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1.
Injury ; 54 Suppl 6: 110650, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36858895

RESUMO

INTRODUCTION: The objective of this study is to assess bone union, infection control, and reoperation rates in a series of patients with infected femoral or tibial nonunion treated with antibiotic-cement-coated rigid nails and to compare the results obtained with custom-made nails versus commercial nails. METHODS: We retrospectively analyzed a series of consecutive patients with infected nonunion of the femur or the tibia treated with antibiotic-cement-coated rigid nails between January 2010 and 2020. We assessed patients' distinctive characteristics, initial injury, type of nail used (custom-made nail with vancomycin or commercial nail with gentamicin), success rate (bone union + infection control), reoperation rate, and failure rate. Comparative analyses were conducted between reoperated and non-reoperated patients regarding the type of nail used. A multivariate regression analysis was performed to assess the risk variables that impacted reoperation rates. RESULTS: We included 54 patients with 22 (40.74%) infected femoral nonunions and 32 (59.25%) tibial nonunions, who were treated with 38 (70.37%) custom-made antibiotic-cement coated nails and 16 (29.62%) commercial nails. Bone union and infection control were achieved in 51 (94.44%) cases. The reoperation rate was 40.74% (n = 22), and the failure rate was 5.55% (n = 3). The use of custom-made nails was associated with a higher risk of reoperation (Odds Ratio 4.71; 95% Confidence Interval 1.10 - 20.17; p = 0.036). CONCLUSION: Antibiotic-cement-coated nails reached a 94.44% success rate. Nails manufactured in the OR coated with vancomycin cement were associated with a higher risk of reoperation than commercial nails loaded with gentamicin cement. LEVEL OF EVIDENCE: III comparative, observational, non-randomized.


Assuntos
Antibacterianos , Doenças Ósseas Infecciosas , Pinos Ortopédicos , Fraturas do Fêmur , Fraturas não Consolidadas , Fraturas da Tíbia , Humanos , Antibacterianos/administração & dosagem , Cimentos Ósseos , Fêmur/lesões , Fêmur/cirurgia , Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Gentamicinas/administração & dosagem , Reoperação , Estudos Retrospectivos , Tíbia/lesões , Tíbia/cirurgia , Fraturas da Tíbia/complicações , Fraturas da Tíbia/tratamento farmacológico , Fraturas da Tíbia/cirurgia , Resultado do Tratamento , Vancomicina/administração & dosagem , Fraturas não Consolidadas/tratamento farmacológico , Fraturas não Consolidadas/etiologia , Fraturas não Consolidadas/cirurgia , Materiais Revestidos Biocompatíveis , Fraturas do Fêmur/complicações , Fraturas do Fêmur/tratamento farmacológico , Fraturas do Fêmur/cirurgia , Doenças Ósseas Infecciosas/tratamento farmacológico , Doenças Ósseas Infecciosas/etiologia
2.
J Mater Chem B ; 10(2): 282-292, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34908091

RESUMO

The treatment of infected bone defects in complex anatomical structures, such as oral and maxillofacial structures, remains an intractable clinical challenge. Therefore, advanced biomaterials that have excellent anti-infection activity and allow convenient delivery are needed. We fabricated an innovative injectable gellan gum (GG)-based hydrogel loaded with nanohydroxyapatite particles and chlorhexidine (nHA/CHX). The hydrogel has a porous morphology, suitable swelling ratio, and good biocompatibility. It exerts strong antibacterial activity against Staphylococcus aureus growth and biofilm formation in vitro. We successfully established an infected calvarial defect rat model. Bacterial colony numbers were significantly lower in tissues surrounding the bone in rats of the GG/nHA/CHX group after debride surgery and hydrogel implantation in the defect regions than in rats of the blank group. Rats in the GG/nHA/CHX group exhibited significantly increased new bone formation compared to those in the blank group at 4 and 8 weeks. These findings indicate that gellan gum-based hydrogel with nHA/CHX can accelerate the repair of infected bone defects.


Assuntos
Antibacterianos/uso terapêutico , Doenças Ósseas Infecciosas/tratamento farmacológico , Hidrogéis/uso terapêutico , Polissacarídeos Bacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Biofilmes/efeitos dos fármacos , Osso e Ossos/microbiologia , Clorexidina/uso terapêutico , Durapatita/química , Durapatita/uso terapêutico , Hidrogéis/química , Masculino , Nanopartículas/química , Nanopartículas/uso terapêutico , Polissacarídeos Bacterianos/química , Ratos Sprague-Dawley , Staphylococcus aureus/fisiologia , Engenharia Tecidual , Tecidos Suporte/química , Cicatrização/efeitos dos fármacos
3.
Clin Microbiol Infect ; 28(1): 135.e1-135.e7, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33962064

RESUMO

OBJECTIVES: Beyond intracellular penetration, acidic lysosomal pH might affect the intracellular activity of some antimicrobials. This study evaluated the ability of lysosomotropic alkalizing agents to potentiate the antimicrobial eradication of an intra-osteoblastic Staphylococcus aureus reservoir in the setting of bone and joint infection (BJI). METHODS: MICs of 16 anti-staphylococcal molecules active against methicillin-sensitive S. aureus (MSSA) were evaluated at pH 5 and pH 7. Additionally, the lysosomal alkalizing potential (spectrofluorometry) and cytotoxicity (MTT assay) of hydroxychloroquine, amantadine and ammonium chloride were assessed. The results led to further investigation of clindamycin, cotrimoxazole, daptomycin and levofloxacin-alone or in combination with hydroxychloroquine-in an in vitro model of osteoblast infection. The impact of hydroxychloroquine on autophagy was finally investigated using Western blot detection of two autophagic flux indicators, the LC3 membrane protein and the SQSTM1 cargo protein. RESULTS: Daptomycin, cotrimoxazole, clindamycin and levofloxacin alone significantly decreased the intracellular staphylococcal reservoir (5.12 log10 CFU/100 000 cells) by 0.14 (95%CI 0.01-0.34), 0.25 (95%CI 0.12-0.43), 0.16 (95%CI 0.004-0.39) and 1.18 (95%CI 1.04-1.38) log10 CFU/100 000 cells, respectively (p < 10-3). Adding hydroxychloroquine (20 mg/L) increased intralysosomal pH from 4.8 to 7, and concomitantly the inoculum of each antimicrobial was reduced by 0.50 (95%CI 0.30-0.84), 0.73 (95%CI 0.59-0.96), 0.59 (95%CI 0.46-0.78) and 1.8 (95%CI 1.66-2.1) log10 CFU/100 000 cells, respectively (p < 10-4). Cellular levels of LC3II and SQSTM1 showed that hydroxychloroquine has direct activity on the autophagic flux, fostering the eradication of intracellular S. aureus by antimicrobials. CONCLUSION: At high concentrations, hydroxychloroquine used as an adjuvant to antimicrobials improves eradication of an S. aureus intra-osteoblastic reservoir in our in vitro cell infection model. These findings advocate further in vivo evaluation of alkalization efficacy and tolerance in S. aureus BJI.


Assuntos
Antibacterianos , Doenças Ósseas Infecciosas/tratamento farmacológico , Hidroxicloroquina , Artropatias/tratamento farmacológico , Infecções Estafilocócicas , Antibacterianos/farmacologia , Doenças Ósseas Infecciosas/microbiologia , Clindamicina , Daptomicina/farmacologia , Humanos , Hidroxicloroquina/farmacologia , Artropatias/microbiologia , Levofloxacino , Lisossomos , Testes de Sensibilidade Microbiana , Proteína Sequestossoma-1 , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Combinação Trimetoprima e Sulfametoxazol
4.
Biomed Pharmacother ; 142: 112053, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34435591

RESUMO

Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R2 adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Doenças Ósseas Infecciosas/tratamento farmacológico , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/farmacocinética , Artropatias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/sangue , Feminino , Fluoroquinolonas/sangue , Humanos , Levofloxacino/administração & dosagem , Levofloxacino/sangue , Levofloxacino/farmacocinética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Método de Monte Carlo , Ofloxacino/administração & dosagem , Ofloxacino/sangue , Ofloxacino/farmacocinética , Estudos Prospectivos , Staphylococcus/efeitos dos fármacos , Adulto Jovem
5.
Sci Rep ; 11(1): 16921, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34413456

RESUMO

An internal fixation composite structure of antibiotic cement plates was created. The aim of this study was to analyse the infection control effect of this structure when applied to treat a bone infection. We retrospectively analysed patients with bone infection admitted to our hospital between January 2013 and June 2019. After debridement, an antibiotic cement plate composite structure was used to fill and stabilize the defects. The treatment effect was evaluated at six months after surgery, and the infection control rate, factors associated with the recurrence of infection, and complications were analysed. If the patients had bone defects, the defect was repaired after infection control, and the infection control rate of all of the patients was re-evaluated at 12 months after surgery. A total of 548 patients were treated with this technique, including 418 men and 130 women. The infection sites included 309 tibias, 207 femurs, 16 radii and ulnae, 13 humeri, and 3 clavicles. After at least 6 months of follow-up, 92 patients (16.79%) had an infection recurrence and needed further treatment. The recurrence rate of the tibia was higher than that of the femur (P = 0.025). Eighty-nine out of 92 patients who relapsed underwent a second debridement with the same method, and the infection control rate after the second debridement was 94.71%. Complications included 8 cases of epidermal necrosis around the incision, 6 cases of internal fixation failure, and 30 cases of lower limb swelling. By the follow-up time of 12 months, another 6 patients had experienced recurrence of infection, and 4 cases were controlled after debridement. Finally, among all 548 cases, 7 patients remained persistently infected, and 6 underwent amputation. The infection control rate was 97.6% at the 1-year follow-up. The clinical efficacy of this new antibiotic cement plate composite structure for internal fixation after debridement of bone infection is stable and reliable.


Assuntos
Antibacterianos/uso terapêutico , Cimentos Ósseos/uso terapêutico , Doenças Ósseas Infecciosas , Desbridamento/métodos , Adolescente , Adulto , Idoso , Doenças Ósseas Infecciosas/tratamento farmacológico , Doenças Ósseas Infecciosas/cirurgia , Placas Ósseas , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
6.
J Biomed Mater Res A ; 109(12): 2580-2596, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34173709

RESUMO

Many osteoconductive and osteoinductive scaffolds have been developed for promoting bone regeneration; however, failures would occur in osteogenesis when the defect area is significantly infected while the biomaterials have no antibacterial performances. Herein, a kind of multipurpose PATGP@PDA + Ag microspheres was prepared via emulsion method by using a conductive aniline tetramer (AT) substituted polyphosphazene (PATGP), followed by polydopamine (PDA) modification and silver nanoparticles (AgNPs) loading. The PATGP@PDA + Ag microspheres demonstrated a strong antibacterial activity against Staphylococcus aureus both in vitro and in vivo, while showing no cytotoxicity at an optimized AgNPs loading amount. Due to the electron-donor structure of the AT moieties, the PATGP@PDA + Ag microspheres displayed antioxidant capacities to scavenge reactive oxygen species (ROS). Due to their phosphorus-rich feature, the PATGP@PDA + Ag microspheres favored the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). As controls, nonconductive microspheres (PAGP@PDA, PAGP@PDA + Ag) were prepared similarly by using poly[(ethylalanine)(ethylglycyl)]phosphazene (PAGP). By co-implanting these microspheres with S. aureus into rat calvarial defects, among them, it was determined that the PATGP@PDA + Ag microspheres achieved the most abundant neo-bone formation, benefiting from their antibacterial, antioxidant and osteogenic activities. These results revealed that AgNPs loaded scaffolds made of conductive polyphosphazenes were promising for the regeneration of infected bone defects.


Assuntos
Antibacterianos/uso terapêutico , Materiais Biocompatíveis/uso terapêutico , Condução Óssea , Doenças Ósseas Infecciosas/tratamento farmacológico , Compostos Organofosforados/uso terapêutico , Polímeros/uso terapêutico , Crânio/patologia , Tecidos Suporte/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Desenvolvimento Ósseo/efeitos dos fármacos , Doenças Ósseas Infecciosas/patologia , Células da Medula Óssea , Sequestradores de Radicais Livres , Células-Tronco Mesenquimais , Nanopartículas Metálicas/química , Microesferas , Osteogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/química , Prata , Staphylococcus aureus/efeitos dos fármacos
7.
Infect Dis Now ; 51(3): 304-307, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33934810

RESUMO

OBJECTIVES: To describe the efficacy and safety of prolonged cefazolin course for Staphylococcus infection and the emergence of multidrug-resistant bacteria carriage after treatment. METHODS: Monocentric retrospective cohort study of patients hospitalized for blood stream infections (BSI) and osteoarticular infections (OAI) by methicillin susceptible staphylococcal species treated with cefazolin from January 2015 to July 2017. Rectal and nasal swabs were performed at cefazolin initiation and end of treatment to detect respectively methicillin resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) producing bacteria. RESULTS: Fifty-eight patients were included, 41 had a bacteremia including 22 endocarditis and 22 OAI. Mean duration of treatment was 21.5 days at a mean daily dose of 6.5g/d. Fifty-five (94.5%) received combination therapy. Fifty-two (89.7%) of patients achieved bacteriological cure. Four patients were ESBL carriers at inclusion. No additional ESBL or MRSA were detected by end of treatment. CONCLUSION: Cefazolin appears as an effective and safe treatment for BSI or osteoarticular infection and does not appear to select MRSA or ESBL.


Assuntos
Antibacterianos/administração & dosagem , Cefazolina/administração & dosagem , Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/tratamento farmacológico , Idoso , Bacteriemia/tratamento farmacológico , Doenças Ósseas Infecciosas/tratamento farmacológico , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Cloxacilina/administração & dosagem , Endocardite Bacteriana/tratamento farmacológico , Feminino , Humanos , Masculino , Meticilina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Retrospectivos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação
8.
Infect Dis Now ; 51(4): 334-339, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33975673

RESUMO

OBJECTIVES: The management of bone and joint infections (BJI) is complex and requires prolonged antimicrobial therapy. Few data exist on adherence to anti-infectious treatment other than HIV, and none on BJI, even though compliance is considered as a major determinant of clinical outcome. This work aimed at evaluating adherence to oral antimicrobial treatment in patients with BJI. PATIENTS AND METHODS: This is a prospective observational blinded pilot study evaluating adherence by a 6-item questionnaire at 6 weeks (W6) and 3 months (M3) post-surgery. The primary endpoint was the proportion of patients with high, moderate and poor adherence at W6. Secondary endpoints included change in adherence between W6 and M3, and the exploration of potential variables influencing adherence. RESULTS: Analysis was performed on 65 questionnaires obtained from 43 patients including 35 with device-associated BJI. At W6, 11 out of 34 patients were highly adherent to oral antibiotic therapy, 22 moderately adherent and 1 poorly adherent. There was no significant change in adherence to antibiotic therapy between W6 and M3. The only variable significantly associated with the level of adherence at W6 and M3 was the number of daily doses of antibiotic (P=0.04 and 0.02 at W6 and M3, respectively). CONCLUSIONS: This study provided a snapshot of patients' adherence in BJI. Adherence to antibiotic therapy appeared to be stable up to 3 months and a higher number of daily doses of antibiotic was associated with poorer adherence. These observations need to be confirmed in future large-scale studies using electronic pill monitoring systems.


Assuntos
Antibacterianos/administração & dosagem , Doenças Ósseas Infecciosas/tratamento farmacológico , Artropatias/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Administração Oral , Idoso , Doenças Ósseas Infecciosas/microbiologia , Feminino , Humanos , Artropatias/microbiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Inquéritos e Questionários
9.
J Chemother ; 33(7): 469-475, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33904369

RESUMO

The presence of methicillin-resistant Staphylococcus aureus (MRSA) in bone infections difficults its treatment and is a sign of concern. The aim of this study was to evaluate in vitro activity of dalbavancin on pre-established adhered cells and 24 h old biofilms of MRSA strains isolated from a human bone infection. Thirty-three MRSA were isolated from osteomyelitis episodes. The antimicrobial susceptibility of these strains was assessed by the Kirby-Bauer disc diffusion method and the presence of resistance genes was screened by PCR. MRSA planktonic minimum inhibitory concentration and minimum bactericidal concentration were assessed. Minimum biofilm eradication concentration (MBEC) was performed by the microtiter biofilm formation assay. All 33 MRSA strains were classified as multidrug-resistant strains and susceptible to dalbavancin. Dalbavancin inhibited the growth of 54.6% and 52% of strains at the concentrations of 0.05 µg/mL and 1 µg/mL, respectively. The MBEC values up to 0.4 µg/mL demonstrated that dalbavancin was active against most strains in pre-established adhered cells and 24 h old biofilms. The current results show that dalbavancin is active against adhered cells and biofilms in vitro, suggesting that this antimicrobial agent may be an option for the treatment of bone infections caused by MRSA.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Teicoplanina/análogos & derivados , Antibacterianos/uso terapêutico , Doenças Ósseas Infecciosas/tratamento farmacológico , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Teicoplanina/farmacologia , Teicoplanina/uso terapêutico
10.
Biomed Res Int ; 2021: 6668617, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33532493

RESUMO

BACKGROUND: The objective of this systematic review was to evaluate current studies available reporting the antibiotic spacer combined with Ilizarov methods in the treatment of infected nonunion of tibia and to perform meta-analysis of bone results and infection recurrence to assess the efficacy of an antibiotic spacer combined with Ilizarov methods. METHODS: The MEDLINE, Embase, Cochrane Library, CNKI, and CBM (Chinese Biological Medicine) databases were searched for articles published between January 2000 and July 2020. Assessment of study quality was performed using a modified version of the Newcastle-Ottawa scale. Effect size and 95% confidence intervals were calculated for the main outcome. Heterogeneity was assessed. Fixed-effect modeling and Stata version 15.1 were used to analyze the data. Sensitivity analyses were conducted with the evidence of heterogeneity. RESULTS: 11 studies involving 210 patients with infected nonunion of tibia were finally included in our meta-analysis. Bone results and infection recurrence were analyzed based on the single-arm meta-analysis. The average of external fixation index (EFI) was 46.88 days/cm in all studies included. The excellent rate in bone results and the rate of infection recurrence was 65% (95% CI: [0.22, 0.97], I 2 = 0.0%, P = 0.932) and 6.99% (95% CI: [0.052, 0.325], I 2 = 0.0%, P = 1.000) in patients with infected nonunion of tibia treated with an antibiotic spacer combined with Ilizarov methods. CONCLUSIONS: Our meta-analysis revealed that the patients with infected nonunion of tibia treated with an antibiotic spacer combined with Ilizarov methods had a high rate of excellent bone results and a low rate of infection recurrence. Therefore, combining the antibiotic spacer with Ilizarov methods may be an applicable choice for repairing and reconstructing infected nonunion of tibia.


Assuntos
Antibacterianos , Doenças Ósseas Infecciosas , Fraturas não Consolidadas/cirurgia , Técnica de Ilizarov , Fraturas da Tíbia/cirurgia , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Doenças Ósseas Infecciosas/tratamento farmacológico , Doenças Ósseas Infecciosas/epidemiologia , Doenças Ósseas Infecciosas/cirurgia , Implantes de Medicamento , Feminino , Consolidação da Fratura , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Tíbia/cirurgia , Adulto Jovem
12.
Infect Dis Now ; 51(1): 61-66, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32360395

RESUMO

OBJECTIVES: We reported the impact of internal guidelines coupled with selective reporting of antibiotic susceptibility tests (srAST) on antibiotic adequacy in healthcare facilities. METHODS: This prospective study involved clinicians from three clinics with medical and surgical activities employing a full-time infectious disease (ID) specialist. Internal guidelines were updated in 2016. The clinics were working with the same laboratory, which delivered the srAST introduced in March 2017. Two weeks per month over a 6-month period, all isolated bacterial specimens, empirical antibiotic therapies (EAT) and the documented ones were analyzed. An EAT listed in the guidelines and a documented therapy mentioned in the srAST defined their adequacy. RESULTS: A total of 257 positive bacterial samples were analyzed in 199 patients, for which 106 infections were studied. Of these, 32% were urinary tract infections, 15% were primary bloodstream infections, 11% were bone infections, and 42% were other types of infection. The three main bacteria were Escherichia coli (27%), Staphylococcus aureus (24%), and Enterococcus faecalis (14%). The total number of antibiotic prescriptions was 168, with 75 (45%) EATs and 93 (55%) documented therapies. There were 35/75 (47%) adequate EATs and 86/93 (92%) adequate documented therapies. The ID specialist was not involved in 90/168 (53.5%) prescriptions, of which 43/90 (48%) were adequate, with 21/35 (60%) EATs and 22/86 (25%) documented therapies. There was a statistical correlation between compliance of the EATs with guidelines and of the documented therapy with srAST (p=0.02). CONCLUSION: Combining internal guidelines and srAST led to a high rate of antibiotic adequacy.


Assuntos
Antibacterianos/uso terapêutico , Infecções/tratamento farmacológico , Testes de Sensibilidade Microbiana/normas , Guias de Prática Clínica como Assunto , Idoso , Idoso de 80 Anos ou mais , Gestão de Antimicrobianos/métodos , Bacteriemia/tratamento farmacológico , Doenças Ósseas Infecciosas/tratamento farmacológico , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Feminino , França , Instalações de Saúde , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/isolamento & purificação , Infecções Urinárias/tratamento farmacológico
13.
Eur J Clin Microbiol Infect Dis ; 40(2): 397-405, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32851509

RESUMO

Tedizolid is a new oxazolidinone antibiotic with little real-life data on use outside of skin and soft tissue infections. There is a paucity of safety evidence in courses greater than 6 days. Our centre uses tedizolid predominantly when linezolid-associated adverse events have occurred. This service evaluation describes our experience to date. We performed a retrospective service evaluation by reviewing case notes, prescription charts, and laboratory system results for each patient prescribed tedizolid at our hospital and recording patient demographics, clinical details, and outcomes. Sixty patients received tedizolid between May 2016 and November 2018. Most were treated for bone or joint infections and had stopped linezolid prior to tedizolid prescription. Mean length of tedizolid therapy was 27 days. Haematological adverse effects were infrequent. Most patients (72%) finished the course and their clinical condition improved during treatment (72%). Adverse events were common, but often not thought to be tedizolid related. Tedizolid appears to be safe in prolonged courses within this context. It may be suitable for longer-term antibiotic therapy within a complex oral and parenteral outpatient antibiotic therapy (COPAT) service. Patients who do not tolerate linezolid can be safely switched to tedizolid if appropriate.


Assuntos
Antibacterianos/uso terapêutico , Doenças Ósseas Infecciosas/tratamento farmacológico , Oxazolidinonas/uso terapêutico , Tetrazóis/uso terapêutico , Antibacterianos/efeitos adversos , Feminino , Hospitais de Ensino , Humanos , Linezolida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxazolidinonas/efeitos adversos , Estudos Retrospectivos , Tetrazóis/efeitos adversos , Resultado do Tratamento , Reino Unido
14.
J Infect Dis ; 222(Suppl 5): S494-S498, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32877541

RESUMO

BACKGROUND: Research is limited on combining outpatient parenteral antimicrobial therapy (OPAT) with addiction treatment for people who inject drugs (PWID) with serious infections. METHODS: This is a retrospective study of PWID (n = 68) requiring intravenous antibiotics evaluated for suitability for our OPAT program with concurrent addiction treatment. RESULTS: Most common infections were bacteremia and/or endocarditis (73.5%), bone and/or joint infections (32.4%), and epidural abscess (22.1%). Of the 20 patients (29.4%) who qualified, 100.0% completed the course of antibiotics, 30.0% experienced a 30-day readmission, and 15.0% relapsed. No overdoses, deaths, or peripherally inserted central catheter-line complications were reported. CONCLUSIONS: Outpatient parenteral antimicrobial therapy with addiction treatment may be feasible and safe for PWID with serious infections.


Assuntos
Assistência Ambulatorial/métodos , Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Doenças Ósseas Infecciosas/tratamento farmacológico , Endocardite Bacteriana/tratamento farmacológico , Abuso de Substâncias por Via Intravenosa/terapia , Administração Intravenosa/efeitos adversos , Administração Intravenosa/instrumentação , Adulto , Assistência Ambulatorial/estatística & dados numéricos , Antibacterianos/efeitos adversos , Bacteriemia/microbiologia , Doenças Ósseas Infecciosas/microbiologia , Cateteres Venosos Centrais/efeitos adversos , Endocardite Bacteriana/microbiologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Abuso de Substâncias por Via Intravenosa/complicações , Resultado do Tratamento
15.
Int J Antimicrob Agents ; 56(3): 106069, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32603683

RESUMO

BACKGROUND: There is increasing interest in the use of oritavancin and dalbavancin for complicated Gram-positive infections as an alternative to in-hospital intravenous or outpatient antimicrobial therapy. OBJECTIVE: To evaluate the efficacy and safety of long-acting lipoglycopeptides (laLGPs) in patients with osteoarticular, cardiovascular, intravascular-catheter-related and other complicated infections. METHODS: A systematic literature search was performed using 'dalbavancin' and 'oritavancin' as search terms. For inclusion in this review, studies had to include at least one human subject treated for an indication other than acute bacterial skin and skin structure infections. The primary outcome for this review was clinical success as defined by each individual study, and patients were stratified by type of infection. RESULTS: In total, 38 studies (18 randomized controlled trials/case series and 20 case reports) met the inclusion criteria. The most common off-label indication for oritavancin and dalbavancin was osteoarticular infection, with a median success rate of 73% [interquartile range (IQR) 58-85%] among the 14 studies with more than one patient. The success rate for endocarditis and cardiac-device-related infections was 68% (IQR 56-86%) among nine studies, and the success rate for catheter-related bloodstream infection was 75% (IQR 59-90%) among seven studies. Among the 16 studies of almost 700 patients receiving laLGPs, there were 98 reports of adverse events, resulting in 13% of treated patients reporting an event. CONCLUSIONS: This review provides evidence that laLGPs are safe and efficacious for osteoarticular, cardiovascular, intravascular-catheter-related and other complicated infections. Further research is needed to confirm these results.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Lipoglicopeptídeos/uso terapêutico , Teicoplanina/análogos & derivados , Antibacterianos/efeitos adversos , Doenças Ósseas Infecciosas/tratamento farmacológico , Infecções Cardiovasculares/tratamento farmacológico , Infecções Relacionadas a Cateter/tratamento farmacológico , Feminino , Humanos , Lipoglicopeptídeos/efeitos adversos , Masculino , Teicoplanina/efeitos adversos , Teicoplanina/uso terapêutico , Resultado do Tratamento
16.
Eur J Drug Metab Pharmacokinet ; 45(5): 587-599, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32440843

RESUMO

BACKGROUND AND OBJECTIVES: Osteoarticular infections (OIs) caused by fluoroquinolone-resistant Pseudomonas aeruginosa, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, have poor outcomes. We evaluated the outcomes of an optimized strategy of continuous beta-lactam infusion (BL-CI) guided by therapeutic drug monitoring (TDM) for OIs caused by fluoroquinolone-resistant P. aeruginosa. METHODS: A prospective observational study of patients with P. aeruginosa OIs in a hospital-based BL-CI program (2016-2018) was carried out. TDM targeting free BL concentrations in plasma (fCss) of at least 3-4 × MIC was performed. We compared failure rates between patients with OIs caused by fluoroquinolone-resistant strains who were treated with BL-CI, with or without colistin, and patients with OIs caused by fluoroquinolone-susceptible strains who were treated with ciprofloxacin. RESULTS: Fifty-two patients were included in the study, 19 (36.5%) of whom had OIs caused by fluoroquinolone-resistant P. aeruginosa (13 (68.4%) MDR/XDR strains; 11 (57.9%) device-related infections). The median duration of BL-CI was 36 days; ten patients (52.6%) received BL-colistin combinations. Eighty-two samples were utilized in the TDM, and most patients were found to have a median fCss of 3-10 × MIC; 17 dose adjustments were performed and eight patients needed dose decreases, five of which were due to chronic kidney disease or acute kidney injury (AKI). BL-CI was well tolerated, with the most frequent adverse event being AKI. Failure occurred to 4 patients (21.1%), which was similar to the failure rate of patients with OIs caused by fluoroquinolone-susceptible P. aeruginosa treated with ciprofloxacin (5/30 [16.7%]) (p = 0.699). TDM was also used in the initial BL treatment of patients with OIs caused by susceptible strains before those patients were switched to treatment with ciprofloxacin alone (33 patients, 110 samples, 19 dose adjustments). CONCLUSIONS: BL-CI used with/without colistin and supported by TDM may be an alternative and effective treatment option for OIs caused by fluoroquinolone-resistant P. aeruginosa, where limited available therapeutic options exist, especially in the setting of multidrug resistance. Future research should elucidate whether this strategy can produce outcomes similar to those of patients treated for OIs caused by fluoroquinolone-susceptible strains.


Assuntos
Antibacterianos/administração & dosagem , Doenças Ósseas Infecciosas/tratamento farmacológico , Artropatias/tratamento farmacológico , beta-Lactamas/administração & dosagem , Idoso , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Doenças Ósseas Infecciosas/microbiologia , Ciprofloxacina/administração & dosagem , Estudos de Coortes , Colistina/administração & dosagem , Monitoramento de Medicamentos , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Infusões Intravenosas , Artropatias/microbiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , beta-Lactamas/farmacocinética
19.
J Pediatric Infect Dis Soc ; 9(3): 382-385, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31194251

RESUMO

A direct-from-source rapid musculoskeletal diagnostic panel (MDP) was validated recently. We compared clinical measures to theoretical time points had MDP results been available. The MDP would have significantly decreased the time to pathogen identification (7 hours), time to definitive antimicrobial therapy (22 hours), and hospital length of stay (26.4 hours).


Assuntos
Infecções Bacterianas/diagnóstico , Doenças Ósseas Infecciosas/diagnóstico , Doenças Ósseas Infecciosas/microbiologia , Antibacterianos/uso terapêutico , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/microbiologia , Infecções Bacterianas/tratamento farmacológico , Doenças Ósseas Infecciosas/tratamento farmacológico , Criança , Humanos , Técnicas de Diagnóstico Molecular , Miosite/diagnóstico , Miosite/microbiologia , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Estudos Retrospectivos
20.
Acta Clin Belg ; 75(4): 275-283, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31023169

RESUMO

BACKGROUND: Outpatient parenteral antibiotic therapy (OPAT) was not used in Belgium before 2013, except for patients with cystic fibrosis. Thus, we have performed a pilot study to evaluate clinical characteristics and outcomes of patient receiving OPAT in a Belgian setting. METHODS: The study was a prospective observational single-center study of patients receiving OPAT between 1 September 2013 and 31 December, 2017. RESULTS: We included 218 OPATs. The median age was 58 years and 71% were men. At the end of the treatment, 92% of the patients on OPAT were cured. Risk factors for treatment failure were obesity, diabetes and diabetic foot infections, longer duration of hospitalization before OPAT, and duration of OPAT >16 days. An average of 24 days of hospitalization per patient discharge was saved, which amounted to 5205 days saved during the project. During the OPAT and 30 days thereafter, 71 (32.6%) of patients were readmitted, but only 26 (12%) readmissions were directly related to OPAT. Risk factors for readmissions were diabetes and diabetic foot infections, endovascular infections, longer duration of hospitalization before OPAT, duration of OPAT >30 days, and history of hospitalizations in the year before OPAT. There were 2.3 intravenous catheter-related events per 1000 days of catheter use. Patients' level of satisfaction was high (99.5%). CONCLUSIONS: In this pilot study, OPAT is found to be efficacious in saving hospitalization's days, with a low rate of readmissions and complications and a high patients' level of satisfaction. We therefore conclude that OPAT is feasible and safe. BACKGROUND: Outpatient parenteral antibiotic therapy (OPAT) was not used in Belgium before 2013, except for patients with cystic fibrosis. Thus, we have performed a pilot study to evaluate clinical characteristics and outcomes of patient receiving OPAT in a Belgian setting. METHODS: The study was a prospective observational single-center study of patients receiving OPAT between 1 September 2013 and 31 December, 2017. RESULTS: We included 218 OPATs. The median age was 58 years and 71% were men. At the end of the treatment, 92% of the patients on OPAT were cured. Risk factors for treatment failure were obesity, diabetes and diabetic foot infections, longer duration of hospitalization before OPAT, and duration of OPAT >16 days. An average of 24 days of hospitalization per patient discharge was saved, which amounted to 5205 days saved during the project. During the OPAT and 30 days thereafter, 71 (32.6%) of patients were readmitted, but only 26 (12%) readmissions were directly related to OPAT. Risk factors for readmissions were diabetes and diabetic foot infections, endovascular infections, longer duration of hospitalization before OPAT, duration of OPAT >30 days, and history of hospitalizations in the year before OPAT. There were 2.3 intravenous catheter-related events per 1000 days of catheter use. Patients' level of satisfaction was high (99.5%). CONCLUSIONS: In our study, OPAT is found to be efficacious in saving hospitalization's days, with a low rate of readmissions and complications and a high patients' level of satisfaction. We therefore conclude that OPAT is feasible and safe.


Assuntos
Assistência Ambulatorial/organização & administração , Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Serviços de Assistência Domiciliar/organização & administração , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/métodos , Artrite Infecciosa/tratamento farmacológico , Bélgica , Doenças Ósseas Infecciosas/tratamento farmacológico , Cateterismo Periférico , Criança , Pré-Escolar , Colangite/tratamento farmacológico , Colecistite/tratamento farmacológico , Cistite/tratamento farmacológico , Diabetes Mellitus , Pé Diabético/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Duração da Terapia , Endocardite/tratamento farmacológico , Feminino , Hospitalização , Humanos , Tempo de Internação/estatística & dados numéricos , Abscesso Hepático/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Obesidade , Readmissão do Paciente/estatística & dados numéricos , Satisfação do Paciente , Projetos Piloto , Estudos Prospectivos , Prostatite/tratamento farmacológico , Pielonefrite/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Fatores de Risco , Falha de Tratamento , Resultado do Tratamento , Infecção dos Ferimentos/tratamento farmacológico , Adulto Jovem
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