RESUMO
Respiratory tract infections are a serious threat to health, especially in the presence of antimicrobial resistance (AMR). Existing AMR detection methods are limited by slow turnaround times and low accuracy due to the presence of false positives and negatives. In this study, we simulate 1,116 clinical metagenomics samples on both Illumina and Nanopore sequencing from curated, real-world sequencing of A. baumannii respiratory infections and build AI models to predict resistance to amikacin. The best performance is achieved by XGBoost on Illumina sequencing (area under the ROC curve = 0.7993 on 5-fold cross-validation).
Assuntos
Acinetobacter baumannii , Amicacina , Farmacorresistência Bacteriana , Metagenômica , Amicacina/farmacologia , Amicacina/uso terapêutico , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Humanos , Farmacorresistência Bacteriana/genética , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologiaRESUMO
INTRODUCTION: An effective rifampicin-resistant tuberculosis (RR-TB) treatment regimen should include prevention of resistance amplification. While bedaquiline (BDQ) has been recommended in all-oral RR-TB treatment regimen since 2019, resistance is rising at alarming rates. This may be due to BDQ's delayed bactericidal effect, which increases the risk of selecting for resistance to fluoroquinolones and/or BDQ in the first week of treatment when the bacterial load is highest. We aim to strengthen the first week of treatment with the injectable drug amikacin (AMK). To limit the ototoxicity risk while maximising the bactericidal effect, we will evaluate the safety of adding a 30 mg/kg AMK injection on the first and fourth day of treatment. METHODS AND ANALYSIS: We will conduct a single-arm clinical trial on 20 RR-TB patients nested within an operational study called ShoRRT (All oral Shorter Treatment Regimen for Drug resistant Tuberculosis). In addition to all-oral RR-TB treatment, patients will receive two doses of AMK. The primary safety endpoint is any grade 3-4 adverse event during the first 2 weeks of treatment related to the use of AMK. With a sample size of 20 patients, we will have at least 80% statistical power to support the alternative hypothesis, indicating that less than 14% of patients treated with AMK experience a grade 3-4 adverse event related to its use. Safety data obtained from this study will inform a larger multicountry study on using two high doses of AMK to prevent acquired resistance. ETHICS AND DISSEMINATION: Approval was obtained from the ethics committee of Rwanda, Rwanda Food and Drug Authority, Universitair Ziekenhuis, the Institute of Tropical Medicine ethics review board. All participants will provide informed consent. Study results will be disseminated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT05555303.
Assuntos
Amicacina , Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Amicacina/administração & dosagem , Amicacina/efeitos adversos , Amicacina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Administração Oral , Adulto , Mycobacterium tuberculosis/efeitos dos fármacos , Masculino , Feminino , Esquema de MedicaçãoRESUMO
Mycobacterium abscessus pulmonary infections are increasingly problematic, especially for immunocompromised individuals and those with underlying lung conditions. Currently, there is no reliable standardized treatment, underscoring the need for improved preclinical drug testing. We present a simplified immunosuppressed mouse model using only four injections of cyclophosphamide, which allows for sustained M. abscessus lung burden for up to 16 days. This model proved effective for antibiotic efficacy evaluation, as demonstrated with imipenem or amikacin.
Assuntos
Amicacina , Antibacterianos , Ciclofosfamida , Modelos Animais de Doenças , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Animais , Ciclofosfamida/farmacologia , Mycobacterium abscessus/efeitos dos fármacos , Camundongos , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Amicacina/farmacologia , Amicacina/uso terapêutico , Imipenem/farmacologia , Imipenem/uso terapêutico , Pulmão/microbiologia , Pulmão/efeitos dos fármacos , Hospedeiro Imunocomprometido , FemininoRESUMO
INTRODUCTION: Mycetoma is a chronic granulomatous inflammatory disease of the subcutaneous tissue, which affects deep structures and bone. Most cases of actinomycetoma are caused by members of the genus Nocardia. CASE PRESENTATION: Here we report the case of a 43-year-old male who presented a disseminated mycetoma on the forearm, chest and neck, characterized by enlarged and erythematous lesions through which seropurulent material drains, and numerous atrophic scars. Molecular identification was performed by 16S gene amplification and sequencing. Nocardia mexicana was identified with 100% identity. Trimethoprim-sulfamethoxazole, diaminodiphenyl sulfone and amikacin was a successful treatment after 6 months. CONCLUSIONS: Nocardia mexicana is a rare organism that causes mycetoma. We report a case of extensive mycetoma on the forearm with spread to the neck and thorax associated with manipulation of the mouth of a calf.
Assuntos
Antibacterianos , Antebraço , Micetoma , Pescoço , Nocardiose , Nocardia , RNA Ribossômico 16S , Tórax , Humanos , Masculino , Adulto , Nocardia/isolamento & purificação , Nocardia/genética , Micetoma/microbiologia , Micetoma/tratamento farmacológico , Micetoma/diagnóstico , Nocardiose/microbiologia , Nocardiose/tratamento farmacológico , Nocardiose/diagnóstico , Antebraço/microbiologia , Antebraço/patologia , Tórax/diagnóstico por imagem , Tórax/microbiologia , Pescoço/patologia , Antibacterianos/uso terapêutico , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Amicacina/uso terapêutico , DNA Ribossômico/genética , DNA Ribossômico/químicaRESUMO
Treatment outcomes for Mycobacteroides abscessus (Mab, also known as Mycobacterium abscessus) disease are still unsatisfactory, mainly due to issues with drug toxicity, tolerability, and efficacy. Treating Mab disease is challenging due to its high baseline antibiotic resistance, initial requirement for intravenous therapy, and poor medication tolerance. Omadacycline, a new tetracycline, is active against Mab. Since any new antibiotic effective against Mab is expected to be used in combination with other antibiotics, we evaluated the efficacy of two triple-drug combinations comprising omadacycline, omadacycline + amikacin + imipenem, and omadacycline + clofazimine + linezolid against two contemporary Mab clinical isolates in a mouse model of Mab lung disease. Antibiotic administration was initiated 1-week post-infection and was given daily, with Mab burden in the lungs at treatment completion serving as the endpoint. Omadacycline alone moderately reduced Mab levels and maintained better health in mice compared to untreated ones, which typically suffered from the infection. The omadacycline + clofazimine + linezolid combination showed immediate bactericidal activity and enhanced efficacy over 6 weeks, particularly against the more resistant strain (M9507). However, the clofazimine + linezolid combination lacked early bactericidal activity. When combined with amikacin and imipenem, omadacycline did not improve the regimen's effectiveness over 4 weeks of treatment. Our study showed that omadacycline + clofazimine + linezolid exhibited significant bactericidal activity over an extended treatment duration. However, adding omadacycline to amikacin and imipenem did not improve regimen effectiveness against the evaluated clinical isolates within 4 weeks. Further research in Mab disease patients is needed to determine the most effective omadacycline-containing regimen.IMPORTANCEMycobacteroides abscessus is a common environmental bacterium that causes infections in people with compromised lung function, including those with bronchiectasis, cystic fibrosis, chronic obstructive pulmonary disease, and weakened immune systems, especially among older individuals. Treating M. abscessus disease is challenging due to the limited effectiveness and toxicity of current antibiotics, which often require prolonged use. Omadacycline, a new antibiotic, shows promise against M. abscessus. Using a mouse model that mimics M. abscessus disease in humans, we studied the effectiveness of including omadacycline with recommended antibiotics. Adding omadacycline to clofazimine and linezolid significantly improved treatment outcomes, rapidly clearing the bacteria from the lungs and maintaining effectiveness throughout. This oral combination is convenient for patients. However, adding omadacycline to amikacin and imipenem did not improve treatment effectiveness within 4 weeks. Further study with M. abscessus patients is necessary to optimize omadacycline-based treatment strategies for this disease.
Assuntos
Amicacina , Antibacterianos , Clofazimina , Modelos Animais de Doenças , Quimioterapia Combinada , Imipenem , Linezolida , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Tetraciclinas , Animais , Clofazimina/administração & dosagem , Clofazimina/uso terapêutico , Linezolida/administração & dosagem , Linezolida/uso terapêutico , Camundongos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Amicacina/administração & dosagem , Amicacina/uso terapêutico , Tetraciclinas/administração & dosagem , Tetraciclinas/uso terapêutico , Tetraciclinas/farmacologia , Mycobacterium abscessus/efeitos dos fármacos , Imipenem/administração & dosagem , Imipenem/uso terapêutico , Imipenem/farmacologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Feminino , Resultado do Tratamento , Testes de Sensibilidade Microbiana , Pneumopatias/tratamento farmacológico , Pneumopatias/microbiologia , Administração Oral , Pulmão/microbiologiaRESUMO
INTRODUCTION: Mycobacterium canariasense is a relatively rare and rapidly growing nontuberculous mycobacterium (NTM) infection. CASE REPORT: This case report describes a 36-year-old man with a Canariasense infection in the lung with solitary cavitation nodules located subpleural on CT scan, for which the final diagnosis was made by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF-mNGS). It was successfully treated with levofloxacin and amikacin. CONCLUSIONS: This experience is instructive because clinical diagnostic and CT imaging characteristics and treatment strategy guidelines for pulmonary infections caused by M. canariasense have not yet been established.
Assuntos
Antibacterianos , Infecções por Mycobacterium não Tuberculosas , Tomografia Computadorizada por Raios X , Humanos , Masculino , Adulto , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/diagnóstico por imagem , Antibacterianos/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Pulmão/microbiologia , Pulmão/patologia , Pulmão/diagnóstico por imagem , Levofloxacino/uso terapêutico , Amicacina/uso terapêutico , Micobactérias não Tuberculosas/isolamento & purificação , Micobactérias não Tuberculosas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Resultado do TratamentoRESUMO
OBJECTIVE: To report the clinical use, adverse events, and outcomes after using amikacin in 30% poloxamer 407 (amikacin-P407) during open wound management or in a closed wound application in dogs. ANIMALS: 29 client-owned dogs. METHODS: Medical records from January 2017 to August 2023 from a single hospital were reviewed for dogs that received amikacin-P407 in an open or closed wound application. Information reviewed included signalment, nature of wound and/or surgical site infection (SSI), bacterial cultures, amikacin dose, gel volume, route of administration, estimated wound surface area, biochemistry parameters, urine casts, wound progression, and general clinical outcome. RESULTS: Amikacin-P407 was applied during open wound care (10 dogs), via injection (5 dogs), and at time of wound closure (13 dogs) and was used both in open and closed wound management (1 dog). Wounds were associated with SSIs in 18 of 30 sites. Multidrug resistance was noted in 21 of 30 preapplication cultures. Median amikacin dose was 14.5 mg/kg (range, 3 to 59.5 mg/kg), median total volume was 5.0 mL (range, 1 to 12 mL), and median tissue surface area was 6.6 cm2 (range, 1.6 to 36 cm2), for a local wound dose of 62.5 mg/cm2 (range, 6.9 to 214.3 mg/cm2). No short-term adverse local or systemic effects were noted in any wounds or dogs. No dehiscence was seen in 17 of 19 closed sites. CLINICAL RELEVANCE: The results of this case series suggested that Amikacin-P407 can be applied in a variety of ways with no adverse effects. Amikacin-P407 may be considered in open wound management or in a closed setting for infected wounds and SSIs.
Assuntos
Amicacina , Antibacterianos , Doenças do Cão , Poloxâmero , Animais , Cães , Amicacina/administração & dosagem , Amicacina/uso terapêutico , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Feminino , Doenças do Cão/tratamento farmacológico , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We report the case of a female patient in her late 20s who visited the clinic with concerns about poor vision, redness, watering and a burning sensation in her left eye 2 weeks after undergoing a small incision lenticule extraction. She had no history of systemic illness or immunosuppressed status. On slit lamp examination, she was found to have corneal stromal infiltrates in the interface at multiple locations. Given the clinical diagnosis of microbial keratitis, corneal scraping of the interface infiltrate was performed and sent for microbiological examination revealing gram-positive, thin, beaded filaments that were acid-fast positive and later identified by growth in culture media as Nocardia species. This case was managed successfully with the use of topical amikacin and systemic trimethoprim-sulfamethoxazole with complete resolution of infection.
Assuntos
Antibacterianos , Infecções Oculares Bacterianas , Ceratite , Nocardiose , Humanos , Feminino , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológico , Ceratite/microbiologia , Ceratite/tratamento farmacológico , Ceratite/diagnóstico , Ceratite/cirurgia , Antibacterianos/uso terapêutico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/tratamento farmacológico , Amicacina/uso terapêutico , Amicacina/administração & dosagem , Adulto , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Nocardia/isolamento & purificação , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/diagnósticoRESUMO
Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.
Assuntos
Acinetobacter baumannii , Antibacterianos , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Sepse Neonatal , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Sepse Neonatal/microbiologia , Sepse Neonatal/tratamento farmacológico , Recém-Nascido , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/genética , Amicacina/farmacologia , Amicacina/uso terapêutico , Fosfomicina/farmacologia , Fosfomicina/uso terapêutico , beta-Lactamases/genética , beta-Lactamases/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Países em Desenvolvimento , Farmacorresistência Bacteriana Múltipla/genética , Quimioterapia Combinada , Serratia marcescens/efeitos dos fármacos , Serratia marcescens/genética , Serratia marcescens/isolamento & purificação , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/genética , Enterobacter cloacae/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismoRESUMO
To analyze the results of proficiency testing for anti-tuberculosis drug susceptibility testing (DST) in China. Number of laboratory participating the proficiency testing performed DST, and the sensitivity, specificity, reproducibility, and accordance rate were calculated from data of 13 rounds proficiency testing results for DST from 2008 to 2021. A total of 30 and 20 strains of Mycobacterium tuberculosis with known susceptibility results were sent to each laboratory in 2008 to 2019, 2020 and 2021, respectively. The number of participating laboratories ranged from 30 in 2009 to 546 in 2021. L-J DST was the predominant method. The specificity presented relatively higher than sensitivity. Improvement of specificity were observed for all drugs through the years, while sensitivity did not show improvement for amikacin and capreomycin. Accordance rate of pyrazinamide and kanamycin and reproducibility of capreomycin and pyrazinamide were not significantly improved through the years. Most of the participating laboratories significantly improved the quality of their DST through the consecutive rounds of proficiency testing except for second-line injectable drugs and pyrazinamide. The results highlight the importance of developing novel and/or improving existing methods for phenotypic DST for certain drugs.
Assuntos
Antituberculosos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Mycobacterium tuberculosis/efeitos dos fármacos , China , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Humanos , Ensaio de Proficiência Laboratorial , Reprodutibilidade dos Testes , Fenótipo , Amicacina/farmacologia , Amicacina/uso terapêutico , Pirazinamida/uso terapêuticoRESUMO
Pseudomonas can lead to peritoneal dialysis-associated peritonitis, which is characterized by a poor prognosis, such as a substantial failure rate and a high death rate. This study aimed to provide an overview of Pseudomonas peritonitis's clinical features, the regimens of antibiotic, antibiotic resistance, and outcomes in peritoneal dialysis (PD) patients. This study observed patients with Pseudomonas peritonitis in two large PD centers in South China from January 2008 to December 2022. The demographics, symptomatology, antibiotics regimens, resistance to common antibiotics, and clinical outcomes of all included patients were reviewed. A total of 3,459 PD patients were included, among them 57 cases of peritonitis caused by Pseudomonas, including 48 cases (84.2%) of Pseudomonas aeruginosa. The incidence rate of Pseudomonas peritonitis was 0.0041 episode per patient-year. Of them, 28.1% (16 cases) of the patients were accompanied by exit site infection (ESI), and all had abdominal pain and turbid ascites at the time of onset. The most commonly used antibiotic combination was ceftazidime combined with amikacin. Approximately 89% of Pseudomonas species were sensitive to ceftazidime, and 88% were sensitive to amikacin. The overall primary response rate was 28.1% (16 patients), and the complete cure rate was 40.4% (23 patients). There was no significant difference in the complete cure rate of peritonitis using three and other antibiotic treatment regimens (44.8% vs 46.4%; P = 0.9). The successful treatment group had higher baseline albumin level (35.9 ± 6.2; P = 0.008) and residual urine volume (650.7 ± 375.5; P = 0.04). Although the incidence of peritonitis caused by Pseudomonas was low, the symptoms were serious, and prognosis was very poor. Pseudomonas was still highly susceptible to first-line antibiotics currently in use against Gram-negative bacteria. Patients with successful treatment had higher albumin levels and higher urine output. IMPORTANCE: Although the incidence of peritoneal dialysis-associated peritonitis caused by Pseudomonas is very low, it seriously affects the technique survival of peritoneal dialysis patients. However, there are few studies and reports on Pseudomonas peritonitis in the Chinese mainland area. Therefore, the purpose of this study is to describe the clinical characteristics, the regimens of antibiotic, drug resistance, and outcome of peritoneal dialysis patients in southern China in the past 15 years and summarize the clinical experience in the treatment of Pseudomonas peritonitis.
Assuntos
Antibacterianos , Diálise Peritoneal , Peritonite , Infecções por Pseudomonas , Pseudomonas , Humanos , Peritonite/tratamento farmacológico , Peritonite/microbiologia , Peritonite/epidemiologia , Antibacterianos/uso terapêutico , China/epidemiologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/epidemiologia , Diálise Peritoneal/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Pseudomonas/efeitos dos fármacos , Pseudomonas/isolamento & purificação , Adulto , Pseudomonas aeruginosa/efeitos dos fármacos , Estudos Retrospectivos , Ceftazidima/uso terapêutico , Testes de Sensibilidade Microbiana , Amicacina/uso terapêuticoAssuntos
Amicacina , Reações Cruzadas , Dessensibilização Imunológica , Neomicina , Humanos , Dessensibilização Imunológica/métodos , Amicacina/efeitos adversos , Amicacina/uso terapêutico , Neomicina/efeitos adversos , Antibacterianos/efeitos adversos , Exantema/induzido quimicamente , Hipersensibilidade a Drogas/terapia , Hipersensibilidade a Drogas/imunologia , Hipersensibilidade a Drogas/diagnóstico , Feminino , Masculino , Pessoa de Meia-IdadeRESUMO
Pulmonary infection due to Mycobacterium abscessus complex (MABC) usually occurs in children with underlying risk factors including cystic fibrosis (CF), chronic lung disease, and immunocompromised status, but rarely in immunocompetent children without underlying lung disease, especially in infants. We present a case of MABC pulmonary disease (MABC-PD) in an otherwise healthy 53-day-old male infant with one week of cough and respiratory distress. Computed tomography showed multiple masses across both lungs. Isolated mycobacteria from his bronchoalveolar lavage fluid were identified as MABC. We describe our complete evaluation, including immunodeficiency evaluation incorporating whole exome sequencing and our therapeutic process given complicated susceptibility pattern of the M. abscessus isolate, and review literature for MABC-PD in immunocompetent children. The infant was successfully treated through prolonged treatment with parenteral Amikacin, Cefoxitin, Linezolid, and Clarithromycin, combined with inhaled Amikacin.
Assuntos
Antibacterianos , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Humanos , Masculino , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium abscessus/isolamento & purificação , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Antibacterianos/uso terapêutico , Lactente , Líquido da Lavagem Broncoalveolar/microbiologia , Amicacina/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/diagnóstico , Resultado do Tratamento , Tomografia Computadorizada por Raios X , Claritromicina/uso terapêutico , Linezolida/uso terapêuticoRESUMO
Catheter-related bloodstream infection (CRBSI) is one of the common healthcare-acquired infections imposing a high burden of morbidity and mortality on the patients. Non-tuberculous mycobacterium is a rare aetiology for CRBSI and poses challenges in laboratory diagnosis and clinical management. This is a case of a woman in her early 60s with underlying end-stage renal failure, diabetes mellitus and hypertension presented with a 2-week history of high-grade fever postregular haemodialysis, vomiting, lethargy and altered mental status.Blood cultures from a permanent catheter and peripheral taken concurrently yielded Mycobacterium senegalense, identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, which established the diagnosis of CRBSI atypically presented with concurrent acute intracranial bleeding and cerebrovascular infarction at initial presentation. She was started on a combination of oral azithromycin, oral amikacin and intravenous imipenem, and the permanent catheter was removed. Despite the treatments instituted, she developed septicaemia, acute myocardial infarction and macrophage activation-like syndrome, causing the patient's death.
Assuntos
Antibacterianos , Infecções Relacionadas a Cateter , Infecções por Mycobacterium não Tuberculosas , Humanos , Feminino , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/diagnóstico , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Evolução Fatal , Bacteriemia/tratamento farmacológico , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Diálise Renal , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Amicacina/uso terapêutico , Amicacina/administração & dosagemRESUMO
Pseudomonas aeruginosa is an opportunistic gram-negative pathogenic microorganism that poses a significant challenge in clinical treatment. Antibiotics exhibit limited efficacy against mature biofilm, culminating in an increase in the number of antibiotic-resistant strains. Therefore, novel strategies are essential to enhance the effectiveness of antibiotics against Pseudomonas aeruginosa biofilms. D-histidine has been previously identified as a prospective anti-biofilm agent. However, limited attention has been directed towards its impact on Pseudomonas aeruginosa. Therefore, this study was undertaken to explore the effect of D-histidine on Pseudomonas aeruginosa in vitro. Our results demonstrated that D-histidine downregulated the mRNA expression of virulence and quorum sensing (QS)-associated genes in Pseudomonas aeruginosa PAO1 without affecting bacterial growth. Swarming and swimming motility tests revealed that D-histidine significantly reduced the motility and pathogenicity of PAO1. Moreover, crystal violet staining and confocal laser scanning microscopy demonstrated that D-histidine inhibited biofilm formation and triggered the disassembly of mature biofilms. Notably, D-histidine increased the susceptibility of PAO1 to amikacin compared to that in the amikacin-alone group. These findings underscore the efficacy of D-histidine in combating Pseudomonas aeruginosa by reducing biofilm formation and increasing biofilm disassembly. Moreover, the combination of amikacin and D-histidine induced a synergistic effect against Pseudomonas aeruginosa biofilms, suggesting the potential utility of D-histidine as a preventive strategy against biofilm-associated infections caused by Pseudomonas aeruginosa.
Assuntos
Amicacina , Infecções por Pseudomonas , Humanos , Amicacina/farmacologia , Amicacina/metabolismo , Amicacina/uso terapêutico , Pseudomonas aeruginosa , Histidina/farmacologia , Histidina/metabolismo , Histidina/uso terapêutico , Biofilmes , Percepção de Quorum , Antibacterianos/química , Infecções por Pseudomonas/microbiologia , Fatores de Virulência/metabolismoRESUMO
The rise in ESBL-producing and carbapenem-resistant Gram-negative bacterial infections is alarming. Aminoglycosides remain attractive for treating urinary tract infections (UTIs). However, aminoglycosides-associated acute kidney injury (AKI) raises concerns, especially in patients with underlying renal impairment. We conducted a retrospective cohort study to evaluate the risk of AKI in patients with UTI empirically treated with amikacin. Among 395 patients (median age 41.9 years [IQR 28.3-67.1], 342 [86.6%] female), 162 (41.0%) received amikacin and 233 (59.0%) were empirically treated with other antibiotics. AKI incidence was low (5.6%) and not associated with amikacin exposure (OR 0.56, 95% CI 0.22-1.43, p = 0.23), even in those with pre-existing renal impairment or AKI on admission. The clinical outcomes (including cure by the third day, AKI, maximal creatinine, length of stay, mortality, and readmission) did not differ between the groups. Once-daily amikacin may offer a safe UTI treatment option amid increasing multi-drug resistance.