Population pharmacokinetics and dosing simulations of meropenem in septic critically ill patients with complicated intra-abdominal infection or pneumonia.

OBJECTIVES: Meropenem pharmacokinetics (PK) may be altered in septic critically ill patients with complicated intra-abdominal infections (cIAI) and pneumonia. We aimed to evaluate the covariates affecting meropenem PK and the performance of different dosing regimens to optimize the PK/pharmacodynamic target. METHODS: Population PK analysis was performed using non-linear mixed-effects modeling. The final model was validated and used to simulate meropenem exposure to assess the probability of attaining the 100%ƒT>MIC target. RESULTS: Forty-six and 14 patients were respectively enrolled for PK analysis and external validation. A one-compartment linear model adequately described the data of 226 concentrations. The typical clearance (CL) and volume of distribution (Vd) were 9.69 L/h and 27.4 L, respectively. Septic shock from cIAI (cIASS) and actual body weight were significant covariates for meropenem Vd in addition to the influential covariates of creatinine clearance (CLCR-CG) and augmented renal clearance for CL. External validation showed the robustness and accuracy of this model. Simulation results proposed continuous infusion (CI) dosing regimens of meropenem against pathogens with MICs ≥ 2 mg/L in patients with cIASS and CLCR-CG ≥ 60 mL/min. CONCLUSIONS: For the patients with cIASS and CLCR-CG ≥ 60 mL/min, CI meropenem is proposed for treatment of less sensitive pathogens with MICs ≥ 2 mg/L.

Microbiological profiles and clinical outcomes of critically ill surgical patients with lower gastrointestinal perforation in Japan: a single-center retrospective observational study.

BACKGROUND: Lower gastrointestinal perforation (LGP) is a surgical emergency disease that can result in secondary bacterial peritonitis. Microbiological studies on LGP are rare. The present study aimed to ascertain the microbiological profile of LGP in patients admitted to the intensive care unit (ICU) at our institute after surgery. In addition, we investigated whether initial empirical therapy with vancomycin was associated with in-hospital mortality, duration of ICU stay, and duration of ventilator support. METHODS: This single-center, retrospective, observational study was conducted at Kobe City Medical Center General Hospital, Japan. The study population included all patients diagnosed with LGP who were admitted to the ICU after emergency surgery between 2017 and 2023. The primary outcome assessed was the microbiological profile of microorganisms isolated from ascites fluid and blood of the participants. The secondary end-points were in-hospital mortality, duration of ICU stay, and duration of ventilator support. We performed univariate and multivariate regression analyses to evaluate the end-points. RESULTS: During the study period, 89 patients were included in the analysis. The most commonly identified pathogen from the ascites cultures was Escherichia coli (65.2%), followed by Enterococcus spp. (51.7%). E. faecium was identified in 16 (18.0%) ascites samples. The microbiological profile of critically ill patients with LGP admitted to the ICU after surgery was similar to that of previous studies on intra-abdominal infection (IAI). Therefore, the initial empirical therapy in the IAI guidelines is more appropriate for LGP. Multivariate regression analysis suggested that the combination of initial empirical therapy with vancomycin was not associated with in-hospital mortality (odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.23-3.00, p = 0.955), duration of ICU stay (coefficient=-0.92, 95% CI -3.04-1.21, p = 0.393), or duration of ventilator-support (coefficient=-9.03, 95%CI -49.69-31.63, p = 0.659). CONCLUSION: The microbiological profile of critically ill patients with LGP admitted to the ICU after surgery was similar to that of previous studies on IAI. However, the frequency of E. faecium in the present study was higher than that in previous studies. Initial empirical therapy with drugs such as meropenem in combination with vancomycin for E. faecium was not associated with in-hospital mortality, duration of ICU stay, and duration of ventilator support, after adjusting for confounding factors.

Correlation between the gut microbiota characteristics of hosts with severe acute pancreatitis and secondary intra-abdominal infection.

Objective: The objective of the study is to investigate the changes in the composition of intestinal microecology in severe acute pancreatitis (SAP) patients with or without intra-abdominal infection and also to analyze the expression of antibiotic resistance genes to provide evidence for early warning of infectious diseases and the rational use of antibiotics. Methods: Twenty patients with SAP were enrolled in the study. According to whether the enrolled patients had a secondary intra-abdominal infection, they were divided into two groups, each consisting of 10 patients. Stool specimens were collected when the patients were admitted to the emergency intensive care unit (EICU), and nucleic acid extraction was performed. Next-generation gene sequencing was used to compare the differences in intestinal microflora diversity and drug resistance gene expression between the two groups. Results: The gut microbiota of patients in the infection group exhibited distribution on multiple clustered branches with some intra-group heterogeneity, and their flora diversity was compromised. The infected group showed an enrichment of various opportunistic bacteria in the gut microbiota, along with a high number of metabolic functions, stress functions to external signals, and genes associated with pathogenesis. Drug resistance genes were expressed in the gut microbiota of both groups, but their abundance was significantly lower in the non-infected group. Conclusion: The intestinal microbiota of patients in the infection group exhibited distribution on multiple clustered branches with some intra-group heterogeneity, and their flora diversity was compromised. Additionally, drug resistance genes were expressed in the gut microbiota of both groups, although their abundance was significantly lower in the non-infected group.

Severe acute pancreatitis complicated with intra-abdominal infection secondary to trauma: A case report.

BACKGROUND: Pancreatic trauma (PT) is rare among traumatic injuries and has a low incidence, but it can still lead to severe infectious complications, resulting in a high mortality rate. Acute pancreatitis (AP) is a common complication after PT, and when combined with organ dysfunction and sepsis, it will result in a poorer prognosis. CASE SUMMARY: We report a 25-year-old patient with multiple organ injuries, including the pancreas, due to abdominal trauma, who developed necrotising pancreatitis secondary to emergency caesarean section, combined with intra-abdominal infection (IAI). The patient underwent performed percutaneous drainage, pancreatic necrotic tissue debridement, and abdominal infection foci debridement on the patient. CONCLUSION: We report a case of severe AP and IAI secondary to trauma. This patient was managed by a combination of conservative treatment such as antibiotic therapy and fluid support with surgery, and a better outcome was obtained.

The Therapeutic Effect of Contezolid in Complex Intra-Abdominal Infections.

Purpose: In this paper, we observed the use of contezolid in patients with complex intra-abdominal infections in the intensive care unit of the Hepatobiliary Surgery department at the Chinese PLA General Hospital. Patients and Methods: The study collected data on complex intra-abdominal infections patients who received the antibiotic contezolid between January 2022 and April 2023. Results: Contezolid was administered to 12 patients, including 8 with severe acute pancreatitis, 3 with intra-abdominal infections following abdominal surgery, and 1 with complicated intra-abdominal infection after trauma. Gram-positive bacteria, such as Enterococcus faecium, Enterococcus casseliflavus, Staphylococcus capitis, and Staphylococcus haemo-lytica, were detected in 11 patients. All patients who received contezolid had previously been treated with other anti-Gram-positive agents, including linezolid for 9 patients, teicoplanin for 6 patients, and vancomycin for 3 patients. The treatment with contezolid began 20.0 (15.0, 34.5) days after admission and lasted for 8.0 (6.0, 10.0) days. At the end of the treatment, the patients' body temperature showed a significant decrease. After concomitant therapy, IL-6 levels decreased, and platelet count increased. Conclusion: Contezolid has shown potential in treating complex intra-abdominal infections caused by Gram-positive bacteria by reducing fever and inflammatory response.

Contradictory Recommendation in the Guideline for Antibiotic Prescription.

How to cite this article: Das PK, Nath SS, Parashar S. Contradictory Recommendation in the Guideline for Antibiotic Prescription. Indian J Crit Care Med 2024;28(7):713-714.

The Surgical Infection Society Guidelines on the Management of Intra-Abdominal Infection: 2024 Update.

Background: The Surgical Infection Society (SIS) published evidence-based guidelines for the management of intra-abdominal infection (IAI) in 1992, 2002, 2010, and 2017. Here, we present the most recent guideline update based on a systematic review of current literature. Methods: The writing group, including current and former members of the SIS Therapeutics and Guidelines Committee and other individuals with content or guideline expertise within the SIS, working with a professional librarian, performed a systematic review using PubMed/Medline, the Cochrane Library, Embase, and Web of Science from 2016 until February 2024. Keyword descriptors combined "surgical site infections" or "intra-abdominal infections" in adults limited to randomized controlled trials, systematic reviews, and meta-analyses. Additional relevant publications not in the initial search but identified during literature review were included. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system was utilized to evaluate the evidence. The strength of each recommendation was rated strong (1) or weak (2). The quality of the evidence was rated high (A), moderate (B), or weak (C). The guideline contains new recommendations and updates to recommendations from previous IAI guideline versions. Final recommendations were developed by an iterative process. All writing group members voted to accept or reject each recommendation. Results: This updated evidence-based guideline contains recommendations from the SIS for the treatment of adult patients with IAI. Evidence-based recommendations were developed for antimicrobial agent selection, timing, route of administration, duration, and de-escalation; timing of source control; treatment of specific pathogens; treatment of specific intra-abdominal disease processes; and implementation of hospital-based antimicrobial agent stewardship programs. Summary: This document contains the most up-to-date recommendations from the SIS on the prevention and management of IAI in adult patients.

Importance of Source Control in the Subgroup of Intra-Abdominal Infections for Septic Shock Patients: Analysis of 390 Cases.

Background: This study aimed to evaluate the epidemiology of septic shock (SS) associated with intraabdominal infections (IAI) as well as associated mortality and efficacy of early source control in a tertiary-care educational hospital. Methods: Patients who had SS with IAI and consulted by Infectious Diseases consultants between December 2013 and October 2022 during night shifts in our centre were analyzed retrospectively. Results: A total number of 390 patients were included. Overall, 30-day mortality was 42.5% on day 3, while day 14 and 30 mortality rates were 63.3% and 71.3%, respectively. Source control by surgical or percutaneous operation was performed in 123 of 390 cases (31.5%), and the mortality rate was significantly lower in cases that were performed source control at any time during SS (65/123-52.8% vs 213/267-79.8%, p<0.001). In 44 of 123 cases (35.7%), source control was performed during the first 12 hours, and mortality was significantly lower in this group versus others (24/44-54.5% vs 254/346-73.4%, p=0.009). On the other hand, female gender (p<0.001, odds ratio(OR)= 2.943, 95%CI=1.714-5.054), diabetes mellitus (p= 0.014, OR=2.284, 95%CI=1.179-4.424), carbapenem-resistant Gram-negative etiology (p=0.011, OR=4.386, 95%CI=1.398-13.759), SOFA≥10 (p<0.001, OR=3.036, 95%CI=1.802-5.114), lactate >3 mg/dl (p<0.001, OR=2.764, 95%CI=1.562-4.891) and lack of source control (p=0.001, OR=2.796, 95%CI=1.523-5.133) were significantly associated with 30-day mortality in logistic regression analysis. Conclusion: Source control has a vital importance in terms of mortality rates for IAI-related septic shock patients. Our study underscores the need for additional research, as the present analysis indicates that early source control does not manifest as a protective factor in logistic regression.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Diverticulitis in Adults and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute diverticulitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Risk Assessment in Adults and Children.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides a recommendation for risk stratification according to severity of illness score. The panel's recommendation is based upon evidence derived from systematic literature reviews and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Utility of Intra-abdominal Fluid Cultures in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining cultures of intra-abdominal fluid in patients with known or suspected intra-abdominal infection. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Intra-abdominal Abscess in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute intra-abdominal abscess. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Appendicitis in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute appendicitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Diagnostic Imaging of Suspected Acute Cholecystitis and Acute Cholangitis in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for diagnostic imaging of suspected acute cholecystitis or acute cholangitis. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Utility of Blood Cultures in Adults, Children, and Pregnant People.

This paper is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this paper, the panel provides recommendations for obtaining blood cultures in patients with known or suspected intra-abdominal infection. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.

2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Risk Assessment, Diagnostic Imaging, and Microbiological Evaluation in Adults, Children, and Pregnant People.

As the first part of an update to the clinical practice guideline on the diagnosis and management of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America, the panel presents twenty-one updated recommendations. These recommendations span risk assessment, diagnostic imaging, and microbiological evaluation. The panel's recommendations are based upon evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

Intra-abdominal infection and sepsis in immunocompromised intensive care unit patients: Disease expression, microbial aetiology, and clinical outcomes.

We compared epidemiology of intra-abdominal infection (IAI) between immunocompromised and non-immunocompromised ICU patients and identified risk factors for mortality. We performed a secondary analysis on the "AbSeS" database, a prospective, observational study with IAI patients from 309 ICUs in 42 countries. Immunocompromised status was defined as either neutropenia or prolonged corticosteroids use, chemotherapy or radiotherapy in the past year, bone marrow or solid organ transplantation, congenital immunodeficiency, or immunosuppressive drugs use. Mortality was defined as ICU mortality at any time or 28-day mortality for those discharged earlier. Associations with mortality were assessed by logistic regression. The cohort included 2589 patients of which 239 immunocompromised (9.2 %), most with secondary peritonitis. Among immunocompromised patients, biliary tract infections were less frequent, typhlitis more frequent, and IAIs were more frequently healthcare-associated or early-onset hospital-acquired compared with immunocompetent patients. No difference existed in grade of anatomical disruption, disease severity, organ failure, pathogens, and resistance patterns. Septic shock was significantly more frequent in the immunocompromised population. Mortality was similar in both groups (31.1% vs. 28.9 %; p = 0.468). Immunocompromise was not a risk factor for mortality (OR 0.98, 95 % CI 0.66-1.43). Independent risk factors for mortality among immunocompromised patients included septic shock at presentation (OR 6.64, 95 % CI 1.27-55.72), and unsuccessful source control with persistent inflammation (OR 5.48, 95 % CI 2.29-12.57). In immunocompromised ICU patients with IAI, short-term mortality was similar to immunocompetent patients, despite the former presented more frequently with septic shock, and septic shock and persistent inflammation after source control were independent risk factors for death.

The burden of antibiotic resistance of the main microorganisms causing infections in humans - review of the literature.

One of the biggest threats to human well-being and public health is antibiotic resistance. If allowed to spread unchecked, it might become a major health risk and trigger another pandemic. This proves the need to develop antibiotic resistance-related global health solutions that take into consideration microdata from various global locations. Establishing positive social norms, guiding individual and group behavioral habits that support global human health, and ultimately raising public awareness of the need for such action could all have a positive impact. Antibiotic resistance is not just a growing clinical concern but also complicates therapy, making adherence to current guidelines for managing antibiotic resistance extremely difficult. Numerous genetic components have been connected to the development of resistance; some of these components have intricate paths of transfer between microorganisms. Beyond this, the subject of antibiotic resistance is becoming increasingly significant in medical microbiology as new mechanisms underpinning its development are identified. In addition to genetic factors, behaviors such as misdiagnosis, exposure to broad-spectrum antibiotics, and delayed diagnosis contribute to the development of resistance. However, advancements in bioinformatics and DNA sequencing technology have completely transformed the diagnostic sector, enabling real-time identification of the components and causes of antibiotic resistance. This information is crucial for developing effective control and prevention strategies to counter the threat.

Effect of preoperative frailty on postoperative infectious complications and prognosis in patients with colorectal cancer: a propensity score matching study.

BACKGROUND: Few studies have explored the impact of preoperative frailty on infectious complications in patients with a diagnosis of colorectal cancer (CRC). Therefore, this study aimed to investigate the effect of preoperative frailty on postoperative infectious complications and prognosis in patients with CRC using propensity score matching (PSM). METHODS: This prospective single-centre observational cohort study included 245 patients who underwent CRC surgery at the Department of Gastrointestinal Surgery, The Affiliated Lianyungang Hospital of Xuzhou Medical University between August 2021 to May 2023. Patients were categorised into two groups: frail and non-frail. They were matched for confounders and 1:1 closest matching was performed using PSM. Rates of infectious complications, intensive care unit (ICU) admission, 30-day mortality, and 90-day mortality, as well as postoperative length of hospital stay, total length of hospital stay, and hospital costs, were compared between the two groups. Binary logistic regression using data following PSM to explore independent factors for relevant outcome measures. RESULTS: After PSM, each confounding factor was evenly distributed between groups, and 75 pairs of patients were successfully matched. The incidence of intra-abdominal infectious complications was significantly higher in the frail group than in the non-frail group (10.7% vs. 1.3%, P < 0.05). There were no significant differences in ICU admission rate, postoperative length of hospital stay, total length of hospital stay, hospital costs, 30-day mortality rate, or 90-day mortality rate between the two groups (P > 0.05). Our logistic regression analysis result showed that preoperative frailty (OR = 12.014; 95% CI: 1.334-108.197; P = 0.027) was an independent factor for intra-abdominal infection. CONCLUSIONS: The presence of preoperative frailty elevated the risk of postoperative intra-abdominal infectious complications in patients undergoing CRC surgery. Therefore, medical staff should assess preoperative frailty in patients with CRC early and provide targeted prehabilitation interventions.

Empirical antifungal therapy for health care-associated intra-abdominal infection: a retrospective, multicentre and comparative study.

BACKGROUND: Current guidelines recommend using antifungals for selected patients with health care-associated intra-abdominal infection (HC-IAI), but this recommendation is based on a weak evidence. This study aimed to assess the association between early empirical use of antifungals and outcomes in intensive care unit (ICU) adult patients requiring re-intervention after abdominal surgery. METHODS: A retrospective, multicentre cohort study with overlap propensity score weighting was conducted in three ICUs located in three medical institutions in France. Patients treated with early empirical antifungals for HC-IAI after abdominal surgery were compared with controls who did not receive such antifungals. The primary endpoint was the death rate at 90 days, and the secondary endpoints were the death rate at 1 year and composite criteria evaluated at 30 days following the HC-IAI diagnosis, including the need for re-intervention, inappropriate antimicrobial therapy and death, whichever occurred first. RESULTS: At 90 days, the death rate was significantly decreased in the patients treated with empirical antifungals compared with the control group (11.4% and 20.7%, respectively, p = 0.02). No differences were reported for the secondary outcomes. CONCLUSION: The use of early empirical antifungal therapy was associated with a decreased death rate at 90 days, with no effect on the death rate at 1 year, the death rate at 30 days, the rate of re-intervention, the need for drainage, and empirical antibiotic and antifungal therapy failure at 30 days.