[The problem of formation of new risks of medicinal resistance of patients with tuberculosis in condition of active use of antibiotics by population under COVID-19].

In pandemic conditions, situation of active and uncontrolled use by population of antimicrobial preparations treating COVID-19 occurs. So, new risks of development of medication resistance among patients with various infectious diseases, tuberculosis included, appear. The purpose of the study is to characterize prevalence of antimicrobial preparations use by population in relationship with development of medication resistance in patients with tuberculosis during COVID-19 pandemic. Material and methods. The analysis of sales of antimicrobial medicines was implemented on the basis of published official data from the joint-stock company DSM Group presenting monthly audit of the Russian pharmaceutical market. The determination of primary antibiotic resistance was carried out in 2018-2020 on 3312 patients with tuberculosis. The modified method of proportions on liquid nutrient medium in system with automated accounting of microorganisms growth, the method of absolute concentrations and the method of polymerase chain reaction with real-time detection were applied. The results of the study. It was established that the most demanding antimicrobial medications among population were ceftriaxone, azithromycin, levofloxacin, moxifloxacin, azithromycin. At the same time, the maximum increase in sales in 2020 up to 150% as compared with of 2019 was determined in medications derived from quinolone moxifloxacin, levofloxacin, which began to be used in treatment of coronavirus infection. At the same time, these medications are traditionally used in tuberculosis treatment. But in 2020, alarming trend was established that limits treatment of tuberculosis patients. The primary resistance of mycobacteria was also established in newly diagnosed tuberculosis patients, also for the same antimicrobial medications of quinolone derivatives, and increasing in proportion of patients with primary medication resistance to levofloxacin, moxifloxacin in 2020 as compared to 2018 was 189-480%. At the same time, increasing of resistance to other antibiotics made up to 60.8% on average. Conclusion. The study results imply alarming scenario of medication resistance shifts towards very virulent and highly medication-resistant genotypes. This trend can result in conditions of successful transmission of deadly medication-resistant mutants that can seriously undermine effectiveness of implemented programs of struggle with tuberculosis worldwide.

Helicobacter pylori eradication rates using clarithromycin and levofloxacin-based regimens in patients with previous COVID-19 treatment: a randomized clinical trial.

BACKGROUND: Helicobacter pylori (H. pylori) is affecting half of the globe. It is considered a main causative organism of chronic gastritis, peptic ulcer disease, and different gastric maliganacies. It has been also correlated to extraintestinal diseases, including refractory iron deficiency anaemia, vitamin B12 deficiency, and immune thrombocytopenic purpura. The misuse of antibiotics during the coronavirus diseases 2019 (COVID-19) pandemic time can affect H. pylori eradication rates. Our aim was to compare the efficacy of clarithromycin versus levofloxacin-based regimens for H. pylori treatment in naïve patients after the COVID-19 pandemic misuse of antibiotics. METHODS: A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were recruited. Patients were randomized to receive either clarithromycin, esomeprazole, and amoxicillin, or levofloxacin, esomeprazole, and amoxicillin. RESULTS: A total of 270 naïve H. pylori infected patients with previous treatment for COVID-19 more than 3 months before enrolment were included, 135 in each arm. In total, 19 patients in the clarithromycin group and 18 patients in the levofloxacin group stopped treatment after 2-4 days because of side effects or were lost for follow-up. Finally, 116 subjects in the clarithromycin group and 117 in the levofloxacin group were assessed. The eradication rates in intention to treat (ITT) and per protocol (PP) analyses were: group I, 55.56% and 64.66%; and Group II, 64.44% and 74.36% respectively (p = 0.11). CONCLUSION: As COVID-19 pandemic has moved forward fast, high resistance rates of H. pylori to both clarithromycin and levofloxacin were developed after less than two years from the start of the pandemic. Molecular & genetic testing is highly recommended to identify antimicrobial resistance patterns. Strategies to prevent antibiotic misuse in the treatment of COVID-19 are needed to prevent more antibiotic resistance. TRIAL REGISTRATION: The trial was registered on Clinicaltrials.gov NCT05035186. Date of registration is 2-09-2021.

Geographic distribution of antibiotic resistance of Helicobacter pylori: A study in Bulgaria.

Prevalence of antibiotic resistant Helicobacter pylori was compared between 50 patients living outside the capital city and 50 matched pairs of capital city residents (CCRs). H. pylori isolates from 2018 to 2022 were included. Resistance rates in CCRs and those living elsewhere were 4.0 and 6.0% to amoxicillin, 48.0 and 42.0% to metronidazole, 30 and 30% to clarithromycin, and 4.0 and 4.0% to tetracycline, respectively. Levofloxacin resistance was higher (38.0%) in the capital city vs 20.0% (P = 0.047) in the country. Odd ratio for levofloxacin resistance between pair-matched groups was 2.45 (95% CI, OR 1.0-6.02, P value = 0.05) and relative risk for fluoroquinolone resistance was 1.90 (95% CI for RR 0.98-3.67) for CCRs vs residents in other regions. Resistance rates to levofloxacin and clarithromycin were worryingly high in our study, most probably due to the high quinolone consumption (2.86 DDD/day in 2017) in Bulgaria and the increase in macrolide, lincosamide and streptogramin consumption, especially of azithromycin, by >42% with the start of COVID-19 pandemic. Briefly, antibiotic resistance of H. pylori has a dynamic change, and it can display different patterns in certain geographic regions. The results imply that antibiotic consumption should be carefully controlled and unjustified use of levofloxacin should be restricted, especially in some large cities. Antibiotic policy should be further strengthened and regular monitoring of resistance in various geographic regions is needed for treatment optimization.

Pneumococcal carriage in adults aged 50 years and older in outpatient health care facility during pandemic COVID-19 in Novi Sad, Serbia.

BACKGROUND: Data related to carriage of Streptococcus pneumoniae (Spn) and antimicrobial resistance patterns in middle-aged and older adults are limited. We assessed the carriage of Spn, and its antibiotic resistance patterns, among participants ≥50 years of age living in the city of Novi Sad during the second year of COVID-19 pandemic. METHODS: Analysis of prospectively collected data among participants with or without symptoms of upper respiratory tract infection who visited their elected physicians in the Primary Health Care Centre of Novi Sad (outpatient facility) was conducted from May 18, 2021 to December 7, 2021. Both nasopharyngeal (NP) and oropharyngeal (OP) samples from each participant were collected. RESULTS: A total of 1042 samples from 521 study subjects (1 NP and 1 OP sample from each person) were collected. Sixteen samples from the same number of persons (3.1%, 95% confidence interval: 1.76%-4.94%) were culture positive for the presence of Spn. Overall, the median age of study participants was 71 years (range, 50-93 years; 90th percentile, 77 years), and most (197/521, 37.8%) of them were 70-79 years of age. A majority of the study subjects were: females (324/521; 62.2%), sampled during May and June 2021 (376/521, 72.2%), those who did not have contact with children aged 0-10 years in the family (403/521; 77.4%), without smokers in the household (443/521; 85.0%), and those who did not receive vaccine against Spn (519/521; 99.6%). Out of 16 Spn positive samples, for six participants, Spn carriage serotypes were obtained and there were four vaccine (6A, 11A, 15B, and 18C) serotypes, and two (6C and 35F) non-vaccine serotypes. Remaining 10 (62.50%) samples were non-typeable isolates of pneumococci. Among four vaccine serotypes, two (6A and 18C) were represented in PCV13, and 18C along with the other two (11A and 15B) in PPSV23 vaccine. The highest level of resistance of Spn isolates was observed for erythromycin, (10 or 62.50%), and tetracycline, (7 or 43.75%), one isolate showed resistance to penicillin, ampicillin, and amoxicillin/amoxicillin-clavulanic acid, while none of them were resistant to ceftriaxone, trimethoprim/sulfamethoxazole and levofloxacin. There were three multi-drug resistant isolates; one was identified as 6C (non-vaccine serotype), and two other were non-typeable isolates of Spn. CONCLUSIONS: In this first study conducted in Serbia on Spn carriage in adults ≥50 years of age, we found low prevalence of Spn carriage and identified 6 serotypes of Spn, four of which were represented in vaccines. These results may support future Spn colonization studies among middle-aged and older adults.

Management of antibacterial therapy of infectious and inflammatory diseases of the urinary tract in children and regional peculiarities during the COVID-19 pandemic.

Urinary tract infections (UTIs) remain an urgent issue in clinical pediatrics. Empirical selection of antibacterial therapy becomes more complicated, and antibacterial drug indication is not always clinically substantiated. This study aimed to compare the antibacterial susceptibility pattern of the main group of urinary tract infectious agents from 2009-2016 with intermediate results from 2020-2021, during the COVID-19 pandemic, among children in the Chernivtsi region. Urine samples were collected from 3089 children (0-17 years old) treated at the health care institutions in the Chernivtsi region (2009-2016). The clinical-laboratory examination of 177 children (0-17 years old) was carried out from 2020 to 2021. The children received specialized medical care at the Department of Nephrology. Preliminary data of regional monitoring (2020-2021) are not considerably different from the previous regional susceptibility of antibiotics: to penicillin (p<0.01), ІІ-ІІІ generation cephalosporin (p<0.01); an increased resistance to levofloxacin (χ2=4,338; p<0.01), tetracycline - χ2=7,277; p<0.01; doxycycline - χ2=5,309; p<0.01) and imipenem - χ2=5,594; p<0.01). The data obtained did not explain an increased resistance to fluoroquinolones completely (ofloxacin, pefloxacin, ciprofloxacin), except for levofloxacin (χ2=4,338; p<0.01). A reliable difference of susceptibility of tetracycline group was registered (tetracycline - χ2=7,277; p<0.01; doxycycline - χ2=5,309; p<0.01). Furthermore, there was a regional increase in some UTI-pathogen strains resistant to carbapenems (imipenem - χ2=5,594; p<0.01). The use of antibiotics from the group of penicillins and II-III generation cephalosporins as the starting antibacterial therapy for STIs during the COVID-19 pandemic should be justified. A regional increase (2020-2021) of some uropathogenic strains resistant to carbapenems administered to treat severe bacterial infections requires their exclusively designated purpose in everyday pediatric practical work.

Bordetella bronchiseptica infections in patients with HIV/AIDS: A case report and review of the literature.

RATIONALE: Bordetella bronchiseptica is a common cause of upper respiratory tract infections in domesticated dogs and cats and a rare zoonotic pathogen in immunocompromised humans. With increasing numbers of people acquiring pets and spending time with them in confined spaces due to COVID-19 lockdowns, it is important to be aware of adverse health consequences brought about by this interaction. We present a case of B bronchiseptica pneumonia in a patient with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and review key characteristics of an additional 30 cases of B bronchiseptica infections in 29 patients with HIV/AIDS that were identified by literature review. PATIENT CONCERNS: A 61-year-old male with HIV/AIDS who was not on antiretroviral therapy and had advanced immunosuppression with a CD4+ T-lymphocyte count of 3 cells/µL sought medical attention for multiple somatic issues including subjective fevers, shortness of breath, and intermittent chest pain. DIAGNOSIS: Computed tomography of the chest identified bilateral nodular opacities in the lower lobes with scattered areas of ground glass opacities. B bronchiseptica was identified in sputum culture by mass spectrometry followed by supplementary biochemical testing. INTERVENTIONS: Empiric broad-spectrum antibiotics were initiated and changed to levofloxacin after susceptibility testing was completed. OUTCOMES: The patient was discharged after symptomatic improvement with levofloxacin. LESSONS: Pneumonia with interstitial infiltrates in the setting of advanced CD4 lymphocyte depletion is the most common clinical syndrome caused by B bronchiseptica in patients with HIV/AIDS, and may be accompanied by sepsis. Advanced immune suppression, as well as chronic medical conditions, for example, alcoholism, diabetes, and renal failure that compromise host defenses are also commonly found in cases of B bronchiseptica infection in patients who do not have HIV infection. Reported animal contact among patients was not universal. Isolates were susceptible to aminoglycosides, carbapenems, fluoroquinolones, but typically resistant to most cephalosporins.

Investigation of the effects of three different generations of fluoroquinolone derivatives on antioxidant and immunotoxic enzyme levels in different rat tissues.

Fluoroquinolones (FQs) are synthetic and broad-spectrum antimicrobial drugs derived from nalidixic acid. FQs are used against SARS-CoV-2 in our country, and for the treatment of some urinary tract diseases, gastrointestinal diseases, respiratory tract diseases, sexually transmitted diseases, and dermatological diseases. The present study investigated the effect of 1-,7-,14-day treatments of three different FQ derivatives; ciprofloxacin (CIP) 80 mg/kg/day, levofloxacin (LVX) 40 mg/kg/day, and moxifloxacin (MXF) 40 mg/kg/day, on biochemical parameters, lipid peroxidation, antioxidant enzymes, and immunotoxicity. 72 Wistar albino male rats were distributed to four groups including 18 rats in each group and were sacrificed on three different time points. The 14-day treatment of MXF significantly reduced the levels of aspartate aminotransferase (AST), glucose, reduced glutathione (GSH), malondialdehyde (MDA), catalase (CAT), myeloperoxidase (MPO), adenosine deaminase (ADA), and glutathione peroxidase (GPx). Furthermore, 14-day treatment of LVX increased liver [GSH, MPO, ADA, superoxide dismutase (SOD)], and GSH (erythrocyte) levels; whereas it significantly reduced the levels of AST, TG (triglycerides) and associated parameters levels in all the tissues (MDA), erythrocytes, and liver (MPO, CAT, SOD, GPx). After 14-day treatment of CIP; the erythrocyte levels of GSH, MPO, GPx, and CAT significantly decreased; whereas the levels of glucose, creatinine, MPO (liver), and GST (kidney and erythrocyte) significantly increased. It has been concluded that FQ derivatives used in this experiment did not display any correlation in terms of the efficacies in the different time points and tissues. Thus, it is recommended to use such FQ derivatives considering the duration of use and target tissue.

Nationwide surveillance of antimicrobial resistance in invasive isolates of Streptococcus pneumoniae in Taiwan from 2017 to 2019.

BACKGROUND/PURPOSE: Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan. METHODS: A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed. RESULTS: Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid. CONCLUSION: Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

The application of in silico experimental model in the assessment of ciprofloxacin and levofloxacin interaction with main SARS-CoV-2 targets: S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLpro)-preliminary molecular docking analysis.

BACKGROUND: The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified at the end of 2019. Despite growing understanding of SARS-CoV-2 in virology as well as many molecular studies, except remdesivir, no specific anti-SARS-CoV-2 drug has been officially approved. METHODS: In the present study molecular docking technique was applied to test binding affinity of ciprofloxacin and levofloxacin-two commercially available fluoroquinolones, to SARS-CoV-2 S-, E- and TMPRSS2 proteins, RNA-dependent RNA polymerase and papain-like protease (PLPRO). Chloroquine and dexamethasone were used as reference positive controls. RESULTS: When analyzing the molecular docking data it was noticed that ciprofloxacin and levofloxacin possess lower binding energy with S protein as compared to the references. In the case of TMPRSS2 protein and PLPRO protease the best docked ligand was levofloxacin and in the case of E proteins and RNA-dependent RNA polymerase the best docked ligands were levofloxacin and dexamethasone. Moreover, a molecular dynamics study also reveals that ciprofloxacin and levofloxacin form a stable complex with E- and TMPRSS2 proteins, RNA polymerase and papain-like protease (PLPRO). CONCLUSIONS: The revealed data indicate that ciprofloxacin and levofloxacin could interact and potentially inhibit crucial SARS-CoV-2 proteins.

Facile Synthesis of Ag/AgVO3/N-rGO Hybrid Nanocomposites for Electrochemical Detection of Levofloxacin for Complex Biological Samples Using Screen-Printed Carbon Paste Electrodes.

Silver vanadate nanorods (ß-AgVO3) with silver nanoparticles (Ag-NPs) decorated on the surface of the rods were synthesized by using simple hydrothermal technique and later anchored onto nitrogen-doped reduced graphene oxide (N-rGO) to make a novel nanocomposite. Experimental analyses were carried out to identify the electronic configuration by X-ray diffraction analysis, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy analysis, which revealed monoclinic patterns of the C12/m1 space group with Wulff construction forming beta silver vanadate (ß-AgVO3) crystals with optical density and phase transformations. Ag nucleation showed consistent results with metallic formation and electronic changes occurring in [AgO5] and [AgO3] clusters. Transmission electron microscopy and field-emission scanning electron microscopy with elemental mapping and EDX analysis of the morphology reveals the nanorod structure for ß-AgVO3 with AgNPs on the surface and sheets for N-rGO. Additionally, a novel electrochemical sensor is constructed by using Ag/AgVO3/N-rGO on screen-printed carbon paste electrodes for the detection of antiviral drug levofloxacin (LEV) which is used as a primary antibiotic in controlling COVID-19. Using differential pulse voltammetry, LEV is determined with a low detection limit of 0.00792 nm for a linear range of 0.09-671 µM with an ultrahigh sensitivity of 152.19 µA µM-1 cm-2. Furthermore, modified electrode performance is tested by real-time monitoring using biological and river samples.

Phylogenic analysis of coronavirus genome and molecular studies on potential anti-COVID-19 agents from selected FDA-approved drugs.

The emergence of 2019 novel Coronavirus (COVID-19 or 2019-nCoV) has caused significant global morbidity and mortality with no consensus specific treatment. We tested the hypothesis that FDA-approved antiretrovirals, antibiotics, and antimalarials will effectively inhibit COVID-19 two major drug targets, coronavirus nucleocapsid protein (NP) and hemagglutinin-esterase (HE). To test this hypothesis, we carried out a phylogenic analysis of coronavirus genome to understand the origins of NP and HE, and also modeled the proteins before molecular docking, druglikeness, toxicity assessment, molecular dynamics simulation (MDS) and ligand-based pharmacophore modeling of the selected FDA-approved drugs. Our models for NP and HE had over 95% identity with templates 5EPW and 3CL5 respectively in the PDB database, with majority of the amino acids occupying acceptable regions. The active sites of the proteins contained conserved residues that were involved in ligand binding. Lopinavir and ritonavir possessed greater binding affinities for NP and HE relative to remdesivir, while levofloxacin and hydroxychloroquine were the most notable among the other classes of drugs. The Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of gyration (Rg), and binding energy values obtained after 100 ns of MDS revealed good stability of these compounds in the binding sites of the proteins while important pharmacophore features were also identified. The study showed that COVID-19 likely originated from bat, owing to the over 90% genomic similarity observed, and that lopinavir, levofloxacin, and hydroxychloroquine might serve as potential anti-COVID-19 lead molecules for additional optimization and drug development for the treatment of COVID-19.Communicated by Ramaswamy H. Sarma.

Effect of triple antimicrobial therapy on electrocardiography parameters in patients with mild-to-moderate coronavirus disease 2019.

OBJECTIVE: The effects of treatment of coronavirus disease 2019 (COVID-19) with a triple combination composed of hydroxychloroquine, an an-tiviral, and an antibiotic on electrocardiography (ECG) parameters in patients with mild-to-moderate symptoms are not wholly understood. We aimed to explore the changes in ECG parameters after treatment with triple combination therapy in patients with mild-to-moderate symptomatic COVID-19. METHODS: This retrospective, single-center case series analyzed 91 patients with mild-to-moderate symptomatic COVID-19 at Ankara Gazi Mus-tafa Kemal State Hospital of Ankara City, Turkey, from April 1, 2020, to April 30, 2020. Forty-three patients were treated with hydroxychloroquine+oseltamivir+azithromycin (Group 1) and 48 patients were treated with hydroxychloroquine+oseltamivir+levofloxacin (Group 2). Heart rate, P wave duration, P wave dispersion, PR interval, QRS duration, corrected QT interval (QTc), QTc dispersion (QTD), delta QTc, Tp-e, Tp-e dispersion, and Tp-e/QTc ratio were all calculated from the baseline and posttreatment 12-lead ECG recordings. RESULTS: The QTc, QRS duration, Tp-e, PR interval, and P wave duration were significantly increased after treatment (p<0.001; p<0.001; p<0.001; p=0.001; p=0.001). The posttreatment C-reactive protein level was significantly lower than at baseline in Group 1 (p=0.014). At admission, 30% of patients had QT prolongation, and 4.3% of them had a QT duration >500 ms. Both Group 1 and Group 2 showed significant prolongation of the QTc interval (Group 1; p<0.001 vs. Group 2; p<0.001), QRS duration (Group 1; p=0.006 vs. Group 2; p=0.014), Tp-e (Group 1; p=0.036 vs. Group 2; p<0.001), and PR interval (Group 1; p=0.002 vs. Group2; p=0.05). The QTD was significantly decreased in Group 1 (p<0.001). None of the patients experienced any overt ventricular arrhythmia. CONCLUSION: To the best of our knowledge, this study is the first to investigate QT prolongation in a population of COVID-19 patients treated with triple combination therapy. We found that there was a significant decrease in the QTD after the treatment in patients who were taking triple therapy including azithromycin.

Endophthalmitis caused by Mycobacterium houstonense: case report.

BACKGROUND: Mycobacterium houstonense is rapidly growing mycobacteria (RGM) that belongs to M. fortuitum group. So far, there have been few associated reports of human diseases induced by M. houstonense worldwide. CASE PRESENTATION: We present a delayed-onset postoperative endophthalmitis caused by M. houstonense after glaucoma drainage implant (GDI) surgery. The ocular infection lasted for 2 months without appropriate treatment that developed into endophthalmitis and the patient underwent an emergency enucleation. CONCLUSION: Implant erosion and a delay in diagnosis of ocular infection could lead to irreversible damage as observed in our case. Ophthalmologists should be alert for ocular RGM infection, and prompt laboratory diagnosis with initiation of effective multidrug therapy might prevent loss of vision.

Fluoroquinolone Antibiotics Exhibit Low Antiviral Activity against SARS-CoV-2 and MERS-CoV.

Repurposing FDA-approved drugs that treat respiratory infections caused by coronaviruses, such as SARS-CoV-2 and MERS-CoV, could quickly provide much needed antiviral therapies. In the current study, the potency and cellular toxicity of four fluoroquinolones (enoxacin, ciprofloxacin, levofloxacin, and moxifloxacin) were assessed in Vero cells and A549 cells engineered to overexpress ACE2, the SARS-CoV-2 entry receptor. All four fluoroquinolones suppressed SARS-CoV-2 replication at high micromolar concentrations in both cell types, with enoxacin demonstrating the lowest effective concentration 50 value (EC50) of 126.4 µM in Vero cells. Enoxacin also suppressed the replication of MERS-CoV-2 in Vero cells at high micromolar concentrations. Cellular toxicity of levofloxacin was not found in either cell type. In Vero cells, minimal toxicity was observed following treatment with ≥37.5 µM enoxacin and 600 µM ciprofloxacin. Toxicity in both cell types was detected after moxifloxacin treatment of ≥300 µM. In summary, these results suggest that the ability of fluoroquinolones to suppress SARS-CoV-2 and MERS-CoV replication in cultured cells is limited.

Could Respiratory Fluoroquinolones, Levofloxacin and Moxifloxacin, Prove to be Beneficial as an Adjunct Treatment in COVID-19?

Since the beginning of the COVID-19 pandemic, researchers have focused on repurposing of existing antibiotics, antivirals and anti-inflammatory drugs to find an effective therapy. Fluoroquinolones are broad spectrum synthetic antimicrobial agents, being chemical derivatives of quinoline, the prodrome of chloroquine. Interestingly, fluoroquinolones may exert antiviral actions against vaccinia virus, papovavirus, CMV, VZV, HSV-1, HSV-2, HCV and HIV. A recent in silico study has shown that the fluoroquinolones, ciprofloxacin and moxifloxacin, may inhibit SARS-CoV-2 replication by exhibiting stronger capacity for binding to its main protease than chloroquine and nelfinavir, a protease inhibitor antiretroviral drug. Remarkably, fluoroquinolones have shown multiple immunomodulatory actions leading to an attenuation of the inflammatory response through the inhibition of pro-inflammatory cytokines. Noteworthy, respiratory fluoroquinolones, levofloxacin and moxifloxacin, constitute fist line therapeutic agents for the management of severe community-acquired pneumonia. They are characterized by advantageous pharmacokinetic properties; higher concentrations in the lungs; and an excellent safety profile comparable to other antibiotics used to treat respiratory infections, such as macrolides and b-lactams. Based on their potential antiviral activity and immunomodulatory properties, the favorable pharmacokinetics and safety profile, we propose the use of respiratory fluoroquinolones as adjuncts in the treatment of SARS-CoV-2 associated pneumonia.

Effectiveness of Streptococcus Pneumoniae Urinary Antigen Testing in Decreasing Mortality of COVID-19 Co-Infected Patients: A Clinical Investigation.

BACKGROUND AND OBJECTIVES: Streptococcus pneumoniae urinary antigen (u-Ag) testing has recently gained attention in the early diagnosis of severe and critical acute respiratory syndrome coronavirus-2/pneumococcal co-infection. The aim of this study is to assess the effectiveness of Streptococcus pneumoniae u-Ag testing in coronavirus disease 2019 (COVID-19) patients, in order to assess whether pneumococcal co-infection is associated with different mortality rate and hospital stay in these patients. MATERIALS AND METHODS: Charts, protocols, mortality, and hospitalization data of a consecutive series of COVID-19 patients admitted to a tertiary hospital in northern Italy during COVID-19 outbreak were retrospectively reviewed. All patients underwent Streptococcus pneumoniae u-Ag testing to detect an underlying pneumococcal co-infection. Covid19+/u-Ag+ and Covid19+/u-Ag- patients were compared in terms of overall survival and length of hospital stay using chi-square test and survival analysis. RESULTS: Out of 575 patients with documented pneumonia, 13% screened positive for the u-Ag test. All u-Ag+ patients underwent treatment with Ceftriaxone and Azithromycin or Levofloxacin. Lopinavir/Ritonavir or Darunavir/Cobicistat were added in 44 patients, and hydroxychloroquine and low-molecular-weight heparin (LMWH) in 47 and 33 patients, respectively. All u-Ag+ patients were hospitalized. Mortality was 15.4% and 25.9% in u-Ag+ and u-Ag- patients, respectively (p = 0.09). Survival analysis showed a better prognosis, albeit not significant, in u-Ag+ patients. Median hospital stay did not differ among groups (10 vs. 9 days, p = 0.71). CONCLUSIONS: The routine use of Streptococcus pneumoniae u-Ag testing helped to better target antibiotic therapy with a final trend of reduction in mortality of u-Ag+ COVID-19 patients having a concomitant pneumococcal infection. Randomized trials on larger cohorts are necessary in order to draw definitive conclusion.

Legionella pneumonia: increased risk after COVID-19 lockdown? Italy, May to June 2020.

We report a case of Legionella pneumonia in a dishwasher of a restaurant in Rome, Italy, just after the end of the lockdown that was in place to control the SARS-CoV-2 epidemic. The case highlights the importance of strict monitoring of water and air systems immediately before reopening business or public sector buildings, and the need to consider Legionella infections among the differential diagnosis of respiratory infections after lockdown due to the ongoing COVID-19 pandemic.

The clinical value of two combination regimens in the Management of Patients Suffering from Covid-19 pneumonia: a single centered, retrospective, observational study.

BACKGROUND: There is no identified pharmacological therapy for COVID-19 patients, where potential therapeutic strategies are underway to determine effective therapy under such unprecedented pandemic. Therefore, combination therapies may have the potential of alleviating the patient's outcome. This study aimed at comparing the efficacy of two different combination regimens in improving outcomes of patients infected by novel coronavirus (COVID-19). METHODS: This is a single centered, retrospective, observational study of 60 laboratory-confirmed COVID-19 positive inpatients (≥18 years old) at two wards of the Baqiyatallah Hospital, Tehran, Iran. Patient's data including clinical and laboratory parameters were recorded. According to the drug regimen, the patients were divided into two groups; group I who received regimen I consisting azithromycin, prednisolone, naproxen, and lopinavir/ritonavir and group II who received regimen II including meropenem, levofloxacin, vancomycin, hydroxychloroquine, and oseltamivir. RESULTS: The oxygen saturation (SpO2) and temperature were positively changed in patients receiving regimen I compared to regimen II (P = 0.013 and P = 0.012, respectively). The serum level of C-reactive protein (CRP) changed positively in group I (P < 0.001). Although there was a significant difference in platelets between both groups (75.44 vs 51.62, P < 0.001), their change did not clinically differ between two groups. The findings indicated a significant difference of the average length of stay in hospitals (ALOS) between two groups, where the patients under regimen I showed a shorter ALOS (6.97 vs 9.93, P = 0.001). CONCLUSION: This study revealed the beneficial effect of the short-term use of low-dose prednisolone in combination with azithromycin, naproxen and lopinavir/ritonavir (regimen I), in decreasing ALOS compared to regimen II. Since there is still lack of evidence for safety of this regimen, further investigation in our ongoing follow-up to deal with COVID-19 pneumonia is underway. Graphical abstract.