RESUMO
Parvimonas micra is a gram-positive anaerobic coccus typically found in the human oral cavity, upper respiratory tract and gastrointestinal system. It occasionally causes intra-abdominal abscesses, spondylodiscitis and other infections. There are very few case reports on mycotic aneurysm related to P. micra We describe a rare case of P. micra orbital cellulitis complicated with meningitis, cerebral venous thrombosis and internal carotid artery mycotic aneurysm, which was successfully treated with the combination of endovascular therapy and antibiotics. Additionally, the patient received 6 months of anticoagulation therapy for cerebral venous thrombosis.
Assuntos
Aneurisma Infectado , Antibacterianos , Celulite Orbitária , Humanos , Celulite Orbitária/microbiologia , Celulite Orbitária/complicações , Antibacterianos/uso terapêutico , Aneurisma Infectado/complicações , Infecções por Bactérias Gram-Positivas/complicações , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/diagnóstico , Masculino , Firmicutes , Trombose Venosa/complicações , Trombose Venosa/tratamento farmacológico , Anticoagulantes/uso terapêutico , Trombose Intracraniana/complicações , Trombose Intracraniana/tratamento farmacológico , Procedimentos Endovasculares/métodos , FemininoRESUMO
BACKGROUND: Enterococcus gallinarum is an infrequently intestinal symbiotic pathogen associated with nosocomial infection in immunocompromised individuals. To date, rare cases of pulmonary infection attributable to Enterococcus gallinarum were reported. Herein, we presented the first case of empyema resulting from Enterococcus gallinarum infection. CASE PRESENTATION: An 81-year-old male presented with fever and dyspnea upon admission. Chest CT scan and thoracic ultrasonography confirmed the presence of right pleural effusion. Thoracoscopy revealed extensive adhesion, purulent fluid, and necrotic materials within the thoracic cavity. Enterococcus gallinarum was identified through pleural effusion culture. The patient underwent an intrathoracic injection of urokinase along with thoracic drainage. Following surgery, He took oral linezolid for over one month. Undergoing comprehensive treatment, the patient exhibited favorable recovery. CONCLUSIONS: We reported the first case of empyema due to Enterococcus gallinarum infection. It should be suspected in patients with impaired immune function and invasive therapies, without responding to conventional anti-infectious treatment.
Assuntos
Enterococcus , Infecções por Bactérias Gram-Positivas , Humanos , Masculino , Idoso de 80 Anos ou mais , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/diagnóstico , Enterococcus/isolamento & purificação , Antibacterianos/uso terapêutico , Empiema Pleural/microbiologia , Empiema Pleural/tratamento farmacológico , Empiema/microbiologia , Empiema/tratamento farmacológico , Tomografia Computadorizada por Raios X , Linezolida/uso terapêuticoRESUMO
BACKGROUND: Enterococcus gallinarum (EG) is typically found in the gastrointestinal tracts of birds and mammals. Although its strains are rarely isolated from clinical specimens, EG can lead to septicemia in immunocompromised individuals. EG infections are uncommon in household settings, but their incidence has been rising due to increased antibiotic usage and invasive treatments, particularly in Neonatal Intensive Care Units (NICUs). EG inherently exhibits resistance to vancomycin but is highly sensitive to linezolid. Despite showing in vitro resistance, vancomycin has shown clinical efficacy in treating EG meningitis. CASE PRESENTATION: A neonate born at 30 + 2 weeks gestation was admitted to the Neonatal Intensive Care Unit (NICU) after EG was detected in blood and cerebrospinal fluid cultures. Susceptibility testing indicated that the bacterial strain was resistant to vancomycin and sensitive to linezolid. Initially, vancomycin was selected for treatment. However, due to persistent EG cultures in the blood and cerebrospinal fluid, the treatment was adjusted to linezolid. This led to a rapid decrease in platelet (PLT) count, suspected to be an adverse reaction. Concurrently, the patient experienced recurrent fever and elevated inflammatory marker levels, prompting the discontinuation of linezolid and a return to vancomycin. Subsequent administration of vancomycin stabilized the patient's condition, as evidenced by improved C-reactive protein (CRP), procalcitonin (PCT), and cerebrospinal fluid parameters, ultimately leading to discharge after an eight-week treatment period. CONCLUSION: This retrospective analysis highlights the efficacy of vancomycin in treating EG infections, suggesting that specific genetic phenotypes may influence treatment sensitivity. Monitoring vancomycin blood levels is crucial for determining treatment effectiveness.
Assuntos
Antibacterianos , Infecções por Bactérias Gram-Positivas , Linezolida , Vancomicina , Humanos , Recém-Nascido , Vancomicina/uso terapêutico , Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/microbiologia , Linezolida/uso terapêutico , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Masculino , FemininoRESUMO
Bacillus cereus is a bacterium capable of causing late-onset neonatal sepsis. By analyzing 11 cases, this study investigates the diagnosis, treatment, and prognosis of Bacillus cereus infections, aiming to provide insights into clinical diagnosis and therapy. The study scrutinized 11 instances of late-onset neonatal sepsis, including two fatalities attributable to Bacillus cereus, one accompanied by cerebral hemorrhage. An examination and analysis of these cases' symptoms, signs, laboratory tests, and treatment processes, along with a review of related literature from 2010 to 2020, revealed a high mortality rate of 41.38% in non-gastrointestinal infections caused by Bacillus cereus. Our findings underscore the critical importance of rapid diagnosis and effective antimicrobial therapy in reducing mortality rates. Once the source of infection is identified, implementing effective infection control measures is essential.
Assuntos
Antibacterianos , Bacillus cereus , Infecções por Bactérias Gram-Positivas , Sepse Neonatal , Humanos , Recém-Nascido , Antibacterianos/uso terapêutico , Bacillus cereus/isolamento & purificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/diagnóstico , Sepse Neonatal/microbiologia , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/diagnósticoRESUMO
BACKGROUND: Mediterraneibacter gnavus is a Gram positive, non-sporulated, obligate anaerobe diplococci. It was first described in 1974 by Moore et al. (under the name Ruminococcus gnavus) from faeces and contents of the gastrointestinal tract of humans. It is a relatively common member of the human gut microbiota, nevertheless its role as a pathogenic bacterium has not been completely elucidated yet and it seems to depend on numerous factors, including those of the host. Here we present a case of prosthetic joint infection following total knee arthroplasty by M. gnavus. CASE PRESENTATION: A 74 years old patient was admitted to the emergency department presenting with acute onset of left knee pain and swelling 20 days after total left knee arthroplasty. Follow-up revealed erythema and oedema without signs of fluctuation or purulent discharge from the surgical wound and elevated inflammatory reactants. Synovial fluid was taken for bacterial culture and antibiotic treatment with ceftazidime and daptomycin was established. Examination of the synovial fluid revealed abundant polymorphonuclear leucocytes, without visualizing bacteria. After four days of incubation, anaerobic culture exhibit growth of small, grey, umbilicated colonies in pure culture on Schaedler agar. The microorganism was identified as R. gnavus by MALDI-TOF (Bruker Daltonics) and M. gnavus by 16S ribosomal bacterial sequencing. The isolated showed susceptibility to the most commonly used anaerobicidal antibiotics except for clindamycin. Surgical treatment and infection source control included DAIR (debridement, antibiotics, and implant retention) and vacuum assisted therapy. The patient was discharged after six weeks with a 3-month course of oral amoxicillin as consolidation therapy. Subsequent follow-up revealed adequate wound healing with no signs of infection. CONCLUSIONS: Mediterraneibacter gnavus have been reported as the causal microorganism in a range of human infections, nevertheless its identification remains challenging. Infection of prosthetic joints by anaerobic microorganisms is uncommon and is not considered in its empirical antibiotic treatment, thus, correct and swift identification of anaerobic bacteria in these cases is paramount.
Assuntos
Antibacterianos , Artroplastia do Joelho , Infecções por Bactérias Gram-Positivas , Infecções Relacionadas à Prótese , Humanos , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/tratamento farmacológico , Artroplastia do Joelho/efeitos adversos , Idoso , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/diagnóstico , Antibacterianos/uso terapêutico , Masculino , RNA Ribossômico 16S/genética , Bactérias Anaeróbias/isolamento & purificação , Bactérias Anaeróbias/genética , Bactérias Anaeróbias/classificação , Líquido Sinovial/microbiologiaRESUMO
INTRODUCTION: Dalbavancin is an antibiotic active against most Gram-positive bacteria approved for acute bacterial skin and skin structure infections (ABSSSI). Owing to its long half-life, it is being increasingly used for other indications. PATIENTS AND METHODS: We present a case series of children and adolescents treated with dalbavancin for osteoarticular, catheter-related and other non-ABSSSI infections. RESULTS: Dalbavancin was prescribed to 15 patients. Six (40%) were female and median age at prescription was 11.9 (IQR 1.3-18.0) years. Most of them (12/15) had significant comorbidities. Patients presented mainly with deep surgical site infections, osteoarticular infections and central-line-associated bloodstream infections. The most common isolate was Staphylococcus aureus followed by Staphylococcus epidermidis. Major reasons to prescribe dalbavancin were to ensure compliance and patients' convenience. Two patients discontinued the drug due to adverse events possibly related to it. The rest of the patients completed the treatment with dalbavancin, with a median duration of 56 days (IQR 17.5, 115.5). All achieved complete resolution and present no relapse after a median follow-up of 9.9 months (IQR 4.8, 16.6). CONCLUSIONS: Dalbavancin was a safe, effective and convenient alternative in selected paediatric patients with complicated non-ABSSSI infections caused by Gram-positive bacteria.
Assuntos
Antibacterianos , Uso Off-Label , Teicoplanina , Humanos , Teicoplanina/análogos & derivados , Teicoplanina/uso terapêutico , Teicoplanina/efeitos adversos , Teicoplanina/administração & dosagem , Feminino , Criança , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Masculino , Pré-Escolar , Lactente , Adolescente , Resultado do Tratamento , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/microbiologiaRESUMO
Background: Enterococcus faecalis (E. faecalis) is one of the main pathogens responsible for refractory root canal infections in the teeth and shows resistance against various antibacterial managements. Effective control of E. faecalis infection is a prerequisite for successful treatment of refractory apical periodontitis. This study aimed to analyze the antibacterial activity and mechanisms of Au@Ag nanoparticles (NPs) combined with photothermal therapy (PTT) against the original and Ag+-resistant E. faecalis. Methods: Au@AgNPs with optimal shell thicknesses were synthesized and characterized. The antibacterial activity of Au@AgNPs with PTT against the original or Ag+-resistant E. faecalis was evaluated, and the antibiofilm activity was tested on E. faecalis biofilm on the dentin of teeth. The potential antibacterial mechanisms of Au@AgNPs combined with PTT against E. faecalis have also been studied. Moreover, its influence on dentin microhardness and cytotoxicity was assessed. Results: This study revealed that Au@AgNPs combined with PTT showed enhanced antibacterial and antibiofilm effects, no negative effects on dentin microhardness, and low cytotoxicity toward human periodontal ligament cells (hPDLCs). Moreover, Au@AgNPs combined with PTT effectively inhibited the growth of Ag+-resistant E. faecalis. Its antibacterial effects may be exerted through the release of silver ions (Ag+), destruction of the cell membrane, production of reactive oxygen species (ROS) and inhibition of adenosine triphosphate (ATP) production. Hyperthermia generated by Au@AgNPs with PTT reduced membrane fluidity and enhanced Ag+ sensitivity by downregulating fabF expression. The upregulated expression of heat shock genes demonstrated that the Ag+ released from Au@AgNPs compromised the heat adaptation of E. faecalis. Conclusion: PTT significantly enhanced Ag+ sensitivity of the original and Ag+-resistant E. faecalis. Au@AgNPs combined with PTT may have the potential to be developed as a new antibacterial agent to control E. faecalis infections in teeth.
Assuntos
Antibacterianos , Biofilmes , Dentina , Enterococcus faecalis , Ouro , Nanopartículas Metálicas , Prata , Prata/química , Prata/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Enterococcus faecalis/efeitos dos fármacos , Humanos , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Dentina/química , Dentina/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Terapia Fototérmica/métodos , Testes de Sensibilidade Microbiana , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Raios Infravermelhos , Espécies Reativas de Oxigênio/metabolismoRESUMO
The primary obstacles in the management of Enterococcus and Streptococcal infections are drug resistance and biofilm formation. Our study revealed that loratadine at a concentration of ≥25 µM exhibited significant inhibitory effects on biofilm formation in 167 clinical strains of Enterococcus faecalis and 15 clinical isolates of Streptococcus agalactiae, Streptococcus pyogenes, and Streptococcus pneumoniae. Additionally, the antibiofilm activity against E. faecalis and Streptococcal was demonstrated by several loratadine derivatives with altered side-chain carbamate moieties. This study investigated the antibacterial activity of the loratadine derivative Lo-7 against clinical strains of S. agalactiae and S. pyogenes, with minimum inhibitory concentrations ranging from 12.5 to 25 µM. The findings revealed that a low concentration of loratadine derivative Lo-7 (3.125 µM) significantly augmented the bactericidal efficacy of vancomycin against multidrug-resistant (MDR) S. agalactiae, both in vitro and in vivo. The loratadine derivative Lo-7, even at low concentrations, demonstrated significant efficacy in eliminating intracellular MDR S. agalactiae within macrophages, potentially indicating a unique advantage over vancomycin, linezolid, and loratadine. Mechanistically, exposure to the loratadine derivative Lo-7 resulted in membrane depolarization without affecting membrane permeability in S. agalactiae. The potential targeting of the SecG subunit of the SecYEG membrane-embedded channel by the loratadine derivative Lo-7 in S. agalactiae was identified through quantitative proteomics, a drug affinity responsive target stability assay, and molecular docking.
Assuntos
Antibacterianos , Biofilmes , Loratadina , Testes de Sensibilidade Microbiana , Infecções Estreptocócicas , Loratadina/farmacologia , Loratadina/química , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/tratamento farmacológico , Humanos , Streptococcus agalactiae/efeitos dos fármacos , Animais , Enterococcus/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Camundongos , Vancomicina/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacosRESUMO
Parvimonas micra, a gram-positive anaerobic bacterium, has garnered increased attention due to its role in infective endocarditis. We present a challenging prosthetic valve endocarditis caused by Parvimonas micra in a patient with a complex cardiac history involving multiple surgeries. The case highlights the difficulties in diagnosis and treatment, emphasizing the importance of advanced diagnostic techniques, including metagenomics next-generation sequencing (mNGS). Additionally, it underscores the need for heightened vigilance regarding oral symptoms and the potential risk of bacteremia in post-valvular surgery patients. This report contributes to a better understanding of Parvimonas micra-associated endocarditis and its unique characteristics.
Assuntos
Endocardite Bacteriana , Firmicutes , Infecções por Bactérias Gram-Positivas , Próteses Valvulares Cardíacas , Infecções Relacionadas à Prótese , Humanos , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/tratamento farmacológico , Próteses Valvulares Cardíacas/efeitos adversos , Próteses Valvulares Cardíacas/microbiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Firmicutes/isolamento & purificação , Firmicutes/genética , Masculino , Antibacterianos/uso terapêutico , Sequenciamento de Nucleotídeos em Larga Escala , Pessoa de Meia-IdadeRESUMO
BACKGROUND: This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms. METHODS: A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS). RESULTS: Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage. CONCLUSION: Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.
Assuntos
Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Linezolida , Testes de Sensibilidade Microbiana , Linezolida/farmacologia , Humanos , China/epidemiologia , Enterococcus faecium/genética , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/isolamento & purificação , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Enterococcus faecalis/genética , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/isolamento & purificação , Feminino , Vancomicina/farmacologia , Antibacterianos/farmacologia , Epidemiologia Molecular , Adulto , Resistência a Vancomicina/genética , Idoso , Estudos Retrospectivos , Enterococos Resistentes à Vancomicina/genética , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/isolamento & purificação , Adulto Jovem , Enterococcus/genética , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificaçãoRESUMO
Enterococcus faecalis is a troublesome nosocomial pathogen that acquired resistance to most available antimicrobial agents. Antivirulence agents represent an unconventional treatment approach. Here, transcription factor decoy (TFD)-loaded cationic liposomes (TLL) were developed as an inhibitor of the Fsr quorum-sensing system and its associated virulence traits, in E. faecalis. The consensus sequence of the FsrA binding site was found conserved among 651 E. faecalis annotated genomes. The TFD was synthesized as an 82 bp DNA duplex, containing the conserved binding sequence, and loaded onto cationic liposomes. The optimum loading capacity, mean particle size, and zeta potential of the TLL were characterized. The developed TLL lacked any effect on E. faecalis growth and significantly inhibited the in vitro production of the proteolytic enzymes controlled by the Fsr system; gelatinase and serine protease, in a concentration-dependent manner. This inhibition was accompanied by a significant reduction in the transcription levels of FsrA-regulated genes (fsrB, gelE, and sprE). The developed TLL were safe as evidenced by the nonhemolytic effect on human RBCs and the negligible cytotoxicity on human skin fibroblast cells. Moreover, in the larvae infection model, TLL displayed a significant abolish in the mortality rates of Galleria mellonella larvae infected with E. faecalis. In conclusion, the developed TLL offer a new safe strategy for combating E. faecalis infection through the inhibition of quorum-sensing-mediated virulence; providing a platform for the development of similar agents to combat many other pathogens.
Assuntos
Proteínas de Bactérias , Enterococcus faecalis , Infecções por Bactérias Gram-Positivas , Percepção de Quorum , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/genética , Animais , Virulência/efeitos dos fármacos , Humanos , Percepção de Quorum/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Antibacterianos/farmacologia , Lipossomos , Larva/microbiologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Fatores de Virulência/genética , Gelatinases/metabolismo , Gelatinases/antagonistas & inibidores , Mariposas/microbiologia , Eritrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Serina Proteases/metabolismo , Serina Proteases/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Nanopartículas/química , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismoRESUMO
BackgroundVancomycin-resistant enterococci (VRE) are increasing in Denmark and Europe. Linezolid and vancomycin-resistant enterococci (LVRE) are of concern, as treatment options are limited. Vancomycin-variable enterococci (VVE) harbour the vanA gene complex but are phenotypically vancomycin-susceptible.AimThe aim was to describe clonal shifts for VRE and VVE in Denmark between 2015 and 2022 and to investigate genotypic linezolid resistance among the VRE and VVE.MethodsFrom 2015 to 2022, 4,090 Danish clinical VRE and VVE isolates were whole genome sequenced. We extracted vancomycin resistance genes and sequence types (STs) from the sequencing data and performed core genome multilocus sequence typing (cgMLST) analysis for Enterococcus faecium. All isolates were tested for the presence of mutations or genes encoding linezolid resistance.ResultsIn total 99% of the VRE and VVE isolates were E. faecium. From 2015 through 2019, 91.1% of the VRE and VVE were vanA E. faecium. During 2020, to the number of vanB E.â¯faecium increased to 254 of 509 VRE and VVE isolates. Between 2015 and 2022, seven E. faecium clusters dominated: ST80-CT14 vanA, ST117-CT24 vanA, ST203-CT859 vanA, ST1421-CT1134 vanA (VVE cluster), ST80-CT1064 vanA/vanB, ST117-CT36 vanB and ST80-CT2406 vanB. We detected 35 linezolid vancomycin-resistant E. faecium and eight linezolid-resistant VVEfm.ConclusionFrom 2015 to 2022, the numbers of VRE and VVE increased. The spread of the VVE cluster ST1421-CT1134 vanA E. faecium in Denmark is a concern, especially since VVE diagnostics are challenging. The finding of LVRE, although in small numbers, ia also a concern, as treatment options are limited.
Assuntos
Antibacterianos , Proteínas de Bactérias , Carbono-Oxigênio Ligases , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Linezolida , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Resistência a Vancomicina , Enterococos Resistentes à Vancomicina , Enterococos Resistentes à Vancomicina/genética , Enterococos Resistentes à Vancomicina/isolamento & purificação , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Enterococcus faecium/genética , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/isolamento & purificação , Humanos , Dinamarca/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Carbono-Oxigênio Ligases/genética , Linezolida/farmacologia , Resistência a Vancomicina/genética , Sequenciamento Completo do Genoma , Vancomicina/farmacologia , Vancomicina/uso terapêutico , GenótipoRESUMO
Introduction: Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and progressive bone destruction. However, conventional root canal disinfectants are highly damaging to the tooth and periodontal tissue and ineffective in treating persistent root canal infections. Antimicrobial materials that are biocompatible with apical tissues and can eliminate PEIs-associated bacteria are urgently needed. Methods: Here, ε-poly (L-lysine) derived carbon quantum dots (PL-CQDs) are fabricated using pyrolysis to remove PEIs-associated bacterial biofilms. Results: Due to their ultra-small size, high positive charge, and active reactive oxygen species (ROS) generation capacity, PL-CQDs exhibit highly effective antibacterial activity against Enterococcus faecalis (E. faecalis), which is greatly dependent on PL-CQDs concentrations. 100 µg/mL PL-CQDs could kill E. faecalis in 5 min. Importantly, PL-CQDs effectively achieved a reduction of biofilms in the isolated teeth model, disrupting the dense structure of biofilms. PL-CQDs have acceptable cytocompatibility and hemocompatibility in vitro and good biosafety in vivo. Discussion: Thus, PL-CQDs provide a new strategy for treating E. faecalis-associated PEIs.
Assuntos
Biofilmes , Carbono , Enterococcus faecalis , Infecções por Bactérias Gram-Positivas , Polilisina , Pontos Quânticos , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/fisiologia , Pontos Quânticos/química , Biofilmes/efeitos dos fármacos , Polilisina/química , Polilisina/farmacologia , Carbono/química , Carbono/farmacologia , Animais , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Espécies Reativas de Oxigênio/metabolismo , CamundongosRESUMO
Slackia exigua, originally classified as Eubacterium exiguum, is a Gram-positive, asaccharolytic, rod-shaped anaerobic bacterium. The virulence factors of S. exigua have not been accurately identified. The objective of the study is to evaluate the pathogenic potential of S. exigua by presenting the cases of infections diagnosed at our hospital laboratory. Additionally, we reviewed the literature to summarize the experience with S. exigua infections to clarify, in the light of current knowledge, the clinical picture, diagnostic, and therapeutic issues related to this anaerobic bacterium. We reported eleven severe human infections caused by S. exigua. All patients required hospitalization. Nine of the cases involved chronic infections in the stomatognathic system, in two patients, skin infections were diagnosed. As it is known, S. exigua is a component of the human microbiota; however, it can cause opportunistic infections, particularly in the case of translocation outside its natural habitat. A critical literature analysis revealed that S. exigua can be responsible for bacteremia, meningitis, tissue necrosis, periprosthetic joint infection, and osteomyelitis. Several studies have been published regarding the determination of drug susceptibility of S. exigua. The isolated strains were susceptible to most antibiotics used for the treatment of anaerobic infections. The interpretation of antimicrobial susceptibility testing for some slow-growing in vitro, infrequently causing infections anaerobic bacteria, such as S. exigua, is based on The European Committee on Antimicrobial Susceptibility Testing (EUCAST) additional guidance taking into account the determination of drug susceptibility for groups of microorganisms for which cut-off values have not been developed.
Assuntos
Antibacterianos , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Antibacterianos/uso terapêutico , Idoso , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/microbiologia , PolôniaRESUMO
Leuconostoc species are regarded as important causes for many infections in immunocompromised patients. In this study, we assessed the characteristics of Leuconostoc spp. causing bacteremia in patients at our center. This observational analysis was conducted in the microbiology laboratory of a tertiary care center in northern India from July 2021 to July 2023. Patients in whom blood culture bottles were positive for Leuconostoc lactis were included in the study. Culture isolates were identified by MALDI-ToF MS as L. lactis and tested for antibiotic sensitivity results by Kirby-Bauer disk diffusion method. Demographic and clinical details were collected and analyzed. During the study period, 6,742 blood culture bottles flagged positive. Among these, L. lactis was isolated from 14 (0.21%) patients. The median patient age was 34 years. The male-to-female ratio was 2.5:1. All the patients with L. lactis bacteremia had an underlying condition leading to immunosuppression (e.g., carcinoma and chronic kidney disease). All the patients with L. lactis bacteremia had an intravascular device present at the time of bacteremia. All isolates in the study were sensitive to doxycycline, high level gentamicin, minocycline, ampicillin-sulbactam, and linezolid. Mortality was attributed to bacteremia by L. lactis in five patients. Appropriate and timely identification of the Leuconostoc species is important for the clinician to tailor regimens for the patients.
Assuntos
Antibacterianos , Bacteriemia , Leuconostoc , Centros de Atenção Terciária , Humanos , Bacteriemia/microbiologia , Bacteriemia/epidemiologia , Bacteriemia/tratamento farmacológico , Índia/epidemiologia , Masculino , Feminino , Leuconostoc/isolamento & purificação , Leuconostoc/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Pessoa de Meia-Idade , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/mortalidade , Adulto Jovem , Testes de Sensibilidade Microbiana , IdosoRESUMO
INTRODUCTION: Infections due to multidrug-resistant organisms (MDRO) are a serious concern for public health with high morbidity and mortality. Though many antibiotics have been introduced to manage these infections, there are remaining concerns regarding the optimal management of Gram-positive MDROs. AREAS COVERED: A literature search on the PubMed/Medline database was conducted. We applied no language and time limits for the search strategy. In this narrative review, we discuss the current options for managing Gram-positive MDROs as well as non-traditional antibacterial agents in development. EXPERT OPINION: Despite their introduction more than 70 years ago, glycopeptides are still the cornerstone in treating Gram-positive infections: all registrative studies of new antibiotics have glycopeptides as control; these studies are designed as not inferior studies, therefore it is almost impossible to give recommendations other than the use of glycopeptides in the treatment of Gram-positive infections. The best evidence on treatments different from glycopeptides comes from post-hoc analysis and meta-analysis. Non-traditional antibacterial agents are being studied to aid in short and effective antibiotic therapies. The use of non-traditional antibacterial agents is not restricted to replacing traditional antibacterial agents with alternative therapies; instead, they should be used in combination with antibiotic therapies.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Glicopeptídeos , Bactérias Gram-Positivas , Infecções por Bactérias Gram-Positivas , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Glicopeptídeos/uso terapêutico , Bactérias Gram-Positivas/efeitos dos fármacos , Desenvolvimento de Medicamentos , AnimaisRESUMO
Background and Objective: Enterococci are typically found in a healthy human gastrointestinal tract but can cause severe infections in immunocompromised patients. Such infections are treated with antibiotics. This study addresses the rising concern of antimicrobial resistance (AMR) in Enterococci, focusing on the prevalence of vancomycin-resistant enterococcus (VRE) strains. Materials and Methods: The pilot study involved 140 Enterococci isolates collected between 2021 and 2022 from two multidisciplinary hospitals (with and without local therapeutic drug monitoring protocol of vancomycin) in Latvia. Microbiological assays and whole genome sequencing were used. AMR gene prevalence with resistance profiles were determined and the genetic relationship and outbreak evaluation were made by applying core genome multi-locus sequence typing (cgMLST). Results: The acquired genes and mutations were responsible for resistance against 10 antimicrobial classes, including 25.0% of isolates expressing resistance to vancomycin, predominantly of the vanB type. Genetic diversity among E. faecalis and E. faecium isolates was observed and seven potential outbreak clusters were identified, three of them containing sequence types ST6, ST78 and ST80. The prevalence of vancomycin resistance was highest in the hospital without a therapeutic drug-monitoring protocol and in E. faecium. Notably, a case of linezolid resistance due to a mutation was documented. Conclusions: The study illustrates the concerning prevalence of multidrug-resistant Enterococci in Latvian hospitals, showcasing the rather widespread occurrence of vancomycin-resistant strains. This highlights the urgency of implementing efficient infection control mechanisms and the need for continuous VRE surveillance in Latvia to define the scope and pattern of the problem, influencing clinical decision making and planning further preventative measures.
Assuntos
Antibacterianos , Humanos , Letônia/epidemiologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Projetos Piloto , Enterococcus/efeitos dos fármacos , Enterococcus/genética , Testes de Sensibilidade Microbiana , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/isolamento & purificação , Farmacorresistência Bacteriana/genética , Tipagem de Sequências Multilocus , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Daptomycin is widely used in critically ill patients for Gram-positive bacterial infections. Extracorporeal membrane oxygenation (ECMO) is increasingly used in this population and can potentially alter the pharmacokinetic (PK) behaviour of antibiotics. However, the effect of ECMO has not been evaluated in daptomycin. Our study aims to explore the effect of ECMO on daptomycin in critically ill patients through population pharmacokinetic (PopPK) analysis and to determine optimal dosage regimens based on both efficacy and safety considerations. METHODS: A prospective, open-label PK study was carried out in critically ill patients with or without ECMO. The total concentration of daptomycin was determined by UPLC-MS/MS. NONMEM was used for PopPK analysis and Monte Carlo simulations. RESULTS: Two hundred and ninety-three plasma samples were collected from 36 critically ill patients, 24 of whom received ECMO support. A two-compartment model with first-order elimination can best describe the PK of daptomycin. Creatinine clearance (CLCR) significantly affects the clearance of daptomycin while ECMO has no significant effect on the PK parameters. Monte Carlo simulations showed that, when the MICs for bacteria are â≥1â mg/L, the currently recommended dosage regimen is insufficient for critically ill patients with CLCRâ>â30â mL/min. Our simulations suggest 10â mg/kg for patients with CLCR between 30 and 90â mL/min, and 12â mg/kg for patients with CLCR higher than 90â mL/min. CONCLUSIONS: This is the first PopPK model of daptomycin in ECMO patients. Optimal dosage regimens considering efficacy, safety, and pathogens were provided for critical patients based on pharmacokinetic-pharmacodynamic analysis.
Assuntos
Antibacterianos , Estado Terminal , Daptomicina , Oxigenação por Membrana Extracorpórea , Método de Monte Carlo , Humanos , Daptomicina/farmacocinética , Daptomicina/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Idoso , Testes de Sensibilidade Microbiana , Espectrometria de Massas em Tandem , Infecções por Bactérias Gram-Positivas/tratamento farmacológicoRESUMO
The rapid increase of antimicrobial-resistant bacteria in humans and livestock is concerning. Antimicrobials are essential for the treatment of disease in modern day medicine, and their misuse in humans and food animals has contributed to an increase in the prevalence of antimicrobial-resistant bacteria. Globally, antimicrobial resistance is recognized as a One Health problem affecting humans, animals, and environment. Enterococcal species are Gram-positive bacteria that are widely distributed in nature. Their occurrence, prevalence, and persistence across the One Health continuum make them an ideal candidate to study antimicrobial resistance from a One Health perspective. The objective of this review was to summarize the role of enterococci as an indicator of antimicrobial resistance across One Health sectors. We also briefly address the prevalence of enterococci in human, animal, and environmental settings. In addition, a 16S RNA gene-based phylogenetic tree was constructed to visualize the evolutionary relationship among enterococcal species and whether they segregate based on host environment. We also review the genomic basis of antimicrobial resistance in enterococcal species across the One Health continuum.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Enterococcus , Saúde Única , Filogenia , Enterococcus/efeitos dos fármacos , Enterococcus/genética , Humanos , Antibacterianos/farmacologia , Animais , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , RNA Ribossômico 16S/genéticaRESUMO
PURPOSE: The principal objective of this project was to review and thoroughly examine the chemical characteristics, pharmacological activity, and quantification methods associated with contezolid. METHODS: The article was based on published and ongoing preclinical and clinical studies on the application of contezolid. These studies included experiments on the physicochemical properties of contezolid, in vitro antimicrobial research, in vivo antimicrobial research, and clinical trials in various phases. There were no date restrictions on these studies. RESULTS: In June 2021, contezolid was approved for treating complicated skin and soft tissue infections. The structural modification of contezolid has resulted in better efficacy compared to linezolid. It inhibits bacterial growth by preventing the production of the functional 70S initiation complex required to translate bacterial proteins. The current evidence has indicated a substantial decline in myelosuppression and monoamine oxidase inhibition without impairing its antibacterial properties. Contezolid was found to have a more significant safety profile and to be metabolised by flavin monooxygenase 5, reducing the risk of harmful effects due to drug-drug interactions. Adjusting doses is unnecessary for patients with mild to moderate renal or hepatic insufficiency. CONCLUSION: As an oral oxazolidinone antimicrobial agent, contezolid is effective against multi-drug resistant Gram-positive bacteria. The introduction of contezolid provided a new clinical option.