RESUMO
In view of the current increase and spread of antimicrobial resistance (AMR), there is an urgent need to find new strategies to combat it. This study had two aims. First, we synthesized highly monodispersed silver nanoparticles (AgNPs) of approximately 17 nm, and we functionalized them with mercaptopoly(ethylene glycol) carboxylic acid (mPEG-COOH) and amikacin (AK). Second, we evaluated the antibacterial activity of this treatment (AgNPs_mPEG_AK) alone and in combination with hyperthermia against planktonic and biofilm-growing strains. AgNPs, AgNPs_mPEG, and AgNPs_mPEG_AK were characterized using a suite of spectroscopy and microscopy methods. Susceptibility to these treatments and AK was determined after 24 h and over time against 12 clinical multidrug-resistant (MDR)/extensively drug-resistant (XDR) isolates of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The efficacy of the treatments alone and in combination with hyperthermia (1, 2, and 3 pulses at 41°C to 42°C for 15 min) was tested against the same planktonic strains using quantitative culture and against one P. aeruginosa strain growing on silicone disks using confocal laser scanning microscopy. The susceptibility studies showed that AgNPs_mPEG_AK was 10-fold more effective than AK alone, and bactericidal efficacy after 4, 8, 24, or 48 h was observed against 100% of the tested strains. The combination of AgNPs_mPEG_AK and hyperthermia eradicated 75% of the planktonic strains and exhibited significant reductions in biofilm formation by P. aeruginosa in comparison with the other treatments tested, except for AgNPs_mPEG_AK without hyperthermia. In conclusion, the combination of AgNPs_mPEG_AK and hyperthermia may be a promising therapy against MDR/XDR and biofilm-producing strains. IMPORTANCE Antimicrobial resistance (AMR) is one of the greatest public health challenges, accounting for 1.27 million deaths worldwide in 2019. Biofilms, a complex microbial community, directly contribute to increased AMR. Therefore, new strategies are urgently required to combat infections caused by AMR and biofilm-producing strains. Silver nanoparticles (AgNPs) exhibit antimicrobial activity and can be functionalized with antibiotics. Although AgNPs are very promising, their effectiveness in complex biological environments still falls below the concentrations at which AgNPs are stable in terms of aggregation. Thus, improving the antibacterial effectiveness of AgNPs by functionalizing them with antibiotics may be a significant change to consolidate AgNPs as an alternative to antibiotics. It has been reported that hyperthermia has a large effect on the growth of planktonic and biofilm-producing strains. Therefore, we propose a new strategy based on AgNPs functionalized with amikacin and combined with hyperthermia (41°C to 42°C) to treat AMR and biofilm-related infections.
Assuntos
Hipertermia Induzida , Nanopartículas Metálicas , Amicacina/farmacologia , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , BiofilmesRESUMO
There is currently an urgent need to find new strategies to tackle antimicrobial resistance and biofilm-related infections. This study has two aims. First, we evaluated the in vitro efficacy of hyperthermia in preventing biofilm formation on the surfaces of polyvinyl chloride discs. Second, we assessed the in vivo efficacy of hyperthermia in preventing biofilm formation in endotracheal tubes (ETTs) of a rabbit model. For the in vitro studies, nine clinical extensively drug-resistant/multidrug-resistant Gram-negative isolates of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa and three clinical methicillin-resistant Staphylococcus aureus strains were studied. For biofilm formation, an adhesion step of 30 or 90 min followed by a growth step of 24 h were performed with application of one, two, and three pulses at 42°C for 15 min each pulse after the adhesion step. For the in vivo studies, New Zealand rabbits were intubated with ETTs previously colonized with K. pneumoniae or P. aeruginosa strains, and three pulses at 42°C for 15 min were applied after the adhesion step. The application of three pulses at 42°C for 15 min each pulse was needed to achieve the prevention of the in vitro biofilm formation of 100% of the tested strains. The application of heat pulses in a rabbit intubation model led to biofilm prevention of 85% against two K. pneumoniae strains and 80% against two P. aeruginosa strains compared to the control group. Hyperthermia application through pulses at 42°C could be a new nonantibiotic strategy to prevent biofilm formation in ETTs. IMPORTANCE Biofilm-producing microorganisms are considered medically crucial since they cause 80% of the infections that occur in the human body. Medical devices such as endotracheal tubes (ETTs) can act as a reservoir for pathogens providing the surface to which microorganisms can adhere and cause biofilm-associated infections in critically ill patients. This biofilm has been related with the development of ventilator-associated pneumonia (VAP), with an incidence of 8 to 28%, a mortality rate up to 17% and its associated high extra costs. Although some VAP-preventive measures have been reported, they have not demonstrated a significant reduction of VAP incidence. Therefore, we present a new nonantibiotic strategy based on hyperthermia application to prevent biofilm formation inside ETTs. This technology could reduce VAP incidence, intubation duration, hospital and intensive care unit (ICU) length stays, and mortality rates. Consequently, this could decrease the antibiotics administered and influence the impact of antibiotic resistance in the ICU.
Assuntos
Hipertermia Induzida , Staphylococcus aureus Resistente à Meticilina , Pneumonia Associada à Ventilação Mecânica , Humanos , Animais , Coelhos , Intubação Intratraqueal/efeitos adversos , Antibacterianos , Pneumonia Associada à Ventilação Mecânica/etiologia , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Biofilmes , Pseudomonas aeruginosa , Hipertermia Induzida/efeitos adversosRESUMO
This is a retrospective single-center study of 24 patients who received ceftazidime-avibactam plus aztreonam (CZA/ATM) for the treatment of VIM-type-producing Gram-negative bacillus (GNB) infections. The bacteria isolated were Enterobacterales in 22 patients and Pseudomonas aeruginosa in 2. Sixteen out of 19 isolates showed synergistic activity. Two patients presented clinical failure at day 14, and the 30-day mortality was 17% (4/24). CZA/ATM could be considered an alternative therapy for VIM-type-producing GNB infections.
Assuntos
Aztreonam , beta-Lactamases , Humanos , Aztreonam/uso terapêutico , Estudos Retrospectivos , Testes de Sensibilidade Microbiana , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Ceftazidima/uso terapêutico , Bactérias Gram-Negativas , Combinação de MedicamentosRESUMO
Introduction: Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are prevalent nosocomial infections with a worrisomely increasing prevalence of multidrug-resistant causative organisms, including those with resistance to carbapenems. The addition of relebactam, a ß-lactamase inhibitor, to imipenem treatment restores the antimicrobial activity against the most of multidrug-resistant Gram-negative bacteria, including some carrying ß-lactamase enzyme-type carbapenemases.Areas covered: The aim of this article is to summarize the current evidence regarding imipenem/relebactam for the treatment of HAP/VAP. The authors discuss its chemistry, pharmacokinetics/pharmacodynamics, microbiology, tolerance and clinical efficacy. The results of clinical trials have demonstrated an efficacy of imipenem/relebactam similar to that of its comparator for the treatment of patients with HAP/VAP. Different studies have also shown its good safety profile, which is better than that of the combination of other ß-lactams with other antibiotics.Expert opinion: This drug should be incorporated as a new therapeutic option for the treatment of patients with HAP/VAP, especially as an alternative treatment in patients with confirmed infections caused by multidrug-resistant Gram-negatives.
Assuntos
Pneumonia Bacteriana , Pneumonia Associada à Ventilação Mecânica , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Cilastatina , Hospitais , Humanos , Imipenem/uso terapêutico , Testes de Sensibilidade Microbiana , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Ventiladores MecânicosRESUMO
One of the current priorities of the World Health Organization is multidrug-resistant bacteria, because they are a global problem due to their rapid spread and the difficulty of their treatment. In addition, they are associated with high morbidity, mortality and high economic costs. There are multidrug-resistant bacteria, both Gram-positive and Gram-negative, including Pseudomonas aeruginosa and Acinetobacter baumannii resistant to carbapenems, enterobacteria producing carbapenemases, Staphylococcus aureus resistant to methicillin and/or with intermediate sensitivity to vancomycin, and Enterococcus faecium (and less frequently Enterococcus faecalis) resistant to vancomycin. This review will comment on the new antibiotics that have been incorporated into the therapeutic arsenal in recent years, as well as other promising antibiotics that are in their final stages of development.
Assuntos
Acinetobacter baumannii , Antibacterianos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Staphylococcus aureusRESUMO
The cost of treating Clostridium difficile infection (CDI) in Spain is substantial. Findings from the randomised, controlled, open-label, phase 3b/4 EXTEND study showed that an extended-pulsed fidaxomicin (EPFX) regimen was associated with improved sustained clinical cure and reduced recurrence of CDI versus vancomycin in patients aged 60 years and older. We assessed the cost-effectiveness of EPFX versus vancomycin for the treatment of CDI in patients aged 60 years and older from the perspective of the National Health System (NHS) in Spain. We used a Markov model with six health states and 1-year time horizon. Health resources, their unit costs and utilities were based on published sources. Key efficacy data and transition probabilities were obtained from the EXTEND study and published sources. A panel of Spanish clinical experts validated all model assumptions. In the analysis, 0.638 and 0.594 quality-adjusted life years (QALYs) per patient were obtained with EPFX and vancomycin, respectively, with a gain of 0.044 QALYs with EPFX. The cost per patient treated with EPFX and vancomycin was estimated to be 10,046 and 10,693, respectively, with a saving of 647 per patient treated with EPFX. For willingness-to-pay thresholds of 20,000, 25,000 and 30,000 per QALY gained, the probability that EPFX was the most cost-effective treatment was 99.3%, 99.5% and 99.9%, respectively. According to our economic model and the assumptions based on the Spanish NHS, EPFX is cost-effective compared with vancomycin for the first-line treatment of CDI in patients aged 60 years and older.
Assuntos
Antibacterianos/administração & dosagem , Infecções por Clostridium/tratamento farmacológico , Análise Custo-Benefício , Fidaxomicina/administração & dosagem , Vancomicina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/economia , Clostridioides difficile , Infecções por Clostridium/economia , Custos de Cuidados de Saúde , Humanos , Pessoa de Meia-Idade , Modelos Econômicos , Programas Nacionais de Saúde , Anos de Vida Ajustados por Qualidade de Vida , Espanha , Resultado do TratamentoRESUMO
This study aimed to evaluate the effectiveness and safety of teicoplanin for treating enterococcal infective endocarditis (EIE). A retrospective analysis of a prospective cohort of definite EIE patients treated with teicoplanin in a Spanish referral centre (2000-2017) was performed. The primary outcome was mortality during treatment. Secondary outcomes were mortality during 3-month follow-up, adverse effects and relapse. A total of 22 patients received teicoplanin, 9 (40.9%) as first-line (8 Enterococcus faecium and 1 Enterococcus faecalis) and 13 (59.1%) as salvage therapy (13 E. faecalis). Median (IQR) age was 71.5 (58.3-78) years and Charlson comorbidity index was 4.5 (3-7). Five (22.7%) affected prosthetic valves. Median duration of treatment in survivors was 53 (42.5-61) days for antibiotics and 27 (17-41.5) days for teicoplanin [median dose 10 (10-10.8) mg/kg/day]. Reasons for teicoplanin use were resistance to ß-lactams (40.9%), adverse events with previous regimens (31.8%) and outpatient parenteral antimicrobial therapy (OPAT) (27.3%). Teicoplanin was withdrawn due to adverse events in 2 patients (9.1%). Five patients (22.7%) died during treatment: four in the first-line (three with surgery indicated but not performed) and one in the salvage therapy group (surgery indicated but not performed). Two deaths (11.8%) occurred over the 3-month follow-up. There were no relapses during a median of 43.2 (22.1-69.1) months. Teicoplanin can be used as an alternative treatment for susceptible E. faecium IE and as a salvage therapy in selected patients with E. faecalis IE when adverse events develop with standard regimens or to allow OPAT.
Assuntos
Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Teicoplanina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/mortalidade , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/mortalidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Teicoplanina/efeitos adversosRESUMO
PURPOSE: The aim of this study was to evaluate the effectiveness of ceftolozane/tazobactam (C/T) for treating extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) infections, and to analyze whether high C/T dosing (2 g ceftolozane and 1 g tazobactam every 8 h) and infection source control have an impact on outcome. METHODS: Retrospective study of all consecutive patients treated with C/T for XDR-PA infection at a tertiary referral hospital (November 2015-July 2017). Main clinical and microbiological variables were analyzed. RESULTS: Thirty-eight patients were included. Median age was 59.5 years and Charlson Comorbidity Index was 3.5. Fourteen (36.8%) patients had respiratory tract infection, six (15.8%) soft tissue, and six (15.8%) urinary tract infection. Twenty-three (60.5%) received high-dose C/T and in 24 (63.2%) C/T was combined with other antibiotics. At completion of treatment, 33 (86.8%) patients showed clinical response. At 90 days of follow-up, 26 (68.4%) achieved clinical cure, and 12 (31.6%) had clinical failure because of persistent infection in one patient, death attributable to the XDR-PA infection in four, and clinical recurrence in seven. All-cause mortality was 5 (13.2%). Lower C/T MIC and adequate infection source control were the only variables significantly associated with clinical cure. CONCLUSIONS: C/T should be considered for treating XDR-PA infections, with infection source control being an important factor to avoid failure and resistance.
Assuntos
Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Ácido Penicilânico/análogos & derivados , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefalosporinas/farmacologia , Feminino , Seguimentos , Humanos , Controle de Infecções , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ácido Penicilânico/farmacologia , Ácido Penicilânico/uso terapêutico , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/classificação , Pseudomonas aeruginosa/genética , Estudos Retrospectivos , Tazobactam , Falha de Tratamento , Resultado do Tratamento , Adulto JovemRESUMO
The aim of the current study was to compare community-acquired acute pyelonephritis (CA-APN) with health care-associated acute pyelonephritis (HCA-APN), describe the outcomes, and identify variables that could predict antimicrobial susceptibility. We conducted an observational study that included all consecutive episodes of acute pyelonephritis (APN) in adults during 2014 at a Spanish university hospital. From each episode, demographic data, comorbidities, clinical presentation, microbiological data, antimicrobial therapy, and outcome were recorded. A multivariable logistic regression model was performed to define the variables associated with antimicrobial resistance. A total of 607 patients, 503 (82.9%) with CA-APN and 104 (17.1%) with HCA-APN, were included in the study. Patients with HCA-APN were older than patients with CA-APN (70.4 versus 50.6 years; P < 0.001) and had higher rates of previous urinary tract infections (UTIs) (56.5% versus 24.5%; P < 0.001) and previous antibiotic use (56.8% versus 22.8%; P < 0.001). Escherichia coli was more frequently isolated from patients with CA-APN than from patients with HCA-APN (79.9% versus 50.5%; P < 0.001). The rates of resistance of Escherichia coli strains from CA-APN patients versus HCA-APN patients were as follows: amoxicillin-clavulanic acid, 22.4% versus 53.2% (P = 0.001); cefuroxime, 7.7% versus 43.5% (P = 0.001); cefotaxime, 4.3% versus 32.6% (P < 0.001); ciprofloxacin, 22.8% versus 74.5% (P < 0.001); and co-trimoxazole, 34.5% versus 58.7% (P = 0.003). The site of acquisition, recurrent UTIs, and previous antibiotic use were independent risk factors for antimicrobial resistance. Relapse rates were significantly higher when definitive antimicrobial treatment was not adequate (37.1% versus 9.3% when definitive antimicrobial treatment was adequate; P < 0.001). Our study reflects the rise of resistance to commonly used antibiotics in acute pyelonephritis. In order to choose the adequate empirical antibiotic therapy, risk factors for resistance should be considered.
Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Farmacorresistência Bacteriana , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Pielonefrite/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Cefotaxima/uso terapêutico , Cefuroxima/uso terapêutico , Ciprofloxacina/uso terapêutico , Estudos de Coortes , Infecções Comunitárias Adquiridas , Infecção Hospitalar/microbiologia , Infecção Hospitalar/patologia , Pesquisa Empírica , Escherichia coli/crescimento & desenvolvimento , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Feminino , Hospitais Universitários , Humanos , Modelos Logísticos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pielonefrite/microbiologia , Pielonefrite/patologia , Fatores de Risco , Espanha , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Infecções Urinárias/microbiologia , Infecções Urinárias/patologiaRESUMO
BACKGROUND: Whether echinocandins could be used to treat candidemia of a urinary tract source (CUTS) is unknown. We aimed to provide current epidemiological information of CUTS and to compare echinocandin to fluconazole treatment on CUTS outcomes. METHODS: A multicenter study of adult patients with candidemia was conducted in 9 hospitals. CUTS was defined as a candidemia with concomitant candiduria by the same organism associated with significant urological comorbidity. The primary outcome assessed was clinical failure (defined by 7-day mortality or persistent candidemia) in patients treated with either an echinocandin or fluconazole. A propensity score was calculated and then entered into a regression model. RESULTS: Of 2176 episodes of candidemia, 128 were CUTS (5.88%). Most CUTS cases were caused by Candida albicans (52.7%), followed by Candida glabrata (25.6%) and Candida tropicalis (16.3%). Clinical failure occurred in 7 patients (20%) treated with an echinocandin and in 15 (17.1%) treated with fluconazole (P = .730). Acute renal failure (adjusted odds ratio [AOR], 3.01; 95% confidence interval [CI], 1.01-8.91; P = .047) was the only independent factor associated with clinical failure, whereas early urinary tract drainage procedures (surgical, percutaneous, or endoscopic) were identified as protective (AOR, 0.08; 95% CI, .02-.31; P < .001). Neither univariate nor multivariate analysis showed that echinocandin therapy altered the risk of clinical failure. CONCLUSIONS: Initial echinocandin therapy was not associated with clinical failure in patients with CUTS. Notably, acute renal failure predicted worse outcomes and performing an early urologic procedure was a protective measure.
Assuntos
Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Equinocandinas/uso terapêutico , Fluconazol/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/administração & dosagem , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candida glabrata/efeitos dos fármacos , Candida glabrata/isolamento & purificação , Candidemia/microbiologia , Candidemia/mortalidade , Estudos de Coortes , Comorbidade , Equinocandinas/administração & dosagem , Feminino , Fluconazol/administração & dosagem , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Pontuação de Propensão , Insuficiência Renal/microbiologia , Resultado do Tratamento , Infecções Urinárias/microbiologiaRESUMO
OBJECTIVES: The effectiveness of anidulafungin versus liposomal amphotericin B (LAmB) for treating experimental Candida parapsilosis catheter-related infection by an antifungal-lock technique was assessed. METHODS: Two clinical strains of C. parapsilosis (CP12 and CP54) were studied. In vitro studies were used to determine the biofilm MICs (MBIC50 and MBIC90) by XTT reduction assay and LIVE/DEAD biofilm viability for anidulafungin and LAmB on 96-well microtitre polystyrene plates and silicone discs. An intravenous catheter was implanted in New Zealand white rabbits. Infection was induced by locking the catheter for 48 h with the inoculum. The 48 h antifungal-lock treatment groups included control, 3.3 mg/mL anidulafungin and 5.5 mg/mL LAmB. RESULTS: Anidulafungin showed better in vitro activity than LAmB against C. parapsilosis growing in biofilm on silicone discs. MBIC90 of LAmB: CP12, >1024 mg/L; CP54, >1024 mg/L. MBIC90 of anidulafungin: CP12, 1 mg/L; CP54, 1 mg/L (Pâ≤â0.05). Moreover, only anidulafungin (1 mg/L) showed >90% non-viable cells in the LIVE/DEAD biofilm viability assay on silicone discs. No differences were observed between the in vitro susceptibility of anidulafungin or LAmB when 96-well plates were used. Anidulafungin achieved significant reductions relative to LAmB in log10 cfu recovered from the catheter tips for both strains (Pâ≤â0.05). Only anidulafungin achieved negative catheter tip cultures (CP12 63%, CP54 73%, Pâ≤â0.05). CONCLUSIONS: Silicone discs may be a more reliable substrate for the study of in vitro biofilm susceptibility of C. parapsilosis. Anidulafungin-lock therapy showed the highest activity for experimental catheter-related infection with C. parapsilosis.
Assuntos
Antifúngicos/uso terapêutico , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Equinocandinas/uso terapêutico , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Anidulafungina , Animais , Antifúngicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida/isolamento & purificação , Candidíase/microbiologia , Cateteres de Demora/microbiologia , Equinocandinas/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Coelhos , SiliconesRESUMO
We report 2 cases of recurrent Campylobacter coli enteritis caused by macrolide- and fluoroquinolone-resistant strains in 2 patients with hypogammaglobulinemia, successfully treated with a prolonged course of fosfomycin-tromethamine with no side effects. Fosfomycin-tromethamine may be a feasible alternative therapy for recurrent enteritis caused by Campylobacter species resistant to first-line drugs.
Assuntos
Antibacterianos/uso terapêutico , Campylobacter/efeitos dos fármacos , Campylobacter/patogenicidade , Enterite/tratamento farmacológico , Fosfomicina/uso terapêutico , Trometamina/uso terapêutico , Agamaglobulinemia/tratamento farmacológico , Idoso de 80 Anos ou mais , Feminino , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-IdadeRESUMO
This is a retrospective study of 15 difficult-to-treat (i.e., exhibiting previous failure, patient side effects, or resistance to ciprofloxacin and co-trimoxazole) chronic bacterial prostatitis infections (5 patients with multidrug-resistant Enterobacteriaceae [MDRE]) receiving fosfomycin-tromethamine at a dose of 3 g per 48 to 72 h for 6 weeks. After a median follow-up of 20 months, 7 patients (47%) had a clinical response, and 8 patients (53%) had persistent microbiological eradication; 4/5 patients with MDRE isolates achieved eradication. There were no side effects. Fosfomycin-tromethamine is a possible alternative therapy for chronic bacterial prostatitis.
Assuntos
Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Fosfomicina/uso terapêutico , Prostatite/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prostatite/microbiologia , Estudos Retrospectivos , Trometamina , Adulto JovemRESUMO
Both bacteremia and infective endocarditis caused by Staphylococcus aureus are common and severe diseases. The prognosis may darken not infrequently, especially in the presence of intracardiac devices or methicillin-resistance. Indeed, the optimization of the antimicrobial therapy is a key step in the outcome of these infections. The high rates of treatment failure and the increasing interest in the influence of vancomycin susceptibility in the outcome of infections caused by both methicillin-susceptible and -resistant isolates has led to the research of novel therapeutic schemes. Specifically, the interest raised in recent years on the new antimicrobials with activity against methicillin-resistant staphylococci has been also extended to infections caused by susceptible strains, which still carry the most important burden of infection. Recent clinical and experimental research has focused in the activity of new combinations of antimicrobials, their indication and role still being debatable. Also, the impact of an appropriate empirical antimicrobial treatment has acquired relevance in recent years. Finally, it is noteworthy the impact of the implementation of a systematic bundle of measures for improving the outcome. The aim of this clinical guideline is to provide an ensemble of recommendations in order to improve the treatment and prognosis of bacteremia and infective endocarditis caused by S. aureus, in accordance to the latest evidence published.
Assuntos
Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Gerenciamento Clínico , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/cirurgia , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Vigilância da População , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Padrão de Cuidado , Infecções Estafilocócicas/diagnóstico por imagemRESUMO
Bacteremia and infective endocarditis caused by Staphylococcus aureus are common and severe diseases. Optimization of treatment is fundamental in the prognosis of these infections. The high rates of treatment failure and the increasing interest in the influence of vancomycin susceptibility in the outcome of infections caused by both methicillin-susceptible and -resistant isolates have led to research on novel therapeutic schemes. The interest in the new antimicrobials with activity against methicillin-resistant staphylococci has been extended to susceptible strains, which still carry the most important burden of infection. New combinations of antimicrobials have been investigated in experimental and clinical studies, but their role is still being debated. Also, the appropriateness of the initial empirical therapy has acquired relevance in recent years. The aim of this guideline is to update the 2009 guidelines and to provide an ensemble of recommendations in order to improve the treatment of staphylococcal bacteremia and infective endocarditis, in accordance with the latest published evidence.
Assuntos
Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Gerenciamento Clínico , Farmacorresistência Bacteriana Múltipla , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/cirurgia , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Vigilância da População , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Padrão de Cuidado , Infecções Estafilocócicas/diagnóstico por imagemRESUMO
BACKGROUND: Concerns have arisen regarding the optimal antifungal regimen for Candida parapsilosis bloodstream infection (BSI) in view of its reduced susceptibility to echinocandins. METHODS: The Prospective Population Study on Candidemia in Spain (CANDIPOP) is a prospective multicenter, population-based surveillance program on Candida BSI conducted through a 12-month period in 29 Spanish hospitals. Clinical isolates were identified by DNA sequencing, and antifungal susceptibility testing was performed by the European Committee on Antimicrobial Susceptibility Testing methodology. Predictors for clinical failure (all-cause mortality between days 3 to 30, or persistent candidemia for ≥72 hours after initiation of therapy) in episodes of C. parapsilosis species complex BSI were assessed by logistic regression analysis. We further analyzed the impact of echinocandin-based regimen as the initial antifungal therapy (within the first 72 hours) by using a propensity score approach. RESULTS: Among 752 episodes of Candida BSI identified, 200 (26.6%) were due to C. parapsilosis species complex. We finally analyzed 194 episodes occurring in 190 patients. Clinical failure occurred in 58 of 177 (32.8%) of evaluable episodes. Orotracheal intubation (adjusted odds ratio [AOR], 2.81; P = .018) and septic shock (AOR, 2.91; P = .081) emerged as risk factors for clinical failure, whereas early central venous catheter removal was protective (AOR, 0.43; P = .040). Neither univariate nor multivariate analysis revealed that the initial use of an echinocandin-based regimen had any impact on the risk of clinical failure. Incorporation of the propensity score into the model did not change this finding. CONCLUSIONS: The initial use of an echinocandin-based regimen does not seem to negatively influence outcome in C. parapsilosis BSI.
Assuntos
Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Equinocandinas/uso terapêutico , Adulto , Idoso , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidemia/epidemiologia , Candidemia/microbiologia , Farmacorresistência Fúngica , Equinocandinas/farmacologia , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Vigilância da População , Pontuação de Propensão , Estudos Prospectivos , Fatores de Risco , Análise de Sequência de DNA , Espanha , Resultado do TratamentoRESUMO
European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints classify Candida strains with a fluconazole MIC < or = 2 mg/liter as susceptible, those with a fluconazole MIC of 4 mg/liter as representing intermediate susceptibility, and those with a fluconazole MIC > 4 mg/liter as resistant. Machine learning models are supported by complex statistical analyses assessing whether the results have statistical relevance. The aim of this work was to use supervised classification algorithms to analyze the clinical data used to produce EUCAST fluconazole breakpoints. Five supervised classifiers (J48, Correlation and Regression Trees [CART], OneR, Naïve Bayes, and Simple Logistic) were used to analyze two cohorts of patients with oropharyngeal candidosis and candidemia. The target variable was the outcome of the infections, and the predictor variables consisted of values for the MIC or the proportion between the dose administered and the MIC of the isolate (dose/MIC). Statistical power was assessed by determining values for sensitivity and specificity, the false-positive rate, the area under the receiver operating characteristic (ROC) curve, and the Matthews correlation coefficient (MCC). CART obtained the best statistical power for a MIC > 4 mg/liter for detecting failures (sensitivity, 87%; false-positive rate, 8%; area under the ROC curve, 0.89; MCC index, 0.80). For dose/MIC determinations, the target was >75, with a sensitivity of 91%, a false-positive rate of 10%, an area under the ROC curve of 0.90, and an MCC index of 0.80. Other classifiers gave similar breakpoints with lower statistical power. EUCAST fluconazole breakpoints have been validated by means of machine learning methods. These computer tools must be incorporated in the process for developing breakpoints to avoid researcher bias, thus enhancing the statistical power of the model.
Assuntos
Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Biologia Computacional , Fluconazol/uso terapêutico , Algoritmos , Candida/efeitos dos fármacos , Humanos , Testes de Sensibilidade MicrobianaRESUMO
Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and clinically important. The rise in MRSA bacteremia and endocarditis is related with the increasing use of venous catheters and other vascular procedures. Glycopeptides have been the reference drugs for treating these infections. Unfortunately their activity is not completely satisfactory, particularly against MRSA strains with MICs > 1 microg/mL. The development of new antibiotics, such as linezolid and daptomycin, and the promise of future compounds (dalvabancin, ceftobiprole and telavancin) may change the expectatives in this field.The principal aim of this consensus document was to formulate several recommendations to improve the outcome of MRSA bacteremia and endocarditis, based on the latest reported scientific evidence. This document specifically analyzes the approach for three clinical situations: venous catheter-related bacteremia, persistent bacteremia, and infective endocarditis due to MRSA.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Endocardite Bacteriana/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/tratamento farmacológico , Antibacterianos/farmacologia , Bacteriemia/etiologia , Bacteriemia/microbiologia , Cateterismo/efeitos adversos , Cateterismo Venoso Central/efeitos adversos , Ensaios Clínicos como Assunto , Remoção de Dispositivo , Farmacorresistência Bacteriana Múltipla , Diagnóstico Precoce , Endocardite Bacteriana/etiologia , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/cirurgia , Contaminação de Equipamentos , Medicina Baseada em Evidências , Próteses Valvulares Cardíacas/efeitos adversos , Implante de Prótese de Valva Cardíaca , Humanos , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Prevalência , Estudos Prospectivos , Infecções Relacionadas à Prótese , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/cirurgia , Vancomicina/uso terapêuticoRESUMO
We report on the correlation of the outcomes for two cohorts of patients who had been treated for candidemia (126 episodes) or oropharyngeal candidiasis (110 episodes) with various doses of fluconazole and the MIC of fluconazole obtained by using the EUCAST standard for fermentative yeasts. Of 145 episodes caused by an isolate with a fluconazole MIC < or =2 mg/liter, 93.7% (136 of 145) responded to fluconazole treatment. The response for those infected with a strain with a MIC of 4 mg/liter was 66% but reached 100% when the dose was greater than 100 mg/day, whereas the response for those infected with strains with MICs > or =8 mg/liter was only 12%. Hence, a MIC of 2 mg/liter or 4 mg/liter was able to predict successful treatment. A cure rate of 93.9% (140 of 149) was achieved when the dose/MIC ratio was > or =100 but fell to 14.6% (16 of 109) when the ratio was less. The dose/MIC required to achieve a response rate of 50% (the 50% effective concentration) was 43.7 for the cohort of patients with oropharyngeal candidiasis. Classification and regression analysis indicated that a dose/MIC of 35.5 was the threshold for the prediction of cure or failure. However, an increase in exposure above this threshold further increased the probability of cure, and all patients were cured when the dose/MIC exceeded 100. Monte Carlo simulations showed a probability of target attainment of 99% at MICs < or =2 mg/liter and a pharmacodynamic target of a dose/MIC ratio of 100, which was equivalent to an unbound fraction of the fluconazole area under the curve versus the MIC of 79.
Assuntos
Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Fungemia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/farmacocinética , Área Sob a Curva , Candidíase/microbiologia , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/microbiologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Fluconazol/farmacocinética , Fungemia/microbiologia , Infecções por HIV/complicações , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Mucosa/microbiologia , Orofaringe/microbiologia , Análise de Regressão , Espanha , Resultado do TratamentoRESUMO
BACKGROUND: Infection is one of the main problems associated with long-term central venous catheters. This study assesses the effectiveness of antibiotic-lock therapy (ALT) for treating catheter-related bacteraemia (CRB). METHODS: CRB was defined as quantitative blood culture counts through any catheter lumen 5-fold greater than concurrent peripheral blood culture, and qualitative blood culture positive for the same microorganism in all samples. Systemic treatment and ALT were started simultaneously using vancomycin (2000 mg/L) for Gram-positive organisms, and ciprofloxacin or amikacin (2000 mg/L) for Gram-negative bacilli. Heparin was added to ALT. Effectiveness was assessed by clinical and microbiological criteria. Cure was defined as negative blood cultures at both sites without catheter removal at 1 month after the completion of therapy. RESULTS: A total of 115 episodes of CRB in 98 patients were analysed. Catheters were used for chemotherapy (50 episodes), haemodialysis (37), total parenteral nutrition (24) and combined chemotherapy and nutrition (4). Median time from catheter placement to CRB onset was 105 days (IQ range 26-210). Aetiologies included Gram-positive organisms [56 coagulase-negative staphylococci (CoNS), 20 Staphylococcus aureus and 5 other organisms] in 81 episodes (70%), Gram-negative bacilli (11 Escherichia coli, 5 Pseudomonas aeruginosa and 10 other organisms) in 26 (23%) and polymicrobial in 8 (7%). A total of 94 episodes were cured (82%). There were 21 therapeutic failures: 9 S. aureus (1 related death), 9 CoNS, 1 P. aeruginosa, 1 Proteus vulgaris and 1 polymicrobial. Median catheter follow-up in therapeutic success was 168 days (range 7-2740). CONCLUSIONS: ALT combined with systemic antibiotics seems to be effective for treating CRB, especially in Gram-negative and CoNS episodes. S. aureus CRB had an elevated rate of therapeutic failure.