RESUMO
This paper presents the results of a pilot study of difficult-to-treat patients (exhibiting several previous treatment failures or detection of extended-spectrum beta-lactamase [ESBL] strains) with chronic bacterial prostatitis (CBP) who underwent treatment with fosfomycin trometamol (FT) and N-acetyl-L-cysteine (NAC). Twenty-eight patients with clinically- and microbiologically-confirmed CBP who attended a single urological institution between January 2018 and March 2019 were treated with oral administration of 3 g FT once a day for 2 days, followed by a dose of 3 g every 48 h for 2 weeks, in combination with oral administration of NAC 600 mg once a day for 2 weeks. Clinical and microbiological analyses were carried out at the time of admission (T0) and during follow-up at 1 month (T1) and 6 months (T2) after the end of treatment. Symptoms were assessed by the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and International Prostatic Symptom Score (IPSS), and quality of life was assessed by Quality of Well-Being (QoL) questionnaires. Isolated strains were Escherichia coli (23 patients), Enterococcus spp. (3 patients), and Klebsiella oxytoca (2 patients). ESBL strain was found in 19 (67.8%) patients. Microbiological eradication was documented in 21 (75%) patients at the second follow-up visit and clinical cure was achieved in 20 (71.4%) patients. Significant changes on questionnaires were recorded between baseline and follow-up visits. Fifteen of 19 patients (78.9%) with ESBL strains were cured. No significant side effects were reported. FT in combination with NAC is a promising alternative therapy in difficult-to-treat CBP patients.
Assuntos
Acetilcisteína/uso terapêutico , Antibacterianos/uso terapêutico , Fosfomicina/uso terapêutico , Prostatite/tratamento farmacológico , Adulto , Farmacorresistência Bacteriana Múltipla , Quimioterapia Combinada , Escherichia coli/efeitos dos fármacos , Humanos , Klebsiella oxytoca/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prostatite/microbiologia , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
Abstract To the moment, there is no ideal substance for home-based denture disinfection. This study assessed in vitro the antimicrobial effect of the hydroalcoholic extract of Eugenia uniflora and the effect on the physical properties of denture polymethylmethacrylate (PMMA). Candida albicans, Staphylococcus aureus, and Klebsiella oxytoca were isolated from samples of saliva collected from denture wearers. The extracts were produced in three concentrations, according to the Brazilian Pharmacopeia. One hundred eighty-eight disc-shaped specimens of thermopolymerizable PMMA were prepared and randomly allocated to five treatment groups: sterile saline solution (0.85%; control); chlorhexidine digluconate (0.2%); and hydroalcoholic extract of E. uniflora (0.2%, 0.8%, and 1.16%). The specimens were disinfected for 8 hours/day for 30 days. Adherence of microorganisms to the surface, PMMA surface roughness, and color stability were assessed. Inferential statistics were performed with one- and two-way ANOVA/Tukey test, and Kruskal Wallis, Mann-Whitney U, and paired t-tests, at α=0.05. The extract of E. uniflora at 0.2% and 1.16% reduced the microbial load of K. oxytoca, while chlorhexidine digluconate significantly reduced microbial load of all microrganisms. Microbial adherence at day 10 was reduced by all experimental substances (p<0.001). Surface roughness was not affected by the disinfecting substances (p>0.05). Nevertheless, all experimental groups produced unacceptable color change at the end of the disinfection protocol (p<0.001). The non-adherent potential against microorganisms isolated from the oral cavity confirm the potential of use of the hydroalcoholic extract of E. uniflora as a denture disinfectant. Yet, unacceptable color changes may occur, regardless of extract concentration.
Assuntos
Humanos , Staphylococcus aureus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Extratos Vegetais/farmacologia , Dentaduras , Klebsiella oxytoca/efeitos dos fármacos , Eugenia/química , Antissépticos Bucais/farmacologia , Polimetil MetacrilatoRESUMO
A new series of copper (II), cobalt (II), zinc (II), nickel (II), manganese (II), iron (II) complexes with a novel Schiff base were synthesized by the condensation of sulphadizine and thiophene-2-carbaldehyde.The ligand and its complexes were characterized by using diverse instrumental procedures like microanalysis, thermo gravimetric examination and spectroscopy. The integrated ligand and its metal complexes were subjected to antibacterial studies. These studies demonstrated the enhanced activity of metal complexes against reported microbes with respect to the Schiff base.
Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Metais/química , Anti-Infecciosos/química , Bacillus pumilus/efeitos dos fármacos , Clostridium butyricum/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Enterobacter aerogenes/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Klebsiella oxytoca/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Bases de Schiff/química , Staphylococcus aureus/efeitos dos fármacos , Tiofenos/químicaRESUMO
This study characterized the ß-lactamase content of baseline pathogens recovered from patients with complicated urinary tract infections (cUTI), including acute pyelonephritis, who were enrolled in two phase 3 clinical trials of ceftazidime-avibactam (RECAPTURE 1 and 2), and correlated the clinical efficacy of ceftazidime-avibactam and the comparator doripenem according to resistance mechanisms. A total of 26.2% (93/355) ceftazidime-avibactam and 26.8% (101/377) doripenem patients had baseline isolates that met the MIC screening criteria. The majority of Enterobacteriaceae (87.5%; 154/176) carried blaCTX-M. This pattern was mainly observed in Escherichia coli (96.8%; 92/95) and Klebsiella pneumoniae (96.0%; 48/50), whereas most Proteus mirabilis (80.0%; 8/10) carried plasmid AmpC genes. Two K. pneumoniae and 1 Klebsiella oxytoca carried blaOXA-48 and 1 K. pneumoniae carried blaNDM-1. Five (13/35; 37.1%) Pseudomonas aeruginosa isolates were screened, and 2 carbapenemase producers (IMP-18 and VIM-2) were detected. Among patients enrolled in the ceftazidime-avibactam arm who were infected by MIC screen-positive Enterobacteriaceae, clinical cure occurred in 85.7-95.5%, regardless of ß-lactamase content; the respective rate in the doripenem arm was 82.1-92.5%. A total of 75.0% in the ceftazidime-avibactam arm and 100.0% in the doripenem arm of patients infected by P. aeruginosa with MIC screen-positive criteria were clinically cured. Ceftazidime-avibactam efficacy was comparable to doripenem efficacy for treating cUTI caused by uropathogens producing extended-spectrum and/or AmpC ß-lactamases.
Assuntos
Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Proteínas de Bactérias/genética , Carbapenêmicos/uso terapêutico , Ceftazidima/uso terapêutico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Pielonefrite/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , beta-Lactamases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Bactérias/metabolismo , Doripenem , Método Duplo-Cego , Combinação de Medicamentos , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/isolamento & purificação , Feminino , Expressão Gênica , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Klebsiella oxytoca/efeitos dos fármacos , Klebsiella oxytoca/genética , Klebsiella oxytoca/crescimento & desenvolvimento , Klebsiella oxytoca/isolamento & purificação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/crescimento & desenvolvimento , Klebsiella pneumoniae/isolamento & purificação , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Plasmídeos/química , Plasmídeos/metabolismo , Proteus mirabilis/efeitos dos fármacos , Proteus mirabilis/genética , Proteus mirabilis/crescimento & desenvolvimento , Proteus mirabilis/isolamento & purificação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/isolamento & purificação , Pielonefrite/microbiologia , Resultado do Tratamento , Infecções Urinárias/microbiologia , beta-Lactamases/metabolismoRESUMO
The emergence of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) infections requires re-assessment of therapeutic choices. Here we report the efficacy of cefoxitin-based antibiotic therapy for ESBL-E prostatitis. A prospective study including patients with ESBL-E prostatitis resistant to trimethoprim/sulfamethoxazole and fluoroquinolones from January 2014 to March 2016 was conducted. Cefoxitin was administered by continuous infusion for 3 weeks in the case of acute bacterial prostatitis or 6 weeks in the case of chronic bacterial prostatitis (CBP), with intravenous fosfomycin for the first 5 days. Urological investigations were performed to diagnose underlying urinary tract pathology. Clinical and microbiological efficacy were evaluated 3 months (M3) and 6 months (M6) after the end of therapy. A total of 23 patients were included in the study. The median patient age was 74 years (range 48-88 years). Of the 23 infections, 14 (61%) were CBP and 12 (52%) were healthcare-associated infections. The bacteria involved were Escherichia coli in 11 cases, Klebsiella pneumoniae in 10 cases and Klebsiella oxytoca in 2 cases. Clinical cure was observed in 19/23 patients (83%) at M3 and in 17/22 patients (77%) at M6. Urocultures were sterile in 13/23 patients (57%) at M3 and in 9/19 patients (47%) and M6. Urinary colonisation was observed in 6/19 patients (32%) with clinical cure at M3 and 5/14 patients (36%) with clinical cure at M6. No resistance to cefoxitin was detected. Surgical treatment was required for 7/23 patients (30%). In conclusion, cefoxitin-based antibiotic therapy is suitable for difficult-to-treat ESBL-E infections such as prostatitis.
Assuntos
Antibacterianos/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella oxytoca/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Prostatite/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Cefoxitina/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Fluoroquinolonas/uso terapêutico , Fosfomicina/uso terapêutico , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella oxytoca/genética , Klebsiella pneumoniae/genética , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Prostatite/microbiologia , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , beta-Lactamases/genética , beta-Lactamases/metabolismoRESUMO
BACKGROUND: Bacterial biofilms exhibit reduced sensitivity to conventional antibiotics and host defence systems and contribute to the persistence of chronic bacterial infections. HYPOTHESIS: The antibiofilm approach using plant alkaloids provides an alternative to antibiotic strategies. STUDY DESIGN: In this study, the antibiofilm activities of various plant alkaloids were investigated against enterohemorrhagic Escherichia coli O157:H7 and Pseudomonas aeruginosa. In the subsequent investigation, the effects of five norharmane derivatives were investigated. RESULT: Harmaline significantly inhibited biofilm formation by E. coli O157:H7, P. aeruginosa PAO1, P. aeruginosa PA14, and Klebsiella oxytoca, and norharmane (ß-carboline) was found to have antibiofilm activity. It was also found that functional groups at the C-1 and C-7 positions of norharmane could play important roles in its antibiofilm activity. Confocal and electron microscopic observations confirmed biofilm inhibition by harmaline and norharmane, and both reduced fimbriae production and swarming and swimming motilities. Furthermore, harmaline and norharmane attenuated the virulence of E. coli O157:H7 in a Caenorhabditis elegans nematode model. CONCLUSION: These findings strongly suggest that harmaline and norharmane could have potential use in antibiofilm strategy against persistent bacterial infections.
Assuntos
Antibacterianos/farmacologia , Carbolinas/farmacologia , Escherichia coli O157/efeitos dos fármacos , Animais , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Caenorhabditis elegans/microbiologia , Carbolinas/química , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli O157/patogenicidade , Escherichia coli O157/fisiologia , Klebsiella oxytoca/efeitos dos fármacos , Klebsiella oxytoca/fisiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologiaRESUMO
Ceftazidime-avibactam (CAZ-AVI) is a recently approved ß-lactam-ß-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.
Assuntos
Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Carbapenêmicos/uso terapêutico , Ceftazidima/uso terapêutico , Idoso , Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Carbapenêmicos/farmacologia , Ceftazidima/farmacologia , Combinação de Medicamentos , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/patogenicidade , Feminino , Humanos , Klebsiella oxytoca/efeitos dos fármacos , Klebsiella oxytoca/patogenicidade , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Terapia de SalvaçãoRESUMO
We characterized 12 clinical isolates of Klebsiella oxytoca with the extended-spectrum ß-lactamase (ESBL) phenotype (high minimum inhibitory concentration [MIC] values of ceftriaxone) recovered over 9 months at a university hospital in Japan. To determine the clonality of the isolates, we used pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), and PCR analyses to detect blaRBI, which encodes the ß-lactamase RbiA, OXY-2-4 with overproduce-type promoter. Moreover, we performed the isoelectric focusing (IEF) of ß-lactamases, and the determination of the MICs of ß-lactams including piperacillin/tazobactam for 12 clinical isolates and E. coli HB101 with pKOB23, which contains blaRBI, by the agar dilution method. Finally, we performed the initial screening and phenotypic confirmatory tests for ESBLs. Each of the 12 clinical isolates had an identical PFGE pulsotype and MLST sequence type (ST9). All 12 clinical isolates harbored identical blaRBI. The IEF revealed that the clinical isolate produced only one ß-lactamase. E. coli HB101 (pKOB23) and all 12 isolates demonstrated equally resistance to piperacillin/tazobactam (MICs, >128 µg/ml). The phenotypic confirmatory test after the initial screening test for ESBLs can discriminate ß-lactamase RbiA-producing K. oxytoca from ß-lactamase CTX-M-producing K. oxytoca. Twelve clinical isolates of K. oxytoca, which were recovered from an outbreak at one university hospital, had identical genotypes and produced ß-lactamase RbiA that conferred resistance to piperacillin/tazobactam. In order to detect K. oxytoca isolates that produce RbiA to promote research concerning ß-lactamase RbiA-producing K. oxytoca, the phenotypic confirmatory test after the initial screening test for ESBLs would be useful.
Assuntos
Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla/genética , Klebsiella oxytoca/efeitos dos fármacos , Klebsiella oxytoca/genética , Ácido Penicilânico/análogos & derivados , Piperacilina/uso terapêutico , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Surtos de Doenças , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Japão , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella oxytoca/isolamento & purificação , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus/métodos , Ácido Penicilânico/uso terapêutico , Tazobactam , beta-Lactamases/genética , beta-Lactamas/uso terapêuticoRESUMO
BACKGROUND: The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum ß-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem. METHODS: Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort. RESULTS: A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45). CONCLUSIONS: PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to ß-lactam/ß-lactamase inhibitor combinations in development, as limited clinical data are available for these agents.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Carbapenêmicos/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Ácido Penicilânico/análogos & derivados , Inibidores de beta-Lactamases/uso terapêutico , Idoso , Bacteriemia/mortalidade , Estudos de Coortes , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/mortalidade , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Feminino , Humanos , Klebsiella oxytoca/efeitos dos fármacos , Klebsiella oxytoca/isolamento & purificação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Pontuação de Propensão , Modelos de Riscos Proporcionais , Proteus mirabilis/efeitos dos fármacos , Proteus mirabilis/isolamento & purificação , Taxa de Sobrevida , Fatores de Tempo , beta-Lactamases/metabolismoRESUMO
Klebsiella oxytoca is an opportunistic pathogen implicated in various clinical diseases in animals and humans. Studies suggest that in humans K. oxytoca exerts its pathogenicity in part through a cytotoxin. However, cytotoxin production in animal isolates of K. oxytoca and its pathogenic properties have not been characterized. Furthermore, neither the identity of the toxin nor a complete repertoire of genes involved in K. oxytoca pathogenesis have been fully elucidated. Here, we showed that several animal isolates of K. oxytoca, including the clinical isolates, produced secreted products in bacterial culture supernatant that display cytotoxicity on HEp-2 and HeLa cells, indicating the ability to produce cytotoxin. Cytotoxin production appears to be regulated by the environment, and soy based product was found to have a strong toxin induction property. The toxin was identified, by liquid chromatography-mass spectrometry and NMR spectroscopy, as low molecular weight heat labile benzodiazepine, tilivalline, previously shown to cause cytotoxicity in several cell lines, including mouse L1210 leukemic cells. Genome sequencing and analyses of a cytotoxin positive K. oxytoca strain isolated from an abscess of a mouse, identified genes previously shown to promote pathogenesis in other enteric bacterial pathogens including ecotin, several genes encoding for type IV and type VI secretion systems, and proteins that show sequence similarity to known bacterial toxins including cholera toxin. To our knowledge, these results demonstrate for the first time, that animal isolates of K. oxytoca, produces a cytotoxin, and that cytotoxin production is under strict environmental regulation. We also confirmed tilivalline as the cytotoxin present in animal K. oxytoca strains. These findings, along with the discovery of a repertoire of genes with virulence potential, provide important insights into the pathogenesis of K. oxytoca. As a novel diagnostic tool, tilivalline may serve as a biomarker for K oxytoca-induced cytotoxicity in humans and animals through detection in various samples from food to diseased samples using LC-MS/MS. Induction of K. oxytoca cytotoxin by consumption of soy may be in part involved in the pathogenesis of gastrointestinal disease.
Assuntos
Toxinas Bacterianas/toxicidade , Benzodiazepinonas/toxicidade , Infecções por Klebsiella/veterinária , Klebsiella oxytoca/patogenicidade , Animais , Sistemas de Secreção Bacterianos/genética , Toxinas Bacterianas/biossíntese , Toxinas Bacterianas/química , Toxinas Bacterianas/isolamento & purificação , Benzodiazepinonas/química , Benzodiazepinonas/isolamento & purificação , Benzodiazepinonas/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Haplorrinos , Células HeLa , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella oxytoca/efeitos dos fármacos , Klebsiella oxytoca/isolamento & purificação , Klebsiella oxytoca/metabolismo , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Glycine max/química , SuínosRESUMO
Escherichia coli (328 isolates), Klebsiella pneumoniae (296), Klebsiella oxytoca (44), and Proteus mirabilis (33) isolates collected during 2012 from the nine U.S. census regions and displaying extended-spectrum-ß-lactamase (ESBL) phenotypes were evaluated for the presence of ß-lactamase genes, and antimicrobial susceptibility profiles were analyzed. The highest ESBL rates were noted for K. pneumoniae (16.0%, versus 4.8 to 11.9% for the other species) and in the Mid-Atlantic and West South Central census regions. CTX-M group 1 (including CTX-M-15) was detected in 303 strains and was widespread throughout the United States but was more prevalent in the West South Central, Mid-Atlantic, and East North Central regions. KPC producers (118 strains [112 K. pneumoniae strains]) were detected in all regions and were most frequent in the Mid-Atlantic region (58 strains). Thirteen KPC producers also carried blaCTX-M. SHV genes encoding ESBL activity were detected among 176 isolates. Other ß-lactamase genes observed were CTX-M group 9 (72 isolates), FOX (10), TEM ESBL (9), DHA (7), CTX-M group 2 (3), NDM-1 (2 [Colorado]), and CTX-M groups 8 and 25 (1). Additionally, 62.9% of isolates carried ≥2 ß-lactamase genes. KPC producers were highly resistant to multiple agents, but ceftazidime-avibactam (MIC50/90, 0.5/2 µg/ml) and tigecycline (MIC50/90, 0.5/1 µg/ml) were the most active agents tested. Overall, meropenem (MIC50, ≤0.06 µg/ml), ceftazidime-avibactam (MIC50, 0.12 to 0.5 µg/ml), and tigecycline (MIC50, 0.12 to 2 µg/ml) were the most active antimicrobials when tested against this collection. NDM-1 producers were resistant to all ß-lactams tested. The diversity and increasing prevalence of ß-lactamase-producing Enterobacteriaceae have been documented, and ceftazidime-avibactam was very active against the vast majority of ß-lactamase-producing strains isolated from U.S. hospitals.
Assuntos
Antibacterianos/uso terapêutico , Ceftazidima/análogos & derivados , Variação Genética , Minociclina/análogos & derivados , Monobactamas/uso terapêutico , Resistência beta-Lactâmica/genética , beta-Lactamases/genética , Ceftazidima/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Escherichia coli/genética , Expressão Gênica , Humanos , Klebsiella oxytoca/efeitos dos fármacos , Klebsiella oxytoca/enzimologia , Klebsiella oxytoca/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Minociclina/uso terapêutico , Plasmídeos , Proteus mirabilis/efeitos dos fármacos , Proteus mirabilis/enzimologia , Proteus mirabilis/genética , Tigeciclina , Estados Unidos/epidemiologia , Resistência beta-Lactâmica/efeitos dos fármacos , beta-Lactamases/metabolismoRESUMO
In this study, 20 samples from three different sources of animal feed were investigated and six bacterial isolates were identified. The susceptibility of four natural antimicrobials, namely, eugenol, cinnamaldehyde, thymol, and carvacrol, against six of these isolates was determined. Carvacrol and eugenol showed better inhibitory effects with larger zones of inhibition. The minimal inhibitory concentration for a range of antibiotics on the susceptibility of two isolates (namely, Sphingomonas paucimobilis and Klebsiella oxytoca) was investigated using the VITEK® 2 microbiological identification system. Both isolates showed a variety of resistance to 18 antibiotics. The minimal inhibitory concentration and fractional inhibitory concentration index of those two isolates for ampicillin and nitrofurantoin in combination with four phenolic compounds was determined. Synergistic interactions were found for most antimicrobial/antibiotic combinations; thymol and carvacrol were very effective (fractional inhibitory concentration ≤0.5) in combination with all antibiotics tested against S. paucimobilis and K. oxytoca, respectively. Ultra performance liquid chromatography techniques were used to investigate the physiological effects of the four natural antimicrobials against those two isolates. Two identical peaks were found to be systematically different between cinnamaldehyde-treated and -untreated cells. The identity of the peaks is unknown and further investigation is needed.
Assuntos
Ração Animal/microbiologia , Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana , Klebsiella oxytoca/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sphingomonas/efeitos dos fármacos , Acroleína/análogos & derivados , Acroleína/farmacologia , Ampicilina/farmacologia , Animais , Bovinos , Cimenos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Patos , Eugenol/farmacologia , Microbiologia de Alimentos , Klebsiella oxytoca/fisiologia , Testes de Sensibilidade Microbiana , Monoterpenos/farmacologia , Nitrofurantoína/farmacologia , Percepção de Quorum/efeitos dos fármacos , Sphingomonas/fisiologia , Suínos , Timol/farmacologiaRESUMO
The aim of this study was to evaluate the effects of the photosensitizers Rose Bengal and erythrosin combined with a light-emitting diode (LED) on Enterobacteriaceae. Twelve Enterobacteriaceae strains isolated from the oral cavities of patients undergoing prolonged antibiotic therapy, including three Escherichia coli, three Enterobacter cloacae, three Klebsiella oxytoca and three Klebsiella pneumoniae, were studied. An Enterobacteriaceae suspension (10(6) cells/ml) was prepared from each clinical strain isolated from the human oral cavity and subjected to the following treatments: LED and Rose Bengal, LED and erythrosin, LED and physiological solution, and physiological solution only as control. A blue LED unit (460 nm), and Rose Bengal and erythrosin at a concentration of 50 micromol/l were used. After incubation at 37 degrees C for 48 h, the number of colony-forming units (CFU) was calculated and subjected to analysis of variance (ANOVA). The Enterobacterial strains were sensitive to photodynamic therapy with Rose Bengal. There was a reduction of approximately 7.14 log10 for Enterobacter cloacae, 7.73 log10 for Escherichia coli, 6.76 log10 for Klebsiella pneumoniae and 7.21 log10 for Klebsiella oxytoca. However, photodynamic therapy using erythrosin did not reduce the numbers of CFUs per milliliter compared to the control group. The use of the LED alone had no toxic effect on the strain tested. The Enterobacteriaceae strains studied were sensitive to photodynamic therapy with Rose Bengal.
Assuntos
Enterobacteriaceae/efeitos dos fármacos , Eritrosina/farmacologia , Corantes Fluorescentes/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Rosa Bengala/farmacologia , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/efeitos da radiação , Enterobacteriaceae/efeitos da radiação , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Humanos , Klebsiella oxytoca/efeitos dos fármacos , Klebsiella oxytoca/efeitos da radiação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/efeitos da radiaçãoAssuntos
Farmacorresistência Bacteriana , Fluoroquinolonas/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Acinetobacter/efeitos dos fármacos , Alabama , Ciprofloxacina/uso terapêutico , Enterobacter cloacae/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Fluoroquinolonas/farmacologia , Gatifloxacina , Infecções por Bactérias Gram-Negativas/microbiologia , Hospitais Comunitários , Humanos , Unidades de Terapia Intensiva , Klebsiella oxytoca/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ofloxacino/uso terapêutico , Proteus mirabilis/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Estudos RetrospectivosRESUMO
Guidelines recommend high doses of beta-lactams for the therapy of endocarditis. This report describes a retrospective study of 15 endocarditis patients (median age 64 years), treated according to guidelines, whose beta-lactam trough plasma concentrations were measured with high-performance liquid chromatography because of tolerance or efficacy concerns. For amoxycillin, the mean level was 86.8 mg/L (range: 30-212 mg/L); five (45%) patients had concentrations > 1000 x MIC. For cloxacillin, the mean level was 47.9 mg/L (range: 16.7-104 mg/L). The consequences of high and unpredicted beta-lactam trough plasma concentrations for a prolonged period have not yet been thoroughly evaluated.
Assuntos
Amoxicilina/farmacocinética , Antibacterianos/farmacocinética , Cloxacilina/farmacocinética , Monitoramento de Medicamentos/métodos , Endocardite Bacteriana/tratamento farmacológico , beta-Lactamas/farmacocinética , Adulto , Idoso , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Cloxacilina/uso terapêutico , Endocardite Bacteriana/microbiologia , Feminino , Cocos Gram-Positivos/efeitos dos fármacos , Humanos , Klebsiella oxytoca/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , beta-Lactamas/uso terapêuticoRESUMO
OBJECTIVES: In this study, we evaluated the performance of a new ESBL Etest configuration based on clavulanate synergy with cefepime compared with cefotaxime-clavulanate and ceftazidime-clavulanate ESBL Etest strips for the detection of extended-spectrum beta-lactamases (ESBL) in an Enterobacteriaceae strain collection, with special focus on Enterobacter spp. METHODS: Overall, a total of 54 clinical isolates of ESBL-producing Enterobacteriaceae species were evaluated: Enterobacter aerogenes (n=3), Enterobacter cloacae (n=10), Escherichia coli (n=10), Klebsiella oxytoca (n=3), Klebsiella pneumoniae (n=25) and Proteus mirabilis (n=3). To check Etest behaviour with resistance phenotypes similar to ESBL, our panel was expanded by six clinical isolates of K. oxytoca that were identified as putative producers of their chromosomal K1 beta-lactamase. RESULTS: With this panel, ESBL Etest was 98% sensitive with cefepime-clavulanate, 83% with cefotaxime-clavulanate, and 74% with ceftazidime-clavulanate strips. Concentrating on Enterobacter spp., reliable ESBL detection could only be achieved by the new cefepime-clavulanate strip since it confirmed ESBL production in all strains (100% sensitivity) whereas only 4/13 (31%) of Enterobacter strains were positive using cefotaxime-clavulanate or ceftazidime-clavulanate strips. A limitation of using the new cefepime strip was less than optimal specificity with K1 phenotypes of K. oxytoca: among six strains, four isolates were scored false-positive by Etest strips containing cefepime-clavulanate. CONCLUSION: The new Etest ESBL strip containing cefepime-clavulanate is a valuable supplement to current methods for detection of ESBLs. In our study collection, the cefepime-clavulanate strip was the best configuration for detection of ESBLs, particularly in Enterobacter spp.
Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Ácido Clavulânico/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , beta-Lactamases/metabolismo , Cefepima , Farmacorresistência Bacteriana , Enterobacter/efeitos dos fármacos , Enterobacter/enzimologia , Infecções por Enterobacteriaceae/microbiologia , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella oxytoca/efeitos dos fármacos , Fenótipo , Inibidores de beta-LactamasesRESUMO
BACKGROUND: Epidemiology and resistance patterns of bacterial pathogens in pediatric UTI show large interregional variability and rates of bacterial resistances are changing due to different antibiotic treatment. We intended to evaluate data from northern Germany. PATIENTS AND METHODS: In 100 children (53 female, 47 male, mean age 4.4 +/- 4.2 years) with community acquired UTI, who presented in the emergency department of our medical school from 2000 - 2002, urine cultures were performed. Inclusion criteria were: acute voiding symptoms, significant bacteriuria with growth of at least 10 (5) colony-forming units/ml urine, leukocyturia > 50/ micro l. Exclusion criteria were underlying renal diseases, anatomic abnormalities of the urinary tract, age < 2 months and recurrent UTI. RESULTS: Patients presented with a mean rectal temperature of 38.6 +/- 1.3 degrees C, mean CRP of 66 +/- 68 mg/dl, mean WBC 13 500 +/- 5 600/ micro l and mean urinary leukocytes of 425 +/- 363/ micro l. In urine cultures E. coli was found in 47 % of the cases, Enterococcus faecalis 23 %, Proteus mirabilis 8 %, Klebsiella oxytoca 4 %, Pseudomonas aeruginosa 5 % and others 13 %. In 76 % one and in 24 % two different bacterial species (60 % Enterococcus faecalis) were cultured. Mean resistance rates were in all bacteria (in E. coli): Ampicillin 53 % (69 %), Ampicillin and Sulbactam 51 % (61 %), Cefalosporin 1 (st) generation (Cefaclor) 48 % (24 %), Cefalosporin 2 (nd) generation (Cefuroxim) 40 % (3 %), Cefalosporin 3 (rd) generation (Cefuroxim) 33 % (0 %), Tobramycin 30 % (2 %), Ciprofloxacine 0 %, Cotrimoxazole 40 % (42 %), Nitrofurantoin 12 % (0 %). CONCLUSION: The resistance rates to Ampicillin (+/- Sulbactam) did not increase as compared to previous analyses (1990 - 1995), however, resistance rates to Cotrimoxazole and 1 (st) generation Cefalosporines increased about 20 %. We conclude that the policies for treatment of UTI in children should be re-evaluated every 5 years according to local resistance rates.