Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 23, Issue 7, 2023

Remdesivir has appeared to be the most effective medication against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is broadly administered to coronavirus disease 2019 (COVID-19) patients around the world. Remdesivir is an RNA polymerase inhibitor with a broad spectrum of antiviral activities against RNA viruses in in-vitro and in-vivo models of SARSCoV, the Middle East respiratory syndrome (MERS), and SARS-CoV-2. Remdesivir is the first Food and Drug Administration (FDA) approved anti-SARS-CoV-2 treatment for adult and pediatric patients and has been used for not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death. However, questions have been raised about the value of remdesivir in treating COVID-19, and governing bodies worldwide have been hesitant to approve this medication. Nevertheless, in the context of the public health emergency and the urgent need for effective treatments for patients with COVID-19, remdesivir has been approved by several authorities worldwide. Here, we discuss the characteristics and applications of remdesivir, and various challenging studies with different outcomes about its efficacy are also reviewed.

Bacterial Persister Cells (BPCs) are quiescent, slow-growing or growth-arrested phenotypic variants of normal bacterial cells that are transiently tolerant to antibiotics. It seems that persister cells are the main cause of the recurrence of various chronic infections. Stress response (RpoS-mediated), Toxin-Antitoxin (TA) systems, inhibition of ATP production, Reactive Oxygen Species (ROS), efflux pumps, bacterial SOS response, cell-to-cell communication and stringent response (ppGpp- mediated) are the primary potential mechanisms for persistence cell formation. However, eradicating persistent cells is challenging as the specific molecular mechanisms that initiate their formation remain fuzzy and unknown. Here we reviewed and summarized the current understanding of how bacterial persister cells are formed, controlled, and destroyed.

Introduction: Earlier reports described the possibility of higher SARS-CoV-2 infection and severity in patients with hematological malignancies. Given the importance and incidence of these malignancies, we aimed to systematically review SARS-CoV-2 infection and severity in patients with hematologic cancers. Methods: We retrieved the relevant records by searching the keywords in online databases of PubMed, Web of Science, Cochrane, and Scopus on December 31st, 2021. A two-step screening; title/abstract and full-text screening, was employed to select the eligible studies. These eligible studies entered the final qualitative analysis. The study is adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to ensure the reliability and validity of the results. Results: Forty studies concerning different hematologic malignancies and the effect of COVID-19 infection on them were included in the final analysis. The findings showed that in general, the prevalence of SARS-CoV-2 infection and the severity of the disease are often higher in hematologic malignancies and the patients could experience higher morbidity and mortality compared to general populations. Conclusion: It appeared that individuals with hematologic malignancies are more vulnerable to COVID-19 infection and they experience more severe disease with higher mortality rates. The presence of other comorbidities could also deteriorate this situation. Further investigation is recommended to evaluate the outcome of COVID-19 infection in different subtypes of hematologic malignancies.

Background: Recent studies have suggested the role of primary laboratory tests in addition to clinical symptoms for patients suspected to have coronavirus disease 2019 (COVID-19), which play a significant role in the diagnosis of COVID-19. However, the results of these studies are contradictory. The present study was conducted to evaluate biochemical, serological, and immunological tests for the diagnosis of COVID-19 patients. Methods: This study was presented in accordance with the PRISMA protocol. This protocol is registered with the code CRD42019145410 in PROSPERO. We conducted a comprehensive literature search in databases, including Web of Science, PubMed/Medline, CINAHL Scopus, Cochrane Library, EMBASE, Science Direct, and EBSCO to find citations from the beginning of January 2019 until the beginning of April 2020 without any restrictions. Results: Finally, 51 studies, including 5,490 COVID-19 patients, were included in the present metaanalysis. The prevalence of different factors observed in laboratory findings was as follows: the prevalence of lymphopenia in patients with COVID-19 accounted for 51.6% (95% CI: 44.0-59.1), elevated C-reactive protein (CRP) was 63.6% (95% CI: 57.0-69.8), elevated erythrocyte sedimentation rate (ESR) was 62.5% (95% CI: 50.1-73.5), elevated tumor necrosis factor alpha (TNFα) was 28.7% (95% CI: 9.0-62.1), elevated serum amyloid-A level was 74.7% (95% CI: 50.0-89.7), elevated procalcitonin level was 72.6% (95% CI: 58.1-83.5), elevated interleukin-6 level was 59.9% (95% CI: 48.2-70.5), reduced CD3 level was 68.3% (95% CI: 50.1-82.2), reduced CD4 level was 62.0% (95% CI: 51.1- 71.6), elevated lactate dehydrogenase (LDH) level accounted for 53.1% (95% CI: 43.6-62.4), elevated brain natriuretic peptide (BNP) accounted for 48.9% (95% CI: 30.4-67.7), reduced albumin and reduced pre-albumin levels in patients with COVID-19 were estimated to be 54.7% (95% CI: 38.1-70.2) and 49.0% (95% CI: 26.6-71.8), and D-dimer level was 44.9% (95% CI: 31.0-59.6). Conclusion: The results show lymphopenia, elevated ESR level, elevated CRP level, elevated serum amyloid-A, elevated TNFα, elevated procalcitonin level, elevated interleukin-6 level, reduced CD3, reduced CD4, elevated BNP, elevated LDH, reduced albumin, reduced pre-albumin, and elevated Ddimer levels as the most common findings at the time of admission.

Introduction: Toxin–antitoxin systems (TAs) are highly conserved in Mycobacterium tuberculosis (Mtb). The TAs role in maintaining and disseminating drug resistance in bacterial populations has been indicated. So, we aimed to analyze the expression level of mazEF-related genes in drugsusceptible and multidrug-resistant (MDR) Mtb isolates under isoniazid (INH) and rifampin (RIF) stress. Methods: We obtained 23 Mtb isolates, including 18 MDR and 5 susceptible isolates, from the Ahvaz Regional TB Laboratory collection. The expression levels of mazF3, mazF6, and mazF9 toxin genes, and mazE3, mazE6, and mazE9 antitoxin genes in MDR and susceptible isolates were evaluated by quantitative real-time PCR (qRT-PCR) after exposure to RIF and INH. Results: The mazF3, F6, and F9 toxin genes were overexpressed in at least two MDR isolates in the presence of RIF and INH, in contrast to mazE antitoxin genes. More MDR isolates were induced to overexpress mazF genes by RIF than INH (72.2% vs. 50%). Compared to the H37Rv strain and susceptible isolates, the expression levels of mazF3,6 by RIF and mazF3,6,9 by INH were significantly upregulated in MDR isolates (p<0.05), but no remarkable difference was detected in the expression level of mazF9 genes by INH between these groups. In susceptible isolates, the expression levels of mazE3,6 by RIF and mazE3,6,9 by INH were induced and enhanced significantly compared to MDR isolates, but there was no difference between MDR and H37Rv strain. Conclusion: Based on the results, we propose that mazF expression under RIF/INH stress may be associated with drug resistance in Mtb in addition to mutations, and the mazE antitoxins may be related to enhanced susceptibility of Mtb to INH and RIF. Further experiments are needed to investigate the exact mechanism underlying the TA system's role in drug resistance.

Background: Leptotrichia spp. are fastidious facultative anaerobic, pencil-shaped, gramnegative rods that reside in the mouths, intestines, and female genital tracts of humans. Bacteremia and septic shock have been rarely reported in the immunocompromised host. We report a case of L. trevisanii bacteremia in a patient recently diagnosed with acute myeloid leukemia (AML) on chemotherapy. Case Presentation: A 75-year-old male with a history of diabetes, chronic kidney disease, and coronary artery disease status post-CABG presented with neutropenic fevers and signs of sepsis after the initiation of chemotherapy. Blood cultures were ordered and extensive gene sequencing helped identify Leptotrichia trevisanii as the causative pathogen. Subsequently, the patient was successfully treated with empiric cefepime. Discussion: Opportunistic pathogens are involved in a variety of diseases and have been isolated from immunocompromised patients undergoing transplantation or in patients with comorbidities, like leukemia, lymphoma, or neutropenia. L. trevisanii has been reported as a cause of bloodstream infections in patients with hematologic malignancies receiving chemotherapy. Conclusion: This case highlights the key role that Leptotrichia trevisanii plays in the introduction of sepsis among immunocompromised patients, particularly with hematologic malignancies, like AML, on chemotherapy.

HFMD is an obvious disease in children mostly below the age of five constituting a public health challenge to Asian-Pacific and developing countries majorly. This disease is often caused by enterovirus 71 (EV71) and Coxsackievirus A16. HFMD is a mild degree fever and general illness which manifests for about 10 days. Young age, male gender, poor hygiene, and high social contacts are some risk factors. HFMD can be diagnosed clinically by isolating the virus from stool and pharynx and identifying it on Light microscopic examination. Polymerase Chain Reaction Assay is a gold standard for confirming the virus from swabbed lesions. Late confirmation could lead to severe complications. There are no specific treatments and vaccines licensed for general use in the treatment of various serotypes of HFMD. The major strategy to prevent and control this disease is to strictly follow the WHO 8 guidelines to curb the spread of the disease.

Introduction: Giardia lamblia is a neglected parasitic infection that typically affects the developing nations of the world. It is a microscopic intestinal parasite that is known to cause stomach cramps, bloating, nausea and bouts of diarrhoea. Case Presentation: Here, we are presenting the case of a 1.5 years-old-baby with an immunocompromised condition who got infected by Giardia lamblia. The baby with fibrosarcoma was receiving treatment in our tertiary care centre, and later developed abdominal and minor systemic complaints. Stool samples were collected, which showed trophozoites and cysts of Giardia. Discussion: To the best of our knowledge, this is the first case of Giardia lamblia infection in a paediatric patient with fibrosarcoma. The patient improved after taking metronidazole for ten days. Conclusion: It is critical to keep a watch out for this neglected parasite, and suggested samples, particularly stool samples, must be sent for investigation in order to diagnose and manage these cases properly.