Adequate Antimicrobial Therapy Research Articles

Treatment of positive catheter tip culture without bloodstream infections in critically ill patients. A case-cohort study from the OUTCOMEREA network

PurposeThis study aimed to evaluate the impact on subsequent infections and mortality of an adequate antimicrobial therapy within 48 h after catheter removal in intensive care unit (ICU) patients with positive catheter tip culture.MethodsWe performed a retrospective analysis of prospectively collected data from 29 centers of the OUTCOMEREA network. We developed a propensity score (PS) for adequate antimicrobial treatment, based on expert opinion of 45 attending physicians. We conducted a 1:1 case-cohort study matched on the PS score of being adequately treated. A PS-matched subdistribution hazard model was used for detecting subsequent infections and a PS-matched Cox model was used to evaluate the impact of antibiotic therapy on mortality.ResultsWe included 427 patients with a catheter tip culture positive with potentially pathogenic microorganisms. We matched 150 patients with an adequate antimicrobial therapy with 150 controls. In the matched population, 30 (10%) subsequent infections were observed and 62 patients died within 30 days. Using subdistribution hazard models, the daily risk to develop subsequent infection up to Day-30 was similar between treated and non-treated groups (subdistribution hazard ratio [sHR] 1.08, 95% confidence interval [CI] 0.62–1.89, p = 0.78). Using Cox proportional hazard models, the 30-day mortality risk was similar between treated and non-treated groups (HR 0.89, 95% CI 0.45–1.74, p = 0.73).ConclusionsAntimicrobial therapy was not associated with decreased risk of subsequent infection or death in short-term catheter tip colonization in critically ill patients. Antibiotics may be unnecessary for positive catheter tip cultures.

Current application and future perspectives of antimicrobial degradable bone substitutes for chronic osteomyelitis.

Chronic osteomyelitis remains a persistent challenge for the surgeons due to its refractory nature. Generally, treatment involves extensive debridement of necrotic bone, filling of dead space, adequate antimicrobial therapy, bone reconstruction, and rehabilitation. However, the optimal choice of bone substitute to manage the bone defect remains debatable. This paper reviewed the clinical evidence for antimicrobial biodegradable bone substitutes in the treatment of osteomyelitis in recent years. Indeed, this combination was proved to eradicate infection and facilitate bone reconstruction, which might reduce the cost and hospital stay. Handling was associated with increased risk of unwanted side effect to affect bone healing. The study provides some valuable insights into the clinical evaluation of treatment outcomes in the aspects of infection eradication, bone reconstruction, and complications caused by materials. However, achieving complete infection eradication and subsequently perfect bone reconstruction remains challenging in compromised conditions, hence advanced innovative bone substitutes are imperative. In this review, we mainly focus on the desired functional effects of advanced bone substitutes on infection eradication and bone reconstruction from the future perspective. Handling property was optimized to simplify surgery process. It is expected that this review will provide an important opportunity to enhance the understanding of the design and application of innovative biomaterials to synergistically eradicate infection and restore integrity and function of bone.

The role of centre and country factors on process and outcome indicators in critically ill patients with hospital-acquired bloodstream infections

PurposeThe primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI).MethodsWe used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators.ResultsTwo thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03–2.14] or within a few hours (OR 1.79, 95% CI 1.34–2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09–1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47–0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44–1.00) or within a few hours (OR 0.51, 95% CI 0.37–0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47–0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00–2.80), and decreasing HDI values were associated with 28-day mortality.ConclusionCentre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.

Development of polyresistance in microorganisms during antibiotic therapy in a multidisciplinary hospital during a pandemic COVID-19

Background. Irrational and excessive use of antimicrobials drugs (AMD) creates conditions for the development of a global crisis of health systems around the world associated with antibiotic resistance.
 Aim. To conduct a retrospective study of the impact of the use of AMD on the change in the microbiological landscape and the sensitivity of microorganisms in the conditions of pandemic of the new coronavirus infection (COVID-19) in 2020–2021 in intensive care departments (ICD) of a multidisciplinary hospital.
 Materials and methods. In the course of the work, strains of microorganisms isolated from patients and from the surfaces of the hospital environment and changes in their sensitivity to significant groups of AMD in ICD for somatic and infectious patients with COVID-19 were compared. The sensitivity of the isolates was evaluated in accordance with the criteria of requirements of European Committee on Antimicrobial Susceptibility Testing – EUCAST, version 10.0, 2020.
 Results. A total of 1,394 isolates were studied, including 1,379 clinical and 15 isolates from the surfaces of the hospital environment. It was found that in all ICD in 2020–2021, gram-negative microorganisms prevailed in infectious loci in 70% of cases or more. In 2021, in the ICD in infectious patients with COVID-19, the persistent dominance of the Acinetobacter baumannii microorganism was revealed with an increase in the number of poly- and pan-resistant strains – 48.7%. While in the ICD for somatic patients Klebsiella Pneumoniae prevailed among gram-negative microorganisms – 37.5% in 2020 and 43.7% in 2021. It has been shown that in one department or in adjacent departments of the same medical institution, various nosocomial microorganisms with an unequal set of resistance genes and sensitivity to AMD may appear over time.
 Conclusion. The necessity of conducting constant microbiological monitoring and a passport of the medical department with mandatory registration of not only isolated strains of microorganisms, but also resistance genes in order to optimize the appointment of timely adequate empirical antimicrobial therapy is substantiated. The period of the latter should be as short as possible, and confirmed by convincing clinical signs of bacterial infection, and subsequently by the isolation of nosocomial flora from the biomaterial of critical loci from patients.

A Systematic Review of the Pulmonary Microbiome in Patients with Acute Exacerbation COPD Requiring ICU Admission.

Background: Chronic obstructive pulmonary disease (COPD) is a major health concern. Acute exacerbations (AECOPD) may require intensive care unit (ICU) admission and mechanical ventilation. Acute infections and chronic colonization of the respiratory system are known to precipitate AECOPD. Detailed knowledge of the respiratory microbiome could lead to effective treatment and prevention of exacerbations. Objective: The aim of this review is to summarize the available evidence on the respiratory microbiome of patients with a severe AECOPD requiring mechanical ventilation and intensive care admission. Methods: A systematic literature search was conducted to identify the published papers until January 2023. The collected data were then subjected to qualitative analysis. After the first analysis, a secondary focused review of the most recent publications studying the relationship between microbiome and mortality in AECOPD was performed. Results: Out of 120 screened articles six articles were included in this review. Potentially pathogenic microorganisms (PPMs) were identified in 30% to 72% of the patients with community-acquired bacteria, gram-negative enteric bacilli, Stenotrophomonas and Pseudomonas being the most frequently isolated. During hospitalization, 21% of patients experienced colonization by PPMs. Adequate antimicrobial therapy resulted in the eradication of 77% of the identified PPMs. However, 24% of the bacteria displayed multi-drug resistance leading to prolonged or failure of eradication. Conclusion: PPMs are prevalent in a significant proportion of patients experiencing an AECOPD. The most identified PPMs include community-acquired pathogens and gram-negative enteric bacilli. Notably, no differences in mortality or duration of ventilation were observed between patients with and without isolated PPMs. However, the included studies did not investigate the virome of the patients, which may influence the microbiome and the outcome of infection. Therefore, further research is essential to comprehensively investigate the complete microbial and viral composition of the lower respiratory system in COPD patients admitted to the ICU.

Detection of Carbapenem Resistance in Enterobacterales Directly From Positive Blood Cultures Using Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry.

Carbapenem-resistant Enterobacterales are disseminated worldwide and associated with infections with high rates of morbidity and mortality. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a useful tool for identification of pathogens directly from blood cultures in clinical microbiology laboratories. Furthermore, it has been applied for the detection of carbapenemase production, by evaluating carbapenem hydrolysis. To determine meropenem hydrolysis to detect carbapenemase production directly from positive blood cultures, using logRQ to establish a quantitative measure of hydrolysis. We evaluated 100 Enterobacterales from positive blood cultures, with 81 carrying a carbapenemase gene (blaKPC, blaGES, blaNDM-1, blaIMP, blaVIM, and blaOXA-48-like), as determined by real-time multiplex polymerase chain reaction with high-resolution melting (HRM-qPCR). Bacterial proteins extracted from positive blood culture bottles were incubated in a meropenem solution (2-4 hours) followed by centrifugation for MALDI-TOF MS analysis. The intensity of peaks of the hydrolyzed and nonhydrolyzed forms were used to calculate the logRQ value. Overall, sensitivity was 86.8% and specificity, 89.5%. Of note, sensitivity varied depending on enzyme type. For blaKPC-positive isolates, sensitivity was 97.9%, while it reduced significantly for blaNDM-1 and blaOXA-48-like isolates: 62.5% (10 of 16) and 66.7% (6 of 9), respectively. Indeed, logRQ was higher in blaKPC-positive isolates (0.37-1.97) than in blaNDM-1 (-1.37 to 0.83) and blaOXA-48-like isolates (-1.08 to 1.79). This is an inexpensive and rapid test to identify carbapenemase activity directly from blood culture bottles, which contributes to early adequate antimicrobial therapy and implementation of infection control measures.

Addressing Antimicrobial Resistance (AMR) on Dairy Farms: A One Health Case Study from Punjab, India

Abstract This case study explores the antimicrobial usage (AMU) practices on Punjab’s dairy farms, aiming to address the challenge of antimicrobial resistance (AMR) through collaborative efforts. It uncovers diverse AMU practices contributing to misuse, particularly on farm management-related diseases, such as mastitis, reproductive disorders, diarrhoeal diseases, and blood parasite infections. Some animal farms displayed high AMU levels of ‘critical importance’ category antibiotics, as per the World Health Organization. Additionally, some farmers exhibited inadequate knowledge and understanding of the importance of completing adequate antimicrobial therapy courses. The key risk factors for incorrect AMU include lack of awareness among the informal animal health service providers (without formal education/qualification), over-the-counter access of antibiotics, self-treatment practices by the farmers, and limited understanding of AMR’s public health implications. The study undertook a series of initiatives to combat AMR, including subject awareness workshops, biosecurity awareness activities comprising proper disposal of farm waste, and workshops for veterinarians, para-veterinarians, and farmers, sensitizing about AMR’s adverse consequences. Recommendations include enhancing access to qualified veterinarians, discouraging reliance on unauthorized practitioners, enhancing diagnostic capabilities, and providing technical support for disease prevention. Establishing AMU and AMR surveillance systems is essential for informed decision-making. Collaborative efforts are vital to raise awareness, promote responsible AMU, and ensure animal and public health security. These joint actions among dairy chain stakeholders are imperative to combat AMR and foster sustainable dairy production while protecting animal and human health. Information © The Authors 2023

Antimicrobial Multidrug Resistance: Clinical Implications for Infection Management in Critically Ill Patients.

The increasing incidence of antimicrobial resistance (AMR) worldwide represents a serious threat in the management of sepsis. Due to resistance to the most common antimicrobials prescribed, multidrug-resistant (MDR) pathogens have been associated with delays in adequate antimicrobial therapy leading to significant increases in mortality, along with prolonged hospital length of stay (LOS) and increases in healthcare costs. In response to MDR infections and the delay of microbiological results, broad-spectrum antibiotics are frequently used in empirical antimicrobial therapy. This can contribute to the overuse and misuse of antibiotics, further promoting the development of resistance. Multiple measures have been suggested to combat AMR. This review will focus on describing the epidemiology and trends concerning MDR pathogens. Additionally, it will explore the crucial aspects of identifying patients susceptible to MDR infections and optimizing antimicrobial drug dosing, which are both pivotal considerations in the fight against AMR. Expert commentary: The increasing AMR in ICUs worldwide makes the empirical antibiotic therapy challenging in septic patients. An AMR surveillance program together with improvements in MDR identification based on patient risk stratification and molecular rapid diagnostic tools may further help tailoring antimicrobial therapies and avoid unnecessary broad-spectrum antibiotics. Continuous infusions of antibiotics, therapeutic drug monitoring (TDM)-based dosing regimens and combination therapy may contribute to optimizing antimicrobial therapy and limiting the emergence of resistance.

Multidisciplinary treatment of thoracic fistulous empyema caused by pulmonary infection: a retrospective study.

In cases of thoracic empyema, the presence of a fistula is known to be difficult to treat and associated with a poor prognosis. Few reports have described the management of fistulous empyema caused by lung parenchymal infection. The aim of this study was to describe the outcomes of multidisciplinary management of fistulous empyema caused by pneumonia or lung abscess due to common bacteria and mycobacteria. Among 108 cases of empyema surgically treated at Kanagawa Hospital over a 10-year period, 14 patients with fistulous empyema due to common bacteria (CBFE) or fistulous empyema due to mycobacteria (MFE) were analyzed. Fistulous empyema due to lung resection was excluded. Eight out of the 9 patients with CBFE and 4 out of the 5 patients with MFE were male. Patients with CBFE were more likely to be >65 years of age (p=0.052) and to have a poor performance status (p=0.078). The time from onset to first surgical treatment was significantly longer in MFE (median, 5 months; p=0.004). Five patients with CBFE and two patients with MFE underwent open window thoracostomy, while three patients with CBFE and four patients with MFE underwent endobronchial occlusion (EBO). Six patients (66%) with CBFE and 3 patients (60%) with MFE achieved fistula closure. Of the patients who underwent EBO, fistula closure was achieved in 3 (100%) of the patients with CBFE and in 2 (50%) of the patients with MFE. Fistula closure was not achieved in any case with non-tuberculous mycobacteria. Fistulous empyema caused by common bacteria or Mycobacterium tuberculosis could be cured by surgical treatment and endobronchial intervention with adequate antimicrobial therapy, but fistulous empyema caused by non-tuberculous mycobacteria proved to be intractable. The challenge in the treatment of fistulous empyema due to non-tuberculous mycobacteria is the achievement of bacterial negativity.

Programa de detección y control de la infección y colonización de enterobacterias productoras de carbapenemasas en una Unidad de Cuidados Intensivos Pediátricos en Colombia

IntroductionCarbapenemase-producing Enterobacteriaceae (CPEs) are one of the multidrug-resistant microorganisms of greatest public health concern because they are a major cause of nosocomial infections, leading to higher costs, hospital stays, and increased mortality. This problem is increasingly frequent in the pediatric population with mortality rates due to associated infections of up to 50%. With this paper we would like to present and describe our experience in the implementation of a CLD detection and control program in our PICU. MethodsA system of detection and screening through a search policy that defines the groups at risk and detects patients at risk of colonization by CLD, makes timely isolation of patients colonized with positive CLD and patients considered at risk of colonization pending the results of the culture, finally the control and monitoring of patients colonized by CLD. ResultsDuring the period from 2017 - 2020, 1548 patients were admitted to the PICU of the Hospital Universitario Fundación Santa Fe de Bogotá and it was determined that 6.1% of these met at least one risk factor for colonization by CLD; consequently, 95 screenings were performed in 4 years. At the end of the period studied, a cumulative incidence of CLD colonization of 18.94% was obtained among patients with risk factors. ConclusionsWe cannot analyze the factors associated with survival or find a significantly lower or higher survival rate by age; but at the end of follow-up we can affirm that this active surveillance strategy favors the rapid stratification of patient risk and the timely initiation of adequate antimicrobial therapy in early stages of infection. Also, timely and targeted treatment has been shown to improve clinical outcomes in high-risk patient populations, including patients with hematologic pathologies, and allows the development of personalized sepsis care plans.

Determinants of Inadequate Empiric Antimicrobial Therapy in ICU Sepsis Patients in Al-Madinah Al-Munawwarah, Saudi Arabia: A Comparison of Artificial Neural Network and Regression Analysis.

In the management of sepsis, providing adequate empiric antimicrobial therapy is one of the most important pillars of sepsis management. Therefore, it is important to evaluate the adequacy of empiric antimicrobial therapy (EAMT) in sepsis patients admitted to intensive care units (ICU) and to identify the determinants of inadequate EAMT. The aim of this study was to evaluate the adequacy of empiric antimicrobial therapy in patients admitted to the ICU with sepsis or septic shock, and the determinants of inadequate EAMT. The data of patients admitted to the ICU units due to sepsis or septic shock in two tertiary healthcare facilities in Al-Madinah Al-Munawwarah were retrospectively reviewed. The current study used logistic regression analysis and artificial neural network (ANN) analysis to identify determinants of inadequate empiric antimicrobial therapy, and evaluated the performance of these two approaches in predicting the inadequacy of EAMT. The findings of this study showed that fifty-three per cent of patients received inadequate EAMT. Determinants for inadequate EAMT were APACHE II score, multidrug-resistance organism (MDRO) infections, surgical history (lower limb amputation), and comorbidity (coronary artery disease). ANN performed as well as or better than logistic regression in predicating inadequate EAMT, as the receiver operating characteristic area under the curve (ROC-AUC) of the ANN model was higher when compared with the logistic regression model (LRM): 0.895 vs. 0.854. In addition, the ANN model performed better than LRM in predicting inadequate EAMT in terms of classification accuracy. In addition, ANN analysis revealed that the most important determinants of EAMT adequacy were the APACHE II score and MDRO. In conclusion, more than half of the patients received inadequate EAMT. Determinants of inadequate EAMT were APACHE II score, MDRO infections, comorbidity, and surgical history. This provides valuable inputs to improve the prescription of empiric antimicrobials in Saudi Arabia going forward. In addition, our study demonstrated the potential utility of applying artificial neural network analysis in the prediction of outcomes in healthcare research.

#6437 INTRABDOMINAL ABSCESS: AN UNEXPECTED CAUSE OF POSTPARTUM SEPSIS IN A VAGINALLY DELIVERED WOMAN WITH PREGNANCY RELATED ACUTE KIDNEY INJURY

Abstract Pregnancy related-Acute kidney injury (PR-AKI) is a life-threatening complication with substantial fetal and maternal mortality and morbidity. AKI is associated with increased risk of infection and/or sepsis. Intra-abdominal infections account for 11.9% of infections that complicate AKI among critically ill patients. The pathophysiology is not fully understood, several theories have been proposed; of which, AKI associated hypervolemia leads to tissue edema and bacterial translocation. Moreover, AKI induces a hyper-inflammatory state and suppresses the immune system, this may present a greater predisposition for infection. Here we report a rare case of intra-abdominal abscess presented in a woman with recovering PR-AKI three months following normal vaginal delivery. Case presentation A 20-year-old, previously healthy female patient, was admitted due to severe postpartum hemorrhage (PPH) complicating a full-term vaginal delivery. On admission, blood pressure was 170/70, heart rate was 100 beats/min, and respiratory rate was 22 breaths/min. The patient developed oliguria, generalized edema, and fever (38.50c). The blood tests are revealed in Table I. The patient had elevated liver enzymes (SGOT 197 IU/L, and SGPT 117 IU/L). The patient was started on supportive treatment with packed RBC, platelet transfusion, and fresh frozen plasma. Empiric antibiotic was administrated. The patient subsequently had general improvement and was discharged 17 days after delivery with partial recovery of kidney function. Three months later, the patient presented with throbbing pain in the lower abdomen and fever. Abdominal examination revealed pelvi-abdominal fullness along with mild tenderness with no guarding or rigidity. No obvious palpable lumps were detected. No abnormities were detected in per vaginal and per rectal examinations. CT scan was performed and revealed a large sized collection in the lower abdomen sized 6.5x5x9 cm. Ultrasound guided aspiration of 60 ml pus confirmed the diagnosis of intraabdominal abscess. Intravenous antibiotics were started with percutaneous drainage of the abscess. Discussion Intraabdominal abscess is a serious ailment, and it is associated with high mortality and morbidity if left untreated. An intra-abdominal abscess can cause symptoms such as prolonged ileus, anorexia, fever, and abdominal pain. Septic shock may eventually develop in case of delayed treatment. However rare, there should be a causative factor. Intraabdominal abscess following a normal vaginal delivery is very rare and not reported with PR-AKI. CT scan is still the most useful technique for diagnosis and treatment. Additionally, it can help guide percutaneous drainage by locating the abscess in relation to the viscera of the abdomen. The use of adequate antimicrobial drug therapy in combination is a fundamental approach. It is therefore of great importance to consider symptoms such as atypical abdominal distension or pain in women in the postpartum period and to provide thorough comprehensive evaluation. Early diagnostic consideration greatly lessens patients’ morbidity and mortality.

Pseudomonas aeruginosa in tracheal aspirate: Colonization, infection, and recurrence.

Pseudomonas aeruginosa respiratory infections are challenging, and the risk of recurrence is a frequent problem. The aim of this study was to investigate the risk factors associated with the presence of P.aeruginosa, and the risk factors related to the recurrence and death of lower airway infections in inpatients in a Brazilian hospital. Retrospective cohort with inpatients that had a sample of airways culture (tracheal aspirate or bronchoalveolar lavage) with the detection of P.aeruginosa. The patients with clinical criteria of infection were classified as ventilator-associated, hospital-acquired, or community-acquired pneumonia. P.aeruginosa in respiratory samples without symptoms was considered colonization. The antimicrobial treatment adequacy and the clinical data were evaluated. Outcome variables included mortality and recurrence. One hundred and fifty-four patients were included in the study, most of them were men, and the majority (102) were considered infected. The average length of stay was superior to 30 days. Previous pulmonary disease was associated with the occurrence of colonization. Aminoglycosides were the most active drug according to susceptibility tests and were successfully used as monotherapy. Septic shock was a risk factor for death in the infected patients. The use of adequate antimicrobial therapy was associated with major survival, independent of the infection classification. It is possible to evaluate clinical data associated with recurrence and mortality in patients with different lung infections by P.aeruginosa. Aminoglycoside monotherapy is safe and effective in P.aeruginosa respiratory infections.

Impact of withholding early antibiotic therapy in nonseptic surgical patients with suspected nosocomial infection: a retrospective cohort analysis

BackgroundSystemic inflammatory responses mimicking infectious complications are often present in surgical patients. MethodsThe objective was to assess the association between withholding early antimicrobial therapy while investigating alternative diagnoses and worse outcomes in nonseptic patients with suspected nosocomial infection in a retrospective cohort of critically ill surgical patients. The initiation of antibiotic therapy within 24 h of the suspicion of infection was defined as the Early Empirical Antibiotic strategy (EEA) group and the initiation after 24 h of suspicion or not prescribed was defined as the Conservative Antibiotic strategy (CA) group. Primary outcome was composite: death, sepsis, or septic shock within 14 days. Main exclusion criteria were sepsis or an evident source of infection at inclusion. ResultsThree hundred and forty patients were eligible for inclusion (74% trauma patients). Age, sex, reason for hospital admission, SAPS3 score, SOFA score, and use of vasopressors or mechanical ventilation were not different between the groups. Within 14 days of inclusion, 100% (130/130) of EEA patients received antibiotics compared to 57% (120/210) of CA patients. After adjusting for confounding variables, there was no association between primary outcome and the groups. In a post hoc subgroup analysis including only patients with a posteriori confirmed infection (by microbiological cultures), delay in initiation of adequate antimicrobial therapy was independently associated with the primary outcome (Odds Ratio = 1.19 per day of delay; 95% CI 1.05–1.37). ConclusionsWithholding early empiric antibiotic therapy was not associated with progression of organ dysfunction within 14 days in nonseptic surgical patients with suspected nosocomial infection without an obvious source.

Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study.

In the critically ill, hospital-acquired bloodstream infections (HA-BSI) are associated with significant mortality. Granular data are required for optimizing management, and developing guidelines and clinical trials. We carried out a prospective international cohort study of adult patients (≥ 18years of age) with HA-BSI treated in intensive care units (ICUs) between June 2019 and February 2021. 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8 [IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%), Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp. (14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%, respectively. Difficult-to-treat resistance (DTR) waspresent in 23.5% and pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within 24h for 51.5%. Antimicrobial resistance was associated with longer delays to adequate antimicrobial therapy. Source control was needed in 52.5% but not achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged alivefrom hospital by day-28. HA-BSI was frequently caused by Gram-negative, carbapenem-resistant and DTR pathogens. Antimicrobial resistance led to delays in adequate antimicrobial therapy. Mortality was high, and at day-28 only a minority of the patients were discharged alive from the hospital. Prevention of antimicrobial resistance and focusing on adequate antimicrobial therapy and source control are important to optimize patient management and outcomes.

Adequacy of Empiric Antibiotics Therapy and Its Impact on Outcomes in Adult Critically Ill Sepsis Patients: A Review.

Sepsis is a medical emergency that involves a systemic immunological response due to an infection, resulting in the end-stage-organs malfunction and death. It is associated with high mortality rate despite a better understanding of the disease pathology and the mechanism involved. This review was designed to summarise the available evidences regarding the adequacy of the empiric antimicrobial therapy (EAMT), its predictors and its impact on the outcomes in intensive care unit (ICU) sepsis patients. Providing an adequate EAMT is considered one of the cornerstones of sepsis management as it has been found to be associated with better survival and is a good predictor for shorter ICU-length-of-stay. In contrast, inadequate EAMT in sepsis patients is associated with poor clinical outcomes including increased mortality and prolonged hospital stay. Evidence from this review suggest that it is important to identify determinants of inadequate EAMT to optimise the antimicrobial therapy provided to sepsis patients. Predictors of inadequate EAMT included co-morbidities (cancer), source and type of infection, higher Acute Physiology and Chronic Health Evaluation (APACHI-II) score and long hospital stay prior to the infection. As EAMT is considered as one of the effective treatment strategies to prevent sepsis associated death, healthcare providers should ensure the adequate antimicrobial therapy is provided for sepsis patients to improve and optimise their management.

TRICUSPID VALVE INFECTIVE ENDOCARDITIS REQUIRING VALVE REPLACEMENT THREE TIMES IN AN IV DRUG USER

TRICUSPID VALVE INFECTIVE ENDOCARDITIS REQUIRING VALVE REPLACEMENT THREE TIMES IN AN IV DRUG USER

Invasiveness of Ventilation Therapy Is Associated to Prevalence of Secondary Bacterial and Fungal Infections in Critically Ill COVID-19 Patients.

Superinfections are a fundamental critical care problem, and their significance in severe COVID-19 cases needs to be determined. This study analyzed data from the Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort focusing on intensive care patients. A retrospective analysis of patient data from 840 cases of COVID-19 with critical courses demonstrated that co-infections were frequently present and were primarily of nosocomial origin. Furthermore, our analysis showed that invasive therapy procedures accompanied an increased risk for healthcare-associated infections. Non-ventilated ICU patients were rarely affected by secondary infections. The risk of infection, however, increased even when non-invasive ventilation was used. A further, significant increase in infection rates was seen with the use of invasive ventilation and even more so with extracorporeal membrane oxygenation (ECMO) therapy. The marked differences among ICU techniques used for the treatment of COVID-19-induced respiratory failure in terms of secondary infection risk profile should be taken into account for the optimal management of critically ill COVID-19 patients, as well as for adequate antimicrobial therapy.

Catheter-related bloodstream infection management in patients receiving home parenteral nutrition: An observational cohort study

Patients with intestinal failure receiving home parenteral nutrition (HPN) are susceptible to central-line associated bloodstream infections (CLABSIs), with crucial roles for adequate (empiric) antimicrobial therapy and effective catheter management strategies. Our aim was to link recent epidemiologic CLABSI data with clinical outcomes and to identify risk factors for therapeutic failure to decide on the safest and most accurate CLABSI management in patients receiving HPN. A retrospective observational cohort study was conducted. All data on CLABSIs (period 2010-2020) in adult patients receiving HPN were retrieved. The efficacy of attempted catheter salvage and empiric antimicrobial treatment (β-lactam antibiotics) in our center, with a low prevalence of methicillin-resistant staphylococci, was investigated. Multivariate cox-regression analysis was performed to identify risk factors for recurrent CLABSI. 389 CLABSIs occurred in 149 patients. The overall infection rate was 0.64 per 1000 central venous catheter (CVC) days. Most CLABSIs were caused by Coagulase-negative staphylococci (37%). Attempted CVC salvage was successful in 70% of the cases. Empiric antimicrobial therapy was found to be adequate in only 47% of cases, mainly because of insufficient Coagulase-negative staphylococci coverage. According to the Cox model, patients with a replaced CVC had a 50% lower risk of a new CLABSI than patients with a retained (salvaged) CVC during follow-up (HR 0.50; 95% CI 0.35-0.72, P<0.001). CVC salvage can be achieved in most CLABSI cases but seems associated with a shorter CLABSI-free survival. Importantly, based on our findings, a glycopeptide containing antibiotic treatment regimen will increase the likelihood of adequate empiric coverage.

Augmented Renal Clearance in Severe Infections-An Important Consideration in Vancomycin Dosing: A Narrative Review.

Vancomycin is a hydrophilic antibiotic widely used in severe infections, including bacteremia and central nervous system (CNS) infections caused by Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci and enterococci. Appropriate antimicrobial dosage regimens can help achieve the target exposure and improve clinical outcomes. However, vancomycin exposure in serum and cerebrospinal fluid (CSF) is challenging to predict due to rapidly changing pathophysiological processes and patient-specific factors. Vancomycin concentrations may be decreased for peripheral infections due to augmented renal clearance (ARC) and increased distribution caused by systemic inflammatory response syndrome (SIRS), increased capillary permeability, and aggressive fluid resuscitation. Additionally, few studies on vancomycin’s pharmacokinetics (PK) in CSF for CNS infections. The relationship between exposure and clinical response is unclear, challenging for adequate antimicrobial therapy. Accurate prediction of vancomycin pharmacokinetics/pharmacodynamics (PK/PD) in patients with high interindividual variation is critical to increase the likelihood of achieving therapeutic targets. In this review, we describe the interaction between ARC and vancomycin PK/PD, patient-specific factors that influence the achievement of target exposure, and recent advances in optimizing vancomycin dosing schedules for severe infective patients with ARC.