Sepsis

A near-infrared broad-spectrum antimicrobial nanoplatform powered by bacterial metabolic activity for enhanced antimicrobial photodynamic-immune therapy

107 - Bacterial and fungal infections

Current guidance on the management of sepsis often applies to infection originating from abdominal or pelvic sources, which presents specific challenges and opportunities for efficient and rapid source control. Advances made in the past decade are presented in this article. A qualitative systematic review was undertaken by searching standard literature databases for English-language studies presenting original data on the clinical management of abdominal and pelvic complex infection in adults over the past 10 years. High-quality studies relevant to five topical themes that emerged during review were included. Important developments and promising preliminary work are presented, relating to: imaging and other diagnostic modalities; antimicrobial therapy and the importance of antimicrobial stewardship; the particular challenges posed by fungal sepsis; novel techniques in percutaneous and endoscopic source control; and current issues relating to surgical source control and managing the abdominal wound. Logistical challenges relating to rapid access to cross-sectional imaging, interventional radiology and operating theatres need to be addressed so that international benchmarks can be met. Important advances have been made in the diagnosis, non-operative and surgical control of abdominal or pelvic sources, which may improve outcomes in the future. Important areas for continued research include the diagnosis and therapy of fungal infection and the challenges of managing the open abdomen.

Natural History of Pediatric Crohn Disease T he natural history of pediatric Crohn disease (CD) remains unpredictable, although some trends are observed that differentiate children from adults. Pediatric CD often presents with more severe disease and more frequent need for immunosuppressive therapy (1). Growth failure, present in 15% to 20% of patients, is a unique characteristic of pediatric CD not seen in adult-onset CD (2). Colonic disease distribution is common in patients younger than 10 years (1). The need for surgical intervention also varies, with 1 study reporting the actuarial risk of having undergone an extensive intestinal resection being 48.6% 5% in a childhood-onset group versus 14.6% 2% in the adult-onset group (P< 0.001) (1). More recently, long-term follow-up of patients enrolled in pediatric registries shows a cumulative surgical rate of 14% to 17% at 5 years and 28% at 10 years (3,4).

Chapter 111 - Sepsis

Veronese, Giacomo; Cipriani, Manlio; Bottiroli, Maurizio; Garascia, Andrea; Mondino, Michele; Pedrotti, Patrizia; Pini, Daniela; Cozzi, Ottavia; Messina, Antonio; Droandi, Ginevra; Petrella, Duccio; Frigerio, Maria; Ammirati, Enrico Author Information

PurposeThe aim of this study was to investigate how rates of surgical site infections (SSI) were changed over 2 years after applying colon SSI bundle in patients who underwent colon surgery.MethodsThe multidisciplinary working group developed a care bundle consisting of 8 components, including several recommendations of Surgical Care Improvement Project and monitoring of medical/surgical hand washing. We implemented the care bundle for each patient who underwent colon surgery from April 2013 to December 2014.ResultsOverall bundle compliance was 87.9% before implementation, 88.2% in 2013, and 90.5% in 2014. In particular, compliance of the following 3 components was substantial improved during the project period; discontinuation of prophylactic antimicrobial agent within 24 hours of surgery (from 88.3% to 100%), surgical hand washing (from 50.0% to 78.9%), and medical hand washing (from 74.7% to 82.8%). The rate of SSI was 8.0% (12/150) during 3 months before implementation, 3.3% (16/480) from April to December in 2013, and 2.3% (14/607) in 2014.ConclusionAfter implementation of multidisciplinary care bundle, the compliance of each component was increased and rates of SSIs were significantly decreased compared to those before the quality improvement project.

Nosocomial infections in the intensive care unit

The incidence of granulomatous mastitis (GLM) in multiparae as seriously affected the quality of life and breastfeeding of pregnant women after delivery, but the treatment is rarely reported. In this article, the development, healing, and lactation of 13 cases were reported and a retrospective analysis was performed. 10 cases of GLM were treated at the Breast Disease Prevention and Treatment Center of Haidian Maternal & Child Health Hospital of Beijing and 3 cases of GLM were treated in the Breast Department of Weihai Municipal Hospital of Shandong province from February 2017 to May 2019.Among the 13 patients, conservative symptomatic treatment was adopted during pregnancy and lactation: anti-infective therapy consisting of oral cephalosporin antibiotic for patients; ultrasound-guided puncture and drainage of pus or incision and drainage after abscess formation. Observation continued during the sinus tract phase. Postpartum breastfeeding was encouraged, especially on the affected side. In this study, the median healing time was 20 months and the average healing time was 30.4 months in 5 healthy breast lactation cases. In 8 cases of bilateral breast lactation, the median healing time was 30 months and the average healing time was 26.5 months. Linear regression test analysis: whether the affected breast was breast-fed after delivery had no effect on the postpartum wound healing time, P = .792. The wounds of 13 patients healed well after lactation, and none of them recurred since the last follow-up visit. There were no adverse events in all infants.Conservative symptomatic treatment for GLM of multiparous women during pregnancy and lactation and encouraging breastfeeding after delivery have no effect on infant health and the recovery time of patients.

Background:Sepsis is a common condition affecting the lives of infants and children worldwide. Although implementation of the surviving sepsis campaign (SSC) care bundles was once believed to be effective in reducing sepsis mortality rates, the approach has recently been questioned.Methods:The study was a prospective, interventional, multicenter trial. Infants and children aged 1 month to 15 years in seven different large academic centers in Thailand who had been diagnosed with severe sepsis or septic shock. They were given treatment based on the SSC care bundles.Results:A total of 519 children with severe sepsis or septic shock were enrolled in the study. Among these, 188 were assigned to the intervention group and 331 were recruited to the historical case–control group. There were no significant differences in the baseline clinical characteristics. The intervention group was administered a significantly higher fluid bolus than was the control group (28.3 ± 17.2 cc/kg vs. 17.7 ± 10.6 cc/kg; P = 0.02) with early vasopressor used (1.5 ± 0.7 h) compared to control group (7.4 ± 2.4 h, P < 0.05). More importantly, our sepsis mortality reduced significantly from 37% ± 20.7% during the preintervention period to 19.4% ± 14.3% during the postintervention period (P < 0.001).Conclusion:Our study demonstrated a significant reduction in sepsis mortality after the implementation of the SSC care bundles. Early diagnosis of the disease, optimum hemodynamic resuscitation, and timely antibiotic administration are the key elements of sepsis management.

PurposeTo determine predictors of mortality among patients with Pseudomonas aeruginosa bacteraemia.MethodsRetrospective study.SettingThis study conducted at the Lausanne University Hospital, Switzerland included adult patients with P. aeruginosa bacteraemia from 2015 to 2021.ResultsDuring the study period, 278 episodes of P. aeruginosa bacteraemia were included. Twenty (7%) isolates were multidrug-resistant. The most common type of infection was low respiratory tract infection (58 episodes; 21%). Sepsis was present in the majority of episodes (152; 55%). Infectious diseases consultation within 48 h of bacteraemia onset was performed in 203 (73%) episodes. Appropriate antimicrobial treatment was administered within 48 h in 257 (92%) episodes. For most episodes (145; 52%), source control was considered necessary, with 93 (64%) of them undergoing such interventions within 48 h. The 14-day mortality was 15% (42 episodes). The Cox multivariable regression model showed that 14-day mortality was associated with sepsis (P 0.002; aHR 6.58, CI 1.95–22.16), and lower respiratory tract infection (P < 0.001; aHR 4.63, CI 1.78–12.06). Conversely, interventions performed within 48 h of bacteraemia onset, such as infectious diseases consultation (P 0.036; HR 0.51, CI 0.27–0.96), and source control (P 0.009; aHR 0.17, CI 0.47–0.64) were associated with improved outcome.ConclusionOur findings underscore the pivotal role of early infectious diseases consultation in recommending source control interventions and guiding antimicrobial treatment for patients with P. aeruginosa bacteraemia.

Future needs—clinical services for infectious diseases

Patients with intra-abdominal sepsis and associated bacteremia have a high mortality rate. However, outcomes studies in this population are limited, in part because of the small numbers of such patients. The objective of this study was to describe characteristics of critically ill patients with secondary blood stream infection (BSI) of intra-abdominal origin and identify predictors of mortality. This retrospective, single-center study evaluated patients admitted between January 2005 and January 2011 with bacteremia because of an intra-abdominal source. Patients were included if they met criteria for severe sepsis based on International Classification of Diseases, 9th Revision (ICD 9) codes for acute organ dysfunction, had a positive blood culture, had at least one ICD 9 code indicative of an intra-abdominal process, and had a confirmed or clinically suspected intra-abdominal infection (IAI) within 72 h of the blood culture. Chart review was performed to confirm the presence of these criteria and also the absence of any other potential source of bacteremia. Data were collected on patient demographics, BSI source, source control procedure details, microorganisms isolated, and antibiotics administered. Multivariable logistic regression analysis was performed to identify independent predictors of mortality. Three hundred six patients with BSI were identified, of which 108 episodes were deemed to be of intra-abdominal origin. Gram-negative organisms comprised 43% of blood isolates, followed by gram-positives (33%), anaerobes (14%), and yeast (9%). Appropriate antimicrobial therapy was administered in 71% of patients. The overall mortality rate was 27.8%. As compared with survivors, non-survivors were older, more likely to have underlying COPD or asthma, and have renal or metabolic failure (p<0.05 for all). Among non-survivors, adequate source control was obtained less frequently (64% vs. 91%, p=0.002) and median time to appropriate antibiotics was longer (23 h vs. 4 h, p=0.004). Logistic regression analysis revealed inadequate source control (p=0.002) and inappropriate antibiotics (p=0.016) to be independently associated with mortality. Critically ill patients with a BSI of abdominal origin are at high risk for mortality. Failure to achieve adequate source control and administration of inappropriate antibiotics were independent predictors of mortality. Thus, these represent potential opportunities to impact outcomes in patients with complicated IAI.

Collateral damage.

Bacterial infections are an imminent global healthcare threat evolving from rapidly advancing bacterial defence mechanisms that antibiotics fail to overcome. Antibiotics have been designed for systemic administration to target planktonic bacteria, leading to difficulties in reaching the site of localized bacterial infection and an inability to overcome the biological, chemical and physical barriers of bacteria, including biofilms, intracellular infections and antimicrobial resistance. The amphiphilic, biomimetic and antimicrobial properties of lipids provide a promising toolbox to innovate and advance antimicrobial therapies, overcoming the barriers presented by bacteria in order to directly and effectively treat recalcitrant infections. Nanoparticulate lipid-based drug delivery systems can enhance antibiotic permeation through the chemical and physical barriers of bacterial infections, as well as fuse with bacterial cell membranes, release antibiotics in response to bacteria and act synergistically with loaded antibiotics to enhance the total antimicrobial efficacy. This review explores the barriers presented by bacterial infections that pose bio-pharmaceutical challenges to antibiotics and how different structural and functional mechanisms of lipids can enhance antimicrobial therapies. Different nanoparticulate lipid-based systems are presented as valuable drug delivery systems to advance the efficacy of antibiotics, including liposomes, liquid crystalline nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers and lipid nanocarriers. In summary, liquid crystalline nanoparticles are emerging with the greatest potential for clinical applications and commercial success as an "all-rounder" advanced lipid-based antimicrobial therapy that overcomes the multiple biological, chemical and physical barriers of bacteria.