RESUMO
Introduction. Sepsis rates are increasing, with Gram-negative organisms representing a large proportion of bloodstream infections. Rapid antibiotic administration, alongside diagnostic investigations, is required for the effective management of these patients.Gap statement. Current diagnostics take ~48 h for a final report; therefore, rapid diagnostics are required.Aim. This study investigated a novel antibiotic sensitivity method, the scattered light integrating collector (SLIC), combined with a rapid identification method using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) technology to determine if an accurate identification and susceptibility result can be provided within 4 h of a positive blood culture report.Methodology. A total of 47 blood cultures containing Gram-negative bacteria from 46 patients were processed using the MALDI-TOF Biotyper Sepsityper for identification directly from the blood and the SLIC instrument for susceptibility testing. All organisms were also tested using the current standard workflow used in the host laboratory. Categorical agreement (CA), major errors (MaEs) and very major errors (VMEs) were determined.Results. SLIC produced susceptibility results with a 71.9% CA, 30.6% MaE and 17.5% VME. The median difference in time to the final result was 44.14 (43â:â05-45â:â15) h earlier compared to the current method.Conclusion. We conclude that SLIC was unable to consistently provide sufficiently accurate antibiotic susceptibility results compared to the current standard method.
Assuntos
Antibacterianos , Hemocultura , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Humanos , Hemocultura/métodos , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/instrumentação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Antibacterianos/farmacologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Sepse/diagnóstico , Sepse/microbiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/microbiologia , LuzRESUMO
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.
Assuntos
Antibacterianos , Colistina , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Colistina/farmacologia , Antibacterianos/farmacologia , Humanos , Bactérias Gram-Negativas/efeitos dos fármacos , Sequenciamento Completo do Genoma , Escherichia coli/efeitos dos fármacos , Escherichia coli/genéticaRESUMO
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.
Assuntos
Antibacterianos , Colistina , Diterpenos , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Colistina/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Camundongos , Diterpenos/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , HumanosRESUMO
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.
Assuntos
Antibacterianos , Infecção Hospitalar , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Humanos , Etiópia/epidemiologia , Estudos Transversais , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/genética , Adulto Jovem , Adolescente , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo , Idoso , Criança , Pré-Escolar , Lactente , Hospitalização/estatística & dados numéricos , Proteínas de Bactérias/genética , Idoso de 80 Anos ou maisRESUMO
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.
Assuntos
Acinetobacter baumannii , Antibacterianos , Glicina , Glifosato , Bactérias Gram-Negativas , Herbicidas , Testes de Sensibilidade Microbiana , Glicina/análogos & derivados , Glicina/farmacologia , Antibacterianos/farmacologia , Herbicidas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Acinetobacter baumannii/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Humanos , Escherichia coli/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Ciprofloxacina/farmacologia , Enterococcus faecium/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Colistina/farmacologia , Vancomicina/farmacologia , Enterobacter/efeitos dos fármacos , Sinergismo Farmacológico , Meropeném/farmacologia , Fenótipo , Gentamicinas/farmacologiaRESUMO
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."
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Humanos , Uganda/epidemiologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Infecções Bacterianas/microbiologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/tratamento farmacológico , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificaçãoRESUMO
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.
Assuntos
Infecções por Bactérias Gram-Negativas , Nanopartículas , Animais , Camundongos , Nanopartículas/química , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/administração & dosagem , Bactérias Gram-Negativas/efeitos dos fármacos , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/metabolismo , Administração por Inalação , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/patologiaRESUMO
BACKGROUND: Bloodstream infections are linked to heightened morbidity and mortality rates. The consequences of delayed antibiotic treatment can be detrimental. Effective management of bacteraemia hinges on rapid antimicrobial susceptibility testing. OBJECTIVES: This retrospective study examined the influence of the VITEK® REVEAL™ Rapid AST system on positive blood culture (PBC) management in a French tertiary hospital. MATERIALS AND METHODS: Between November 2021 and March 2022, 79 Gram-negative monomicrobial PBC cases underwent testing with both VITEK®REVEAL™ and VITEK®2 systems. RESULTS: The study found that VITEK®REVEAL™ yielded better results than the standard of care, significantly shortening the time to result (7.0â h compared to 9.6â h) as well as the turnaround time (15â h compared to 31.1â h) when applied for all isolates. CONCLUSIONS: This study implies that the use of VITEK®REVEAL™ enables swift adaptations of antibiotic treatment strategies. By considerably minimizing the turnaround time, healthcare professionals can promptly make necessary adjustments to therapeutic regimens. Notably, these findings underscore the potential of VITEK®REVEAL™ in expediting appropriate antibiotic interventions, even in less ideal conditions. Further studies in varied laboratory contexts are required to validate these encouraging outcomes.
Assuntos
Antibacterianos , Bacteriemia , Hemocultura , Testes de Sensibilidade Microbiana , Humanos , Estudos Retrospectivos , Hemocultura/métodos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Fatores de Tempo , Genótipo , Fenótipo , Centros de Atenção Terciária , FrançaRESUMO
Antimicrobial resistance is a critical global health issue, with rising resistance among bacteria and fungi. Marine organisms have emerged as promising, but underexplored, sources of new antimicrobial agents. Among them, marine polychaetes, such as Halla parthenopeia, which possess chemical defenses, could attract significant research interest. This study explores the antimicrobial properties of hallachrome, a unique anthraquinone found in the purple mucus of H. parthenopeia, against Gram-negative bacteria (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027), Gram-positive bacteria (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228), and the most common human fungal pathogen Candida albicans ATCC 10231. Antibacterial susceptibility testing revealed that Gram-negative bacteria were not inhibited by hallachrome at concentrations ≤2 mM. However, Gram-positive bacteria showed significant growth inhibition at 0.12-0.25 mM, while C. albicans was inhibited at 0.06 mM. Time-kill studies demonstrated dose-dependent growth inhibition of susceptible strains by hallachrome, which exerted its effect by altering the membrane permeability of C. albicans, E. faecalis, and S. epidermidis after 6 h and S. aureus after 24 h. Additionally, hallachrome significantly reduced biofilm formation and mature biofilm in S. aureus, E. faecalis, and C. albicans. Additionally, it inhibited hyphal growth in C. albicans. These findings highlight hallachrome's potential as a novel antimicrobial agent, deserving further exploration for clinical experimentation.
Assuntos
Antraquinonas , Candida albicans , Testes de Sensibilidade Microbiana , Poliquetos , Candida albicans/efeitos dos fármacos , Animais , Antraquinonas/farmacologia , Antraquinonas/química , Antraquinonas/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Bactérias Gram-Negativas/efeitos dos fármacos , Organismos Aquáticos , Biofilmes/efeitos dos fármacosRESUMO
The World Health Organization has identified antibiotic resistance as one of the three greatest threats to human health. The need for antibiotics is a pressing matter that requires immediate attention. Here, computer-aided drug design is used to develop a structurally unique antibiotic family targeting holo-acyl carrier protein synthase (AcpS). AcpS is a highly conserved enzyme essential for bacterial survival that catalyzes the first step in lipid synthesis. To the best of our knowledge, there are no current antibiotics targeting AcpS making this drug development program of high interest. We synthesize a library of > 700 novel compounds targeting AcpS, from which 33 inhibit bacterial growth in vitro at ≤ 2 µg/mL. We demonstrate that compounds from this class have stand-alone activity against a broad spectrum of Gram-positive organisms and synergize with colistin to enable coverage of Gram-negative species. We demonstrate efficacy against clinically relevant multi-drug resistant strains in vitro and in animal models of infection in vivo including a difficult-to-treat ischemic infection exemplified by diabetic foot ulcer infections in humans. This antibiotic family could form the basis for several multi-drug-resistant antimicrobial programs.
Assuntos
Antibacterianos , Desenho Assistido por Computador , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Humanos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Colistina/farmacologia , Camundongos , Pé Diabético/tratamento farmacológico , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Sinergismo FarmacológicoRESUMO
SUMMARYThe discovery of bacterial efflux pumps significantly advanced our understanding of how bacteria can resist cytotoxic compounds that they encounter. Within the structurally and functionally distinct families of efflux pumps, those of the Resistance-Nodulation-Division (RND) superfamily are noteworthy for their ability to reduce the intracellular concentration of structurally diverse antimicrobials. RND systems are possessed by many Gram-negative bacteria, including those causing serious human disease, and frequently contribute to resistance to multiple antibiotics. Herein, we review the current literature on the structure-function relationships of representative transporter proteins of tripartite RND efflux pumps of clinically important pathogens. We emphasize their contribution to bacterial resistance to clinically used antibiotics, host defense antimicrobials and other biocides, as well as highlighting structural similarities and differences among efflux transporters that help bacteria survive in the face of antimicrobials. Furthermore, we discuss technical advances that have facilitated and advanced efflux pump research and suggest future areas of investigation that will advance antimicrobial development efforts.
Assuntos
Antibacterianos , Proteínas de Bactérias , Bactérias Gram-Negativas , Proteínas de Membrana Transportadoras , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/química , Humanos , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Relação Estrutura-Atividade , Farmacorresistência Bacteriana , Bactérias/metabolismo , Bactérias/efeitos dos fármacosRESUMO
Bryophyllum pinnatum is used to cure infections worldwide. Although the flavonoids of this plant are well known, it is still unknown how much of the plant's Ag and ZnO nanoparticles are beneficial. In the current research work, silver and zinc oxide nanoparticles were prepared using Bryophyllum pinnatum extract. The synthesized particles were characterized by UV-visible spectroscopy, SEM, EDS, XRD and FTIR. Synthesized particles were subjected to evaluation of their bactericidal and antifungal activity at various doses. Uv vis spectra at 400 nm corresponding to AgNPs confirmed their synthesis. Strong peaks in the EDS spectra of Ag and ZnO indicate the purity of the sample. The scanning electron microscopic images of ZnONPs showed a size of about 60 nm ± 3 nm, which demonstrated the presence of triangular-shaped ZnO nanoparticles. Green synthesized nanoparticles showed bactericidal activity against both Gram-positive (Micrococcus luteus, Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Agrobacterium tumifaciens, Salmonella setubal, Enterobacter aerogenes) strains. AgNPs proved to be more effective against Gram-negative bacterial strains compared to Gram-positive owing to MIC values (10 ppm and 20 ppm respectively). Whereas, ZnONPs were found more effective against Gram-positive bacteria with lower MIC values (10 ppm) as compared to Gram-negative ones (20 ppm). Also, the synthesized nanoparticles exhibited moderate dose-dependent antifungal activity against tested fungal strains ranging from 10 to 70%. Cytotoxicity of nanoparticles was found significant using Brine shrimp's lethality assay with IC50 values of 4.09 ppm for AgNPs, 13.72 ppm for ZnONPs, and 24.83 ppm for plant extract. Conclusively, Ag and ZnO nanoparticles were more effective than plant extract and AgNPs had higher activities than those of ZnONPs. Further research is warranted to explore the precise mechanism of action and the potential applications of these nanoparticles in the medical field.
Assuntos
Kalanchoe , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Extratos Vegetais , Prata , Óxido de Zinco , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Nanopartículas Metálicas/química , Kalanchoe/química , Prata/química , Prata/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Antifúngicos/farmacologia , Antifúngicos/química , Artemia/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacosRESUMO
Background Intensive care unit (ICU) is the especial department of the hospital where critically ill patients are treated with the unique type of technologies to revert back to functional by body's own mechanism. Therefore, there are lots of external intervention with chance of getting bacterial infections. Antibiotics are medicines used to prevent and treat such bacterial infections. However, due to selective broad spectrum antibiotic pressure there is great chances to develop antimicrobial resistance at any time during hospital stay in intensive care unit. Objective To find out the antibiotic resistance pattern among Gram negative bacteria in Intensive Care Unit. Method A Descriptive cross-sectional study was conducted in Department of Microbiology of Tertiary care center for 18 months On the basis of previous sample load census method was used to include 500 sample from intensive care unit during study period. Among them only Gram negative bacteria were included in the study. All the samples were processed following standard methodology. Result Out of 500 samples, growth was observed in 451 (90.2%) samples. Among all the isolates Escherichia coli (29.6%) was predominant organism. It had shown high resistance towards Ciprofloxacin (93.5%) even in urine sample Ciprofloxacin (86.9%). Conclusion Our study showed Escherichia coli as a major organism in intensive care unit. This was resistant to commonly used oral antibiotic leaving restricted option for use of higher antibiotics. Therefore, continuous surveillance of such bacterial pathogen is warranted with implementation of effective Infection Prevention and Control measures in Health Care setting with emphasis to critical care units.
Assuntos
Antibacterianos , Unidades de Terapia Intensiva , Centros de Atenção Terciária , Humanos , Nepal , Estudos Transversais , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Testes de Sensibilidade Microbiana , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Farmacorresistência Bacteriana , Ciprofloxacina/uso terapêutico , Ciprofloxacina/farmacologiaRESUMO
Colistin resistance poses a major therapeutic challenge and resistant strains have now been reported worldwide. However, the occurrence of such bacteria in aquatic environments is considerably less understood. This study aimed to isolate and characterize colistin-resistant strains from water and plastic litter collected in an urban recreational estuary. Altogether, 64 strains with acquired colistin resistance were identified, mainly Acinetobacter spp. and Enterobacter spp. From these, 40.6% were positive for at least one mcr variant (1-9), 26.5% harbored, extended-spectrum beta-lactamases, 23.4% harbored, sulfonamide resistance genes, and 9.3% harbored, quinolone resistance genes. merA, encoding mercury resistance, was detected in 10.5% of these strains, most of which were also strong biofilm producers. The minimum inhibitory concentration toward colistin was determined for the mcr-positive strains and ranged from 2 to ≥512 µg ml-1. Our findings suggest that Gram-negative bacteria highly resistant to a last-resort antimicrobial can be found in recreational waters and plastic litter, thereby evidencing the urgency of the One Health approach to mitigate the antimicrobial resistance crisis.
Assuntos
Antibacterianos , Colistina , Farmacorresistência Bacteriana , Estuários , Testes de Sensibilidade Microbiana , Plásticos , Colistina/farmacologia , Antibacterianos/farmacologia , Microbiologia da Água , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificaçãoRESUMO
INTRODUCTION: This study aims to investigate the changing epidemiology and antimicrobial susceptibility of bacteria isolated from cerebrospinal fluid (CSF) in the Shandong region. METHODOLOGY: We conducted a retrospective analysis of bacterial distribution and resistance patterns in CSF samples, utilizing data from the SPARSS network and analyzed with WHONET 5.6 software. RESULTS: A total of 3968 pathogenic bacterial strains were isolated, consisting of 70.6% Gram-positive bacteria, 27.2% Gram-negative bacteria, and 0.2% fungi. The six most commonly detected bacteria were coagulase-negative staphylococcus, Acinetobacter baumannii, Klebsiella pneumoniae, Streptococcus pneumoniae, Escherichia coli, and staphylococcus aureus. Analysis revealed gender and seasonal variations in the distribution of CSF pathogens, with a higher incidence observed in males and during autumn compared to other seasons. The susceptibility profiles of these bacterial species varied significantly, with many exhibiting multidrug resistances. A. baumannii showed a high resistance rate to cephalosporins and carbapenems but was sensitive to tigecycline and polymyxins. For treating multidrug-resistant A. baumannii infections, polymyxin-based combinations with tigecycline or sulbactam are recommended for adults, while tigecycline combined with meropenem is suggested for children. Enterobacteriaceae species were generally sensitive to carbapenems, such as meropenem and other carbapenems that can penetrate the blood-brain barrier can be recommended. Linezolid and vancomycin are the first choice for treating common gram-positive bacterial infections. CONCLUSIONS: The high resistance rates observed among common CSF isolates and their varied distributions across different demographics highlight the necessity for customized treatment strategies.
Assuntos
Antibacterianos , Meningites Bacterianas , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Humanos , China/epidemiologia , Meningites Bacterianas/microbiologia , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/líquido cefalorraquidiano , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Prevalência , Masculino , Feminino , Adulto , Criança , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Farmacorresistência Bacteriana Múltipla , Pessoa de Meia-Idade , Farmacorresistência Bacteriana , Pré-Escolar , Lactente , Adolescente , Adulto Jovem , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificaçãoRESUMO
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.
Assuntos
Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Alemanha , Humanos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Prevalência , Antibacterianos/uso terapêuticoRESUMO
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.
Assuntos
Antibacterianos , Carbapenêmicos , Cefiderocol , Cefalosporinas , Infecções por Bactérias Gram-Negativas , Sideróforos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Cefiderocol/farmacologia , Cefiderocol/uso terapêutico , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Sideróforos/farmacologiaRESUMO
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.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Humanos , Feminino , Masculino , Fiji , Adulto , Estudos Transversais , Pessoal de Saúde/psicologia , Adulto Jovem , Inquéritos e Questionários , Adolescente , Controle de Infecções/métodos , Pessoa de Meia-Idade , Infecção Hospitalar/microbiologia , Hospitais Militares , Atitude do Pessoal de Saúde , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-NegativasRESUMO
The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC90) of 0.03-2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously ( https://clinicaltrials.gov/study/NCT05088421 ) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Animais , Feminino , Masculino , Adulto , Bactérias Gram-Negativas/efeitos dos fármacos , Camundongos , Pessoa de Meia-Idade , Adulto Jovem , Ratos , Voluntários Saudáveis , Bactérias Gram-Positivas/efeitos dos fármacosRESUMO
The human gut presents a complex ecosystem harboring trillions of microorganisms living in close association with each other and the host body. Any perturbation or imbalance of the normal gut microbiota may prove detrimental to human health. Enteric infections and treatment with antibiotics pose major threats to gut microbiota health. Recent genomics-driven research has provided insights into the transmission and evolutionary dynamics of major enteric pathogens such as Escherichia coli, Klebsiella pneumoniae, Vibrio cholerae, Helicobacter pylori and Salmonella spp. Studies entailing the identification of various dominant lineages of some of these organisms based on artificial intelligence and machine learning point to the possibility of a system for prediction of antimicrobial resistance (AMR) as some lineages have a higher propensity to acquire virulence and fitness advantages. This is pertinent in the light of emerging AMR being one of the immediate threats posed by pathogenic bacteria in the form of a multi-layered fitness manifesting as phenotypic drug resistance at the level of clinics and field settings. To develop a holistic or systems-level understanding of such devastating traits, present methodologies need to be advanced with the high throughput techniques integrating community and ecosystem/niche level data across different omics platforms. The next major challenge for public health epidemiologists is understanding the interactions and functioning of these pathogens at the community level, both in the gut and outside. This would provide new insights into the dimensions of enteric bacteria in different environments and niches and would have a plausible impact on infection control strategies in terms of tackling AMR. Hence, the aim of this review is to discuss virulence and AMR in Gram-negative pathogens, the spillover of AMR and methodological advancements aimed at addressing it through a unified One Health framework applicable to the farms, the environment, different clinical settings and the human gut.