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1.
Artigo em Inglês | MEDLINE | ID: mdl-38423349

RESUMO

BACKGROUND & AIMS: The association between antibiotic exposure and inflammatory bowel disease (IBD) remains controversial, especially whether there is a dose-response relationship. We aimed to conduct a systematic review and meta-analysis to thoroughly evaluate the risk of new-onset IBD associated with antibiotic exposure. METHODS: Four databases were searched from their inception to September 30, 2023 for all relevant studies. The risk estimates were pooled together using random-effects models, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, stratified by IBD subtype, age, exposure period, study type, and antibiotic classes. Dose-response relationship between the number of antibiotic prescriptions and IBD risk was assessed using generalized least squares regression analysis. RESULTS: Twenty-eight studies involving 153,027 patients with IBD were included. Antibiotic exposure was significantly associated with an increased risk of new-onset IBD for prescription-based studies (pooled OR, 1.41; 95% CI, 1.29-1.53) and for questionnaire-based studies (pooled OR, 1.35; 95% CI, 1.08-1.68). This association existed for both Crohn's disease and ulcerative colitis, as well as in children and adults for prescription-based studies. The majority of antibiotic classes were associated with an increased IBD risk, with metronidazole (OR, 1.70; 95% CI, 1.38-2.10) and quinolones (OR, 1.56; 95% CI, 1.37-1.77) having relatively higher risk estimates. A positive nonlinear dose-response association was observed between the number of antibiotic prescriptions and IBD risk. CONCLUSIONS: Antibiotic exposure was significantly associated with an increased risk of new-onset IBD, and a positive nonlinear dose-response relationship was observed. Antibiotic stewardship may be important for reducing IBD risk.

2.
Ann Hematol ; 102(2): 421-427, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36648505

RESUMO

Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54-64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.


Assuntos
Anti-Infecciosos , Microbioma Gastrointestinal , Mucosite , Humanos , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Projetos Piloto , Fluconazol/efeitos adversos , Seguimentos , Estudos Prospectivos , Citrulina/farmacologia , Transplante de Células-Tronco , Anti-Infecciosos/efeitos adversos , Ciprofloxacina/efeitos adversos
3.
Ecotoxicol Environ Saf ; 251: 114536, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36634479

RESUMO

Although predation risk exists under natural conditions, its role is usually ignored when evaluating the ecotoxicity of environmental contaminants, and the interaction between predation risk and antibiotic ecotoxicity is not yet clear. To investigate the nonconsumptive effects (NCEs) of predation on the ecotoxicity evaluation of antibiotics, the median lethal concentration (LC50), relative population growth rate (RGR), and activities of three antioxidases were measured in the ciliate Paramecium jenningsi exposed to graded concentrations of the antibiotics nitrofurazone (NFZ) or erythromycin (ERY) in the presence or absence of a predator, i.e., the ciliate Didinium nasutum. The results showed that (1) NCEs significantly reduced the LC50 of NFZ but had no effect on that of ERY; (2) predation pressure alone had no significant effect on the inhibitory rate of the P. jenningsi population, but the interaction with NFZ was synergistic, while that with CRY was additive; (3) the concentrationresponse (i.e., mortality) model for each antibiotic exposure with and without predation pressure differed significantly in the parameter slope; (4) RGRs were significantly reduced by antibiotic exposure or NCEs; only in NFZ-exposed groups did the RGRs decrease linearly with increasing exposure concentration; and (5) the activities of all three antioxidases significantly increased due to NCEs or following exposure to antibiotics. In brief, NCEs were detected in P. jenningsi, and these had additive or synergistic effects on antibiotic ecotoxicity, but their magnitude depended on the properties and exposure concentrations of the antibiotics. Our findings suggest that it is necessary to consider the roles of NCEs in the ecotoxicity evaluation of environmental contaminants.


Assuntos
Cilióforos , Paramecium , Animais , Crescimento Demográfico , Antibacterianos/toxicidade , Comportamento Predatório/fisiologia , Nitrofurazona/toxicidade
4.
Ecotoxicol Environ Saf ; 262: 115196, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37506555

RESUMO

Antibiotic exposure even in low-dose could have potential adverse health effects, especially during early life. There is a lack of data on antibiotic burdens in early infancy. We aim to assess antibiotic exposure in infants from birth to 6 months of age, their related affecting factors and the association between antibiotic exposure and infancy growth. Urine samples were collected at ages of 3 days, 42 days, 3 months and 6 months from 197 term-born Chinese infants. A total of 33 representative antibiotics were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Urinary antibiotics were detectable in 69.4%, 63.2%, 75.0% and 84.3% of infants at ages of 3 days, 42 days, 3 and 6 months, respectively. The dominant antibiotic categories detected were: Preferred as Veterinary Antibiotics (PVAs), Human Antibiotics (HAs), and Veterinary Antibiotics (VAs). The detectable rates were 30.6%, 45.8%, 58.9%, and 81.4% for PVAs, 34.1%, 20.8%, 28.6%, and 45.1% for HAs, and 36.5%, 12.5%, 6.3%, and 5.9% for VAs, at age 3 days, 42 days, 3 and 6 months, respectively. Urinary concentrations of HAs and preferred as human antibiotics (PHAs) in newborns at age 3 days were not associated with maternal intrapartum antibiotic prophylaxis. Similarly, no associations were observed between urinary antibiotics concentration and antibiotics use in infants at age 42 days or 6 months. The numbers and concentrations of urine detectable antibiotics were similar between infants with exclusive breastfeeding and infants fed with formula or mixed-feeding at all ages of 42 days, 3 and 6 months. At age of 42 days, infants in the low tertile of total antibiotics concentration or with one antibiotic detected had higher weight-for-length Z score and greater head circumference, compared to infants with no antibiotics detected. No associations were found between urinary antibiotics and any of the infant anthropometric measures at age 6 months. In conclusion, urinary antibiotics were detectable in most infants during the first 6 months of life, and PVAs, HAs and VAs were the most commonly detected antibiotics. This suggested the possibility of a foods-originated antibiotics exposure in children. No strong nor consistent associations were found between urinary antibiotic concentration and infant growth at the first six months of life. Still, attention is needed on the adverse health effect of early life exposure to antibiotics in future studies.

5.
Eur J Clin Microbiol Infect Dis ; 41(1): 109-117, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34625886

RESUMO

Necrotizing soft-tissue infection (NSTI) is a life-threatening pathology that often requires management in intensive care unit (ICU). Therapies consist of early diagnosis, adequate surgical source control, and antimicrobial therapy. Whereas guidelines underline the need for appropriate routine microbiological cultures before starting antimicrobial therapy in patients with suspected sepsis or septic shock, delaying adequate therapy also strongly increases mortality. The aim of the present study was to compare the characteristics and outcomes of patients hospitalized in ICU for NSTI according to their antimicrobial therapy exposure > 24 h before surgery (called the exposed group) or not (called the unexposed group) before surgical microbiological sampling. We retrospectively included 100 consecutive patients admitted for severe NSTI. The exposed group consisted of 23(23%) patients, while 77(77%) patients belonged to the unexposed group. The demographic and underlying disease conditions were similar between the two groups. Microbiological cultures of surgical samples were positive in 84 patients and negative in 16 patients, including 3/23 (13%) patients and 13/77 (17%) patients in the exposed and unexposed groups, respectively (p = 0.70). The distribution of microorganisms was comparable between the two groups. The main antimicrobial regimens for empiric therapy were also similar, and the proportions of adequacy were comparable (n = 60 (84.5%) in the unexposed group vs. n = 19 (86.4%) in the exposed group, p = 0.482). ICU and hospital lengths of stay and mortality rates were similar between the two groups. In conclusion, in a population of severe ICU NSTI patients, antibiotic exposure before sampling did not impact either culture sample positivity or microbiological findings.


Assuntos
Antibacterianos/uso terapêutico , Infecções dos Tecidos Moles/tratamento farmacológico , Idoso , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Feminino , França , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/mortalidade , Resultado do Tratamento
6.
Ann Clin Microbiol Antimicrob ; 21(1): 46, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329476

RESUMO

BACKGROUND: Early-life antibiotic exposure is associated with the development of later obesity through the disruption of gut microbiota in the animal models. However, the related epidemiological evidence is still conflicting. METHODS: A birth cohort was consisted of 2140 mother-infant pairs in Chaoyang District Maternal and Child Health Care Hospital in this study. Here, their available antibiotic exposure during the first one year of life was ascertained using a open-ended questionnaire and related anthropometric parameters from the health screening program. The compositions of gut microbiota were comprehensively analyzed by16S rRNA high throughput sequencing. Then the spearman correlations were performed by the multiple covariance-adjusted regressions between the antibiotic exposure with anthropometric parameters and compositions of gut microbiota. RESULTS: Among the 2140 subjects, the antibiotic exposure during the first one year of life was 53.04%, mainly by Cephalosporins (53.39%) and Erythromycins(27.67%) for the treatment of respiratory tract infection (79.56%), which were not significantly different among the subgroups. Compared to the control group, both childhood overweight and obesity at two and a half years were higher in the antibiotic exposed group, with higher percents of Faecalibacterium, Agathobacter and Klebsiella, and lower percentage of Bifidobacterium. Moreover, there were positively potential associations between early-life antibiotic exposure with the accelerated anthropometric parameters and disruption of Faecalibacterium, Agathobacter, Klebsiella and Bifidobacterium at two and a half years. CONCLUSION: These above results proved that early-life antibiotic exposure was positively associated with the accelerated childhood overweight and obesity from one year to two and a half years by impacting the disorders of Faecalibacterium, Agathobacter, Klebsiella and Bifidobacterium, which would propose the theoretical basis for rationalizing the personalized antibiotic exposure among the infants to truly reflect the fairness of public health.


Assuntos
Microbioma Gastrointestinal , Obesidade Infantil , Humanos , Animais , Disbiose , Obesidade Infantil/epidemiologia , Estudos de Coortes , Antibacterianos/efeitos adversos , Coorte de Nascimento , Klebsiella/genética
7.
Ecotoxicol Environ Saf ; 247: 114234, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36326554

RESUMO

Sulfamethoxazole (SMZ) is an important antibiotic used to prevent and treat infections in both clinical settings and animal husbandry. High levels of SMZ may exhibit endocrine toxicity. Environmental SMZ enters the human body via food and water; however, the toxicity of environmental doses of SMZ and its effects on reproductive health are unknown. In the present study, zebrafish were exposed to low concentrations of SMZ (1000 and 5000 ng/L) from 2 h post-fertilization to 120 d post-fertilization. Consequently, the proportion of mature oocytes in adult female zebrafish ovarian tissue increased by 98.2 %, indicating that SMZ promotes ovarian maturation. Metabolomics analysis revealed significant changes in ovarian lipid and amino acid levels after SMZ treatment. An enzyme-linked immunoassay used to detect sex hormones in the ovaries showed that SMZ exposure significantly increased the levels of estradiol, a follicle-stimulating hormone, and of luteinizing hormone. Furthermore, an association analysis showed that most of the differentially expressed metabolites in the ovary were strongly correlated with the levels of sex hormones secreted by the pituitary gland. Therefore, significantly increased transcript levels of gonadotropin-releasing hormone (GnRH) and follicle-stimulating hormone detected in brain tissue suggested that SMZ may exhibit ovarian toxicity via the hypothalamus. In vitro experiments were performed to demonstrate that SMZ targets neurons in the hypothalamus. Exposure to SMZ significantly increased the GnRH content in GnRH neurons. Finally, molecular docking simulations indicated the potential interaction of SMZ with G protein-coupled receptor 54; this molecular binding can activate, synthesize, and release GnRH in neurons. In conclusion, long-term environmental exposure to SMZ may induce ovarian toxicity by affecting the hypothalamus-pituitary-gonad axis.


Assuntos
Ovário , Peixe-Zebra , Adulto , Animais , Feminino , Humanos , Hormônio Foliculoestimulante , Hormônios Esteroides Gonadais , Hormônio Liberador de Gonadotropina , Lipídeos , Simulação de Acoplamento Molecular , Oócitos , Sulfametoxazol/toxicidade , Aminoácidos/metabolismo
8.
J Infect Dis ; 224(12 Suppl 2): S209-S217, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469562

RESUMO

BACKGROUND: Sensitivity of culture for the detection of Streptococcus pneumoniae is limited by prior antibiotic exposure. Immunochromatographic test (ICT) is highly sensitive and specific for pneumococcal antigen detection in the cerebrospinal fluid (CSF) of meningitis cases. We determined the specificity and sensitivity of culture, ICT, and polymerase chain reaction (PCR) and the effect of antibiotic exposure on their performance. METHODS: CSF specimens from suspected meningitis cases admitted to Dhaka Shishu Hospital, Bangladesh, were tested using culture, ICT and PCR. Additionally, 165 specimens collected from 69 pneumococcal cases after antibiotic treatment were tested. RESULTS: Of 1883 specimens tested, culture detected 9, quantitative PCR (qPCR) detected 184, and ICT detected 207 pneumococcal cases (including all culture and qPCR positives). In comparison to ICT, sensitivity of culture was 4.4% and of qPCR was 90.6%; both were 100% specific. After antibiotic exposure, culture sensitivity plummeted rapidly; conventional PCR and qPCR sensitivity disappeared after day 6 and 20, respectively. ICT detected pneumococcal antigen for >10 weeks. CONCLUSIONS: While culture provides the most information about bacterial characteristics, in high antibiotic exposure settings, ICT exhibits maximum sensitivity. We recommend culture and ICT as mainstay for pneumococcal diagnosis and surveillance; qPCR can generate additional molecular data where possible.


Assuntos
Antígenos de Bactérias , Líquido Cefalorraquidiano/microbiologia , Cromatografia de Afinidade/métodos , Meningite Pneumocócica/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Streptococcus pneumoniae/genética , Antibacterianos , Bangladesh/epidemiologia , Criança , Humanos , Lactente , Meningite Pneumocócica/líquido cefalorraquidiano , Meningite Pneumocócica/epidemiologia , Vigilância em Saúde Pública , Sensibilidade e Especificidade , Streptococcus pneumoniae/isolamento & purificação
9.
Clin Infect Dis ; 72(3): 455-462, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31994697

RESUMO

BACKGROUND: The potential for prenatal antibiotic exposure to influence asthma risk is not clear. We aimed to determine the effect of timing, dose, and spectrum of prenatal antibiotic exposure on the risk of childhood asthma. METHODS: We conducted a population-based cohort study of 84 214 mother-child dyads to examine the association of prenatal antibiotic exposure and childhood asthma using multivariable logistic regression models. RESULTS: Sixty-four percent of pregnant women received antibiotics. Prenatal antibiotic exposure was associated dose-dependently with increased odds of childhood asthma (adjusted odds ratio [aOR] for interquartile increase of 2 courses [interquartile range, 0-2], 1.26 [95% confidence interval {CI}, 1.20-1.33]). Among children exposed to at least 1 course in utero, the effect of timing at the first course was moderated by total maternal courses. Among pregnant women receiving a single antibiotic course, timing of exposure had no effect on childhood asthma risk. Among women receiving > 1 course, early exposure of the first course was associated with greater childhood asthma risk. Compared to narrow spectrum-only antibiotic use, broad spectrum-only antibiotic exposure was associated with increased odds of asthma (aOR, 1.14 [95% CI, 1.05-1.24]). There were effect modifications (P < .001) by maternal asthma on total courses, and on timing of the first course, significant only among those without maternal asthma. CONCLUSIONS: Increased cumulative dose, early pregnancy first course, and broad-spectrum antibiotic exposure were associated with childhood asthma risk. Our study provides important evidence supporting judicious prenatal antibiotic use, particularly timing of use and choice of antibiotics, in preventing subsequent childhood asthma.


Assuntos
Asma , Efeitos Tardios da Exposição Pré-Natal , Antibacterianos/efeitos adversos , Asma/induzido quimicamente , Asma/epidemiologia , Criança , Estudos de Coortes , Feminino , Humanos , Razão de Chances , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fatores de Risco
10.
Appl Microbiol Biotechnol ; 105(21-22): 8441-8456, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34651253

RESUMO

Increasing evidence suggests that antibiotic administration causes gut injury, negatively affecting nutrient digestion, immune regulation, and colonization resistance against pathogens due to the disruption of gut microbiota. However, the time-course effects of therapeutic antibiotics on alterations of gut microbes and short-chain fatty acids (SCFAs) in young swine are still unknown. In this study, twenty piglets were assigned into two groups and fed commercial diets with or without lincomycin in the first week for a 28-day trial period. Results showed that 1-week lincomycin exposure (LE) did reduce the body weight on day 14 (p = 0.0450) and 28 (p = 0.0362). The alpha-diversity notably reduced after 1-week LE, and then gradually raised and reached the control group level in the second week on cessation of LE, indicated by the variation of Sobs, Chao, Shannon, and ACE index (p < 0.05). Beta-diversity analysis revealed that the distinct microbial cluster existed persistently for the whole trial period between two groups (p < 0.001). The relative abundance of most microbes including fiber-degrading (e.g., Agathobacter and Coprococcus), beneficial (e.g., Lactobacillus and Mitsuokella), or pathogenic bacteria (e.g., Terrisporobacter and Lachnoclostridium) decreased (LDA score > 3), and the concentration of SCFAs also diminished in the feces of 1-week lincomycin-administrated young swine, indicating that therapeutic LE killed most bacteria and reduced SCFA production with gut dysbiosis occurring. After the LE stopped, the state of gut dysbiosis gradually attenuated and formed new gut-microbe homeostasis distinct from microbial homeostasis of young pigs unexposed to lincomycin. The increased presence of potential pathogens, such as Terrisporobacter, Negativibacillus, and Escherichia-Shigella, and decreased beneficial bacteria, such as Lactobacillus and Agathobacter, were observed in new homeostasis reshaped by short-lincomycin administration (LDA score > 3 or p < 0.05), adversely affecting gut development and health of young pigs. Collectively, these results suggested that severe disruption of the commensal microbiota occurred after short-term LE or termination of LE in young swine. KEY POINTS: • Therapeutic lincomycin exposure induced gut dysbiosis, killing most bacteria and reducing short-chain fatty acid production. • Gut dysbiosis gradually attenuated and formed new homeostasis after lincomycin exposure stopped. • The new homeostasis, increased Escherichia-Shigella etc. and decreased Lactobacillus etc., was potentially harmful to gut health.


Assuntos
Microbioma Gastrointestinal , Animais , Disbiose , Ácidos Graxos Voláteis , Fezes , Lincomicina , Suínos
11.
Acta Paediatr ; 110(6): 1911-1915, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33368616

RESUMO

AIM: To assess the association between taking antibiotics in pregnancy and the occurrence of infections in children at four years of age. METHODS: We studied children who participated in the follow-up of the birth cohort Generation XXI, Porto-Portugal, at the age of four years. We evaluated the associations between the use of antibiotics by the mother at any time in pregnancy with the occurrence of infections. Data were analysed using logistic regression, controlling for potential confounding variables. RESULTS: We studied 7459 children (50.7% boys). The use of antibiotics at any stage of pregnancy, and not only in the third trimester, was associated with the occurrence of tonsillitis at four years, even after controlling for potential confounders (OR 1.19, 95% CI 1.03-1.38). Other infections did not show association. CONCLUSION: Maternal use of antibiotics during pregnancy was associated with an increased risk of tonsillitis reported at four years of age. Antibiotics could favour the potential transmission of an unfavourable microbiome from mother to child.


Assuntos
Antibacterianos , Efeitos Tardios da Exposição Pré-Natal , Antibacterianos/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Mães , Portugal/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fatores de Risco
12.
J Paediatr Child Health ; 57(7): 1023-1030, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33586839

RESUMO

AIM: Most prescribed medicines during pregnancy are antibiotics, with unknown effects on a fetus and on the infant's acquired microbiome. This study investigates associations between in utero antibiotic exposure and ear infection trajectories over the first decade of life, hypothesising effects on early or persistent, rather than later-developing, ear infections. METHODS: Design and participants: The Longitudinal Study of Australian Children birth cohort recruited a nationally-representative sample of 5107 infants in 2004. MEASURES: Mothers reported antibiotic use in pregnancy when a child was 3-21 months old (wave 1), and ongoing problems with ear infection every 2 years spanning ages 0-1 to 10-11 years (waves 1-6). ANALYSIS: Latent class models identified ear infection trajectories, and univariable and multivariable multinomial logistic regression determined odds of adverse trajectories by antibiotic exposure. RESULTS: A total of 4500 (88.1% of original sample) children contributed (mean baseline age 0.7 years; 51.3% boys); 10.4% of mothers reported antibiotic use in pregnancy. Four probability trajectories for ear infection emerged: 'consistently low' (86.2%), 'moderate to low' (5.6%), 'low to moderate' (6.7%) and 'consistently high' (1.4%). Antibiotic use in pregnancy was associated with children following 'consistently high' (adjusted odds ratio 2.04, 95% confidence interval 1.08-3.88, P = 0.03) and 'moderate to low' (adjusted odds ratio 1.78, 95% confidence interval 1.25-2.53, P = 0.001) trajectories. CONCLUSIONS: Antibiotic use in pregnancy is associated with an increased risk of persistent and early childhood ear infections. This highlights the wisdom of cautious antibiotic use during pregnancy, and the need for the study of potential mechanisms underlying these associations.


Assuntos
Antibacterianos , Otite , Antibacterianos/efeitos adversos , Austrália/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Gravidez , Fatores de Risco
13.
Ecotoxicol Environ Saf ; 223: 112546, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34330038

RESUMO

Trace levels of oxytetracycline (OTC)-a veterinary antibiotic and feed additive-are widespread in the environment. Studies revealed that OTC potentially impairs thyroid function, which may affect neurobehaviour; however, the impact of exposure to environmental concentrations of OTC on adult neurobehaviour is unknown. In this study, the effects of OTC on zebrafish after 30-day exposure were investigated. The total swimming distance was significantly increased under vibration and light/dark stimulation, while time spent in the white area was prolonged during the black/white preference test, indicating that the zebrafish became bolder and more impulsive under low OTC exposure. Additionally, monoamine neurotransmitter (5-hydroxytryptamine, dopamine, norepinephrine) levels were decreased and gene expression of monoamine oxidase (mao) involved in neurotransmitter metabolism was upregulated at the transcription level after OTC exposure. Because triiodothyronine (T3) levels were enhanced following exposure to OTC, we speculated that T3 may mediate OTC damage to the nervous system. Our simulated molecular docking analysis showed that OTC combined with the sodium iodide cotransporter protein may result in excessive T3 synthesis. We further exposed zebrafish to T3, and they exhibited similar behaviour to the OTC exposure group. In conclusion, environmental OTC may activate monoamine oxidase and enhance the metabolism of monoaminergic neurotransmitters via T3, thereby inducing abnormal neurobehaviour.


Assuntos
Oxitetraciclina , Animais , Antibacterianos/toxicidade , Simulação de Acoplamento Molecular , Oxitetraciclina/toxicidade , Tri-Iodotironina , Peixe-Zebra
14.
Clin Infect Dis ; 71(12): 3244-3247, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32478813

RESUMO

Nursing home (NH) patients often acquire colonization with antibiotic-resistant organisms (AROs). We show that patients exposed to broad-spectrum antibiotics during previous hospitalizations have elevated enterococcal relative abundances on NH admission and higher risk of subsequent ARO acquisition. Our findings suggest that interventions preventing ARO spread should extend beyond NH doors.


Assuntos
Antibacterianos , Microbioma Gastrointestinal , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Hospitalização , Humanos , Casas de Saúde , Instituições de Cuidados Especializados de Enfermagem
15.
Mov Disord ; 35(3): 431-442, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31737957

RESUMO

BACKGROUND: Gut microbiota alterations have been found in prodromal and established Parkinson's disease (PD). Antibiotic exposure can have long-term effects on the composition of human intestinal microbiota, but a potential connection between antibiotic exposure and risk of PD has not been studied previously. OBJECTIVE: To evaluate the impact of antibiotic exposure on the risk of PD in a nationwide, register-based, case-control study. METHODS: We identified all patients who were diagnosed with PD in Finland during the years 1998 to 2014. Information was obtained on individual purchases of orally administered antibiotics during the years 1993 to 2014. We assessed the association between prior antibiotic exposure and PD using conditional logistic regression. RESULTS: The study population consisted of 13,976 PD cases and 40,697 controls. The strongest connection with PD risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416; 95% confidence interval, 1.053-1.904). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10 to 15 years before the index date, sulfonamides and trimethoprim 1 to 5 years before the index date, and antifungal medications 1 to 5 years before the index date were positively associated with PD risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics. CONCLUSIONS: Exposure to certain types of oral antibiotics seems to be associated with an elevated risk of PD with a delay that is consistent with the proposed duration of a prodromal period. The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to PD, but further studies are needed to confirm this. © 2019 International Parkinson and Movement Disorder Society.


Assuntos
Microbioma Gastrointestinal , Doença de Parkinson , Antibacterianos/efeitos adversos , Estudos de Casos e Controles , Finlândia/epidemiologia , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia
16.
Helicobacter ; 25(6): e12755, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32914914

RESUMO

OBJECTIVE: This study aims to evaluate the efficacy and safety of three bismuth-based quadruple regimens for eradication of Helicobacter pylori (H pylori) infection in a large number of H pylori-positive patients with or without previous eradication therapy. METHODS: Consecutive adult patients with H pylori infection, regardless of previous eradication therapy, were eligible for the present study. Three bismuth-based quadruple regimens were selected according to the past history of antibiotics use: (A) esomeprazole, amoxicillin, clarithromycin, and colloidal bismuth tartrate; (B) esomeprazole, amoxicillin, furazolidone, and colloidal bismuth tartrate; and (C) esomeprazole, doxycycline, furazolidone, and colloidal bismuth tartrate. All patients received a 14-day course of treatment, and 13 C/14 C urea breath test was utilized at four weeks after the completion of treatment to determine the H pylori eradication. Then, the eradication rates were calculated in terms of intention-to-treat (ITT) and per-protocol (PP) analyses. Adverse events (AEs) were recorded during the treatment. RESULTS: Overall, 1,226 patients were recruited, and 331, 57, and 838 patients were allocated to receive regimens A, B, and C, respectively. The H pylori eradication rates were 84.0%, 82.5%, and 82.9% (ITT) and 94.6%, 92.2%, and 93.7% (PP), respectively, in regimens A, B, and C. However, there was no significant difference among these three regimens. The incidence of AEs was 4.6% for all patients during the study, that is, 3.3%, 10.5%, and 4.7% for regimens A, B, and C, respectively. All AEs were mild and recovered at the follow-up visit. CONCLUSION: All three bismuth-based quadruple regimens based on the previous antibiotic use can achieve satisfactory eradication rates for H pylori infection and are safe.


Assuntos
Antibacterianos , Bismuto , Infecções por Helicobacter , Adulto , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , China , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Humanos , Estudos Prospectivos , Resultado do Tratamento
17.
BMC Pediatr ; 20(1): 312, 2020 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-32593308

RESUMO

BACKGROUND: Early antibiotic exposure may be contributing to the onset of childhood allergies. The main objective of this study was to conduct a systematic review on the relationship between early life antibiotic exposure and childhood asthma, eczema and hay fever. METHODS: Pubmed and Embase were searched for studies published between 01-01-2008 and 01-08-2018, examining the effects of (1) prenatal antibiotic exposure and (2) infant antibiotic administration (during the first 2 years of life) on childhood asthma, eczema and hay fever from 0 to 18 years of age. These publications were assessed using the Newcastle Ottawa Scale (NOS) and analysed narratively. RESULTS: (1) Prenatal antibiotics: Asthma (12 studies): The majority of studies (9/12) reported significant relationships (range OR 1.13 (1.02-1.24) to OR 3.19 (1.52-6.67)). Three studies reported inconsistent findings. Eczema (3 studies): An overall significant effect was reported in one study and in two other studies only when prenatal antibiotic exposure was prolonged. (2) Infant antibiotics: Asthma (27 studies): 17/27 studies reported overall significant findings (range HR 1.12 (1.08-1.16) to OR 3.21 (1.89-5.45)). Dose-response effects and stronger effects with broad-spectrum antibiotic were often reported. 10/27 studies reported inconsistent findings depending on certain conditions and types of analyses. Of 19 studies addressing reverse causation or confounding by indication at least somewhat, 11 reported overall significant effects. Eczema (15 studies): 6/15 studies reported overall significant effects; 9 studies had either insignificant or inconsistent findings. Hay fever (9 studies): 6/9 reported significant effects, and the other three insignificant or inconsistent findings. General: Multiple and broad-spectrum antibiotics were more strongly associated with allergies. The majority of studies scored a 6 or 7 out of 9 based on the NOS, indicating they generally had a medium risk of bias. Although most studies showed significant findings between early antibiotic exposure and asthma, the actual effects are still unclear as intrapartum antibiotic administration, familial factors and confounding by maternal and child infections were often not addressed. CONCLUSIONS: This review points to a moderate amount of evidence for a relationship between early life antibiotics (especially prenatal) and childhood asthma, some evidence for a relationship with hay fever and less convincing evidence for a relationship with eczema. More studies are still needed addressing intra-partum antibiotics, familial factors, and possible confounding by maternal and childhood infections. Children exposed to multiple, broad-spectrum antibiotics early in life appear to have a greater risk of allergies, especially asthma; these effects should be investigated further.


Assuntos
Asma , Eczema , Hipersensibilidade , Efeitos Tardios da Exposição Pré-Natal , Antibacterianos/efeitos adversos , Asma/tratamento farmacológico , Criança , Eczema/induzido quimicamente , Eczema/tratamento farmacológico , Feminino , Humanos , Lactente , Parto , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
19.
Appl Microbiol Biotechnol ; 103(9): 3597-3614, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30810776

RESUMO

This review covers the current knowledge of the cytochrome P450 enzymes (CYPs) of the human pathogen Mycobacterium tuberculosis (Mtb) and their endogenous redox partners, focusing on their biological function, expression, regulation, involvement in antibiotic resistance, and suitability for exploitation as antitubercular targets. The Mtb genome encodes twenty  CYPs and nine associated redox partners required for CYP catalytic activity. Transposon insertion mutagenesis studies have established the (conditional) essentiality of several of these enzymes for in vitro growth and host infection. Biochemical characterization of a handful of Mtb CYPs has revealed that they have specific physiological functions in bacterial virulence and persistence in the host. Analysis of the transcriptional response of Mtb CYPs and redox partners to external insults and to first-line antibiotics used to treat tuberculosis showed a diverse expression landscape, suggesting for some enzymes a potential role in drug resistance. Combining the knowledge about the physiological roles and expression profiles indicates that, at least five Mtb CYPs, CYP121A1, CYP125A1, CYP139A1, CYP142A1, and CYP143A1, as well as two ferredoxins, FdxA and FdxC, can be considered promising novel therapeutic targets.


Assuntos
Proteínas de Bactérias/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Mycobacterium tuberculosis/enzimologia , Animais , Antituberculosos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Biocatálise , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/genética , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Oxirredução , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
20.
BMC Public Health ; 19(1): 949, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307422

RESUMO

BACKGROUND: Community-driven projects that aim to address public concerns about health risks from H. pylori infection in Indigenous Arctic communities (estimated H. pylori prevalence = 64%) show frequent failure of treatment to eliminate the bacterium. Among project participants, treatment effectiveness is reduced by antibiotic resistance of infecting H. pylori strains, which in turn, is associated with frequent exposure to antibiotics used to treat other infections. This analysis compares antibiotic dispensation rates in Canadian Arctic communities to rates in urban and rural populations in Alberta, a southern Canadian province. METHODS: Project staff collected antibiotic exposure histories for 297 participants enrolled during 2007-2012 in Aklavik, Tuktoyaktuk, and Fort McPherson in the Northwest Territories, and Old Crow, Yukon. Medical chart reviews collected data on systemic antibiotic dispensations for the 5-year period before enrolment for each participant. Antibiotic dispensation data for urban Edmonton, Alberta (average population ~ 860,000) and rural northern Alberta (average population ~ 450,000) during 2010-2013 were obtained from the Alberta Government Interactive Health Data Application. RESULTS: Antibiotic dispensation rates, estimated as dispensations/person-years (95% confidence interval) were: in Arctic communities, 0.89 (0.84, 0.94); in Edmonton, 0.55 (0.55, 0.56); in rural northern Alberta, 0.63 (0.62, 0.63). Antibiotic dispensation rates were higher in women and older age groups in all regions. In all regions, the highest dispensation rates occurred for ß-lactam and macrolide antibiotic classes. CONCLUSIONS: These results show more frequent antibiotic dispensation in Arctic communities relative to an urban and rural southern Canadian population.


Assuntos
Antibacterianos/uso terapêutico , Características de Residência/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Regiões Árticas , Canadá , Criança , Pré-Escolar , Feminino , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , População Rural/estatística & dados numéricos , Falha de Tratamento , População Urbana/estatística & dados numéricos , Adulto Jovem
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