Complicated Intra-abdominal Infections Research Articles

On the assessment of the role of new antibiotics in pharmacotherapy algorithms for complicated intra-abdominal infections (literature review)

The goal: To analyze the topical problems in the use of the newest antibiotics in abdominal surgical interventions and approaches to their solution. Material and methods: The large-scale (as a rule) publications mostly of 2019–2023 on the issue were analyzed. The searching had been executed according to keywords in Pubmed (ncbi.nlm.nih.gov). Findings: Modern protected cephalosporins and carbapenems, as well as eravacycline, appear to be valuable tools in the treatment of surgical intra-abdominal infection, caused in particular by resistant microflora, especially when taking into account local data. The value of tigecycline in this nosology seems less obvious.

Case of Tigecycline Induced Liver Injury: A Cautionary Tale

Tigecycline, the inaugural glycylcycline antibiotic in clinical use, is experiencing rising global utilization owing to its effectiveness against multidrug-resistant (MDR) bacteria. Although gastrointestinal side effects like nausea and vomiting are more prevalent, it is important to recognize that tigecycline can also lead to liver injury. The manufacturer has issued a warning regarding tigecycline's potential to elevate total bilirubin (TB) and transaminase levels. [1] We present the case of a 74-year-old female with a history of multiple comorbidities who developed severe hepatotoxicity following tigecycline therapy for a complicated intra-abdominal infection. The patient shows an abnormal liver function test with hyperbilirubinemia. Later on she developed jaundice. This case underscores the importance of considering TILI in patients receiving tigecycline, particularly those with preexisting liver disease or receiving other potentially hepatotoxic medications.

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.

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 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 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 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: 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 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: 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.

Imipenem/Cilastatin/Relebactam for Complicated Infections: A Real-World Evidence.

(1) Background: Infections caused by multidrug-resistant (MDR) bacteria represent one of the major global public health problems of the 21st century. Beta-lactam antibacterial agents are commonly used to treat infections due to Gram-negative pathogens. New β-lactam/β-lactamase inhibitor combinations are urgently needed. Combining relebactam (REL) with imipenem (IMI) and cilastatin (CS) can restore its activity against many imipenem-nonsusceptible Gram-negative pathogens. (2) Methods: we performed a systematic review of the studies reporting on the use of in vivo REAL/IPM/CS. (3) Results: A total of eight studies were included in this review. The primary diagnosis was as follows: complicated urinary tract infection (n = 234), complicated intra-abdominal infections (n = 220), hospital-acquired pneumonia (n = 276), and ventilator-associated pneumonia (n = 157). Patients with normal renal function received REL/IPM/CS (250 mg/500 mg/500 mg). The most frequently reported AEs occurring in patients treated with imipenem/cilastatin plus REL/IPM/CS were nausea (11.5%), diarrhea (9.8%), vomiting (9.8%), and infusion site disorders (4.0%). Treatment outcomes in these high-risk patients receiving REL/IPM/CS were generally favorable. A total of 70.6% of patients treated with REL/IPM/CS reported a favorable clinical response at follow-up. (4) Conclusions: this review indicates that REL/IPM/CS is active against important MDR Gram-negative organisms.

Risk Factors for Invasive Candidiasis in Critically Ill Patients Who Underwent Emergency Gastrointestinal Surgery for Complicated Intra-Abdominal Infection.

Background: Candida species account for approximately 15% of hospital-associated infections, causing fatal consequences, especially in critically ill patients. This study aimed to evaluate invasive candidiasis (IC) risk factors in critically ill patients undergoing surgery. Patients and Methods: We retrospectively reviewed the medical records of 583 patients who underwent emergency surgery for complicated intra-abdominal infections between January 2016 and December 2021. Patients were divided into two groups according to the presence or absence of IC during their hospital stay. IC was defined as culture-proven candidemia and intra-abdominal candidiasis. Results: This study included 373 patients for the final analysis, of whom 320 were discharged without IC (IC absent group) and 53 presented with IC (IC present group) during their hospital stay. The IC present group showed a higher in-hospital mortality rate (35.8 vs. 8.8%; p < 0.001), with 66.0% of the patients diagnosed within 10 days, whereas only 6.5% were diagnosed beyond 20 days after admission. Stomach (odds ratio [OR], 4.188; 95% confidence interval [CI], 1.204-14.561; p = 0.024) and duodenum (OR, 7.595; 95% CI, 1.934-29.832; p = 0.004) as infection origin, higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR, 1.097; 95% CI, 1.044-1.152; p < 0.001), and lower initial systolic blood pressure (OR, 0.983; 95% CI, 0.968-0.997; p = 0.018) were risk factors of IC after emergency gastrointestinal surgery. Conclusions: Patients who had stomach and duodenum as infection origin, higher APACHE II scores, and lower initial systolic blood pressure had a higher risk of developing IC during their hospital stay after emergency gastrointestinal surgery. Prophylactic antifungal agents can be carefully considered for critically ill patients with these features.

Urea to Albumin Ratio Is an Excellent Predictor of Death in Patients With Complicated Intra-Abdominal Infections.

Background: The urea to albumin ratio (UAR) has shown a prognostic value in various clinical settings, however, no study has yet investigated its ability to predict outcome in complicated intra-abdominal infections (cIAIs). Therefore, our aim was to evaluate the association between UAR and mortality in such patients. Patients and Methods: A single-center prospective study including 62 patients with cIAIs was performed at a University Hospital Stara Zagora for the period November 2018 to August 2021. Various routine laboratory and clinical parameters were recorded before surgery and on post-operative day 3. We used serum levels of urea and albumin to calculate the UAR. Results: The observed in-hospital mortality was 14.5%. Non-survivors had higher pre- and post-operative median of UAR than survivors (88.39 vs. 30.99, p < 0.0001 and 106.18 vs. 26.58, p < 0.0001, respectively). Lethal outcome was predicted successfully both by UAR before surgery (area under receiver operating characteristics [AUROC] curves = 0.889; p < 0.0001) at a threshold of 61.42 and on third post-operative day (AUROC = 0.943; p < 0.0001) at a threshold = 55.89. Conclusions: Peri-operative UAR showed an excellent ability for prognostication of fatal outcome in patients with cIAIs.

Ceftolozane/Tazobactam for the Treatment of Complicated Infections in Hospital Settings-A French Real-world Study.

This study describes the conditions of use of ceftolozane/tazobactam (C/T) and associated outcomes in French hospital settings. This was a prospective, multicenter, French observational study. Patients who received at least 1 dose of C/T were included and followed up as per routine clinical practice, until stop of C/T. A total of 260 patients were enrolled between October 2018 and December 2019 in 30 centers across France. Of these, 177 (68.0%) received C/T as per indication of usage following the results of the antibiogram (documented cases). Among documented patients, the mean age was 61.8 years, 73.4% were males, and 93.8% presented with multidrug-resistant (MDR) bacteria at inclusion. C/T was most frequently prescribed for pneumonia (48.6%), bacteremia (14.7%), complicated intra-abdominal infections (13.0%), or complicated urinary tract infections (9.6%). Pseudomonas aeruginosa was the species most frequently isolated with 212 strains from 155 patients, and 96.2% of these strains were susceptible to C/T. The median duration of C/T treatment was 16.1 days (1-115, n = 176). Complete or partial cure was achieved in 71.7% of patients, C/T was discontinued upon adaptation to microbiology results in 11.3% of patients for the following reasons: treatment failure in 2.8%, death in 4.0%, adverse events in 1.7%, and other in 8.5%. This is the first prospective observational study of C/T utilization in a health care setting enrolling many patients in France. C/T demonstrated a high rate of clinical effectiveness in MDR infections, confirming it as an effective treatment option for complicated infections in a high-risk population.

Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA)

ObjectivesTo assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. MethodsA prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. ResultsThe cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8–29.6), 10.6% (7.2–15.2), and 8.4% (6.5–10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3–20.0), (HR, 2.57; 95% CI, 1.55–4.26; p < 0.001), and 15.4% (95% CI, 10.5–20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57–5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99–3.50; p 0.06) and 3.65 (95% CI, 2.29–5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78–2.67; p 0.24). DiscussionCRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality.

Perspectives on the use of ceftolozane/tazobactam: a review of clinical trial data and real-world evidence.

Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are common healthcare-associated infections linked to high morbidity and mortality. Gram-negative pathogens, such as Pseudomonasaeruginosa, exhibit multidrug resistance and are recognized as major public health concerns, particularly among critically ill patients with HABP/VABP. Ceftolozane/tazobactam is a novel combination antibacterial agent comprising ceftolozane (a potent antipseudomonal cephalosporin) and tazobactam (a β-lactamase inhibitor). Phase III trials have demonstrated non-inferiority of ceftolozane/tazobactam to comparators, leading to the approval of ceftolozane/tazobactam for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and nosocomial pneumonia. In this article, we review the clinical trial evidence and key real-world effectiveness data of ceftolozane/tazobactam for the treatment of serious healthcare-associated Gram-negative infections, focusing on patients with HABP/VABP.

Animal Models in Regulatory Breakpoint Determination: Review of New Drug Applications of Approved Antibiotics from 2014-2022.

We sought to better understand the utility and role of animal models of infection for Food and Drug Administration (FDA)-approved antibiotics for the indications of community-, hospital-acquired-, and ventilator-associated bacterial pneumonia (CABP, HABP, VABP), complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), and acute bacterial skin and structural infections (ABSSSIs). We reviewed relevant documents from new drug applications (NDA) of FDA-approved antibiotics from 2014-2019 for the above indications. Murine neutropenic thigh infection models supported the choice of a pharmacokinetic-pharmacodynamic (PKPD) target in 11/12 NDAs reviewed. PKPD targets associated with at least a 1-log bacterial decrease were commonly considered ideal (10/12 NDAs) to support breakpoints. Plasma PK, as opposed to organ specific PK, was generally considered most reliable for PKPD correlation. Breakpoint determination was multi-disciplinary, accounting at minimum for epidemiologic cutoffs, non-clinical PKPD, clinical exposure-response and clinical efficacy. Non-clinical PKPD targets in combination with probability of target attainment (PTA) analyses generated breakpoints that were consistent with epidemiologic cutoffs and clinically derived breakpoints. In 6/12 NDAs, there was limited data to support clinically derived breakpoints, and hence the non-clinical PKPD targets in combination with PTA analyses played a heightened role in the final breakpoint determination. Sponsor and FDA breakpoint decisions were in general agreement. Disagreement may have arisen from differences in the definition of the optimal PKPD index or the ability to extrapolate protein binding from animals to humans. Overall, murine neutropenic thigh infection models supported the reviewed NDAs by providing evidence of pre-clinical efficacy and PKPD target determination, and played, in combination with PTA analysis, a significant role in breakpoint determination for labeling purposes.

Better chance of survival is associated with higher neutrophil CD16 expression in patients with complicated intra-abdominal infections.

The ability of neutrophil CD16 (nCD16) expression to predict outcome in complicated intra-abdominal infections (cIAIs) has not yet been studied; therefore we aimed to evaluate its potential prognostic value in such patients. Between November 2018 and August 2021 a single-center prospective study was performed in the Department of Surgical Diseases at a University Hospital Stara Zagora. A flow cytometry was used to measure the levels of nCD16 before surgery and on the 3rd postoperative day (POD) in 62 patients with cIAIs. We observed a mortality rate of 14.5% during hospitalization. Survivors had significantly higher perioperative expression of nCD16 than non-survivors (P = 0.02 preoperatively and P = 0.006 postoperatively). As predictor of favorable outcome we found a good predictive performance of preoperative nCD16 (AUROC = 0.745) and a very good predictive performance of postoperative levels (AUROC = 0.846). An optimal preoperative threshold nCD16 = 34.75 MFI permitted prediction of survival with sensitivity and specificity of 66.7% and 77.8%, respectively. A better sensitivity of 72.5% and specificity of 85.7% were observed for threshold = 54.8 MFI on the 3rd POD. Perioperative neutrophil CD16 expression shows a great potential as a predictor of favorable outcome in patients with cIAIs.

P14 Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam Real-world Analysis (SPECTRA): results from a multinational, multicentre observational study

Abstract Background Ceftolozane/tazobactam (C/T) has demonstrated efficacy to treat complicated intra-abdominal infections (cIAI), complicated urinary tract infections (cUTI) and hospital acquired bacterial and ventilator-associated bacterial pneumonia. However, physicians, providers, and other stakeholders including payers want broader real-world evidence to inform clinical decisions and optimize healthcare resource use. Methods SPECTRA is a multinational, multicentre, retrospective, inpatient, observational study of patients treated with C/T in Australia, Austria, Germany, Italy, Mexico, Spain and the UK. Adult inpatients treated with ≥48 h of C/T were included. Demographics, clinical characteristics, treatment management patterns, and outcomes were analysed. Results There were 687 patients from 38 participating hospitals in 7 countries. The average age was 57.6 years (SD ±17.3), and most were male (456, 66.4%). The majority had at least one comorbidity (563, 82.0%), with the most common being heart disease (208, 30.3%), immunocompromised state (207, 30.1%) and chronic pulmonary disease (195, 28.4%). The most common indications were pneumonia (204, 29.7%), sepsis (147, 21.4%) and cIAI (106, 15.4%); 162 (23.6%) had multiple sites of infection and 245 (35.7%) were polymicrobial infections. Median C/T treatment was 12.0 days (IQR 11.0). Half of the patients were admitted to the ICU (343, 49.9%), 43.4% of which was related to the infection. Clinical success was 66.1%. All-cause in-hospital mortality was 22.0% with 8.7% being infection related. The 30 day all-cause readmission was 9.8% and 4.7% were infection related. Conclusions C/T was used to treat infections among critically ill patients and for multi-source, polymicrobial infections. Despite the complexity of the patients in this real-world analysis, most C/T patients had beneficial outcomes that are similar to results of controlled clinical trials.

PP118 The Value Of New Antibiotic Treatment Strategies In Zhejiang Province, China

IntroductionThe rising antimicrobial resistance (AMR) and the difficulty in developing new antibiotics are causing a global public health problem. This analysis aims to better understand the clinical and economic value of new antibiotic treatment strategies, in order to inform clinical and antibiotic formulary decisions.MethodsWe applied a published and validated dynamic disease transmission and cost-effectiveness model of AMR with a 10-year time horizon and discount rate of five percent to evaluate the clinical and economic outcomes of introducing a new antibiotic, namely, Ceftazidime/Avibactam (CAZ-AVI) for treating AMR infections in Zhejiang Province, China. Together with piperacillin-tazobactam (pip/taz) and meropenem, we explored the impact of six treatment strategies across three common infections (complicated intra-abdominal infection (cIAI), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) and infections with limited treatment options (LTO)), and pathogens (Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa). These treatment strategies included (i) current treatment strategy (pip/taz and meropenem, no CAZ-AVI), (ii) CAZ-AVI at the third line, (iii) CAZ-AVI at the second line, (iv) CAZ-AVI at the first line, (v) first line diversity (i.e., equal pip/taz and CAZ-AVI at the first line; meropenem at the last line) and (vi) all-lines diversity (pip/taz, meropenem and CAZ-AVI used randomly and only once). The data with a total of 10,905 patients were collected from a tier-3 hospital from 2018 to 2021.ResultsUnder the current treatment strategy, the hospital length of stay (LOS) and costs over ten years were estimated to be 1,588,763 days and CNY3,898,198,802 (USD559,781,348), respectively, associated with 142,999 quality-adjusted life-years (QALYs) lost, resulting in the resistance of pip/taz and meropenem being 42.0 percent and 49.9 percent respectively. In contrast, the other five treatment strategies all have shown improved outcomes, among which the “all-lines diversity” carried the greatest benefit, saving CNY1,646.04 (USD236.37) for each additional QALY gained, with the net monetary benefit being CNY24,727,102,215 (USD3,550,811,878).ConclusionsIntroducing CAZ-AVI had positive impact on clinical and economic outcomes for treating AMR, and diversifying early the antibiotics might yield the best benefits.