key: cord-342084-fbtx7rwi
authors: Ceccarelli, Giancarlo; Alessandri, Francesco; d'Ettorre, Gabriella; Borrazzo, Cristian; Spagnolello, Ornella; Oliva, Alessandra; Ruberto, Franco; Mastroianni, Claudio M.; Pugliese, Francesco; Venditti, Mario
title: IS TEICOPLANIN A COMPLEMENTARY TREATMENT OPTION FOR COVID-19? THE QUESTION REMAINS
date: 2020-05-23
journal: Int J Antimicrob Agents
DOI: 10.1016/j.ijantimicag.2020.106029
sha: 
doc_id: 342084
cord_uid: fbtx7rwi

nan

We read with great interest the editorial by Baron Coronavirus (MERS-CoV), but also Ebola virus, influenza A and B viruses, and feline infectious peritonitis virus (FIPV), were reported as potential targets of teicoplanin and its chemical derivatives. [2] [3] [4] [5] Recently, additional studies provided evidences that SARS-CoV2, similarly to SARS-CoV, is a cathepsin L-dependent virus: in fact, these viruses require a multistep infection process including 1) receptor binding, 2) changes in S glycoprotein conformation, and finally 3) cathepsin L proteolysis, crucial for virus entry. Teicoplanin was found to specifically inhibit the activity of cathepsin L and potentially to play critical role in blocking the cellular entry of the virus [3, [6] [7] .

Based on the aforementioned, teicoplanin has been used either as a potential antiviral agent and treatment of possible Staphylococcus aureus superinfection in our critical patients with severe SARS-CoV-2 pneumonia, since this latter may represent a major complication of respiratory viral infections. [8] We preliminary observed a cohort of 21 patients affected by severe COVID-19 lung involvement, At follow-up after a 12-day course, peripheral lymphocyte count, a marker of favourable prognosis, was progressively and significantly improved; C reactive protein (CRP) and procalcitonin (PCT) also showed a statistically significant slope down ( fig. 1 ). On the other hand, kidney and liver function did not significantly change and PaO 2 /FiO 2 was not significantly modified, but 5 (23,8%) patients were weaned from mechanical ventilation.

On day 7 of treatment, out of 21 patients observed, 2 (9,5%) achieved virus clearance; on day 12, 1 (4,7%) patient was discharged from ICU and 3 (14.2%) patients died (at day 6,7 and11). Overall on day 21, ICU mortality, ICU discharge rate and viral clearance rate were 42,8% (9/21 patients), Therapeutic drug monitoring (TDM) was not available in our patients. However, teicoplanin was administered at the dosage of 600 mg/die, which corresponded to 6-8 mg/kg/die (following a 600 mg loading dose every 12h for 3 doses), that usually results in serum through concentration >10 mg/L, regarded as adequate for treatment of bacterial infections [10] . Moreover, a recent study showed that teicoplanin potently prevents the entrance of SARS-CoV2 into the cytoplasm with an IC50 of only 1.66 μM which is much lower than the routine trough serum drug concentration (approximately 7-8 μM/L). Therefore, the routinely-used teicoplanin doses adopted in our series might be considered as potentially adequate for treatment of patients with SARS-CoV2 infection.

This study has many obvious limitations including its non-comparative retrospective observational nature, the small simple size, the short follow up, the lack of TDM and the impossibility of 

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