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1.
Artículo en Inglés | MEDLINE | ID: mdl-39375250

RESUMEN

BACKGROUND: Diagnosis of Lyme borreliosis (LB) relies on clinical symptoms and detection of Borrelia-specific antibodies. Guidelines recommend a two-tier testing (TTT) strategy for disseminated LB: serological screening with a sensitive enzyme immunoassay (EIA) and confirmation with a specific immunoblot. Searching for the most sensitive and specific approach, this retrospective study evaluated standard (STTT) and modified (MTTT) strategies using a well-defined study population. METHODS: Cases included patients with active Lyme neuroborreliosis (LNB; n = 29) or Lyme arthritis (LA; n = 17). Controls comprised patients treated for LNB (n = 36) or LA (n = 8), healthy individuals who were either untreated (n = 75) or treated for LB (n = 15) in the past, and patients with potentially cross-reactive diseases (n = 16). Sera were subjected to three EIAs and two immunoblots. Reactive screening results were confirmed by immunoblot (STTT) or EIA (MTTT). Solitary IgM results in the screening assay and effects of antibiotic treatment on isotype-specific seropositivity rates were also assessed. RESULTS: Sensitivities of STTT strategies ranged from 90%-97% for LNB and were 100% for LA. MTTT strategies were 100% sensitive. Specificities ranged from 89%-95% for STTT and from 88%-93% for MTTT strategies. Differences between STTT and MTTT strategies were not statistically significant. Solitary IgM reactivity was common among controls. Antibiotic treatment significantly reduced IgM/IgG positivity for LNB patients; for LA patients, a decline was only observed for IgM. CONCLUSION: In conclusion, MTTT strategies showed a slightly higher sensitivity and similar specificity compared to STTT strategies. Since EIAs are more time- and cost-efficient, MTTT strategies seem more favorable for clinical use. IgG testing enhances specificity with minimal sensitivity loss.

2.
Microbiol Spectr ; 12(10): e0283123, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39269158

RESUMEN

Lower respiratory tract infections (LRTIs) remain a significant global cause of infectious disease-related mortality. Accurate discrimination between acute bacterial and viral LRTIs is crucial for optimal patient care, prevention of unnecessary antibiotic prescriptions, and resource allocation. Plasma samples from LRTI patients with bacterial (n = 36), viral (n = 27; excluding SARS-CoV-2), SARS-CoV-2 (n = 22), and mixed bacterial-viral (n = 38) etiology were analyzed for protein profiling. Whole-blood RNA samples from a subset of patients (bacterial, n = 8; viral, n = 8; and SARS-CoV-2, n = 8) were analyzed for transcriptional profiling. Lasso regression modeling identified a seven-protein signature (CRP, IL4, IL9, IP10, MIP1α, MIP1ß, and TNFα) that discriminated between patients with bacterial (n = 36) vs viral (n = 27) infections with an area under the curve (AUC) of 0.98. When comparing patients with bacterial and mixed bacterial-viral infections (antibiotics clinically justified; n = 74) vs patients with viral and SARS-CoV-2 infections (antibiotics clinically not justified; n = 49), a 10-protein signature (CRP, bFGF, eotaxin, IFNγ, IL1ß, IL7, IP10, MIP1α, MIP1ß, and TNFα) with an AUC of 0.94 was identified. The transcriptional profiling analysis identified 232 differentially expressed genes distinguishing bacterial (n = 8) from viral and SARS-CoV-2 (n = 16) etiology. Protein-protein interaction enrichment analysis identified 20 genes that could be useful in the differentiation between bacterial and viral infections. Finally, we examined the performance of selected published gene signatures for bacterial-viral differentiation in our gene set, yielding promising results. Further validation of both protein and gene signatures in diverse clinical settings is warranted to establish their potential to guide the treatment of acute LRTIs. IMPORTANCE: Accurate differentiation between bacterial and viral lower respiratory tract infections (LRTIs) is vital for effective patient care and resource allocation. This study investigated specific protein signatures and gene expression patterns in plasma and blood samples from LRTI patients that distinguished bacterial and viral infections. The identified signatures can inform the design of point-of-care tests that can aid healthcare providers in making informed decisions about antibiotic prescriptions in order to reduce unnecessary use, thereby contributing to reduced side effects and antibiotic resistance. Furthermore, the potential for faster and more accurate diagnoses for improved patient management in acute LRTIs is compelling.


Asunto(s)
Infecciones Bacterianas , Biomarcadores , COVID-19 , Infecciones del Sistema Respiratorio , SARS-CoV-2 , Humanos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/microbiología , Biomarcadores/sangre , Persona de Mediana Edad , Masculino , Femenino , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , SARS-CoV-2/genética , Anciano , Adulto , Virosis , Antibacterianos/uso terapéutico , Perfilación de la Expresión Génica
3.
Acta Paediatr ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227731

RESUMEN

AIM: To assess the duration of antimicrobial treatment; hospital length of stay; and invasive bacterial infections rates in hospitalised infants following the adoption of a management guideline. METHODS: Faculty agreed to a standard of 24 h of antibiotic treatment for well-appearing febrile infants with proven viral infection and no growth on bacterial cultures. The outcomes were the duration of hospitalisation and antibiotic treatment of febrile infants less than 8 weeks of age who have enterovirus, parechovirus, respiratory viruses detected. We monitored re-admissions and missed invasive infections. RESULTS: Of the total 1696 infants studied, the median antibiotic treatment duration decreased from 31.5 to 24.8 h in virus-infected infants ≤21 days of age (p = 0.02) and from 26 to 19.7 h in infants 22-56 days of age (p < 0.001). The decrease was less in infants not infected with a virus. No patient had an invasive infection identified after discharge. CONCLUSION: The implementation of our care standard resulted in reduction in antibiotic treatment duration without known delayed diagnosis of bacterial infections. Infants without a proven viral aetiology may need further study to inform management decisions.

4.
Med Pharm Rep ; 97(3): 280-297, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39234464

RESUMEN

Background and aim: Infections caused by pathogenic bacteria increase patient morbidity and mortality and significantly raise treatment costs. The use of silver nanoparticles as an alternative treatment for S aureus, E coli, MRSA, E faecalis, K pneumoniae and P aeruginosa indicates their antibacterial effect and prompts medical research to consider the next generation of antibacterial drugs that could change antibiotic therapy. By combining silver nanoparticles with different classes of antibiotics, the antibacterial effect is evidenced by increased values of the inhibition zone compared to the values obtained for some antibiotics commonly used in the treatment of bacterial infections. This study focuses on comparing the antibacterial activity of antibiotics versus antibiotics combined with silver nanoparticles against various bacteria, by comparing inhibition zones obtained for both. We aim to prove that the size of the inhibition zone for antibiotics combined with silver nanoparticles is greater, thus confirming the improved antibacterial effect. Metods: In this study we tested the antibacterial activity of solutions of silver nanoparticles alone or in combination with different antibiotics. We used standard bacterial strains, ATCC, both Gram positive bacteria Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, as well as Gram negative bacteria Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, but also on clinical isolates: a strain MRSA (Methicillin Resistant Staphylococcus aureus) and a PDR strain (pan drug resistant) of Klebsiella pneumoniae. Bacterial identification was performed using Vitek MS analyzer (bioMerieux). Antibiotic susceptibility determination was performed with VITEK2 COMPACT SYSTEM (bio Merieux, Inc Durham NC) with ready to use VITEK AST cards. The interpretation of the results was done in compliance with EUCAST 2023-2024 standards. Testing was performed for several classes of antibiotics, silver nanoparticle solutions in 2 concentrations (10 µg/mL and 100 µg/mL) and for combinations of antibiotics with silver nanoparticle solutions. The diameter of the inhibition zone (ZOI) for silver nanoparticles, antibiotics and silver nanoparticles combined with antibiotic against each bacterium was expressed in millimeters. The Kirby-Bauer disk-diffusion method, in accordance with current EUCAST standards, was used to analyze the antibacterial effect of antibiotics, silver nanoparticles, and antibiotics combined with silver nanoparticles at biocompatible doses of 10 and 100 µg/mL. The experiments were conducted in triplicate, and the results were almost identical. Results: The results of this study show that the silver nanoparticles displayed antibacterial activity, proven by the appearance of the inhibition zone, in various sizes, for all bacteria studied. The antibiotic classes tested were beta-lactamins, first, second, third and fourth generation cephalosporins, macrolides, fluoroquinolones, lincosamides, aminoglycosides, glycopeptides, tetracyclines, oxazolidinones, sulfonamides, rifamycins, amphenicols. Testing S aureus ATCC 29213, the highest zone of inhibition was demonstrated for cephalosporins (32.6667 ± 0.701 mm), macrolides (31.6667 ± 0.701 mm, and lincosamides (29.6667 ± 0.701 mm). Testing MRSA (internal code GR0333), the highest zone of inhibition for combination of silver nanoparticles and antibiotics was demonstrated for fluoroquinolones (36.3333 ± 0.701 mm), lincosamides (32.3333 ± 0.701 mm), Fusid acid (32.3333 ± 0.701 mm) and aminoglicosides (31.3333 ± 0.701 mm). Testing E coli ATCC 25922 the highest zone of inhibition was for Fosfomycine, 39 mm and for E faecalis ATCC 29212 for aminoglicosides was 19 mm. For K pneumoniae (internal code GQ8575) the inhibition zone for silver nanoparticles 100 µg/mL was 12.3333 ± 0.701 mm and for P aeruginosa ATCC 27253 was 16 ± 1.214 mm. Conclusions: The use of metallic nanoparticles, especially silver ones, as antimicrobial agents with definite bactericidal activity has led medical specialists to consider this new treatment which may change antibacterial therapy. Studies of in vitro combinations between silver nanoparticles and different classes of antibiotics represent a highly efficient and effective new antibacterial treatment against multidrug-resistant bacteria. To avoid the problem of antimicrobial resistance associated with conventional antibiotics, it is necessary to understand the adaptive mechanisms of bacteria under the action of metal nanoparticles, which could be exploited in future studies. Further in vitro and in vivo studies that would assess specify the biocompatibility and toxicity of silver nanoparticles will make these super nanomaterials the medicines of the future.

5.
J Wound Care ; 33(9): 702-707, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39287037

RESUMEN

OBJECTIVE: The effect of continuous topical oxygen therapy (cTOT) on Pseudomonas aeruginosa biofilm gene transcription profiles following inoculation onto porcine skin, using a customised molecular assay was determined. METHOD: Sterilised porcine skin explants were inoculated with Pseudomonas aeruginosa in triplicate: 0 hours as negative control; 24 hours cTOT device on; 24 hours cTOT device off. The oxygen delivery system of the cTOT device was applied to the inoculated tissue and covered with a semi-occlusive dressing. All samples were incubated at 37±2°C for 24 hours, with the 0 hours negative control inoculated porcine skin samples recovered immediately. Planktonic suspensions and porcine skin biopsy samples were taken at 0 hours and 24 hours. Samples were processed and quantifiably assessed using gene specific reverse transcription-quantitative polymerase chain reaction assays for a panel of eight Pseudomonas aeruginosa genes (16S, pelA, pslA, rsaL, pcrV, pscQ, acpP, cbrA) associated with biofilm formation, quorum sensing, protein secretion/translocation and metabolism. RESULTS: Transcriptional upregulation of pelA, pcrV and acpP, responsible for intracellular adhesion, needletip protein production for type-3 secretion systems and fatty acid synthesis during proliferation, respectively, was observed when the cTOT device was switched on compared to when the device was switched off. Data suggest increased metabolic activity within bacterial cells following cTOT treatment. CONCLUSION: cTOT is an adjunctive therapy that supports faster healing and pain reduction in non-healing hypoxic wounds. Oxygen has previously been shown to increase susceptibility of biofilms to antibiotics through enhancing metabolism. Observed gene expression changes highlighted the impact of cTOT on biofilms, potentially influencing antimicrobial treatment success in wounds. Further in vitro and clinical investigations are warranted.


Asunto(s)
Biopelículas , Oxígeno , Pseudomonas aeruginosa , Animales , Biopelículas/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Porcinos , Oxígeno/metabolismo , Modelos Animales de Enfermedad , Infecciones por Pseudomonas/terapia , Piel/metabolismo , Piel/microbiología , Infección de Heridas/terapia , Administración Tópica , Cicatrización de Heridas
6.
Cureus ; 16(8): e66952, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39280493

RESUMEN

Small bowel diverticulitis occurs at a rate of 0.06% to 1.3%, mainly in individuals over 50, peaking between ages 60 and 70. Duodenal diverticula are the most common (79% of cases), followed by jejunal or ileal diverticula (18%), and diverticula in all segments combined (3%). This condition typically presents with sporadic abdominal pain and vague gastrointestinal symptoms, making diagnosis difficult. We report an 80-year-old male who presented to the emergency department with sudden, left-sided abdominal pain and nausea due to perforated jejunal diverticulitis. Despite undergoing side-to-side jejunojejunostomy and incidental appendectomy, the patient rapidly declined and expired 45 hours post-operation due to septic shock. This case highlights the scarcity of literature on jejunal diverticulitis and its treatment guidelines.

7.
Intensive Care Med ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39320462

RESUMEN

Many dogmas influence daily clinical practice, and critical care medicine is no exception. We previously highlighted the weak, questionable, and often contrary evidence base underpinning four established medical managements-loop diuretics for acute heart failure, routine use of heparin thromboprophylaxis, rate of sodium correction for hyponatremia, and 'every hour counts' for treating bacterial meningitis. We now provide four further examples in this "Dogma II" piece (a week's course of antibiotics, diabetic ketoacidosis algorithms, sodium bicarbonate to improve ventricular contractility during severe metabolic acidosis, and phosphate replacement for hypophosphatemia) where routine practice warrants re-appraisal.

8.
Medicina (Kaunas) ; 60(9)2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39336571

RESUMEN

Background and Objectives: Patients with infections caused by Elizabethkingia species require prompt identification and effective antibiotic treatment since these spp. are typically resistant to multiple antibiotics and variable susceptibility patterns. Understanding the mortality risk of this disease is difficult because of the relatively low incidence of infections caused by Elizabethkingia spp. and the lack of published systematic evaluations of the risk factors for mortality. The aim of the present study was to investigate risk factors for mortality in patients with infections caused by Elizabethkingia spp. by conducting a meta-analysis of existing studies on these infections. Materials and Methods: Studies comparing patients who died from infections caused by Elizabethkingia spp. with patients who survived were considered for inclusion. Studies that reported one or more risk factors for mortality were considered. Clinical predisposing variables, predisposing comorbidities, and clinical outcomes of antibiotic treatment were among the risk factors for mortality. Results: The meta-analysis included twenty studies with 990 patients, and 298 patients (30.1%) died. The following risk factors for mortality were identified: intensive care unit admission, the need for mechanical ventilation, immunosuppressive or steroid therapy use, pneumonia, comorbid liver disease, and the use of inappropriate antimicrobial therapy. Conclusions: The use of appropriate antimicrobial therapy is critical for the effective management of infections caused by Elizabethkingia spp. Antimicrobial susceptibility testing would be a more reliable means of guiding treatment. The identification of the best antimicrobial drugs is needed to ensure optimal treatment recommendations for treating Elizabethkingia-related infections.


Asunto(s)
Antibacterianos , Infecciones por Flavobacteriaceae , Humanos , Antibacterianos/uso terapéutico , Infecciones por Flavobacteriaceae/tratamiento farmacológico , Infecciones por Flavobacteriaceae/mortalidad , Factores de Riesgo , Flavobacteriaceae/efectos de los fármacos
9.
Infection ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196517

RESUMEN

OBJECTIVES: We aimed to investigate the impact of enterococci on initial antibiotic treatment (IAT) failure and prolonged hospitalization in complicated urinary tract infection (cUTI) cases, and to identify risk factors for enterococcal cUTI. METHODS: Adult cUTI patients were analyzed to compare the differences between the Enterococcus and non-Enterococcus groups. Univariate and multivariate analyses were employed to identify independent risk factors. RESULTS: This study included 419 patients, with the Enterococcus group showing significantly higher IAT failure rates and an extended average length of stay by 4.4 days compared to the non-Enterococcus group. Multivariate analysis identified enterococci, hospital-acquired UTIs (HA-UTI), indwelling catheters, and bed rest (bedridden) as independent risk factors for IAT failure. Enterococci were notably linked to prolonged hospitalization, other independent risk factors included IAT failure, prior antimicrobial use, age-adjusted Charlson comorbidity index (ACCI) ≥ 4, hypoalbuminemia, and bed rest. Urological cancer, HA-UTI, indwelling catheters, urinary retention, and urologic surgery were risk factors for enterococcal cUTI. CONCLUSION: We provide the first evidence that enterococci independently increase the risk for IAT failure and prolonged hospitalization in adults with cUTIs, highlighting the significance of timely identification to optimize measures including antibiotic regimens. Risk factors for enterococcal cUTI have also been identified to aid clinicians in managing this condition.

10.
Microbiol Res ; 287: 127863, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39106785

RESUMEN

High-throughput sequencing studies have shown that diet or antimicrobial treatments impact animal gut microbiota equilibrium. However, properties related to the gut microbial ecosystem stability, such as resilience, resistance, or functional redundancy, must be better understood. To shed light on these ecological processes, we combined advanced statistical methods with 16 S rRNA gene sequencing, functional prediction, and fitness analyses in the gut microbiota of the cockroach Blattella germanica subject to three periodic pulses of the antibiotic (AB) kanamycin (n=512). We first confirmed that AB did not significantly affect cockroaches' biological fitness, and gut microbiota changes were not caused by insect physiology alterations. The sex variable was examined for the first time in this species, and no statistical differences in the gut microbiota diversity or composition were found. The comparison of the gut microbiota dynamics in control and treated populations revealed that (1) AB treatment decreases diversity and completely disrupts the co-occurrence networks between bacteria, significantly altering the gut community structure. (2) Although AB also affected the genetic composition, functional redundancy would explain a smaller effect on the functional potential than on the taxonomic composition. (3) As predicted by Taylor's law, AB generally affected the most abundant taxa to a lesser extent than the less abundant taxa. (4) Taxa follow different trends in response to ABs, highlighting "resistant taxa," which could be critical for community restoration. (5) The gut microbiota recovered faster after the three AB pulses, suggesting that gut microbiota adapts to repeated treatments.


Asunto(s)
Antibacterianos , Bacterias , Blattellidae , Microbioma Gastrointestinal , Kanamicina , ARN Ribosómico 16S , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Antibacterianos/farmacología , ARN Ribosómico 16S/genética , Blattellidae/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Kanamicina/farmacología , Masculino , Femenino , Biodiversidad , Cucarachas/microbiología , Cucarachas/efectos de los fármacos , Filogenia , Adaptación Fisiológica , Secuenciación de Nucleótidos de Alto Rendimiento
11.
Cureus ; 16(7): e64987, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39161484

RESUMEN

Post-treatment Lyme disease syndrome (PTLDS), which may also be referred to incorrectly as "chronic Lyme disease," is defined by the Infectious Diseases Society of America (IDSA) as the presence of fatigue, pain, and/or cognitive complaints with the functional impact that persists for more than six months after completing treatment for Lyme disease (LD). These symptoms occur in 10%-20% of patients previously diagnosed with LD caused by the bacteria Borrelia burgdorferi and appropriately treated with a course of antibiotics. The symptoms of PTLDS can be easily overlooked or misdiagnosed as a psychiatric manifestation in geographic locations that rarely see LD. In contrast, geographic locations with a higher prevalence of LD may be more aware of PTLDS symptoms and have higher clinical suspicion leading to this diagnosis. The pathophysiology behind the persistent symptoms some people experience from a primary infection is still largely unknown. Some mechanisms that have been proposed include permanent tissue damage and inflammation, immune system dysfunction, autoimmune response, co-infection, and even persistent infection refractory to treatment. We propose that ongoing PTLDS symptoms seem to be related to an autoimmune response to the tissue damage and inflammation caused by the viable or nonviable spirochete pathogen. At this point, PTLDS is diagnosed clinically as no quantifiable methods are available from laboratory or tissue diagnostics as of 2024. Similar pathophysiological features of PTLDS are seen in diseases such as COVID-19 or chronic fatigue syndrome (CFS). More effective diagnostic approaches might include further studies looking at a possible connection in the genomes of individuals developing PTLDS, quantifiable biomarkers, common inflammatory markers/pathways, and careful histopathological studies of human tissues.

12.
Int J Colorectal Dis ; 39(1): 128, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115694

RESUMEN

PURPOSE: To explore whether previous participation in clinical studies increases adherence to management guidelines in acute uncomplicated diverticulitis (AUD). METHODS: This retrospective cohort study was designed to give a SNAPSHOT of the management of AUD at six hospitals, three of which had participated in the AVOD trial comparing antibiotic versus non-antibiotic treatment of AUD. Patients with AUD were included from March 2019 through June 2020 and followed for 90 days. The primary outcome was treatment of AUD categorised by antibiotic treatment and inpatient or outpatient management compared between AVOD and non-AVOD hospitals. Descriptive statistics were compiled, and differences between hospitals were assessed with Pearson's chi-squared test. RESULTS: The cohort included 449 patients with AUD of which 63% were women and the median age was 63 (IQR: 52-73) years. Patient characteristics were comparable across the hospitals. Antibiotics were administered to 84 (19%) patients and 113 (25%) patients were managed as inpatients. Management varied significantly between AVOD and non-AVOD hospitals. The mean proportion of patients treated with antibiotics was 7% at AVOD hospitals compared to 38% at non-AVOD hospitals (p < 0.001). The mean proportion of in-hospital management was 18% at AVOD hospitals versus 38% at non-AVOD hospitals (p < 0.001). CONCLUSION: Most patients with AUD were managed according to current guidelines. However, the management varies between hospitals and previous participation in clinical studies may increase knowledge of and adherence to guidelines.


Asunto(s)
Antibacterianos , Diverticulitis , Adhesión a Directriz , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Enfermedad Aguda , Antibacterianos/uso terapéutico , Diverticulitis/terapia , Diverticulitis/tratamiento farmacológico , Estudios Retrospectivos , Guías de Práctica Clínica como Asunto , Resultado del Tratamiento
13.
Antimicrob Agents Chemother ; 68(10): e0080824, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39194210

RESUMEN

Osteomyelitis caused by Staphylococcus aureus can involve the persistent infection of osteocytes. We sought to determine if current clinically utilized antibiotics were capable of clearing an intracellular osteocyte S. aureus infection. Rifampicin, vancomycin, levofloxacin, ofloxacin, amoxicillin, oxacillin, doxycycline, linezolid, gentamicin, and tigecycline were assessed for their minimum inhibitory concentration (MIC) and minimum bactericidal concentrations against 12 S. aureus strains, at pH 5.0 and 7.2 to mimic lysosomal and cytoplasmic environments, respectively. Those antibiotics whose bone estimated achievable concentration was commonly above their respective MIC for the strains tested were further assayed in a human osteocyte infection model under acute and chronic conditions. Osteocyte-like cells were treated at 1×, 4×, and 10× the MIC for 1 and 7 days following infection (acute model), or at 15 and 21 days of infection (chronic model). The intracellular effectivity of each antibiotic was measured in terms of CFU reduction, small colony variant formation, and bacterial mRNA expression change. Only rifampicin, levofloxacin, and linezolid reduced intracellular CFU numbers significantly in the acute model. Consistent with the transition to a non-culturable state, few if any CFU could be recovered from the chronic model. However, no treatment in either model reduced the quantity of bacterial mRNA or prevented non-culturable bacteria from returning to a culturable state. These findings indicate that S. aureus adapts phenotypically during intracellular infection of osteocytes, adopting a reversible quiescent state that is protected against antibiotics, even at 10× their MIC. Thus, new therapeutic approaches are necessary to cure S. aureus intracellular infections in osteomyelitis.


Asunto(s)
Antibacterianos , Gentamicinas , Levofloxacino , Linezolid , Pruebas de Sensibilidad Microbiana , Osteocitos , Osteomielitis , Rifampin , Infecciones Estafilocócicas , Staphylococcus aureus , Vancomicina , Antibacterianos/farmacología , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Staphylococcus aureus/efectos de los fármacos , Humanos , Osteocitos/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Levofloxacino/farmacología , Rifampin/farmacología , Rifampin/uso terapéutico , Vancomicina/farmacología , Linezolid/farmacología , Gentamicinas/farmacología , Tigeciclina/farmacología , Ofloxacino/farmacología , Doxiciclina/farmacología , Amoxicilina/farmacología , Oxacilina/farmacología
14.
Liver Int ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148354

RESUMEN

With the increasing rate of infections caused by multidrug-resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis. METHODS: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472). All predictors were measured at the time of infection. Both culture-positive and culture-negative infections were included. The model was developed using logistic regression with backward stepwise predictor selection. We externally validated the optimism-adjusted model using calibration and discrimination statistics and evaluated its clinical utility. RESULTS: The prevalence of MDRO infections was 19% and 22% in the development and external validation datasets, respectively. The model's predictors were sex, prior antibiotic use, type and site of infection, MELD-Na, use of vasopressors, acute-on-chronic liver failure, and interaction terms. Upon external validation, the calibration slope was 77 (95% CI .48-1.05), and the area under the ROC curve was .68 (95% CI .61-.73). The application of the model significantly changed the post-test probability of having an MDRO infection, identifying patients with nosocomial infection at very low risk (8%) and patients with community-acquired infections at significant risk (36%). CONCLUSION: This model achieved adequate performance and could be used to improve the selection of empiric antibiotics, aligning with other antibiotic stewardship program strategies.

15.
J Appl Microbiol ; 135(8)2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39066496

RESUMEN

AIMS: Staphylococcus aureus is an opportunistic pathogen whose treatment is further complicated by its ability to form biofilms. In this study, we examine the impact of growing S. aureus biofilms on different polymerizing surfaces, specifically agar and agarose, on the pathogen's tolerance to fluoroquinolones. METHODS AND RESULTS: Biofilms of two methicillin-resistant strains of S. aureus were grown on agar or agarose in the presence of the same added nutrients, and their antibiotic susceptibility to two fluoroquinolones, moxifloxacin (MXF) and delafloxacin (DLX), were measured. We also compared the metabolism and extracellular polymeric substances (EPS) production of biofilms that were grown on agar and agarose. CONCLUSIONS: Biofilms that were grown on agarose were consistently more susceptible to antibiotics than those grown on agar. We found that in biofilms that were grown on agar, extracellular protein composition was higher, and adding EPS to agarose-grown biofilms increased their tolerance to DLX to levels that were comparable to agar-grown biofilms.


Asunto(s)
Agar , Antibacterianos , Biopelículas , Fluoroquinolonas , Pruebas de Sensibilidad Microbiana , Sefarosa , Staphylococcus aureus , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Fluoroquinolonas/farmacología , Antibacterianos/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Staphylococcus aureus/crecimiento & desarrollo , Medios de Cultivo/química , Moxifloxacino/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/fisiología
17.
Cureus ; 16(6): e61895, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38975447

RESUMEN

Retropharyngeal abscesses (RPAs) are rare in the adult population and rarer without an inciting event or comorbidity such as recent oral surgery, neck infection, or pharyngeal trauma. The definitive treatment is incision and drainage of the abscess. Clinical researchers have recently questioned whether invasive surgical intervention is necessary and posed the question of what role antibiotics play in management. Sequelae of RPAs are severe and include rupture of the abscess, erosion of the carotid artery, thrombophlebitis, and most seriously, airway compromise. We present a case where an atypical presentation of an RPA caused a disagreement among specialists, and the debate of whether the described case represented an abscess or malignancy caused a delay in diagnosis and treatment for the patient. Only after invasive and emergent surgical intervention was a final diagnosis able to be made. This case demonstrates the need for more research and official guidance on the management of new neck masses to hasten diagnosis and prevent devastating outcomes.

18.
Intern Med ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38987181

RESUMEN

Necrotizing fasciitis (NF) is a life-threatening disease with high mortality and rapidly progressive clinical manifestations1. Early detection and surgical management coupled with antibiotic treatment are crucial for the survival, and the patient survival is heavily dependent on clinical decisions2,3. However, it is not widely known that NF does not always follow a typical clinical course, and there have been no case reports of NF following an atypical clinical course. Although the course of the disease depends on the individual patient, it remains a challenge for physicians to determine the precise timing when patients are most likely to survive multiple surgical interventions. We encountered a challenging case presenting with an atypical clinical course. We herein report a 31-year-old man who followed a deteriorating biphasic-like clinical course and presented with extensive NF and streptococcal toxic shock syndrome due to Group A Streptococcus. This case serves to inform physicians of the existence of NF with an atypical and deteriorating biphasic-like clinical course, emphasizing the need for a careful evaluation of the patient condition.

19.
Cureus ; 16(6): e61943, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38978903

RESUMEN

In patients receiving vancomycin therapy, serum drug levels are routinely monitored to ensure therapeutic dosing and minimize toxicity. In rare cases, vancomycin levels may be falsely or persistently elevated without any apparent cause. In this case report, we explore a rare case of persistently elevated vancomycin levels despite discontinuation of the drug for days.  This is a case of a 69-year-old female admitted for altered mental status secondary to sepsis from leg cellulitis. Antibiotic therapy included vancomycin. To ensure proper dosing, vancomycin trough levels were collected before the fourth dose, and the result showed a high value of 39 ug/ml. Vancomycin doses were adjusted as per the Bayesian dosing software, and the same remained to be in supratherapeutic levels. The patient eventually deteriorated, and due to persistently high vancomycin levels, the antibiotic regimen was switched to a different antibiotic. Despite normal renal functions, the vancomycin levels remained high, between 27 ug/ml and 32 ug/ml, even in the absence of any further doses. Subsequently, vancomycin serum concentration was determined by another method using high-performance liquid chromatography (HPLC). Blood cultures grew both coagulase-negative Staphylococcus aureus and Achromobacter xylosoxidans. Vancomycin levels remained high a week after discontinuation of the drug. Vancomycin by HPLC assay eventually showed that vancomycin was undetectable in the blood, but, unfortunately, the results came at a time when the patient had already expired. In conclusion, clinicians should maintain a high level of suspicion if persistently higher vancomycin levels cannot be accounted for by renal function or other causes. In patients with persistently high vancomycin levels who continue to clinically deteriorate, it is crucial to consider that assay interference can result in inaccurately elevated vancomycin levels.

20.
Antibiotics (Basel) ; 13(7)2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39061317

RESUMEN

This retrospective study aimed to assess and compare guideline adherence and treatment costs in the management of urinary tract infections (UTIs) and bloodstream infections (BSIs) in German tertiary hospitals from January 2019 to December 2020. The study analyzed 586 patient records, with 65% diagnosed with UTIs and 35% with BSIs. Antibiotic treatment was given to 98% of patients, but only 65% received microbiological diagnostics. Bacterial growth was observed in 86% of patients with cultures taken, with Escherichia coli being the leading pathogen. The treatment was intravenous in 63% of cases, with Ceftriaxone as the leading antibiotic agent. The guideline adherence was found to be low, at 33%. Multivariable logistic regression analysis revealed that patients with urogenital risk factors (OR = 1.589; p < 0.001) and increasing age (OR = 1.01; p = 0.007) were significantly more likely to receive guideline-concordant treatment for UTIs and BSIs. Additionally, complicating factors such as diabetes and renal dysfunction were associated with higher adherence rates, underscoring the importance of targeted antibiotic stewardship interventions.

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