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1.
J Vet Sci ; 21(3): e40, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476314

RESUMO

The purpose of this study was to investigate the high-level mupirocin resistance (HLMR) in Gram-positive bacteria isolated from companion animals. A total of 931 clinical specimens were collected from diseased pets. The detection of mupirocin-resistant bacteria and plasmid-mediated mupirocin resistance genes were evaluated by antimicrobial susceptibility tests, polymerase chain reactions, and sequencing analysis. Four-hundred and six (43.6%) bacteria were isolated and 17 (4.2%), including 14 staphylococci and 3 Corynebacterium were high-level mupirocin-resistant (MICs, ≥ 1,024 ug/mL) harboring mupA. Six staphylococci of HLMR strains had plasmid-mediated mupA-IS257 flanking regions. The results show that HLMR bacteria could spread in veterinary medicine in the near future.


Assuntos
Antibacterianos/farmacologia , Corynebacterium/efeitos dos fármacos , Farmacorresistência Bacteriana , Mupirocina/farmacologia , Staphylococcus/efeitos dos fármacos , Animais , Doenças do Gato/tratamento farmacológico , Gatos , Infecções por Corynebacterium/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Cães , Testes de Sensibilidade Microbiana/veterinária , Reação em Cadeia da Polimerase/veterinária , Análise de Sequência de DNA/veterinária , Infecções Estafilocócicas/tratamento farmacológico
2.
Sci Rep ; 10(1): 2854, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071320

RESUMO

The current study aimed to formulate Selenium-Chitosan-Mupirocin (M-SeNPs-CCH) complex. The nanohybrid system was prepared using chitosan-cetyltrimethylammonium bromide (CTAB)-based hydrogel (CCH) that entrapped mupirocin (M) and selenium nanoparticles (SeNPs). The in vitro studies were performed by evaluation of the antibacterial activity and toxicity on L929 mouse fibroblast cell line. The in vivo study was conducted on rat diabetic wound infection model that was infected by mupirocin-methicillin-resistant Staphylococcus aureus (MMRSA). The wounds were treated by M-SeNPs-CCH nanohybrid system with concentrations of M; 20 mg/ml, CCH; 2 mg/ml and SeNPs; 512 µg/ml in two times/day for 21 days. The therapeutic effect of this nanohybrid system was evaluated by monitoring wound contraction and histopathological changes. Evaluation of the average wound healing time showed a significant difference between the treatment and control groups (P≤0.05). The histopathological study indicated that the amount of wound healing was considerable in M-SeNPs-CCH nanohybrid system groups compared to the control and M groups. The M-SeNPs-CCH nanohybrid system formulated in this study was able to reduce 3-fold MIC of mupirocin with synergistic antibacterial activity as well as to play a significant role in wound contraction, angiogenesis, fibroblastosis, collagenesis, proliferation of hair follicle, and epidermis growth compared to the control group (P ≤ 0.05). This research suggests that this nanohybrid system might be a development for the treatment of diabetic wound infection at mild stage.


Assuntos
Antibacterianos/farmacologia , Complicações do Diabetes/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/química , Quitosana/química , Quitosana/farmacologia , Complicações do Diabetes/microbiologia , Complicações do Diabetes/patologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Mupirocina/química , Mupirocina/farmacologia , Nanoestruturas/química , Ratos , Selênio/química , Selênio/farmacologia , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
3.
Int J Biol Macromol ; 146: 110-118, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881300

RESUMO

A novel composite hydrogel was prepared as a dual drug delivery carrier. Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles were prepared to encapsulate simultaneously ketoprofen and mupirocin, as hydrophobic drug models. These microparticles were embedded in a physically crosslinked hydrogel of κ-carrageenan/locust bean gum. This composite hydrogel showed for both drugs a slower release than the obtained release from microparticles and hydrogel separately. The release of both drugs was observed during a period of 7 days at 37 °C. Different kinetic models were analyzed and the results indicated the best fitting to a Higuchi model suggesting that the release was mostly controlled by diffusion. Also, the drug loaded microparticles were spherical with average mean particle size of 1.0 µm, mesoporous, and distributed homogeneously in the hydrogel. The composite hydrogel showed a thermosensitive swelling behavior reaching 183% of swelling ratio at 37 °C. The composite hydrogel showed the elastic component to be higher than the viscous component, indicating characteristics of a strong hydrogel. The biocompatibility was evaluated with in vitro cytotoxicity assays and the results indicated that this composite hydrogel could be considered as a potential biomaterial for dual drug delivery, mainly for wound healing applications.


Assuntos
Carragenina , Portadores de Fármacos , Galactanos , Cetoprofeno , Mananas , Mupirocina , Gomas Vegetais , Poliésteres , Animais , Carragenina/química , Carragenina/farmacocinética , Carragenina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Galactanos/química , Galactanos/farmacocinética , Galactanos/farmacologia , Cetoprofeno/química , Cetoprofeno/farmacocinética , Cetoprofeno/farmacologia , Mananas/química , Mananas/farmacocinética , Mananas/farmacologia , Camundongos , Mupirocina/química , Mupirocina/farmacocinética , Mupirocina/farmacologia , Células NIH 3T3 , Gomas Vegetais/química , Gomas Vegetais/farmacocinética , Gomas Vegetais/farmacologia , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia
4.
BMC Infect Dis ; 19(1): 1023, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791276

RESUMO

BACKGROUND: Staphylococcus aureus carriage is a known risk factor for staphylococcal disease. However, the carriage rates vary by country, demographic group and profession. This study aimed to determine the S. aureus carriage rate in children in Eastern Uganda, and identify S. aureus lineages that cause infection in Uganda. METHODS: Nasopharyngeal samples from 742 healthy children less than 5 years residing in the Iganga/Mayuge Health and Demographic Surveillance Site in Eastern Uganda were processed for isolation of S. aureus. Antibiotic susceptibility testing based on minimum inhibitory concentrations (MICs) was determined by the BD Phoenix™ system. Genotyping was performed by spa and SCCmec typing. RESULTS: The processed samples yielded 144 S. aureus isolates (one per child) therefore, the S. aureus carriage rate in children was 19.4% (144/742). Thirty one percent (45/144) of the isolates were methicillin resistant (MRSA) yielding a carriage rate of 6.1% (45/742). All isolates were susceptible to rifampicin, vancomycin and linezolid. Moreover, all MRSA were susceptible to vancomycin, linezolid and clindamycin. Compared to methicillin susceptible S. aureus (MSSA) isolates (68.8%, 99/144), MRSA isolates were more resistant to non-beta-lactam antimicrobials -trimethoprim/sulfamethoxazole 73.3% (33/45) vs. 27.3% (27/99) [p < 0.0001]; erythromycin 75.6% (34/45) vs. 24.2% (24/99) [p < 0.0001]; chloramphenicol 60% (27/45) vs. 19.2% (19/99) [p < 0.0001]; gentamicin 55.6% (25/45) vs. 25.3% (25/99) [p = 0.0004]; and ciprofloxacin 35.6% (16/45) vs. 2% (2/99) [p < 0.0001]. Furthermore, 42 MRSA (93.3%) were multidrug resistant (MDR) and one exhibited high-level resistance to mupirocin. Overall, 61 MSSA (61.6%) were MDR, including three mupirocin and clindamycin resistant isolates. Seven spa types were detected among MRSA, of which t037 and t064 were predominant and associated with SCCmec types I and IV, respectively. Fourteen spa types were detected in MSSA which consisted mainly of t645 and t4353. CONCLUSIONS: S. aureus carriage rate in healthy children in Eastern Uganda is high and comparable to rates for hospitalized patients in Kampala. The detection of mupirocin resistance is worrying as it could rapidly increase if mupirocin is administered in a low-income setting. S. aureus strains of spa types t064, t037 (MRSA) and t645, t4353 (MSSA) are prevalent and could be responsible for majority of staphylococcal infections in Uganda.


Assuntos
Antígenos de Bactérias/análise , Portador Sadio/epidemiologia , Farmacorresistência Bacteriana , Nariz/microbiologia , Faringe/microbiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antígenos de Bactérias/classificação , Antígenos de Bactérias/genética , Portador Sadio/microbiologia , Pré-Escolar , Estudos Transversais , Farmacorresistência Bacteriana/genética , Feminino , Técnicas de Genotipagem/métodos , Humanos , Lactente , Recém-Nascido , Masculino , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem Molecular/métodos , Mupirocina/farmacologia , Mupirocina/uso terapêutico , Mucosa Nasal/microbiologia , Vigilância da População/métodos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/genética , Uganda/epidemiologia
5.
J Control Release ; 316: 292-301, 2019 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-31715276

RESUMO

Staphylococcus aureus is a major cause of severe invasive infections. The increasing incidence of infections caused by antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA), calls for exploration of new approaches to treat these infections. Mupirocin is an antibiotic with a unique mode of action that is active against MRSA, but its clinical use is restricted to topical administration because of its limited plasma stability and rapid degradation to inactive metabolites. Mupirocin was identified by a machine learning approach to be suitable for nano-liposome encapsulation. The computational predictions were verified experimentally and PEGylated nano-liposomal formulation of mupirocin (Nano-mupirocin) was developed. The aim of this study was to investigate the efficacy of this formulation when administered parenterally for the treatment of S. aureus invasive infections. Nano-mupirocin exhibited prolonged half-life of active antibiotic and displayed superior antimicrobial activity against S. aureus than free mupirocin in the presence of plasma. Parenteral application of Nano-mupirocin in a murine model of S. aureus bloodstream infection resulted in improved antibiotic distribution to infected organs and in a superior therapeutic efficacy than the free drug. Parenterally administered Nano-mupirocin was also more active against MRSA than free mupirocin in a neutropenic murine lung infection model. In addition, Nano-mupirocin was very efficiently taken up by S. aureus-infected macrophages via phagocytosis leading to enhanced delivery of mupirocin in the intracellular niche and to a more efficient elimination of intracellular staphylococci. The outcome of this study highlights the potential of Nano-mupirocin for the treatment of invasive MRSA infections and support the further clinical development of this effective therapeutic approach.


Assuntos
Antibacterianos/administração & dosagem , Mupirocina/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Feminino , Meia-Vida , Lipossomos , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Mupirocina/farmacocinética , Mupirocina/farmacologia , Nanoestruturas , Infecções Estafilocócicas/microbiologia
6.
Clin Lab ; 65(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625356

RESUMO

BACKGROUND: Resistance to methicillin and mupirocin in coagulase-negative staphylococci (CoNS) is considered as one of the most important issues. Meanwhile, use of phenotypic methods in detecting the resistance to methicillin and mupirocin has a lower accuracy and speed compared to other molecular methods, such as High-Resolution Melting Analysis (HRM). In this study, HRM technique was used to identify CoNS resistance stains. METHODS: This experimental study was done on 86 isolates of CoNS strains isolated at Hamadan Hospital. Pheno-typic tests were used to identify Staphylococcus saprophyticus and S. epidermidis. Methicillin and Mupirocin resistant strains were tested using the MIC and HRM methods, and sensitivity and specificity of the primers were determined based on melting curve temperature range. In addition, data was analyzed by Applied Biosystems StepOne v 2.3 and Applied Biosystems HRM v 3.0.1 software. RESULTS: Eighty-six (86) coagulase-negative isolates were isolated from different clinical specimens. Among these, 69 isolates of S. epidermidis and 17 isolates of S. saprophyticus were identified. Of the 69 S. epidermidis isolates, 19 isolates with oxacillin MIC ≥ 0.5 µg/mL and methicillin-resistant, and 11 isolates with mupirocin MIC ≥ 32 µg/mL and resistant to mupirocin. Of the 17 S. saprophyticus isolates, three isolates with oxacillin MIC ≥ 0.5 µg/mL were also methicillin-resistant, and one isolate with mupirocin MIC ≥ 32 µg/mL was resistant to mupirocin. Melting curve analysis for mecA and mupA primers was determined 81.7 ± 0.5°C and 74 ± 0.5°C, respectively. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HRM assay for detection of methicillin and mupirocin strains testing were 100%. CONCLUSIONS: Identification of methicillin and mupirocin resistance in CoNSs using the HRM method has high sensitivity and specificity. Molecular methods are more accurate and faster than phenotypic methods and can identify a large number of resistant isolates in a short time.


Assuntos
DNA Bacteriano/genética , Farmacorresistência Bacteriana/genética , Meticilina/farmacologia , Mupirocina/farmacologia , Desnaturação de Ácido Nucleico , Staphylococcus/efeitos dos fármacos , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Coagulase/genética , Coagulase/metabolismo , DNA Bacteriano/análise , Humanos , Resistência a Meticilina/genética , Testes de Sensibilidade Microbiana , Especificidade da Espécie , Infecções Estafilocócicas/microbiologia , Staphylococcus/classificação , Staphylococcus/genética
7.
Molecules ; 24(17)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461850

RESUMO

Because of the bacterial drug resistance development, it is reasonable to investigate chemical compounds capable of preventing the spread of resistance to mupirocin (MUP), commonly used in staphylococcal eradication. The objective of the study was to verify the influence of essential oil compounds (EOCs) on the antibacterial activity of MUP against mupirocin-susceptible (MupS) and induced low-level mupirocin-resistant (MupRL) methicillin-resistant Staphylococcus aureus (MRSA) strains. The following parameters were examined: MRSAMupS and MRSAMupRL susceptibility to EOCs (1,8-cineole, eugenol, carvacrol, linalool, (-)-menthone, linalyl acetate, and trans-anethole), the bacterial cell size distribution, and chemical composition by the use of Fourier Transform Infrared Spectroscopy (FTIR) and Raman spectroscopies. The MRSAMupS and MRSAMupRL strains were susceptible to all tested EOCs. 1,8-cineole and (-)-menthone showed synergistic activity against MRSAMupS in combination with mupirocin, whereas 1,8-cineole exhibited synergistic activity against MRSAMupRL as well. In-depth analysis showed that both MRSAMupS and MRSAMupRL displayed similar distributions of the bacterial cell size. The FTIR and Raman spectra of the MRSAMupS and MRSAMupRL strains showed differences in some regions. New bands in the MRSAMupRL Raman spectrum were observed. It was concluded that the use of 1,8-cineole in combination with mupirocin can increase the mupirocin activity against the MRSAMupS and MRSAMupRL strains.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Óleos Voláteis/farmacologia , Antibacterianos/isolamento & purificação , Sinergismo Farmacológico , Eucaliptol/isolamento & purificação , Eucaliptol/farmacologia , Humanos , Mentol/isolamento & purificação , Mentol/farmacologia , Viabilidade Microbiana/efeitos dos fármacos , Mupirocina/farmacologia , Óleos Voláteis/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman
8.
BMC Vet Res ; 15(1): 238, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291949

RESUMO

BACKGROUND: Mupirocin is one of the few antimicrobials active against methicillin-resistant Staphylococcus aureus (MRSA), and is frequently used for the eradication of MRSA nasal colonisation in humans. Initially, mupirocin resistance was recognised in human S. aureus, including MRSA isolates, then also among coagulase-negative staphylococci (CoNS). Nowadays, mupirocin resistance is occasionally observed in canine staphylococci, along with Staphylococcus pseudintermedius (MRSP) strains, as well as CoNS, which usually show methicillin resistance. In the current study, high-level mupirocin resistance in methicillin-resistant staphylococci isolated from diseased dogs and cats was investigated. RESULTS: Among 140 methicillin-resistant staphylococci isolates from dogs and cats, three showed high-level mupirocin resistance in a screening test using the agar disk diffusion method. One was recognised as methicillin-resistant S. aureus, one as methicillin-resistant S. pseudintermedius, and one as methicillin-resistant Staphylococcus haemolyticus. S. pseudintermedius and S. aureus were isolated from dogs, S. haemolyticus was obtained from a cat. All isolates showed high-level mupirocin resistance, confirmed by minimum inhibitory concentration (MIC) values of above 1024 µg/ml and the presence of the plasmid-located gene ileS2. This is the first report on the detection of high-level mupirocin resistance (HLMR) in S. haemolyticus of feline origin. CONCLUSIONS: This study revealed the occurrence of HLMR in three Staphylococcus isolates obtained from companion animals in Poland. The results of this study indicate that the monitoring of mupirocin resistance in staphylococci of animal origin, especially in methicillin-resistant isolates, is strongly recommended.


Assuntos
Doenças do Gato/microbiologia , Doenças do Cão/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Mupirocina/farmacologia , Infecções Estafilocócicas/veterinária , Animais , Antibacterianos/farmacologia , Gatos , Cães , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia
9.
Microb Drug Resist ; 25(10): 1424-1429, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31314694

RESUMO

Aim: The aim of this study was to evaluate the effect of subinhibitory concentrations of trans-anethole on antibacterial and antibiofilm properties of mupirocin against mupirocin-resistant Staphylococcus aureus strains. Methods: Following parameters were examined: isolates susceptibility to antibiotics, minimum inhibitory concentration (MIC) of trans-anethole, antibacterial activity of mupirocin/trans-anethole combination, detection of ileS2 gene, genotypic relativity of isolates using pulsed-field gel electrophoresis method, and the influence of mupirocin/trans-anethole combination on S. aureus biofilm formation. Results: Our study revealed that trans-anethole combined with mupirocin increased the growth inhibition zone diameter around the mupirocin disk, independently on S. aureus strains susceptibility to this antibiotic. Moreover, combination of subinhibitory (MIC50) concentration of mupirocin and trans-anethole significantly decreased biofilm biomass. Conclusions: trans-Anethole appeared efficient in increasing susceptibility to mupirocin and decreasing biofilm formation in S. aureus strains used in this study. Reduction of biofilm formation can potentially protect against S. aureus recolonization. Moreover, use of trans-anethole in combination with mupirocin can increase the mupirocin activity against methicillin-resistant and mupirocin-resistant S. aureus strains.


Assuntos
Anisóis/farmacologia , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Mupirocina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Anisóis/administração & dosagem , Antibacterianos/administração & dosagem , Farmacorresistência Bacteriana , Quimioterapia Combinada , Humanos , Testes de Sensibilidade Microbiana , Mupirocina/administração & dosagem , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação
10.
Am J Infect Control ; 47(11): 1319-1323, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31204092

RESUMO

BACKGROUND: The widespread of methicillin-resistant Staphylococcus aureus (MRSA) antimicrobial decolonization in the clinical setting may lead to an increase in the prevalence of multiresistance to coagulase-negative staphylococci (CoNS) owing to their selection. This study aimed to investigate the impact of MRSA decolonization strategies, using mupirocin and chlorhexidine, on their CoNS susceptibility. METHODS: A total of 312 CoNS isolates were collected before starting the decolonization protocols "baseline strains" (BLS) group, 330 isolates were collected after application of the targeted decolonization protocol "targeted decolonization strains" group, and 355 isolates were collected after application of the universal decolonization protocol "universal decolonization strains" group. Methicillin-resistant CoNS (MR-CoNS) were identified and tested for mupirocin and chlorhexidine susceptibilities. Heptaplex polymerase chain reaction assay was applied for simultaneous screening for chlorhexidine (CHX-R) and mupirocin resistance (Mu-R) genes. RESULTS: Mu-R prevalence of MR-CoNS among the BLS group was considered moderate (9.1%); however, CHX-R in the BLS group was 5.8%, the rate of which significantly increased among the universal decolonization strains group. DISCUSSION: Both MRSA decolonization strategies have an additional benefit in reducing the prevalence of MR-CoNS. The prevalence Mu-R rate didn't change significantly during either of the MRSA decolonization practices that may be due to the local nature of mupirocin application on the nasal mucosa only. In contrast CHX-R that was found to be significantly higher among the UDS group. CONCLUSIONS: Our findings indicate that both MRSA decolonization strategies have an additional benefit in reducing the prevalence of MR-CoNS. Although the universal MRSA decolonization has superior efficacy in decolonization of CoNS, it may increase the risk of selecting CHX-R and Mu-R. In addition, other potential resistance genes should be studied.


Assuntos
Antibacterianos/farmacologia , Clorexidina/farmacologia , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina , Mupirocina/farmacologia , Portador Sadio , Humanos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia
11.
Int Wound J ; 16(4): 1029-1033, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148374

RESUMO

After the introduction of cocaine to the medical practice, local anaesthetics (LA) became essential in pain control. LA infiltration along the incision may be used to provide surgical anaesthesia or postoperative analgesia. This study aimed to compare the antimicrobial effects of the topical antimicrobial agent mupirocine with those of the LA lidocaine and the combination of lidocaine and adrenalin. In our study, the in vitro antimicrobial effects of 1 mL sterile saline, 20 mg/mL mupirocine, 20 mg/mL Lidocaine, and 20 mg/mL Lidocaine and Adrenaline were tested against Staphylococcus aureus American type culture collection (ATCC) 29213, Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922 as Group C (Control), Group M (Mupirocine), Group L (Lidocaine), and Group LA (Lidocaine + adrenaline), respectively. S aureus ATCC 29213, P aeruginosa ATCC 27853, and E coli ATCC 25922 were cultured onto Mueller-Hinton agar (Oxoid, UK) plates for 18 to 24 hours at 37°C. Colonies from these plates were suspended in sterile saline and a 0.5 McFarland turbidity standard suspension (corresponding to 1.5 × 108 CFU/mL) of each isolate was prepared. S Aureus ATCC 29213 inhibition zone diameter values of Group M, Group LA, and Group L were significantly higher compared with the group C (P ˂ 0.05). P aeruginosa ATCC 27853 inhibition zone diameter values of Group M and Group LA were significantly higher compared with the group C (P ˂ 0.05). E coli ATCC 25922 inhibition zone diameter values of Group M, Group LA, and Group L were significantly higher compared to the group C (P ˂ 0.05). LA infiltration along the incision may be used to provide surgical anaesthesia or postoperative analgesia. Considering that LAs show antimicrobial effects besides their analgesic effects, they may contribute to preventing the development and reducing the rate of surgical infections, decreasing the requirement to administer antibiotics. However, caution should be exercised not to antagonise the effective treatment of surgical infections, remembering that controversy on the antimicrobial effects of LAs remains in the literature. Therefore, further comprehensive studies with larger patient populations are warranted to demonstrate the antimicrobial effects of LAs.


Assuntos
Anestésicos Locais/farmacologia , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Lidocaína/farmacologia , Mupirocina/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Anestésicos Locais/uso terapêutico , Antibacterianos/uso terapêutico , Humanos , Lidocaína/uso terapêutico , Mupirocina/uso terapêutico
13.
Future Med Chem ; 11(7): 677-691, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947530

RESUMO

Aim: To determine the computer-predicted anticancer activity of mupirocin and to compare its activities with those determined for another polyene antibiotic, batumin. Materials & methods: Molecular docking, cytotoxicity assays, cell microscopy and cell cycle progression were studied in cancer and nontumorigenic cell lines. Results & conclusion: Cytotoxicity of mupirocin against several cancerous cell lines was detected with the highest one (IC50 = 5.4 µg/ml) against melanoma cell line. The profile of cytotoxicity of mupirocin was similar to that reported for batumin. Nevertheless, the morphology of cells treated with these antibiotics and alterations in cell cycle progression suggested possible dissimilarity in their mechanisms of action. Selective cytotoxicity of mupirocin against melanoma cells potentiates further studies to discover nontoxic drugs for melanoma prevention.


Assuntos
Antibacterianos/química , Antineoplásicos/química , Melanoma/tratamento farmacológico , Mupirocina/química , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular , Desenho de Fármacos , Humanos , Simulação de Acoplamento Molecular , Mupirocina/farmacologia , Compostos Orgânicos/química , Compostos Orgânicos/farmacologia , Polienos/química , Polienos/farmacologia
14.
Pharmacology ; 103(5-6): 320-323, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30889613

RESUMO

BACKGROUND: Nasal carriage of Staphylococcus aureus is very common among health care workers, and treatment with mupirocin is one of the choicest antibiotics available. But with the rampant usage of mupirocin like other antibiotics, the emergence of mupirocin resistance is also on rise. This resistance is both low level as well as high level among the isolated strains. AIM: To screen for the high-level mupirocin resistance among the isolated Staphylococcus strains by Kirby Bauer disk diffusion method. MATERIALS AND METHODS: A total of 200 clinical isolates were tested for high level mupirocin resistance by disk diffusion method using Himedia disks. RESULTS: Among the 200 nasal swabs, 26 (13%) showed growth of S. aureus, whereas 174 (87%) showed the growth of coagulase negative staphylococcus (CONS) spp. Mupirocin resistance was observed only among CONS spp, which was 15% for low-level mupirocin and 8% for high-level mupirocin resistance. No mupirocin resistance was observed among the Staphylococcus spp. CONCLUSION: The identification of Mupirocin resistance will guide us to utilize the antibiotic in a judicious way to treat the nasal carriage effectively.


Assuntos
Antibacterianos/farmacologia , Mupirocina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus/efeitos dos fármacos , Antibacterianos/administração & dosagem , Portador Sadio/microbiologia , Estudos Transversais , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana , Feminino , Pessoal de Saúde , Humanos , Masculino , Mupirocina/administração & dosagem , Cavidade Nasal/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus/enzimologia , Staphylococcus/isolamento & purificação
15.
Biotechnol Lett ; 41(4-5): 495-502, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30927135

RESUMO

Mupirocin is an antibiotic from monocarboxylic acid class used as antibacterial agent against methicillin-resistant Staphylococcus aureus (MRSA) and can be obtained as a mixture of four pseudomonic acids by Pseudomonas fluorescens biosynthesis. Nowadays improving antibiotics occupies an important place in the pharmaceutical industry as more and more resistant microorganisms are developing. Mupirocin is used to control the MRSA outbreaks, for infections of soft tissue or skin and for nasal decolonization. Due to its wide use without prescription, the microorganism's resistance to Mupirocin increased from up to 81%, thus becoming imperative its control or improvement. As the biotechnological production of Mupirocin has not been previously reviewed, in the present paper we summarize some consideration on the biochemical process for the production of pseudomonic acids (submerged fermentation and product recovery). Different strains of Pseudomonas, different culture medium and different conditions for the fermentation were analysed related to the antibiotics yield and the product recovery step is analysed in relation to the final purity. However, many challenges have to be overcome in order to obtain pseudomonic acid new versions with better properties related to antibacterial activity.


Assuntos
Antibacterianos/biossíntese , Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Mupirocina/biossíntese , Mupirocina/farmacologia , Pseudomonas fluorescens/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Portador Sadio/tratamento farmacológico , Portador Sadio/microbiologia , Farmacorresistência Bacteriana , Fermentação , Humanos , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Infecções Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/microbiologia , Tecnologia Farmacêutica/métodos
16.
Am J Infect Control ; 47(8): 902-905, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30926216

RESUMO

BACKGROUND: Preoperative colonization with Staphylococcus aureus (SA) increases risk of surgical site infection. Screening for SA followed by skin and nasal decolonization can help to reduce the risk of postoperative infections. Risk factors for colonization are, however, not completely understood. METHODS: A case-control study using questionnaires and patient demographics specifically designed to observe SA colonization risk factors in a presurgical orthopedic population. A total of 115 subjects with a positive preoperative screen for SA nasal colonization prior to orthopedic surgery completed a questionnaire to assess for SA risk factors: these subjects served as our cases. An additional 476 controls completed similar questionnaires. Data collected included demographic, health, and lifestyle information. Multivariable logistic regression was used to generate odds ratios (OR) for risk of SA colonization. RESULTS: Several risk factors were identified. Male sex (OR 2.3; 95% confidence interval [CI], [1.4-3.8]) and diabetes (OR 3.8 [1.8-7.8]) significantly increased the risk of SA colonization. Older age, visiting public places (OR 0.2 [0.1-0.3]), recent antibiotic use (OR 0.2 [0.1-0.6]), and the presence of facial hair (OR 0.3 [0.1-0.6]) significantly lowered the risk of SA colonization. CONCLUSIONS: By identifying patients who may be at greater risk of SA colonization, we can better streamline our presurgical techniques to help reduce risk of surgical site infections and improve patient outcomes.


Assuntos
Procedimentos Ortopédicos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Infecção da Ferida Cirúrgica/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Portador Sadio , Estudos de Casos e Controles , Criança , Diabetes Mellitus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mupirocina/administração & dosagem , Mupirocina/farmacologia , Nariz/microbiologia , Cuidados Pré-Operatórios/métodos , Fatores de Risco , Infecções Estafilocócicas/prevenção & controle , Infecção da Ferida Cirúrgica/microbiologia , Adulto Jovem
17.
Perit Dial Int ; 39(2): 126-133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30739095

RESUMO

INTRODUCTION: The adoption of the International Society for Peritoneal Dialysis guideline of using mupirocin ointment has been limited by fear of developing mupirocin-resistant organisms. We performed a surveillance program of a large peritoneal dialysis (PD) unit. METHODS: We performed 1,175 surveillance swabs from anterior nares, PD catheter exit site, groin, and axilla, from 240 patients. The mean interval between swabs was 3.3 months. RESULTS: Colonization by Staphylococcus aureus (S. aureus) or Pseudomonas species was 9.5% and 10.9%, respectively. Despite adopting a universal policy of applying mupirocin to PD catheter exit sites in 2001, no instances of mupirocin-resistant S. aureus were identified. Moreover, patients who grew S. aureus from surveillance swabs did not experience higher peritonitis rates than those with "no growth." This was in contrast to patients who grew Pseudomonas or enteric organisms. There were no differences in patient demographics for those who grew S. aureus, Pseudomonas, or enteric organisms (compared with "no-growth" patients). CONCLUSION: Our results suggest that the application of mupirocin ointment appeared to minimize peritonitis of patients colonized with S. aureus. The use of mupirocin in this patient cohort has not led to mupirocin resistance. The increased peritonitis rate of patients who grew Pseudomonas or enteric organisms is of interest. We propose that greater attention to hygiene and catheter care in these patients is warranted. The increasing use of paid healthcare workers attending patients daily to help perform PD (assisted PD) gives an opportunity for us to address these wider issues.


Assuntos
Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres de Demora/microbiologia , Contaminação de Equipamentos/prevenção & controle , Mupirocina/uso terapêutico , Diálise Peritoneal , Peritonite/microbiologia , Peritonite/prevenção & controle , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana , Humanos , Mupirocina/farmacologia , Pomadas , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação
18.
Proc Natl Acad Sci U S A ; 116(5): 1745-1754, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30635416

RESUMO

The past two decades have witnessed an alarming expansion of staphylococcal disease caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). The factors underlying the epidemic expansion of CA-MRSA lineages such as USA300, the predominant CA-MRSA clone in the United States, are largely unknown. Previously described virulence and antimicrobial resistance genes that promote the dissemination of CA-MRSA are carried by mobile genetic elements, including phages and plasmids. Here, we used high-resolution genomics and experimental infections to characterize the evolution of a USA300 variant plaguing a patient population at increased risk of infection to understand the mechanisms underlying the emergence of genetic elements that facilitate clonal spread of the pathogen. Genetic analyses provided conclusive evidence that fitness (manifest as emergence of a dominant clone) changed coincidently with the stepwise emergence of (i) a unique prophage and mutation of the regulator of the pyrimidine nucleotide biosynthetic operon that promoted abscess formation and colonization, respectively, thereby priming the clone for success; and (ii) a unique plasmid that conferred resistance to two topical microbiocides, mupirocin and chlorhexidine, frequently used for decolonization and infection prevention. The resistance plasmid evolved through successive incorporation of DNA elements from non-S. aureus spp. into an indigenous cryptic plasmid, suggesting a mechanism for interspecies genetic exchange that promotes antimicrobial resistance. Collectively, the data suggest that clonal spread in a vulnerable population resulted from extensive clinical intervention and intense selection pressure toward a pathogen lifestyle that involved the evolution of consequential mutations and mobile genetic elements.


Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Staphylococcus aureus Resistente à Meticilina/genética , Virulência/genética , Animais , Antibacterianos/farmacologia , Criança , Clorexidina/farmacologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Genoma Bacteriano/genética , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana/métodos , Mupirocina/farmacologia , Filogenia , Plasmídeos/genética , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
19.
Arch Argent Pediatr ; 117(1): 48-51, 2019 02 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30652446

RESUMO

In Latin America, few studies have been done in mupirocin resistance and biofilm formation in methicillin-resistant Staphylococcus aureus (MRSA). This study investigated mupirocin-resistance in MRSA isolates from pediatric patients with bacteremia and their ability to form biofilm. Antibiotic resistance was analyzed with the Kirby-Bauer test and the broth microdilution method. Bacterial biofilm formation was measured using the crystal violet assay. Among MRSA isolates, 2.3 % (5/217) exhibited a high level of mupirocin-resistance with a minimum inhibitory concentration of >512 µg/mL, in addition to cross-resistance with clindamycin, erythromycin, gentamicin, and ciprofloxacin. Remarkably, biofilm formation in such isolates was moderate to high. This is the first report published in Argentina on clinical isolates of mupirocin-resistant MRSA and it is critical for following its evolution over time at a local level and in the Latin American region.


Assuntos
Antibacterianos/farmacologia , Bacteriemia/microbiologia , Biofilmes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Mupirocina/farmacologia , Argentina , Criança , Farmacorresistência Bacteriana , Hospitais Pediátricos , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Centros de Atenção Terciária
20.
BMC Infect Dis ; 19(1): 1093, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31888515

RESUMO

BACKGROUND: Accurate determination of the efficacy of antimicrobial agents requires neutralization of residual antimicrobial activity in the samples before microbiological assessment of the number of surviving bacteria. Sodium polyanethol sulfonate (SPS) is a known neutralizer for the antimicrobial activity of aminoglycosides and polymyxins. In this study, we evaluated the ability of SPS to neutralize residual antimicrobial activity of antimicrobial peptides [SAAP-148 and pexiganan; 1% (wt/v) in PBS], antibiotics [mupirocin (Bactroban) and fusidic acid (Fucidin) in ointments; 2% (wt/wt))] and disinfectants [2% (wt/wt) silver sulfadiazine cream (SSD) and 0.5% (v/v) chlorhexidine in 70% alcohol]. METHODS: Homogenates of human skin models that had been exposed to various antimicrobial agents for 1 h were pipetted on top of Methicillin-resistant Staphylococcus aureus (MRSA) on agar plates to determine whether the antimicrobial agents display residual activity. To determine the optimal concentration of SPS for neutralization, antimicrobial agents were mixed with PBS or increasing doses of SPS in PBS (0.05-1% wt/v) and then 105 colony forming units (CFU)/mL MRSA were added. After 30 min incubation, the number of viable bacteria was assessed. Next, the in vitro efficacy of SAAP-148 against various gram-positive and gram-negative bacteria was determined using PBS or 0.05% (wt/v) SPS immediately after 30 min incubation of the mixture. Additionally, ex vivo excision wound models were inoculated with 105 CFU MRSA for 1 h and exposed to SAAP-148, pexiganan, chlorhexidine or PBS for 1 h. Subsequently, samples were homogenized in PBS or 0.05% (wt/v) SPS and the number of viable bacteria was assessed. RESULTS: All tested antimicrobials displayed residual activity in tissue samples, resulting in a lower recovery of surviving bacteria on agar. SPS concentrations at ≥0.05% (wt/v) were able to neutralize the antimicrobial activity of SAAP-148, pexiganan and chlorhexidine, but not of SSD, Bactroban and Fucidin. Finally, SPS-neutralization in in vitro and ex vivo efficacy tests of SAAP-148, pexiganan and chlorhexidine against gram-positive and gram-negative bacteria resulted in significantly higher numbers of CFU compared to control samples without SPS-neutralization. CONCLUSIONS: SPS was successfully used to neutralize residual activity of SAAP-148, pexiganan and chlorhexidine and this prevented an overestimation of their efficacy.


Assuntos
Antibacterianos/farmacologia , Descoberta de Drogas/métodos , Testes de Sensibilidade Microbiana/métodos , Polianetolsulfonato/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Clorexidina/farmacologia , Desinfetantes/farmacologia , Epiderme/efeitos dos fármacos , Ácido Fusídico/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Mupirocina/farmacologia , Concentração Osmolar , Polianetolsulfonato/química
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