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1.
Medicine (Baltimore) ; 98(38): e17185, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567961

RESUMO

Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures.


Assuntos
Toxinas Bacterianas/metabolismo , Exotoxinas/metabolismo , Leucocidinas/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/metabolismo , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Pneumonia Necrosante/microbiologia , Estudos Retrospectivos , Infecções dos Tecidos Moles/microbiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/patologia , Infecções Estafilocócicas/terapia
3.
Medicine (Baltimore) ; 98(27): e16015, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277095

RESUMO

The aim of this study was to describe the clinical features of bone and joint infections (BJI) due to Panton-Valentine Leukocidin producing (PVL+) Staphylococcus aureus (SA) in French Guiana.A multicenter study that consists of a retrospective charts review of children admitted for PVL+ S. aureus BJI between January 2010 and December 2015.Six patients with SA-PVL BJI were identified during the study period: 2 osteomyelitis, 1 septic arthritis, and 3 disseminated BJI. The median age was 11 years old (4-14 years), and fever lasted for 3.2 days (2-5 days) before diagnosis. An open skin wound preceded the BJI in 5/6 patients. One patient presented with a septic thrombophlebitis of the femoral-popliteal vein on admission. Methicillin-susceptible Staphylococcus aureus (MSSA) were identified for all patients. Three patients had complications: 2 cases of necrotizing pneumonia and 2 pericarditis, with 1 death caused by cardiac tamponade.SA-PVL BJI was not frequent. Strains were susceptible to methicillin, but responsible of severe BJI. Early diagnosis and a multidisciplinary management of these infections are essential to prevent further complications.


Assuntos
Artrite Infecciosa/microbiologia , Toxinas Bacterianas/análise , Exotoxinas/análise , Leucocidinas/análise , Osteomielite/microbiologia , Infecções Estafilocócicas/microbiologia , Adolescente , Antibacterianos/uso terapêutico , Artrite Infecciosa/terapia , Proteína C-Reativa/análise , Criança , Pré-Escolar , Guiana Francesa , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Osteomielite/terapia , Estudos Retrospectivos , Infecções Estafilocócicas/terapia
4.
Appl Microbiol Biotechnol ; 103(11): 4279-4289, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30997551

RESUMO

Bacteriophage has become an attractive alternative for the treatment of antibiotic-resistant Staphylococcus aureus. For the success of phage therapy, phage host range is an important criterion when considering a candidate phage. Most reviews of S. aureus (SA) phages have focused on their impact on host evolution, especially their contribution to the spread of virulence genes and pathogenesis factors. The potential therapeutic use of SA phages, especially detailed characterizations of host recognition mechanisms, has not been extensively reviewed so far. In this report, we provide updates on the study of SA phages, focusing on host recognition mechanisms with the recent discovery of phage receptor-binding proteins (RBPs) and the possible applications of SA phages in phage therapy.


Assuntos
Especificidade de Hospedeiro , Terapia por Fagos/métodos , Infecções Estafilocócicas/terapia , Fagos de Staphylococcus/crescimento & desenvolvimento , Staphylococcus aureus/virologia
5.
South Med J ; 112(4): 238-243, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30943544

RESUMO

OBJECTIVE: To determine whether there are differences in the outcomes of native joint septic arthritis (SA) in adults, based on medical versus surgical management. METHODS: A 10-year retrospective single-center study was conducted of patients admitted to a tertiary care hospital between January 1, 2006 and December 31, 2015 with a diagnosis of SA to compare outcomes based on the management approach taken: medical (bedside closed-needle joint aspiration) versus surgical (arthrotomy/arthroscopy). Evaluated outcomes included joint recovery, time to recovery, length of stay, disposition to home versus rehabilitation unit, recurrence of SA in the same joint, and mortality. RESULTS: Of 118 confirmed cases of SA, 48 were in prosthetic joints and 70 were in native joints, and 61 met our inclusion criteria. Forty-one (67%) patients received surgery, and 20 (33%) received closed-needle aspiration. There was no statistically significant difference in long-term outcomes between the two groups at 12 months. Patients managed medically were more likely to experience full recovery at 3 months and were less likely to need short-term rehabilitation. CONCLUSIONS: Medical management with closed-needle aspiration may be an adequate approach to the treatment of native joint infections.


Assuntos
Antibacterianos/uso terapêutico , Artrite Infecciosa/terapia , Artrocentese/métodos , Artroscopia/métodos , Drenagem/métodos , Infecções Estafilocócicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Articulação do Tornozelo , Artrite Infecciosa/fisiopatologia , Candidíase/terapia , Articulação do Cotovelo , Feminino , Infecções por Bactérias Gram-Negativas/terapia , Infecções por Bactérias Gram-Positivas/terapia , Articulação do Quadril , Hospitalização , Humanos , Articulação do Joelho , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Estudos Retrospectivos , Articulação do Ombro , Articulação Esternoclavicular , Infecções Estreptocócicas/terapia , Centros de Atenção Terciária , Articulação do Punho
6.
ACS Appl Mater Interfaces ; 11(13): 12298-12307, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30855125

RESUMO

Craniotomy involves the removal of a skull fragment to access the brain, such as during tumor or epilepsy surgery, which is immediately replaced intraoperatively. The infection incidence after craniotomy ranges from 0.8 to 3%, with approximately half caused by Staphylococcus aureus ( S. aureus). To mitigate infectious complications following craniotomy, we engineered a three-dimensional (3D) bioprinted bone scaffold to harness the potent antibacterial activity of macrophages (MΦs) together with antibiotics using a mouse S. aureus craniotomy-associated biofilm model that establishes a persistent infection on the bone flap, subcutaneous galea, and brain. The 3D scaffold contained rifampin and daptomycin printed in a composite slurry, with viable MΦs incorporated into a hydrogel-based bioink, which was assessed for both the treatment and prevention of craniotomy-associated infections in the mouse model. For the treatment paradigm, the bone flap was removed at day 7 post infection after a mature biofilm had formed and was replaced with a 3D printed antibiotic scaffold, with or without MΦ incorporation. Bacterial burdens in the galea and brain were reduced by at least 100-fold at early time points, which was potentiated by bioprinting viable MΦs into the 3D antibiotic scaffold. We also examined a prevention paradigm, where the scaffolds were placed at the time of surgery and challenged with S. aureus one day later at the surgical site. Interestingly, unlike the treatment paradigm, the incorporation of viable MΦs into the 3D antibiotic scaffold did not enhance bacterial clearance compared to that of antibiotic alone. With further refinement, our 3D bioprinted scaffold represents a potential treatment modality, as it delivers therapeutic antibiotic levels more rapidly than systemic administration, based on its proximity to the infection site. In addition, the incorporation of viable MΦs into the 3D scaffold is an important advance, which demonstrated an improved therapeutic benefit for the treatment of established biofilms that represent the most clinically challenging scenario.


Assuntos
Antibacterianos , Craniotomia , Macrófagos , Impressão Tridimensional , Infecções Estafilocócicas , Staphylococcus aureus/fisiologia , Infecção dos Ferimentos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Linhagem Celular , Feminino , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/patologia , Infecções Estafilocócicas/terapia , Infecção dos Ferimentos/metabolismo , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia , Infecção dos Ferimentos/terapia
7.
Biomed Res Int ; 2019: 3756939, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30891455

RESUMO

Background: The incidence of septic arthritis of the shoulder joint is increasing as the population ages. The prevalence of shoulder infection is also increasing because of the growing use of arthroscopy and expansion of procedures in the shoulder. However, cultures do not always identify all microorganisms, even in symptomatic patients. The incidence of negative cultures ranges from 0% to 25%. Few studies have reported clinical features and treatment outcomes of culture-negative shoulder infections. This cohort study addresses culture-negative shoulder joint infections in nonarthroplasty patients. This study aimed to compare clinical characteristics and treatment outcomes of patients with culture-negative results to those with culture-positive results. Our hypothesis was that culture-negative infections would have more favorable outcomes than culture-positive infections. Methods: We retrospectively reviewed data of 36 patients (17 culture-negative and 19 culture-positive) with shoulder infections between June 2004 and March 2015. The minimum follow-up duration was 1.2 years (mean, 5 ± 3.8 years; range, 1.2-11 years). We assessed preoperative demographic data and characteristics, laboratory markers, imaging and functional scores, intraoperative findings, and postoperative findings of both groups. Results: Culture-negative patients (17/36, 47.2%) had a significantly lower occurrence of repeated surgical debridement (culture-negative vs. culture-positive: 1.2 ± 0.4 vs. 2.4 ± 1.7, p = 0.002) without osteomyelitis. In the multiple logistic regression analysis, the presence of osteomyelitis [odds ratio (OR) = 9.7, 95% confidence interval (CI): 1.0-91.8, p=0.04)] and the number of surgical debridements (OR = 5.3, 95% CI: 1.3-21.6, p=0.02) were significantly associated with culture-positive infections. Conclusions: Culture-negative infections without osteomyelitis are less severe than culture-positive infections. Culture-negative infections can be controlled more easily and are not necessarily a negative prognostic factor for shoulder joint infections.


Assuntos
Articulação do Ombro/microbiologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroscopia , Feminino , Humanos , Inflamação/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Manguito Rotador/cirurgia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/patologia , Articulação do Ombro/cirurgia , Resultado do Tratamento
8.
Int J Artif Organs ; 42(5): 258-262, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30819024

RESUMO

Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infections are rare but associated with very high mortality rates. We report the case of a 14-year-old patient with Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infection and Influenza B pneumonia requiring veno-arterial extra-corporeal membrane oxygenator for refractory shock. In the absence of response to conventional therapy, we have inserted a Cytosorb® cartridge within the extra-corporeal membrane oxygenator circuit. A spectacular decrease in vasopressor requirements followed. Since clindamycin, a key component of Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus treatment, might be removed by Cytosorb® hemoadsorption, we have performed serial plasma concentrations measurements of the drug. Based on these measurements, we were able to develop a pharmacokinetic model incorporating variable plasma clearance. Patient's exposure was estimated before, during and after Cytosorb® hemoadsorption. According to this model, Cytosorb® hemoadsorption did not seem to result in significant clindamycin removal. Cytosorb® hemoadsorption during Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infection appears safe and feasible and no adaptation of clindamycin dosage seems necessary.


Assuntos
Clindamicina , Oxigenação por Membrana Extracorpórea/métodos , Hemoperfusão/métodos , Taxa de Depuração Metabólica , Desintoxicação por Sorção/métodos , Infecções Estafilocócicas , Adolescente , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Clindamicina/administração & dosagem , Clindamicina/farmacocinética , Exotoxinas/sangue , Humanos , Leucocidinas/sangue , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/fisiopatologia , Infecções Estafilocócicas/terapia , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidade
10.
Clin Orthop Relat Res ; 477(1): 116-126, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30794234

RESUMO

BACKGROUND: Irrigation and débridement are frequently utilized in the management of surgical infections, but even with aggressive débridement, it is difficult to remove all the suture material from the tissues and retained suture material may harbor bacteria and/or biofilm. The degree to which barbed or braided sutures may differentially influence the risk of infection has not been defined in a well-controlled animal model. QUESTIONS/PURPOSES: We compared braided and barbed monofilament sutures after irrigation of an infected mouse air pouch model to determine whether the suture type influenced the effectiveness of the irrigation. After irrigation of infected pouches, sutures were compared for (1) bacterial adherence and bacterial retention; (2) qualitative and quantitative pouch thickness and cellular density; and (3) quantitative biofilm formation. METHODS: Soft tissue air pouches were created on the backs of 60 female, mature 10-week-old BALB/cJ mice by sequentially introducing air into the subcutaneous tissue and allowing the pouch to mature. The pouches were inoculated with Staphylococcus aureus and braided or barbed monofilament sutures were implanted. Pouch irrigation was performed Day 7 after suture implantation. Suture segments were collected before and after irrigation. After euthanasia on Day 14, pouch tissues with residual suture segments were collected for analysis: microbiologic analysis done using optical density as a measure of the concentration of bacteria in the culture (the larger concentration indicates higher number of bacteria) and histologic evaluation of the pouch tissues were semiquantitative, whereas environmental scanning electron microscopy (ESEM) and confocal analyses of the biofilm and bacteria on the sutures were qualitative. RESULTS: Histologic evaluation of pouch tissue showed all groups had inflammatory responses. Quantitatively microbiology showed no difference in bacterial number calculated from the optical density (OD) values between the two suture materials at any time point in the irrigation group. In the no-irrigation group, for the Day 7 time point, mean (± SD) OD was greater in the barbed than the OD in the braided sutures (0.52 ± 0.12 versus 0.37 ± 0.16, mean difference 0.43 [95% confidence interval, 0.08-0.13]; p = 0.007). Qualitatively, ESEM showed more bacterial retention by braided sutures before and after irrigation. Confocal imaging of the sutures demonstrated penetration of biofilm into the interstices of braided sutures and less adhesion in barbed monofilament sutures. The quantification of the biomass showed no differences between groups at all time points (before-irrigation biomass was 11.2 ± 9.3 for braided versus 5.2 ± 4.7 for barbed sutures, p = 0.196; and after-irrigation biomass was 7.2 ± 7.5 for braided versus 3.3 ± 4.3 for barbed suture, p = 0.259). CONCLUSIONS: All sutures can retain bacteria and biofilm, but it is rarely possible to remove all suture material at the time of irrigation to treat infection. After an irrigation procedure, qualitatively braided sutures appeared to harbor more bacteria and to retain more biofilm than barbed monofilaments. CLINICAL RELEVANCE: When saline irrigation was used to simulate infection treatment in an infected mouse air pouch model, bacteria/biofilm was not completely eliminated from either braided or barbed monofilament sutures. The irrigation appeared to clear more bacteria and biofilm from the monofilament despite having barbs. Unfortunately, current technologies do not allow direct quantitative comparisons of biofilm retention. Clinicians should be aware that in the face of infection, any retained sutures may harbor bacteria despite irrigation.


Assuntos
Biofilmes/crescimento & desenvolvimento , Infecções Estafilocócicas/terapia , Staphylococcus aureus/crescimento & desenvolvimento , Infecção da Ferida Cirúrgica/terapia , Técnicas de Sutura/efeitos adversos , Técnicas de Sutura/instrumentação , Suturas/microbiologia , Irrigação Terapêutica , Animais , Aderência Bacteriana , Modelos Animais de Doenças , Desenho de Equipamento , Feminino , Camundongos Endogâmicos C57BL , Microscopia Confocal , Microscopia Eletrônica de Varredura , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/ultraestrutura , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/microbiologia , Fatores de Tempo
11.
PLoS One ; 14(1): e0209390, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30650088

RESUMO

Phage therapy is drawing more interest as antibiotic resistance becomes an ever more serious threat to public health. Bacterial biofilms represent a major obstacle in the fight against bacterial infections as they are inherently refractory to many types of antibiotics. Treating biofilms with phage has shown promise in a handful of experimental and case studies. However, quantification of the effect of phage combined with antibiotics is needed to pave the way for larger clinical trials. Here we explore the effect of using phage in combination with a total of nine antibiotics, applied simultaneously or as a pretreatment before antibiotics are applied to in vitro biofilms of Staphylococcus aureus. Most antibiotics alone were ineffective at low concentration (2×MIC), but the addition of phage to treatment regimens led to substantial improvements in efficacy. At high concentration (10×MIC), antibiotics alone were effective, and in most cases the addition of phage to treatment regimens did not improve efficacy. Using phage with rifampin was also very effective at reducing the outgrowth of resistant strains during the course of treatment.


Assuntos
Antibacterianos/administração & dosagem , Biofilmes/efeitos dos fármacos , Terapia por Fagos , Staphylococcus aureus/efeitos dos fármacos , Bacteriófagos/ultraestrutura , Biofilmes/crescimento & desenvolvimento , Terapia Combinada , Farmacorresistência Bacteriana , Humanos , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Infecções Estafilocócicas/terapia , Staphylococcus aureus/fisiologia
13.
BMC Infect Dis ; 19(1): 58, 2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30654745

RESUMO

BACKGROUND: Iliopsoas abscess is a collection of pus in the iliopsoas muscle compartment. It can be primary or secondary in origin. Primary iliopsoas abscess occurs as a result of hematogenous or lymphatic seeding from a distant site. This is commonly associated with a chronic immunocompromised state and tends to occur in children and young adults. Secondary iliopsoas abscess occurs as a result of the direct spread of infection to the psoas muscle from an adjacent structure, and this may be associated with trauma and instrumentation in the inguinal region, lumbar spine, or hip region. The incidence of iliopsoas abscess is rare and often the diagnosis is delayed because of non-specific presenting symptoms. CASE PRESENTATION: We describe a patient with iliopsoas abscess who presented to the Emergency Department at X Hospital on three separate occasions with non-specific symptoms of thigh pain and fever before finally being admitted for treatment. This case illustrates how the diagnosis can be delayed due to its atypical presentation. Hence, highlighting the need for clinicians to have a high index of clinical suspicion for iliopsoas abscess in patients presenting with thigh pain and fever. CONCLUSION: The classic triad of fever, flank pain, and hip movement limitation is presented in only 30% of patients with iliopsoas abscess. Clinicians should consider iliopsoas abscess as a differential diagnosis in patients presenting with fever and thigh pain. The rare condition with the varied clinical presentation means that cross-sectional imaging should be considered early to reduce the risk of fulminant sepsis.


Assuntos
Mialgia/diagnóstico , Abscesso do Psoas/diagnóstico , Infecções Estafilocócicas/diagnóstico , Adulto , Cloxacilina/uso terapêutico , Diagnóstico Diferencial , Drenagem , Humanos , Masculino , Mialgia/etiologia , Mialgia/terapia , Abscesso do Psoas/complicações , Abscesso do Psoas/terapia , Infecções Estafilocócicas/terapia , Coxa da Perna
14.
Viruses ; 11(1)2019 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-30669652

RESUMO

Bacteriophages, viruses that only kill specific bacteria, are receiving substantial attention as nontraditional antibacterial agents that may help alleviate the growing antibiotic resistance problem in medicine. We describe the design and preclinical development of AB-SA01, a fixed-composition bacteriophage product intended to treat Staphylococcus aureus infections. AB-SA01 contains three naturally occurring, obligately lytic myoviruses related to Staphylococcus phage K. AB-SA01 component phages have been sequenced and contain no identifiable bacterial virulence or antibiotic resistance genes. In vitro, AB-SA01 killed 94.5% of 401 clinical Staphylococcus aureus isolates, including methicillin-resistant and vancomycin-intermediate ones for a total of 95% of the 205 known multidrug-resistant isolates. The spontaneous frequency of resistance to AB-SA01 was ≤3 × 10-9, and resistance emerging to one component phage could be complemented by the activity of another component phage. In both neutropenic and immunocompetent mouse models of acute pneumonia, AB-SA01 reduced lung S. aureus populations equivalently to vancomycin. Overall, the inherent characteristics of AB-SA01 component phages meet regulatory and generally accepted criteria for human use, and the preclinical data presented here have supported production under good manufacturing practices and phase 1 clinical studies with AB-SA01.


Assuntos
Staphylococcus aureus Resistente à Meticilina/virologia , Myoviridae/fisiologia , Terapia por Fagos , Infecções Estafilocócicas/terapia , Fagos de Staphylococcus/fisiologia , Animais , Feminino , Genoma Viral , Camundongos , Myoviridae/genética , Fagos de Staphylococcus/genética
15.
Mater Sci Eng C Mater Biol Appl ; 97: 84-95, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30678975

RESUMO

The purpose of the present work was to evaluate in vivo different antimicrobial therapies to eradicate osteomyelitis created in the femoral head of New Zealand rabbits. Five phosphate-based cements were evaluated: calcium phosphate cements (CPC) and calcium phosphate foams (CPF), both in their pristine form and loaded with doxycycline hyclate, and an intrinsic antimicrobial magnesium phosphate cement (MPC; not loaded with an antibiotic). The cements were implanted in a bone previously infected with Staphylococcus aureus to discern the effects of the type of antibiotic administration (systemic vs. local), porosity (microporosity, i.e. <5 µm vs. macroporosity, i.e. >5 µm) and type of antimicrobial mechanism (release of antibiotic vs. intrinsic antimicrobial activity) on the improvement of the health state of the infected animals. A new method was developed, with a more comprehensive composite score that integrates 5 parameters of bone infection, 4 parameters of bone structural integrity and 4 parameters of bone regeneration. This method was used to evaluate the health state of the infected animals, both before and after osteomyelitis treatment. The results showed that the composite score allows to discern statistically significant differences between treatments that individual evaluations were not able to identify. Despite none of the therapies completely eradicated the infection, it was observed that macroporous materials (CPF and CPFd, the latter loaded with doxycycline hyclate) and intrinsic antimicrobial MPC allowed a better containment of the osteomyelitis. This study provides novel insights to understand the effect of different antimicrobial therapies in vivo, and a promising comprehensive methodology to evaluate the health state of the animals was developed. We expect that the implementation of such methodology could improve the criteria to select a proper antimicrobial therapy.


Assuntos
Antibacterianos/farmacologia , Cimentos para Ossos/farmacologia , Osteomielite/terapia , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Cimentos para Ossos/química , Doenças Ósseas Infecciosas/tratamento farmacológico , Doenças Ósseas Infecciosas/terapia , Regeneração Óssea/efeitos dos fármacos , Fosfatos de Cálcio/química , Doxiciclina/administração & dosagem , Doxiciclina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Implantes de Medicamento/química , Implantes de Medicamento/farmacologia , Liberação Controlada de Fármacos , Feminino , Fêmur/diagnóstico por imagem , Fêmur/patologia , Osteomielite/tratamento farmacológico , Porosidade , Coelhos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/terapia , Resultado do Tratamento , Substâncias Viscoelásticas/química
18.
J Photochem Photobiol B ; 191: 107-115, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30599381

RESUMO

Staphylococcus aureus is one of the major microorganisms that cause human diseases, leading from mild skin infections to serious diseases. With the use of semi-synthetic penicillins, methicillin-resistant strains called Methicillin-resistant Staphylococcus aureus (MRSA) have emerged, whose resistance pattern extends to other beta-lactam antibiotics. It has already been shown that photodynamic therapy is capable of inactivating MRSA as the laser excites the photosensitizer responsible for transferring its electrons to the molecular oxygen, generating extremely reactive molecules, such as singlet oxygen, being these reactive components the chemicals that promote the bacterial clearance. Thus, the research aiming at the development of new photosensitizers becomes important, especially to increase the amount of therapeutic resources available for the treatment of persistent infections related to this bacterium. In this context, Myrciaria cauliflora is a plant that has antimicrobial action and there are no reports of the use of its crude extract as a photosensitizer in antimicrobial photodynamic therapy. In that way, this work conveys an innovative way of the use of M. cauliflora extract as a photosensitizer, comprising its use as an antimicrobial agent when activated by light, against S. aureus. In vitro tests were performed where it was observed that after the photoactivation with blue LED light, the extract presented an augment in its antimicrobial activity, together with production of singlet oxygen. In the model of intradermal infection in Balb/c mice, a reduction in bacterial load was also detected, with raised expression of TNF-α, IL-17A, and MPO. Here, we demonstrate that the extract of M. cauliflora has photosensitizing action, promoting the production of singlet oxygen, besides IL-17A, TNF-α, and MPO.


Assuntos
Myrtaceae/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Infecções Estafilocócicas/terapia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Carga Bacteriana/efeitos dos fármacos , Citocinas/sangue , Citocinas/efeitos dos fármacos , Humanos , Staphylococcus aureus Resistente à Meticilina , Camundongos , Camundongos Endogâmicos BALB C , Projetos Piloto , Extratos Vegetais/química , Oxigênio Singlete/metabolismo
19.
J Wound Ostomy Continence Nurs ; 46(1): 25-29, 2019 Jan/Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30608337

RESUMO

PURPOSE: This study was conducted to evaluate the antimicrobial effects of medicinal maggots of Lucilia sericata on Staphylococcus aureus and Pseudomonas aeruginosa on diabetic foot ulcers (DFUs). DESIGN: Randomized controlled trial. SUBJECTS AND SETTING: The sample comprised 50 adult patients from the clinic of the Academic Center for Education, Culture and Research of Tehran University of Medical Sciences, Iran. All participants who had at least 1 DFU present for at least 12 weeks, an arterial brachial index value of more than 0.6, and a hemoglobin A1c value of less than 8% were included in this study. METHODS: Subjects were randomly selected for the maggot-treated (treatment) or conventional treatment (control) group. Conventional treatments such as antibiotic therapy, debridement, and offloading were done for both groups, but maggot therapy (MT) was added to the protocol of the treatment group. Bacterial burden was monitored and compared for both groups using cultures collected using swab technique. Wound secretions were measured and compared in both groups. RESULTS: The number of infected cases with S aureus in the treatment group was significantly reduced after 48 hours in comparison with the control group (P = .047). The number of infected cases with P aeruginosa was significantly reduced after 96 hours (P = .002). We also found that wound secretions in the treatment group were significantly higher than in the control group (P < .00). CONCLUSIONS: Our findings indicate that MT is a safe and efficacious treatment of DFUs.


Assuntos
Desbridamento/normas , Pé Diabético/terapia , Larva , Infecções por Pseudomonas/terapia , Infecções Estafilocócicas/terapia , Idoso , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Desbridamento/métodos , Desbridamento/estatística & dados numéricos , Diabetes Mellitus , Pé Diabético/epidemiologia , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Estatísticas não Paramétricas , Cicatrização/fisiologia
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