Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

OBJECTIVETo assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen.

Background

Intestinal flora contains a reservoir of Gram-negative bacilli (GNB) resistant to cephalosporins, which are potentially pathogenic for intensive care unit (ICU) patients; this has led to increasing use of carbapenems. The emergence of carbapenem resistance is a major concern for ICUs. Therefore, in this study, we aimed to assess the intestinal carriage of imipenem-resistant GNB (IR-GNB) in intensive care patients. For 6 months, 523 consecutive ICU patients were screened for rectal IR-GNB colonization upon admission and weekly thereafter. The phenotypes and genotypes of all isolates were determined, and a case control study was performed to identify risk factors for colonization. The IR-GNB colonization rate increased regularly from 5.6% after 1 week to 58.6% after 6 weeks in the ICU. In all, 56 IR-GNB strains were collected from 50 patients: 36 Pseudomonas aeruginosa strains, 12 Stenotrophomonas maltophilia strains, 6 Enterobacteriaceae strains, and 2 Acinetobacter baumannii strains. In P. aeruginosa, imipenem resistance was due to chromosomally encoded resistance (32 strains) or carbapenemase production (4 strains). In the Enterobacteriaceae strains, resistance was due to AmpC cephalosporinase and/or extended-spectrum ␤-lactamase production with porin loss. Genomic comparison showed that the strains were highly diverse, with 8 exceptions (4 VIM-2 carbapenemaseproducing P. aeruginosa strains, 2 Klebsiella pneumoniae strains, and 2 S. maltophilia strains). The main risk factor for IR-GNB colonization was prior imipenem exposure. The odds ratio for colonization was already as high as 5.9 (95% confidence interval [95% CI], 1.5 to 25.7) after 1 to 3 days of exposure and increased to 7.8 (95% CI, 2.4 to 29.8) thereafter. In conclusion, even brief exposure to imipenem is a major risk factor for IR-GNB carriage.

Faecal microbiota transplantation Neomycin a b s t r a c t Objectives: Intestinal carriage with extended spectrum b-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE. Methods: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 Â 10 6 IU 4Â/day; neomycin sulphate 500 mg 4Â/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35e48 days after randomization (V4). ClinicalTrials.gov NCT02472600. The trial was funded by the European Commission (FP7). Results: Thirty-nine patients (G ¼ 14; P ¼ 16; U ¼ 7; T ¼ 2) colonized by ESBL-E (n ¼ 36) and/or CPE (n ¼ 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4 e6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT).

Our findings highlight an increased survival in teaching centres with high-volume NSTI procedures. If confirmed in other settings, these findings reinforce the importance of expertise in early diagnosis and management of this condition.

No abstract

An increase in amoxicillin-induced crystal nephropathy (AICN) incidence has been recently suggested. The aims of this study were to investigate the trend of AICN incidence through Paris' regional centers of pharmacovigilance (Paris RCPVs) and better describe this rare adverse drug reaction. Forty-five AICN cases were identified between 1985 and 2016. All cases, except one, were reported since 2010. Amoxicillin (AMX) was administered intravenously (65 [interquartile range {IQR}, 43 to 110] mg/kg of body weight/day) in all patients, either for treating infection ( = 15) or as surgical prophylaxis ( = 30). Delay between AMX administration and AICN onset was 1 (IQR, 1 to 3) day; 30, 4, and 11 patients developed KDIGO stage 1, 2, and 3 acute kidney injury, respectively. Delay between AICN onset and kidney function recovery was 4 (IQR, 2 to 6) days. Precipitating factors were identified in only one-third of cases. Twelve patients required intensive care unit admission, and 8 needed renal replacement therapy. Neither chronic kidney disease nor death was observed. We confirmed the recent and dramatic increase of AICN in the Paris RCPVs since 2010. The absence of precipitating factors in the majority of cases and the onset of AICN in apparent routine indications, such as surgical prophylaxis, are alarming and justify a high vigilance from all AMX prescribers.