Identification of Multi Drug Resistant Bacteria from Drinking Water Samples - A Microbial Survey

Antimicrobial resistance may result from rising resistance patterns of commercially available antibiotics, which is one of the most serious threats to global health and should not be overlooked while the world is focused on the COVID-19 disaster. Waterborne resistant bacteria have been shown to be capable of spreading to people in a lot of circumstances, particularly crowded places in urban living environment with heavy human behavior, such as drinking in public systems and swimming pools. Four hundred drinking water samples were collected from different zones in district Lahore, Pakistan. Multidrug resistance bacterial strains of waterborne pathogens have been isolated and characterized on the basis of colony characteristics, microscopic visuality and biochemical tests. The outcomes of this project revealed that Staphylococcus aureus was (26%), Escheria coli was (45%), Salmonella typhi (15%), Shigella dysenteriae (10%) and Enterococcus faecalis (4%) in district Lahore, Pakistan. These multidrug resistance bacteria showed high resistant patterns against amoxicillin, penicillin, streptomycin, tetracycline, erythromycin, gentamycin, amikacin whereas susceptible for chloramphenicol, cefixime, ofloxacin and ciprofloxacin. The prevalence of associated risk factors such as polluted drinking water (32%), children<5year age (22%), adults >45year age (18%), excessive use of antibiotics (8%), health status of individual (5%), smoking habits (6%), and emotional variables (6%) were observed in this research. These investigations have demonstrated infectious bacterial contamination in surface and groundwater, which caused significant bowel syndrome.Copyright © 2022 Indian Veterinary Assocaition. All rights reserved.

Molecularly imprinted polymer-modified carbon paste electrodes (MIP-CPE): A review on sensitive electrochemical sensors for pharmaceutical determinations

Recent years have been associated with the development of various sensor-based technologies in response to the undeniable need for the rapid and precise analysis of an immense variety of pharmaceuticals. In this regard, special attention has been paid to the design and fabrication of sensing platforms based on electrochemical detection methods as they can offer many advantages, such as portability, ease of use, relatively cheap instruments, and fast response times. Carbon paste electrodes (CPEs) are among the most promising conductive electrodes due to their beneficial properties, including ease of electrode modification, facile surface renewability, low background currents, and the ability to modify with different analytes. However, their widespread use is affected by the lack of sufficient selectivity of CPEs. Molecularly imprinted polymers (MIPs) composed of tailor-made cavities for specific target molecules are appealing complementary additives that can overcome this limitation. Accordingly, adding MIP to the carbon paste matrix can contribute to the required selectivity of sensing platforms. This review aims to present a categorized report on the recent research and the outcomes in the combinatory fields of MIPs and CPEs for determining pharmaceuticals in complex and simple matrices. CPEs modified with MIPs of various pharmaceutical compounds, including analgesic drugs, antibiotics, antivirals, cardiovascular drugs, as well as therapeutic agents affecting the central nervous system (CNS), will be addressed in detail.Copyright © 2023 Elsevier B.V.

Evolution of Helicobacter pylori Resistance to Antibiotics: A Topic of Increasing Concern.

Antibiotic resistance among Helicobacter pylori strains is the major cause of eradication failure. Resistance prevalence is dynamic and can greatly vary among countries over the years. We revealed H. pylori resistance trends for five antibiotics in 14 countries through articles predominantly published in 2018-2022, since the latest data can best show the most recent trends in resistance evolution. Amoxicillin resistance generally exhibited no evolution, yet it increased in Bulgaria, Iran, China, and Vietnam. Metronidazole resistance exhibited different trends, including an increase, a decrease and no evolution in six, three, and five studies, respectively. Clarithromycin resistance increased in Australia, Belgium, Bulgaria, Italy, Iran, and Taiwan, but remained stable in France, Spain, Russia, China, Chile, and Colombia. Tetracycline resistance was low and stable except in Iran. Levofloxacin resistance increased in four European and six other countries/regions, without significant increases in France, Spain, and Chile. In Chile, triple resistance also increased. In countries such as France and Spain, resistance to most antibiotics was stabilized, while in Bulgaria, Belgium, Iran and Taiwan, resistance to three or more agents was reported. Use of non-recommended regimens, national antibiotic consumption, patient's compliance, host factors, strain virulence, migrations, and azithromycin overuse during the COVID-19 pandemic can influence resistance evolution. New drugs, eradication regimens and diagnostic methods, such as next-generation sequencing can improve H. pylori infection control.

The improvement of levofloxacin and tetracycline removal from simulated water by thermosensitive flocculant: Mechanisms and simulation

[Display omitted] • P(DAC-NIPAM) significantly improved the removal of levofloxacin and tetracycline. • P(DAC-NIPAM) had strong interaction with antibiotics for its multiple functional groups. • The hydrophobic groups on P(DAC-NIPAM) tightly bridged micelles of antibiotics and SDS. • Compact flocs were formed for shrinkage of P(DAC-NIPAM) molecule at the LCST. • Flocculation simulation further confirmed application feasibility of thermosensitive flocculants. Antibiotics were detected in worldwide natural water especially in COVID-19 period. The common flocculants rarely removed the dissolved antibiotics from natural water and wastewater. The flocculation improvement of organic polymer flocculants might solve the issue of antibiotic pollution or promote the removal efficiencies of antibiotics in water/wastewater treatment plants. Herein, a thermosensitive flocculant, P(DAC-NIPAM), was prepared via one-step method. It was investigated that the relationship between the various functional groups of P(DAC-NIPAM) and its flocculation performances in the treatment of simulated water containing levofloxacin, tetracycline, colloidal particles and natural organic matters. The removal mechanisms were discussed. The results indicated that the rich cationic, hydrophilic and hydrophobic groups of P(DAC-NIPAM) enhanced the interaction between flocculants and pollutants. The bridging of P(DAC-NIPAM) among micelles, charge neutralization, hydrogen bond between P(DAC-NIPAM) and two antibiotics, the shrinkage of P(DAC-NIPAM) molecule and enhancement of hydrophobicity when water temperature was above low critical solution temperature (LCST), co-flocculation and co-settlement of multiple pollutants all contributed to the efficient removal of levofloxacin and tetracycline from water. Flocculation simulation further confirmed that thermosensitive flocculant combined with heating plates was a potential candidate for antibiotic treatment in actual water treatment plants. [ FROM AUTHOR]

Insight into core -shell microporous zinc silicate adsorbent to eliminate antibiotics in aquatic environment under the COVID-19 pandemic.

Under the new crown pneumonia (COVID-19) epidemic, the intensive use of therapeutic drugs has caused certain hidden danger to the safety of the water environment. Therefore, the core-shell microporous zinc silicate (SiO2@ZSO) was successfully prepared and used for the adsorption of chloroquine phosphate (CQ), tetracycline (TC) and ciprofloxacin (CIP) for eliminating the threat of COVID-19. The adsorption efficiencies of 20 mg L-1 of CQ, TC and CIP by SiO2@ZSO were all up to 60% after 5 min. The adsorption capacity of SiO2@ZSO for CQ, TC and CIP can reach 49.01 mg g-1, 56.06 mg g-1 and 104.77 mg g-1, respectively. The adsorption process is primarily physical adsorption, which is heterogeneous, spontaneous and preferential. Moreover, the effects of temperature, pH, salinity, and reusability on the adsorption of CQ, TC, and CIP on SiO2@ZSO were investigated. The adsorption mechanism mainly involves electrostatic attraction, partitioning and hydrogen bonding, which is insightful through the changes of the elements and functional groups before and after adsorption. This work provides a solution to the problems faced by the treatment of pharmaceuticals wastewater under the COVID-19 epidemic.

Community-acquired Methicillin-resistant Staphylococcus aureus Pneumonia and Parapneumonic Effusion in a Male Patient with Diabetes: A Case Report

Methicillin-resistant Staphylococcus aureus (MRSA) infections are a primary health concern. They are commonly differentiated as hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) and community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, based on their epidemiology, susceptibility findings, and molecular typing patterns. Therefore, appropriate contact precautions and isolation measures should be implemented. CA-MRSA mostly causes skin and soft-tissue infections, but the probability and incidence of it causing sepsis and invasive infections have increased dramatically in recent years. In this study, we report a case of CA-MRSA pneumonia with pan-pneumonic effusion in a 59-year-old male diabetic patient with preexisting comorbidities such as diabetic ketoacidosis and non-ST elevated myocardial infarction. The early reporting of the organism's identity and its antimicrobial susceptibility, as well as timely initiation of antibiotic therapy, aided in the successful management and cure of the patient.

TULAREMIA PRESENTING AS LARGE GI ULCERATION AND HEMORRHAGE

SESSION TITLE: Critical Care Infections SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Francisella tularensis is a zoonotic disease by an aerobic, gram negative coccobacillus. It is transmitted by exposure to infected animal or vectors in individuals who landscape or camp. Common symptoms are fever, chills, anorexia, and headache. Abdominal tularemia can present with abdominal pain, emesis, diarrhea, and rarely intestinal ulceration and hemorrhage. It is treated with aminoglycosides, fluoroquinolones and tetracycline. CASE PRESENTATION: 38-year-old male presented with fever, cough, anorexia, and black stool for 5 days. Patient worked as a landscaper. He has no pets, travel history or sick contacts. He does not take any medications at home. Physical exam was significant for sinus tachycardia and rhonchi of right upper lobe. Significant labs include WBC of 9.8 with 41% bands, hemoglobin 15.5, sodium 125, procalcitonin 27.3, and lactic acid 1.8. COVID-19, MRSA, Legionella and Pneumococcal urine antigen were negative. CTA chest revealed mass-like opacity in right upper lobe with multiple bilateral pulmonary nodules. Lower respiratory culture showed Candida albicans. Patient was empirically started on ceftriaxone and azithromycin. He was transferred to intensive care for worsening respiratory status and was placed on non-invasive ventilation on hospital day 1. Antibiotics were broadened to ceftaroline and levofloxacin due to suspicion of tularemia. Amphotericin B was added. Labs for Histoplasma, Blastomyces, TB, Leptospira, and HIV were negative. Patient then suffered a cardiac arrest on hospital day 2 after having large brown secretions pouring from his mouth. Cardiopulmonary resuscitation was initiated and patient was intubated and started on vasopressors with return of spontaneous circulation. Massive blood transfusion protocol was initiated. Emergent bedside upper endoscopy showed large blood clot adherent to duodenal ulcer. Interventional radiology planned on performing gastric duodenal artery embolization. However, patient suffered two more cardiac arrest with resuscitation efforts terminated per family request. Karius Digital Culture later was positive for Francisella tularensis. Autopsy revealed diffuse alveolar hemorrhage, hilar lymphadenopathy, and perforated duodenal ulceration with large adherent clot. DISCUSSION: Gastrointestinal tularemia is rare and usually from drinking contaminated water or oral inoculation of bacteria. Intestinal tract involvement can present with mesenteric lymphadenopathy and ulcerative lesions resulting in gastrointestinal bleeding with case fatality rate of 50%. Even though this is noted in the literature, to our knowledge no case reports have been published. CONCLUSIONS: Careful history taking and early identification of risk factors are important when severe tularemia infection is suspected such as in individuals with extensive outdoor activities. Treatment should be empirically initiated in high risk patients. Reference #1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585636/ Reference #2: https://casereports.bmj.com/content/2017/bcr-2017-22125. Reference #3: Altman GB, Wachs JE. Tularemia: A pathogen in nature and a biological weapon. Aaohn Journal. 2002 Aug;50(8):373-9. DISCLOSURES: No relevant relationships by Maria Haider Baig

A CASE OF BORDETELLA BRONCHISEPTICA AND PNEUMOCYSTIS JIROVECI PNEUMONIA IN A YOUNG PATIENT

SESSION TITLE: Procedures in Chest Infections Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Pneumonia is a common condition that is seen in hospitals. Pneumocystis Jirovecii is an opportunist fungal pathogen. Bordetella bronchiseptica is a gram negative bacteria that causes infectious bronchitis in dogs and other animals, but rarely infects humans. CASE PRESENTATION: Patient is a 34 year old African American female with history of sickle cell trait, reported Lupus (not on treatment), asthma, COVID pneumonia who was admitted for worsening shortness of breath & productive cough with yellow sputum. She was previously hospitalized and discharged after being treated for Community-Acquired Pneumonia. In the ER, she was febrile, tachycardic, tachypneic, & hypoxic requiring BiPAP. CXR obtained showed findings concerning for multifocal pneumonia. Chest CT Angiogram was negative for PE. Patient was started on Vancomycin & Meropenem for treatment of her pneumonia. Blood cultures, Legionella, Strep pneumoniae, Aspergillus, Beta-D-glucan, Sputum culture, & MRSA screen were ordered for further evaluation of her infection. ANA screen reflex panel, lupus anticoagulant, anticardiolipin antibodies, beta-2 glycoprotein antibodies were also ordered given patient's reported history of SLE and the concern for SLE pneumonitis: ANA & Sjogren's Anti-SSA were positive;otherwise, autoimmune workup was unremarkable. During hospitalization, patient was eventually weaned down to nasal cannula and antibiotic was de-escalated to levaquin. However, sputum culture eventually grew Bordetella Bronchiseptica that was resistant to Levaquin so antibiotic regimen was switched to Doxycycline. In addition, Beta-D-glucan was noted to be elevated. Bronchoscopy was done for further evaluation;multiple transbronchial biopsies were positive Pneumocystis Jirovecii. Patient was then initiated on Bactrim for treatment of PJP Pneumonia along with a steroid taper. Patient was tested for HIV and it was negative. DISCUSSION: In this case, patient was found to have two rare pathogens, that are more common in immunocompromised patients such as those with HIV/AIDS, on high-dose corticosteroids or malignancy. This patient had a unconfirmed diagnosis of SLE and past COVID Pneumonia. Patient had Bordetella bronchiseptica pneumonia that is frequently isolated in the respiratory tract of animals but can cause severe respiratory infection in humans. This microorganism can cause upper respiratory tract infections, pneumonitis, endocarditis, peritonitis, meningitis, sepsis and recurrent bacteremia. Upon further discussion with the patient, she was found to have a recent pet dog. CONCLUSIONS: High level of clinical suspicious is needed in patient presenting with recurrent pneumonia with chest imaging findings suggestive of multifocal pneumonia. The mainstay of treatment for PJP is TMP-SMX and steroid. We recommend Fluoroquinolones or tetracycline for Bordetella bronchiseptica pneumonia. Reference #1: Benfield T, Atzori C, Miller RF, Helweg-Larsen J. Second-line salvage treatment of AIDS-associated Pneumocystis jirovecii pneumonia: a case series and systematic review. J Acquir Immune Defic Syndr. 2008 May 1;48(1):63-7. Reference #2: de la Fuente J, Albo C, Rodríguez A, Sopeña B, Martínez C. Bordetella bronchiseptica pneumonia in a patient with AIDS. Thorax. 1994 Jul;49(7):719-20. doi: 10.1136/thx.49.7.719. PMID: 8066571;PMCID: PMC475067. DISCLOSURES: No relevant relationships by Priya George No relevant relationships by ELINA MOMIN No relevant relationships by Mohammedumer Nagori

TIGECYCLINE INDUCED ACUTE PANCREATITIS: A RARE CASE PRESENTATION

CASE: An 81-year-old female with multiple co-morbidities including recent covid-19, presented to the emergency room with shortness of breath. On arrival, she was febrile with a temperature of 101F, pulse 100 beats/min, respiratory rate 14, blood pressure 196/163 and saturating at 75% on 10 L non-rebreather mask. Initial blood work showed WBC 10.9, lactic acid 1.7, BUN/creatinine 27/1.7 (consistent with her baseline), ABG showed pH 7.37, PCO2 49, PO2 88, HCO3 27.9. Chest x-ray demonstrated volume loss in the left hemithorax, airspace disease in the left mid lung and lung base. Due to suspicion for superimposed bacterial pneumonia and positive blood cultures for staphylococcus haemolyticus, she was started on vancomycin and azithromycin. Choice of antibiotics was challenging as she was allergic to penicillin and cephalosporins. During hospitalization, her kidney function deteriorated, vancomycin was substituted with tigecycline on day 3. Day 5 of treatment, she developed multiple episodes of vomiting with epigastric pain, lipase was 4523. Acute pancreatitis was diagnosed with tigecycline presumed to be the inciting agent in the absence of other risk factors such as gall stones, chronic alcohol use, elevated triglycerides, previous known episodes of pancreatitis or any other causative medications. Tigecycline was switched back to vancomycin and she received aggressive IV fluid hydration which also improved her kidney function. Within 48 hours, the patient had improved oxygen saturation, resolution of her abdominal pain, and good oral intake marking significant overall clinical progress. She was discharged on home oxygen and few more days of IV vancomycin for bacteremia. IMPACT/DISCUSSION: Tigecycline is a broad-spectrum glycylcycline antimicrobial agent belonging to the tetracycline class of antibiotics. Tetracyclines have been associated with acute pancreatitis in literature, and concerns about tigecycline-induced acute pancreatitis have been raised over the past decade in post marketing surveys, we described one such case above. Using the Naranjo Adverse Drug reaction probability scale, a score of 6 was achieved, indicating that the patient's pancreatitis was probably related to tigecycline. CONCLUSION: We recommend physicians monitor patients for signs and symptoms of pancreatitis including abdominal pain after initiating treatment with tigecycline. There should be a low threshold for ordering lipase levels and abdominal CT imaging where indicated. If the patient has symptoms concerning for acute pancreatitis, consider stopping tigecycline and switching to a different class of antibiotics immediately.

UPPER RESPIRATORY TRACT BACTERIAL INFECTION FOR POST COVID-19 PATIENTS

This study was conducted in the College of Medicine, Wasit University Cooperation with the Al Zahraa Teaching Hospital, Al Kut Hospital laboratory in Wasit, Al-Karama hospital and private clinics of internal from the period of November 2020 to April 2021. It has been carried out on 150 samples of nasal and throat swabs from post COVID-19 patients who suffered from nasal and throat infection from both sex (male &female). The infections were in age group between (4-88) years. The results of throat swabs showed that 84(56%) were infected with bacteria and 66(44%) non-infected and the results of nasal swabs showed that 67(44.66%) were infected with bacteria and 83(55.33%) non-infected. The results of culture appeared that from 150 throat swab sample found that 66(44%) samples were no growth and 84(56%) were infected with bacteria. The results were Pseudomonas aeruginosa 12/150(8%), E. coli 9/150(6%), Enterobacter spp. 2/150(1.33), Pseudomonas spp. 2/ 150(1.33%), Klebsiella spp. 2/150(1.33%), Staphylococcus spp. 4/150(2.66%), Staphylococcus aureus 4/150(2.66%), Streptococcus viridans 43/150(28.66%) and mix of Staphylococcus spp. and Streptococcus viridans 6/150(4%). Out of 150 nasal swab sample found that 83/150(55.33%) sample were no growth and 67/150(44.67%) were infected with bacteria. The result were Pseudomonas aeruginosa 7/150(4.66%), E.coli 3/150(2%), Enterobacter spp. 2/150(1.33), Pseudomonas spp. 5/ 150(3.33%), Klebsiella spp. 6/150(4%), Staphylococcus spp. 12/150(8%), Staphylococcus aureus 3/150(2%), Streptococcus viridans 24/150(16%) and mix of Staphylococcus spp. and Streptococcus viridans 3/150(5.33%) and mix of E. coli and Pseudomonas spp. 2/150(1.33%). Antimicrobial sensitivity for Pseudomonas aeruginosa showed sensitivity to Amikacin (100%), levofloxacin (90%), Meropenem (90%), Cefipime (70%), Imipenem (60%), Aztreonam (30%), Chloramphenicol (5%), and don’t show sensitive to Tetracycline, Pipracillin, Ampicillin, Trimethoprim-Sulphamethoxazole and Clarithromycin. To facilitate species identification, used molecular methods (PCR analysis) by 16s rRNA primers gene for more predominant bacteria isolates (Pseudomonas aeruginosa) isolates studied were detected by 16S rRNA gene and there virulence factors based on multiplex polymerase chain reaction technique amplifying five virulence factors primer for Pseudomonas aeruginosa (aprA, filC, toxA, pilA, pslA). In this study, we concluded that the production of virulence factors genes in Pseudomonas aeruginosa is important to human infection especially (ToxA) gene and the PCR technique was very specific and fast method in detection virulence factor genes in Pseudomonas aeruginosa.

Impact of telehealth appointments on pharmaceutical management of dermatological conditions

The impact of the COVID-19 pandemic caused dermatology providers to use telemedicine to safely arrange clinic appointments during lockdowns. This study aimed to evaluate the impact of telehealth on antibiotic prescription length. Specifically, we sought to compare antibiotic length prescription for virtual vs. in-person visits before, during, and after COVID-19 shutdowns. A retrospective cohort study was performed using all documented pharmaceutical prescriptions of tetracycline in 2019-2021 prescribed by dermatology providers at a large academic tertiary referral center. Results show an increase in telemedicine visits from 0.75% (2019) to 18.51% (2020), with a decrease to 3.98% in 2021 (p<0.0001). Analysis demonstrates that a tetracycline prescription of over 91 days was given in 37.90% vs. 28.83% of visits for virtual vs. in-person visits respectively (p<0.0001). Interestingly, 52.64% of antibiotic prescriptions written by staff physician dermatologists exceeded 91 days vs. 18.18% for dermatology fellows, 25.74% for resident physicians, and 21.35% for physician-assistants (p<0.001). The demonstrated increase in duration of tetracycline prescription during virtual visits is perhaps indicative of less data available for clinical decision-making, longer wait times between provider appointments during this era of lockdowns, and providers desire to make the visit worthwhile. Future studies should explore factors related to provider decision-making in virtual compared to in-person visits. This research is important in laying a foundation for how virtual visits may play a greater role in dermatologic care as we move towards a post-COVID world.

Fluorescence in the Sclera, Nails, and Teeth Secondary to Favipiravir Use for COVID-19 Infections

Favipiravir, an antiviral agent originally used for influenza infections, has become popular due to its beneficial signals in coronavirus disease. It is currently used in some countries within COVID-19 treatment protocols. This is an initial report of favipiravir-related fluorescence observed in three healthcare providers working in the same ward in our hospital. All three individuals had been diagnosed with COVID-19 two months earlier and were treated with favipiravir. None of the three individuals received hydroxychloroquine or tetracyclines. Wood’s light examination led to an incidental discovery of favipiravir-induced fluorescence involving the sclera, nails, and teeth. In all patients, white linear, square, and band-like specks of fluorescence were noticed on the sclera of both eyes, some teeth, and the proximal part of all fingernails and toenails. Exposure of the eyes to the Wood’s light was for a brief duration of 3 to 5 seconds during examination and photodocumentation. Favipiravir might cause bright white fluorescence of nails, sclera, and teeth, detectable by Wood’s light even two months after its cessation.

Physiological response of Simocephalus vetulus to five antibiotics and their mixture under 48-h acute exposure.

Antibiotics, widely known as major environmental xenobiotics, are increasingly being released into ecosystems due to their essential functions in human health and production. During the COVID-19 pandemic waves, antibiotic use increases remarkably in treating bacterial coinfections. Antibiotics were initially expected only to affect prokaryotes, but recent research has shown that they can disturb the biological systems of eukaryotes, especially vulnerable aquatic creatures, through both direct and indirect processes. However, their toxicity to the freshwater cladoceran Simocephalus vetulus, an essential link in the aquatic food web, has never been evaluated. The effects of four fluoroquinolones (ciprofloxacin: CFX, ofloxacin: OFX, gatifloxacin: GFX, delafloxacin: DFX), tetracycline (TET), and a mixture of these medicines (MIX) on S. vetulus thoracic limb rate (TLR) were examined in this study. After S. vetulus was exposed to 20 and 40 mg GFX L-1, 90% and 100% mortality rates were recorded. At 2.5-10 mg L-1, GFX dramatically lowered the TLR of S. vetulus, resulting in a median effective concentration of 9.69 mg L-1. TLRs increased when the organisms were exposed to 10-40 mg L-1 of CFX and 1.25-40 mg L-1 of OFX. However, DFX and TET exposures did not affect TLRs. Exposure to MIX reduced TLR only at 40 mg L-1, suggesting an antagonistic interaction among the five pharmaceuticals. This study demonstrated that S. vetulus physiological responses to antibiotics, even in the same class, are complex and elusive. Beyond a common additive concentration principle, the antagonistic interaction of antibiotic mixture indicates a high level of uncertainty in terms of ecological dangers. We initially introduce S. vetulus to ecotoxicological studies of antibiotics, presenting the species as a low-cost model for physiological investigations of environmental xenobiotics.

Modulatory Effects of Caffeine and Pentoxifylline on Aromatic Antibiotics: A Role for Hetero-Complex Formation.

Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and their impact on antibiotic antibacterial activity. UV-vis spectroscopy, statistical-thermodynamical modeling, and isothermal titration calorimetry were used to quantitatively evaluate xanthine-antibiotic interactions. The antibacterial profiles of xanthines, and xanthine-antibiotic mixtures, towards important human pathogens Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter cloacae were examined. Caffeine and pentoxifylline directly interact with ciprofloxacin and tetracycline, with neighborhood association constant values of 15.8-45.6 M-1 and enthalpy change values up to -4 kJ·M-1. Caffeine, used in mixtures with tested antibiotics, enhanced their antibacterial activity in most pathogens tested. However, antagonistic effects of caffeine were also observed, but only with ciprofloxacin toward Gram-positive pathogens. Xanthines interact with aromatic antibiotics at the molecular and in vitro antibacterial activity level. Given considerable exposure to caffeine and pentoxifylline, these interactions might be relevant for the effectiveness of antibacterial pharmacotherapy, and may help to identify optimal treatment regimens in the era of multidrug resistance.

Tetracycline as an inhibitor to the SARS-CoV-2.

The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains an extant threat against public health on a global scale. Cell infection begins when the spike protein of SARS-CoV-2 binds with the human cell receptor, angiotensin-converting enzyme 2 (ACE2). Here, we address the role of tetracycline as an inhibitor for the receptor-binding domain (RBD) of the spike protein. Targeted molecular investigation show that tetracycline binds more favorably to the RBD (-9.40 kcal/mol) compared to doxycycline (-8.08 kcal/mol), chloroquine (-6.31 kcal/mol), or gentamicin (-4.83 kcal/mol) while inhibiting attachment to ACE2 to a greater degree (binding efficiency of 2.98 kcal/(mol nm2 ) for tetracycline-RBD, 5.16 kcal/(mol nm2 ) for doxycycline-RBD, 5.59 kcal/(mol nm2 ) for chloroquine-RBD, and 7.02 kcal/(mol nm2 ) for gentamicin-RBD. Stronger inhibition by tetracycline is verified with nonequilibrium PMF calculations, for which the tetracycline-RBD complex exhibits the lowest free energy profile along the dissociation pathway from ACE2. Tetracycline binds to tyrosine and glycine residues on the viral contact interface that are known to modulate molecular recognition and bonding affinity. These RBD residues also engage in significant hydrogen bonding with the human receptor ACE2. The ability to preclude cell infection complements the anti-inflammatory and cytokine suppressing capability of tetracycline; this may reduce the duration of ICU stays and mechanical ventilation induced by the coronavirus SARS-CoV-2.

Tetracycline plus macrolide: A potential therapeutic regimen for COVID-19?

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that struck in late 2019 and early 2020 is a serious threat to human health. Since there are no approved drugs that satisfactorily treat this condition, all efforts at drug design and/or clinical trials are warranted and reasonable. Drug repurposing is a well-known strategy that seeks to deploy existing licensed drugs for newer indications and that provides the quickest possible transition from the bench to the bedside to meet therapeutic needs. At present, several existing licensed drugs such as chloroquine, hydroxychloroquine, methylprednisolone, dexamethasone, and remdesivir have been used because of their potential efficacy in inhibiting COVID-19. Recently, antibiotics such as tetracyclines and macrolides have been reported to be effective against COVID-19. A combination of tetracyclines and macrolides may be a potential treatment for COVID-19 because there are some differences in the mechanism of action of tetracyclines and macrolides.

Combining hydroxychloroquine and minocycline: potential role in moderate to severe COVID-19 infection.

INTRODUCTION: Patients with moderate to severe COVID-19 infection require specific drugs to prevent the morbidity and mortality. Hydroxychloroquine (HCQ) has shown some promise in the management of COVID 19. Minocycline, because of its anticytokine and other useful properties can be an ideal candidate for combining with HCQ. AREAS COVERED: Here we review the need and mechanisms and reasons for combining HCQ and minocycline moderate to severe COVID-19 infection. We also reviewed the advantages, potential safety concerns and precautions to be taken, while combining HCQ and minocycline. EXPERT OPINION: Combining HCQ and minocycline offers many advantages in the management of moderate to severe COVID-19 infection. Both drugs are cheaper, widely available and long-term safety data and contraindications are well known. We do not recommend this combination for prophylaxis or use in asymptomatic or mild disease patients as this can lead to unnecessary safety concerns. Additive antimicrobial and anticytokine effects of both drugs may reduce the morbidity and mortality among patients with COVID-19 and may act as a cheaper alternative to the costlier drugs, however, thorough clinical research is warranted. We call upon public and private healthcare bodies to come up with large well-designed clinical studies for generating evidence-based recommendations.

In silico identification of widely used and well-tolerated drugs as potential SARS-CoV-2 3C-like protease and viral RNA-dependent RNA polymerase inhibitors for direct use in clinical trials.

Despite strict measures taken by many countries, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be an issue of global concern. Currently, there are no clinically proven pharmacotherapies for coronavirus disease 2019, despite promising initial results obtained from drugs such as azithromycin and hydroxychloroquine. Therefore, the repurposing of clinically approved drugs for use against SARS-CoV-2 has become a viable strategy. Here, we searched for drugs that target SARS-CoV-2 3C-like protease (3CLpro) and viral RNA-dependent RNA polymerase (RdRp) by in silico screening of the U.S. Food and Drug Administration approved drug library. Well-tolerated and widely used drugs were selected for molecular dynamics (MD) simulations to evaluate drug-protein interactions and their persistence under physiological conditions. Tetracycline, dihydroergotamine, ergotamine, dutasteride, nelfinavir, and paliperidone formed stable interactions with 3CLpro based on MD simulation results. Similar analysis with RdRp showed that eltrombopag, tipranavir, ergotamine, and conivaptan bound to the enzyme with high binding free energies. Docking results suggest that ergotamine, dihydroergotamine, bromocriptine, dutasteride, conivaptan, paliperidone, and tipranavir can bind to both enzymes with high affinity. As these drugs are well tolerated, cost-effective, and widely used, our study suggests that they could potentially to be used in clinical trials for the treatment of SARS-CoV-2-infected patients.Communicated by Ramaswamy H. Sarma.