RESUMEN

Infections with multidrug-resistant gram-negative bacterial species are a great concern in clinics in Germany. By limiting therapeutic options dramatically, these bacteria pose a significant threat to patient health and cause extensive pressure on hygiene systems and patient management. In Germany, the recommendations on how to deal with these bacteria are called MRGN classification, using the terms 3MRGN and 4MRGN for bacteria resistant to three or four major classes of antibiotics. To be resistant to this large number of antibiotics and become classified as 3MRGN or 4MRGN, bacterial strains need to acquire multiple resistance mechanisms with beta-lactamases, especially carbapenemases, being the most important ones. According to established surveillance systems like national reporting systems, KISS or the National Reference Centre, multidrug-resistant bacteria are constantly on the rise in Germany. Although several novel therapeutic options have been approved recently, these bacteria represent a constant challenge and it may be necessary to discuss if the present hygiene recommendations need an update for an efficient and targeted prevention of transmission.

Asunto(s)

Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Alemania , Humanos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/epidemiología , Bacterias Gramnegativas/efectos de los fármacos , Prevalencia , Antibacterianos/uso terapéutico

RESUMEN

Colistin resistance testing methods such as broth microdilution (BMD) are time-consuming and labour intensive for clinical laboratories. MBT Lipid Xtract Kit on MALDI Biotyper Sirius System (Bruker, Billerica, MA, USA) utilizes lipidomic analysis to identify specific cell wall modifications associated with colistin resistance. We compared MBT to BMD (ComASP Colistin, Liofilchem) across 36 Gram-negative isolates (non-resistant MIC ≤2 µg ml-1, resistant MIC ≥4 µg ml-1). All samples were tested twice on MBT with discrepant results repeated before assessing categorical agreement between MBT and BMD. 44.4% (16/36) of isolates were colistin resistant via BMD. MBT Lipid Xtract had 80.6% agreement (29/36) with BMD, with 5/7 discrepancies corrected to match upon repeat testing. There was 100% agreement for Escherichia coli isolates (n=16). The whole-genome sequencing was completed on the two discrepant Klebsiella pneumoniae isolates, with variants within colistin resistance-associated loci identified (MIC 0.5 µg ml-1: arnC S30T, pmrB T246A, lapB N212T, lpxM S253G, crrB Q287K and MIC >16 µg ml-1: arnC S30T, pmrB R90insRN, pmrB T246A, pmrA E57G, lpxM S253G). Further evaluation, particularly for non-E. coli, of MBT is required prior to implementation in clinical laboratories.

Asunto(s)

Antibacterianos , Colistina , Farmacorresistencia Bacteriana , Pruebas de Sensibilidad Microbiana , Colistina/farmacología , Antibacterianos/farmacología , Humanos , Bacterias Gramnegativas/efectos de los fármacos , Secuenciación Completa del Genoma , Escherichia coli/efectos de los fármacos , Escherichia coli/genética

RESUMEN

We evaluated the performance of Zybio EXS2600 matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Zybio Inc., Chongqing, China) for the identification of bacteria from positive blood culture (BC) bottles using Blood Culture Positive Sample Pretreatment Kit (Zybio Inc., Chongqing, China) in comparison to an in-house saponin method. Following a positive signal by the BACTEC™ FX system, confirmation of identification was achieved using subcultured growing biomass used for MALDI-TOF MS analysis. A total of 94 positive BC bottles with 97 bacterial isolates were analyzed. The overall identification rates at the genus and species levels for the saponin method were 89.7% (87/97) and 74.2% (72/97), respectively. With the Zybio Kit, 88.7% (86/97) and 80.4% (78/97) of microorganisms were correctly identified to the genus and species levels, respectively. The saponin method identified 65.3% (32/49) of Gram-positive bacteria at the species level, whereas the Zybio Kit achieved a higher species-level identification rate of 79.6% (39/49) (p = 0.1153). The saponin method with additional on-plate formic acid extraction showed a significantly higher overall identification rate in comparison to the saponin method without that step for both genus (87.6% [85/97] vs. 70.1% [68/97], p = 0.0029) and species level (70.1% [68/97] vs. 46.4% [45/97], p = 0.0008). Identification rates of Gram-negative bacteria showed a higher identification rate, however, not statistically significant with additional Zybio Kit protocol step on both genus (85.4% [41/48] vs. 81.3% [39/48], p = 0.5858) and species level (77.1% [37/48] vs. 75% [36/48], p = 0.8120). Zybio Kit could offer an advantage in species-level identification, particularly for Gram-positive bacteria. The inclusion of on-plate formic acid extraction in the saponin method notably enhanced identification at both genus and species levels for Gram-positive bacteria. The extended protocol provided by the Zybio Kit could potentially offer an advantage in the identification of Gram-negative bacteria at both genus and species levels. Enhancements to the Zybio EXS2600 MALDI-TOF instrument software database are necessary.

Asunto(s)

Bacterias , Cultivo de Sangre , Saponinas , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Saponinas/química , Saponinas/análisis , Humanos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias/química , Cultivo de Sangre/métodos , Bacterias Gramnegativas/aislamiento & purificación , Juego de Reactivos para Diagnóstico , Bacterias Grampositivas/aislamiento & purificación , Bacterias Grampositivas/clasificación , Técnicas de Tipificación Bacteriana/métodos

RESUMEN

Colistin is one of the last-resort antibiotics in treating infections caused by multidrug-resistant (MDR) pathogens. Unfortunately, the emergence of colistin-resistant gram-negative strains limit its clinical application. Here, we identify an FDA-approved drug, valnemulin (Val), exhibit a synergistic effect with colistin in eradicating both colistin-resistant and colistin-susceptible gram-negative pathogens both in vitro and in the mouse infection model. Furthermore, Val acts synergistically with colistin in eliminating intracellular bacteria in vitro. Functional studies and transcriptional analysis confirm that the combinational use of Val and colistin could cause membrane permeabilization, proton motive force dissipation, reduction in intracellular ATP level, and suppression in bacterial motility, which result in bacterial membrane disruption and finally cell death. Our findings reveal the potential of Val as a colistin adjuvant to combat MDR bacterial pathogens and treat recalcitrant infections.

Asunto(s)

Antibacterianos , Colistina , Diterpenos , Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Colistina/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Animales , Antibacterianos/farmacología , Ratones , Diterpenos/farmacología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Bacterias Gramnegativas/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Humanos

RESUMEN

BACKGROUND: Antimicrobial resistance is a major global public health issue. Infections caused by resistant species are associated with higher mortality rates, longer hospital stays, medication failure, and rising medical costs. The World Health Organisation has declared multidrug resistance-associated infections as an epidemic of public health concern. OBJECTIVE: This study aimed to evaluate the antimicrobial resistance profile and associated factors of hospital-acquired Gram-negative bacterial pathogens among hospitalized patients in Northeast Ethiopia. MATERIALS AND METHODS: A health facility-based cross-sectional study was conducted among hospitalized patients from March 2021 to February 2022. About 810 clinical specimens were collected, transported, and processed from admitted patients following the standard bacteriological procedures. The clinical samples were inoculated onto blood agar, MacConkey agar, and chocolate agar. Furthermore, the species identification was done using gram reactions, colony morphology, and color and biochemical tests. Antimicrobial susceptibility tests, extended-spectrum beta-lactamase, and carbapenemase production were performed as per the clinical laboratory standard institute guidelines. For analysis, the information was entered into Epi-data and exported to SPSS. A P value of < 0.05 with a 95% confidence interval was considered as a statistically significant association. RESULTS: Out of 810 clinical specimens, 285/810 (35.2%) developed bacterial infections. From the isolated bacteria, E. coli was the predominant bacteria accounting for 78/285 (27.4%) followed by K. pneumoniae, 69/285(24.42%), whereas P. vulgaris accounted for the least, 7/285 (2.5%). Overall, 132/285 (46.3%) and 99/285 (34.7%) of culture-positive patients were infected by extended-spectrum beta-lactamase and carbapenemase-producing bacteria. The overall multidrug resistance rate of the isolated bacteria was 89.4%. The highest antibiotic resistance rates were detected for doxycycline (92.9%), amoxicillin-clavulanic acid (83.9%), and ampicillin (93%). The least antibiotic resistance rate was observed for meropenem at 41.1% and amikacin at 1.7%, respectively. CONCLUSIONS AND RECOMMENDATIONS: In the study area, significant health concerns include a range of hospital-acquired bacterial infections associated with elevated rates of multidrug resistance, Extended-spectrum beta-lactamase (ESBL), and carbapenemase-producing bacterial pathogens. Consequently, it is recommended to conduct drug-susceptibility testing of isolates and molecular detection at a national level to optimize antibiotic usage for treating prevalent bacterial infections in this area.

Asunto(s)

Antibacterianos , Infección Hospitalaria , Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Humanos , Etiopía/epidemiología , Estudios Transversales , Masculino , Femenino , Adulto , Persona de Mediana Edad , Antibacterianos/farmacología , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Gramnegativas/clasificación , Bacterias Gramnegativas/genética , Adulto Joven , Adolescente , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/genética , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Anciano , Niño , Preescolar , Lactante , Hospitalización/estadística & datos numéricos , Proteínas Bacterianas/genética , Anciano de 80 o más Años

RESUMEN

Silver nanoparticles (AgNPs) synthesized from plant extracts have gained attention for their potential applications in biomedicine. Calotropis gigantea has been utilized to synthesize AgNPs, called AgNPs-LCg, and exhibit antibacterial activities against both Gram-positive and Gram-negative bacteria as well as antifungal. However, further enhancement of their antimicrobial properties is needed. The aim of this study was to synthesize AgNPs-LCg and to enhance their antimicrobial and antifungal activities through a hybrid green synthesis reaction using patchouli oil (PO), as well as to characterize the synthesized AgNPs-LCg. Optimization was conducted using the response surface method (RSM) with a central composite design (CCD). AgNPs-LCg were synthesized under optimal conditions and hybridized with different forms of PO-crude, distillation wastewater (hydrolate), and heavy and light fractions-resulting in PO-AgNPs-LCg, PH-AgNPs-LCg, LP-AgNPs-LCg, and HP-AgNPs-LCg, respectively. The samples were then tested for their antibacterial (both Gram-positive and Gram-negative bacteria) and antifungal activities. Our data indicated that all samples, including those with distillation wastewater, had enhanced antimicrobial activity. HP-AgNPs-LCg, however, had the highest efficacy; therefore, only HP-AgNPs-LCg proceeded to the characterization stage for comparison with AgNPs-LCg. UV-Vis spectrophotometry indicated surface plasmon resonance (SPR) peaks at 400 nm for AgNPs-LCg and 360 nm for HP-AgNPs-LCg. The Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of O-H, N-H, and C-H groups in C. gigantea extract and AgNP samples. The smallest AgNPs-LCg were 56 nm, indicating successful RSM optimization. Scanning electron microscopy (SEM) analysis revealed spherical AgNPs-LCg and primarily cubic HP-AgNPs-LCg, with energy-dispersive X-ray spectroscopy (EDX) confirming silver's predominance. This study demonstrated that PO in any form significantly enhances the antimicrobial properties of AgNPs-LCg. The findings pave the way for the exploration of enhanced and environmentally sustainable antimicrobial agents, capitalizing on the natural resources found in Aceh Province, Indonesia.

Asunto(s)

Calotropis , Tecnología Química Verde , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Hojas de la Planta , Plata , Nanopartículas del Metal/química , Plata/química , Plata/farmacología , Tecnología Química Verde/métodos , Hojas de la Planta/química , Calotropis/química , Bacterias Grampositivas/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Aceites de Plantas/farmacología , Aceites de Plantas/química

RESUMEN

The emergence of multidrug-resistant (MDR) infections in wounds is a significant public health issue. The aim of this study was to investigate the prevalence and antimicrobial resistance profiles of MDR bacterial isolates in wound infections. Through a cross-sectional study, 1,035 bacterial isolates were collected from wound infection patients at Tugurejo Hospital in Semarang, Indonesia, over a three-year period (from January 2020 to December 2022). Initial identification involved Gram staining and colony morphology assessment, followed by biochemical assays and antimicrobial susceptibility testing using the VITEK®2 Compact system. Gram-negative bacteria constituted the majority of isolates (60.77%, n=629). The predominant strains included were Staphylococcus spp. (30.92%, n=320), Escherichia coli (18.45%, n=191), and Klebsiella pneumoniae (13.04%, n=135). Notably, Gram-negative bacteria exhibited a significantly higher likelihood of MDR development compared to their Gram-positive counterparts (p<0.001), with Gram-negative bacteria having a 2.05 times higher probability of acquiring MDR. These findings underscore the urgent need for comprehensive surveillance of antimicrobial resistance patterns and the implementation of tailored antimicrobial stewardship programs to address the pressing public health challenge of MDR wound infections. Further research is warranted to elucidate the complex interplay of factors contributing to MDR development in wound infections, thereby informing targeted intervention strategies and improving patient outcomes.

Asunto(s)

Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Infección de Heridas , Humanos , Indonesia/epidemiología , Estudios Transversales , Infección de Heridas/microbiología , Infección de Heridas/epidemiología , Infección de Heridas/tratamiento farmacológico , Prevalencia , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Anciano

RESUMEN

BACKGROUND: Gram-negative bacteria resistant to carbapenems are also known as critical antimicrobial resistant organisms. Their emergence at Colonial War Memorial Hospital (CWMH), the largest hospital in Fiji, is a major clinical concern. This study was conducted to determine the knowledge, attitudes, and readiness of healthcare workers (HCW) at CWMH regarding management of patients with infections caused by critical antimicrobial resistant organisms. METHODS: A questionnaire was designed using a Likert scale to assess knowledge, attitudes, and readiness. Two cross-sectional studies were conducted, before and after the implementation of targeted educational activities which were informed by the pre-intervention study findings. RESULTS: A total of 393 and 420 HCW participated in the pre- and post-intervention studies, respectively. The majority of respondents were female (77.3%) and 18-34 years of age (67%). HCW professional roles included nurses (56.3%), doctors (31.6%), and laboratory personnel (12.2%). In the post-intervention study, significantly more HCW reported having received infection prevention and control (IPC) and antimicrobial resistance education and training (26.8% in pre to 45.5% in post intervention, p < 0.001). The majority of nurses and doctors (> 85% to ≥ 95%) were aware of how AMR organisms spread in healthcare settings and knew the IPC measures to prevent transmission of AMR infections including hand hygiene, standard and transmission-based precautions. Attitudes towards AMR were positive, with 84.2% pre intervention and 84.8% of HCW post intervention expressing their willingness to change their work environment to assist with AMR prevention. Perceived readiness to address the problem showed mixed results. Improvements in laboratory AMR surveillance data availability were noted (29.4-52.4%, p < 0001). Modest improvement in the hospital's capacity for outbreak response (44-51.9%, p = 0.01), and treatment of AMR infections (38.9-44.4%, p = 0.01) was reported. CONCLUSIONS: Our data revealed high levels of staff awareness and knowledge about AMR and IPC. However, readiness for outbreak response and treatment of critical AMR infections requires more attention. Improving AMR prevention and containment in CWMH will likely require sustained and multisectoral interventions with strong administrative commitment.

Asunto(s)

Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Humanos , Femenino , Masculino , Fiji , Adulto , Estudios Transversales , Personal de Salud/psicología , Adulto Joven , Encuestas y Cuestionarios , Adolescente , Control de Infecciones/métodos , Persona de Mediana Edad , Infección Hospitalaria/microbiología , Hospitales Militares , Actitud del Personal de Salud , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas

RESUMEN

Current pharmacotherapy remains futile in acute alveolar inflammation induced by Gram-negative bacteria (GNB), eliciting consequent respiratory failure. The release of lipid polysaccharides after antibiotic treatment and subsequent progress of proinflammatory cascade highlights the necessity to apply effective inflammation management simultaneously. This work describes modular self-assembling peptides for rapid anti-inflammatory programming (SPRAY) to form nanoparticles targeting macrophage specifically, having anti-inflammation and bactericidal functions synchronously. SPRAY nanoparticles accelerate the self-delivery process in macrophages via lysosomal membrane permeabilization, maintaining anti-inflammatory programming in macrophages with efficacy close to T helper 2 cytokines. By pulmonary deposition, SPRAY nanoparticles effectively suppress inflammatory infiltration and promote alveoli regeneration in murine aseptic acute lung injury. Moreover, SPRAY nanoparticles efficiently eradicate multidrug-resistant GNB in alveoli by disrupting bacterial membrane. The universal molecular design of SPRAY nanoparticles provides a robust and clinically unseen local strategy in reverse acute inflammation featured by a high accumulation of proinflammatory cellularity and drug-resistant bacteria.

Asunto(s)

Infecciones por Bacterias Gramnegativas , Nanopartículas , Animales , Ratones , Nanopartículas/química , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Péptidos/química , Péptidos/farmacología , Péptidos/administración & dosificación , Bacterias Gramnegativas/efectos de los fármacos , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/patología , Alveolos Pulmonares/metabolismo , Administración por Inhalación , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Inflamación/patología

RESUMEN

The emission of glyphosate and antibiotic residues from human activities threatens the diversity and functioning of the microbial community. This study examines the impact of a glyphosate-based herbicide (GBH) and common antibiotics on Gram-negative bacteria within the ESKAPEE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli). Ten strains, including type and multidrug-resistant strains for each species were analysed and eight antibiotics (cefotaxime, meropenem, aztreonam, ciprofloxacin, gentamicin, tigecycline, sulfamethoxazole-trimethoprim, and colistin) were combined with the GBH. While most combinations yielded additive or indifferent effects in 70 associations, antagonistic effects were observed with ciprofloxacin and gentamicin in five strains. GBH notably decreased the minimum inhibitory concentration of colistin in eight strains and displayed synergistic activity with meropenem against metallo-ß-lactamase (MBL)-producing strains. Investigation into the effect of GBH properties on outer membrane permeability involved exposing strains to a combination of this GBH and vancomycin. Results indicated that GBH rendered strains sensitive to vancomycin, which is typically ineffective against Gram-negative bacteria. Furthermore, we examined the impact of GBH in combination with three carbapenem agents on 14 strains exhibiting varying carbapenem-resistance mechanisms to assess its effect on carbapenemase activity. The GBH efficiently inhibited MBL activity, demonstrating similar effects to EDTA (ethylenediaminetetraacetic acid). Chelating effect of GBH may have multifaceted impacts on bacterial cells, potentially by increasing outer membrane permeability and inactivating metalloenzyme activity.

Asunto(s)

Acinetobacter baumannii , Antibacterianos , Glicina , Glifosato , Bacterias Gramnegativas , Herbicidas , Pruebas de Sensibilidad Microbiana , Glicina/análogos & derivados , Glicina/farmacología , Antibacterianos/farmacología , Herbicidas/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Acinetobacter baumannii/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Humanos , Escherichia coli/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Ciprofloxacina/farmacología , Enterococcus faecium/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Colistina/farmacología , Vancomicina/farmacología , Enterobacter/efectos de los fármacos , Sinergismo Farmacológico , Meropenem/farmacología , Fenotipo , Gentamicinas/farmacología

RESUMEN

BACKGROUND: Continuous monitoring of antimicrobial resistance (AMR) in Uganda involves testing bacterial isolates from clinical samples at national and regional hospitals. Although the National Microbiology Reference Laboratory (NMRL) analyzes these isolates for official AMR surveillance data, there's limited integration into public health planning. To enhance the utilization of NMRL data to better inform drug selection and public health strategies in combating antibiotic resistance, we evaluated the trends and spatial distribution of AMR to common antibiotics used in Uganda. METHODS: We analyzed data from pathogenic bacterial isolates from blood, cerebrospinal, peritoneal, and pleural fluid from AMR surveillance data for 2018-2021. We calculated the proportions of isolates that were resistant to common antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR resistance over the study period. RESULTS: Out of 537 isolates with 15 pathogenic bacteria, 478 (89%) were from blood, 34 (6.3%) were from pleural fluid, 21 (4%) were from cerebrospinal fluid, and 4 (0.7%) were from peritoneal fluid. The most common pathogen was Staphylococcus aureus (20.1%), followed by Salmonella species (18.8%). The overall change in resistance over the four years was 63-84% for sulfonamides, fluoroquinolones macrolides (46-76%), phenicols (48-71%), penicillins (42-97%), ß-lactamase inhibitors (20-92%), aminoglycosides (17-53%), cephalosporins (8.3-90%), carbapenems (5.3-26%), and glycopeptides (0-20%). There was a fluctuation in resistance of Staphylococcus aureus to methicillin (60%-45%) (using cefoxitin resistance as a surrogate for oxacillin resistance) Among gram-negative organisms, there were increases in resistance to tetracycline (29-78% p < 0.001), ciprofloxacin (17-43%, p = 0.004), ceftriaxone (8-72%, p = 0.003), imipenem (6-26%, p = 0.004), and meropenem (7-18%, p = 0.03). CONCLUSION: The study highlights a concerning increase in antibiotic resistance rates over four years, with significant increase in resistance observed across different classes of antibiotics for both gram-positive and gram-negative organisms. This increased antibiotic resistance, particularly to commonly used antibiotics like ceftriaxone and ciprofloxacin, makes adhering to the WHO's Access, Watch, and Reserve (AWaRe) category even more critical. It also emphasizes how important it is to guard against the growing threat of antibiotic resistance by appropriately using medicines, especially those that are marked for "Watch" or "Reserve."

Asunto(s)

Antibacterianos , Farmacorresistencia Bacteriana , Humanos , Uganda/epidemiología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/tratamiento farmacológico , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación

RESUMEN

Antimicrobial resistance is currently recognized as an urgent concern against public health in worldwide. Carbapenem-resistant (CR) Gram-negative bacteria, such as Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii are listed as critical pathogens which are widely spread and can cause severe and often deadly infections in WHO guidance. Cefiderocol (Fetroja®), a novel and first siderophore cephalosporin, was approved for the infections caused by these problematic CR Gram-negative bacteria in Japan on November 30, 2023. Cefiderocol has unique mechanisms to be incorporated into bacterial cells using bacterial iron transportation system and to be highly stable against most ß-lactamases, which lead to promising antibacterial activity against these Gram-negative bacteria including CR strains in vitro. In CREDIBLE-CR Ph3 trial, cefiderocol showed the good efficacy and safety for patients with CR Gram-negative bacteria. In APEKS-cUTI and APEKS-NP trials, cefiderocol showed non-inferiority and suggested superiority to imipenem/cilastatin in complicated urinary tract infection (cUTI) patients, and non-inferiority to high dose of meropemen in pneumonia patients, respectively. Cefiderocol is expected to be an optimal treatment for CR Gram-negative infections with limited treatment options and would be an important drug to combat the threat of CR bacteria.

Asunto(s)

Antibacterianos , Carbapenémicos , Cefiderocol , Cefalosporinas , Infecciones por Bacterias Gramnegativas , Sideróforos , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Cefiderocol/farmacología , Cefiderocol/uso terapéutico , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Sideróforos/farmacología

RESUMEN

Bacterial growing resistance to antibiotics poses a critical threat to global health. This study investigates, for the first time, the antibiofilm properties of Vicia ervilia agglutinin (VEA) from six different V. ervilia accessions against pathogenic bacteria, and the yeast Candida albicans. In the absence of antimicrobial properties, purified VEA significantly inhibited biofilm formation, both in Gram-positive and Gram-negative bacteria, but not in C. albicans. With an inhibitory concentration ranging from 100 to 500 µg/ml, the VEA antibiofilm activity was more relevant against the Gram-positive bacteria Streptococcus aureus and Staphylococcus epidermidis, whose biofilm was reduced up to 50% by VEA purified from accessions #5 and #36. VEA antibiofilm variability between accessions was observed, likely due to co-purified small molecules rather than differences in VEA protein sequences. In conclusion, VEA seed extracts from the accessions with the highest antibiofilm activity could represent a valid approach for the development of an effective antibiofilm agent.

Asunto(s)

Antibacterianos , Biopelículas , Candida albicans , Bacterias Gramnegativas , Bacterias Grampositivas , Pruebas de Sensibilidad Microbiana , Biopelículas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Candida albicans/fisiología , Antibacterianos/farmacología , Lectinas de Plantas/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Semillas/química

RESUMEN

Endophytic bacteria found in marine macroalgae have been studied for their potential antimicrobial activity, consequently, they could serve as a valuable source of bioactive compounds to control pathogenic bacteria, yeasts, and fungi. Algae endophytic bacteria were isolated from Caulerpa sp., Ulva sp., Ahnfeltiopsis sp., and Chondracantus chamissoi from Yacila and Cangrejo Beaches (Piura, Peru). Antimicrobial assays against pathogenic bacteria were evaluated using cross-culture, over-plate, and volatile organic compound tests. Afterward, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of selected crude extracts were determined, also ITS molecular analysis, antifungal activity, and PCR of iturin, fengycin, and surfactin genes were performed for bacteria strains exhibiting better activity. Forty-six algae endophytic bacteria were isolated from algae. Ten strains inhibited gram-positive pathogenic bacteria (Enterococcus faecalis, Staphylococcus epidermidis, S. aureus, and Listeria monocytogenes), and 12 inhibited gram-negative bacteria (Escherichia coli and Salmonella enteric sv typhimurium). Bacteria with better activity belong to Bacillus sp., Kluyvera ascorbata, Pantoea agglomerans, Leclercia adecarboxylata, and Enterobacter sp., which only four showed antifungal activities against Candida albicans, C. tropicalis, Colletotrichium sp., Fusarium sp., Fusarium oxysporum, and Alternaria sp. Furthermore, K. ascorbata YAFE21 and Bacillus sp. YCFE4 exhibited iturin and fengycin genes. The results indicate that the algae endophytic bacteria found in this study, particularly K. ascorbata YAFE21, Bacillus sp. YCFR6, L. adecarboxylata CUFE2, Bacillus sp. YUFE8, Enterobacter sp. YAFL1, and P. agglomerans YAFL6, could be investigated as potential producers of antimicrobial compounds due to their broad activity against various microorganisms.

Asunto(s)

Endófitos , Pruebas de Sensibilidad Microbiana , Algas Marinas , Endófitos/aislamiento & purificación , Endófitos/genética , Endófitos/metabolismo , Endófitos/química , Endófitos/clasificación , Algas Marinas/microbiología , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Antiinfecciosos/farmacología , Antiinfecciosos/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/aislamiento & purificación , Antifúngicos/farmacología , Antifúngicos/aislamiento & purificación , Hongos/efectos de los fármacos , Hongos/aislamiento & purificación , Hongos/clasificación , Bacterias Gramnegativas/efectos de los fármacos , Ulva/microbiología , Caulerpa/microbiología , Bacterias Grampositivas/efectos de los fármacos

RESUMEN

PURPOSE OF REVIEW: This review describes the latest information in the management of bloodstream infections caused by multidrug-resistant Gram-negative bacilli (MDRGNB) in critically ill patients. RECENT FINDINGS: The prevalence of bloodstream infections due to MDRGNB is high, and they pose a significant risk in critically ill patients. Recently, novel antimicrobial agents, including new ß-lactam/ß-lactamase inhibitor combinations and cefiderocol, have been introduced for treating these infections. Concurrently, updated guidelines have been issued to aid in treatment decisions. Prompt diagnosis and identification of resistance patterns are crucial for initiating effective antibiotic therapy. Current studies, especially with observational design, and with limited sample sizes and patients with bacteremia, suggest that the use of these new antibiotics is associated with improved outcomes in critically ill patients with MDRGNB bloodstream infections. SUMMARY: For critically ill patients with bloodstream infections caused by MDRGNB, the use of newly developed antibiotics is recommended based on limited observational evidence. Further randomized clinical trials are necessary to determine the most effective antimicrobial therapies among the available options.

Asunto(s)

Antibacterianos , Bacteriemia , Enfermedad Crítica , Farmacorresistencia Bacteriana Múltiple , Infecciones por Bacterias Gramnegativas , Humanos , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Bacterias Gramnegativas/efectos de los fármacos , Unidades de Cuidados Intensivos

RESUMEN

Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against Syncephalastrum racemosum, Talaromyces marneffei, Candida lipolytica, and Trichophyton rubrum. The MIC values varied between fungal strains, and T. marneffei exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against Staphylococcus epidermidis, Proteus vulgaris, and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, S. epidermidis, and P. vulgaris strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections.

Asunto(s)

Biopelículas , Pruebas de Sensibilidad Microbiana , Cofactor PQQ , Proteómica , Biopelículas/efectos de los fármacos , Cofactor PQQ/farmacología , Cofactor PQQ/química , Antibacterianos/farmacología , Antibacterianos/química , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Antiinfecciosos/farmacología , Antiinfecciosos/química , Simulación por Computador , Hongos/efectos de los fármacos , Simulación del Acoplamiento Molecular , Antifúngicos/farmacología , Antifúngicos/química

RESUMEN

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a rapidly expanding life-support technique worldwide. The most common indications are severe hypoxemia and/or hypercapnia, unresponsive to conventional treatments, primarily in cases of acute respiratory distress syndrome. Concerning potential contraindications, there is no mention of microbiological history, especially related to multi-drug resistant (MDR) bacteria isolated before V-V ECMO placement. Our study aims to investigate: (i) the prevalence and incidence of MDR Gram-negative (GN) bacteria in a cohort of V-V ECMOs; (ii) the risk of 1-year mortality, especially in the case of predetected MDR GN bacteria; and (iii) the impact of annual hospital V-V ECMO volume on the probability of acquiring MDR GN bacteria. METHODS: All consecutive adults admitted to the Intensive Care Units of 5 Italian university-affiliated hospitals and requiring V-V ECMO were screened. Exclusion criteria were age < 18 years, pregnancy, veno-arterial or mixed ECMO-configuration, incomplete records, survival < 24 h after V-V ECMO. A standard protocol of microbiological surveillance was applied and MDR profiles were identified using in vitro susceptibility tests. Cox-proportional hazards models were applied for investigating mortality. RESULTS: Two hundred and seventy-nine V-V ECMO patients (72% male) were enrolled. The overall MDR GN bacteria percentage was 50%: 21% (n.59) detected before and 29% (n.80) after V-V ECMO placement. The overall 1-year mortality was 42%, with a higher risk observed in predetected patients (aHR 2.14 [1.33-3.47], p value 0.002), while not in 'V-V ECMO-acquired MDR GN bacteria' group (aHR 1.51 [0.94-2.42], p value 0.090), as compared to 'non-MDR GN bacteria' group (reference). Same findings were found considering only infections. A larger annual hospital V-V ECMO volume was associated with a lower probability of acquiring MDR GN bacteria during V-V ECMO course (aOR 0.91 [0.86-0.97], p value 0.002). CONCLUSIONS: 21% of MDR GN bacteria were detected before; while 29% after V-V ECMO connection. A history of MDR GN bacteria, isolated before V-V ECMO, was an independent risk factor for mortality. The annual hospital V-V ECMO volume affected the probability of acquiring MDR GN bacteria. Trial Registration ClinicalTrial.gov Registration Number NCTNCT06199141, date 12.26.2023.

Asunto(s)

Farmacorresistencia Bacteriana Múltiple , Oxigenación por Membrana Extracorpórea , Bacterias Gramnegativas , Humanos , Oxigenación por Membrana Extracorpórea/métodos , Oxigenación por Membrana Extracorpórea/estadística & datos numéricos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Bacterias Gramnegativas/efectos de los fármacos , Italia/epidemiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/mortalidad , Anciano

RESUMEN

We investigated the activity of cefiderocol/ß-lactamase inhibitor combinations against clinical strains with different susceptibility profiles to cefiderocol to explore the potentiality of antibiotic combinations as a strategy to contain the major public health problem of multidrug-resistant (MDR) pathogens. Specifically, we evaluated the synergistic activity of cefiderocol with avibactam, sulbactam, or tazobactam on three of the most "Critical Priority" group of MDR bacteria (carbapenem-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii). Clinical isolates were genomically characterized by Illumina iSeq 100. The synergy test was conducted with time-kill curve assays. Specifically, cefiderocol/avibactam, /sulbactam, or /tazobactam combinations were analyzed. Synergism was assigned if bacterial grow reduction reached 2 log10 CFU/mL. We reported the high antimicrobial activity of the cefiderocol/sulbactam combination against carbapenem-resistant Enterobacterales, P. aeruginosa, and A. baumannii; of the cefiderocol/avibactam combination against carbapenem-resistant Enterobacterales; and of the cefiderocol/tazobactam combination against carbapenem-resistant Enterobacterales and P. aeruginosa. Our results demonstrate that all ß-lactamase inhibitors (BLIs) tested are able to enhance cefiderocol antimicrobial activity, also against cefiderocol-resistant isolates. The cefiderocol/sulbactam combination emerges as the most promising combination, proving to highly enhance cefiderocol activity in all the analyzed carbapenem-resistant Gram-negative isolates, whereas the Cefiderocol/tazobactam combination resulted in being active only against carbapenem-resistant Enterobacterales and P. aeruginosa, and cefiderocol/avibactam was only active against carbapenem-resistant Enterobacterales.

Asunto(s)

Antibacterianos , Compuestos de Azabiciclo , Cefiderocol , Cefalosporinas , Sinergismo Farmacológico , Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Sulbactam , Tazobactam , Compuestos de Azabiciclo/farmacología , Tazobactam/farmacología , Sulbactam/farmacología , Cefalosporinas/farmacología , Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Carbapenémicos/farmacología , Humanos , Acinetobacter baumannii/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Inhibidores de beta-Lactamasas/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Combinación de Medicamentos

RESUMEN

BACKGROUND: Antibiotic resistance among Gram-negative bacteria in intensive care units (ICUs) is linked with high morbidity and mortality in patients. In this study, we estimated the therapeutic coverage of various antibiotics, focusing on cefiderocol and comparators, administered empirically against an infection of unknown origin in the ICU. METHODS: In the ARTEMIS surveillance study, susceptibilities of 624 Italian Gram-negative isolates to amikacin, aztreonam-avibactam, cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, colistin, imipenem-relebactam, meropenem, and meropenem-vaborbactam were tested by broth microdilution, and results were interpreted by European Committee on Antimicrobial Susceptibility Testing breakpoints. The susceptibility rates from the ARTEMIS study were extrapolated to Gram-negative isolates obtained from 5,774 patients in Italian ICUs in 2021. The sum of the predicted susceptibilities of individual pathogens represented the overall likelihood of in vitro activity of each antibiotic as early targeted therapy for ICU patients. RESULTS: A total of 624 Italian Gram-negative isolates included 206 Pseudomonas aeruginosa, 138 Acinetobacter baumannii, 187 Klebsiella pneumoniae, and 93 Escherichia coli. Against A. baumannii, K. pneumoniae, P. aeruginosa, and E. coli, the overall susceptibility rates for cefiderocol were 87.7%, 96.8%, 99%, and 100%, respectively; and for comparator agents, 8.7-96.4%, 25.7-100%, 73.3-100%, and 89.2-100%, respectively. Among the subset of meropenem-resistant isolates, susceptibility rates of A. baumannii, K. pneumoniae, and P. aeruginosa to cefiderocol were 86.4%, 96.2% and 100%, respectively. Corresponding susceptibility rates to comparator agents were 0-96.8%, 0-100%, and 6.4-100%, respectively. There were no meropenem-resistant isolates of E. coli. The extrapolation of data to isolates from Italian ICUs showed that the highest likelihood of therapeutic coverage, both overall and among meropenem-resistant isolates, was reported for colistin (96.8% and 72.2%, respectively) and cefiderocol (95.7% and 71.4%, respectively). All other antibiotics were associated with a likelihood below 73% overall and between 0% and 41.4% for meropenem-resistant isolates. CONCLUSIONS: Based on confirmed susceptibility rates and reported ICU prevalence of multiple Gram-negative species, cefiderocol showed a higher predicted therapeutic coverage and utility in ICUs compared with comparator beta-lactam-beta-lactamase inhibitor antibiotics. Cefiderocol may be a promising early treatment option for patients at high risk of carbapenem-resistant Gram-negative bacterial infections in the ICU.

Asunto(s)

Antibacterianos , Carbapenémicos , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas , Unidades de Cuidados Intensivos , Pruebas de Sensibilidad Microbiana , Humanos , Italia/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/epidemiología , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Bacterias Gramnegativas/efectos de los fármacos , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , Klebsiella pneumoniae/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Acinetobacter baumannii/efectos de los fármacos , Meropenem/farmacología , Meropenem/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Cefiderocol , Colistina/farmacología , Colistina/uso terapéutico

RESUMEN

The early detection of bacterial species plays a crucial role in patient prognosis and the development of effective therapeutic regimens. This study introduces an accessible and promising colorimetric sensor array designed to classify gram-positive (G+) and gram-negative (G-) bacterial species. The classification relies on 6 chemical ligands with dimethylamino/amino groups as sensing elements and silver nanotriangles as colorimetric probes. Using these specific sensor arrays, we successfully differentiated G- and G+ bacterial species and discriminated individual bacterial strains, and the sensors exhibited remarkable reproducibility and high sensitivity. Moreover, the sensor array can identify bacterial mixtures and bacteria at varying concentrations, underscoring its versatility. In summary, this sensor array offers an effective tool for bacterial analysis with promising applications in the field of biomedical diagnostics.

Asunto(s)

Colorimetría , Ligandos , Colorimetría/métodos , Plata/química , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Gramnegativas/clasificación , Bacterias Grampositivas/aislamiento & purificación , Nanopartículas del Metal/química , Reproducibilidad de los Resultados