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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1068-1073, 2020.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33051420

RESUMO

OBJECTIVES: To analyze the pathogenic distribution, antibiotic susceptibility and prognostic factors for acute leukemia (AL) patients with Gram negative (G-) bacterial bloodstream infection (BSI), in order to provide theoretical basis for reducing the infection-related mortality of AL patients. METHODS: The clinical data of 1 055 AL patients with BSI admitted to the hematology ward of three large-scale hospitals in Hunan Province from January 2010 to December 2018 were collected. The etiology, antibiotic susceptibility data and clinical features of patients with G- bacterial infection were analyzed. RESULTS: G- bacterial infection accounted for 622 AL patients with BSI, and the main pathogens were Escherichia coli (277 strains, 44.53%), Klebsiella pneumoniae (138 strains, 22.19%), and Pseudomonas aeruginosa (81 strains, 13.02%). Most G- bacteria were highly sensitive to carbapenems and ß-lactam/ß-lactamase inhibitor. State of disease, Pitt score ≥4, treatment with vasoactive agents and sensitive antibiotic >48 h were independent risk factors of 30-day mortality. CONCLUSIONS: Rational antibacterial treatment of G- bacterial BSI in AL patients requires adequate acquaintance of the local pathogenic epidemiology and antibiotic susceptibility-monitored data. Broad-spectrum antibiotics covering the most common and more virulent pathogens should be timely applicated and adjusted according to antibiotic susceptibility results and efficacy.


Assuntos
Bacteriemia , Farmacorresistência Bacteriana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Prognóstico
2.
BMC Infect Dis ; 20(1): 729, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028225

RESUMO

BACKGROUND: This study describes the disease burden, clinical characteristics, antibiotic management, impact of multidrug resistance and outcome of Pseudomonas aeruginosa bloodstream infection (PABSI) among children admitted to a tertiary referral hospital for children in Cape Town, South Africa. METHODS: A retrospective descriptive study was conducted at a paediatric referral hospital in Cape Town, South Africa. Demographic and clinical details, antibiotic management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the National Health Laboratory Service database. RESULTS: The incidence risk of PABSI was 5.4 (95% CI: 4.34-6.54) PABSI episodes / 10,000 hospital admissions and the most common presenting feature was respiratory distress, 34/91 (37.4%). Overall, 69/91 (75.8%) of the PA isolates were susceptible to all antipseudomonal antibiotic classes evaluated. Fifty (54.9%) of the PABSI episodes were treated with appropriate empiric antibiotic therapy. The mortality rate was 24.2% and in multivariable analysis, empiric antibiotic therapy to which PA isolates were not susceptible, infections present on admission, and not being in the intensive care unit at the time that PABSI was diagnosed were significantly associated with 14-day mortality. CONCLUSIONS: PABSI caused appreciable mortality, however, appropriate empiric antibiotic therapy was associated with reduced 14-day mortality.


Assuntos
Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Hospitais Pediátricos , Humanos , Lactente , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/mortalidade , Pseudomonas aeruginosa/efeitos dos fármacos , Estudos Retrospectivos , África do Sul/epidemiologia , Taxa de Sobrevida , Centros de Atenção Terciária
4.
Nat Commun ; 11(1): 4365, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868761

RESUMO

Current approaches explore bacterial genes that change transcriptionally upon stress exposure as diagnostics to predict antibiotic sensitivity. However, transcriptional changes are often specific to a species or antibiotic, limiting implementation to known settings only. While a generalizable approach, predicting bacterial fitness independent of strain, species or type of stress, would eliminate such limitations, it is unclear whether a stress-response can be universally captured. By generating a multi-stress and species RNA-Seq and experimental evolution dataset, we highlight the strengths and limitations of existing gene-panel based methods. Subsequently, we build a generalizable method around the observation that global transcriptional disorder seems to be a common, low-fitness, stress response. We quantify this disorder using entropy, which is a specific measure of randomness, and find that in low fitness cases increasing entropy and transcriptional disorder results from a loss of regulatory gene-dependencies. Using entropy as a single feature, we show that fitness and quantitative antibiotic sensitivity predictions can be made that generalize well beyond training data. Furthermore, we validate entropy-based predictions in 7 species under antibiotic and non-antibiotic conditions. By demonstrating the feasibility of universal predictions of bacterial fitness, this work establishes the fundamentals for potentially new approaches in infectious disease diagnostics.


Assuntos
Bactérias/genética , Evolução Molecular Direcionada , Farmacorresistência Bacteriana/genética , Estresse Fisiológico , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Fenômenos Fisiológicos Bacterianos , Doenças Transmissíveis/diagnóstico , Entropia , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Genoma Bacteriano , Análise de Sequência de RNA , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/metabolismo , Transcriptoma
5.
Nat Commun ; 11(1): 4648, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938927

RESUMO

Emergence of tigecycline-resistance tet(X) gene orthologues rendered tigecycline ineffective as last-resort antibiotic. To understand the potential origin and transmission mechanisms of these genes, we survey the prevalence of tet(X) and its orthologues in 2997 clinical E. coli and K. pneumoniae isolates collected nationwide in China with results showing very low prevalence on these two types of strains, 0.32% and 0%, respectively. Further surveillance of tet(X) orthologues in 3692 different clinical Gram-negative bacterial strains collected during 1994-2019 in hospitals in Zhejiang province, China reveals 106 (2.7%) tet(X)-bearing strains with Flavobacteriaceae being the dominant (97/376, 25.8%) bacteria. In addition, tet(X)s are found to be predominantly located on the chromosomes of Flavobacteriaceae and share similar GC-content as Flavobacteriaceae. It also further evolves into different orthologues and transmits among different species. Data from this work suggest that Flavobacteriaceae could be the potential ancestral source of the tigecycline resistance gene tet(X).


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Infecções por Flavobacteriaceae/epidemiologia , Flavobacteriaceae/genética , Tigeciclina/farmacologia , China/epidemiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Evolução Molecular , Flavobacteriaceae/efeitos dos fármacos , Flavobacteriaceae/isolamento & purificação , Infecções por Flavobacteriaceae/microbiologia , Humanos , Filogenia
6.
Chemosphere ; 254: 126911, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32957300

RESUMO

Trivalent organoarsenicals such as methylarsenite (MAs(III)) are considerably more toxic than inorganic arsenate (As(V)) or arsenite (As(III)). In microbial communities MAs(III) exhibits significant antimicrobial activity. Although MAs(III) and other organoarsenicals contribute to the global arsenic biogeocycle, how they exert antibiotic-like properties is largely unknown. To identify possible targets of MAs(III), a genomic library of the gram-negative bacterium, Shewanella putrefaciens 200, was expressed in Escherichia coli with selection for MAs(III) resistance. One clone contained the S. putrefaciens murA gene (SpmurA), which catalyzes the first committed step in peptidoglycan biosynthesis. Overexpression of SpmurA conferred MAs(III) resistance to E. coli. Purified SpMurA was inhibited by MAs(III), phenylarsenite (PhAs(III)) or the phosphonate antibiotic fosfomycin but not by inorganic As(III). Fosfomycin inhibits MurA by binding to a conserved residue that corresponds to Cys117 in SpMurA. A C117D mutant was resistant to fosfomycin but remained sensitive to MAs(III), indicating that the two compounds have different mechanisms of action. New inhibitors of peptidoglycan biosynthesis are highly sought after as antimicrobial drugs, and organoarsenicals represent a new area for the development of novel compounds for combating the threat of antibiotic resistance.


Assuntos
Alquil e Aril Transferases/antagonistas & inibidores , Farmacorresistência Bacteriana/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Peptidoglicano/biossíntese , Shewanella putrefaciens/efeitos dos fármacos , Alquil e Aril Transferases/genética , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Peptidoglicano/metabolismo , Shewanella putrefaciens/genética
7.
PLoS One ; 15(9): e0236442, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32925914

RESUMO

The goal of this study was to determine the frequency of resistance to extended-spectrum cephalosporins (ESCs) in Escherichia coli and other Enterobacterales from turkeys in Canada and characterize the associated resistance determinants. Pooled fecal samples were collected in 77 turkey farms across British Columbia, Québec, and Ontario. Isolates were obtained with and without selective enrichment cultures and compared to isolates from diagnostic submissions of suspected colibacillosis cases in Ontario. Isolates were identified using MALDI-TOF and susceptibility to ESCs was assessed by disk diffusion. The presence of blaCMY, blaCTX-M, blaTEM, and blaSHV was tested by PCR. Transformation experiments were used to characterize blaCMY plasmids. Genome sequencing with short and long reads was performed on a representative sample of blaCTX-M-positive isolates to assess isolates relatedness and characterize blaCTX-M plasmids. For the positive enrichment cultures (67% of total samples), 93% (587/610) were identified as E. coli, with only a few other Enterobacterales species identified. The frequency of ESC resistance was low in E. coli isolates from diagnostic submission (4%) and fecal samples without selective enrichment (5%). Of the ESC-resistant Enterobacterales isolates from selective enrichments, 71%, 18%, 14%, and 8% were positive for blaCMY, blaTEM, blaCTX-M, and blaSHV, respectively. IncI1 followed by IncK were the main incompatibility groups identified for blaCMY plasmids. The blaCTX-M-1 gene was found repeatedly on IncI1 plasmids of the pMLST type 3, while blaCTX-M-15, blaCTX-M-55, and blaCTX-M-65 were associated with a variety of IncF plasmids. Clonal spread of strains carrying blaCTX-M genes between turkey farms was observed, as well as the presence of an epidemic blaCTX-M-1 plasmid in unrelated E. coli strains. In conclusion, Enterobacterales resistant to ESCs were still widespread at low concentration in turkey feces two years after the cessation of ceftiofur use. Although blaCMY-2 is the main ESC resistance determinant in E. coli from Canadian turkeys, blaCTX-M genes also occur which are often carried by multidrug resistance plasmids. Both clonal spread and horizontal gene transfer are involved in parallel in the spread of blaCTX-M genes in Enterobacterales from Canadian turkeys.


Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Infecções por Enterobacteriaceae/veterinária , Enterobacteriaceae/efeitos dos fármacos , Doenças das Aves Domésticas/tratamento farmacológico , Perus/microbiologia , Animais , Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Doenças das Aves Domésticas/microbiologia
8.
Antimicrob Resist Infect Control ; 9(1): 153, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962731

RESUMO

BACKGROUND: A considerable proportion of patients hospitalized with coronavirus disease 2019 (COVID-19) acquired secondary bacterial infections (SBIs). The etiology and antimicrobial resistance of bacteria were reported and used to provide a theoretical basis for appropriate infection therapy. METHODS: This retrospective study reviewed electronic medical records of all the patients hospitalized with COVID-19 in the Wuhan Union Hospital between January 27 and March 17, 2020. According to the inclusion and exclusion criteria, patients who acquired SBIs were enrolled. Demographic, clinical course, etiology, and antimicrobial resistance data of the SBIs were collected. Outcomes were also compared between patients who were classified as severe and critical on admission. RESULTS: Among 1495 patients hospitalized with COVID-19, 102 (6.8%) patients had acquired SBIs, and almost half of them (49.0%, 50/102) died during hospitalization. Compared with severe patients, critical patients had a higher chance of SBIs. Among the 159 strains of bacteria isolated from the SBIs, 136 strains (85.5%) were Gram-negative bacteria. The top three bacteria of SBIs were A. baumannii (35.8%, 57/159), K. pneumoniae (30.8%, 49/159), and S. maltophilia (6.3%, 10/159). The isolation rates of carbapenem-resistant A. baumannii and K. pneumoniae were 91.2 and 75.5%, respectively. Meticillin resistance was present in 100% of Staphylococcus aureus and Coagulase negative staphylococci, and vancomycin resistance was not found. CONCLUSIONS: SBIs may occur in patients hospitalized with COVID-19 and lead to high mortality. The incidence of SBIs was associated with the severity of illness on admission. Gram-negative bacteria, especially A. baumannii and K. pneumoniae, were the main bacteria, and the resistance rates of the major isolated bacteria were generally high. This was a single-center study; thus, our results should be externally examined when applied in other institutions.


Assuntos
Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Farmacorresistência Bacteriana/fisiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções Estafilocócicas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Betacoronavirus , China/epidemiologia , Coinfecção/mortalidade , Infecções por Coronavirus/patologia , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico
9.
Am J Perinatol ; 37(S 02): S5-S9, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32898875

RESUMO

Despite continued advances and developments in neonatal medicine, neonatal sepsis is the third leading cause of neonatal mortality and a major public health problem, especially in developing countries. Sepsis accounts for mortality for almost 50% of global children under 5 years of age.Over the past 50 years, there have been many advances in the diagnosis, prevention, and treatment of neonatal infections. The diagnostic advances include better culture techniques that permit more rapid confirmation of the diagnosis, advent of polymerase chain reaction (PCR) to rapidly diagnose viral infections, use of biologic markers indicating evidence of infection, and a better understanding of immunoglobulin markers of infection. From a therapeutic stand point, there have been a variety of antibiotics, antifungals, and antiviral agents, better approaches to prevent sepsis, specific immunotherapy, for example, respiratory syncytial virus (RSV); bundled approach to prevention of deep-line infection and better antibiotic stewardship, leading to earlier discontinuation of antibiotic therapy.Hand hygiene remains the benchmark and gold standard for late-onset sepsis prevention. The challenge has been that each decade, newer resistant bacteria dominate as the cause of sepsis and newer viruses emerge, for example, human immunodeficiency virus, zika virus, and novel coronavirus disease 2019.Future treatment options might include stem cell therapy, other antimicrobial protein and peptides, and targeting of pattern recognition receptors in an effort to prevent and/or treat sepsis in this vulnerable population. Also, the microbiome of premature infants has a smaller proportion of beneficial bacteria and higher numbers of pathogenic bacteria compared with term infants, likely owing to higher frequencies of cesarean sections, antibiotic use, exposure to the hospital environment, and feeding nonhuman milk products. Modifying the microbiome with more mother's milk and shorter duration of antibiotics in noninfected babies should be a goal. KEY POINTS: · Neonatal sepsis remains a leading cause of mortality.. · Challenges include bacterial resistance and newer viruses.. · Future treatments may include newer antibiotics/antivirals and stem cell therapy..


Assuntos
Antibacterianos/uso terapêutico , Unidades de Terapia Intensiva Neonatal , Sepse Neonatal/mortalidade , Sepse Neonatal/prevenção & controle , Antivirais/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/mortalidade , Doenças do Prematuro/prevenção & controle , Sepse Neonatal/tratamento farmacológico
10.
Nat Commun ; 11(1): 4379, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873785

RESUMO

The gut microbiome harbors a 'silent reservoir' of antibiotic resistance (AR) genes that is thought to contribute to the emergence of multidrug-resistant pathogens through horizontal gene transfer (HGT). To counteract the spread of AR, it is paramount to know which organisms harbor mobile AR genes and which organisms engage in HGT. Despite methods that characterize the overall abundance of AR genes in the gut, technological limitations of short-read sequencing have precluded linking bacterial taxa to specific mobile genetic elements (MGEs) encoding AR genes. Here, we apply Hi-C, a high-throughput, culture-independent method, to surveil the bacterial carriage of MGEs. We compare two healthy individuals with seven neutropenic patients undergoing hematopoietic stem cell transplantation, who receive multiple courses of antibiotics, and are acutely vulnerable to the threat of multidrug-resistant infections. We find distinct networks of HGT across individuals, though AR and mobile genes are associated with more diverse taxa within the neutropenic patients than the healthy subjects. Our data further suggest that HGT occurs frequently over a several-week period in both cohorts. Whereas most efforts to understand the spread of AR genes have focused on pathogenic species, our findings shed light on the role of the human gut microbiome in this process.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Microbioma Gastrointestinal/genética , Transferência Genética Horizontal , Genes Bacterianos/efeitos dos fármacos , Adulto , Idoso , Antibacterianos/uso terapêutico , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Microbioma Gastrointestinal/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Sequências Repetitivas Dispersas/efeitos dos fármacos , Pessoa de Meia-Idade
11.
Western Pac Surveill Response J ; 11(1): 41-46, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963890

RESUMO

Problem: Emerging bacterial antimicrobial (antibiotic) resistance (AMR) is a global threat to human health. However, most lower income countries do not have microbiological diagnostic testing for prompt, reliable confirmation of bloodstream infection and identification of AMR. Context: Clinicians in Pacific island nations are increasingly challenged by patients who have infection due to antimicrobial-resistant bacteria. Treatment of infection remains empirical because of a lack of diagnostic testing capacity and may follow guidelines that were formulated without reference to local measures of AMR prevalence. There is limited understanding among clinicians of microbiology testing and test interpretation. Action: Examine the lessons learnt from pilot laboratory development programmes in two Pacific island nations that focused on establishing standard procedures for micrological diagnostics and antimicrobial susceptibility testing (AST) and on improving the training of clinicians to increase their use of laboratory services. Outcome: The pilot programmes addressed a range of logistical difficulties and evaluated two blood culture systems. They also examined and improved internal QC implementation and evaluated the prevalence of AMR. Discussion: Continued development of microbiological diagnostic capability in the Pacific region is paramount. Pacific Island nations need to develop the capability of at least one central laboratory to culture AMR pathogens and subject them to quality-controlled AST or arrange for suitable referral to a nearby country. Discussion: This study demonstrated a persistently high prevalence of three major bacterial STIs across four countries in WHO's Western Pacific Region during nearly two decades. Further strengthening of strategies to control and prevent STIs is warranted.


Assuntos
Antibacterianos/farmacologia , Técnicas Bacteriológicas/normas , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana/normas , Técnicas de Diagnóstico Molecular/normas , Humanos , Ilhas do Pacífico , Projetos Piloto , Controle de Qualidade
12.
Cochrane Database Syst Rev ; 9: CD001912, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32997797

RESUMO

BACKGROUND: Staphylococcus aureus causes pulmonary infection in young children with cystic fibrosis. Prophylactic antibiotics are prescribed hoping to prevent such infection and lung damage. Antibiotics have adverse effects and long-term use might lead to infection with Pseudomonas aeruginosa. This is an update of a previously published review. OBJECTIVES: To assess continuous oral antibiotic prophylaxis to prevent the acquisition of Staphylococcus aureus versus no prophylaxis in people with cystic fibrosis, we tested the following hypotheses to investigate whether prophylaxis: 1. improves clinical status, lung function and survival; 2. leads to fewer isolates of Staphylococcus aureus; 3. causes adverse effects (e.g. diarrhoea, skin rash, candidiasis); 4. leads to fewer isolates of other common pathogens from respiratory secretions; 5. leads to the emergence of antibiotic resistance and colonisation of the respiratory tract with Pseudomonas aeruginosa. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Companies manufacturing anti-staphylococcal antibiotics were contacted. Most recent search of the Group's Register: 27 February 2020. Online trials registries were also searched. Most recent search of online trials registries: 15 September 2020. SELECTION CRITERIA: Randomised trials of continuous oral prophylactic antibiotics (given for at least one year) compared to intermittent antibiotics given 'as required', in people with cystic fibrosis of any disease severity. DATA COLLECTION AND ANALYSIS: The authors assessed studies for eligibility and methodological quality and extracted data. The quality of the evidence was assessed using the GRADE criteria. The review's primary outcomes of interest were lung function by spirometry (forced expiratory volume in one second (FEV1)) and the number of people with one or more isolates of Staphylococcus aureus (sensitive strains). MAIN RESULTS: We included four studies, with a total of 401 randomised participants aged zero to seven years on enrolment; one study is ongoing. The two older included studies generally had a higher risk of bias across all domains, but in particular due to a lack of blinding and incomplete outcome data, than the two more recent studies. We only regarded the most recent study as being generally free of bias, although even here we were not certain of the effect of the per protocol analysis on the study results. Evidence quality was judged to be low for all outcomes assessed after being downgraded based on GRADE assessments. Downgrading decisions were due to limitations in study design (all outcomes), for imprecision and for inconsistency . Prophylactic anti-staphylococcal antibiotics probably make little or no difference to lung function measured as FEV1 % predicted after six years (mean difference (MD) -2.30, 95% confidence interval (CI) -13.59 to 8.99, one study, n = 119, low-quality evidence); but may reduce the number of children having one or more isolates of Staphylococcus aureus at two years (odds ratio (OR) 0.21, 95% CI 0.13 to 0.35, three studies, n = 315, low-quality evidence). At the same time point, there may be little or no effect on nutrition as reported using weight z score (MD 0.06, 95% CI -0.33 to 0.45, two studies, n = 140, low-quality evidence), additional courses of antibiotics (OR 0.18, 95% CI 0.01 to 3.60, one study, n = 119, low-quality evidence) or adverse effects (low-quality evidence). There was no difference in the number of isolates of Pseudomonas aeruginosa between groups at two years (OR 0.74, 95% CI 0.45 to 1.23, three studies, n = 312, low-quality evidence), though there was a trend towards a lower cumulative isolation rate of Pseudomonas aeruginosa in the prophylaxis group at two and three years and towards a higher rate from four to six years. As the studies reviewed lasted six years or less, conclusions cannot be drawn about the long-term effects of prophylaxis. AUTHORS' CONCLUSIONS: Anti-staphylococcal antibiotic prophylaxis may lead to fewer children having isolates of Staphylococcus aureus, when commenced early in infancy and continued up to six years of age. The clinical importance of this finding is uncertain. Further research may establish whether the trend towards more children with CF with Pseudomonas aeruginosa, after four to six years of prophylaxis, is a chance finding and whether choice of antibiotic or duration of treatment might influence this.


Assuntos
Antibioticoprofilaxia , Fibrose Cística/microbiologia , Infecções Respiratórias/prevenção & controle , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus , Viés , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Volume Expiratório Forçado , Crescimento , Humanos , Lactente , Recém-Nascido , Pseudomonas aeruginosa/isolamento & purificação , Ensaios Clínicos Controlados Aleatórios como Assunto , Staphylococcus aureus/isolamento & purificação
13.
PLoS One ; 15(8): e0238016, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866193

RESUMO

BACKGROUND: Since a meta-analysis showed little or no effect of second-line injectables on treatment success, and using injectables may induce ototoxicity, injectable-free rifampicin-resistant tuberculosis (RR-TB) treatment regimens are recommended. However, acquired resistance preventing activity was overlooked. No previous study assessed the effect of shortening the duration of kanamycin administration to 2 months during the intensive phase of the RR-TB shorter treatment regimen (STR). METHODS: Retrospective cohort study of the effect of using 2 months of kanamycin instead of the standard 4(+) months (extension if lack of smear conversion at 4 months) on recurrence (either treatment failure or relapse) and fluoroquinolone acquired drug resistance, in patients treated with a gatifloxacin-based STR in Damien Foundation supported clinics in Bangladesh. Logistic regression was used to estimate associations. RESULTS: Five of 52 (9.6%) treated with a STR containing two months of kanamycin had recurrence, compared to 21 of 738 (2.8%) patients treated with the standard STR containing 4(+) months of kanamycin (OR 3.7; 95%CI:1.5-10.3). In those with initially fluoroquinolone-susceptible TB, acquired resistance to fluoroquinolone was detected in none of 639 patients treated with 4(+) months of kanamycin and two (4.5%) of 44 treated with two months of kanamycin (OR 75.2; 95%CI:3.6-1592.1). CONCLUSION: Two months of kanamycin was insufficient to prevent recurrence with acquired resistance to gatifloxacin, the core drug of the most effective RR-TB STR. Injectable mediated resistance prevention is important to reach high effectiveness, to safeguard all treatment options after recurrence, and to prevent the spread of resistant TB. Studies on all-oral regimens should also assess the effect of regimen composition on resistance acquisition. Until evidence shows that other drugs can assure at least the same strong resistance preventing activity of the injectables, it seems wise to continue using this group of drugs, and adapt the regimen if any ototoxicity is detected.


Assuntos
Farmacorresistência Bacteriana/efeitos dos fármacos , Rifampina/farmacologia , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Injeções , Canamicina/administração & dosagem , Canamicina/farmacologia , Canamicina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Urologiia ; (4): 124-130, 2020 Sep.
Artigo em Russo | MEDLINE | ID: mdl-32897026

RESUMO

The review describes large-scale microbiological studies performed in Russia over the past 20 years to study urinary tract infections (UTIs). The article analyzes data on the structure of UTI pathogens, as well as on the antibiotic resistance of the main uropathogens, compares the data with similar foreign studies. From 1999 year, 7 large multicenter microbiological studies were carried out in Russia to obtain the data of the antimicrobial resistance of uropathogens caused community-acquired UTIs. An analysis of the data allows described trends in antimicrobial resistance - high level of resistance of uropathogens to aminopenicillins, co-trimoxazole, fluoroquinolones, an increase antimicrobial resistance to amoxicillin / clavulanate, and third generation cephalosporins. In review discussed a critical assessment of various approaches to the use of data on the sensitivity of uropathogens to antimicrobial drugs when antimicrobial therapy is provided. The necessity of comparing not only microbiological data obtained from different sources, but also clinical data, characteristics of pharmacodynamics and pharmacokinetics of antimicrobial drugs is discussed. The review discusses the difficulties associated with the clinical interpretation of data on the sensitivity of microorganisms, primarily in the limited objective information describing the correlation of in vitro data with the clinical efficacy of therapy. The publication substantiates the need for a wider conduct of not only microbiological, but also clinical studies to obtain data on the comparative efficacy of the used antimicrobial drugs.


Assuntos
Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Federação Russa
16.
Chemosphere ; 258: 127392, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947654

RESUMO

Discharge of urban stormwater containing organic matter, heavy metals and sometime human feces, to the natural aquatic reservoirs without any treatment is not only an environmental problem. It can lead to prevalence of antibiotic resistant bacteria in stormwater systems and transmission of antibiotic resistance genes to the environment. We performed antibiotic resistome identification and virus detection in stormwater samples from Stockholm, using publicly available metagenomic sequencing MinION data. A MinION platform offers low-cost, precise environmental metagenomics analysis. 37 groups of antibiotic resistant bacteria (ARB), 11 resistance types with 26 resistance mechanisms - antibiotic resistance genes (ARGs) giving tolerance to the aminoglycoside, beta-lactams, fosmidomycin, MLS, multidrug and vancomycin were identified using ARGpore pipeline. The majority of the identified bacteria species were related to the natural environment such as soil and were not dangerous to human. Alarmingly, human pathogenic bacteria carrying resistance to antibiotics currently used against them (Bordetella resistant to macrolides and multidrug resistant Propionibacterium avidum) were also found in the samples. Most abundant viruses identified belonged to Caudovirales and Herpesvirales and they were not carrying ARGs. Unlike the virome, resistome and ARB were not unique for stormwater sampling points. This results underline the need for extensive monitoring of the microbial community structure in the urban stormwater systems to assess antimicrobial resistance spread.


Assuntos
Farmacorresistência Bacteriana/genética , Metagenoma , Bactérias/efeitos dos fármacos , Monitoramento Ambiental , Fezes/microbiologia , Genes Bacterianos/efeitos dos fármacos , Humanos , Macrolídeos , Metagenômica/métodos , Microbiota/efeitos dos fármacos , Águas Residuárias/microbiologia , beta-Lactamas
17.
Zhonghua Xue Ye Xue Za Zhi ; 41(8): 643-648, 2020 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-32942817

RESUMO

Objective: To investigate the distribution of pathogens and the antibiotic resistance profile of bloodstream infections in adult patients with hematological diseases in the period 2014-2018 to provide evidence for the rational use of antibiotics. Methods: We retrospectively analyzed the bloodstream infections in patients with hematological diseases from January 2014 to December 2018 at the institute of Hematology & Blood Diseases Hospital; this included an assessment of the clinical characteristics, distribution of pathogens, and antibiotic resistance data. Results: There were 1935 episodes of BSIs in the 1478 patients who were studied; among these, 1700 episodes occurred in the neutropenic phase. The 7-day and 30-day all-cause mortality rates were 5.5% and 8.2%, respectively. Bloodstream infection was usually accompanied by respiratory tract, perianal zone mucositis, and digestive tract symptoms; the respective proportions were 12.4%, 12.3%, and 9.1%, respectively. Total 2025 strains were isolated; 1551 (76.6%) of the pathogens were gram-negative bacteria, mainly Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa; 423 (20.9%) were gram-positive bacteria, mainly Staphylococcus spp. and Streptococcus spp. Viridans; 51 (2.5%) were fungi, mainly Candida tropicalis. The resistance rates of Enterobateriaceae to piperacillin/tazobactam, carbapenems, amikacin were <10%. The resistance rates of K. pneumoniae to cefepime, piperacillin/tazobactam and meropenem increased annually. The resistance rates of Pseudomonas aeruginosa to piperacillin/tazobactam, quinolones, Aminoglycosides were <5% even when compared to carbapenems. Eleven stains of methicillin-resistant S. aureus and 1 stain of vancomycin-resistant Enterococcus faecium were detected. Conclusion: The pathogens of bloodstream infection in adult patients with hematological diseases are widely distributed. The resistance rates of different strains vary; the rates in some species had a tendency to increase. Antibiotics should be selected rationally as per the distribution of pathogens and resistance to antibiotics in different patient groups.


Assuntos
Bacteriemia , Doenças Hematológicas , Staphylococcus aureus Resistente à Meticilina , Adulto , Antibacterianos , Farmacorresistência Bacteriana , Bactérias Gram-Negativas , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
18.
Zhonghua Xue Ye Xue Za Zhi ; 41(8): 655-660, 2020 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-32942819

RESUMO

Objective: To investigate the microbiologic and clinical characteristics of bloodstream infection in neutropenic pediatric patients with hematological malignancies and provide data support for the rational use of antimicrobial agents in these patients. Methods: A retrospective analysis was performed on the clinical data, pathogen species distribution, and drug sensitivity data of bloodstream infection in neutropenic pediatric patients with hematological malignancies from the Institute of Hematology & Blood Diseases Hospital from January 2014 to December 2018. Results: Total 537 episodes of bloodstream infections occurred in 427 neutropenic children with hematological malignancies; the 30-day all-cause mortality rate was 3.7%. The clinical feature of 44.7% patients with bloodstream infection was only fever, and the pathogenic bacteria were mainly enterobacteriaceae bacteria. Bloodstream infection was usually accompanied by oral mucosa (20.7%) , respiratory tract (20.5%) , and digestive tract (14.3%) symptoms. The distribution of pathogens in patients with different symptoms of bloodstream infection varied (χ(2)=40.561, P=0.001) . Total 550 strains of pathogens were isolated, and the top 5 bacteria were Streptococcus aureus (109 strains, 19.8%) , Escherichia coli (99 strains, 18.0%) , Staphylococcus epidermidis (75 strains, 13.6%) , Klebsiella pneumoniae (67 strains, 12.2%) , and Staphylococcus aureus (32 strains, 5.8%) . The resistance rates of Enterobacteriaceae and Pseudomonas aeruginosa to piperacillin/tazobactam and carbapenems were <5%. The proportion of methicillin-resistant Staphylococcus aureus (MRSA) in Staphylococcus aureus was 9.7%. Conclusion: The proportion of pathogenic bacteria gram-positive cocci and gram-negative bacilli in the bloodstream infection of neutropenic children with hematological malignancies was approximately the same, suggesting that the use of antimicrobial agents should be broad-spectrum. Carbapenems, glycopeptides, and enzyme inhibitor complexes still have good effects.


Assuntos
Bacteriemia , Neoplasias Hematológicas , Staphylococcus aureus Resistente à Meticilina , Antibacterianos , Bacteriemia/complicações , Criança , Farmacorresistência Bacteriana , Neoplasias Hematológicas/complicações , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos
19.
Ecotoxicol Environ Saf ; 205: 111267, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32992213

RESUMO

Arsenic is a common contaminant in gold mine soil and tailings. Microbes present an opportunity for bio-treatment of arsenic, since it is a sustainable and cost-effective approach to remove arsenic from water. However, the development of existing bio-treatment approaches depends on isolation of arsenic-resistant microbes from arsenic contaminated samples. Microbial cultures are commonly used in bio-treatment; however, it is not established whether the structure of the cultured isolates resembles the native microbial community from arsenic-contaminated soil. In this milieu, a culture-independent approach using Illumina sequencing technology was used to profile the microbial community in situ. This was coupled with a culture-dependent technique, that is, isolation using two different growth media, to analyse the microbial population in arsenic laden tailing dam sludge based on the culture-independent sequencing approach, 4 phyla and 8 genera were identified in a sample from the arsenic-rich gold mine. Firmicutes (92.23%) was the dominant phylum, followed by Proteobacteria (3.21%), Actinobacteria (2.41%), and Bacteroidetes (1.49%). The identified genera included Staphylococcus (89.8%), Pseudomonas (1.25), Corynebacterium (0.82), Prevotella (0.54%), Megamonas (0.38%) and Sphingomonas (0.36%). The Shannon index value (3.05) and Simpson index value (0.1661) indicated low diversity in arsenic laden tailing. The culture dependent method exposed significant similarities with culture independent methods at the phylum level with Firmicutes, Proteobacteria and Actinobacteria, being common, and Firmicutes was the dominant phylum whereas, at the genus level, only Pseudomonas was presented by both methods. It showed high similarities between culture independent and dependent methods at the phylum level and large differences at the genus level, highlighting the complementarity between the two methods for identification of the native population bacteria in arsenic-rich mine. As a result, the present study can be a resource on microbes for bio-treatment of arsenic in mining waste.


Assuntos
Actinobacteria/efeitos dos fármacos , Arsênico/toxicidade , Firmicutes/efeitos dos fármacos , Metagenômica/métodos , Proteobactérias/efeitos dos fármacos , Poluentes do Solo/toxicidade , Actinobacteria/citologia , Actinobacteria/genética , Arsênico/análise , Biodegradação Ambiental , Meios de Cultura/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Firmicutes/citologia , Firmicutes/genética , Ouro , Testes de Sensibilidade Microbiana , Microbiota/efeitos dos fármacos , Microbiota/genética , Mineração , Proteobactérias/citologia , Proteobactérias/genética , RNA Ribossômico 16S/genética , Solo/química , Microbiologia do Solo , Poluentes do Solo/análise
20.
PLoS One ; 15(9): e0237948, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877437

RESUMO

The lack of new antibiotics necessitates the improvement of existing ones, many of which are limited by toxic side effects. Aminoglycosides, antibiotics with excellent activity and low bacterial resistance, are hampered by dose-dependent toxic effects in patients (nephrotoxicity, ototoxicity). High antibiotic concentrations are often required to treat dormant, non-dividing bacteria, though previous studies show that aminoglycosides can be activated against such bacteria by specific metabolites. Here, we employed this mechanism to greatly boost the activity of low concentrations of aminoglycosides against prevalent Gram-negative pathogens (Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae), suggesting that less toxic drug concentrations might be used effectively in patients. We go on to show that this effect improved treatment of biofilms, did not increase aminoglycoside resistance, and was due to the generation of proton-motive force (PMF). By single-cell microscopy, we demonstrate that stationary-phase cells, while non-dividing, actively maintain a growth-arrested state that is not reversed by metabolite addition. Surprisingly, within starved populations, we observed rare cells (3%) that divided without added nutrients. Additionally, we discovered that mannitol could directly protect human kidney cells from aminoglycoside cytotoxicity, independent of the metabolite's effect on bacteria. This work forwards a mechanism-based strategy to improve existing antibiotics by mitigating their toxic side effects.


Assuntos
Aminoglicosídeos/química , Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/tratamento farmacológico , Biofilmes/crescimento & desenvolvimento , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Antibacterianos/química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana
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