A sepse é uma doença de alta mortalidade e o uso adequado de antimicrobianos no seu manuseio é essencial na obtenção de melhores resultados. O objetivo deste estudo foi avaliar o consumo de antimicrobianos em pacientes com sepse hospitalar com agente etiológico identificado no sangue, comparando a reação em cadeia da polimerase (PCR) - LightCycler® SeptiFast (SF) para a detecção rápida de microorganismos à hemocultura convencional nos primeiros 14 dias de tratamento. Os objetivos secundários incluíram descrever o percentual de positividade e a concordância entre o teste molecular e a hemocultura, o tempo de internação hospitalar, os custos diretos dos antimicrobianos utilizados e a letalidade em 10 e 28 dias. Entre outubro de 2012 e maio de 2016, foram incluídos 200 pacientes adultos com sepse hospitalar: 100 alocados no grupo intervenção onde a terapia antimicrobiana foi ajustada após a identificação do micro-organismo pelo SF (dentro de 6 a 12 horas) e 100 pacientes no grupo controle onde a terapia antimicrobiana foi ajustada após a identificação do microrganismo pela hemocultura (dentro de 48 a 72 horas). O consumo de antimicrobianos foi de 1429 (1071-2000) DOT por 1000 pacientes-dia no grupo intervenção versus 1889 (1357-2563) DOT por 1000 pacientes-dia no grupo controle (p = 0.017). O SF apresentou positividade de 25,9% enquanto a positividade da hemocultura foi de 22,9% (p = 0,452). O tempo de descalonamento antimicrobiano foi de 8 horas (7-14) versus 54 horas (38-75) (p < 0,001), enquanto a mortalidade em 10 e 28 dias foi de 21% e 36,8% no grupo de intervenção versus 37% e 44% no grupo controle, (p = 0,710 e p = 0,632), respectivamente. Não houve diferença no tempo de internação hospitalar e no custo direto dos antimicrobianos utilizados nos dois grupos. A duração média da terapia antimicrobiana em dias foi menor no grupo intervenção (12 ± 5 versus 15 ± 4, p = 0,039) em comparação com o grupo controle / Sepsis is a high mortality disease. Appropriate use of antimicrobials is essential to improve outcomes. The aim of the present study was to determine whether the use of the multiplex polymerase chain reaction LightCycler® SeptiFast (SF) assay reduces the antibiotic consumption through early de-escalation in patients with nosocomial sepsis compared with conventional blood cultures (BC) in the first 14 days of treatment. Secondary outcomes included the percentage of microorganisms identified through SF and BC (in both groups), timing of antimicrobial de-escalation, length of stay, direct costs of the antimicrobial drugs and mortality at 10 and 28 days. Between October 2012 and May 2016 adult patients with nosocomial sepsis were randomized in intervention group and control group: antimicrobial therapy was adjusted following the identification of microorganisms by SF (within 6 to 12 hours) or BCs (within 48 to 72 hours), respectively. A total of 200 patients were included (100 in each group). The median antimicrobial consumption was 1429 (1071-2000) DOT/1000 patients-day in the intervention group versus 1889 (1357-2563) DOT/1000 patients-day in the control (p = 0.017). Microorganism identification was 25.9% versus 22.9% (p = 0.452), timing of antimicrobial de-escalation was 8 hours (7-14) versus 54 hours (38-75) (p < 0.001) while the mortality rate at 10 and 28 days was 21% and 36.8% in the intervention group versus 37% and 44% in the control group, (p = 0.710 and p = 0.632), respectively. There was no difference in length of stay and antimicrobial costs between groups. The mean duration of antimicrobial therapy was lower in the SF group (12 ± 5 vs. 15 ± 4, p = 0.039) comparing to BC group. The use of a rapid molecular blood test resulted in a reduction in the antimicrobial consumption and a more rapid de-escalation in patients with nosocomial sepsis when compared to the standard management of blood culture

From June 2017 to June 2019, 291 cases of Staphylococcus aureus bacteraemia (SAB) were evaluated retrospectively. Patient baseline characteristics, clinical presentations, empiric and targeted treatment, and clinical outcomes were assessed. Our study aimed to evaluate the adherence to a designated SAB care bundle and to assess whether proper adherence improved patient survival. Furthermore, as data for spa type distributions in MSSA-SAB are scarce for Germany, we aimed to describe circulating spa types and spa Clonal Complexes (spa CC) in our epidemiological setting.

Background Vancomycin dosing strategies targeting trough concentrations of 15–20 mg/L are no longer supported due to lack of efficacy evidence and increased risk of nephrotoxicity. Area-under-the-curve (AUC24) nomograms have demonstrated adequate attainment of AUC24 goals ≥ 400 mg h/L with more conservative troughs (10–15 mg/L). Objective The purpose of this study is to clinically validate a vancomycin AUC24 dosing nomogram compared to conventional dosing methods with regards to therapeutic failure and rates of acute kidney injury. Setting This study was conducted at a tertiary, community, teaching hospital in the United States. Method This retrospective, cohort study compared the rates of therapeutic failures between AUC24-extrapolated dosing and conventional dosing methods. Main outcome measure Primary outcome was treatment failure, defined as all-cause mortality within 30 days, persistent positive methicillin-resistant Staphylococcus aureus blood culture, or clinical failure. Rates of acute kidney injury in non-dialysis patients was a secondary endpoint. Results There were 96 participants in the extrapolated-AUC24 cohort and 60 participants in the conventional cohort. Baseline characteristics were similar between cohorts. Failure rates were 11.5% (11/96) in the extrapolated-AUC24 group compared to 18.3% (11/60) in the conventional group (p = 0.245). Reasons for failure were 6 deaths and 5 clinical failures in the extrapolated-AUC24 cohort and 10 deaths and 1 clinical failure in the conventional group. Acute kidney injury rates were 2.7% (2/73) and 16.4% (9/55) in the extrapolated-AUC24 and conventional cohorts, respectively (p = 0.009). Conclusion Extrapolated-AUC24 dosing was associated with less nephrotoxicity without an increase in treatment failures for bloodstream infections compared to conventional dosing. Further investigation is warranted to determine the relationship between extrapolated-AUC24 dosing and clinical failures.

Background Vancomycin dosing strategies targeting trough concentrations of 15–20 mg/L are no longer supported due to lack of efficacy evidence and increased risk of nephrotoxicity. Area-under-the-curve (AUC24) nomograms have demonstrated adequate attainment of AUC24 goals ≥ 400 mg h/L with more conservative troughs (10–15 mg/L). Objective The purpose of this study is to clinically validate a vancomycin AUC24 dosing nomogram compared to conventional dosing methods with regards to therapeutic failure and rates of acute kidney injury. Setting This study was conducted at a tertiary, community, teaching hospital in the United States. Method This retrospective, cohort study compared the rates of therapeutic failures between AUC24-extrapolated dosing and conventional dosing methods. Main outcome measure Primary outcome was treatment failure, defined as all-cause mortality within 30 days, persistent positive methicillin-resistant Staphylococcus aureus blood culture, or clinical failure. Rates of acute kidney injury in non-dialysis patients was a secondary endpoint. Results There were 96 participants in the extrapolated-AUC24 cohort and 60 participants in the conventional cohort. Baseline characteristics were similar between cohorts. Failure rates were 11.5% (11/96) in the extrapolated-AUC24 group compared to 18.3% (11/60) in the conventional group (p = 0.245). Reasons for failure were 6 deaths and 5 clinical failures in the extrapolated-AUC24 cohort and 10 deaths and 1 clinical failure in the conventional group. Acute kidney injury rates were 2.7% (2/73) and 16.4% (9/55) in the extrapolated-AUC24 and conventional cohorts, respectively (p = 0.009). Conclusion Extrapolated-AUC24 dosing was associated with less nephrotoxicity without an increase in treatment failures for bloodstream infections compared to conventional dosing. Further investigation is warranted to determine the relationship between extrapolated-AUC24 dosing and clinical failures.

BACKGROUND: Evidence supporting beta-lactam plus vancomycin synergy for methicillin-resistant (MRSA) continues to grow. Current evidence demonstrates that combination therapy is associated with shorter time to blood sterilization than vancomycin monotherapy. However, this combination has not been reported as salvage therapy for persistent MRSA bacteremia. CASE REPORT: We report a case of an 81-year-old male who was successfully treated with vancomycin plus nafcillin after failing vancomycin monotherapy, daptomycin monotherapy, and daptomycin plus gentamicin combination therapy. The patient originally presented with sepsis from a suspected urinary tract infection. Blood cultures drawn on days 1, 3, 5, 15, 19, 23, and 28 remained positive for MRSA despite multiple antimicrobial therapy changes. On day 29, therapy was changed to vancomycin plus nafcillin. Blood cultures drawn on day 32 remained negative. After 11 days, nafcillin was changed to piperacillin-tazobactam due to an infected decubitus ulcer. The combination was continued for 42 days after achieving blood sterility, 71 days after the patient originally presented. Evidence regarding salvage therapy for persistent bacteremia is sparse and is limited to case reports and case series. CONCLUSION: This case report supports that vancomycin plus an anti-staphylococcal beta-lactam combination should be further studied as salvage therapy for persistent MRSA bacteremia.

Identifying antibiotic resistance in blood infections requires separating bacteria from whole blood. A hollow spinning disk rapidly removes suspended red blood cells by leveraging hydrodynamic differences between bacteria and whole blood components in a centrifugal field. Once the red cells are removed, the supernatant plasma which contains bacteria is collected for downstream antibiotic testing. This work improves upon previous work by modifying the disk design to maximize fractional plasma recovery and minimize fractional red cell recovery. V-shaped channels induce plasma flow and increase fractional plasma recovery. Additionally, diluting a blood sample spiked with bacteria prior to spinning it increased the fractional bacteria recovery. A numerical model for red cell sedimentation shows that red cells are removed from solution more rapidly as the blood is diluted. Diluting blood is beneficial but may create too much biological waste. The benefits of diluting are formulated as an optimization problem subject to the end user’s needs.

Expressão aumentada do receptor Fc de IgA (CD89) e da cadeia g associada, avaliadas respectivamente por citometria de fluxo e por “immunobloting", foram encontradas em fagócitos do sangue de pacientes com bacteremia por germes gram-negativos, em comparação com controles e pacientes com bacteremia por gram-positivos. A Mr do CD89 avaliada por SDS-PAGE estava diminuída, com núcleo protéico de 32kDa, sugerindo alteração de glicosilação. O aumento da expressão do CD89 correlacionou-se com aumento dos níveis séricos de IL-6. A cadeia g estava fosforilada nos neutrófilos, sugerindo participação do CD89 na sepsis por gram-negativos. / The expression and function of FcaRI (CD89) were analyzed on blood monocytes and neutrophils of patients with gram-positive and gram-negative bacteremia. Eighteen patients with gram-positive bacteremia, sixteen patients with gram-negative bacteremia and twenty healthy individuals were studied. CD89 expression were analyzed by flow cytometry using specific stained antibodies. Analysis of the surface iodinated CD89 molecules by SDS-PAGE and of the CD89 g-associated chain by immunoblotting also were performed. A marked increase in expression of the a and g subunits of the FcaRI were found on both types of cells in patients with gram-negative bacteremia, but not in patients with gram-positive bacteremia. This increase was independent of serum IgA levels. FcaRI Mr was lower on cells from gram negative patients than on cells from controls (50-65 kDa vs 55-75 kDa) despite of similar 32 kDa backbone, indicating altered glycosylation. Increased levels of FcaRI on blood phagocytes correlated with enhanced serum IL-6 levels, but not with IFN-g or TNF-a levels. The CD89 g-associated chain was phosphorylated on neutrophils, suggesting an engagement of CD89 during gram negative sepsis.

Submitted by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-29T15:37:00Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇAO LUCIANO MEIRELES.pdf: 1043230 bytes, checksum: 20c7f97cfba9488935ee9dcde38c164c (MD5) / Approved for entry into archive by Ana Lúcia Torres (bfmhuap@gmail.com) on 2017-09-29T15:37:08Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇAO LUCIANO MEIRELES.pdf: 1043230 bytes, checksum: 20c7f97cfba9488935ee9dcde38c164c (MD5) / Made available in DSpace on 2017-09-29T15:37:08Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) DISSERTAÇAO LUCIANO MEIRELES.pdf: 1043230 bytes, checksum: 20c7f97cfba9488935ee9dcde38c164c (MD5) Previous issue date: 2013 / Instituto Nacional do Câncer / As infecções de corrente sanguínea (ICS) são complicações frequentes em pacientes com câncer. O objetivo deste estudo foi descrever as características epidemiológicas, clínicas e microbiológicas das ICS em pacientes com câncer ginecológico. Método: uma série de 311 episódios de ICS com comprovação microbiológica (ICS-CM) detectadas em 288 pacientes com câncer ginecológico assistidas no Hospital do Câncer II de janeiro/2002 a dezembro/2009. Para análise das variáveis categóricas, foram utilizados o teste do qui-quadrado ou o teste exato de Fisher e, para as variáveis contínuas, os testes t de Student, Mann-Whitney ou de regressão linear com cálculo do coeficiente de correlação (R2). P-valores ≤ 0,05 foram considerados estatisticamente significativos. Resultados: 205 (66%) episódios foram hospitalares; 85 (27%) comunitários, 13 (4%) relacionados à assistência à saúde e 8 (2,57%) corresponderam a neutropenia febril. As ICS secundárias foram mais frequentes (148; 47,58%) do que as primárias (141; 45,34%); dentre as secundárias, grande parte deveu-se a infecções urinárias (79; 53,4%). Dentre os 336 microrganismos isolados, os mais frequentes foram Escherichia coli (70; 20,83%), Staphylococcus aureus (66; 19,64%), staphylococcus coagulase negativo (SCN; 37; 11,01%), Klebsiella pneumoniae (33; 9,82%) e Pseudomonas aeruginosa (26; 7,74%). A prevalência global de microrganismos multirresistentes (MMR) foi 17,56% (59 MMR em 336 amostras): 11 (3,27%) amostras de S. aureus resistentes à oxacilina (MRSA), 14 (4,2%) amostras de gramnegativos entéricos resistentes às cefalosporinas de 3ª/4ª geração, 29 (8,63%) amostras de gramnegativos não fermentadores (GNNF) resistentes às cefalosporinas de 3ª/4ª geração, 5 (1,5%) amostras de GNNF resistentes aos carbapenemas. Em 224 (72%) episódios, o escore de Pitt foi ≥2. A mortalidade bruta foi 39,86% (114) com 57,89% (66) dos óbitos relacionados às ICS. Conclusão: as ICS são eventos associados a elevada mortalidade. Estes dados sugerem que as infecções urinárias, de evolução geralmente benigna na população geral, devem ser nas pacientes com câncer ginecológico, objeto de uma abordagem preventiva, diagnóstica e terapêutica mais cuidadosa. Estudos futuros, que avaliem os fatores determinantes para o óbito serão fundamentais para um melhor entendimento do prognóstico dessas pacientes / Bloodstream infections (BSI) are frequent complications in patients with cancer. The goal of this study was to describe the epidemiological, clinical and microbiological characteristics of these infections in patients with gynecological cancer. Method: a case-series of 311 episodes of laboratory-confirmed BSI detected in 288 patients with gynecological cancer assisted at Hospital do Cancer II from January 2002 to December 2009. Chi-squared test or Fisher's exact test were used for analysis of categorical variables and Student's t test, Mann-Whitney or linear regression with correlation coefficients (R2) were used with continuous variables. P-values ≤0.05 were considered statistically significant. Results: 205 (66%) BSI episodes were hospital-acquired; 85 (27%) community acquired; 13 (4%) healthcare-associated and 8 (2.57%) related to febrile neutropenia episodes. Secondary BSI episodes were more frequent (148; 47.58%) than primary cases (141; 45.34%); among the secondary BSI, many resulted from urinary tract infections (79; 53.4%). The most frequent agents among 336 microorganisms detected were Escherichia coli (70, 20.83%), Staphylococcus aureus (66, 19.64%), coagulase-negative Staphylococcus (CoNS; 37, 11.01%), Klebsiella pneumoniae (33, 9.82%) and Pseudomonas aeruginosa (26, 7.74%). The overall prevalence of multidrug resistant (MDR) agents were 17.56% (59 MDR in 336 isolates): 11 (3.27%) methicillin resistant S. aureus (MRSA) isolates, 14 (4.2%) enteric gram-negative isolates resistant to 3rd/4th generation cephalosporins, 29 (8.63%) non-fermentative gramnegative isolates resistant to 3rd/4th generation cephalosporins, 5 (1.5%) non-fermentative gramnegative isolates resistant to carbapenems. In 224 (72%) episodes had Pitt score ≥2. The crude mortality rate was 39.86% (114) with 57.89% (66) deaths were related to BSI. Conclusion: BSI are severe events associated with high mortality. These data suggest that urinary tract infection, mostly a nonthreatening illness in the general population, must have a special preventive, diagnostic and therapeutic approach in patients with gynecological cancer. Further studies assessing the factors predisposing to death will be necessary to a better understand of the prognosis in this population.

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 4 uppsatser.

Introdução: estudos de farmacocinética/farmacodinâmica (FC/FD) observaram que a probabilidade de alcançar o alvo FC/FD é maior quando a dose do beta-lactâmico é otimizada. Porém, poucos estudos demonstraram que a otimização de dose resulta em melhores desfechos clínicos. Métodos: Fatores associados com mortalidade em 30 dias foram avaliados em 100 pacientes com bacteremia por enterobactérias tratados com cefepime, piperacilina-tazobactam ou meropenem em um estudo de coorte prospectivo. Posologia dos antibióticos foi classificada em otimizada, apropriada e potencialmente inapropriada. Resultados: Cinquenta e dois (52%) episódios foram causados por E. coli, seguidos por K. pneumoniae (10%). Dezesseis (16%) episódios foram causados por isolados resistentes à cefepime e não houve nenhum caso de resistência à carbapenêmicos. A maioria dos isolados apresentou concentrações inibitórias mínimas (CIMs) baixas para as drogas prescritas (≤0.5, ≤1.0, ≤1/4 mg/L, para meropenem, cefepime e piperacilina-tazobactam respectivamente). Cefepime foi o antimicrobiano mais frequentemente prescrito para tratamento empírico e definitivo. Terapia otimizada foi observada em 42% dos pacientes e terapia adequada em 58%. A mortalidade em 30 dias foi 37%. Escore de Pitt, Charlson e apresentação com sepse severa foram independentemente associados à mortalidade. Não houve diferença em mortalidade entre os pacientes que receberam terapia otimizada e terapia adequada. Conclusões: os resultados mostram que a otimização das doses de cefepime, piperacilina-tazobactam e meropenem não teve impacto em mortalidade Em pacientes recebendo terapia empírica apropriada para bacteremias por Enterobacteriaceae. Este achado pode ser devido aos baixos valores de CIM apresentados pelas bactéria. Comorbidades e a severidade da apresentação são fatores associados à pior evolução. / Background: Pharmacokinetic/pharmacodynamic (PK/PD) studies have shown that the probability of PK/PD target attainment is higher when optimized dosage regimes of beta-lactams are employed, but few studies have shown clinical benefit of such strategy. Methods: We investigated the effect of dosage regimes in 30-day mortality in 100 patients with Enterobacteriaceae bloodstream infections (BSIs) receiving appropriate empirical therapy with cefepime, piperacillin-tazobactam or meropenem. Posology of antibiotic was classified as optimized, adequate and possibly inadequate. Results: Most isolates presented relatively low MIC for the prescribed drugs (≤0.5, ≤1.0, ≤1/4 μg/mL, for meropenem, cefepime and piperacillin-tazobactam respectively). Cefepime was the most common prescribed drug for empirical and main therapy. Optimized posology was prescribed in 42% of patients and adequate in 58%. The overall 30-day mortality was 27.0%. Charlson score, Pitt score and presentation with severe sepsis were independently associated with the 30-day mortality. Patients receiving optimized dosage regime presented no distinct 30-day mortality of those with adequate ones (25.0% versus 28.3%, P=0.89), even after inclusion in multivariate model. Conclusion: Our results suggest that dosage regime optimization of cefepime, piperacillin-tazobactam and meropenem may have no effect on mortality when infecting bacteria with low MICs for these drugs. In patients receiving appropriate empirical therapy for Enterobacteriaceae BSI, baseline comorbidity is an independent predictor of death and the severity of BSI presentation is also significantly associated with this outcome is such patients. Studies in population with higher MIC heterogeneity are required to evaluate the role of optimized doses in clinical setting.