Metagenomics revolutionized the understanding of the relations among the human microbiome, health and diseases, but generated a countless number of sequences that have not been assigned to a known microorganism¹. The pure culture of prokaryotes, neglected in recent decades, remains essential to elucidating the role of these organisms². We recently introduced microbial culturomics, a culturing approach that uses multiple culture conditions and matrix-assisted laser desorption/ionization–time of flight and 16S rRNA for identification². Here, we have selected the best culture conditions to increase the number of studied samples and have applied new protocols (fresh-sample inoculation; detection of microcolonies and specific cultures of Proteobacteria and microaerophilic and halophilic prokaryotes) to address the weaknesses of the previous studies^3–5. We identified 1,057 prokaryotic species, thereby adding 531 species to the human gut repertoire: 146 bacteria known in humans but not in the gut, 187 bacteria and 1 archaea not previously isolated in humans, and 197 potentially new species. Genome sequencing was performed on the new species. By comparing the results of the metagenomic and culturomic analyses, we show that the use of culturomics allows the culture of organisms corresponding to sequences previously not assigned. Altogether, culturomics doubles the number of species isolated at least once from the human gut.

The increasing prevalence of hospital- and community-acquired infections caused by multidrug-resistant bacterial pathogens is limiting the options for effective antibiotic therapy. Moreover, this alarming spread of antimicrobial resistance has not been paralleled by the development of novel antimicrobials. Resistance to the scarce new antibiotics is also emerging. In this context, the rational use of older antibiotics could represent an alternative for the treatment of multidrug-resistant bacterial pathogens. This strategy would help to optimize the armamentarium of antibiotics so as to preserve the effectiveness of new antibiotics and avoid the prescription of drugs known to favor the spread of resistance (i.e., quinolones). Furthermore, from a global economic perspective, this strategy could be useful in public health, given that several of these cheapest “forgotten” antibiotics are not available in many countries. We will review here the successful treatment of multidrug-resistant bacterial infections with old antibiotics and discuss their place in current practice.

In our institute in Marseille, France, we initiated early and massive screening for coronavirus disease 2019 (COVID-19). Hospitalization and early treatment with hydroxychloroquine and azithromycin (HCQ-AZ) was proposed for the positive cases. We retrospectively report the clinical management of 3,737 screened patients, including 3,119 (83.5%) treated with HCQ-AZ (200 mg of oral HCQ, three times daily for ten days and 500 mg of oral AZ on day 1 followed by 250 mg daily for the next four days, respectively) for at least three days and 618 (16.5%) patients treated with other regimen (“others”). Outcomes were death, transfer to the intensive care unit (ICU), ≥10 days of hospitalization and viral shedding. The patients’ mean age was 45 (sd 17) years, 45% were male, and the case fatality rate was 0.9%. We performed 2,065 low-dose computed tomography (CT) scans highlighting lung lesions in 592 of the 991 (59.7%) patients with minimal clinical symptoms (NEWS score = 0). A discrepancy between spontaneous dyspnoea, hypoxemia and lung lesions was observed. Clinical factors (age, comorbidities, NEWS-2 score), biological factors (lymphocytopenia; eosinopenia; decrease in blood zinc; and increase in D-dimers, lactate dehydrogenase, creatinine phosphokinase, troponin and C-reactive protein) and moderate and severe lesions detected in low-dose CT scans were associated with poor clinical outcome. Treatment with HCQ-AZ was associated with a decreased risk of transfer to ICU or death (Hazard ratio (HR) 0.18 0.11–0.27), decreased risk of hospitalization ≥10 days (odds ratios 95% CI 0.38 0.27–0.54) and shorter duration of viral shedding (time to negative PCR: HR 1.29 1.17–1.42). QTc prolongation (>60 ms) was observed in 25 patients (0.67%) leading to the cessation of treatment in 12 cases including 3 cases with QTc> 500 ms. No cases of torsade de pointe or sudden death were observed. Although this is a retrospective analysis, results suggest that early diagnosis, early isolation and early treatment of COVID-19 patients, with at least 3 days of HCQ-AZ lead to a significantly better clinical outcome and a faster viral load reduction than other treatments.

Severe Clostridium difficile infections (CDI) are associated with a high mortality rate despite medical and/or surgical treatment. Faecal microbiota transplantation (FMT) prevents recurrences, but its effect on survival has been shown only in O27 ribotype CDI patients. Here, we investigated whether early FMT could improve survival in hospitalized CDI patients, particularly those with severe infection. We performed a retrospective cohort study between May 2013 and April 2016 at the infectious diseases department of the North University Hospital of Marseille, France. Patients received either medical treatment alone or treatment with early FMT. The primary outcome was the 3-month mortality rate. A total of 111 patients were included: 66 in the FMT group and 45 in the non-FMT group. No patient underwent surgery. The O27 ribotype (odds ratio 3.64, 95% confidence interval 1.05– 12.6, P = .04), severe CDI (9.62, 2.16–42.8, P = .003) and FMT (0.13, 0.04–0.44, P = .001) were independent predictors of 3-month mortality. FMT improved survival in severe cases (0.08, 0.016–0.34, P = .001) but not in non-severe cases (1.07, 0.02–56.3, P = .97), independently of age, sex, comorbidities (Charlson score) and ribotype. The number of severe patients who needed to be treated to save one life at 3 months was 2. Early FMT dramatically reduces mortality and should be proposed as a first-line treatment for severe CDI. Further studies are needed to clarify complications and contraindications. Surgery should be reassessed in this context.