Anti-Infective Agents - Volume 19, Issue 3, 2021

The rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics, which have transformed medicine and saved millions of lives. Antibiotic resistance has become a major clinical problem today. In addition, multidrug resistance also develops various structurally and functionally unrelated toxic compounds. To overcome this problem, a new target efflux pump was recognized that, if inhibited, reduces the level of resistance or potentiates or produces a synergistic effect in combination with antibiotics. Keeping this in view, the present review article aims to describe the families of efflux pumps and the various natural components to be employed as good efflux pump inhibitors.

Tuberculosis is an epidemic requiring new molecules with high potency and minimum side effects for its treatment. In the same respect, this review emphasises on important target enoyl-acyl carrier protein reductase or INHA crucial in the completion of the FAS II cycle. INHA has retained its fame since the inception of the drug Isoniazid, as inhibitors have a long residence time hence good activity. One of the causes of the failure of conventional drugs is resistance towards activating or target genes. Here, we propose direct inhibitors that do not need prior activation by Kat G. Some of the categories are Aryl amide, Piperazine, Thiadiazole, Benzamide, etc., that are specifically active against INHA, along with their structure-activity relationship. Many of them are efficient in micromolar concentration, whereas Pyrazole carboxamide is active in nanomolar concentration and derivative of 4-hydroxy pyridones was effective in vivo. Natural products are also in the way to combat tuberculosis. Furthermore, from available proteins of wild and mutant strains, new leads can be designed successfully by utilizing information of co-crystallized ligands.

A novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appeared and expanded globally by the end of the year 2019 from Wuhan, China, causing the severe acute respiratory syndrome. During its initial stage, the disease was called the novel coronavirus (2019-nCoV). It was named COVID-19 by the World Health Organization (WHO) on 11th February, 2020. The WHO declared the SARS-CoV-2 virus a pandemic in March 2020. On 30th January, 2020, the first case of Corona Virus Disease 2019 (COVID-19) was reported in India. Currently, the virus has spread to almost every part of the province and the rest of the globe. On the basis of novel published evidence, we efficiently summarized the reported work with reference to COVID-19 epidemiology, pathogen, clinical symptoms, treatment, and prevention. Several worldwide electronic scientific databases such as Pubmed, Medline, Embase, Science Direct, Scopus, etc., were utilized for extensive investigation of relevant literature. This review is written in the hope of encouraging people with the key learning points from the underway efforts to perceive and manage SARS-CoV-2, suggesting salient points for expanding future research.

The enigmatic coronavirus outburst on December 31, 2019, originated from Wuhan city of China, is now declared as Coronavirus Disease (COVID-19) by the World Health Organization (WHO). The causative agent is highly contagious, and its rapid blowout has affected almost every country of the world, endangering thousands of lives. Recently, the WHO has raised the COVID-19 epidemic threat to the “very high” level. Pathophysiological mechanisms are related to the inter-related functioning of various viral polyproteins, structural proteins as well as Non-Structural Proteins (NSP). These proteins play a crucial role in accelerating pathogenesis by promoting viral replication, viral assembly, and virion release, thereby disabling the overall host distinctive immunological system. Presently, there is no specific treatment for COVID-19. The majority of the treatments focus on symptomatic relief and supportive therapy only. Although several drugs have been investigated against coronavirus in numerous clinical trials, only a few exhibited mild-moderate signs of clinical recovery. Drugs that are being repurposed and researched include an anti-- malarial drug, hydroxychloroquine; anti-HIV drugs, lopinavir, Remdesivir alone, or in combination; anti-influenza drugs like umifenovir, and favilavir; anti-arthritic baracitinib, and anti-interleukins. Various research articles demonstrated the excellent potential of hydroxychloroquine either alone or in combination with anti-HIV drugs lopinavir, and Remdesivir at the cellular level; however, exhaustive clinical support and validation are still desirable for repurposing these drugs. Profound identification of cellular targets involved in disease pathogenesis may warrant successful re-profiling of the candidate drugs or their combinations aiming against COVID-19.

Introduction: Helicobacter pylori eradication remains a problematic issue. We are in an urgent need for finding a treatment regimen that achieves eradication at a low cost and with less side effect. Recent published results have shown a high rate of resistance with clarithromycinbased treatment regimens. The aim of the study was to compare moxifloxacin therapy and classic clarithromycin triple therapy in H. pylori eradication. Methods: This was a pilot study that enrolled 60 patients with helicobacter pylori associated gastritis. Diagnosis was done by assessment of H. pylori Ag in the stool. The patients were randomly assigned to receive either moxifloxacin based therapy (Group A), or clarithromycin based therapy (Group B) for two weeks. We stopped the treatment for another two weeks and then re-evaluation for cure was done. Results: 90% of patients had negative H. pylori Ag in the stool after 2 weeks of stoppage of the treatment in group A versus 66.7% in Group B. None of the patients in both the groups had major side effects. Conclusion: Moxifloxacin-based therapy showed higher eradication power and less resistance when compared to clarithromycin triple therapy.

Background: The emergence of multidrug-resistant uropathogenic strains, mainly the global spread of extended-spectrum beta-lactamase (ESBL) genes accompanied both by the uncontrolled use of antibacterial agents and a considerable decrease in their activities, makes the monitoring of the resistance pattern one of the necessary means that could help the medical practitioners to choose the best treatment. For this purpose and during four months from March 1 to June 30 (2019), an experimental study has been carried out on urine specimens of 123 inpatients (IP) and outpatients (OP) at infectious disease service Boudjemaa TOURABI Public Hospital of Bechar (Algeria), aiming the detection of ESBL-producing Enterobacteriaceae uropathogenic strains. Methods: Firstly, the antibiotic susceptibility testing has been carried out by using the disk diffusion method to determine not only the multidrug resistance patterns, but also the multiple antibiotic resistance MAR indexes of uropathogenic strains that were isolated from clinical IP and OP samples. Secondly, the ESBL detection was done using the following methods: synergy tests based on the synergy between a third-generation cephalosporin and clavulanate, double-disc synergy test (DDST) and phenotypic tests on a cloxacillin-containing agar. Results: As a result, 56 patients had a urinary tract infection (UTI) in overall 123 patients; thus, a frequency of 45,52%. Through a UTI’s frequency of 64,7%, the female gender was the most affected. All age groups were affected by UTI, with a mean age of 38,47±19,97 years old. Knowing that UTIs’ patients aging from 16 to 49 years old were the most affected compared to other ages’ groups, with a frequency of 66,6 and 50% for female and male gender, respectively. The microbial strains represented by the bacteria group were predominant, i.e. (98,22%) followed by yeasts (1,78%), where Gramnegative bacilli showed (96,36%) of the uropathogenic agents, so (3,64%) were Gram-positive bacteria. The antibiotic resistance profile of isolated Enterobacteriaceae showed very high resistance rates for the species of Escherichia coli, Klebsiella spp, and Proteus spp to aminopenicillins, cephalosporins, and less against carbapenems and other drug groups. E. coli had presented the highest multidrug resistance followed by Klebsiella spp with a MAR index ranged from 0,53 to 0,82. Within this range, a total of 28 isolate (25 E. coli, 2 Klebsiella spp, and 1 Proteus mirabilis) had shown resistance against 9 to 14 out of the 17 tested antibiotics. The rate of ESBL-producing Enterobacteriaceae strains was 23,07 and 55,26% for inpatients and outpatients, respectively, where E. coli was the most important ESBL producers out of all isolated strains. Conclusion: An alarming ESBLs rate for outpatients is usually higher among inpatients with UTI, who receive several classes of antibiotics. Such conditions should be considered as a major public health concern, and measures must be taken to establish the sources and drivers of this issue. Thus, the findings of this research push the health sector stakeholders as well as the scientific communities to act on reducing the transmission of the multidrug-resistant strains that threaten several classes of life-saving antibiotics.

Objective: This study was undertaken to evaluate the effect of titanium dioxide (TiO2) nanoparticles (NPs) and methanolic extract of Persian Gulf brown algae (Sargassum oligocystum) on the growth and cell death of T. gondii tachyzoites in vitro and in vivo. Methods: Six- to eight-week-old female BALB/c mice (n = 28) were used for the treatment experiment and infected with 10⁵ T. gondii tachyzoites. Four days after treatment, IFN-γ and the levels of splenic lymphocyte proliferation were measured. All the groups were challenged with T. gondii, and the survival rate of experimental mice was assessed. The effects of TiO2NPs and S. oligocystum on the proliferation of T. gondii were evaluated by MTT and annexin V staining in vitro. Results: Based on the results, the combination of S. oligocystum extract and TiO2NPs exhibited a more cytotoxic effect compared to their use separately. The results of the challenge test also revealed that mice which received combined treatment had the highest life time expectancy than those receiving the treatment alone. Conclusion: The simultaneous use of immunomodulatory compounds for the stimulation of the immune system as well as S. oligocystum and TiO2NPs with antiparasitic activity can be promising to develop an effective drug for the treatment of toxoplasmosis.

Background: Fungal infections have always remained a problem and they are getting worse with the passage of each year due to their resistance against available antibiotics. Natural ways of treatment with homeopathic medicines made of mother tinctures of plants have no reported side effects and have been proved effective against many bacterial and fungal infections. Materials and Methods: Preparation of mother tinctures of plants Cressa cretica, Leptadenia pyrotechnica, and Pulicaria crispa was done and used to evaluate the anti-fungal potential of these plants against potentially pathogenic fungal species like Aspergillus niger, Aspergillus flavus, Aspergillus ustus, and Candida albicans by agar disc diffusion method. Each tincture was evaluated at 0.25 ml, 0.5 ml, and 1 ml volume per disc and zone of inhibition was measured in millimeters and compared with commercial drug Fluconazole (2 mg/ml), which was used as standard. Results: The results showed the satisfactory anti-fungal activity of these plants in comparison to the standard drug Fluconazole. The ratio of anti-fungal activity of Cressa cretica measured as the zone of growth inhibition of these cultures against Aspergillus niger, Aspergillus flavus, Aspergillus ustus, and Candida albicans was 24 mm / 27 mm, 30mm / 28 mm, 23 mm/ 30 mm, and 32 mm/ 30 mm, respectively. In the case of Leptadenia pyrotechnica, the mother tincture’s antifungal activity was 32 mm / 27 mm, 30 mm / 28 mm, 17 mm/ 30 mm, and 24 mm/ 30 mm, respectively. In the case of our third plant Pulicaria crispa, anti-fungal activity was found to be 23 mm/ 27 mm, 26 mm/ 28 mm, 26 mm / 30 mm and 24 mm/ 30 mm, respectively. Conclusion: Our study proved that the mother tincture of these plants could be a potential new therapy to treat fungal infections and has the potential to rule out fungal problems. Further research using the mother tincture of these plants against other fungal species has the potential to prove them a safer and widespread anti-fungal homeopathic medicine.

Background: Coronavirus disease 2019 (COVID-19) is a pandemic disease that has significant implications on the global health burden. Currently, there is no widely accepted pharmacologic treatment for COVID-19. Remdesivir has been shown effective against various types of viruses, including coronaviruses. This study aimed at synthesizing the latest evidence regarding the effectiveness and safety of remdesivir as a potential treatment candidate against COVID-19. Methods: This systematic review has been registered in PROSPERO (CRD42020183707). A systematic search of the literature was conducted in PubMed, PubMed Central, and Google Scholar through June 5th, 2020. Statistical analysis was done by using the Review Manager 5.4 tool. The risk of bias was evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) and GRADE analysis was performed to determine the certainty of the evidence. Results: Two studies with a total of 1,300 patients were included. Meta-analysis showed that remdesivir was associated with faster time to clinical improvement (MD -4.75 days; 95% CI -4.84 days to -4.65 days; p < 0.00001), reduction in mortality rate (RR 0.39; 95% CI 0.27 – 0.56; p < 0.00001) and fewer incidence of serious adverse events (RR 0.77; 95% CI 0.63 – 0.94; p = 0.01). GRADE analysis showed a high certainty for serious adverse events and moderate certainty for time to clinical improvement and mortality rate. Conclusion: Remdesivir is more effective and safer compared with standard care of treatment for the treatment of COVID-19 because it was associated with faster time to clinical improvement, reduction in mortality rate, and fewer incidence of serious adverse events.

The effect of a novel beta coronavirus named SARS-CoV-2 or COVID-19 on pregnancy outcomes and the neonatal prognosis is not fully documented yet. Case Presentation: In this article, we describe a patient presented with frequent seizure and blurred vision 6 days after delivery without symptoms and laboratory data in favor of preeclampsia/eclampsia and evaluations consistent with Posterior Reversible Encephalopathy Syndrome. Also, there was mild clinical and radiological evidence of COVID-19 infection. Conclusion: In conclusion, as pregnancy is a high-risk state, pregnant women may be more vulnerable to severe COVID-19 infection and also pregnancy complications.