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1.
Z Gastroenterol ; 58(2): 160-170, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32050286

RESUMO

Typhoid fever and paratyphoid fever are systemic infectious diseases of global significance caused by Salmonella enterica subspecies enterica Serovar Typhi (short name: Salmonella Typhi) or Serovar Paratyphi (short name: Salmonella Paratyphi). The course of these fecal-orally transmitted diseases is mainly characterized by a high fever. Left untreated, the course of typhoid fever can be severe and lethal. The infection is almost always acquired outside of Europe (mainly in India) and is notifiable in Germany, Austria and Switzerland. Paratyphoid is an attenuated disease of typhoid fever caused by Salmonella Paratyphi. Available vaccines only protect against Salmonella Typhi. Antibiotic resistance reflects the situation in endemic countries and shows a worrying increase of multi-drug resistant isolates. Currently, third-generation cephalosporins such as ceftriaxone are recommended as first-line therapy; if sensitive to quinolones, fluoroquinolones such as ciprofloxacin may continue to be administered. Crucial preventive measures for travelers to endemic regions include consistent water and food hygiene as well as vaccination, whereby only protection rates of 50-70 % are achieved by currently available vaccines. In the light of increasing multi-drug resistance, a more effective conjugate vaccine against Salmonella Typhi with cross-reactivity against Salmonella Paratyphi is needed more than ever.


Assuntos
Antibacterianos/farmacologia , Febre Paratifoide/tratamento farmacológico , Febre Paratifoide/prevenção & controle , Salmonella paratyphi A/efeitos dos fármacos , Salmonella typhi/efeitos dos fármacos , Febre Tifoide/tratamento farmacológico , Febre Tifoide/prevenção & controle , Vacinas Conjugadas/administração & dosagem , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Fluoroquinolonas/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Febre Paratifoide/diagnóstico , Febre Paratifoide/microbiologia , Quinolonas/uso terapêutico , Salmonella enterica , Salmonella paratyphi A/isolamento & purificação , Salmonella typhi/isolamento & purificação , Febre Tifoide/diagnóstico , Febre Tifoide/microbiologia
2.
BMC Infect Dis ; 20(1): 57, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952493

RESUMO

BACKGROUND: Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics. Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic targets of beta-lactam antibiotics, with only 30% in fluoroquinolones. Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance. The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU. METHODS: A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and cost-effectiveness of model-based TDM of beta-lactam and fluoroquinolones. Four hundred fifty patients will be included within 24 months after start of inclusion. Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM). In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model. The primary outcome will be ICU length of stay. Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included. DISCUSSION: No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients. The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics. In short, to TDM or not to TDM? TRIAL REGISTRATION: EudraCT number: 2017-004677-14. Sponsor protocol name: DOLPHIN. Registered 6 March 2018 . Protocol Version 6, Protocol date: 27 November 2019.


Assuntos
Antibacterianos/farmacocinética , Monitoramento de Medicamentos , Fluoroquinolonas/farmacocinética , beta-Lactamas/farmacocinética , Adulto , Antibacterianos/sangue , Antibacterianos/uso terapêutico , Teorema de Bayes , Estado Terminal/terapia , Fluoroquinolonas/sangue , Fluoroquinolonas/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Qualidade de Vida , beta-Lactamas/sangue , beta-Lactamas/uso terapêutico
3.
Int J Infect Dis ; 92: 241-246, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31978580

RESUMO

OBJECTIVES: To compare the prevalence of levofloxacin (LFX) resistance and the population structure of Mycobacterium tuberculosis (MTB) with different mutations conferring LFX resistance between 2005 and 2015. METHODS: A total 542 MTB isolates were randomly selected from pulmonary tuberculosis (TB) patients in 2005 and 2015 and analyzed regarding minimum inhibitory concentrations (MICs) and quinolone resistance-determining regions (QRDR). RESULTS: One hundred and eleven of the 542 MTB isolates analyzed (20.5%) were resistant to LFX. There were 42 and 69 LFX-resistant isolates from 2005 and 2015, respectively, and MIC high-level LFX resistance was significantly higher in 2015 (40.6%, 28/69) than in 2005 (16.7%, 7/42) (p = 0.02). There were 87 (78.4%) mutations of these 111 LFX-resistant isolates. In addition, a significant difference in proportion was observed in the isolates with mutations in codon 90 of the gyrA gene between 2005 and 2015 (11.9% in 2005 versus 29.0% in 2015, p = 0.04). CONCLUSIONS: There was an alarming increase in prevalence of LFX-resistant TB in China between 2005 and 2015. This dynamic change is mostly attributed to the increase in high-level LFX resistance. Moreover, a significant difference was noted in the proportion of LFX-resistant isolates harboring specific mutations within the gyrA gene between 2005 and 2015.


Assuntos
Farmacorresistência Bacteriana , Levofloxacino/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/tratamento farmacológico , Adulto , China/epidemiologia , DNA Girase/genética , Feminino , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Humanos , Levofloxacino/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/isolamento & purificação , Prevalência , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia
4.
BMC Infect Dis ; 19(1): 1018, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791267

RESUMO

BACKGROUND: Although, India has made steady progress in reducing deaths in children younger than 5 years, the proportional mortality accounted by diarrhoeal diseases still remains high. The present hospital based cross sectional study was carried out to understand the prevalence of various bacterial pathogens associated with the diarrhoea cases in under 5 years age group. METHODS: During, 1st September, 2015 to 30th November 2017, all the childhood diarrhoea cases (≤5 yrs) of SCB Medical College in Odisha, India were included in the study. Stool samples were collected and processed for the isolation of causative bacterial pathogen and the isolated bacterial pathogens were subjected to antibiotic sensitivity testing, molecular analysis of drug resistance. Clinical and demographic data were collected and analyzed. RESULTS: Three hundred twenty patients were enrolled in the study during the study period from whom 82 bacterial isolates were obtained indicating a proportional causality of 25.6% for bacterial diarrhoea among children in this region. Entero toxigenic E.coli (ETEC) accounted for majority of the cases and and more than 50% of the strains were found to be multi-drug resistant (resistant to more than 3 class of antibiotics). More than 50% of the strains were resistant to current choice of treatment like ciprofloxacin, ofloxacin and ceftriaxone and 2.4% being resistant to Imipenem. ESBL production was also observed in some of the strains and one isolate harboured the NDM-1 gene. Fluoroquinolone resistance was found to be linked with multiple mutations in the QRDR region followed by PMQR determinants. CONCLUSION: The current study, to the best of our knowledge is first of its kind which demonstrated the etiology of bacterial diarrhoea in children less than 5 years old and identified diarrheogenic E. coli as the predominant enteropathogen in Odisha. Majority of the isolates being multi-drug resistance calls for a continuous surveillance system in the region which will be helpfulin identifying emerging resistance pattern and for developing suitable intervention stategies.


Assuntos
Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Diarreia/diagnóstico , Diarreia/etiologia , Resistência Microbiana a Medicamentos/genética , Tipagem Molecular/métodos , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Pré-Escolar , Ciprofloxacino/uso terapêutico , Estudos Transversais , Diarreia/epidemiologia , Diarreia/microbiologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Feminino , Fluoroquinolonas/uso terapêutico , Gastroenterite/diagnóstico , Gastroenterite/tratamento farmacológico , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Técnicas de Diagnóstico Molecular/métodos , Prevalência , Centros de Atenção Terciária
5.
BMC Infect Dis ; 19(1): 959, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711418

RESUMO

BACKGROUND: An infected aneurysm of the thoracic aorta is a rare clinical condition with significant morbidity and mortality. Patients with fast-growing aortic aneurysms show a high incidence of rupture. Gram-positive organisms, such as the Staphylococcus and Enterococcus species, are the most common cause of infection. CASE PRESENTATION: A 91-year-old man presented at our facility with high grade fever and tachypnea, which he had experienced for the previous two days. He had a history of end-stage renal disease and had been undergoing regular chest computed tomography (CT) follow-up for a left lower lung nodule. CT imaging with intravenous contrast media showed a thoracic aortic aneurysm with hemothorax. Rupture of the aneurysm was suspected. CT imaging performed a year ago showed a normal aorta. Blood samples showed a Bacillus cereus infection. The patient was successfully treated for a mycotic aortic aneurysm secondary to Bacillus cereus bacteremia. CONCLUSIONS: Here, we report a rare of an infected aneurysm of the thoracic aorta probably caused by Bacillus cereus. Although infected aneurysms have been described well before, an aneurysm infected with Bacillus cereus is rare. Bacillus cereus, a gram-positive spore-building bacterium, can produce biofilms, which attach to catheters. It has recently emerged as a new organism that can cause serious infection.


Assuntos
Aneurisma Infectado/microbiologia , Aorta Torácica/microbiologia , Aorta Torácica/patologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Bacillus cereus/isolamento & purificação , Administração Intravenosa , Administração Oral , Idoso de 80 Anos ou mais , Aneurisma Infectado/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/uso terapêutico , Hemotórax/diagnóstico por imagem , Humanos , Masculino , Insuficiência Respiratória , Choque Séptico/tratamento farmacológico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vancomicina/administração & dosagem , Vancomicina/uso terapêutico
6.
BMC Infect Dis ; 19(1): 898, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31660876

RESUMO

BACKGROUND: Salmonella infection poses significant public health threat globally, especially in resource-limited countries. Emergence and spread of antibiotic resistant strains to fluoroquinolones have led to treatment failures and increased mortality in Salmonella infection. However, there is dearth of information regarding mechanisms of resistance to fluoroquinolones in Ghana. This study therefore sought to identify chromosomal mutations and plasmid-mediated resistance as possible mechanisms of fluoroquinolone resistance from clinical isolates in Ghana. METHODS: This was a retrospective study of archived isolates biobanked at Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana. Isolates were obtained from blood, stool and oropharynx samples at two hospitals, between May, 2016 and January, 2018. Salmonella identification was done using standard microbiological protocols and antibiotic susceptibility testing performed by Kirby-Bauer disc diffusion method. Isolates with intermediate susceptibility and/or resistance to nalidixic acid and/or ciprofloxacin were selected and examined for chromosomal mutations by Sanger sequencing and plasmid-mediated resistance by PCR. RESULTS: Of 133 biobanked isolates cultured, 68 (51.1%) and 16 (12%) were identified as Salmonella Typhi and non-typhoidal Salmonella (NTS), respectively. Sequence analysis of gyrA gene revealed the presence of 5 different nonsynonymous mutations, with the most frequent mutation (Ile203Ser) occurring in 12 out of 13 isolates tested. Gyrase B (gyrB) gene had 1 nonsynonymous mutation in 3 out of 13 isolates, substituting phenylalanine with leucine at codon 601 (Phe601Leu). No mutation was observed in parC and parE genes. Two NTS isolates were found to harbour qnrS plasmid-mediated resistant gene of molecular size 550 bp with high ciprofloxacin MIC of 0.5 µg/ml. CONCLUSION: This study reports for the first time in Ghana plasmid-mediated fluoroquinolone resistant gene qnrS in Salmonella clinical isolates. Nonsynonymous mutations of gyrA and gyrB genes likely to confer Salmonella reduced susceptibility to ciprofloxacin were also reported.


Assuntos
Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Genes Bacterianos/genética , Plasmídeos/metabolismo , Infecções por Salmonella/tratamento farmacológico , Salmonella enterica/genética , Adolescente , Pré-Escolar , Ciprofloxacino/efeitos adversos , Ciprofloxacino/uso terapêutico , DNA Girase/genética , DNA Topoisomerase IV/genética , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Feminino , Gana , Humanos , Masculino , Mutação , Estudos Retrospectivos , Salmonella enterica/isolamento & purificação , Adulto Jovem
7.
Molecules ; 24(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470632

RESUMO

Antimicrobial resistance in bacteria is frightening, especially resistance in Gram-negative Bacteria (GNB). In 2017, the World Health Organization (WHO) published a list of 12 bacteria that represent a threat to human health, and among these, a majority of GNB. Antibiotic resistance is a complex and relatively old phenomenon that is the consequence of several factors. The first factor is the vertiginous drop in research and development of new antibacterials. In fact, many companies simply stop this R&D activity. The finding is simple: there are enough antibiotics to treat the different types of infection that clinicians face. The second factor is the appearance and spread of resistant or even multidrug-resistant bacteria. For a long time, this situation remained rather confidential, almost anecdotal. It was not until the end of the 1980s that awareness emerged. It was the time of Vancomycin-Resistance Enterococci (VRE), and the threat of Vancomycin-Resistant MRSA (Methicillin-Resistant Staphylococcus aureus). After this, there has been renewed interest but only in anti-Gram positive antibacterials. Today, the threat is GNB, and we have no new molecules with innovative mechanism of action to fight effectively against these bugs. However, the war against antimicrobial resistance is not lost. We must continue the fight, which requires a better knowledge of the mechanisms of action of anti-infectious agents and concomitantly the mechanisms of resistance of infectious agents.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Drogas em Investigação/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Saúde Global/tendências , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/patogenicidade , Acinetobacter baumannii/fisiologia , Aminoglicosídeos/síntese química , Aminoglicosídeos/economia , Aminoglicosídeos/uso terapêutico , Antibacterianos/síntese química , Antibacterianos/economia , Aprovação de Drogas/organização & administração , Drogas em Investigação/síntese química , Drogas em Investigação/economia , Enterobacteriaceae/patogenicidade , Enterobacteriaceae/fisiologia , Fluoroquinolonas/síntese química , Fluoroquinolonas/economia , Fluoroquinolonas/uso terapêutico , Saúde Global/economia , Glicopeptídeos/síntese química , Glicopeptídeos/economia , Glicopeptídeos/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Negativas/fisiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/patologia , Humanos , Macrolídeos/síntese química , Macrolídeos/economia , Macrolídeos/uso terapêutico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/fisiologia , beta-Lactamas/síntese química , beta-Lactamas/economia , beta-Lactamas/uso terapêutico
8.
BMC Res Notes ; 12(1): 614, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547848

RESUMO

OBJECTIVES: Molecular typing such as spa typing is used to control and prevent Staphylococcus aureus widespread in hospitals and communities. Hence, the aim of this study was to find the most common types of S. aureus strain circulating in Shiraz via spa and SCCmec typing methods. RESULTS: Total of 159 S. aureus isolates were collected from two tertiary hospitals in Shiraz. Isolates were identified by biochemical tests. Antimicrobial susceptibility tests were performed by standard disk diffusion method and then genetic analysis of bacteria was performed using SCCmec and spa typing. In this study 31.4% of the isolates were methicillin-resistant S. aureus. The majority of isolates were SSCmec type III. Spa type t030 was the most prominent type among MRSA strains. For the first time in Iran, spa003, t386, t1877, t314, t186, t1816, t304, t325, t345 were reported in this study. It was shown that there is a possibility that these spa types are native to this region. Our findings showed that SCCmec II, III and IV disseminate from hospital to community and vice versa. Thus, effective monitoring of MRSA in hospital and community is necessary.


Assuntos
Antibacterianos/uso terapêutico , Antígenos de Bactérias/genética , Resistência a Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/tratamento farmacológico , Aminoglicosídeos/uso terapêutico , Técnicas de Tipagem Bacteriana , Fluoroquinolonas/uso terapêutico , Expressão Gênica , Glicopeptídeos/uso terapêutico , Humanos , Pacientes Internados , Irã (Geográfico)/epidemiologia , Macrolídeos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Pacientes Ambulatoriais , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Centros de Atenção Terciária , beta-Lactamas/uso terapêutico
9.
Emerg Infect Dis ; 25(9): 1760-1762, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31441763

RESUMO

Resistance to second-line tuberculosis drugs for patients with multidrug-resistant tuberculosis has emerged globally and is a potential risk factor for unfavorable outcomes of shorter duration drug regimens. We assessed the proportion of patients eligible for a shorter drug regimen in Uttar Pradesh, India, which had the highest rate of multidrug-resistant tuberculosis in India.


Assuntos
Antituberculosos/uso terapêutico , Fluoroquinolonas/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Antituberculosos/administração & dosagem , Esquema de Medicação , Fluoroquinolonas/administração & dosagem , Humanos , Índia/epidemiologia , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia
10.
J Vet Pharmacol Ther ; 42(5): 556-563, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31424100

RESUMO

Avian pathogenic Escherichia coli could cause localized and systemic infection in the poultry, and danofloxacin is usually used to treat avian colibacillosis through oral administration. To promote prudent use of danofloxacin and reduce the emergence of drug-resistant E. coli strains, it is necessary to understand the population pharmacokinetics (PopPK) of danofloxacin in chicken intestines. In this study, reversed-phase high performance liquid chromatography (HPLC) with fluorescence detection was used to detect the concentrations of danofloxacin in the contents of duodenum, jejunum, and ileum of the healthy and infected chickens after single oral administration (5 mg/kg body weight). Then, the PopPK of danofloxacin in intestines were analyzed using NONMEM software. As a result, a two-compartment PK model best described the time-concentration profile of duodenal, jejunal, and ileal contents. Interestingly, absorption rate (Ka ), distribution volume (V), and clearance (CL) for danofloxacin from duodenal, jejunal to ileal contents were sequentially decreased in the healthy chickens. However, the trend of Ka , V, and CL of danofloxacin was changed dramatically in the intestine of infected chickens. Ka and V of danofloxacin in the jejunum were higher than in the ileum and duodenum. Compared with healthy chickens, Ka and V of danofloxacin in the duodenum decreased significantly, while increased in jejunum, respectively. It has been noted that Ka decreased and V increased in the ileum of infected chickens. Besides, CL in the duodenum, jejunum, and ileum of infected chickens was, respectively, lower than those of healthy chickens. Interestingly, the relative bioavailability (F) of danofloxacin in the ileum was relatively higher in both healthy and infected chickens. In addition, F in the duodenal, jejunal, and ileal contents of infected chickens was respectively higher than healthy chickens. In summary, the PopPK for danofloxacin in infected chicken intestines was quite different from healthy chickens. The absorption, distribution, and clearance of danofloxacin in healthy chickens decreased from duodenum to jejunum and to ileum. Moreover, the pharmacokinetic characteristics in the intestine of infected chickens changed significantly, and the pharmacokinetic characteristics in the ileum can be used as a representative of all intestinal segments.


Assuntos
Galinhas , Infecções por Escherichia coli/veterinária , Fluoroquinolonas/farmacocinética , Conteúdo Gastrointestinal/química , Doenças das Aves Domésticas/microbiologia , Animais , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Fluoroquinolonas/uso terapêutico , Modelos Biológicos , Doenças das Aves Domésticas/tratamento farmacológico
11.
Muscle Nerve ; 60(6): 693-699, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31469909

RESUMO

INTRODUCTION: The etiology of acute exacerbations of myasthenia gravis (MG) is not well understood and further characterization can lead to improved preventative measures. This study aims to characterize factors contributing to MG exacerbations. METHODS: A total of 127 MG patient charts were reviewed retrospectively (2011-2016) to obtain demographics, immunizations, pharmaceutical records, contributing factors of each MG exacerbation, emergency department (ED) visits, hospitalizations, and duration. RESULTS: There were 212 exacerbations requiring 106 ED visits and 141 hospitalizations (average admission 6.5 days). Highest contributors were infections (30%) and medications that may worsen MG (19%), with 24% unattributed. Infection related exacerbations were associated with 44.3% of ED visits and 39.7% of hospitalizations. Patients prescribed beta-blockers were associated with more exacerbations (P < .01). Patients prescribed medications that may worsen MG had a higher exacerbation frequency shortly after administration. DISCUSSION: Infections and cautioned medications are frequently factors in acute MG exacerbations needing urgent medical attention and warrant caution.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antibacterianos/uso terapêutico , Glucocorticoides/uso terapêutico , Miastenia Gravis/fisiopatologia , Exacerbação dos Sintomas , Idoso , Idoso de 80 Anos ou mais , Azitromicina/uso terapêutico , Progressão da Doença , Serviço Hospitalar de Emergência , Feminino , Fluoroquinolonas/uso terapêutico , Gentamicinas/uso terapêutico , Hospitalização , Humanos , Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de Risco
12.
S Afr Med J ; 109(6): 378-381, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31266554

RESUMO

The systemic fluoroquinolones (FQs) have recently been reported to be associated with significant side-effects in susceptible individuals. This has prompted the Food and Drug Administration (FDA) in the USA and the European Medicines Agency (EMA) to issue warnings regarding their use. The FQs should not be used for common bacterial infections, such as urinary tract infections, travellers' diarrhoea and upper and lower respiratory tract infections, unless it is not possible to use another oral agent. There are situations, however, in which these agents are not only effective, but their benefit outweighs the risk. These include the management of conditions such as acute prostatitis, typhoid fever, prosthetic joint infections, multidrug-resistant tuberculosis, certain hospital-acquired infections and situations where the organism is susceptible to FQs, which could then be administered orally. Alternatively, the patient would have to be admitted to hospital for parenteral therapy.


Assuntos
Infecção Hospitalar/tratamento farmacológico , Fluoroquinolonas/efeitos adversos , Prostatite/tratamento farmacológico , Infecções Relacionadas à Prótese/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Febre Tifoide/tratamento farmacológico , Aneurisma Dissecante/induzido quimicamente , Ansiedade/induzido quimicamente , Fluoroquinolonas/uso terapêutico , Alucinações/induzido quimicamente , Humanos , Prótese Articular , Masculino , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Psicoses Induzidas por Substâncias/etiologia , Ruptura/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Síndrome , Tendinopatia/induzido quimicamente
13.
BMC Pulm Med ; 19(1): 124, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291943

RESUMO

BACKGROUND: Pulmonary tuberculosis is a leading cause of morbidity and mortality in developing countries. Drug resistance, a huge problem in this contagious disease, is driven by point mutations in the Mycobacterium tuberculosis genome however, their frequencies vary geographically and this affects applicability of molecular diagnostics for rapid detection of resistance. Here, we report the frequency and patterns of mutations associated with resistance to second-line anti-TB drugs in multidrug-resistant (MDR) M. tuberculosis isolates from eSwatini, Somalia and Uganda that were resistant to a second-line anti-TB drug. METHODS: The quinolone resistance determining region (QRDR) of gyrA/gyrB genes and the drug resistance associated fragment of rrs gene from 80 isolates were sequenced and investigated for presence of drug resistance mutations. Of the 80 isolates, 40 were MDR, of which 28 (70%) were resistant to a second-line anti-TB injectable drug, 18 (45%) were levofloxacin resistant while 12 (30%) were extensively drug resistant (XDR). The remaining 40 isolates were susceptible to anti-TB drugs. MIRU-VNTR analysis was performed for M/XDR isolates. RESULTS: We successfully sub-cultured 38 of the 40 M/XDR isolates. The gyrA resistance mutations (Gly88Ala/Cys/Ala, Ala90Val, Ser91Pro, Asp94Gly/Asn) and gyrB resistance mutations (Asp500His, Asn538Asp) were detected in 72.2% (13/18) and 22.2% (4/18) of the MDR and levofloxacin resistant isolates, respectively. Overall, drug resistance mutations in gyrA/gyrB QRDRs occurred in 77.8% (14/18) of the MDR and levofloxacin resistant isolates. Furthermore, drug resistance mutations a1401g and g1484 t in rrs occurred in 64.3% (18/28) of the MDR isolates resistant to a second-line anti-TB injectable drug. Drug resistance mutations were not detected in drug susceptible isolates. CONCLUSIONS: The frequency of resistance mutations to second-line anti-TB drugs in MDR-TB isolates resistant to second line anti-TB drugs from eSwatini, Somalia and Uganda is high, implying that rapid molecular tests are useful in detecting second-line anti-TB drug resistance in those countries. Relatedly, the frequency of fluoroquinolone resistance mutations in gyrB/QRDR is high relative to global estimates, and they occurred independently of gyrA/QRDR mutations implying that their absence in panels of molecular tests for detecting fluoroquinolone resistance may yield false negative results in our setting.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Mutação , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Amicacina/uso terapêutico , Antituberculosos/uso terapêutico , Capreomicina/uso terapêutico , Estudos Transversais , Fluoroquinolonas/uso terapêutico , Frequência do Gene , Humanos , Canamicina/uso terapêutico , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/isolamento & purificação , Análise de Sequência de DNA , Somália/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Uganda/epidemiologia
14.
J Zoo Wildl Med ; 50(2): 470-473, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260217

RESUMO

Two nonrelated Goeldi's monkeys (Callimico goeldii) from the same enclosure developed multifocal alopecia with hyperkeratotic to ulcerative skin lesions on the lower abdomen and inner thighs. Necropsy samples of the first animal showed hyperplastic dermatitis together with in situ carcinoma and intralesional Demodex organisms. The second monkey developed similar lesions 2.5 yr later. Skin scrapings and biopsies also revealed Demodex mites within hyperplastic dermatitis. Long-term treatment with ivermectin, imidacloprid-moxidectin, and sarolaner resolved the demodicosis but skin lesions progressed to actinic keratosis and carcinoma. Both cutaneous neoplasia and demodicosis are rarely described in New World monkeys and these are the first reported cases in Goeldi's monkeys. Since the animals had access to ultraviolet (UV) light, as recommended for indoor-housed callitrichids, the skin tumors were likely UV-induced and the mites have settled particularly within impaired regions. Thus, apparent demodicosis can indicate cutaneous immunosuppression and might alert caretakers to adjust the UV regime.


Assuntos
Callimico , Carcinoma de Células Escamosas/veterinária , Infestações por Ácaros/veterinária , Doenças dos Macacos/etiologia , Neoplasias Cutâneas/veterinária , Raios Ultravioleta/efeitos adversos , Animais , Animais de Zoológico , Antibacterianos/uso terapêutico , Antiparasitários/administração & dosagem , Antiparasitários/uso terapêutico , Azetidinas/administração & dosagem , Azetidinas/uso terapêutico , Carcinoma de Células Escamosas/patologia , Combinação de Medicamentos , Feminino , Fluoroquinolonas/uso terapêutico , Inseticidas/administração & dosagem , Inseticidas/uso terapêutico , Ivermectina/uso terapêutico , Macrolídeos/administração & dosagem , Macrolídeos/uso terapêutico , Masculino , Infestações por Ácaros/tratamento farmacológico , Infestações por Ácaros/parasitologia , Doenças dos Macacos/parasitologia , Doenças dos Macacos/patologia , Neonicotinoides/administração & dosagem , Neonicotinoides/uso terapêutico , Nitrocompostos/administração & dosagem , Nitrocompostos/uso terapêutico , Neoplasias Cutâneas/etiologia , Compostos de Espiro/administração & dosagem , Compostos de Espiro/uso terapêutico
16.
BMC Infect Dis ; 19(1): 554, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238896

RESUMO

BACKGROUND: The objective of this study is to describe the changes in prescribing practices of antibiotics to treat acute pyelonephritis (APN) in Korea. METHODS: The claim data base of the Health Insurance Review and Assessment Service in Korea was used to select patients with ICD-10 codes N10 (acute tubulo-interstitial nephritis) or N12 (tubulo-interstitial nephritis, not specified as acute nor chronic) as the primary discharge diagnosis during 2010-2014. Consumption of each class of antibiotics was converted to Defined Daily Dose (DDD)/event. RESULTS: Throughout the five-year period, the average antibiotic consumption were 11.3 DDD per inpatient event and 6.0 DDD per outpatient event. The annual average antibiotic consumption increased for inpatients (P = 0.002), but remained stable for outpatients (P = 0.066). The use of parenteral antibiotics increased for inpatients (P < 0.001), but decreased for outpatients (P = 0.017). As for the the antibiotic classes, 3rd generation cephalosporins (3rd CEPs) was the most commonly prescribed (41.4%) for inpatients, followed by fluoroquinolones (FQs) (28.5%); for outpatient, FQs (54.8%) was the most commonly prescribed, followed by 3rd CEPs (13.1%). The use of 3rd CEPs (P < 0.001), beta-lactam/beta-lactamase inhibitors (P = 0.007), and carbapenems (P < 0.001) increased substantially for the treatment of hospitalized APN patients. In particular, carbapenems use increased 3.1-fold over the 5 years. CONCLUSIONS: Prescription of broad-spectrum antibiotics increased much for the treatment of APN in Korea during 2010-2014.


Assuntos
Antibacterianos/uso terapêutico , Uso de Medicamentos/tendências , Pielonefrite/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Gestão de Antimicrobianos/tendências , Cefalosporinas/uso terapêutico , Bases de Dados Factuais , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Revisão da Utilização de Seguros , Infecções Intra-Abdominais/tratamento farmacológico , Infecções Intra-Abdominais/epidemiologia , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências , Pielonefrite/epidemiologia , República da Coreia/epidemiologia , Adulto Jovem , Inibidores de beta-Lactamases/uso terapêutico
17.
Indian J Med Res ; 149(2): 146-150, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31219078

RESUMO

The mismatch amplification assay is a modified version of polymerase chain reaction (PCR) that permits specific amplification of gene sequences with single base pair change. The basis of the technique relies on primer designing. The single nucleotide mismatch at the 3' proximity of the reverse oligonucleotide primer makes Taq DNA polymerase unable to carry out extension process. Thus, the primers produce a PCR fragment in the wild type, whereas it is not possible to yield a product with a mutation at the site covered by the mismatch positions on the mismatch amplification mutation assay (MAMA) primer from any gene. The technique offers several advantages over other molecular methods, such as PCR-restriction fragment length polymorphism (RFLP) and oligonucleotide hybridization, which is routinely used in the detection of known point mutations. Since multiple point mutations in the quinolone resistance determining region play a major role in high-level fluoroquinolone resistance in Gram-negative bacteria, the MAMA-PCR technique is preferred for detecting these mutations over PCR-RFLP and sequencing technology.


Assuntos
Reparo de Erro de Pareamento de DNA/genética , Farmacorresistência Bacteriana/genética , Fluoroquinolonas/efeitos adversos , Bactérias Gram-Negativas/genética , Sequência de Bases , Fluoroquinolonas/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/patogenicidade , Humanos , Hibridização de Ácido Nucleico/métodos , Oligonucleotídeos/genética , Mutação Puntual/genética , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição/genética
18.
Indian J Med Res ; 149(2): 164-179, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31219080

RESUMO

The Indian Council of Medical Research, in 2013, initiated the Antimicrobial Resistance Surveillance & Research Network (AMRSN) to enable compilation of data on six pathogenic groups on antimicrobial resistance from the country. The overarching aim of this network was to understand the extent and pattern of antimicrobial resistance (AMR) and use this evidence to guide strategies to control the spread of AMR. This article describes the conception and implementation of this AMR surveillance network for India. Also described are the challenges, limitations and benefits of this approach. Data from the Network have shown increasing resistance in Gram-negative bacteria in the hospitals that are part of this network. Combined resistance to third-generation cephalosporins and fluoroquinolones and increasing carbapenem resistance are worrisome, as it has an important bearing on the patients' outcome and thus needs to be addressed urgently. Data generated through this Network have been used to develop treatment guidelines, which will be supportive in harmonizing treatment practices across the tertiary level healthcare institutions in the country. While, the major benefit of having a surveillance system is the collection of real-time accurate data on AMR including the mechanisms of resistance, representativeness to community, sustaining the current effort and expanding the current activities to next levels of healthcare settings are the major challenges. The data emanating from the network besides providing evidence, expose several gaps and lacunae in the ecosystem and highlight opportunities for action by multiple stakeholders.


Assuntos
Infecções Bacterianas/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Bactérias Gram-Negativas/efeitos dos fármacos , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Bactérias Gram-Negativas/patogenicidade , Humanos , Índia/epidemiologia , Testes de Sensibilidade Microbiana
19.
Indian J Med Res ; 149(2): 192-198, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31219083

RESUMO

Background & objectives: Infection from fluoroquinolone-resistant extra-intestinal Escherichia coli is a global concern. In this study, isolation and characterization of fluoroquinolone-resistant extra-intestinal E. coli isolates obtained from hospital samples were undertaken to detect plasmid-mediated quinolone resistance (PMQR) genes. Methods: Forty three isolates of E. coli obtained from patients with extra-intestinal infections were subjected to antibiogram to detect fluoroquinolone resistance. The mechanism of fluoroquinolone resistance was determined by the detection of PMQR genes and mutations in quinolone resistance determining region (QRDR). Results: Of the 43 isolates, 36 were resistant to nalidixic acid (83.72%) and 28 to ciprofloxacin (65.11%). Eight E. coli isolates showed total resistance to both the antimicrobials without any minimum inhibitory concentration. The detection of PMQR genes with qnr primers showed the presence of qnrA in two, qnrB in six and qnrS in 21 isolates. The gene coding for quinolone efflux pump (qepA) was not detected in any of the isolates tested. The presence of some unexpressed PMQR genes in fluoroquinolone sensitive isolates was also observed. Interpretation & conclusions: The detection of silent PMQR genes as observed in the present study presents a risk of the transfer of the silent resistance genes to other microorganisms if present in conjugative plasmids, thus posing a therapeutic challenge to the physicians. Hence, frequent monitoring is to be done for all resistance determinants.


Assuntos
Farmacorresistência Bacteriana/genética , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Fluoroquinolonas/efeitos adversos , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Ciprofloxacino/efeitos adversos , Ciprofloxacino/farmacologia , DNA Topoisomerases/efeitos dos fármacos , DNA Topoisomerases/genética , Escherichia coli/patogenicidade , Infecções por Escherichia coli/microbiologia , Fluoroquinolonas/uso terapêutico , Humanos , Plasmídeos/efeitos dos fármacos , Plasmídeos/genética
20.
J Med Microbiol ; 68(8): 1167-1172, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199227

RESUMO

OBJECTIVES: Elizabethkingia meningoseptica is a multi-drug-resistant organism that is associated with high mortality and morbidity in newborn and immunocompromised patients. This study aimed to identify the best antimicrobial therapy for treating this infection. METHODS: A retrospective descriptive study was conducted from 2010 to 2017 in a tertiary paediatric hospital in Singapore. Paediatric patients aged 0 to 18 years old with a positive culture for E. meningoseptica from any sterile site were identified from the hospital laboratory database. The data collected included clinical characteristics, antimicrobial susceptibility and treatment, and clinical outcomes. RESULTS: Thirteen cases were identified in this study. Combination therapy with piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluoroquinolone resulted in a cure rate of 81.8  %. The mortality rate was 15.4  % and neurological morbidity in patients with bacteraemia and meningitis remained high (75 %). CONCLUSIONS: Treatment with combination therapy of piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluroquinolone was effective in this study, with low mortality rates being observed.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Flavobacteriaceae/tratamento farmacológico , Fluoroquinolonas/uso terapêutico , Combinação Piperacilina e Tazobactam/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Antibacterianos/farmacologia , Criança , Pré-Escolar , Feminino , Flavobacteriaceae/efeitos dos fármacos , Flavobacteriaceae/isolamento & purificação , Infecções por Flavobacteriaceae/epidemiologia , Infecções por Flavobacteriaceae/microbiologia , Fluoroquinolonas/farmacologia , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Combinação Piperacilina e Tazobactam/farmacologia , Estudos Retrospectivos , Fatores de Risco , Singapura/epidemiologia , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/farmacologia
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