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1.
Chemosphere ; 247: 125813, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31951953

RESUMO

Heterogeneous electro-Fenton (HEF) is as an alternative to the conventional electro-Fenton (EF) process. HEF uses a solid phase catalyst, whereas EF employs a solubilized one. This implies that in HEF, material can be recovered through a simple separation process such as filtration or magnetic separation in HEF. HEF also has the advantage of not requires a previous pH adjustment, which facilitates working in a higher pH range. In this work, Fe, Cu and Fe/Cu bimetallic nanoparticles (Fe/Cu NPs) were synthesized, characterized and used for the degradation of Nafcillin (NAF). The effect of the adsorption and the anodic oxidation (AO-H2O2) process was tested to assess their influence on HEF. NAF adsorption did not exceed 24% of antibiotic removal and the AO-H2O2 process eliminated the total NAF after 240 min of electrolysis. Through the HEF process, the antibiotic was completely removed using Fe/Cu NPs after 7.0 min of electrolysis, while these NPs, mineralization reached 41% after 240 min. In this case, NAF degradation occurs mainly due to the generation of hydroxyl radicals in the BDD electrode, and the Fenton reaction with Fe and Cu NPs. The main organic intermediates produced during the degradation of NAF by HEF were identified allowing the proposal of degradation pathway. Finally, the antibiotic was also completely eliminated from a wastewater from slaughterhouse after 15 min of treatment by HEF and using Fe/Cu bimetallic NPs.


Assuntos
Cobre/química , Peróxido de Hidrogênio/química , Ferro/química , Nanopartículas Metálicas/química , Nafcilina/química , Antibacterianos/química , Catálise , Técnicas Eletroquímicas , Eletrólise/instrumentação , Eletrólise/métodos , Radical Hidroxila/química , Oxirredução , Águas Residuárias/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química
2.
Sci Data ; 6(1): 43, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-31028276

RESUMO

Cation adjusted-Mueller Hinton Broth (CA-MHB) is the standard bacteriological medium utilized in the clinic for the determination of antibiotic susceptibility. However, a growing number of literature has demonstrated that media conditions can cause a substantial difference in the efficacy of antibiotics and antimicrobials. Recent studies have also shown that minimum inhibitory concentration (MIC) tests performed in standard cell culture media (e.g. RPMI and DMEM) are more indicative of in vivo antibiotic efficacy, presumably because they are a better proxy for the human host's physiological conditions. The basis for the bacterial media dependent susceptibility to antibiotics remains undefined. To address this question, we characterized the physiological response of methicillin-resistant Staphylococcus aureus (MRSA) during exposure to sub-inhibitory concentrations of the beta-lactam antibiotic nafcillin in either CA-MHB or RPMI + 10% LB (R10LB). Here, we present high quality transcriptomic, exo-metabolomic and morphological data paired with growth and susceptibility results for MRSA cultured in either standard bacteriologic or more physiologic relevant medium.


Assuntos
Antibacterianos/farmacologia , Técnicas Bacteriológicas , Meios de Cultura , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana/normas , Nafcilina/farmacologia , Técnicas Bacteriológicas/métodos , Técnicas Bacteriológicas/normas , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Transcriptoma
3.
J Med Microbiol ; 68(2): 255-262, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30556803

RESUMO

PURPOSE: Potent extracellular toxins including alpha-haemolysin, Panton-Valentine leukocidin (PVL) and toxic-shock syndrome toxin 1 (TSST-1) significantly contribute to Staphylococcus aureus pathogenesis, thus, toxin suppression is a primary focus in treatment of staphylococcal disease. S. aureus maintains complex strategies to regulate toxin expression and previous data have demonstrated that subinhibitory concentrations of beta-lactam antibiotics can adversely increase S. aureus exotoxin production. The current study evaluates the effects of subinhibitory concentrations of tedizolid, a second-generation oxazolidinone derivative, on expression of staphylococcal exotoxins in both methicillin-resistant and methicillin-sensitive S. aureus. METHODOLOGY: S. aureus exotoxin expression levels were compared at 12 and 24 h following treatment with tedizolid, linezolid, nafcillin or vehicle control. RESULTS: Our findings show that the level of antibiotic required to alter toxin production was strain-dependent and corresponds with the quantity of toxin produced, but both tedizolid and linezolid could effectively reduce expression of alpha-haemolysin, PVL and TSST-1 toxin at subinhibitory concentrations. In contrast, nafcillin showed less attenuation and, in some S. aureus strains, led to an increase in toxin expression. Tedizolid consistently inhibited toxin production at a lower overall drug concentration than comparator agents. CONCLUSION: Together, our data support that tedizolid has the potential to improve outcomes of infection due to its superior ability to inhibit S. aureus growth and attenuate exotoxin production.


Assuntos
Antibacterianos/farmacologia , Toxinas Bacterianas/biossíntese , Meticilina/farmacologia , Oxazolidinonas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Tetrazóis/farmacologia , Animais , Antibacterianos/administração & dosagem , Toxinas Bacterianas/análise , Toxinas Bacterianas/antagonistas & inibidores , Relação Dose-Resposta a Droga , Enterotoxinas/análise , Enterotoxinas/antagonistas & inibidores , Enterotoxinas/biossíntese , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Exotoxinas/análise , Exotoxinas/antagonistas & inibidores , Exotoxinas/biossíntese , Proteínas Hemolisinas/análise , Proteínas Hemolisinas/antagonistas & inibidores , Proteínas Hemolisinas/biossíntese , Humanos , Leucocidinas/análise , Leucocidinas/antagonistas & inibidores , Leucocidinas/biossíntese , Linezolida/administração & dosagem , Linezolida/farmacologia , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Staphylococcus aureus Resistente à Meticilina/metabolismo , Testes de Sensibilidade Microbiana , Nafcilina/administração & dosagem , Nafcilina/farmacologia , Oxazolidinonas/administração & dosagem , Coelhos , Ovinos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/metabolismo , Superantígenos/análise , Superantígenos/biossíntese , Tetrazóis/administração & dosagem
4.
PLoS One ; 13(10): e0202439, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30281600

RESUMO

INTRODUCTION: Vancomycin associated acute kidney injury (vAKI) is a well known complication in pediatric patients. Identification and characterization of the incidence and risk factors for vAKI in the pediatric population would assist clinicians in potentially preventing or mitigating vAKI. METHODS AND MATERIALS: A 6 year retrospective cohort study was designed. Patients were included if they were < 19 years of age, received vancomycin as inpatients, and had a baseline SCr and one other SCr drawn during and up to 72 hours after the discontinuation of vancomycin. Data collection included patient demographics, vancomycin doses and length of therapy, vancomycin serum concentrations, and concomitant medications. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to characterize acute kidney injury. Descriptive statistical methods were used and ordinal logistic regression was employed to determine variables significantly associated with vAKI. RESULTS: A total of 7,095 patients met study criteria (55.4% male, median age 4.1 years (IQR 0.67-11.2 years)). Mechanical ventilation was used in 7.9% (n = 563) and mortality was 4.9% (n = 344). A total of 153 concomitant medications were identified. A median of 5 (IQR 3-7) SCr values were obtained and median SCr prior to vancomycin was 0.39 (IQR 0.28-0.57) mg/dL (CrCl 134±58 mL/min/1.73m2). Vancomycin was administered for a median of 2 (IQR 1-3) days (14.9±1.6 mg/kg/dose). vAKI was present in 12.2% (n = 862: KDIGO stage 1 (8.30%, n = 589), KDIGO stage 2 (1.94%, n = 138) KDIGO stage 3 (1.89%, n = 134)). Mean vancomycin serum concentration at 6-8 hours after a dose for patients with vAKI (10.7±8.9 mg/L) was significantly, but not clinically different for patients with no vAKI (7.5±6.3 mg/L). (p<0.05) Ordinal logistic regression identified total dose of vancomycin, vancomycin administration in the intensive care unit, and concomitant medication administration as significant for vAKI. In particular, concomitant administration of several different medications, including nafcillin, clindamycin, and acetazolamide, were noted for strong associations with vAKI. (p<0.05). CONCLUSIONS: Moderate to severe acute kidney injury due to vancomycin is infrequent in children and associated with concomitant medication use and total dose of vancomycin. Serum vancomycin concentrations are not useful predictors of vAKI in the pediatric population.


Assuntos
Lesão Renal Aguda/terapia , Rim/efeitos dos fármacos , Vancomicina/toxicidade , Acetazolamida/administração & dosagem , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/patologia , Criança , Pré-Escolar , Clindamicina/administração & dosagem , Feminino , Mortalidade Hospitalar , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Rim/lesões , Rim/patologia , Modelos Logísticos , Masculino , Nafcilina/administração & dosagem , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , Vancomicina/sangue
5.
Rev Soc Bras Med Trop ; 51(4): 554-556, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30133645

RESUMO

Staphylococcus lugdunensis is a rare virulent coagulase-negative staphylococcus (CoNS) that behaves similarly to Staphylococcus aureus in causing deep abscesses, skin and soft tissue infections, and central nervous system infections. Additionally, there can be certain blood stream infections including sepsis, septic shock, toxic shock syndrome, and endocarditis complicated by embolic events. Reports of septic arthritis of a native joint associated with this organism have been infrequent, justifying the presentation and discussion of this case.


Assuntos
Artrite Infecciosa/microbiologia , Articulação do Quadril/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus lugdunensis/isolamento & purificação , Antibacterianos/uso terapêutico , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Nafcilina/uso terapêutico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Tomografia Computadorizada por Raios X
7.
Sci Total Environ ; 624: 1095-1105, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29625524

RESUMO

The elimination of the antibiotic Nafcillin (NAF), which is usually used in hospitals and veterinary clinics around the world, was assessed through a combination of three advanced electrochemical oxidation processes followed by anaerobic digestion process. In the first stage different electrochemical advanced oxidation processes (EAOPs) were used: electro-oxidation with hydrogen peroxide (EO-H2O2), electro-Fenton (EF) and Photo electro-Fenton (PEF). After PEF, almost complete and highly efficient degradation and elimination of NAF was achieved, with the concomitant elimination of the associated antimicrobial activity. The fast degradation rate produced by PEF is explained by the oxidative action of hydroxyl radicals (•OH) together with the direct UV photolysis of complexes formed between Fe3+ and some organic intermediates. Total removal of NAF occurs after 90min of electrolysis by PEF, with the generation of organic intermediates that remain in solution. However, when this post PEF process solution was treated with an anaerobic biological process, the intermediates generated in the electrochemical degradation of NAF were completely eliminated after 24h. The kinetic degradation of NAF as well as the identification/quantification of products and intermediates formed during the degradation of antibiotic, such as inorganic ions, carboxylic acids and aromatic compounds, were determined by chromatographic and photometric methods. Finally, an oxidation pathway is proposed for the complete conversion to CO2.


Assuntos
Antibacterianos/isolamento & purificação , Técnicas Eletroquímicas , Nafcilina/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Peróxido de Hidrogênio , Oxirredução , Fotólise , Água
8.
Artigo em Inglês | MEDLINE | ID: mdl-29555635

RESUMO

Increasing utilization of vancomycin due to the high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections has led to the emergence of vancomycin-intermediate S. aureus (VISA) and heterogeneous VISA (hVISA) strains. In vitro data suggest the potential for potent synergy between several beta-lactams and vancomycin. The objective of this study is to evaluate the synergy between beta-lactams and vancomycin against MRSA that is vancomycin susceptible, vancomycin-susceptible Staphylococcus aureus (VSSA), hVISA, and VISA. Fifty randomly selected clinical MRSA strains with various susceptibility levels to vancomycin were evaluated for vancomycin alone and vancomycin in combination with various concentrations of cefazolin (CFZ), cefepime (FEP), ceftaroline (CPT), and nafcillin (NAF). The potential for synergy was assessed by 24-h time-kill studies. Beta-lactams reduced vancomycin MIC values against all strains (4- to 16-fold reduction). In time-kill studies against MRSA, CFZ, FEP, CPT, and NAF all demonstrated similar degrees of killing at 24 h, and all showed synergistic activity with vancomycin against VSSA, hVISA, and VISA. Each of these combinations was also superior to any single agent against isolates of all three phenotypes, and each was bactericidal (P < 0.001 for all comparisons). All single-agent exposures demonstrated no activity at 24 h. The combination of vancomycin and beta-lactams significantly improved antibacterial activity against VSSA, hVISA, and VISA strains compared to the activity of any agent alone, supporting the potential use of vancomycin-beta-lactam combination therapy in infections caused by MRSA. Further clinical research is warranted to investigate the synergy of vancomycin against these Staphylococcus strains.


Assuntos
Cefazolina/farmacologia , Cefepima/farmacologia , Cefalosporinas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nafcilina/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/farmacologia , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/epidemiologia , beta-Lactamas/farmacologia
9.
J Infect Public Health ; 11(5): 727-731, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29526442

RESUMO

BACKGROUND: Anti-staphylococcal penicillins have long been the first-line treatment option for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Recent retrospective data comparing nafcillin and cefazolin report similar clinical efficacy despite concerns about high inoculum MSSA infections. METHODS: This was a retrospective, non-inferiority, cohort study comparing treatment failure rates between nafcillin and cefazolin in patients with MSSA bacteremia from any source, other than meningitis. Multiple logistic regression was used to adjust for confounding variables. RESULTS: A total of 142 patients were included in the study. The overall treatment failure rate among patients receiving cefazolin was non-inferior to nafcillin (11.3% versus 8.5%; 90% confidence interval -5.2% to 10.8%). Rates of adverse drug events were significantly higher in the nafcillin arm (19.7% versus 7%; p=0.046). After adjustment for confounding variables, no difference between treatment groups was found in treatment failure (adjusted odds ratio (OR)=1.2; 95% CI, 0.3-4.5), but nafcillin was associated with significantly higher nephrotoxicity (adjusted odds ratio (OR)=5.4; 95% CI, 1.1-26.8). CONCLUSION: Cefazolin was associated with lower nephrotoxicity and similar treatment failure rates compared to nafcillin suggesting that cefazolin is an appealing first line agent for most MSSA bloodstream infections.


Assuntos
Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Cefazolina/administração & dosagem , Nafcilina/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Cefazolina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Nefropatias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Nafcilina/efeitos adversos , Ensaios Clínicos Controlados não Aleatórios como Assunto , Estudos Retrospectivos , Falha de Tratamento
10.
BMC Infect Dis ; 18(1): 60, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29378565

RESUMO

BACKGROUND: Studies have shown that the prognosis of the treatment of methicillin-susceptible S. aureus (MSSA) with glycopeptides is inferior compared to treatment with ß-lactam. However, there are only few studies comparing treatment with antistaphylococcal penicillin alone to glycopeptide treatment. The aim of this study was to compare the efficacy of nafcillin, an antistaphylococcal penicillin, with that of glycopeptides as a definitive therapy for MSSA bacteremia. METHODS: Patients with MSSA bacteremia recruited from a tertiary referral hospital were enrolled in this retrospective cohort study. Demographic characteristics, laboratory data, and clinical outcome of the treatment were compared between a group receiving nafcillin and a group receiving glycopeptides. RESULTS: A total of 188 patients with MSSA bacteremia were included in this study. The glycopeptide group had a higher rate of malignancy (28.6 vs. 60.8%, p < 0.001) and proportion of healthcare-associated infections (47.3 vs. 72.2%, p < 0.001) compared to the nafcillin group. The ratio of skin and soft tissue infections (30.0 vs. 16.7%, p = 0.037) and bone and joint infections (17.8 vs. 6.3%, p = 0.022), as well as levels of C-reactive protein (139.60 vs. 107.61 mg/dL, p = 0.022) were higher in the nafcillin group. All-cause 28-day mortality was significantly high in the glycopeptide group (7.7 vs. 20.6%, p = 0.013). CONCLUSION: In patients with MSSA bacteremia, all-cause 28-day mortality rate was higher in a group treated with glycopeptides than in a group treated with nafcillin. Therefore, the use of nafcillin should be considered as a definitive therapy for MSSA bacteremia.


Assuntos
Antibacterianos/uso terapêutico , Glicopeptídeos/uso terapêutico , Nafcilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Adulto , Idoso , Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Proteína C-Reativa/análise , Estudos de Coortes , Infecção Hospitalar/complicações , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Meticilina/farmacologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Centros de Atenção Terciária
11.
Chemotherapy ; 63(6): 345-351, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30965335

RESUMO

BACKGROUND: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are conflicting. OBJECTIVE: This study compared treatment failure and adverse effects associated with nafcillin and cefazolin for MSSA BSI. METHODS: Adult inpatients with MSSA BSI between January 1, 2009 and August 31, 2015 were included in this retrospective cohort study if they received ≥72 h of nafcillin or cefazolin as directed therapy after no more than 72 h of any empiric therapy. The primary composite endpoint was treatment failure defined by clinician documentation, 30-day recurrence of infection, all-cause 30-day in-hospital mortality, or loss to follow-up. Secondary outcomes included antibiotic-related acute kidney injury (AKI), acute interstitial nephritis (AIN), hepatotoxicity, and rash. RESULTS: Among 157 patients, 116 (73.9%) received nafcillin and 41 (26.1%) received cefazolin. The baseline characteristics were similar except cefazolin-treated patients had higher APACHE II scores and more frequent renal dysfunction. No difference in the composite treatment failure outcome (28.4 vs. 31.7%; p = 0.69) was detected between the nafcillin and cefazolin groups, respectively. In a sensitivity analysis excluding patients without known follow-up, there was no significant difference of treatment failure. AKI, AIN, hepatotoxicity, and rash were all numerically more frequent among nafcillin-treated patients. CONCLUSIONS: Among nafcillin- or cefazolin-treated patients with MSSA BSI, there was no significant difference in treatment failure. Observing more frequent presumptive adverse effects associated with nafcillin receipt, future prospective studies evaluating cefazolin appear warranted.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Cefazolina/uso terapêutico , Nafcilina/uso terapêutico , Staphylococcus aureus/enzimologia , beta-Lactamases/metabolismo , Lesão Renal Aguda/etiologia , Adulto , Idoso , Antibacterianos/efeitos adversos , Bacteriemia/microbiologia , Bacteriemia/patologia , Cefazolina/efeitos adversos , Creatinina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nafcilina/efeitos adversos , Estudos Retrospectivos , Índice de Gravidade de Doença , Staphylococcus aureus/isolamento & purificação , Centros de Atenção Terciária , Resultado do Tratamento
12.
J Med Microbiol ; 67(1): 83-86, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29154747

RESUMO

INTRODUCTION: When clinicians think about Staphylococcus aureus bacteria, what comes to the mind of most is the dreaded methicillin-resistant form. However, clinicians should not forget the methicillin-susceptible type, which is just as virulent. CASE PRESENTATION: The authors present the case of a 20-year-old woman who was admitted with septic shock and multi-organ failure and was found to have disseminated methicillin-susceptible Staphylococcus aureus (MSSA) infection. The patient had persistent blood cultures positive for MSSA. A transesophageal echocardiogram showed a 1.1 cm vegetation in the mitral valve, and the patient had bilateral pleural effusions that grew MSSA. An MRI of the brain showed multiple areas consistent with infarctions thought to be secondary to septic emboli. The patient underwent a mitral valve replacement and was treated with a prolonged course of parenteral nafcillin. DISCUSSION: This case illustrates a severe clinical presentation and management of MSSA infections.


Assuntos
Meticilina/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Adulto , Antibacterianos/uso terapêutico , Feminino , Humanos , Nafcilina/uso terapêutico , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/efeitos dos fármacos , Adulto Jovem
13.
Clin Microbiol Infect ; 24(2): 152-158, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28694202

RESUMO

OBJECTIVES: No randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. METHODS: A prospective observational cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics. RESULTS: Among the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group. CONCLUSIONS: Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Cefazolina/uso terapêutico , Nafcilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Idoso , Antibacterianos/administração & dosagem , Bacteriemia/microbiologia , Cefazolina/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Masculino , Meticilina/uso terapêutico , Pessoa de Meia-Idade , Nafcilina/administração & dosagem , Estudos Prospectivos , República da Coreia , Infecções Estafilocócicas/microbiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-28483961

RESUMO

Certain Staphylococcus aureus strains exhibit an inoculum effect (InE) with cefazolin (CFZ) that has been associated with therapeutic failures in high-inoculum infections. We assessed the in vitro activities of ceftaroline (CPT), CFZ, and nafcillin (NAF) against 17 type A ß-lactamase (ßla)-producing, methicillin-susceptible S. aureus (MSSA) strains, including the previously reported TX0117, which exhibits the CFZ InE, and its ßla-cured derivative, TX0117c. Additionally, we determined the pharmacokinetics of CPT in rats after single intramuscular doses of 20 and 40 mg/kg of body weight and evaluated the activities of CPT (40 mg/kg every 8 h [q8h]), CFZ, and NAF against TX0117 and TX0117c in a rat model of infective endocarditis. No InE was observed for CPT or NAF, whereas a marked InE was detected for CFZ (MIC, 8 to ≥128 µg/ml). CPT and NAF treatment against TX0117 resulted in mean bacterial counts of 2.3 and 2.1 log10 CFU/g in vegetations, respectively, compared to a mean of 5.9 log10 CFU/g in the CFZ-treated group (CPT and NAF versus CFZ, P = 0.001; CPT versus NAF, P = 0.9830). Both CFZ and CPT were efficacious against the ßla-cured derivative, TX0117c, compared to time zero (t0) (P = <0.0001 and 0.0015, respectively). Our data reiterate the in vivo consequences of the CFZ InE and show that CPT is not affected by this phenomenon. CPT might be considered for high-inoculum infections caused by MSSA exhibiting the CFZ InE.


Assuntos
Antibacterianos/farmacologia , Cefazolina/uso terapêutico , Cefalosporinas/uso terapêutico , Endocardite/tratamento farmacológico , Endocardite/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Animais , Peso Corporal/efeitos dos fármacos , Masculino , Meticilina/uso terapêutico , Testes de Sensibilidade Microbiana , Nafcilina/uso terapêutico , Ratos , Ratos Sprague-Dawley , beta-Lactamases/metabolismo
17.
Transpl Infect Dis ; 19(2)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28067989

RESUMO

Tacrolimus (TAC) is subject to many drug interactions as a result of its metabolism primarily via CYP450 isoenzyme 3A4. Numerous case reports of TAC and CYP3A4 inducers and inhibitors have been described including antimicrobials, calcium channel antagonists, and antiepileptic drugs. We present the case of a 13-year-old patient with cystic fibrosis and a history of liver transplantation, where subtherapeutic TAC concentrations were suspected to be a result of concomitant TAC and nafcillin (NAF) therapy. The observed drug interaction occurred on two separate hospital admissions, during both of which the patient exhibited therapeutic TAC concentrations prior to exposure to NAF, a CYP3A4 inducer. Upon discontinuation of NAF, TAC concentrations recovered in both instances. This case represents a drug-drug interaction between TAC and NAF that has not previously been reported to our knowledge. Despite the lack of existing reports of interaction between these two agents, this case highlights the importance of therapeutic drug monitoring and assessing for any potential drug-drug or drug-food interactions in patients receiving TAC therapy.


Assuntos
Antibacterianos/farmacologia , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/farmacologia , Transplante de Fígado/efeitos adversos , Nafcilina/farmacologia , Tacrolimo/farmacologia , Adolescente , Antibacterianos/uso terapêutico , Fibrose Cística/cirurgia , Citocromo P-450 CYP3A/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas , Monitoramento de Medicamentos , Humanos , Imunossupressores/uso terapêutico , Masculino , Nafcilina/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Tacrolimo/uso terapêutico , Suspensão de Tratamento
18.
Pharmacotherapy ; 36(9): 994-1002, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27485941

RESUMO

PRIMARY OBJECTIVE: To retrospectively review nafcillin plasma concentrations (CNAF ) and determine nafcillin clearance (CLNAF ) in a diverse sample of patients treated with nafcillin administered as a continuous infusion. SECONDARY OBJECTIVE: To identify clinical variables associated with CLNAF and nafcillin-related adverse drug reactions (ADRs). METHODS: Retrospective chart review of patients receiving nafcillin via continuous infusion at University of Utah Health Care from 2006 to 2013 who had at least one steady-state CNAF measured. CLNAF was determined by dividing the nafcillin rate of infusion by CNAF . Adverse drug reactions (ADRs) were defined using the National Institutes of Health, Division of Microbiology and Infectious Diseases criteria and scored for probability of association with nafcillin by using Naranjo criteria. Multivariate models were constructed to identify independent variables associated with CLNAF and ADRs. MAIN RESULTS: Seventy-six CNAF from 54 patients were included. Median CLNAF was 13.9 L/hour (range ≤ 4.2 to 36.9 L/hr). Congestive heart failure (p=0.007), hyperbilirubinemia (p<0.0001), and serum creatinine (p<0.0001) were associated with reduced CLNAF , and Hispanic race (p=0.002) was associated with increased CLNAF by multivariate analysis. Twenty patients (37.0%) experienced an ADR. CNAF were significantly higher between patients that experienced an ADR and those that did not (66.0 vs 25.5 mg/L, p<0.001). Individual ADRs associated with CNAF included hepatotoxicity (62.8 vs 27.0 mg/L, p=0.001), nausea/vomiting (80.0 vs 28.5 mg/L, p=0.01), and diarrhea (66.5 vs 26.5 mg/L, p<0.001). Multivariate analysis identified CNAF as being independently associated with ADRs. A putative toxicity relationship between CNAF and predicted probability of ADR was established. CONCLUSIONS: Several patient variables were associated with impaired CLNAF , and elevated CNAF were associated with ADRs. Additional studies assessing the utility of nafcillin therapeutic drug monitoring to minimize toxicity are warranted.


Assuntos
Nafcilina/efeitos adversos , Nafcilina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Eur J Clin Microbiol Infect Dis ; 35(9): 1441-7, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27234592

RESUMO

Recent studies have demonstrated that anti-staphylococcal beta-lactam antibiotics, like nafcillin, render methicillin-resistant Staphylococcus aureus (MRSA) more susceptible to killing by innate host defense peptides (HDPs), such as cathelicidin LL-37. We compared the effects of growth in 1/4 minimum inhibitory concentration (MIC) of nafcillin or vancomycin on the LL-37 killing of 92 methicillin-susceptible S. aureus (MSSA) isolates. For three randomly selected strains among these, we examined the effects of nafcillin, vancomycin, daptomycin, or linezolid on LL-37 killing and autolysis. Growth in the presence of subinhibitory nafcillin significantly enhanced LL-37 killing of MSSA compared to vancomycin and antibiotic-free controls. Nafcillin also reduced MSSA production of the golden staphylococcal pigment staphyloxanthin in 39 % of pigmented strains vs. 14 % for vancomycin. Among the antibiotics tested, only nafcillin resulted in significantly increased MSSA autolysis. These studies point to additional mechanisms of anti-staphylococcal activity of nafcillin beyond direct bactericidal activity, properties that vancomycin and other antibiotic classes do not exhibit. The ability of nafcillin to enhance sensitivity to innate HDPs may contribute to its superior effectiveness against MSSA, as suggested by studies comparing clinical outcomes to vancomycin treatment.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bacteriemia/microbiologia , Viabilidade Microbiana/efeitos dos fármacos , Nafcilina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia , Bacteriólise/efeitos dos fármacos , Interações Medicamentosas , Humanos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/fisiologia
20.
Antimicrob Agents Chemother ; 60(8): 4684-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27216053

RESUMO

Recent observational studies have suggested possible reductions in mortality in patients receiving cefazolin versus antistaphylococcal penicillins. We examined 90-day mortality in patients receiving cefazolin compared to nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infection (BSI). We identified persons with MSSA BSI admitted to San Francisco General Hospital from January 2008 to July 2013 through a hospital-wide infection surveillance system and confirmed 90-day mortality using U.S. national vital registries. We included persons receiving cefazolin or nafcillin as the predominant intravenous antimicrobial agent; all participants received inpatient Infectious Diseases service consultation. We estimated the association between receipt of cefazolin and 90-day risk of death by multivariate logistic regression, including a propensity score for receiving cefazolin as the second predictor. Of 230 MSSA BSI cases, 30 received nafcillin and 70 received cefazolin as the predominant antimicrobial; 10 died within 90 days, 5 from each group. Unadjusted analysis showed substantial but not statistically significant reduced odds of death in those receiving cefazolin (odds ratio, 0.38; 95% confidence interval [CI], 0.10 to 1.44). Multivariate analysis with propensity scores found a similar adjusted odds ratio (0.40; 95% CI, 0.09 to 1.74; P = 0.22). We found a large reduction in 90-day mortality in those receiving cefazolin compared to nafcillin for MSSA BSI, but this finding was not statistically significant. The magnitude of effect seen in this and other studies justifies further study.


Assuntos
Bacteriemia/tratamento farmacológico , Cefazolina/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Meticilina/uso terapêutico , Nafcilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , California , Infecção Hospitalar/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Penicilinas/uso terapêutico , Centros de Atenção Terciária
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