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1.
BMC Infect Dis ; 21(1): 183, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596848

RESUMO

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) are unsatisfied to treat, pressing more effective and innovative treatment regimens. New efficient regimens for MDR-TB have obtained high treatment success rates. However, those regimens without drug susceptibility testing (DST) are also likely to contribute to the emergence of resistance. Precision treatments guided by DST might optimize the patients' treatment outcome individually and minimize resistance amplification. METHODS: TB-TRUST is a phase III, multicenter, open-label, randomized controlled clinical trial of non-inferiority comparing the treatment success rate between the World Health Organization (WHO) shorter regimen and the refined ultra-short regimen for fluoroquinolones and second-line injectable drugs susceptible rifampicin-resistant TB. The control arm uses the WHO injectable-containing shorter regimen for 36-44 weeks depending on time of sputum smear conversion. The investigational arm uses a refined ultra-short regimen guided by molecular DST to pyrazinamide via whole-genome sequencing (WGS) to optimize the treatment of pyrazinamide-susceptible patients with levofloxacin, linezolid, cycloserine and pyrazinamide for 24-32 weeks and pyrazinamide-resistant with levofloxacin, linezolid, cycloserine and clofazimine for 36-44 weeks. The primary outcome is the treatment success rate without relapse at 84 weeks after treatment initiation. Secondary outcomes include the time of sputum culture conversion and occurrence of adverse events. Assuming α = 0.025 level of significance (one-sided test), a power of 80%, a < 10% difference in treatment success rate between control arm and investigational (80% vs. 82%), and a 5% lost follow-up rate, the number of participants per arm to show non-inferiority was calculated as 177(354 in total). DISCUSSION: Rapid molecular testing distinguishes patients who are eligible for shorter regimen with fluoroquinolone and the WGS-guided results shorten the treatment to 6 months for pyrazinamide susceptible patients. It's foreseeable that not only novel developed medicines, but also traditional powerful medicines with the susceptibility confirmed by DST are the key factors to ensure the effect of anti-MDR-TB drugs. As a DST-guided precision treatment, TB-TRUST are expected to optimize therapy outcome in more patients who cannot afford the expensive new medicines and minimize and even avoid resistance amplification with the rational use of anti-TB drugs. TRAIL REGISTRATION: ClinicalTrial.gov, NCT03867136 . Registered on March 7, 2019.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Idoso , Antituberculosos/efeitos adversos , Protocolos Clínicos , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Feminino , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Pirazinamida/efeitos adversos , Pirazinamida/uso terapêutico , Escarro/microbiologia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Sequenciamento Completo do Genoma , Adulto Jovem
2.
BMC Infect Dis ; 21(1): 159, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557769

RESUMO

BACKGROUND: Complicated urinary tract infection (cUTI) is common among hospitalized patients. Though carbapenems are an effective treatment in the face of rising resistance, overuse drives carbapenem resistance (CR). We hypothesized that resistance to routinely used antimicrobials is common, and, despite frequent use of carbapenems, associated with an increased risk of inappropriate empiric treatment (IET), which in turn worsens clinical outcomes. METHODS: We conducted a retrospective cohort study of patients hospitalized with a culture-positive non-CR cUTI. Triple resistance (TR) was defined as resistance to > 3 of the following: 3rd generation cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin. Multivariable models quantified the impact of TR and inappropriate empiric therapy (IET) on mortality, hospital LOS, and costs. RESULTS: Among 23,331 patients with cUTI, 3040 (13.0%) had a TR pathogen. Compared to patients with non-TR, those with TR were more likely male (57.6% vs. 47.7%, p < 0.001), black (17.9% vs. 13.6%, p < 0.001), and in the South (46.3% vs. 41.5%, p < 0.001). Patients with TR had higher chronic (median [IQR] Charlson score 3 [2, 4] vs. 2 [1, 4], p < 0.001) and acute (mechanical ventilation 7.0% vs. 5.0%, p < 0.001; ICU admission 22.3% vs. 18.6%, p < 0.001) disease burden. Despite greater prevalence of empiric carbapenem exposure (43.3% vs. 16.2%, p < 0.001), patient with TR were also more likely to receive IET (19.6% vs. 5.4%, p < 0.001) than those with non-TR. Although mortality was similar between groups, TR added 0.38 (95% CI 0.18, 0.49) days to LOS, and $754 (95% CI $406, $1103) to hospital costs. Both TR and IET impacted the outcomes among cUTI patients whose UTI was not catheter-associated (CAUTI), but had no effect on outcomes in CAUTI. CONCLUSIONS: TR occurs in 1 in 8 patients hospitalized with cUTI. It is associated with an increase in the risk of IET exposure, as well as a modest attributable prolongation of LOS and increase in total costs, particularly in the setting of non-CAUTI.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções Urinárias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carbapenêmicos/uso terapêutico , Doença Crônica , Combinação de Medicamentos , Fluoroquinolonas/uso terapêutico , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sulfadoxina/uso terapêutico , Trimetoprima/uso terapêutico , Estados Unidos/epidemiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/patologia
4.
BMC Infect Dis ; 20(1): 950, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33308173

RESUMO

BACKGROUND: Antimicrobial resistance in M. genitalium is a growing clinical problem. We investigated the mutations associated with macrolide and fluoroquinolone resistance, two commonly used medical regimens for treatment in China. Our aim is to analyze the prevalence and diversity of mutations among M. genitalium-positive clinical specimens in Guangzhou, south China. METHODS: A total of 154 stored M. genitalium positive specimens from men and women attending a STI clinic were tested for macrolide and fluoroquinolone mutations. M. genitalium was detected via TaqMan MGB real-time PCR. Mutations associated with macrolide resistance were detected using primers targeting region V of the 23S rRNA gene. Fluoroquinolone resistant mutations were screened via primers targeting topoisomerase IV (parC) and DNA gyrase (gyrA). RESULTS: 98.7% (152/154), 95.5% (147/154) and 90.3% (139/154) of M. genitalium positive samples produced sufficient amplicon for detecting resistance mutations in 23S rRNA, gyrA and parC genes, respectively. 66.4% (101/152), 0.7% (1/147) and 77.7% (108/139) samples manifested mutations in 23S rRNA, gyrA and parC genes, respectively. A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively. Two samples had amino acid substitutions in gyrA (M95I and A96T, respectively). Two samples had two amino acid substitutions in parC (S83I + D87Y). 48.6% (67/138) of samples harbored both macrolide and fluoroquinolone resistance-associated mutations. The most common combination of mutations was A2072G (23S rRNA) and S83I (parC) (40/67, 59.7%). One sample had three amino acid changes in 23S rRNA, gyrA and parC genes (A2072G + A96T + S83I). CONCLUSIONS: The high antimicrobial resistance rate of M. genitalium in Guangzhou is a very worrying problem and suggests that antimicrobial resistance testing and the development of new antibiotic regimens are crucially needed.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Fluoroquinolonas/uso terapêutico , Macrolídeos/uso terapêutico , Mutação , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/genética , Doenças Bacterianas Sexualmente Transmissíveis/tratamento farmacológico , China/epidemiologia , DNA Girase/genética , DNA Topoisomerase IV/genética , DNA Bacteriano/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Masculino , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/microbiologia , Mycoplasma genitalium/isolamento & purificação , Prevalência , RNA Ribossômico 23S/genética , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Doenças Bacterianas Sexualmente Transmissíveis/epidemiologia , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia
5.
BMC Infect Dis ; 20(1): 785, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087051

RESUMO

BACKGROUND: Literature is scarce regarding oral step down to beta-lactams in bacteremic urinary tract infections. Oral fluoroquinolones are an accepted and common step down for bacteremic urinary tract infections; however, their use is associated with mounting safety concerns. We compared clinical cure in patients with E. coli bacteremic urinary tract infections who were stepped down to oral beta-lactams compared to oral fluoroquinolones. METHODS: This multicentre retrospective cohort study included patients with first positive concurrent urine and blood cultures from January 2016 to December 2016. Patients were included if they received empiric intravenous beta-lactam therapy with step down to either oral beta-lactam or fluoroquinolone for treatment completion. The primary outcome was clinical cure. Secondary outcomes were length of hospitalization, all-cause mortality and C. difficile infection. Multivariate analysis and propensity score were used to control for confounding. RESULTS: A total of 207 patients were identified with bacteremic E.coli urinary tract infections. Clinical cure was achieved in 72/77 (94%) in the oral beta-lactam group versus 127/130 (98%) in the oral fluoroquinolone group (absolute difference - 4.2, 95% confidence interval [CI] -10.3 to 1.9%, p = 0.13). The adjusted odds ratio (OR) for clinical cure with oral beta-lactams was 0.31 (95% CI 0.05-1.90, p = 0.21); propensity score adjusted analysis showed a similar result. There was no statistically significant difference in secondary outcomes. CONCLUSIONS: Oral beta-lactams appear to be a safe and effective step down option in bacteremic E. coli urinary tract infections compared to oral fluoroquinolones.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/isolamento & purificação , Fluoroquinolonas/uso terapêutico , Infecções Urinárias/tratamento farmacológico , beta-Lactamas/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Bacteriemia/microbiologia , Hemocultura , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Infecções por Escherichia coli/microbiologia , Feminino , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/efeitos adversos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Infecções Urinárias/microbiologia , beta-Lactamas/administração & dosagem , beta-Lactamas/efeitos adversos
6.
Medicine (Baltimore) ; 99(37): e21896, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925724

RESUMO

This study aimed to determine the differences in antibiotic usage patterns in the treatment of acute pyelonephritis according to hospital type and region in Korea.The claims database of the Health Insurance Review and Assessment Service in Korea was used to select patients with the International Classification of Diseases, Tenth Revision code N10 (acute tubulo-interstitial nephritis) or N12 (tubulo-interstitial nephritis, neither acute nor chronic) as the primary discharge diagnosis in 2010-2014. Usage of each class of antibiotics was expressed as the defined daily dose (DDD)/event.The average antibiotic usage per inpatient event was 11.3 DDD. The average antibiotic usage was the highest among patients admitted to tertiary hospitals (13.8 DDD), followed by those admitted to secondary hospitals (11.5 DDD), clinics (10.0 DDD), and primary hospitals (9.8 DDD). According to the geographic analyses, third-generation cephalosporins were highly prescribed in some southern regions; fluoroquinolones and aminoglycosides were highly prescribed in some centrally located regions of the Korean peninsula. The hotspots for carbapenem usage included Seoul and Gyeonggi province cluster and Busan cluster: these regions include the capital city and the second biggest city in Korea, respectively.In conclusion, the antibiotic usage patterns for acute pyelonephritis in Korea differ according to the hospital type and region.


Assuntos
Antibacterianos/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Pielonefrite/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Aminoglicosídeos/uso terapêutico , Cefalosporinas/uso terapêutico , Bases de Dados Factuais , Feminino , Fluoroquinolonas/uso terapêutico , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Centros de Cuidados de Saúde Secundários/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
7.
PLoS One ; 15(8): e0237987, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841259

RESUMO

OBJECTIVE: We conducted a quality improvement initiative to restrict fluoroquinolone prescribing on two inpatient units housing high-risk patients and applied a human factors approach to understanding the barriers and facilitators to success of this intervention by front-line providers. METHODS: This was a mixed-methods, quasi-experimental study. This study was conducted on two inpatient units at a tertiary care academic medical center: the medical-surgical intensive care and abdominal solid organ transplant units. Unit-level data were collected retrospectively for 24 months pre- and post- fluoroquinolone restriction intervention, implemented in July 2016, for all admissions to the study units. Our restriction intervention required antimicrobial stewardship pre-approval for fluoroquinolone prescribing. We explored barriers and facilitators to optimal fluoroquinolone prescribing using semi-structured interviews attending, fellow and resident physicians, advanced practice providers and pharmacists on these units. RESULTS: Hospital-onset C. difficile infection did not decrease significantly, but fluoroquinolone use declined significantly from 111.6 to 19.8 days of therapy per 1000 patient-days without negatively impacting length of stay, readmissions or mortality. Third generation cephalosporin and aminoglycoside use increased post-restriction. Providers identified our institution's strong antimicrobial stewardship program and pharmacy involvement in antimicrobial decision making as key facilitators of fluoroquinolone optimization and patient complexity, lack of provider education and organizational culture as barriers to optimal prescribing. CONCLUSIONS: Fluoroquinolones can be safely restricted even among high-risk patients without negatively impacting length of stay, readmissions or mortality. Our study provides a framework for successful antimicrobial stewardship interventions informed by perceptions of front line providers.


Assuntos
Gestão de Antimicrobianos/estatística & dados numéricos , Fluoroquinolonas/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Pessoal de Saúde/estatística & dados numéricos , Humanos , Pacientes Internados/estatística & dados numéricos , Farmácia/estatística & dados numéricos , Risco , Atenção Terciária à Saúde/estatística & dados numéricos
8.
PLoS One ; 15(8): e0237603, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841261

RESUMO

BACKGROUND/PURPOSE: To date, studies examining polymicrobial infections in ocular disease have mostly been limited to keratitis or endophthalmitis. We characterized polybacterial infections compared to monobacterial infections in prior clinical studies evaluating besifloxacin ophthalmic suspension 0.6% for the treatment of bacterial conjunctivitis and report on associated microbiological outcomes. METHODS: In this post-hoc analysis, microbiological data for subjects with conjunctivitis due to one or more than one bacterial species in three previous studies (two vehicle-, one active-controlled) of besifloxacin were extracted. Bacterial species identified at baseline were deemed causative if their colony count equaled or exceeded species-specific prespecified threshold criteria. In subjects with polybacterial infections, the fold-increase over threshold was used to rank order the contribution of individual species. Baseline pathogens and their minimum inhibitory concentrations (MICs) for common ophthalmic antibiotics were compared by infection type, as were microbial eradication rates following treatment with besifloxacin. RESULTS: Of 1041 subjects with culture-confirmed conjunctivitis, 17% had polybacterial and 83% had monobacterial conjunctivitis at baseline. In polybacterial compared to monobacterial infections, Haemophilus influenzae and Streptococcus pneumoniae were identified less frequently as the dominant infecting species (P = 0.042 and P<0.001, respectively), whereas Streptococcus mitis/S. mitis group was identified more frequently as dominant (P<0.001). Viral coinfection was also identified more frequently in polybacterial infections (P<0.001). Staphylococcus aureus was the most common coinfecting species in polybacterial infections and the second most common dominant species in such infections. With few exceptions, MICs for individual species were comparable regardless of infection type. Clinical microbial eradication rates with besifloxacin were high regardless of infection type (P≤0.016 vs vehicle at follow-up visits). CONCLUSIONS: Approximately one in five subjects with bacterial conjunctivitis are infected with more than one bacterial species underscoring the need for a broad-spectrum antibiotic for such infections. Besifloxacin treatment resulted in robust eradication rates of these infections comparable to monobacterial infections. TRIAL REGISTRATION: NCT000622908, NCT00347932, NCT00348348.


Assuntos
Antibacterianos/uso terapêutico , Azepinas/uso terapêutico , Bactérias/classificação , Bactérias/efeitos dos fármacos , Conjuntivite Bacteriana/tratamento farmacológico , Fluoroquinolonas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Conjuntivite Bacteriana/microbiologia , Conjuntivite Bacteriana/patologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto Jovem
9.
PLoS One ; 15(8): e0237787, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822375

RESUMO

INTRODUCTION: Afghanistan is affected by one of the world's longest protracted armed conflicts, frequent natural disasters, disease outbreaks and large population movements and it suffers from a high burden of tuberculosis (TB), including rifampicin-resistant TB (RR-TB). The study shows Médecins Sans Frontières' experiences with care for patients with RR-TB in Kandahar Province. We describe the uptake of RR-TB treatment, how World Health Organisation criteria for the choice between the short and an individualized regimen were implemented, and treatment outcomes. METHODS: This is a retrospective cohort analysis of routinely collected data from RR-TB patients enrolled in care from 2016 until 2019. Descriptive analysis was performed to present characteristics of patients and treatment outcomes. Multivariable Cox analysis was performed to identify risk factors for having an unfavourable treatment outcome. RESULTS: Out of 146 enrolled RR-TB patients, 112 (76.7%) started treatment: 41 (36.6%) and 71 (63.4%) with the short and individualized treatment regimen, respectively. Of 82 with results for fluoroquinolone susceptibility, 39 (47.6%) had fluoroquinolone-resistant TB. Seven patients with initially fluoroquinolone-resistant TB and three pregnant women started the short regimen and 18 patients eligible for the short regimen started the injectable-free individualized regimen. Overall, six-month smear and culture conversion were 98.7% and 97.1%, respectively; treatment success was 70.1%. Known initial fluoroquinolone resistance (aHR 3.77, 95%CI:1.53-9.27) but not choice of regimen predicted having an unfavourable outcome. CONCLUSION: Even though criteria for the choice of treatment regimen were not applied strictly, we have achieved acceptable outcomes in this cohort. To expand RR-TB care, treatment regimens should fit provision at primary health care level and take patient preferences into account.


Assuntos
Antituberculosos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Afeganistão/epidemiologia , Feminino , Humanos , Masculino , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Organização Mundial da Saúde , Adulto Jovem
10.
J Assoc Physicians India ; 68(8): 30-36, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32738837

RESUMO

Background: Levonadifloxacin is a novel broad-spectrum anti-MRSA agents belonging to the benzoquinolizine subclass of quinolone. It is developed for oral or intravenous administration for the treatment of infections caused by Gram-positive organisms including methicillin-resistant Staphylococcus aureus (MRSA). Objectives: To establish the non-inferiority of levonadifloxacin compared with linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and to compare the safety of the two antimicrobials. Subjects and methods: This was a Phase 3, multicentre, randomized, open-label, active- comparator study with 500 subjects. Oral levonadifloxacin 1000 mg was compared with oral linezolid 600 mg whereas IV levonadifloxacin 800mg was compared with IV linezolid 600 mg, each treatment was administered twice daily for 7-10 days. Non-inferiority was evaluated by comparing oral levonadifloxacin to oral linezolid and IV levonadifloxacin to IV linezolid for overall clinical response at TOC (Test of Cure) Visit. Results: The clinical cure rates observed at the TOC in the mITT (modified Intent to treat) populations for levonadifloxacin was numerically higher compared to linezolid in the IV sub-group [(91.0% verses 87.8%); treatment difference of 3.2% (95%CI, -4.5 to 10.9)] and in the oral sub-group (95.2% versus 93.6%); treatment difference of 1.6 % [95%CI, -4.2 to 7.3]). As the lowerbound of the 95% CI around the treatment difference was greater than -15% for both subgroups, the primary objective of the study was met. Therefore, both IV levonadifloxacin and oral levonadifloxacin were non-inferior to IV linezolid and oral linezolid, respectively. The majority of subjects in the micro-ITT population had a baseline infection caused by S. aureus with approximately 30% of subjects having MRSA. Levonadifloxacin (IV and oral) had a higher clinical cure rate at TOC for MRSA patients compared with linezolid (IV and oral), (95.0% vs. 89.3% respectively). Levonadifloxacin showed evidence of favourable clinical and microbiological efficacy in subjects with concurrent bacteraemia as well as in subjects with diabetes including diabetic foot infections caused by Gram-positive pathogens including MRSA. Pharmacokinetic analysis showed that bioavailability of oral levonadifloxacin was 90% and similar pharmacokinetic profile of levonadifloxacin by both routes provide an option for IV to oral switch for the treatment of subjects. Incidences of treatment-emergent adverse events (TEAEs) were similar between treatment groups and between IV (20.8% vs. 22.4%, for levonadifloxacin and linezolid, respectively) and oral therapy (16.0% vs. 13.5%, respectively), There were no SAEs or deaths related to study drug and the majority of the AEs observed were mild in nature. Overall, the administration of both IV and oral levonadifloxacin was well-tolerated in subjects with ABSSSI. Conclusions: The results demonstrate that IV and oral levonadifloxacin therapy has excellent clinical activity against MRSA and offers advantage compared to other quinolones which generally lack MRSA coverage. Levonadifloxacin is safe and well tolerated in the treatment of ABSSSI caused by Gram -positive pathogens including MRSA as well as non-inferior to IV and oral linezolid, respectively. Similar pharmacokinetic profile of IV and oral levonadifloxacin provides an option for IV to oral switch for the treatment of subjects. Both oral and IV levonadifloxacin have recently been granted approval in India for the treatment of ABSSSI including diabetic foot infections and concurrent bacteraemia in adults (18 years of age or older). ClinicalTrials.gov Registration: NCT03405064. CTRI No.: CTRI/2017/06/008843.


Assuntos
Antibacterianos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas/tratamento farmacológico , Adolescente , Adulto , Humanos , Índia , Linezolida , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus , Resultado do Tratamento
11.
Medicine (Baltimore) ; 99(34): e21860, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846837

RESUMO

BACKGROUND: The use of fluoroquinolone antibiotics has been restricted in children because of their potential to cause adverse musculoskeletal events. This study was performed to systematically evaluate whether there is a difference between fluoroquinolone and non-fluoroquinolone antibiotics in terms of their associated risk of adverse musculoskeletal events in children. METHODS: Cochrane Library, Embase, and PubMed databases were used to retrieve studies related to fluoroquinolone and non-fluoroquinolone-induced musculoskeletal adverse events in children. A meta-analysis was performed using Stata 11. RESULTS: A total of 10 studies were included in the analysis. The combined results showed that there was no statistical difference between fluoroquinolone and non-fluoroquinolone groups in terms of musculoskeletal adverse events in children (risk ratio = 1.145, 95% confidence interval = 0.974 - 1.345, P = .101). Subgroup analysis was performed using a random-effects model. Here, the effects on the trovafloxacin and levofloxacin groups were significantly different from that of the control group. However, musculoskeletal adverse events due to either drug was not reported after long-term follow-up. CONCLUSIONS: The results showed that fluoroquinolone and non-fluoroquinolone antibiotics were not different in terms of their ability to cause musculoskeletal adverse events in children. For this reason, fluoroquinolone antibiotics can be used in children as appropriate. PROSPERO REGISTRATION NUMBER: CRD42019133900.


Assuntos
Antibacterianos/efeitos adversos , Infecções Bacterianas/tratamento farmacológico , Fluoroquinolonas/efeitos adversos , Sistema Musculoesquelético/efeitos dos fármacos , Adolescente , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Lactente , Recém-Nascido , Levofloxacino/efeitos adversos , Levofloxacino/uso terapêutico , Masculino , Naftiridinas/efeitos adversos , Naftiridinas/uso terapêutico , Estudos Retrospectivos , Sensibilidade e Especificidade , Inibidores da Topoisomerase II/efeitos adversos , Inibidores da Topoisomerase II/uso terapêutico
12.
PLoS One ; 15(7): e0235797, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32645105

RESUMO

BACKGROUND: Although combination therapy using clarithromycin, rifampicin, and ethambutol is recommended for patients with pulmonary Mycobacterium avium complex (MAC) disease, some patients do not tolerate it because of adverse effects or underlying diseases. The efficacy and safety of fluoroquinolone-containing combination regimens as an alternative remain uncertain. This study aimed to compare the efficacy and safety of fluoroquinolone-containing regimens with those of the standard regimens for treating pulmonary MAC disease. METHODS: We retrospectively included consecutive MAC patients who were treated in our hospital between January 2011 and May 2019. Patients treated with fluoroquinolone-containing regimens who had relapsed after treatment with standard regimens were excluded. A propensity score analysis was conducted to reduce selection bias, and the proportions of clinical improvement, defined by chest imaging findings and sputum conversion, were compared between the fluoroquinolone-containing regimen and standard regimen groups. RESULTS: We analyzed 28 patients who received fluoroquinolone-containing regimens and 46 who received the standard regimen. Fluoroquinolone-containing regimens were more likely selected for patients with cavitary lesions, diabetes mellitus, culture negativity, a low daily physical activity level, a decreased lymphocyte count and an increased CRP level. The propensity score was calculated using these variables (C-statistic of the area under the receiver operating characteristic curve of the propensity score: 0.807, p < 0.0001). The fluoroquinolone-containing regimens were significantly inferior to the standard regimen in clinical improvements (p = 0.002, Log-rank test) in the univariate analysis, but the significance was lost after adjusting for the propensity score (HR 0.553, 95% CI 0.285-1.074, p = 0.080). Six (21%) patients in the fluoroquinolone-containing regimen group and ten (22%) patients in the standard regimen group experienced low-grade adverse effects. CONCLUSIONS: There was no significant difference in clinical improvement between these regimens after propensity score adjustment. A large-scale prospective study is required to validate these results.


Assuntos
Antibacterianos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Idoso , Antibacterianos/efeitos adversos , Feminino , Fluoroquinolonas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
13.
Am J Trop Med Hyg ; 103(4): 1443-1446, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32618257

RESUMO

We report a case of acquired fluoroquinolone (FQ) resistance under short-course multidrug-resistant tuberculosis (MDR-TB) treatment. The patient was managed at Kabutare hospital, one of the two specialized MDR-TB clinics in Rwanda. A low dose of moxifloxacin was used in the first three critical months. Acquired resistance was identified at the ninth month of treatment, 3 months after stopping kanamycin in a strain initially susceptible only to FQs, kanamycin, and clofazimine. Fluoroquinolone resistance was detected in the same month by deep sequencing as routinely used second-line line probe assay and phenotypic drug susceptibility testing. High-dose FQ, preferably gatifloxacin, should be used to maximize effectiveness.


Assuntos
Fluoroquinolonas/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/uso terapêutico , Clofazimina/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Gatifloxacina/uso terapêutico , Genes Bacterianos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Canamicina/uso terapêutico , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Moxifloxacina/uso terapêutico , Mycobacterium tuberculosis/genética , Ruanda , Análise de Sequência de DNA
14.
BMC Infect Dis ; 20(1): 518, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677920

RESUMO

BACKGROUND: Campylobacter jejuni is a leading cause of bacterial diarrhea worldwide, and increasing rates of fluoroquinolone (FQ) resistance in C. jejuni are a major public health concern. The rapid detection and tracking of FQ resistance are critical needs in developing countries, as these antimicrobials are widely used against C. jejuni infections. Detection of point mutations at T86I in the gyrA gene by real-time polymerase chain reaction (RT-PCR) is a rapid detection tool that may improve FQ resistance tracking. METHODS: C. jejuni isolates obtained from children with diarrhea in Peru were tested by RT-PCR to detect point mutations at T86I in gyrA. Further confirmation was performed by sequencing of the gyrA gene. RESULTS: We detected point mutations at T86I in the gyrA gene in 100% (141/141) of C. jejuni clinical isolates that were previously confirmed as ciprofloxacin-resistant by E-test. No mutations were detected at T86I in gyrA in any ciprofloxacin-sensitive isolates. CONCLUSIONS: Detection of T86I mutations in C. jejuni is a rapid, sensitive, and specific method to identify fluoroquinolone resistance in Peru. This detection approach could be broadly employed in epidemiologic surveillance, therefore reducing time and cost in regions with limited resources.


Assuntos
Infecções por Campylobacter/diagnóstico , Campylobacter jejuni/genética , DNA Girase/genética , Farmacorresistência Bacteriana/genética , Fluoroquinolonas/uso terapêutico , Mutação Puntual , Reação em Cadeia da Polimerase em Tempo Real/métodos , Substituição de Aminoácidos , Infecções por Campylobacter/tratamento farmacológico , Infecções por Campylobacter/microbiologia , Campylobacter jejuni/isolamento & purificação , Criança , Ciprofloxacino/uso terapêutico , Análise Mutacional de DNA/métodos , Diarreia/diagnóstico , Diarreia/tratamento farmacológico , Diarreia/microbiologia , Humanos , Isoleucina/genética , Testes de Sensibilidade Microbiana , Peru , Treonina/genética
15.
Drugs Today (Barc) ; 56(6): 365-376, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32525135

RESUMO

Lascufloxacin hydrochloride (AM-1977) is a novel 8-methoxy fluoroquinolone antibacterial agent with a unique pharmacophore at the 1st and 7th positions of the quinoline nucleus developed by Kyorin Pharmaceutical Co., Ltd. (Tokyo, Japan). It has been approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for treatment of respiratory tract and ear, nose and throat infections including community-acquired pneumonia and otorhinolaryngological infections, and shows great promise against fluoroquinolone-resistant strains of major pathogens which infect the respiratory tract. It is suitable for treating infections caused by Staphylococcus, Streptococcus, Pneumococcus, Moraxella (Branhamella) catarrhalis, Klebsiella, Enterobacter, Haemophilus influenzae, Legionella pneumophila, Prevotella and Mycoplasma pneumoniae that are sensitive to this drug.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Fluoroquinolonas/uso terapêutico , Farmacorresistência Bacteriana , Humanos , Japão
16.
BMC Infect Dis ; 20(1): 446, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576154

RESUMO

BACKGROUND: The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea. METHODS: Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15-34 years), middle (35-59 years), and older (≥60 years) to compare drug-resistance patterns. To evaluate trends in age-stratified drug-resistance, chi-square test for linear trends was performed. RESULTS: Among enrolled native patients aged ≥15 years, 4.1% (179/4417), 1.2% (53/4417) and 7.2% (316/4417) were multidrug-resistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were 5.4% (40/734), 7.2% (114/1593), and 7.8% (162/2090) in the younger, middle and older age groups, respectively. MDR/RR-TB case rates decreased significantly with age from 8.6% (63/734) in younger age group to 3.3% (68/2090) in older age group. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups. CONCLUSIONS: The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients.


Assuntos
Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Fluoroquinolonas/uso terapêutico , Isoniazida/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
BMC Infect Dis ; 20(1): 431, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32563248

RESUMO

BACKGROUND: Good's syndrome (GS) is characterized by immunodeficiency, and can lead to severe infection, which is the most significant complication. Although Mycobacterium rarely causes infection in patients with GS, disseminated nontuberculous mycobacterial (NTM) infection frequently occurs in GS patients that are also positive for the human immunodeficiency virus (HIV) or anti-interferon (IFN)-γ autoantibodies. Here, we report a rare case of GS with NTM without HIV or IFN-γ autoantibodies. CASE PRESENTATION: A 57-year-old Japanese male with GS and myasthenia gravis (treated with prednisolone and tacrolimus) was diagnosed with disseminated NTM infection caused by Mycobacterium abscessus subsp. massiliense. He presented with fever and back pain. Blood, lumbar tissue, urine, stool, and sputum cultures tested positive for M. abscessus. Bacteremia, spondylitis, intestinal lumber abscess, and lung infection were confirmed by bacteriological examination and diagnostic imaging; urinary and intestinal tract infections were suspected by bacteriological examination but not confirmed by imaging. Despite multidrug combination therapy, including azithromycin, imipenem/cilastatin, levofloxacin, minocycline, linezolid, and sitafloxacin, the patient ultimately died of the infection. The patient tested negative for HIV and anti-IFN-γ autoantibodies. CONCLUSIONS: Since myasthenia gravis symptoms interfere with therapy, patients with GS and their physicians should carefully consider the antibacterial treatment options against disseminated NTM.


Assuntos
Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus , Doenças da Imunodeficiência Primária/complicações , Antibacterianos/uso terapêutico , Autoanticorpos/sangue , Quimioterapia Combinada , Evolução Fatal , Fluoroquinolonas/uso terapêutico , Soronegatividade para HIV , Humanos , Interferon gama/imunologia , Pneumopatias/complicações , Pneumopatias/imunologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/complicações , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/imunologia , Síndrome
19.
PLoS One ; 15(5): e0233500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32421749

RESUMO

BACKGROUND: Meta-analyses on impact of isoniazid-resistant tuberculosis informed the World Health Organization recommendation of a levofloxacin-strengthened rifampicin-based regimen. We estimated the effect of initial rifampicin resistance (Rr) and/or isoniazid resistance (Hr) on treatment failure or relapse. We also determined the frequency of missed initial and acquired Rr to estimate the impact of true Hr. METHODS: Retrospective analysis of 7291 treatment episodes with known initial isoniazid and rifampicin status obtained from individual patient databases maintained by the Damien Foundation Bangladesh over 20 years. Drug susceptibility test results were confirmed by the programme's designated supra-national tuberculosis laboratory. To detect missed Rr among isolates routinely classified as Hr, rpoB gene sequencing was done randomly and on a sample selected for suspected missed Rr. RESULTS: Initial Hr caused a large recurrence excess after the 8-month regimen for new cases (rifampicin for two months), but had little impact on rifampicin-throughout regimens: (6 months, new cases; 3.8%; OR 0.8, 95%CI:0.3,2.8; 8 months, retreatment cases: 7.3%, OR 1.8; 95%CI:1.3,2.6). Rr was missed in 7.6% of randomly selected "Hr" strains. Acquired Rr was frequent among recurrences on rifampicin-throughout regimens, particularly after the retreatment regimen (31.9%). It was higher in mono-Hr (29.3%; aOR 3.5, 95%CI:1.5,8.5) and poly-Hr (53.3%; aOR 10.2, 95%CI 4.4,23.7) than in susceptible tuberculosis, but virtually absent after the 8-month new case regimen. Comparing Bangladesh (low Rr prevalence) with a high Rr prevalence setting,true Hr corrected for missed Rr caused only 2-3 treatment failures per 1000 TB cases (of whom 27% were retreatments) in both. CONCLUSIONS: Our analysis reveals a non-negligible extent of misclassifying as isoniazid resistance of what is actually missed multidrug-resistant tuberculosis. Recommending for such cases a "strengthened" regimen containing a fluoroquinolone provokes a direct route to extensive resistance while offering little benefit against the minor role of true Hr tuberculosis in rifampicin-throughout first-line regimen.


Assuntos
Resistência a Medicamentos , Isoniazida/farmacologia , Rifampina/farmacologia , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Bangladesh , Erros de Diagnóstico , Resistência a Medicamentos/efeitos dos fármacos , Fluoroquinolonas/uso terapêutico , Humanos , Isoniazida/uso terapêutico , Recidiva , Estudos Retrospectivos , Rifampina/uso terapêutico , Falha de Tratamento , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos
20.
Parasitol Res ; 119(6): 1955-1968, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32399722

RESUMO

Coccidiosis is a crucial parasitic disease of the poultry industry. As a result of the enormous global economic losses and the increased resistance to the conventional anticoccidial agents, there is a continuous need to find new anticoccidials. Here, the anticoccidial effect of the fluoroquinolone lomefloxacin versus diclazuril in experimentally infected broilers was tested for the treatment of Eimeria tenella infection. Ninety 14-day-old Cobb strain broiler chickens were allocated into five groups, each with 18 chicks. Group 1 (G1) was separated as an uninfected negative control and received no treatment; group 2 (G2), infected untreated (positive control); group 3 (G3), infected and treated with lomefloxacin at a dose rate of 100 ppm in drinking water; group 4 (G4), infected and treated with diclazuril at a dose rate of 2.5 ppm in drinking water; group 5 (G5), infected and treated with lomefloxacin at a dose rate of 100 ppm plus diclazuril at dose rate of 2.5 ppm in drinking water. Clinical signs, mortality rates, number of oocysts per gram of faeces (OPG), growth performance parameters (weight gain: WG and feed conversion ratio: FCR), lesion scoring, haematological and serum biochemical analyses, antioxidant biomarkers and histopathologic inspection of the caeca were used as evaluation criteria for the anticoccidial efficacy of both lomefloxacin and diclazuril. The findings herein showed that administration of lomefloxacin and/or diclazuril improved growth performance parameters (WG, FCR) and significantly (P ≤ 0.05) reduced OPG, and diminished the severity of bloody diarrhoea and mortalities. Additionally, haematological indices and serum biochemical parameters such as ALT, AST, ALP, creatinine, uric acid, total proteins, albumin and globulin were improved. Finally, a significant elevation in the levels of the antioxidant biomarkers was observed in the chicks of G3, G4 and G5 as compared with those of G2.


Assuntos
Galinhas/parasitologia , Coccidiose/veterinária , Coccidiostáticos/farmacologia , Eimeria tenella , Fluoroquinolonas/uso terapêutico , Doenças das Aves Domésticas/tratamento farmacológico , Animais , Ceco/patologia , Coccidiose/tratamento farmacológico , Fezes/parasitologia , Nitrilos/uso terapêutico , Oocistos/efeitos dos fármacos , Doenças das Aves Domésticas/parasitologia , Triazinas/uso terapêutico , Ganho de Peso/efeitos dos fármacos
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