Appropriateness Of Antibiotic Therapy Research Articles

Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: data from the multicenter, randomized ALBIOS trial.

Presepsin is a soluble fragment of the cluster-of-differentiation marker protein 14 (CD14) involved in pathogen recognition by innate immunity. We evaluated the relation between its circulating concentration, host response, appropriateness of antibiotic therapy, and mortality in patients with severe sepsis. Plasma presepsin was measured 1, 2, and 7 days after enrollment of 997 patients with severe sepsis or septic shock in the multicenter Albumin Italian Outcome Sepsis (ALBIOS) trial. They were randomized to albumin or crystalloids. We tested with univariate and adjusted models the association of single measurements of presepsin or changes over time with clinical events, organ dysfunctions, appropriateness of antibiotic therapy, and ICU or 90-day mortality. Presepsin concentration at baseline (946 [492-1,887] ng/L) increased with the SOFA score, the number of prevalent organ dysfunctions or failures, and the incidence of new failures of the respiratory, coagulation, liver, and kidney systems. The concentration decreased in ICU over 7 days in patients with negative blood cultures, and in those with positive blood cultures and appropriate antibiotic therapy; it increased with inappropriate antibiotic therapy (p = 0.0009). Baseline presepsin was independently associated with, and correctly reclassified, the risk of ICU and 90-day mortality. Increasing concentrations of presepsin from day 1 to day 2 predicted higher ICU and 90-day mortality (adjusted p < 0.0001 and 0.01, respectively). Albumin had no effect on presepsin concentration. Presepsin is an early predictor of host response and mortality in septic patients. Changes in concentrations over time seem to reflect the appropriateness of antibiotic therapy.

Impact of a computerized alert system for bacteremia notification on the appropriate antibiotic treatment of Staphylococcus aureus bloodstream infections

A computerized alert system (CAS) has been introduced to notify bacteremia in real time. We evaluated the impact of the CAS on the administration of appropriate antibiotics in patients with Staphylococcus aureus bloodstream infections (BSIs). We retrospectively reviewed the medical records of patients with S. aureus BSI for each 1-year control and intervention periods, before and after the implementation of the CAS. The proportions of appropriate antibiotic treatment were compared between the control and intervention periods. The 30-day mortality of S. aureus bacteremia was also assessed in the study population. A total of 313 patients were included in the study. Appropriate antibiotics were initiated 7 h earlier in the intervention period (mean time, 13.5 h vs. 20.0 h; p = 0.136). The administration of appropriate antibiotics within the 24 h after blood acquisition was similar between the two periods, but this significantly increased from 3.3% in the control period to 10.6% in the intervention during the 24-36 h interval (p = 0.012). In the subgroup analysis, similar trends were observed in patients with methicillin-resistant isolates (6.7% vs. 18.2%; p = 0.032) and hospital-onset infection (3.5% vs. 17.1 %; p = 0.004). The independent risk factors for 30-day mortality of S. aureus bacteremia were age, a high Pitt bacteremia score, an increased Charlson's weighted index of comorbidity, and hospital-onset infection, although the appropriateness of antibiotic therapy within 36 h and the CAS were not identified as predictors. The CAS increased the proportion of appropriate antimicrobial therapy during the 24-36 h interval after bacteremia onset in patients with S. aureus BSIs.

Strategies of initiation and streamlining of antibiotic therapy in 41 French intensive care units.

IntroductionFew studies have addressed the decision-making process of antibiotic therapy (AT) in intensive care unit (ICU) patients.MethodsIn a prospective observational study, all consecutive patients admitted over a one-month period (2004) to 41 French surgical (n = 22) or medical/medico-surgical ICUs (n = 19) in 29 teaching university and 12 non-teaching hospitals were screened daily for AT until ICU discharge. We assessed the modalities of initiating AT, reasons for changes and factors associated with in ICU mortality including a specific analysis of a new AT administered on suspicion of a new infection.ResultsA total of 1,043 patients (61% of the cohort) received antibiotics during their ICU stay. Thirty percent (509) of them received new AT mostly for suspected diagnosis of pneumonia (47%), bacteremia (24%), or intra-abdominal (21%) infections. New AT was prescribed on day shifts (45%) and out-of-hours (55%), mainly by a single senior physician (78%) or by a team decision (17%). This new AT was mainly started at the time of suspicion of infection (71%) and on the results of Gram-stained direct examination (21%). Susceptibility testing was performed in 261 (51%) patients with a new AT. This new AT was judged inappropriate in 58 of these 261 (22%) patients. In ICUs with written protocols for empiric AT (n = 25), new AT prescribed before the availability of culture results (P = 0.003) and out-of-hours (P = 0.04) was more frequently observed than in ICUs without protocols but the appropriateness of AT was not different. In multivariate analysis, the predictive factors of mortality for patients with new AT were absence of protocols for empiric AT (adjusted odds ratio (OR) = 1.64, 95% confidence interval (95%CI): 1.01 to 2.69), age ≥60 (OR = 1.97, 95% CI: 1.19 to 3.26), SAPS II score >38 (OR = 2.78, 95% CI: 1.60 to 4.84), rapidly fatal underlying diseases (OR = 2.91, 95% CI: 1.52 to 5.56), SOFA score ≥6 (OR = 4.48, 95% CI: 2.46 to 8.18).ConclusionsMore than 60% of patients received AT during their ICU stay. Half of them received new AT, frequently initiated out-of-hours. In ICUs with written protocols, empiric AT was initiated more rapidly at the time of suspicion of infection and out-of-hours. These results encourage the establishment of local recommendations for empiric AT.

What procalcitonin brings to management of sepsis in the ICU

In inflammatory states, particularly in response to infectious stimuli, local procalcitonin (PCT) production rises, and because these tissues cannot further process PCT into calcitonin, serum levels increase. In the critical care setting, PCT should be considered a useful tool to help physicians in some specific, although frequent, situations. Serial measurements of PCT levels may indicate the effectiveness of medical decisions such as the appropriateness of antibiotic therapy, the detection of new infections, and the exclusion of a diagnosis of sepsis. PCT-guided algorithms may also help to decrease the duration of antimicrobial therapy. However, the role of PCT as a prognostic marker in critically ill patients is controversial. In a study by Karlsson and colleagues, PCT concentrations did not differ between hospital survivors and nonsurvivors, but the outcome was better in patients whose PCT concentrations decreased more than 50%. The study of PCT kinetics thus could offer an individual risk assessment in patients with severe sepsis.

Rational antibiotic use

Development of resistance to antimicrobial agents and increase of cost as the result of unnecessary and inappropriate use of antibiotics has become a global health problem. Therefore many strategies, which are aimed at optimizing antibiotic therapy, have been developed until now. In Turkey, an antibiotic restriction policy as a governmental solution was applied to decrease the antibiotic use and especially costs by Ministry of Health in 2003. The aim of this study is to evaluate the rational antibiotic use and the impact of the implementation of new restriction policy, with their reinforcement by infectious disease specialist, on the hospital wide use of antibiotics. The data of the inpatients received antibiotics (n=495) during January-June 2006 were compared with our previous study performed by the same methodology before the restriction policy in 1998. In both studies, prospective active daily surveillance of patients was performed by three infectious disease specialists. The appropriateness of antibiotic therapy was determined using the criteria described by Kunin and Jones. The data were analyzed by using SPSS for Windows. While the rate of antibiotic use decreased from 16.6% to 11.3%, rational use increased after the restriction policy (p<0.001). Besides the specific antibiotic use increasing, prophylactic antibiotic use was found decreased (p<0.001). Mostly determined irrationality was the prophylactic uses in both studies. As expected, infectious disease specialist examinations resulted in an increase in the appropriate antibiotic use. The restriction policy was effective in decreasing the antibiotic consumption and increasing the rational antibiotic prescription in our hospital.

Procalcitonin kinetics within the first days of sepsis: relationship with the appropriateness of antibiotic therapy and the outcome

IntroductionManagement of the early stage of sepsis is a critical issue. As part of it, infection control including appropriate antibiotic therapy administration should be prompt. However, microbiological findings, if any, are generally obtained late during the course of the disease. The potential interest of procalcitonin (PCT) as a way to assess the clinical efficacy of the empirical antibiotic therapy was addressed in the present study.MethodsAn observational cohort study including 180 patients with documented sepsis was conducted in our 15-bed medical intensive care unit (ICU). Procalcitonin measurement was obtained daily over a 4-day period following the onset of sepsis (day 1 (D1) to D4). The PCT time course was analyzed according to the appropriateness of the first-line empirical antibiotic therapy as well as according to the patient outcome.ResultsAppropriate first-line empirical antibiotic therapy (n = 135) was associated with a significantly greater decrease in PCT between D2 and D3 (ΔPCT D2–D3) (-3.9 (35.9) vs. +5.0 (29.7), respectively; P < 0.01). In addition, ΔPCT D2–D3 was found to be an independent predictor of first-line empirical antibiotic therapy appropriateness. In addition, a trend toward a greater rise in PCT between D1 and D2 was observed in patients with inappropriate antibiotics as compared with those with appropriate therapy (+5.2 (47.4) and +1.7 (35.0), respectively; P = 0.20). The D1 PCT level failed to predict outcome, but higher levels were measured in the nonsurvivors (n = 51) when compared with the survivors (n = 121) as early as D3 (40.8 (85.7) and 21.3 (41.0), respectively; P = 0.04). Moreover, PCT kinetics between D2 and D3 were also found to be significantly different, since a decrease ≥ 30% was expected in the survivors (log-rank test, P = 0.04), and was found to be an independent predictor of survival (odds ratio = 2.94; 95% confidence interval 1.22 to 7.09; P = 0.02).ConclusionsIn our study in an ICU, appropriateness of the empirical antibiotic therapy and the overall survival were associated with a greater decline in PCT between D2 and D3. Further studies are needed to assess the utility of the daily monitoring of PCT in addition to clinical evaluation during the early management of sepsis.

Impact of an Institution‐Specific Hospital‐Acquired Pneumonia Protocol on the Appropriateness of Antibiotic Therapy and Patient Outcomes

To evaluate the impact of a hospital-acquired pneumonia (HAP) protocol on appropriateness of empiric antibiotic therapy, antibiotic deescalation, antibiotic duration, patient mortality, and length of stay. Before- and after-study of protocol implementation. A 450-bed, academic medical center. One hundred consecutive patients with proven or suspected HAP. Implementation of an HAP protocol that was based on the 2005 American Thoracic Society-Infectious Diseases Society of America guidelines and included extensive education of clinicians and monitoring by pharmacists. Before protocol implementation, 50 patients with HAP were evaluated against protocol criteria. After protocol implementation, a second cohort of 50 patients with HAP was evaluated. Compared with the preprotocol group, implementation of the protocol led to an increase in both the proportion of patients who received appropriate empiric antibiotic coverage (17 [34%] vs 31 [62%] patients, p=0.005) and appropriate antibiotic deescalation (21 [42%] vs 36 [72%] patients, p=0.002) according to protocol recommendations but did not affect the appropriateness of empiric antibiotic therapy based on final lung culture data (34 [68%] vs 41 [82%] patients, p=0.11). Compared with the preprotocol group, use of the protocol decreased the duration of intravenous antibiotic therapy (median [range] 9 [2-21] vs 7 [1-16] days, p=0.024), was associated with a trend for a shorter duration of stay in the intensive care unit (median [range] 19 [2-57] vs 11 [3-76] days, p=0.065), and did not significantly affect mortality (5 [10%] vs 8 [16%] patients, p=0.37). Pharmacists performed 59 interventions to support the protocol in 29 patients in the postprotocol group, of which 48% were accepted. Implementation of an HAP protocol improved appropriate empiric antibiotic use and decreased the duration of antibiotic therapy without adversely affecting patient outcomes.

When appropriate antibiotic therapy is relevant in bacteremic septic patients

In the past 10 years different authors have published higher mortality in severe infection related to inappropriate antibiotic therapy (IAT). A systematic review [1] recommends defining groups of patients that could benefit more with appropriate antibiotic therapy (AAT).

Appropriateness of antibiotic therapy on weekends versus weekdays

To compare the appropriateness of antibiotic treatment prescribed in an emergency department (ED) of a tertiary medical centre on weekdays and weekends. During a 1 month period, medical charts of 1029 ED visits for patients who were discharged from the ED were reviewed. Data of patients who were discharged with antibiotics were blind evaluated by two infectious disease specialists, and an 'appropriateness score' was given to the antibiotic prescription. Antibiotics were prescribed at discharge for 182 (17.7%) patients. Appropriate antibiotic treatment was administered significantly less frequently on weekends when compared with weekdays (P = 0.004). Appropriateness scores were higher for the surgical and urological wings (P = 0.011) and for diagnoses of pneumonia and urinary tract infection (P = 0.005). Time of the day and patient's age and sex did not have a significant effect on the appropriateness score. Adjusting for all variables, only weekends remained significantly associated with less appropriate antibiotic treatment, odds ratio 0.35 and 95% confidence intervals 0.16-0.78. This study shows less appropriate antibiotic prescription in an ED on weekends than weekdays. More studies are required to clarify measures to improve appropriate antibiotic therapy at weekends.

Évaluation des soins et pneumopathies aiguës communautaires

Evaluations of care strategies for patients with community acquired pneumonia (CAP) tend to focus more on their necessity (variation in practice...) than on efficacy (adherence, impact of markers of disease severity or medico-economic factors...). A number of studies are reported in the literature based on a simple evaluation of practice at a given moment on time or else on the impact of guidelines. These evaluations relate either to outcome criteria (mortality, and duration of stay especially) or the economic impact of CAP (rate of hospitalization, duration of stay, costs of the treatments or hospitalizations...), or on process of care (evaluation of initial severity, delay in administration of antibiotics, appropriateness of antibiotic therapy, evaluation of oxygenation and taking of specimens prior to treatment). Taken together these studies demonstrate the need to improve and standardise care. Where studies have not found a benefit from guidelines this can often be attributed to problems with assessment or study design and there are many studies showing the benefit of guideline based management and the introduction of standardised care pathways.

Design of clinical trials in sepsis: problems and pitfalls.

The pathophysiology of sepsis has been studied intensively in recent years and a variety of opportunities for therapeutic intervention have been identified. A number of biological products including endotoxin antibodies, cytokine inhibitors and receptor antagonists have been evaluated after the failure of pharmacological doses of steroids to influence survival in septic shock. Despite a number of large, international multi-centre studies, the therapeutic promise of these various interventions remains unfulfilled. These trials have largely been conducted in intensive care units in a heterogeneous population of patients with various entry criteria and end-points of response. While the clinical trial must remain the standard for assessing safety and efficacy of new interventions there are opportunities to improve on the design, execution and analysis of these studies. Factors such as the appropriateness of antibiotic therapy, the adequacy of medical and surgical management, and the issue of withdrawal or withholding of life support are discussed in relation to these studies. Furthermore the role of an independent scientific extramural review committee is stressed, particularly in relation to the impact of confounding events of an unforeseen nature. The potential for improving the quality of the analyses of clinical trials of sepsis is illustrated by a recently completed study of the efficacy of a murine monoclonal antibody to human tumour necrosis factor-alpha.

Factors influencing prognosis in bacteremia due to gram-negative organisms: evaluation of 448 episodes in a Turkish university hospital.

A total of 448 episodes of bacteremia due to gram-negative organisms observed during the 7-year period between 1983 and 1989 at Hacettepe University Hospitals were studied for evaluating the factors influencing the prognosis. The overall mortality rate was 45.0%. The mortality rates were not significantly different in "rapidly fatal" and "ultimately fatal" disease groups (48.3% and 45.5%, respectively), whereas it was significantly less (34.8%) in the "nonfatal" disease group compared with the "rapidly fatal" category. There were great differences in the mortality rates among different diseases within the same disease category. Shock, multi-organ failure, source of infection, hospital service, appropriateness of antibiotic therapy, and place of acquisition of infection were found to affect prognosis significantly in multivariate analysis. In conclusion, the identification of prognostic factors is a further step for making necessary interventions in reducing the mortality rate associated with bacteremia due to gram-negative organisms. Underlying disease is still an important prognostic factor; however, a new approach is needed for classification of underlying diseases.

Use of Microbiology Reports by Physicians in Prescribing Antimicrobial Agents

The purpose of this study was to examine the use of microbiologic reports by physicians in prescribing antimicrobial agents in a community hospital setting. Patients were identified by daily review of all blood, urine, and sputum cultures that grew pathogen(s) during a 7-week period. Appropriateness of antibiotic therapy was based on results of antibiotic susceptibility testing of isolated pathogen(s). The physician response to culture results was evaluated on changes made in antimicrobial therapy. Seventy-one patients with 73 cultures (infections) were identified; 70% of the infections were community acquired. The frequency of each infection during the study period was: bacteremia (N = 12), pneumonia (N = 18), definite urinary tract infection (N = 26) and probable urinary tract infection (N = 17). Initial treatment was appropriate in 49 of 73 (67%) episodes; the organism(s) isolated were resistant to initial therapy in 24 of 85 (33%) episodes. After culture results were available, 34 of 73 (47%) regimens were changed, but only 50% of the changes were considered appropriate. Overall, there was no significant difference in the proportion of all treatment regimens considered appropriate before (67%) and after (56%) culture results were known. We conclude that results of cultures and antibiotic susceptibility data had little influence on appropriateness of antibiotic prescribing in the hospital setting.