Changing profile of encephalitis: Results of a 4-year study in France.

CONTEXT: In 2007, we performed a nationwide prospective study to assess the epidemiology of encephalitis in France. We aimed to evaluate epidemiological changes 10years later. METHODS: We performed a 4-year prospective cohort study in France (ENCEIF) from 2016 to 2019. Medical history, comorbidities, as well as clinical, biological, imaging, and demographic data were collected. For the comparison analysis, we selected similar data from adult patients enrolled in the 2007 study. We used Stata statistical software, version 15 (Stata Corp). Indicative variable distributions were compared using Pearson's Chi2 test, and means were compared using Student's t-test for continuous variables. RESULTS: We analyzed 494 cases from 62 hospitals. A causative agent was identified in 65.7% of cases. Viruses represented 81.8% of causative agents, Herpesviridae being the most frequent (63.6%). Arboviruses accounted for 10.8%. Bacteria and parasites were responsible for respectively 14.8% and 1.2% of documented cases. Zoonotic infections represented 21% of cases. When comparing ENCEIF with the 2007 cohort (222 adults patients from 59 hospitals), a higher proportion of etiologies were obtained in 2016-2019 (66% vs. 53%). Between 2007 and 2016-2019, the proportions of Herpes simplex virus and Listeria encephalitis cases remained similar, but the proportion of tuberculosis cases decreased (P=0.0001), while tick-borne encephalitis virus (P=0.01) and VZV cases (P=0.03) increased. In the 2016-2019 study, 32 causative agents were identified, whereas only 17 were identified in the 2007 study. CONCLUSION: Our results emphasize the need to regularly perform such studies to monitor the evolution of infectious encephalitis and to adapt guidelines.

Characteristics and outcome of varicella-zoster virus central nervous system infections in adults.

We conducted an observational retrospective study of all adults hospitalized for documented varicella-zoster virus (VZV) meningitis or encephalitis during years 2000-2015 in one referral centre. Thirty-six patients (21 males, 15 females) were included, with meningitis (n = 21), or meningoencephalitis (n = 15). Median age was 51 years [interquartile range, 35-76], and 6 patients (17%) were immunocompromised. Aciclovir was started in 32 patients (89%), with a median dose of 11 mg/kg/8 h [10-15]. No patient died, but 12 (33%) had neurological sequelae at discharge. Age was the only variable associated with adverse outcome (OR 1.98 [1.17-3.35] per 10-year increment, P = 0.011).

Impact of extracorporeal membrane oxygenation (ECMO) support on piperacillin exposure in septic patients: a case-control study.

OBJECTIVES: To describe the impact of extracorporeal membrane oxygenation (ECMO) devices on piperacillin exposure in ICU patients. METHODS: This observational, prospective, multicentre, case-control study was performed in the ICUs of two tertiary care hospitals in France. ECMO patients with sepsis treated with piperacillin/tazobactam were enrolled. Control patients were matched according to SOFA score and creatinine clearance. The pharmacokinetics of piperacillin were described based on a population pharmacokinetic model, calculating the proportion of time the piperacillin plasma concentration was above 64 mg/L (i.e. 4× MIC breakpoint for Pseudomonas aeruginosa). RESULTS: Forty-two patients were included. Median (IQR) age was 60 years (49-66), SOFA score was 11 (9-14) and creatinine clearance was 47 mL/min (5-95). There was no significant difference in the proportion of time piperacillin concentrations were ≥64 mg/L in patients treated with ECMO and controls during the first administration (P = 0.184) or at steady state (P = 0.309). Following the first administration, 36/42 (86%) patients had trough piperacillin concentrations <64 mg/L. Trough concentrations at steady state were similar in patients with ECMO and controls (P = 0.535). Creatinine clearance ≥40 mL/min was independently associated with piperacillin trough concentration <64 mg/L at steady state [OR = 4.3 (95% CI 1.1-17.7), P = 0.043], while ECMO support was not [OR = 0.5 (95% CI 0.1-2.1), P = 0.378]. CONCLUSIONS: ECMO support has no impact on piperacillin exposure. ICU patients with sepsis are frequently underexposed to piperacillin, which suggests that therapeutic drug monitoring should be strongly recommended for severe infections.

Determinants and consequences of positive valve culture when cardiac surgery is performed during the acute phase of infective endocarditis.

The optimal timing of cardiac surgery in infective endocarditis (IE) remains debated: Early surgery decreases the risk of embolism, and heart failure, but is associated with an increased rate of positive valve culture. To determine the determinants, and the consequences, of positive valve culture when cardiac surgery is performed during the acute phase of IE, we performed a retrospective study of adult patients who underwent cardiac surgery for definite left-sided IE (Duke Criteria), in two referral centres. During the study period (2002-2016), 148 patients fulfilled inclusion criteria. Median age was 65 years [interquartile range, 53-73], male-to-female ratio was 2.9 (110/38). Cardiac surgery was performed after 14 days [5-26] of appropriate antibiotics. Valve cultures returned positive in 46 cases (31.1%). Factors independently associated with positive valve culture were vegetation size ≥ 10 mm (OR 2.83 [1.16-6.89], P = 0.022) and < 14 days of appropriate antibacterial treatment before surgery (OR 4.68 [2.04-10.7], P < 0.001). Positive valve culture was associated with increased risk of postoperative acute respiratory distress syndrome (37.0% vs. 15.7%, P = 0.008) but was associated neither with an increased risk of postoperative relapse nor with the need for additional cardiac surgery. Duration of appropriate antibacterial treatment and vegetation size are independently predictive of positive valve culture in patients operated during the acute phase of IE. Positive valve culture is associated with increased risk of postoperative acute respiratory distress syndrome.

Crimean-Congo hemorrhagic fever: An update.

Crimean-Congo hemorrhagic fever (CCHF) is a severe form of hemorrhagic fever caused by a virus of the genus Nairovirus. The amplifying hosts are various mammal species that remain asymptomatic. Humans are infected by tick bites or contact with animal blood. CCHF has a broad geographic distribution and is endemic in Africa, Asia (in particular the Middle East) and South East Europe. This area has expanded in recent years with two indigenous cases reported in Spain in 2016 and 2018. The incubation period is short with the onset of symptoms in generally less than a week. The initial symptoms are common to other infectious syndromes with fever, headache, myalgia and gastrointestinal symptoms. The hemorrhagic syndrome occurs during a second phase with sometimes major bleeding in and from the mucous membranes and the skin. Strict barrier precautionary measures are required to prevent secondary and nosocomial spread. CCHF may be documented by PCR detection of the virus genome during the first days after the onset of illness, and then by serological testing for IgM antibodies as from the 2nd week after infection. Patient management is mainly based on supportive care. Despite a few encouraging retrospective reports, there is no confirmed evidence that supports the use of ribavirin for curative treatment. Nevertheless, the World Health Organization continues to recommend the use of ribavirin to treat CCHF, considering the limited medical risk related to short-term treatment. The prescription of ribavirin should however be encouraged post-exposure for medical professionals, to prevent secondary infection.

Infectious encephalitis: Management without etiological diagnosis 48hours after onset.

INTRODUCTION: The etiological diagnosis of infectious encephalitis is often not established 48hours after onset. We aimed to review existing literature data before providing management guidelines. METHOD: We performed a literature search on PubMed using filters such as "since 01/01/2000", "human", "adults", "English or French", and "clinical trial/review/guidelines". We also used the Mesh search terms "encephalitis/therapy" and "encephalitis/diagnosis". RESULTS: With Mesh search terms "encephalitis/therapy" and "encephalitis/diagnosis", we retrieved 223 and 258 articles, respectively. With search terms "encephalitis and corticosteroid", we identified 38 articles, and with "encephalitis and doxycycline" without the above-mentioned filters we identified 85 articles. A total of 210 articles were included in the analysis. DISCUSSION: Etiological investigations must focus on recent travels, animal exposures, age, immunodeficiency, neurological damage characteristics, and potential extra-neurological signs. The interest of a diagnosis of encephalitis for which there is no specific treatment is also to discontinue any empirical treatments initially prescribed. Physicians must consider and search for autoimmune encephalitis.

[Pneumocystosis in non-HIV-infected immunocompromised patients]. / Pneumocystose chez les patients immunodéprimés non infectés par le VIH.

Pneumocystis jiroveci (formerly P. carinii) is an opportunistic fungus responsible for pneumonia in immunocompromised patients. Pneumocystosis in non-HIV-infected patients differs from AIDS-associated pneumocystosis in mostly two aspects: diagnosis is more difficult, and prognosis is worse. Hence, efforts should be made to target immunocompromised patients at higher risk of pneumocystosis, so that they are prescribed long-term, low-dose, trimethoprime-sulfamethoxazole, highly effective for pneumocystosis prophylaxis. Patients at highest risk include those with medium and small vessels vasculitis, lymphoproliferative B disorders (chronic or acute lymphocytic leukaemia, non-Hodgkin lymphoma), and solid cancer on long-term corticosteroids. Conversely, widespread use of prophylaxis in all patients carrier of inflammatory diseases on long-term corticosteroids is not warranted. The management of pneumocystosis in non-AIDS immunocompromised patients follows the rules established for AIDS patients. The diagnosis relies on the detection of P. jiroveci cyst on respiratory samples, while PCR does not reliably discriminate infection from colonization, in 2015. High-doses trimethoprim-sulfamethoxazole is, by far, the treatment of choice. The benefit of adjuvant corticosteroid therapy for hypoxic patients, well documented in AIDS patients, has a much lower level of evidence in non-HIV-infected patients, most of them being already on corticosteroid by the time of pneumocystosis diagnosis anyway. However, based on its striking impact on morbi-mortality in AIDS patients, adjuvant corticosteroid is recommended in hypoxic, non-HIV-infected patients with pneumocystosis by many experts and scientific societies.

Human herpes virus co-infection is associated with mortality in HIV-negative patients with Pneumocystis jirovecii pneumonia.

The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori-Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim-sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p < 0.0001), shock (p < 0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p = 0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5-121.9], p < 0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.

Distinctive features between community-acquired pneumonia (CAP) due to Chlamydophila psittaci and CAP due to Legionella pneumophila admitted to the intensive care unit (ICU).

The spectrum of community-acquired pneumonia (CAP) due to Chlamydophila psittaci ranges from mild, self-limited CAP, to acute respiratory failure. We performed a retrospective study of 13 consecutive patients with CAP due to C. psittaci and 51 patients with legionellosis admitted in one intensive care unit (ICU) (1993-2011). As compared to patients with legionellosis, patients with psittacosis were younger (median age 48 [38-59] vs. 60 [50-71] years, p = 0.007), less frequently smokers (38 vs. 79 %, p < 0.001), with less chronic disease (15 vs. 57 %, p = 0.02), and longer duration of symptoms before admission (median 6 [5-13] vs. 5 [3-7] days, p = 0.038). They presented with lower Simplified Acute Physiology Score II (median 28 [19-38] vs. 39 [28-46], p = 0.04) and less extensive infiltrates on chest X-rays (median 2 [1-3] vs. 3 [3-4] lobes, p = 0.007). Bird exposure was mentioned in 100 % of psittacosis cases, as compared to 5.9 % of legionellosis cases (p < 0.0001). Extrapulmonary manifestations, biological features, and mortality (15.4 vs. 21.6 %, p = 0.62) were similar in both groups. In conclusion, severe psittacosis shares many features with severe legionellosis, including extrapulmonary manifestations, biological features, and outcome. Psittacosis is an important differential diagnosis for legionellosis, especially in cases of bird exposure, younger age, and more limited disease progression over the initial few days.