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1.
J Burn Care Res ; 36(4): e244-52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25185930

RESUMO

This study aimed to develop optimal amikacin dosing regimens for the empirical treatment of Gram-negative bacterial sepsis in pediatric patients with burn injuries. A pharmacodynamic (PD) target in which the peak concentration (Cmax) is ≥8 times the minimum inhibitory concentration (MIC) (Cmax/MIC ≥ 8) is reflective of optimal bactericidal activity and has been used to predict clinical outcomes. Population pharmacokinetic modeling was performed in NONMEM 7.2 for pediatric patients with and without burn injuries. Amikacin pharmacokinetic parameters were compared between the two groups and multiple dosing regimens were simulated using MATLAB to achieve the PD target in ≥90% of patients with burn injuries. The pharmacokinetic analysis included 282 amikacin concentrations from 70 pediatric patients with burn injuries and 99 concentrations from 32 pediatric patients without burns. A one-compartment model with first-order elimination described amikacin pharmacokinetics well for both groups. Clearance (CL) was significantly higher in patients with burn injuries than in patients without (7.22 vs 5.36 L/h, P < .001). The volume of distribution (V) was also significantly increased in patients with burn injuries (22.7 vs 18.7 L, P < .01). Weight significantly influenced amikacin CL (P < .001) and V (P < .001) for both groups. Model-based simulations showed that a higher amikacin dose (≥25 mg/kg) achieved a Cmax/MIC ≥8 in ≥90% of patients with assumed infections of organisms with an MIC = 8 mg/L. Amikacin pharmacokinetics are altered in patients with burn injuries, including a significant increase in CL and V. In simulations, increased doses (≥25 mg/kg) led to improved PD target attainment rates. Further clinical evaluation of this proposed dosing regimen is warranted to assess clinical and microbiological outcomes in pediatric patients with burn wound sepsis.


Assuntos
Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Queimaduras/complicações , Sepse/tratamento farmacológico , Amicacina/farmacocinética , Antibacterianos/farmacocinética , Peso Corporal , Criança , Relação Dose-Resposta a Droga , Humanos , Modelos Estatísticos , Sepse/etiologia
2.
J Burn Care Res ; 35(5): e304-11, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25144811

RESUMO

The purpose of this retrospective study was to collate data dealing with organisms cultured from the burn patients and evaluate trends in antimicrobial susceptibility. All cultures collected from each acute admission patient between 2004 and 2011 in the 30-bed pediatric burn hospital were evaluated for their annual frequency and antimicrobial susceptibility. Duplicate cultures were excluded. Staphylococcus aureus was isolated most frequently (25% of total isolates; range, 69-408 isolates/yr), followed by Pseudomonas aeruginosa (13%; range, 40-202 isolates/yr), coagulase-negative staphylococci (9%; range, 2-188 isolates/yr), Enterobacter cloacae (8%; range, 22-128 isolates/yr), and Escherichia coli (6%; range, 19-91 isolates/yr). This rank order remained relatively consistent during the period of study. The emergence of methicillin-resistant S. aureus increased from 20% in 2004 to about 45% in 2009 to 2011. Susceptibility to vancomycin was still 100%. In comparing periods 2004 to 2007 and 2008 to 2011, P. aeruginosa showed increased susceptibility to cefepime (from 76% to 84%) and the aminoglycosides (from 68% to 81%), whereas susceptibility to piperacillin-tazobactam remained high (from 91% to 93%). E. cloacae demonstrated 90 to 100% susceptibility to aminoglycosides, cefepime, and imipenem. E. coli showed an increased rate of resistance to ceftazidime but was still susceptible to imipenem and amikacin. S. aureus and P. aeruginosa continue to be the most prevalent organisms cultured from our pediatric burn population. Almost half of the staphylococcal isolates were methicillin-resistant S. aureus. Despite widespread use of piperacillin-tazobactam, P. aeruginosa susceptibility remained high. Several classes of antimicrobials continued to demonstrate good to excellent activity against the majority of organisms cultured from the burn patients.


Assuntos
Antibacterianos/uso terapêutico , Queimaduras/microbiologia , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Criança , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Ohio , Estudos Retrospectivos
3.
J Burn Care Res ; 35(2): 143-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24445373

RESUMO

Existing practice guidelines designed to minimize invasive catheter infections and insertion-related complications in general intensive care unit patients are difficult to apply to the burn population. Burn-specific guidelines for optimal frequency for catheter exchange do not exist, and great variation exists among institutions. Previously, the authors' practice was to follow a new site insertion at 48 hours by an exchange over a guidewire, which was followed 48 hours later by a second guidewire exchange (48h group). As a performance improvement initiative, the authors attempted to determine whether there would be any advantage or disadvantage to extending these intervals to 72 hours (72h). All patients with centrally placed intravascular catheters from October 2007 to August 2008 were included in the 48h group, and all patients with catheters placed from September 2008 to December 2009 comprised the 72h group. Catheter infection rates were determined using the National Healthcare Safety Network definition for central line-associated bloodstream infections (CLABSIs) and calculated as CLABSIs/1000 catheter days. The two groups were not significantly different for age, sex, burn etiology, total burn size, or percent third-degree burn. There were 3.1 CLABSIs/1000 catheter days for the 48h group and 2.8 CLABSIs/1000 catheter days for the 72h group (NS). The authors conclude that increasing the central catheter change interval from 48 to 72 hours did not result in any increase in their CLABSI rate. Implementation of this change in practice is expected to decrease supply costs by $28,000 annually in addition to reducing clinical support services needed to perform these procedures.


Assuntos
Bacteriemia/prevenção & controle , Queimaduras/complicações , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central , Controle de Infecções/métodos , Melhoria de Qualidade , Bacteriemia/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Criança , Feminino , Humanos , Masculino , Ohio/epidemiologia , Fatores de Tempo
4.
J Burn Care Res ; 35(4): e217-23, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24043243

RESUMO

Amish burn wound ointment (ABO) contains honey, lanolin, oils, glycerin, bees wax, and other natural additives. Although there are many anecdotal reports that this ointment covered with a burdock leaf (BL) dressing promotes burn wound healing, little scientific testing of this treatment has occurred. The goal of this study was to evaluate in vitro some of the components of this treatment modality for antimicrobial and cytotoxic activities. The ABO was tested for sterility using standard microbiological techniques. Because of the semisolid, lipid-based nature of the salve, the at-use product could not be tested in bioassays. Samples of BL and the dry ingredients (DI) used in the ointment were provided by the Amish vendor. Aqueous extracts of the DI and of the BL were prepared and freeze dried. The freeze-dried extracts were reconstituted, filtered, and tested separately on keratinocyte and fibroblast cell cultures for cytotoxicity (growth inhibition assay) and against a panel of susceptible and resistant microbes for antimicrobial activity (Nathan's agar-well diffusion assay) in a series of concentrations (% wt/vol). Neither DI nor BL extracts demonstrated antimicrobial activity against any of organisms tested. The DI extract inhibited growth of both keratinocytes and fibroblasts at the 0.1% concentration. The 0.1 and 0.03% concentrations of the BL extract were cytotoxic to both keratinocytes and fibroblasts. Although tests for microbial growth from the at-use preparation of the ABO were negative, extracts of the DI and BL did not demonstrate any antimicrobial activity. Additionally, both extracts inhibited the growth of skin cells in vitro at higher concentrations. These results suggest caution in the use of ABO and BL dressings if there is more than a minimal risk of complications from the burn injury.


Assuntos
Anti-Infecciosos/farmacologia , Arctium , Bandagens , Fitoterapia , Queimaduras/terapia , Candida albicans/efeitos dos fármacos , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Glicerol , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Mel , Humanos , Queratinócitos/efeitos dos fármacos , Lanolina , Pomadas , Extratos Vegetais , Folhas de Planta , Ceras , Infecção dos Ferimentos/prevenção & controle
5.
J Burn Care Res ; 33(6): 741-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23147213

RESUMO

Burn-specific guidelines for optimal catheter rotation, catheter type, insertion methods, and catheter site care do not exist, and practices vary widely from one burn unit to another. The purpose of this study was to define current practices and identify areas of practice variation for future clinical investigation. An online survey was sent to the directors of 123 U.S. burn centers. The survey consisted of 23 questions related to specific practices in placement and maintenance of central venous catheters (CVCs), arterial catheters, and peripherally inserted central catheters (PICCs). The overall response rate was 36%; response rate from verified centers was 52%. Geographic representation was wide. CVC and arterial catheter replacement varied from every 3 days (24% of sites) to only for overt infection (24% of sites); 23% of sites did not use the femoral position for CVC placement. Nearly 60% of units used some kind of antiseptic catheter. Physicians inserted the majority of catheters, and 22% of sites used nonphysicians for at least some insertions. Ultrasound was routinely used by less than 50% of units. A wide variety of post-insertion dressing protocols were followed. PICCs were used in some critically injured patients in 37% of units; the majority of these users did not rotate PICCs. Thus, it can be surmised that wide practice variation exists among burn centers with regard to insertion and maintenance of invasive catheters. Areas with particular variability that would be appropriate targets of clinical investigation are line rotation protocols, catheter site care protocols, and use of PICCs in acute burns.


Assuntos
Unidades de Queimados , Cateterismo/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Cateterismo/normas , Humanos , Inquéritos e Questionários , Estados Unidos
6.
J Burn Care Res ; 32(1): e7-11, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21099435

RESUMO

Multidrug resistance in Gram-negative bacteria has led to a resurgence in colistin use. No pharmacokinetic data exist for burn patients. A 17-year-old boy suffered a 71% TBSA full-thickness burn with deep necrosis and compartment syndrome. He developed multidrug-resistant Acinetobacter baumannii burn wound sepsis/septic shock with acute renal failure requiring dialysis. The organism was resistant to all tested antibiotics except colistin. He received colistin 2.5 mg/kg every 24 hours. Peak and trough serum concentrations, area under the concentration-time curve, and elimination half-lives of colistin were 3.6 ± 1.0 µg/ml, 0.9 ± 0.5 µg/ml, 47.1 ± 14.4 mg · hr/L, and 12.3 ± 9.4 hours (mean ± SD), respectively. Serum levels were at or above the minimum inhibitory concentration for >90% of therapy. Nevertheless, salvage therapy with colistin proved futile as the patient developed acidosis, coagulopathy, and was vasopressor-dependent without any wound healing. He died on hospital day 52. Microbiologically, the serum levels of colistin were seemingly adequate, as repeat cultures were negative. Given the peak and trough levels of colistin relative to the minimum inhibitory concentration for the organism (0.5 µg/ml), it would seem that the dosage of 2.5 mg/kg administered every 24 hours for this patient on dialysis was appropriate. Patients on dialysis infected with an organism possessing a higher inhibitory concentration (≥1 µg/ml) should probably receive the same dosage every 12 hours to avoid subtherapeutic concentrations. Large-scale study of the pharmacokinetics of colistin in patients with burn injury is urgently needed.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/uso terapêutico , Queimaduras/complicações , Colistina/uso terapêutico , Choque Séptico/tratamento farmacológico , Infecções por Acinetobacter/etiologia , Acinetobacter baumannii/efeitos dos fármacos , Injúria Renal Aguda/etiologia , Adolescente , Farmacorresistência Bacteriana Múltipla , Evolução Fatal , Humanos , Masculino , Choque Séptico/microbiologia
7.
Burns ; 35(7): 949-55, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19501982

RESUMO

Antibiotic usage is essential for infection control but hastens emergence of antibiotic resistant microbes. In particular, Acinetobacter baumannii is an important pathogen because of its heightened ability to acquire drug resistance. The need for novel antibacterial agents led us to evaluate the sensitivity of drug-resistant bacteria to the antimicrobial activity of human beta defensin 4 (HBD-4). Clinical isolates of A. baumannii (N=14), Pseudomonas aeruginosa (N=15), and Staphylococcus aureus (N=20), including 10 methicillin-resistant (MRSA) isolates, were examined. All bacterial strains were susceptible to HBD-4 antimicrobial activity, with no correlation between antibiotic resistance and HBD-4 sensitivity. The results demonstrate that antibiotic resistant microorganisms, including MRSA, can be inhibited by HBD-4, which may represent an effective therapeutic agent for infections involving drug-resistant microorganisms.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Queimaduras/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , beta-Defensinas/farmacologia , Acinetobacter baumannii/isolamento & purificação , Avaliação de Medicamentos , Farmacorresistência Bacteriana Múltipla , Humanos , Resistência a Meticilina , Testes de Sensibilidade Microbiana/métodos , Pseudomonas aeruginosa/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Infecção dos Ferimentos/microbiologia
8.
Shock ; 31(2): 157-63, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18650781

RESUMO

A dysfunctional immune system is known to be part of the pathophysiology after burn trauma. However, reports that support this have used a variety of methods, with numerous variables, to induce thermal injury. We hypothesized that, all other parameters being equal, an injury infliction by a scald would yield different immunological responses than one inflicted by a flame. Here, we demonstrated that both burn methods produced a full-thickness burn, yet there was more of an increase in subdermal temperature, hematocrit, mortality, and serum IL-6 concentrations associated with the scald burn. On postinjury day 1, the scald-burned mice showed diminished lymphocyte numbers, interferon gamma production, and lymphocyte T-bet expression as compared with sham- and flame-burned mice. On postburn day 8, spleens from both sets of thermally injured animals showed an increase in proinflammatory myeloid cells as compared with sham-burned mice. Furthermore, the T-cell numbers, T-bet expression, and phenotype were changed such that interferon gamma production was higher in scald-burned mice than in sham- and flame-burned mice. Altogether, the data show that differential immunological phenotypes were observed depending on the thermal injury method used.


Assuntos
Queimaduras/imunologia , Queimaduras/terapia , Proteínas com Domínio T/biossíntese , Animais , Citocinas/metabolismo , Citometria de Fluxo , Hematócrito , Inflamação , Interferon gama/metabolismo , Interleucina-6/sangue , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Baço/citologia , Baço/metabolismo , Linfócitos T/metabolismo
9.
J Burn Care Res ; 30(1): 19-29, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19060725

RESUMO

An increasing number of bacteria are resistant to multiple systemic antibiotics. The purpose of this study was to determine if topical antimicrobials are still effective against multi-drug resistant organisms (MDROs). MDROs, including Acinetobacter, Pseudomonas, Klebsiella, Staphylococcus, and Enterococcus, were collected from four burn hospitals. The sensitivity of 47 MDROs to 11 commonly used topical agents (mafenide acetate, nystatin, mafenide + nystatin, silver nitrate, Dakin's, polymyxin B, neomycin, polymyxin + neomycin, silver sulfadiazine, bacitracin, silver sulfadiazine + bacitracin) was tested using the agar well diffusion assay and compared with the sensitivity of 27 non-MDROs of similar genera. Overall 88% of the tests of the non-MDROs showed susceptibility to the topicals compared with 80% for the MDROs (P < .05). Specific findings included: all of the gram-positive non-MDROs were sensitive to bacitracin compared with only 67% of the MDROs (P < .05); 74% of the non-MDROs were sensitive to neomycin vs 26% of the MDROs (P < .01). Even for the susceptible isolates, the zones of inhibition were smaller for the MDROs than for the non-MDROs (P < .002), indicating decreased susceptibility of the MDROs. Specifically, while the MDRO Acinetobacter were sensitive to most of the topicals, the zones of inhibition for silvadene, silvadene + bacitracin, neomycin, and neomycin + polymyxin were significantly smaller (P < .001) for the Acinetobacter MDROs than the non-MDROs. Although many topicals are still effective against some MDROs, MDROs are more resistant to topicals than are non-MDROs. Some treatment assumptions based historically on the efficacy of topical antimicrobial agents against non-MDROs need to be re-evaluated for MDROs.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Queimaduras/microbiologia , Infecção dos Ferimentos/tratamento farmacológico , Administração Tópica , Bactérias/isolamento & purificação , Queimaduras/complicações , Distribuição de Qui-Quadrado , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Infecção dos Ferimentos/microbiologia
10.
Clin Vaccine Immunol ; 15(4): 590-7, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18272666

RESUMO

The O antigen is both a major structural outer membrane component and the dominant epitope of most gram-negative bacteria. Pseudomonas aeruginosa 1244 produces a type IV pilus and covalently links an O-antigen repeating unit to each pilin monomer. Here we show that immunization of mice with pure pilin from strain 1244 by use of either the mouse respiratory model or the thermal injury model resulted in protection from challenge with a pilus-null O-antigen-producing 1244 mutant. These results provide evidence that the pilin glycan stimulates a protective response that targets the O antigen, suggesting that this system could be used as the basis for the development of a variety of bioconjugate vaccines protective against gram-negative bacteria.


Assuntos
Proteínas de Fímbrias/imunologia , Glicoconjugados/farmacologia , Antígenos O/imunologia , Infecções por Pseudomonas/imunologia , Vacinas contra Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Animais , Especificidade de Anticorpos , Ensaio de Imunoadsorção Enzimática , Proteínas de Fímbrias/administração & dosagem , Fímbrias Bacterianas/imunologia , Glicoconjugados/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos ICR , Polissacarídeos/imunologia , Polissacarídeos/farmacologia , Infecções por Pseudomonas/prevenção & controle , Vacinas contra Pseudomonas/farmacologia , Coelhos
11.
J Burn Care Res ; 29(1): 73-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18182900

RESUMO

Cultures of allograft sites on burn patients occasionally show microbes that were not previously cultured from that patient. Our purpose was to determine 1) if microbes on allograft sites could have been transferred to the burn patient from the allograft donor and 2) if microbial transfer is different if the allograft was fresh or frozen. All allografts were cultured by the skin bank after recovery (pre-antimicrobial) and after the skin had been in an antimicrobial solution (post-antimicrobial). These culture results were compared with the results of cultures taken at the hospital from the allograft sites of burn patients. All allograft recipients at the burn hospital during 2005 were included in this Institutional Review Board approved study. Sixty-one donors provided 143 allografts for 38 patients. From the 61 donors, 114 precultures were taken; 19.5% were positive for at least one organism. Only 6.8% of 118 post-antimicrobial cultures were positive. Of the 143 allografts on burn patients, 111 were used fresh and 32 had been cryopreserved. During dressing changes, 124 cultures were taken from sites that received fresh allograft and 27 from sites that received frozen; 54.8% of cultures from fresh allograft sites and 41.5% from frozen sites (not significant, chi) were positive for microbes, which were mostly the patient's own flora. None of the microbes isolated from the burn patient allograft sites matched organisms on the pre- or post-antimicrobial cultures from the donor allografts. Regardless of whether the allografts were fresh or frozen, no instances were identified in which donor microorganisms were transferred from a donor to a recipient.


Assuntos
Infecções Bacterianas/etiologia , Queimaduras/cirurgia , Sobrevivência de Enxerto , Transplante de Pele/efeitos adversos , Doadores de Tecidos , Transplante Homólogo/efeitos adversos , Infecções Bacterianas/transmissão , Humanos , Estudos Retrospectivos , Fatores de Risco , Pele/microbiologia
12.
J Burn Care Res ; 28(6): 776-90, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17925660

RESUMO

Because of their extensive wounds, burn patients are chronically exposed to inflammatory mediators. Thus, burn patients, by definition, already have "systemic inflammatory response syndrome." Current definitions for sepsis and infection have many criteria (fever, tachycardia, tachypnea, leukocytosis) that are routinely found in patients with extensive burns, making these current definitions less applicable to the burn population. Experts in burn care and research, all members of the American Burn Association, were asked to review the literature and prepare a potential definition on one topic related to sepsis or infection in burn patients. On January 20, 2007, the participants met in Tucson, Arizona to develop consensus for these definitions. After review of the definitions, a summary of the proceedings was prepared. The goal of the consensus conference was to develop and publish standardized definitions for sepsis and infection-related diagnoses in the burn population. Standardized definitions will improve the capability of performing more meaningful multicenter trials among burn centers.


Assuntos
Queimaduras/complicações , Infecções/diagnóstico , Sepse/diagnóstico , Queimaduras/microbiologia , Cateterismo Venoso Central/efeitos adversos , Humanos , Insuficiência de Múltiplos Órgãos/diagnóstico , Pneumonia/diagnóstico , Índice de Gravidade de Doença , Lesão por Inalação de Fumaça/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
13.
Proc Natl Acad Sci U S A ; 104(11): 4624-9, 2007 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-17360574

RESUMO

Surface-expressed bacterial polysaccharides are often immunodominant, protective antigens. However, these antigens are chemically and serologically highly heterogeneous, and conjugation to protein carriers is often necessary to enhance their immunogenicity. Here we show the efficacy of intranasal immunization of mice with attenuated Salmonella enterica serovar Typhimurium expressing the O antigen portion of Pseudomonas aeruginosa lipopolysaccharide. P. aeruginosa is an ideal model system because it can cause a myriad of localized and systemic infections. In particular, this bacterium is a leading cause of hospital-acquired pneumonia and is responsible for infections after burns and after eye injury. In addition, there are mouse models of infection that mimic the clinical manifestations of P. aeruginosa infections. Immunized mice were highly protected against infection, with long-lasting immunity to acute P. aeruginosa pneumonia, whereas mice immunized with Salmonella containing only the cloning vector or PBS were not. Prophylactic and therapeutic administration of sera from vaccinated animals protected naive mice. Intranasal vaccination also provided complete protection from infections after burns and reduced pathology after corneal abrasions. These results indicate that intranasal delivery of heterologously expressed polysaccharide antigens provides protection at distinct sites of infection. This approach for the expression and delivery of polysaccharide antigens as recombinant immunogens could be easily adapted to develop vaccines for many infectious agents, without the need for complicated purification and conjugation procedures.


Assuntos
Administração Intranasal , Polissacarídeos/administração & dosagem , Polissacarídeos/metabolismo , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/metabolismo , Animais , Líquido da Lavagem Broncoalveolar , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Antígenos O/metabolismo , Fagocitose , Pneumonia/prevenção & controle , Salmonella enterica/metabolismo
14.
J Burn Care Res ; 28(1): 127-32, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17211212

RESUMO

Defensins are cationic peptides of the innate host defense system with antimicrobial activity against many of the microorganisms commonly found in burn units. Beta defensins are variably expressed in the epithelia of skin and other organs. Human beta defensin 4 reportedly has antimicrobial activity against Pseudomonas aeruginosa and is not normally expressed in intact skin. Genetic modification was used to ectopically express human beta defensin 4 in cultured primary epidermal keratinocytes. Keratinocytes expressing human beta defensin 4 showed significantly elevated antimicrobial activity against clinically-isolated P. aeruginosa compared with controls. These results suggest that genetic modification of keratinocytes can increase their resistance to microbial contamination. Bioengineered skin replacements containing human beta defensin 4-modified keratinocytes may be useful for transplantation to contaminated burn wounds.


Assuntos
Queratinócitos/metabolismo , Queratinócitos/microbiologia , Pseudomonas aeruginosa/patogenicidade , beta-Defensinas/metabolismo , Adulto , Células Cultivadas , Feminino , Vetores Genéticos , Humanos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução Genética , beta-Defensinas/genética
15.
Nutr Clin Pract ; 21(6): 610-6, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17119167

RESUMO

BACKGROUND: Procedural changes for hospitalized patients must always balance safety with fiscal constraints. Microbiologic contamination of enteral feeding solutions has been previously associated with nosocomial infections. Formula manipulation and hang time contribute to microbial load, and there is considerable variation in hang time recommendations in the medical literature. With cost containment in mind, the purpose of this performance improvement study was to determine if an increase in hang time of a modular tube feeding product would increase microbial load or affect the nosocomial infection rate in pediatric burn patients. METHODS: This biphasic trial initially evaluated the microbial load of the feeding after delivery of two 4-hour aliquots into a container using the same delivery set (total hang time of 8 hours; number of tests = 20). Second, once this feeding procedure was deemed microbiologically safe, tube feedings were administered to patients, and both microbial load and nosocomial infection rate were monitored for 1 year. RESULTS: Contamination levels at the end of the 8-hour period using the same feeding set with 2 consecutive 4-hour feeding aliquots (number of tests = 38) were lower than standard recommendations. The hospital's nosocomial infection rate was not altered by this procedural change, and feeding-set expenses were reduced. CONCLUSIONS: The hang time of our enteral feeding administration set can be increased safely from 4 hours to 8 hours, with the tube feeding preparation added as two 4-hour aliquots without a significant change in microbial load or nosocomial infection rate, thus promoting simultaneous fiscal responsibility and patient safety.


Assuntos
Unidades de Queimados/normas , Nutrição Enteral/economia , Nutrição Enteral/normas , Microbiologia de Alimentos , Hospitais , Satisfação do Paciente , Unidades de Queimados/economia , Queimaduras , Infecção Hospitalar/prevenção & controle , Alimentos Formulados/microbiologia , Humanos , Guias de Prática Clínica como Assunto , Fatores de Tempo
16.
Am J Infect Control ; 34(5): 281-4, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16765206

RESUMO

BACKGROUND: Patients with tracheostomies carry a case for suctioning supplies. A returned case cultured positive for Staphylococcus aureus even after it had been cleaned with a disinfectant. The purposes of this study were to determine (1) the source of the S aureus and (2) how to provide a microbiologically safe case for the next patient. METHODS: Reviews of patient and environmental cultures plus pulsed-field gel electrophoresis (PFGE) were used to determine the source of the S aureus. Repeated wiping with various detergents/disinfectants did not remove the S aureus from the case, which could not be immersed for cleaning because of a chipboard component. We designed a case made of denim with a washable synthetic fiber to provide shape. The new cases were purposefully contaminated and laundered and then cultured. RESULTS: PFGE indicated that the S aureus was from the patient who had most recently used the case. Contamination of the denim case with the original S aureus, followed by laundering, resulted in a case that was free of the S aureus. These results were repeated for other pathogens. CONCLUSION: Commercially available cases for suction equipment can become contaminated with pathogens from the user and may be difficult to disinfect. By making the case out of washable materials, less expensive cases, which could be readily disinfected, resulted.


Assuntos
Desinfecção/métodos , Engenharia Sanitária/métodos , Staphylococcus aureus/isolamento & purificação , Sucção/instrumentação , Contaminação de Equipamentos , Desenho de Equipamento , Humanos
17.
Proc Natl Acad Sci U S A ; 103(8): 2839-44, 2006 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-16477007

RESUMO

The opportunistic pathogen Pseudomonas aeruginosa is responsible for systemic infections in immunocompromised individuals and chronic respiratory disease in patients with cystic fibrosis. Cyclic nucleotides are known to play a variety of roles in the regulation of virulence-related factors in pathogenic bacteria. A set of P. aeruginosa genes, encoding proteins that contain putative domains characteristic of diguanylate cyclases (DGCs) and phosphodiesterases (PDEs) that are responsible for the maintenance of cellular levels of the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) was identified in the annotated genomes of P. aeruginosa strains PAO1 and PA14. Although the majority of these genes are components of the P. aeruginosa core genome, several are located on presumptive horizontally acquired genomic islands. A comprehensive analysis of P. aeruginosa genes encoding the enzymes of c-di-GMP metabolism (DGC- and PDE-encoding genes) was carried out to analyze the function of c-di-GMP in two disease-related phenomena, cytotoxicity and biofilm formation. Analysis of the phenotypes of DGC and PDE mutants and overexpressing clones revealed that certain virulence-associated traits are controlled by multiple DGCs and PDEs through alterations in c-di-GMP levels. A set of mutants in selected DGC- and PDE-encoding genes exhibited attenuated virulence in a mouse infection model. Given that insertions in different DGC and PDE genes result in distinct phenotypes, it seems likely that the formation or degradation of c-di-GMP by these enzymes is in highly localized and intimately linked to particular targets of c-di-GMP action.


Assuntos
Proteínas de Bactérias/metabolismo , GMP Cíclico/análogos & derivados , Diester Fosfórico Hidrolases/metabolismo , Fósforo-Oxigênio Liases/metabolismo , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/patogenicidade , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , GMP Cíclico/metabolismo , GMP Cíclico/fisiologia , Proteínas de Escherichia coli , Genes Bacterianos , Genoma Bacteriano , Genômica , Mutação , Fenótipo , Diester Fosfórico Hidrolases/química , Diester Fosfórico Hidrolases/genética , Fósforo-Oxigênio Liases/química , Fósforo-Oxigênio Liases/genética , Estrutura Terciária de Proteína , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/fisiologia , Virulência
18.
Infect Immun ; 73(7): 4395-8, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15972536

RESUMO

In this study, we tested the contribution of flagellar motility, flagellin structure, and its glycosylation in Pseudomonas aeruginosa using genetically defined flagellar mutants. All mutants and their parent strains were tested in a burned-mouse model of infection. Motility and glycosylation of the flagellum appear to be important determinants of flagellar-mediated virulence in this model. This is the first report where genetically defined flagellar variants of P. aeruginosa were tested in the burned-mouse model of infection.


Assuntos
Queimaduras/complicações , Flagelina/metabolismo , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa/patogenicidade , Infecção dos Ferimentos/etiologia , Animais , Flagelina/química , Glicosilação , Dose Letal Mediana , Camundongos , Movimento
19.
J Burn Care Rehabil ; 26(3): 238-46, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15879745

RESUMO

Cultured skin substitutes (CSS) have become a useful adjunctive treatment for closure of burn wounds, but CSS are avascular and remain susceptible to microbial destruction longer than split-thickness skin grafts. Irrigation of CSS grafted to burn wounds with a topical antimicrobial solution (TAS) has been shown to promote engraftment of CSS, but TAS usage has potential limitations. Acticoat Burn Dressing (Acticoat; Westaim Biomedical, Exeter, NH) is a silver-coated barrier dressing reported to exhibit antimicrobial activity and to reduce infection in partial-thickness and full-thickness wounds. This study evaluated the cytotoxicity of Acticoat with CSS and the efficacy of Acticoat for the management of microbial contamination in CSS grafted to full-thickness wounds in athymic mice. The cytotoxicity of Acticoat was assessed in preliminary studies after 1 week of exposure to CSS during in vitro maturation or healing on wounds in athymic mice. Histologies were analyzed and cellular viability in the CSS was determined by MTT conversion on days 0, 1, and 7 of Acticoat exposure. At 1, 2, 3, and 4 weeks after grafting, wounds were traced, and areas of healing CSS were calculated by image analysis. At 4 weeks, wound biopsies were evaluated and scored for engraftment of human cells. In a subsequent study, wounds were inoculated with strain SBI-N of Pseudomonas aeruginosa at 1 x 10(5) cfu/wound before the application of CSS or inoculated onto the surface of Acticoat. At 4 weeks, swab cultures were collected from the surface of CSS and scored for the presence of SBI-N. Statistical significance was accepted at the 95% confidence level (P <.05). The data show that exposure in vitro of CSS to Acticoat was cytotoxic within 1 day, but 1 week of exposure in vivo did not injure CSS or inhibit wound healing. Contaminated wounds treated with Acticoat healed similarly to control treatments, with comparable rates of engraftment, and detection of SBI-N on the surface of only one graft. No SBI-N was detected on CSS after inoculation onto the surface of Acticoat. These results suggest that Acticoat may be suitable as a protective dressing to reduce environmental contamination of CSS, if used in conjunction with additional antimicrobials to control organisms present in the wound.


Assuntos
Queimaduras/cirurgia , Poliésteres , Polietilenos , Pele Artificial , Cicatrização , Infecção dos Ferimentos/prevenção & controle , Animais , Anti-Infecciosos Locais/farmacologia , Queimaduras/microbiologia , Queimaduras/patologia , Sobrevivência Celular , Células Cultivadas , Fibroblastos/fisiologia , Humanos , Queratinócitos/fisiologia , Camundongos , Camundongos Nus , Infecções por Pseudomonas/terapia , Pseudomonas aeruginosa , Sulfadiazina de Prata/farmacologia
20.
Am J Infect Control ; 33(4): 233-7, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15877019

RESUMO

Computer hardware has been implicated as a potential reservoir for infectious agents. Leaders of a 22-hospital system, which spans North America and serves pediatric patients with orthopedic or severe burns, sought to develop recommendations for the cleaning and disinfection of computer hardware within its myriad patient care venues. A task force comprising representatives from infection control, medical affairs, information services, and outcomes management departments was formed. Following a review of the literature and of procedures within the 22 hospitals, criteria for cleaning and disinfection were established and recommendations made. The recommendations are consistent with general environmental infection control cleaning and disinfection guidelines, yet flexible enough to be applicable to the different locales, different computer and cleaning products available, and different patient populations served within this large hospital system.


Assuntos
Computadores/normas , Desinfecção/métodos , Contaminação de Equipamentos/prevenção & controle , Controle de Infecções/métodos , Sistemas Multi-Institucionais
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