RESUMO
Introduction: The decreasing Helicobacter pylori eradication rate is primarily attributed to antibiotic resistance, and further exacerbated by uniform drug administration disregarding a host's metabolic capability. Consequently, applying personalized treatment based on antibiotic resistance-associated variants and the host's metabolic phenotype can potentially increase the eradication rate. Method: A custom next-generation sequencing panel for personalized H. pylori eradication treatment (NGS-PHET) was designed which targeted the regions for amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin-resistance in H. pylori and human proton-pump inhibitor (PPI) metabolism. The libraries were constructed following customized methods and sequenced simultaneously. The customized framework criteria, grounded in previously reported antibiotic resistance associated variants and the host's PPI metabolism, was applied to the NGS-PHET results and suggested a personalized treatment for each subject, which was validated through each subject's actual eradication outcome. Results: Both previously reported and novel variants were identified from H. pylori sequencing results. Concurrently, five CYP2C19 homozygous extensive metabolizers and three CYP3A4 intermediate metabolizers were identified. Among the total of 12 subjects, clarithromycin triple therapy was suggested for five subjects, bismuth quadruple therapy was suggested for six subjects, and rifabutin triple therapy was suggested for one subject by following the customized framework criteria. The treatment suggestion for nine of the 12 subjects was consistent with the treatment that each subject achieved eradication with. Discussion: Applying the methodology using the NGS-PHET and customized framework helps to perform eradication treatment quickly and effectively in most patients with antibiotic-resistant H. pylori strains, and is also useful in research to find novel antibiotic-resistance candidates.
Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Sequenciamento de Nucleotídeos em Larga Escala , Medicina de Precisão , Humanos , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Medicina de Precisão/métodos , Inibidores da Bomba de Prótons/uso terapêutico , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Masculino , Farmacorresistência Bacteriana/genética , Pessoa de Meia-Idade , Feminino , Adulto , Quimioterapia Combinada , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Amoxicilina/uso terapêutico , Amoxicilina/farmacologia , Citocromo P-450 CYP2C19/genética , Testes de Sensibilidade Microbiana , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Tetraciclina/farmacologia , Tetraciclina/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. METHODS: This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. RESULTS: Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). CONCLUSIONS: The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.
Assuntos
Antituberculosos , Clofazimina , Ciclosserina , Diarilquinolinas , Levofloxacino , Linezolida , Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Masculino , Feminino , Adulto , Clofazimina/uso terapêutico , Clofazimina/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Linezolida/uso terapêutico , Linezolida/administração & dosagem , Diarilquinolinas/uso terapêutico , Diarilquinolinas/administração & dosagem , Pessoa de Meia-Idade , China/epidemiologia , Ciclosserina/uso terapêutico , Ciclosserina/administração & dosagem , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Rifampina/uso terapêutico , Rifampina/administração & dosagem , Estudos Prospectivos , Quimioterapia Combinada , Resultado do Tratamento , Adulto Jovem , IdosoRESUMO
We present the case of a 71-year-old man who developed sepsis caused by Capnocytophaga canimorsus as a result of being bitten by his own dog. Positive blood cultures were obtained, but due to difficulties in determining the bacterial species, the patient was treated empirically with ceftriaxone and levofloxacin. After using the recommended empirical therapy, the patient's condition improved. Capnocytophaga canimorsus is difficult to identify, among others, due to its long growth time and specific development conditions (capnophiles). These Gram-negative bacilli cause a number of diseases in humans, ranging from infections of the skin and subcutaneous tissue, through peritonitis, to sepsis. The portal of infection with these bacteria is most often a wound caused by an animal bite. Additional risk factors that increase the risk of developing a severe infection and even death include older age, concomitant chronic diseases, and immunosuppression.
Assuntos
Antibacterianos , Mordeduras e Picadas , Capnocytophaga , Infecções por Bactérias Gram-Negativas , Humanos , Cães , Mordeduras e Picadas/microbiologia , Mordeduras e Picadas/complicações , Animais , Masculino , Idoso , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/diagnóstico , Capnocytophaga/isolamento & purificação , Antibacterianos/uso terapêutico , Sepse/microbiologia , Sepse/etiologia , Sepse/tratamento farmacológico , Levofloxacino/uso terapêutico , Ceftriaxona/uso terapêuticoRESUMO
Perioperative antibiotic prophylaxis (PAP) in lung transplant recipients (LuTRs) has high heterogeneity between centers. Our aim was to investigate retrospectively the approach to PAP in our center over a 20-year period (2002-2023), and its impact on early post-operative infections (EPOIs) after lung transplantation (LuT). Primary endpoint was diagnosis of EPOI, defined as any bacterial infection including donor-derived events diagnosed within 30 days from LuT. Main exposure variables were type of PAP (combination vs. monotherapy) and PAP duration. We enrolled 111 LuTRs. PAP consisted of single-agent or combination regimens in 26 (25.2%) and 85 (74.8%) LuTR. Median PAP duration was 10 days (IQR 6-13) days. Piperacillin/tazobactam was the most common agent used either as monotherapy (n = 21, 80.7%) or as combination with levofloxacin (n = 79, 92.9%). EPOIs were diagnosed in 30 (27%) patients. At multivariable analysis no advantages were found for combination regimens compared to single-agent PAP in preventing EPOI (OR: 1.57, 95% CI: 0.488-5.068, p:0.448). The impact of PAP duration on EPOIs development was investigated including duration of PAP ≤6 days as main exposure variables, without finding a significantly impact (OR:2.165, 95% CI: 0.596-7.863, p: 0.240). Our results suggest no advantages for combination regimens PAP in preventing EPOI in LuTR.
Assuntos
Antibacterianos , Antibioticoprofilaxia , Transplante de Pulmão , Humanos , Transplante de Pulmão/efeitos adversos , Antibioticoprofilaxia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Adulto , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Idoso , Combinação Piperacilina e Tazobactam/uso terapêutico , Combinação Piperacilina e Tazobactam/administração & dosagem , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/etiologia , Complicações Pós-Operatórias/prevenção & controle , Quimioterapia CombinadaRESUMO
Brucellosis is a difficult to treat infection that requires antibiotic combinations administered over several weeks for clearance of infection and relapse prevention. This systematic review summarizes current evidence for antibiotic treatment of human brucellosis. PubMed, EMBASE, Scopus, CINAHL, Web of Science, and China Academic Journal databases were searched for prospective studies that had compared different antibiotic regimens for treating human brucellosis in the last 25 years. Thirty-four studies recruiting 4182 participants were eligible. Standard dual therapy with doxycycline + rifampicin had a higher risk of treatment failure compared to triple therapy which added streptomycin (RR: 1.98, 95% CI 1.17-3.35, p = 0.01) or levofloxacin (RR: 2.98, 95% CI 1.67-5.32, p = 0.0002), but a similar or lower risk compared to alternative dual antibiotic combinations (p > 0.05). The same combination had a higher risk of relapses compared to triple therapy which added streptomycin (RR: 22.12, 95% CI 3.48-140.52, p = 0.001), or levofloxacin (RR: 4.61, 95% CI 2.20-9.66, p < 0.0001), but a similar or lower risk compared to other dual antibiotic combinations (p > 0.05). Triple antibiotic therapy is more effective than standard dual therapy with rifampicin and doxycycline. However, the latter is also efficacious and suitable for uncomplicated disease.
Assuntos
Antibacterianos , Brucelose , Humanos , Antibacterianos/uso terapêutico , Brucelose/tratamento farmacológico , Doxiciclina/uso terapêutico , Quimioterapia Combinada , Levofloxacino/uso terapêutico , Rifampina/uso terapêutico , Estreptomicina/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Fluoroquinolones are the most commonly prescribed antibiotics. Because of their known tendency to drive antimicrobial resistance, their prescribing patterns need to be more restricted. This study aimed to describe the clinical practice of fluoroquinolone prescription, dose adjustments for renal impairment patients and bacterial resistance profiles, eventually providing evidence-based recommendations to optimize antibiotic prescribing practices in the local population. METHODS: This retrospective, cross-sectional study was conducted at An-Najah National University Hospital in Palestine. The data were collected from admitted patients who were given ciprofloxacin or levofloxacin from July 2021 to June 2023. Data from 692 inpatients across various hospital departments were examined (409 for levofloxacin and 283 for ciprofloxacin). Statistical analysis was performed via IBM SPSS version 23.0 to summarize the demographic, clinical, and epidemiological data. RESULTS: The sociodemographic profile revealed diverse age distributions, with 25.4% and 39% older than 50 years for ciprofloxacin and levofloxacin, respectively. Ciprofloxacin was predominantly used in the oncology department (28.2%), with surgical prophylaxis (22.6%) and febrile or afebrile neutropenia (21.1%) being the most common indications. Levofloxacin was predominantly used in the medical ward (45.7%), mainly for lower respiratory tract infection (58.8%) and prophylaxis for bone marrow transplantation (16.5%). Enterococcus and methicillin-resistant Staphylococcus aureus were the most commonly isolated pathogens, with 62.5% of the isolates demonstrating resistance to ciprofloxacin. Moreover, extended-spectrum beta-lactamase-producing Enterobacterales were the most common pathogen isolated, with 33.3% being resistant to levofloxacin. Statistical analysis revealed a significant association between the choice of antibiotic and the approach to therapy. Levofloxacin was significantly more likely than ciprofloxacin to be used as empiric therapy (p < 0.001), whereas ciprofloxacin was more likely to be used as targeted therapy (p < 0.001). CONCLUSIONS: This study investigated prescribing practices and resistance to levofloxacin and ciprofloxacin in a large hospital in a developing country. According to the bacterial resistance profiles, we conclude that there is a need for hospital departments to exercise greater restraint on the use of these antibiotics. To this end, further studies addressing the clinical efficacy of fluoroquinolones against the current treatment guidelines to evaluate their appropriateness should be carried out.
Assuntos
Antibacterianos , Fluoroquinolonas , Levofloxacino , Centros de Atenção Terciária , Humanos , Estudos Retrospectivos , Estudos Transversais , Masculino , Pessoa de Meia-Idade , Feminino , Centros de Atenção Terciária/estatística & dados numéricos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Adulto , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/farmacologia , Idoso , Levofloxacino/uso terapêutico , Levofloxacino/farmacologia , Ciprofloxacina/uso terapêutico , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais , Padrões de Prática Médica/estatística & dados numéricos , Testes de Sensibilidade Microbiana , Oriente Médio/epidemiologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificaçãoRESUMO
Amidst the COVID-19 pandemic, hydroxychloroquine (HCQ) was widely administered despite limited data on its safety and efficacy. This study assesses the acute and chronic impacts of HCQ on electrocardiography (ECG) parameters alongside the effects of azithromycin and levofloxacin coadministration in patients with COVID-19. A comprehensive analysis was conducted on 109 COVID-19 patients receiving HCQ, with or without Azithromycin and/or Levofloxacin, and 51 long-term HCQ-treated Sjogren's syndrome (SS) patients. ECG parameters, including QTc interval, were meticulously evaluated against a control group of 109 COVID-19 patients without HCQ treatment. HCQ monotherapy, in combination with Levofloxacin, significantly prolonged the QTc interval in COVID-19 patients compared to controls. Notably, the combination of HCQ and Azithromycin demonstrated a mitigated impact on QTc prolongation. Long-term HCQ use in SS patients did not significantly affect QTc intervals, illustrating a distinct safety profile from short-term use in COVID-19 treatment. HCQ's impact on QTc prolongation is influenced by therapeutic context, coadministered drugs, and patient demographics. The findings underscore the necessity of cautious HCQ use, particularly in acute settings like COVID-19, where monitoring and consideration of drug interactions and patient-specific factors are critical.
Assuntos
Azitromicina , Tratamento Farmacológico da COVID-19 , Eletrocardiografia , Hidroxicloroquina , Síndrome do QT Longo , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Hidroxicloroquina/administração & dosagem , Eletrocardiografia/efeitos dos fármacos , Feminino , Masculino , Pessoa de Meia-Idade , Azitromicina/uso terapêutico , Azitromicina/efeitos adversos , Azitromicina/administração & dosagem , Síndrome do QT Longo/induzido quimicamente , Idoso , Síndrome de Sjogren/tratamento farmacológico , Quimioterapia Combinada , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Levofloxacino/efeitos adversos , Adulto , SARS-CoV-2 , COVID-19Assuntos
Antibacterianos , Levofloxacino , Meningites Bacterianas , Infecções por Mycoplasma , Mycoplasma hominis , Humanos , Levofloxacino/uso terapêutico , Recém-Nascido , Mycoplasma hominis/isolamento & purificação , Antibacterianos/uso terapêutico , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/microbiologia , Masculino , Ofloxacino/uso terapêutico , FemininoRESUMO
OBJECTIVES: We aimed to assess whether there is a difference between ciprofloxacin and levofloxacin as prophylaxis in hematopoietic stem cell transplant (SCT) recipients. METHODS: This is a prospective, randomized trial in patients receiving SCT at Henry Ford Health in the United States of America. We randomly assigned patients (1:1) to receive ciprofloxacin or levofloxacin. The primary outcome was incidence of bloodstream bacterial infections (BSI) up to day 60 after SCT. RESULTS: Between June 4, 2018, and May 23, 2022, we randomly assigned 308 consecutive patients to receive ciprofloxacin (154 patients) or levofloxacin (154 patients). BSI was similar in both the ciprofloxacin and levofloxacin groups (18 [11.7%] vs 18 [11.7%]). Pneumonia was more frequent in the ciprofloxacin group compared to the levofloxacin group (18 [18%] vs 7 [23%]; relative risk 2.57, 95% CI 1.11-5.98; p = 0.028). There were no differences in neutrophil engraftment, fever, Clostridium difficile infection, relapse incidence, overall survival, nonrelapse mortality, length of stay post-SCT, or intensive care unit admission. CONCLUSION: Although both prophylaxis regimens demonstrated the same efficacy in SCT recipients, levofloxacin prophylaxis led to less pneumonia in the first 60 days post-SCT. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, NCT03850379.
Assuntos
Antibacterianos , Antibioticoprofilaxia , Ciprofloxacina , Transplante de Células-Tronco Hematopoéticas , Levofloxacino , Humanos , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ciprofloxacina/uso terapêutico , Ciprofloxacina/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Antibioticoprofilaxia/métodos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Estudos Prospectivos , Adulto , Idoso , Bacteriemia/prevenção & controle , Bacteriemia/epidemiologiaRESUMO
Bloodstream infections (BSI) are one of the leading causes of morbidity and mortality in children and young adults receiving chemotherapy for malignancy or undergoing hematopoietic stem cell transplantation (HSCT). Antibiotic prophylaxis is commonly used to decrease the risk of BSI; however, antibiotics carry an inherent risk of complications. The aim of this manuscript is to review levofloxacin prophylaxis in pediatric oncology patients and HSCT recipients. We reviewed published literature on levofloxacin prophylaxis to prevent BSI in pediatric oncology patients and HSCT recipients. Nine manuscripts were identified. The use of levofloxacin is indicated in neutropenic children and young adults receiving intensive chemotherapy for leukemia or undergoing HSCT. These results support the efficacy of levofloxacin in pediatric patients with leukemia receiving intensive chemotherapy and should be considered in pediatric patients undergoing HSCT prior to engraftment.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Levofloxacino , Humanos , Levofloxacino/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Criança , Adolescente , Masculino , Pré-Escolar , Feminino , Antibioticoprofilaxia/métodos , Neoplasias , Leucemia/terapia , Antibacterianos/uso terapêutico , Adulto , Adulto JovemRESUMO
BACKGROUND: With the increasing prevalence of antibiotic resistance, real-world data on the optimal empirical second-line therapy for Helicobacter pylori are still limited. OBJECTIVES: To evaluate the real-world efficacy of various second-line therapies for H. pylori. PATIENTS AND METHODS: This was a retrospective population-based cohort study of all H. pylori-infected patients who had received the second-line treatment after the failure of primary clarithromycin triple therapy in Hong Kong between 2003 and 2018. The retreatment success rates of different second-line therapies were evaluated. RESULTS: A total of 7591 patients who received second-line treatment were included. Notably, the most commonly prescribed regimen was still clarithromycin triple therapy, but the frequency of use had decreased from 59.5% in 2003-06 to 28.7% in 2015-18. Concomitant non-bismuth quadruple therapy had emerged as the commonest regimen (from 3.3% to 43.9%). In a validation analysis, the sensitivity and specificity of retreatment-inferred second-line treatment failure were 88.3% and 97.1%, respectively. The overall success rate of second-line therapies was 73.6%. Bismuth quadruple therapy had the highest success rate of 85.6%, while clarithromycin triple therapy had the lowest success rate of 63.5%. Specifically, bismuth/metronidazole/tetracycline quadruple, metronidazole/tetracycline triple, levofloxacin/metronidazole/tetracycline quadruple, rifabutin/amoxicillin triple and amoxicillin/levofloxacin triple therapies had relatively higher success rates over 80%. Age, treatment duration, baseline conditions and first-line treatment used were associated with success rate. CONCLUSIONS: Bismuth quadruple therapy was the most effective second-line regimen for H. pylori in this real-world study. Despite a very low success rate, clarithromycin-containing triple therapies were still commonly used as second-line regimens.
Assuntos
Antibacterianos , Claritromicina , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Estudos Retrospectivos , Feminino , Masculino , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Claritromicina/uso terapêutico , Hong Kong , Adulto , Idoso , Resultado do Tratamento , Metronidazol/uso terapêutico , Retratamento , Amoxicilina/uso terapêutico , Falha de Tratamento , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Levofloxacino/uso terapêuticoRESUMO
BACKGROUND & OBJECTIVES: The purpose of present study is to analyse the distribution and pattern of genetic mutations in PRE-XDR-TB and extensive drug resistant Mycobacterium tuberculosis (XDR-TB) using second-line line probe assay and to compare them with different parameters. METHOD: Sputum, Lymph node aspirate and cold accesses from patients with rifampicin resistant Tuberculosis were subjected to first line and second line Probe Assay (Genotype MTBDRsl by Hain Life Science, Germany) to assess additional drug resistance to fluroquinolones (Levofloxacin & Moxifloxacin) and Aminoglycosides (Amikacin, Ofloxacin and Kanamycin). The genetic mutation pattern was analysed and compared with demographic, clinical and other parameters. RESULTS: The final study population included 123 fluoroquinolone resistant isolates including 14 isolates with additional second line aminoglycosides drug resistance. The most frequent mutation observed among Gyr A drug resistance mutation was D94G (Gyr A MUT3C, 50/123,40%) corresponding to high level resistance to levofloxacin and moxifloxacin. The most frequent wild type mutant among Gyr A gene locus was WT 3 (85/123,69%). The most common mutation among second line aminoglycoside resistant isolates was at eis WT2 (7/14,50%) followed by rrs MUT 2 (4/14,29%). CONCLUSIONS: GyrA MUT3C (Asp94Gly) was the most common mutation in Gyr A gene locus in M. tuberculosis causing high level levofloxacin and moxifloxacin resistance. Patients with Asp94Gly mutation was significantly associated with underweight body mass index (p = 0.026). This study also observed that history of anti-tuberculosis therapy is a risk factor for FQ drug resistance mutations (p < 0.001).
Assuntos
Antituberculosos , Mutação , Mycobacterium tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Masculino , Feminino , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Pessoa de Meia-Idade , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Testes de Sensibilidade Microbiana , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Moxifloxacina/uso terapêutico , Moxifloxacina/farmacologia , Adulto JovemRESUMO
SETTING: On a programmatic basis, a new regimen was introduced in the National Tuberculosis Elimination Programme for isoniazid monoresistant tuberculosis in a few states in India. OBJECTIVE: To describe the clinical attributes and treatment outcomes of isoniazid mono-resistant tuberculosis patients on the new 6-month levofloxacin-containing regimen in Puducherry, India. DESIGN: The study is designed as a convergent parallel mixed-methods study: a retrospective cohort study and a descriptive qualitative study. A total of 180 Hr-TB patient health records were reviewed, and in-depth interviews with 35 participants were conducted. (20 Hr-TB patients and 15 HCWs). RESULTS: Of the total 180 Hr-TB patients included, we documented unfavourable outcomes in 26.1% of cases, and the KatG gene mutation was the most common mutation observed (63.9%). A significant risk of unfavourable outcomes was associated with low adherence and positive sputum at the third-month culture report. In interviewing the stakeholders, major challenges observed were the increased pill burden, delay in diagnosis, shortage of drugs, and lack of staff. CONCLUSION: Hr-TB patients have difficulty in adhering to the 6-month levofloxacin regimen, with the need for rigorous early 3-month follow-up and assessment.
Assuntos
Antituberculosos , Isoniazida , Levofloxacino , Mycobacterium tuberculosis , Humanos , Índia/epidemiologia , Isoniazida/uso terapêutico , Antituberculosos/uso terapêutico , Masculino , Feminino , Adulto , Estudos Retrospectivos , Levofloxacino/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Resultado do Tratamento , Pessoa de Meia-Idade , Tuberculose Pulmonar/tratamento farmacológico , Adulto Jovem , Escarro/microbiologia , Catalase/genética , Adesão à Medicação/estatística & dados numéricos , Mutação , Pesquisa Qualitativa , Proteínas de Bactérias/genética , Farmacorresistência BacterianaRESUMO
OBJECTIVE: The non-invasive detection of Helicobacter pylori (H. pylori) and its resistance to clarithromycin and levofloxacin significantly improves the management of infected patients by enabling tailored eradication treatments without the need for endoscopic procedures. This study aimed to assess the effectiveness of real-time PCR (RT-PCR) assays in identifying H. pylori infection and antibiotic resistance in stool and gastric biopsy specimens. PATIENTS AND METHODS: Stool and gastric biopsy samples were collected from patients within three days of post-hospitalization. A total of 115 samples were analyzed for H. pylori infection, and an additional 115 samples were evaluated for resistance to clarithromycin and levofloxacin using an RT-PCR-based molecular test. Statistical analyses were performed using (SPSS 26.0 IBM Corp., Armonk, NY, USA). RESULTS: Among 115 patients (53 males, average age 50.8±13.2 years), H. pylori was detected in 93.1% of stool samples and 93.9% of gastric biopsies. The RT-PCR assay demonstrated a sensitivity of 99.1% and a specificity of 100%, with an overall diagnostic accuracy of 99.1%. Clarithromycin resistance was found in 37.3% of stool and 46.9% of gastric biopsy specimens, with the assay showing 79.6% sensitivity and 98.4% specificity. Levofloxacin resistance was identified in 32.1% of stool samples and 31.3% of gastric biopsies, with 86.3% sensitivity and 91.1% specificity of the molecular test. CONCLUSIONS: The RT-PCR-based detection of H. pylori and its resistance to clarithromycin and levofloxacin in stool samples represents a promising approach to enhance eradication therapy outcomes, potentially improving treatment efficacy. Chictr.org.cn: ChiCTR2300070267.
Assuntos
Antibacterianos , Claritromicina , Farmacorresistência Bacteriana , Fezes , Infecções por Helicobacter , Helicobacter pylori , Levofloxacino , Reação em Cadeia da Polimerase em Tempo Real , Humanos , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Claritromicina/farmacologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/genética , Fezes/microbiologia , Masculino , Pessoa de Meia-Idade , Feminino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Adulto , Idoso , Testes de Sensibilidade MicrobianaRESUMO
There are conflicting recommendations on whether to use or not to use fluoroquinolone prophylaxis in pediatric oncology patients. An international pediatric clinical practice guideline (CPG) recommends administering levofloxacin prophylaxis in patients with acute myeloblastic leukemia and relapsed acute lymphoblastic leukemia receiving intensive chemotherapy as this practice has been found to reduce episodes of fever and bacteremia. A separate European CPG does not recommend levofloxacin prophylaxis because of concerns for adverse effects, including potentiation of fluoroquinolone resistance and possible increased resistance to other classes of antibiotics. The nuance of the decision to give or not give prophylaxis is discussed in the context of published evidence defining the risks and benefits of levofloxacin prophylaxis for pediatric leukemia patients at high risk for bacterial infection. Knowledge gaps are also identified to guide further investigations to optimize the use of fluoroquinolone prophylaxis in pediatric patients receiving chemotherapy for cancer or undergoing a hematopoietic cell transplantation.
Assuntos
Antibacterianos , Antibioticoprofilaxia , Levofloxacino , Humanos , Criança , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Guias de Prática Clínica como Assunto , Neoplasias/tratamento farmacológico , Bacteriemia/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/tratamento farmacológicoRESUMO
The aim of the present study was first to isolate Helicobacter pylori from gastric biopsy specimens and to test their antibiotic susceptibility. Second, it was to evaluate the efficacy of the standard triple therapy from patients of the west central region of Colombia. H. pylori positive patients received standard triple therapy with proton pump inhibitor (PPI) (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1 g b.i.d.) for 14 days. Thereafter, antibiotic susceptibility of the isolates was assessed by E-Test. From 94 patients enrolled, 67 were positive for H. pylori by histology or culture. Overall resistance to metronidazole, levofloxacin, rifampicin, clarithromycin, and amoxicillin was 81%, 26.2%, 23.9%, 19%, and 9.5%, respectively. No resistance was found for tetracycline. A total of 54 patients received standard triple therapy, 48 attended follow-ups testing, and of them, 30 had resistance test reports. Overall eradication rate was 81.2%. Second-line treatment was given to eight patients, four of whom were followed up with a 13C urea breath test (UBT) and remained positive for H. pylori. Eradication was significantly higher in patients with clarithromycin susceptible than in resistant strains (95.6% vs 42.8% P = 0.001). The updated percentages of resistance to clarithromycin in this geographical area had increased, so this value must be considered when choosing the treatment regimen.IMPORTANCEAntibiotic resistance in Helicobacter pylori has increased worldwide, as has resistance to multiple antimicrobials (MDRs), which seriously hampers the successful eradication of the infection. The ideal success rate in eradicating H. pylori infection (≥90%) was not achieved in this study (81.2%). This is the first time that MDR is reported (14.3%) in the region; the resistance to clarithromycin increased over time (3.8%-19%), and levofloxacin (26.2%) and rifampicin (23%) resistant isolates were detected for the first time. With these results, strain susceptibility testing is increasingly important, and the selection of treatment regimen should be based on local antibiotic resistance patterns.
Assuntos
Amoxicilina , Antibacterianos , Claritromicina , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Testes de Sensibilidade Microbiana , Humanos , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/genética , Colômbia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Adulto , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Amoxicilina/uso terapêutico , Amoxicilina/farmacologia , Idoso , Inibidores da Bomba de Prótons/uso terapêutico , Farmacorresistência Bacteriana , Adulto Jovem , Metronidazol/uso terapêutico , Metronidazol/farmacologia , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.
Assuntos
Antibacterianos , Infecções Comunitárias Adquiridas , Levofloxacino , Quinolonas , Humanos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Levofloxacino/uso terapêutico , Levofloxacino/efeitos adversos , Levofloxacino/administração & dosagem , Método Duplo-Cego , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Adulto , Idoso , Resultado do Tratamento , Quinolonas/uso terapêutico , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Administração Intravenosa , Infusões Intravenosas , Adulto Jovem , Pneumonia/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Idoso de 80 Anos ou maisRESUMO
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
Antibiotic resistance among bacteria is recognized as the primary factor contributing to the failure of treatment. In this research, our objective was to examine the prevalence of antibiotic resistance in H. pylori bacteria in Palestine. We enlisted 91 individuals suffering from dyspepsia, comprising 49 females and 42 males. These participants underwent esophagogastroduodenoscopy procedures with gastric biopsies. These biopsies were subsequently subjected to microbiological assessments and tested for their susceptibility to various antimicrobial drugs. Among the 91 patients, 38 (41.7%) exhibited the presence of H. pylori. Notably, Ciprofloxacin displayed the highest efficacy against H. pylori, followed by Levofloxacin, Moxifloxacin, and Amoxicillin, with resistance rates of 0%, 0%, 2.6%, and 18.4%, respectively. On the contrary, Metronidazole and Clarithromycin demonstrated the lowest effectiveness, with resistance percentages of 100% and 47.4%, respectively. The outcomes of this investigation emphasize that H. pylori strains within the Palestinian patient group exhibit substantial resistance to conventional first-line antibiotics like clarithromycin and metronidazole. However, alternative agents such as fluoroquinolones and amoxicillin remain efficacious choices. Consequently, we recommend favoring quinolone-based treatment regimens for H. pylori infections and adopting a more judicious approach to antibiotic usage among the Palestinian population.
Assuntos
Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Humanos , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Feminino , Masculino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/epidemiologia , Estudos Transversais , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Adulto , Prevalência , Pessoa de Meia-Idade , Farmacorresistência Bacteriana , Hospitais Universitários , Testes de Sensibilidade Microbiana , Amoxicilina/uso terapêutico , Amoxicilina/farmacologia , Claritromicina/uso terapêutico , Claritromicina/farmacologia , Metronidazol/uso terapêutico , Metronidazol/farmacologia , Levofloxacino/uso terapêutico , Levofloxacino/farmacologiaRESUMO
Serratia marcescens, as a Gram-negative opportunistic pathogen, is a rare cause of peritonitis and has worse clinical outcomes than Gram-positive peritonitis. In this case report, we describe a case of Serratia marcescens associated peritonitis that was successfully cured without catheter removal. A 40-year-old male patient with peritoneal dialysis who worked in the catering industry was admitted to the hospital for 16 hours after the discovery of cloudy peritoneal dialysate and abdominal pain. Ceftazidime and cefazolin sodium were immediately given intravenously as an empirical antibiotic regimen. After detecting Serratia marcescens in the peritoneal diasate culture, the treatment was switched to ceftazidime and levofloxacin. The routine examination of peritoneal dialysate showed a significant decrease in white blood cells, the peritoneal dialysate became clear, and the peritoneal dialysis catheter was retained. The patient was treated for 2 weeks and treated with oral antibiotics for 1 week. It is necessary to further strengthen the hygiene of work environment to prevent Serratia marcescens infection in peritoneal dialysis patients. We recommend that patients with Serratia marcescens associated peritonitis should be treated with a combination of antibiotics as early as possible empirically, and at the same time, the peritoneal dialysis fluid culture should be improved, and the antibiotic regimen should be timely adjusted according to the drug sensitivity results. For patients with clinical symptoms for more than 3 days, considering the strong virulence of Serratia marcescens, whether to use meropenem directly or not can provide a reference for clinical decision-making. Further clinical studies are needed to achieve more precise anti-infective treatment.