De-escalation Of Antibiotic Therapy Research Articles

Association of hospital spending with care patterns and mortality in patients hospitalized with community-acquired pneumonia.

Pneumonia is a leading cause of mortality and intensive therapy is costly. However, it is unclear whether more spending is associated with better patient outcomes or how hospitals could decrease costs. This study investigates the association between hospital spending and 14-day inpatient mortality among community-acquired pneumonia inpatients. This retrospective cohort study focused on adult pneumonia patients discharged between July 2010 and June 2015 from 260 UShospitals in the Premier database. Hospitals were divided into four pneumonia cost-of-care quartiles and average cost was calculated for each hospital. Odds of 14-day inpatient mortality and care practices were compared among high and low-cost hospitals. The study population comprised 534,038 patients with a mean age 69.5 (SD 16.3); 51.9% were female, 75% White, and 71.9% covered by Medicare. Hospitals were largely medium-sized (40.4%), located in the South (49.2%), and in urban areas (82.3%). The fully adjusted population-averaged cost was 14,486 US dollars (95% confidence interval [CI] 13,982-14,867). Hospital practices associated with cost included intensity of diagnostic work-up +$14 (95% CI+12 to +18; p < .0001) and de-escalation of antibiotic therapy, +$6836 (95% CI+2291 to +11,160; p = .004). There was no significant difference in odds of 14-day inpatient mortality between hospitals in the highest and lowest cost quartiles. Greater spending at the hospital level was not associated with lower mortality. Lower diagnostic costs were associated with lower cost of care, suggesting that judicious use of diagnostic testing might reduce costs without worsening patient outcomes.

Impact of serum procalcitonin on antibiotic stewardship in surgical high-dependency unit and intensive care unit settings

Background Procalcitonin (PCT) testing is used as a biomarker for bacterial infection. We assessed the impact of using a PCT-guided algorithm in Ninewells hospital &amp; Medical School (Dundee, Scotland, UK). Methods We conducted a retrospective analysis of the use of PCT-testing to evaluate the escalation or de-escalation of antibiotic therapy. For this, we analysed patients admitted to the intensive care unit (ICU) and surgical high dependency unit (SHDU) from November 2018 to April 2019. Results We analysed a dataset of 235 adult patients, 23% of which were at the hospital’s ICU and 77% at the SHDU. Within the ICU, 49% of admitted patients were already on antibacterial therapy, compared to 93% at SHDU. The PCT results influenced the prescription of antibiotics in 33% of total patients (89% and 16% of all ICU and SHDU patients, respectively). Escalation of the antimicrobial therapy was prescribed to 34% of ICU patients after PCT testing, compared to 20% of SHDU patients. Continuation of the previously-established antibacterial scheme was more pronounced in SHDU patients (43% against 23% ICU). In contrast, while discontinuation of the therapy was observed in similar levels on both units (27% SHDU, 28% ICU). Conclusion PCT has become a useful tool in antimicrobial stewardship. Its use aided the prescription of antibiotics in 33% of the overall total cases in ICU and SHDU. Further work should be carried out to assess its role in other clinical environments.

Deeskalace antibiotické terapie jako součást strategie péče o kriticky nemocné

Jednim z největsich problemů soucasne mediciny je extremni narůst rezistence bakterii k antibiotikům. Lecba antibiotiky se tak výrazně komplikuje, a to nejen u pacientů na jednotkach intenzivni pece, ale i v komunitě. Pro zachovani ucinnosti stavajicich antibiotik je nutna multioborova spoluprace jak na urovni diagnostiky infekci, tak předevsim spravne volby antibiotik, aby byla použivana pouze na lecbu bakterialnich infekci, nikoliv kolonizace pacienta. Jednou ze strategii antibiotickeho stewardshipu je deeskalace antibioticke terapie, avsak u pacientů v intenzivni peci neni jeji role zcela jasna. Vždy je třeba vzit v uvahu nejenom mikrobiologicke nalezy, ale předevsim klinický stav pacienta, aby nebyl upravou antibioticke lecby poskozen.

Evaluation of the Accelerate Pheno™ System for the Identification and Antimicrobial Susceptibilty Testing of Gram-negative Bacteria, Compared with Conventional Laboratory Testing

BackgroundThe current standard technique for diagnosis of bloodstream infection (BSI) is through the detection of micro-organisms using automated blood culture systems and subsequent phenotypic antimicrobial susceptibilty testing (AST) techniques that require 24–48 hours to generate results. The aim of this study was to evaluate the Accelerate Pheno™ system (AXDX), which utilises fluorescent in situ hybridization and morphokinetic cellular analysis to identify bacteria from positive blood cultures and perform AST in less than 7 hours.MethodsThe Accelerate PhenoTest™ BC kit was used to test 15 gram-negative isolates with a range of AST profiles, from simulated blood cultures. Isolates included 10 target organisms; Escherichia coli (n = 2), Enterobacter sp. (n = 2), Klebsiella sp., Proteus sp., Citrobacter sp., Pseudomonas aeruginosa, Acinetobacter baumannii, Serratia marcescens and 5 non-target organisms. AXDX results were compared with MALDI-ToF MS identification and BD Phoenix™ automated AST results. To evaluate the reproducibility of AXDX analysis, all isolates were tested at two different sites, six in duplicate.ResultsA total of 37 tests were performed. AXDX correctly identified 90% (9/10) of the target organisms, and correctly identified 100% (5/5) of non-target organisms as such. One isolate of Citrobacter sp. was initially misidentified as Enterobacter sp. but was correctly identified twice on repeat testing. The AST results demonstrated 93% (244/262) essential agreement (MIC within <1 dilution) and 90% (237/262) categorical agreement (same S/I/R interpretation) compared with conventional laboratory methods. For AST results, between-site reproducibility (MIC within <1 dilution) was 97%.ConclusionThe Accelerate PhenoTest™ BC kit can provide rapid identification alongside phenotypic AST results direct from positive blood cultures. In this study, the assay demonstrated high reproducibility and good correlation with conventional laboratory methods. By reducing the time to AST results the Accelerate Pheno™ system has the potential to produce actionable results for the management of BSI and enable earlier escalation or de-escalation of antibiotic therapy. This also has the potential to improve patient outcomes by reducing morbidity and mortality.Disclosures K. Roulston, Accelerate Diagnostics: Investigator, Research support; R. Gorton, Accelerate Diagnostics: Investigator, Research support; E. Kazantzaki, Accelerate Diagnostics: Investigator, Research support; M. Rebec, Accelerate Diagnostics: Investigator, Research support; S. Hopkins, Accelerate Diagnostics: Investigator, Research support; G. Satta, Accelerate Diagnostics: Investigator, Research support; D. Mack, Accelerate Diagnostics: Investigator, Research support

Impact of PBP2a Assay on Antibiotic Therapy of Patients with Non-Blood, Non-Urine Staphylococcus aureus Infections

BackgroundRapid diagnostic tests can reduce time to organism identification and susceptibility results, allowing for more rapid optimization of antibiotic therapy. We sought to determine whether a qualitative immunochromatographic assay (Alere™ PBP2a Culture Colony test) that differentiates methicillin-susceptible S. aureus (MSSA) from methicillin-resistant S. aureus (MRSA) could optimize time to appropriate therapy for patients with skin and soft-tissue infections (SSTIs) and nosocomial pneumonia caused by S. aureus.MethodsAdult patients admitted to The Johns Hopkins Hospital with a respiratory or wound culture growing S. aureus between July-October 2015 (baseline period) and July-October 2016 (intervention period) were included. The primary outcome was time to optimal antibiotic therapy from specimen collection before and after implementation of the PBP2a assay. Secondary outcomes were (1) time to antibiotic de-escalation from specimen collection, (2) length of hospital stay, and (3) number of vancomycin levels. An unadjusted analysis was conducted using Chi-square or Fisher’s exact test for categorical variables and Wilcoxon rank-sum test for continuous variables.Results189 patients met eligibility criteria (119 baseline, 70 intervention). There were no significant differences in characteristics of patients between periods. Overall time to optimal therapy decreased during the intervention period compared with baseline (IQR 0–24.7 hours vs. 0–64.2 hours, P = 0.02). In the subset of patients with SSTIs, time to optimal and de-escalation of antibiotic therapy was reduced during the intervention period compared with baseline (IQR 0–6.6 vs. 0-70.8, P = 0.02 and IQR 0–26.5 vs. 0-65.5, P = 0.05, respectively), but not with pneumonia. Length of hospital stay (median 6 days in each, P = 0.60) and number of vancomycin levels (median 0 vs. 1, P = 0.33) were similar before and after assay implementation.ConclusionThere was a reduction in time to optimal antibiotic therapy after implementation of the PBP2a assay driven by changes in SSTI regimens but not pneumonia regimens. Incorporation of a rapid test to differentiate MSSA from MRSA be a useful addition to antibiotic stewardship initiatives to optimize therapy for patients with MSSA infection.Disclosures P. Simner, bioMerieux: Research Contractor, Research support Check-Points Health BV: Research Contractor, Research support

Ventilator-associated pneumonia: the influence of bacterial resistance, prescription errors, and de-escalation of antimicrobial therapy on mortality rates

Ventilator-associated pneumonia is the most prevalent nosocomial infection in intensive care units and is associated with high mortality rates (14–70%). AimThis study evaluated factors influencing mortality of patients with Ventilator-associated pneumonia (VAP), including bacterial resistance, prescription errors, and de-escalation of antibiotic therapy. MethodsThis retrospective study included 120 cases of Ventilator-associated pneumonia admitted to the adult adult intensive care unit of the Federal University of Uberlândia. The chi-square test was used to compare qualitative variables. Student's t-test was used for quantitative variables and multiple logistic regression analysis to identify independent predictors of mortality. FindingsDe-escalation of antibiotic therapy and resistant bacteria did not influence mortality. Mortality was 4 times and 3 times higher, respectively, in patients who received an inappropriate antibiotic loading dose and in patients whose antibiotic dose was not adjusted for renal function. Multiple logistic regression analysis revealed the incorrect adjustment for renal function was the only independent factor associated with increased mortality. ConclusionPrescription errors influenced mortality of patients with Ventilator-associated pneumonia, underscoring the challenge of proper Ventilator-associated pneumonia treatment, which requires continuous reevaluation to ensure that clinical response to therapy meets expectations.

Lower Mortality with De-escalation of Antibiotic Therapy in Sepsis

Surviving Sepsis Campaign guidelines recommend the use of broad-spectrum antibiotics in the initial management of patients with severe sepsis or septic

SP27-2 Treatment for healthcare associated pneumonia

SP27-2 Treatment for healthcare associated pneumonia W.-H. Sheng*. National Taiwan University Hospital, Taiwan Hospital acquired pneumonia (HAP) is one of the leading cause of healthcare associated infections in intensive care units (ICU). Ventilator-associated pneumonia (VAP) is the most common type of HAP. Patients who acquire HAP/VAP have higher mortality rates and longer ICU and hospital stays. HAP/VAP also is characterized with severe underlying systemic diseases and causative pathogens of multi-drug resistance, such as methicillin-resistant Staphylococcus aureus , Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae. Delayed administration of adequate antibiotic therapy is linked to an increased mortality rate. Therefore, the initial antibiotic therapy should be to rapidly provide coverage for all likely pathogens and to then narrow the antibiotic spectrum based on the results of quantitative cultures by bronchoscopic examination. The optimal antibiotic strategy for the treatment of HAP remains controversial. According to the ATS/IDSA guideline, initial treatment for mild– moderate HAP without risk for multidrug resistant microorganisms (MDRO), a fluoroquinolone (levofloxacin or moxifloxacin), or amoxicillin/clavulanate plus a macrolide has been suggested. For patients with severe HAP/VAP, late onset of VAP, with risk for MDRO, an antipseudomonal cephalosporin (cefepime, ceftazidime), or an antipseudomonal carbapenem (imipenem, meropenem), or a b-lactam/b-lactamase inhibitor (piperacillin/tazobactam) plus an antipseudomonal fluoroquinolone (levofloxacin, ciprofloxacin), or an aminoglycoside (amikacin, gentamicin, tobramycin) plus either linezolid or vancomycin is suggested. Clinical improvement usually takes 48 to 72h, therefore, unless the patient is declining clinically, antibiotics should not be modified during this time unless dictated by the results of microbiologic sensitivity. Eight days of antibiotic therapy appears equivalent to 15 daysof therapy except when treating non-glucose fermenting Gram-negative bacteria. A guideline-based approach using the local hospital or ICU antibiogram can increase the likelihood that adequate initial antibiotic therapy is used and reduce the overall use of antibiotics and the associated selection pressure for MDRO. In conclusion, a systematically applied strategy that addresses early intervention with broad-spectrum antibiotics based on the risks for MDRO, and which is appropriate to the local antibiogram, can improve outcomes. This strategy also includes quantitative culture of respiratory secretions, de-escalation of antibiotic therapy once culture results are available, and discontinuation of antibiotics after 8 daysof treatment in patients without Pseudomonas or Acinetobacter as the causative pathogens.

SP27-3 Treatment of noscomial pneumonia

SP27-2 Treatment for healthcare associated pneumonia W.-H. Sheng*. National Taiwan University Hospital, Taiwan Hospital acquired pneumonia (HAP) is one of the leading cause of healthcare associated infections in intensive care units (ICU). Ventilator-associated pneumonia (VAP) is the most common type of HAP. Patients who acquire HAP/VAP have higher mortality rates and longer ICU and hospital stays. HAP/VAP also is characterized with severe underlying systemic diseases and causative pathogens of multi-drug resistance, such as methicillin-resistant Staphylococcus aureus , Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae. Delayed administration of adequate antibiotic therapy is linked to an increased mortality rate. Therefore, the initial antibiotic therapy should be to rapidly provide coverage for all likely pathogens and to then narrow the antibiotic spectrum based on the results of quantitative cultures by bronchoscopic examination. The optimal antibiotic strategy for the treatment of HAP remains controversial. According to the ATS/IDSA guideline, initial treatment for mild– moderate HAP without risk for multidrug resistant microorganisms (MDRO), a fluoroquinolone (levofloxacin or moxifloxacin), or amoxicillin/clavulanate plus a macrolide has been suggested. For patients with severe HAP/VAP, late onset of VAP, with risk for MDRO, an antipseudomonal cephalosporin (cefepime, ceftazidime), or an antipseudomonal carbapenem (imipenem, meropenem), or a b-lactam/b-lactamase inhibitor (piperacillin/tazobactam) plus an antipseudomonal fluoroquinolone (levofloxacin, ciprofloxacin), or an aminoglycoside (amikacin, gentamicin, tobramycin) plus either linezolid or vancomycin is suggested. Clinical improvement usually takes 48 to 72h, therefore, unless the patient is declining clinically, antibiotics should not be modified during this time unless dictated by the results of microbiologic sensitivity. Eight days of antibiotic therapy appears equivalent to 15 daysof therapy except when treating non-glucose fermenting Gram-negative bacteria. A guideline-based approach using the local hospital or ICU antibiogram can increase the likelihood that adequate initial antibiotic therapy is used and reduce the overall use of antibiotics and the associated selection pressure for MDRO. In conclusion, a systematically applied strategy that addresses early intervention with broad-spectrum antibiotics based on the risks for MDRO, and which is appropriate to the local antibiogram, can improve outcomes. This strategy also includes quantitative culture of respiratory secretions, de-escalation of antibiotic therapy once culture results are available, and discontinuation of antibiotics after 8 daysof treatment in patients without Pseudomonas or Acinetobacter as the causative pathogens.

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Introduction: Though procalcitonin (PCT) is produced at low levels in the human body, inflammatory processes such as bacterial infections may result in increased production. Research related to PCT use has resulted in 2 primary hypotheses for use: diagnosis of infection and de-escalation of antibiotic therapy. However, there continue to be conflicting reports regarding use of PCT in the management of infectious patients. Hypothesis: We hypothesized that patients with a positive PCT (> 0.5 mcg/L) would have an increased incidence of infections. Methods: This retrospective study was conducted at 4 adult hospitals within a health system and evaluated the presence of infection in patients with whom PCT levels were assessed. Included patients were divided into positive and negative PCT groups, and the presence of infection, both clinical or microbiologic, was compared. PCT levels were also stratified by sepsis severity and compared based on infectious location and organism. Results: A total of 300 patients were included, with 153 patients having a positive PCT (51%). There was no difference in the diagnosis of clinical infection between groups (43.8% vs 39.5%, p=0.45). However, the positive PCT group had an increased percentage of patients with any microbiologic infection (49.7% vs 22.4%, p<0.001), blood stream infections (21.7% vs 5.5%, p=0.001), and Gram-negative infections (29.4% vs 15.4%, p=0.015). With respect to increasing illness severity, there was a difference in the median PCT values between sepsis classifications (p<0.001). Overall, positive PCT values demonstrated a sensitivity and specificity of 61.1% and 84.8% for clinical infection; however, this decreased to 69.7% and 59.7% when microbiologic infections were assessed. Conclusions: To our knowledge, this is the first clinical study within the community health setting to assess infectious diagnoses in patients with positive PCT values. Our study demonstrates only moderate sensitivity and specificity of PCT for infectious diagnoses, which decreased further in microbiologically positive patients. Though PCT levels may correlate to an infection, this study demonstrates that the optimal use of PCT as a diagnostic aid in infectious patients remains unclear.

Lumbar Puncture for Suspected Meningitis After Intensive Care Unit Admission is Likely to Change Management

Purpose: The aim of this study was to determine the outcome of lumbar punctures (LPs) in critically ill medical patients and how likely the results were to change case management. Materials and Methods: A retrospective review was conducted on the medical records of all 168 patients who underwent LP during their medical intensive care unit (MICU) admission at a university hospital during a 4.5-year period beginning in January 2000. Results: Lumbar puncture was performed a mean of 2.8 days after MICU admission. The most common symptoms that prompted LP were changes in mental status and fever. Seventy-four percent of patients were on antibiotics at the time of LP, and 98% of patients had a computed tomography scan of the head performed before the procedure. Lumbar puncture confirmed meningitis in 47 (30%) patients and provided a specific bacteriologic diagnosis in 5 (3%) patients. The results of the procedure led to a change in management in 50 (30%) patients. The presence of meningeal signs and use of antibiotics at the time of the procedure were the factors that predicted change in management. Conclusion: Although the likelihood that LP will yield a specific bacteriologic diagnosis in critically ill patients is low, the procedure frequently provides important information that can lead to a change in case management, most commonly de-escalation of antibiotic therapy.

Does De-Escalation of Antibiotic Therapy for Ventilator-Associated Pneumonia Affect the Likelihood of Recurrent Pneumonia or Mortality in Critically Ill Surgical Patients?

Does De-Escalation of Antibiotic Therapy for Ventilator-Associated Pneumonia Affect the Likelihood of Recurrent Pneumonia or Mortality in Critically Ill Surgical Patients?

Beatmungsassoziierte Pneumonie und multiresistente bakterielle Erreger

Ventilator-associated pneumonia remains the most serious nosocomial infection in critically ill patients. Providing appropriate antibiotic therapy promptly is crucial for successful treatment; whereas the diagnostic approach seems to play a minor role. The empirical antibiotic therapy should be guided by the risk for infections due to multiresistant bacteria. For patients at risk a combination therapy, considering local resistance data and formerly applied antibiotic substances, is recommended. Reevaluation and deescalation of antibiotic therapy based on microbiological culture results and discontinuation of antimicrobial treatment after one week is essential for the control of broadspectrum antibiotic use and antibiotic resistance.

Indication, intérêts et limites de la désescalade antibiotique en réanimation

De-escalation of antibiotic therapy is a strategy aiming both to provide adequate initial antimicrobial therapy and to minimize the risk of emerging resistance. Theoretically, de-escalation was only possible in patients exhibiting, 48–72 hours after the beginning of antimicrobial treatment, positive bacteriological cultures and clinical improvement. De-escalation is a switch from an initial broad-spectrum antibiotic therapy to a specific antibiotic therapy based on microbiological data. This management strategy is now considered as the best therapeutic approach in hospital-acquired pneumonia. It could be proposed for most infectious diseases encountered in ICU, subject to know the value of microbiological testing and to be able to evaluate the clinical outcome.