RESUMO
BACKGROUND: Evidence supporting combination treatment with a beta-lactam plus an aminoglycoside (C-BA) for endocarditis caused by viridans and gallolyticus group streptococci (VGS-GGS) with intermediate susceptibility to penicillin (PENI-I) is lacking. We assessed the clinical characteristics and outcomes of PEN-I VGS-GGS endocarditis and compared the effectiveness and safety of C-BA with third-generation cephalosporin monotherapy. METHODS: Retrospective analysis of prospectively collected data of a cohort of definite endocarditis caused by penicillin-susceptible and PENI-I VGS-GGS (penicillin minimum inhibitory concentration ranging from 0.25 to 2 mg/L) between 2008 and 2018 in 40 Spanish hospitals. We compared cases treated with monotherapy or with C-BA and performed multivariable analyses of risk factors for in-hospital and 1-year mortality. RESULTS: A total of 914 consecutive cases of definite endocarditis caused by VGS-GGS with complete or intermediate susceptibility to penicillin were included. A total of 688 (75.3%) were susceptible to penicillin and 226 (24.7%) were PENI-I. Monotherapy was used in 415 (45.4%) cases (cephalosporin in 331 cases) and 499 (54.6%) cases received C-BA. In-hospital mortality was 11.9%, and 190 (20.9%) patients developed acute kidney injury. Heart failure (odds ratio [OR]: 6.06; 95% confidence interval [CI]: 1.37-26.87; P = .018), central nervous system emboli (OR: 9.83; 95% CI: 2.17-44.49; P = .003) and intracardiac abscess (OR: 13.47; 95% CI: 2.24-81.08; P = .004) were independently associated with in-hospital mortality among PEN-I VGS-GGS cases, while monotherapy was not (OR: 1.01; 95% CI: .26-3.96; P = .982). CONCLUSIONS: Our findings support the use of cephalosporin monotherapy in PEN-I VGS-GGS endocarditis in order to avoid nephrotoxicity without adversely affecting patient outcomes.
Assuntos
Anti-Infecciosos , Endocardite Bacteriana , Endocardite , Infecções Estreptocócicas , Humanos , Penicilinas/uso terapêutico , Estudos Retrospectivos , Endocardite Bacteriana/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Antibacterianos/uso terapêutico , Endocardite/tratamento farmacológico , Anti-Infecciosos/uso terapêutico , Estreptococos Viridans , Resultado do Tratamento , Cefalosporinas/uso terapêuticoRESUMO
BACKGROUND: Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors. METHODS: Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections. RESULTS: Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40-62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection. CONCLUSIONS: Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.
Assuntos
Infecções por Mycobacterium não Tuberculosas , Transplante de Órgãos , Humanos , Masculino , Pessoa de Meia-Idade , Criança , Feminino , Estudos de Casos e Controles , Transplantados , Estudos Retrospectivos , Antifúngicos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Transplante de Órgãos/efeitos adversos , Fatores de Risco , Micobactérias não TuberculosasRESUMO
We aimed to compare the efficacy of ceftazidime-avibactam (CAZ-AVI) versus the best available therapy (BAT) in solid organ transplant (SOT) recipients with bloodstream infection caused by carbapenemase-producing Klebsiella pneumoniae (CPKP-BSI). A retrospective (2016-2021) observational cohort study was performed in 14 INCREMENT-SOT centers (ClinicalTrials.gov identifier: NCT02852902; Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to ESBL- or Carbapenemase-producing Enterobacterales in Solid Organ Transplantation: an Observational Multinational Study). Outcomes were 14-day and 30-day clinical success (complete resolution of attributable manifestations, adequate source control, and negative follow-up blood cultures) and 30-day all-cause mortality. Multivariable logistic and Cox regression analyses adjusted for the propensity score to receive CAZ-AVI were constructed. Among 210 SOT recipients with CPKP-BSI, 149 received active primary therapy with CAZ-AVI (66/149) or BAT (83/149). Patients treated with CAZ-AVI had higher 14-day (80.7% vs 60.6%, P = .011) and 30-day (83.1% vs 60.6%, P = .004) clinical success and lower 30-day mortality (13.25% vs 27.3%, P = .053) than those receiving BAT. In the adjusted analysis, CAZ-AVI increased the probability of 14-day (adjusted odds ratio [aOR], 2.65; 95% confidence interval [CI], 1.03-6.84; P = .044) and 30-day clinical success (aOR, 3.14; 95% CI, 1.17-8.40; P = .023). In contrast, CAZ-AVI therapy was not independently associated with 30-day mortality. In the CAZ-AVI group, combination therapy was not associated with better outcomes. In conclusion, CAZ-AVI may be considered a first-line treatment in SOT recipients with CPKP-BSI.
Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Sepse , Humanos , Antibacterianos/uso terapêutico , Klebsiella pneumoniae , Estudos Retrospectivos , Combinação de Medicamentos , Testes de Sensibilidade Microbiana , Infecções por Klebsiella/tratamento farmacológicoRESUMO
Current guidelines recommend against systematic screening or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of post-transplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR]: 1.1 - 10.5). Most episodes (96.4% [132/137]) were caused by gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum ß-lactamase-producing Enterobacterales [20.4%] and carbapenem-resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [95%CI]: 31.9 - 48.9) for the whole cohort and 42.3% (95%CI: 31.2 - 54.0) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR]: 2.42; 95%CI: 1.11 - 5.29; P-value = 0.027) and use of fosfomycin as salvage therapy (OR: 8.31; 95%CI: 1.67 - 41.35; P-value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse event were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.
RESUMO
BACKGROUND: Infections caused by carbapenemase-producing Enterobacterales (CPE) are not well represented in pivotal trials with ceftazidime/avibactam. The best strategy for the treatment of these infections is unknown. METHODS: We conducted a multicentre retrospective observational study of patients who received ≥48â h of ceftazidime/avibactam or best available therapy (BAT) for documented CPE infections. The primary outcome was 30â day crude mortality. Secondary outcomes were 21â day clinical response and microbiological response. A multivariate logistic regression model was used to identify factors predictive of 30â day crude mortality. A propensity score to receive treatment with ceftazidime/avibactam was used as a covariate in the analysis. RESULTS: The cohort included 339 patients with CPE infections. Ceftazidime/avibactam treatment was used in 189 (55.8%) patients and 150 (44.2%) received BAT at a median of 2â days after diagnosis of infection. In multivariate analysis, ceftazidime/avibactam treatment was associated with survival (OR 0.41, 95% CI 0.20-0.80; P = 0.01), whereas INCREMENT-CPE scores of >7 points (OR 2.57, 95% CI 1.18-1.5.58; P = 0.01) and SOFA score (OR 1.20, 95% CI 1.08-1.34; P = 0.001) were associated with higher mortality. In patients with INCREMENT-CPE scores of >7 points, ceftazidime/avibactam treatment was associated with lower mortality compared with BAT (16/73, 21.9% versus 23/49, 46.9%; P = 0.004). Ceftazidime/avibactam was also an independent factor of 21â day clinical response (OR 2.43, 95% CI 1.16-5.12; P = 0.02) and microbiological eradication (OR 0.40, 95% CI 0.18-0.85; P = 0.02). CONCLUSIONS: Ceftazidime/avibactam is an effective alternative for the treatment of CPE infections, especially in patients with INCREMENT-CPE scores of >7 points. A randomized controlled trial should confirm these findings.
Assuntos
Antibacterianos , Ceftazidima , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Proteínas de Bactérias , Ceftazidima/uso terapêutico , Combinação de Medicamentos , Humanos , Testes de Sensibilidade Microbiana , beta-LactamasesRESUMO
OBJECTIVES: (1) To describe the incidence, clinical characteristics, treatment and outcome of Aspergillus Endocarditis (AE) in a nationwide multicentric cohort (GAMES). (2) To compare the AE cases of the GAMES cohort, with the AE cases reported in the literature since 2010. (3) To identify variables related to mortality. METHODS: We recruited 10 AE cases included in the GAMES cohort (January 2008-December 2018) and 51 cases from the literature published from January 2010 to July 2019. RESULTS: 4528 patients with infectious endocarditis (IE) were included in the GAMES cohort, of them 10 (0.2%) were AE. After comparing our 10 cases with the 51 of the literature, no differences were found. Analysing the 61 AE cases together, 55.7% were male, median age 45 years. Their main underlying conditions were as follows: prosthetic valve surgery (34.4%) and solid organ transplant (SOT) (19.7%). Mainly affecting mitral (36.1%) and aortic valve (29.5%). Main isolated species were as follows: Aspergillus fumigatus (47.5%) and Aspergillus flavus (24.6%). Embolisms occurred in 54%. Patients were treated with antifungals (90.2%), heart surgery (85.2%) or both (78.7%). Overall, 52.5% died. A greater mortality was observed in immunosuppressed patients (59.4% vs. 24.1%, OR = 4.09, 95%CI = 1.26-13.19, p = .02), and lower mortality was associated with undergoing cardiac surgery plus azole therapy (28.1% vs. 65.5%, OR = 0.22, 95%CI = 0.07-0.72, p = .01). CONCLUSIONS: AE accounts for 0.2% of all IE episodes of a national multicentric cohort, mainly affecting patients with previous valvular surgery or SOT recipients. Mortality remains high especially in immunosuppressed hosts and azole-based treatment combined with surgical resection are related to a better outcome.
Assuntos
Aspergilose , Endocardite , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergillus , Aspergillus fumigatus , Endocardite/tratamento farmacológico , Endocardite/terapia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.
Assuntos
Bacteriemia , Transplante de Rim , Infecções Urinárias , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Estudos de Coortes , Ertapenem , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Infecções Urinárias/tratamento farmacológico , beta-LactamasesRESUMO
BACKGROUND: The diagnosis of invasive aspergillosis (IA) can be problematic in solid organ transplantation (SOT). The prognosis greatly varies according to the type of transplant, and the impact of prophylaxis is not well defined. PATIENTS AND METHODS: The Diaspersot cohort analyses the impact of IA in SOT in Spain during the last 10 years. Proven and probable/putative IA was included. RESULTS: We analysed 126 cases of IA. The incidences of IA were as follows: 6.5%, 2.9%, 1.8% and 0.6% for lung, heart, liver and kidney transplantation, respectively. EORTC/MSG criteria confirmed only 49.7% of episodes. Tree-in-bud sign or ground-glass infiltrates were present in 56.3% of patients, while serum galactomannan (optical density index >0.5) was positive in 50.6%. A total of 41.3% received combined antifungal therapy. Overall mortality at 3 months was significantly lower (p < 0.001) in lung transplant recipients (14.8%) than in all other transplants [globally: 48.6%; kidney 52.0%, liver 58.3%, heart 31.2%, and combined 42.9%]. Fifty-four percent of episodes occurred despite the receipt of antifungal prophylaxis, and in 10%, IA occurred during prophylaxis (breakthrough infection), with both nebulised amphotericin (in lung transplant recipients) and candins (in the rest). CONCLUSIONS: Invasive aspergillosis diagnostic criteria, applied to SOT patients, may differ from those established for haematological patients. IA in lung transplants has a higher incidence, but is associated with a better prognosis than other transplants. Combination therapy is frequently used for IA in SOT. Prophylactic measures require optimisation of its use within this population.
Assuntos
Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/terapia , Transplante de Órgãos , Adulto , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Causalidade , Estudos de Coortes , Feminino , Humanos , Aspergilose Pulmonar Invasiva/epidemiologia , Aspergilose Pulmonar Invasiva/etiologia , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , Espanha/epidemiologia , Voriconazol/efeitos adversos , Voriconazol/uso terapêutico , Adulto JovemRESUMO
Oral fosfomycin may constitute an alternative for the treatment of lower urinary tract infections (UTIs) in kidney transplant recipients (KTRs), particularly in view of recent safety concerns with fluroquinolones. Specific data on the efficacy and safety of fosfomycin in KTR are scarce. We performed a retrospective study in 14 Spanish hospitals including KTRs treated with oral fosfomycin (calcium and trometamol salts) for posttransplant cystitis between January 2005 and December 2017. A total of 133 KTRs developed 143 episodes of cystitis. Most episodes (131 [91.6%]) were produced by gram-negative bacilli (GNB), and 78 (54.5%) were categorized as multidrug resistant (including extended-spectrum ß-lactamase-producing Enterobacteriaceae [14%] or carbapenem-resistant GNB [3.5%]). A median daily dose of 1.5 g of fosfomycin (interquartile range [IQR]: 1.5-2) was administered for a median of 7 days (IQR: 3-10). Clinical cure (remission of UTI-attributable symptoms at the end of therapy) was achieved in 83.9% (120/143) episodes. Among those episodes with follow-up urine culture, microbiological cure at month 1 was achieved in 70.2% (59/84) episodes. Percutaneous nephrostomy was associated with a lower probability of clinical cure (adjusted odds ratio: 10.50; 95% confidence interval: 0.98-112.29; P = 0.052). In conclusion, fosfomycin is an effective orally available alternative for treating cystitis among KTRs.
Assuntos
Antibacterianos/administração & dosagem , Fosfomicina/administração & dosagem , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Transplante de Rim , Complicações Pós-Operatórias/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antibacterianos/uso terapêutico , Feminino , Seguimentos , Fosfomicina/uso terapêutico , Infecções por Bactérias Gram-Negativas/etiologia , Infecções por Bactérias Gram-Positivas/etiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Resultado do Tratamento , Infecções Urinárias/etiologiaRESUMO
BACKGROUND: Streptococcus tigurinus was recently described as a new streptococcal species within the viridans group streptococci (VGS). The objectives of the present work were to analyse the clinical and microbiological characteristics of S. tigurinus isolated from patients with bacteraemias, to determine the prevalence of S. tigurinus among VGS endocarditis in Spain, and to compare the clinical characteristics and outcomes of endocarditis caused by S. tigurinus and other VGS. METHODS: Retrospective nationwide study, performed between 2008 and 2016 in 9 Spanish hospitals from 7 different provinces comprising 237 cases of infective endocarditis. Streptococcal isolates were identified by sequencing fragments of their 16S rRNA, sodA and groEL genes. Clinical data of patients with streptococcal endocarditis were prospectively collected according to a pre-established protocol. RESULTS: Patients with endocarditis represented 7/9 (77.8%) and 26/86 (30.2%) of the bacteraemias caused by S. tigurinus and other VGS, respectively (p < 0.001), in two of the hospital participants. Among patients with streptococcal endocarditis, 12 different Streptococcus species were recognized being S. oralis, S. tigurinus and S. mitis the three more common. No relevant statistical differences were observed in the clinical characteristics and outcomes of endocarditis caused by the different VGS species. CONCLUSIONS: In this multicenter study performed in Spain, S. tigurinus showed a higher predilection for the endocardial endothelium as compared to other VGS. However, clinical characteristics and outcomes of endocarditis caused by S. tigurinus did not significantly differ from endocarditis caused by other oral streptococci.
Assuntos
Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/epidemiologia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/epidemiologia , Estreptococos Viridans/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/diagnóstico , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Endocardite Bacteriana/microbiologia , Monitoramento Epidemiológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/microbiologia , Estreptococos Viridans/classificação , Estreptococos Viridans/fisiologia , Adulto JovemRESUMO
Background: Seasonal influenza infection may cause significant morbidity and mortality in transplant recipients. The purpose of this study was to assess the epidemiology of symptomatic influenza infection posttransplant and determine risk factors for severe disease. Methods: Twenty centers in the United States, Canada, and Spain prospectively enrolled solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT) recipients with microbiologically confirmed inï¬uenza over 5 consecutive years (2010-2015). Demographics, microbiology data, and outcomes were collected. Serial nasopharyngeal swabs were collected at diagnosis and upto 28 days, and quantitative polymerase chain reaction for influenza A was performed. Results: We enrolled 616 patients with confirmed influenza (477 SOT; 139 HSCT). Pneumonia at presentation was in 134 of 606 (22.1%) patients. Antiviral therapy was given to 94.1% for a median of 5 days (range, 1-42 days); 66.5% patients were hospitalized and 11.0% required intensive care unit (ICU) care. The receipt of vaccine in the same influenza season was associated with a decrease in disease severity as determined by the presence of pneumonia (odds ratio [OR], 0.34 [95% confidence interval {CI}, .21-.55], P < .001) and ICU admission (OR, 0.49 [95% CI, .26-.90], P = .023). Similarly, early antiviral treatment (within 48 hours) was associated with improved outcomes. In patients with influenza A, pneumonia, ICU admission, and not being immunized were also associated with higher viral loads at presentation (P = .018, P = .008, and P = .024, respectively). Conclusions: Annual influenza vaccination and early antiviral therapy are associated with a significant reduction in influenza-associated morbidity, and should be emphasized as strategies to improve outcomes of transplant recipients.
Assuntos
Influenza Humana/epidemiologia , Transplantados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Canadá/epidemiologia , Criança , Pré-Escolar , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Vacinas contra Influenza/uso terapêutico , Influenza Humana/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Estados Unidos/epidemiologia , Vacinação , Adulto JovemRESUMO
Transplantation activity is increasing, leading to a growing number of patients at risk for toxoplasmosis. We reviewed toxoplasmosis prevention practices, prevalence, and outcomes for hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT; heart, kidney, or liver) patients in Europe. We collected electronic data on the transplant population and prevention guidelines/regulations and clinical data on toxoplasmosis cases diagnosed during 2010-2014. Serologic pretransplant screening of allo-hematopoietic stem cell donors was performed in 80% of countries, screening of organ donors in 100%. SOT recipients were systematically screened in 6 countries. Targeted anti-Toxoplasma chemoprophylaxis was heterogeneous. A total of 87 toxoplasmosis cases were recorded (58 allo-HSCTs, 29 SOTs). The 6-month survival rate was lower among Toxoplasma-seropositive recipients and among allo-hematopoietic stem cell and liver recipients. Chemoprophylaxis improved outcomes for SOT recipients. Toxoplasmosis remains associated with high mortality rates among transplant recipients. Guidelines are urgently needed to standardize prophylactic regimens and optimize patient management.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Órgãos/efeitos adversos , Toxoplasmose/epidemiologia , Toxoplasmose/etiologia , Adulto , Europa (Continente)/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , TransplantadosRESUMO
PURPOSE: To analyze the influence of adding gentamicin to a regimen consisting of ß-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). METHODS: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on ß-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. RESULTS: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84-11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03-6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29-3.38) in the multivariable analysis. CONCLUSIONS: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.
Assuntos
Antibacterianos/administração & dosagem , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/mortalidade , Gentamicinas/administração & dosagem , Próteses Valvulares Cardíacas/microbiologia , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/mortalidade , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/mortalidade , Idoso , Antibacterianos/uso terapêutico , Cloxacilina/administração & dosagem , Cloxacilina/uso terapêutico , Endocardite Bacteriana/complicações , Feminino , Gentamicinas/uso terapêutico , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/etiologia , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/administração & dosagem , Vancomicina/uso terapêuticoRESUMO
BACKGROUND: Influenza vaccine effectiveness is not optimal in solid organ transplant recipients (SOTR). We hypothesized that a booster dose might increase it. METHODS: TRANSGRIPE 1-2 is a phase 3, randomized, controlled, multicenter, open-label clinical trial. Patients were randomly assigned (1:1 stratified by study site, type of organ, and time since transplantation) to receive 1 dose (control group) or 2 doses (booster group) of the influenza vaccine 5 weeks apart. RESULTS: A total of 499 SOTR were enrolled. Although seroconversion at 10 weeks did not meet significance in the modified intention-to-treat population, seroconversion rates were significantly higher in the booster arm for the per-protocol population (53.8% vs 37.6% for influenza A(H1N1)pdm; 48.1% vs 32.3% for influenza A(H3N2); and 90.7% vs 75% for influenza B; P < .05). Furthermore, seroprotection at 10 weeks was higher in the booster group: 54% vs 43.2% for A(H1N1)pdm; 56.9% vs 45.5% for A(H3N2); and 83.4% vs 71.8% for influenza B (P < .05). The number needed to treat to seroprotect 1 patient was <10. The clinical efficacy (99.2% vs 98.8%) and serious adverse events (6.4% vs 7.5%) were similar for both groups. CONCLUSIONS: In SOTR, a booster strategy 5 weeks after standard influenza vaccination is safe and effective and induces an increased antibody response compared with standard influenza vaccination consisting of a single dose. CLINICAL TRIALS REGISTRATION: EudraCT (2011-003243-21).
Assuntos
Imunidade , Imunomodulação , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Transplantados , Vacinas de Produtos Inativados/imunologia , Anticorpos Antivirais/imunologia , Comorbidade , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Transplante de Órgãos , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversosRESUMO
OBJECTIVE: The objective of this study was to determine risk factors for nosocomial infections (NIs) and predictors of mortality in patients with prosthetic vascular grafts (PVGs). METHODS: This was a prospective cohort study of all consecutive patients who underwent PVG of the abdominal aorta with or without iliac-femoral involvement and peripheral PVG from April 2008 to August 2009 at a university hospital. Patients younger than 15 years and those with severe immunodeficiency were excluded. The follow-up period was until 3 years after surgery or until death. RESULTS: There were 261 patients included; 230 (88.12%) were male, and the mean age was 67.57 (standard deviation, 10.82) years. The reason for operation was aortic aneurysm in 49 (18.77%) patients or lower limb arteriopathy in 212 (81.23%) patients. NIs occurred in 71 (27.20%) patients. Of these, 42 were surgical site infections (SSIs), of which 61.9% occurred in the lower extremities (14 superficial, 10 deep, and 2 PVG infections) and 38.1% in the abdomen (7 superficial, 7 deep, and 2 PVG infections); 15 were respiratory tract infections; and 15 were urinary tract infections. Active lower extremity skin and soft tissue infection (SSTI) at the time of surgery was a significant predictor of NI for both types of PVG (abdominal aortic PVG: adjusted odds ratio [OR], 12.6; 95% confidence interval [CI], 1.15-138.19; peripheral PVG: adjusted OR, 2.43; 95% CI, 1.08-5.47). Other independent predictors of NI were mechanical ventilation (adjusted OR, 55.96; 95% CI, 3.9-802.39) for abdominal aortic PVG and low hemoglobin levels on admission (adjusted OR, 0.84; 95% CI, 0.71-0.99) and emergent surgery (adjusted OR, 4.39; 95% CI, 1.51-12.74) for peripheral PVG. The in-hospital mortality rate was 1.92%. The probability of surviving the first month was 0.96, and significant predictors of mortality were active lower extremity SSTI (adjusted risk ratio [RR], 12.07; 95% CI, 1.04-154.75), high postsurgical glucose levels (adjusted RR, 1.02; 95% CI, 1.00-1.04), and noninfectious surgical complications (adjusted RR, 19.38; 95% CI, 2.25-167.29). The long-term mortality rate was 11.88%. The probability of surviving at 12, 24, and 36 months was 0.94, 0.92, and 0.87, respectively. Variables significantly associated with long-term death were older age (adjusted RR, 1.08; 95% CI, 1.01-1.15), high values of creatinine on discharge (adjusted RR, 1.91; 95% CI, 1.08-3.38), and an SSI with the highest adjusted RR (6.35; 95% CI, 1.87-21.53). CONCLUSIONS: SSI was the primary NI. The risk of NI depended primarily on the presence of a lower extremity SSTI at the time of surgery, whereas mortality was determined by age, surgical complications during the operation, and SSI. These findings suggest that in those cases in which surgery is reasonably delayed, surgery should be deferred until the lower extremity SSTIs are resolved.
Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Prótese Vascular/efeitos adversos , Infecção Hospitalar/microbiologia , Doenças Vasculares Periféricas/cirurgia , Infecções Relacionadas à Prótese/microbiologia , Infecções Respiratórias/microbiologia , Infecção da Ferida Cirúrgica/microbiologia , Infecções Urinárias/microbiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Implante de Prótese Vascular/mortalidade , Distribuição de Qui-Quadrado , Creatinina/sangue , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/mortalidade , Infecção Hospitalar/terapia , Feminino , Mortalidade Hospitalar , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Prospectivos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/mortalidade , Infecções Relacionadas à Prótese/terapia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/mortalidade , Infecções Respiratórias/terapia , Fatores de Risco , Espanha , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/mortalidade , Infecção da Ferida Cirúrgica/terapia , Fatores de Tempo , Resultado do Tratamento , Infecções Urinárias/diagnóstico , Infecções Urinárias/mortalidade , Infecções Urinárias/terapiaRESUMO
BACKGROUND: The most common cause of implant failure is aseptic loosening (AL), followed by prosthetic joint infection (PJI). This study evaluates the incidence of PJI among patients operated with suspected AL and whether the diagnosis of PJI was predictive of subsequent implant failure including re-infection, at 2 years of follow up. METHODS: Patients undergoing revision hip or knee arthroplasty due to presumed AL from February 2009 to September 2011 were prospectively evaluated. A sonication fluid of prosthesis and tissue samples for microbiology and histopathology at the time of the surgery were collected. Implant failure include recurrent or persistent infection, reoperation for any reason or need for chronic antibiotic suppression. RESULTS: Of 198 patients with pre-and intraoperative diagnosis of AL, 24 (12.1 %) had postoperative diagnosis of PJI. After a follow up of 31 months (IQR: 21 to 38 months), 9 (37.5 %) of 24 patients in the PJI group had implant failure compared to only 1 (1.1 %) in the 198 of AL group (p < 0.0001). Sensitivity of sonicate fluid culture (>20 CFU) and peri-prosthetic tissue culture were 87.5 % vs 66.7 %, respectively. Specificities were 100 % for both techniques (95 % CI, 97.9-100 %). A greater number of patients with PJI (79.1 %) had previous partial arthroplasty revisions than those patients in the AL group (56.9 %) (p = 0.04). In addition, 5 (55.5 %) patients with PJI and implant failure had more revision arthroplasties during the first year after the last implant placement than those patients with PJI without implant failure (1 patient; 6.7 %) (RR 3.8; 95 % CI 1.4-10.1; p = 0.015). On the other hand, 6 (25 %) patients finally diagnosed of PJI were initially diagnosed of AL in the first year after primary arthroplasty, whereas it was only 16 (9.2 %) patients in the group of true AL (RR 2.7; 95 % CI 1.2-6.1; p = 0.03). CONCLUSIONS: More than one tenth of patients with suspected AL are misdiagnosed PJI. Positive histology and positive peri-implant tissue and sonicate fluid cultures are highly predictive of implant failure in patients with PJI. Patients with greater number of partial hip revisions for a presumed AL had more risk of PJI. Early loosening is more often caused by hidden PJI than late loosening.
Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Bactérias/isolamento & purificação , Falha de Prótese/etiologia , Infecções Relacionadas à Prótese/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Bactérias/classificação , Técnicas Bacteriológicas , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/patologia , Reoperação , Sonicação , Manejo de EspécimesRESUMO
BACKGROUND: Serious infections are common in patients undergoing autologous stem cell transplantation (ASCT) mainly because of the effects of immunosuppression. The innate immune system plays an important role in the defense against different infections. Mannose binding lectin (MBL) is a central molecule of the innate immune system. There are several promoter polymorphisms and structural variants of the MBL2 gene that encodes for this protein. These variants produce low levels of MBL and have been associated with an increased risk for infections. METHODS: Prospective cohort study. The incidence, severity of infections and mortality in 72 consecutive patients with hematologic diseases who underwent ASCT between February 2006 and June 2008 in a tertiary referral center were analyzed according to their MBL2 genotype. INNO-LiPA MBL2 was used for MBL2 gene amplification and genotyping. Relative risks (RR) (IC95%) as measure of association were calculated. Multivariate analysis was performed using logistic regression. RESULTS: A statistically significant higher number of fungal infections was found in patients with MBL2 variants causing low MBL levels (21.1%versus1.9%, p=0.016). In this MBL2 variant group infection was more frequently the cause of mortality than in the MBL2 wild-type group (p=0.05). Although not statistically significant, there was a higher incidence of major infections in the MBL2 variant group as well as a higher number of infections caused by gram-positive bacteria. CONCLUSIONS: Low-producer MBL2 genotypes were associated with an increased number of fungal infections in ASCT patients, which would suggest that MBL has a protective role against such infections. ASCT patients with MBL2 variant genotypes are more likely to die as a result of an infection.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções/etiologia , Lectina de Ligação a Manose/genética , Lectinas de Ligação a Manose/genética , Adulto , Idoso , Feminino , Genótipo , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante AutólogoRESUMO
The emergence and spread of carbapenemase-producing Enterobacteriaceae is an important and very concerning problem. There is an urgent need of new antibimicrobials for treating these infections. Currently there are some options in the pipeline. Several new beta-lactamase and carbapenemase inhibitors as avibactam and MK-7655, combined with old or new betalactams are a very interesting option. Some combinations as ceftazidime-avibactam are in the late stages of clinical development and could reach the market in the next years. New aminoglycosides as plazomicin, tetracycline derivates as eravacycline, and several other new molecules as monosulfactams are currently in different stages of development.
Assuntos
Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla , Drogas em Investigação/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/enzimologia , Resistência beta-Lactâmica , beta-Lactamases/metabolismo , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Carbapenêmicos/metabolismo , Carbapenêmicos/uso terapêutico , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Farmacorresistência Bacteriana Múltipla/genética , Quimioterapia Combinada , Drogas em Investigação/metabolismo , Drogas em Investigação/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Previsões , Humanos , Resistência beta-Lactâmica/genética , beta-Lactamases/genéticaRESUMO
Antimicrobial resistance poses a significant challenge in modern medicine, affecting public health. Klebsiella pneumoniae infections compound this issue due to their broad range of infections and the emergence of multiple antibiotic resistance mechanisms. Efficient detection of its capsular serotypes is crucial for immediate patient treatment, epidemiological tracking and outbreak containment. Current methods have limitations that can delay interventions and increase the risk of morbidity and mortality. Raman spectroscopy is a promising alternative to identify capsular serotypes in hypermucoviscous K. pneumoniae isolates. It provides rapid and in situ measurements with minimal sample preparation. Moreover, its combination with machine learning tools demonstrates high accuracy and reproducibility. This study analyzed the viability of combining Raman spectroscopy with one-dimensional convolutional neural networks (1-D CNN) to classify four capsular serotypes of hypermucoviscous K. pneumoniae: K1, K2, K54 and K57. Our approach involved identifying the most relevant Raman features for classification to prevent overfitting in the training models. Simplifying the dataset to essential information maintains accuracy and reduces computational costs and training time. Capsular serotypes were classified with 96 % accuracy using less than 30 Raman features out of 2400 contained in each spectrum. To validate our methodology, we expanded the dataset to include both hypermucoviscous and non-mucoid isolates and distinguished between them. This resulted in an accuracy rate of 94 %. The results obtained have significant potential for practical healthcare applications, especially for enabling the prompt prescription of the appropriate antibiotic treatment against infections.
Assuntos
Cápsulas Bacterianas , Klebsiella pneumoniae , Análise Espectral Raman , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/efeitos dos fármacos , Análise Espectral Raman/métodos , Cápsulas Bacterianas/química , Sorogrupo , Redes Neurais de Computação , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/diagnóstico , HumanosRESUMO
BACKGROUND: There is limited recent evidence about infective endocarditis (IE) in HIV-infected patients. Our aim was to compare IE according to HIV infection presence. METHODS: Consecutive inclusion of IE patients at 46 Spanish hospitals between 2008 and 2021. RESULTS: From 5667 patients, 99 were HIV-infected (1·7%; 50 intravenous drugs users). Compared to patients without HIV, HIV-infected patients were more frequently male (84% vs. 67%), had younger median age (46 vs. 69 years), and less comorbidities, except liver disease (52% vs. 9%) and intravenous drug use (51% vs. 1%). They had more common tricuspid location (36% vs. 5%) and community-acquired IE (82% vs. 63%), vascular (29% vs. 17%) and cutaneous (22% vs. 7%) foci of infection, and Staphylococcus aureus aetiology (46% vs. 22%). Vegetations (84% vs. 72%), vascular phenomena (17% vs. 9%), splenomegaly (30% vs. 11%), and embolisation (41% vs 21%) were also more common. Surgical indication and surgery were less frequent in HIV-infected patients (54% vs 67%, 28% vs 47%, respectively). Median CD4 count in HIV-infected patients was 318 cells/mm3. In-hospital mortality (23% vs. 26%) and one-year mortality (25% vs. 32%) were similar in both groups. HIV infection was not independently associated with in-hospital (odds ratio 1·1, 95% CI 0·6-1·9) nor one-year mortality (hazard ratio 0·8, 95% CI 0·4-1·3). CONCLUSIONS: In the combined antiretroviral therapy era, less than 2% of IE patients have HIV infection. HIV-infected patients have a different clinical profile than those without HIV, but the presence of HIV does not seem to impact on IE prognosis.