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1.
PLoS Pathog ; 20(5): e1012143, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38696356

RESUMO

With the escalating global antimicrobial resistance crisis, there is an urgent need for innovative strategies against drug-resistant microbes. Accumulating evidence indicates microbial extracellular vesicles (EVs) contribute to antimicrobial resistance. Therefore, comprehensively elucidating the roles and mechanisms of microbial EVs in conferring resistance could provide new perspectives and avenues for novel antimicrobial approaches. In this review, we systematically examine current research on antimicrobial resistance involving bacterial, fungal, and parasitic EVs, delineating the mechanisms whereby microbial EVs promote resistance. Finally, we discuss the application of bacterial EVs in antimicrobial therapy.


Assuntos
Bactérias , Vesículas Extracelulares , Vesículas Extracelulares/metabolismo , Humanos , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos , Farmacorresistência Bacteriana , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia
2.
ACS Infect Dis ; 10(5): 1483-1519, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38691668

RESUMO

The development of effective antibacterial solutions has become paramount in maintaining global health in this era of increasing bacterial threats and rampant antibiotic resistance. Traditional antibiotics have played a significant role in combating bacterial infections throughout history. However, the emergence of novel resistant strains necessitates constant innovation in antibacterial research. We have analyzed the data on antibacterials from the CAS Content Collection, the largest human-curated collection of published scientific knowledge, which has proven valuable for quantitative analysis of global scientific knowledge. Our analysis focuses on mining the CAS Content Collection data for recent publications (since 2012). This article aims to explore the intricate landscape of antibacterial research while reviewing the advancement from traditional antibiotics to novel and emerging antibacterial strategies. By delving into the resistance mechanisms, this paper highlights the need to find alternate strategies to address the growing concern.


Assuntos
Antibacterianos , Infecções Bacterianas , Farmacorresistência Bacteriana , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Bactérias/efeitos dos fármacos
3.
Eur J Med Chem ; 271: 116451, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38691892

RESUMO

The potent antibacterial activity and low resistance of antimicrobial peptides (AMPs) render them potential candidates for treating multidrug-resistant bacterial infections. Herein, a minimalist design strategy was proposed employing the "golden partner" combination of arginine (R) and tryptophan (W), along with a dendritic structure to design AMPs. By extension, the α/ε-amino group and the carboxyl group of lysine (K) were utilized to link R and W, forming dendritic peptide templates αRn(εRn)KWm-NH2 and αWn(εWn)KRm-NH2, respectively. The corresponding linear peptide templates R2nKWm-NH2 and W2nKRm-NH2 were used as controls. Their physicochemical properties, activity, toxicity, and stability were compared. Among these new peptides, the dendritic peptide R2(R2)KW4 was screened as a prospective candidate owing to its preferable antibacterial properties, biocompatibility, and stability. Additionally, R2(R2)KW4 not only effectively restrained the progression of antibiotic resistance, but also demonstrated synergistic utility when combined with conventional antibiotics due to its unique membrane-disruptive mechanism. Furthermore, R2(R2)KW4 possessed low toxicity (LD50 = 109.31 mg/kg) in vivo, while efficiently clearing E. coli in pulmonary-infected mice. In conclusion, R2(R2)KW4 has the potential to become an antimicrobial regent or adjuvant, and the minimalist design strategy of dendritic peptides provides innovative and encouraging thoughts in designing AMPs.


Assuntos
Antibacterianos , Arginina , Testes de Sensibilidade Microbiana , Triptofano , Triptofano/química , Triptofano/farmacologia , Animais , Arginina/química , Arginina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Camundongos , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/síntese química , Relação Estrutura-Atividade , Estrutura Molecular , Membrana Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Infecções Bacterianas/tratamento farmacológico , Humanos , Escherichia coli/efeitos dos fármacos
4.
Pediatrics ; 153(6)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712446

RESUMO

BACKGROUND: Route of administration is an important component of antimicrobial stewardship. Early transition from intravenous to enteral antibiotics in hospitalized children is associated with fewer catheter-related adverse events, as well as decreased costs and length of stay. Our aim was to increase the percentage of enteral antibiotic doses for hospital medicine patients with uncomplicated common bacterial infections (community-acquired pneumonia, skin and soft tissue infection, urinary tract infection, neck infection) from 50% to 80% in 6 months. METHODS: We formed a multidisciplinary team to evaluate key drivers and design plan-do-study-act cycles. Interventions included provider education, structured discussion at existing team huddles, and pocket-sized printed information. Our primary measure was the percentage of antibiotic doses given enterally to patients receiving other enteral medications. Secondary measures included antibiotic cost, number of peripheral intravenous catheters, length of stay, and 7-day readmission. We used statistical process control charts to track our measures. RESULTS: Over a 6-month baseline period and 12 months of improvement work, we observed 3183 antibiotic doses (888 in the baseline period, 2295 doses during improvement work). We observed an increase in the percentage of antibiotic doses given enterally per week for eligible patients from 50% to 67%. We observed decreased antibiotic costs and fewer peripheral intravenous catheters per encounter after the interventions. There was no change in length of stay or readmissions. CONCLUSIONS: We observed increased enteral antibiotic doses for children hospitalized with common bacterial infections. Interventions targeting culture change and communication were associated with sustained improvement.


Assuntos
Antibacterianos , Humanos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Criança , Gestão de Antimicrobianos , Infecções Bacterianas/tratamento farmacológico , Tempo de Internação , Pré-Escolar , Readmissão do Paciente/estatística & dados numéricos , Criança Hospitalizada , Hospitalização , Feminino , Masculino
5.
Korean J Intern Med ; 39(3): 413-429, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38715231

RESUMO

Biomarkers are playing an increasingly important role in antimicrobial stewardship. Their applications have included use in algorithms that evaluate suspected bacterial infections or provide guidance on when to start or stop antibiotic therapy, or when therapy should be repeated over a short period (6-12 h). Diseases in which biomarkers are used as complementary tools to determine the initiation of antibiotics include sepsis, lower respiratory tract infection (LRTI), COVID-19, acute heart failure, infectious endocarditis, acute coronary syndrome, and acute pancreatitis. In addition, cut-off values of biomarkers have been used to inform the decision to discontinue antibiotics for diseases such as sepsis, LRTI, and febrile neutropenia. The biomarkers used in antimicrobial stewardship include procalcitonin (PCT), C-reactive protein (CRP), presepsin, and interleukin (IL)-1ß/IL-8. The cut-off values vary depending on the disease and study, with a range of 0.25-1.0 ng/mL for PCT and 8-50 mg/L for CRP. Biomarkers can complement clinical diagnosis, but further studies of microbiological biomarkers are needed to ensure appropriate antibiotic selection.


Assuntos
Antibacterianos , Gestão de Antimicrobianos , Biomarcadores , Humanos , Biomarcadores/sangue , Antibacterianos/uso terapêutico , COVID-19/sangue , COVID-19/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/sangue , Infecções Bacterianas/microbiologia , Valor Preditivo dos Testes , Pró-Calcitonina/sangue , Proteína C-Reativa/análise
6.
Arch Microbiol ; 206(6): 250, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722362

RESUMO

The widespread evolution of phenotypic resistance in clinical isolates over the years, coupled with the COVID-19 pandemic onset, has exacerbated the global challenge of antimicrobial resistance. This study aimed to explore changes in bacterial infection patterns and antimicrobial resistance during the COVID-19 pandemic. This study involved the periods before and during COVID-19: the pre-pandemic and pandemic eras. The surveillance results of bacterial isolates causing infections in cancer patients at an Egyptian tertiary oncology hospital were retrieved. The Vitek®2 or Phoenix systems were utilized for species identification and susceptibility testing. Statistical analyses were performed comparing microbiological trends before and during the pandemic. Out of 2856 bacterial isolates, Gram-negative bacteria (GNB) predominated (69.7%), and Gram-positive bacteria (GPB) comprised 30.3% of isolates. No significant change was found in GNB prevalence during the pandemic (P = 0.159). Elevated rates of Klebsiella and Pseudomonas species were demonstrated during the pandemic, as was a decrease in E. coli and Acinetobacter species (P < 0.001, 0.018, < 0.001, and 0.046, respectively) in hematological patients. In surgical patients, Enterobacteriaceae significantly increased (P = 0.012), while non-fermenters significantly decreased (P = 0.007). GPB species from either hematological or surgical wards exhibited no notable changes during the pandemic. GNB resistance increased in hematological patients to carbapenems, amikacin, and tigecycline and decreased in surgical patients to amikacin and cefoxitin (P < 0.001, 0.010, < 0.001, < 0.001, and 0.016, respectively). The study highlights notable shifts in the microbial landscape during the COVID-19 pandemic, particularly in the prevalence and resistance patterns of GNB in hematological and surgical wards.


Assuntos
Antibacterianos , COVID-19 , Farmacorresistência Bacteriana , SARS-CoV-2 , Centros de Atenção Terciária , Humanos , COVID-19/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Egito/epidemiologia , Antibacterianos/farmacologia , SARS-CoV-2/efeitos dos fármacos , Neoplasias , Testes de Sensibilidade Microbiana , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/tratamento farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/classificação , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Institutos de Câncer , Pandemias
8.
BMC Pediatr ; 24(1): 324, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734642

RESUMO

BACKGROUND: The impact of inadequate empirical antibiotic treatment on patient outcomes and hospitalization duration for non-life-threatening infections in children remains poorly understood. We aimed to assess the effects of inadequate empirical antibiotic treatment on these factors in pediatric patients. METHODS: The medical records of children admitted for infectious diseases with bacteria isolated from sterile sites between 2018 and 2020 were retrospectively reviewed. Patients who received adequate empirical treatment were compared with those who received inadequate treatment in terms of demographic, clinical, and laboratory variables. RESULTS: Forty-eight patients who received inadequate empirical antimicrobial treatment were compared to 143 patients who received adequate empirical treatment. Inadequate empirical antimicrobial treatment did not significantly affect the length of hospital stay or the incidence of complications in non-critically ill children with bacterial infections. Younger age and underlying renal abnormalities were identified as risk factors for inadequate antimicrobial treatment, while associated bacteremia was more common in the adequate antimicrobial treatment group. CONCLUSIONS: inadequate antibiotic treatment did not affect the outcomes of non-critically ill children with bacterial infectious diseases. Therefore, routine empirical broad-spectrum treatment may not be necessary for these cases, as it can lead to additional costs and contribute to antibiotic resistance. Larger prospective studies are needed to confirm these findings.


Assuntos
Antibacterianos , Infecções Bacterianas , Tempo de Internação , Humanos , Antibacterianos/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Pré-Escolar , Criança , Infecções Bacterianas/tratamento farmacológico , Lactente , Tempo de Internação/estatística & dados numéricos , Resultado do Tratamento , Fatores de Risco , Adolescente
9.
Molecules ; 29(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731407

RESUMO

The problem of bacterial resistance has become more and more common with improvements in health care. Worryingly, the misuse of antibiotics leads to an increase in bacterial multidrug resistance and the development of new antibiotics has virtually stalled. These challenges have prompted the need to combat bacterial infections with the use of radically different approaches. Taking lessons from the exciting properties of micro-/nano-natural-patterned surfaces, which can destroy cellular integrity, the construction of artificial surfaces to mimic natural functions provides new opportunities for the innovation and development of biomedicine. Due to the diversity of natural surfaces, functional surfaces inspired by natural surfaces have a wide range of applications in healthcare. Nature-inspired surface structures have emerged as an effective and durable strategy to prevent bacterial infection, opening a new way to alleviate the problem of bacterial drug resistance. The present situation of bactericidal and antifouling surfaces with natural and biomimetic micro-/nano-structures is briefly reviewed. In addition, these innovative nature-inspired methods are used to manufacture a variety of artificial surfaces to achieve extraordinary antibacterial properties. In particular, the physical antibacterial effect of nature-inspired surfaces and the functional mechanisms of chemical groups, small molecules, and ions are discussed, as well as the wide current and future applications of artificial biomimetic micro-/nano-surfaces. Current challenges and future development directions are also discussed at the end. In the future, controlling the use of micro-/nano-structures and their subsequent functions will lead to biomimetic surfaces offering great potential applications in biomedicine.


Assuntos
Antibacterianos , Nanoestruturas , Propriedades de Superfície , Antibacterianos/farmacologia , Antibacterianos/química , Nanoestruturas/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Humanos , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controle
10.
Biomacromolecules ; 25(5): 3190-3199, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38693753

RESUMO

Intracellular bacteria in dormant states can escape the immune response and tolerate high-dose antibiotic treatment, leading to severe infections. To overcome this challenge, cascade-targeted nanoplatforms that can target macrophages and intracellular bacteria, exhibiting synergetic antibiotic/reactive oxygen species (ROS)/nitric oxide (NO)/immunotherapy, were developed. These nanoplatforms were fabricated by encapsulating trehalose (Tr) and vancomycin (Van) into phosphatidylserine (PS)-coated poly[(4-allylcarbamoylphenylboric acid)-ran-(arginine-methacrylamide)-ran-(N,N'-bisacryloylcystamine)] nanoparticles (PABS), denoted as PTVP. PS on PTVP simulates a signal of "eat me" to macrophages to promote cell uptake (the first-step targeting). After the uptake, the nanoplatform in the acidic phagolysosomes could release Tr, and the exposed phenylboronic acid on the nanoplatform could target bacteria (the second-step targeting). Nanoplatforms can release Van in response to infected intracellular overexpressed glutathione (GSH) and weak acid microenvironment. l-arginine (Arg) on the nanoplatforms could be catalyzed by upregulated inducible nitric oxide synthase (iNOS) in the infected macrophages to generate nitric oxide (NO). N,N'-Bisacryloylcystamine (BAC) on nanoplatforms could deplete GSH, allow the generation of ROS in macrophages, and then upregulate proinflammatory activity, leading to the reinforced antibacterial capacity. This nanoplatform possesses macrophage and bacteria-targeting antibiotic delivery, intracellular ROS, and NO generation, and pro-inflammatory activities (immunotherapy) provides a new strategy for eradicating intracellular bacterial infections.


Assuntos
Antibacterianos , Nanopartículas , Óxido Nítrico , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Óxido Nítrico/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Animais , Células RAW 264.7 , Nanopartículas/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Imunoterapia/métodos , Vancomicina/farmacologia , Vancomicina/química , Vancomicina/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Trealose/química , Trealose/farmacologia
11.
Int J Biol Macromol ; 267(Pt 1): 131372, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580024

RESUMO

Clinically, open wounds caused by accidental trauma and surgical lesion resection are easily infected by external bacteria, hindering wound healing. Antibacterial photodynamic therapy has become a promising treatment strategy for wound infection. In this study, a novel antibacterial nanocomposite material (QMC NPs) was synthesized by curcumin, quaternized chitosan and mesoporous polydopamine nanoparticles. The results showed that 150 µg/mL QMC NPs had good biocompatibility and exerted excellent antibacterial activity against Staphylococcus aureus and Escherichia coli after blue laser irradiation (450 nm, 1 W/cm2). In vivo, QMC NPs effectively treated bacterial infection and accelerated the healing of infected wounds in mice.


Assuntos
Antibacterianos , Quitosana , Curcumina , Escherichia coli , Indóis , Nanopartículas , Polímeros , Staphylococcus aureus , Quitosana/química , Quitosana/farmacologia , Indóis/química , Indóis/farmacologia , Curcumina/farmacologia , Curcumina/química , Polímeros/química , Polímeros/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Animais , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Porosidade , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Cicatrização/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico
12.
Zhongguo Zhong Yao Za Zhi ; 49(3): 653-660, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621869

RESUMO

Quorum sensing system regulates the expression of genes related to bacterial growth, metabolism and other behaviors by sensing bacterial density, and controls the unified action of the entire bacterial population. This mechanism can ensure the normal secretion of bacterial metabolites and the stability of the biofilm microenvironment, providing protection for the formation of biofilms and the normal growth and reproduction of bacteria. Traditional Chinese medicine, capable of quorum sensing inhibition, can inhibit the formation of bacterial biofilms, reduce bacterial resistance, and enhance the anti-infection ability of antibiotics when combined with antibiotics. In recent years, the combination of traditional Chinese and Western medicine in the treatment of drug-resistant bacterial infections has become a research hotspot. Starting with the associations between quorum sensing, biofilm and drug-resistant bacteria, this paper reviews the relevant studies about the combined application of traditional Chinese medicines as quorum sensing inhibitors with antibiotics in the treatment of drug-resistant bacteria. This review is expected to provide ideas for the development of new clinical treatment methods and novel anti-infection drugs.


Assuntos
Infecções Bacterianas , Percepção de Quorum , Humanos , Percepção de Quorum/genética , Medicina Tradicional Chinesa , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/genética , Biofilmes , Infecções Bacterianas/tratamento farmacológico
13.
J Med Chem ; 67(9): 7487-7503, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38688020

RESUMO

Although bactericidal cationic antimicrobial peptides (AMPs) have been well characterized, less information is available about the antibacterial properties and mechanisms of action of nonbactericidal AMPs, especially nonbactericidal anionic AMPs. Herein, a novel anionic antimicrobial peptide (Gy-CATH) with a net charge of -4 was identified from the skin of the frog Glyphoglossus yunnanensis. Gy-CATH lacks direct antibacterial effects but exhibits significantly preventive and therapeutic capacities in mice that are infected with Staphylococcus aureus, Enterobacteriaceae coli, methicillin-resistant Staphylococcus aureus (MRSA), or carbapenem-resistant E. coli (CREC). In vitro and in vivo investigations proved the regulation of Gy-CATH on neutrophils and macrophages involved in the host immune defense against infection. Moreover, Gy-CATH significantly reduced the extent of pulmonary fibrin deposition and prevented thrombosis in mice, which was attributed to the regulatory role of Gy-CATH in physiological anticoagulants and platelet aggregation. These findings show that Gy-CATH is a potential candidate for the treatment of bacterial infection.


Assuntos
Antibacterianos , Peptídeos Antimicrobianos , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/uso terapêutico , Anuros , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controle , Escherichia coli/efeitos dos fármacos , Fibrinolíticos/farmacologia , Fibrinolíticos/química , Fibrinolíticos/uso terapêutico , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Fatores Imunológicos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Trombose/prevenção & controle , Trombose/tratamento farmacológico
14.
Molecules ; 29(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38611953

RESUMO

Bacterial virulence factors and biofilm development can be controlled by the quorum-sensing (QS) system, which is also intimately linked to antibiotic resistance in bacteria. In previous studies, many researchers found that quorum-sensing inhibitors (QSIs) can affect the development of bacterial biofilms and prevent the synthesis of many virulence factors. However, QSIs alone have a limited ability to suppress bacteria. Fortunately, when QSIs are combined with antibiotics, they have a better therapeutic effect, and it has even been demonstrated that the two together have a synergistic antibacterial effect, which not only ensures bactericidal efficiency but also avoids the resistance caused by excessive use of antibiotics. In addition, some progress has been made through in vivo studies on the combination of QSIs and antibiotics. This article mainly expounds on the specific effect of QSIs combined with antibiotics on bacteria and the combined antibacterial mechanism of some QSIs and antibiotics. These studies will provide new strategies and means for the clinical treatment of bacterial infections in the future.


Assuntos
Antibacterianos , Infecções Bacterianas , Humanos , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Percepção de Quorum , Biofilmes , Fatores de Virulência
15.
Cell Biochem Funct ; 42(3): e4022, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38655589

RESUMO

Over the years, the administration of antibiotics for the purpose of addressing bacterial infections has become increasingly challenging due to the increased prevalence of antimicrobial resistance exhibited by various strains of bacteria. Multidrug-resistant (MDR) bacterial species are rising due to the unavailability of novel antibiotics, leading to higher mortality rates. With these conditions, there is a need for alternatives in which phage therapy has made promising results. Phage-derived endolysins, phage cocktails, and bioengineered phages are effective and have antimicrobial properties against MDR and extensively drug-resistant strains. Despite these, it has been observed that phages can give antimicrobial activity to more than one bacterial species. Thus, phage cocktail against resistant strains provides broad spectrum treatment and magnitude of effectivity, which is many folds higher than antibiotics. Many commercially available endolysins such as Staphefekt SA.100, Exebacase (CF-301), and N-Rephasin®SAL200 are used in biofilm penetration and treating plant diseases. The role of CMP1 phage endolysin in transgenic tomato plants in preventing Clavibacter michiganensis infection and the effectiveness of phage in protecting Atlantic salmon from vibriosis have been reported. Furthermore, phage-derived endolysin therapy, such as TSPphg phage exogenous treatment, can aid in disrupting cell walls, leading to bacterial cell lysis. As animals in aquaculture and slaughterhouses are highly susceptible to bacterial infections, effective phage therapy instead of antibiotics can help treat poultry animals, preserve them, and facilitate disease-free trade. Using bioengineered phages and phage cocktails enhances the effectiveness by providing a broad spectrum of phages and target specificity. Research is currently being conducted on clinical trials to confirm the efficacy of engineered phages and phage cocktails in humans. Although obtaining commercial approval may be time-consuming, it will be beneficial in the postantibiotic era. This review provides an overview of the significance of phage therapy as a potential alternative to antibiotics in combating resistant bacterial strains and its application to various fields and emphasizes the importance of safeguarding and ensuring treatment efficacy.


Assuntos
Antibacterianos , Bacteriófagos , Endopeptidases , Terapia por Fagos , Antibacterianos/farmacologia , Humanos , Animais , Infecções Bacterianas/terapia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Bactérias/efeitos dos fármacos , Bactérias/virologia
16.
Arch Dermatol Res ; 316(5): 136, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676739

RESUMO

This study investigates the frequency of infections in autoimmune blistering disease (AIBD) patients treated with rituximab and evaluates the difference in infectious complications in patients on concomitant antibiotic and/or antiviral prophylaxis. The study retrospectively reviewed 43 AIBD patients who received rituximab over a five-year interval. The patients were categorized based on prophylaxis type (antibiotic, antiviral, or both) and concomitant immunosuppression status, which we defined as treatment with an immunosuppressive medication during the time frame they were given Rituximab. Our findings suggest that concomitant immunosuppression alongside rituximab did not significantly increase the risk of developing infectious complications compared to rituximab monotherapy. Results revealed that 34.4% of patients with concomitant immunosuppression had a secondary bacterial infection, defined as bacterial complications requiring hospitalization, consistent with prior studies. Moreover, antibiotic prophylaxis did not significantly reduce infection risk in patients on rituximab, with 45.1% of these patients experiencing bacterial complications. There was an absence of pneumocystis pneumonia in the study population. Despite the small sample size and limited timeline, this study suggests that antibiotic prophylaxis may not significantly mitigate the risk of infections in AIBD patients receiving rituximab, and the risk of infection with concomitant immunosuppression with rituximab requires additional investigation for definitive causal risk.


Assuntos
Doenças Autoimunes , Rituximab , Humanos , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/tratamento farmacológico , Adulto , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Idoso de 80 Anos ou mais , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Antibioticoprofilaxia/métodos , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico
17.
BioDrugs ; 38(3): 387-404, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38605260

RESUMO

Antimicrobial resistance (AMR) can potentially harm global public health. Horizontal gene transfer (HGT), which speeds up the emergence of AMR and increases the burden of drug resistance in mobile genetic elements (MGEs), is the primary method by which AMR genes are transferred across bacterial pathogens. New approaches are urgently needed to halt the spread of bacterial diseases and antibiotic resistance. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), an RNA-guided adaptive immune system, protects prokaryotes from foreign DNA like plasmids and phages. This approach may be essential in limiting horizontal gene transfer and halting the spread of antibiotic resistance. The CRISPR-Cas system has been crucial in identifying and understanding resistance mechanisms and developing novel therapeutic approaches. This review article investigates the CRISPR-Cas system's potential as a tool to combat bacterial AMR. Antibiotic-resistant bacteria can be targeted and eliminated by the CRISPR-Cas system. It has been proven to be an efficient method for removing carbapenem-resistant plasmids and regaining antibiotic susceptibility. The CRISPR-Cas system has enormous potential as a weapon against bacterial AMR. It precisely targets and eliminates antibiotic-resistant bacteria, facilitates resistance mechanism identification, and offers new possibilities in diagnostics and therapeutics.


Assuntos
Bactérias , Sistemas CRISPR-Cas , Farmacorresistência Bacteriana , Humanos , Farmacorresistência Bacteriana/genética , Bactérias/genética , Bactérias/efeitos dos fármacos , Transferência Genética Horizontal , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Plasmídeos/genética
18.
Life Sci ; 346: 122643, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38614308

RESUMO

Lectins are protein or glycoprotein molecules with a specific ability to bind to carbohydrates. From viruses to mammals, they are found in various organisms and exhibit remarkable diverse structures and functions. They are significant contributors to defense mechanisms against microbial attacks in plants. They are also involved in functions such as controlling lymphocyte migration, regulating glycoprotein biosynthesis, cell-cell recognition, and embryonic development in animals. In addition, lectins serve as invaluable molecular tools in various biological and medical disciplines due to their reversible binding ability and enable the monitoring of cell membrane changes in physiological and pathological contexts. Microbial lectins, often referred to as adhesins, play an important role in microbial colonization, pathogenicity, and interactions among microorganisms. Viral lectins are located in the bilayered viral membrane, whereas bacterial lectins are found intracellularly and on the bacterial cell surface. Microfungal lectins are typically intracellular and have various functions in host-parasite interaction, and in fungal growth and morphogenesis. Although microbial lectin studies are less extensive than those of plants and animals, they provide insights into the infection mechanisms and potential interventions. Glycan specificity, essential functions in infectious diseases, and applications in the diagnosis and treatment of viral and bacterial infections are critical aspects of microbial lectin research. In this review, we will discuss the application and therapeutic potential of viral, bacterial and microfungal lectins.


Assuntos
Lectinas , Humanos , Lectinas/metabolismo , Animais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/metabolismo , Viroses/tratamento farmacológico , Viroses/metabolismo , Bactérias/metabolismo , Vírus/metabolismo , Vírus/patogenicidade
19.
Int Wound J ; 21(4): e14864, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619084

RESUMO

Multidrug-resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta-analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%-59.78%). The prevalence of MDR gram-positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%-25.91%), and the prevalence of MDR gram-negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%-39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%-15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%-5.07%)) were the main MDR-GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR-GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%-8.95%), 6.01% (95% CI: 4.03%-8.33%), 3.59% (95% CI: 0.42%-9.30%), 3.50% (95% CI: 2.31%-4.91%), and 3.27% (95% CI: 1.74%-5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non-MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non-MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR-GNB was greater than that of MDR-GPB in DFUs. MDR S. aureus was the main MDR-GPB in DFUs, and MDR E. coli was the main MDR-GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.


Assuntos
Infecções Bacterianas , Diabetes Mellitus , Pé Diabético , Osteomielite , Doenças Vasculares Periféricas , Humanos , Pé Diabético/epidemiologia , Escherichia coli , Prevalência , Staphylococcus aureus , Antibacterianos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia
20.
J Colloid Interface Sci ; 665: 855-862, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38564949

RESUMO

Bacterial infections are the primary causes of infectious diseases in humans. In recent years, the abuse of antibiotics has led to the widespread enhancement of bacterial resistance. Concerns have been raised about the identification of a common treatment platform for bacterial infections. In this study, a composite nanomaterial was used for near-infrared II (NIR-II) photothermal antibacterial treatment. Red blood cell membrane was peeled and coated onto the surface of the Au/polydopamine nanoparticle-containing aptamer. The composite nanomaterials based on Au/polydopamine exhibit highest photothermal conversion capability. Moreover, these assembled nanoparticles can quickly enter the body's circular system with a specific capability to recognise bacteria. In vivo experiments demonstrated that the composites could kill bacteria from infected blood while significantly reducing the level of bacteria in various organs. Such assemblies offer a paradigm for the treatment of bacterial infections caused by the side effects of antibiotics.


Assuntos
Infecções Bacterianas , Indóis , Nanopartículas , Polímeros , Humanos , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Bactérias , Membrana Celular
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