Anti-Infective Agents - Volume 19, Issue 1, 2021

Background: During the last 30 years, an Antimicrobial Stewardship Program (ASP) was implemented in a facility with periods of weakness. We aim to describe the history of sustainability failure in the local ASP. Methods: A historical review was conducted using original data from the facility library and papers published. An analysis of factors related to the failure was conducted based on the Doyle approach. Results: The first ASP was implemented from 1989 to 1996 based on the international experiences and contributed to the improvement in the quality of prescription, reduction of 52%in cost and in the incidence of nosocomial infection. The second program restarted in 2008 and declined in 2015, while, the third program was guided by the Pan-American Health Organization from 2019. This program, in progress, is more comprehensive than previous ones and introduced as a novel measure the monitoring of antibiotic prophylaxis in surgery. The factors related to the sustainability were considered including the availability of antimicrobials, the leader´s support, safety culture, and infrastructure. Conclusion: The history behind thirty years of experiences in antimicrobial stewardship programs has allowed us to identify the gaps that require proactive strategies and actions to achieve sustainability and continuous quality improvement.

Background and Purpose: Curcuma longa L. is one of the most important medicinal plants used in traditional medicine. Its main compound, curcumin, has been widely reported for its biological properties. Here, we performed a systematic review of the effects of C. longa L. and its derivative curcumin on Aspergillus infections. Although some limitations in this systematic review study have been identified such as (i) the number of studies evaluating the efficacy of turmeric and its derivatives, such as curcumin, in fungal diseases such as Aspergillus is very small, and further in vitro and in vivo studies should be performed to better evaluate the efficacy of the plant; (ii) studies of the effects of turmeric and curcumin in different countries; (iii) the duration of treatment for in vivo studies was 2 to 12 weeks, so longer treatment intervals and longer duration are needed to better evaluate the treatment. Materials and Methods: In this review article, antifungal effects of C. longa and its derivative curcumin on the different strains of Aspergillus are discussed. The study data were obtained from various databases, including Scopus, PubMed, Web of Science, Embase and Google Scholar, which were published by December 2019. The main criterion for entering data into the survey data was access to the English abstract at the search stage. The keywords used in the search included C. longa, curcumin, antifungal effect and Aspergillus. Of the 2,500 studies in the initial search, only 15 qualified for study inclusion, among which 9 (60%) were performed on the effect of curcumin against Aspergillus spp. The other 6 studies (40%) had focused on the antifungal effect of C. longa. Moreover, 9 studies (60%) were performed in vitro, 4 studies (27%) were performed in vivo and 2 studies (13%) were performed both in vivo and in vitro. Results: Studies have shown that C. longa has a significant effect on the development of the majority of microorganisms. Its predominant metabolite, curcumin, plays a major role in the biological activities of C. longa. Conclusion: Due to increased drug resistance, particularly antifungal, curcumin and its derivatives may be an appropriate option for the treatment of aspergillosis infections.

Background: According to the World Health Organization (WHO), two-fifths of the world population is at risk of infection by DENV. There are no safe and effective vaccines established. Sulfated glycosaminoglycans such as heparin, used as anticoagulants, inhibit the initial step of dengue viral replication. Recently, an isolated heparin analogue Goniopsis cruentata (cCTH) has presented a low anticoagulant effect with reduced bleeding risk. Methods: The antiviral activity of cCTH and heparin compounds against DENV-2 in Vero cell culture was determined by quantitative RT-PCR (qRT-PCR) and titration. For this, four trials were carried out: treatment of the cells for 2 h before viral inoculation, concomitant viral inoculation treatment, treatment after viral inoculation and virucidal assay. Subsequently, the culture supernatants were collected for periods of 24, 48 and 72 h. Results: Our results demonstrated that cCTH and heparin showed antiviral activity against DENV-2. Conclusion: These data suggest that both compounds prevented viral replication in cultured Vero cells.

Aims: Synthesis and biological evaluation of some [(5-oxazolyl)-phenyl]-thiourea derivatives as potential antiviral agents. Background: (5-Oxazolyl)-phenyl derivatives were derived from the design of mycophenolic acid structurally related analogues. The (5-oxazolyl)-phenyl fragment is an excellent composition for many novel structure compounds having good pharmaceutical properties, such as immunosuppressive, antiviral and anticancer. In the present study, we present combinations of thiourea group and (5-oxazolyl)-phenyl fragment. The antiviral activity, cytotoxicity and IMPDH activity of the title compounds were evaluated in vitro bioassay. Objective: [(5-Oxazolyl)-phenyl]-thiourea derivatives containing different substituted benzene rings were synthesized by introducing thiourea linker. All the synthesized derivatives were screened for their in vitro antiviral evaluation and inosine monophosphate dehydrogenase activity. Methods: A series of [(5-oxazolyl)-phenyl]-thiourea derivatives were synthesized by the reaction of thiocarbonyldiimidazole with amines. This was an effective method for introducing the thiourea group in the (5-oxazolyl)-phenyl structure. All of the synthesized derivatives were screened for their in vitro antiviral activity against influenza A virus, coxsackievirus B3, herpes simplex virus type 1 and inosine monophosphate dehydrogenase activity. Results: The results of the screening revealed that compounds 4i, 4j, 4k, 7m, 7n and 7o showed comparable activity towards IMPDH as compared to the control drug. Compounds 4k, 4l, 7m and 7n exhibited potent activity towards both RNA virus influenza A virus, coxsackievirus B3 and DNA virus HSV-1 at low micromolar concentrations. The activities of most compounds directly linked to the substituted benzene ring by the thiourea group were superior to those of the compounds which had the methylene linkage. Conclusion: The in vitro biological assays indicated that most of target molecules having combinations of thiourea group and (5-oxazolyl)-phenyl fragment exhibited antiviral activity and IMPDH activity compared the control drugs.

Background: Acinetobacter is one of the most important pathogens that causes a high prevalence of infection in clinical centers. Natural products are major sources of new anti-infective agents and considered as an alternative medicine for the treatment of infectious diseases. Objective: This study aims to evaluate the antibacterial activity of aqueous and methanol extract of Artemisia annua on the clinically isolated Acinetobacter and the combination of the plant extract with amikacin and imipenem. Methods: The aqueous and methanol extract of the aerial parts of this plant was prepared by maceration. Antibacterial activity was determined by the Broth microdilution method . The presence of adeI and adeB genes in Acinetobacter isolates was investigated. The combination effects of antibiotics were performed using the checkerboard method. The effect of plant extract on bacterial efflux pumps was also investigated. Results: MIC values of the methanol extract of A. annua were from 4.46 mg/ml to 8.92 mg/ml. The effects of the interaction of the plant extract with the amikacin and imipenem represent a significant synergistic influence. Findings indicated that the plant extract was able to inhibit the efflux pump remarkably. Conclusion: The combination of the plant extract with amikacin and imipenem can be used in the treatment of infections caused by antibiotic-resistant Acinetobacter and probably other infectious diseases.

Background: Several drugs are currently in use to treat fungal infections; however, recent studies indicate that the consumption of these drugs is associated with serious complications. This study was done to examine the chemical composition and antifungal effects of Nectaroscordum tripedale against several yeast strains. Methods: The antifungal activity of N. tripedale extract on Saccharomyces cerevisiae and Candida albicans, C. glabrata was examined via the assessment of minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) according to the broth micro dilution technique (M27-A3 protocol). By means of gas chromatography/mass spectroscopy (GC/MS), the major constituents of this extract were identified. Results: The findings exhibited that N. tripedale extract represents not only fungistatic but also fungicidal activity with an average MIC and MFC of 12.5 to 66.6 μg/ml, respectively, for tested yeasts. The results also demonstrated that decadienal (11.1%), hexadecanoic acid (10.3%), and heptadecane (9.5%), were the major constituents of this extract. Conclusion: The findings demonstrated the preliminary anti-yeast effects of this plant and suggest the use of N. tripedale for yeast infections in the traditional medicine. This study for the first time showed N. tripedale as a new antifungal patent to treat the candidiasis and other yeast infections; however, more studies are required to assess the precise anti-candida effects of this plant against other Candida spp. as well as in human subjects.

Background and Objectives: Probiotics are nonpathogenic and beneficial viable microorganisms that exhibit potential health welfare for human beings. Probiotics are found in various food products. They also occur as natural microflora in the intestine of mammals. Main goal of this study was to isolate probiotics conferring antibacterial activity and cholesterol lowering ability from different fruits. Materials and Methods: Present research reveals the usefulness of probiotics, in which twenty one bacterial cultures were isolated from different fruit samples including figs, coconut water and grapes. These strains were explored for their antibacterial and cholesterol reduction ability by conducting in vitro experiments. Results and Discussion: Among twenty one isolates, nine probiotic cultures FgC2, FgC7, FgC14, G2C5, G1C, GrC18 and StCW showed maximum antibacterial activity against different human clinical pathogens. This suggests that these microbes produce inhibitory metabolites which are extracellular and diffusible. For cholesterol assimilation assay, six strains FgC2, FgC7, FgC12, FgC13, GrC7 and GrC18 presented remarkable cholesterol lowering efficacy (up to 98%) when grown in the presence of bile salts. Only potential probiotic cultures were identified and characterized as lactic acid bacteria (LAB), on the basis of Bergey’s Manual of Determinative Bacteriology. Conclusion: Thus, this study is helpful to exploit the bioactive and therapeutic potential of beneficial microorganisms so that they can be utilized in the generation of functional food and other health promoting products.

Introduction: This study was undertaken to assess the antimicrobial, antioxidant, antiinflammatory and antimalarial potential of fruit extract of Ananas comosus Linn. Bromelain is the major protease enzyme present in the pineapple. Methods: Screening of compounds using fluorescence-based assay was performed for antimalarial activity by Trager and Jenson method. Ethanolic extract of ananas cosmosus showed good antimalarial activity (EC50 = 1.94 ug/ml) as compared to the standard drug primaquine (EC50 = 0.07 ug/ml). In the case of antibacterial activity, ethanolic extract of pineapple showed the good MIC value, i.e. S. aureus (MIC= 3.12 ug/ml), S. typhi (MIC = 3.12 ug/ml) as compared to the standard drug ofloxacin (MIC= 0.43 ug/ml). Results: In the case of antifungal activity extract showed the remarkable activity A. niger (MIC= 1.56 ug/ml) as compared to the standard drug fluconazole (MIC = 0.10 ug/ml). In the case of antioxidant activity, % inhibition was found i.e. 44.13 %, which is nearly equal to the standard drug 48 %. Conclusion: Ananas cosmosus showed excellent antioxidant potential.

Background: At present, skin problems need to be addressed seriously. Antibiotic resistance development is very fast in skin infectious bacteria. For the prevention of all types of skin infections, natural plant extracts can provide suitable defense lines because they contain active compounds. Wrinkles, sunburn, itching, blackheads, whiteheads, and uneven tone of the skin are some of the issues related to skin. Extensive use of antibiotics for skin diseases is restricted due to the development of worse antibiotic resistance. Objective: In this study, the antibacterial potential of plant extracts was assessed against skin infectious bacteria to get an alternative cure for skin diseases. Methods: Staphylococcus aureus and Staphylococcus epidermidis strains were isolated from clinical samples and E.coli was used as a non-pathogenic control strain from the Jinnah University for Women strain repository. Their antibacterial activity was performed against eight plant extracts through a well diffusion method. Results: Among eight plant extracts, Neem (Azadirachta indica), Turmeric (Curcuma longa), Sandalwood (Santalum album), Shahtara (Fumaria parviflora), Chirayata (Swertia chirayita), and commercially available mixed Citrus peel showed good inhibition of bacterial growth. Discussion: Natural sources such as fruits, herbs, minerals, leaves, flowers, roots, honey, and rose water are now becoming part of skin care and treatment products because they possess antimicrobial activities. Conclusion: Skin products with herbal ingredients are now evolving as suitable solutions to the existing skin problems.

Background: Nanosponge is a novel approach to topical drug delivery, especially for fungal infections. Nanosponges are a unique class of nanoparticles with three-dimensional nanostructure and nanometers wide cavities, which can encapsulate both hydrophilic and lipophilic substances providing increased efficacy and safety. Objective: To formulate and evaluate Bifonazole loaded nanosponges in hydrogels for the treatment of fungal diseases. Methods: Bifonazole-loaded nanosponges were formulated using the emulsion solvent diffusion technique. Interaction of drug-ethyl cellulose polymer along with other excipients’ was done by using FTIR as well as DSC. The nanosponges formulations were evaluated with different parameters. Results: Particle size and Zeta potential of Bifonazole loaded nanosponges for formulations were between the range of 183.7 to 560.2 nm and –17.77 to –21.9 mV, respectively. The surface morphology of nanosponges by SEM disclosed that it was spherical and porous in nature. Drug entrapment efficiency was found to be 45.44 to 79.71%. The drug release study was done by using a phosphate buffer with a pH of 6.8. Further in vitro release data was fitted into kinetic models. The optimized formulation M6 was incorporated with hydrogels; to further evaluated using parameters such as in vitro drug release studies, viscosity, pH and skin irritation studies using rat model. Stability studies of hydrogel formulation MH2 revealed no changes in in-vitro drug release, pH and drug content study at the completion of 6 months. Conclusion: Thus, the findings indicated that the prepared Bifonazole loaded nanosponges into hydrogel were stable. Hence, it could be a suitable dosage form for the cure of fungal infections in the skin.

Background: Medicinal herbs such as Pistacia Atlantica (P. Atlantica) subsp. Kurdica have antimicrobial effects. The present study is aimed to investigate the nanocluster structure of P. atlantica subsp. Kurdica turpentine and its composing elements and antibacterial effect. Methods: 100 μl ethanol was used to dissolve oily turpentine. 2, 2.2, 2.4, and 2.6 μg/μl of turpentine were used for investigating the antibacterial effects using disk and well diffusion methods. Elemental and nanocluster structure analyses were performed by Energy-Dispersive X-Ray Microanalysis (EDXMA) and Field Emission (FE)-scanning electron. Two-way analysis of variance (ANOVA) and Bonferroni test were used for data analysis (p ≤ 0.001). Results and Discussion: EDXMA elemental analysis of turpentine included: Zinc (Zn), Magnesium (Mg), Fluorine (F), Oxygen (O), Silicon (Si), Carbon (C), and Argentum (Ag). A topography image of the turpentine showed a nanocluster surface with bright clusters in the background. The largest diameters of the growth inhibition zones (24.67 ± 0.58 mm in the disk diffusion and 23.67 ± 1.53 mm in the well diffusion) that were created by turpentine were observed against S. aureus ATCC 25923 at the concentration of 2.6 μg/μl. The diameter of the inhibition zone around bacterial growth had a direct relationship with turpentine concentration (p ≤ 0.001). Conclusion: The nanocluster structure of turpentine and its composed elements were detected in this research. Moreover, the antibacterial effects of turpentine were proved. Herbal substances are widely used in medical applications. Different elements of P. atlantica subsp. Kurdica turpentine can be used as antibacterial agents, but more in-vitro and in-vivo studies should be performed in this field.

Objective: The main objective of this review is to provide a platform to learn about the importance of Ocimum. A genus known to the entire population of India as Tulsi. Special attention has been paid to literature reports describing the use of Tulsi and cancer. Methods: The importance of the plant and the active ingredient is described here in the relevant bibliographic references. The use of the plant would be much more important for the drug distribution scientist to develop a special formulation of the crude drug, which, in the future, will be a magical therapeutic agent with many benefits. Examples have been presented in which the plant is used and its use for its antibacterial activity. Results: A prestigious group showed an inhibitory effect on the growth of aqueous and alcoholic extracts of OS in E. coli and V. cholera. Conclusion: The pooled information focuses on the fact that O. canum extracts were found to be the largest and most active zone of inhibition.

Background: Medicinal plants have been used for the treatments of various health ailments and the practices as a remedial for thousands of years. Currently, plant-derived compounds are used as alternative ways of treatment for multidrug-resistant pathogens. Objective: In the present study, various parts of six medical plants such as Solanum nigrum, Azadirachta indica, Vitex negundo, Mentha arvensis, Gloriosa superba, and Ocimum sanctum were extracted for obtaining active biological constituents. Methods: Soxhlet method of extraction was used for obtaining crude extracts. Agar disc diffusion and 96-well plate spectroscopic reading were used to detect the extract’s antibacterial and antibiofilm properties. Results: The obtained extracts were tested for antimicrobial and antibiofilm properties at 25 mg/mL concentrations. Maximum antibacterial activity was observed in O. sanctum chloroform extracted (TUCE) against Staphylococcus aureus (24.33±1.52 mm), S. nigrum acetone extract (MAAC) against Salmonella Typhimurium (12.6 ± 1.5 mm) and Pseudomonas aeruginosa (15.0 ±2.0 mm). Only TUCE exhibited antibacterial activity at least a minimum inhibitory concentration of 0.781 mg/mL. Better antibiofilm activities were also exhibited by petroleum extracts of G. superba (KAPE) and S. nigrum (MAPE) against Escherichia coli, S. Typhimurium, P. aeruginosa and S. aureus. Moreover, S. nigrum acetone extract (MAAC) and O. sanctum chloroform extract (TUCE) showed anti-swarming activity with a reduction of motility 56.3% against P. aeruginosa and 37.2% against S. aureus. MAAC also inhibits LasA activity (63.3% reduction) in P. aeruginosa. Conclusion: Extracts of TUCE, MAAC, MAPE, and KAPE exhibited antibacterial and antibiofilm properties against the Gram-positive and Gram-negative pathogenic bacteria. GC-MS identified that chemical constituents are responsible for being biologically active.

Background: Several computational tools assist in predicting the chemical properties, toxicity, solubility, and binding affinity of the drugs. Objective: The study aims to experimentally analyze the efficiency of the antimalarial drug “sulfadiazine” in a higher dose in contrast to its conventional use. Methods: The antimalarial drug was screened, and its application was assessed on the host (mice). Results: The results showed that parasitemia of the infected control group was significantly higher than the others (P<0.0001) on days 3, 5, 7, and 9. The parasitemia of the IT+4 group was significantly lower than the parasitemia of the IT-4 group on the 15^th day. Conclusion: It was concluded that increased potency for the antimalarials is because they are nontoxic.

Introduction: An attractive antibiotic-adjuvant strategy consisting of the design and synthesis of polyaminoisoprenyl molecules able to restore the antibiotic activity of tetracycline antibiotics against resistant Pseudomonas aeruginosa bacterial strains has been developed. Methods: These chemo-sensitizers are readily prepared from geraniol and farnesol in an efficient two steps synthesis with good to moderate yields varying from 38 to 64% and leading to a significant decrease in antibiotic resistance. Results: Thus, the influence of the nature of the tetracycline antibiotic used as well as the structure of the polyaminoisoprenyl derivatives involved in the outcome of the antibiotic-adjuvant combination against P. aeruginosa resistance to tetracyclines were investigated. Conclusion: Additionally, our data suggested that their mechanism of action is closely associated with the increase of the outer-membrane permeability.

Background: Conventional laboratory culture-based methods for diagnosis of Streptococcus pneumoniae are time-consuming and yield false negative results. Molecular methods including real-time (RT)-PCR rapid methods and conventional PCR due to higher sensitivity and accuracy have replaced traditional culture assay. The aim of the current study was to evaluate lytA gene for the detection of Streptococcus pneumoniae in the cerebrospinal fluid of human patients with meningitis using real-time PCR assay. Material and Methods: In this cross-sectional study, a total of 30 clinical specimens were collected from patients in a period from September to December 2018. In order to evaluate the presence of lytA gene, conventional and real-time PCR methods were used without culture. Results: From 30 sputum samples, five (16.66%) isolates were identified as S. pneumoniae by lytA PCR and sequencing. Conclusion: In this research, an accurate and rapid real-time PCR method was used, which is based on lytA gene for diagnosis of bacteria. Based on the sequencing results, the sensitivity for the detection of lytA gene was 100% (5/5).