Administration Of Appropriate Antimicrobials Research Articles

Prompt antimicrobial therapy and source control on survival and defervescence of adults with bacteraemia in the emergency department: the faster, the better

BackgroundBacteraemia is a critical condition that generally leads to substantial morbidity and mortality. It is unclear whether delayed antimicrobial therapy (and/or source control) has a prognostic or defervescence effect on patients with source-control-required (ScR) or unrequired (ScU) bacteraemia.MethodsThe multicenter cohort included treatment-naïve adults with bacteraemia in the emergency department. Clinical information was retrospectively obtained and etiologic pathogens were prospectively restored to accurately determine the time-to-appropriate antibiotic (TtAa). The association between TtAa or time-to-source control (TtSc, for ScR bacteraemia) and 30-day crude mortality or delayed defervescence were respectively studied by adjusting independent determinants of mortality or delayed defervescence, recognised by a logistic regression model.ResultsOf the total 5477 patients, each hour of TtAa delay was associated with an average increase of 0.2% (adjusted odds ratio [AOR], 1.002; P < 0.001) and 0.3% (AOR 1.003; P < 0.001) in mortality rates for patients having ScU (3953 patients) and ScR (1524) bacteraemia, respectively. Notably, these AORs were augmented to 0.4% and 0.5% for critically ill individuals. For patients experiencing ScR bacteraemia, each hour of TtSc delay was significantly associated with an average increase of 0.31% and 0.33% in mortality rates for overall and critically ill individuals, respectively. For febrile patients, each additional hour of TtAa was significantly associated with an average 0.2% and 0.3% increase in the proportion of delayed defervescence for ScU (3085 patients) and ScR (1266) bacteraemia, respectively, and 0.5% and 0.9% for critically ill individuals. For 1266 febrile patients with ScR bacteraemia, each hour of TtSc delay respectively was significantly associated with an average increase of 0.3% and 0.4% in mortality rates for the overall population and those with critical illness.ConclusionsRegardless of the need for source control in cases of bacteraemia, there seems to be a significant association between the prompt administration of appropriate antimicrobials and both a favourable prognosis and rapid defervescence, particularly among critically ill patients. For ScR bacteraemia, delayed source control has been identified as a determinant of unfavourable prognosis and delayed defervescence. Moreover, this association with patient survival and the speed of defervescence appears to be augmented among critically ill patients.

Comparing the Prognostic Impacts of Delayed Administration of Appropriate Antimicrobials in Older Patients with Afebrile and Febrile Community-Onset Bacteremia

Although prompt administration of an appropriate antimicrobial therapy (AAT) is crucial for reducing mortality in the general population with community-onset bacteremia, the prognostic effects of delayed AAT in older individuals with febrile and afebrile bacteremia remain unclear. A stepwise and backward logistic regression analysis was used to identify independent predictors of 30-day mortality. In a 7-year multicenter cohort study involving 3424 older patients (≥65 years) with community-onset bacteremia, febrile bacteremia accounted for 27.1% (912 patients). A crucial association of afebrile bacteremia and 30-day mortality (adjusted hazard ratio [AHR], 1.69; p &lt; 0.001) was revealed using Cox regression and Kaplan–Meier curves after adjusting for the independent predictors of mortality. Moreover, each hour of delayed AAT was associated with an average increase of 0.3% (adjusted odds ratio [AOR], 1.003; p &lt; 0.001) and 0.2% (AOR, 1.002; p &lt; 0.001) in the 30-day crude mortality rates among patients with afebrile and febrile bacteremia, respectively, after adjusting for the independent predictors of mortality. Similarly, further analysis based on Cox regression and Kaplan–Meier curves revealed that inappropriate empirical therapy (i.e., delayed AAT administration &gt; 24 h) had a significant prognostic impact, with AHRs of 1.83 (p &lt; 0.001) and 1.76 (p &lt; 0.001) in afebrile and febrile patients, respectively, after adjusting for the independent predictors of mortality. In conclusion, among older individuals with community-onset bacteremia, the dissimilarity of the prognostic impacts of delayed AAT between afebrile and febrile presentation was evident.

Molecular point-of-care testing for lower respiratory tract pathogens improves safe antibiotic de-escalation in patients with pneumonia in the ICU: Results of a randomised controlled trial

Effective treatment of pneumonia requires timely administration of appropriate antimicrobials but standard diagnostic tests take around 48h to generate results. Highly accurate, rapid molecular tests have been developed for identifying organisms in lower respiratory tract samples, however their impact on antibiotic use is unknown. The aim of this study was to assess the impact of syndromic molecular point-of-care testing compared to conventional diagnostic testing, on antibiotic use. In this pragmatic, randomised controlled trial, we enrolled critically ill adults with pneumonia. Patients were assigned (1:1) to molecular testing of samples at the point-of-care or routine clinical care. The primary outcome was the proportion of patients who received results-directed antimicrobial therapy. 200 patients were randomly assigned to point-of-care testing (n=100) or the control group (n=100). 85 patients had community acquired pneumonia (42 in the mPOCT group and 43 in the control group), 69 hospital acquired pneumonia (30 in mPOCT and 39 in control) and 46 ventilator associated pneumonia (28 in mPOCT and 18 in control). The median [IQR] time to results was 1.7 [1.6-1.9] hours for point-of-care testing and 66.7 [56.7-88.5] hours for standard diagnostics (difference of -65.0h, 95%CI -68.0 to -62.0; p<0.0001). 71 (71%) patients in the point-of-care testing arm had pathogens detected compared to 51 (51%) in the control arm (difference of 20%, 95%CI 7 to 33; p=0.004). 80 (80%) of patients in the point-of-care group received results-directed therapy, compared with 29 (29%) of 99 in the control group (difference of 51%, 95%CI 39-63; p<0.0001). Time to results-directed therapy was 2.3 [1.8-7.2] hours in the mPOCT group and 46.1 [23.0-51.5] hours in the control group (difference of -43.8h, 95% CI -48.9 to -38.6; p<0.0001). 42 (42%) patients in mPOCT group had antibiotics de-escalated compared with 8 (8%) of 98 in the control group (difference of 34%, 95%CI 23-45; p<0.0001). Time to de-escalation was 4.8 [2.4-13.0] hours in the mPOCT group compared with 46.5 [26.3-48.6] hours in the control group (difference of -41.4h, 95%CI -53 to -29.7; p<0.0001). There was no major difference in antibiotic duration or in clinical or safety outcomes between the two groups. Use of molecular point-of-care testing in patients with pneumonia returned results more rapidly and identified more pathogens than conventional testing. This was associated with improvements in appropriate antimicrobial use and appeared safe.

Prognostic Effects of Delayed Administration of Appropriate Antimicrobials in Bacteraemic Adults Initially Presenting with Various Body Temperatures.

PurposeTo investigate the different impact of delayed administration of appropriate antimicrobial therapy (AAT) on short-term mortality of bacteraemia patients initially presenting with various body temperatures (BTs).Materials and MethodsA six-year, two-center cohort consisting of adults with community-onset bacteraemia in emergency departments (EDs) was retrospectively collected. Through the multivariable analyses, clinical impacts of delayed AAT, assessed by the time gap between the first dose of AAT and ED arrival, on 30-day mortality (primary outcomes) were respectively examined in the different groups of initial BTs (iBTs).ResultsOf the 3171 adults, despite the similarities of delayed AAT in six iBT categories, hourly AAT delay was associated with an average increase in 30-day mortality rates of 0.24% in the group of iBT <36.0℃, 0.40% in the 36.0℃–36.9℃ group, 0.48% in the 37.0℃–37.9℃ group, 0.59% in the 38.0℃–38.9℃ group, 0.58% in the 39.0℃–39.9℃ group, and 0.71% in the ≥40.0℃ group, after respective adjusting independent predictors of mortality. Furthermore, for 589 patients who inappropriately received empirical antimicrobial treatment (ie, delayed AAT ≥ 24 hours), with a cutoff of 34.0℃, each 1℃ increase in iBTs was independently associated with an average increase in 30-day mortality rates of 42%.ConclusionFor adults with community-onset bacteraemia, the iBT-related differences in the prognostic impacts of delayed administration of appropriate antimicrobials might be evident.

Metabolic preference assay for rapid diagnosis of bloodstream infections

Bloodstream infections (BSIs) cause >500,000 infections and >80,000 deaths per year in North America. The length of time between the onset of symptoms and administration of appropriate antimicrobials is directly linked to mortality rates. It currently takes 2–5 days to identify BSI pathogens and measure their susceptibility to antimicrobials – a timeline that directly contributes to preventable deaths. To address this, we demonstrate a rapid metabolic preference assay (MPA) that uses the pattern of metabolic fluxes observed in ex-vivo microbial cultures to identify common pathogens and determine their antimicrobial susceptibility profiles. In a head-to-head race with a leading platform (VITEK 2, BioMérieux) used in diagnostic laboratories, MPA decreases testing timelines from 40 hours to under 20. If put into practice, this assay could reduce septic shock mortality and reduce the use of broad spectrum antibiotics.

Microorganism Distributions and Antimicrobial Susceptibility in Community-Onset Bacteremia: A 6-Year Longitudinal Multicenter Cohort in Southern Taiwan.

Prompt administration of appropriate antimicrobials has been correlated with improved prognoses in patients with bacteremia. Because the Clinical and Laboratory Standards Institute (CLSI) has numerously revised the interpretive criteria of susceptibility to numerous antimicrobials, the updated susceptibility is useful for empirical administration. In the multicenter retrospective cohort study consisting of adults with community-onset bacteremia in the emergency department (ED) during the period between January 2010 and December 2015, causative microorganisms were identified by the Vitek 2 system and prospectively collected. Antimicrobial susceptibility were respectively tested by the disk diffusion method for aerobes and the agar dilution method for anaerobes, in accordance with the contemporary CLSI criteria. Clinical information was retrospectively retrieved by reviewing the medical records. Of the total 3,194 patients and 3,583 causative microorganisms, the leading source of bacteremia was the urinary tract infection (1,034 patients, 32.4%), and Escherichia coli accounted for the majority (1,332 isolates, 37.2%) of the total microorganisms. Overall, the lowest (58.2%) and highest (93.5%) susceptibility to cefazolin and piperacillin/tazobactam were, respectively, observed. In the leading five sources of bacteremia, in terms of the urinary tract infections, pneumonia, intraabdominal infections, skin and soft-tissue infections, and biliary tract infections, cefazolin or cefuroxime was only active against 49.3%-62.3% or 63.2%-74.1% of causative microorganisms, respectively. Notably, E. coli , Klebsiella species, and Proteus mirabilis (EKP) with the production of extended-spectrum beta-lactamases (ESBLs) accounted for 7.4% (142 isolates) of 1,908 EKP and 4.0% of all 3,583 microorganisms; and methicillin-resistant Staphylococcus aureus (MRSA) accounted for 37.7% (158 isolates) of S . aureus and 4.4% of all causative isolates. For adults with community-onset bacteremia, a low incidence (approximate 4%) of ESBL-producing EKP and MRSA among all causative microorganisms, but low susceptibility to cefazolin and cefuroxime were recognized. To achieve favorable prognoses by prompt administration of appropriate antimicrobials in EDs, our findings might offer useful information for the antimicrobial stewardship program.

Current spectrum of causative pathogens in sepsis: A prospective nationwide cohort study in Japan

BackgroundThere is no one-size-fits-all empiric antimicrobial therapy for sepsis because the pathogens vary according to the site of infection and have changed over time. Therefore, updating knowledge on the spectrum of pathogens is necessary for the rapid administration of appropriate antimicrobials. ObjectiveThe aim of this study was to elucidate the current spectrum of pathogens and its variation by site of infection in sepsis. MethodsThis was a prospective nationwide cohort study of consecutive adult patients with sepsis in 59 intensive care units in Japan. The spectrum of pathogens was evaluated in all patients and in subgroups by site of infection. Regression analyses were conducted to evaluate the associations between the pathogens and mortality. ResultsThe study cohort comprised 1184 patients. The most common pathogen was Escherichia coli (21.5%), followed by Klebsiella pneumoniae (9.0%). However, the pattern varied widely by site of infection; for example, gram-positive bacteria were the dominant pathogen in bone/soft tissue infection (55.7%) and cardiovascular infection (52.6%), but were rarely identified in urinary tract infection (6.4%). In contrast, gram-negative bacteria were the predominant pathogens in abdominal infection (38.4%) and urinary tract infection (72.0%). The highest mortality of 47.5% was observed in patients infected with methicillin-resistant Staphylococcus aureus, which was significantly associated with an increased risk of death (odds ratio 1.88, 95% confidence interval 1.22–2.91). ConclusionsThis study revealed the current spectrum of pathogens and its variation based on the site of infection, which is essential for empiric antimicrobial therapy against sepsis.

Antimicrobial Treatment Duration in Sepsis and Serious Infections.

Sepsis mortality has improved following advancements in early recognition and standardized management, including emphasis on early administration of appropriate antimicrobials. However, guidance regarding antimicrobial duration in sepsis is surprisingly limited. Decreased antibiotic exposure is associated with lower rates of de novo resistance development, Clostridioides difficile-associated disease, antibiotic-related toxicities, and health care costs. Consequently, data weighing safety versus adequacy of shorter treatment durations in sepsis would be beneficial. We provide a narrative review of evidence to guide antibiotic duration in sepsis. Evidence is significantly limited by noninferiority trial designs and exclusion of critically ill patients in many trials. Potential challenges to shorter antimicrobial duration in sepsis include inadequate source control, treatment of multidrug-resistant organisms, and pharmacokinetic alterations that predispose to inadequate antimicrobial levels. Additional studies specifically targeting patients with clinical indicators of sepsis are needed to guide measures to safely reduce antimicrobial exposure in this high-risk population while preserving clinical effectiveness.

Optimizing Pharmacokinetics-Pharmacodynamics of Antimicrobial Management in Patients with Sepsis: A Review

Critically ill patients with sepsis or septic shock are at an increased risk of death. Early and aggressive interventions are essential for improving clinical outcomes. There are a number of therapeutic and practical challenges in the management of antimicrobials in patients with sepsis. These include the timely selection and administration of appropriate antimicrobials, significant physiological alterations that can influence antimicrobial pharmacokinetics, and significant interpatient variability of antimicrobial concentrations using standard dosing approaches. Understanding the impact of these factors on the probability of attaining pharmacokinetic-pharmacodynamic target goals is essential to guide optimal therapy. Using rapid diagnostic technology could facilitate timely selection of antimicrobials, and therapeutic drug monitoring would provide a more individualized dosing approach. Using an interdisciplinary sepsis team would also be beneficial in coordinating efforts to overcome the challenges encountered during this critical period to ensure optimal care.

Bloodstream Infections and Delayed Antibiotic Coverage Are Associated With Negative Hospital Outcomes in Hematopoietic Stem Cell Transplant Recipients

Bloodstream infections (BSIs) are common after hematopoietic stem cell transplantation (HSCT) and are associated with increased long-term morbidity and mortality. However, short-term outcomes related to BSI in this population remain unknown. More specifically, it is unclear whether choices related to empiric antimicrobials for potentially infected patients are associated with patient outcomes. Are potential delays in appropriate antibiotics associated with hospital outcomes among HSCT recipients with BSI? We conducted a retrospective cohort study at a large comprehensive inpatient academic cancer center between January 2014 and June 2017. We identified all admissions for HSCT and prior recipients of HSCT. We defined potential delay in appropriate antibiotics as > 24h between positive blood culture results and the initial dose of an antimicrobial with activity against the pathogen. We evaluated 2,751 hospital admissions from 1,086 patients. Of these admissions, 395 (14.4%) involved one or more BSIs. Of these 395 hospitalizations, 44 (11.1%) involved potential delays in appropriate antibiotics. The incidence of mortality was higher in BSI hospitalizations than in those without BSI (23%vs4.5%; P< .001). In multivariable analysis, BSI was an independent predictor of mortality (OR, 8.14; 95%CI, 5.06-13.1; P< .001). Mortality was higher for admissions with potentially delayed appropriate antibiotics than for those with appropriate antibiotics (48%vs20%; P< .001). Potential delay in antibiotics was also an independent predictor of mortality in multivariable analysis (OR, 13.8; 95%CI, 5.27-35.9; P< .001). BSIs were common and independently associated with increased morbidity and mortality. Delays in administration of appropriate antimicrobials were identified as an important factor in hospital morbidity and mortality. These findings may have important implications for our current practice of empiric antibiotic treatment in HSCT patients.

Beneficial effects of early empirical administration of appropriate antimicrobials on survival and defervescence in adults with community-onset bacteremia

BackgroundBloodstream infections are associated with high morbidity and mortality, both of which contribute substantially to healthcare costs. The effects of early administration of appropriate antimicrobials on the prognosis and timing of defervescence of bacteremic patients remain under debate.MethodsIn a 6-year retrospective, multicenter cohort, adults with community-onset bacteremia at the emergency departments (EDs) were analyzed. The period from ED arrival to appropriate antimicrobial administration and that from appropriate antimicrobial administration to defervescence was regarded as the time-to-appropriate antibiotic (TtAa) and time-to-defervescence (TtD), respectively. The primary study outcome was 30-day mortality after ED arrival. The effects of TtAa on 30-day mortality and delayed defervescence were examined after adjustment for independent predictors of mortality, which were recognized by a multivariate regression analysis.ResultsOf the total 3194 patients, a TtAa-related trend in the 30-day crude (γ = 0.919, P = 0.01) and sepsis-related (γ = 0.909, P = 0.01) mortality rate was evidenced. Each hour of TtAa delay was associated with an average increase in the 30-day crude mortality rate of 0.3% (adjusted odds ratio [AOR], 1.003; P < 0.001) in the entire cohort and 0.4% (AOR, 1.004; P < 0.001) in critically ill patients, respectively, after adjustment of independent predictors of 30-day crude mortality. Of 2469 febrile patients, a TtAa-related trend in the TtD (γ = 0.965, P = 0.002) was exhibited. Each hour of TtAa delay was associated with an average 0.7% increase (AOR, 1.007; P < 0.001) in delayed defervescence (TtD of ≥ 7 days) after adjustment of independent determinants of delayed defervescence. Notably, the adverse impact of the inappropriateness of empirical antimicrobial therapy (TtAa > 24 h) on the TtD was noted, regardless of bacteremia severity, bacteremia sources, or causative microorganisms.ConclusionsThe delay in the TtAa was associated with an increasing risk of delayed defervescence and 30-day mortality for adults with community-onset bacteremia, especially for critically ill patients. Thus, for severe bacteremia episodes, early administration of appropriate empirical antimicrobials should be recommended.

Predicting in-hospital mortality in pneumonia-associated septic shock patients using a classification and regression tree: a nested cohort study

BackgroundPneumonia complicated by septic shock is associated with significant morbidity and mortality. Classification and regression tree methodology is an intuitive method for predicting clinical outcomes using binary splits. We aimed to improve the prediction of in-hospital mortality in patients with pneumonia and septic shock using decision tree analysis.MethodsClassification and regression tree models were applied to all patients with pneumonia-associated septic shock in the international, multicenter Cooperative Antimicrobial Therapy of Septic Shock database between 1996 and 2015. The association between clinical factors (time to appropriate antimicrobial therapy, severity of illness) and in-hospital mortality was evaluated. Accuracy in predicting clinical outcomes, sensitivity, specificity, and area under receiver operating curve of the final model was evaluated in training (n = 2111) and testing datasets (n = 2111).ResultsThe study cohort contained 4222 patients, and in-hospital mortality was 51%. The mean time from onset of shock to administration of appropriate antimicrobials was significantly higher for patients who died (17.2 h) compared to those who survived (5.0 h). In the training dataset (n = 2111), a tree model using Acute Physiology and Chronic Health Evaluation II Score, lactate, age, and time to appropriate antimicrobial therapy yielded accuracy of 73% and area under the receiver operating curve 0.75. The testing dataset (n = 2111) had accuracy of 69% and area under the receiver operating curve 0.72.ConclusionsOverall mortality (51%) in patients with pneumonia complicated by septic shock is high. Increased time to administration of antimicrobial therapy, Acute Physiology and Chronic Health Evaluation II Score, serum lactate, and age were associated with increased in-hospital mortality. Classification and regression tree methodology offers a simple prognostic model with good performance in predicting in-hospital mortality.

Timing of appropriate empirical antimicrobial administration and outcome of adults with community-onset bacteremia

BackgroundEarly administration of appropriate antimicrobials has been correlated with a better prognosis in patients with bacteremia, but the optimum timing of early antibiotic administration as one of the resuscitation strategies for severe bacterial infections remains unclear.MethodsIn a retrospective cohort study, adults with community-onset bacteremia at the emergency department (ED) were analyzed. Effects of different cutoffs of time to appropriate antibiotic (TtAa) administration after arrival at the ED on 28-day mortality were examined, after adjustment for independent predictors of mortality identified by multivariate regression analysis.ResultsAmong 2349 patients, the mean (interquartile range) TtAa was 2.0 (<1 to 12) hours. All selected cutoffs of TtAa, ranging from 1 to 96 hours, were significantly associated with 28-day mortality (adjusted odds ratio (AOR), 0.54–0.65, all P < 0.001), after adjustment of the following prognostic factors: fatal comorbidities (McCabe classification), critical illness (Pitt bacteremia score (PBS) ≥4) on arrival at the ED, polymicrobial bacteremia, extended-spectrum beta-lactamase-producer bacteremia, underlying malignancies or liver cirrhosis, and bacteremia caused by pneumonia or urinary tract infections. The adverse impact of TtAa on 28-day mortality was most evident at the cutoff of 48 hours, as the lowest AOR was identified (0.54, P < 0.001). In subgroup analyses, the most evident TtAa cutoff (i.e., the lowest AOR) remained at 48 hours in mildly ill (PBS = 0; AOR 0.47; P = 0.04) and moderately ill (PBS = 1–3; AOR 0.55; P = 0.02) patients, but shifted to 1 hour in critically ill patients (PBS ≥4; AOR 0.56; P < 0.001).ConclusionsThe time from triage to administration of appropriate antimicrobials is one of the primary determinants of mortality. The optimum timing of appropriate antimicrobial administration is the first 48 hours after non-critically ill patients arrive at the ED. As bacteremia severity increases, effective antimicrobial therapy should be empirically prescribed within 1 hour after critically ill patients arrive at the ED.

Diabetic foot infection in hospitalized adults.

Acute infections of the diabetic foot (DFI) are a common and complex condition. Patients are generally managed in the ambulatory setting and epidemiological data pertaining to hospitalized patients is lacking. The aim of this study was to analyze the epidemiology, microbiology and outcomes of hospitalized patients with DFI, who are managed at a referral center equipped with hyperbaric oxygen (HBO) therapy. A retrospective cohort study of adult patients admitted to a tertiary referral center with DFI over a six-month period in 2013 was undertaken. Predictors of clinical outcomes and efficacy of treatment modalities were analyzed by Cox regression. Sixty-one patients with DFI were identified. Most patients were elderly (67±13 years), with long-standing (17±9 years), poorly controlled (HbA1c 9±3%) diabetes. Most patients had polymicrobial infection (80%); specifically, anaerobic (39%) and multi or extensively-drug resistant organisms (61%). Administration of appropriate antimicrobials was delayed for >48h in 83%. Advanced age was associated with worse outcomes. Sicker patients with severe peripheral vascular disease were managed with HBO. The use of HBO was associated with higher costs and increased functional deterioration, and did not prevent future limb amputation. Our study illustrates the descriptive epidemiology of hospitalized adults with DFI predominantly of polymicrobial etiology. MDROs and anaerobic organisms are common causative pathogens, and appropriate antibiotics were frequently delayed. HBO treatment may delay the need for limb amputation, but not obviate this eventual outcome.

The role of antimicrobials in the treatment of sepsis and critical illness-related bacterial infections: examination of the evidence.

To appraise the evidence behind the Surviving Sepsis Campaign Guidelines on antimicrobial therapy in sepsis and evaluate relevant literature in small animal veterinary critical care. Electronic searches using MEDLINE and EMBASE databases. Current recommendations are to administer appropriate antimicrobials within 1 hour of a diagnosis of severe sepsis or septic shock. Evidence is supportive of this recommendation in septic shock but the evidence is less compelling in milder forms of critical illness-related infections. It is unclear when the administration of appropriate antimicrobials is most beneficial and when it should be considered essential. Evidence supports shorter courses of antimicrobial therapy for many infections seen in the critical care unit with the biomarkers procalcitonin and C-reactive protein helpful in guiding the duration of therapy. Current evidence is lacking to support the use of early and aggressive use of antimicrobials in all patients with critical illness-related bacterial infections. Two studies failed to demonstrate improved survival in patients with pulmonary or abdominal infections administered appropriate vs inappropriate empirical antimicrobials. One study failed to show an improved survival when dogs with abdominal infections were administered antimicrobials within 1 hour vs 6 hours of diagnosis of infection. Information regarding ideal duration of antimicrobial therapy and use of biomarkers to guide therapy is currently lacking. Clinicians should aim to administer early and appropriate antimicrobials; however, the impact this will have on patient outcome remains uncertain. The ability to administer early and appropriate antimicrobials may be considered a measure of the quality of medical practice rather than a prognostic indicator.

Impact of appropriate antimicrobial therapy for patients with severe sepsis and septic shock--a quality improvement study.

BackgroundThere is ample literature available on the association between both time to antibiotics and appropriateness of antibiotics and clinical outcomes from sepsis. In fact, the current state of debate surrounds the balance to be struck between prompt empirical therapy and care in the choice of appropriate antibiotics (both in terms of the susceptibility of infecting organism and minimizing resistance arising from use of broad-spectrum agents). The objective of this study is to determine sepsis bundle compliance and the appropriateness of antimicrobial therapy in patients with severe sepsis and septic shock and its impact on outcomes.MaterialThis study was conducted in the ICU of a tertiary care, private hospital in São Paulo, Brazil. A retrospective cohort study was conducted from July 2005 to December 2012 in patients with severe sepsis and septic shock.ResultsA total of 1,279 patients were identified with severe sepsis and septic shock, of which 358 (32.1%) had bloodstream infection (BSI). The inpatient mortality rate was 29%. In evaluation of the sepsis bundle, over time there was a progressive increase in serum arterial lactate collection, obtaining blood cultures prior to antibiotic administration, administration of broad-spectrum antibiotics within 1 hour, and administration of appropriate antimicrobials, with statistically significant differences in the later years of the study. We also observed a significant decrease in mortality. In patients with bloodstream infection, after adjustment for other covariates the administration of appropriate antimicrobial therapy was associated with a decrease in mortality in patients with severe sepsis and septic shock (p = 0.023).ConclusionsThe administration of appropriate antimicrobial therapy was independently associated with a decline in mortality in patients with severe sepsis and septic shock due to bloodstream infection. As protocol adherence increased over time, the crude mortality rate decreased, which reinforces the need to implement institutional guidelines and monitor appropriate antimicrobial therapy compliance.

Comparison of narrow-band imaging cystoscopy and white-light imaging cystoscopy to detect bladder lesions – Northern Ireland initial experience

Comparison of narrow-band imaging cystoscopy and white-light imaging cystoscopy to detect bladder lesions – Northern Ireland initial experience

Initial Emergency Department Diagnosis and Management of Adult Patients with Severe Sepsis and Septic Shock

Severe sepsis is a medical emergency affecting up to 18 million individuals world wide, with an annual incidence of 750,000 in North America alone. Mortality ranges between 28-50% of those individuals stricken by severe sepsis. Sepsis is a time critical illness, requiring early identification and prompt intervention in order to improve outcomes. This observation has led to increased awareness and education in the field of Emergency Medicine; it has also led to the implementation of critical interventions early in the course of patient management, specifically Early-Goal Directed Therapy, and rapid administration of appropriate antimicrobials. This review begins with a brief summary of the pathophysiology of sepsis, and then addresses the fundamental clinical aspects of ED identification and resuscitation of the septic patient.

Rapid Detection of Pathogens Causing Sepsis in Neutropenic Hematologic Patients by a Multiplex PCR-Based Assay

Abstract 4921 BACKGROUND:Febrile neutropenia and sepsis are frequent and life-threatening complications in patients with hematological malignancies. Prompt administration of appropriate antimicrobials is crucial to decrease the high morbidity and mortality rates of these conditions. Blood cultures (BC) identify a pathogen in only 20 to 30% of febrile episodes, with even lower sensitivity in patients already receiving antibiotics at time of sampling. Moreover the culturing and pathogen identification process is lengthy, postponing the start of a pathogen-targeted treatment, a particularly relevant issue when highly aggressive or rare agents are involved. Thereby the setup of molecular tools able to promptly recognize pathogens causing sepsis even despite ongoing antimicrobial therapy is of potential clinical relevance. METHODS:We assessed the diagnostic usefulness of the LightCycler SeptiFast test (SF), a PCR-based multiplex assay which can be performed on peripheral blood in hematological patients. In this study, blood samples from febrile oncohaematological patients were tested by traditional blood culture (BacT/Alert 3D; bioMerieux) and by a novel commercial real-time PCR assay (LightCycler SeptiFast; Roche Molecular Systems) performed concomitantly at the onset of febrile neutropenia. RESULTS:A total of 869 blood samples were collected from 273 consecutive patients treated for febrile neutropenia at the San Raffaele Hematology Unit over the last three years (July 2009–July 2011). Out of the total 869 episodes examined, positive results were detected in 246 samples by SF (28.3%), and in 143 by BC (16.4%). Together, the two methods identified a total of 345 microorganisms in 312 (36%) episodes: Gram-positive bacterial species (74%), Gram-negative bacterial species (23%), and fungal species (3%). Concordance between the two methods was 73%, mainly due to samples that tested negative by culture but positive using the molecular approach (54% of the total positive samples). The cases positive by SF alone were mostly samples from patients with initial concordant results on samples harvested before the administration of a specific antimicrobial therapy, or, importantly, sample positive for a clinically relevant agent such as Aspergillus fumigatus, which is hard to detect by the traditional approaches. CONCLUSION:The LightCycler SeptiFast test gives new insights into the natural history of infection and in the development of new algorithms for the diagnosis of sepsis in critical patients. Using SF combined with BC improves microbiological documentation in febrile neutropenia particularly in persistent fever despite antibacterial therapy, when a nonresponding bacterial infection or an invasive fungal infection is suspected; results of SF may lead to a more targeted antibiotic therapy early after the onset of fever. Disclosures:No relevant conflicts of interest to declare.

Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis

PurposeThe objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. MethodsA prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. ResultsDeath occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). ConclusionsChanges of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials.