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1.
Antimicrob Resist Infect Control ; 11(1): 114, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104710

RESUMO

BACKGROUND: Staphylococcus aureus is one of the leading causes of bloodstream infections (BSI) worldwide. In Brazil, the hospital-acquired methicillin-resistant S. aureus USA100/SCCmecII lineage replaced the previously well-established clones. However, the emergence of community-associated (CA) MRSA lineages among hospitalized patients is an increasing issue. METHODS: Consecutive S. aureus isolates recovered from BSI episodes of patients admitted between January 2016 and December 2018 in a Brazilian teaching hospital were tested for antimicrobial resistance, their genotypic features were characterized, and the clinical characteristics of the patients were evaluated. RESULTS: A total of 123 S. aureus isolates were recovered from 113 patients. All isolates were susceptible to linezolid, teicoplanin and vancomycin and 13.8% were not susceptible to daptomycin. Vancomycin MIC50 and MIC90 of 2 mg/L were found for both MRSA and MSSA isolates. The MRSA isolation rate was 30.1% (37/123), and 51.4% of them carried the SCCmec type II, followed by SCCmecIV (40.5%). Among the 37 MRSA isolates, the main lineages found were USA100/SCCmecII/ST5 and ST105 (53.7%) and USA800/ST5/SCCmecIV (18.9%). Surprisingly, six (16%) CA-MRSA isolates, belonging to USA300/ST8/SCCmecIVa that carried PVL genes and the ACME cassette type I, were detected. These six patients with USA300 BSI had severe comorbidities, including cancer, and most had a Charlson score ≥ 5; furthermore, they were in wards attended by the same health professionals. MRSA isolates were associated with hospital acquired infections (p = 0.02) in more elderly patients (p = 0.03) and those diagnosed with hematologic cancer (p = 0.04). Among patients diagnosed with MRSA BSI, 19 (54.3%) died. CONCLUSIONS: The pandemic MRSA USA300 was detected for the first time in the Brazilian teaching hospital under study, and its cross-transmission most probably occurred between patients with BSI. This lineage may already be circulating among other Brazilian hospitals, which highlights the importance of carrying out surveillance programs to fight multidrug resistant and hypervirulent isolates.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Sepse , Idoso , Brasil/epidemiologia , Células Clonais , Hospitais , Humanos , Pandemias , Staphylococcus aureus , Vancomicina
2.
J Pharm Biomed Anal ; 220: 114964, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36084471

RESUMO

Linezolid, vancomycin, teicoplanin, tigecycline, imipenem, meropenem, voriconazole, and micafungin are eight special-grade antimicrobials commonly used for patients with severe infections. Changes in the pharmacodynamics and pharmacokinetics of critically ill patients severely affect the efficacy of antimicrobial drugs. Therefore, conventional or standard dosing regimens do not achieve satisfactory anti-infective effects. In the current study a simple and specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneously determining the concentrations of the above-mentioned eight antimicrobials in human plasma only 3 min after one-step magnetic solid phase extraction pre-treatment. Multiple-reaction monitoring and positive ion modes were used for detection. The calibration curves were established over a concentration range of 0.1-25.0 µg/mL for teicoplanin, linezolid, micafungin, voriconazole, imipenem, igecyclin, and meropenem, and 0.2-50.0 µg/mL for vancomycin; the coefficient of correlation was > 0.9971 for all the compounds. The inter- and intra-day coefficients of variation were < 6.88% at the lower limit of quantification and quality control (QC) levels (low concentration-QC, medium concentration-QC, and high-concentration QC). The UPLC-MS/MS method was successfully used for clinical therapeutic drug monitoring of linezolid, vancomycin, teicoplanin, tigecycline, imipenem, meropenem, voriconazole, and micafungin for critically ill patients.


Assuntos
Anti-Infecciosos , Teicoplanina , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Estado Terminal , Monitoramento de Medicamentos/métodos , Humanos , Imipenem , Linezolida , Meropeném , Micafungina , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , Tigeciclina , Vancomicina , Voriconazol
3.
Arch Microbiol ; 204(10): 624, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36112329

RESUMO

The present study aimed to evaluate the effects of new Lactobacillus plantarum strain isolated from dairy products as well as chitosan nanoparticles on reducing aflatoxin B1 (AFB1) toxicity In vitro. After collection and preparation of yogurt, cheese, milk, and whey products, lactic acid bacteria (LABs) were isolated and identified using biochemical and molecular methods. pH, bile, and salt tolerance tests were used to measure probiotic activity. Then, the antimicrobial activity of LABs against gastrointestinal pathogens was studied. The strain isolated from cheese (C1) was selected as the appropriate strain and antibiotic susceptibility test was performed for this strain. Then, the effect of C1 isolate and chitosan nanoparticles on reducing aflatoxin B1 (AFB1) in the medium was studied by measuring AFB1 using the enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). The results of biochemical evaluations indicated the separation of different strains of L. plantarum. Antimicrobial activity test showed extensive antimicrobial activity of C1 isolate. The results showed that this strain has good probiotic activities. This strain was shown to be resistant to erythromycin, fusidic acid, gentamicin, kanamycin, nalidixic acid, neomycin, ofloxacin, and vancomycin antibiotics. C1 strain together with chitosan nanoparticles was able to reduce AFB1 in the medium and, when both were used simultaneously, a synergistic effect was seen in reducing AFB1 from the medium. Based on the findings, it can be concluded that the new C1 L. plantarum strains together with chitosan nanoparticles had synergistic effects on reducing AFB1 toxin in food products.


Assuntos
Quitosana , Lactobacillales , Lactobacillus plantarum , Probióticos , Aflatoxina B1 , Antibacterianos/farmacologia , Quitosana/farmacologia , Eritromicina , Ácido Fusídico , Gentamicinas , Canamicina , Ácido Nalidíxico , Neomicina , Ofloxacino , Probióticos/farmacologia , Vancomicina
4.
Sci Transl Med ; 14(662): eabj2381, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36103517

RESUMO

Drug-resistant Gram-positive bacterial infections are still a substantial burden on the public health system, with two bacteria (Staphylococcus aureus and Streptococcus pneumoniae) accounting for over 1.5 million drug-resistant infections in the United States alone in 2017. In 2019, 250,000 deaths were attributed to these pathogens globally. We have developed a preclinical glycopeptide antibiotic, MCC5145, that has excellent potency (MIC90 ≤ 0.06 µg/ml) against hundreds of isolates of methicillin-resistant S. aureus (MRSA) and other Gram-positive bacteria, with a greater than 1000-fold margin over mammalian cell cytotoxicity values. The antibiotic has therapeutic in vivo efficacy when dosed subcutaneously in multiple murine models of established bacterial infections, including thigh infection with MRSA and blood septicemia with S. pneumoniae, as well as when dosed orally in an antibiotic-induced Clostridioides difficile infection model. MCC5145 exhibited reduced nephrotoxicity at microbiologically active doses in mice compared to vancomycin. MCC5145 also showed improved activity against biofilms compared to vancomycin, both in vitro and in vivo, and a low propensity to select for drug resistance. Characterization of drug action using a transposon library bioinformatic platform showed a mechanistic distinction from other glycopeptide antibiotics.


Assuntos
Anti-Infecciosos , Infecções por Bactérias Gram-Positivas , Staphylococcus aureus Resistente à Meticilina , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/farmacologia , Biofilmes , Glicopeptídeos/farmacologia , Glicopeptídeos/uso terapêutico , Lipoglicopeptídeos/uso terapêutico , Mamíferos , Camundongos , Testes de Sensibilidade Microbiana , Streptococcus pneumoniae , Vancomicina/farmacologia , Vancomicina/uso terapêutico
5.
BMC Musculoskelet Disord ; 23(1): 853, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088338

RESUMO

BACKGROUND: Deep surgical site infection (DSSI) is one of the most challenging complications in lumbar fusion surgery. Few investigations examined the effect of vancomycin powder mixed with autogenic bone graft (ABG) and bone substitutes on preventing DSSI in degenerative lumbar fusion surgeries as well as any interference with bony fusion. The aim of the study was to investigate the effects of ABG along with bone substitutes as a local vancomycin delivery system on preventing DSSI in lumbar instrumented fusion and compared with those who did not use vancomycin powder. METHODS: From January, 2015 through December, 2015, a one-year prospective study using vancomycin powder mixed with ABG and bone substitute for degenerative lumbar fusion surgeries as vancomycin (V) group, 1 gm vancomycin for 2 and 3-level, and 2 gm for more than 3-level instrumentation. From December, 2013 through December 2014, patients received degenerative lumbar fusion surgeries without using vancomycin before the vancomycin protocol were retrospectively enrolled as non-vancomycin (NV) group. Vancomycin concentration was checked at post-operative days 1 and 3 for both the serum and drainage. Patients' demographic data, microbiology reports, fusion status and functional outcomes were evaluated. RESULTS: One hundred and ten patients were enrolled prospectively in the V group, and 86 for the NV group. After an average 41 months follow-up (range, 36-54), 3 patients (3.48%) developed postoperative DSSIs in the NV group, thereby requiring revision surgeries and parenteral antibiotics treatment versus no DSSIs (0%, 0/100) in the V group. (p = 0.048). The postoperative serum vancomycin levels were undetectable and no vancomycin related side effects was encountered. The mean vancomycin concentration of drainage at postoperative days 1 and 3 were 517.96 ± 174.4 and 220.14 ± 102.3 µg/mL, respectively. At final follow-up, there was no statistical difference observed in terms of clinical and radiologic outcomes. CONCLUSIONS: Our vancomycin protocol may reduce the incidence of DSSI in degenerative lumbar fusion surgery without affecting bony fusion. LEVEL OF EVIDENCE: Level III ambispective comparative study.


Assuntos
Substitutos Ósseos , Vancomicina , Substitutos Ósseos/uso terapêutico , Humanos , Pós , Estudos Prospectivos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Vancomicina/efeitos adversos
6.
J Nanobiotechnology ; 20(1): 400, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064405

RESUMO

BACKGROUND: Sepsis is caused mainly by infection in the blood with a broad range of bacterial species. It can be diagnosed by molecular diagnostics once compounds in the blood that interfere with molecular diagnostics are removed. However, this removal relies on ultracentrifugation. Immunomagnetic separation (IMS), which typically uses antibody-conjugated silica-coated magnetic nanoparticles (Ab-SiO2-MNPs), has been widely applied to isolate specific pathogens in various types of samples, such as food and environmental samples. However, its direct use in blood samples containing bacteria is limited due to the aggregation of SiO2-MNPs in the blood and inability to isolate multiple species of bacteria causing sepsis. RESULTS: In this study, we report the synthesis of vancomycin-conjugated polydopamine-coated (van-PDA-MNPs) enabling preconcentration of multiple bacterial species from blood without aggregation. The presence of PDA and van on MNPs was verified using transmission electron microscopy, X-ray photoelectron spectroscopy, and energy disruptive spectroscopy. Unlike van-SiO2-MNPs, van-PDA-MNPs did not aggregate in the blood. Van-PDA-MNPs were able to preconcentrate several species of Gram-positive bacteria in the blood, lowering the limit of detection (LOD) to 10 colony forming units/mL by polymerase chain reaction (PCR) and quantitative PCR (qPCR). This is 10 times more sensitive than the LOD obtained by PCR and qPCR using van-SiO2-MNPs. CONCLUSION: These results suggest that PDA-MNPs can avoid aggregation in blood and be conjugated with receptors, thereby improving the sensitivity of molecular diagnostics of bacteria in blood samples.


Assuntos
Nanopartículas de Magnetita , Sepse , Bactérias , Bactérias Gram-Positivas , Humanos , Indóis , Nanopartículas de Magnetita/química , Patologia Molecular , Polímeros , Dióxido de Silício , Vancomicina/química
7.
J Med Case Rep ; 16(1): 340, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36068562

RESUMO

BACKGROUND: We present a case of fungal keratitis caused by Scedosporium apiospermum, which is a rare agent. Case description A 34-year-old Caucasian male patient was admitted to our clinic with complaints of pain and blurred vision in the left eye. The patient had a history of wearing contact lenses for 3 years. According to the Snellen chart, the patient's visual acuity was 20/20 and counting fingers at 30 cm, for right and left eyes, respectively. A 3 × 3 mm corneal abscess at the center of the cornea with hypopyon in the patient's left eye was observed. After the patient was hospitalized, fortified gentamicin and fortified cefazolin drops were started 24 times per day. Intravenous fluconazole 1 × 800 mg loading, 1 × 400 mg maintenance dose, intravenous vancomycin 4 × 500 mg and intravenous cefoperazone + sulbactam 2 × 2 g treatments were started. We observed S. apiospermum in the corneal scraping sample, which the identification was performed by combined phenotypic characteristics and matrix-assisted laser-desorption ionization time-of-flight mass spectrometry on the sixth day of treatment. The drops were revised as fortified vancomycin, ceftazidime, and voriconazole drops 24 times per day. Intravenous voriconazole 2 × 6 mg/kg loading and 2 × 4 mg/kg maintenance dose treatments were started. Three weeks later, left eye visual acuity increased to 20/40, and the corneal abscess regressed. On second-year follow-up, his visual acuity increased to 20/25 for the left eye and the cornea was transparent. CONCLUSION: Scedosporium group is an opportunistic filamentous fungus that is very rarely seen and causes severe keratitis infections. In the literature, to the best of our knowledge, three cases of keratitis due to S. apiospermum after contact lenses were reported, and all were treated with penetrating keratoplasty. In this case, unlike the others, only medical treatment was applied. In cases with suspected fungal keratitis, medical treatment should be started without waiting for the culture result, the findings should be followed and penetrating keratoplasty should be performed in the case of no response to treatment.


Assuntos
Úlcera da Córnea , Infecções Oculares Fúngicas , Ceratite , Scedosporium , Abscesso/tratamento farmacológico , Adulto , Antifúngicos/uso terapêutico , Córnea , Úlcera da Córnea/tratamento farmacológico , Infecções Oculares Fúngicas/tratamento farmacológico , Humanos , Ceratite/tratamento farmacológico , Masculino , Vancomicina/uso terapêutico , Voriconazol/uso terapêutico
8.
Molecules ; 27(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36080354

RESUMO

Since its first use as a drug delivery system, mesoporous silica has proven to be a surprisingly efficient vehicle due to its porous structure. Unfortunately, most synthesis methods are based on using large amounts of surfactants, which are then removed by solvent extraction or heat treatment, leading to an undesired environmental impact because of the generated by-products. Hence, in the present study, we followed the synthesis of a silica material with a wormhole-like pore arrangement, using two FDA-approved substances as templates, namely Tween-20 and starch. As far as we know, it is the first study using the Tween-20/starch combo as a template for mesoporous silica synthesis. Furthermore, we investigated whether the obtained material using this novel synthesis had any potential in using it as a DDS. The material was further analyzed by XRD, TEM, FT-IR, N2 adsorption/desorption, and DLS to investigate its physicochemical features. Vancomycin was selected as the active molecule based on the extensive research engaged towards improving its bioavailability for oral delivery. The drug was loaded onto the material by using three different approaches, assuming its full retention in the final system. Thermal analysis confirmed the successful loading of vancomycin by all means, and pore volume significantly decreased upon loading, especially in the case of the vacuum-assisted method. All methods showed a slower release rate compared to the same amount of the pure drug. Loadings by physical mixing and solvent evaporation released the whole amount of the drug in 140 min, and the material loaded by the vacuum-assisted method released only 68.2% over the same period of time, leading us to conclude that vancomycin was adsorbed deeper inside the pores. The kinetic release of the three systems followed the Higuchi model for the samples loaded by physical mixing and vacuum-assisted procedures, while the solvent evaporation loading method was in compliance with the first-order model.


Assuntos
Dióxido de Silício , Vancomicina , Adsorção , Portadores de Fármacos/química , Polissorbatos , Porosidade , Dióxido de Silício/química , Solubilidade , Solventes , Espectroscopia de Infravermelho com Transformada de Fourier , Amido
9.
J Biomed Mater Res A ; 110(11): 1786-1800, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36082973

RESUMO

A local drug delivery system that attempts to find a suitable balance between antimicrobial and regenerative actions was developed for osteomyelitis treatment (OM). This system combines the angiogenic and immunomodulatory peptide LLKKK18 (LL18) and vancomycin hydrochloride (VH), loaded into an injectable oxidized dextrin (ODEX)-based hydrogel (HG). In vitro cytotoxicity was analyzed in MC3T3-E1 pre-osteoblasts and erythrocytes. The kinetics of LL18 release was studied. Antimicrobial activity was assessed in vitro against a clinical Methicillin-Resistant Staphylococcus aureus (MRSA) strain. A rat model of acute OM was developed by direct inoculation into a tibia defect, concomitantly with the implantation of the drug-loaded HG. The local bioburden was quantified and damage in surrounding tissues was examined histologically. In vitro, ODEX-based HG displayed a safe hemolytic profile. Half of LL18 (53%) is released during the swelling phase at physiological pH, then being gradually released until complete HG degradation. LL18-loaded HG at 300 µM was the most effective peptide formulation in decreasing in vivo infection among concentrations ranging from 86 to 429 µM. The histopathological scores observed in vivo varied with the LL18 concentration in a dose-dependent manner. VH at 28 mM completely eradicated bacteria, although with substantial tissue injury. We have found that sub-millimolar doses of VH combined with LL18 at 300 µM may suffice to eradicate the infection, with reduced tissue damage. We propose an easy-to-handle, shape-fitting HG formulation with the potential to treat MRSA-infected bone with low VH doses associated with LL18.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Osteomielite , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Osteomielite/microbiologia , Ratos , Infecções Estafilocócicas/patologia , Vancomicina/farmacologia
10.
PLoS One ; 17(9): e0274324, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36083990

RESUMO

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) has a high mortality and requires effective treatment with anti-MRSA agents such as vancomycin (VCM). Management of the efficacy and safety of VCM has been implemented with the assignment of pharmacists in hospital wards and the establishment of teams related to infectious diseases. However, there are no reports evaluating the association between these factors and the efficacy and safety of VCM in large populations. METHODS: This study used the Japanese administrative claims database accumulated from 2010 to 2019. The population was divided into two groups, therapeutic drug monitoring (TDM) group and non-TDM group, and adjusted by propensity score matching. We performed multivariate logistic regression analysis to determine the influence of pharmacists and infection control teams or antimicrobial stewardship teams on acute kidney injury (AKI) and 30-day mortality. RESULTS: The total number of patients was 73 478 (TDM group, n = 55 269; non-TDM group, n = 18 209). After propensity score matching, 18 196 patients were matched in each group. Multivariate logistic regression analysis showed that pharmacological management for each patient contributed to the reduction of AKI (odds ratio [OR]: 0.812, 95% confidence interval [CI]: 0.723‒0.912) and 30-day mortality (OR: 0.538, 95% CI: 0.503‒0.575). However, the establishment of infectious disease associated team in facilities and the assignment of pharmacists in the hospital wards had no effect on AKI and 30-day mortality. In addition, TDM did not affect the reduction in AKI (OR: 1.061, 95% CI: 0.948‒1.187), but reduced 30-day mortality (OR: 0.873, 95% CI: 0.821‒0.929). CONCLUSION: Pharmacologic management for individual patients, rather than assignment systems at facilities, is effective to reduce AKI and 30-day mortality with VCM administration.


Assuntos
Injúria Renal Aguda , Gestão de Antimicrobianos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/epidemiologia , Antibacterianos/efeitos adversos , Humanos , Controle de Infecções , Japão , Farmacêuticos , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/efeitos adversos
11.
Biomed Res Int ; 2022: 3682757, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046462

RESUMO

For the treatment of various infections, a variety of antimicrobial drugs are formulated. Nevertheless, many bacterial infections now exhibit antibiotic resistance due to the widespread utilization antibiotics. Methicillin-resistant among the most dangerous multidrug-resistant bacteria is Staphylococcus aureus (MRSA). Vancomycin became a viable therapy option due to MRSA resistance to methicillin medicines. One of the well-informed antibacterial compounds with wideband antibacterial activity is silver nanoparticles (AgNPs). AgNPs are thus suitable candidates for usage in conjunction alongside vancomycin to increase its antibacterial effect. The goal of the present research work is to boost the antibacterial potency of the glycopeptide antibiotic vancomycin towards Gram-positive (Staphylococcus aureus) but also Gram-negative (Escherichia coli) bacteria. The chemical reduction approach is used to create a colloidal solution of silver nanoparticles utilizing silver nitrate as a precursor in the environment of the ionic surfactant trisodium citrate that serves as covering including reducing reagent. Vancomycin was used to functionalize the synthesized nanoparticles and create the nanodrug complex (Van@AgNPs). The synergistic antibacterial potential of silver nanoparticles coated with vancomycin on both test pathogens was investigated using the agar well diffusion technique. The antibacterial potency for both classes of bacteria has significantly increased, according to the well diffusion test. It has been noted that this improvement is synergistic instead of additive.


Assuntos
Nanopartículas Metálicas , Infecções Estafilocócicas , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias , Escherichia coli , Humanos , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Prata/farmacologia , Staphylococcus aureus , Vancomicina/química , Vancomicina/farmacologia
12.
Biol Pharm Bull ; 45(9): 1332-1339, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36047202

RESUMO

In therapeutic drug monitoring of vancomycin (VCM), the area under the concentration-time curve (AUC) is related to clinical efficacy and toxicity. Determining the maintenance for patient is necessary since VCM concentrations are affected by factors such as renal function. We constructed a machine learning-based model to estimate the maintenance dose to target an AUC of 400-600 mg⋅h/L in each combination of patient's factors. This retrospective observational study was conducted at two hospitals. Patients who received VCM intravenously with measured trough and another point (e.g., peak) concentrations within the November 2011 to March 2019 period were enrolled. We extracted the factors that affect VCM concentration and constructed a decision tree model using a classification and regression tree algorithm. Of the 1380 patients, 822 were included. Training data were split up to four times and included 24 subgroups. The average corrected VCM daily doses ranged 17.6-59.4 mg/kg. Estimated glomerular filtration rate, age, and body mass index were selected as predictive variables that affected the recommended daily dose. In the validation data, our model had slightly higher proportions of AUC of 400-600 mg⋅h/L than other nomograms. However, our model was based only on limited patients. Thus, further clinical studies are needed to develop a general-purpose model in the future. We successfully constructed a model that recommends VCM maintenance daily doses with AUC of 400-600 mg⋅h/L for each combination of independent variables. Our model has the potential for application as a simple decision-making tool for medical staff.


Assuntos
Antibacterianos , Vancomicina , Antibacterianos/uso terapêutico , Área Sob a Curva , Monitoramento de Medicamentos , Humanos , Japão , Aprendizado de Máquina , Estudos Retrospectivos , Vancomicina/uso terapêutico
13.
Biol Pharm Bull ; 45(9): 1398-1402, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36047211

RESUMO

Vancomycin (VCM) is a standard treatment for bacterial meningitis. However, little is known about the transferability of VCM to cerebrospinal fluid (CSF), thus evidence of the transferability of VCM to CSF during bacterial meningitis is needed. In this study, we evaluated the concentration of VCM in the plasma and CSF of postoperative neurosurgical patients with bacterial meningitis and evaluated the factors that affect the transferability of VCM to CSF. The concentrations of VCM in plasma (trough) and CSF were determined in eight patients (four males and four females) with bacterial meningitis who were treated with VCM using HPLC. The ratio of the VCM concentrations in CSF/plasma was also calculated by estimating the blood VCM concentration at the same time as the VCM concentration in CSF was measured. The results showed that the VCM concentration in CSF was 0.9-12.7 µg/mL and the CSF/plasma VCM concentration ratio was 0.02-0.62. We examined the effect of drainage on the transferability of VCM to CSF, which showed that the VCM concentration in CSF and the CSF/plasma VCM concentration ratio were significantly higher in patients not undergoing drainage than in patients who were undergoing drainage. The CSF protein and glucose concentrations, which are diagnostic indicators of meningitis, were positively correlated with the VCM concentration in CSF and the CSF/plasma VCM concentration ratio. Thus, VCM transferability to CSF may be affected by changes in the status of the blood-brain barrier and blood-cerebrospinal fluid barrier due to drainage or meningitis.


Assuntos
Meningites Bacterianas , Vancomicina , Antibacterianos/uso terapêutico , Transporte Biológico , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/tratamento farmacológico , Vancomicina/uso terapêutico
14.
Curr Microbiol ; 79(11): 326, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36125553

RESUMO

This study aimed to investigate the prevalence of Methicillin- and Vancomycin-Resistant Staphylococcus aureus (MRSA, VRSA) and Vancomycin-Resistant Enterococcus (VRE) of hospital food samples in Mashhad, Iran. A total of 357 hospital food samples were collected from 13 hospitals. Enterococcus spp. and Staphylococcus aureus were identified using conventional cultural techniques following genotypic confirmation by PCR. The antibiotic resistance patterns of MRSA, VRSA, and VRE strains were analyzed using the disk diffusion methods. The prevalence of S. aureus and MRSA were 24.37% (87/357) and 22.98% (20.87), respectively. In addition, the vanB gene involved in vancomycin resistance was detected in 1.14% of the S. aureus strains. Enterococci and VRE had a prevalence of 15.4% (55/357) and 21.81% (12/55), respectively. Meat, chicken barbecues, and salad were the most commonly contaminated samples with S. aureus, MRSA, Enterococci, and VRE. PCR detected two vancomycin resistance genes, including vanA (1.81%, 1.55) and vanC2 (20%, 11.55) genes. MRSA strains revealed the highest resistance against penicillin, erythromycin, clindamycin, azithromycin, tetracycline, and gentamicin. The VRSA isolates were resistant to penicillin, ampicillin, oxacillin, cefoxitin, clindamycin, erythromycin, gentamicin, and trimethoprim-sulfamethoxazole. Furthermore, VRE isolates exhibited the highest resistance against quinupristin-dalfopristin, erythromycin, and tetracycline. The results of this study indicated that hospital foods might act as a reservoir of Enterococci spp. and S. aureus strains, which can transfer antibiotic resistance. Moreover, multidrug resistance (MDR) in some MRSA, VRSA, and VRE isolates represents a serious threat to susceptible persons in hospitals.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Enterococos Resistentes à Vancomicina , Ampicilina , Antibacterianos/farmacologia , Azitromicina , Cefoxitina , Clindamicina , Farmacorresistência Bacteriana/genética , Gentamicinas , Hospitais , Meticilina , Testes de Sensibilidade Microbiana , Oxacilina , Prevalência , Staphylococcus aureus , Tetraciclinas , Combinação Trimetoprima e Sulfametoxazol , Vancomicina/farmacologia , Enterococos Resistentes à Vancomicina/genética , Staphylococcus aureus Resistente à Vancomicina
15.
Wiad Lek ; 75(8 pt 2): 2003-2009, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36129086

RESUMO

OBJECTIVE: The aim: To determine the current prevalence of healthcare-associated tubo-ovarian infections in female and antimicrobial resistance of the responsible pathogens in Ukraine. PATIENTS AND METHODS: Materials and methods: We performed a retrospective multicenter cohort study was based on healthcare-associated infections surveillance data. Definitions of health¬care-associated tubo-ovarian infections were used from the CDC/ NHSN. The susceptibility to antibiotics was determined by disk diffusion method according to the EUCAST. RESULTS: Results: Among all the 1,528 of women in this study, the prevalence of healthcare-associated tubo-ovarian infections was 31.2%. Of these cases, Salpingitis, Oophoritis, and tubo-ovarian abscess were 47.5%, 34% and 18.5%, respectively. Of all cases tubo-ovarian infections in female, 74.7% were detected after hospital discharge. The predominant pathogens were: Escherichia coli (27.7%), Enterobacter spp. (12.2%), Klebsiella pneumoniae (9.6%), Staphylococcus aureus (8.2%), Pseudomonas aeruginosa (8.1%), and Enterococcus faecalis (7.5%), followed by Proteus mirabilis (5.1%), Streptococcus spp. (4.5%), Staphylococcus epidermidis (4.4%), and Acinetibacter spp. (4%). Methicillin-resistance was ob¬served in 16.8% of S. aureus (MRSA). No strains S.aureus and E. faecalis resistant to vancomycin. The overall proportion of extended spectrum beta-lactamases (ESBL) production among Enterobacteriaceae was 24.7%. The prevalence of ESBL production among E. coli isolates was 28.6% and among K. pneumoniae 12.8%. Resistance to third-generation cephalosporins was observed in 14.9% E.coli and 11.3% K. pneumoniae isolates. Carbapenem resistance was identified in 11.3% of P.aeruginosa isolates. CONCLUSION: Conclusions: A healthcare-associated tubo-ovarian infections of the female in Ukraine is a common occurrence and many cases are caused by pathogens that are resistant to antibiotics.


Assuntos
Infecção Hospitalar , Farmacorresistência Bacteriana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos , Cefalosporinas , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Atenção à Saúde , Escherichia coli , Feminino , Humanos , Klebsiella pneumoniae , Meticilina , Pseudomonas aeruginosa , Staphylococcus aureus , Ucrânia/epidemiologia , Vancomicina , beta-Lactamases
16.
BMJ Open ; 12(9): e058697, 2022 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115667

RESUMO

INTRODUCTION: Periprosthetic infection is one of the most severe complications following implant-based breast reconstruction affecting 5%-10% of the women. Currently, many surgeons apply antibiotics locally on the breast implant to reduce the risk of postoperative infection, but no randomised, placebo-controlled trials have tested the treatment's efficacy. METHODS AND ANALYSIS: The BREAST-AB trial (BREAST-AntiBiotics) is an investigator-initiated, multicentre, randomised, placebo-controlled, double-blind trial of local treatment with gentamicin, vancomycin and cefazolin on breast implants in women undergoing implant-based breast reconstruction. The trial drug consists of 80 mg gentamicin, 1 g vancomycin and 1 g cefazolin dissolved in 500 mL of isotonic saline. The placebo solution consists of 500 mL isotonic saline. The trial drug is used to wash the dissected tissue pocket and the breast implant prior to insertion. The primary outcome is all-cause explantation of the breast implant within 180 days after the breast reconstruction surgery. This excludes cases where the implant is replaced with a new permanent implant, for example, for cosmetic reasons. Key long-term outcomes include capsular contracture and quality of life. The trial started on 26 January 2021 and is currently recruiting. ETHICS AND DISSEMINATION: The trial was approved by the Regional Ethics Committee of the Capital Region (H-20056592) on 1 January 2021 and the Danish Medicines Agency (2020070016) on 2 August 2020. The main paper will include the primary and secondary outcomes and will be submitted to an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04731025.


Assuntos
Implantes de Mama , Mamoplastia , Antibacterianos/uso terapêutico , Implantes de Mama/efeitos adversos , Cefazolina/uso terapêutico , Feminino , Gentamicinas/uso terapêutico , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Vancomicina/uso terapêutico
17.
Front Cell Infect Microbiol ; 12: 981823, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118040

RESUMO

Preterm infants or those with low birth weight are highly susceptible to invasive fungal disease (IFD) and other microbial or viral infection due to immaturity of their immune system. Antibiotics are routinely administered in these vulnerable infants in treatment of sepsis and other infectious diseases, which might cause perturbation of gut microbiome and hence development of IFD. In this study, we compared clinical characteristics of fungal infection after antibiotic treatment in preterm infants. As determined by 16S rRNA sequencing, compared with non-IFD patients with or without antibiotics treatment, Clostridium species in the intestinal tracts of patients with IFD were almost completely eliminated, and Enterococcus were increased. We established a rat model of IFD by intraperitoneal inoculation of C. albicans in rats pretreated with meropenem and vancomycin. After pretreatment with antibiotics, the intestinal microbiomes of rats infected with C. albicans were disordered, as characterized by an increase of proinflammatory conditional pathogens and a sharp decrease of Clostridium species and Bacteroides. Immunofluorescence analysis showed that C. albicans-infected rats pretreated with antibiotics were deficient in IgA and IL10, while the number of Pro-inflammatory CD11c+ macrophages was increased. In conclusion, excessive use of antibiotics promoted the imbalance of intestinal microbiome, especially sharp decreases of short-chain fatty acids (SCFA)-producing Clostridium species, which exacerbated the symptoms of IFD, potentially through decreased mucosal immunomodulatory molecules. Our results suggest that inappropriate use of broad-spectrum antibiotics may promote the colonization of invasive fungi. The results of this study provide new insights into the prevention of IFD in preterm infants.


Assuntos
Infecções Fúngicas Invasivas , Micoses , Animais , Antibacterianos/efeitos adversos , Clostridium/genética , Ácidos Graxos Voláteis , Humanos , Imunoglobulina A , Recém-Nascido , Recém-Nascido Prematuro , Interleucina-10 , Meropeném , RNA Ribossômico 16S/genética , Ratos , Vancomicina/efeitos adversos
18.
ACS Appl Mater Interfaces ; 14(37): 41671-41683, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36083296

RESUMO

The formation of microbial biofilms is acknowledged as a major virulence factor in a range of persistent local infections. Failures to remove biofilms with antibiotics foster the emergence of antibiotic-resistant bacteria and result in chronic infections. As a result, the construction of effective biofilm-inhibiting and biofilm-eradicating chemicals is urgently required. Herein, we designed a water-soluble probe APDIS for membrane-active fluorescence and broad-spectrum antimicrobial actions, particularly against methicillin-resistant Staphylococcus aureus (MRSA), which shows multidrug resistance. In vitro and in vivo experiments demonstrate its high antibacterial effects comparable to vancomycin. Furthermore, it inhibits biofilm formation by effectively killing planktonic bacteria at low inhibitory concentrations, without toxicity to mammalian cells. More importantly, this probe can efficiently penetrate through biofilm barriers and exterminate bacteria that are enclosed within biofilms and startle existing biofilms. In the mouse model of implant-related biofilm infections, this probe exhibits strong antibiofilm activity against MRSA biofilms, thus providing a novel theranostic strategy to disrupt biofilms in vivo effectively. Our results indicate that this probe has the potential to be used for the development of a combinatorial theranostic platform with synergistic enhanced effects for the treatment of multidrug-resistant bacterial infections and antibiofilm medications.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Animais , Antibacterianos/farmacologia , Biofilmes , Mamíferos , Camundongos , Testes de Sensibilidade Microbiana , Medicina de Precisão , Vancomicina/farmacologia , Fatores de Virulência/farmacologia , Água
19.
ACS Appl Mater Interfaces ; 14(37): 41764-41778, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36087275

RESUMO

3D-printed porous tantalum scaffold has been increasingly used in arthroplasty due to its bone-matching elastic modulus and good osteoinductive ability. However, the lack of antibacterial ability makes it difficult for tantalum to prevent the occurrence and development of periprosthetic joint infection. The difficulty and high cost of curing periprosthetic joint infection (PJI) and revision surgery limit the further clinical application of tantalum. Therefore, we fabricated vancomycin-loaded porous tantalum scaffolds by combining the chemical grafting of (3-aminopropyl)triethoxysilane (APTES) and the electrostatic assembly of carboxymethyl chitosan and vancomycin for the first time. Our in vitro experiments show that the scaffold achieves rapid killing of initially adherent bacteria and effectively prevents biofilm formation. In addition, our modification preserves the original excellent structure and biocompatibility of porous tantalum and promotes the generation of mineralized matrix and osteogenesis-related gene expression by mesenchymal stem cells on the surface of scaffolds. Through a rat subcutaneous infection model, the composite bioscaffold shows efficient bacterial clearance and inflammation control in soft tissue and creates an immune microenvironment suitable for tissue repair at an early stage. Combined with the economic friendliness and practicality of its preparation, this scaffold has great clinical application potential in the treatment of periprosthetic joint infection.


Assuntos
Quitosana , Infecções Relacionadas à Prótese , Animais , Antibacterianos/farmacologia , Biofilmes , Quitosana/farmacologia , Osteogênese , Porosidade , Impressão Tridimensional , Ratos , Tantálio/farmacologia , Tecidos Suporte/química , Vancomicina/farmacologia
20.
Microb Pathog ; 171: 105745, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36057414

RESUMO

This study aimed to investigate the presence of eight virulence genes (ace, asa1, esp, efaA, gelE, cylA, agg, fsr) in Enterococcus from a variety of animals and to explore the drug resistance and pathogenicity. This could provide a theoretical basis for clinical treatment of Enterococcus infections. Anal swabs from pigs, chickens, cattle, and dogs in farms and pet hospitals were collected for Enterococcus isolation and identification. Eight virulence genes were detected (PCR method), and drug resistance was assessed (drug-sensitive paper method). The strains containing different virulence genes were then divided into EV1, EV2, and EV3 groups. The LD50 and pathogenicity was examined by intra-peritoneal injection to infect mice. Differences were found in the detection rates of virulence genes in Enterococcus from the different animals. The highest overall detection rate was for the esp gene (78.0%), and the lowest for the cylA gene (15.5%). Eight genes were detected most frequently in Enterococcus from dogs and least frequently from cattle. Among the Enterococcus strains from four variety of animals, drug resistance was highest against sulfamethoxazole (100%), cefotaxime (>97%), and cefotaxitin (>93%). Drug resistance was lowest against vancomycin (0%), levofloxacin (<12%) and ciprofloxacin (<13%). The LD50 for each of the three groups was EV1LD50=8.71×109CFU, EV2LD50=2.34×1010CFU,and EV3LD50=9.33×1010CFU. The Enterococcus12LD50 dose group caused significant clinical symptoms in mice, with pathological effects on the heart, liver, lungs, and kidneys, and particularly on the urinary system. The abundance of Enterococcus virulence genes, drug resistance, and pathogenicity vary among different animal origins, and the pathology caused by Enterococcus requires effective treatment protocols based on species and regional characteristics.


Assuntos
Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Animais , Animais Domésticos , Antibacterianos/farmacologia , Bovinos , Cefotaxima/farmacologia , Galinhas , Ciprofloxacina/farmacologia , Cães , Resistência a Medicamentos , Farmacorresistência Bacteriana/genética , Enterococcus , Enterococcus faecalis , Infecções por Bactérias Gram-Positivas/veterinária , Levofloxacino/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Sulfametoxazol/farmacologia , Suínos , Vancomicina/farmacologia , Virulência/genética , Fatores de Virulência/genética
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