During the current pandemic, the gap between fundamental research and clinical practice has been narrowing at a faster pace than ever before. While clinical trials play the main role of confirming the safety and efficacy of new drugs, a drug’s introduction into clinical practice creates the need for further research in order to best position the use of the novel drug in terms of when, to whom, and how it would be best administered to achieve the best possible outcome under feasible clinical circumstances. We briefly present the results of a retrospective analysis of the characteristics of outpatients treated with molnupiravir in a tertiary care infectious disease hospital in Bucharest, Romania, between February and March 2022, when Romania was experiencing its fifth wave of COVID-19. A total of 46 outpatients received molnupiravir treatment and had complete clinical data available; of them, 56.5% (n = 20) were males and the median age was 48.5 years (IQR: 37.8, 67.0 years). A total of 54.2% (n = 26) of patients had at least one chronic condition. Of the 45 patients who underwent lung CT imaging evaluation, 13 (28.9%) showed changes suggestive of COVID-19 pneumonia. COVID-19 vaccination status was strongly protective for pneumonia (p = 0.002). All patients were symptomatic, and molnupiravir was initiated at a mean time from onset of symptoms of 3.5 (±1.5) days. At phone follow-up 5 days after the initial evaluation and initiation of molnupiravir treatment, all patients, except for one, confirmed a favorable course under treatment, with no worsening of COVID-19 severity and improvement in symptoms; none of them progressed to respiratory failure or required hospitalization. In conclusion, treatment was well tolerated and associated a favorable outcome of COVID-19 in routine practice in a clinical population that was slightly older and had a smaller burden of comorbidities and a higher rate of COVID-19 vaccination compared to that from the pivotal trial.

Table of contentsA1 The outcome of patients with recurrent versus non-recurrent pneumococcal meningitis in a tertiary health-care hospital in BucharestCristian-Mihail Niculae, Eliza Manea, Raluca Jipa, Simona Merisor, Ruxandra Moroti, Serban Benea, Adriana HristeaA2 Influence of bacteriophages on sessile Gram-positive and Gram-negative bacteriaAlina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Dana Mărculescu, Magdalena Lorena Andrei, Veronica Ilie, Marcela Popa, Coralia Bleotu, Carmen Chifiriuc, Mircea Ioan Popa, Adrian Streinu-CercelA3 The utility of inflammatory biomarkers in the prognostic evaluation of septic patients – past, present and futureAlina Orfanu, Cristina Popescu, Anca Leuștean, Remulus Catană, Anca Negru, Alexandra Badea, Radu Orfanu, Cătălin Tilișcan, Victoria Aramă, Ştefan Sorin AramăA4 Etiologic and clinical features of bacterial meningitis in infantsConstanța-Angelica Vișan, Anca-Cristina Drăgănescu, Anuța Bilașco, Camelia Kouris, Mădălina Merișescu, Magdalena Vasile, Diana-Maria Slavu, Sabina Vintilă, Endis Osman, Alina Oprea, Sabina Sandu, Monica LuminosA5 The diagnostic and prognostic role of neutrophil to lymphocyte count ratio in sepsisAlina Orfanu, Victoria Aramă, Ştefan Sorin Aramă, Anca Leuştean, Remulus Catană, Anca Negru, Gabriel Adrian Popescu, Cristina PopescuA6 Whooping cough in a HIV positive patientRamona Georgiana Stanculete, Ana Vaduva Enoiu, Adelina Raluca Marinescu, Voichita LazureanuA7 Cronobacter sakazakii sepsis in varicella patientAdelina-Raluca Marinescu, Alexandru Crișan, Voichița Lăzureanu, Virgil Musta, Narcisa Nicolescu, Ruxandra LazaA8 Anaerobes an underdiagnosed cause of prosthesis joint infectionAnca-Ruxandra Negru, Daniela-Ioana Munteanu, Raluca Mihăilescu, Remulus Catană, Olga Dorobăț, Alexandru Rafila, Emilia Căpraru, Marius Niculescu, Rodica Marinescu, Olivera Lupescu, Vlad Predescu, Adrian Streinu-Cercel, Victoria Aramă, Daniela TălăpanA9 Streptococcus pneumoniae meningitis presenting with normal CSF – case presentationRamona Ștefania Popescu, Luminița Bradu, Dragoș Florea, Adrian Streinu-CercelA10 Extrapulmonary manifestations of infection with Mycoplasma pneumoniae – study on 24 casesDaniela Anicuta Leca, Elena Bunea, Andra Teodor, Egidia MiftodeA11 The molecular diagnosis of severe bacterial sepsis in pediatric populationMădălina Merișescu, Gheorghiță Jugulete, Adrian Streinu-Cercel, Dragoș Florea, Monica LuminosA12 Acute Staphylococcus aureus endocarditis with multiple septic complications in a patient with diabetes mellitus – case presentationRamona Ștefania Popescu, Anamaria Dobrotă, Adina Ilie, Liliana Lucia PreoțescuA13 Is Streptococcus suis meningitis an under-diagnosed zoonosis?Adriana Hristea, Raluca Jipa, Nicoleta Irimescu, Irina Panait, Eliza Manea, Simona Merisor, Cristian Niculae, Daniela TălăpanA14 Klebsiella pneumoniae isolated from blood. Antimicrobial resistance – past and presentLiana Cătălina Gavriliu, Otilia Elisabeta Benea, Șerban Benea, Alexandru Rafila, Olga Dorobăț, Mona PopoiuA15 Antibiotics resistance in Staphylococcus a...

Background: Trans Sodium Crocetinate (TSC) is a bipolar synthetic carotenoid under development as a drug to enhance oxygenation to hypoxic tissue in addition to standard of care. TSC acts via a novel mechanism of action, improving the diffusivity of oxygen in blood plasma. Thus, it is based on physical-chemical principles, unlike most drugs which are based on biochemistry-based mechanisms. We explored the use of escalating doses and multiple daily dosing of TSC as a potential therapeutic for patients suffering from hypoxemia due to SARS-CoV-2 infection. Methods: Individuals ≥18 years who were hospitalized with confirmed SARS-CoV-2 infection and hypoxemia, defined as SpO2 < 94% on room air or requiring supplemental oxygen, WHO ordinal scale 3 through 7 (exclusive of Extra Corporeal Membrane Oxygenation [ECMO]) were enrolled in cohorts of six subjects, each of whom received the same dose (0.25, 0.5, 1.0, or 1.5 mg/kg) of TSC via intravenous bolus every 6 hours in addition to standard of care (SOC). This report describes the safety and efficacy results from the lead-in phase of the study and the population pharmacokinetics (PK) analyses. Safety was assessed as the number of serious adverse events and dose-limiting toxicities (DLTs) observed with each dose. Several efficacy parameters were examined in the lead-in phase and descriptive statistics of efficacy parameters are provided. No formal statistical analyses were performed. The population PK analyses were based on previous analyses and examination of the concentration profiles, and two-compartment linear pharmacokinetic models were evaluated and validated. Covariates, including body size, age, sex, organ function, and dose level, were evaluated for inclusion into the model. Results: TSC was well tolerated. There were no treatment emergent adverse events (TEAEs) reported. There were 2 serious adverse events (SAEs) reported during the study, neither were considered treatment-related. A total of 24 (96%) subjects survived. One subject (4.0%) died during the study as a result of an SAE (respiratory failure), and that event was determined to be due to COVID-19 complications and not related to study drug. There was an observed reduction in the time to improvement in WHO Ordinal Scale with increasing dose. The median time to 1-point reduction in subjects receiving 0.25 mg/kg was 11.5 days versus 7.5 days in the 1.5 mg/kg treatment cohort. The overall range across all doses was 1 day to 28 days. A total of 36.0% of subjects had a 1-point improvement in WHO Ordinal Scale to Day 7. The 1.5 mg/kg dose resulted in observed superior outcomes for multiple secondary clinical outcomes: time to 1-point WHO Ordinal Score improvement through Day 29/discharge, 1-point improvement by Day 7, days to return to room air, and hospital length of stay. The PK results showed that the two-compartment model fit the data well. Clearance decreased with increasing dose level and there was no evidence that clearance was affected by covariates other than dose level. Conclusions: These findings suggest that TSC administration every 6 hours at doses up to 1.5 mg/kg for up to 15 days is safe and well tolerated with predictable pharmacokinetics and demonstrated an observed clinical benefit in the treatment of COVID-19-related hypoxemia.

The implementation into clinical practice of syndromic testing by multiplex polymerase chain reaction allows early etiological diagnosis and paves the way towards timely targeted treatment. However, there is stringent need for diagnostic stewardship, as multiplex testing can also come with a high risk of misdiagnosis if improperly ordered or interpreted. We report two cases that illustrate proper and improper diagnostic stewardship, having important implications for correct patient management and application of antimicrobial stewardship into current clinical practice.