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Pharmacological importance of TG12 from tachykinin and its toxicological behavior against multidrug-resistant bacteria Klebsiella pneumonia

Raju SV, Sarkar P, Pasupuleti M, Saraswathi NT, Arasu MV, Al-Dhabi NA, et al.

Comp Biochem Physiol C Toxicol Pharmacol, 2021 Jul;245:108974.
PMID: 33465517 DOI: 10.1016/j.cbpc.2021.108974

Development of antimicrobial drugs against multidrug-resistant (MDR) bacteria is a great focus in recent years. TG12, a short peptide molecule used in this study was screened from tachykinin (Tac) protein of an established teleost Channa striatus (Cs) transcriptome. Tachykinin cDNA has 345 coding sequence, that denotes a protein contained 115 amino acids; in which a short peptide (TG12) was identified at 83-94. Tachykinin mRNA upregulated in C. striatus treated with Aeromonas hydrophila and Escherichia coli lipopolysaccharide (LPS). The mRNA up-regulation was studied using real-time PCR. The up-regulation tachykinin mRNA pattern confirmed the immune involvement of tachykinin in C. striatus during infection. Further, the identified peptide, TG12 was synthesized and its toxicity was demonstrated in hemolytic and cytotoxic assays using human erythrocytes and human dermal fibroblast cells, respectively. The toxicity study exhibited that the toxicity of TG12 was similar to negative control, phosphate buffer saline (PBS). Moreover, the antibiogram of TG12 was active against Klebsiella pneumonia ATCC 27736, a major MDR bacterial pathogen. Further, the antimicrobial activity of TG12 against pathogenic bacteria was screened using minimum inhibitory concentration (MIC) and anti-biofilm assays, altogether TG12 showed potential activity against K. pneumonia. Fluorescence assisted cell sorter flow cytometer analysis (FACS) and field emission scanning electron microscopy (FESEM) was carried on TG12 with K. pneumonia; the results showed that TG12 significantly reduced K. pneumonia viability as well as TG12 disrupt its membrane. In conclusion, TG12 of CsTac is potentially involved in the antibacterial immune mechanisms, which has a prospectus efficiency in pharma industry against MDR strains, especially K. pneumonia.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial/drug effects*
Virulence properties and pathogenicity of multidrug-resistant Vibrio harveyi associated with luminescent vibriosis in Pacific white shrimp, Penaeus vannamei

Nurhafizah WWI, Lee KL, Laith A AR, Nadirah M, Danish-Daniel M, Zainathan SC, et al.

J Invertebr Pathol, 2021 11;186:107594.
PMID: 33878330 DOI: 10.1016/j.jip.2021.107594

Global high demand for Pacific white shrimp Penaeus vannamei has led to intensified cultivation and a wide range of disease problems, including bacterial diseases due to vibrios. Three presumptive luminescent Vibrio harveyi strains (Vh5, Vh8 and Vh10) were isolated from the hepatopancreas (Vh5) and haemolymph (Vh8 and Vh10) of diseased growout Pacific white shrimp from a farm in Setiu, Terengganu, Malaysia, using Vibrio harveyi agar (VHA) differential medium. All three strains were identified as V. harveyi by biochemical characteristics. 16S rRNA gene-based phylogenetic analyses by neighbour-joining, maximum likelihood and maximum parsimony methods showed all three strains in the V. harveyi cluster. All three strains were β-haemolytic and positive for motility, biofilm formation and extracellular products (caseinase, gelatinase, lipase, DNase, amylase and chitinase). Vh10 was subjected to pathogenicity test in Pacific white shrimp by immersion challenge and determined to have a LC50 of 6.0 × 108 CFU mL-1 after 168 h of exposure. Antibiotic susceptibility tests showed that all strains were resistant to oxytetracycline (OXT30), oleandomycin (OL15), amoxicillin (AML25), ampicillin (AMP10) and colistin sulphate (CT25) but sensitive to doxycycline (DO30), flumequine (UB30), oxolinic acid (OA2), chloramphenicol (C30), florfenicol (FFC30), nitrofurantoin (F5) and fosfomycin (FOS50). Each strain was also resistant to a slightly different combination of eight other antibiotics, with an overall multiple antibiotic resistance (MAR) index of 0.40, suggesting prior history of heavy exposure to the antibiotics. Vh10 infection resulted in pale or discoloured hepatopancreas, empty guts, reddening, necrosis and luminescence of uropods, as well as melanised lesions in tail muscle. Histopathological examination showed necrosis of intertubular connective tissue and tubule, sloughing of epithelial cells in hepatopancreatic tubule, haemocytic infiltration, massive vacuolation and loss of hepatopancreatic tubule structure.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
Fulltext Exploring Cefiderocol Resistance Mechanisms in Burkholderia pseudomallei

Hall CM, Somprasong N, Hagen JP, Nottingham R, Sahl JW, Webb JR, et al.

Antimicrob Agents Chemother, 2023 Jun 15;67(6):e0017123.
PMID: 37133377 DOI: 10.1128/aac.00171-23

Cefiderocol is a siderophore cephalosporin designed mainly for treatment of infections caused by β-lactam and multidrug-resistant Gram-negative bacteria. Burkholderia pseudomallei clinical isolates are usually highly cefiderocol susceptible, with in vitro resistance found in a few isolates. Resistance in clinical B. pseudomallei isolates from Australia is caused by a hitherto uncharacterized mechanism. We show that, like in other Gram-negatives, the PiuA outer membrane receptor plays a major role in cefiderocol nonsusceptibility in isolates from Malaysia.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics
The Impacts and Changes Related to the Cancer Drug Resistance Mechanism

Varshney P, Sharma V, Yadav D, Kumar Y, Singh A, Kagithala NR, et al.

Curr Drug Metab, 2023;24(12):787-802.
PMID: 38141188 DOI: 10.2174/0113892002266408231207150547

BACKGROUND: Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism.
OBJECTIVE: This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge.
METHODS: A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined.
RESULTS: The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy.
CONCLUSION: This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.

Matched MeSH terms: Drug Resistance, Multiple/genetics
Fulltext Emergence of ST131 H30-Rx Subclones among Uropathogenic Escherichia coli Isolates from two large hospitals of Kota Kinabalu, Sabah, Malaysia

Yun, Mei Lai, Myo, Thura Zaw, Nor Amalina Emran, Lin, Zaw

Borneo Journal of Medical Sciences, 2017;11(3):19-24.
MyJurnal

Escherichia coli sequence type 131 (ST131) carries multiple drug resistance (MDR) genes as well as virulence genes. Drug resistant characteristics give a management problem to health care personnel. Four MDR Escherichia coli ST131 H30-Rx subclones were identified among 80 Uropathogenic E. coli (UPEC) isolates by using 4 allelic-specific Polymerase Chain Reactions (PCR) in two hospitals of Kota Kinabalu, Sabah, Malaysia. There is emergence of multidrug resistant E. coli in Kota Kinabalu.

Matched MeSH terms: Drug Resistance, Multiple
Prevalence of multi-antimicrobial resistant non-typhoidal Salmonella isolated from filth flies at wet markets in Klang, Malaysia, and their survival in the simulated gastric fluid

Sandrasaigaran P, Mohan S, Segaran NS, Lee TY, Radu S, Hasan H

Int J Food Microbiol, 2023 Dec 16;407:110390.
PMID: 37722349 DOI: 10.1016/j.ijfoodmicro.2023.110390

Filth flies at wet markets can be a vector harbouring multiple antimicrobial-resistant (MAR) nontyphoidal Salmonella (NTS), and such strains are a significant threat to public health as they may cause severe infections in humans. This study aims to investigate the prevalence of antimicrobial-resistant NTS, especially Salmonella Enteritidis and S. Typhimurium harboured by filth flies at wet markets, and investigate their survival in the simulated gastric fluid (SGF). Filth flies (n = 90) were captured from wet markets in Klang, Malaysia, and processed to isolate Salmonella spp. The isolates (n = 16) were identified using the multiplex-touchdown PCR and assessed their antimicrobial susceptibility against 11 antimicrobial agents. Finally, three isolates with the highest MAR index were subjected to SGF survival tests. It was observed that 17.8 % of flies (n = 16/90) harbouring Salmonella, out of which 10 % (n = 9/90) was S. Enteritidis, 2.2 % (n = 2/90) was S. Typhimurium, and 5.6 % was unidentified serotypes of Salmonella enterica subsp. I. 43.8 % (n = 7/16) were confirmed as MAR, and they were observed to be resistant against ampicillin, chloramphenicol, kanamycin, streptomycin, and nalidixic acid. Three strains, F35, F75, and F85 demonstrated the highest MAR index and were able to survive (>6-log10) in the SGF (180 min), indicating their potential virulence and invasiveness. This study provides significant insights into the prevalence and severity of MAR nontyphoidal Salmonella harboured by filth flies in wet markets, which may help inform strategies for controlling the spread and outbreak of foodborne disease.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Typhoid fever and other salmonellosis: a continuing challenge

Pang T, Bhutta ZA, Finlay BB, Altwegg M

Trends Microbiol, 1995 Jul;3(7):253-5.
PMID: 7551636
Matched MeSH terms: Drug Resistance, Multiple
Cytotoxic effects and reversal of multidrug resistance by ibogan and related indole alkaloids

Kam TS, Sim KM, Pang HS, Koyano T, Hayashi M, Komiyama K

Bioorg Med Chem Lett, 2004 Sep 6;14(17):4487-9.
PMID: 15357977

A series of indole alkaloids of the ibogan-type was assessed for their cytotoxic effects as well as their potential in reversing MDR in vincristine-resistant KB cells. Of a total of 25 compounds tested, 3(S)-cyanocoronaridine, 3(S)-cyanoisovoacangine, 3(S)-cyanovoacangine, and 10,11-demethoxychippiine were found to show appreciable cytotoxicity toward KB cells, while coronaridine, heyneanine, 19-epi-heyneanine, dippinine B, and dippinine C, were found to reverse MDR in vincristine-resistant KB cells.

Matched MeSH terms: Drug Resistance, Multiple/drug effects*; Drug Resistance, Multiple/physiology
Strategies and validation for siRNA-based therapeutics for the reversal of multi-drug resistance in cancer

Fatemian T, Othman I, Chowdhury EH

Drug Discov Today, 2014 Jan;19(1):71-8.
PMID: 23974068 DOI: 10.1016/j.drudis.2013.08.007

Resistance of cancer cells to anticancer drugs is the main reason for the failure of traditional cancer treatments. Various cellular components and different loops within the signaling pathways contribute to drug resistance which could be modulated with the aim to restore drug efficacy. Unveiling the molecular mechanisms for cancer drug resistance has now paved the way for the development of novel approaches to regulate the response rates to anticancer drugs at the genetic level. The recent progress on identification and validation of the vital genes directly or indirectly involved in development of cancer drug resistance with the aid of the specific knock down ability of RNA interference technology is discussed in this review.

Matched MeSH terms: Drug Resistance, Multiple/drug effects; Drug Resistance, Multiple/genetics*
Fulltext Draft Genome Sequence of Dematiaceous Coelomycete Pyrenochaeta sp. Strain UM 256, Isolated from Skin Scraping

Yew SM, Chan CL, Soo-Hoo TS, Na SL, Ong SS, Hassan H, et al.

Genome Announc, 2013;1(3).
PMID: 23723391 DOI: 10.1128/genomeA.00158-13

Pyrenochaeta, classified under the order Pleosporales, is known to cause diseases in plants and humans. Here, we report a draft genome sequence of a Pyrenochaeta sp. isolated from a skin scraping, with an estimated genome size of 39.4 Mb. Genes associated with the synthesis of proteases, toxins, plant cell wall degradation, and multidrug resistance were found.

Matched MeSH terms: Drug Resistance, Multiple
Fulltext Effects of phenylpyruvate feeding with polymyxin B in Klebsiella pneumoniae

Wong, A. S-L., Nusaibah Abdul Rahim

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):5-5.
MyJurnal

Introduction: Polymyxin B (PMB) is one of the remaining antibiotics that is effective against multidrug resistant (MDR) Gram-negative bacteria. However, PMB monotherapy is not able to achieve sustained killing hence, combination with other antibiotics are usually employed. Besides antibiotics, studies are now moving towards non-antibiotic alternatives such as metabolite feeding against MDR pathogens. This study aimed to investigate the susceptibility
and bacterial killing of PMB in combination with metabolite phenylpyruvate against Klebsiella pneumoniae isolates. Methods: Broth microdilution was used to determine PMB minimum inhibitory concentration (MIC) alone and with phenylpyruvate against two Klebsiella pneumoniae isolates. Time kill studies were performed over 24 h (initial inoculum: ~106 CFU/mL), using PMB 2 mg/L and phenylpyruvate 2 mmol/L, alone and in combination, against the
PMB-resistant isolate. Microbiological responses were examined using the log-change method. Results: The MIC of PMB was reduced by phenylpyruvate in both isolates. In the time kill studies, during the first hour, PMB monotherapy demonstrated the highest bacterial killing activity even compared to the combination. Phenylpyruvate monotherapy showed negligible activity against K. pneumoniae. A significant reduction in bacterial burden was seen at 1 h following PMB monotherapy and combination therapy but an equally rapid regrowth was seen at 4 h. Notably at 24 h, the regrowth following combination therapy was >1-log10 CFU/mL less than PMB monotherapy. Conclusion: Our results suggest that phenylpyruvate increased PMB susceptibility in K. pneumoniae and may minimise the emergence of resistance to PMB. Future studies investigating phenylpyruvate at higher concentrations against more isolates are
warranted.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Rising horizon in circumventing multidrug resistance in chemotherapy with nanotechnology

Choudhury H, Pandey M, Yin TH, Kaur T, Jia GW, Tan SQL, et al.

Mater Sci Eng C Mater Biol Appl, 2019 Aug;101:596-613.
PMID: 31029353 DOI: 10.1016/j.msec.2019.04.005

Multidrug resistance (MDR) is one of the key barriers in chemotherapy, leading to the generation of insensitive cancer cells towards administered therapy. Genetic and epigenetic alterations of the cells are the consequences of MDR, resulted in drug resistivity, which reflects in impaired delivery of cytotoxic agents to the cancer site. Nanotechnology-based nanocarriers have shown immense shreds of evidence in overcoming these problems, where these promising tools handle desired dosage load of hydrophobic chemotherapeutics to facilitate designing of safe, controlled and effective delivery to specifically at tumor microenvironment. Therefore, encapsulating drugs within the nano-architecture have shown to enhance solubility, bioavailability, drug targeting, where co-administered P-gp inhibitors have additionally combat against developed MDR. Moreover, recent advancement in the stimuli-sensitive delivery of nanocarriers facilitates a tumor-targeted release of the chemotherapeutics to reduce the associated toxicities of chemotherapeutic agents in normal cells. The present article is focused on MDR development strategies in the cancer cell and different nanocarrier-based approaches in circumventing this hurdle to establish an effective therapy against deadliest cancer disease.

Matched MeSH terms: Drug Resistance, Multiple
Fulltext War against COVID-19: looming threat of XDR typhoid battle in Pakistan

Tanveer M, Ahmed A, Siddiqui A, Rehman IU, Hashmi FK

Public Health, 2021 09;198:e15-e16.
PMID: 34187703 DOI: 10.1016/j.puhe.2021.05.019
Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Resistance Mechanism in a Terbinafine-Resistant Strain of Microsporum canis

Kano R, Hsiao YH, Siew HH, Chen C, Hasegawa A, Kamata H

Mycopathologia, 2018 Jan 16.
PMID: 29340910 DOI: 10.1007/s11046-018-0242-0

To clarify the terbinafine (TRF) resistance mechanism in a TRF-resistant strain of Microsporum canis, the expression of the pleiotropic drug resistance (PDR1), multidrug resistance (MDR1), MDR2 and MDR4 genes were investigated by real-time quantitative PCR (RT-qPCR) analysis, given the known interaction of the corresponding proteins with antifungals and with the efflux blocker FK506. The expression of the PDR1, MDR1, MDR2 and MDR4 genes was 2-4 times higher in the TRF-resistant strain grown in the presence of 0.14 µg/mL of TRF than in TRF-susceptible strains cultured in the absence of TRF. The TRF-resistant strain exhibited MICs of > 32 µg/mL for TRF alone; this resistance was attenuated to an MIC of 8 µg/mL in the presence of FK506, indicating that the TRF inhibitory concentration index value was

Matched MeSH terms: Drug Resistance, Multiple
Fulltext High prevalence of antimicrobial resistance and multidrug resistance among bacterial isolates from diseased pets: Retrospective laboratory data (2015-2017)

Haulisah NA, Hassan L, Jajere SM, Ahmad NI, Bejo SK

PLoS One, 2022;17(12):e0277664.
PMID: 36477195 DOI: 10.1371/journal.pone.0277664

Laboratory surveillance and the monitoring of antimicrobial resistance (AMR) trends and patterns among local isolates have been highly effective in providing comprehensive information for public health decision-making. A total of 396 cases along with 449 specimens were received for antibiotic susceptibility testing at a public university veterinary diagnostic laboratory in Malaysia between 2015 and 2017. Escherichia coli was the most frequently isolated (n = 101, 13%) bacteria, followed by Staphylococcus pseudintermedius (n = 97, 12%) and Streptococcus canis (n = 62, 8%). In cats, S. pseudintermedius isolates were highly resistant to azithromycin (90%), while the E. coli isolates were highly resistant to doxycycline (90%), tetracycline (81%), and cephalexin (75%). About 55% of S. pseudintermedius and 82% of E. coli were multi-drug resistant (MDR). In dogs, S. intermedius isolates were highly resistant to aminoglycosides neomycin (90.9%) and gentamicin (84.6%), and tetracycline (75%). Whereas the E. coli isolates were highly resistant to cephalexin (82.1%) and amoxicillin/clavulanic acid (76.5%). MDR was observed in 60% of S. intermedius and 72% of E. coli from dogs. Generally, the bacterial isolates from cats demonstrated higher levels of resistance to multiple antibiotics compared to those from dogs.

Matched MeSH terms: Drug Resistance, Multiple
Fulltext Global genome comparative analysis reveals insights of resistome and life-style adaptation of Pseudomonas putida strain T2-2 in oral cavity

Chan XY, Chua KO, How KY, Yin WF, Chan KG

ScientificWorldJournal, 2014;2014:930727.
PMID: 25436236 DOI: 10.1155/2014/930727

Most Pseudomonas putida strains are environmental microorganisms exhibiting a wide range of metabolic capability but certain strains have been reported as rare opportunistic pathogens and some emerged as multidrug resistant P. putida. This study aimed to assess the drug resistance profile of, via whole genome analysis, P. putida strain T2-2 isolated from oral cavity. At the same time, we also compared the nonenvironmental strain with environmentally isolated P. putida. In silico comparative genome analysis with available reference strains of P. putida shows that T2-2 has lesser gene counts on carbohydrate and aromatic compounds metabolisms, which suggested its little versatility. The detection of its edd gene also suggested T2-2's catabolism of glucose via ED pathway instead of EMP pathway. On the other hand, its drug resistance profile was observed via in silico gene prediction and most of the genes found were in agreement with drug-susceptibility testing in laboratory by automated VITEK 2. In addition, the finding of putative genes of multidrug resistance efflux pump and ATP-binding cassette transporters in this strain suggests a multidrug resistant phenotype. In summary, it is believed that multiple metabolic characteristics and drug resistance in P. putida strain T2-2 helped in its survival in human oral cavity.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics*
Fulltext Multidrug resistant yeasts in synanthropic wild birds

Lord AT, Mohandas K, Somanath S, Ambu S

Ann Clin Microbiol Antimicrob, 2010;9:11.
PMID: 20307325 DOI: 10.1186/1476-0711-9-11

The aim of this study was to investigate the presence of multidrug resistant yeasts in the faeces of synanthropic wild birds from the Bangsar suburb of Kuala Lumpur.

Matched MeSH terms: Drug Resistance, Multiple, Fungal*
Fulltext Computational, crystallographic studies, cytotoxicity and anti-tubercular activity of substituted 7-methoxy-indolizine analogues

Venugopala KN, Chandrashekharappa S, Pillay M, Abdallah HH, Mahomoodally FM, Bhandary S, et al.

PLoS One, 2019;14(6):e0217270.
PMID: 31163040 DOI: 10.1371/journal.pone.0217270

Indolizines are heteroaromatic compounds, and their synthetic analogues have reportedly showed promising pharmacological properties. In this study, a series of synthetic 7-methoxy-indolizine derivatives were synthesised, characterised and evaluated for in vitro whole-cell anti-tuberculosis (TB) screening against susceptible (H37Rv) and multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) using the resazurin microplate assay method. The cytotoxicity was evaluated using the MTT assay. In silico molecular-docking study was conducted for compounds 5a-j against enoyl-[acyl-carrier] protein reductase, a key enzyme of the type II fatty acid synthesis that has attracted much interest for the development of novel anti-TB compounds. Thereafter, molecular dynamic (MD) simulation was undertaken for the most active inhibitors. Compounds 5i and 5j with the methoxy functional group at the meta position of the benzoyl group, which was at the third position of the indolizine nucleus, demonstrated encouraging anti-TB activity against MDR strains of MTB at 16 μg/mL. In silico studies showed binding affinity within the range of 7.07-8.57 kcal/mol, with 5i showing the highest binding affinity. Hydrogen bonding, π-π- interactions, and electrostatic interactions were common with the active site. Most of these interactions occurred with the catalytic amino acids (Pro193, Tyr158, Phe149, and Lys165). MD simulation showed that 5j possessed the highest binding affinity toward the enzyme, according to the two calculation methods (MM/PBSA and MM/GBSA). The single-crystal X-ray studies of compounds 5c and 5d revealed that the molecular arrangements in these two structures were mostly guided by C-H···O hydrogen-bonded dimeric motifs and C-H···N hydrogen bonds, while various secondary interactions (such as π···π and C-H···F) also contributed to crystal formation. Compounds 5a, 5c, 5i, and 5j exhibited no toxicity up to 500 μg/mL. In conclusion, 5i and 5j are promising anti-TB compounds that have shown high affinity based on docking and MD simulation results.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial/drug effects*
The global prevalence of multidrug-resistance among Acinetobacter baumannii causing hospital-acquired and ventilator-associated pneumonia and its associated mortality: A systematic review and meta-analysis

Mohd Sazlly Lim S, Zainal Abidin A, Liew SM, Roberts JA, Sime FB

J Infect, 2019 12;79(6):593-600.
PMID: 31580871 DOI: 10.1016/j.jinf.2019.09.012

OBJECTIVE: The objective of this works was to assess the global prevalence of multidrug-resistance among A. baumannii causing hospital-acquired (HAP) and ventilator-associated pneumonia (VAP), and describe its associated mortality.
METHODS: We performed a systematic search of four databases for relevant studies. Meta-analysis was done based on United Nations geoscheme regions, individual countries and study period. We used a random-effects model to calculate pooled prevalence and mortality estimates with 95% confidence intervals (CIs), weighted by study size.
RESULTS: Among 6445 reports screened, we identified 126 relevant studies, comprising data from 29 countries. The overall prevalence of multidrug-resistance among A. baumannii causing HAP and VAP pooled from 114 studies was 79.9% (95% CI 73.9-85.4%). Central America (100%) and Latin America and the Caribbean (100%) had the highest prevalence, whereas Eastern Asia had the lowest (64.6%; 95% CI, 50.2-77.6%). The overall mortality estimate pooled from 27 studies was 42.6% (95% CI, 37.2-48.1%).
CONCLUSIONS: We observed large amounts of variation in the prevalence of multidrug-resistance among A. baumannii causing HAP and VAP and its mortality rate among regions and lack of data from many countries. Data from this review can be used in the development of customized strategies for infection control and antimicrobial stewardship.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
Reversal of multidrug resistance (MDR) by aspidofractinine-type indole alkaloids

Kam TS, Subramaniam G, Sim KM, Yoganathan K, Koyano T, Toyoshima M, et al.

Bioorg Med Chem Lett, 1998 Oct 06;8(19):2769-72.
PMID: 9873619

A series of indole alkaloids of the aspidofractinine-type was assessed for their potential in reversing MDR in vincristine-resistant KB cells. Of the compounds tested, kopsiflorine, kopsamine, pleiocarpine, 11-methoxykopsilongine, lahadinine A and N-methoxycarbonyl-11,12-methylenedioxy-delta 16,17-kopsinine were found to show appreciable activity.

Matched MeSH terms: Drug Resistance, Multiple*

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