Analysis of Six tonB Gene Homologs in Bacteroides fragilis Revealed That tonB3 is Essential for Survival in Experimental Intestinal Colonization and Intra-Abdominal Infection.

The opportunistic, anaerobic pathogen and commensal of the human large intestinal tract, Bacteroides fragilis strain 638R, contains six predicted TonB proteins, termed TonB1-6, four ExbBs orthologs, ExbB1-4, and five ExbDs orthologs, ExbD1-5. The inner membrane TonB/ExbB/ExbD complex harvests energy from the proton motive force (Δp), and the TonB C-terminal domain interacts with and transduces energy to outer membrane TonB-dependent transporters (TBDTs). However, TonB's role in activating nearly one hundred TBDTs for nutrient acquisition in B. fragilis during intestinal colonization and extraintestinal infection has not been established. In this study, we show that growth was abolished in the ΔtonB3 mutant when heme, vitamin B12, Fe(III)-ferrichrome, starch, mucin-glycans, or N-linked glycans were used as a substrate for growth in vitro. Genetic complementation of the ΔtonB3 mutant with the tonB3 gene restored growth on these substrates. The ΔtonB1, ΔtonB2, ΔtonB4, ΔtonB5, and ΔtonB6 single mutants did not show a growth defect. This indicates that there was no functional compensation for the lack of TonB3, and it demonstrates that TonB3, alone, drives the TBDTs involved in the transport of essential nutrients. The ΔtonB3 mutant had a severe growth defect in a mouse model of intestinal colonization compared to the parent strain. This intestinal growth defect was enhanced in the ΔtonB3 ΔtonB6 double mutant strain, which completely lost its ability to colonize the mouse intestinal tract compared to the parent strain. The ΔtonB1, ΔtonB2, ΔtonB4, and ΔtonB5 mutants did not significantly affect intestinal colonization. Moreover, the survival of the ΔtonB3 mutant strain was completely eradicated in a rat model of intra-abdominal infection. Taken together, these findings show that TonB3 was essential for survival in vivo. The genetic organization of tonB1, tonB2, tonB4, tonB5, and tonB6 gene orthologs indicates that they may interact with periplasmic and nonreceptor outer membrane proteins, but the physiological relevance of this has not been defined. Because anaerobic fermentation metabolism yields a lower Δp than aerobic respiration and B. fragilis has a reduced redox state in its periplasmic space-in contrast to an oxidative environment in aerobes-it remains to be determined if the diverse system of TonB/ExbB/ExbD orthologs encoded by B. fragilis have an increased sensitivity to PMF (relative to aerobic bacteria) to allow for the harvesting of energy under anaerobic conditions.

Antimicrobial Lessons From a Large Observational Cohort on Intra-abdominal Infections in Intensive Care Units.

Severe intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae, resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed.

Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections.

BACKGROUND: In premature infants, complicated intraabdominal infections (cIAIs) are a leading cause of morbidity and mortality. Although universally prescribed, the safety and effectiveness of commonly used antibiotic regimens have not been established in this population. METHODS: Infants ≤33 weeks gestational age and <121 days postnatal age with cIAI were randomized to ≤10 days of ampicillin, gentamicin, and metronidazole (group 1); ampicillin, gentamicin, and clindamycin (group 2); or piperacillin-tazobactam and gentamicin (group 3) at doses stratified by postmenstrual age. Due to slow enrollment, a protocol amendment allowed eligible infants already receiving study regimens to enroll without randomization. The primary outcome was mortality within 30 days of study drug completion. Secondary outcomes included adverse events, outcomes of special interest, and therapeutic success (absence of death, negative cultures, and clinical cure score >4) 30 days after study drug completion. RESULTS: One hundred eighty infants [128 randomized (R), 52 nonrandomized (NR)] were enrolled: 63 in group 1 (45 R, 18 NR), 47 in group 2 (41 R, 6 NR), and 70 in group 3 (42 R, 28 NR). Thirty-day mortality was 8%, 7%, and 9% in groups 1, 2, and 3, respectively. There were no differences in safety outcomes between antibiotic regimens. After adjusting for treatment group and gestational age, mortality rates through end of follow-up were 4.22 [95% confidence interval (CI): 1.39-12.13], 4.53 (95% CI: 1.21-15.50), and 4.07 (95% CI: 1.22-12.70) for groups 1, 2, and 3, respectively. CONCLUSIONS: Each of the antibiotic regimens are safe in premature infants with cIAI. CLINICAL TRIAL REGISTRATION: NCT0199499.

First case of abdominal infection caused by bacteroides fluxus.

Bacteroides fluxus is a Gram-negative anaerobic bacillus isolated from human faeces in healthy individuals. Until now, this bacterium had not been involved in human diseases. We report the first case of abdominal infection due to this microorganism in an elderly patient. A 76-year-old man with a history of chronic pulmonary obstructive disease presented with dyspnea, orthopnea and cough. The clinical evolution worsened with both a colonic ischemia and further diffuse peritonitis of pancreatic origin. Peritoneal fluid was obtained and the culture yielded B. fluxus in pure culture. Resistance to penicillin, amoxicillin-clavulanate, clindamycin and moxifloxacin was documented. Treatment with meropenem + linezolid was started, but the patient finally died due to a multiorganic failure.

Clinical implications of multidrug-resistant microorganisms and fungi isolated from patients with intra-abdominal infections in the Republic of Korea: a multicenter study.

The purpose of this study was to evaluate the clinical significance of fungi and multidrug-resistant organisms (MDROs) isolated from patients with intra-abdominal infections (IAIs). This multicenter study included consecutive patients admitted for microbiologically proven IAIs at 6 university-affiliated hospitals in South Korea between 2016 and 2018. A total of 1571 patients were enrolled. Multivariable logistic regression analysis revealed that the isolation of MDROs, isolation of Candida spp., underlying renal diseases, Charlson comorbidity score ≥ 3, septic shock, failure to receive a required surgery or invasive intervention, secondary bacteremia due to IAIs, and lower body mass index were found to be independent predictors for 28-day mortality. However, the isolation of Enterococcus spp. was not identified as a significant risk factor. MDROs and Candida spp. were found in 42 (2.7%) and 395 (25.1%), patients respectively. The isolation of MDROs or Candida spp. was a surrogate marker of 28-day mortality.

Candidemia indicates poor outcome in patients with infected pancreatic necrosis.

BACKGROUND: Intra-abdominal fungal infection (AFI) and candidemia are common in patients with acute pancreatitis (AP), but with limited and conflicting reports on their clinical impacts. This study aims to evaluate the clinical impacts of AFI and candidemia in infected pancreatic necrosis (IPN). METHODS: A single-centre, prospective cohort including 235 consecutive patients with IPN between January 2010 and September 2020 was analysed to study the clinical impacts of AFI and candidemia. RESULTS: Of the 235 patients with IPN, 69 patients (29.4%) developed AFI and 13 patients (5.5%) developed candidemia. AFI was associated with higher intestinal leakage rate (27.5% vs 12.7%, P = .006), higher pancreatic fistula rate (53.6% vs 34.3%, P = .006) and longer hospital stays (72 vs 58 days, P = .003), but with similar mortality rate compared with patients without AFI (23.2% vs 24.7%, P = .806). However, candidemia was associated with significantly higher mortality rate compared with patients without candidemia (69.2% vs 21.6%, P < .001). Patients with candidemia had higher rate of multiple organ failure and AFI (69.2% vs 36.5%, P = .018; 69.2% vs 27.0%, P = .001, respectively). Multivariable analysis showed that age ≥ 50 years (OR = 2.8; 95% CI, 1.3-5.8; P = .007), severe category (OR = 11.2; 95% CI, 3.5-35.7; P < .001), multidrug-resistant organisms infection (OR = 2.5; 95% CI, 1.0-6.2; P = .039), candidemia (OR = 11.8; 95% CI, 2.5-56.5; P = .002), step-down surgical approach (OR = 3.2; 95% CI, 1.5-7.0; P = .004) were the independent predictors associated with higher mortality in IPN patients. CONCLUSION: Although AFI did not increase the mortality of IPN, patients with candidemia carried significantly higher mortality.

Development and internal validation of clinical prediction models for outcomes of complicated intra-abdominal infection.

BACKGROUND: Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse. METHODS: A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further. RESULTS: Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and - 0.01 (- 0.17 to -0.03) respectively. CONCLUSION: Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, these now require external validation.

Endoscopic drainage with local infusion of antibiotics to avoid necrosectomy of infected walled-off necrosis.

BACKGROUND: Current treatment of infected pancreatic necrosis (IPN) follows a step-up approach. Our group designed a step-up protocol that associates endoscopic drainage with local infusion of antibiotics through transmural nasocystic catheter. Aim of our study was to evaluate our step-up protocol for IPN in terms of proportion of patients avoiding necrosectomy. METHODS: Retrospective analysis of patients admitted with acute pancreatitis (AP) between January 2015 and December 2018. The number of patients who responded to each therapeutic step were analysed: step 1, systemic antibiotics; step 2, endoscopic transmural drainage and local infusion of antibiotics; step 3, endoscopic necrosectomy. RESULTS: 1158 patients with AP were included. 110 patients (8.4%) suffered from necrotising pancreatitis; 48 of them had IPN (42.6% of necrotising pancreatitis) and were treated with systemic antibiotics. Nineteen patients (39.6% of IPN) responded and did not required any invasive therapy. Six patients with IPN on systemic antibiotics died within the first 4 weeks of disease before step 2 could be applied. Urgent surgical necrosectomy in the first 4 weeks was performed in three additional patients. Endoscopic drainage and local antibiotic therapy was performed in the remaining 20 patients; 9 (45% of them) did well and 9 patients underwent necrosectomy (18.7% of IPN). Two patients died on drainage. Overall mortality of the total cohort of AP was 2.53% CONCLUSIONS: Addition of local infusion of antibiotics to endoscopic drainage avoids the need of necrosectomy in half of patients with IPN not responding to systemic antibiotics.

Time to clearance of abdominal septic focus and mortality in patients with sepsis. / Tempo para evacuação de foco séptico abdominal e mortalidade em portadores de sepse.

OBJECTIVE: To assess the relationship between time to focus clearance and hospital mortality in patients with sepsis and septic shock. METHODS: This was an observational, single-center study with a retrospective analysis of the time to clearance of abdominal septic focus. Patients were classified according to the time to focus clearance into an early (≤ 12 hours) or delayed (> 12 hours) group. RESULTS: A total of 135 patients were evaluated. There was no association between time to focus clearance and hospital mortality (≤ 12 hours versus > 12 hours): 52.3% versus 52.9%, with p = 0.137. CONCLUSION: There was no difference in hospital mortality among patients with sepsis or septic shock who had an infectious focus evacuated before or after 12 hours after the diagnosis of sepsis.

Can the Cecal Ligation and Puncture Model Be Repurposed To Better Inform Therapy in Human Sepsis?

A recent report by the National Institutes of Health on sepsis research has implied there is a trend to move away from mouse models of sepsis. The most commonly used animal model to study the pathogenesis of human sepsis is cecal ligation and puncture (CLP) in mice. The model has been the mainstay of sepsis research for decades and continues to be considered the gold standard to inform novel pathways of sepsis physiology and its therapeutic direction. As there have been many criticisms of the model, particularly regarding its relevance to human disease, how this model might be repurposed to be more reflective of the human condition begs discussion. In this piece, we compare and contrast the mouse microbiome of the CLP model to the emerging science of the microbiome of human sepsis and discuss the relevance for mice to harbor the specific pathogens present in the human microbiome during sepsis, as well as an underlying disease process to mimic the characteristics of those patients with undesirable outcomes. How to repurpose this model to incorporate these "human factors" is discussed in detail and suggestions offered.

Hypoalbuminemia as a predictor of mortality in abdominal sepsis.

BACKGROUND: A level < 35 g/L of albumin (hypoalbuminemia) has been determined as a parameter to predict mortality and morbidity. METHOD: Prospective observational study, in a period of 12 months, to patients diagnosed with sepsis of abdominal origin, they are divided into two groups based on albumin levels (cut: 3.5 g/dL) to assess mortality between both groups. RESULTS: We studied 23 patients admitted to the intensive care unit. The mean albumin was 2.77 g/dL (± 0.71). When calculating the odds ratio (OR) that was a 23-fold greater risk of dying when hypoalbuminemia presented compared to the normal albumin group (OR = 23.3; 95% CI: 1,948 to 279.42). The mean albumin for patients who died was 2.04 g/dL (± 0.31) vs. 3.03 g/dL (± 0.35) (p = 0.02; 95% CI: -1.551 to -0.416). We do not assess morbidity, however, we identify a certain tendency to a longer stay in the ICU which is accompanied by a higher risk of complications and in the end a higher risk of mortality. CONCLUSION: We conclude that hypoalbuminemia represents a predictor of mortality in patients with abdominal sepsis.

ANTECEDENTES: Un valor de albúmina < 35 g/l (hipoalbuminemia) ha demostrado ser un parámetro para predecir mortalidad y morbilidad. MÉTODO: Estudio observacional, prospectivo, en un periodo de 12 meses, en pacientes con diagnóstico de sepsis de origen abdominal a quienes se dividió en dos grupos según las cifras de albúmina (corte: 3.5 g/dl) para valorar la mortalidad en ambos grupos. RESULTADOS: Estudiamos 23 pacientes ingresados a la unidad de terapia intensiva. La media de albúmina fue de 2.77 g/dl (± 0.71). Al calcular la odds ratio (OR) identificamos un riesgo 23 veces mayor de fallecer al presentar hipoalbuminemia en comparación con el grupo con albúmina normal (OR = 23.3; intervalo de confianza del 95% [IC 95%]: 1.948 a 279.42). La media de los valores de albúmina para los pacientes que fallecieron fue de 2.04 g/dl (± 0.31) vs. a 3.03 g/dl (± 0.35) para el otro grupo (IC 95%: −1.551 a −0.416; p = 0.02)]. Aunque no valoramos la morbilidad, identificamos cierta tendencia a un mayor tiempo de estancia en la unidad de terapia intensiva, lo que se acompaña de mayor riesgo de complicaciones y de un mayor riesgo de muerte. CONCLUSIÓN: La hipoalbuminemia representa un predictor de mortalidad en los pacientes con sepsis abdominal.

Tempo para evacuação de foco séptico abdominal e mortalidade em portadores de sepse / Time to clearance of abdominal septic focus and mortality in patients with sepsis

RESUMO Objetivo: Aferir a relação entre tempo para evacuação de foco e mortalidade hospitalar em portadores de sepse e choque séptico. Métodos: Estudo observacional, unicêntrico, com análise retrospectiva do tempo para evacuação de foco séptico abdominal. Os pacientes foram classificados conforme o tempo para evacuação do foco em grupo precoce (≤ 12 horas) ou tardio (> 12 horas). Resultados: Foram avaliados 135 pacientes. Não houve associação entre tempo para evacuação do foco e mortalidade hospitalar (≤ 12 horas versus > 12 horas): 52,3% versus 52,9%, com p = 0,137. Conclusão: Não houve diferença na mortalidade hospitalar entre pacientes com sepse ou choque séptico que tiveram foco infeccioso evacuado antes ou após 12 horas do diagnóstico de sepse.

ABSTRACT Objective: To assess the relationship between time to focus clearance and hospital mortality in patients with sepsis and septic shock. Methods: This was an observational, single-center study with a retrospective analysis of the time to clearance of abdominal septic focus. Patients were classified according to the time to focus clearance into an early (≤ 12 hours) or delayed (> 12 hours) group. Results: A total of 135 patients were evaluated. There was no association between time to focus clearance and hospital mortality (≤ 12 hours versus > 12 hours): 52.3% versus 52.9%, with p = 0.137. Conclusion: There was no difference in hospital mortality among patients with sepsis or septic shock who had an infectious focus evacuated before or after 12 hours after the diagnosis of sepsis.

Open abdomen treatment for complicated intra-abdominal infection patients with gastrointestinal fistula can reduce the mortality.

To evaluate the effect of the open abdomen (OA) and closed abdomen (CA) approaches for treating intestinal fistula with complicated intra-abdominal infection (IFWCIAI), and analyze the risk factors in OA treatment.IFWCIAI is associated with high mortality rates and healthcare costs, as well as longer postoperative hospital stay. However, OA treatment has also been linked with increased mortality and development of secondary intestinal fistula.A total of 195 IFWCIAI patients who were operated over a period of 7 years at our hospital were retrospectively analyzed. These patients were divided into the OA group (n = 112) and CA group (n = 83) accordingly, and the mortality rates, hospital costs, and hospital stay duration of both groups were compared. In addition, the risk factors in OA treatment were also analyzed.OA resulted in significantly lower mortality rates (9.8% vs 30.1%, P < .001) and hospital costs ($11721.40 ±â€Š$9368.86 vs $20365.36 ±â€Š$21789.06, P < .001) compared with the CA group. No incidences of secondary intestinal fistula was recorded and the duration of hospital stay was similar for both groups (P = .151). Delayed OA was an independent risk factor of death following OA treatment (hazard ratio [HR] = 1.316; 95% confidence interval [CI] = 1.068-1.623, P = .010), whereas early enteral nutrition (EN) exceeding 666.67 mL was a protective factor (HR = 0.996; 95% CI = 0.993-0.999, P = .018). In addition, Acinetobacter baumannii, Pseudomonas aeruginosa, and Candida albicans were the main pathogens responsible for the death of patients after OA treatment.OA decreased mortality rates and hospital costs of IFWCIAI patients, and did not lead to any secondary fistulas. Early OA and EN also reduced mortality rates.

Risk Factors and Molecular Epidemiology of Complicated Intra-Abdominal Infections With Carbapenem-Resistant Enterobacteriaceae: A Multicenter Study in China.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with poor patient outcomes. Data on risk factors and molecular epidemiology of CRE in complicated intra-abdominal infections (cIAI) in China are limited. This study examined the risk factors of cIAI with CRE and the associated mortality based on carbapenem resistance mechanisms. METHODS: In this retrospective analysis, we identified 1024 cIAI patients hospitalized from January 1, 2013 to October 31, 2018 in 14 intensive care units in China. Thirty CRE isolates were genotyped to identify ß-lactamase-encoding genes. RESULTS: Escherichia coli (34.5%) and Klebsiella pneumoniae (21.2%) were the leading pathogens. Patients with hospital-acquired cIAI had a lower rate of E coli (26.0% vs 49.1%; P < .001) and higher rate of carbapenem-resistant Gram-negative bacteria (31.7% vs 18.8%; P = .002) than those with community-acquired cIAI. Of the isolates, 16.0% and 23.4% of Enterobacteriaceae and K pneumoniae, respectively, were resistant to carbapenem. Most carbapenemase-producing (CP)-CRE isolates carried blaKPC (80.9%), followed by blaNMD (19.1%). The 28-day mortality was 31.1% and 9.0% in patients with CRE vs non-CRE (P < .001). In-hospital mortality was 4.7-fold higher for CP-CRE vs non-CP-CRE infection (P = .049). Carbapenem-containing combinations did not significantly influence in-hospital mortality of CP and non-CP-CRE. The risk factors for 28-day mortality in CRE-cIAI included septic shock, antibiotic exposure during the preceding 30 days, and comorbidities. CONCLUSIONS: Klebsiella pneumoniae had the highest prevalence in CRE. Infection with CRE, especially CP-CRE, was associated with increased mortality in cIAI.

Measuring outcomes in complicated intra-abdominal infections.

PURPOSE OF REVIEW: Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. Clinical trials should help guide and improve the management of cIAIs. However, inappropriate selection or measurement of outcomes in cIAIs clinical trials can lead to misleading results on the effectiveness of interventions. This review aims to describe how outcomes are reported in randomized controlled trials evaluating antibiotic treatment for cIAIs and discuss how outcome reporting may be improved. RECENT FINDINGS: Commonly used primary outcomes are treatment success or failure, and these outcomes are endorsed by regulatory bodies. However, a consensus objective definition of either is not available and current measures are prone to bias. Variation exists in timing of outcome evaluation and analysis populations, which can lead to further bias. Use of core outcome sets can help standardize outcome reporting. SUMMARY: Inconsistency in outcome selection and reporting can lead to misleading results and impedes meta-analysis of data. Further progress, engaging clinical trialists, regulatory authorities, clinicians and patients is required to achieve consensus on which outcomes should be reported and how and when to measure them.

A combination of C-reactive protein and quick sequential organ failure assessment (qSOFA) score has better prognostic accuracy than qSOFA alone in patients with complicated intra-abdominal infections.

INTRODUCTION: Complicated intra-abdominal infections (cIAIs) remain a serious challenge because of their unacceptably high mortality rates. Among different prognostic scoring systems quick-sequential organ failure assessment (qSOFA) score is the most recent. However, as mortality predictor in surgical patients, qSOFA showed lack of sensitivity. The aim of this study was to find prognostic superiority of our new qSOFA-CRP score in patients with cIAIs. MATERIALS AND METHODS: We retrospectively analyzed 78 patients presented to ED and admitted to Department of Surgical Diseases between January 2017 and October 2018 with diagnosis cIAIs. CRP levels, qSOFA score and systemic inflammatory response syndrome (SIRS) were established at admission. We analyzed area under receiver operating characteristics (AUROC) curves of SIRS, qSOFA and qSOFA-CRP and performed a comparison to explore their prognostic values. RESULTS: The identified in-hospital mortality was 25.6%. qSOFA-CRP score showed the best prognostic performance compared to qSOFA alone (AUROC = 0.818 vs. 0.746, p = .0219) and SIRS (AUROC = 0.818 vs. 0.579, p = .0009). The new qSOFA-CRP score ≥2 points showed excellent specificity (91.4%) and the highest sensitivity in comparison to qSOFA ≥2 and SIRS ≥2 (60% vs. 35% vs. 40%) for mortality prediction. CONCLUSIONS: qSOFA-CRP score showed better prognostic value than quick-SOFA alone in patients with cIAIs.

Infectious Complications in Severe Acute Pancreatitis: Pathogens, Drug Resistance, and Status of Nosocomial Infection in a University-Affiliated Teaching Hospital.

BACKGROUND: Secondary infection is an important factor affecting mortality and quality of life in patients with severe acute pancreatitis. The characteristics of secondary infection, which are well known to clinicians, need to be re-examined in detail, and their understanding among clinicians needs to be updated accordingly. AIM: This study aims to investigate the characteristics and drug resistance of pathogens causing severe acute pancreatitis (SAP) secondary infection, to objectively present infection situation, and to provide reference for improved clinical management. METHODS: A retrospective analysis was performed on 55 consecutive patients with SAP who developed secondary infection with an accurate evidence of bacterial/fungal culture from 2016 to 2018. The statistics included the spectrum and distribution of pathogens, the drug resistance of main pathogens, and associations between multiple infectious parameters and mortality. RESULTS: A total of 181 strains of pathogens were isolated from (peri)pancreas; bloodstream; and respiratory, urinary, and biliary systems in 55 patients. The strains included 98 g-negative bacteria, 58 g-positive bacteria, and 25 fungi. Bloodstream infection (36.5%) was the most frequent infectious complication, followed by (peri)pancreatic infection (32.0%). Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Stenotrophomonas maltophilia were predominant among gram-negative bacteria. Gram-positive bacterial infections were mainly caused by Enterococcus faecium and Staphylococcus spp. Fungal infections were predominantly caused by Candida spp. The drug resistance of pathogens causing SAP secondary infection was generally higher than the surveillance level. Patients in the death group were older (55 ± 13 years vs. 46 ± 14 years; p = 0.039) and had longer intensive care unit (ICU) stay (14 vs. 8; p = 0.026) than those in the survival group. A. baumannii infection (68.4% vs. 33%; p = 0.013), number of pathogens ≥ 4 (10 vs. 6; p = 0.005), pancreatic infection (14 vs. 15, p = 0.024), and urinary infection (8 vs. 5; p = 0.019) were significantly associated with mortality. CONCLUSION: Gram-negative bacteria are the main pathogens causing SAP secondary infection, in which nosocomial infections play a major role. The drug resistance profile of gram-negative bacteria is seriously threatening, and the commonly used antibiotics in SAP are gradually losing their effectiveness. Much attention should be paid to the rational use of antibiotics, and strategies should be established for infection prevention in SAP.

Added value of inflammatory markers to vital signs to predict mortality in patients suspected of severe infection.

OBJECTIVE: To evaluate the added value of inflammatory markers to vital signs to predict mortality in patients suspected of severe infection. METHODS: This study was conducted at an acute care hospital (471-bed capacity). Consecutive adult patients suspected of severe infection who presented to either ambulatory care or the emergency department from April 2015 to March 2017 were retrospectively evaluated. A prognostic model for predicting 30-day in-hospital mortality based on previously established vital signs (systolic blood pressure, respiratory rate, and mental status) was compared with an extended model that also included four inflammatory markers (C-reactive protein, neutrophil-lymphocyte ratio, mean platelet volume, and red cell distribution width). Measures of interest were model fit, discrimination, and the net percentage of correctly reclassified individuals at the pre-specified threshold of 10% risk. RESULTS: Of the 1015 patients included, 66 (6.5%) died. The extended model including inflammatory markers performed significantly better than the vital sign model (likelihood ratio test: p < 0.001), and the c-index increased from 0.69 (range 0.67-0.70) to 0.76 (range 0.75-0.77) (p = 0.01). All included markers except C-reactive protein showed significant contribution to the model improvement. Among those who died, 9.1% (95% CI -2.8-21.8) were correctly reclassified by the extended model at the 10% threshold. CONCLUSIONS: The inflammatory markers except C-reactive protein showed added predictive value to vital signs. Future studies should focus on developing and validating prediction models for use in individualized predictions including both vital signs and the significant markers.

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

What´s new in intraabdominal candidiasis in critically ill patients, a review.

A high prevalence of invasive candidiasis has been reported in recent years. Patients admitted to an intensive care unit are at the highest risk for invasive candidiasis, mostly due to the severity of their disease, immune-suppressive states, prolonged length of stay, broad-spectrum antibiotics, septic shock, and Candida colonization. Intraabdominal candidiasis comprises a range of clinical manifestations, from just the suspicion based on clinical scenario to fever, leukocytosis, increase in biomarkers to the isolation of the responsible microorganism. In critically ill patients with IAC prompt treatment and adequate source control remains the ultimate goal.