Displaying publications 1 - 20 of 126 in total

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  1. Ngoi ST, Chong CW, Ponnampalavanar SSS, Tang SN, Idris N, Abdul Jabar K, et al.
    Antimicrob Resist Infect Control, 2021 04 23;10(1):70.
    PMID: 33892804 DOI: 10.1186/s13756-021-00936-5
    BACKGROUND: Knowledge on the epidemiology, genotypic and phenotypic features of antimicrobial-resistant (AMR) ESKAPEE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli) and their association with hospital-acquired infections (HAIs) are limited in Malaysia. Therefore, we evaluated the AMR features and resistance mechanisms of the ESKAPEE pathogens collected in a tertiary hospital located in the capital of Malaysia.

    METHODS: A total of 378 AMR-ESKAPEE strains were obtained based on convenience sampling over a nine-month study period (2019-2020). All strains were subjected to disk diffusion and broth microdilution assays to determine the antimicrobial susceptibility profiles. Polymerase chain reaction (PCR) and DNA sequence analyses were performed to determine the AMR genes profiles of the non-susceptible strains. Chi-square test and logistic regression analyses were used to correlate the AMR profiles and clinical data to determine the risk factors associated with HAIs.

    RESULTS: High rates of multidrug resistance (MDR) were observed in A. baumannii, K. pneumoniae, E. coli, and S. aureus (69-89%). All organisms except E. coli were frequently associated with HAIs (61-94%). Non-susceptibility to the last-resort drugs vancomycin (in Enterococcus spp. and S. aureus), carbapenems (in A. baumannii, P. aeruginosa, and Enterobacteriaceae), and colistin (in Enterobacteriaceae) were observed. Both A. baumannii and K. pneumoniae harbored a wide array of extended-spectrum β-lactamase genes (blaTEM, blaSHV, blaCTX-M, blaOXA). Metallo-β-lactamase genes (blaVEB, blaVIM, blaNDM) were detected in carbapenem-resistant strains, at a higher frequency compared to other local reports. We detected two novel mutations in the quinolone-resistant determining region of the gyrA in fluoroquinolone-resistant E. coli (Leu-102-Ala; Gly-105-Val). Microbial resistance to ampicillin, methicillin, and cephalosporins was identified as important risk factors associated with HAIs in the hospital.

    CONCLUSION: Overall, our findings may provide valuable insight into the microbial resistance pattern and the risk factors of ESKAPEE-associated HAIs in a tertiary hospital located in central Peninsular Malaysia. The data obtained in this study may contribute to informing better hospital infection control in this region.

    Matched MeSH terms: Acinetobacter baumannii
  2. Anbazhagan D, Mui WS, Mansor M, Yan GO, Yusof MY, Sekaran SD
    Braz J Microbiol, 2011 Apr;42(2):448-58.
    PMID: 24031653 DOI: 10.1590/S1517-83822011000200006
    Nosocomial infections are major clinical threats to hospitalised patients and represent an important source of morbidity and mortality. It is necessary to develop rapid detection assays of nosocomial pathogens for better prognosis and initiation of antimicrobial therapy in patients. In this study, we present the development of molecular methods for the detection of six common nosocomial pathogens including Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. Conventional multiplex PCR and SYBR Green based real time PCR assays were performed using genus and species specific primers. Blind testing with 300 clinical samples was also carried out. The two assays were found to be sensitive and specific. Eubacterial PCR assay exhibited positive results for 46 clinical isolates from which 43 samples were detected by real time PCR assay. The sensitivity of the assay is about 93.7% in blind test isolates. The PCR results were reconfirmed using the conventional culture method. This assay has the potential to be a rapid, accurate and highly sensitive molecular diagnostic tool for simultaneous detection of Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. This assay has the potential to detect nosocomial pathogens within 5 to 6 hours, helping to initiate infection control measures and appropriate treatment in paediatric and elderly (old aged) patients, pre-and post surgery patients and organ transplant patients and thus reduces their hospitalization duration.
    Matched MeSH terms: Acinetobacter
  3. Basri R, Zueter AR, Mohamed Z, Alam MK, Norsa'adah B, Hasan SA, et al.
    Nagoya J Med Sci, 2015 Feb;77(1-2):59-68.
    PMID: 25797971
    To describe the clinical characteristics and the risk factors associated with mortality in patients with meningitis. This is a retrospective review of patients diagnosed to have meningitis with positive culture of the cerebrospinal fluid (CSF) specimen. All cases aged 19 > years who were admitted to Hospital USM between January 2004 and December 2011 were included in the study. The CSF results database were obtained from the Department of Medical Microbiology and Parasitology, Hospital USM, Kelantan. A checklist was used to record the clinical characteristics. A total of 125 cases met the inclusion criteria. The age of patients ranged between newborn and 19 years old (Mean±SD, 74.5±80.6 months). The majority of them were males (65.6%). Fever was the most common presentation (73.6%) followed by poor oral intake (48.0%), seizure (36.0%) and headache (24.8%). The mortality rate was 31.2%. Coagulase negative staphylococcus was the most frequent pathogens isolated (21.6%), followed by Acinetobacter spp. (17.6%), Staphylococcus aureus (13.6%), Streptococcus spp. (11.2%) and Klebsiella pneumoniae (6.4%). There were significant association of in-hospital death with age (p=0.020) and conscious level (p=0.001). Infectious meningitis is a big health concern, especially among children. We found that coagulase negative staphylococcus, Acinetobacter species, S. aureus, Streptococcus spp and K. pneumoniae were prevalent in our hospital. These microorganisms were hospital associated pathogens. The 31% mortality linked to hospital acquired meningitis specifies the need for focused physician attention especially among younger aged patients.
    Matched MeSH terms: Acinetobacter
  4. Ng, C. S., Vadivelu, M., Chan, K. Y.
    MyJurnal
    Abstract: Ampicillin-sulbactam combination is the most frequently prescribed antibiotic in diabetic foot ulcers. We conducted a retrospective study to evaluate the antibiotic sensitivity of bacteria isolated to this antibiotic. In 33 patients with diabetic foot ulcer (September 2008-March 2009), 67% were culture positive in which Citrobacter spp accounted for 36% of these isolates. The rest isolated included Pseudomonas aeruginosa (22%), Proteus spp (18%), Acinetobacter spp (9%), Klebsiella pneumoniae (5%), Escherichia coli (5%) and Staphylococcus aureus (5%). These isolates were more likely to be ampicillin-resistant (n=18) than were ampicillin-sensitive isolates (n=4). Ampicillin resistance has raised our concern about current practice of prescribing ampicillin/ sulbactam as monotherapy for majority of our patients with such ulcers.
    Matched MeSH terms: Acinetobacter
  5. Noor Fazdilah Mustari, Zafira Ayushah Zainul Alamin, Noraziah Mohammad Zin, Dayang Fredalina Basri
    MyJurnal
    The objective of this study was to evaluate the antimicrobial potential of methanol, acetone and distilled water stem
    bark extracts from Canarium odontophyllum against Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 6633,
    Escherichia coli ATCC 25932, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii strain sensitive, Candida
    albicans ATCC 64677, Candida glabrata ATCC 90028, Aspergillus niger and Fusarium solani M2781. The extracts from
    C. odontophyllum stem bark from 3.125 mg/ml to 25 mg/ml were screened against the tested microorganisms using disc
    diffusion method. The Minimum inhibitory concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the
    extracts against susceptible organisms were determined using microbroth dilution method and streak-plate technique,
    respectively. From the antibacterial screening assay, the growth of S. aureus, B. cereus and A. baumannii were inhibited
    by methanol extract whereas the acetone extract was capable of inhibiting all the tested microorganisms except E.coli,
    F. solani and A. niger. The lowest MIC value for methanol extract was against A. baumannii (0.195 mg/ml) whereas
    its MBC value was twice its MIC value (0.391 mg/ml), indicating that methanol extract was bacteriostatic against A.
    baumannii. While for acetone extract, S. aureus showed bactericidal effect with equal MIC and MBC values at 0.195 mg/
    ml. In conclusion, stem bark of C. odontophyllum has the potential to be the source of antibacterial agent and can be
    exploited as an alternative phytoantimicrobial.
    Matched MeSH terms: Acinetobacter baumannii
  6. Mohd R, Nesam T, Kamaruzaman L, Cader RA, Mustafar R, Kong WY
    Respir Med Case Rep, 2018;24:147-149.
    PMID: 29977783 DOI: 10.1016/j.rmcr.2018.05.019
    Acinetobacter baumannii is an aerobic Gram-negative coccobacillus that is associated with hospital acquired pneumonia. There is increased reporting of emergent cases of community acquired multidrug resistance (MDR) acinetobacter associated with a higher mortality due to antibiotic resistance. Community acquired MDR acinetobacter pneumonia has not been reported in Malaysia. Here we report a case of a 19-year-old army officer who presented with fever and respiratory symptoms for 5 days. He had no known medical illness before and no history of hospitalization. Upon arrival, he was in septicaemic shock, requiring invasive ventilator support and renal replacement therapy in intensive care unit. Chest radiograph showed bilateral lung consolidations and bronchoscopy revealed haemoserous and greenish bronchiole secretion. He was treated with broad spectrum antibiotics and oseltamivir. Unfortunately he died on day 3 of hospital admission. His bronchial lavage culture came back positive for MDR Acinetobacter baumannii. This case illustrates that clinicians need to be aware that MDR Acinetobacter baumannii can cause severe community acquired pneumonia. We may need to consider this diagnosis in patients who do not respond to standard therapy.
    Matched MeSH terms: Acinetobacter baumannii
  7. Cheng-Yee Fish-Low, Chee HY, Ainon Hamzah
    Sains Malaysiana, 2015;44:1625-1633.
    Microbial communities of two oil reservoirs from Malaysia, denoted as Platform Bo and Platform Pe were studied using
    culture-independent approach. Environmental DNA was extracted and the universal amplified ribosomal region (UARR)
    was target amplified for both prokaryotes and eukaryotes. The amplified products were purified and cloned into pTZ57R/T
    vector to construct the 16S/18S rDNA library. Restriction endocucleases HhaI and MspI were used to screen the library.
    From that, 125 and 253 recombinant plasmid representative clones from Platform Bo and Platform Pe, respectively, were
    sent for DNA sequencing. Twenty-six operational taxonomic units (OTUs) consist of 20 genera detected at Platform Bo
    and 17 OTUs consist of 13 genera detected at Platform Pe. Marinobacter and Acinetobacter species co-occurred in both
    platforms whereas the rest are site-specific. Gammaproteobacteria accounted for 86.0% of the microbial community in
    Platform Bo, where OTUs affiliated to Marinobacter, Pseudomonas and Marinobacterium that were the most abundant. The
    major OTUs in the Platform Pe were with affinities to Achromobacter, followed by Stenotrophomonas and Serratia. The
    only archaeal isolates were detected in Platform Pe, which affiliated to Thermocladium. The singletons and doubletons
    accounted for about 50.0% of the OTU abundance in both platforms, which considerably significant despite their rare
    occurrence.
    Matched MeSH terms: Acinetobacter
  8. Phoon HYP, Hussin H, Hussain BM, Lim SY, Woon JJ, Er YX, et al.
    J Glob Antimicrob Resist, 2018 09;14:132-140.
    PMID: 29540306 DOI: 10.1016/j.jgar.2018.02.022
    OBJECTIVES: Hospital environments are potential reservoirs of bacteria associated with nosocomial infections. In this study, the distribution of cultivable environmental bacteria of clinical importance from a Malaysian tertiary hospital was determined and their resistotypes and genotypes were investigated.

    METHODS: Swab and fluid samples (n=358) from healthcare workers' hands, frequently touched surfaces, medical equipment, patients' immediate surroundings, ward sinks and toilets, and solutions or fluids of 12 selected wards were collected. Biochemical tests, PCR and 16S rRNA sequencing were used for identification following isolation from CHROMagar™ Orientation medium. Clinically important bacteria such as Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter spp., Pseudomonas aeruginosa and Enterobacter spp. were further characterised by disc diffusion method and rep-PCR.

    RESULTS: The 24 Gram-negative and 19 Gram-positive bacteria species identified were widely distributed in the hospital environment. Staphylococci were predominant, followed by Bacillus spp. and P. aeruginosa. Frequently touched surfaces, medical equipment, and ward sinks and toilets were the top three sources of bacterial species. Nine S. aureus, four Acinetobacter spp., one K. pneumoniae and one Enterobacter spp. were multidrug-resistant (MDR). The ESKAPE organisms were genetically diverse and widely dispersed across the hospital wards. A MDR MRSA clone was detected in a surgical ward isolation room.

    CONCLUSION: The large variety of cultivable, clinically important bacteria, especially the genetically related MDR S. aureus, K. pneumoniae, Acinetobacter spp. and Enterobacter spp., from various sampling sites indicated that the surfaces and fomites in the hospital were potential exogenous sources of nosocomial infection in the hospital.

    Matched MeSH terms: Acinetobacter
  9. Deris ZZ
    Malays J Med Sci, 2015 Sep;22(5):1-6.
    PMID: 28239263
    The global emergence and dissemination of multidrug-resistant Gram-negative superbugs, particularly carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae, lead to the limited effectiveness of antibiotics for treating nosocomial infections. In most cases, polymyxins are the last resort therapy, and these antibiotics must be used intelligently to prolong their efficacy in clinical practice. Polymyxin B and colistin (polymyxin E) were introduced prior to modern drug regulation, and the majority of the 'old' drug information is unreliable. Recent pharmacokinetic data do not support the renal dose adjustment of intravenous (IV) polymyxin B as suggested by the manufacturer, and this drug must be scaled by the total body weight. Whereas IV colistin is formulated as an inactive prodrug, colistin methanesulfonate (CMS) has different pharmacokinetic profiles than polymyxin B. To achieve maximum efficacy, CMS should be administered as a loading dose scaled to body weight and a maintenance dose according to the renal profiles. Polymyxin combination therapy is suggested due to a sub-therapeutic plasma concentration in a significant proportion of patients and a high incidence of polymyxin hetero-resistance among Gram-negative superbugs. In conclusion, polymyxins must be reserved as a last resort and should be wisely used when truly indicated.
    Matched MeSH terms: Acinetobacter baumannii
  10. Chew YK, Cheong JP, Ramesh N, Noorafidah MD, Brito-Mutunayagam S, Khir A, et al.
    Ear Nose Throat J, 2014 Jun;93(6):E5-8.
    PMID: 24932831
    We conducted a retrospective observational study to determine the spectrum and antibiotic sensitivity pattern of organisms isolated in otorhinolaryngologic (ORL) infections. We reviewed the laboratory culture and sensitivity records of 4,909 patients-2,773 males (56.5%) and 2,136 females (43.5%), aged 2 to 90 years (mean: 45.3 ± 12.6)-who had been seen at two government hospitals in Malaysia. Of this group, 4,332 patients had a respiratory tract infection (88.2%), 206 had an ear infection (4.2%), 188 had a deep neck infection (3.8%), and 183 had an oropharyngeal infection (3.7%). The most common isolated organisms were Klebsiella spp, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, methicillin-susceptible S aureus, coagulase-negative S aureus, and Acinetobacter baumannii. We also identified the antimicrobial susceptibility of these organisms. We conclude that since the spectrum of causative pathogens in some infections differs between tropical and nontropical areas of the world, tropical hospitals should not completely adopt the antibiotic guidelines for ORL infections that have been recommended for hospitals in nontropical regions. We hope that our review and analysis of local data will help practitioners in Malaysia develop an appropriate prescribing policy with respect to ORL pathogens and antimicrobial susceptibility. The goal is to reduce the morbidity and mortality associated with these infections.
    Matched MeSH terms: Acinetobacter baumannii/drug effects
  11. Khoo YT, Halim AS, Singh KK, Mohamad NA
    PMID: 20815896 DOI: 10.1186/1472-6882-10-48
    Full-thickness burn wounds require excision and skin grafting. Multiple surgical procedures are inevitable in managing moderate to severe full-thickness burns. Wound bed preparations prior to surgery are necessary in order to prevent wound infection and promote wound healing. Honey can be used to treat burn wounds. However, not all the honey is the same. This study aims to evaluate the wound contraction and antibacterial properties of locally-produced Tualang honey on managing full-thickness burn wounds in vivo.
    Matched MeSH terms: Acinetobacter baumannii/drug effects
  12. Haseeb A, Faidah HS, Bakhsh AR, Malki WH, Elrggal ME, Saleem F, et al.
    Int J Infect Dis, 2016 Jun;47:92-4.
    PMID: 27312582 DOI: 10.1016/j.ijid.2016.06.006
    OBJECTIVE: To identify commonly reported community-acquired organisms and antimicrobial resistance patterns exhibited by Gram-positive and Gram-negative pathogens among pilgrims visiting emergency care departments in Makkah.
    METHOD: The study was designed as a retrospective audit of all patients (pilgrims) admitted to two hospitals and residing in the city of Makkah, Saudi Arabia.
    RESULTS: Among 374 isolates, Gram-negative pathogens accounted for 280 (75%), while the remaining 94 (25%) were Gram-positive organisms. Among all isolated pathogens, the highest resistance was observed for amoxicillin-clavulanic acid. Klebsiella pneumoniae had the highest resistance to amoxicillin-clavulanic acid and ampicillin. Most of the organisms were sensitive to tobramycin except Acinetobacter baumannii (n=3, 50%), Escherichia coli (n=4, 57%), and K. pneumoniae (n=6, 46%).
    CONCLUSION: Overall, a high resistance was observed for beta-lactam antibiotics. In addition, a high resistance was noted for ceftazidime with A. baumannii species (n=16, 77%). However, for quinolones, the highest resistance to ciprofloxacin was observed for E. coli, A. baumannii, methicillin-resistant Staphylococcus aureus, and K. pneumoniae.
    KEYWORDS: Antimicrobial resistance; Community-acquired organisms; Makkah; Pilgrims
    Matched MeSH terms: Acinetobacter baumannii/drug effects
  13. Williams JD, Moosdeen F, Teoh-Chan CH, Lim VK, Jayanetra P
    Eur J Epidemiol, 1989 Jun;5(2):207-13.
    PMID: 2504618
    Antibiotic resistance in Gram-negative bacteria, particularly Salmonella and Shigella, requires surveillance worldwide. This study describes results of surveys in Hong Kong, Bangkok and Kuala Lumpur. All strains were isolated in hospitals which have large community catchment areas in addition to specialised hospital units. The prevalence of resistant strains was high in all areas. Gram-negative bacteria such as Enterobacter associated with hospital infections were resistant to penicillins and cephalosporins, with gentamicin resistance ranging from about 20% in Kuala Lumpur and Hong Kong, to 35% in Bangkok. Ninety-seven percent of Shigella isolated in Thailand were resistant to ampicillin. About 10% of Salmonella were resistant to chloramphenicol in all three centres.
    Matched MeSH terms: Acinetobacter/drug effects
  14. Thong KL, Lai MY, Teh C SJ, Chua KH
    Trop Biomed, 2011 Apr;28(1):21-31.
    PMID: 21602765 MyJurnal
    A PCR-based assay that can simultaneously detect and differentiate five different types of nosocomial bacterial pathogens was developed. Six pairs of selected primers targeting femA (132 bp) and mecA (310 bp) of methicillin-resistant Staphylococcus aureus, gltA (722 bp) of Acinetobacter baumannii, phoA (903 bp) of Escherichia coli, mdh (364 bp) of Klebsiella pneumoniae and oprL (504 bp) of Pseudomonas aeruginosa were used in this study. The conditions were optimized for the multiplex PCR to ensure specific amplification of the selected targets. Sensitivity and specificity tests were also carried out using a blind test approach on 50 bacterial cultures and resulted in 100% for both positive and negative predictive values.
    Matched MeSH terms: Acinetobacter baumannii/isolation & purification
  15. Teerawattanapong N, Kengkla K, Dilokthornsakul P, Saokaew S, Apisarnthanarak A, Chaiyakunapruk N
    Clin Infect Dis, 2017 May 15;64(suppl_2):S51-S60.
    PMID: 28475791 DOI: 10.1093/cid/cix112
    Background: This study evaluated the relative efficacy of strategies for the prevention of multidrug-resistant gram-negative bacteria (MDR-GNB) in adult intensive care units (ICUs).

    Methods: A systematic review and network meta-analysis was performed; searches of the Cochrane Library, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) included all randomized controlled trials and observational studies conducted in adult patients hospitalized in ICUs and evaluating standard care (STD), antimicrobial stewardship program (ASP), environmental cleaning (ENV), decolonization methods (DCL), or source control (SCT), simultaneously. The primary outcomes were MDR-GNB acquisition, colonization, and infection; secondary outcome was ICU mortality.

    Results: Of 3805 publications retrieved, 42 met inclusion criteria (5 randomized controlled trials and 37 observational studies), involving 62068 patients (median age, 58.8 years; median APACHE [Acute Physiology and Chronic Health Evaluation] II score, 18.9). The majority of studies reported extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and MDR Acinetobacter baumannii. Compared with STD, a 4-component strategy composed of STD, ASP, ENV, and SCT was the most effective intervention (rate ratio [RR], 0.05 [95% confidence interval {CI}, .01-.38]). When ENV was added to STD+ASP or SCT was added to STD+ENV, there was a significant reduction in the acquisition of MDR A. baumannii (RR, 0.28 [95% CI, .18-.43] and 0.48 [95% CI, .35-.66], respectively). Strategies with ASP as a core component showed a statistically significant reduction the acquisition of ESBL-producing Enterobacteriaceae (RR, 0.28 [95% CI, .11-.69] for STD+ASP+ENV and 0.23 [95% CI, .07-.80] for STD+ASP+DCL).

    Conclusions: A 4-component strategy was the most effective intervention to prevent MDR-GNB acquisition. As some strategies were differential for certain bacteria, our study highlighted the need for further evaluation of the most effective prevention strategies.

    Matched MeSH terms: Acinetobacter baumannii/drug effects
  16. Monowar T, Rahman MS, Bhore SJ, Raju G, Sathasivam KV
    Biomed Res Int, 2019;2019:6951927.
    PMID: 30868071 DOI: 10.1155/2019/6951927
    Secondary bioactive compounds of endophytes are inevitable biomolecules of therapeutical importance. In the present study, secondary metabolites profiling of an endophytic bacterial strain, Acinetobacter baumannii, were explored using GC-MS study. Presence of antioxidant substances and antioxidant properties in chloroform (CHL), diethyl ether (DEE), and ethyl acetate (EA) crude extracts of the endophytic bacteria were studied. Total phenolic content (TPC), total flavonoid content (TFC), total antioxidant capacity (TAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and ferrous ion chelating assay were evaluated. A total of 74 compounds were identified from the GC-MS analysis of the EA extract representing mostly alkane compounds followed by phenols, carboxylic acids, aromatic heterocyclic compounds, ketones, aromatic esters, aromatic benzenes, and alkenes. Among the two phenolic compounds, namely, phenol, 2,4-bis(1,1-dimethylethyl)- and phenol, 3,5-bis(1,1-dimethylethyl)-, the former was found in abundance (11.56%) while the latter was found in smaller quantity (0.14%). Moreover, the endophytic bacteria was found to possess a number of metal ions including Fe(II) and Cu(II) as 1307.13 ± 2.35 ppb and 42.38 ± 0.352 ppb, respectively. The extracts exhibited concentration dependent antioxidant and prooxidant properties at high and low concentrations, respectively. The presence of phenolic compounds and metal ions was believed to play an important role in the antioxidant and prooxidant potentials of the extracts. Further studies are suggested for exploring the untapped resource of endophytic bacteria for the development of novel therapeutic agents.
    Matched MeSH terms: Acinetobacter baumannii/metabolism*
  17. Li Y, Ouyang Y, Wu H, Wang P, Huang Y, Li X, et al.
    Eur J Med Chem, 2022 Jan 15;228:113979.
    PMID: 34802838 DOI: 10.1016/j.ejmech.2021.113979
    The shortage of new antibiotics makes infections caused by gram-negative (G-) bacteria a significant clinical problem. The key enzymes involved in folate biosynthesis represent important targets for drug discovery, and new antifolates with novel mechanisms are urgently needed. By targeting to dihydrofolate reductase (DHFR), a series of 1,3-diamino-7H-pyrrol[3,2-f]quinazoline (PQZ) compounds were designed, and exhibited potent antibacterial activities in vitro, especially against multi-drug resistant G- strains. Multiple experiments indicated that PQZ compounds contain a different molecular mechanism against the typical DHFR inhibitor, trimethoprim (TMP), and the thymidylate synthase (TS) was identified as another potential but a relatively weak target. A significant synergism between the representative compound, OYYF-175, and sulfamethoxazole (SMZ) was observed with a strong cumulative and significantly bactericidal effect at extremely low concentrations (2 μg/mL for SMZ and 0.03 pg/mL for OYYF-175), which could be resulted from the simultaneous inhibition of dihydropteroate synthase (DHPS), DHFR and TS. PQZ compounds exhibited therapeutic effects in a mouse model of intraperitoneal infections caused by Escherichia coli (E. coli). The co-crystal structure of OYYF-175-DHFR was solved and the detailed interactions were provided. The inhibitors reported represent innovative chemical structures with novel molecular mechanism of action, which will benefit the generation of new, efficacious bactericidal compounds.
    Matched MeSH terms: Acinetobacter baumannii/drug effects
  18. Kuan KB, Othman R, Abdul Rahim K, Shamsuddin ZH
    PLoS One, 2016;11(3):e0152478.
    PMID: 27011317 DOI: 10.1371/journal.pone.0152478
    Plant growth-promoting rhizobacteria (PGPR) may provide a biological alternative to fix atmospheric N2 and delay N remobilisation in maize plant to increase crop yield, based on an understanding that plant-N remobilisation is directly correlated to its plant senescence. Thus, four PGPR strains were selected from a series of bacterial strains isolated from maize roots at two locations in Malaysia. The PGPR strains were screened in vitro for their biochemical plant growth-promoting (PGP) abilities and plant growth promotion assays. These strains were identified as Klebsiella sp. Br1, Klebsiella pneumoniae Fr1, Bacillus pumilus S1r1 and Acinetobacter sp. S3r2 and a reference strain used was Bacillus subtilis UPMB10. All the PGPR strains were tested positive for N2 fixation, phosphate solubilisation and auxin production by in vitro tests. In a greenhouse experiment with reduced fertiliser-N input (a third of recommended fertiliser-N rate), the N2 fixation abilities of PGPR in association with maize were determined by 15N isotope dilution technique at two harvests, namely, prior to anthesis (D50) and ear harvest (D65). The results indicated that dry biomass of top, root and ear, total N content and bacterial colonisations in non-rhizosphere, rhizosphere and endosphere of maize roots were influenced by PGPR inoculation. In particular, the plants inoculated with B. pumilus S1r1 generally outperformed those with the other treatments. They produced the highest N2 fixing capacity of 30.5% (262 mg N2 fixed plant-1) and 25.5% (304 mg N2 fixed plant-1) of the total N requirement of maize top at D50 and D65, respectively. N remobilisation and plant senescence in maize were delayed by PGPR inoculation, which is an indicative of greater grain production. This is indicated by significant interactions between PGPR strains and time of harvests for parameters on N uptake and at. % 15Ne of tassel. The phenomenon is also supported by the lower N content in tassels of maize treated with PGPR, namely, B. pumilus S1r1, K. pneumoniae Fr1, B. subtilis UPMB10 and Acinetobacter sp. S3r2 at D65 harvest. This study provides evidence that PGPR inoculation, namely, B. pumilus S1r1 can biologically fix atmospheric N2 and provide an alternative technique, besides plant breeding, to delay N remobilisation in maize plant for higher ear yield (up to 30.9%) with reduced fertiliser-N input.
    Matched MeSH terms: Acinetobacter*
  19. Ariffin H, Navaratnam P, Kee TK, Balan G
    J Trop Pediatr, 2004 Feb;50(1):26-31.
    PMID: 14984166
    The pattern of antibiotic resistance amongst gram-negative bacteria (GNB) in paediatric units, which have heavy empirical usage of broad-spectrum antibiotics, was studied prospectively over a 6-month period. A total of 200 consecutive, non-duplicate gram-negative isolates were obtained from 109 patients admitted to intensive care and oncology units in two hospitals. The commonest isolates were Klebsiella spp (36.5 per cent) and Pseudomonas (20.0 per cent). The isolates showed lower susceptibility rates to the third-generation cephalosporins (47-62 per cent) compared with cefepime (91 per cent), imipenem (90 per cent) and ciprofloxacin (99 per cent). Fifty-four (52.8 per cent) Klebsiella and Escherichia coli isolates were determined to be extended-spectrum beta-lactamase (ESBL) producing strains. Antibiotics found to be effective against ESBL-producers were imipenem and ciprofloxacin. The high resistance rate amongst GNB to third-generation cephalosporins is a likely consequence of heavy empirical usage of this group of antibiotics. The carbapenems and quinolones remain useful agents in the management of patients admitted to these units.
    Matched MeSH terms: Acinetobacter/drug effects; Acinetobacter/isolation & purification
  20. Ismail B, Shafei MN, Harun A, Ali S, Omar M, Deris ZZ
    J Microbiol Immunol Infect, 2018 Dec;51(6):763-769.
    PMID: 28716359 DOI: 10.1016/j.jmii.2017.03.007
    BACKGROUND: With increasing prevalence and spread of multidrug resistant Gram-negative infections, parenteral polymyxins resurged in clinical practice. The primary aim of the study was to determine the predictors of treatment failure and in-hospital mortality among critically ill patients treated with polymyxin B.

    METHODS: Demographic data, underlying diseases, procedures and details on polymyxin B therapy were retrospectively analyzed in a cohort of 84 patients who received intravenous polymyxin B in an intensive care unit from 2010 to 2014.

    RESULTS: Polymyxin B was used to treat bacteremia (46.4% of cases) and pneumonia (53.6%). Majority of the pathogens isolated were Acinetobacter spp. (96.4%). The mortality rate was 48.8%, of which 82.9% was attributed to polymyxin B treatment failure. The independent predictors of treatment failure were low doses of polymyxin B (p = 0.002), shorter duration of therapy (p = 0.009), not combining with cefoperazone/sulbactam (p = 0.030), female gender (p = 0.004), administered for treatment of bacteremia (p = 0.023) and renal impairment (p = 0.021). Low polymyxin B doses (p = 0.007), not combining with cefoperazone/sulbactam (p = 0.024), female gender (p = 0.048) and renal impairment (p = 0.022) were also significant predictors for in-hospital mortality.

    CONCLUSIONS: To the best of our knowledge, this is the first report on the association of inadequate dose of polymyxin B (<15,000 units/kg/day) with poor outcome in critically ill patients. Besides that, further clinical studies are warranted to evaluate the use of cefoperazone/sulbactam as second antibiotic in the combination therapy.

    Matched MeSH terms: Acinetobacter Infections/drug therapy; Acinetobacter Infections/mortality
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