In vitro susceptibility to fosfomycin in clinical and environmental extended-spectrum beta-lactamase producing and/or ciprofloxacin-non-susceptible Escherichia coli isolates

ABSTRACT Extended-spectrum beta-lactamase producing and ciprofloxacin-non-susceptible Escherichia coli are clinical and environmental issues. We evaluated the susceptibility profile of fosfomycin in non-susceptible E. coli isolated from urine and the environment. We measured the activity of fosfomycin against 319 and 36 E. coli strains from urine and environmental isolates, respectively, collected from rivers. Fosfomycin resistance profiles were investigated using the minimal inhibitory concentration (MIC), according to the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) guidelines. Antibiotic susceptibility testing revealed that 5% and 6.6% of urine samples were non-susceptible to fosfomycin according to CLSI and EUCAST guidelines, respectively. The fosfomycin MIC50/90 was 0.5/4 mg/L. Of the 36 E. coli isolates from river water, 11.1% and 13,8% were non-susceptible to fosfomycin according to CLSI and EUCAST, respectively (range ≤0.25 ≥512 mg/L). All the isolates with MIC ≥512 mg/L for fosfomycin showed the fosA3 gene. Fosfomycin resistance was more frequent in the environment than in clinical samples.

Evaluación de la formación de biopelículas en aislamientos bacterianos y fúngicos por el método semicuantitativo de microtitulación con cristal violeta y el cualitativo de agar con rojo Congo / Assessment of biofilms formation of bacterial and fungal isolates using qualitative Congo red agar and semiquantitative crystal violet microtiter methods

Introducción. El 65 % de las infecciones humanas son producidas por bacterias o levaduras, cuya capacidad de formar biopelículas las hace más resistentes a los antimicrobianos y antifúngicos. Objetivo. Determinar la capacidad de formación de biopelículas en aislamientos bacterianos y fúngicos por medio de los métodos cuantitativo de microtitulación con cristal violeta y cualitativo de cultivo en agar con rojo Congo. Materiales y métodos. Con el método cuantitativo, se utilizaron los medios de cultivo infusión cerebro-corazón, tripticasa de soya y Müeller-Hinton para aislamientos bacterianos; para levaduras, se usaron caldo infusión cerebro-corazón y Sabouraud dextrosa. Para el método cualitativo de cultivo en agar, se utilizaron los mismos medios de cultivo más una solución con 3 % de rojo Congo y 10 % de dextrosa. Cómo método de referencia, se utilizó la propuesta de Stepanovic et al. Resultados. Se evaluaron 103 aislamientos bacterianos y 108 de levaduras. No es recomendable sustituir el caldo infusión cerebro-corazón por los caldos tripticasa de soya y Müeller-Hinton en el método cuantitativo, para evaluar la formación de biopelículas en los aislamientos bacterianos. El medio Sabouraud dextrosa, en caldo y agar, puede sustituir al de infusión de cerebro-corazón para evaluar la formación de biopelículas en levaduras, tanto por el método cuantitativo como por el cualitativo. Conclusión. El estudio de las biopelículas en el laboratorio de microbiología, a partir del método cualitativo de cultivo en agar con rojo Congo, es un procedimiento sencillo, rápido y de bajo costo, que proporciona información útil para el diagnóstico y la terapéutica de infecciones persistentes causadas por bacterias y levaduras.

Introduction. Sixty-five percent of human infections are caused by bacteria or yeasts able to form biofilms. This feature makes them more resistant to antimicrobials and antifungals. Objective. To determine biofilm formation capacity of bacterial and fungal isolates by quantitative crystal violet microtiter and qualitative Congo red agar methods. Materials and methods. Brain-heart infusion, trypticase soy broth and Müeller-Hinton culture media were used in bacterial isolates for the quantitative method; brain-heart infusion broth and Sabouraud dextrose were used for yeasts. The same culture media plus 3% Congo red and 10% dextrose were used to apply the qualitative method in agar. The proposal by Stepanovic, et al. was used as a reference method. Results. We evaluated 103 bacterial isolates and 108 yeasts isolates. We did not recommend substitute brain-heart infusion broth for trypticase soy and Müeller-Hinton broths for biofilm formation assessment in bacterial isolates using the quantitative method. Sabouraud dextrose medium, both broth and agar, can replace brain-heart infusion to assess biofilm formation in yeasts, quantitatively and qualitatively. Conclusion. The study of biofilms in the microbiology laboratory, using Congo red agar qualitative method, is a simple, fast, and inexpensive procedure that provides precise information for the diagnosis and treatment of persistent infections caused by bacteria and yeasts.

Phytochemical Screening and Antibacterial Activity of Chrysophyllum albidum Collected in Nsukka, South East Nigeria

Background: Chrysophyllum albidum is widely used by African people for the treatment of various types of diseases such as ear infection, sore throat, typhoid, cellulites, septicaemia, bactericemia, abscesses and tooth infections. Aim: The study was conducted to investigate the chemical components and antibacterial activity of the extract and fractions from the root bark of Chrysophyllum albidum from Nsukka, South-east Nigeria. Methodology: The fresh roots were collected, washed, cut into small pieces, air dried and pulverized to powder using mechanical grinder. Extraction and fractionation were done by cold maceration method and technique of liquid–liquid extraction respectively. The phytochemical analysis of the methanol extract and, n-hexane, butanol, aqueous and ethylacetate fractions of the plant part was carried out using standard method. The antibacterial activities were determined using cup-plate agar diffusion and agar dilution methods. Results: The phytochemical screening of the extract revealed the presence of tannins, flavonoids, saponins, terpenoids, alkaloids, reducing sugar and cardiac glycosides. The inhibition zone diameter (IZD) produced by the agents against some selected Gram positive bacteria (GPB) and Gram negative bacteria (GNB) pathogens ranged from 6 – 25 mm and 6 – 12 mm respectively. The MIC and MBC values produced by the extract and fractions of the plant’s part against the GPB ranged from 1.25 – 40 mg/ml and 5 – 80 mg/ml respectively Many of the GNB were not sensitive to the agents tested except Pseudomonas aeruginosa and Klebsiella spp that exhibited mild to moderate sensitivity to the agents. Conclusion: These agents, therefore, exhibited a potent antibacterial activity against all the GPB and a few GNB pathogens tested due to their potent phytochemicals. The results of this work have corroborated the trado-medical use of root of Chrysophyllum albidum for treating ear infection, sore throat, typhoid, cellulites, septicaemia, bactericemia, boils and tooth infection/decay.

Comamonas Testosteroni Emerging Gastrointestinal Pathogen

Comamonas testosteroni newly emerging microorganism previously known as Pseudomonas testosteroni is common environmental bacterium that is not known to be a part of the human commensal organism. Since its identification as a human pathogen in 1987, numerous reports have drizzled in, implicating this organism for various infections. Comamonas testosteroni are rare isolates in microbiology laboratories and have been infrequently reported as an infectious agent in routine clinical practice. Comamonas testosteroni has been rarely observed as an infectious agent in clinical practice. Comamonas testosteroni is rarely recognized as a human pathogen. Most of the reported cases are bloodstream infections. We report this pathogen from the stool of an immunocompromised 48-year-old male. The aim of this case report is to alert clinicians and laboratory physicians for the potential diagnosis and clinical approach of gastrointestinal infections caused by this organism.

A cross-sectional study to estimate the serum level of C-reactive protein among pediatric meningitis with bacterial etiology

Background: Bacterial meningitis is a global public health issue. C-reactive protein (CRP) has suitable diagnostic value in distinguishing between bacterial and aseptic meningitis especially in cases of negative bacterial culture of the blood and spinal fluid. Aim and Objective: The objective of this study was to estimate the serum level of CRP among pediatric meningitis cases with bacterial etiology. Materials and Methods: The hospital-based descriptive cross-sectional study was performed in a tertiary care pediatric hospital in Eastern India from June to August, 2021 with 150 samples. Patients fulfilling the inclusion criteria were selected for this study after obtaining informed consent. Cerebrospinal fluid sample was collected as per standard guidelines. Phenotypic identification of bacteria including antimicrobial susceptibility testing was done by automation (Vitek 2 compact, bioMerieux). Quantitative estimation of CRP was performed in a solid phase and sandwich-format immunometric assay using a gold antibody conjugate. Human rights, welfare, and autonomy were protected as per national ethical guidelines. Results: Median age (Inter Quartile Range) of 150 cases was 3(1–4.5) year. Escherichia coli (60.52%, 23/38) was the commonest isolate (P < 0.00000001 by Binomial test calculation) followed by Klebsiella pneumoniae (34.24%, i.e., 13/38). A total of 43/150 (28.66%) participants had higher serum CRP. Serum CRP was raised more in Gram-negative bacterial etiology (36 out of 38, 94.73%). Mean serum CRP was higher in Gram-negative cases (P < 0.05). Conclusion: Serum CRP was found significantly higher in meningitis caused by Gram-negative bacteria.

Frecuencia de Bacilos Gram Negativos en la cavidad bucal de estudiantes de una Universidad de Asunción

Introducción: La cavidad bucal hospeda una gran cantidad de microorganismos, como los bacilos Gram negativos, y entre ellas, bacterias de gran importancia médica debido a su capacidad de producir enfermedades graves para el ser humano, especialmente en pacientes inmunodeprimidos. El objetivo de este trabajo fue determinar la presencia de Bacilos Gram Negativos y sus patrones de resistencia a antibióticos, en una población estudiantil de la ciudad de Asunción, en los años 2019 y 2020. Materiales y métodos: Se realizó un estudio observacional, descriptivo de corte transversal, donde se realizaron hisopados de la cavidad bucal a 35 alumnos de entre 18 a 24 años, de una universidad privada en la ciudad de Asunción. Se requirió consentimiento informado firmado por los participantes y fueron excluidos quienes tuvieron tratamientos antibióticos. Las muestras fueron obtenidas con un hisopo de algodón, posteriormente se colocaron en un medio de transporte para luego ser cultivadas en Agar MacConkey. El cultivo se realizó por 48 horas a 37° centígrados, luego se procedió a la identificación bacteriana. Por último, se realizó el antibiograma. Resultados: De los 35 alumnos se encontró una frecuencia de 48,57% de bacilos Gram negativos. Cepas de Klebsiella pneumoniae fueron las más frecuentes (35,29%). Se observó que las bacterias eran altamente resistentes a la Amoxicilina/Ácido Clavulánico. Conclusiones: La presencia de estos tipos de microorganismos puede ser peligrosa para la salud general de las personas, específicamente de los pacientes con algún tipo de inmunodepresión, debido a la gran la resistencia a antibióticos presentadas por algunas cepas.

Introduction: The oral cavity hosts a large number of microorganisms, such as Gram negative bacilli, and among them, bacteria of great medical importance due to their capacity to cause serious diseases for humans, especially in immunosuppressed patients. The objective of this work was to determine the presence of Gram Negative Bacilli and their patterns of resistance to antibiotics, in a student population of the city of Asunción, in the years 2019 and 2020. Materials and methods: An observational, descriptive cross-sectional study was carried out, where oral cavity swabs were made from 35 students between 18 and 24 years of age, from a private university in the city of Asunción. Informed consent signed by the participants was required and those who had antibiotic treatments were excluded. The samples were obtained with a cotton swab, later they were placed in a transport medium to later be cultured in MacConkey Agar. The culture was carried out for 48 hours at 37° Celsius, then the bacterial identification was carried out. Finally, the antibiogram was performed. Results: Of the 35 students, a frequency of 48,57% of Gram negative bacilli was found. Klebsiella pneumoniae strains were the most frequent (35.29%). The bacteria were found to be highly resistant to Amoxicillin/Clavulanic Acid. Conclusions: The presence of these types of microorganisms can be dangerous for the general health of people, specifically of patients with some type of immunosuppression, due to the great resistance to antibiotics presented by some strains.

Identificación y sensibilidad antibiótica directas desde el hemocultivo positivo para bacilos gram negativos. Rendimiento comparativo de los sistemas Vitek 2C y Phoenix / Direct identification and susceptibility testing from positive blood cultures. A head-to-head performance comparison between Vitek 2C and Phoenix systems / Identificação e sensibilidade antibiótica diretas a partir da hemocultura positiva para bacilos gram negativos. Desempenho comparativo dos sistemas Vitek 2C e Phoenix

Resumen El objetivo de este estudio fue comparar los resultados de las pruebas de identificación y sensibilidad antimicrobiana obtenidos por los sistemas Vitek 2C (bioMérieux, Francia) y Phoenix (Becton Dickinson, EE.UU.) directamente a partir de hemocultivos positivos. Se realizó un estudio observacional prospectivo en el Hospital Naval Pedro Mallo de Buenos Aires, Argentina, que incluyó 70 bacteriemias monomicrobianas por gram negativos. Se obtuvo una identificación correcta por Vitek® 2C y por Phoenix del 100% y 97% respectivamente [p: no significativa (NS)]. La concordancia categórica para todos los antimicrobianos fue 97,1% y 98,1% (p: NS) con Vitek 2C y con Phoenix respectivamente. El tiempo medio para obtener un resultado fue de 10,19 h y 13,8 h (p: NS), respectivamente. Vitek 2C y Phoenix son herramientas importantes, rápidas y confiables para la identificación y las pruebas de sensibilidad realizadas directamente a partir de hemocultivos positivos.

Abstract The aim of this study was to compare the results of identification and antimicrobial susceptibility tests obtained by the Vitek 2C (bioMérieux, France) and Phoenix (Becton Dickinson, USA) systems directly from positive blood cultures. A prospective observational study was performed at the Pedro Mallo Navy Hospital in Buenos Aires, Argentina, which included 70 monomicrobial bacteremias by gram negative rods. Correct identification by Vitek® 2C and Phoenix was 100% and 97%, respectively [p: not significant (NS)]. Categorical agreement for all antimicrobials was 97.1% and 98.1% (p: NS) with Vitek 2C and Phoenix, respectively. The mean time to result was 10.19 h and 13.8 h (p: NS), respectively. Vitek 2C and Phoenix are important, rapid and reliable tools for identification and susceptibility testing when performed directly from positive blood cultures.

Resumo O objetivo deste estudo foi comparar os resultados dos testes de identificação e de suscetibilidade antimicrobiana obtidos pelos sistemas Vitek 2C (bioMérieux, França) e Phoenix (Becton Dickinson, EUA) diretamente a partir de culturas de sangue positivas. Foi realizado um estudo observacional prospectivo no Hospital Naval Pedro Mallo em Buenos Aires, Argentina, incluindo 70 bacteriemias monomicrobianas devido a gram negativos. A identificação correcta por Vitek® 2C e Phoenix obtida foi de 100% e 97% respectivamente [p: não significativo (NS)]. O acordo categórico para todos os antimicrobianos foi de 97,1% e 98,1% (p: NS) com Vitek 2C e Phoenix respectivamente. O tempo médio para obter o resultado foi de 10,19 h e 13,8 h (p: NS), respectivamente. Vitek 2C e Phoenix são ferramentas importantes, rápidas e fiáveis para a identificação e testes de sensibilidade realizados diretamente a partir de hemoculturas positivas.

Clinicobacteriological profile and antibiotic susceptibility pattern of chronic dacryocystitis in adults

Background: Chronic dacryocystitis is a constant menace to delicate ocular structures. If left untreated, it can lead to sight as well as life-threatening complications. However, such complications may be prevented by timely intervention along with appropriate antibiotic prophylaxis. The objectives are to investigate the current bacterial community profile in adult patients with chronic dacryocystitis attending a referral eye care center in Odisha and to determine their drug susceptibility pattern to commonly used antimicrobial agents. Materials and Methods: An observational study was conducted on 70 adult patients with chronic dacryocystitis. The discharge from the punctum was collected by doing a regurgitation test or lacrimal passage irrigation and sent for microbiological analysis. Results: Out of 70 samples collected, 54 (77.1%) samples showed bacterial growth after 24–48 h of incubation. Among various isolates recovered, 68.5% were gram-positive and 27.8% were gram-negative organisms. Staphylococcus aureus was found to be the most common isolate among gram-positive, and Pseudomonas aeruginosa was most common among gram-negative organisms. Among all drugs used in the susceptibility test; amikacin, piperacilin + tazobactam, and netilmycin were found to be most sensitive and cefixime, and amoxycilin + clavulinic acid was found to be most resistant to gram-positive as well as for gram-negative organisms. Conclusion: Knowledge about the microbiological profile and the drug susceptibility pattern responsible for chronic dacryocystitis in a geographical area is important and should be kept in mind while treating these patients.

Efficacy and safefy of Polymyxin B treatment for neutropenic patients suffering from refractory Gram-negative bacterial bloodstream infection / 中华血液学杂志

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.

Distribution and drug resistance of pathogenic bacteria of biliary tract infection in patients subjected to hepatobiliary surgery / 中国基层医药

Objective:To study the distribution and drug resistance of pathogenic bacteria of biliary tract infection in patients with hepatobiliary surgery.Methods:A total of 103 patients with biliary tract infection who received treatment in the Department of Hepatobiliary Surgery, Lanxi People's Hospital from May 2020 to October 2022 were included in this study. Their bile was cultured to analyze the distribution and drug resistance of pathogenic bacteria. The data were processed using the WHONET5.5 software system.Results:Fifty-eight pathogenic bacteria-positive samples were cultured from the bile of 103 patients with biliary tract infection, with a pathogenic bacteria-positive rate of 56.31%. Among 58 strains of pathogenic bacteria, 38 strains (65.52%) were gram-negative bacteria, mainly Escherichia coli and Klebsiella pneumonia, and 5 strains (8.62%) were fungal strains. Escherichia coli and Klebsiella pneumoniae were highly resistant to sulfamethoxazole-trimethoprim, ciprofloxacin, and other antibacterial drugs, and were completely sensitive to imipenem and meropenem. Enterococcus faecalis was mainly resistant to ampicillin and penicillin G,and it was completely sensitive to vancomycin and teicoplanin. Staphylococcus aureus was resistant to vancomycin, ciprofloxacin, cefotaxime, and other drugs. A total of 13 strains of ultrabroad-spectrum beta-lactamase bacteria were isolated from 25 strains of Escherichia coli and 7 strains of Klebsiella pneumonia, with the positive detection rate of 40.63%. Conclusion:The main pathogenic bacteria of biliary tract infection are Gram-negative bacteria, which are widely distributed and have serious drug resistance. In clinical practice, antimicrobial drugs should be reasonably selected according to the results of bile drug sensitivity tests.

Distribution and drug resistance characteristics of pathogens in recipients undergoing simultaneous pancreas-kidney transplantation / 器官移植

Objective To investigate the distribution and drug resistance characteristics of pathogens in donors and recipients undergoing simultaneous pancreas-kidney transplantation (SPK). Methods Clinical data of 231 pairs of donors and recipients undergoing SPK were analyzed retrospectively. The pathogens of samples from donors and recipients were identified by VITEK-2 analyzer, and drug sensitivity test was performed by K-B method. The source distribution and composition ratio of pathogens in donor and recipient samples, distribution characteristics of multi-drug resistant organism, infection of recipients and drug resistance characteristics of pathogens were analyzed. Results A total of 395 strains of pathogens were cultured from 1 294 donor samples, and the detection rate was 30.53%. Gram-negative bacteria mainly consisted of klebsiella pneumoniae, Gram-positive bacteria mainly comprised staphylococcus aureus, and fungi primarily included candida albicans, respectively. In total, 2 690 strains of pathogens were cultured from 10 507 recipient samples, and the detection rate was 25.60%. Gram-negative bacteria mainly consisted of pseudomonas maltophilia, Gram-positive bacteria primarily comprised enterococcus faecalis, and fungi mainly included candida albicans, respectively. Among 395 pathogens of donors, 15 strains of methicillin-resistant staphylococcus aureus (MRSA), 16 strains of extended-spectrum β-lactamase (ESBL) positive drug-resistant bacteria, 8 strains of carbapenem-resistant pseudomonas aeruginosa (CR-PA), 21 strains of carbapenem-resistant acinetobacter baumannii (CR-AB), 2 strains of carbapenem-resistant enterobacteriaceae (CRE) and 1 strain of multiple-drug/pan-drug resistant pseudomonas aeruginosa (MDR/PDR-PA) were identified. Among 2 690 strains of recipient pathogens, 73 strains of ESBL positive drug-resistant bacteria, 44 strains of CR-PA, 31 strains of CR-AB and 3 strains of MDR/PDR-PA were detected. One recipient developed donor-derived infection, 69 cases of pneumonia, 52 cases of urinary tract infection, 35 cases of abdominal infection and 2 cases of hematogenous infection were reported within postoperative 1 year. Gram-negative bacteria were resistant to certain antibiotics. Gram-positive bacteria were sensitive to vancomycin. Fungi were sensitive to amphotericin B. Conclusions Gram-negative bacteria are the main pathogens of SPK recipients, which are resistant to certain antibiotics. Empirical use of antibiotics can be delivered before culture results are obtained. Subsequently, sensitive antibiotics should be chosen according to the culture results to improve the survival rate of SPK recipients.

Evolution and development of potent monobactam sulfonate candidate IMBZ18g as a dual inhibitor against MDR Gram-negative bacteria producing ESBLs

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Temporal association between antibiotic use and resistance in Gram-negative bacteria / Associação temporal entre o uso de antibióticos e resistência em bactérias gram-negativas

The β-lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p<0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.

Os medicamentos combinados de β-lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p < 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.

Temporal association between antibiotic use and resistance in Gram-negative bacteria

Abstract The -lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p 0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.

Resumo Os medicamentos combinados de -lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.

Temporal association between antibiotic use and resistance in Gram-negative bacteria / Associação temporal entre o uso de antibióticos e resistência em bactérias gram-negativas

Abstract The β-lactam/lactamase inhibitors (BLBLIs) combination drugs are considered an effective alternative to carbapenems. However, there is a growing concern that the increased use of BLBLIs may lead to increased resistance. This study determined the temporal association between the consumption of BLBLI and the antimicrobial resistance in Gram-negative bacteria. In this retrospective study, electronic data on the Gram-negative bacterial isolates, including A. baumannii, P. aeruginosa, E. coli, and K. pneumoniae from in-patients and susceptibility testing results were retrieved from the medical records of the clinical laboratory. A linear regression and cross-correlation analysis were performed on the acquired data. Increasing trends (p<0.05) in the consumption of BIBLI and carbapenem with a median use of 27.68 and 34.46 DDD/1000 PD per quarter were observed, respectively. A decreased trend (p=0.023) in the consumption of fluoroquinolones with a median use of 29.13 DDD/1000 PD per quarter was observed. The resistance rate of K. pneumoniae was synchronized with the BIBLI and carbapenem consumptions with a correlation coefficient of 0.893 (p=0.012) and 0.951 (p=0.016), respectively. The cross-correlation analysis against the consumption of BIBLI and meropenem resistant K. pneumoniae was peaked at 0-quarter lag (r=951, p=0.016). There was an increasing trend in the consumption of BLBLI and carbapenems. The increasing trend in the rates of resistance to piperacillin/tazobactam, in line with the increasing consumption of BLBLI, suggests that BLBLI has to be used with caution and cannot be directly considered as a long-term alternative to carbapenems.

Resumo Os medicamentos combinados de β-lactâmicos / inibidores da lactamase (BLBLIs) são considerados uma alternativa eficaz aos carbapenêmicos. No entanto, existe uma preocupação crescente de que o aumento do uso de BLBLIs pode levar ao aumento da resistência. Este estudo determinou a associação temporal entre o consumo de BLBLI e a resistência antimicrobiana em bactérias gram-negativas. Neste estudo retrospectivo, os dados eletrônicos sobre as bactérias gram-negativas isoladas, incluindo A. baumannii, P. aeruginosa, E. coli e K. pneumoniae de pacientes internados e os resultados dos testes de suscetibilidade foram recuperados dos registros médicos do laboratório clínico. Uma regressão linear e análise de correlação cruzada foram realizadas nos dados adquiridos. Foram observadas tendências crescentes (p < 0,05) no consumo de BIBLI e carbapenem com uma mediana de uso de 27,68 e 34,46 DDD/1000 PD por trimestre, respectivamente. Foi observada uma tendência de diminuição (p = 0,023) no consumo de fluoroquinolonas com uma mediana de uso de 29,13 DDD/1000 PD por trimestre. A taxa de resistência de K. pneumoniae foi sincronizada com os consumos de BIBLI e carbapenem com coeficiente de correlação de 0,893 (p = 0,012) e 0,951 (p = 0,016), respectivamente. A análise de correlação cruzada contra o consumo de BIBLI e K. pneumoniae resistente ao meropenem atingiu o pico no intervalo de 0 quarto (r = 951, p = 0,016). Houve uma tendência de aumento no consumo de BLBLI e carbapenêmicos. A tendência crescente nas taxas de resistência a piperacilina/tazobactam, em linha com o consumo crescente de BLBLI, sugere que BLBLI deve ser usado com cautela e não pode ser considerado diretamente como alternativa de longo prazo aos carbapenêmicos.

Evaluation of in-vitro susceptibility of ß-lactam-resistant Gram-negative bacilli to ceftazidime-avibactam and ceftolozane-tazobactam from clinical samples of a general hospital in southern Brazil

ABSTRACT Background: The spread of carbapenemase- and extended-spectrum β-lactamase (ESBL)-producing gram-negative bacilli (GNB) represent a global public health threat that limits therapeutic options for hospitalized patients. This study aimed to evaluate the in-vitro susceptibility of β-lactam-resistant GNB to ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T), and investigate the molecular determinants of resistance. Methods: Overall, 101 clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected from a general hospital in Brazil were analyzed. Susceptibility to the antimicrobial agents was evaluated using an automated method, and the minimum inhibitory concentrations (MIC50/90) of C/A and C/T were determined using Etest®. The β-lactamase-encoding genes were investigated using polymerase chain reaction. Results: High susceptibility to C/A and C/T was observed among ESBL-producing Enterobacterales (100% and 97.3% for CLSI and 83.8% for BRCAST, respectively) and carbapenem-resistant P. aeruginosa (92.3% and 87.2%, respectively). Carbapenemase-producing Klebsiella pneumoniae exhibited high resistance to C/T (80%- CLSI or 100%- BRCAST) but high susceptibility to C/A (93.4%). All carbapenem-resistant K. pneumoniae isolates were susceptible to C/A, whereas only one isolate was susceptible to C/T. Both antimicrobials were inactive against metallo-β-lactamase-producing K. pneumoniae isolates. Resistance genes were concomitantly identified in 44 (44.9%) isolates, with bla CTX-M and bla SHV being the most common. Conclusions: C/A and C/T were active against microorganisms with β-lactam-resistant phenotypes, except when resistance was mediated by metallo-β-lactamases. Most C/A- and C/T-resistant isolates concomitantly carried two or more β-lactamase-encoding genes (62.5% and 77.4%, respectively).

Prevalence of bloodstream infection pathogens in hemato-oncological patients and predictors of carbapenem-resistant gram-negative bacterial infections during febrile neutropenia

ABSTRACT Background: Carbapenem-Resistant Gram-Negative (CRGN) Bloodstream Infections (BSI) represent a therapeutic challenge, especially in the context of Febrile Neutropenia (FN) in cancer patients. Methods: We characterized pathogens causing BSI in patients aged ≥18 years who had undergone systemic chemotherapy for solid or hematological cancers between 2012 and 2021 in Porto Alegre, Brazil. Predictors of CRGN were evaluated through a case-control analysis. Each case was matched to two controls from whom CRGN were not isolated and had the same sex and year of inclusion in the study. Results: From 6094 blood cultures evaluated, 1512 (24.8%) showed positive results. Gram-negative bacteria accounted for 537 (35.5%) of the isolated bacteria, of which 93 (17.3%) were carbapenem-resistant. From 105 patients included in the case-control analysis, all cases had baseline hematological malignancies (60% acute myeloid leukemia). Variables related to CRGN BSI in Cox regression analysis were the first chemotherapy session (p<0.01), chemotherapy performed in the hospital setting (p = 0.03), intensive care unit admission (p<0.01), and CRGN isolation in the previous year (p<0.01). Patients with CRGN BSI received 75% less empirical active antibiotics and had 27.2% higher 30-day mortality rates than controls. Conclusions: A CRGN risk-guided approach should be considered for empirical antibiotic therapy in patients with FN.

BRICS report of 2021: The distribution and antimicrobial resistance profile of clinical bacterial isolates from blood stream infections in China / 中华临床感染病杂志

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.

Randomized Control Study of Nebulized Colistin as an Adjunctive Therapy in Ventilator?Associated Pneumonia in Pediatric Postoperative Cardiac Surgical Population

Background:Ventilator?associated pneumonia (VAP) with multidrug?resistant (MDR) gram negative organisms is a common problem in intensive care unit (ICU). Aerosolized antibiotics enhance the efficacy of systemic antibiotics when added as adjuvants. Aim: The primary objective of the study was to compare the clinical and bacteriological outcome of patients with VAP who were administered intravenous (IV) antibiotics alone with those patients who were treated with adjunctive nebulized colistin (NC) along with IV antibiotics. The secondary objective was to study the occurrence of any adverse events during colistin nebulization. Settings and Design: The study was a prospective, randomized, double?blinded controlled study conducted at a tertiary?care teaching institution. Materials and Methods: Ninety?eight children from surgical ICU aged less than 12 years who were diagnosed with VAP due to gram negative bacteria following cardiac surgery were chosen and divided randomly into two groups. The experimental group (NC group) was treated with systemic antibiotics along with NC, whereas the control group (NS group) was administered systemic antibiotics with nebulized normal saline (NS). Clinical and bacteriological outcomes were noted. Statistical analysis was done using SPSS Version 20.0 software. The patient characteristics were compared using independent Student’s t test and Chi?square test. Results: There was a statistically significant reduction in the duration of mechanical ventilation, postoperative ICU and hospital stay (P < 0.05) in the NC group compared with the NS group. Conclusion: Aerosolized colistin may be considered as an adjunct to systemic IV antibiotics in pediatric patients with VAP due to gram negative bacteria susceptible to colistin.

Infección urinaria de presentación atípica: caso clínico y revisión de literatura

Introducción: el síndrome de orina púrpura es una presentación clínica poco frecuente en el ámbito de urgencias, caracterizado por coloración anormal de la orina secundaria a una reacción química de algunos patógenos que producen infección de vías urinarias, siendo más frecuente en pacientes con múltiples comorbilidades y diferentes factores de riesgo. Objetivo: el objetivo de este manuscrito es presentar el caso de un paciente con síntomas atípicos de infección de vías urinarias. Presentación del caso: varón de 88 años de edad, con antecedente de diabetes mellitus no insulino-requiriente, con hiperplasia prostática benigna que ingresó al servicio de urgencias por síntomas irritativos urinarios asociados a uso de sonda vesical, con orina de coloración violeta en bolsa recolectora. El urocultivo reportó la presencia de Proteus vulgaris multisensible, por lo que se decidió dar manejo con cefepima de 1 gr cada ocho horas, con lo cual se obtuvo una adecuada evolución clínica. Discusión y conclusión: el síndrome de la bolsa de orina púrpura es una presentación clínica atípica, pero muy llamativa de la infección urinaria. Esta se genera como resultado de la conversión del triptófano en la dieta en indoxil sulfato que, una vez se elimina por la orina, se transforma en índigo (color violeta) e indirrubina (color rojo), dando este aspecto clínico.

Background: Purple urine syndrome is a rare clinical presentation in the emergency room, characterized by abnormal colouration of the urine secondary to a chemical reaction of some pathogens that cause urinary tract infection, being more frequent in patients with multiple comorbidities and different risk factor's. Purpose: The objective of the article is present the case of a patient with atypical symptoms of urinary tract infection. Clinical case: An 88-year-old male, with a history of non-insulin diabetes mellitus, benign prostatic hyperplasia, who was admitted to the emergency room due to irritative urinary symptoms associated with the use of a urinary catheter, with purple urine in a collection bag. Urine culture reported the presence of multisensitive Proteus vulgaris, for which it was decided to give treatment with Cefepime 1 g every 8 hours, with which it was obtained with adequate clinical evolution. Conclusions: Purple urine bag syndrome is an atypical but very striking clinical presentation of urinary tract infection. This is generated as a result of the conversion of tryptophan in the diet into indoxyl sulfate, which, once it is eliminated in the urine, transforms into indigo (purple color) and indirubin (red color), giving this clinical appearance.