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2.
FEMS Microbiol Lett ; 3712024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38740525

RESUMEN

Enterococcus raffinosus, named by Collins et al. in 1989, is a cocci-shaped bacterium that typically appears in pairs or short chains. As a Gram-positive and non-motile bacterium, it grows at 10°C-45°C, exhibiting negative peroxidase activity [1]. It is a normal flora in the oropharynx and gastrointestinal tract of domestic cats [2] and can also be isolated from human rectal swabs [3], it belongs to the same genus Enterococcus as Enterococcus faecalis and Enterococcus faecium. Enterococcus faecalis and Enterococcus faecium constitute 90% of clinically isolated strains. However, the incidence of other enterococci, excluding E. faecalis and E. faecium, is on the rise [4]. In this case report, a patient with pediatric urinary tract infections caused by E. raffinosus was presented, and a summary of relevant literature was provided.


Asunto(s)
Antibacterianos , Enterococcus , Infecciones por Bacterias Grampositivas , Infecciones Urinarias , Humanos , Infecciones Urinarias/microbiología , Infecciones Urinarias/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Enterococcus/efectos de los fármacos , Enterococcus/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Masculino , Remisión Espontánea , Niño
3.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38732016

RESUMEN

Enterococcus spp. are normal intestinal tract microflorae found in poultry. However, the last decades have shown that several species, e.g., Enterococcus cecorum, have become emerging pathogens in broilers and may cause numerous losses in flocks. In this study, two combinations (H1 and H2) of menthol, 1,8-cineol, linalool, methyl salicylate, γ-terpinene, p-cymene, trans-anethole, terpinen-4-ol and thymol were used in an in vitro model, analyzing its effectiveness against the strains E. cecorum, E. faecalis, E. faecium, E. hirae and E. gallinarum isolated from broiler chickens from industrial farms. To identify the isolated strains classical microbiological methods and VITEK 2 GP cards were used. Moreover for E. cecorum a PCR test was used.. Antibiotic sensitivity (MIC) tests were performed for all the strains. For the composition H1, the effective dilution for E. cecorum and E. hirae strains was 1:512, and for E. faecalis, E. faecium and E. gallinarum, 1:1024. The second mixture (H2) showed very similar results with an effectiveness at 1:512 for E. cecorum and E. hirae and 1:1024 for E. faecalis, E. faecium and E. gallinarum. The presented results suggest that the proposed composition is effective against selected strains of Enterococcus in an in vitro model, and its effect is comparable to classical antibiotics used to treat this pathogen in poultry. This may suggest that this product may also be effective in vivo and provide effective support in the management of enterococcosis in broiler chickens.


Asunto(s)
Antibacterianos , Pollos , Enterococcus , Pruebas de Sensibilidad Microbiana , Animales , Pollos/microbiología , Enterococcus/efectos de los fármacos , Enterococcus/genética , Enterococcus/aislamiento & purificación , Antibacterianos/farmacología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Probióticos/farmacología , Infecciones por Bacterias Grampositivas/veterinaria , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico
4.
ACS Infect Dis ; 10(5): 1725-1738, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38602352

RESUMEN

Host-acting compounds are emerging as potential alternatives to combating antibiotic resistance. Here, we show that bosutinib, an FDA-approved chemotherapeutic for treating chronic myelogenous leukemia, does not possess any antibiotic activity but enhances macrophage responses to bacterial infection. In vitro, bosutinib stimulates murine and human macrophages to kill bacteria more effectively. In a murine wound infection with vancomycin-resistant Enterococcus faecalis, a single intraperitoneal bosutinib injection or multiple topical applications on the wound reduce the bacterial load by approximately 10-fold, which is abolished by macrophage depletion. Mechanistically, bosutinib stimulates macrophage phagocytosis of bacteria by upregulating surface expression of bacterial uptake markers Dectin-1 and CD14 and promoting actin remodeling. Bosutinib also stimulates bacterial killing by elevating the intracellular levels of reactive oxygen species. Moreover, bosutinib drives NF-κB activation, which protects infected macrophages from dying. Other Src kinase inhibitors such as DMAT and tirbanibulin also upregulate expression of bacterial uptake markers in macrophages and enhance intracellular bacterial killing. Finally, cotreatment with bosutinib and mitoxantrone, another chemotherapeutic in clinical use, results in an additive effect on bacterial clearance in vitro and in vivo. These results show that bosutinib stimulates macrophage clearance of bacterial infections through multiple mechanisms and could be used to boost the host innate immunity to combat drug-resistant bacterial infections.


Asunto(s)
Compuestos de Anilina , Macrófagos , Nitrilos , Fagocitosis , Quinolinas , Nitrilos/farmacología , Fagocitosis/efectos de los fármacos , Animales , Quinolinas/farmacología , Macrófagos/efectos de los fármacos , Compuestos de Anilina/farmacología , Ratones , Humanos , Enterococcus faecalis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/farmacología , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Supervivencia Celular/efectos de los fármacos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico
5.
J Pak Med Assoc ; 74(3): 469-475, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38591280

RESUMEN

Objectives: To investigate the isolation rates, antimicrobial resistance rates, minimum inhibitory concentration values of antimicrobial agents, and clonal relationships of Enterococcus faecalis and Enterococcus faeciumdue to the relocation of a hospital to a newly constructed building. METHODS: The comparative, prospective study was conducted at adult general intensive care units of the Mus State Hospital, Mus, Turkey, in two phases; before the relocation from January 25 to December 1, 2014, and after the relocation from February 10 to May 24, 2015. Rectal swab samples were collected 72 hours post-hospitalisation. Identification of Enterococcus faecalis and Enterococcus faeciumisolates was determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial resistance with minimum inhibitory concentration values was detected with Vitek 2 system. The clonal relatedness among the strains was investigated by pulsed-field gel electrophoresis. Data was analysed using SPSS 23. RESULTS: Of the 69 patients, 37(53.62%) were related to pre-relocation phase; 20(54.1%) females and 17(45.9%) males with mean age 62.81±21.71 years. There were 32(46.37%) patients in the post-relocation phase; 13(40.6%) females and 19(59.4%) males with mean age 62.69±21.35 years (p>0.05). Of the 84 enterococci strains isolated, 51(60.7%) were Enterococcus faecium; 28(55%) before relocation and 23(45%) after relocation (p=0.77). The remaining 33(39.3%) isolates were Enterococcus faecalis; 16(48.5%) before relocation and 17(51.5%) after relocation (p=0.73). Multiple strains were located in 7(18.9%) patients before relocation and in 7(21.9%) after relocation. In 1(3.1%) patient after relocation, 2(8.7%) Enterococcus faecium isolates with different resistance and pulsed-field gel electrophoresis patterns were detected. There were no significant differences between the isolation and antibiotic resistance rates before and after relocation (p>0.05), and a clonal relation between the isolates was not detected (p>0.05). Decreased minimum inhibitory concentration values were noted for some antibiotics. CONCLUSIONS: Clonal relationship between the isolates and change in the rates of isolation and antimicrobial resistance of Enterococcus faecalis and Enterococcus faecium was not detected due to relocation. Minimum inhibitory concentration values could be used to reveal relocation-related changes in isolates obtained from patients hospitalised in intensive care units.


Asunto(s)
Enterococcus faecium , Infecciones por Bacterias Grampositivas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Enterococcus , Enterococcus faecalis , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Hospitales , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos
6.
BMC Infect Dis ; 24(1): 425, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649870

RESUMEN

BACKGROUND: Necrotising fasciitis (NF) is a life-threatening soft-tissue infection that rapidly destroys the epidermis, subcutaneous tissue, and fascia. Despite their low virulence, Lactobacillus spp. can cause NF, and because of its rare incidence, there is limited information about its molecular and clinicopathological characteristics. We report a rare case of NF in a patient with type 2 diabetes mellitus diagnosed on admission and severe obesity due to infection with two types of Lactobacillus spp. that manifested in extensive necrosis. CASE PRESENTATION: A 48-year-old woman was referred to our hospital with a complaint of difficulty walking due to severe bilateral thigh pain. She presented with mild erythema, swelling, and severe skin pain extending from the pubic region to the groin. The patient was morbidly obese, had renal dysfunction, and had diabetes mellitus diagnosed on admission.; her LRINEC (Laboratory Risk Indicator for Necrotising Fasciitis) score was 9, indicating a high risk of NF. An exploratory surgical incision was made, and NF was diagnosed based on fascial necrosis. Emergent surgical debridement was performed, and cultures of the tissue culture and aspirated fluid/pus revealed two types of Lactobacillus spp.: Lactobacillus salivarius and L. iners. The patient was admitted to the intensive care unit (ICU), where antibiotics were administered and respiratory and circulatory management was performed. Diabetic ketoacidosis was detected, which was treated by controlling the blood glucose level stringently via intravenous insulin infusion. The patient underwent a second debridement on day 11 and a skin suture and skin grafting on day 36. The patient progressed well, was transferred from the ICU to the general ward on day 41, and was discharged unassisted on day 73. CONCLUSIONS: Lactobacillus spp. are rarely pathogenic to healthy individuals and can scarcely trigger NF. However, these bacteria can cause rare infections such as NF in immunocompromised individuals, such as those with diabetes and obesity, and an early diagnosis of NF is imperative; surgical intervention may be required for the prevention of extensive necrosis. The LRINEC score may be useful for the early diagnosis of NF, even for less pathogenic bacteria such as Lactobacillus.


Asunto(s)
Fascitis Necrotizante , Lactobacillus , Humanos , Fascitis Necrotizante/microbiología , Fascitis Necrotizante/patología , Femenino , Persona de Mediana Edad , Lactobacillus/aislamiento & purificación , Diabetes Mellitus Tipo 2/complicaciones , Antibacterianos/uso terapéutico , Desbridamiento , Necrosis/microbiología , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/patología
7.
Am J Health Syst Pharm ; 81(Supplement_2): S40-S48, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38465838

RESUMEN

PURPOSE: Persons who inject drugs (PWID) are at risk for severe gram-positive infections and may require prolonged hospitalization and intravenous (IV) antibiotic therapy. Dalbavancin (DBV) is a long-acting lipoglycopeptide that may reduce costs and provide effective treatment in this population. METHODS: This was a retrospective review of PWID with severe gram-positive infections. Patients admitted from January 1, 2017, to November 1, 2019 (standard-of-care [SOC] group) and from November 15, 2019, to March 31, 2022 (DBV group) were included. The primary outcome was the total cost to the healthcare system. Secondary outcomes included hospital days saved and treatment failure. RESULTS: A total of 87 patients were included (37 in the DBV group and 50 in the SOC group). Patients were a median of 34 years old and were predominantly Caucasian (82%). Staphylococcus aureus (82%) was the most common organism, and bacteremia (71%) was the most common type of infection. Compared to the SOC group, the DBV group would have had a median of 14 additional days of hospitalization if they had stayed to complete their therapy (P = 0.014). The median total cost to the healthcare system was significantly lower in the DBV group than in the SOC group ($31,698.00 vs $45,093.50; P = 0.035). The rate of treatment failure was similar between the groups (32.4% in the DBV group vs 36% in the SOC group; P = 0.729). CONCLUSION: DBV is a cost-saving alternative to SOC IV antibiotics for severe gram-positive infections in PWID, with similar treatment outcomes. Larger prospective studies, including other patient populations, may demonstrate additional benefit.


Asunto(s)
Antibacterianos , Infecciones por Bacterias Grampositivas , Hospitalización , Teicoplanina , Humanos , Teicoplanina/análogos & derivados , Teicoplanina/uso terapéutico , Teicoplanina/economía , Teicoplanina/administración & dosificación , Estudios Retrospectivos , Antibacterianos/economía , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Masculino , Femenino , Adulto , Hospitalización/economía , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/economía , Persona de Mediana Edad , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , Tiempo de Internación , Nivel de Atención , Índice de Severidad de la Enfermedad , Adulto Joven
8.
Am J Trop Med Hyg ; 110(5): 1006-1009, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38507800

RESUMEN

Weissella species are mistaken for Lactobacillus or Leuconostoc because of their Gram-staining property and resistance to vancomycin. In this study, we aimed to evaluate the demographic pattern, presenting symptoms, risk factors, associated pathologies, and clinical outcomes in patients with Weissella infection. We also analyzed the antibiotic susceptibility pattern of the Weissella species isolated. This retrospective observational study was done from January 2021 to August 2023 in a tertiary care referral center in Uttar Pradesh. All Weissella species isolated from blood cultures or cerebrospinal fluid (CSF) samples during this period were included in the study. Twenty-four-hour growth from a positive blood culture or CSF sample was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Demographic and clinical details of the patients were extracted from the hospital information system. Kirby-Bauer disk diffusion was used for antibiotic susceptibility testing. During the 3-year study, 13 isolates of Weissella species were identified in our laboratory. Among the patients, male predominance was seen. The age range of the patients was 5-53 years. The samples were blood samples (n = 11) and CSF samples (n = 2). Of these isolates, 12 (92.3%) were identified as Weissella confusa and 1 (7.69%) was identified as Weissella viridescens. Common risk factors were anemia, prolonged hospital stay, indwelling catheter, chemotherapy, and chronic kidney disease. All the isolates in this study were sensitive to amikacin, daptomycin, amoxicillin-clavulanate, minocycline, and linezolid. Death was attributed to Weissella infection in three patients. Weissella species are opportunistic organisms that need to be identified quickly and precisely to guarantee the right course of treatment.


Asunto(s)
Antibacterianos , Weissella , Humanos , Masculino , Weissella/aislamiento & purificación , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Niño , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Adolescente , Preescolar , Adulto Joven , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/microbiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , India/epidemiología , Factores de Riesgo
9.
BMC Microbiol ; 24(1): 103, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38539119

RESUMEN

Vancomycin-resistant enterococci (VRE) are major opportunistic pathogens and the causative agents of serious diseases, such as urinary tract infections and endocarditis. VRE strains mainly include species of Enterococcus faecium and E. faecalis which can colonise the gastrointestinal tract (GIT) of patients and, following growth and persistence in the gut, can transfer to blood resulting in systemic dissemination in the body. Advancements in genomics have revealed that hospital-associated VRE strains are characterised by increased numbers of mobile genetic elements, higher numbers of antibiotic resistance genes and often lack active CRISPR-Cas systems. Additionally, comparative genomics have increased our understanding of dissemination routes among patients and healthcare workers. Since the efficiency of currently available antibiotics is rapidly declining, new measures to control infection and dissemination of these persistent pathogens are urgently needed. These approaches include combinatory administration of antibiotics, strengthening colonisation resistance of the gut microbiota to reduce VRE proliferation through commensals or probiotic bacteria, or switching to non-antibiotic bacterial killers, such as bacteriophages or bacteriocins. In this review, we discuss the current knowledge of the genomics of VRE isolates and state-of-the-art therapeutic advances against VRE infections.


Asunto(s)
Enterococcus faecium , Microbioma Gastrointestinal , Infecciones por Bacterias Grampositivas , Enterococos Resistentes a la Vancomicina , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Enterococos Resistentes a la Vancomicina/genética , Enterococcus faecium/genética , Microbioma Gastrointestinal/genética , Genómica , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Pruebas de Sensibilidad Microbiana
10.
Clin Transplant ; 38(3): e15285, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38516923

RESUMEN

Bloodstream infections (BSIs) account for 18% of bacterial infections in the first year after solid organ transplantation (SOT). Enterococcus accounts for up to 20% of BSIs in this population, with vancomycin-resistant enterococcus (VRE) posing a particular risk. This is a retrospective, case-control study of adult liver and kidney transplant recipients between 01/01/2016 and 06/30/2021 that characterizes the epidemiology and outcomes of enterococcal BSIs in liver and kidney transplantations at a single institution. Subjects with an enterococcal BSI within the first 6 months post-transplant were compared to those with non-enterococcal BSIs in the same period. We identified 26 subjects with enterococcal BSIs and 28 controls with non-enterococcal BSIs (n = 54; 10.3%). Cases were mostly liver transplant recipients (n = 20; 77%) with a median MELD at transplant of 33 (range 14-43); controls included 14 KT recipients (50%). Groups differed significantly (all p < .05) by factors including perioperative transfusion requirements, need for reoperation, and number of interventions post-transplant. Cases had a median time of 25.5 days to infection and controls 100.5 days (p < .0001). There were no differences in 1-year mortality between the groups. Enterococcus faecium was the predominant species of Enterococcus (n = 23; 88.5%), with a majority (91.3%) of the isolates being VRE. In our liver and kidney transplants, enterococcal BSIs occurred early among liver transplant recipients. The high incidence of VRE among E. faecium isolates in this population warrants further investigation into the optimal approach to empiric antimicrobials for bacteremia in the early post-transplant period.


Asunto(s)
Bacteriemia , Infecciones por Bacterias Grampositivas , Trasplante de Riñón , Enterococos Resistentes a la Vancomicina , Adulto , Humanos , Antibacterianos/uso terapéutico , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Estudios de Casos y Controles , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/etiología , Bacteriemia/etiología , Bacteriemia/microbiología , Hígado , Factores de Riesgo
11.
Phytomedicine ; 128: 155400, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38518641

RESUMEN

BACKGROUND: The emergence and spread of vancomycin-resistant enterococci (VRE) have posed a significant challenge to clinical treatment, underscoring the need to develop novel strategies. As therapeutic options for VRE are limited, discovering vancomycin enhancer is a feasible way of combating VRE. Gambogic acid (GA) is a natural product derived from the resin of Garcinia hanburyi Hook.f. (Clusiaceae), which possesses antibacterial activity. PURPOSE: This study aimed to investigate the potential of GA as an adjuvant to restore the susceptibility of VRE to vancomycin. METHODS: In vitro antibacterial and synergistic activities were evaluated against vancomycin-susceptible and resistant strains by the broth microdilution method for the Minimal Inhibitory Concentrations (MICs) determination, and checkerboard assay and time-kill curve analysis for synergy evaluation. In vivo study was conducted on a mouse multi-organ infection model. The underlying antibacterial mechanism of GA was also explored. RESULTS: GA showed a potent in vitro activity against all tested strains, with MICs ranging from 2 to 4 µg/ml. The combination of GA and vancomycin exhibited a synergistic effect against 18 out of 23 tested VRE strains, with a median fractional inhibitory concentration index (FICI) of 0.254, and demonstrated a synergistic effect in the time-kill assay. The combination therapy exhibited a significant reduction in tissue bacterial load compared with either compound used alone. GA strongly binds to the ParE subunit of topoisomerase IV, a bacterial type II DNA topoisomerase, and suppresses its activity. CONCLUSIONS: The study suggests that GA has a significant antibacterial activity against enterococci, and sub-MIC concentrations of GA can restore the activity of vancomycin against VRE in vitro and in vivo. These findings indicate that GA has the potential to be a new antibacterial adjuvant to vancomycin in the treatment of infections caused by VRE.


Asunto(s)
Antibacterianos , Sinergismo Farmacológico , Pruebas de Sensibilidad Microbiana , Enterococos Resistentes a la Vancomicina , Vancomicina , Xantonas , Xantonas/farmacología , Animales , Enterococos Resistentes a la Vancomicina/efectos de los fármacos , Antibacterianos/farmacología , Vancomicina/farmacología , Ratones , Garcinia/química , Femenino , Infecciones por Bacterias Grampositivas/tratamiento farmacológico
12.
J Food Prot ; 87(5): 100267, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38492644

RESUMEN

Bacitracin is an antimicrobial used in the feed or water of poultry in the U.S. for the prevention, treatment, and control of clostridial diseases such as necrotic enteritis. Concern has been raised that bacitracin can select for antimicrobial-resistant bacteria that can be transmitted to humans and subsequently cause disease that is more difficult to treat because of the resistance. The objective of the present study was to perform a quantitative risk assessment (QRA) to estimate the potential risk in the U.S. of human infection with antimicrobial-resistant Enterococcus faecalis and E. faecium derived from chicken and turkey products as a result of bacitracin usage in U.S. poultry. The modeling approach estimated the annual number of healthcare-associated enterococcal infections in the U.S. that would be resistant to antimicrobial therapy and that would be derived from poultry sources because of bacitracin use in poultry. Parameter estimates were developed to be "maximum risk" to overestimate the risk to humans. While approximately 60% of E. faecalis and E. faecium derived from poultry were predicted to possess bacitracin resistance based on the presence of the bcrABDR gene locus, very few human-derived isolates possessed this trait. Furthermore, no vancomycin or linezolid-resistant strains of E. faecalis or E. faecium were detected in poultry sources between the years 2002 and 2019. The model estimated the number of antimicrobial-resistant E. faecalis and E. faecium cases per year that might resist therapy due to bacitracin use in poultry as 0.86 and 0.14, respectively, which translates to an annual risk estimate for E. faecalis of less than 1 in 350 million and for E. faecium of less than 1 in 2 billion for members of the U.S. population. Even with the use of risk-maximizing assumptions, the results indicate that there is a high probability that the use of bacitracin according to label instructions in U.S. poultry presents a negligible risk to human health.


Asunto(s)
Antibacterianos , Bacitracina , Farmacorresistencia Bacteriana , Bacitracina/farmacología , Animales , Humanos , Antibacterianos/farmacología , Medición de Riesgo , Enterococcus faecalis/efectos de los fármacos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Aves de Corral , Pollos , Enterococcus faecium/efectos de los fármacos
13.
Antimicrob Agents Chemother ; 68(3): e0108323, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38349158

RESUMEN

Infective endocarditis (IE) caused by Enterococcus spp. represents the third most common cause of IE, with high rates of relapse compared with other bacteria. Interestingly, late relapses (>6 months) have only been described in Enterococcus faecalis, but here we describe the first reported IE relapse with Enterococcus faecium more than a year (17 months) after the initial endocarditis episode. Firstly, by multi locus sequence typing (MLST), we demonstrated that both isolates (EF646 and EF641) belong to the same sequence type (ST117). Considering that EF641 was able to overcome starvation and antibiotic treatment conditions surviving for a long period of time, we performed bioinformatic analysis in identifying potential genes involved in virulence and stringent response. Our results showed a 13-nucleotide duplication (positions 1638-1650) in the gene relA, resulting in a premature stop codon, with a loss of 167 amino acids from the C-terminal domains of the RelA enzyme. RelA mediates the stringent response in bacteria, modulating levels of the alarmone guanosine tetraphosphate (ppGpp). The relA mutant (EF641) was associated with lower growth capacity, the presence of small colony variants, and higher capacity to produce biofilms (compared with the strain EF646), but without differences in antimicrobial susceptibility patterns according to standard procedures during planktonic growth. Instead, EF641 demonstrated tolerance to high doses of teicoplanin when growing in a biofilm. We conclude that all these events would be closely related to the long-term survival of the E. faecium and the late relapse of the IE. These data represent the first clinical evidence of mutations in the stringent response (relA gene) related with E. faecium IE relapse.


Asunto(s)
Endocarditis Bacteriana , Endocarditis , Enterococcus faecium , Infecciones por Bacterias Grampositivas , Humanos , Enterococcus faecium/genética , Enterococcus faecium/metabolismo , Tipificación de Secuencias Multilocus , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/microbiología , Endocarditis/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/metabolismo , Guanosina Tetrafosfato/metabolismo , Enterococcus faecalis/metabolismo , Recurrencia , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología
14.
Eur J Clin Microbiol Infect Dis ; 43(4): 767-775, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38372832

RESUMEN

OBJECTIVE: The aim of the study was to determine the resistance profile of linezolid-resistant Enterococcus faecium (LREfm) and to investigate risk factors and outcomes associated with LREfm infections. MATERIAL AND METHODS: A prospective case-control study was undertaken (2019 to 2022) and included 202 patients with LREfm infections (cases) and 200 controls with LSEfm infections. Clinical data was prospectively collected and analysed for risk factors and outcomes. Antimicrobial susceptibility was performed, and resistance profile was studied using WHOnet. RESULTS: Risk factors associated with LREfm infection were site of infection UTI (OR 5.87, 95% CI 2.59-13.29, p ≤ 0.001), prior use of carbapenem (OR 2.85 95% CI 1.62-5.02, p ≤ 0.001) and linezolid (OR 10.13, 95% CI 4.13-24.82, p ≤ 0.001), use of central line (OR 5.54, 95% CI 2.35-13.09, p ≤ 0.001), urinary catheter (OR 0.29, 95% CI 0.12-0.70, p ≤ 0.001) and ventilation (OR 14.87, 95% CI 7.86-28.11, p ≤ 0.007). The hospital stay 8-14 days (< 0.001) prior to infection and the mortality rate (p = 0.003) were also significantly high among patients with LREfm infections. Linezolid and vancomycin resistance coexisted; further, MDR, XDR and PDR phenotypes were significantly higher among LREfm. CONCLUSION: This study provided insight into epidemiology of MDR LREfm in a setting where linezolid use is high. The main drivers of infections with LREfm are multiple, including use of carbapenems and linezolid. Invasive procedures and increased hospital stay facilitate spread through breach in infection control practises. As therapeutic options are limited, ongoing surveillance of LREfm and VRE is critical to guide appropriate use of linezolid and infection control policies.


Asunto(s)
Enterococcus faecium , Infecciones por Bacterias Grampositivas , Humanos , Linezolid/farmacología , Linezolid/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Enterococcus faecium/genética , Estudios de Casos y Controles , Centros de Atención Terciaria , Enterococcus , Carbapenémicos/uso terapéutico , Factores de Riesgo , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/microbiología
15.
J Antimicrob Chemother ; 79(4): 801-809, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38334390

RESUMEN

OBJECTIVES: To investigate the genomic diversity and ß-lactam susceptibilities of Enterococcus faecalis collected from patients with infective endocarditis (IE). METHODS: We collected 60 contemporary E. faecalis isolates from definite or probable IE cases identified between 2018 and 2021 at the University of Pittsburgh Medical Center. We used whole-genome sequencing to study bacterial genomic diversity and employed antibiotic checkerboard assays and a one-compartment pharmacokinetic-pharmacodynamic (PK/PD) model to investigate bacterial susceptibility to ampicillin and ceftriaxone both alone and in combination. RESULTS: Genetically diverse E. faecalis were collected, however, isolates belonging to two STs, ST6 and ST179, were collected from 21/60 (35%) IE patients. All ST6 isolates encoded a previously described mutation upstream of penicillin-binding protein 4 (pbp4) that is associated with pbp4 overexpression. ST6 isolates had higher ceftriaxone MICs and higher fractional inhibitory concentration index values for ampicillin and ceftriaxone (AC) compared to other isolates, suggesting diminished in vitro AC synergy against this lineage. Introduction of the pbp4 upstream mutation found among ST6 isolates caused increased ceftriaxone resistance in a laboratory E. faecalis isolate. PK/PD testing showed that a representative ST6 isolate exhibited attenuated efficacy of AC combination therapy at humanized antibiotic exposures. CONCLUSIONS: We find evidence for diminished in vitro AC activity among a subset of E. faecalis IE isolates with increased pbp4 expression. These findings suggest that alternate antibiotic combinations against diverse contemporary E. faecalis IE isolates should be evaluated.


Asunto(s)
Endocarditis Bacteriana , Endocarditis , Infecciones por Bacterias Grampositivas , Humanos , Ceftriaxona/farmacología , Ceftriaxona/uso terapéutico , Enterococcus faecalis , Ampicilina/farmacología , Ampicilina/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/microbiología , Endocarditis/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Quimioterapia Combinada
16.
Sci Rep ; 14(1): 4786, 2024 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413672

RESUMEN

Increasing antimicrobial resistance in Enterococcus faecium necessitates the search for novel treatment agents, such as bacteriocins. In this study, we conducted an in vivo assessment of five bacteriocins, namely Lacticin Z, Lacticin Q, Garvicin KS (ABC), Aureocin A53 and Microbisporicin (NAI-107), against vanB-resistant Enterococcus faecium using a Galleria mellonella model. Our in vitro experiments demonstrated the efficacy of all five bacteriocins against vanB-resistant E. faecium with only NAI-107 demonstrating in vivo efficacy. Notably, NAI-107 exhibited efficacy across a range of tested doses, with the highest efficacy observed at a concentration of 16 µg/mL. Mortality rates in the group treated with 16 µg/mL NAI-107 were lower than those observed in the linezolid-treated group. These findings strongly suggest that NAI-107 holds promise as a potential alternative therapeutic agent for treating infections caused by resistant E. faecium and warrants further investigation.


Asunto(s)
Bacteriocinas , Enterococcus faecium , Infecciones por Bacterias Grampositivas , Mariposas Nocturnas , Enterococos Resistentes a la Vancomicina , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Vancomicina/farmacología , Bacteriocinas/farmacología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana
17.
PLoS One ; 19(2): e0298018, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38324576

RESUMEN

The clinical significance of enterococci in intra-abdominal infections, particularly those caused by multiple organisms, remains unclear. There are no definitive guidelines regarding the use of empiric therapy with antimicrobial agents targeting enterococci. In this study, we evaluated the impact of the initial antimicrobial therapy administration of anti-enterococcal agents on the treatment of intra-abdominal infections in patients with cancer in whom enterococci were isolated from ascitic fluid cultures. This retrospective study was conducted at Shizuoka Cancer Center between January 1, 2014, and December 31, 2020, on all adult patients with cancer with enterococci in their ascitic fluid cultures. The primary outcome was all-cause mortality, and the secondary outcomes were composite outcomes consisting of three components (mortality, recurrence, and treatment failure) and the risk factors associated with all-cause mortality and composite outcomes. In total, 103 patients were included: 61 received treatment covering enterococci, and 42 did not. The mortality rates did not differ significantly between the treated and untreated groups (treated: 8/61 [13.1%]; untreated: 5/42 [11.9%]; p = 1.00). Additionally, no significant difference was observed between the groups in terms of composite outcomes (treated group: 11/61 [18.0%]; untreated group: 9/42 [21.4%]; p = 0.80). Multivariate analysis showed that performance status (PS2-4; p < 0.0001) was an independent risk factor for mortality. The composite outcome was also significantly higher for PS2-4 (p = 0.007). Anti-enterococcal treatment was not associated with mortality or the composite outcome. In patients with cancer and intra-abdominal infections caused by enterococci, anti-enterococcal therapy was not associated with prognosis, whereas PS2 or higher was associated with prognosis. The results of this study suggest that the initial routine administration of anti-enterococcal agents for intra-abdominal infections may not be essential for all patients with cancer. To substantiate these findings, validation by a prospective randomized trial is warranted.


Asunto(s)
Antiinfecciosos , Infecciones por Bacterias Grampositivas , Infecciones Intraabdominales , Neoplasias , Humanos , Adulto , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Enterococcus , Antiinfecciosos/uso terapéutico , Infecciones Intraabdominales/complicaciones , Infecciones Intraabdominales/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico
18.
Infect Disord Drug Targets ; 24(4): 53-57, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38178665

RESUMEN

Background: Infections caused by anaerobic bacteria occur frequently and can be serious and life-threatening. Anaerobes are a rare cause of community-acquired pneumonia with Streptococcus pneumonia and respiratory viruses being the most frequently detected pathogens. We, herein, report a case of Fusobacterium/Peptostreptococcus parapneumonic effusion with empyema in a patient without risk factors for aspiration pneumonia. This case presents an opportunity to discuss an unusual case of community-acquired empyema secondary to anaerobic infection in a patient without the common risk factors for aspiration.

Case Presentation: A 59-year-old male patient without significant past medical history apart from a twenty-five-year history of smoking presented due to left flank pain and shortness of breath. Findings of a complicated parapneumonic effusion were found on imaging, resulting in surgical decortication and prolonged antibiotic therapy.

Discussion: Parapneumonic effusions and empyema are relatively common complications of pneumonia. It is important to note that the incidence of anaerobic empyema has been on the rise due to more modern culturing techniques.

Conclusion: This case highlights an unusual presentation of community-acquired empyema secondary to anaerobes without any risk factors for aspiration pneumonia. Therefore, clinicians should consider the possibility of anaerobic coverage in the treatment of community-acquired empyema in the appropriate setting.

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Asunto(s)
Antibacterianos , Infecciones Comunitarias Adquiridas , Fusobacterium , Peptostreptococcus , Humanos , Masculino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Peptostreptococcus/aislamiento & purificación , Fusobacterium/aislamiento & purificación , Empiema Pleural/microbiología , Empiema Pleural/tratamiento farmacológico , Empiema/microbiología , Infecciones por Fusobacterium/tratamiento farmacológico , Infecciones por Fusobacterium/microbiología , Infecciones por Fusobacterium/complicaciones , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología
19.
Infection ; 52(2): 567-576, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38165594

RESUMEN

PURPOSE: Dalbavancin, approved in 2014 for Gram-positive acute bacterial skin and skin structure infections (ABSSSI), has pharmacokinetics enabling treatment with one or two doses. Dalbavancin might be useful in outpatient parenteral antibiotic therapy (OPAT) of deep-seated infections, otherwise requiring inpatient admission. We documented our experience with pragmatic dalbavancin use to assess its effectiveness for varied indications, on- and off-label, as primary or sequential consolidation therapy. METHODS: Patients prescribed dalbavancin between 1 December 2021 and 1 October 2022 were screened for demographics of age, sex, Charlson comorbidity index (CCI), allergies, pathogens, doses of dalbavancin, other antibiotics administered and surgery. Where available, infection markers were recorded. The primary outcome was a cure at the end of treatment. Secondary outcomes included any adverse events and for those with treatment failures, response to salvage antibiotics. RESULTS: Sixty-seven per cent of patients were cured. Cure rates by indication were 93% for ABSSSI, 100% for bacteraemia, 90% for acute osteomyelitis, 0% for chronic osteomyelitis, 75% for native joint septic arthritis and 33% for prosthetic joint infection. Most bone and joint infections that were not cured did not have source control, and the goal of treatment was suppressive. Successful suppression rates were greater at 48% for chronic osteomyelitis and 66% for prosthetic joint infections. Adverse events occurred in 14 of 102 patients. CONCLUSION: This report adds to clinical experience with dalbavancin for off-label indications whilst further validating its role in ABSSSI. Dalbavancin as primary therapy in deep-seated infections merits investigation in formal clinical trials.


Asunto(s)
Infecciones por Bacterias Grampositivas , Osteomielitis , Enfermedades Cutáneas Infecciosas , Teicoplanina/análogos & derivados , Humanos , Antibacterianos/efectos adversos , Teicoplanina/efectos adversos , Osteomielitis/microbiología , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Bacterias Grampositivas , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología
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