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Short cationic lipopeptides as effective antibacterial agents: Design, physicochemical properties and biological evaluation

Azmi F, Elliott AG, Marasini N, Ramu S, Ziora Z, Kavanagh AM, et al.

Bioorg Med Chem, 2016 05 15;24(10):2235-41.
PMID: 27048775 DOI: 10.1016/j.bmc.2016.03.053

The spread of drug-resistant bacteria has imparted a sense of urgency in the search for new antibiotics. In an effort to develop a new generation of antibacterial agents, we have designed de novo charged lipopeptides inspired by natural antimicrobial peptides. These short lipopeptides are composed of cationic lysine and hydrophobic lipoamino acids that replicate the amphiphilic properties of natural antimicrobial peptides. The resultant lipopeptides were found to self-assemble into nanoparticles. Some were effective against a variety of Gram-positive bacteria, including strains resistant to methicillin, daptomycin and/or vancomycin. The lipopeptides were not toxic to human kidney and liver cell lines and were highly resistant to tryptic degradation. Transmission electron microscopy analysis of bacteria cells treated with lipopeptide showed membrane-damage and lysis with extrusion of cytosolic contents. With such properties in mind, these lipopeptides have the potential to be developed as new antibacterial agents against drug-resistant Gram-positive bacteria.

Matched MeSH terms: Gram-Positive Bacterial Infections/drug therapy
On-Demand Guided Bone Regeneration with Microbial Protection of Ornamented SPU Scaffold with Bismuth-Doped Single Crystalline Hydroxyapatite: Augmentation and Cartilage Formation

Selvakumar M, Srivastava P, Pawar HS, Francis NK, Das B, Sathishkumar G, et al.

ACS Appl Mater Interfaces, 2016 Feb 17;8(6):4086-100.
PMID: 26799576 DOI: 10.1021/acsami.5b11723

Guided bone regeneration (GBR) scaffolds are futile in many clinical applications due to infection problems. In this work, we fabricated GBR with an anti-infective scaffold by ornamenting 2D single crystalline bismuth-doped nanohydroxyapatite (Bi-nHA) rods onto segmented polyurethane (SPU). Bi-nHA with high aspect ratio was prepared without any templates. Subsequently, it was introduced into an unprecedented synthesized SPU matrix based on dual soft segments (PCL-b-PDMS) of poly(ε-caprolactone) (PCL) and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, undoped pristine nHA rods were also ornamented into it. The enzymatic ring-opening polymerization technique was adapted to synthesize soft segments of PCL-b-PDMS copolymers of SPU. Structure elucidation of the synthesized polymers is done by nuclear magnetic resonance spectroscopy. Sparingly, Bi-nHA ornamented scaffolds exhibit tremendous improvement (155%) in the mechanical properties with excellent antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast cells (in vitro), the scaffolds were implanted in rabbits by subcutaneous and intraosseous (tibial) sites. Various histological sections reveal the signatures of early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks of the critical defects filled with ornamented scaffold compared to SPU scaffold. This implies osteogenic potential and ability to provide an adequate biomimetic microenvironment for mineralization for GBR of the scaffolds. Organ toxicity studies further confirm that no tissue architecture abnormalities were observed in hepatic, cardiac, and renal tissue sections. This finding manifests the feasibility of fabricating a mechanically adequate nanofibrous SPU scaffold by a biomimetic strategy and the advantages of Bi-nHA ornamentation in promoting osteoblast phenotype progression with microbial protection (on-demand) for GBR applications.

Matched MeSH terms: Bacterial Infections/drug therapy*
Fulltext Bacterial infection of central venous catheters in short-term total parenteral nutrition

Chan L, Ngeow YF, Parasakthi N

Med J Malaysia, 1998 Mar;53(1):10-5.
PMID: 10968131

Fourteen severely ill ventilated patients in an intensive care unit, requiring short-term total parenteral nutrition, were examined for catheter-related infection. Microbiological analysis using Maki's SQ technique was carried out on catheter exit site, catheter hub, proximal subcutaneous segment of catheter and catheter up. Qualitative cultures were carried out on total parenteral nutrition and peripheral blood samples. Twenty six of 29 catheters removed (90%) were culture positive but only 7 catheters were related to positive blood cultures, giving a catheter-related bacteremia (CRB) rate of 24%. Haematogenous seeding was strongly implicated in 7/29 (24%) of catheters. Patients' skin flora appeared to be the main source of catheter-related infection. The organisms isolated for patients with CRB included coagulase-negative staphylococci, Acinetobacter and Klebsiella. It is suggested that to control infective complications of central venous catheters, emphasis should be focused on specialised intravenous therapy teams and the use of strict protocols for insertion and care of central lines.

Matched MeSH terms: Bacterial Infections/etiology*
Fulltext Nosocomial bacterial sepsis in babies weighing 1000-1499 g in Kelantan

Halder D, Haque ME, Zabidi MH, Kamaruzzaman A

Med J Malaysia, 1999 Mar;54(1):52-7.
PMID: 10972005

From January to December 1992, 92 babies weighing 1000-1499 gm here to referred as very low birth weight (VLBW) were admitted to NICU (Neonatal Intensive Care Unit), Hospital University Sains Malaysia (HUSM). Sixty babies were inborn giving a VLBW rate of 7.5 per 1000 live births. Incidence of nosocomial sepsis was 32.6% (30/92) of whom 43.3% (13/30) died. Eighty percent (24/30) of the septic babies had blood culture positive for gram negative organisms of which 40% (12/30) were sensitive only to imipenem. Ventilator support within 24 hours of life was required in 41.3% (38/94) babies of whom 42% (16/38) babies developed nosocomial sepsis. Delayed initiation of feeding was significantly associated with nosocomial sepsis. A strict asepsis policy and early feeding of the VLBW infant are essential components of any strategy to prevent of sepsis due to nosocomial infection.

Matched MeSH terms: Bacterial Infections/epidemiology*
Childhood non-traumatic coma in Kuala Lumpur, Malaysia

Sofiah A, Hussain IH

Ann Trop Paediatr, 1997 Dec;17(4):327-31.
PMID: 9578792

All post-neonatal children with acute non-traumatic coma admitted over an 8-month period were analysed and followed up for 18-24 months to determine the aetiology and outcome of their coma. One hundred and sixteen children, 72 boys and 44 girls, were recruited. Half the children were under 1 year of age and only 16 (14%) were more than 6 years of age. Eighty cases (69%) were due to infection, 15 (13%) to toxic metabolic causes, six (5%) to hypoxic ischaemic insults, four (3.5%) had intracranial haemorrhage, nine (7.8%) were due to miscellaneous causes and in two (1.7%) the cause was unknown. Seven cases were lost to follow-up. Of the remainder, 39 (35.7%) died, 32 (29.3%) developed permanent neurological deficit, and 38 (35%) were discharged well. The outcome was worst in the infectious group. Age of onset and sex did not significantly affect outcome. Our findings are similar to experience in Japan, where infection accounts for 74% of non-traumatic coma, but differ considerably from Western data on childhood coma where only a third of cases are due to infection.

Matched MeSH terms: Bacterial Infections/complications
Fulltext Cytokines in infection

Pang T

Med J Malaysia, 1993 Mar;48(1):9-11.
PMID: 8341179

Cytokines are central to the development of effective immunity against microbial pathogens and their beneficial effects in the control of a variety of infections of man and animals are well-documented. However, it appears that cytokines may also have detrimental effects in infections by actually enhancing microbial growth. These observations emphasise the fact that many successful pathogens possess mechanisms enabling them to evade the immune response and that caution needs to be exercised in using cytokines as therapeutic agents to control infections in various human diseases.

Matched MeSH terms: Bacterial Infections/therapy
Fulltext Bacterial peritonitis in peritoneal dialysis

Cheong IKS, Lim VKE, Ujang K

Med J Malaysia, 1981 Mar;36(1):17-9.
PMID: 7321932

38 episodes of peritonitis in 28 patients were recorded among 97 patients undergoing a total of 159 peritoneal dialysis at the Nephrology Unit, General Hospital, Kuala Lumpur between November 1979 to June 1980. Of these only 14 episodes were associated with a positive bacterial culture. Organism of the Moraxella-Acinetobacter group were responsible in 8 episodes. There were 16 positive cultures in patients who had no clinical evidence of peritonitis. The interpretation of bacterial peritonitis in patients undergoing peritoneal dialysis must be made on the basis of clinical findings and bacteriological reports.

Matched MeSH terms: Bacterial Infections/etiology*
Trimethoprim-sulphamethoxazole in the treatment of infections in obstetrical and gynaecological practice. A bacteriological and clinical study

Hing NK, Hai CK, Ping WW

Med J Malaysia, 1974 Jun;28(4):260-2.
PMID: 4278676
Matched MeSH terms: Bacterial Infections/drug therapy*
Vector competence of Malaysian Aedes albopictus with and without Wolbachia to four dengue virus serotypes

Joanne S, Vythilingam I, Teoh BT, Leong CS, Tan KK, Wong ML, et al.

Trop Med Int Health, 2017 09;22(9):1154-1165.
PMID: 28653334 DOI: 10.1111/tmi.12918

OBJECTIVE: To determine the susceptibility status of Aedes albopictus with and without Wolbachia to the four dengue virus serotypes.
METHODS: Two newly colonised colonies of Ae. albopictus from the wild were used for the study. One colony was naturally infected with Wolbachia while in the other Wolbachia was removed by tetracycline treatment. Both colonies were orally infected with dengue virus-infected fresh blood meal. Dengue virus load was measured using quantitative RT-PCR at four-time intervals in the salivary glands, midguts and ovaries.
RESULTS: Wolbachia did not significantly affect Malaysian Ae. albopictus dengue infection or the dissemination rate for all four dengue virus serotypes. Malaysian Ae. albopictus had the highest replication kinetics for DENV-1 and the highest salivary gland and midgut infection rate for DENV-4.
CONCLUSION: Wolbachia, which naturally exists in Malaysian Ae. albopictus, does not significantly affect dengue virus replication. Malaysian Ae. albopictus is susceptible to dengue virus infections and capable of transmitting dengue virus, especially DENV-1 and DENV-4. Removal of Wolbachia from Malaysian Ae. albopictus would not reduce their susceptibility status.

Matched MeSH terms: Bacterial Infections/complications
Gastrointestinal infections in children in the Southeast Asia region: emerging issues

Lee WS

J Pediatr Gastroenterol Nutr, 2000 Mar;30(3):241-5.
PMID: 10749405
Matched MeSH terms: Bacterial Infections/drug therapy
Safety of probiotics: translocation and infection

Liong MT

Nutr Rev, 2008 Apr;66(4):192-202.
PMID: 18366533 DOI: 10.1111/j.1753-4887.2008.00024.x

The long history of safety has contributed to the acceptance of probiotics as a safe food adjunct. Consequently, many probiotic products and their applications have been granted GRAS (generally regarded as safe) status. However, this classification has been frequently generalized for all probiotic strains regardless of their application. Cases of probiotics from the genera Lactobacillus, Leuconostoc, Pediococcus, Enterococcus, and Bifidobacterium have been isolated from infection sites, leading to the postulation that these probiotics can translocate. Probiotic translocation is difficult to induce in healthy humans, and even if it does occur, detrimental effects are rare. Despite this, various reports have documented health-damaging effects of probiotic translocation in immunocompromised patients. Due to probiotics' high degree of safety and their morphological confusion with other pathogenic bacteria, they are often overlooked as contaminants and are least suspected as pathogens. However, the antibiotic resistance of some strains has increased the complexity of their eradication. Probiotic translocation and infection deserve further investigation and should become a facet of safety assessment so the negative effects of probiotics do not outweigh the benefits.

Matched MeSH terms: Bacterial Infections/epidemiology*
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 Bacterial Infections/microbiology*
Fulltext Bacteria fauna from the house fly, Musca domestica (L.)

Nazni WA, Seleena B, Lee HL, Jeffery J, T Rogayah TA, Sofian MA

Trop Biomed, 2005 Dec;22(2):225-31.
PMID: 16883292 MyJurnal

The house fly, Musca domestica has long been considered a potential agent for disease transmission ever since its existence. The general truth of this assertion remains undisputed till the present day in spite of increasing awareness toward an improved sanitation and better hygiene. The habitual movement of house fly from filthy substrata such as human faeces, animal excreta, carcasses, garbage, etc. makes them ideal candidates for disease transmission such as cholera, shigellosis, salmonellosis and others when settling on food. Fly as a potential mechanical vector of pathogenic bacteria was elucidated in this study by examining flies from various breeding sites such as food courts, dumping ground, food processing areas and poultry farm in Peninsular Malaysia. The flies were baited with 10% sugar solution on a glass slide in the field. All materials used for collection of samples were sterile. Bacteria from fly sample were isolated using the normal isolation technique. Bacillus sp., Coccobacillus sp., Staphylococcus sp., Microccus sp., Streptococcus sp., Acinetobacter sp., Enterobacter sp., Proteus sp., Escherichia sp., Klebsiella sp. and yeast cells were isolated from feaces, vomitus, external surfaces and internal organs of house fly. Newly emerged house fly did not harbour any bacteria.

Matched MeSH terms: Bacterial Infections/transmission
Cellulitis due to Shewanella algae: Crucial diagnostic clues from basic microbiological tests

Ding CH, Wahab AA, Muttaqillah NAS, Kamarudin N, Saarah WR

Trop Biomed, 2019 Dec 01;36(4):883-887.
PMID: 33597461

Shewanella spp. are infrequently implicated in human infections but they are emerging pathogens with particular significance in regions with warm climates, such as Southeast Asia. This is a case of a middle-aged diabetic and hypertensive man who presented with worsening congestive heart failure symptoms associated with fever and a painful right leg. His right leg had numerous scabs and was tender, warm and erythematous. He was provisionally diagnosed with decompensated heart failure precipitated by cellulitis and uncontrolled hypertension. His blood grew non-fermentative, oxidase-positive and motile gram-negative bacilli which produced hydrogen sulfide on triple sugar iron agar. When cultured on blood agar, mucoid and weakly β-haemolytic colonies were observed after 48 hours. API 20 NE named the isolate as Shewanella putrefaciens but 16S rRNA sequence analysis identified the organism as Shewanella algae. The patient was treated with a 10-day course of ceftazidime, which resulted in the resolution of the cellulitis.

Matched MeSH terms: Gram-Negative Bacterial Infections/diagnosis*
The bacterial causes of diarrhoea in Malaysia

Jegathesan M, Singh RB, Kanaganayagi M, Soon LE

Med J Malaysia, 1976 Sep;31(1):46-56.
PMID: 799233
Matched MeSH terms: Bacterial Infections/complications*
Characterization of the relationship between polar and lateral flagellar genes in clinical Aeromonas dhakensis: phenotypic, genetic and biochemical analyses

Lau TV, Puah SM, Tan JMA, Puthucheary SD, Chua KH

Braz J Microbiol, 2021 Jun;52(2):517-529.
PMID: 33768508 DOI: 10.1007/s42770-021-00457-8

Flagellar-mediated motility is a crucial virulence factor in many bacterial species. A dual flagellar system has been described in aeromonads; however, there is no flagella-related study in the emergent human pathogen Aeromonas dhakensis. Using 46 clinical A. dhakensis, phenotypic motility, genotypic characteristics (flagellar genes and sequence types), biochemical properties and their relationship were investigated in this study. All 46 strains showed swimming motility at 30 °C in 0.3% Bacto agar and carried the most prevalent 6 polar flagellar genes cheA, flgE, flgG, flgH, flgL, and flgN. On the contrary, only 18 strains (39%) demonstrated swarming motility on 0.5% Eiken agar at 30 °C and they harbored 11 lateral flagellar genes lafB, lafK, lafS, lafT, lafU, flgCL, flgGL, flgNL, fliEL, fliFL, and fliGL. No association was found between biochemical properties and motility phenotypes. Interestingly, a significant association between swarming and strains isolated from pus was observed (p = 0.0171). Three strains 187, 277, and 289 isolated from pus belonged to novel sequence types (ST522 and ST524) exhibited fast swimming and swarming profiles, and they harbored > 90% of the flagellar genes tested. Our findings provide a fundamental understanding of flagellar-mediated motility in A. dhakensis.

Matched MeSH terms: Gram-Negative Bacterial Infections/microbiology*
The antibacterial activity of fluoroquinolone derivatives: An update (2018-2021)

Jia Y, Zhao L

Eur J Med Chem, 2021 Nov 15;224:113741.
PMID: 34365130 DOI: 10.1016/j.ejmech.2021.113741

Bacterial infection is amongst the most common diseases in community and hospital settings. Fluoroquinolones, exerting the antibacterial activity through binding to type II bacterial topoisomerase enzymes, DNA gyrase and topoisomerase IV, are mainstays of chemotherapy. At present, fluoroquinolones are the most valuable antibacterial agents used popularly. However, the emergence of more virulent and resistant pathogens by the development of either mutated DNA-binding proteins or efflux pump mechanism for fluoroquinolones results in an urgent demand to develop new fluoroquinolones to withstand the drug resistance and to obtain a broader spectrum of activity. This review aims to outline the recent advances of fluoroquinolone derivatives with antibacterial potential and to summarize the structure-activity relationship (SAR) so as to provide an insight for rational design of more active candidates, covering articles published between January 2018 and June 2021.

Matched MeSH terms: Bacterial Infections/drug therapy*
Effect of dietary prebiotics and probiotics on snakehead (Channa striata) health: Haematology and disease resistance parameters against Aeromonas hydrophila

Munir MB, Hashim R, Nor SAM, Marsh TL

Fish Shellfish Immunol, 2018 Apr;75:99-108.
PMID: 29407616 DOI: 10.1016/j.fsi.2018.02.005

This study examined the effect of dietary prebiotics and probiotics after 16 weeks, followed by 8 weeks of post feeding trial with the control unsupplemented diet on haematological and immune response against Aeromonas hydrophila infection in Channa striata fingerlings. Fish were raised on a 40% protein and 12% lipid feed containing three commercial prebiotics (β-glucan, GOS or galacto-oligosaccharide, MOS or mannan-oligosaccharide); and two probiotics- (Saccharomyces cerevisiae, Lactobacillus acidophilus), respectively and a control. Throughout the study, supplementation with dietary prebiotics and probiotics led to significant (P 

Matched MeSH terms: Gram-Negative Bacterial Infections/immunology
Fulltext Chromobacterium violaceum septicaemia in Malaysia

Sagin DD, Tan PT, Dolkadir J

Singapore Med J, 1994 Aug;35(4):426.
PMID: 7899912
Matched MeSH terms: Gram-Negative Bacterial Infections/diagnosis*
Fulltext Fatal Chromobacterium violaceum septicaemia

Hassan H, Suntharalingam S, Dhillon KS

Singapore Med J, 1993 Oct;34(5):456-8.
PMID: 8153700

A 19-year-old Malay male succumbed to a septicaemia caused by Chromobacterium violaceum 11 days after onset of illness. The organism is a common soil saprophyte and may be considered as contaminant on culture. It is essential to recognise its clinical significance in purulent processes so that appropriate therapy can be instituted. We report the first fatal case of Chromobacterium violaceum infection in the University Hospital, Kuala Lumpur.

Matched MeSH terms: Gram-Negative Bacterial Infections*

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