Postoperative lymphopaenia as a risk factor for postoperative infections in cancer surgery: A prospective multicentre cohort study (the EVALYMPH study).

BACKGROUND: Stress due to surgical trauma decreases postoperative lymphocyte counts (LCs), potentially favouring the occurrence of postoperative infections (PIs). OBJECTIVES: We aimed to determine whether postoperative lymphopaenia following thoracic or gastrointestinal cancer surgery is an independent risk factor for PIs and to identify modifiable factors related to anaesthesia and surgical procedures that might affect its occurrence. STUDY DESIGN: The EVALYMPH study was a prospective, multicentre cohort study with a 30-day patient follow-up. Multivariate analyses were performed to determine the risk factors for PIs and for postoperative lymphopaenia. SETTING: Patients were included from January 2016 to September 2017 in 25 French centres. PATIENTS: Adult patients admitted for thoracic or gastrointestinal cancer surgery were eligible for inclusion. MAIN OUTCOME MEASURE: PIs within 30 days after surgery were defined as urinary tract infections, pneumonia, surgical site infections and other infections (bloodstream infections or pleurisy). RESULTS: Of 1207 patients included, 273 (22.6%) developed at least one infection within 30 days after surgery, with a median [IQR] time to onset of 8 [5 to 11] days. An increased risk of PI was significantly associated with an ASA score of IV: hazard ratio (HR) 4.27 (95% confidence interval (CI), 1.87 to 9.72), surgery > 200 min (HR 1.58 (1.15 to 2.17) and lymphopaenia on postoperative day 1 (POD1) (HR 1.56 (1.08 to 2.25). This risk was associated with changes in postoperative LC over time (P = 0.001) but not with preoperative LC (P = 0.536).POD1 lymphopenia was related to patient characteristics and duration of surgery but not to potentially modifiable other surgical or anaesthetics factors. CONCLUSIONS: POD1 lymphopaenia was associated with PIs in patients undergoing thoracic or gastrointestinal cancer surgery. To individualise care, patient characteristics and surgery duration should be taken into account. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02799251.

Divergent effects of tumor necrosis factor (TNF) in sepsis: a meta-analysis of experimental studies.

INTRODUCTION: Experimental studies in animals have yielded conflicting results on the role of Tumor Necrosis Factor (TNF) in sepsis and endotoxemia, with some reporting adaptive and others inappropriate effects. A meta-analysis of the available literature was performed to determine the factors explaining this discrepancy. METHODS: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered with PROSPERO (CRD42020167384) prior to data collection. PubMed and Embase were the databases queried. Risk of bias was evaluated using the SYRCLE Risk of Bias Tool. All animal studies investigating sepsis-related mortality and modified TNF signaling were considered eligible. The exclusion criteria were: lack of mortality data, 7-day mortality rates below 10% in both wild type and TNF-altered pathway animals, and absence of an English abstract. To determine the role of TNF according to the experimental protocol, three approaches were used: first an approach based on the statistical significance of each experiment, then the pooled mortality was calculated, and finally the weighted risk ratio for mortality was assessed. RESULTS: A total of 175 studies were included in the analysis, comprising a total of 760 experiments and involving 19,899 animals. The main species used were mice (77%) and rats (21%). The most common method of TNF pathway modulation was TNF pathway inactivation that was primarily associated with an inappropriate secretion of TNF. At the opposite, TNF injection was associated with an adaptive role of TNF. Lipopolysaccharide (LPS) injection was the most used stimulus to establish an infectious model (42%) and was strongly associated with an inappropriate role of TNF. Conversely, live bacterial models, especially the cecal ligation and puncture (CLP) model, pneumonia, meningitis, and gastrointestinal infection, were associated with an adaptive role. This was particularly evident for Listeria monocytogenes, Streptococcus pneumoniae. CONCLUSION: The role of TNF during infection varies depending on the experimental model used. Models that mimic clinical conditions, based on virulent bacteria that cause high mortality even at low inocula, demonstrated an adaptive role of TNF. Conversely, models based on LPS or low-pathogenic live bacteria, administered at doses well above physiological thresholds and combined with early antibiotic therapy, were associated with an inappropriate role.

How safe is lung transplantation in patients of 65 years or older? A single-center retrospective cohort.

INTRODUCTION: With increasing experience in high-volume centers, age alone should not be an absolute contra-indication to lung transplantation (LT) but be considered as part of the patient's initial characteristics. The objective of this study is to provide early and long-term outcomes of LT in recipients aged 65 or older, compared with their younger counterparts. METHODS: This is a retrospective study, including all patients undergoing LT in Bichat Hospital (Paris, France) from January 2014 to March 2019. Two groups were defined depending on the patients' age when they were transplanted: patients older than 65 were defined as the "elderly group" and patients younger than 65 years old were defined as the « younger group ¼. Primary endpoint was 90-day mortality. Secondary endpoints included 1-year mortality, 1-year FEV1 (forced expiratory volume in one second), and 5-year overall survival. RESULTS: From September 2014 to March 2019, 22 patients were included in the "elderly group" and 213 were included in the « younger group ¼. The elderly group had more single LT (SLT) (82% vs. 29%, p < 0.001), with a shorter cold ischemic time (243 min vs. 310 min, p = 0.001) and a lower rate of early humoral rejection (9% vs. 30%, p = 0.045) compared to the younger group. Ninety-day mortality was not significantly different between elderly and younger group (9% vs. 14%, p = 0.95, respectively), nor were 1-year mortality (23% vs. 25%, p = 0.9, respectively) and 5-year overall survival. Six months after LT, FEV1 was significantly better in the elderly group compared to the younger group (77.0% vs. 65.5%, p = 0.037 respectively), but the difference did not reach statistical significance after one year (78.5 vs. 68.3%, p = 0.18 respectively). CONCLUSION: Elderly patients underwent more frequently single LT, and achieved similar short and long term postoperative outcomes compared to their younger counterparts. LT for patients 65 years or older should be routinely considered when carefully selected.

Size-matching in lung transplantation by computed tomography for end-stage interstitial disease: a retrospective analysis.

Background: Size matching between donors and recipients is a major issue in lung transplantation (LTx), especially in patients with restrictive lung disease (RLD). This study aims to evaluate computed tomography (CT) as an additional method for defining the total lung capacity (TLC) in patients with end-stage interstitial disease awaiting LTx. Methods: Clinical data and CT scans from patients who underwent a first LTx from January 2014 to July 2018 in Bichat Hospital, Paris, were prospectively included in a database. CT TLC (ctTLC) was retrospectively calculated after semi-automatic contouring of the parenchyma and compared with measured TLC (mTLC) and predicted TLC (pTLC) values. Results: The study group included 89 patients (male:female =68:21; mean age, 59.5±10.0 years). The time between pulmonary function tests (PFTs) and CT scan was 162±270 days [median, 67 days; interquartile range (IQR), 0-233 days]. ctTLC was inferior to mTLC and pTLC (respectively 2,979±1,001 mL, 3,530±1,077 and 6,381±955 mL, P<0.001). The relative difference between CT lung volume (ctLV) and measured lung volume (mLV) was higher on the left than on the right side (25.4% vs. 16.3%, respectively, P=0.11). After exclusion of two outliers, we found a significant correlation between ctTLC and mTLC (r=0.762, P<0.001). Conclusions: CT volume is a feasible method to assess TLC in patients with end-stage interstitial disease awaiting LTx. This study highlights potential size-mismatch for graft selection before LTx and opens the perspective of a prospective trial evaluating impact of size-matching by donor-recipient (D-R) ctTLC ratio on postoperative outcomes.

Is Night Surgery a Nightmare for Lung Transplantation?

Night work is frequently associated with sleep deprivation and is associated with greater surgical and medical complications. Lung transplantation (LT) is carried out both at night and during the day and involves many medical healthcare workers. The goal of the study was to compare morbidity and mortality between LT recipients according to LT operative time. We performed a retrospective, observational, single-center study. When the procedure started between 6 AM and 6 PM, the patient was allocated to the Daytime group. If the procedure started between 6 PM and 6 AM, the patient was allocated to the Nighttime group. Between January 2015 and December 2020, 253 patients were included. A total of 168 (66%) patients were classified into the Day group, and 85 (34%) patients were classified into the Night group. Lung Donors' general characteristics were similar between the groups. The 90-day and one-year mortality rates were similar between the groups (90-days: n = 13 (15%) vs. n = 26 (15%), p = 0.970; 1 year: n = 18 (21%) vs. n = 42 (25%), p = 0.499). Daytime LT was associated with more one-year airway dehiscence (n = 36 (21%) vs. n = 6 (7.1%), p = 0.004). In conclusion, among patients who underwent LT, there was no significant association between operative time and survival.

Neuromuscular blocking agent drug challenge: a literature review and protocol proposal with biological evaluation.

BACKGROUND: Drug challenge is the gold standard for identifying causative agents of drug allergies. Although clinical guidelines have recently been published, they do not recommend neuromuscular blocking agent (NMBA) drug challenges. NMBA challenges are rendered difficult by the lack of homogeneity of routine allergy work-ups and the necessity of a specialised setting. Several scenarios support NMBA challenges, such as an ambiguous allergy work-up, a high suspicion of a false-positive skin test or identification of a well tolerated alternative NMBA strategy. Furthermore, routine allergy work-ups may not recognise non-IgE mechanisms, such as IgG or MRGPRX2, whereas drug challenges may reveal them. Finally, if the culprit NMBA is not identified, subsequent anaesthesia regimens will be challenging to implement, resulting in increased risk. OBJECTIVES: This literature review discusses the indications, strategies, doses, monitoring methods, limitations, and unresolved issues related to drug challenges for NMBAs. DESIGN: The literature review included randomised controlled trials, observational studies, reviews, case reports, series, and comments on humans. DATA SOURCES: Studies were retrieved from databases (PubMed) and electronic libraries (OVID, EMBASE, Scopus, etc.). ELIGIBILITY CRITERIA: All studies that referred to the NMBA challenge were included without publication date limitations. RESULTS: NMBA challenge may be considered in NMBA anaphylaxis patients with inconclusive or ambivalent IgE diagnostic work-up under controlled conditions (presence of anaesthetists and allergists with continuous monitoring in a secured environment). To illustrate its utility, a case report of a double NMBA challenge in a patient with NMBA cross-reactivity is presented, along with biological explorations to detect subclinical cellular activation, a novel aspect of this procedure. CONCLUSION: Drug challenges could be implemented during the NMBA allergy work-up under strict safety conditions at specialised centres with close collaboration between anaesthetists and allergists. This could decrease uncertainty and contribute to defining a safer strategy for subsequent anaesthetic drug regimens.

Intra-abdominal infections survival guide: a position statement by the Global Alliance For Infections In Surgery.

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.

COVID-19 PBMCs are doubly harmful, through LDN-mediated lung epithelial damage and monocytic impaired responsiveness to live Pseudomonas aeruginosa exposure.

Introduction: Although many studies have underscored the importance of T cells, phenotypically and functionally, fewer have studied the functions of myeloid cells in COVID disease. In particular, the potential role of myeloid cells such as monocytes and low-density neutrophils (LDNs) in innate responses and particular in the defense against secondary bacterial infections has been much less documented. Methods: Here, we compared, in a longitudinal study, healthy subjects, idiopathic fibrosis patients, COVID patients who were either hospitalized/moderate (M-) or admitted to ICU (COV-ICU) and patients in ICU hospitalized for other reasons (non-COV-ICU). Results: We show that COVID patients have an increased proportion of low-density neutrophils (LDNs), which produce high levels of proteases (particularly, NE, MMP-8 and MMP-9) (unlike non-COV-ICU patients), which are partly responsible for causing type II alveolar cell damage in co-culture experiments. In addition, we showed that M- and ICU-COVID monocytes had reduced responsiveness towards further live Pseudomonas aeruginosa (PAO1 strain) infection, an important pathogen colonizing COVID patients in ICU, as assessed by an impaired secretion of myeloid cytokines (IL-1, TNF, IL-8,…). By contrast, lymphoid cytokines (in particular type 2/type 3) levels remained high, both basally and post PAO1 infection, as reflected by the unimpaired capacity of T cells to proliferate, when stimulated with anti-CD3/CD28 beads. Discussion: Overall, our results demonstrate that COVID circulatory T cells have a biased type 2/3 phenotype, unconducive to proper anti-viral responses and that myeloid cells have a dual deleterious phenotype, through their LDN-mediated damaging effect on alveolar cells and their impaired responsiveness (monocyte-mediated) towards bacterial pathogens such as P. aeruginosa.

Femoro-axillary versus femoro-femoral veno-arterial extracorporeal membrane oxygenation for refractory cardiogenic shock: A monocentric retrospective study.

RATIONALE: For veno-arterial extracorporeal membrane oxygenation (ECMO), the femoral artery is the preferred cannulation site (femoro-femoral: Vf-Af). This results in retrograde aortic flow, which increases the left ventricular afterload and can lead to severe pulmonary edema and thrombosis of the cardiac chambers. Right axillary artery cannulation (femoral-axillary: Vf-Aa) provides partial anterograde aortic flow, which may prevent some complications. This study aimed to compare the 90-day mortality and complication rates between VF-AA and VF-AF. METHODS: Consecutive adult patients with cardiogenic shock who received peripheral VA-ECMO between 2013 and 2019 at our institution were retrospectively included. The exclusion criteria were refractory cardiac arrest, multiple VA-ECMO implantations due to vascular access changes, weaning failure, or ICU readmission. A statistical approach using inverse probability of treatment weighting was used to estimate the effect of the cannulation site on the outcomes. The primary endpoint was the 90-day mortality. The secondary endpoints were vascular access complications, stroke, and other complications related to retrograde blood flow. Outcomes were estimated using logistic regression analysis. RESULTS: VA-ECMO was performed on 534 patients. Patients with refractory cardiac arrest (n = 77 (14%)) and those supported by multiple VA-ECMO (n = 92, (17%)) were excluded. Out of the 333 patients studied (n = 209 Vf-Aa; n = 124 VF-AF), the main indications for VA-ECMO implantation were post-cardiotomy (33%, n = 109), dilated cardiomyopathy (20%, n = 66), post-cardiac transplantation (15%, n = 50), acute myocardial infarction (14%, n = 46) and other etiologies (18%, n = 62). The median SOFA score was 9 [7-11], and the crude 90-day mortality rate was 53% (n = 175). After IPTW, the 90-day mortality was similar in the Vf-Aa and VF-AF groups (54% vs 58%, IPTW-OR = 0.84 [0.54-1.29]). Axillary artery cannulation was associated with significantly fewer local infections (OR = 0.21, 95% CI:0.09-0.51), limb ischemia (OR = 0.37, 95% CI:0.17-0.84), bowel ischemia (OR = 0.16, 95% CI:0.05-0.51) and pulmonary edema (OR = 0.52, 95% CI:0.29-0.92) episodes, but with a higher rate of stroke (OR = 2.87, 95% CI:1.08-7.62) than femoral artery cannulation. CONCLUSION: Compared to VF-AF, axillary cannulation was associated with similar 90-day mortality rates. The high rate of stroke associated with axillary artery cannulation requires further investigation.

Thromboembolic events after major bleeding events in patients with mechanical heart valves: a 13-year analysis.

Anticoagulation in patients with mechanical heart valves (MHV) is associated with a risk of major bleeding episodes (MBE). In case of MBE, anticoagulant interruption is advocated. However, there is lack of data regarding the thrombo-embolic events (TE) risk associated with anticoagulant interruption. The main objective of the study was to evaluate the rate and risk factors of 6-months of TEs in patients with MHV experiencing MBE. This observational study was conducted over a 13-year period. Adult patients with a MHV presenting with a MBE were included. The main study endpoint was 6-month TEs, defined by clinical TEs or an echocardiographic documented thrombosis, occurring during an ICU stay or within 6-months. Thromboembolic events were recorded at ICU discharge, and 6 months after discharge. Seventy-nine MBEs were analysed, the rate of TEs at 6-months was 19% CI [11-29%]. The only difference of presentation and management between 6-month TEs and free-TE patients was the time without effective anticoagulation (TWA). The Receiver Operator Characteristic curve identified the value of 122 h of TWA as a cut-off. The multivariate analysis identified early bleeding recurrences (OR 3.62, 95% CI [1.07-12.25], p = 0.039), and TWA longer than 122 h (OR 4.24, 95% CI [1.24-14.5], p = 0.021), as independent risk factors for 6-month TEs. A higher rate of TE was associated with anticoagulation interruption longer than 5 days and early bleeding recurrences. However, the management should still be personalized and discussed for each case given the heterogeneity of causes of MBE and possibilities of haemostatic procedures.

Protocol for venoarterial ExtraCorporeal Membrane Oxygenation to reduce morbidity and mortality following bilateral lung TransPlantation: the ECMOToP randomised controlled trial.

INTRODUCTION: Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control 'on-demand' arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental 'systematic' arm, VA-ECMO will be pre-emptively initiated. We hypothesise a 'systematic' strategy will increase the number of ventilatory-free days at day 28. METHODS AND ANALYSIS: We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events. ETHICS AND DISSEMINATION: The sponsor is the Assistance Publique-Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT05664204.

Toxic Shock Syndrome: A Literature Review.

Toxic shock syndrome (TSS) is a rare, life-threatening, toxin-mediated infectious process linked, in the vast majority of cases, to toxin-producing strains of Staphylococcus aureus or Streptococcus pyogenes. The pathophysiology, epidemiology, clinical presentation, microbiological features, management and outcome of TSS are described in this review. Bacterial superantigenic exotoxins induces unconventional polyclonal lymphocyte activation, which leads to rapid shock, multiple organ failure syndrome, and death. The main described superantigenic exotoxins are toxic shock syndrome toxin-1 (TSST-1) and enterotoxins for Staphylococcus aureus and Streptococcal pyrogenic exotoxins (SpE) A, B, and C and streptococcal superantigen A (SsA) for Streptococcus pyogenes. Staphylococcal TSS can be menstrual or nonmenstrual. Streptococcal TSS is linked to a severe group A streptococcal infection and, most frequently, to a necrotizing soft tissue infection. Management of TSS is a medical emergency and relies on early detection, immediate resuscitation, source control and eradication of toxin production, bactericidal antibiotic treatment, and protein synthesis inhibiting antibiotic administration. The interest of polyclonal intravenous immunoglobulin G administration as an adjunctive treatment for TSS requires further evaluation. Scientific literature on TSS mainly consists of observational studies, clinical cases, and in vitro data; although more data on TSS are required, additional studies will be difficult to conduct due to the low incidence of the disease.

Are changes in antibiotic prophylaxis recommendations responsible for an increased risk of cefazolin allergy?

BACKGROUND: The first line of prevention of surgical site infection relies on the timely administration of antibiotic prophylaxis. First- and second-generation cephalosporins are the most recommended antibiotics in elective surgery. The incidence of cefazolin allergy has increased worldwide over the years. The sensitization mechanism of cefazolin is currently unknown, and data supporting cross-reactivity between penicillins and cephalosporins are lacking. Sensitization could occur through previous exposure either to cefazolin or to structurally related chemical agents. The objective of this study was to evaluate sensitization agents towards cefazolin. METHODS: The OpenBabel chemoinformatics toolbox was used to search for similarities between cefazolin and other molecules in an extensive drug database. Using the pholcodine-rocuronium similarity score as a threshold, we selected drugs with the most similar structure to that of cefazolin. Exposure to those drugs and cefazolin was assessed in a cohort of patients with skin test-proven cefazolin allergy at a specialized allergy centre via a self-administered anonymous questionnaire. RESULTS: Using the pholcodine-rocuronium similarity score as a threshold (score≥0.7), 42 molecules were found to be similar to cefazolin (all cephalosporins). Only 8 were marketed in France. None of the 14 cefazolin-allergic patients who answered the questionnaire (65% female, median age 56 years) reported exposure to any identified antibiotics. In contrast, 11 (78%) had at least one previous surgery requiring cefazolin before the index case. CONCLUSION: Direct previous cefazolin exposure was identified in 78% of cefazolin-allergic patients. Cefazolin started to take a central place in antibiotic prophylaxis after 2010, when cefamandole usage decreased drastically. Changes in antibiotic prophylaxis over the past 14 years in France could have been the turning point for the increased incidence of cefazolin allergy.

Epidemiology and risk factors for mortality in critically ill patients with pancreatic infection.

Background: The AbSeS-classification defines specific phenotypes of patients with intra-abdominal infection based on the (1) setting of infection onset (community-acquired, early onset, or late-onset hospital-acquired), (2) presence or absence of either localized or diffuse peritonitis, and (3) severity of disease expression (infection, sepsis, or septic shock). This classification system demonstrated reliable risk stratification in intensive care unit (ICU) patients with intra-abdominal infection. This study aimed to describe the epidemiology of ICU patients with pancreatic infection and assess the relationship between the components of the AbSeS-classification and mortality. Methods: This was a secondary analysis of an international observational study ("AbSeS") investigating ICU patients with intra-abdominal infection. Only patients with pancreatic infection were included in this analysis (n=165). Mortality was defined as ICU mortality within 28 days of observation for patients discharged earlier from the ICU. Relationships with mortality were assessed using logistic regression analysis and reported as odds ratio (OR) and 95% confidence interval (CI). Results: The overall mortality was 35.2% (n=58). The independent risk factors for mortality included older age (OR=1.03, 95% CI: 1.0 to 1.1 P=0.023), localized peritonitis (OR=4.4, 95% CI: 1.4 to 13.9 P=0.011), and persistent signs of inflammation at day 7 (OR=9.5, 95% CI: 3.8 to 23.9, P<0.001) or after the implementation of additional source control interventions within the first week (OR=4.0, 95% CI: 1.3 to 12.2, P=0.013). Gram-negative bacteria were most frequently isolated (n=58, 49.2%) without clinically relevant differences in microbial etiology between survivors and non-survivors. Conclusions: In pancreatic infection, a challenging source/damage control and ongoing pancreatic inflammation appear to be the strongest contributors to an unfavorable short-term outcome. In this limited series, essentials of the AbSeS-classification, such as the setting of infection onset, diffuse peritonitis, and severity of disease expression, were not associated with an increased mortality risk.ClinicalTrials.gov number: NCT03270345.

Identifying patients with difficult-to-treat acute bacterial skin infections.

PURPOSE OF REVIEW: The early recognition of acute bacterial skin infections (ABSIs) and their swift and adequate care are the major determinants of success. The features that can hamper or delay surgical and medical management can lead to 'difficult-to-treat' ABSIs. RECENT FINDINGS: Delayed diagnosis and belated management are the key obstacles to be overcome. Clinicians should be careful about underestimating the severity of ABSIs and overlooking comorbidities, especially immunosuppression. Many conditions can lead to delayed source control, including a misdiagnosis, interhospital transfers, delayed re-exploration, or extensive injuries. Difficult therapeutic issues can occur, including rapidly destructive infections from highly pathogenic microorganisms (Group-A-streptococci, Vibrio spp., Clostridium spp. and Staphylococcus aureus ) or inadequate antibiotic therapy resulting from multidrug-resistant bacteria. Impaired pharmacokinetic capacities of antibiotic agents should also be considered as a source of clinical failure due to insufficient antimicrobial activity at the site of infection. SUMMARY: Microbiological samples should be used for guiding antimicrobial therapy. Risk factors for multidrug-resistant bacteria should be considered, including local epidemiology and comorbidities. The optimization of antibiotic therapy should be achieved. Optimized care should be achieved through multidisciplinary management involving professionals with sufficient and appropriate training.

Microbiological profile of patients treated for postoperative peritonitis: temporal trends 1999-2019.

BACKGROUND: Temporal changes in the microbiological resistance profile have been reported in several life-threatening infections. However, no data have ever assessed this issue in postoperative peritonitis (POP). Our purpose was to assess the rate of multidrug-resistant organisms (MDROs) in POP over a two-decade period and to analyse their influence on the adequacy of empirical antibiotic therapy (EAT). METHODS: This retrospective monocentric analysis (1999-2019) addressed the changes over time in microbiologic data, including the emergence of MDROs and the adequacy of EAT for all intensive care unit adult patients treated for POP. The in vitro activities of 10 antibiotics were assessed to determine the most adequate EAT in the largest number of cases among 17 antibiotic regimens in patients with/without MDRO isolates. Our primary endpoint was to determine the frequency of MDRO and their temporal changes. Our second endpoint assessed the impact of MDROs on the adequacy of EAT per patient and their temporal changes based on susceptibility testing. In this analysis, the subgroup of patients with MDRO was compared with the subgroup of patients free of MDRO. RESULTS: A total of 1,318 microorganisms were cultured from 422 patients, including 188 (45%) patients harbouring MDROs. The growing proportions of MDR Enterobacterales were observed over time (p = 0.016), including ESBL-producing strains (p = 0.0013), mainly related to Klebsiella spp (p < 0.001). Adequacy of EAT was achieved in 305 (73%) patients. Decreased adequacy rates were observed when MDROs were cultured [p = 0.0001 vs. MDRO-free patients]. Over the study period, decreased adequacy rates were reported for patients receiving piperacillin/tazobactam in monotherapy or combined with vancomycin and imipenem/cilastatin combined with vancomycin (p < 0.01 in the three cases). In patients with MDROs, the combination of imipenem/cilastatin + vancomycin + amikacin or ciprofloxacin reached the highest adequacy rates (95% and 91%, respectively) and remained unchanged over time. CONCLUSIONS: We observed high proportions of MDRO in patients treated for POP associated with increasing proportions of MDR Enterobacterales over time. High adequacy rates were only achieved in antibiotic combinations involving carbapenems and vancomycin, while piperacillin/tazobactam is no longer a drug of choice for EAT in POP in infections involving MDRO.

Ultrasonography in thoracic and abdominal stab wound injury: results from the FETTHA study.

BACKGROUND: While the role of Extended Focused Assessment with Sonography in Trauma (eFAST) is well defined in the management of severe blunt trauma, its performance in injuries caused by stab wounds has been poorly assessed. METHODS: Prospective single centre study which included all patients with stab wounds to the thorax or abdomen between December 2016 and December 2018. All patients underwent initial investigation with both eFAST and CT scan, except in cases of haemodynamic or respiratory instability, and in cases with a positive diagnosis by eFAST in which case surgery without CT scan was performed. RESULTS: Of the 200 consecutive patients included, 14 unstable patients underwent surgery immediately after eFAST. In these 14 patients, 9 had cardiac tamponade identified by eFAST and all were confirmed by surgery. In the remaining 186 patients, the median time between eFAST and CT scan was 30 min (IQR 20-49 min). Test characteristics (including 95% CI) for eFAST compared with reference standard of CT scan for detecting pneumothorax were as follows: sensitivity 77% (54%-92%), specificity 93% (90%-97%), positive predictive value (PPV) 60% (49%-83%), negative predictive value (NPV) 97% (93%-99%). Test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemothorax were as follows: sensitivity 97% (74%-99%), specificity 96% (92%-98%), PPV 83% (63%-93%) and NPV 99% (96%-100%). Finally, test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemoperitoneum were as follows: sensitivity 75% (35%-97%), specificity 97% (93%-99%), PPV 55% (23%-83%) and NPV 99% (96%-99%). CONCLUSIONS: In patients admitted with stab wounds to the torso, eFAST was not sensitive enough to diagnose pneumothorax and haemoperitoneum, but performed better in the detection of cardiac tamponade and haemothorax than the other injuries. More robust multicentre studies are needed to better define the role of eFAST in this specific population.