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1.
Sci Rep ; 12(1): 180, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996996

RESUMO

Pseudomonas aeruginosa is an opportunistic bacterium causing several health problems and having many virulence factors like biofilm formation on different surfaces. There is a significant need to develop new antimicrobials due to the spreading resistance to the commonly used antibiotics, partly attributed to biofilm formation. Consequently, this study aimed to investigate the anti-biofilm and anti-quorum sensing activities of Dioon spinulosum, Dyer Ex Eichler extract (DSE), against Pseudomonas aeruginosa clinical isolates. DSE exhibited a reduction in the biofilm formation by P. aeruginosa isolates both in vitro and in vivo rat models. It also resulted in a decrease in cell surface hydrophobicity and exopolysaccharide quantity of P. aeruginosa isolates. Both bright field and scanning electron microscopes provided evidence for the inhibiting ability of DSE on biofilm formation. Moreover, it reduced violacein production by Chromobacterium violaceum (ATCC 12,472). It decreased the relative expression of 4 quorum sensing genes (lasI, lasR, rhlI, rhlR) and the biofilm gene (ndvB) using qRT-PCR. Furthermore, DSE presented a cytotoxic activity with IC50 of 4.36 ± 0.52 µg/ml against human skin fibroblast cell lines. For the first time, this study reports that DSE is a promising resource of anti-biofilm and anti-quorum sensing agents.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Chromobacterium/efeitos dos fármacos , Extratos Vegetais/farmacologia , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Dermatopatias Bacterianas/prevenção & controle , Zamiaceae , Animais , Antibacterianos/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Chromobacterium/crescimento & desenvolvimento , Chromobacterium/metabolismo , Modelos Animais de Doenças , Feminino , Regulação Bacteriana da Expressão Gênica , Indóis/metabolismo , Testes de Sensibilidade Microbiana , Extratos Vegetais/isolamento & purificação , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/metabolismo , Ratos , Dermatopatias Bacterianas/microbiologia , Dermatopatias Bacterianas/patologia , Zamiaceae/química
2.
Int J Antimicrob Agents ; 56(4): 106107, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32721599

RESUMO

Dalbavancin is a novel lipoglycopeptide antibiotic with a chemical structure similar to teicoplanin. Dalbavancin has been approved and marketed since 2014 in the USA and 2015 in the European Union for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) caused by Gram-positive cocci. ABSSSIs include infectious syndromes such as erysipelas, cellulitis, major cutaneous abscesses that require incision and drainage, and both surgical and traumatic wound infections. In current clinical practice, dalbavancin is also used for cardiac implantable electronic device-related soft tissue infection and other prosthetic infections, and therefore when the presence of biofilm is a concern. In this review, we aimed to highlight our experience with the use of dalbavancin for some of the most hard-to-treat Gram-positive infections, as well as a promising strategy in terms of pharmacoeconomic effectiveness. We describe our current real-life clinical practice with the use of dalbavancin, depicting a few representative clinical cases in order to share our own practice in the hospital setting.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Dermatopatias Bacterianas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico , Teicoplanina/análogos & derivados , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Discite/tratamento farmacológico , Discite/microbiologia , Farmacoeconomia , Endocardite/tratamento farmacológico , Endocardite/microbiologia , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Dermatopatias Bacterianas/microbiologia , Infecções dos Tecidos Moles/microbiologia , Teicoplanina/uso terapêutico
4.
Photodiagnosis Photodyn Ther ; 29: 101624, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31866531

RESUMO

BACKGROUND: It has recently been shown that endogenous photosensitization of Gram-positive bacteria is achieved through the accumulation of the heme precursor coproporphyrin III and not protoporphyrin IX, as was previously assumed. As previous studies have operated under this assumption, the efficacy of optimal targeting of the absorption peaks of coproporphyrin III has not been explored. METHODS: Staphylococcus aureus was endogenously photosensitized through the addition of either the small molecule VU0038882, aminolevulinic acid, or both. The efficacy of five different LEDs whose wavelengths target different coproporphyrin III absorption peaks were determined in vitro. Based on these in vitro measurements, the effectiveness of utilizing these LEDs to treat a skin infection was predicted using a Monte Carlo simulation to estimate the fluence rates and resulting bacterial reductions as a function of depth. RESULTS: Optimal targeting of the Soret band provided a 4.7-log improvement as compared to previously utilized wavelengths. Activation of the Q-bands was found to provide similar cytotoxic effects but required significantly larger doses of light. Despite near sterilization in vitro, it was predicted that Soret band targeted light would only provide at least a 2 log-reduction up to 430 µm into the skin while Q-band targeted light could remain effective up to 1 mm in depth. Multiplexing these different wavelengths was found to provide a further 0.5-1.0 log-reduction in bacterial viability. CONCLUSIONS: Accurate targeting of coproporphyrin III has shown that endogenous photodynamic therapy has the potential to be further developed into an effective treatment of skin and soft tissue infections caused by Gram-positive bacteria.


Assuntos
Coproporfirinas/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Ácido Aminolevulínico/farmacologia , Técnicas In Vitro , Método de Monte Carlo , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia
5.
Clin Infect Dis ; 68(Suppl 3): S193-S199, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30957165

RESUMO

The US burden of acute skin infections is substantial. While Staphylococcus aureus and Streptococcus spp. are the most common causes, gram-negative bacteria and mixed infections can occur in some settings. These mixed infections are more likely to result in inappropriate empiric antibiotic therapy. Important challenges remain in diagnosing and treating acute skin infections.


Assuntos
Efeitos Psicossociais da Doença , Dermatopatias Bacterianas/epidemiologia , Dermatopatias Bacterianas/microbiologia , Doença Aguda , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Vigilância em Saúde Pública , Fatores de Risco , Dermatopatias Bacterianas/diagnóstico , Dermatopatias Bacterianas/terapia , Infecções dos Tecidos Moles/diagnóstico , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/terapia , Resultado do Tratamento , Estados Unidos/epidemiologia
6.
Expert Opin Drug Metab Toxicol ; 14(2): 197-206, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29258361

RESUMO

INTRODUCTION: Acute bacterial skin and skin structure infections (ABSSIs), defined as a bacterial infection of the skin with a lesion size area of at least 75 cm, are a leading cause of hospital admission and ambulatory care visits worldwide. Dalbavancin is a lipoglycopeptide antibiotic recently approved by the United States Food and Drug Administration (FDA) and by European Medicines Agency (EMA) for ABSSSIs. The authors review and provide updates of efficacy and safety by several studies on dalbavancin. Areas covered: A PubMed search was performed for relevant literature. We especially focused our attention on pharmacokinetics. Expert opinion: Dalbavancin provides an important new therapy for management of ABSSI, maintaining a spectrum of activity similar to vancomycin against gram-positive organisms. Use of dalbavancin, with its 1-week-shot treatment, consist in a reduction of the length of hospital stay or in a reduction of hospital admissions, with important cost savings.


Assuntos
Antibacterianos/administração & dosagem , Dermatopatias Bacterianas/tratamento farmacológico , Teicoplanina/análogos & derivados , Animais , Antibacterianos/economia , Antibacterianos/farmacocinética , Redução de Custos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/economia , Infecções por Bactérias Gram-Positivas/microbiologia , Hospitalização/estatística & dados numéricos , Humanos , Tempo de Internação , Dermatopatias Bacterianas/economia , Dermatopatias Bacterianas/microbiologia , Teicoplanina/administração & dosagem , Teicoplanina/economia , Teicoplanina/farmacocinética , Vancomicina/uso terapêutico
7.
J Chemother ; 29(3): 154-158, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27376439

RESUMO

Thirty-two patients affected by SSTIs including DFIs were enrolled between 2013 and 2014. Superficial swab was obtained before and after cleansing with sterile saline, and after ultrasonic debridement; deep tissue biopsy was obtained from ulcer base. Samples were diluted with 1 mL of saline, serial 10-fold dilutions to 10-6 were made and 50 µL of each dilution was plated onto appropriate media. Bacteria were identified by Vitek II system. Microbial load was expressed as CFU/mL. Statistical analysis was performed by χ2. Incidence of Gram positives was higher than Gram negatives (S. aureus and P. aeruginosa being the most frequent); concordance (same bacteria isolated before and after debridement) never exceeded 60%. Ultrasonic debridement significantly reduced bacterial load or even suppressed bacterial growth. While reliability of superficial swab is poor for microbiological diagnosis of SSTIs, swabbing after ultrasonic debridement and biopsy of the ulcer base may be equally reliable.


Assuntos
Pseudomonas aeruginosa/isolamento & purificação , Dermatopatias Bacterianas/diagnóstico , Infecções dos Tecidos Moles/diagnóstico , Staphylococcus aureus/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carga Bacteriana/efeitos da radiação , Biópsia , Desbridamento , Pé Diabético/complicações , Pé Diabético/microbiologia , Pé Diabético/terapia , Feminino , Hospitais Universitários , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/efeitos da radiação , Encaminhamento e Consulta , Dermatopatias Bacterianas/complicações , Dermatopatias Bacterianas/epidemiologia , Dermatopatias Bacterianas/microbiologia , Úlcera Cutânea/complicações , Úlcera Cutânea/microbiologia , Úlcera Cutânea/terapia , Infecções dos Tecidos Moles/complicações , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/microbiologia , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/efeitos da radiação , Ondas Ultrassônicas
8.
Clin Microbiol Infect ; 20(10): 993-1000, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24673973

RESUMO

The objective of this study was to document pan-European real-world treatment patterns and healthcare resource use and estimate opportunities for early switch (ES) from intravenous (IV) to oral antibiotics and early discharge (ED) in hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections (cSSTIs). This retrospective observational medical chart review study enrolled 342 physicians across 12 European countries who collected data from 1542 patients with documented MRSA cSSTI who were hospitalized (July 2010 to June 2011) and discharged alive (by July 2011). Data included clinical characteristics and outcomes, hospital length of stay (LOS), MRSA-targeted IV and oral antibiotic use, and ES and ED eligibility according to literature-based and expert-validated criteria. The most frequent initial MRSA-active antibiotics were vancomycin (50.2%), linezolid (15.1%), clindamycin (10.8%), and teicoplanin (10.4%). Patients discharged with MRSA-active antibiotics (n = 480) were most frequently prescribed linezolid (42.1%) and clindamycin (19.8%). IV treatment duration (9.3 ± 6.5 vs. 14.6 ± 9.9 days; p <0.001) and hospital LOS (19.1 ± 12.9 vs. 21.0 ± 18.2 days; p 0.162) tended to be shorter for patients switched from IV to oral treatment than for patients who received IV treatment only. Of the patients, 33.6% met ES criteria and could have discontinued IV treatment 6.0 ± 5.5 days earlier, and 37.9% met ED criteria and could have been discharged 6.2 ± 8.2 days earlier. More than one-third of European patients hospitalized for MRSA cSSTI could be eligible for ES and ED, resulting in substantial reductions in IV days and bed-days, with potential savings of €2000 per ED-eligible patient.


Assuntos
Antibacterianos/administração & dosagem , Tempo de Internação/tendências , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Dermatopatias Bacterianas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Administração Intravenosa , Administração Oral , Idoso , Feminino , Humanos , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos Retrospectivos , Dermatopatias Bacterianas/microbiologia , Infecções dos Tecidos Moles/microbiologia , Infecções Estafilocócicas/complicações
9.
Am J Health Syst Pharm ; 70(12): 1057-64, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23719884

RESUMO

PURPOSE: The budgetary impact of adding ceftaroline fosamil to a hospital formulary for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) was evaluated. METHODS: A three-year hospital budget impact model was constructed with three initial treatment options for ABSSSIs: ceftaroline fosamil, vancomycin plus aztreonam, and other vancomycin-containing regimens. The target population was hospitalized adult patients with an ABSSSI. Clinical cure rates with initial treatment were assumed to be similar to those from ceftaroline fosamil clinical trials. Patients who did not respond to initial treatment were assumed to be treated successfully with second-line antimicrobial therapy. Length of stay and cost per hospital day (by success or failure with initial treatment) were estimated based on a large database from more than 100 U.S. hospitals. Other model inputs included the annual number of ABSSSI admissions, projected annual case growth rate, proportion of ABSSSI target population receiving vancomycin-containing regimen, expected proportion of ABSSSI target population to be treated with ceftaroline fosamil, drug acquisition cost, cost of antibiotic administration, and cost of vancomycin monitoring. Sensitivity analysis using 95% confidence limits of clinical cure rates was also performed. RESULTS: The estimated total cost of care for treating a patient with an ABSSSI was $395 lower with ceftaroline fosamil ($15,087 versus $15,482) compared with vancomycin plus aztreonam and $72 lower ($15,087 versus $15,159) compared with other vancomycin-containing regimens. CONCLUSION: Model estimates indicated that adding ceftaroline fosamil to the hospital formulary would not have a negative effect on a hospital's budget for ABSSSI treatment.


Assuntos
Antibacterianos/economia , Cefalosporinas/economia , Dermatopatias Bacterianas/economia , Vancomicina/economia , Doença Aguda , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Aztreonam/administração & dosagem , Aztreonam/economia , Aztreonam/uso terapêutico , Cefalosporinas/administração & dosagem , Cefalosporinas/uso terapêutico , Custos e Análise de Custo , Quimioterapia Combinada , Economia Hospitalar , Formulários de Hospitais como Assunto , Humanos , Tempo de Internação/economia , Modelos Econômicos , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia , Vancomicina/administração & dosagem , Vancomicina/uso terapêutico , Ceftarolina
10.
Clin Microbiol Infect ; 19(9): E377-85, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23663184

RESUMO

Complicated skin and soft tissue infections (cSSTI) are common and frequently require treatment in hospital. Comprehensive current data on management practices in patients hospitalized with cSSTI are limited. REACH was a retrospective, observational cohort study designed to provide data on current clinical management of moderate to severe cSSTI in European hospitals. Data were collected via an electronic case report form from 129 sites in ten European countries. The study population comprised patients ≥18 years, hospitalized between March 2010 and February 2011 with cSSTI who received intravenous antibiotic treatment. Presented here is an analysis of the disease characteristics, treatment patterns during hospitalization and clinical outcomes identified by the study. The total population included 1995 patients (mean age 60.6 years; 57.7% male). Initial antibiotic treatment modification was reported in 39.6% (n = 791) of patients; it was more common in patients with co-morbidities (42.6%), those requiring surgical intervention (43.4%), those with more severe infections such as bacteraemia (51.6%) or with fascia affected (49.0%), those admitted to the intensive care unit (56.2%) and those with lesions > 50 cm(2) (44.3%). A switch to narrower-spectrum antibiotic treatment (streamlining) occurred in 5.6% of patients. Mean length of hospital stay was 18.5 days (±19.9; median 12.0) and the total mortality rate was 3.4%. The data collected in REACH give a comprehensive and current view of real-life clinical management of cSSTI in European hospitals and provide evidence of a high rate of initial antibiotic treatment modification.


Assuntos
Antibacterianos/uso terapêutico , Dermatopatias Bacterianas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Infecção Hospitalar/tratamento farmacológico , Europa (Continente) , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Estudos Retrospectivos , Dermatopatias Bacterianas/complicações , Dermatopatias Bacterianas/microbiologia , Infecções dos Tecidos Moles/complicações , Infecções dos Tecidos Moles/microbiologia , Resultado do Tratamento , Adulto Jovem
11.
Curr Med Res Opin ; 29(7): 869-77, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23659559

RESUMO

OBJECTIVE: The FDA recently issued guidance for the types of infections that should be included in trials to support an indication for antibacterial treatment. The latest FDA guidance recommends assessing response to drug therapy at 48 to 72 hours as the primary endpoint in clinical trials. This study evaluated clinical and economic outcomes among acute bacterial skin and skin structure infections (ABSSSI) patients hospitalized at a 3000-bed healthcare system in New Jersey. RESEARCH DESIGN AND METHODS: In this retrospective cohort analysis, adult ABSSSI patients hospitalized between July 2010 and December 2011 were stratified based on infection type: cellulitis/erysipelas and major cutaneous abscess, wound infection, and all ABSSSI. Initial antibiotic therapy was assessed by individual agent, regimen, and MRSA coverage. Day 3 response to initial antibiotic therapy was evaluated based on temperature and lesion cessation outcomes; clinical response rates were assessed by initial therapy and pathogen for each cohort. The impact of response on length of stay (LOS), cost of care, and antibiotic treatment duration were also evaluated. RESULTS: Commonly used antibiotics included vancomycin, cefazolin, piperacillin-tazobactam, and ampicillin-sulbactam; over 40% of patients received empiric therapy with activity against MRSA. Clinical non-response to initial antimicrobial therapy at Day 3 was 39.9%, 30.3%, and 60.7%, for all ABSSSI, cellulitis/abscess, and wound infection patients, respectively. The cost of care among non-responders was over 1.5 times that of responders (p < 0.0001). Non-response to initial therapy was associated with a 3.7 day increase in duration of antibiotic treatment (p < 0.0001). CONCLUSIONS: Results of this study demonstrate that a significant percentage of ABSSSI patients, particularly those with wound infection, were not achieving clinical response at Day 3 of therapy. Failure to respond to drug therapy is associated with substantial increases in LOS, antibiotic treatment duration, and cost of care. LIMITATIONS: This had the inherent limitations associated with a retrospective chart review; because data was initially collected for clinical rather than research purposes, certain information may have been absent, incomplete, or missed by data abstractors.


Assuntos
Antibacterianos/uso terapêutico , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Infecciosas/tratamento farmacológico , Idoso , Ampicilina/uso terapêutico , Cefazolina/uso terapêutico , Feminino , Hospitalização , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Estudos Retrospectivos , Dermatopatias Bacterianas/microbiologia , Dermatopatias Infecciosas/microbiologia , Sulbactam/uso terapêutico , Resultado do Tratamento , Vancomicina/uso terapêutico
12.
Przegl Lek ; 68(4): 196-201, 2011.
Artigo em Polonês | MEDLINE | ID: mdl-21853673

RESUMO

The bacterial skin and soft-tissue infections occur commonly and are characterized by more or less intensified changes within skin and subcutaneous tissue. The bacterial skin infections give rise to significant therapeutic problems associated with increasing resistance etiological agents of these infections to antibiotics and chemotherapeutics. The aim of this study was to assess the distribution of various Gram-positive microorganisms in skin lesion observed in ambulatory patients in a period from June 2005 to December 2006. There were 116 bacterial strains isolated and identified from clinical samples: Staphylococcus aureus, coagulase - negative staphylococi (S.epidermidis, S. xylosus, S.capitis, S.saccharolyticus), Propionobacterium acnes, Streptococcus spp. (S.agalactiae, S.pyogenes) i Corynebacterium spp. (C. striatum, C. amycolatum, C. aquaticum). In the further part of this study we analyzed a profile of their susceptibility to antibiotics and chemotherapeutics in relation to drugs recommended for the empirical therapy. The resultant resistance patterns among the examined bacterial isolates are indicative of certain divergence between recommended empirical antibiotic therapy and actual antimicrobial susceptibility of many etiologic factors of skin and soft-tissue infections.


Assuntos
Bactérias Gram-Positivas/classificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Assistência Ambulatorial , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Especificidade da Espécie
14.
J Antimicrob Chemother ; 66(2): 387-97, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20926396

RESUMO

BACKGROUND: Skin and soft tissue infections (SSTIs) are caused by bacterial invasion of the skin and underlying soft tissues and can present with a wide spectrum of signs, symptoms and illness severity. They are a common indication for antimicrobial therapy. However, there are few data on treatment outcomes or the validity of clinical severity scores. METHODS: Two hundred and five adult patients admitted to Ninewells Hospital, Scotland in 2005, and treated with antibiotics for SSTI, were identified. They were stratified into four classes of severity (class IV = most severe) based on sepsis, co-morbidity and their standardized early warning score (SEWS). Empirical antimicrobial therapy by severity class was compared with the recommendations of a UK guideline. RESULTS: Thirty-five different empirical antimicrobial regimens were prescribed. Overall, 43% of patients were over-treated, this being particularly common in the lowest severity class I (65% patients). Thirty-day mortality was 9% (18/205) and 17 patients (8%) died during their index admission. Mortality (30 day) and inadequate therapy increased with severity class: I, no sepsis or co-morbidity (45% patients, 1% mortality, 14% therapy inadequate); II, significant co-morbidity but no sepsis (32% patients, 11% mortality, 39% therapy inadequate); III, sepsis but SEWS <4 (17% of patients, 17% mortality, 39% therapy inadequate); and IV, sepsis plus SEWS ≥ 4 (6% of patients, 33% mortality, 92% therapy inadequate). CONCLUSIONS: SSTI in hospital is associated with significant mortality. Choice of empirical therapy is not evidence based, with significant under-treatment of severely ill patients.


Assuntos
Dermatopatias Bacterianas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Coortes , Feminino , Hospitalização , Humanos , Inflamação/microbiologia , Masculino , Resistência a Meticilina , Pessoa de Meia-Idade , Escócia , Dermatopatias Bacterianas/microbiologia , Dermatopatias Bacterianas/mortalidade , Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/mortalidade , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Resultado do Tratamento
15.
J Clin Pharmacol ; 48(9): 1063-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18633123

RESUMO

Dalbavancin is a novel glycopeptide with a 2-dose, once-weekly dosing regimen that is being developed for the treatment of complicated skin and skin structure infections caused by gram-positive bacteria. Monte Carlo simulations were performed for dalbavancin using population pharmacokinetic data and minimum inhibitory concentrations (MICs) for clinical trial isolates. The time-dependent target was the maintenance of free drug concentrations above the MIC for 14 days (t>MIC). The concentration-dependent target was an area under the concentration-time curve (AUC)/MIC ratio of approximately 1000 for Staphylococcus aureus and 100 for Streptococcus sp. These targets were used to estimate susceptibility breakpoints for dalbavancin. For S aureus, the estimated susceptibility breakpoint was MIC. For Streptococcus sp, the estimated susceptibility breakpoint was at least 2 mug/mL. Because dalbavancin MIC(90)s for these species are well below these values, the analysis supports the use of once-weekly dosing regimens of dalbavancin in the treatment of complicated skin and skin structure infections.


Assuntos
Antibacterianos/farmacocinética , Simulação por Computador , Modelos Biológicos , Dermatopatias Bacterianas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Teicoplanina/análogos & derivados , Antibacterianos/administração & dosagem , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Esquema de Medicação , Humanos , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Dermatopatias Bacterianas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Streptococcus/efeitos dos fármacos , Streptococcus/crescimento & desenvolvimento , Teicoplanina/administração & dosagem , Teicoplanina/farmacocinética , Vancomicina/farmacocinética
16.
Br J Dermatol ; 158(4): 698-704, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18294320

RESUMO

BACKGROUND: Actinomycetoma is a chronic infection caused by several aerobic actinomycetes; it is a relatively frequent condition in tropical countries like Mexico. It is important to be aware of the extension and depth of the disease (bone and visceral) to make the prognosis and select treatment. OBJECTIVES: Our objective was to evaluate actinomycetomas using helical computed tomography (HCT) as well as its three-dimensional (3D) reconstruction. MATERIAL AND METHODS: Prospective study of clinically and microbiologically proven cases of actinomycetomas, all of them recently diagnosed and untreated or unresponsive to various treatments. All patients underwent simple and contrast HCT with various helical slices of the involved zones. Then three-dimensional reconstructions on the sagittal and coronal planes were made. RESULTS: Twenty-one patients with actinomycetomas were included, 19 males and two females, with a mean age of 35.5 years and mean duration of disease of 4.1 years. The disease was located in the lower limbs in 81%, and in the upper limbs and trunk in 19%. Twenty of the 21 cases were caused by Nocardia brasiliensis and one by Actinomadura madurae. In all patients the disease was localized to the skin and subcutaneous tissue; 76.2% had muscular involvement; 23.8% visceral involvement; 9.5% had bone involvement and 9.5% vascular involvement. The affected area was determined in each case. CONCLUSIONS: HCT provides precise information about the grade of invasion at diverse levels such as visceral, muscular and vascular systems, and the calculation of the affected area.


Assuntos
Infecções por Actinomycetales/diagnóstico , Actinomycetales/isolamento & purificação , Imageamento Tridimensional/métodos , Doenças Profissionais/diagnóstico , Dermatopatias Bacterianas/diagnóstico , Tomografia Computadorizada Espiral/métodos , Infecções por Actinomycetales/microbiologia , Infecções por Actinomycetales/terapia , Adolescente , Adulto , Idoso , Análise Custo-Benefício , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/microbiologia , Doenças Profissionais/terapia , Estudos Prospectivos , Índice de Gravidade de Doença , Dermatopatias Bacterianas/microbiologia , Dermatopatias Bacterianas/terapia , Tomografia Computadorizada Espiral/economia
17.
Trop Med Int Health ; 10(11): 1199-206, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16262747

RESUMO

OBJECTIVE: The current standard of treatment of Buruli ulcer disease (BUD) is surgical excision of lesions. Excision size is determined macroscopically assuming the complete removal of all infected tissue. However, dissemination of infection beyond the excision margins into apparently healthy tissue, possibly associated with recurrences, cannot be excluded in this way. To assess the central to peripheral progression of Mycobacterium ulcerans infection and the mycobacterial infiltration of excision margins, excised tissue was examined for signs of infection. METHODS: 20 BUD lesions were excised in general anaesthesia including all necrotic and subcutaneous adipose tissue down to the fascia and at an average of 40 mm into the macroscopically unaffected tissue beyond the border of the lesion. Tissue samples were subjected to PCR and histopathology. RESULTS: Although the bacillary load decreased from central to peripheral, M. ulcerans infection was detected throughout all examined tissue specimens including the peripheral segments as well as excision margins of all patients. During the post-operative hospitalization period (averaging 2 months) no local recurrences were observed. CONCLUSION: Available data suggest a correlation of surgical techniques with local recurrences. The results of this study indicate the unnoticed early progression of mycobacterial infection into macroscopically healthy tissue. Thus, the removal of all infected tissue cannot always be verified visually by the surgeon. Provided that long-term follow up of patients with positive excision margins will establish the clinical relevance of these findings, on-site laboratory assessment of excised tissue in combination with follow up may contribute to reduce recurrence rates.


Assuntos
Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium ulcerans/isolamento & purificação , Dermatopatias Bacterianas/microbiologia , Adolescente , Adulto , Criança , DNA Bacteriano/análise , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/patologia , Infecções por Mycobacterium não Tuberculosas/cirurgia , Reação em Cadeia da Polimerase/métodos , Período Pós-Operatório , Dermatopatias Bacterianas/patologia , Dermatopatias Bacterianas/cirurgia , Úlcera Cutânea/microbiologia , Úlcera Cutânea/patologia , Úlcera Cutânea/cirurgia
18.
JAMA ; 291(16): 1994-8, 2004 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-15113818

RESUMO

CONTEXT: Little is known about potential long-term health effects of bioterrorism-related Bacillus anthracis infection. OBJECTIVE: To describe the relationship between anthrax infection and persistent somatic symptoms among adults surviving bioterrorism-related anthrax disease approximately 1 year after illness onset in 2001. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 15 of 16 adult survivors from September through December 2002 using a clinical interview, a medical review-of-system questionnaire, 2 standardized self-administered questionnaires, and a review of available medical records. MAIN OUTCOME MEASURES: Health complaints summarized by the body system affected and by symptom categories; psychological distress measured by the Revised 90-Item Symptom Checklist; and health-related quality-of-life indices by the Medical Outcomes Study 36-Item Short-Form Health Survey (version 2). RESULTS: The anthrax survivors reported symptoms affecting multiple body systems, significantly greater overall psychological distress (P<.001), and significantly reduced health-related quality-of-life indices compared with US referent populations. Eight survivors (53%) had not returned to work since their infection. Comparing disease manifestations, inhalational survivors reported significantly lower overall physical health than cutaneous survivors (mean scores, 30 vs 41; P =.02). Available medical records could not explain the persisting health complaints. CONCLUSION: The anthrax survivors continued to report significant health problems and poor life adjustment 1 year after onset of bioterrorism-related anthrax disease.


Assuntos
Antraz , Bioterrorismo , Qualidade de Vida , Sobreviventes , Absenteísmo , Adulto , Antraz/fisiopatologia , Antraz/psicologia , Bioterrorismo/psicologia , Estudos Transversais , Seguimentos , Nível de Saúde , Indicadores Básicos de Saúde , Humanos , Pessoa de Meia-Idade , Infecções Respiratórias/microbiologia , Infecções Respiratórias/fisiopatologia , Infecções Respiratórias/psicologia , Dermatopatias Bacterianas/microbiologia , Dermatopatias Bacterianas/fisiopatologia , Dermatopatias Bacterianas/psicologia , Estresse Psicológico , Sobreviventes/psicologia , Estados Unidos
19.
Diagn Microbiol Infect Dis ; 44(3): 281-8, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12493176

RESUMO

We report the results of pathogen frequency and antimicrobial susceptibility of isolates collected from skin and soft tissue infections (SSTIs) in Latin American medical centers during the first 4 years (1997-2000) of the SENTRY Antimicrobial Surveillance Program. Ten laboratories participated each year distributed among nine cities in six countries. A total of 1,789 bacterial isolates were susceptibility tested by reference broth microdilution at the coordinating central laboratory. Results from isolates collected during the year 2000 were compared with those from isolates collected during the prior three years. Selected carbapenem-resistant Pseudomonas aeruginosa were genotyped by automated ribotyping to evaluate the occurrence of clonal, epidemic dissemination. The five most frequently isolated species were (n/%): Staphylococcus aureus (584/32.8%), Escherichia coli (233/13.1%), P. aeruginosa (211/11.9%), Enterococcus spp. (137/7.7%), and Klebsiella spp. (127/5.8%). The most problematic antimicrobial resistances were related to the high prevalence of multi-drug resistant (MDR) Gram-negative bacilli. Carbapenem resistance among non-fermentative Gram-negative bacilli was much higher than that reported in other regions evaluated in the SENTRY Program. Only 74.9% of P. aeruginosa and 84.9% of Acinetobacter spp. were considered susceptible to imipenem. The antimicrobial susceptibility rates of P. aeruginosa decreased during the study period for most antimicrobial agents evaluated. More than 40% of K. pneumoniae and nearly 10% of E. coli showed an extended spectrum beta-lactamase phenotype. Only 73.4% of E. coli and 76.0% of Enterobacter spp. were susceptible to ciprofloxacin. The molecular typing of carbapenem-resistant P. aeruginosa demonstrated clonal dissemination in two institutions. These reported results indicate that rates of resistance among isolates causing SSTI continue to raise in Latin America, with specific concerns for the high prevalence of MDR Gram-negative bacilli. National and international surveillance programs as a guide to focusing intervention strategies should assist in the control of escalating antimicrobial resistance in this geographic area.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Hospitais , Vigilância de Evento Sentinela , Dermatopatias Bacterianas/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Bactérias/isolamento & purificação , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Farmacorresistência Bacteriana Múltipla , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Humanos , América Latina/epidemiologia , Testes de Sensibilidade Microbiana , Prevalência , Dermatopatias Bacterianas/microbiologia , Infecções dos Tecidos Moles/microbiologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/isolamento & purificação
20.
Int J Infect Dis ; 4(2): 75-84, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10737843

RESUMO

OBJECTIVES: This study was conducted to evaluate the frequency of occurrence and antimicrobial susceptibility of bacterial isolates collected from patients with skin and soft tissue infections (SSTI) in Latin American hospitals, as part of the SENTRY Antimicrobial Surveillance Program. The dissemination of multidrug-resistant methicillin-resistant Staphylococcus aureus (MDR-MRSA) among the Latin American countries also was studied. MATERIAL AND METHODS: A total of 885 bacterial isolates were analyzed. At the monitoring laboratory, antimicrobial susceptibility testing utilizing the reference broth microdilution method and confirmation of species identification were performed. Enterobacteriaceae possibly producing extended-spectrum beta-lactamases (ESBL) and MDR-MRSA isolates were genotyped by ribotyping using the RiboPrinter and by pulsed-field gel electrophoresis. RESULTS: Staphylococcus aureus (31%) was the most common etiologic agent causing SSTI, followed by Escherichia coli (13.4%) and Pseudomonas aeruginosa (11%). Thirty-one percent of S. aureus isolates were resistant to oxacillin (methicillin). The presence of ESBL phenotypes was markedly higher among the Klebsiella pneumoniae (35.5%) than E. coli isolates (10. 2%). Meropenem was the compound with the highest susceptibility rate among the Enterobacteriaceae (100%) and P. aeruginosa (95%) isolates. A great genetic similarity was observed among the MDR-MRSA in Latin America. CONCLUSION: High resistance rates to antimicrobial drugs among the most frequent bacterial pathogens were observed in 10 medical centers in Latin America. This study also demonstrated a clonal dissemination of a MDR-MRSA strain in several nations.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Infecção Hospitalar/microbiologia , Dermatopatias Bacterianas/microbiologia , Infecções dos Tecidos Moles/microbiologia , Bactérias/isolamento & purificação , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/epidemiologia , Resistência Microbiana a Medicamentos , Resistência a Múltiplos Medicamentos , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Humanos , América Latina/epidemiologia , Resistência a Meticilina/genética , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Vigilância de Evento Sentinela , Dermatopatias Bacterianas/epidemiologia , Infecções dos Tecidos Moles/epidemiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética
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