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1.
Chemosphere ; 262: 127768, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32777611

RESUMO

Heavy metals and antimicrobial resistant bacteria in livestock and poultry environments can cause declines in production and significant economic losses, leading to potential environmental and public health issues. In this study, the heavy metal pollution status of livestock breeding water bodies in the Dawen river basin of Shandong Province in China was evaluated, and a total of 10 heavy metals were measured. In addition, antimicrobial susceptibility tests were conducted for Escherichia coli strains isolated from the water samples. The results showed that among all the metals, copper, zinc, and iron were detected at each sampling point, followed by nickel (detection rate of 95.74%), arsenic (detection rate of 89.36%), selenium (detection rate of 68.09%), lead (detection rate of 27.66%), and mercury (detection rate of 12.77%). Cadmium and hexavalent chromium were not detected. The contents of nine heavy metals were below the existing water standard values in China, whereas the iron pollution index in the water body in the study area was large and may pose a potential risk. A total of 17 E. coli isolates showed different resistance to ß-lactams, aminoglycosides, tetracyclines, quinolone antibiotics and chloramphenicol, but were mainly resistant to ß-lactams and tetracyclines. The detection rate of the tetA resistance gene was relatively high, indicating the overuse of cephalosporins and tetracyclines. The results of the present study might provide evidence of metal pollution and theoretical basis on the treatment of colibacillosis in the livestock industries.


Assuntos
Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Monitoramento Ambiental/métodos , Escherichia coli/isolamento & purificação , Metais Pesados/análise , Águas Residuárias/química , Poluentes Químicos da Água/análise , Antibacterianos/farmacologia , China , Indústria de Laticínios , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Fazendas , Rios/química , Rios/microbiologia , Águas Residuárias/microbiologia
2.
BMC Infect Dis ; 20(1): 816, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33167886

RESUMO

BACKGROUND: The prevalence of Staphylococcus aureus varies depending on the healthcare facility, region and country. To understand its genetic diversity, transmission, dissemination, epidemiology and evolution in a particular geographical location, it is important to understand the similarities and variations in the population being studied. This can be achieved by using various molecular characterisation techniques. This study aimed to provide detailed molecular characterisation of South African mecA-positive S. aureus blood culture isolates by describing the SCCmec types, spa types and to lesser extent, the sequence types obtained from two consecutive national surveillance studies. METHODS: S. aureus blood culture isolates from a national laboratory-based and enhanced surveillance programme were identified and antimicrobial susceptibility testing was performed using automated systems. A real-time PCR assay confirmed the presence of the methicillin-resistance determinant, mecA. Conventional PCR assays were used to identify the SCCmec type and spa type, which was subsequently analysed using the Ridom StaphType™ software. Multilocus sequence typing was performed on selected isolates using conventional methods. MRSA clones were defined by their sequence type (ST), SCCmec type and spa type. RESULTS: A detailed description of findings is reported in this manuscript. SCCmec type III predominated overall followed by type IV. A total of 71 different spa types and 24 novel spa types were observed. Spa type t037 was the most common and predominated throughout followed by t1257. Isolates were multidrug resistant; isolates belonging to all SCCmec types were resistant to most of the antibiotics with the exception of type I; isolates with spa type t045 showed resistance to all antibiotics except vancomycin. The most diverse SCCmec-spa type complex was composed of the SCCmec type IV element and 53 different spa types. CONCLUSION: Although ST data was limited, thereby limiting the number of clones that could be identified, the circulating clones were relatively diverse.


Assuntos
Proteínas de Bactérias/genética , Variação Genética , Sequências Repetitivas Dispersas/genética , Staphylococcus aureus Resistente à Meticilina/genética , Proteínas de Ligação às Penicilinas/genética , Infecções Estafilocócicas/epidemiologia , Proteína Estafilocócica A/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/sangue , Hemocultura , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Meticilina/farmacologia , Meticilina/uso terapêutico , Resistência a Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Proteínas de Ligação às Penicilinas/sangue , Reação em Cadeia da Polimerase em Tempo Real , África do Sul/epidemiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Vancomicina/farmacologia , Vancomicina/uso terapêutico
3.
BMC Infect Dis ; 20(1): 833, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176714

RESUMO

BACKGROUND: Alcaligenes faecalis is usually causes opportunistic infections in humans. Alcaligenes faecalis infection is often difficult to treat due to its increased resistance to several antibiotics. The results from a clinical study of patients with Alcaligenes faecalis infection may help improve patients' clinical care. METHODS: We conducted a retrospective analysis of all patients presenting with Alcaligenes faecalis infection from January 2014 to December 2019. The medical records of all patients were reviewed for demographic information, clinical symptoms and signs, comorbidities, use of intravenous antibiotics within the past three months, bacterial culture, antibiotics sensitivity test, and clinical outcomes. RESULTS: Sixty-one cases of Alcaligenes faecalis infection were seen during the study period, including 25 cases of cystitis, nine cases of diabetic foot infection, eight cases of pneumonia, seven cases of acute pyelonephritis, three cases of bacteremia, and nine cases of infection at specific sites. Thirty-seven patients (60.7%) had a history of receiving intravenous antibiotics within three months of the diagnosis. Fifty-one (83.6%) cases were mixed with other bacterial infections. Extensively drug-resistant infections have been reported since 2018. The best sensitivity rate to Alcaligenes faecalis was 66.7% for three antibiotics (imipenem, meropenem, and ceftazidime) in 2019. Two antibiotics (ciprofloxacin and piperacillin/tazobactam) sensitivity rates to A. faecalis were less than 50%. CONCLUSIONS: The most frequent Alcaligenes faecalis infection sites, in order, are the bloodstream, urinary tract, skin and soft tissue, and middle ear. The susceptibility rate of Alcaligenes faecalis to commonly used antibiotics is decreasing. Extensively drug-resistant Alcaligenes faecalis infections have emerged.


Assuntos
Alcaligenes faecalis/efeitos dos fármacos , Antibacterianos/uso terapêutico , Ceftazidima/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Imipenem/uso terapêutico , Meropeném/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcaligenes faecalis/genética , Alcaligenes faecalis/isolamento & purificação , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
4.
BMC Infect Dis ; 20(1): 752, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054726

RESUMO

BACKGROUND: Molecular epidemiological studies of Mycobacterium tuberculosis (MTB) are the core of current research to find out the association of the M. tuberculosis genotypes with its outbreak and transmission. The high prevalence of the Beijing genotype strain among multidrug resistance (MDR) TB has already been reported in various studies around India. The overall objective of this study was to detect the prevalence of Beijing genotype strains of MDR M. tuberculosis and their association with the clinical characteristics of TB patients. METHODS: In this study 381 M. tuberculosis clinical isolates were obtained from sputum samples from 2008 to 2014. The multiplex-PCR and Spoligotyping (n = 131) methods were used to investigate the prevalence of the Beijing genotype strain by targeting the Rv2820 gene and their association with drug resistance and clinical characteristics of TB patients. The drug susceptibility testing of first-line anti-TB drugs was performed by using the proportion method and MGIT960. A collection of isolates having Beijing and non-Beijing strains were also characterized to see if Beijing genotype strains had a higher rate of mutations at codons 516, 526 and 531 of the 81-bp region of the rpoB gene, codon 315 of the katG gene, and codon 306 of the embB gene. RESULTS: The sensitivities and specificities of multiplex-PCR assay compared to that of standard Spoligotyping was detected to be 100%. Further, we observe that the multi drug-resistance was significantly associated with Beijing genotype strains (p = 0.03) and a strong correlation between Beijing genotype strains and specific resistance mutations at the katG315, rpoB531, and embB306 codons (p = < 0.0001, < 0.0001 & 0.0014 respectively) was also found. CONCLUSIONS: This rapid, simple, and cost-effective multiplex PCR assay can effectively be used for monitoring the prevalence of Beijing genotype strains in low resource settings. Findings of this study may provide a scientific basis for the development of new diagnostic tools for detection and effective management of DR-TB in countries with a higher incidence rate of Beijing genotype strains.


Assuntos
Proteínas de Bactérias/genética , Catalase/genética , RNA Polimerases Dirigidas por DNA/genética , Mycobacterium tuberculosis/genética , Pentosiltransferases/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/farmacologia , Criança , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Genótipo , Humanos , Índia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex/métodos , Taxa de Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto Jovem
5.
BMC Infect Dis ; 20(1): 804, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121455

RESUMO

BACKGROUND: Misuse and overuse of antibiotics by physicians in the treatment of children is common in China. This study aimed to reveal the overall use of antibiotics to treat children hospitalized in four types of pediatric wards. METHODS: Seven independent point prevalence surveys (PPSs) were conducted in Shanghai Children's Hospital of Shanghai Jiao Tong University over the period 2012 to 2018. Pediatric ward types were defined general pediatric medical, pediatric surgical, pediatric intensive care units (PICU), and neonatal. RESULTS: A total of 3975 pediatric patients were included in the study, of which 63.9% received at least one dose antibiotic. The top five classes of antibiotics administered were cephalosporins (43.8%, n = 1743), penicillins (13.2%, n = 526), carbapenems (8.7%, n = 347), nitroimidazoles (7.1%, n = 281) and macrolides (6.5%, n = 257). The five most commonly used generic antibiotics were cefuroxime (14.9%, n = 594), ceftriaxone (9.7%, n = 387), cefotaxime (9.0%, n = 358), meropenem (8.1%, n = 320) and ampicillin/sulbactam (6.0%, n = 239). Meropenem was among top five antibiotics prescribed in the general pediatric, PICU and neonatal wards and sixth in the pediatric surgical wards. Of all children on antibiotics, 23.4% received prophylactic treatment, and prophylaxis accounted for 68.1% of indications for treatment in the pediatric surgical wards. CONCLUSIONS: Given that over-treatment with third-generation cephalosporins and carbapenems has been associated with treatment-resistant infections, the prescription of these drugs should be strictly controlled and monitored, and measures should be taken to improve the management of surgical prophylaxis in hospitalized children in China.


Assuntos
Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Cefalosporinas/uso terapêutico , Hospitais Pediátricos , Penicilinas/uso terapêutico , Centros de Atenção Terciária , Adolescente , Antibioticoprofilaxia , Carbapenêmicos/efeitos adversos , Cefalosporinas/efeitos adversos , Criança , Pré-Escolar , China , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Prescrições , Prevalência , Inquéritos e Questionários
6.
Isr Med Assoc J ; 22(10): 628-632, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33070487

RESUMO

BACKGROUND: Antimicrobial resistance is the main determinant for Helicobacter pylori treatment failure. Regional antimicrobial susceptibility testing is essential for appropriate antibiotic selection to achieve high eradication rates. OBJECTIVES: To assess primary and secondary H. pylori resistance in isolates recovered from Israeli naïve and treatment failures. To identify predictors of resistance. METHODS: In this retrospective study, in vitro activity of isolated H. pylori in Israel was tested against metronidazole, clarithromycin, tetracycline, amoxicillin, and levofloxacin in 128 isolates: 106 from treatment failures and 22 from naïve untreated patients. The minimal inhibitory concentration values were determined according to the Etest instructions. Treatment failures previously failed at least one treatment regimen. RESULTS: No resistance to amoxicillin and tetracycline was detected. Resistance to metronidazole and clarithromycin was high in H. pylori isolates both from treated and untreated patients: 68.9%, 68.2% for metronidazole (P = 0.95); 53.8%, 59.1% for clarithromycin (P = 0.64), respectively. Dual resistance to clarithromycin and metronidazole was seen in 45.3% and 50%, respectively (P = 0.68). Resistance to levofloxacin was detected in two (1.9%) isolates from treated patients. Simultaneous resistance to clarithromycin, metronidazole, and levofloxacin was seen in an isolate from a treated patient. Age was the only predictor of resistance to metronidazole and clarithromycin. CONCLUSIONS: The resistance rates to both single and dual metronidazole and clarithromycin in isolates recovered from both Israeli naïve and treated patients is high. Low resistance renders levofloxacin an attractive option for second or third line treatment. Therapeutic outcome would benefit from susceptibility testing after treatment failure.


Assuntos
Claritromicina/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Metronidazol/farmacologia , Centros Médicos Acadêmicos , Adulto , Distribuição de Qui-Quadrado , Estudos de Coortes , Estudos Transversais , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Israel , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Estatísticas não Paramétricas
7.
Mem Inst Oswaldo Cruz ; 115: e200215, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32965331

RESUMO

The human-adapted strains of the Mycobacterium tuberculosis complex (MTBC) comprise seven phylogenetic lineages originally associated with their geographical distribution. Here, we report the genomes of three drug-resistant clinical isolates of the Latin American-Mediterranean (LAM) family collected in Kazakhstan. We utilised whole-genome sequencing to study the distribution and drug resistance of these isolates. Phylogenetic analysis grouped the genomes described in this study with the sequences from Russia, Uzbekistan, and Kazakhstan belonging to the LAM family. One isolate has acquired extensive drug resistance to seven antituberculosis drugs. Our results suggest at least two multi-drug resistant (MDR)/extensively drug-resistant (XDR)-associated genotypes of the LAM family circulate in Kazakhstan.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Genômica , Genótipo , Humanos , Cazaquistão , América Latina , Filogenia , Tuberculose Resistente a Múltiplos Medicamentos/genética
8.
PLoS Biol ; 18(9): e3000856, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941420

RESUMO

Antibiotic combination therapies are important for the efficient treatment of many types of infections, including those caused by antibiotic-resistant pathogens. Combination treatment strategies are typically used under the assumption that synergies are conserved across species and strains, even though recent results show that the combined treatment effect is determined by specific drug-strain interactions that can vary extensively and unpredictably, both between and within bacterial species. To address this problem, we present a new method in which antibiotic synergy is rapidly quantified on a case-by-case basis, allowing for improved combination therapy. The novel CombiANT methodology consists of a 3D-printed agar plate insert that produces defined diffusion landscapes of 3 antibiotics, permitting synergy quantification between all 3 antibiotic pairs with a single test. Automated image analysis yields fractional inhibitory concentration indices (FICis) with high accuracy and precision. A technical validation with 3 major pathogens, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, showed equivalent performance to checkerboard methodology, with the advantage of strongly reduced assay complexity and costs for CombiANT. A synergy screening of 10 antibiotic combinations for 12 E. coli urinary tract infection (UTI) clinical isolates illustrates the need for refined combination treatment strategies. For example, combinations of trimethoprim (TMP) + nitrofurantoin (NIT) and TMP + mecillinam (MEC) showed synergy, but only for certain individual isolates, whereas MEC + NIT combinations showed antagonistic interactions across all tested strains. These data suggest that the CombiANT methodology could allow personalized clinical synergy testing and large-scale screening. We anticipate that CombiANT will greatly facilitate clinical and basic research of antibiotic synergy.


Assuntos
Antibacterianos/administração & dosagem , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana/métodos , Algoritmos , Andinocilina/administração & dosagem , Andinocilina/farmacologia , Antibacterianos/farmacologia , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Humanos , Testes de Sensibilidade Microbiana/instrumentação , Nitrofurantoína/administração & dosagem , Nitrofurantoína/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Reprodutibilidade dos Testes , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Trimetoprima/administração & dosagem , Trimetoprima/farmacologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
9.
Nat Commun ; 11(1): 4522, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908144

RESUMO

A unique, protective cell envelope contributes to the broad drug resistance of the nosocomial pathogen Acinetobacter baumannii. Here we use transposon insertion sequencing to identify A. baumannii mutants displaying altered susceptibility to a panel of diverse antibiotics. By examining mutants with antibiotic susceptibility profiles that parallel mutations in characterized genes, we infer the function of multiple uncharacterized envelope proteins, some of which have roles in cell division or cell elongation. Remarkably, mutations affecting a predicted cell wall hydrolase lead to alterations in lipooligosaccharide synthesis. In addition, the analysis of altered susceptibility signatures and antibiotic-induced morphology patterns allows us to predict drug synergies; for example, certain beta-lactams appear to work cooperatively due to their preferential targeting of specific cell wall assembly machineries. Our results indicate that the pathogen may be effectively inhibited by the combined targeting of multiple pathways critical for envelope growth.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Infecção Hospitalar/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Parede Celular/efeitos dos fármacos , Parede Celular/genética , Parede Celular/metabolismo , Infecção Hospitalar/microbiologia , Análise Mutacional de DNA , Elementos de DNA Transponíveis/genética , DNA Bacteriano/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade Microbiana , Mutação
10.
Niger J Clin Pract ; 23(8): 1155-1162, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32788495

RESUMO

Objective: The blaOXA resistance genes and ISAba1 were examined in 70 samples from lower respiratory tract of hospitalized patients. Materials and Methods: Of the 67 isolates obtained, almost half (46.3%) of them were from endotracheal aspirate, and most were collected from the intensive care units of the reanimation (37.3%) and internal medicine (32.8%) units. Results: Three samples from the internal medicine intensive care unit had positive cultures. Of the multidrug resistant (MDR) samples, 70 isolates (>50%) were moderately sensitive, while fewer (10%) were resistant to tigecycline. In contrast, 100% were sensitive to colistin. All strains were found to be positive for blaOXA-23-like and blaOXA-51-like genes, whereas no blaOXA-40-like and blaOXA-58-like genes were detected. The ISAba1 positivity rate was 90.0%. Pattern 5 was mainly identified among the 22 different patterns. Of note, 50% of Pattern 5 was found in the patients of the internal medicine intensive care unit, and a third was associated with ventilator-associated pneumonia. Importantly, the internal medicine unit's equipment was found to be culture positive. Conclusion: Findings obtained from this study suggest that isolates can easily spread through the hospital via isolate cross-contamination caused by health personnel. These contaminating isolates may be able to maintain their presence within the hospital for a long time.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , beta-Lactamases/genética , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Bactérias/genética , Colistina/farmacologia , DNA Bacteriano/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Genes Bacterianos , Humanos , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem Molecular , Reação em Cadeia da Polimerase Multiplex , Centros de Atenção Terciária
11.
Expert Opin Pharmacother ; 21(15): 1805-1811, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32820669

RESUMO

INTRODUCTION: The addition of the ß-lactamase inhibitor relebactam to imipenem restores the antibacterial activity against the majority of multidrug resistant Gram-negative bacteria. Complicated urinary tract infections (UTIs) are predominantly caused by Gram-negative uropathogens. The rise in antibiotic resistance, including to carbapenems, is an increasing challenge in daily practice. AREAS COVERED: In the current review, the use of imipenem/relebactam in complicated UTI is evaluated by discussing its chemistry, pharmacokinetics/dynamics, microbiology, safety, and clinical efficacy. The authors also provide their expert perspectives onto its use and its future place in the treatment armamentarium. EXPERT OPINION: With respect to complicated UTI, it should be noted that, to our knowledge, there are no data yet upon the clinical efficacy of imipenem/relebactam in patients with severe urosepsis or men with suspected prostatitis. Further studies upon these specific groups of UTI patients are needed including additional pharmacokinetic studies upon its tissue penetration of the prostate which is currently unknown. However, in our opinion, imipenem/relebactam can be used in complicated UTI when other treatment options are limited.


Assuntos
Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Cilastatina/uso terapêutico , Imipenem/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Compostos Azabicíclicos/administração & dosagem , Compostos Azabicíclicos/farmacocinética , Cilastatina/administração & dosagem , Cilastatina/farmacocinética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Quimioterapia Combinada , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Imipenem/administração & dosagem , Imipenem/farmacocinética , Masculino , Testes de Sensibilidade Microbiana , Infecções Urinárias/microbiologia
12.
BMC Infect Dis ; 20(1): 635, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847524

RESUMO

BACKGROUND: Data regarding the prevalence of metallo-ß-lactamases (MBLs) among Pseudomonas aeruginosa isolates in cystic fibrosis patients are scarce. Furthermore, there is limited knowledge on the effect of MBL production on patient outcomes. Here we describe a fatal respiratory infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient and the results of the subsequent epidemiological investigation. CASE PRESENTATION: P. aeruginosa isolates collected in the index patient and among patients temporally or spatially linked with the index patient were analyzed in terms of antibiotic susceptibility profile and MBL production. Whole-genome sequencing and phylogenetic reconstruction were also performed for all P. aeruginosa isolates producing VIM-type MBLs. A VIM-producing P. aeruginosa strain was identified in a lung biopsy of a lung transplant recipient with cystic fibrosis. The strain was VIM-1-producer and belonged to the ST308. Despite aggressive treatment, the transplant patient succumbed to the pulmonary infection due to the ST308 strain. A VIM-producing P. aeruginosa strain was also collected from the respiratory samples of a different cystic fibrosis patient attending the same cystic fibrosis center. This isolate harbored the blaVIM-2 gene and belonged to the clone ST175. This patient did not experience an adverse outcome. CONCLUSIONS: This is the first description of a fatal infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient. The circulation of P. aeruginosa isolates harboring MBLs pose a substantial risk to the cystic fibrosis population due to the limited therapeutic options available and their spreading potential.


Assuntos
Antibacterianos/uso terapêutico , Transplante de Pulmão , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/enzimologia , Infecções Respiratórias/tratamento farmacológico , Transplantados , Adulto , Fibrose Cística/cirurgia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Evolução Fatal , Feminino , Humanos , Pulmão/microbiologia , Pulmão/patologia , Testes de Sensibilidade Microbiana , Filogenia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Infecções Respiratórias/microbiologia , beta-Lactamases/genética , beta-Lactamases/metabolismo
13.
BMC Infect Dis ; 20(1): 557, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32736605

RESUMO

BACKGROUND: Multi-drug resistance pathogens such as Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE) are of great global health concern, since they are associated with increased morbidity and mortality. Even in the absence of infections caused by these pathogens, colonization is a great threat and can lead to cross transfer among hospitalized patients. To date data on carriage of these pathogens is still limited in Tanzania. Therefore, this study aimed to determine ESBL-PE fecal carriage rate and associated factors among hospitalized patients at Referral hospitals in Dar es Salaam. METHODS: This was a cross sectional study conducted from May to July 2017 among patients admitted in three referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were collected and screened for ESBL production using MacConkey agar supplemented with Ceftazidime 2 µg/ml. Phenotypic confirmation of ESBL-PE was done by double disk diffusion method. Statistical analysis was performed using Statistical Package for Social Sciences (SPPS) software version 20. RESULTS: Of the 196 enrolled participants, 59.7% (117/196) were confirmed to carry ESBL-PE. Diarrheic patients (57/79) had statistically significant high prevalence of ESBL colonization compared to those without diarrhea (60/117) (p = 0.01). A total of 131 ESBL-PE were isolated from 117 patients, whereby, Escherichia coli accounted for 68.7%, Klebsiella pneumoniae 28.2% and Citrobacter species 0.8%. ESBL-PE carriage was significantly higher in patients with diarrhea compared to those without diarrhea (72% vs 53.1%, p = 0.01). Recent antibiotic use was independently associated with carriage of ESBL-PE (aOR 14.65, 95%CI 3.07-69.88, p = 0.01). CONCLUSIONS: High prevalence of fecal carriage of ESBL-PE was observed in patients admitted in tertiary hospitals in Dar es Salaam, Tanzania. The use of antibiotics was associated with carriage of ESBL producers among the study population.


Assuntos
Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Fezes/microbiologia , beta-Lactamases/biossíntese , Adolescente , Adulto , Antibacterianos/uso terapêutico , Ceftazidima , Estudos Transversais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/epidemiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Encaminhamento e Consulta , Tanzânia/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
14.
PLoS Biol ; 18(8): e3000805, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32810152

RESUMO

Antibiotics are losing efficacy due to the rapid evolution and spread of resistance. Treatments targeting bacterial virulence factors have been considered as alternatives because they target virulence instead of pathogen viability, and should therefore exert weaker selection for resistance than conventional antibiotics. However, antivirulence treatments rarely clear infections, which compromises their clinical applications. Here, we explore the potential of combining antivirulence drugs with antibiotics against the opportunistic human pathogen Pseudomonas aeruginosa. We combined two antivirulence compounds (gallium, a siderophore quencher, and furanone C-30, a quorum sensing [QS] inhibitor) together with four clinically relevant antibiotics (ciprofloxacin, colistin, meropenem, tobramycin) in 9×9 drug concentration matrices. We found that drug-interaction patterns were concentration dependent, with promising levels of synergies occurring at intermediate drug concentrations for certain drug pairs. We then tested whether antivirulence compounds are potent adjuvants, especially when treating antibiotic resistant (AtbR) clones. We found that the addition of antivirulence compounds to antibiotics could restore growth inhibition for most AtbR clones, and even abrogate or reverse selection for resistance in five drug combination cases. Molecular analyses suggest that selection against resistant clones occurs when resistance mechanisms involve restoration of protein synthesis, but not when efflux pumps are up-regulated. Altogether, our work provides a first systematic analysis of antivirulence-antibiotic combinatorial treatments and suggests that such combinations have the potential to be both effective in treating infections and in limiting the spread of antibiotic resistance.


Assuntos
Antibacterianos/farmacologia , Ciprofloxacino/farmacologia , Colistina/farmacologia , Furanos/farmacologia , Gálio/farmacologia , Meropeném/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Tobramicina/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade Microbiana , Biossíntese de Proteínas/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/metabolismo , Percepção de Quorum/efeitos dos fármacos , Virulência
15.
Mymensingh Med J ; 29(3): 622-627, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32844803

RESUMO

Acinetobacter species are important opportunistic and nosocomial pathogens capable of causing both community and health care-associated infections. The aim of this study was to determine the prevalence of Acinetobacter species and determination of the antibiotic susceptibility patterns of Acinetobacter. A total of 341 specimens were collected over a period of one year from January 2017 to January 2018 from ICU and Surgery unit of Mymensingh Medical College Hospital, Mymensingh, Bangladesh. Antimicrobial susceptibility testing of all Acinetobacter isolates was done using Kirby Bauer's disc diffusion technique as per recommendations of Clinical Laboratory Standards Institute (CLSI). MIC of commonly used Imipenem and newly introduced Tigecycline by agar dilution method was done and was compared it with disc diffusion method. From total 341 specimens, 119(34.8%) pathogen were isolated. Among 119 isolates total 46(38.6%) Acinetobacter were isolated. Maximum number of Acinetobacter was isolated from respiratory samples- endotracheal secretions. Regarding antimicrobial resistance, 42(91.3%), 33(71.7%), 20(43.5%), 28(60.9%) and 1(2.2%) were resistant to Piperacillin-Tazobactam, Doxycycline, Imipenem, Colistin and Tigecycline. Regarding, MIC of Imipenem, 41.3% was resistant, 32.6% was intermediate and 26.1% was sensitive. Regarding MIC of Tigecycline none was resistant, 39.1% was intermediate and 60.9% was sensitive. Acinetobacter species is emerging as a predominant healthcare associated multidrug resistant pathogen. The findings of this study will help our clinicians to apply appropriate antibiotics for treatment of patients.


Assuntos
Infecções por Acinetobacter , Acinetobacter/efeitos dos fármacos , Antibacterianos/farmacologia , Bangladesh , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária
16.
PLoS Genet ; 16(8): e1008965, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760058

RESUMO

The mobilizable resistance island Salmonella genomic island 1 (SGI1) is specifically mobilized by IncA and IncC conjugative plasmids. SGI1, its variants and IncC plasmids propagate multidrug resistance in pathogenic enterobacteria such as Salmonella enterica serovars and Proteus mirabilis. SGI1 modifies and uses the conjugation apparatus encoded by the helper IncC plasmid, thus enhancing its own propagation. Remarkably, although SGI1 needs a coresident IncC plasmid to excise from the chromosome and transfer to a new host, these elements have been reported to be incompatible. Here, the stability of SGI1 and its helper IncC plasmid, each expressing a different fluorescent reporter protein, was monitored using fluorescence-activated cell sorting (FACS). Without selective pressure, 95% of the cells segregated into two subpopulations containing either SGI1 or the helper plasmid. Furthermore, FACS analysis revealed a high level of SGI1-specific fluorescence in IncC+ cells, suggesting that SGI1 undergoes active replication in the presence of the helper plasmid. SGI1 replication was confirmed by quantitative PCR assays, and extraction and restriction of its plasmid form. Deletion of genes involved in SGI1 excision from the chromosome allowed a stable coexistence of SGI1 with its helper plasmid without selective pressure. In addition, deletion of S003 (rep) or of a downstream putative iteron-based origin of replication, while allowing SGI1 excision, abolished its replication, alleviated the incompatibility with the helper plasmid and enabled its cotransfer to a new host. Like SGI1 excision functions, rep expression was found to be controlled by AcaCD, the master activator of IncC plasmid transfer. Transient SGI1 replication seems to be a key feature of the life cycle of this family of genomic islands. Sequence database analysis revealed that SGI1 variants encode either a replication initiator protein with a RepA_C domain, or an alternative replication protein with N-terminal replicase and primase C terminal 1 domains.


Assuntos
Proteínas de Bactérias/genética , Conjugação Genética/genética , Ilhas Genômicas/genética , Fosfoproteínas/genética , Plasmídeos/genética , Antibacterianos/farmacologia , Cromossomos/efeitos dos fármacos , Cromossomos/genética , DNA Helicases/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Plasmídeos/efeitos dos fármacos , Proteus mirabilis/genética , Salmonella enterica/genética , Transativadores/genética
17.
PLoS One ; 15(8): e0238195, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845920

RESUMO

Nosocomial infections caused by extensively drug-resistant (XDR) or Pan-Drug resistant (PDR) Acinetobacter (A.) baumannii have recently increased dramatically creating a medical challenge as therapeutic options became very limited. The aim of our study was to investigate the antibiotic-resistance profiles and evaluate the various combinations of ciprofloxacin (CIP) or levofloxacin (LEV) with antimicrobial agents and non-antimicrobial agents to combat antimicrobial resistance of XDR A. baumannii. A total of 100 (6.25%) A. baumannii clinical isolates were recovered from 1600 clinical specimens collected from hospitalized patients of two major university hospitals in Upper Egypt. Antimicrobial susceptibility tests were carried out according to CLSI guidelines. Antimicrobial susceptibility testing of the respective isolates showed a high percentage of bacterial resistance to 19 antimicrobial agents ranging from 76 to99%. However, a lower percentage of resistance was observed for only colistin (5%) and doxycycline (57%). The isolates were categorized as PDR (2; 2%), XDR (68; 68%), and multi-drug resistant (MDR) (30; 30%). Genotypic analysis using ERIC-PCR on 2 PDR and 32 selected XDR isolates showed that they were not clonal. Combinations of CIP or LEV with antibiotics (including, ampicillin, ceftriaxone, amikacin, or doxycycline) were tested on these A. baumannii non-clonal isolates using standard protocols where fractional inhibitory concentrations (-FICs) were calculated. Results of the respective combinations showed synergism in 23.5%, 17.65%, 32.35%, 17.65% and 26.47%, 8.28%, 14.71%, 26.47%, of the tested isolates, respectively. CIP or LEV combinations with either chlorpromazine (CPZ) 200 µg/ml, propranolol (PR) in two concentrations, 0.5 mg/ml and 1.0 mg/ml or diclofenac (DIC) 4 mg/ml were carried out and the MIC decrease factor (MDF) of each isolate was calculated and results showed synergism in 44%, 50%, 100%, 100% and 94%, 85%, 100%, 100%, of the tested isolates, respectively. In conclusion, combinations of CIP or LEV with CPZ, PR, or DIC showed synergism in most of the selected PDR and XDR A. baumannii clinical isolates. However, these combinations have to be re-evaluated in vivo using appropriate animal models infected by XDR- or PDR- A. baumannii.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Clorpromazina/farmacologia , Diclofenaco/farmacologia , Fluoroquinolonas/farmacologia , Propranolol/farmacologia , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Ciprofloxacino/farmacologia , Infecção Hospitalar/microbiologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Egito , Humanos , Levofloxacino/farmacologia
18.
BMC Infect Dis ; 20(1): 576, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758169

RESUMO

BACKGROUND: China ranks second in the world in terms of numbers of tuberculosis (TB) cases and is one of the top three countries with the largest number of multidrug-resistant and rifampicin-resistant TB (MDR/RR-TB). It also has high mortality and low cure rates of human immunodeficiency virus (HIV)-positive TB patients. This study aimed to analyse, under the integrated TB control model, the characteristics of TB patients seeking healthcare in the largest designated TB hospital in Chongqing. METHODS: This was a retrospective study of TB registers in a health facility. Record data of 1827 TB patients who had attended the Chongqing Public Health Medical Center (CPHMC) from 1 January to 31 December 2018 were included. The Statistical Package for Social Science (SPSS 18.0; IBM Corporation, Armonk, NY, USA) was used to analyse the data. Counting data were compared using the chi-square test or Fisher' s exact test. Among the results of the univariate analysis, the variables with statistical significance were included in the binomial stepwise logistic regression, with odds ratio and 95% confidence interval calculated. A two-tailed probability level of P < 0.05 was considered statistically significant. RESULTS: The majority of registered patients were men (1197), of Han ethnicity (1670), aged 21-60 years (1331), farmer/unemployed (1075), and living in county/district (1207). Approximately 24.9% of patients (455/1827) contracted DR-TB, 6% (110/1827) were co-infected with HIV, and 41.0% (749/1827) had drug-related hepatotoxicity. Among those patients, DR-TB was more likely to develop among farmers who received retreatment and had drug-related hepatotoxicity (P < 0.05). Women who received retreatment and lived in county/district were less likely to be HIV positive (P < 0.05). Compared with farmers, patients who were unemployed were more likely to be HIV positive, and those aged 21-60 years had a higher risk of being tested as HIV positive (P < 0.05). CONCLUSION: Farmers who received retreatment and had drug-related hepatotoxicity are more susceptible to DR-TB; young unemployed men have a higher risk of contracting HIV-positive TB. The demographic and clinical characteristics of TB patients should be taken into consideration in DR-TB and HIV-positive TB screening in the future.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Coinfecção/epidemiologia , HIV , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , China/epidemiologia , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Fazendeiros , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Desemprego , Adulto Jovem
19.
BMC Infect Dis ; 20(1): 597, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787942

RESUMO

BACKGROUND: Multidrug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors and overall mortality for MDR/XDR Acinetobacter baumannii infected pediatric patients. METHODS: This retrospective study included 102 pediatric patients who developed MDR/XDR Acinetobacter baumannii infection in the pediatric intensive care unit (PICU) of Shanghai Children's Hospital in China from December 2014 to May 2018. Acinetobacter baumannii clinical isolates were recovered from different specimens including blood, sputum, bronchoalveolar lavage fluid, cerebrospinal fluid, ascites, hydrothorax, and urine. Antibiotic susceptibility test was determined according to the Clinical and Laboratory Standards Institute interpretive criteria. Clinical and biological data were obtained from the patients' medical records. RESULTS: 102 patients with Acinetobacter baumannii infection were enrolled. The median age was 36 (9.6, 98.8) months, and there were 63 male in the case group. The overall mortality rate was 29.4%, while the Acinetobacter baumannii-associated mortality rate was 16.7% (17/102, 12 bloodstream infections, 4 meningitis and 1 intra-abdominal infection). Bloodstream infections occurred in 28 patients (27.5%), and 10 patients (9.8%) among them had central line-associated bloodstream infections (6 central venous catheters, 2 PICCs, 1 venous infusion port and 1 arterial catheter). Cerebrospinal fluid (CSF) cultures were positive in 4(3.9%) patients. 14(13.7%) patients got positive cultures in ascites and hydrothorax. Lower respiratory isolates (56/102) accounted for 54.9% of all patients. Non-survival patients appeared to have a lower NK cell activity (6.2% ± 3.61% vs. 9.15% ± 6.21%, P = 0.029), higher CD4+ T cell ratio (39.67% ± 12.18% vs. 32.66% ± 11.44%, P = 0.039),and a higher serum level of interlukin-8 (IL-8, 15.25 (1.62, 47.22)pg/mL vs. 0.1 (0.1, 22.99)pg/mL, P = 0.01) when Acinetobacter baumannii infection developed. Multivariate logistic analysis indicated that high serum level of Cr (RR, 0.934, 95%CI, 0.890-0.981; P = 0.007) and high BUN/ALB level (RR, 107.893, 95%CI, 1.425-870.574; p = 0.005) were associated with high risk of mortality in MDR/XDR Acinetobacter baumannii infected patients. CONCLUSION: MDR/XDR Acinetobacter baumannii infection is a serious concern in pediatric patients with high mortality. Bloodstream and central nervous system infection accounted for high risk of death. Acute kidney injury is associated with high risk of mortality.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/mortalidade , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/mortalidade , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Unidades de Terapia Intensiva Pediátrica , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/isolamento & purificação , Lesão Renal Aguda/mortalidade , Bacteriemia/mortalidade , Infecções do Sistema Nervoso Central/mortalidade , Criança , Pré-Escolar , China , Infecção Hospitalar/microbiologia , Feminino , Hospitais , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
20.
Am J Trop Med Hyg ; 103(4): 1443-1446, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32618257

RESUMO

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


Assuntos
Fluoroquinolonas/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/uso terapêutico , Clofazimina/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Gatifloxacina/uso terapêutico , Genes Bacterianos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Canamicina/uso terapêutico , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Moxifloxacina/uso terapêutico , Mycobacterium tuberculosis/genética , Ruanda , Análise de Sequência de DNA
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