Drug treatment for Covid-19 - three years later.

There has been a profusion of trials for SARS CoV2 drugs. A review dating from May 2020 listed 115 medicines, most of which previously existed, having been investigated since the onset of the pandemic. Over an exceedingly short lapse of time, the perspective of the arrival of a new antiviral treatment specifically targeting COVID-19 appeared highly improbable. Three years later, only one treatment is recommended in France: the nirmatrelvir + ritonavir combination. While remdesivir remains available, it is only proposed when this combination is officially contraindicated. Three monoclonal antibodies, taken alone or in association, are currently available in France:: tixagevimab/cilgavimab, casirivimab/imdevimab and sotrovimab. While all three of them have received European market authorization for patients presenting with an increased risk of evolution toward a severe form of COVID-19, and while early access is possible, they are no longer recommended, the reason being a loss or alteration of activity on variants carrying a Spike protein mutation. RoActemra is a humanized monoclonal antibody that blocks the action of interleukin 6 receptors; it is exclusively reserved for adult patients receiving systemic corticotherapy and necessitating oxygen supplementation, while patients under invasive mechanical ventilation are excluded. All in all, since the onset of the pandemic dozens of products have been subjected to tests or trials; three years later, only a highly limited number of "candidates" remain, and definitive assessment has yet to be achieved.

[When the antibiotic miracle turns into a nightmare]. / Quand le miracle antibiotique vire au cauchemar.

Antibiotics have been a true miracle. Would it end in a nightmare? Possibly. Since 1941, the antibiotic treatment of bacterial infections has been a revolution. The golden age lasted half a century, a period during which infectious diseases were considered definitely defeated. And although from the beginning some kind of bacterial resistance was observed, a strong long-lasting belief was that continuous innovation and invention of new molecules would keep providing a step ahead in the war waged between the human and microbes. For twenty years the resistances became each year a greater concern. Having first hit the hospital, they now affect the community. New effective antibiotics are scarce, and innovation once thought endless, stopped. Today, to escape the nightmare of a return to the pre-antibiotic era, we must find a way to curb the spread of resistant bacteria, change radically our irresponsible squander of antibiotics, and give ways to new treatments effective against future resistant pathogens. These topics are developed in the present paper dealing with the real risk that these 20th century wonder of the medical science, become an object of memory.

Levofloxacin 500 mg once daily versus cefuroxime 250 mg twice daily in patients with acute exacerbations of chronic obstructive bronchitis: clinical efficacy and exacerbation-free interval.

The long-term outcome time to relapse determined as the exacerbation-free interval (EFI) has been proposed as a standard measure for comparing the efficacy of antimicrobial therapies in acute exacerbation of chronic obstructive bronchitis (AECOB). In this 6-month, randomised, open-label study, the efficacy of 10 days of oral levofloxacin 500 mg once daily or cefuroxime 250 mg twice daily was evaluated in 689 well-defined patients experiencing AECOB episodes. In the clinically evaluable per-protocol (PPc) population and the modified intent-to-treat population, the clinical cure rates at test of cure were, respectively, 94.6% for levofloxacin versus 93.8% for cefuroxime (0.8% difference, 95% confidence interval (CI) -3.2 to 4.8) and 94.5% for levofloxacin versus 92.2% for cefuroxime (2.3% difference, 95% CI -1.8 to 6.2), whilst the probability that 25% of patients would relapse during follow-up was reached within 93 days for levofloxacin compared with 81 days for cefuroxime in the PPc population (P=0.756). A multivariate analysis revealed that only congestive heart failure and number of AECOB episodes in the previous 12 months were predictive of relapse. Safety was comparable in the two treatment groups, with possibly related treatment-emergent adverse events occurring in 5.0% and 2.9% of subjects in the levofloxacin and cefuroxime groups, respectively. In addition to demonstrating the non-inferiority of levofloxacin compared with cefuroxime in AECOB, the data from this study raise the question of whether EFI is a useful discriminative endpoint for comparing antimicrobial therapies.

[Short or long course antibiotics. Is there a debate on the duration of treatment?]. / Antibiothérapies courtes ou longues. Y a-t-il débat sur la durée des traitements?

FROM EMPIRIC DATA: The duration of antibiotic treatments in most cases is comprised between 7 and 14 days. However, although a duration is indicated on prescribing an antibiotic, the true duration, for a precise patient, can vary depending on the organ infected, the causal agent, the time passed since the first symptoms and the onset of treatment, eventual complications and notably the presence of suppuration or deep bacterial centers, not necessarily accessible to the antibiotic, its localization, the progress during treatment and the quality of the treatment selected. NORMAL, SHORT OR LONG TREATMENT CYCLES: For common infections, the normal treatment cycles indicated are extracted from the literature. Short (or shortened) cycles have been and are the subject of studies predominantly on upper respiratory and lower urinary tracts infections. When indisputable studies, with wide experience, have validated short treatment cycles, explicit marketing authorizations have been issued. An exhaustive list exists. There are also situations in which long or even very long treatment cycles are required. DAY ZERO: The debate on the shortening of treatment cycles must not serve as an alibi to the consensus that is required in France, which is that the prescription of antibiotics in affections that do not require them must cease: 10 to 20 million treatments are prescribed every year for no good reason. The list of infections targeted is clearly established by the official guidelines of the AFSSAPS (French Medicines Agency). For such infections, the aim is not to shorten the duration of the antibiotic, but not to prescribe one.