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Antibiotics' susceptibility patterns of bacterial isolates causing lower respiratory tract infections in ICU patients at referral hospitals in Namibia

Simeon P, Godman B, Kalemeera F

Hosp Pract (1995), 2021 Dec;49(5):356-363.
PMID: 34436942 DOI: 10.1080/21548331.2021.1973825

BACKGROUND: Lower respiratory tract infections (LRTIs) are a particular public health concern especially among sub-Saharan African countries. This is especially the case in Namibia, where LRTIs are currently the third leading cause of death, 300 deaths in children under 5 years of age. To reduce the burden of LRTIs on health systems and ensure appropriate patient management, it is critical to know the most prevalent pathogens leading to LRTIs and their susceptibility patterns in the local setting. Consequently, the objective of this study was to formulate cumulative antibiograms for Intensive Care Units (ICUs) of referral hospitals in Namibia to guide future antibiotic use.
METHODS: A retrospective analytical cross-sectional study was conducted over 2 years. The cumulative antibiograms were constructed in accordance with current guidelines.
RESULTS: A total of 976 first isolate cultures were obtained from ICUs of the different referral hospitals. K. pneumoniae (8.8%, 8.1%) was a predominant pathogen in Windhoek Central hospital ICU in 2017 and 2018. In Oshakati intermediate hospital ICU, Enterobacter sp. (22.2%) and P. aeruginosa (37.5%) were the common pathogens in 2017 and 2018, respectively. A. baumannii isolates were >90% susceptibility to colistin, carbapenems, and tigecycline in 2017. In 2017, K. pneumoniae isolates were more susceptible to carbapenems (94% and 93.8% among isolates), amikacin (89.3%), and tigecycline (88.7%). In 2018, K. pneumoniae isolates were 100% susceptible amikacin, colistin, and carbapenems. S. maltophilia isolates were more than 80% susceptible to all the tested antibiotics. S. aureus isolates were 100% susceptible to linezolid, rifampicin, teicoplanin, and vancomycin in 2017 and in 2018. Its susceptibility to these antibiotics did not change.
CONCLUSION: The susceptibility patterns of the common isolated gram-negative pathogens were highly variable. Meropenem in combination with gentamicin is now the recommended antibiotic combination for empiric therapy for patients with LRTIs in Windhoek Central Hospital ICU.

Matched MeSH terms: Gram-Negative Bacteria/drug effects*
Fulltext Development and Characterization of Calcium-Alginate Beads of Apigenin: In Vitro Antitumor, Antibacterial, and Antioxidant Activities

Aldawsari MF, Ahmed MM, Fatima F, Anwer MK, Katakam P, Khan A

Mar Drugs, 2021 Aug 20;19(8).
PMID: 34436306 DOI: 10.3390/md19080467

The objective of this work was to develop sustained-release Ca-alginate beads of apigenin using sodium alginate, a natural polysaccharide. Six batches were prepared by applying the ionotropic gelation technique, wherein calcium chloride was used as a crosslinking agent. The beads were evaluated for particle size, drug loading, percentage yield, and in vitro drug release. Particle size was found to decrease, and drug entrapment efficiency was enhanced with an increase in the polymer concentration. The dissolution study showed sustained drug release from the apigenin-loaded alginate beads with an increase in the polymer proportion. Based on the dissolution profiles, BD6 formulation was optimized and characterized for FTIR, DSC, XRD, and SEM, results of which indicated successful development of apigenin-loaded Ca alginate beads. MTT assay demonstrated a potential anticancer effect against the breast cancer MCF-7 cell lines. The antimicrobial activity exhibited effective inhibition in the bacterial and fungal growth rate. The DPPH measurement revealed that the formulation had substantial antioxidant activity, with EC50 value slightly lowered compared to pure apigenin. A stability study demonstrated that the BD6 was stable with similar (f2) drug release profiles in harsh condition. In conclusion, alginate-based beads could be used for sustaining the drug release of poorly water-soluble apigenin while also improving in vitro antitumor, antimicrobial, and antioxidant activity.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Detection of mobile colistin-resistance gene variants (mcr-1 and mcr-2) in urinary tract pathogens in Bangladesh: the last resort of infectious disease management colistin efficacy is under threat

Ara B, Urmi UL, Haque TA, Nahar S, Rumnaz A, Ali T, et al.

Expert Rev Clin Pharmacol, 2021 Apr;14(4):513-522.
PMID: 33691556 DOI: 10.1080/17512433.2021.1901577

Background: Currently, colistin-resistant pathogens emerged has become a global health concern. This study assessed the distribution of mcr-1 to mcr-5 variants with the phenotypic colistin-resistance in bacterial isolates from urinary tract infection (UTI) patients in Bangladesh.Methods: A cross-sectional study was conducted between April 2017 and March 2018 to enroll uncomplicated UTI patients, and 142 urine samples were analyzed. Uropathogens were identified using the API-20E biochemical panel and 16s rRNA gene sequencing. Polymerase chain reactions detected the mcr gene variants in the UTI isolates. The phenotypic colistin-susceptibility was determined by the Kirby-Bauer disc-diffusion method and the minimal inhibitory concentration (MIC) measurement.Results: The combined carriage of mcr-1 and mcr-2 genes in 11.4% (14/123) of urinary tract pathogens. The mcr-positive pathogens include five Escherichia coli, three Klebsiella pneumoniae, three Pseudomonas putida, two Enterobacter cloacae, and one Enterobacter hormaechei. The mcr-positive variant showed significantly higher phenotypic colistin resistance with MIC between >16 µg/mL and >128 µg/mL (pdrug may lead to a lack of treatment options for the infectious diseases and spread of infection to the unaffected cohorts.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Novel antimicrobial development using genome-scale metabolic model of Gram-negative pathogens: a review

Chung WY, Zhu Y, Mahamad Maifiah MH, Shivashekaregowda NKH, Wong EH, Abdul Rahim N

J Antibiot (Tokyo), 2021 02;74(2):95-104.
PMID: 32901119 DOI: 10.1038/s41429-020-00366-2

Antimicrobial resistance (AMR) threatens the effective prevention and treatment of a wide range of infections. Governments around the world are beginning to devote effort for innovative treatment development to treat these resistant bacteria. Systems biology methods have been applied extensively to provide valuable insights into metabolic processes at system level. Genome-scale metabolic models serve as platforms for constraint-based computational techniques which aid in novel drug discovery. Tools for automated reconstruction of metabolic models have been developed to support system level metabolic analysis. We discuss features of such software platforms for potential users to best fit their purpose of research. In this work, we focus to review the development of genome-scale metabolic models of Gram-negative pathogens and also metabolic network approach for identification of antimicrobial drugs targets.

Matched MeSH terms: Gram-Negative Bacteria/drug effects*
Fulltext Antimicrobial activities of Bacillus velezensis strains isolated from stingless bee products against methicillin-resistant Staphylococcus aureus

Baharudin MMA, Ngalimat MS, Mohd Shariff F, Balia Yusof ZN, Karim M, Baharum SN, et al.

PLoS One, 2021;16(5):e0251514.
PMID: 33974665 DOI: 10.1371/journal.pone.0251514

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have reached epidemic proportions globally. Therefore, there is an urgent need for a continuous supply of antibiotics to combat the problem. In this study, bacteria initially identified as species belonging to the Bacillus amyloliquefaciens operational group were re-identified based on the housekeeping gene, gyrB. Cell-free supernatants (CFS) from the strains were used for antimicrobial tests using the agar well diffusion assay against MRSA and various types of pathogenic bacteria. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and physicochemical characteristics of the CFS were determined. Based on gyrB sequence analysis, five strains (PD9, B7, PU1, BP1 and L9) were identified as Bacillus velezensis. The CFS of all B. velezensis strains showed broad inhibitory activities against Gram-negative and -positive as well as MRSA strains. Strain PD9 against MRSA ATCC 33742 was chosen for further analysis as it showed the biggest zone of inhibition (21.0 ± 0.4 mm). The MIC and MBC values obtained were 125 μl/ml. The crude antimicrobial extract showed bactericidal activity and was stable at various temperatures (40-80°C), pH (4-12), surfactants (Tween 20, Tween 80, SDS and Triton X-100) and metal ions (MgCI2, NaCI2, ZnNO3 and CuSO4) when tested. However, the crude extract was not stable when treated with proteinase K. All these properties resembled the characteristics of peptides. The antimicrobial compound from the selected strain was purified by using solvent extraction method and silica gel column chromatography. The purified compound was subjected to High Performance Liquid Chromatography which resulted in a single peak of the anti-MRSA compound being detected. The molecular weight of the anti-MRSA compound was determined by using SDS-PAGE and zymogram. The size of the purified antimicrobial peptide was approximately ~ 5 kDa. The antimicrobial peptide produced from B. velezensis strain PD9 is a promising alternative to combat the spread of MRSA infections in the future.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Sesquiterpenes rich essential oil from Garcinia celebica L. and its cytotoxic and antimicrobial activities

Tan WN, Tan ZH, Zulkifli NI, Nik Mohamed Kamal NNS, Rozman NAS, Tong WY, et al.

Nat Prod Res, 2020 Dec;34(23):3404-3408.
PMID: 30773054 DOI: 10.1080/14786419.2019.1569012

Garcinia celebica L., locally known as "manggis hutan" in Malaysia is widely used in folkloric medicine to treat various diseases. The present study was aimed to examine the chemical composition of the essential oil from the leaves of G. celebica L. (EO-GC) and its cytotoxic and antimicrobial potential. EO-GC obtained by hydrodistillation was analysed using capillary GC and GC-MS. Twenty-two compounds were identified, dominated by α-copaene (61.25%), germacrene D (6.72%) and β-caryophyllene (5.85%). In the in vitro MTT assay, EO-GC exhibited significant anti-proliferative effects towards MCF-7 human breast cancer cells with IC50 value of 45.2 μg/mL. Regarding the antimicrobial activity, it showed better inhibitory effects on Gram-positive bacteria than Gram-negative bacteria and none on the fungi and yeasts tested.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Fulltext Sustainable drug release from polycaprolactone coated chitin-lignin gel fibrous scaffolds

Abudula T, Gauthaman K, Mostafavi A, Alshahrie A, Salah N, Morganti P, et al.

Sci Rep, 2020 11 24;10(1):20428.
PMID: 33235239 DOI: 10.1038/s41598-020-76971-w

Non-healing wounds have placed an enormous stress on both patients and healthcare systems worldwide. Severe complications induced by these wounds can lead to limb amputation or even death and urgently require more effective treatments. Electrospun scaffolds have great potential for improving wound healing treatments by providing controlled drug delivery. Previously, we developed fibrous scaffolds from complex carbohydrate polymers [i.e. chitin-lignin (CL) gels]. However, their application was limited by solubility and undesirable burst drug release. Here, a coaxial electrospinning is applied to encapsulate the CL gels with polycaprolactone (PCL). Presence of a PCL shell layer thus provides longer shelf-life for the CL gels in a wet environment and sustainable drug release. Antibiotics loaded into core-shell fibrous platform effectively inhibit both gram-positive and -negative bacteria without inducting observable cytotoxicity. Therefore, PCL coated CL fibrous gel platforms appear to be good candidates for controlled drug release based wound dressing applications.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Design, synthesis and antimicrobial evaluation of novel glycosylated-fluoroquinolones derivatives

Mohammed AAM, Suaifan GARY, Shehadeh MB, Okechukwu PN

Eur J Med Chem, 2020 Sep 15;202:112513.
PMID: 32623216 DOI: 10.1016/j.ejmech.2020.112513

Herein we report the design, synthesis and biological evaluation of structurally modified ciprofloxacin, norfloxacin and moxifloxacin standard drugs, featuring amide functional groups at C-3 of the fluoroquinolone scaffold. In vitro antimicrobial testing against various Gram-positive bacteria, Gram-negative bacteria and fungi revealed potential antibacterial and antifungal activity. Hybrid compounds 9 (MIC 0.2668 ± 0.0001 mM), 10 (MIC 0.1358 ± 00025 mM) and 13 (MIC 0.0898 ± 0.0014 mM) had potential antimicrobial activity against a fluoroquinolone-resistant Escherichia coli clinical isolate, compared to ciprofloxacin (MIC 0.5098 ± 0.0024 mM) and norfloxacin (MIC 0.2937 ± 0.0021 mM) standard drugs. Interestingly, compound 10 also exerted potential antifungal activity against Candida albicans (MIC 0.0056 ± 0.0014 mM) and Penicillium chrysogenum (MIC 0.0453 ± 0.0156 mM). Novel derivatives and standard fluoroquinolone drugs exhibited near-identical cytotoxicity levels against L6 muscle cell-line, when measured using the MTT assay.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Fulltext Evaluation of two transformation protocols and screening of positive plasmid introduction into Bacillus cereus EB2, a gram-positive bacterium using qualitative analyses

Sirajuddin SA, Sundram S

Braz J Microbiol, 2020 Sep;51(3):919-929.
PMID: 32078730 DOI: 10.1007/s42770-020-00241-0

Both Gram-positive and Gram-negative bacteria can take up exogenous DNA when they are in a competent state either naturally or artificially. However, the thick peptidoglycan layer in Gram-positive bacteria's cell wall is considered as a possible barrier to DNA uptake. In the present work, two transformation techniques have been evaluated in assessing the protocol's ability to introduce foreign DNA, pBBRGFP-45 plasmid which harbors kanamycin resistance and green fluorescent protein (GFP) genes into a Gram-positive bacterium, Bacillus cereus EB2. B. cereus EB2 is an endophytic bacterium, isolated from oil palm roots. A Gram-negative bacterium, Pseudomonas aeruginosa EB35 was used as a control sample for both transformation protocols. The cells were made competent using respective chemical treatment to Gram-positive and Gram-negative bacteria, and kanamycin concentration in the selective medium was also optimized. Preliminary findings using qualitative analysis of colony polymerase chain reaction (PCR)-GFP indicated that the putative positive transformants for B. cereus EB2 were acquired using the second transformation protocol. The positive transformants were then verified using molecular techniques such as observation of putative colonies on specific media under UV light, plasmid extraction, and validation analyses, followed by fluorescence microscopy. Conversely, both transformation protocols were relatively effective for introduction of plasmid DNA into P. aeruginosa EB35. Therefore, this finding demonstrated the potential of chemically prepared competent cells and the crucial step of heat-shock in foreign DNA transformation process of Gram-positive bacterium namely B. cereus was required for successful transformation.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Antibacterial and antioxidant activity of naphthofuranquinones from the twigs of tropical mangrove Avicennia officinalis

Assaw S, Mohd Amir MIH, Khaw TT, Bakar K, Mohd Radzi SA, Mazlan NW

Nat Prod Res, 2020 Aug;34(16):2403-2406.
PMID: 30600710 DOI: 10.1080/14786419.2018.1538220

Mangrove plants are endowed with various biologically active compounds which have potent antibacterial and antioxidant properties. In present study, a bioactivity-guided fractionation for antibacterial and antioxidant active metabolites from the twigs of Avicennia officinalis collected from Kuala Selangor Nature Park, Selangor, Malaysia gave 13 major fractions. The antibacterial activity of A. officinalis fractions using well-diffusion showed strong selectivity on the Gram-positive bacteria (Staphylococcus epidermidis, S. aureus and Bacillus subtilis) with minimum inhibition concentration (MIC) values of 0.156-5.00 mg/mL. However, no antibacterial activities were observed on the Gram-negative bacteria (Vibrio cholera, Enterobacter cloacae and Escherichia coli). The active antibacterial fractions were further isolated using several chromatographic techniques to give two naphthofuranquinones, namely, avicenol C (1) and stenocarpoquinone B (2). Meanwhile, the antioxidant activity of A. officinalis fractions were evaluated using DPPH radical scavenging assay exhibited low antioxidant activities. Molecular structure of the naphthofuranquinones was elucidated using 1 D and 2 D NMR spectroscopy.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Fulltext Clinical and bacteriological profile of diabetic foot infections in a tertiary care

Goh TC, Bajuri MY, C Nadarajah S, Abdul Rashid AH, Baharuddin S, Zamri KS

J Foot Ankle Res, 2020 Jun 16;13(1):36.
PMID: 32546270 DOI: 10.1186/s13047-020-00406-y

BACKGROUND: Diabetic foot infection is a worldwide health problem is commonly encountered in daily practice. This study was conducted to identify the microbiological profile and antibiotic sensitivity patterns of causative agents identified from diabetic foot infections (DFIs). In addition, the assessment included probable risk factors contributing to infection of ulcers that harbour multidrug-resistant organisms (MDROs) and their outcomes.
METHODS: We carried out a prospective analysis based on the DFI samples collected from 2016 till 2018. Specimens were cultured with optimal techniques in addition to antibiotic susceptibility based on recommendations from The Clinical and Laboratory Standards Institute (CLSI). A total of 1040 pathogens were isolated with an average of 1.9 pathogens per lesion in 550 patients who were identified with having DFIs during this interval.
RESULTS: A higher percentage of Gram-negative pathogens (54%) were identified as compared with Gram-positive pathogens (33%) or anaerobes (12%). A total of 85% of the patients were found to have polymicrobial infections. Pseudomonas aeruginosa (19%), Staphylococcus aureus (11%) and Bacteroides species (8%) appeared to be the predominant organisms isolated. In the management of Gram-positive bacteria, the most efficacious treatment was seen with the use of Vancomycin, while Imipenem and Amikacin proved to be effective in the treatment of Gram-negative bacteria.
CONCLUSION: DFI's are common among Malaysians with diabetes, with a majority of cases displaying polymicrobial aetiology with multi-drug resistant isolates. The data obtained from this study will be valuable in aiding future empirical treatment guidelines in the treatment of DFIs. This study investigated the microbiology of DFIs and their resistance to antibiotics in patients with DFIs that were managed at a Tertiary Care Centre in Malaysia.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Antimicrobial properties of starch films incorporated with chitosan nanoparticles: In vitro and in vivo evaluation

Shapi'i RA, Othman SH, Nordin N, Kadir Basha R, Nazli Naim M

Carbohydr Polym, 2020 Feb 15;230:115602.
PMID: 31887886 DOI: 10.1016/j.carbpol.2019.115602

Chitosan nanoparticles (CNP) were synthesized via ionic gelation and used for the preparation of starch-based nanocomposite films containing different concentration of CNP (0, 5, 10, 15, 20% w/w). Antimicrobial properties of starch/CNP films was evaluated via in vitro (disc diffusion analysis) and in vivo (microbial count in wrapped cherry tomatoes) study. It was found that inhibitory zone of the 15 and 20% of starch/CNP films were clearly observed for all the tested bacteria including Bacillus cereus, Staphylococcus aureus, Escherichia coli and Salmonella typhimurium. In vivo study revealed that the starch/CNP film (15% w/w) was more efficient to inhibit the microbial growth in cherry tomatoes (7 × 102 CFU/g) compared to neat starch film (2.15 × 103 CFU/g) thus confirmed the potential application of the films as antimicrobial food packaging.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Sulfur and nitrogen containing plasma polymers reduces bacterial attachment and growth

Siow KS, Abdul Rahman AS, Ng PY, Majlis BY

Mater Sci Eng C Mater Biol Appl, 2020 Feb;107:110225.
PMID: 31761201 DOI: 10.1016/j.msec.2019.110225

Role of sulfur (S) and nitrogen (N) groups in promoting cell adhesion or commonly known as biocompatibility, is well established, but their role in reducing bacterial attachment and growth is less explored or not well-understood. Natural sulfur-based compounds, i.e. sulfide, sulfoxide and sulfinic groups, have shown to inhibit bacterial adhesion and biofilm formation. Hence, we mimicked these surfaces by plasma polymerizing thiophene (ppT) and air-plasma treating this ppT to achieve coatings with S of similar oxidation states as natural compounds (ppT-air). In addition, the effects of these N and S groups from ppT-air were also compared with the biocompatible amine-amide from n-heptylamine plasma polymer. Crystal violet assay and live and dead fluorescence staining of E. coli and S. aureus showed that all the N and S coated surfaces generated, including ppHA, ppT and ppT-air, produced similarly potent, growth reduction of both bacteria by approximately 65% at 72 h compared to untreated glass control. The ability of osteogenic differentiation in Wharton's jelly mesenchymal stem cells (WJ-MSCs) were also used to test the cell biocompatibility of these surfaces. Alkaline phosphatase assay and scanning electron microscopy imaging of these WJ-MSCs growths indicated that ppHA, and ppT-air were cell-friendly surfaces, with ppHA showing the highest osteogenic activity. In summary, the N and S containing surfaces could reduce bacteria growth while promoting mammalian cell growth, thus serve as potential candidate surfaces to be explored further for biomaterial applications.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Synergistic antibacterial actions of graphene oxide and antibiotics towards bacteria and the toxicological effects of graphene oxide on human epidermal keratinocytes

Pulingam T, Thong KL, Appaturi JN, Nordin NI, Dinshaw IJ, Lai CW, et al.

Eur J Pharm Sci, 2020 Jan 15;142:105087.
PMID: 31626968 DOI: 10.1016/j.ejps.2019.105087

Graphene oxide (GO) has displayed antibacterial activity that has been investigated in the past, however, information on synergistic activity of GO with conventional antibiotics is still lacking. The objectives of the study were to determine the combinatorial actions of GO and antibiotics against Gram-positive and Gram-negative bacteria and the toxicological effects of GO towards human epidermal keratinocytes (HaCaT). Interactions at molecular level between GO and antibiotics were analyzed using Attenuated Total Reflectance-Fourier-transform infrared spectroscopy (ATR-FTIR). Changes in the antibacterial activity of antibiotics towards bacteria through the addition of GO was investigated. Toxicity of GO towards HaCaT cells were examined as skin cells play a role as the first line of defense of the human body. The ATR-FTIR characterizations of GO and antibiotics showed adsorption of tested antibiotics onto GO. The combinatorial antibacterial activity of GO and antibiotics were found to increase when compared to GO or antibiotic alone. This was attributed to the ability of GO to disrupt bacterial membrane to allow for better adsorption of antibiotics. Cytotoxicity of GO was found to be dose-dependent towards HaCaT cell line, it is found to impose negligible toxic effects against the skin cells at concentration below 100 μg/mL.

Matched MeSH terms: Gram-Negative Bacteria/drug effects*
Design, Synthesis, SAR Study, Antimicrobial and Anticancer Evaluation of Novel 2-Mercaptobenzimidazole Azomethine Derivatives

Tahlan S, Narasimhan B, Lim SM, Ramasamy K, Mani V, Shah SAA

Mini Rev Med Chem, 2020;20(15):1559-1571.
PMID: 30179132 DOI: 10.2174/1389557518666180903151849

BACKGROUND: Various analogues of benzimidazole are found to be biologically and therapeutically potent against several ailments. Benzimidazole when attached with heterocyclic rings has shown wide range of potential activities. So, from the above provided facts, we altered benzimidazole derivatives so that more potent antagonists could be developed. In the search for a new category of antimicrobial and anticancer agents, novel azomethine of 2-mercaptobenzimidazole derived from 3-(2- (1H-benzo[d]imidazol-2-ylthio)acetamido)benzohydrazide were synthesized.
RESULTS AND DISCUSSION: The synthesized analogues were characterized by FT-IR, 1H/13C-NMR and MS studies as well C, H, N analysis. All synthesized compounds were evaluated for in vitro antibacterial activity against Gram-positive (B. subtilis), Gram-negative (E. coli, P. aeruginosa, K. pneumoniae and S. typhi) strains and in vitro antifungal activity against C. albicans and A. niger strains by serial dilution method, the minimum inhibitory concentration (MIC) described in μM/ml. The in vitro anticancer activity of synthesized compounds was determined against human colorectal carcinoma cell line (HCT- 116) using 5-fluorouracil as standard drug.
CONCLUSION: In general, most of the synthesized derivatives exhibited significant antimicrobial and anticancer activities. Compounds 8, 10, 15, 16, 17, 20 and 22 showed significant antimicrobial activity towards tested bacterial and fungal strains and compound 26 exhibited significant anticancer activity.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
An Overview of the Activities of Cefiderocol Against Sensitive and Multidrug- Resistant (MDR) Bacteria

AlMatar M, Albarri O, Makky EA, Var I, Köksal F

Mini Rev Med Chem, 2020;20(18):1908-1916.
PMID: 32811410 DOI: 10.2174/1389557520666200818211405

The need for new therapeutics and drug delivery systems has become necessary owing to the public health concern associated with the emergence of multidrug-resistant microorganisms. Among the newly discovered therapeutic agents is cefiderocol, which was discovered by Shionogi Company, Japan as an injectable siderophore cephalosporin. Just like the other β-lactam antibiotics, cefiderocol exhibits antibacterial activity via cell wall synthesis inhibition, especially in Gram negative bacteria (GNB); it binds to the penicillin-binding proteins, but its unique attribute is that it crosses the periplasmic space of bacteria owing to its siderophore-like attribute; it also resists the activity of β-lactamases. Among all the synthesized compounds with the modified C-7 side chain, cefiderocol (3) presented the best and well-balanced activity against multi-drug resistant (MDR) Gram negative bacteria, including those that are resistant to carbapenem. İn this article, an overview of the recent studies on cefiderocol was presented.

Matched MeSH terms: Gram-Negative Bacteria/drug effects*
Antimicrobial Exploration Between Counterpart Endosymbiont and Host Plant (Tamarindus indica Linn.)

Chigurupati S, Vijayabalan S, Selvarajan KK, Aldubayan M, Alhowail A, Mani V, et al.

Curr Pharm Biotechnol, 2020;21(5):384-389.
PMID: 31657678 DOI: 10.2174/1389201020666191028105325

BACKGROUND: Endophytic bacteria produce various bioactive secondary metabolites, which benefit human health. Tamarindus indica L. is well known for its medicinal value in human health care. Several studies have reported on its biological effects from various parts of T. indica, but only a few studies have been devoted to examining the biological activity of endophytes of T. indica.
OBJECTIVES: In the present study, an endophyte was isolated from the leaves of T. indica and screened for its antimicrobial potential.
METHODS: The selected endophyte was identified by 16s rRNA partial genome sequencing and investigated for their antimicrobial potency. The preliminary phytochemical tests were conducted for the affirmation of phytoconstituents in the endophytic crude ethyl acetate extract of T. indica (TIM) and total phenolic content was performed. The antimicrobial potential of TIM was evaluated against human pathogenic ATCC gram-positive and gram-negative bacterial strains.
RESULTS: TIM exhibited an appreciable amount of gallic acid equivalent phenolic content (21.6 ± 0.04 mg GAE/g of crude extract). TIM showed the Minimum Inhibitory Concentration (MIC) at 250 μg/mL and Minimum Bactericidal Concentration (MBC) at 500 μg/mL among the selected human pathogenic ATCC strains. At MIC of 500 μg/mL, TIM displayed a significant zone of inhibition against P. aeruginosa and N. gonorrhoeae.
CONCLUSION: The results from our study highlighted for the first time the antimicrobial potential of endophytic bacterial strain Bacillus velezensis in T. indica leaves and it could be further explored as a source of natural antimicrobial agents.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Fulltext Long-term impact of oral surgery with or without amoxicillin on the oral microbiome-A prospective cohort study

Menon RK, Gomez A, Brandt BW, Leung YY, Gopinath D, Watt RM, et al.

Sci Rep, 2019 12 10;9(1):18761.
PMID: 31822712 DOI: 10.1038/s41598-019-55056-3

Routine postoperative antibiotic prophylaxis is not recommended for third molar extractions. However, amoxicillin still continues to be used customarily in several clinical practices worldwide to prevent infections. A prospective cohort study was conducted in cohorts who underwent third molar extractions with (group EA, n = 20) or without (group E, n = 20) amoxicillin (250 mg three times daily for 5 days). Further, a control group without amoxicillin and extractions (group C, n = 17) was included. Salivary samples were collected at baseline, 1-, 2-, 3-, 4-weeks and 3 months to assess the bacterial shift and antibiotic resistance gene changes employing 16S rRNA gene sequencing (Illumina-Miseq) and quantitative polymerase chain reaction. A further 6-month follow-up was performed for groups E and EA. Seven operational taxonomic units reported a significant change from baseline to 3 months for group EA (adjusted p bacteria and β-lactamase resistance genes (TEM-1) was observed over 6 months for any group (adjusted p > 0.05). In conclusion, the salivary microbiome is resilient to an antibiotic challenge by a low-dose regimen of amoxicillin. Further studies evaluating the effect of routinely used higher dose regimens of amoxicillin on gram-negative bacteria and antibiotic resistance genes are warranted.

Matched MeSH terms: Gram-Negative Bacteria/drug effects
Graphene oxide exhibits differential mechanistic action towards Gram-positive and Gram-negative bacteria

Pulingam T, Thong KL, Ali ME, Appaturi JN, Dinshaw IJ, Ong ZY, et al.

Colloids Surf B Biointerfaces, 2019 Sep 01;181:6-15.
PMID: 31103799 DOI: 10.1016/j.colsurfb.2019.05.023

The antibacterial nature of graphene oxide (GO) has stimulated wide interest in the medical field. Although the antibacterial activity of GO towards bacteria has been well studied, a deeper understanding of the mechanism of action of GO is still lacking. The objective of the study was to elucidate the difference in the interactions of GO towards Gram-positive and Gram-negative bacteria. The synthesized GO was characterized by Ultraviolet-visible spectroscopy (UV-vis), Raman and Attenuated Total Reflectance-Fourier-transform infrared spectroscopy (ATR-FTIR). Viability, time-kill and Lactose Dehydrogenase (LDH) release assays were carried out along with FESEM, TEM and ATR-FTIR analysis of GO treated bacterial cells. Characterizations of synthesized GO confirmed the transition of graphene to GO and the antibacterial activity of GO was concentration and time-dependent. Loss of membrane integrity in bacteria was enhanced with increasing GO concentrations and this corresponded to the elevated release of LDH in the reaction medium. Surface morphology of GO treated bacterial culture showed apparent differences in the mechanism of action of GO towards Gram-positive and Gram-negative bacteria where cell entrapment was mainly observed for Gram-positive Staphylococcus aureus and Enterococcus faecalis whereas membrane disruption due to physical contact was noted for Gram-negative Escherichia coli and Pseudomonas aeruginosa. ATR-FTIR characterizations of the GO treated bacterial cells showed changes in the fatty acids, amide I and amide II of proteins, peptides and amino acid regions compared to untreated bacterial cells. Therefore, the data generated further enhance our understanding of the antibacterial activity of GO towards bacteria.

Matched MeSH terms: Gram-Negative Bacteria/drug effects*
Antibacterial and antioxidant potential of biosynthesized copper nanoparticles mediated through Cissus arnotiana plant extract

Rajeshkumar S, Menon S, Venkat Kumar S, Tambuwala MM, Bakshi HA, Mehta M, et al.

J. Photochem. Photobiol. B, Biol., 2019 Aug;197:111531.
PMID: 31212244 DOI: 10.1016/j.jphotobiol.2019.111531

Environment friendly methods for the synthesis of copper nanoparticles have become a valuable trend in the current scenario. The utilization of phytochemicals from plant extracts has become a unique technology for the synthesis of nanoparticles, as they possess dual nature of reducing and capping agents to the nanoparticles. In the present investigation we have synthesized copper nanoparticles (CuNPs) using a rare medicinal plant Cissus arnotiana and evaluated their antibacterial activity against gram negative and gram positive bacteria. The morphology and characterization of the synthesized CuNPs were studied and done using UV-Visible spectroscopy at a wavelength range of 350-380 nm. XRD studies were performed for analyzing the crystalline nature; SEM and TEM for evaluating the spherical shape within the size range of 60-90 nm and AFM was performed to check the surface roughness. The biosynthesized CuNPs showed better antibacterial activity against the gram-negative bacteria, E. coli with an inhibition zone of 22.20 ± 0.16 mm at 75 μg/ml. The antioxidant property observed was comparatively equal with the standard antioxidant agent ascorbic acid at a maximum concentration of 40 μg/ ml. This is the first study reported on C. arnotiana mediated biosynthesis of copper nanoparticles, where we believe that the findings can pave way for a new direction in the field of nanotechnology and nanomedicine where there is a significant potential for antibacterial and antioxidant activities. We predict that, these could lead to an exponential increase in the field of biomedical applications, with the utilization of green synthesized CuNPs, due to its remarkable properties. The highest antibacterial property was observed with gram-negative strains mainly, E. coli, due to its thin peptidoglycan layer and electrostatic interactions between the bacterial cell wall and CuNPs surfaces. Hence, CuNPs can be potent therapeutic agents in several biomedical applications, which are yet to be explored in the near future.

Matched MeSH terms: Gram-Negative Bacteria/drug effects

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