Background:The clinical presentation of European patients with mild-to-moderate infection is still unknown.Objective: To study the clinical presentation of Covid-19 in Europe. Methods:Patients with positive diagnosis of Covid-19 were recruited from 18 European hospitals.Epidemiological and clinical data were obtained through a standardized questionnaire. Bayesian analysis was used for analyzing the relationship between outcomes.Results: 1,420 patients completed the study (962 females, 30.7% of health care workers). The mean age of patients was 39.17±12.09 years. The most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhea (60.1%), gustatory dysfunction (54.2%) and sore throat (52.9%).Fever was reported by on 45.4%. The mean duration of Covid-19 symptoms of mild-to-moderate cured patients was 11.5±5.7 days. The prevalence of symptoms significantly varied according to age and sex. Young patients more frequently had ear, nose, and throat complaints, whereas elderly individuals often presented fever, fatigue and loss of appetite. Loss of smell, headache, nasal obstruction and fatigue were more prevalent in female patients. The loss of smell was a key symptom of mild-to-moderate Covid19 patients and was not associated with nasal obstruction and rhinorrhea. Loss of smell persisted at least 7 days after the disease in 37.5% of cured patients. Conclusion:The clinical presentation of mild-to-moderate Covid-19 substantially varies according to the age and the sex characteristics of patients. Olfactory dysfunction seems to be an important underestimated symptom of mild-to-moderate Covid-19 that needs to be recognized as such by the WHO.

Pseudomonas aeruginosa is a major cause of nosocomial infections. This organism shows a remarkable capacity to resist antibiotics, either intrinsically (because of constitutive expression of beta-lactamases and efflux pumps, combined with low permeability of the outer-membrane) or following acquisition of resistance genes (e.g., genes for beta-lactamases, or enzymes inactivating aminoglycosides or modifying their target), over-expression of efflux pumps, decreased expression of porins, or mutations in quinolone targets. Worryingly, these mechanisms are often present simultaneously, thereby conferring multiresistant phenotypes. Susceptibility testing is therefore crucial in clinical practice. Empirical treatment usually involves combination therapy, selected on the basis of known local epidemiology (usually a beta-lactam plus an aminoglycoside or a fluoroquinolone). However, therapy should be simplified as soon as possible, based on susceptibility data and the patient's clinical evolution. Alternative drugs (e.g., colistin) have proven useful against multiresistant strains, but innovative therapeutic options for the future remain scarce, while attempts to develop vaccines have been unsuccessful to date. Among broad-spectrum antibiotics in development, ceftobiprole, sitafloxacin and doripenem show interesting in-vitro activity, although the first two molecules have been evaluated in clinics only against Gram-positive organisms. Doripenem has received a fast track designation from the US Food and Drug Administration for the treatment of nosocomial pneumonia. Pump inhibitors are undergoing phase I trials in cystic fibrosis patients. Therefore, selecting appropriate antibiotics and optimising their use on the basis of pharmacodynamic concepts currently remains the best way of coping with pseudomonal infections.

Mycobacterium tuberculosis strains resistant to almost all available anti-tuberculosis drugs are an increasing threat to public health worldwide. Among existing drugs with potential antimycobacterial effects, the combination of meropenem with clavulanate has been shown to have potent in vitro bactericidal activity against extensively drug-resistant tuberculosis (XDR-TB). To explore its potential clinical efficacy, a meropenem-clavulanate-containing salvage regimen was started in six patients with severe pulmonary XDR-TB, in association with the only one or two remaining active second-line drugs. Encouraging preliminary data are detailed and discussed.

Vancomycin and teicoplanin are still the only glycopeptide antibiotics available for use in humans. Emergence of resistance in enterococci and staphylococci has led to restriction of their use to severe infections caused by Gram-positive bacteria for which no other alternative is acceptable (because of resistance or allergy). In parallel, considerable efforts have been made to produce semisynthetic glycopeptides with improved pharmacokinetic and pharmacodynamic properties, and with activity towards resistant strains. Several molecules have now been obtained, helping to better delineate structure-activity relationships. Two are being currently evaluated for skin and soft tissue infections and are in phases II/III. The first, oritavancin (LY333328), is the 4'-chlorobiphenylmethyl derivative of chloroeremomycin, an analogue to vancomycin. It is characterised by: i) a spectrum covering vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and to some extent glycopeptide-intermediate S. aureus (GISA); ii) rapid bactericidal activity including against the intracellular forms of enterococci and staphylococci; and iii) a prolonged half-life, allowing for daily administration. The second molecule is dalbavancin (BI397), a derivative of the teicoplanin analogue A40926. Dalbavancin has a spectrum of activity similar to that of oritavancin against vancomycin-sensitive strains, but is not active against VRE. It can be administered once a week, based on its prolonged retention in the organism. Despite these remarkable properties, the use of these potent agents should be restricted to severe infections, as should the older glycopeptides, with an extension towards resistant or poorly sensitive bacteria, to limit the risk of potential selection of resistance.

Among 359 healthcare workers (HCW) employed in Panzi General Referral Hospital located in Bukavu in the Democratic Republic of Congo, 148 (41.2%) tested positive for SARS-CoV-2 antibodies. Thirty-three (22.3%) of the 148 personnel with positive serology reported symptoms evoking a prior COVID-19 illness. None of the infected HCWs reported COVID-related hospitalization, and all of them recovered. Our findings indicate high and underestimated circulation of SARS-CoV-2 within the Bukavu area.

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NoteVariation assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted.

During an 8-year period, 14 adult patients were hospitalized with typhoid fever confirmed by positive blood cultures for Salmonella typhi. Among these patients, we have retrospectively (n = 7) and prospectively (n = 7) evaluated pancreatic disturbance by serum amylase and lipase measurements at the time of admission. In 7 (50%) biological signs of pancreatitis were noted: mean amylase level 81 IU (range 30-201 IU, normal value less than 40 IU), mean lipase level 949 IU (range 468-2,000 IU, normal value less than 300 IU). Clinical signs of pancreatitis were observed in 4 cases, one of whom had a concomitant salmonella biliary tract infection and gall stones demonstrated by laparotomy and the others a normal biliary ultrasonographic examination with a swelling of the pancreas. No alcohol or drug use or other infection were noted before admission. This study suggests that biological or clinical pancreatitis should be considered as a frequent complication of typhoid fever. S. typhi should therefore be added to the list of pathogens implicated in the pathogenesis of non-alcoholic or non-lithiasic pancreatitis.