiary care hospital from July 2013 to September 2013. All the uropathogenic isolates were identified up to species level by conventional methods. The prevalence of potential ESBL producers was explored. Antibiotic resistance test of the urinary isolates was done by disc-diffusion method and the results were interpreted according to Clinical Laboratory Standards Institute-2013 guidelines. Results: A total of 670 urine samples from male and female patients visiting the outpatient department (OPD) and inpatient department (IPD) of our hospital were collected. A significantly higher number of IPD and OPD males (55.1% and 55.5%) were found to be culture positive. Escherichia coli (55.3%) was the most frequently isolated uropathogen followed by Klebsiella pneumoniae (23%). However, strains of Escherichia coli (41.6%) were the highest ESBL producing isolates followed by Pseudomonas aeruginosa (36.1%). ESBL producing isolates were found to be multidrug-resistant when compared to non-ESBL producers. However, excessive drug-resistance among non-ESBL producing isolates can’t be ignored. Conclusion: Our study confirms a global trend toward increased resistance to beta-lactam antibiotics. We emphasize on the formulation of antibiotic policy for a particular geographical area.

Evaluation of Ampicillin and Ceftriaxone on Ethanol Consumption as Compared to Naltrexone in Alcohol Dependant Rats.

Context: Extracellular glutamate level in reward centre of brain increases during ethanol drinking sessions. Hence, it can be hypothesized that drugs which decrease extracellular glutamate might have deaddictive properties. It has been shown that β-lactam antibiotics are potent stimulators of glutamate transporter 1(GLT1) expression. Previous studies have shown that ceftriaxone decreases ethanol consumption but this has not been compared to standard line of treatment (naltrexone). Also, no study was conducted for testing ampicillin even if in an in-vitro experiment ampicillin has shown to increase GLT1 levels more than ceftriaxone. Hence, our study’s objectives were to compare efficacy of ceftriaxone and ampicillin with naltrexone on ethanol consumption in rats. Methods: Permission of ethics committee was taken. Study was divided into two parts. Part I included standardization of model & Part II included 8 groups of six rats each. Group 1: vehicle control, Group 2: 1mg/kg/d naltrexone, Group 3: 100mg/kg/d ceftriaxone, Group 4: 200mg/kg/d ceftriaxone, Group 5: 100mg/kg/d ampicillin, Group 6: 200mg/kg/d ampicillin were given i.p injections for 15 days and Group 7: 200mg/kg ceftriaxone & Group 8: 200mg/kg ampicillin i.p. single dose. Parameters measured were ethanol & water intake per day for 15 days. Results: Groups 2 to 8 showed statistically significant decrease in ethanol intake as compared to vehicle control. Also, group 3 & 4 showed an increase in water consumption as compared to Group 1. Conclusions: Our study recommends that drugs acting on glutamate pathways like ceftriaxone and ampicillin can be explored for treatment of alcohol dependence.

Beta-Lactam Antibiotic Sensitization and Its Relationship to Allergic Diseases in Tertiary Hospital Nurses

PURPOSE: Skin allergies through type 1 and 4 hypersensitivity reactions are the most frequent manifestations of drug allergies. We had previously experienced a case of a nurse with cefotiam-induced contact urticaria syndrome. To aid in preventing the progression of drug-induced allergic disease in nurses, we conducted a survey of tertiary hospital nurses who were likely to have been exposed professionally to antibiotics. METHODS: All 539 staff nurses at a tertiary hospital were asked to respond to a questionnaire regarding antibiotic exposure. Of the 457 nurses (84.8%) who responded, 427 (79.2%) received a physical examination of the hands and 318 (59.0%) received skin prick tests with the beta-lactam antibiotics cefotiam, cefoperazone, ceftizoxime, flomoxef, piperacillin and penicillin G. RESULTS: A positive response to at least one of the antibiotics occurred in 8 (2.6%) of the 311 subjects included in the analysis and stages 1 and 2 contact urticaria syndrome were observed in 38 (8.9%) and 3 (0.7%) of 427 nurses, respectively. The frequencies of a positive antibiotic skin test (6.9 versus 1.3%, chi-square=7.15, P=0.018), stage 1 contact urticaria syndrome (14.4 versus 7.4%, chi-square=4.33, P=0.038) and drug allergy (15.3 versus 3.6%, chi-square=18.28, P=0.000) were higher in subjects with a positive skin allergy history than in those without. Allergic rhinitis (P=0.02, OR=3.86, CI=1.23-12.06), night cough (P=0.04, OR=3.12, CI=1.03-9.41) and food allergy (P=0.00, OR=9.90, CI=3.38-29.98) were significant risk factors for drug allergy. CONCLUSIONS: Antibiotic sensitization and drug allergy occurred more frequently in nurses with a positive skin allergy history. Atopy may be an important risk factor for drug allergy.

Beta-Lactam Antibiotic Sensitization and Its Relationship to Allergic Diseases in Tertiary Hospital Nurses

PURPOSE: Skin allergies through type 1 and 4 hypersensitivity reactions are the most frequent manifestations of drug allergies. We had previously experienced a case of a nurse with cefotiam-induced contact urticaria syndrome. To aid in preventing the progression of drug-induced allergic disease in nurses, we conducted a survey of tertiary hospital nurses who were likely to have been exposed professionally to antibiotics. METHODS: All 539 staff nurses at a tertiary hospital were asked to respond to a questionnaire regarding antibiotic exposure. Of the 457 nurses (84.8%) who responded, 427 (79.2%) received a physical examination of the hands and 318 (59.0%) received skin prick tests with the beta-lactam antibiotics cefotiam, cefoperazone, ceftizoxime, flomoxef, piperacillin and penicillin G. RESULTS: A positive response to at least one of the antibiotics occurred in 8 (2.6%) of the 311 subjects included in the analysis and stages 1 and 2 contact urticaria syndrome were observed in 38 (8.9%) and 3 (0.7%) of 427 nurses, respectively. The frequencies of a positive antibiotic skin test (6.9 versus 1.3%, chi-square=7.15, P=0.018), stage 1 contact urticaria syndrome (14.4 versus 7.4%, chi-square=4.33, P=0.038) and drug allergy (15.3 versus 3.6%, chi-square=18.28, P=0.000) were higher in subjects with a positive skin allergy history than in those without. Allergic rhinitis (P=0.02, OR=3.86, CI=1.23-12.06), night cough (P=0.04, OR=3.12, CI=1.03-9.41) and food allergy (P=0.00, OR=9.90, CI=3.38-29.98) were significant risk factors for drug allergy. CONCLUSIONS: Antibiotic sensitization and drug allergy occurred more frequently in nurses with a positive skin allergy history. Atopy may be an important risk factor for drug allergy.

Determinación de la calidad composicional y de residuos antibióticos betalactámicos en leche cruda expendida en el sector urbano del municipio de ipiales

El estudio se realizó con el fin de determinar la calidad composicional e higiénica de la leche cruda que consumen los habitantes de la zona urbana del municipio de Ipiales. Se determinó el porcentaje de muestras que no cumplen con las características óptimas para su comercialización y el porcentaje de muestras positivas a residuos de antibióticos betalactámicos. En la zona urbana del municipio de Ipiales, existen 180 expendedores ambulantes reportados, de leche cruda, Para calcular el tamaño de la muestra se aplicó la fórmula estadística de Blaha, con un nivel de confianza del 95%, con un error máximo admitido del 10% lo cual dio un total de 96 muestras, las cuales se procesaron en el laboratorio de análisis lácteo de la empresa Alquería de la ciudad de Ipiales. Los resultados que se obtuvieron en este estudio determinaron que ninguna de las muestras tomadas a los diferentes expendedores, cumplen totalmente con los requisitos en calidad composicional (decreto 616 de 2006 del Ministerio de la protección Social) e higiénica (decreto 2838 del 2006 sobre las características óptimas de la leche cruda) necesarios para asegurar un consumo inocuo de este producto. Para la presencia de antibióticos betalactámicos con SNAP test, el 5,2% de las muestras resultaron positivas y el 94,8% fueron negativas. La adición de neutralizantes en este estudio fue del 0%. En cuanto a la detección de adulterantes se encontró un 2% que corresponde a la adición de harinas.

The study was conducted to determine the compositional and hygienic quality of raw milk consumed by inhabitants of the urban area in the town of Ipiales. The percentage of samples that do not meet the optimal characteristics for marketing and the percentage of positive samples for beta-lactam antibiotic residues were determined. There are 180 reported raw milk sellers in the urban area of the municipality of Ipiales. To calculate the size of the sample the statistical formula Blaha was applied with a 95% of reliability and a maximum error of 10%. 96 not homogenized samples of raw milk, sold in the area were collected and later processed in the milk laboratory of “Alqueria” in Ipiales. The results obtained in this study determined that none of the samples of raw collected from different vendors complies with all quality (decree 616 of 2006 from the Ministry of Social protection) and hygienic requirements (decree 2838, 2006 concerned with the best characteristics of raw milk) necessary to ensure that the human consumption of this product is harmless. 5, 2% of the samples were positive for the presence of beta-lactam antibiotics with Snap test, while 94, 8% tested negative. The addition of neutralizers in this study was 0%. Additionally, it was found that regarding the detection of adulterants 2% corresponded to the addition of flour.

Relationship between beta-Lactam Antimicrobial Use and Antimicrobial resistance in Klebsiella pneumoniae Clinical Isolates at 5 Tertiary Hospitals in Korea

BACKGROUND: This study was performed to evaluate the prescribing pattern of beta-lactam antibiotics and the relationship between antimicrobial resistance and antimicrobial use in 5 tertiary care hospitals in Korea. MATERIALS AND METHODS: Data on annual patient-days and annual consumption (defined daily dose (DDD) per 100 patient-days) of beta-lactam antibiotics from 2003 to 2005 in 5 tertiary hospitals were analyzed. To determine the antimicrobial resistance in K. pneumoniae, broth microdilution test and double disk synergy were performed according to the CLSI performance standards. Spearman's correlation coeffient was used to determine the relationship between antibiotic consumption and resistance. RESULTS: The prescription of beta-lactam antibiotics in 5 tertiary hospitals markedly varied. In two hospitals, increase in consumption of beta-lactam antibiotics was more than 30% during recent 3 years. The higher consumption of beta-lactam antibiotics significantly correlated with the higher rate of antibiotic-resistant K. pneumoniae in 5 tertiary care hospitals. CONCLUSION: Continuous surveillance of antibiotic use is needed to encourage appropriate prescribing of antibiotics and to reduce antibiotic resistance.

Relationship between beta-Lactam Antimicrobial Use and Antimicrobial resistance in Klebsiella pneumoniae Clinical Isolates at 5 Tertiary Hospitals in Korea

BACKGROUND: This study was performed to evaluate the prescribing pattern of beta-lactam antibiotics and the relationship between antimicrobial resistance and antimicrobial use in 5 tertiary care hospitals in Korea. MATERIALS AND METHODS: Data on annual patient-days and annual consumption (defined daily dose (DDD) per 100 patient-days) of beta-lactam antibiotics from 2003 to 2005 in 5 tertiary hospitals were analyzed. To determine the antimicrobial resistance in K. pneumoniae, broth microdilution test and double disk synergy were performed according to the CLSI performance standards. Spearman's correlation coeffient was used to determine the relationship between antibiotic consumption and resistance. RESULTS: The prescription of beta-lactam antibiotics in 5 tertiary hospitals markedly varied. In two hospitals, increase in consumption of beta-lactam antibiotics was more than 30% during recent 3 years. The higher consumption of beta-lactam antibiotics significantly correlated with the higher rate of antibiotic-resistant K. pneumoniae in 5 tertiary care hospitals. CONCLUSION: Continuous surveillance of antibiotic use is needed to encourage appropriate prescribing of antibiotics and to reduce antibiotic resistance.