Synthesis and evaluation of in vitro anti-microbial and anti-tubercular activity of 2-styryl benzimidazoles

A new series of novel 5-(nitro/bromo)-styryl-2-benzimidazoles (1–12) has been synthesized by simple, mild and efficient synthetic protocol by attempted condensation of 5-(nitro/bromo)-o-phenylenediamine with trans-cinnamic acids in ethylene glycol. Screening for in vitro anti-tubercular activity against Mycobacterium tuberculosis H₃₇ Rv, anti-bacterial activity against Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae bacterial strains and anti-fungal activity against Candida albicans and Asperigillus fumigatus fungal strains were carried out. Compounds 5, 7, 8, 9, 11 showed higher anti-tubercular activity and compounds 7, 8, 10, 11, 12 have proved to be effective with MIC (μg/ml) and emerged as lead molecules showing excellent activities against a panel of microorganisms. All synthesized compounds were characterized using IR, ¹H, ¹³C NMR, GC–MS and elemental analysis.     

Anti-diarrhoeal and anti-microbial activity of Flos populi (male inflorescence of Populus tomentosa Carrière) aqueous extracts

Ethnopharmacological relevance

Flos populi (male inflorescence of Populus tomentosa Carrière) has been traditionally used in East Asian countries for the treatment of various inflammatory diseases, strengthening the spleen and stomach, anti-rheumatic, anti-tumor and anti-diarrhoeal.

Aim of the study

To evaluate the in vivo or in vitro anti-diarrhoeal and anti-microbial activity of Flos populi aqueous extract.

Materials and methods

Acute toxicity of Flos populi aqueous extract (FPAE) was investigated. Castor oil-induced diarrhoea method was used to evaluate the anti-diarrhoeal activity, inhibition of defecation and diarrhoea were determined in mice, effects on castor oil-induced enteropooling, intestinal transit and intestinal fluid secretion in rats or mice. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of FPAE against strains of three clinical bacterial isolates and one reference strain were used to test the anti-microbial activity.

Results

The FPAE reduced the frequency of diarrhoea episodes and decreased the propulsion of charcoal meal through the gastrointestinal tract in a dose dependent manner. FPAE (100–500 mg/kg, p.o.) produced dose-dependent and significant (P<0.01) protection of mice against castor oil-induced diarrhoea. FPAE, dose-dependently and significantly (P< 0.01) delayed the onset of castor-oil induced diarrhoea, decreased the frequency of defecation, and reduced the severity of diarrhoea. Compared with control animals, FPAE, dose-dependently and significantly (P< 0.01) decreased the volume of castor oil-induced intestinal fluid secretion, and reduced the number, weight and wetness of faecal droppings. There was no deaths or abnormalities in behaviour seen in the acute toxicity test. The aqueous extract displayed anti-microbial effects to three species of bacteria in anti-microbial test.

Conclusion

The findings of this study indicate that FPAE possesses anti-diarrhoeal property in rats and mice and confirm the ethnomedicinal use of Flos Populi as a valuable natural remedy for the treatment, management and/or control of diarrhoea. These results may support the fact that this plant is traditionally used to cure diarrhoea.     

Synthesis and anti-microbial activity of some 1- substituted amino-4,6-dimethyl-2-oxo-pyridine-3-carbonitrile derivatives

A new series of 1- substituted amino-4,6-dimethyl-2-oxo-pyridine-3-carbonitrile such as hydrazide hydrazones 3a-h; ethane-1,2-diaminopyridine 6; phthalimidopyridines 8a,b; hydrazides 10a,b; urea 11a and thiourea 11b were synthesized in a good to excellent yield in step efficient process, using 1-amino-4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (1) as a key intermediate. The antibacterial and antifungal activities of the synthesized compounds were evaluated. The obtained data indicated that the majority of the tested compounds exhibited both antibacterial and antifungal activities, particularly compounds 8a and 8b showed a comparable effect to a well known antibacterial and antifungal agents.     

Genotypic characterization of carbapenem resistant Enterobacterales in clinical isolates from western Maharashtra

PurposeTo study distribution of carbapenemase genes namely; New Delhi metallo-beta-lactamase (blaNDM), Oxacillinase-48 (blaOXA48), Verona Integron-Encoded Metallo-beta-lactamase (blaVIM) and Imipenemase (blaIMP) in carbapenem resistant Enterobacterales (CRE), isolated from clinical samples.MethodThis cross-sectional study was conducted at a tertiary care hospital of western Maharashtra over six months period. CREs were identified by conventional disc diffusion and modified carbapenem inactivation method (mCIM). A total of 50 consecutive CRE isolates from clinical samples were subjected to home brewed polymerase chain reaction (PCR) for detection of carbapenemases.ResultsOut of the 50 CRE isolates, at least one of the four carbapenemase genes was detected in 49 (98%) isolates. The frequency of distribution of these genes were NDM 90% (n = 45), OXA48 60% (n = 30) and VIM 12% (n = 6). Dual combination of blaNDM and blaOXA48 (50%) was the commonest pattern observed, which was frequently associated with Klebsiella pneumoniae.ConclusionsThe study indicate high prevalence of NDM warranting strict anti-microbial stewardship practices. Surveillance of CRE and resistance mechanism is essential to monitor the trend and take informed decision for appropriate anti-microbial therapy.     

Breast infections – Microbiology and treatment in an era of antibiotic resistance

IntroductionPrimary breast abscesses occur in <1% of non-lactating women, rising to 11% in women with lactational mastitis. In patients undergoing breast cancer surgery, the inflammatory response to post-operative surgical site infection (SSI) has been implicated in recurrence. Anti-microbial resistance increasingly hampers treatment in each group.AimsDescribe the demographic and predisposing characteristics of patients with primary breast abscesses and secondary infections, identify the microbial and antimicrobial patterns and formulate an evidence-based protocol for treating breast infections.MethodsRetrospective cohort study of all breast infections (primary and post-operative) treated at UHL from 2014 to 2017. Data collected from microbiology databases and patient records was analysed using Minitab V18.Results537 cultures from 108 patients were analysed. 47 (43.5%) had primary abscesses, 12 (11.1%) were lactational and 49 (45.4%) were post-operative SSI. For primary infections, the mean age was 41.9 (±12.2) and reinfection rate 33%. For SSIs the mean age was 51.8 (±14.52) and reinfection rate 11.8%. Overall, 29.3% were smokers, 6.4% diabetic and 2.9% pregnant. 60 (43%) patients required radiological drainage and 2 (1%) surgical drainage. 57.5% had mixed growth. The most common isolate was Staphylococcus aureus; cultured in 16.7% of primary abscesses and 24% of SSIs. 13 empiric antibiotic regimes were prescribed before 26.4% of patients changed to 12 different targeted regimes.ConclusionBreast infections are frequently polymicrobial with a wide variety of organisms isolated, suggesting the need for broad spectrum coverage until culture results become available. Based on our local culture results, the addition of clindamycin to flucloxacillin would provide excellent empiric coverage for all categories of breast infection. An evidence-based treatment guideline is required and should be formulated in close collaboration with microbiology specialists.     

Anti-microbial principles of selected remedial plants from Southern India

Objective

To examine the anti-bacterial activity of leaf extracts of Morus alba L. (Moraceae) and Piper betel L. (Piperaceae), and seed extracts of Bombax ceiba L. (Borabacaceae).

Methods

We have partially purified plant extracts by solvent extraction method, and evaluated the effect of individual fractions on bacterial growth using Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) bacterial strains.

Results

Compared with Morus and Bombax fractions, Piper fractions showed significant growth inhibition on all the three types of bacteria studied. The EtOAc-hexane fractions of Piper leaves exhibited significant anti-bacterial activity with minimum inhibitory concentrations (MIC) of 50 µg/mL culture against both gram-positive and gram-negative bacteria. The EtOAc-fractions I, II, and IV inhibited bacterial colony formation on soft agar in addition to growth inhibition. A combination treatment of piper fractions with ampicillin resulted in significant growth inhibition in E. coli and P. aeruginosa, and combination with anticancer drug geldanamycin (2µg/mL) showed selective growth inhibition against P. aeruginosa and S. aureus. Three major compounds, i.e., eugenol, 3-hexene-ol and stigmasterol, were primarily identified from Piper betel leaf extractions. Among the individual compounds, eugenol treatment showed improved growth inhibition compared with stigmasterol and 3-hexene-ol.

Conclusions

We are reporting potential anti-bacterial compounds from Piper betel against both gram-positive and gram-negative bacteria either alone or in combination with drug treatment.     

Crotoxin: Novel activities for a classic β-neurotoxin

Crotoxin, the main toxin of South American rattlesnake (Crotalus durissus terrificus) venom, was the first snake venom protein to be purified and crystallized. Crotoxin is a heterodimeric β-neurotoxin that consists of a weakly toxic basic phospholipase A₂ and a non-enzymatic, non-toxic acidic component (crotapotin). The classic biological activities normally attributed to crotoxin include neurotoxicity, myotoxicity, nephrotoxicity and cardiotoxicity. However, numerous studies in recent years have shown that crotoxin also has immunomodulatory, anti-inflammatory, anti-microbial, anti-tumor and analgesic actions. In this review, we describe the historical background to the discovery of crotoxin and its main toxic activities and then discuss recent structure-function studies and investigations that have led to the identification of novel pharmacological activities for the toxin.     

抗生素涂层中心静脉置管对导管相关深静脉血栓的影响

目的评价和比较抗生素涂层与普通中心静脉置管对导管相关深静脉血栓(catheterassociated deep venous thrombosis,CADVT)的影响。方法回顾分析2017年1~6月行颈内静脉、腋-锁骨下静脉或股静脉穿刺置管的择期手术患者1 359例,年龄26~82岁,ASAⅠ~Ⅲ级。采用倾向性评分法按1∶1匹配分为两组,即抗生素涂层中心静脉置管组(A组)和普通中心静脉置管组(B组)。匹配因素包括性别、年龄、ASA分级、术前血栓风险(Caprini评分)、中心静脉置管部位、手术部位、是否采用超声引导穿刺置管、是否接受抗凝治疗等。分析术后CADVT的风险和血栓程度,以及置管相关并发症。结果共938例患者匹配成功,共323例患者(34.4%)经床旁超声诊断为CADVT,其中A组172例(36.7%),B组151例(32.2%),两组CADVT发生率和血栓程度差异无统计学意义;亚组分析结果表明,高危血栓风险(Caprini评分≥5分)(OR 1.34,95%CI 1.01~1.78)、体表标志定位穿刺置管(OR 1.69,95%CI 1.04~2.74)和未接受抗凝治疗(OR 1.39,95%CI 1.01~1.92)的患者使用抗生素涂层中心静脉导管CADVT的风险高于普通中心静脉导管;A组患者导管相关感染发生率明显低于B组(0.9%vs 4.1%,P0.05);其余置管相关并发症发生率差异均无统计学意义。结论抗生素涂层中心静脉置管不增加CADVT的发生率。     

The judicious use of antibiotics—An investment towards optimized health care

During the past century the excitement of discovering antibiotics as a treatment of infectious diseases has given way to a sense of complacency and acceptance that when faced with antimicrobial resistance there will always be new and better antimicrobial agents to use. Now, with clear indications of a decline in pharmaceutical company interest in anti-infective research, at the same time when multi-drug resistant micro-organisms continue to be reported, it is very important to review the prudent use of the available agents to fight these micro-organisms. Injudicious use of antibiotics is a global problem with some countries more affected than others. There is no dearth of interest in this subject with scores of scholarly articles written about it. While over the counter access to antibiotics is mentioned as an important contributor towards injudicious antibiotic use in developing nations, as shown in a number of studies, there are many provider, practice and patient characteristics which drive antibiotic overuse in developed nations such as the United States. Recognizing that a thorough review of this subject goes far and beyond the page limitations of a review article we provide a summary of some of the salient aspects of this global problem with a focus towards readers practicing in developing nations.     

Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in combined injured mice

Purpose: A combination therapy for combined injury (CI) using a non-specific immunomodulator, synthetic trehalose dicorynomycolate and monophosphoryl lipid A (STDCM-MPL), was evaluated to augment oral antimicrobial agents, levofloxacin (LVX) and amoxicillin (AMX), to eliminate endogenous sepsis and modulate cytokine production.

Materials and methods: Female B6D2F₁/J mice received 9.75 Gy cobalt-60 gamma-radiation and wound. Bacteria were isolated and identified in three tissues. Incidence of bacteria and cytokines were compared between treatment groups.

Results: Results demonstrated that the lethal dose for 50% at 30 days (LD_50/30) of B6D2F₁/J mice was 9.42 Gy. Antimicrobial therapy increased survival in radiation-injured (RI) mice. Combination therapy increased survival after RI and extended survival time but did not increase survival after CI. Sepsis began five days earlier in CI mice than RI mice with Gram-negative species predominating early and Gram-positive species increasing later. LVX plus AMX eliminated sepsis in CI and RI mice. STDCM-MPL eliminated Gram-positive bacteria in CI and most RI mice but not Gram-negative. Treatments significantly modulated 12 cytokines tested, which pertain to wound healing or elimination of infection.

Conclusions: Combination therapy eliminates infection and prolongs survival time but does not assure CI mouse survival, suggesting that additional treatment for proliferative-cell recovery is required.