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耐药时代腹腔感染抗菌药物临床应用新策略
New clinical application strategies for antimicrobial drugs in abdominal infections in the era of drug resistance
腹腔感染(IAI)是普通外科常见感染性疾病,造成巨大疾病负担。近年来,碳青霉烯类耐药革兰阴性菌、万古霉素耐药肠球菌及唑类耐药念珠菌分离率呈上升趋势,同时病原体二代测序等病原检测方法及新抗菌药物的开发应用为耐药菌IAI诊治带来新的应对手段。IAI的病原体主要为肠道来源的革兰阴性菌、革兰阳性菌、厌氧菌、念珠菌,且通常表现为混合感染。IAI的治疗包括基于病人分层的经验性治疗和病原学明确后的目标治疗。新近国内上市的新β内酰胺类-β内酰胺酶抑制剂复方制剂、新四环素衍生物、康替唑胺等,为IAI治疗提供了新的选择。
Intra-abdominal infection (IAI) is a common infectious disease in surgical practice, posing a substantial disease burden. In recent years, the isolation rates of carbapenem-resistant Gram-negative bacteria, vancomycin-resistant Enterococci, and azole-resistant Candida have shown an increasing trend. Concurrently, advances in pathogen detection methods such as next-generation sequencing and the development of novel antimicrobial agents have provided new strategies for the diagnosis and treatment of IAI caused by drug-resistant pathogens. The predominant pathogens involved in IAI are enteric Gram-negative bacteria, Gram-positive bacteria, anaerobic bacteria, and Candida species, often presenting as polymicrobial infections. Therapeutic approaches for IAI include empirical antibiotic regimens based on patient stratification, followed by a targeted treatment strategies against common IAI pathogens. The recently approved agents in China, including novel β-lactam/ β-lactamase inhibitor combinations, newer tetracycline derivatives, and contezolid, provide new treatment options for IAI.
intra-abdominal infection / pathogen distribution / antibacterial therapy / multi-drug resistant bacteria
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中华医学会外科学分会外科感染与重症医学学组, 中国医师协会外科医师分会急重症外科专家工作组, 江苏省医学会外科学分会感染与危重症学组. 腹腔感染常见耐药菌诊治与防控中国专家共识(2026版)[J]. 中国实用外科杂志, 2026, 46(1):96-107. DOI:10.19538/j.cjps.issn1005-2208.2026.01.15.
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Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient's clinical condition, and the host's immune status should be assessed continuously to optimize the management of patients with complicated IAIs.© 2024. The Author(s).
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Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU.We performed a case-control study in 26 European ICUs during the period January 2015-December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study.During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65-72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98-21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73-25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04-17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32-10.52, p = 0.01) were independently associated with IAC.Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment.© 2022. The Author(s).
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中华医学会外科学分会外科感染与重症医学学组, 中国医师协会外科医师分会肠瘘外科医师专业委员会. 中国腹腔感染诊治指南(2019版)[J]. 中国实用外科杂志, 2020, 40(1):1-16. DOI: 10.19538/j.cjps.issn1005-2208.2020.01.01.
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Postoperative intra-abdominal infection (PIAI) is one of the most serious complications of abdominal surgery, increasing the risk of postoperative morbidity and mortality and prolonging hospital stay. Rapid diagnosis of PIAI is of great clinical value. Unfortunately, the current diagnostic methods of PIAI are not fast and accurate enough.We performed an exploratory study to establish a rapid and accurate diagnostic method of PIAI. We explored the turnaround time and accuracy of metagenomic next-generation sequencing (mNGS) in diagnosing PIAI. Patients who underwent elective abdominal surgery and routine abdominal drainage with suspected PIAI were enrolled in the study. The fresh midstream abdominal drainage fluid was collected for mNGS and culturing.We found that the median sample-to-answer turnaround time of mNGS was dramatically decreased than that of culture-based methods (less than 24 h vs. 59.5 to 111 h). The detection coverage of mNGS was much broader than culture-based methods. We found 26 species from 15 genera could only be detected by mNGS. The accuracy of mNGS was not inferior to culture-based methods in the 8 most common pathogens detected from abdominal drainage fluid (sensitivity ranged from 75% to 100%, specificity ranged from 83.3% to 100%, and kappa values were higher than 0.5). Moreover, the composition of the microbial spectrum established by mNGS varied between upper and lower gastrointestinal surgery, enhancing the understanding of PIAI pathogenesis.This study preliminarily revealed the clinical value of mNGS in the rapid diagnosis of PIAI and provided a rationale for further research.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.
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We developed a metagenomic next-generation sequencing (mNGS) test using cell-free DNA from body fluids to identify pathogens. The performance of mNGS testing of 182 body fluids from 160 patients with acute illness was evaluated using two sequencing platforms in comparison to microbiological testing using culture, 16S bacterial PCR and/or 28S-internal transcribed ribosomal gene spacer (28S-ITS) fungal PCR. Test sensitivity and specificity of detection were 79 and 91% for bacteria and 91 and 89% for fungi, respectively, by Illumina sequencing; and 75 and 81% for bacteria and 91 and 100% for fungi, respectively, by nanopore sequencing. In a case series of 12 patients with culture/PCR-negative body fluids but for whom an infectious diagnosis was ultimately established, seven (58%) were mNGS positive. Real-time computational analysis enabled pathogen identification by nanopore sequencing in a median 50-min sequencing and 6-h sample-to-answer time. Rapid mNGS testing is a promising tool for diagnosis of unknown infections from body fluids.
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The effectiveness of procalcitonin-based algorithms in guiding antibiotic usage for febrile acute necrotizing pancreatitis (ANP) remains controversial. Metagenomic next-generation sequencing (mNGS) has been applied to diagnose infectious diseases. We aimed to evaluate the effectiveness of blood mNGS in guiding antibiotic stewardship for febrile ANP.The prospective multicenter clinical trial was conducted at seven hospitals in China. Blood samples were collected during fever (T ≥38.5°C) from ANP patients. The effectiveness of blood mNGS, procalcitonin, and blood culture in diagnosing pancreatic infection was evaluated and compared. Additionally, the real-world utilization of antibiotics and the potential mNGS-guided antimicrobial strategy in febrile ANP were also analyzed.From May 2023 to October 2023, a total of 78 patients with febrile ANP were enrolled and 30 patients (38.5%) were confirmed infected pancreatic necrosis (IPN). Compared with procalcitonin and blood culture, mNGS showed a significantly higher sensitivity rate (86.7% vs. 56.7% vs. 26.7%, P<0.001). Moreover, mNGS outperformed procalcitonin (89.5% vs. 61.4%, P<0.01) and blood culture (89.5% vs. 69.0%, P<0.01) in terms of negative predictive value. Blood mNGS exhibited the highest accuracy (85.7%) in diagnosing IPN and sterile pancreatic necrosis (SPN), significantly superior to both procalcitonin (65.7%) and blood culture (61.4%). In the multivariate analysis, positive blood mNGS (OR=60.2, P<0.001) and lower fibrinogen level (OR=2.0, P<0.05) were identified as independent predictors associated with IPN, whereas procalcitonin was not associated with IPN, but with increased mortality (OR=11.7, P=0.006). Overall, the rate of correct use of antibiotics in the cohort was only 18.6% (13/70) and would be improved to 81.4% (57/70) if adjusted according to the mNGS results.Blood mNGS represents important progress in the early diagnosis of IPN, with particular importance in guiding antibiotic usage for patients with febrile ANP.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
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Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries with different clinical backgrounds. The aim of the document is to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs.© 2021. The Author(s).
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To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock).We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis.The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation.This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection.
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复旦大学附属华山医院抗生素研究所. CHINET监测网历年耐药监测报告[EB/OL]. [2026-03-13]. http://www.chinets.com.
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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.
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\n Ceftolozane-tazobactam (TOL-TAZ) is a novel antibacterial with activity against\n Pseudomonas aeruginosa\n and other common Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producing\n Enterobacteriaceae\n, that are associated with complicated intra-abdominal infections (cIAIs). This prospective, double-blind, randomized, multicenter, phase II trial assessed patient clinical and microbiological responses to and the safety of TOL-TAZ plus metronidazole compared with those of meropenem. Hospitalized adults with cIAIs that required surgical intervention were randomized (2:1) to receive intravenous (i.v.) TOL-TAZ (1.5 g [containing 1,000 mg TOL and 500 mg TAZ] every 8 h [q8h]) with or without i.v. metronidazole (500 mg q8h) or i.v. meropenem (1 g q8h) for 4 to 7 days. The primary endpoint was the clinical response at the test-of-cure visit in the microbiologically modified intent-to-treat (mMITT) and microbiologically evaluable (ME) populations. Secondary measures included the patients' microbiological response and safety. In total, 82 patients received TOL-TAZ (90.2% with metronidazole), and 39 received meropenem. For the mMITT population, clinical cure was seen in 83.6% of the patients (51/61; 95% confidence interval [CI], 71.9 to 91.8) who received TOL-TAZ and 96.0% of the patients (24/25; 95% CI, 79.6 to 99.9) who received meropenem (difference, −12.4%; 95% CI, −34.9% to 11.1%); in the ME population, clinical cure was seen in 88.7% and 95.8% of the patients (difference, −7.1%; 95% CI, −30.7% to 16.9%) who received TOL-TAZ and meropenem, respectively. TOL-TAZ demonstrated microbiological success against\n Escherichia coli\n (89.5%),\n Klebsiella pneumoniae\n (100%), and\n P. aeruginosa\n (100%). The adverse event rates were similar in the groups (50.0% with TOL-TAZ and 48.8% with meropenem). TOL-TAZ in combination with metronidazole was well tolerated and resulted in clinical and microbiological success rates supportive of further clinical development in patients with cIAIs. (This study has been registered at ClinicalTrials.gov under registration no. NCT01147640.)\n
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Increasing antimicrobial resistance among pathogens causing complicated intra-abdominal infections (cIAIs) supports the development of new antimicrobials. Ceftolozane/tazobactam, a novel antimicrobial therapy, is active against multidrug-resistant Pseudomonas aeruginosa and most extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae.ASPECT-cIAI (Assessment of the Safety Profile and Efficacy of Ceftolozane/Tazobactam in Complicated Intra-abdominal Infections) was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) every 8 hours or meropenem (1 g) every 8 hours intravenously for 4-14 days. The prospectively defined objectives were to demonstrate statistical noninferiority in clinical cure rates at the test-of-cure visit (24-32 days from start of therapy) in the microbiological intent-to-treat (primary) and microbiologically evaluable (secondary) populations using a noninferiority margin of 10%. Microbiological outcomes and safety were also evaluated.Ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in the primary (83.0% [323/389] vs 87.3% [364/417]; weighted difference, -4.2%; 95% confidence interval [CI], -8.91 to.54) and secondary (94.2% [259/275] vs 94.7% [304/321]; weighted difference, -1.0%; 95% CI, -4.52 to 2.59) endpoints, meeting the prespecified noninferiority margin. In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 95.8% (23/24) and 88.5% (23/26) in the ceftolozane/tazobactam plus metronidazole and meropenem groups, respectively, and 100% (13/13) and 72.7% (8/11) in patients with CTX-M-14/15 ESBLs. The frequency of adverse events (AEs) was similar in both treatment groups (44.0% vs 42.7%); the most common AEs in either group were nausea and diarrhea.Treatment with ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in adult patients with cIAI, including infections caused by multidrug-resistant pathogens.NCT01445665 and NCT01445678.© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
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中华医学会呼吸病学分会感染学组. 中国铜绿假单胞菌下呼吸道感染诊治专家共识(2022年版)[J]. 中华结核和呼吸杂志, 2022, 45(8):739-752. DOI: 10.3760/cma.j.cn112147-20220407-00290.
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Complicated intra-abdominal infections (cIAI) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria. The efficacy and safety of tigecycline, an expanded broad-spectrum glycylcycline antibiotic, was compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI.
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Safety concerns over bone marrow suppression and thrombocytopenia may inhibit the use of linezolid to treat intraabdominal infection (IAI). To evaluate the effectiveness, safety, and prognosis of linezolid in the treatment of severe IAI (SIAI). Patients were divided into a linezolid group and nonlinezolid group according to whether linezolid was prescribed. Subgroup analysis (thrombocytopenia treated with linezolid group (I), and thrombocytopenia treated with nonlinezolid group (II) also was performed. We evaluated the effectiveness of linezolid by analyzing the changes in white blood cells (WBC) and procalcitonin, evaluated safety by analyzing the changes in platelet counts, and evaluated patient outcomes by analyzing the length of hospital stay, the length of ICU stay, and the rates of clinical improvement. Sixty-six adult SIAI patients were treated with anti-gram-positive (G+) bacteria drugs for more than 7 days from January 1, 2014, to December 31, 2020. The length of hospital stay, the length of ICU stay, and the rates of clinical improvement were not significantly different between the linezolid group and nonlinezolid group. On the 15th day after anti-G + bacteria treatment, the WBC of the linezolid group was significantly lower than in the nonlinezolid group (9.00 ± 4.30 vs 13.1 ± 6.19, P <.05). The time for a statistical difference in the decrease of procalcitonin in the linezolid group was earlier than in the nonlinezolid group (day 6 vs day 7, P <.05). There was no statistically significant difference in the changes of platelet counts in the subgroup I (P >.05), but compared with the baseline data (day 0), the time for the statistical difference in the increase of platelets in thrombocytopenia treated with linezolid group was earlier (day 5 vs day 6, P <.05). There was no statistical difference in the changes of platelets in subgroup II (P >.05). In the treatment of severe intraabdominal infection in a single-center, retrospective study, linezolid was not inferior to other antibiotics in patient clinical outcomes or seral WBC and procalcitonin values. Linezolid also induced no evident bone marrow suppression or thrombocytopenia. Linezolid is a good choice for treatment of SIAI.
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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.The study collected data on complex intra-abdominal infections patients who received the antibiotic contezolid between January 2022 and April 2023.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.Contezolid has shown potential in treating complex intra-abdominal infections caused by Gram-positive bacteria by reducing fever and inflammatory response.© 2024 Zhao et al.
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Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
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