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1.
J Urol ; 204(6): 1249-1255, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32602771

RESUMO

PURPOSE: We evaluate the prevalent microorganisms, antibiotic sensitivity patterns and associated outcomes in patients with Fournier's gangrene. MATERIALS AND METHODS: A retrospective chart review of patients with Fournier's gangrene was conducted between October 2011 and April 2018 at our institution. Univariate analysis was performed using the independent t-test or Kruskal-Wallis H test for continuous variables and exact test for categorical variables. RESULTS: Of the 143 patients included in this study, wound culture was available in 131 (92%) patients with a median number of 3 microorganisms per wound. The most commonly grown pathogens were Staphylococcus species (66, 46%), Streptococcus species (53, 37%), Bacteroides species (34, 24%), Candida species (31, 22%), Escherichia coli (28, 20%) and Prevotella species (26, 18%). Most bacteria were sensitive to ampicillin-sulbactam, ceftriaxone, piperacillin-tazobactam, amikacin and cefepime, and resistant to ampicillin, trimethoprim-sulfamethoxazole, levofloxacin and clindamycin. Enterococcus faecalis and Streptococcus anginosus were resistant to vancomycin. The overall Fournier's gangrene mortality count was 14 (10%) patients. No association was noted between the type of infection and Fournier's gangrene severity index, length of hospital stay or mortality. CONCLUSIONS: At our institution Candida is a prevalent pathogen in the wound culture of patients with Fournier's gangrene. The resistance patterns for clindamycin and vancomycin are concerning. Addition of an antifungal agent to the empiric treatment should be considered based on clinical presentation.


Assuntos
Antibacterianos/farmacologia , Bactérias/isolamento & purificação , Candida/isolamento & purificação , Gangrena de Fournier/microbiologia , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Candida/efeitos dos fármacos , Clindamicina/farmacologia , Clindamicina/uso terapêutico , Desbridamento , Farmacorresistência Bacteriana , Farmacorresistência Fúngica , Feminino , Gangrena de Fournier/diagnóstico , Gangrena de Fournier/mortalidade , Gangrena de Fournier/terapia , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Pessoa de Meia-Idade , Períneo/microbiologia , Períneo/cirurgia , Estudos Retrospectivos , Índice de Gravidade de Doença , Centros de Atenção Terciária/estatística & dados numéricos , Vancomicina/farmacologia , Vancomicina/uso terapêutico
2.
PLoS Pathog ; 16(6): e1008559, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32497109

RESUMO

Antibiotics continue to be the standard-of-care for bacterial vaginosis (BV), although recurrence rates are high. Vaginal probiotics may improve durability of BV treatment, although few probiotics for vaginal health contain Lactobacillus spp. that commonly colonize the lower female genital tract. Characteristics of vaginal Lactobacillus strains from South African women were evaluated for their probiotic potential in vitro compared to strains from commercial vaginal products, including growth at varying pHs, ability to lower pH, produce D-/L-lactate and H2O2, influence growth of BV-associated Gardnerella vaginalis and Prevotella bivia, adherence to cervical cells and susceptibility to antibiotics. Fifty-seven Lactobacillus strains were purified from cervico-vaginal fluid, including L. crispatus, L. jensenii, L. gasseri, L. mucosae, and L. vaginalis. L crispatus strains grew better at pHs below 4.5 and lowered pH more effectively than other strains. Production of D-/L-lactate and H2O2 varied between Lactobacillus species and strains. Lactobacillus strains generally inhibited P. bivia more uniformly than G. vaginalis isolates. All vaginal Lactobacillus isolates were resistant to metronidazole while susceptibility to clindamycin varied. Furthermore, vaginal Lactobacillus strains tended to be broadly susceptible to penicillin, amoxicillin, rifampicin and rifabutin. Whole-genome-sequencing of five of the best-performing vaginal Lactobacillus strains confirmed their likely safety, due to antimicrobial resistance elements being largely absent, while putative intact prophages were present in the genomes of two of the five strains. Overall, vaginal Lactobacillus strains largely performed better in these in vitro assays than probiotic strains currently used in probiotics for vaginal health. Including the best-performing vaginal Lactobacillus isolates in a region-specific probiotic for vaginal health may result in improved BV treatment options.


Assuntos
Infecções por Bacteroidaceae/microbiologia , Gardnerella vaginalis , Infecções por Bactérias Gram-Positivas/microbiologia , Lactobacillus , Prevotella , Vaginose Bacteriana/microbiologia , Adolescente , Adulto , Infecções por Bacteroidaceae/tratamento farmacológico , Infecções por Bacteroidaceae/genética , Infecções por Bacteroidaceae/metabolismo , Clindamicina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/genética , Infecções por Bactérias Gram-Positivas/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Ácido Láctico/metabolismo , Lactobacillus/genética , Lactobacillus/isolamento & purificação , Lactobacillus/metabolismo , Metronidazol/farmacologia , África do Sul , Especificidade da Espécie , Vaginose Bacteriana/tratamento farmacológico , Vaginose Bacteriana/genética
3.
Lett Appl Microbiol ; 71(4): 394-399, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32557652

RESUMO

The aims of the present study were to examine the occurrence of Staphylococcus spp. in the tonsils of slaughtered pigs in a regional slaughterhouse in Greece, the antibiotic resistance of the Staphylococcus spp. isolates, and the enteroxigenicity of the S. aureus isolates. Staphylococcus spp. were isolated in 70 (48·61%) out of the total 144 tonsil samples. The predominant species was S. aureus in coagulase-positive staphylococci (CoPS), while the predominant species were Staphylococcus epidermidis and Staphylococcus saprophyticus in the coagulase-negative staphylococci (CoNS). Staphylococcus spp. isolates presented high antibiotic resistance frequencies to tetracycline (97·1%) or clindamycin (80·0%) and low antibiotic resistance frequencies to fusidic acid (14·3%). No methicillin-resistant S. aureus (MRSA) strains were identified, and all Staphylococcus spp. isolates were susceptible to vancomycin. Among the 26 S. aureus isolates, 21 (80·76%) possessed staphylococcal enterotoxin genes with seven different enterotoxin gene profiles. The predominant enterotoxin profile was seg, sei and sej with seven S. aureus isolates. The occurrence of multidrug resistant Staphylococcus spp. in pig tonsils indicate public health risk to pork consumers and handlers in developing antimicrobial resistance.


Assuntos
Farmacorresistência Bacteriana , Enterotoxinas/metabolismo , Tonsila Palatina/microbiologia , Infecções Estafilocócicas/veterinária , Staphylococcus/isolamento & purificação , Doenças dos Suínos/microbiologia , Matadouros/estatística & dados numéricos , Animais , Antibacterianos/farmacologia , Clindamicina/farmacologia , Grécia/epidemiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus/classificação , Staphylococcus/efeitos dos fármacos , Staphylococcus/genética , Suínos , Doenças dos Suínos/epidemiologia
4.
Toxicon ; 183: 11-19, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32450143

RESUMO

Staphylococcus aureus is an opportunistic human pathogens, with the ability to produce a series of virulence factors that contribute to the severity of infections. Exfoliative toxins (ETs) are one of the important virulence factors that participating in staphylococcal scalded skin syndrome. Melittin has different biological activities, comprising of antiviral, broad spectrum antibacterial, antiprotozoal, antifungal and anti-inflammatory effects. Twelve clinical isolates of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) were obtained from wound infection in the burn patients. The MIC plus three sub-inhibitory concentrations (I, II and III) of clindamycin and melittin were tested. Next, the synergistic effects of melittin and clindamycin were evaluated using the broth microdilution checkerboard assay. The detection of exfoliative toxin A and B genes were examined by PCR method. Then the effects of sub-MIC melittin on the expression levels of eta and etb were assessed by quantitative real-time PCR (qRT-PCR) assay. Melittin MIC values against MRSA and MSSA planktonic cells were 0.25-0.5 and 0.25-1 µg/ml, respectively. The clindamycin MIC values against MRSA and MSSA were between 0.5 and 8 µg/ml and 0.5-2 µg/ml, respectively. The results of the time-kill kinetics assay (3.5log10 and 3log10) against MSSA and MRSA planktonic cells were determined within 24 h using melittin. The mean expression of eta in MRSA and MSSA was significantly downregulated to approximately 3.5 and 4 fold, respectively. Moreover, the mean expression of etb in MRSA and MSSA were significantly downregulated to approximately 2.5 and 3 fold, respectively. Hemolytic assay showed that the extracted melittin indicates a strong hemolytic activity (HD50 = 2 µg/ml). Melittin at 0.5 µg/ml induced cell lysis and stimulated the formation of vesicles in S. aureus strains. Melittin could reduce the expression of eta and etb as encoding exfoliative toxin A and B genes. This component appears to be a good candidate for the treatment of MRSA and MSSA strains. So, melittin in combination with clindamycin can be classified as a complementary treatment of wound infections in burn patients.


Assuntos
Antibacterianos/farmacologia , Clindamicina/farmacologia , Meliteno/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Exfoliatinas/genética , Humanos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas , Fatores de Virulência/genética
5.
PLoS One ; 15(4): e0231274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32271828

RESUMO

We evaluated the minimum inhibitory concentrations of clindamycin and erythromycin toward 98 Bacillus licheniformis strains isolated from several types of fermented soybean foods manufactured in several districts of Korea. First, based on recent taxonomic standards for bacteria, the 98 strains were separated into 74 B. licheniformis strains and 24 B. paralicheniformis strains. Both species exhibited profiles of erythromycin resistance as an acquired characteristic. B. licheniformis strains exhibited acquired clindamycin resistance, while B. paralicheniformis strains showed unimodal clindamycin resistance, indicating an intrinsic characteristic. Comparative genomic analysis of five strains showing three different patterns of clindamycin and erythromycin resistance identified 23S rRNA (adenine 2058-N6)-dimethyltransferase gene ermC and spermidine acetyltransferase gene speG as candidates potentially involved in clindamycin resistance. Functional analysis of these genes using B. subtilis as a host showed that ermC contributes to cross-resistance to clindamycin and erythromycin, and speG confers resistance to clindamycin. ermC is located in the chromosomes of strains showing clindamycin and erythromycin resistance and no transposable element was identified in its flanking regions. The acquisition of ermC might be attributable to a homologous recombination. speG was identified in not only the five genome-analyzed strains but also eight strains randomly selected from the 98 test strains, and deletions in the structural gene or putative promoter region caused clindamycin sensitivity, which supports the finding that the clindamycin resistance of Bacillus species is an intrinsic property.


Assuntos
Bacillus licheniformis/genética , Bacillus/genética , Clindamicina/farmacologia , Farmacorresistência Bacteriana/genética , Genes Bacterianos , Genômica , Bacillus/efeitos dos fármacos , Bacillus/crescimento & desenvolvimento , Bacillus licheniformis/classificação , Bacillus licheniformis/efeitos dos fármacos , Bacillus licheniformis/crescimento & desenvolvimento , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/genética , Bacillus subtilis/crescimento & desenvolvimento , Sequência de Bases , Farmacorresistência Bacteriana/efeitos dos fármacos , Eritromicina/farmacologia , Testes de Sensibilidade Microbiana
6.
Nat Commun ; 11(1): 1108, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111839

RESUMO

Directed evolution of the ribosome for expanded substrate incorporation and novel functions is challenging because the requirement of cell viability limits the mutations that can be made. Here we address this challenge by combining cell-free synthesis and assembly of translationally competent ribosomes with ribosome display to develop a fully in vitro methodology for ribosome synthesis and evolution (called RISE). We validate the RISE method by selecting active genotypes from a ~1.7 × 107 member library of ribosomal RNA (rRNA) variants, as well as identifying mutant ribosomes resistant to the antibiotic clindamycin from a library of ~4 × 103 rRNA variants. We further demonstrate the prevalence of positive epistasis in resistant genotypes, highlighting the importance of such interactions in selecting for new function. We anticipate that RISE will facilitate understanding of molecular translation and enable selection of ribosomes with altered properties.


Assuntos
Ribossomos/genética , Ribossomos/metabolismo , Antibacterianos/farmacologia , Clindamicina/farmacologia , Evolução Molecular Direcionada , Farmacorresistência Bacteriana/genética , Epistasia Genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Biblioteca Gênica , Genótipo , Mutação , Peptidil Transferases/genética , Peptidil Transferases/metabolismo , Inibidores da Síntese de Proteínas/farmacologia , RNA Ribossômico/genética , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Ribossomos/efeitos dos fármacos , Biologia Sintética
7.
J Dairy Sci ; 103(4): 3459-3469, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32037172

RESUMO

The purpose of this study was to determine the effect of intramammary pirlimycin on the fecal microbiome of dairy cattle. Primiparous heifers were enrolled and assigned to a treatment or control group at a ratio of 2:1. In part 1 of the study, treated heifers (T1) were given intramammary pirlimycin into one infected quarter once daily for 2 d at 24-h intervals, according to the label instructions. Control heifers received no treatment. In part 2 of the study, treated heifers (T2) were given intramammary pirlimycin into one infected quarter once daily for 8 d at 24-h intervals, according to the label instructions. All enrolled heifers (T1, T2, and control) had quarter-level milk samples aseptically collected for bacterial culture and fecal samples collected for 16S rRNA gene sequencing on d 0, 2, 7, 14, 21, and 28. Milk samples were plated on Columbia blood agar and incubated at 37°C for 24 h. Bacteria were identified using MALDI-TOF mass spectrometry. The DNA was extracted from feces using PowerFecal kits (Qiagen, Venlo, the Netherlands). The 16S rRNA gene amplicon library construction and sequencing was performed at the University of Missouri DNA Core facility. Testing for differences in fecal community composition was performed via one-way permutational multivariate ANOVA of Bray-Curtis and Jaccard similarities using Past 3.13 (https://folk.uio.no/ohammer/past/). Mean total count of operational taxonomic units and Chao1, Shannon, and Simpson α-diversity indices were determined and compared via t-test or Wilcoxon rank sum test. A treatment-dependent effect was present in the observed and predicted richness of feces from cows in the T1 group at d 2 posttreatment. Additionally, intramammary pirlimycin induced a significant change in the composition of the fecal microbiota by d 2 in the treated groups. Based on calculated intra-subject similarities, intramammary pirlimycin was associated with a significant acute change in the fecal microbiota of dairy heifers and that chance reversed when the antimicrobial exposure was brief, but sustained following longer exposure. Overall, intramammary pirlimycin administration affected the fecal microbiome of lactating dairy heifers. Further work is necessary to determine the effect of these changes on the heifer and the dairy environment as well as if treatment is influencing antimicrobial resistance among enteric and environmental bacteria.


Assuntos
Antibacterianos/farmacologia , Bovinos/microbiologia , Clindamicina/análogos & derivados , Fezes/microbiologia , Microbiota/efeitos dos fármacos , Animais , Antibacterianos/administração & dosagem , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Clindamicina/administração & dosagem , Clindamicina/farmacologia , Feminino , Lactação , Glândulas Mamárias Animais , Mastite Bovina/microbiologia , Leite , Países Baixos , RNA Ribossômico 16S/análise
8.
Infect Dis (Lond) ; 52(3): 196-201, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31778089

RESUMO

Introduction: Clostridium perfringens and other gas gangrene-forming clostridia are commensals of the human gut and vaginal microbiota, but can cause serious or even fatal infections. As there are relatively few published studies on antibiotic susceptibility of these bacteria, we decided to perform a 10-year retrospective study in a South-Eastern Hungarian clinical centre.Methods: A total of 372 gas gangrene-forming Clostridium spp. were isolated from clinically relevant samples and identified with rapid ID 32A (bioMérieux, France) and MALDI-TOF MS (Bruker Daltinics, Germany) methods. Antibiotic susceptibility was determined with E-tests.Results: We identified 313 C. perfringens, 20 C. septicum, 10 C. sordellii, 10 C. sporogenes, 9 C. tertium, 6 C. bifermentans, 4 C. histolyticum isolates. In C. perfringens isolates, the rate of penicillin resistance was 2.6% and the rate of clindamycin resistance 3.8%. Penicillin resistance was found in 6.8% and clindamycin resistance in 8.5% of the non-perfringens Clostridium spp. isolates.Conclusion: The antibiotic susceptibility of C. perfringens isolates was in good agreement with previous publications. The rates of resistance to penicillin and clindamycin were very low. The resistance rates of non-perfringens Clostridium spp. isolates were higher than those of C. perfringens strains, but lower than those published in the literature.


Assuntos
Antibacterianos/farmacologia , Clindamicina/farmacologia , Clostridium/efeitos dos fármacos , Gangrena Gasosa/microbiologia , Penicilinas/farmacologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Cefoxitina/farmacologia , Criança , Pré-Escolar , Clostridium/isolamento & purificação , Clostridium bifermentans/efeitos dos fármacos , Clostridium bifermentans/isolamento & purificação , Clostridium histolyticum/efeitos dos fármacos , Clostridium histolyticum/isolamento & purificação , Clostridium perfringens/efeitos dos fármacos , Clostridium perfringens/isolamento & purificação , Clostridium septicum/efeitos dos fármacos , Clostridium septicum/isolamento & purificação , Clostridium sordellii/efeitos dos fármacos , Clostridium sordellii/isolamento & purificação , Clostridium tertium/efeitos dos fármacos , Clostridium tertium/isolamento & purificação , Farmacorresistência Bacteriana , Feminino , Gangrena Gasosa/tratamento farmacológico , Humanos , Hungria , Imipenem/farmacologia , Lactente , Concentração Inibidora 50 , Masculino , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Tigeciclina/farmacologia , Adulto Jovem
9.
Pediatr Infect Dis J ; 39(3): 204-210, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31725114

RESUMO

BACKGROUND: Despite the absence of adequate safety or efficacy data, clindamycin is widely prescribed in the neonatal intensive care unit. We evaluated the association between clindamycin exposure and adverse events, as well as antibiotic effectiveness in infants. METHODS: This was a retrospective cohort study of infants receiving clindamycin before postnatal day 121 who were discharged from a Pediatrix Medical Group neonatal intensive care unit (1997-2015). Using a previously developed pharmacokinetic model, we performed simulations to predict clindamycin exposure based on available dosing data. We used multivariable logistic regression to evaluate the association between clindamycin exposure and safety outcomes during and after clindamycin therapy. We reported the proportion of infants with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and clearance of MRSA bacteremia. RESULTS: A total of 4089 infants received clindamycin at a median (25th-75th percentile) dose of 15 mg/kg/d (12-16). Clearance increased with older gestational age. Infants with the highest total clindamycin exposure had marginally increased odds of necrotizing enterocolitis within 7 days (adjusted odds ratio = 1.95 [1.04-3.63]), but exposure was not associated with death, sepsis, seizures, intestinal perforation or intestinal strictures. Of 25 infants who had MRSA bacteremia, 19 (76%) cleared the infection by the end of the clindamycin course. CONCLUSIONS: Higher clindamycin exposure was not associated with increased odds of death or nonlaboratory adverse events. The use of pharmacokinetic models combined with available electronic health record data offers a valuable, cost-effective approach to analyzing the safety and effectiveness of drugs in infants when large-scale trials are not feasible.


Assuntos
Antibacterianos , Clindamicina , Uso de Medicamentos/estatística & dados numéricos , Fatores Etários , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Clindamicina/farmacologia , Clindamicina/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Razão de Chances , Farmacoepidemiologia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
10.
Rev Chilena Infectol ; 36(4): 455-460, 2019 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-31859769

RESUMO

BACKGROUND: The double disc diffusion method is an alternative diagnostic that allows the identification of Staphylococcus aureus isolates apparently susceptible to clindamycin but that may develop resistance due to an induction phenomena, mainly asociated to the increase in resistance to methicillin, thus increasing the possibility of failure in the treatment. AIM: To determine the frequency of induced clindamycin resistance in methicillin-resistant S. aureus (MRSA) isolated from Paraguayan children. MATERIALS AND METHODS: In this cross sectional study, we collected 145 S. aureus isolates that caused skin and soft tissue and osteoarticular infections in pediatric patients of the Central Hospital I.P.S. in the period from December-2012 to November-2013. Resistance to clindamycin was determined by automated methods and double disc diffusion. PCR was performed for ermA, ermB, ermC and msrA genes from representative isolates. RESULTS: The global resistance to methicillin and clindamycin was 67 and 13%, respectively (11% attributable to the inducible mechanism). The ermC and msrA genes were detected individually in 25 and 17% of the isolates respectively while an isolate presented both genes simultaneously. DISCUSSION: The frequency of inducible resistance to clindamycin indicates the importance of double disc diffusion methods in microbiological practice, as well as being within the cut off points considered acceptable for the use of this antibiotic for skin infections. and osteoarticular caused by MRSA.


Assuntos
Antibacterianos/farmacologia , Clindamicina/farmacologia , Farmacorresistência Bacteriana/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/microbiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana/efeitos dos fármacos , Genes Bacterianos , Humanos , Lactente , Recém-Nascido , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Paraguai , Reação em Cadeia da Polimerase
11.
Biomolecules ; 9(10)2019 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-31548510

RESUMO

The prevalence of Staphylococcus aureus in 2160 bulk ready-to-eat foods from the Sichuan province of China during 2013-2016 was investigated. The antibiotic resistance and the associated genes, as well as biofilm formation capacity of the S. aureus isolates were measured. Furthermore, the relationship between the antibiotic resistance and the resistant genes was discussed. It was found that 54 S. aureus isolates were recovered, and their prevalence in meat products, dairy, fruit and vegetables, and desserts were 31 (2.6%), six (3.0%), nine (2.2%) and eight (2.3%), respectively. Most strains (52/54) were resistant to at least one of the antibiotics, and 21 isolates were identified as multidrug-resistant (MDR) S. aureus. Three isolates were found to be methicillin-resistant S. aureus. Penicillin, erythromycin, clindamycin, tetracycline and inducible clindamycin resistance were determined as the predominant antibiotics, and the isolates with the phenotypic resistance on these five antibiotics were all determined positive for the resistant gene associated. In total, 33 of 54 S. aureus isolates showed biofilm formation capacity, including two strong biofilm producers, one moderate and 30 weak ones. Two S. aureus isolates with strong biofilm formation abilities showed multi-drug resistance, and one moderate biofilm producer was resistant to two categories of antibiotics.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Resistência Microbiana a Medicamentos , Microbiologia de Alimentos/estatística & dados numéricos , Staphylococcus aureus/crescimento & desenvolvimento , Biofilmes/efeitos dos fármacos , China/epidemiologia , Clindamicina/farmacologia , Laticínios/microbiologia , Eritromicina/farmacologia , Frutas/microbiologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Carne/microbiologia , Penicilinas/farmacologia , Prevalência , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Tetraciclina/farmacologia , Verduras/microbiologia
12.
Infect Immun ; 87(12)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31527126

RESUMO

Severe manifestations of group A Streptococcus (GAS) infections are associated with massive tissue destruction and high mortality. Clindamycin (CLI), a bacterial protein synthesis inhibitor, is recommended for treating patients with severe invasive GAS infection. Nonetheless, the subinhibitory concentration of CLI induces the production of GAS virulent exoproteins, such as streptolysin O (SLO) and NADase, which would enhance bacterial virulence and invasiveness. A better understanding of the molecular mechanism of how CLI triggers GAS virulence factor expression will be critical to develop appropriate therapeutic approaches. The present study shows that CLI activates SLO and NADase expressions in the emm1-type CLI-susceptible wild-type strain but not in covS or control of virulence sensor (CovS) phosphatase-inactivated mutants. Supplementation with Mg2+, which is a CovS phosphatase inhibitor, inhibits the CLI-mediated SLO upregulation in a dose-dependent manner in CLI-susceptible and CLI-resistant strains. These results not only reveal that the phosphorylation of response regulator CovR is essential for responding to CLI stimuli, but also suggest that inhibiting the phosphatase activity of CovS could be a potential strategy for the treatment of invasive GAS infection with CLI.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Clindamicina/farmacologia , Histidina Quinase/metabolismo , Proteínas Repressoras/metabolismo , Streptococcus pyogenes/metabolismo , Estreptolisinas/biossíntese , Proteínas de Bactérias/biossíntese , Histidina Quinase/antagonistas & inibidores , Histidina Quinase/genética , Magnésio/farmacologia , Monoéster Fosfórico Hidrolases/metabolismo , Streptococcus pyogenes/patogenicidade
13.
Infez Med ; 27(3): 266-273, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31545770

RESUMO

Staphylococcus aureus is responsible for life-threatening conditions, while in the meantime it has rapidly acquired resistance to several antibiotic classes. In the context of an effective empirical antibiotic therapy, an accurate evaluation of the resistance rates of S. aureus may be critical. The aim of this study was to determine the resistance rates of S. aureus in the years 2015-2018 and to assess the impact of specimen stratification on the resistance rates. We have retrospectively analysed S. aureus strains isolated from blood, bronchial aspirate, pus, sputum and urine collected from hospitalized and ambulatory care patients. The comparison between resistance rates from 2015 to 2018 and among different specimens was assessed by Fisher's exact test followed by Benjamini and Hochberg's correction of the p-values. Higher resistance rates were detected for penicillin followed by oxacillin, levofloxacin, erythromycin and clindamycin. Differences in the annual resistance rates were not statistically significant after the BH's correction. The comparison between cumulative S. aureus resistance rates stratified by specimens showed some statistically relevant differences among the five specimen types. In particular, p-values were statistically significant for clindamycin, erythromycin, gentamicin, levofloxacin, oxacillin, penicillin and vancomycin. Annual resistance rates of S. aureus clinical isolates remained constant over the course of time. Moreover, the stratification of the data by specimen may significantly impact on the evaluation of the resistance rates, at least for some antibiotics. Therefore, if the number of data is high, stratification by specimens may be recommendable to better approach an empirical antibiotic therapy.


Assuntos
Farmacorresistência Bacteriana , Staphylococcus aureus/efeitos dos fármacos , Clindamicina/farmacologia , Eritromicina/farmacologia , Feminino , Gentamicinas/farmacologia , Humanos , Itália , Levofloxacino/farmacologia , Masculino , Oxacilina/farmacologia , Resistência às Penicilinas , Estudos Retrospectivos , Fatores de Tempo
14.
Euro Surveill ; 24(31)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31387670

RESUMO

BackgroundCampylobacter is the main cause of bacterial gastroenteritis worldwide. The main transmission route is through consumption of food contaminated with Campylobacter species or contact with infected animals. In Latvia, the prevalence of campylobacteriosis is reported to be low (4.6 cases per 100,000 population in 2016).AimTo determine prevalence, species spectrum and antimicrobial resistance (AMR) of Campylobacter spp. in Latvia, using data from various livestock and human clinical samples.MethodsWe analysed data of Campylobacter microbiological monitoring and AMR (2008 and 2014-16) in Latvia. Data from broilers, poultry, pigs, calves and humans were used to determine prevalence of Campylobacter. Additionally, 45 different origin isolates (22 human) were sequenced on the Illumina MiSeq platform; for each isolate core genome multilocus sequence typing was used and relevant antimicrobial resistance mechanisms were identified.ResultsOverall, Campylobacter prevalence in was 83.3% in pigs, 50.2% in broilers, 16.1% in calves and 5.3% in humans; C. jejuni was the predominant species in all sources except pigs where C. coli was main species. High level of resistance in Campylobacter were observed against fluoroquinolones, tetracycline and streptomycin, in most of sequenced isolates genetic determinants of relevant AMR profiles were identified.ConclusionsIn Latvia, prevalence of Campylobacter in livestock is high, especially in pigs and broilers; prevalence in poultry and humans were lower than in other European countries. AMR analysis reveals increase of streptomycin and tetracycline resistant broiler origin C. jejuni strains. WGS demonstrates a high compliance between resistance phenotype and genotype for quinolones and tetracyclines.


Assuntos
Antibacterianos/farmacologia , Infecções por Campylobacter/tratamento farmacológico , Campylobacter coli/efeitos dos fármacos , Campylobacter coli/genética , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/genética , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genética , Animais , Infecções por Campylobacter/diagnóstico , Infecções por Campylobacter/epidemiologia , Infecções por Campylobacter/veterinária , Campylobacter coli/isolamento & purificação , Campylobacter jejuni/isolamento & purificação , Bovinos , Galinhas/microbiologia , Ciprofloxacino/farmacologia , Clindamicina/farmacologia , Eritromicina/farmacologia , Genótipo , Gentamicinas/farmacologia , Humanos , Letônia/epidemiologia , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Aves Domésticas/microbiologia , Prevalência , Vigilância de Evento Sentinela , Suínos/microbiologia , Tetraciclinas/farmacologia , Sequenciamento Completo do Genoma
15.
Lett Appl Microbiol ; 69(4): 286-293, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31392736

RESUMO

The prevalence of Listeria monocytogenes in the retail fish markets of the Kerala, India was investigated by screening 227 samples comprising of marine finfish (n = 97) shellfish (n = 19), ready-to-cook fish products (n = 47), ready-to-eat fish products (n = 10), dried fish (n = 11) and retail ice (n = 43). The prevalence of L. monocytogenes and L. innocua was 2·7% and 17·2% respectively. Sample category wise, prevalence of L. monocytogenes was higher in marine finfish (1·8%) and retail ice (0·9%). All the L. monocytogenes isolates carried virulent genes namely inlA, inlC, inlJ, hlyA, iap, plcA, prfA genes and majority (82%) belonged to 1/2a, 3a serogroups. L. monocytogenes isolates were multidrug-resistant and showed resistance to ampicillin, penicillin, erythromycin, tetracycline and clindamycin. Enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) delineated 58% genetic heterogeneity among the L. monocytogenes strains. The study reports that genetic similarities of the isolates were interlinked to their serogroup and sample origin. SIGNIFICANCE AND IMPACT OF THE STUDY: Prevalence of Listeria monocytogenes, in the retail fish markets of Kerala, India was low but their relatively higher presence in marine finfish and retail ice and virulent nature of the isolates signifies food safety concerns. Moreover, multidrug-resistant nature of these isolates may potentially lead to spread of antimicrobial resistance. This study identified retail ice as a vehicle for entry of L. monocytogenes in retail fish and hence, there is a need to ensure quality of retail ice used for maintaining the cold-chain.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Listeria monocytogenes/efeitos dos fármacos , Alimentos Marinhos/microbiologia , Frutos do Mar/microbiologia , Ampicilina/farmacologia , Animais , Clindamicina/farmacologia , Eritromicina/farmacologia , Pesqueiros , Peixes/microbiologia , Microbiologia de Alimentos , Inocuidade dos Alimentos , Heterogeneidade Genética , Gelo/análise , Índia , Listeria monocytogenes/genética , Listeria monocytogenes/isolamento & purificação , Penicilinas/farmacologia , Prevalência , Sorogrupo , Tetraciclina/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-31346458

RESUMO

Background: Clindamycin is a lincosamide antibiotic used to treat staphylococcal and streptococcal infections. Reports of clinical Streptococcus agalactiae isolates with the rare lincosamide resistance/macrolide susceptibility (LR/MS) phenotype are increasing worldwide. In this study, we characterised three clinical S. agalactiae strains with the unusual L phenotype from China. Methods: Three clinical S. agalactiae strains, Sag3, Sag27 and Sag4104, with the L phenotype were identified from 186 isolates collected from 2016 to 2018 in Shanghai, China. The MICs of clindamycin, erythromycin, tetracycline, levofloxacin, and penicillin were determined using Etest. PCR for the lnu(B) gene was conducted. Whole genome sequencing and sequence analysis were carried out to investigate the genetic context of lnu(B). Efforts to transfer lincomycin resistance by conjugation and to identify the circular form by inverse PCR were made. Results: Sag3, Sag27, and Sag4104 were susceptible to erythromycin (MIC ≤0.25 mg/L) but resistant to clindamycin (MIC ≥1 mg/L). lnu(B) was found to be responsible for the L phenotype. lnu(B) in Sag3 and Sag27 were chromosomally located in an aadE-spw-lsa(E)-lnu(B) resistance gene cluster adjacent to an upstream 7-kb tet(L)-cat resistance gene cluster. Two resistance gene clusters were flanked by the IS6-like element, IS1216. Sag4104 only contained partial genes of aadE-spw-lsa(E)-lnu(B) resistance gene cluster and was also flanked by IS1216. Conclusion: These results established the presence of the L phenotype associated with lnu(B) in clinical S. agalactiae isolates in China. The lnu(B)-containing multi-resistance gene cluster possibly acts as a composite transposon flanked by IS1216 and as a vehicle for the dissemination of multidrug resistance among S. agalactiae.


Assuntos
Proteínas de Bactérias/genética , Clindamicina/farmacologia , Farmacorresistência Bacteriana , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/genética , China , Cromossomos Bacterianos/genética , Conjugação Genética , Feminino , Humanos , Testes de Sensibilidade Microbiana , Família Multigênica , Fenótipo , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/isolamento & purificação , Sequenciamento Completo do Genoma/métodos
17.
Mol Cell Biochem ; 461(1-2): 23-36, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31309409

RESUMO

Antibiotics are the front-line treatment against many bacterial infectious diseases in human. The excessive and long-term use of antibiotics in human cause several side effects. It is important to understand the underlying molecular mechanisms of action of antibiotics in the host cell to avoid the side effects due to the prevalent uses. In the current study, we investigated the crosstalk between mitochondria and lysosomes in the presence of widely used antibiotics: erythromycin (ERM) and clindamycin (CLDM), which target the 50S subunit of bacterial ribosomes. We report here that both ERM and CLDM induced caspase activation and cell death in several different human cell lines. The activity of the mitochondrial respiratory chain was compromised in the presence of ERM and CLDM leading to bioenergetic crisis and generation of reactive oxygen species. Antibiotics treatment impaired autophagy flux and lysosome numbers, resulting in decreased removal of damaged mitochondria through mitophagy, hence accumulation of defective mitochondria. We further show that over-expression of transcription factor EB (TFEB) increased the lysosome number, restored mitochondrial function and rescued ERM- and CLDM-induced cell death. These studies indicate that antibiotics alter mitochondria and lysosome interactions leading to apoptotsis and may develop a novel approach for targeting inter-organelle crosstalk to limit deleterious antibiotic-induced side effects.


Assuntos
Apoptose/efeitos dos fármacos , Clindamicina/farmacologia , Eritromicina/farmacologia , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Biogênese de Organelas , Antibacterianos/farmacologia , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagia/efeitos dos fármacos , Linhagem Celular , Humanos , Lisossomos/efeitos dos fármacos , Fusão de Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Modelos Biológicos , Espécies Reativas de Oxigênio/metabolismo , Subunidades Ribossômicas Maiores de Bactérias/metabolismo
18.
Jpn J Infect Dis ; 72(6): 420-422, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31257242

RESUMO

Streptococcus agalactiae (Group B Streptococcus, GBS) is a pathogen which causes neo natal sepsis, meningitis, and invasive infections in the elderly and people with medical conditions. Macrolide and lincosamide resistance rates of GBS strains have been increasing worldwide. A macrolide resistance gene, erythromycin ribosomal methylase (erm), typically confers macrolides, lincosamides, streptogramin B resistance phenotype. However, in the current study, we recovered and characterized 3 clinical ermB-PCR-positive isolates of GBS with L phenotype. The presence of ermB and lnuB (lincosamide nucleotidyltransferase) genes in all 3 clinical isolates was confirmed using PCR. The ermB gene of the clinical isolates harbored C222T (N74N), T224C (I75T), and A299G (N100S) nucleotide (amino acid) substitutions, and insertion of an IS1216E element at nucleotide position 643, resulted in the deletion of a segment spanning nucleotides 643-738 of ermB gene, which suggested the loss-of-function of ErmB protein in the 3 clinical isolates. Since these clinical isolates show positive PCR result for a drug resistance gene despite its partial deletion, these results contradict their drug resistance phenotype. These factors must be considered while performing PCR-based detection of antimicrobial drug resistance genes.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Clindamicina/farmacologia , Eritromicina/farmacologia , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/genética , Farmacorresistência Bacteriana/genética , Humanos , Testes de Sensibilidade Microbiana , Fenótipo , Infecções Estreptocócicas/microbiologia
19.
J Appl Microbiol ; 127(5): 1381-1390, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31342602

RESUMO

AIMS: This study investigated the potential synergy between erythromycin and nisin against clinical Group B Streptococcus (GBS) strains. METHODS AND RESULTS: The combination of erythromycin and nisin was examined for synergistic activity using checkerboard and time-kill assays against invasive and colonizing GBS strains. Additionally, the immunological effect of the antibiotic combination was investigated in vitro using human U937 cells and ELISA analysis. Checkerboard assays confirmed an additive effect when the antimicrobials were combined, while time-kill assays demonstrated a synergistic effect when antimicrobials were combined for invasive GBS isolates. Furthermore, a significantly lower TNF-alpha response (P < 0·05) was observed in U937 cells challenged with GBS when erythromycin and nisin were used in combination. CONCLUSIONS: The results suggest that erythromycin and nisin can act synergistically to inhibit the growth of GBS. SIGNIFICANCE AND IMPACT OF THE STUDY: Group B Streptococcus is the leading cause of invasive neonatal disease worldwide and is becoming increasingly more prevalent in adults. Resistance to some conventionally used antibiotics, such as erythromycin and clindamycin, continue to rise among GBS, indicating a need for alternative treatments. This study demonstrates the potential of an erythromycin-nisin combination for treatment of GBS infections and encourages further investigation of this treatment option.


Assuntos
Antibacterianos/farmacologia , Eritromicina/farmacologia , Nisina/farmacologia , Streptococcus agalactiae/efeitos dos fármacos , Clindamicina/farmacologia , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade Microbiana , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/crescimento & desenvolvimento , Streptococcus agalactiae/isolamento & purificação , Células U937
20.
Ann Pharmacother ; 53(11): 1153-1161, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31177803

RESUMO

Objective: To review the evidence for trimethoprim-sulfamethoxazole (TMP-SMX), clindamycin, doxycycline, and minocycline in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Data Source: MEDLINE, PubMed, EMBASE, Google, Google Scholar, Cochrane Central Register of Controlled Trials from 1946 to May 20, 2019. The search was performed with the keywords methicillin-resistant Staphylococcus aureus, MRSA, Staphylococcus aureus, pneumonia, trimethoprim, sulfamethoxazole drug combination, trimethoprim, sulfamethoxazole, TMP-SMX, co-trimoxazole, clindamycin, doxycycline, and minocycline. Data Extraction: Studies reporting the use of the above antibiotics for MRSA pneumonia treatment with clinical outcomes were included. Search parameters were limited to English language and human studies only. Data Synthesis: The search yielded 16 relevant articles: 6 TMP-SMX, 8 clindamycin, zero doxycycline, and 2 minocycline. For TMP-SMX, prospective randomized trials showed variable results; however, these studies were not specifically designed to assess MRSA pneumonia treatment. Retrospective studies with clindamycin suggested that it could be used as monotherapy or in combination with other anti-MRSA antibiotics. There was no evidence for doxycycline use, but 2 small retrospective reviews appeared to support minocycline as a treatment option. Relevance to Patient Care and Clinical Practice: These antibiotics are often used in clinical practice as potential treatment options for MRSA pneumonia. This article reviews the evidence for the clinical efficacy and safety of these agents. Conclusions: There are limited data to support use of TMP-SMX, clindamycin, doxycycline, or minocycline in MRSA pneumonia treatment. Randomized controlled trials are required to determine the effectiveness of these antibiotics. Clinicians should base their decision to use these agents on a case-by-case basis depending on clinical status and susceptibility results.


Assuntos
Clindamicina/uso terapêutico , Terapia Combinada/métodos , Doxiciclina/uso terapêutico , Minociclina/uso terapêutico , Pneumonia/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Clindamicina/farmacologia , Doxiciclina/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Minociclina/farmacologia , Estudos Retrospectivos , Combinação Trimetoprima e Sulfametoxazol/farmacologia
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