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We investigated links between antimicrobial resistance in community-onset bacteremia and 1-year bacteremia recurrence by using the clinical data warehouse of Europe's largest university hospital group in France. We included adult patients hospitalized with an incident community-onset Staphylococcus aureus, Escherichia coli, or Klebsiella spp. bacteremia during 2017-2019. We assessed risk factors of 1-year recurrence using Fine-Gray regression models. Of the 3,617 patients included, 291 (8.0%) had >1 recurrence episode. Third-generation cephalosporin (3GC)-resistance was significantly associated with increased recurrence risk after incident Klebsiella spp. (hazard ratio 3.91 [95% CI 2.32-6.59]) or E. coli (hazard ratio 2.35 [95% CI 1.50-3.68]) bacteremia. Methicillin resistance in S. aureus bacteremia had no effect on recurrence risk. Although several underlying conditions and infection sources increased recurrence risk, 3GC-resistant Klebsiella spp. was associated with the greatest increase. These results demonstrate a new facet to illness induced by 3GC-resistant Klebsiella spp. and E. coli in the community setting.

Background Sepsis is a complex health condition, leading to long-term morbidity and mortality. Understanding the risk factors for recurrent sepsis, as well as its impact on mid- and long-term mortality among other risk factors, is essential to improve patient survival. Methods A risk factor analysis, based on French nationwide medico-administrative data, was conducted on a cohort of patients above 15 years old, hospitalized with an incident sepsis in metropolitan France between 1st January 2018 and 31st December 2018 and who survived their index hospitalization. Two main analyses, focusing on outcomes occurring 1-year post-discharge, were conducted: a first one to assess risk factors for recurrent sepsis and a second to assess risk factors for mortality. Results Of the 178017 patients surviving an incident sepsis episode in 2018 and included in this study, 22.3% died during the 1-year period from discharge and 73.8% had at least one hospital readmission in acute care, among which 18.1% were associated with recurrent sepsis. Patients aged between 56 and 75, patients with cancer and renal disease, with a long index hospital stay or with mediastinal or cardiac infection had the highest odds of recurrent sepsis. One-year mortality was higher for patients with hospital readmission for recurrent sepsis (aOR 2.93; 99% CI 2.78–3.09). Among all comorbidities, patients with cancer (aOR 4.35; 99% CI 4.19–4.52) and dementia (aOR 2.02; 99% CI 1.90–2.15) had the highest odds of 1-year mortality. Conclusion Hospital readmission for recurrent sepsis is one of the most important risk factors for 1-year mortality of septic patients, along with age and comorbidities. Our study suggests that recurrent sepsis, as well as modifiable or non-modifiable other risk factors identified, should be considered in order to improve patient care pathway and survival.

Background.Little is known about the incidence of inadequate treatment of severe Staphylococcus aureus infection in Europe. We aimed to evaluate the adequacy of antibiotic therapy for S. aureus bacteremia (SAB), to identify determinants of inadequate treatment, and to determine the effect of inadequate treatment on patient outcome in a representative selection of hospitals in 9 Western European countries. Methods.In this retrospective cohort study, all adult patients with SAB (due to methicillin-susceptible S. aureus [MSSA] or methicillin-resistant S. aureus [MRSA]) who were admitted to 60 randomly selected hospitals from 1 November 2007 through 31 December 2007 were included. Adequate antimicrobial therapy was defined as intravenous administration of at least 1 antibiotic to which the isolate showed in vitro susceptibility that was initiated within 2 days after onset of SAB. Results.A total of 334 SAB episodes (257 due to MSSA and 77 due to MRSA) were included. Ninety-four patients (28%) received inadequate empirical therapy (21% in the MSSA group and 52% in the MRSA group). Both length of stay before SAB onset and methicillin-resistant infection were associated with inadequate therapy, with adjusted odds ratios (ORs) of 1.01 (95% confidence interval [CI], 1.00–1.03) and 3.7 (95% CI, 2.2–6.4), respectively. Age (OR, 1.06; 95% CI, 1.03–1.10), Charlson comorbidity score (OR, 2.1; 95% CI, 1.2–3.6), severe sepsis or septic shock (OR, 2.7; 95% CI, 1.5–4.8), and intensive care unit stay at onset of SAB (OR, 2.9; 95% CI, 1.5–5.6) but not inadequate treatment (OR, 0.7; 95% CI, 0.4–1.3) were associated with increased 30-day mortality. Conclusion.Inadequate empirical antimicrobial therapy for SAB is common in Western Europe and is strongly associated with infection caused by MRSA. In this study, inadequate treatment was not associated with increased 30-day mortality rates.

Rationale Increased right ventricle (RV) afterload during acute respiratory distress syndrome (ARDS) may induce acute cor pulmonale (ACP). Objectives To determine the prevalence and prognosis of ACP and build a clinical risk score for the early detection of ACP. Methods This was a prospective study in which 752 patients with moderate-to-severe ARDS receiving protective ventilation were assessed using transesophageal echocardiography in 11 intensive care units. The study cohort was randomly split in a derivation ( n  = 502) and a validation ( n  = 250) cohort. Measurements and main results ACP was defined as septal dyskinesia with a dilated RV [end-diastolic RV/left ventricle (LV) area ratio >0.6 (≥1 for severe dilatation)]. ACP was found in 164 of the 752 patients (prevalence of 22 %; 95 % confidence interval 19–25 %). In the derivation cohort, the ACP risk score included four variables [pneumonia as a cause of ARDS, driving pressure ≥18 cm H 2 O, arterial oxygen partial pressure to fractional inspired oxygen (PaO 2 /FiO 2 ) ratio <150 mmHg, and arterial carbon dioxide partial pressure ≥48 mmHg]. The ACP risk score had a reasonable discrimination and a good calibration. Hospital mortality did not differ between patients with or without ACP, but it was significantly higher in patients with severe ACP than in the other patients [31/54 (57 %) vs. 291/698 (42 %); p  = 0.03]. Independent risk factors for hospital mortality included severe ACP along with male gender, age, SAPS II, shock, PaO 2 /FiO 2 ratio, respiratory rate, and driving pressure, while prone position was protective. Conclusions We report a 22 % prevalence of ACP and a poor outcome of severe ACP. We propose a simple clinical risk score for early identification of ACP that could trigger specific therapeutic strategies to reduce RV afterload.

ObjectiveThis study aims to provide a case definition of sepsis of presumed bacterial aetiology based on 10th revision of the International Classification of Diseases (ICD-10) codes, to assess trends in sepsis incidence and mortality between 2015 and 2019 in France, and to describe the characteristics of affected patients and hospital stays.DesignNationwide, population-based, retrospective observational study.SettingMetropolitan France between 2015 and 2019.ParticipantsBetween 2015 and 2019, 1 224 433 patients with sepsis of presumed bacterial aetiology were selected from the French National Hospital Discharge Database (Programme de Médicalisation des Systèmes d’Information) and were identified from corresponding ICD-10 codes for explicit sepsis or implicit sepsis.Main outcomes measuresAnnual overall and age-specific and gender-specific incidence and 95% CI, as well as trends in sepsis incidence and mortality, were estimated. Comorbidities, length of hospital stay and outcomes were described.ResultsThe sex-standardised and age-standardised incidence per 100 000 (95% CI) increased from 357 (356.0 to 359.0) in 2015 to 403 (401.9 to 405.0) in 2019 and remained higher for males compared with females. Children under 1 year and patients over 75 years consistently had the highest incidence. The most common comorbidities were cancer and chronic heart failure. The median hospital length of stay was 12 days. Most patients came from home, but only half returned home after their hospital stay and approximately 15% were discharged to long-term care. In-hospital mortality was about 25% and declined along the study period.ConclusionsMedico-administrative databases can be used to provide nationwide estimates of the in-hospital burden of bacterial sepsis. The results confirm the high burden of sepsis in France. These data should be complemented by estimating the additional burden associated with fungal and viral infections during the COVID-19 pandemic.

Selective decontamination of the digestive tract (SDD) is an infection prevention measure for intensive care unit (ICU) patients that was proposed more than 30 years ago, and that is currently considered standard of care in the Netherlands, but only used sporadically in ICUs in other countries. In this narrative review, we first describe the rationale of the individual components of SDD and then review the evidence base for patient-centered outcomes, where we distinguish ICUs with low prevalence of antibiotic resistance from ICUs with moderate–high prevalence of resistance. In settings with low prevalence of antibiotic resistance, SDD has been associated with improved patient outcome in three cluster-randomized studies. These benefits were not confirmed in a large international cluster-randomized study in settings with moderate-to-high prevalence of antibiotic resistance. There is no evidence that SDD increases antibiotic resistance. We end with future directions for research.

Abstract Rationale Despite their controversial role, corticosteroids are often administered to patients with adult respiratory distress syndrome (ARDS) secondary to viral pneumonia. Objectives To analyze the impact of corticosteroid therapy on outcomes of patients having ARDS associated with influenza A/H1N1 pneumonia. Methods Patients from the French registry of critically ill patients with influenza A/H1N1v 2009 infection were selected if fulfilling criteria for ARDS, excluding patients having other indication for corticosteroids, or decompensated underlying disease as the primary cause for intensive care unit admission. Survival to hospital discharge was analyzed using Cox regression, accounting for the time to administration of steroids, and after adjustment on the propensity for receiving steroid therapy. Measurements and Main Results Of 208 patients with ARDS, 83 (39.9%) received corticosteroids (median initial dose of 270 mg equivalent hydrocortisone per day for a median of 11 d). Steroid therapy was associated with death, both in crude analysis (33.7 vs. 16.8%; hazard ratio, 2.4; 95% CI, 1.3–4.3; P = 0.004) and after propensity score–adjusted analysis (adjusted hazard ratio, 2.82; 95% CI, 1.5–5.4; P = 0.002), controlling for an admission severity Simplified Acute Physiology Score, version 3, greater than 50, initial administration of vasopressors, and immunodepression. Early therapy (≤ 3 d of mechanical ventilation) appeared more strongly associated with mortality than late administration. Patients receiving steroids had more acquired pneumonia and a trend to a longer duration of ventilation. Conclusions Our study provides no evidence of a beneficial effect of corticosteroids in patients with ARDS secondary to influenza pneumonia, but suggests that very early corticosteroid therapy may be harmful.

Intensive care units (ICUs) are high-risk areas for transmission of antimicrobial-resistant bacteria, but no controlled study has tested the effect of rapid screening and isolation of carriers on transmission in settings with best-standard precautions. We assessed interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in European ICUs. We did this study in three phases at 13 ICUs. After a 6 month baseline period (phase 1), we did an interrupted time series study of universal chlorhexidine body-washing combined with hand hygiene improvement for 6 months (phase 2), followed by a 12–15 month cluster randomised trial (phase 3). ICUs were randomly assigned by computer generated randomisation schedule to either conventional screening (chromogenic screening for meticillin-resistant Staphylococcus aureus [MRSA] and vancomycin-resistant enterococci [VRE]) or rapid screening (PCR testing for MRSA and VRE and chromogenic screening for highly resistant Enterobacteriaceae [HRE]); with contact precautions for identified carriers. The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk, for which we calculated step changes and changes in trends after the introduction of each intervention. We assessed acquisition by microbiological surveillance and analysed it with a multilevel Poisson segmented regression model. We compared screening groups with a likelihood ratio test that combined step changes and changes to trend. This study is registered with ClinicalTrials.gov, number NCT00976638. Seven ICUs were assigned to rapid screening and six to conventional screening. Mean hand hygiene compliance improved from 52% in phase 1 to 69% in phase 2, and 77% in phase 3. Median proportions of patients receiving chlorhexidine body-washing increased from 0% to 100% at the start of phase 2. For trends in acquisition of antimicrobial-resistant bacteria, weekly incidence rate ratio (IRR) was 0·976 (0·954–0·999) for phase 2 and 1·015 (0·998–1·032) for phase 3. For step changes, weekly IRR was 0·955 (0·676–1·348) for phase 2 and 0·634 (0·349–1·153) for phase 3. The decrease in trend in phase 2 was largely caused by changes in acquisition of MRSA (weekly IRR 0·925, 95% CI 0·890–0·962). Acquisition was lower in the conventional screening group than in the rapid screening group, but did not differ significantly (p=0·06). Improved hand hygiene plus unit-wide chlorhexidine body-washing reduced acquisition of antimicrobial-resistant bacteria, particularly MRSA. In the context of a sustained high level of compliance to hand hygiene and chlorhexidine bathings, screening and isolation of carriers do not reduce acquisition rates of multidrug-resistant bacteria, whether or not screening is done with rapid testing or conventional testing. European Commission.

Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting. In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667. Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21·2% [65/307] vs 20·4% [64/314]; absolute difference 0·8%, 90% CI −4·6 to 6·2) and day 60 (30·0% [92/307] vs 26·1% [82/314]; 3·8%, −2·1 to 9·7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14·3 days [SD 9·1] vs 11·6 days [SD 8·2]; absolute difference 2·7 days, 95% CI 1·4 to 4·1, p<0·0001). A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes. Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.

Abstract Rationale Fever control may improve vascular tone and decrease oxygen consumption, but fever may contribute to combat infection. Objectives To determine whether fever control by external cooling diminishes vasopressor requirements in septic shock. Methods In a multicenter randomized controlled trial, febrile patients with septic shock requiring vasopressors, mechanical ventilation, and sedation were allocated to external cooling (n = 101) to achieve normothermia (36.5–37°C) for 48 hours or no external cooling (n = 99). Vasopressors were tapered to maintain the same blood pressure target in the two groups. The primary endpoint was the number of patients with a 50% decrease in baseline vasopressor dose after 48 hours. Measurements and Main Results Body temperature was significantly lower in the cooling group after 2 hours of treatment (36.8 ± 0.7 vs. 38.4 ± 1.1°C; P < 0.01). A 50% vasopressor dose decrease was significantly more common with external cooling from 12 hours of treatment (54 vs. 20%; absolute difference, 34%; 95% confidence interval [95% CI], −46 to −21; P < 0.001) but not at 48 hours (72 vs. 61%; absolute difference, 11%; 95% CI, −23 to 2). Shock reversal during the intensive care unit stay was significantly more common with cooling (86 vs. 73%; absolute difference, 13%; 95% CI, 2 to 25; P = 0.021). Day-14 mortality was significantly lower in the cooling group (19 vs. 34%; absolute difference, –16%; 95% CI, −28 to −4; P = 0.013). Conclusions In this study, fever control using external cooling was safe and decreased vasopressor requirements and early mortality in septic shock.