Variable impact of an antimicrobial stewardship programme in three intensive care units: time-series analysis of 2012-2017 surveillance data.

BACKGROUND: Preprescription authorization (PPA) and postprescription review with feedback (PPRF) were successively implemented in 2012 and 2016 in our 1500-bed hospital. AIM: The impact of PPA and PPRF on carbapenems use and resistance levels of Pseudomonas aeruginosa was assessed in three intensive care units (ICUs). METHODS: Carbapenems use (in DDDs/1000 occupied bed-days) and resistance of P. aeruginosa (percentage of non-susceptible (I+R) isolates to imipenem and/or meropenem) were analysed using a controlled interrupted time-series method. Two periods were compared: 2012-2015 (PPA) and 2016-2017 (PPA+PPRF). Models were adjusted on the annual incidence of extended-spectrum ß-lactamase-producing enterobacteriacae. FINDINGS: Carbapenem use was stable over the PPA period in all ICUs, with a significant change of slope over the PPA+PPRF period only in ICU1 (ß2 = -12.8, 95% confidence interval (CI) = -19.5 to -6.1). There was a switch from imipenem to meropenem during the PPA period in all three units. Resistances of P. aeruginosa were stable over the study period in ICU1 and ICU2, and significantly decreased over the PPA+PPRF period in ICU3 (ß2 = -0.18, CI = -0.3 to -0.03). CONCLUSION: In real-life conditions and with the same antimicrobial stewardship programme (AMSP) led by a single team, the impact of PPRF was heterogeneous between ICUs. Factors driving the impact of AMSPs should be further assessed in comparable settings through real-life data, to target where they could prove cost-effective.

Diabetic ketoacidosis, a common disease with life-threatening pitfalls.

Diabetic ketoacidosis (DKA) is a common cause for admission in Emergency Department. Its treatment is well defined. Nevertheless, in some cases, type I diabetes combines with auto-immune polyendocrine syndrome, which can carry life-threatening consequences. Here we report the case of a young man with inaugural DKA who exhibited ventricular fibrillation and cardiac arrest due to significant hypokalaemia, following undiagnosed thyrotoxicosis with periodic paralysis.

Major traumatic complications after out-of-hospital cardiac arrest: Insights from the Parisian registry.

AIM: Due to collapse and cardiopulmonary resuscitation (CPR) maneuvers, major traumatic injuries may complicate the course of resuscitation for out-of-hospital cardiac arrest patients (OHCA). Our goals were to assess the prevalence of these injuries, to describe their characteristics and to identify predictive factors. METHODS: We conducted an observational study over a 9-year period (2007-2015) in a French cardiac arrest (CA) center. All non-traumatic OHCA patients admitted alive in the ICU were studied. Major injuries identified were ranked using a functional two-level scale of severity (life-threatening or consequential) and were classified as CPR-related injuries or collapse-related injuries, depending of the predominant mechanism. Factors associated with occurrence of a CPR-related injury and ICU survival were identified using multivariable logistic regression. RESULTS: A major traumatic injury following OHCA was observed in 91/1310 patients (6.9%, 95%CI: 5.6, 8.3%), and was classified as a life-threatening injury in 36% of cases. The traumatic injury was considered as contributing to the death in 19 (21%) cases. Injuries were related to CPR maneuvers in 65 patients (5.0%, (95%CI: 3.8, 6.1%)). In multivariable analysis, age [OR 1.02; 95%CI (1.00, 1.04); p = 0.01], male gender [OR 0.53; 95%CI (0.31, 0.91); p = 0.02] and CA occurring at home [OR 0.54; 95%CI (0.31, 0.92); p = 0.02] were significantly associated with the occurrence of a CPR-related injury. CPR-related injuries were not associated with the ICU survival [OR 0.69; 95%CI (0.36, 1.33); p = 0.27]. CONCLUSIONS: Major traumatic injuries are common after cardiopulmonary resuscitation. Further studies are necessary to evaluate the interest of a systematic traumatic check-up in resuscitated OHCA patients in order to detect these injuries.

Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units.

OBJECTIVE: The clinical characteristics and prognosis of patients treated for Candida peritonitis (CP) were compared according to the type of systemic antifungal therapy (SAT), empiric (EAF) or targeted (TAF) therapies, and the final diagnosis of infection. METHODS: Patients in intensive care units (ICU) treated for CP were selected among the AmarCAND2 cohort, to compare patients receiving EAF for unconfirmed suspicion of CP (EAF/nonCP), to those with suspected secondarily confirmed CP (EAF/CP), or with primarily proven CP receiving TAF. RESULTS: In all, 279 patients were evaluated (43.4% EAF/nonCP, 29.7% EAF/CP and 25.8% TAF patients). At SAT initiation, the severity of illness was similar among EAF/nonCP and EAF/CP patients, lower among TAF patients (median Simplified Acute Physiology Score II (SAPS II) 49 and 51 versus 35, respectively; p 0.001). Candida albicans was involved in 67%, Candida glabrata in 15.6%. All strains were susceptible to echinocandin; 84% to fluconazole. Echinocandin was administered to 51.2% EAF/nonCP, 49% EAF/CP and 40% TAF patients. At day 28, 72%, 76% and 75% of EAF/nonCP, EAF/CP and TAF patients, respectively, were alive. An increased mortality was observed in patients with a Sequential Organ Failure Assessment (SOFA) score <7 if SAT was delayed by ≥6 days (p 0.04). Healthcare-associated CP (OR 3.82, 95% CI 1.52-9.64, p 0.004), SOFA ≥8 at ICU admission (OR 2.61, 95% CI 1.08-6.34; p 0.03), and SAPS II ≥45 at SAT initiation (OR 5.08, 95% CI 1.04-12.67; p 0.001) impacted the 28-day mortality. CONCLUSIONS: In summary, only 56.6% of ICU patients receiving SAT had CP. Most strains were susceptible to SAT. A similar 28-day mortality rate was observed among groups; the late administration of SAT significantly worsened the prognosis of patients with less severe CP.

Hypoxic hepatitis after out-of-hospital cardiac arrest: Incidence, determinants and prognosis.

AIM: Hypoxic hepatitis (HH) may complicate the course of resuscitated out-of-hospital cardiac arrest (OHCA) patients admitted in intensive care unit (ICU). Aims of this study were to assess the prevalence of HH, and to describe the factors associated with HH occurrence and outcome. METHODS: We conducted an observational study over a 6-year period (2009-2014) in a cardiac arrest center. All non-traumatic OHCA patients admitted in the ICU after return of spontaneous circulation (ROSC) and who survived more than 24h were included. HH was defined as an elevation of alanine aminotransferase over 20 times the upper limit of normal during the first 72h after OHCA. Factors associated with HH and ICU mortality were picked up by multivariate logistic regression. RESULTS: Among the 632 OHCA patients included in the study, HH was observed in 72 patients (11.4% (95% CI: 9.0%, 14.1%)). In multivariate analysis, time from collapse to ROSC [OR 1.02 per additional minute; 95% CI (1.00, 1.04); p=0.01], male gender [OR 0.53; 95% CI (0.29, 0.95); p=0.03] and initial shockable rhythm [OR 0.35; 95% CI (0.19, 0.65); p<0.01] were associated with HH occurrence. After adjustment for confounding factors, HH was associated with ICU mortality [OR 4.39; 95% CI (1.71, 11.26); p<0.01] and this association persisted even if occurrence of a post-CA shock was considered in the statistical model [OR 3.63; 95% CI (1.39, 9.48); p=0.01]. CONCLUSIONS: HH is not a rare complication after OHCA. This complication is mainly triggered by the duration of resuscitation and is associated with increased ICU mortality.

Ilio-psoas hematoma in the intensive care unit: a multicentric study.

BACKGROUND: Clinical features and outcomes of patients with spontaneous ilio-psoas hematoma (IPH) in intensive care units (ICUs) are poorly documented. The objectives of this study were to determine epidemiological, clinical, biological and management characteristics of ICU patients with IPH. METHODS: We conducted a retrospective multicentric study in three French ICUs from January 2006 to December 2014. We included IPH diagnosed both at admission and during ICU stay. Surgery and embolization were available 24 h a day for each center, and therapeutic decisions were undertaken after pluridisciplinary discussion. All IPHs were diagnosed using CT scan. RESULTS: During this period, we identified 3.01 cases/1000 admissions. The mortality rate of the 77 included patients was 30 %. In multivariate analysis, we observed that mortality was independently associated with SAPS II (OR 1.1, 95 % CI [1.013-1.195], p = 0.02) and with the presence of hemorrhagic shock (OR 67.1, 95 % CI [2.6-1691], p = 0.01). We found IPH was related to anticoagulation therapy in 56 cases (72 %), with guideline-concordant reversal performed in 33 % of patients. We did not found any association between anticoagulant therapy type and outcome. CONCLUSION: We found IPH is an infrequent disease, with a high mortality rate of 30 %, mostly related to anticoagulation therapy and usually affecting the elderly. Management of anticoagulation-related IPH includes a high rate of no reversal of 38 %.

Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

BACKGROUND: Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. OBJECTIVES: To assess the predictive value of cTnI in patients with TTP for death or refractoriness. PATIENTS/METHODS: The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. RESULTS: Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 µg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 µg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). CONCLUSIONS: A CTnI level of > 0.25 µg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP.

Markers of intestinal injury are associated with endotoxemia in successfully resuscitated patients.

AIMS: Gut dysfunction is suspected to play a major role in the pathophysiology of post-resuscitation disease through an increase in intestinal permeability and endotoxin release. However this dysfunction often remains occult and is poorly investigated. The aim of this pilot study was to explore intestinal failure biomarkers in post-cardiac arrest patients and to correlate them with endotoxemia. METHODS: Following resuscitation after cardiac arrest, 21 patients were prospectively studied. Urinary intestinal fatty acid-binding protein (IFABP), which marks intestinal permeability, plasma citrulline, which reflects the functional enterocyte mass, and whole blood endotoxin were measured at admission, days 1-3 and 6. We explored the kinetics of release and the relationship between IFABP, citrulline and endotoxin values. RESULTS: IFABP was extremely high at admission and normalized at D3 (6668 pg/mL vs 39 pg/mL, p=0.01). Lowest median of citrulline (N=20-40 µmol/L) was attained at D2 (11 µmol/L at D2 vs 24 µmol/L at admission, p=0.01) and tended to normalize at D6 (21 µmol/L). During ICU stay, 86% of patients presented a detectable endotoxemia. Highest endotoxin level was positively correlated with highest IFABP level (R(2)=0.31, p=0.01) and was inversely correlated with lowest plasma citrulline levels (R(2)=0.55, p<0.001). Endotoxin levels increased between admission and D2 in patients with post-resuscitation shock, whereas it decreases in patients with no shock (median +0.33 EU vs -0.19 EU, p=0.03). Highest endotoxin level was positively correlated with D3 SOFA score (R(2)=0.45, p=0.004). CONCLUSION: Biomarkers of intestinal injury are altered after cardiac arrest and are associated with endotoxemia. This could worsen post-resuscitation shock and organ failure.

Necrotizing fasciitis and septic shock related to the uncommon gram-negative pathogen Sphingobacterium multivorum.

We report the first case of necrotizing fasciitis due to the uncommon Gram-negative pathogen Sphingobacterium multivorum in an immunocompromised patient, who presented with septic shock. This case adds necrotizing fasciitis to the spectrum of S. multivorum-related infections and highlights the emergence of Gram-negative bacteria in severe soft tissue infections.

Profound and persistent decrease of circulating dendritic cells is associated with ICU-acquired infection in patients with septic shock.

PURPOSE: Septic shock induces a decrease in dendritic cells (DCs) that may contribute to sepsis-induced immunosuppression. We analyzed the time course of circulating DCs in patients with septic shock and its relation to susceptibility to intensive care unit (ICU)-acquired infections. METHODS: We enrolled adult patients with septic shock (n = 43), non-septic shock (n = 29), and with sepsis without organ dysfunction (n = 16). Healthy controls (n = 16) served as reference. Blood samples were drawn on the day of shock (day 1), then after 3 and 7 days. Myeloid (mDC) and plasmacytoid (pDC) DCs were counted by flow cytometry. Cell surface HLA-DR expression was analyzed in both DC subsets. RESULTS: At day 1, median mDC and pDC counts were dramatically lower in septic shock patients as compared to healthy controls (respectively, 835 mDCs and 178 pDCs/ml vs. 19,342 mDCs and 6,169 pDCs/ml; P < 0.0001) but also to non-septic shock and sepsis patients (P < 0.0001). HLA-DR expression was decreased in both mDCs and pDCS within the septic shock group as compared to healthy controls. DC depletion was sustained for at least 7 days in septic shock patients. Among them, 10/43 developed ICU-acquired infections after a median of 9 [7.5-11] days. At day 7, mDC counts increased in patients devoid of secondary infections, whereas they remained low in those who subsequently developed ICU-acquired infections. CONCLUSION: Septic shock is associated with profound and sustained depletion of circulating DCs. The persistence of low mDC counts is associated with the development of ICU-acquired infections, suggesting that DC depletion is a functional feature of sepsis-induced immunosuppression.

[Management of acute and severe complications in adults with cystic fibrosis]. / Prise en charge des complications aiguës sévères chez l'adulte mucoviscidosique.

The natural history of cystic fibrosis (CF) may be associated both with acute respiratory complications (respiratory exacerbations, haemoptysis, pneumothorax) and with non-respiratory complications (distal intestinal obstruction syndrome, dehydration) that may result in hospitalizations. The aim of this article is to describe the main therapeutic approaches that are adopted in the management of acute complications occurring in CF adults, and to discuss indications for admission of these patients to intensive care units. Adult CF patients admitted to intensive care unit often benefit from antibiotic courses adapted to their chronic bronchial infection, especially when the hospitalization is related to respiratory disease (including haemoptysis and pneumothorax). Nutritional support, including hypercaloric diet, control of hyperglycemia and pancreatic enzyme supplementation is warranted. The recommended therapy for major haemoptysis is bronchial artery embolization. Patient with significant pneumothorax should have a chest tube inserted, while the treatment of distal intestinal obstruction syndrome will most often be medical. In case of respiratory failure, non-invasive ventilation is the preferred mode of ventilatory support because invasive ventilation is associated with poor outcomes. Therapeutic options should always have been discussed between the patient, family members and the CF medical team to allow for informed decision making.

A multicentre study of antifungal strategies and outcome of Candida spp. peritonitis in intensive-care units.

Information on the species causing Candida peritonitis, their in vitro susceptibility, antifungal strategies in this setting and patient outcome is still scarce. AmarCand was a prospective, non-interventional study in 271 adult intensive-care unit (ICU) patients with proven invasive Candida infection who received systemic antifungal therapy (France, 2005-2006). Of these ICU patients, 93 (median age 65 years, simplified acute physiology score II 52) had Candida peritonitis, including 73 nosocomial peritonitis, 53 concomitant bacterial peritoneal infections and 26 candidaemias. Candida species were C. albicans (n = 63/108 isolates, 58%), C. glabrata (n = 22, 20%), C. krusei (n = 9), C. kefyr (n = 5), C. parapsilosis (n = 3), C. tropicalis (n = 3), C. ciferii (n = 2) and C. lusitaniae (n = 1). Of tested isolates, 28% were fluconazole-resistant or susceptible dose-dependent (C. albicans 3/32, C. glabrata 9/14, C. krusei 4/4). Empiric antifungal treatment was started 1 day (median) after peritonitis diagnosis, with fluconazole (n = 2 patients), caspofungin (n = 12), voriconazole (n = 3), amphotericin B (n = 2), or a combination (n = 4). Following susceptibility testing, empiric antifungal treatment was judged inadequate in 9/45 (20%) patients and modified in 30 patients (fluconazole was replaced by caspofungin (n = 14) or voriconazole (n = 4)). Mortality in ICU was 38% (35/93) and was not influenced by type of Candida species, fluconazole susceptibility, time to treatment, candidaemia, nosocomial acquisition, or concomitant bacterial infection. No specific factors for death were identified. In summary, a high proportion of fluconazole-resistant or susceptible dose-dependent strains was cultured. These results confirm the high mortality rates of Candida peritonitis and plead for additional investigation in this population. Antifungal treatment for severe cases of Candida peritonitis in ICU patients remains the standard care.

Multifocal community-acquired necrotizing fasciitis caused by a Panton-Valentine leukocidin-producing methicillin-sensitive Staphylococcus aureus.

We describe a rare case of multifocal necrotizing fasciitis (NF) complicating a single vaccine injection. Injection of hepatitis B vaccine of a 16-year-old immunocompetent woman developed into rapidly spreading multifocal NF of the right arm and the thighs, with septic shock. Treatment with antimicrobial therapy and surgical debridements allowed amputation to be avoided with a favourable outcome. The etiological agent was a methicillin-sensitive Staphylococcus aureus (MSSA) isolate harboring the Panton-Valentine leukocidin (PVL) and five enterotoxins. PVL has recently been reported in large series of methicillin-resistant SA cases and has been associated with necrotizing infections. Some strains of MSSA could harbor PVL and enterotoxins. PCR investigation is not frequent but could improve the understanding of the mechanisms of lesions. This case is in keeping with the increasing incidence of MSSA harboring PVL and enterotoxins with multifocal dissemination NF and emphasizes the necessary precautions for skin decontamination before vaccine injection.

[Invasive candidiasis in ICU: analysis of antifungal treatments in the French study AmarCand]. / Candidoses invasives en réanimation: analyse des traitements antifongiques au cours de l'enquête française AmarCand.

OBJECTIVE: Comparison of treatments initiated during invasive candidiasis in intensive care units with current French guidelines. STUDY DESIGN: Prospective, observational, French multicenter study (October 2005-May 2006). PATIENTS AND METHODS: Selection of patients with Candida species identification and in vitro antifungal susceptibility determination. The empiric treatments instituted before the microbiologic documentation of infection and the curative treatments instituted after identification of the causative Candida and determination of its susceptibility were collected and compared with treatments proposed by the French clinical practice guidelines (2004) for the management of patients with invasive candidiasis. RESULTS: One hundred and eighty-six patients were studied. Invasive candidiasis was due to fluconazole-resistant or susceptible-dose dependent Candida in 18.3% of patients, without any significant influence of a previous treatment with azoles. Empiric and curative treatments were both in accordance with recommendations for 47% of patients. Recommendations were mainly not respected when proposed therapy was amphotericin B that disappeared from therapeutics used in ICU. Finally, 16.9% of episodes of invasive candidiasis, for which fluconazole was the recommended treatment, were due to fluconazole-resistant or susceptible-dose dependent Candida. CONCLUSION: The support of French ICU physicians to current French guidelines was observed in 47% of cases. The infrequent use of amphotericin B must be emphasized. The nonnegligible incidence of fluconazole-resistant or susceptible-dose dependent Candida sp., particularly in patients without any prior exposition to azole agents, and the inability to predict this resistance should lead to propose a revision of 2004 guidelines.

[Endothelial progenitor cells: new biomarkers and potential therapy in intensive care]. / Progéniteurs endothéliaux circulants: nouveaux biomarqueurs et thérapeutique du futur en réanimation.

One of the most important breakthroughs in the field of vascular biology in the last decade was the discovery of endothelial progenitor cells (EPCs). These angiogenic cells dwell in bone marrow, and may be found in the general circulation spontaneously or in response to various stimuli such as ischemia, growth factor, pro-inflammatory cytokines, and drugs such as statins. There is growing evidence that EPCs can differentiate into mature endothelial cells and facilitate endothelial repair and angiogenesis in vivo. In recent years, consistent publications have shown that EPCs provide both diagnostic and prognostic information with respect to cardiovascular diseases, acute lung injury, and sepsis. Activation of EPCs from the bone marrow or injection of these cells may be used as a therapeutic option for the treatment of ischemic cardiovascular diseases.

[Pneumonia with septicemia caused by Pasteurella multocida in an immunocompetent patient]. / Pneumonie à Pasteurella multocida compliquée de choc septique chez un patient non immunodéprimé

Pneumonia with septicemia caused by Pasteurella multocida was diagnosed in an immunocompetent patient exposed to a dog. This case is remarkable by two aspects: first the absence of visible cutaneous lesion, and second the localization and severity of the infection caused by P. multocida even though the patient was immunocompetent. P. multocida can cause respiratory and systemic infection, and it is a possible diagnosis in case of exposure to animals, even without history of bite or scratch. Furthermore, severe infections caused by this pathogen can occur in immunocompetent patients, so that the implication of specific host factors in the severity of the disease can be suspected. Genetic features could be one of these.

Changes in aortic blood flow induced by passive leg raising predict fluid responsiveness in critically ill patients.

INTRODUCTION: Esophageal Doppler provides a continuous and non-invasive estimate of descending aortic blood flow (ABF) and corrected left ventricular ejection time (LVETc). Considering passive leg raising (PLR) as a reversible volume expansion (VE), we compared the relative abilities of PLR-induced ABF variations, LVETc and respiratory pulsed pressure variations (DeltaPP) to predict fluid responsiveness. METHODS: We studied 22 critically ill patients in acute circulatory failure in the supine position, during PLR, back to the supine position and after two consecutive VEs of 250 ml of saline. Responders were defined by an increase in ABF induced by 500 ml VE of more than 15%. RESULTS: Ten patients were responders and 12 were non-responders. In responders, the increase in ABF induced by PLR was similar to that induced by a 250 ml VE (16% versus 20%; p = 0.15). A PLR-induced increase in ABF of more than 8% predicted fluid responsiveness with a sensitivity of 90% and a specificity of 83%. Corresponding positive and negative predictive values (PPV and NPV, respectively) were 82% and 91%, respectively. A DeltaPP threshold value of 12% predicted fluid responsiveness with a sensitivity of 70% and a specificity of 92%. Corresponding PPV and NPV were 87% and 78%, respectively. A LVETc of 245 ms or less predicted fluid responsiveness with a sensitivity of 70%, and a specificity of 67%. Corresponding PPV and NPV were 60% and 66%, respectively. CONCLUSION: The PLR-induced increase in ABF and a DeltaPP of more than 12% offer similar predictive values in predicting fluid responsiveness. An isolated basal LVETc value is not a reliable criterion for predicting response to fluid loading.