Timing of antibiotic therapy in the ICU

Severe or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for β-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics

Diagnosis and management of temperature abnormality in ICUs: a EUROBACT investigators' survey.

Although fever and hypothermia are common abnormal physical signs observed in patients admitted to intensive care units (ICU), little data exist on their optimal management. The objective of this study was to describe contemporary practices and determinants of management of temperature abnormalities among patients admitted to ICUs. Site leaders of the multi-national EUROBACT study were surveyed regarding diagnosis and management of temperature abnormalities among patients admitted to their ICUs. Of the 162 ICUs originally included in EUROBACT, responses were received from 139 (86%) centers in 23 countries in Europe (117), South America (8), Asia (5), North America (4), Australia (3) and Africa (2). A total of 117 (84%) respondents reported use of a specific temperature threshold in their ICU to define fever. A total of 14 different discrete levels were reported with a median of 38.2°C (inter-quartile range, IQR, 38.0°C to 38.5°C). The use of thermometers was protocolized in 91 (65%) ICUs and a wide range of methods were reportedly used, with axillary, tympanic and urinary bladder sites as the most common as primary modalities. Only 31 (22%) of respondents indicated that there was a formal written protocol for temperature control among febrile patients in their ICUs. In most or all cases practice was to control temperature, to use acetaminophen, and to perform a full septic workup in febrile patients and that this was usually directed by physician order. While reported practice was to treat nearly all patients with neurological impairment and most patients with acute coronary syndromes and infections, severe sepsis and septic shock, this was not the case for most patients with liver failure and fever. A wide range of definitions and management practices were reported regarding temperature abnormalities in the critically ill. Documenting temperature abnormality management practices, including variability in clinical care, is important to inform planning of future studies designed to optimize infection and temperature management strategies in the critically ill

Model for predicting short-term mortality of severe sepsis

International audienceABSTRACT: INTRODUCTION: To establish a prognostic model for predicting 14-day mortality in ICU patients with severe sepsis overall and according to place of infection acquisition and to sepsis episode number. METHODS: In this prospective multicentre observational study on a multicentre database (OUTCOMEREA) including data from 12 ICUs, 2268 patients with 2737 episodes of severe sepsis were randomly divided into a training cohort (n=1458) and a validation cohort (n=810). Up to four consecutive severe sepsis episodes per patient occurring within the first 28 ICU days were included. We developed a prognostic model for predicting death within 14 days after each episode, based on patient data available at sepsis onset. RESULTS: Independent predictors of death were logistic organ dysfunction (OR, 1.22 per point, p<10-4), septic shock (OR, 1.40; p=0.01), rank of severe sepsis episode (1 reference, 2: OR, 1.26; p=0.10 [greater than or equal to]3: OR, 2.64 ;10-3), multiple sources of infection (OR; 1.45, p=0.03), simplified acute physiology score II (OR, 1.02 per point; p<10-4), McCabe score ([greater than or equal to]2)(OR, 1.96; p<10-4), and number of chronic co-morbidities (1: OR, 1.75; p=10-3, [greater than or equal to]2: OR, 2.24, p= 10-3). Validity of the model was good in whole cohorts (AUC-ROC, 0.76; 95%CI [0.74; 0.79] and HL Chi-square: 15.3 (p=0.06) for all episodes pooled). CONCLUSIONS: In ICU patients, a prognostic model based on a few easily obtained variables is effective in predicting death within 14 days after the first to fourth episode of severe sepsis complicating community-, hospital-, or ICU-acquired infection

Colonization with methicillin-resistant Staphylococcus aureus in ICU patients: morbidity, mortality, and glycopeptide use.

peer reviewed[en] OBJECTIVE: To determine the impact of methicillin-resistant Staphylococcus aureus (MRSA) colonization on the occurrence of S. aureus infections (methicillin-resistant and methicillin-susceptible), the use of glycopeptides, and outcome among intensive care unit (CU) patients. DESIGN: Prospective observational cohort survey. SETTING: A medical-surgical ICU with 10 single-bed rooms in a 460-bed, tertiary-care, university-affiliated hospital. PATIENTS: A total of 1,044 ICU patients were followed for the detection of MRSA colonization from July 1, 1995, to July, 1 1998. METHODS: MRSA colonization was detected using nasal samples in all patients plus wound samples in surgical patients within 48 hours of admission or within the first 48 hours of ICU stay and weekly thereafter. MRSA infections were defined using Centers for Disease Control and Prevention standard definitions, except for ventilator-associated pneumonia and catheter-related infections, which were defined by quantitative distal culture samples. RESULTS: One thousand forty-four patients (70% medical patients) were included in the analysis. Mean age was 61+/-18 years; mean Simplified Acute Physiologic Score (SAPS) II was 36.4+/-20; and median ICU stay was 4 (range, 1-193) days. Two hundred thirty-one patients (22%) died in the ICU. Fifty-four patients (5.1%) were colonized with MRSA on admission, and 52 (4.9%) of 1,044 acquired MRSA colonization in the ICU. Thirty-five patients developed a total of 42 S. aureus infections (32 MRSA, 10 methicillin-susceptible). After factors associated with the development of an S. aureus infection were adjusted for in a multivariate Cox model (SAPS II >36: hazard ratio [HR], 1.64; P=.09; male gender: HR, 2.2; P=.05), MRSA colonization increased the risk of S. aureus infection (HR, 3.84; P=.0003). MRSA colonization did not influence ICU mortality (HR, 1.01; P=.94). Glycopeptides were used in 11.4% of the patients (119/1,044) for a median duration of 5 days. For patients with no colonization, MRSA colonization on admission, and ICU-acquired MRSA colonization, respectively, glycopeptide use per 1,000 hospital days was 37.7, 235.2, and 118.3 days. MRSA colonization per se increased by 3.3-fold the use of glycopeptides in MRSA-colonized patients, even when an MRSA infection was not demonstrated, compared to non-colonized patients. CONCLUSIONS: In our unit, MRSA colonization greatly increased the risk of S. aureus infection and of glycopeptide use in colonized and non-colonized patients, without influencing ICU mortality. MRSA colonization influenced glycopeptide use even if an MRSA infection was not demonstrated; thus, an MRSA control program is warranted to decrease vancomycin use and to limit glycopeptide resistance in gram-positive cocci

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project.

PURPOSE: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). METHODS: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. RESULTS: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. CONCLUSION: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

International survey of antibiotic dosing and monitoring in adult intensive care units

AVAILABILITY OF DATA AND MATERIALS : All data generated or analyzed during this study are included in this published article [and its supplementary information files].SUPPLEMENTARY INFORMATION : TABLE S1. Definition of infusion types and duration; TABLE S2. Online survey questions; TABLE S3. Exclusions; TABLE S4. Respondents as per Region and Economy; TABLE S5. Results according to Region and Economy; Table S6. TDM utilization and beta-lactam prolonged infusion administration according to hospital type.BACKGROUND : In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time. METHODS : A cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing, administration and monitoring of vancomycin, piperacillin/tazobactam, meropenem and aminoglycosides. RESULTS : A total of 538 respondents (71% physicians and 29% pharmacists) from 409 hospitals in 45 countries completed the survey. Vancomycin was mostly administered as an intermittent infusion, and loading doses were used by 74% of respondents with 25 mg/kg and 20 mg/kg the most favoured doses for intermittent and continuous infusions, respectively. Piperacillin/tazobactam and meropenem were most frequently administered as an extended infusion (42% and 51%, respectively). Therapeutic drug monitoring was undertaken by 90%, 82%, 43%, and 39% of respondents for vancomycin, aminoglycosides, piperacillin/tazobactam, and meropenem, respectively, and was more frequently performed in high-income countries. Respondents rarely used dosing software to guide therapy in clinical practice and was most frequently used with vancomycin (11%). CONCLUSION : We observed numerous changes in practice since the ADMIN-ICU 2015 survey was conducted. Betalactams are more commonly administered as extended infusions, and therapeutic drug monitoring use has increased, which align with emerging evidence.Clinician Researcher Fellowship funding from Sunshine Coast Hospital, Health Service Study Education Research Trust Fund (SERTF), Wishlist, the Australian National Health and Medical Research Council, an Investigator Grant and an Advancing Queensland Clinical Fellowship.https://ccforum.biomedcentral.comam2024PharmacologySDG-03:Good heatlh and well-bein