Anti-Infective Agents - Volume 22, Issue 4, 2024

Corynebacterium diphtheriae is a Gram-positive, rod-shaped, nonmotile bacillus. Lysogenic strains carry the diphtheria toxin gene (tox) on corynebacteriophages. It's categorized into biotypes and lysotypes based on colony morphology and phage sensitivity. The disease involves the upper respiratory tract, causing symptoms like fever and painful throat, with severe cases forming airway-blocking pseudomembranes [1-3]. Different types of diphtheria exist; incomplete immunization and poor healthcare facilities increase the risk. Diphtheria is treated with diphtheria antitoxin administered intravenously or intramuscularly, along with antibiotics. Timely treatment improves outcomes and reduces transmission. Lifetime immunity is achieved through a three-dose primary series during infancy and booster shots during childhood and adolescence [4]. Since epidemiological week 26, concluding on July 2, 2023, Nigeria has witnessed a significant surge in diphtheria cases spanning multiple states. Between June 30 and August 31, 2023, 5,898 suspected cases were documented across 59 Local Government Areas (LGAs) in 11 states. In week 34, ending on August 27, 2023, 234 suspected cases were reported from 20 LGAs in five states, with one laboratory-confirmed case out of 22 samples collected. Among these cases, 18 were linked through epidemiological analysis, and 141 were categorized as clinically compatible [5]. Diphtheria incidence has decreased due to widespread DTaP vaccination in children, but declining childhood immunity necessitates booster shots. Recent outbreaks in some nations emphasize the need to maintain high vaccination rates. In Nigeria, a 2022 outbreak resulted in over 600 tragic deaths and around 14,000 suspected cases, a stark contrast to the 2011 outbreak with only 98 reported cases [6]. In response to the ongoing diphtheria outbreak in Nigeria, the country has implemented several strategies and precautions to combat the disease. Here are the key measures being taken.

Respiratory failure and increasing hypoxia in the era of coronavirus infection is the cause of fatal outcomes in patients with SARS. The bronchoalveolar obstruction prevents the normal passage of air, resulting in decreased oxygenation. The available methods of oxygenation (ECMO) are often not cost-effective and are not readily available in pandemic settings. Hence, the search for alternatives has prompted the discovery of a new pharmacological group - pyolytics, the use of which is very promising due to its simplicity and availability.

Objective: This policy report aimed at two goals, that is, to report the findings of the literature review and explore the perceptions of the key stakeholders in seeking better insight into the antimicrobial stewardship program (AMSP), and to develop antimicrobial resistance (AMR) policy recommendations for the Ministry of Health and Family Welfare (MoHFW), India, based on the findings from the rapid systematic review of the literature (both published and grey) and the views of key stakeholders. Methods: A mixed method approach using literature review and qualitative interviews has been applied. A rapid systematic literature review focusing on the antimicrobial stewardship program's key achievements and its implementation and impact, implementation challenges, gaps and barriers, and opportunities, has been carried out, which has been followed by conducting interviews of key stakeholders and reporting the findings along with the recommendations. Results: The findings have shown significant progress towards AMSP, such as expanding to 90 secondary-level hospitals and district-level hospitals/nursing homes, and the Indian Council of Medical Research antimicrobial resistance surveillance and research network (ICMR AMRSN) program. Education, training, and microbiological testing have been found to be the current focus areas. However, there exist challenges, including a lack of leadership support, diagnostic stewardship, and staffing of clinical pharmacists and infectious control nurses. Key gaps and barriers identified include setting up microbiology laboratories and hiring ICN nurses and clinical pharmacists. Opportunities have also been identified. Based on these findings, we have made succinct recommendations to address the themes and issues identified. Conclusion: Without new medicines, India will struggle to manage antimicrobial resistance. This situation calls for national oversight. This study has demonstrated AMSP as crucial for fighting this silent pandemic. The Indian government and policymakers must swiftly address critical challenges, gaps, and opportunities. These findings and recommendations might potentially strengthen the future antimicrobial resistance national action plan (AMR NAP).

Antimicrobial resistance (AMR) is a major public health concern worldwide. It raises morbidity and mortality and is connected with substantial/significant economic costs. Effective prevention and treatment of an increasing number of diseases caused by pathogens that can no longer be treated with conventional drugs are threatened by antimicrobial resistance. AMS programme helps to encourage the appropriate use of antimicrobials. The rise and spread of antibiotic resistance and strategies to combat it are the main topics of this review. Antimicrobial stewardship programme is a healthcare strategy that optimizes the use of antibiotics and promotes the appropriate use of antimicrobials through the adoption of evidencebased interventions. AMS programme helps to encourage the right use of antimicrobials. This coordinated approach enhances patient outcomes, reduces microbial resistance, and slows the spread of diseases brought on by multidrug-resistant organisms. The growth of antibiotic resistance and the strategies for battling it have been the main topics of this review.

Background: Biflavonoids are natural phytocompounds that received enormous attention in various remedies due to their diverse biological activities. Biflavonoids have antiinflammatory, anti-leishmanial, anti-plasmodial, anti-viral and β-secretase inhibitory activity in medicine. Ochnaflavone is a biflavone class natural phytochemical isolated from plants belonging to the Ochnaceae family. Methods: Scientific information on ochnaflavone was collected and analyzed in the present investigation to investigate the biological activities of ochnaflavone. The present paper describes the pharmacological activities and bioanalytical aspects of ochnaflavone based on the available scientific research on ochnaflavone in research work, books and other literature databases. Scientific data on ochnaflavone were collected from various scientific databases (Google, Science Direct, Scopus and PubMed) in this paper in order to investigate the health-beneficial potential of ochnaflavone in medicine. Further, the pharmacological activity of ochnaflavone was also collected in a detailed manner and discussed here in order to know the health-beneficial aspects of ochnaflavone. Results: The therapeutic importance of ochnaflavone has been summarized in the present paper through available literature data on ochnaflavone in the scientific fields. Ochnaflavone was found to be an active phytochemical of Campylospermum excavatum, Cespedesia spathulata, Godoya antioquiensis, Lonicera japonica, Lonicerae Japonicae, Ochna afzelii, Ochna beddomei, Ochna beddomi, Ochna integerrima, Ochna kibbiensis, Ochna pretoriensis, Ochna squarrosa Linn., Selaginella trichoclada and Triclisia gilletii. Scientific data revealed the biological importance of ochnaflavone for its effectiveness on inflammation, SARS-CoV-2, fungal arthritis, enzymes, mutagenic effect, lymphocyte proliferation, and inhibition of arachidonate release. However, its antimycobacterial activity, cytotoxic effect, anti-HIV-1 activity, and antioxidant potential were also presented in this work. Further, analytical data on ochnaflavone has also been described. Conclusion: The present paper describes the therapeutic role of ochnaflavone in human disorders with their analytical aspects.

Background: The outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) resulted in a widespread pandemic. Various approaches involved the repositioning of antiviral remedies and other medications. Several therapies, including oral antiviral treatments, represent some approaches to adapting to the long existence of the COVID-19 pandemic. In silico studies provide valuable insights throughout drug discovery and development in compliance with global efforts to overcome the pandemic. The main protease is an essential target in the viral cycle. Computer-aided drug design accelerates the identification of potential treatments, including oral therapy. Aims: This work aims to identify potential SARS-CoV-2 main protease inhibitors using different aspects of in silico approaches. Methods: In this work, we conducted a hierarchical virtual screening of SARS-CoV-2 main protease inhibitors. A similarity search was conducted to screen molecules similar to the inhibitor PF-07321332. Concurrently, structure-based pharmacophores, besides ligand-based pharmacophores, were derived. A drug-likeness filter filtered the compounds retrieved from similarity search and pharmacophore modeling before being subjected to molecular docking. The candidate molecules that showed higher affinity to the main protease than the reference inhibitor were further filtered by absorption, distribution, metabolism, and excretion (ADME) parameters. Results: According to binding affinity and ADME analysis, four molecules (CHEMBL218022, PubChem163362029, PubChem166149100, and PubChem 162396459) were prioritized as promising hits. The compounds above were not reported before; no previous experimental studies and bioactive assays are available. Conclusion: Our time-saving approach represents a strategy for discovering novel SARS-CoV- 2 main protease inhibitors. The ultimate hits may be nominated as leads in discovering novel SARS-CoV-2 main protease inhibitors.

Background: Hospital-acquired infections, also known as nosocomial infections, affect thousands of patients worldwide. In Algeria, these infections raise significant concerns and give rise to numerous questions due to hygiene deficits and non-compliance with preventive measures. Objective: The main objective of this study was to investigate the antibacterial and antifungal properties of Origanum vulgare, Lavandula officinalis, and Syzygium aromaticum, as well as their combinations, to discover new antibacterial and antifungal agents to combat nosocomial infections related to hospital and medical care environments. Materials and Methods: Essential oils were obtained by a Clevenger-type apparatus and analyzed using GC and GC/MS. The antimicrobial and antifungal activity was tested against several bacteria responsible for nosocomial infections in in-vitro tests using the gas contact method in sealed containers. Results: The essential oil extracted from S. aromaticum buds was primarily composed of eugenol (59.4%), E-β-caryophyllene (16.5%), and eugenyl acetate (10.5%). The analysis of the chemical composition of L. officinalis essential oil identified 1,8-cineole (22.8%), β-pinene (12.4%), and linalool (8.5%) as the main compounds. As for O. vulgare essential oil, its major components were carvacrol (72.6%) and thymol (10.5%). The results revealed that the essential oils of L. officinalis, O. vulgare and S. aromaticum, as well as their combinations, used at a concentration of 1/10, had a remarkable effect on the E. coli, P. aeruginosa and K. pneumoniae strains. In contrast, they had a limited effect on the Gram-positive strain, S. aureus. The antifungal effectiveness of the essential oil of O. vulgare, as well as the combination of O. vulgare and S. aromaticum, has been remarkable against the C. albicans species, leading to a complete inhibition of yeast growth. Conclusion: Our results indicate that our essential oils have a broad spectrum of antimicrobial activity, which makes them particularly useful as disinfectants in health facilities and could be used as a valuable medicine to control nosocomial infections and avoid infections acquired during a stay in a health facility such as respiratory tract infections and urinary tract infections.

Background: During COVID-19 pandemic a major conflict facing the clinician where to prove cure of the patients. Aims: The idea of confirming curability is based on clinical evaluation of the symptoms, laboratory investigations, and specific IgM, IgG anti-SARS-CoV-2 antibodies. Materials and Methods: All patients had presented with clinical features of COVID-19 positive PCR attended private clinic doctors consultant in internal medicine and infectious diseases, they did investigations in Lagash land private medical laboratory in Baghdad investigated and screened for COVID-19 by S. ferritin, D-dimer, Complete blood picture and LDH. All were reevaluated in the first month of infection by clinical examination, retesting, and screening for COVID-19 IgM IgG later to prove cure or evidence of viral infection in PCR negative cases. Results: All patients are of different ages with maximum years affected from adulthood till the age of one hundred years. Male were 170(54.3%) patients and females were 143 (45.7%) total 313 patients (100%). Most are moderate socioeconomic status, with a significant number having comorbidities. Conclusion: SARS-COVID-19 IgM, IgG levels can be used to confirm a cure of the infection.

Background: In recent times, there has been incontrovertible evidence regarding the propensity of various bacteria that barge through the immune system of an already debilitated individual. In this regard, combination therapy presents us with a more effective approach than conventional monotherapy. A specific combination of antibiotics exhibits a synergistic antibacterial effect, which can be seen with kanamycin, which shows moderate antibacterial activity alone but acts synergistically with particular adjuvants, displaying a high degree of antibacterial activity. Objective: This study aimed to carry out an in vitro evaluation of the interaction between kanamycin and adjuvants against various bacterial species. Methods: The interaction between kanamycin and adjuvants against various bacterial isolates was determined by checkerboard assay, and the synergistic interactions were further evaluated by time-kill kinetic assay under in vitro settings. Results: The interaction between kanamycin and citric acid was found to be synergistic against all strains of E. coli. Both kanamycin and citric reduced their MICs by at least 4 fold in combination. This synergistic interaction was further confirmed by the time-kill kinetic assay. The result of time kill kinetic assay of combination revealed that at MIC, there was a 2.36 log10 CFU/ml reduction compared to kanamycin (the most active antimicrobial agent alone), at 24 hours at 2 fold MIC, 2.41 log10 CFU/ml reduction was seen in comparison to kanamycin at 24 hours at its one fold MIC. For other bacterial species, the combination of citric acid and kanamycin showed additive or indifferent interactions. In the case of our second combination (kanamycin and sodium salicylate), all the bacterial species displayed additive and indifferent interaction. Conclusion: It has been concluded that the combination of kanamycin and citric acid (adjuvant) demonstrated a remarkable synergistic interaction against E. coli.

Aims: The study was aimed to determine the molecular characteristics of extendedspectrum beta-lactamases (ESBL) producing cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolated from children below ten years of age. Background: Geographically diverse variations in the prevalence of ESBL genes were reported. No data were available on the prevalence of ESBL genes in central Kerala, India, among children below 10 years of age. Methods: A cross-sectional study was performed to analyze ESBL genes in cephalosporin-resistant E. coli and K. pneumoniae strains isolated from samples received in the Microbiology laboratory of a tertiary care centre during the period between May 2021 and July 2022. The strains showed that ESBL + cephalosporin resistance was subjected to PCR-based genotyping for the genes such as bla (beta-lactamase) CTX-M-1, blaCTX-M-15, blaCTX-M-U, blaTEM, blaPER and SHV. Results: Among the total 228 samples analyzed, 136 (60%) had no growth. Ninety-two (40 %) samples showed growth of E. coli and K. pneumoniae. Among the isolates that showed growth, 39 (42%) were sensitive, and the remaining 53 (57%) were resistant to third-generation cephalosporins. Among the isolates showed resistance, 22 (42%) were ESBL positive and 31 (58%) were ESBL negative. Among the positive ESBL, nine E. coli strains (60%) were positive for CTX-M-15 and CTX-M-1. CTX-M-15 and CTX-M-U were present in six (85%) K. pneumoniae with ESBL +. Conclusion: E. coli and K. pneumoniae isolated from specimens of children below ten years of age showed 41-42% ESBL producers. Prevalent ESBL-producing genes in E. coli were CTX-M- 15 and CTX-M-1. CTX-M-15 and CTX-M-U were prevalent in ESBL-producing K. pneumoniae.