Antibiotic Prescriptions in Critically Ill Patients with Bloodstream Infection Due to ESBL-Producing Enterobacteriaceae: Compliance with the French Guidelines for the Treatment of Infections with Third-Generation Cephalosporin-Resistant Enterobacteriaceae-A Multicentric Retrospective Cohort Study.

National and international guidelines were recently published regarding the treatment of Enterobacteriaceae resistant to third-generation cephalosporins infections. We aimed to assess the implementation of the French guidelines in critically ill patients suffering from extended-spectrum ß-lactamase-producing Enterobacteriaceae bloodstream infection (ESBL-E BSI). We conducted a retrospective observational cohort study in the ICU of three French hospitals. Patients treated between 2018 and 2022 for ESBL-E BSI were included. The primary assessment criterion was the proportion of adequate empirical carbapenem prescriptions, defined as prescriptions consistent with the French guidelines. Among the 185 included patients, 175 received an empirical anti-biotherapy within 24 h of ESBL-E BSI onset, with a carbapenem for 100 of them. The proportion of carbapenem prescriptions consistent with the guidelines was 81%. Inconsistent prescriptions were due to a lack of prescriptions of a carbapenem, while it was recommended in 25% of cases. The only factor independently associated with adequate empirical carbapenem prescription was ESBL-E colonization (OR: 107.921 [9.303-1251.910], p = 0.0002). The initial empirical anti-biotherapy was found to be appropriate in 83/98 patients (85%) receiving anti-biotherapy in line with the guidelines and in 56/77 (73%) patients receiving inadequate anti-biotherapy (p = 0.06). Our results illustrate the willingness of intensivists to spare carbapenems. Promoting implementation of the guidelines could improve the proportion of initial appropriate anti-biotherapy in critically ill patients with ESBL-E BSI.

Severe secondary peritonitis: impact of inappropriate initial antimicrobial therapy on prognosis and potential carbapenem-sparing.

BACKGROUND: Initiation of antimicrobial therapy (IAT) with broad-spectrum antibiotics is usual in Intensive Care Unit (ICU) patients with secondary peritonitis. Carbapenems are widely proposed by recent guidelines contrasting with current antibiotic stewardship policies of carbapenem-sparing. However, prognosis of inappropriate IAT remains unclear in these patients and broad-spectrum antibiotics are probably overused. We aimed to assess the role of inappropriate IAT in ICU patients with secondary peritonitis and the use of carbapenems in our IAT regimens. METHODS: We performed a retrospective analysis during a six-year period including 131 ICU patients with secondary peritonitis. We collected data concerning comorbidities, source and severity of peritonitis, management of IAT, peritoneal samples and outcome. RESULTS: Forty-one patients presented with community acquired peritonitis (CAP) and 90 with postoperative peritonitis (POP). Thirty-seven (28.2%) patients died during ICU stay. IAT was inappropriate in 35 (26.7%) patients. Inappropriate IAT was not associated with reduced survival with respectively 26 (27%) deaths when IAT was adequate and 11 (31.4%) deaths when IAT was inadequate (P=0.87). Inappropriate IAT was not associated with the need of re-operation and duration of ICU stay. Carbapenems were delivered in 29 patients but were only necessary for eight patients without alternative treatment. CONCLUSIONS: In our study, inappropriate IAT was not associated with a worse prognosis and carbapenems were overused. Extensive delivery of carbapenems proposed by recent guidelines could be reconsidered in the management of these patients.

A three-step support strategy for relatives of patients dying in the intensive care unit: a cluster randomised trial.

BACKGROUND: In relatives of patients dying in intensive care units (ICUs), inadequate team support can increase the prevalence of prolonged grief and other psychological harm. We aimed to evaluate whether a proactive communication and support intervention would improve relatives' outcomes. METHODS: We undertook a prospective, multicentre, cluster randomised controlled trial in 34 ICUs in France, to compare standard care with a physician-driven, nurse-aided, three-step support strategy for families throughout the dying process, following a decision to withdraw or withhold life support. Inclusion criteria were relatives of patients older than 18 years with an ICU length of stay 2 days or longer. Participating ICUs were randomly assigned (1:1 ratio) into an intervention cluster and a control cluster. The randomisation scheme was generated centrally by a statistician not otherwise involved in the study, using permutation blocks of non-released size. In the intervention group, three meetings were held with relatives: a family conference to prepare the relatives for the imminent death, an ICU-room visit to provide active support, and a meeting after the patient's death to offer condolences and closure. ICUs randomly assigned to the control group applied their best standard of care in terms of support and communication with relatives of dying patients. The primary endpoint was the proportion of relatives with prolonged grief (measured with PG-13, score ≥30) 6 months after the death. Analysis was by intention to treat, with the bereaved relatives as the unit of observation. The study is registered with ClinicalTrials.gov, NCT02955992. FINDINGS: Between Feb 23, 2017, and Oct 8, 2019, we enrolled 484 relatives of ICU patients to the intervention group and 391 to the control group. 379 (78%) relatives in the intervention group and 309 (79%) in the control group completed the 6-month interview to measure the primary endpoint. The intervention significantly reduced the number of relatives with prolonged grief symptoms (66 [21%] vs 57 [15%]; p=0·035) and the median PG-13 score was significantly lower in the intervention group than in the control group (19 [IQR 14-26] vs 21 [15-29], mean difference 2·5, 95% CI 1·04-3·95). INTERPRETATION: Among relatives of patients dying in the ICU, a physician-driven, nurse-aided, three-step support strategy significantly reduced prolonged grief symptoms. FUNDING: French Ministry of Health.

Continuous Infusion of High Doses of Cefepime in Intensive Care Unit: Assessment of Steady-State Plasma Level and Incidence on Neurotoxicity.

Continuous infusion (CI) with high doses of cefepime is recommended in the empirical antimicrobial regimen of critically ill patients with suspected Gram-negative sepsis. This study aimed to determine factors associated with cefepime overdosing and the incidence of cefepime-induced neurotoxicity (CIN) in these patients. We performed a retrospective study including all patients receiving cefepime treatment between January 2019 and May 2022. The plasma level of cefepime defining overdosing was over 35 mg/L. Neurotoxicity was defined according to strict criteria and correlated with concomitant steady-state concentration of cefepime. Seventy-eight courses of cefepime treatment were analyzed. The mean cefepime plasma level at steady state was 59.8 ± 29.3 mg/L, and overdosing occurred in 80% of patients. Renal failure and a daily dose > 5 g were independently associated with overdosing. CIN was present in 30% of patients. In multivariate analysis, factors associated with CIN were chronic renal failure and a cefepime plasma concentration ≥ 60 mg/L. CIN was not associated with mortality. Overdosing is frequent in patients receiving high doses of cefepime by CI. Steady-state levels are higher than targeted therapeutic pharmacokinetic/pharmacodynamic objectives. The risk of CIN is important when the plasma concentration is ≥60 mg/L.

Combination Therapy with Aminoglycoside in Bacteremiasdue to ESBL-Producing Enterobacteriaceae in ICU.

OBJECTIVES: Evaluation of the efficacy of empirical aminoglycoside in critically ill patients with bloodstream infections caused by extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-E BSI). METHODS: Patients treated between 2011 and 2018 for ESBL-E BSI in the ICU of six French hospitals were included in a retrospective observational cohort study. The primary endpoint was mortality on day 30. RESULTS: Among 307 patients, 169 (55%) were treated with empirical aminoglycoside. Death rate was 40% (43% with vs. 39% without aminoglycoside, p = 0.55). Factors independently associated with death were age ≥70 years (OR: 2.67; 95% CI: 1.09-6.54, p = 0.03), history of transplantation (OR 5.2; 95% CI: 1.4-19.35, p = 0.01), hospital acquired infection (OR 8.67; 95% CI: 1.74-43.08, p = 0.008), vasoactive drugs >48 h after BSI onset (OR 3.61; 95% CI: 1.62-8.02, p = 0.001), occurrence of acute respiratory distress syndrome (OR 2.42; 95% CI: 1.14-5.16, p = 0.02), or acute renal failure (OR 2.49; 95% CI: 1.14-5.47, p = 0.02). Antibiotherapy appropriateness was more frequent in the aminoglycoside group (91.7% vs. 77%, p = 0.001). Rate of renal impairment was similar in both groups (21% vs. 24%, p = 0.59). CONCLUSIONS: In intensive care unit (ICU) patients with ESBL-E BSI, empirical treatment with aminoglycoside was frequent. It demonstrated no impact on mortality, despite increasing treatment appropriateness.

Lithium: one drug, five complications.

BACKGROUND: Lithium poisoning could trigger multiple complications. We report the case of a lithium poisoning with five complications that are described for the first time together. CASE REPORT: A 60-year-old woman was admitted in our intensive care unit for altered consciousness. Severe lithium intoxication was diagnosed (lithium plasmatic level 8.21 mmol/l) associated with acute oliguric kidney failure. Continuous renal replacement therapy was started immediately. Orotracheal intubation was quickly required because of status epilepticus. Medullary aplasia happened 48 h after the patient was intubated. Infectious and immunological causes were ruled out and lithium poisoning was considered as the most likely etiology. Iterative blood and platelet transfusion were required. Severe polyneuropathy was diagnosed on the 5th day after admission. The patient showed a peripheral tetraparesia and cranial nerve failure while lithium plasmatic level had decreased to a therapeutic level. Conversely, urine output increased and hypernatremia promptly occurred, which led to diabetes insipidus diagnosis. Neuropathy decreased in 72 h and the patient was definitely extubated by the 11th day. Hematologic disturbances decreased and no blood transfusion would be required after the 8th day. The patient would keep sequellas of the poisoning. Thin motricity would still be altered and polyuria would remain. Diffuse alopecia was promptly observed, with no iron deficiency or thyroid disturbance. CONCLUSION: In addition to presenting this case report, we herein discuss the drug causality, the consequences, and the plausible pathophysiology of these five situations.

Impact of combination therapy and early de-escalation on outcome of ventilator-associated pneumonia caused by Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa is a common cause of ventilator-associated pneumonia (VAP). Guidelines recommend dual coverage of P. aeruginosa, but the beneficial effect of combination therapy is controversial. We described antibiotic prescriptions and evaluated the clinical impact of initial combination antibiotic therapy and de-escalation strategy in patients with VAP caused by P. aeruginosa. METHODS: Between 1994 and 2014, all 100 patients with VAP caused by P. aeruginosa in our intensive care unit (ICU) were included in a retrospective cohort study to evaluate the prognostic impact of initial combination antibiotic therapy. RESULTS: Eighty-five patients received initial combination antibiotic therapy and 15 monotherapy. Nine patients received inadequate initial antibiotic therapy. De-escalation was performed in 42 patients. Thirty-nine patients died in the ICU. Factors independently associated with death were SAPS II score [SAPS II ≥40 versus <40: hazard ratio (HR) 2.49, 95% confidence interval (CI) 1.08-5.70, p = 0.03] and septic shock (HR = 4.80, 95% CI = 1.90-12.16, p < 0.01) at onset of VAP. Initial combination antibiotic therapy (HR = 1.97, 95% CI = 0.56-6.93, p = 0.29) and early de-escalation (HR = 0.59, 95% CI = 0.27-1.31, p = 0.19) had no impact on mortality. In multivariate analysis, the risk for inappropriate initial antibiotic therapy was higher in cases with multi-drug resistant P. aeruginosa [odd ratio (OR) = 7.11, 95% CI = 1.42-35.51, p = 0.02], but lower in cases with initial combination antibiotic therapy (OR = 0.12, 95% CI = 0.02-0.63, p = 0.01). CONCLUSION: In our cohort, combination therapy increased the likelihood of appropriate therapy but did not seem to impact on mortality.

Intra-abdominal aortic graft infection: prognostic factors associated with in-hospital mortality.

BACKGROUND: Mortality associated with aortic graft infection is considerable. The gold standard for surgical treatment remains explantation of the graft. However, prognostic factors associated with early mortality due to this surgical procedure are not well-known. METHODS: Retrospective analysis of patients admitted in our center between January 2006 and October 2011 for aortic graft infection. The primary endpoint was in-hospital mortality. A bivariate analysis of characteristics of patients associated with in-hospital outcome was performed. RESULTS: Twenty five evaluable patients were studied. All patients were male. Their mean age was 67 ± 8.4 years. Most of them (92%) had severe underlying diseases. An in situ prosthetic graft replacement, mainly using cryopreserved arterial allografts, was performed in all patients, excepted one who underwent extra-anatomic bypass. Causative organisms were identified in 23 patients (92%). The in-hospital mortality rate was 48%. Among pre-operative characteristics, age ≥ 70 years, creatinine ≥ 12 mg/L and C reactive protein ≥ 50 mg/L were significantly associated with in-hospital mortality. Hospital mortality rates increased with the number of risk factor present on ICU admission, and were 0%, 14.3%, 85.7% and 100% for 0, 1, 2 and 3 factors, respectively. The only intra-operative factor associated with prognosis was an associated intestinal procedure due to aorto-enteric fistula. SAPS II, SOFA score and occurrence of medical or surgical complications were postoperative characteristics associated with in-hospital mortality. CONCLUSION: Morbidity and mortality associated with surgical approach of aortic graft infections are considerable. Age and values of creatinine and C Reactive protein on hospital admission appear as the most important determinant of in hospital mortality. They could be taken into account for guiding the surgical strategy.

Improvement in process of care and outcome in patients requiring intensive care unit admission for community acquired pneumonia.

BACKGROUND: The present study was performed to assess the prognosis of patients admitted to the intensive care unit (ICU) for community acquired pneumonia (CAP) after implementation of new processes of care. METHODS: Two groups of patients with CAP were admitted to a 16-bed multidisciplinary ICU in an urban teaching hospital during two different periods: the years 1995-2000, corresponding to the historical group; and 2005-2010, corresponding to the intervention group. New therapeutic procedures were implemented during the period 2005-2010. These procedures included a sepsis management bundle derived from the Surviving Sepsis Campaign, use of a third-generation cephalosporin and levofloxacin as the initial empirical antimicrobial regimen, and noninvasive mechanical ventilation following extubation. RESULTS: A total of 317 patients were studied: 142 (44.8%) during the historical period and 175 (55.2%) during the intervention period. Sequential Organ Failure Assessment scores were higher in patients in the intervention group (7.2 ± 3.7 vs 6.2 ± 2.8; p=0.008). Mortality changed significantly between the two studied periods, decreasing from 43.6% in the historical group to 30.9% in the intervention group (p < 0.02). A restrictive transfusion strategy, use of systematic postextubation noninvasive mechanical ventilation in patients with severe chronic respiratory or cardiac failure patients, less frequent use of dobutamine and/or epinephrine in patients with sepsis or septic shock, and delivery of a third-generation cephalosporin associated with levofloxacin as empirical antimicrobial therapy were independently associated with better outcomes. CONCLUSION: Positive outcomes in ICU patients with CAP have significantly increased in our ICU in recent years. Many new interventions have contributed to this improvement.

Survival in critically ill patients with acute kidney injury treated with early hemodiafiltration.

PURPOSE: Early renal replacement therapy (RRT) initiation should theoretically influence many physiological disorders related to acute kidney injury (AKI). Currently, there is no consensus about RRT timing in intensive care unit (ICU) patients. METHODS: We performed a retrospective analysis of all critically ill patients who received RRT in our ICU during a 3 year-period. Our goal was to identify mortality risk factors and if RRT initiation timing had an impact on survival. RRT timing was calculated from the moment the patient was classified as having acute kidney injury in the RIFLE classification. RESULTS: A hundred and ten patients received RRT. We identified four independent mortality risk factors: need for mechanical ventilation (OR = 12.82 (1.305 - 125.868, p = 0.0286); RRT initiation timing >16 h (OR = 5.66 (1.954 - 16.351), p = 0.0014); urine output on admission <500 ml/day (OR = 4.52 (1.666 - 12.251), p = 0.003); and SAPS II on admission >70 (OR = 3.45 (1.216 - 9.815), p = 0.02). The RRT initiation =16 h and RRT initiation >16 h groups presented the same baseline characteristics, except for more severe gravity scores and kidney failure in the early RRT group. CONCLUSIONS: Early RRT in ICU patients with acute kidney injury or failure was associated with increased survival.