Displaying publications 241 - 260 of 2190 in total

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  1. Saeed SI, Vivian L, Zalati CWSCW, Sani NIM, Aklilu E, Mohamad M, et al.
    BMC Vet Res, 2023 Jan 14;19(1):10.
    PMID: 36641476 DOI: 10.1186/s12917-022-03560-6
    BACKGROUND: S. aureus is one of the causative agents of bovine mastitis. The treatment using conventional antimicrobials has been hampered due to the development of antimicrobial resistance and the ability of the bacteria to form biofilms and localize inside the host cells.

    OBJECTIVES: Here, the efficacy of graphene oxide (GO), a carbon-based nanomaterial, was tested against the biofilms and intracellular S. aureus invitro. Following that, the mechanism for the intracellular antimicrobial activities and GO toxicities was elucidated.

    METHODS: GO antibiofilm properties were evaluated based on the disruption of biofilm structure, and the intracellular antimicrobial activities were determined by the survival of S. aureus in infected bovine mammary cells following GO exposure. The mechanism for GO intracellular antimicrobial activities was investigated using endocytosis inhibitors. GO toxicity towards the host cells was assessed using a resazurin assay.

    RESULTS: At 100 ug/mL, GO reduced between 30 and 70% of S. aureus biofilm mass, suggesting GO's ability to disrupt the biofilm structure. At 200 ug/mL, GO killed almost 80% of intracellular S. aureus, and the antimicrobial activities were inhibited when cells were pre-treated with cytochalasin D, suggesting GO intracellular antimicrobial activities were dependent on the actin-polymerization of the cell membrane. At

    Matched MeSH terms: Anti-Bacterial Agents/pharmacology
  2. Koh CL, Tay SH
    Singapore Med J, 1984 Oct;25(5):300-3.
    PMID: 6523137
    A clinical isolate of Proteus sp., resistant to ampicillin, carbenicillin, cephaloridine, chloramphenicol, cotrimoxazole, gentamicin,
    kanamycin and tetracycline, was examined for the presence of conjugative R plasmids. Results from conjugation, agarose gel
    electrophoresis and transformation experiments showed that it harboured a large self-transmissible R plasmid which coded for all
    the resistance traits.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology*
  3. Loong LS, Siew Mei Lai P, Jamaluddin NAH, Naina-Mohamed I, Periyasamy P, Lau CL, et al.
    J Infect Dev Ctries, 2022 Dec 31;16(12):1877-1886.
    PMID: 36753656 DOI: 10.3855/jidc.15925
    INTRODUCTION: Malaysia is an upper-middle-income country with national antimicrobial stewardship programs in place. However, hospitals in this country are faced with a high incidence of multidrug-resistant organisms and high usage of broad-spectrum antibiotics. Therefore, this study aimed to use a standardized audit tool to assess clinical appropriateness, guideline compliance, and prescribing patterns of antimicrobial use among medical patients in two tertiary hospitals in Malaysia to benchmark practice.

    METHODOLOGY: A prospective hospital-wide point prevalence survey was carried out by a multidisciplinary team in April 2019 at the University Malaya Medical Centre (UMMC) and the Hospital Canselor Tuanku Muhriz (HCTM), Kuala Lumpur, Malaysia. Data was collected from the patient's electronic medical records and recorded using the Hospital National Antimicrobial Prescribing Survey toolkit developed by the National Centre for Antimicrobial Stewardship, Australia.

    RESULTS: The appropriateness of prescriptions was 60.1% (UMMC) and 67% (HCTM), with no significant difference between the two hospitals. Compliance with guidelines was 60.0% (UMMC) and 61.5% (HCTM). Amoxicillin-clavulanic acid was the most commonly prescribed antimicrobial (UMMC = 16.9%; HCTM = 11.9%).

    CONCLUSIONS: The appropriateness of antimicrobial prescribing in medical wards, compliance with guidelines, and prescribing patterns were similar between the two hospitals in Malaysia. The survey identified several areas of prescribing that would need targeted AMS interventions.

    Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
  4. Bouyahya A, Taha D, Benali T, Zengin G, El Omari N, El Hachlafi N, et al.
    Biomed Pharmacother, 2023 May;161:114337.
    PMID: 36812715 DOI: 10.1016/j.biopha.2023.114337
    Cynaroside is a flavonoid, isolated from several species belonging to the Apiaceae, Poaceae, Lamiaceae, Solanaceae, Zingiberaceae, Compositae and other families and it can be extracted from seeds, roots, stems, leaves, barks, flowers, fruits, aerial parts, and the whole plant of these species. This paper discloses the current state of knowledge on the biological/pharmacological effects and mode of action to better understand the numerous health benefits of cynaroside. Several research works revealed that cynaroside could have beneficial effects on various human pathologies. Indeed, this flavonoid exerts antibacterial, antifungal, antileishmanial, antioxidant, hepatoprotective, antidiabetic, anti-inflammatory, and anticancer effects. Additionally, cynaroside exhibits its anticancer effects by blocking MET/AKT/mTOR axis by decreasing the phosphorylation level of AKT, mTOR, and P70S6K. For antibacterial activity, cynaroside reduces biofilm development of Pseudomonas aeruginosa and Staphylococcus aureus. Moreover, the incidence of mutations leading to ciprofloxacin resistance in Salmonella typhimurium was reduced after the treatment with cynaroside. In addition, cynaroside inhibited the production of reactive oxygen species (ROS), which reduced the damage to mitochondrial membrane potential caused by hydrogen peroxide (H2O2). It also enhanced the expression of the anti-apoptotic protein Bcl-2 and lowered that of the pro-apoptotic protein Bax. Cynaroside abrogated the up-regulation of c-Jun N-terminal kinase (JNK) and p53 protein expression triggered by H2O2. All these findings suggest that cynaroside could be used to prevent certain human diseases.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology
  5. Mhadi AA, Ong SC, Abed Y, Abu Ali KA
    Int J Pharm Pract, 2023 Apr 10;31(2):165-175.
    PMID: 36595471 DOI: 10.1093/ijpp/riac082
    OBJECTIVE: This study aimed to analyse the patterns of the irrational use of medicines in Arab countries and to determine the factors contributing to these patterns.

    METHODS: A systematic literature review was conducted using two major databases: PubMed and Scopus. The systematic search targeted original studies conducted in Arab countries from 2000 to 2019. A conceptual framework was adopted from a previous study and was utilized to assess the irrational use of medicines and its influencing factors.

    RESULTS: A total of 136 studies from 16 Arab countries were included. Almost all were cross-sectional studies. Most focused on evaluating the irrational use of medicines rather than investigating the cause. The number of medications per encounter was 2.3 which is within the limits of developed countries (2.7). The percentage of antibiotics per 100 encounter was 50.1% and the percentage of injections prescribed per 100 encounter was 15.2%. The consumption of antibiotic and injections was much higher than that recommended by WHO. At the same time, the review identified that one fourth of all medications were unnecessarily prescribed.

    SUMMARY: The literature review revealed that the irrational use of medicine is prevalent in most Arab countries. Excessive use of antibiotics was the most commonly observed pattern. Therefore, there is a need to conduct further research to identify the factors that drive the irrational use of medicines in Arab countries and then to make recommendations to mitigate this issue.

    Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
  6. Garg P, Khor WB, Roy A, Tan DT, APAX consortium
    Int Ophthalmol, 2023 Nov;43(11):4151-4162.
    PMID: 37526782 DOI: 10.1007/s10792-023-02816-w
    PURPOSE: To determine current institutional practice patterns for the use of perioperative antibiotics and other measures to prevent infection after cataract surgery in Asia.

    METHODS: An online survey-based study of leading eye institutions in China, Hong Kong, India, Indonesia, Japan, Malaysia, Pakistan, Philippines, Singapore, South Korea, Taiwan, Thailand and Vietnam was conducted. The survey was administered to 26 representative key opinion leaders from prominent tertiary eye institutions that are also national academic teaching institutions in Asia. Survey responses were collated and anonymized during analysis.

    RESULTS: All surveyed institutions used povidone iodine for the preoperative antiseptic preparation of the eye, with notable variations in the concentration of povidone iodine used for conjunctival sac instillation. Preoperative topical antibiotics were prescribed by 61.5% and 69.2% of institutions in low-risk and high-risk cases, respectively. Regarding the use of intra-operative antibiotics, 60.0% and 66.7% of institutions administered intracameral antibiotics in low-risk and high-risk patients, respectively. Postoperative topical antibiotics use patterns were generally very similar in low-risk and high-risk patients. Over half of the institutions (52.2% and 68.0% in low-risk and high-risk patients, respectively) also indicated prolonged postoperative use of topical antibiotics (> 2 weeks). Not all surveyed institutions had established policies/protocols for perioperative antibiotic use in cataract surgery, endophthalmitis surveillance, and/or a monitoring program for emerging antimicrobial resistance.

    CONCLUSION: There are variations in antimicrobial prophylaxis approaches to preoperative, intra-operative and postoperative regimens in cataract surgery in Asia. More evidence-based research is needed to support the development of detailed guidelines for perioperative antibiotic prophylaxis to reduce postoperative infections.

    Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
  7. Tsai MA, See MS, Chiu CH, Wang PC, Chen SC
    J Fish Dis, 2023 Nov;46(11):1239-1248.
    PMID: 37519120 DOI: 10.1111/jfd.13842
    Elizabethkingia meningoseptica is a hazardous bacterium for agriculture production and human health. The present study identified E. meningoseptica from the bullfrog, human and reference strain BCRC 10677 by API 20NE, 50S ribosome protein L27 sequencing and pulse field gel electrophoresis to differentiate isolates of E. meningoseptica from aquatic animals and humans. All isolates from bullfrogs and humans were identified as E. meningoseptica by DNA sequencing with 98.8%-100% sequence identity. E. meningoseptica displayed significant genetic diversity when analysed using pulsed-field gel electrophoresis (PFGE). There were six distinct pulsotypes, including one pulsotype found in bullfrog isolates and five pulsotypes found in human isolates. However, E. meningoseptica from bullfrog exhibited one genotype only by PFGE. Overall, molecular epidemiological analysis of PFGE results indicated that the frog E. meningoseptica outbreaks in Taiwan were produced by genetically identical clones. The bullfrog isolates were not genetically related to other E. meningoseptica from human and reference isolates. This research provided the first comparisons of biochemical characteristics and genetic differences of E. meningoseptica from human and bullfrog isolates.
    Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
  8. Dwiyanto J, Huët MAL, Hussain MH, Su TT, Tan JBL, Toh KY, et al.
    NPJ Biofilms Microbiomes, 2023 Aug 12;9(1):55.
    PMID: 37573460 DOI: 10.1038/s41522-023-00425-0
    The prevalence of antibiotic-resistant bacteria in Southeast Asia is a significant concern, yet there is limited research on the gut resistome and its correlation with lifestyle and environmental factors in the region. This study aimed to profile the gut resistome of 200 individuals in Malaysia using shotgun metagenomic sequencing and investigate its association with questionnaire data comprising demographic and lifestyle variables. A total of 1038 antibiotic resistance genes from 26 classes were detected with a mean carriage rate of 1.74 ± 1.18 gene copies per cell per person. Correlation analysis identified 14 environmental factors, including hygiene habits, health parameters, and intestinal colonization, that were significantly associated with the resistome (adjusted multivariate PERMANOVA, p 
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology
  9. Islam MB, Islam MI, Nath N, Emran TB, Rahman MR, Sharma R, et al.
    Biomed Res Int, 2023;2023:9967591.
    PMID: 37250749 DOI: 10.1155/2023/9967591
    Multidrug-resistant (MDR) pathogens have created a fatal problem for human health and antimicrobial treatment. Among the currently available antibiotics, many are inactive against MDR pathogens. In this context, heterocyclic compounds/drugs play a vital role. Thus, it is very much essential to explore new research to combat the issue. Of the available nitrogen-bearing heterocyclic compounds/drugs, pyridine derivatives are of special interest due to their solubility. Encouragingly, some of the newly synthesized pyridine compounds/drugs are found to inhibit multidrug-resistant S. aureus (MRSA). Pyridine scaffold bearing poor basicity generally improves water solubility in pharmaceutically potential molecules and has led to the discovery of numerous broad-spectrum therapeutic agents. Keeping these in mind, we have reviewed the chemistry, recent synthetic techniques, and bacterial preventative activity of pyridine derivatives since 2015. This will facilitate the development of pyridine-based novel antibiotic/drug design in the near future as a versatile scaffold with limited side effects for the next-generation therapeutics.
    Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
  10. Abbasi M, Gholizadeh R, Kasaee SR, Vaez A, Chelliapan S, Fadhil Al-Qaim F, et al.
    Sci Rep, 2023 Apr 12;13(1):5987.
    PMID: 37046068 DOI: 10.1038/s41598-023-33095-1
    In recent years, mesoporous silica nanoparticles (MSNs) have been applied in various biomedicine fields like bioimaging, drug delivery, and antibacterial alternatives. MSNs could be manufactured through green synthetic methods as environmentally friendly and sustainable synthesis approaches, to improve physiochemical characteristics for biomedical applications. In the present research, we used Rutin (Ru) extract, a biocompatible flavonoid, as the reducing agent and nonsurfactant template for the green synthesis of Ag-decorated MSNs. Transmission electron microscopy (TEM), zeta-potential, x-ray powder diffraction (XRD), fourier transform infrared (FTIR) spectroscopy analysis, scanning electron microscopy (SEM), brunauer-emmett-teller (BET) analysis, and energy-dispersive system (EDS) spectroscopy were used to evaluate the Ag-decorated MSNs physical characteristics. The antimicrobial properties were evaluated against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and also different types of candida. The cytotoxicity test was performed by using the MTT assay. Based on the findings, the significant antimicrobial efficacy of Ru-Ag-decorated MSNs against both gram positive and gram negative bacteria and different types of fungi was detected as well as acceptable safety and low cytotoxicity even at lower concentrations. Our results have given a straightforward and cost-effective method for fabricating biodegradable Ag-decorated MSNs. The applications of these MSNs in the domains of biomedicine appear to be promising.
    Matched MeSH terms: Anti-Bacterial Agents/chemistry
  11. Fitzrol DN, Ang SY, Suhaimi A, Yeap TB
    BMJ Case Rep, 2023 Apr 11;16(4).
    PMID: 37041040 DOI: 10.1136/bcr-2022-253959
    Polymyxin B (PB) is a polypeptide bactericidal antibiotic that is commonly used for extensively drug-resistant (XDR) microorganisms such as Acinetobacter baumanii and Klebsiella pneumoniae It can be administered intravenously or intrathecally. Common side effects are nephrotoxicity, neurotoxicity, pruritus and skin hyperpigmentation (SH). The latter is an uncommon adverse reaction of intravenously administered PB. We report a rare occurrence of PB-induced SH secondary to intrathecal administration of PB in a child with A. baumanii XDR ventriculitis. We describe the management of him and a brief review of PB.
    Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
  12. Riaz F, Hossain MS, Roney M, Ali Y, Qureshi S, Muhammad R, et al.
    J Biomol Struct Dyn, 2023 Nov;41(19):9756-9769.
    PMID: 36399018 DOI: 10.1080/07391102.2022.2146200
    Antimicrobial drug resistance (AMR) is a severe global threat to public health. The increasing emergence of drug-resistant bacteria requires the discovery of novel antibacterial agents. Quinoline derivatives have previously been reported to exhibit antimalarial, antiviral, antitumor, antiulcer, antioxidant and, most interestingly, antibacterial properties. In this study, we evaluated the binding affinity of three newly designed hydroxyquinolines derived from sulfanilamide (1), 4-amino benzoic acid (2) and sulfanilic acid (3) towards five bacterial protein targets (PDB ID: 1JIJ, 3VOB, 1ZI0, 6F86, 4CJN). The three derivatives were designed considering the amino acid residues identified at the active site of each protein involved in the binding of each co-crystallized ligand and drug-likeness properties. The ligands displayed binding energy values with the target proteins ranging from -2.17 to -8.45 kcal/mol. Compounds (1) and (3) showed the best binding scores towards 1ZI0/3VOB and 1JIJ/4CJN, respectively, which may serve as new antibiotic scaffolds. Our in silico results suggest that sulfanilamide (1) or sulfanilic acid (3) hydroxyquinoline derivatives have the potential to be developed as bacterial inhibitors, particularly MRSA inhibitors. But before that, it must go through the proper preclinical and clinical trials for further scientific validation. Further experimental studies are warranted to explore the antibacterial potential of these compounds through preclinical and clinical studies.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology
  13. Nie J, Aweya JJ, Yu Z, Zhou H, Wang F, Yao D, et al.
    J Immunol, 2022 Aug 01;209(3):476-487.
    PMID: 35851542 DOI: 10.4049/jimmunol.2200078
    Although invertebrates' innate immunity relies on several immune-like molecules, the diversity of these molecules and their immune response mechanisms are not well understood. Here, we show that Penaeus vannamei hemocyanin (PvHMC) undergoes specific deacetylation under Vibrio parahaemolyticus and LPS challenge. In vitro deacetylation of PvHMC increases its binding capacity with LPS and antibacterial activity against Gram-negative bacteria. Lysine residues K481 and K484 on the Ig-like domain of PvHMC are the main acetylation sites modulated by the acetyltransferase TIP60 and deacetylase HDAC3. Deacetylation of PvHMC on K481 and K484 allows PvHMC to form a positively charged binding pocket that interacts directly with LPS, whereas acetylation abrogates the positive charge to decrease PvHMC-LPS attraction. Besides, V. parahaemolyticus and LPS challenge increases the expression of Pvhdac3 to induce PvHMC deacetylation. This work indicates that, during bacterial infections, deacetylation of hemocyanin is crucial for binding with LPS to clear Gram-negative bacteria in crustaceans.
    Matched MeSH terms: Anti-Bacterial Agents/metabolism
  14. Muzahid NH, Md Zoqratt MZH, Ten KE, Hussain MH, Su TT, Ayub Q, et al.
    Sci Rep, 2023 Aug 03;13(1):12596.
    PMID: 37537198 DOI: 10.1038/s41598-023-39642-0
    Acinetobacter species are widely known opportunistic pathogens causing severe community and healthcare-associated infections. One such emerging pathogen, Acinetobacter colistiniresistens, is known to exhibit intrinsic resistance to colistin. We investigated the molecular characteristics of A. colistiniresistens strain C-214, isolated from the fecal sample of a healthy community member, as part of a cohort study being conducted in Segamat, Malaysia. Comparison of the whole genome sequence of C-214 with other A. colistiniresistens sequences retrieved from the NCBI database showed 95% sequence identity or more with many of the genome sequences representing that species. Use of the Galleria mellonella killing assay showed that C-214 was pathogenic in this model infection system. The strain C-214 had a colistin and polymyxin B MIC of 32 and 16 mg/L, respectively. Besides, it was resistant to cefotaxime, amikacin, and tetracycline and showed moderate biofilm-producing ability. Different genes associated with virulence or resistance to major classes of antibiotics were detected. We observed mutations in lpxA/C/D in C-214 and other A. colistiniresistens strains as probable causes of colistin resistance, but the biological effects of these mutations require further investigation. This study provides genomic insights into A. colistiniresistens, a potentially pathogenic bacterium isolated from a community member and notes the public health threat it may pose.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology
  15. Jha N, Thapa B, Pathak SB, Kafle S, Mudvari A, Shankar PR
    PLoS One, 2023;18(11):e0294644.
    PMID: 37983218 DOI: 10.1371/journal.pone.0294644
    INTRODUCTION: The access, watch, and reserve (AWaRe) classification of antibiotics was developed in 2019 by the WHO Expert Committee on the Selection and Use of Essential Medicines as a tool to support antibiotic stewardship efforts at local, national, and global levels. The objectives of this study were to assess the availability of antibiotics as per WHO AWaRe classification at community pharmacies located around a tertiary care hospital in Lalitpur and to compare these antibiotics with the national essential medicine list of Nepal.

    METHOD: The cross-sectional study was conducted at community pharmacies located within a two-kilometer radius of a teaching hospital from August to November 2022. A total of 82 community pharmacies registered with the Nepal Chemist and Druggists Association and the Department of Drug Administration were studied. Data was collected using a standard proforma containing the names of the antibiotics classified as per the WHO's AWaRe classification.

    RESULTS: Access group of antibiotics, Ampicillin, (82;100%), Amoxycillin, (82;100%), Flucloxacillin, (82;100%), and Metronidazole, (82;100%) were available in all community pharmacies. Results from the watch group showed that Azithromycin, (80; 97.6%) was available in all pharmacies followed by Cefixime, (80; 97.6%), Ciprofloxacin, (73; 89%), Levofloxacin, (74; 90.2%)and Ofloxacin, (74; 90.2%). Linezolid, (24; 29.3%) was the most common antibiotics available from the reserve group of antibiotics. Colistin was the second commonly available antibiotic. The most available antibiotic from the not recommended group were Ampicillin/Cloxacillin (82; 100%), followed by Piperacillin/Sulbactam, (39; 47.6%). There were differences in the classification of antibiotics between the WHO AWaRe list and the Essential Medicines list of Nepal in terms of numbers of antibiotics listed.

    CONCLUSION: Antibiotics from the not recommended and reserve groups were commonly available in community pharmacies. The implementation of antibiotic guidelines should be emphasized along with strict monitoring of the sale of antibiotics without a prescription in community pharmacy settings.

    Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
  16. Chang CY
    J Ayub Med Coll Abbottabad, 2023;35(2):348-350.
    PMID: 37422837 DOI: 10.55519/JAMC-02-11390
    BACKGROUND: Splenic abscess is an uncommon condition, with autopsy studies estimating an incidence rate of 0.14-0.70%. Causative organisms can be extremely diverse. Burkholderia pseudomallei is the most common cause of splenic abscess in melioidosis-endemic areas.

    METHODS: We reviewed 39 cases of splenic abscesses in a district hospital in Kapit, Sarawak, from January 2017 to December 2018. The demographics, clinical characteristics, underlying diseases, causative organisms, therapeutic methods, and mortality rates were investigated.

    RESULTS: There were 21 males and 18 females (mean age, 33.7±2.7 years). Almost all patients (97.4%) had a history of pyrexia. Diabetes mellitus was present in 8 patients (20.5%). Splenic abscesses were diagnosed using ultrasonography and were multiple in all 39 cases. Positive blood cultures were obtained in 20 patients (51.3%), and all yielded B. pseudomallei. Melioidosis serology was positive in 9 of 19 patients (47.4%) with negative blood cultures. All patients were treated for melioidosis with antibiotics without the need for surgical intervention. All splenic abscesses resolved after anti-melioidosis treatment was completed. One patient died (2.6%) as a result of B. pseudomallei septicaemia with multiorgan failure.

    CONCLUSIONS: Ultrasonography is a valuable tool for diagnosing splenic abscesses in resource-limited settings. B. pseudomallei was the most common etiological agent of splenic abscesses in our study.

    Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
  17. Chang CY, Lee HL
    J Ayub Med Coll Abbottabad, 2023;35(2):331-333.
    PMID: 37422833 DOI: 10.55519/JAMC-02-11131
    Burkholderia pseudomallei is a Gram-negative bacterium that causes melioidosis. Melioidosis is a potentially fatal disease that is endemic in Southeast Asia and Northern Australia and is being increasingly recognized in other regions worldwide. Melioidosis can affect any organ system and present with a wide range of clinical manifestations including pneumonia, bone, skin/soft tissue, or central nervous system infections. In this report, we describe a diabetic farmer who succumbed to persistent B. pseudomallei bacteraemia with multiorgan involvement despite treatment with meropenem and ceftazidime.
    Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
  18. Hanafin PO, Abdul Rahim N, Sharma R, Cess CG, Finley SD, Bergen PJ, et al.
    CPT Pharmacometrics Syst Pharmacol, 2023 Mar;12(3):387-400.
    PMID: 36661181 DOI: 10.1002/psp4.12923
    Carbapenemase-resistant Klebsiella pneumoniae (KP) resistant to multiple antibiotic classes necessitates optimized combination therapy. Our objective is to build a workflow leveraging omics and bacterial count data to identify antibiotic mechanisms that can be used to design and optimize combination regimens. For pharmacodynamic (PD) analysis, previously published static time-kill studies (J Antimicrob Chemother 70, 2015, 2589) were used with polymyxin B (PMB) and chloramphenicol (CHL) mono and combination therapy against three KP clinical isolates over 24 h. A mechanism-based model (MBM) was developed using time-kill data in S-ADAPT describing PMB-CHL PD activity against each isolate. Previously published results of PMB (1 mg/L continuous infusion) and CHL (Cmax : 8 mg/L; bolus q6h) mono and combination regimens were evaluated using an in vitro one-compartment dynamic infection model against a KP clinical isolate (108 CFU/ml inoculum) over 24 h to obtain bacterial samples for multi-omics analyses. The differentially expressed genes and metabolites in these bacterial samples served as input to develop a partial least squares regression (PLSR) in R that links PD responses with the multi-omics responses via a multi-omics pathway analysis. PMB efficacy was increased when combined with CHL, and the MBM described the observed PD well for all strains. The PLSR consisted of 29 omics inputs and predicted MBM PD response (R2  = 0.946). Our analysis found that CHL downregulated metabolites and genes pertinent to lipid A, hence limiting the emergence of PMB resistance. Our workflow linked insights from analysis of multi-omics data with MBM to identify biological mechanisms explaining observed PD activity in combination therapy.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology
  19. En ETS, Ismail N, Nasir NSM, Ismadi YKM, Zuraina NMNN, Hassan SA
    J Infect Public Health, 2023 Jul;16(7):1089-1092.
    PMID: 37224619 DOI: 10.1016/j.jiph.2023.05.015
    Hypervirulent Klebsiella pneumoniae (hvKp) is an emerging pathotype in addition to classical Klebsiella pneumoniae, with its ability to cause life-threatening, community-acquired metastatic infections even in healthy individuals. We presented a case of cerebral abscess preceded by otitis media in a 10-year-old child caused by hvKp. The isolates from blood pus aspirate were later identified as K. pneumoniae capsular serotype K2 and closely related to sequence type (ST65), with multiple hypervirulent genes detected (rmpA, rmpA2, iucA and peg344). She succumbed to death despite surgical drainage and susceptible antibiotic therapy. Clinicians should be cognizant of the rising incidence of hvKp infections in pediatric populations.
    Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
  20. Mohan A, Yeong LC, Kumarasamy G, Manan K
    J Infect Dev Ctries, 2023 Jun 30;17(6):886-890.
    PMID: 37406064 DOI: 10.3855/jidc.17821
    A 12-year-old boy was admitted after 11 days of fever and 2 days of nasal obstruction as well as swelling of a right cervical lymph node. Nasal endoscopy and computed tomography of the neck showed a nasopharyngeal mass occupying the entire nasopharynx, extending into the nasal cavity, and obliterating the fossa of Rosenmuller. Abdominal ultrasonography revealed a small solitary splenic abscess. Although a nasopharyngeal tumor or malignancy was initially considered, biopsy of the mass showed only suppurative granulomatous inflammation, and bacterial culture from the enlarged cervical lymph node yielded Burkholderia pseudomallei. The symptoms, nasopharyngeal mass, and cervical lymph node enlargement resolved with melioidosis-directed antibiotic therapy. Although rarely reported, the nasopharynx may be an important primary site of infection in melioidosis patients, especially in pediatric patients.
    Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
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