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Review: dalbavancin--a novel lipoglycopeptide antimicrobial for gram positive pathogens

Das B, Sarkar C, Biswas R, Pandey S

Pak J Pharm Sci, 2008 Jan;21(1):78-87.
PMID: 18166524

Glycopeptide antibiotics represent an important class of microbial compounds produced by several genera of actinomycetes. The emergence of resistance to glycopeptides among enterococci and staphylococci has prompted the search for second-generation drugs of this class and semi-synthetic derivatives are currently under clinical trials. Antimicrobial resistance among gram-positive organisms has been increasing steadily during the past several decades. Dalbavancin, a novel lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has in vitro activity against a variety of Gram-positive organisms specially multidrug resistant Staphylococcus aureus, but no activity against Gram-negative or vancomycin-resistant enterococci that possess vanA gene. Due to its prolonged half-life (6-10 days), dalbavancin can be administered intravenously once weekly. In Phase II and III clinical trials, dalbavancin was effective and well-tolerated for the treatment of skin and soft-tissue infections, catheter-related bloodstream infections, and skin and skin-structure infections. To date, adverse events have been mild and limited; the most common being pyrexia, headache, diarrhea. Dalbavancin appears to be a promising antimicrobial agent for the treatment of Gram-positive infections. Additional clinical data are required to fully assess its use. Despite the remarkable and favorable pharmacokinetic and pharmacodynamic properties, the use of this potent agent should be restricted to severe infections due to multidrug resistant organisms to limit the risk of selection of resistance. It is active against Gram-positive aerobes and anerobes, including resistant pathogens, with the exception of strains producing vanA-mediated resistance. Its approval by the FDA is expected soon. The extent to which dalbavancin will supplant vancomycin and whether it will be preferred over other newer agents such as linezolid in the next decade remains to be seen.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Fulltext Bacteremia in patients with febrile neutropenia after chemotherapy at a university medical center in Malaysia

Baskaran ND, Gan GG, Kamarulzaman A, Sam IC

Int J Infect Dis, 2007 Nov;11(6):513-7.
PMID: 17459753

OBJECTIVES: This study was initiated to determine the local profile of blood culture isolates and antibiotic sensitivities in febrile neutropenic patients following chemotherapy, and to establish if any modifications to treatment guidelines are necessary.
DESIGN: A total of 116 episodes of febrile neutropenia admitted to the adult hematology ward at a university medical center in Malaysia were studied retrospectively from January 2004 to January 2005.
RESULTS: The study showed 43.1% of febrile neutropenic episodes had established bacteremia. Gram-negative bacteria accounted for 60.3% of isolates. Sensitivities of Gram-negative bacteria to the antibiotics recommended in the Infectious Diseases Society of America (IDSA) guidelines were 86.1-97.2%. Coagulase-negative staphylococci were the most common Gram-positive organisms isolated (23.3%). The majority of these were methicillin-resistant.
CONCLUSIONS: Carbapenem monotherapy, as recommended in the 2002 IDSA guidelines, is effective treatment for the infections most often encountered at our center. Combination therapy with an aminoglycoside should be considered when using ceftazidime, cefepime or piperacillin-tazobactam, particularly in high-risk patients. Vancomycin should be used if a Gram-positive organism is suspected or isolated.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Prevalence and antibiotic resistance of Salmonella Enteritidis and Salmonella Typhimurium in raw chicken meat at retail markets in Malaysia

Thung TY, Mahyudin NA, Basri DF, Wan Mohamed Radzi CW, Nakaguchi Y, Nishibuchi M, et al.

Poult Sci, 2016 Aug 01;95(8):1888-93.
PMID: 27118863 DOI: 10.3382/ps/pew144

Salmonellosis is one of the major food-borne diseases in many countries. This study was carried out to determine the occurrence of Salmonella spp., Salmonella Enteritidis, and Salmonella Typhimurium in raw chicken meat from wet markets and hypermarkets in Selangor, as well as to determine the antibiotic susceptibility profile of S. Enteritidis and S. Typhimurium. The most probable number (MPN) in combination with multiplex polymerase chain reaction (mPCR) method was used to quantify the Salmonella spp., S. Enteritidis, and S. Typhimurium in the samples. The occurrence of Salmonella spp., S. Enteritidis, and S. Typhimurium in 120 chicken meat samples were 20.80%, 6.70%, and 2.50%, respectively with estimated quantity varying from <3 to 15 MPN/g. The antibiogram testing revealed differential multi-drug resistance among S. Enteritidis and S. Typhimurium isolates. All the isolates were resistance to erythromycin, penicillin, and vancomycin whereas sensitivity was recorded for Amoxicillin/Clavulanic acid, Gentamicin, Tetracycline, and Trimethoprim. Our findings demonstrated that the retail chicken meat could be a source of multiple antimicrobial-resistance Salmonella and may constitute a public health concern in Malaysia.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Management and treatment outcomes of MDR-TB: results from a setting with high rates of drug resistance

Ahmad N, Javaid A, Basit A, Afridi AK, Khan MA, Ahmad I, et al.

Int J Tuberc Lung Dis, 2015 Sep;19(9):1109-14, i-ii.
PMID: 26260834 DOI: 10.5588/ijtld.15.0167

Although Pakistan has a high burden of multidrug-resistant tuberculosis (MDR-TB), little is known about the management and treatment outcomes of MDR-TB patients in Pakistan.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Keratinase production and biodegradation of polluted secondary chicken feather wastes by a newly isolated multi heavy metal tolerant bacterium-Alcaligenes sp. AQ05-001

Yusuf I, Ahmad SA, Phang LY, Syed MA, Shamaan NA, Abdul Khalil K, et al.

J Environ Manage, 2016 Dec 01;183:182-95.
PMID: 27591845 DOI: 10.1016/j.jenvman.2016.08.059

Biodegradation of agricultural wastes, generated annually from poultry farms and slaughterhouses, can solve the pollution problem and at the same time yield valuable degradation products. But these wastes also constitute environmental nuisance, especially in Malaysia where their illegal disposal on heavy metal contaminated soils poses a serious biodegradation issue as feather tends to accumulate heavy metals from the surrounding environment. Further, continuous use of feather wastes as cheap biosorbent material for the removal of heavy metals from effluents has contributed to the rising amount of polluted feathers, which has necessitated the search for heavy metal-tolerant feather degrading strains. Isolation, characterization and application of a novel heavy metal-tolerant feather-degrading bacterium, identified by 16S RNA sequencing as Alcaligenes sp. AQ05-001 in degradation of heavy metal polluted recalcitrant agricultural wastes, have been reported. Physico-cultural conditions influencing its activities were studied using one-factor-at-a-time and a statistical optimisation approach. Complete degradation of 5 g/L feather was achieved with pH 8, 2% inoculum at 27 °C and incubation period of 36 h. The medium optimisation after the response surface methodology (RSM) resulted in a 10-fold increase in keratinase production (88.4 U/mL) over the initial 8.85 U/mL when supplemented with 0.5% (w/v) sucrose, 0.15% (w/v) ammonium bicarbonate, 0.3% (w/v) skim milk, and 0.01% (w/v) urea. Under optimum conditions, the bacterium was able to degrade heavy metal polluted feathers completely and produced valuable keratinase and protein-rich hydrolysates. About 83% of the feathers polluted with a mixture of highly toxic metals were degraded with high keratinase activities. The heavy metal tolerance ability of this bacterium can be harnessed not only in keratinase production but also in the bioremediation of heavy metal-polluted feather wastes.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens

Hong W, Li J, Chang Z, Tan X, Yang H, Ouyang Y, et al.

J Antibiot (Tokyo), 2017 Jul;70(7):832-844.
PMID: 28465626 DOI: 10.1038/ja.2017.55

The emergence of drug resistance in bacterial pathogens is a growing clinical problem that poses difficult challenges in patient management. To exacerbate this problem, there is currently a serious lack of antibacterial agents that are designed to target extremely drug-resistant bacterial strains. Here we describe the design, synthesis and antibacterial testing of a series of 40 novel indole core derivatives, which are predicated by molecular modeling to be potential glycosyltransferase inhibitors. Twenty of these derivatives were found to show in vitro inhibition of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Four of these strains showed additional activity against Gram-negative bacteria, including extended-spectrum beta-lactamase producing Enterobacteriaceae, imipenem-resistant Klebsiella pneumoniae and multidrug-resistant Acinetobacter baumanii, and against Mycobacterium tuberculosis H37Ra. These four compounds are candidates for developing into broad-spectrum anti-infective agents.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Fulltext In vitro activity of ceftazidime-avibactam and comparators against Gram-negative bacterial isolates collected in the Asia-Pacific region as part of the INFORM program (2015-2017)

Ko WC, Stone GG

Ann Clin Microbiol Antimicrob, 2020 Apr 01;19(1):14.
PMID: 32238155 DOI: 10.1186/s12941-020-00355-1

BACKGROUND: Antimicrobial resistance among nosocomial Gram-negative pathogens is a cause for concern in the Asia-Pacific region. The aims of this study were to measure the rates of resistance among clinical isolates collected in Asia-Pacific countries, and to determine the in vitro antimicrobial activities of ceftazidime-avibactam and comparators against these isolates.
METHODS: CLSI broth microdilution methodology was used to determine antimicrobial activity and EUCAST breakpoints version 9.0 were used to determine rates of susceptibility and resistance. Isolates were also screened for the genes encoding extended-spectrum β-lactamases (ESBLs) or carbapenemases (including metallo-β-lactamases [MBLs]).
RESULTS: Between 2015 and 2017, this study collected a total of 7051 Enterobacterales isolates and 2032 Pseudomonas aeruginosa isolates from hospitalized patients in Australia, Japan, South Korea, Malaysia, the Philippines, Taiwan, and Thailand. In the Asia-Pacific region, Enterobacterales isolates that were ESBL-positive, carbapenemase-negative (17.9%) were more frequently identified than isolates that were carbapenemase-positive, MBL-negative (0.7%) or carbapenemase-positive, MBL-positive (1.7%). Multidrug-resistant (MDR) isolates of P. aeruginosa were more commonly identified (23.4%) than isolates that were ESBL-positive, carbapenemase-negative (0.4%), or carbapenemase-positive, MBL-negative (0.3%), or carbapenemase-positive, MBL-positive (3.7%). More than 90% of all Enterobacterales isolates, including the ESBL-positive, carbapenemase-negative subset and the carbapenemase-positive, MBL-negative subset, were susceptible to amikacin and ceftazidime-avibactam. Among the carbapenemase-positive, MBL-positive subset of Enterobacterales, susceptibility to the majority of agents was reduced, with the exception of colistin (93.4%). Tigecycline was active against all resistant subsets of the Enterobacterales (MIC90, 1-4 mg/L) and among Escherichia coli isolates, > 90% from each resistant subset were susceptible to tigecycline. More than 99% of all P. aeruginosa isolates, including MDR isolates and the carbapenemase-positive, MBL-positive subset, were susceptible to colistin.
CONCLUSIONS: In this study, amikacin, ceftazidime-avibactam, colistin and tigecycline appear to be potential treatment options for infections caused by Gram-negative pathogens in the Asia-Pacific region.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Fulltext Iron and Virulence in Stenotrophomonas Maltophilia: All We Know So Far

Kalidasan V, Joseph N, Kumar S, Awang Hamat R, Neela VK

Front Cell Infect Microbiol, 2018;8:401.
PMID: 30483485 DOI: 10.3389/fcimb.2018.00401

Stenotrophomonas maltophilia is a multi-drug-resistant global opportunistic nosocomial pathogen, which possesses a huge number of virulence factors and antibiotics resistance characteristics. Iron has a crucial contribution toward growth and development, cell growth and proliferation, and pathogenicity. The bacterium found to acquire iron for its cellular process through the expression of two iron acquisition systems. Two distinct pathways for iron acquisition are encoded by the S. maltophilia genome-a siderophore-and heme-mediated iron uptake system. The entAFDBEC operon directs the production of the enterobactin siderophore of catecholate in nature, while heme uptake relies on hgbBC and potentially hmuRSTUV operon. Fur and sigma factors are regulators of S. maltophilia under iron-limited condition. Iron potentially act as a signal which plays an important role in biofilm formation, extracellular polymeric substances (EPS), extracellular enzymes production, oxidative stress response, diffusible signal factor (DSF) and siderophore production in S. maltophilia. This review summarizes the current knowledge of iron acquisition in S. maltophilia and the critical role of iron in relation to its pathogenicity.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Fulltext Detection and characterization of ESBL-producing Enterobacteriaceae from the gut of subsistence farmers, their livestock, and the surrounding environment in rural Nepal

Subramanya SH, Bairy I, Metok Y, Baral BP, Gautam D, Nayak N

Sci Rep, 2021 01 22;11(1):2091.
PMID: 33483551 DOI: 10.1038/s41598-021-81315-3

The increasing trend of gut colonization by extended-spectrum β-lactamase (ESBL) producing Enterobacterales has been observed in conventional farm animals and their owners. Still, such colonization among domesticated organically fed livestock has not been well studied. This study aimed to determine the gut colonization rate of ESBL-producing Enterobacteriaceae and carbapenemase-producing Enterobacteriaceae (CPE) among rural subsistence farming communities of the Kaski district in Nepal. Rectal swabs collected by systematic random sampling from 128 households of subsistence farming communities were screened for ESBL-producing Enterobacteriaceae and CPE by phenotypic and molecular methods. A total of 357 (57%) ESBL-producing Enterobacteriaceae isolates were obtained from 626 specimens, which included 97 ESBL-producing Enterobacteriaceae (75.8%) from 128 adult humans, 101 (79.5%) from 127 of their children, 51 (47.7%) from 107 cattle, 26 (51%) from 51 goats, 30 (34.9%) from 86 poultry and 52 (42%) from 127 environmental samples. No CPE was isolated from any of the samples. blaCTX-M-15 was the most predominant gene found in animal (86.8%) and human (80.5%) isolates. Out of 308 Escherichia coli isolates, 16 human and two poultry isolates were positive for ST131 and were of clade C. Among non-cephalosporin antibiotics, the resistance rates were observed slightly higher in tetracycline and ciprofloxacin among all study subjects. This is the first one-health study in Nepal, demonstrating the high rate of CTX-M-15 type ESBL-producing Enterobacteriaceae among gut flora of subsistence-based farming communities. Gut colonization by E. coli ST131 clade C among healthy farmers and poultry birds is a consequential public health concern.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Fulltext Genome sequence of multidrug-resistant Escherichia coli EC302/04, isolated from a human tracheal aspirate

Ho WS, Gan HM, Yap KP, Balan G, Yeo CC, Thong KL

J Bacteriol, 2012 Dec;194(23):6691-2.
PMID: 23144425 DOI: 10.1128/JB.01804-12

Escherichia coli is an important etiologic agent of lower respiratory tract infections (LRTI). Multidrug-resistant E. coli EC302/04 was isolated from a tracheal aspirate, and its genome sequence is expected to provide insights into antimicrobial resistance as well as adaptive and virulence mechanisms of E. coli involved in LRTI.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Fulltext Detection of blaIMP4 and blaNDM1 harboring Klebsiella pneumoniae isolates in a university hospital in Malaysia

Hamzan NI, Yean CY, Rahman RA, Hasan H, Rahman ZA

Emerg Health Threats J, 2015;8:26011.
PMID: 25765342 DOI: 10.3402/ehtj.v8.26011

Background : Antibiotic resistance among Enterobacteriaceae posts a great challenge to the health care service. The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is attracting significant attention due to its rapid and global dissemination. The infection is associated with significant morbidity and mortality, thus creating challenges for infection control and managing teams to curb the infection. In Southeast Asia, there have been limited reports and subsequent research regarding CRKP infections. Thus, the study was conducted to characterize CRKP that has been isolated in our setting. Methods : A total of 321 K. pneumoniae were included in the study. Each isolate went through an identification process using an automated identification system. Phenotypic characterization was determined using disk diffusion, modified Hodge test, Epsilometer test, and inhibitor combined disk test. Further detection of carbapenemase genes was carried out using polymerase chain reaction and confirmed by gene sequence analysis. Results : All together, 13 isolates (4.05%) were CRKP and the majority of them were resistant to tested antibiotics except colistin and tigercycline. Among seven different carbapenemase genes studied (blaKPC, bla IMP, bla SME, bla NDM, bla IMI, bla VIM, and bla OXA), only two, bla IMP4 (1.87%) and bla NDM1 (2.18%), were detected in our setting. Conclusion : Evidence suggests that the prevalence of CRKP in our setting is low, and knowledge of Carbapenem-resistant Enterobacteriaceae and CRKP has improved and become available among clinicians.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Fulltext Emergence of SCCmec type III with variable antimicrobial resistance profiles and spa types among methicillin-resistant Staphylococcus aureus isolated from healthcare- and community-acquired infections in the west of Iran

Mohammadi S, Sekawi Z, Monjezi A, Maleki MH, Soroush S, Sadeghifard N, et al.

Int J Infect Dis, 2014 Aug;25:152-8.
PMID: 24909489 DOI: 10.1016/j.ijid.2014.02.018

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of public health importance. The prevalence of MRSA and its antimicrobial resistance pattern, as well as SCCmec and spa types, remain unclear both in the community and in the hospitals of the western region of Iran.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Characterization of drug resistant Salmonella enterica serotype Typhimurium by antibiograms, plasmids, integrons, resistance genes and PFGE

Benacer D, Thong KL, Watanabe H, Puthucheary SD

J Microbiol Biotechnol, 2010 Jun;20(6):1042-52.
PMID: 20622506

Forty-seven Salmonella Typhimurium (33 zoonotic, 14 clinical) strains were tested for antimicrobial resistance using the standard disk diffusion method. Presence of relevant resistance genes and class 1 integrons were investigated by using PCR. Pulsed-field gel electrophoresis (PFGE) and plasmid profiling were carried out to determine the genomic diversity of Salmonella Typhimurium. Approximately 57.4% of S. Typhimurium were multidrug resistant (MDR) and showed high resistance rates to tetracycline (70.2%), sulphonamides (57.4%), streptomycin (53.1%), ampicillin (29.7%), nalidixic acid (27.6%), kanamycin (23.4%), chloramphenicol (21.2%) and trimethoprim (19.1%). Resistance towards cephalosporins was noted for cephalothin (27.6%), cephradine (21.2%), amoxicillin clavulanic acid (17.0%) and cephalexin (17.0%). Resistance genes, blaTEM, strA, aadA, sul1, sul2, tet(A), tet(B) and tet(C) were detected among the drug resistant strains. Thirty-three strains (70.2%) carried class 1 integrons, which were grouped in 9 different profiles. DNA sequencing identified sat, aadA, pse-1 and dfrA genes in variable regions on class 1 integrons. Thirty-five strains (74.4%) were subtyped to 22 different plasmid profiles, each with 1 - 6 plasmids (2.0 to 95 kb). PFGE subtyped the 47 strains into 39 profiles. In conclusion, high rates of multidrug-resistance were found among the Malaysian Salmonella Typhimurium strains. The emergence of multidrug-resistant Salmonella Typhimurium to cephalosporin antibiotics was also observed. The strains were very diverse and no persistent clone was observed. The emergence of MDR Salmonella Typhimurium is a worldwide problem and this report provides information for the better understanding of the prevalence and epidemiology of MDR S. Typhimurium in Malaysia.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Fulltext In-vitro activity of quinupristin/dalfopristin, levofloxacin and moxifloxacin against fusidic acid and rifampicin-resistant strains of methicillin-resistant Staphylococcus aureus (MRSA) from Malaysian hospitals

Norazah A, Lim VKE, Rohani MY, Kamel AGM

Med J Malaysia, 2005 Oct;60(4):411-5.
PMID: 16570701

The in-vitro susceptibility of quinupristin/dalfopristin, levofloxacin and moxifloxacin against methicillin-resistant Staphylococcus aureus (MRSA) strains, which are also resistant to fusidic acid and rifampicin were carried out to determine whether these antibiotics can be used as an alternative treatment for multiply resistant MRSA strains. The minimum inhibitory concentrations (MIC) of these antibiotics were determined by E-test. Quinupristin/dalfopristin had good activity (MIC90 = 1 mg/L) against these strains while most of the strains showed intermediate resistance to moxifloxacin with MIC90 = 2 mg/L). However, more than 90% of these strains were resistant to levofloxacin with the MICs that ranged from 8 mg/L to 16 mg/L with the majority inhibited at 8 mg/L.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Deep Infections after Endoprosthetic Replacement Operations in Orthopedic Oncology Patients

Dhanoa A, Ajit Singh V, Elbahri H

Surg Infect (Larchmt), 2015 Jun;16(3):323-32.
PMID: 26046246 DOI: 10.1089/sur.2014.049

Numerous studies have described various complications after endoprosthetic reconstructive operations. However, there are limited reports that focus specifically on deep infections (e.g., deep incisional surgical site infections), which remain one of the most dreaded complications of these operations, with rates ranging from 10% to 17%. Thus, this study was undertaken to determine the deep infection rates and to analyze possible risk factors, clinico-pathologic characteristics, and treatment modalities of endoprosthetic infections.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Fulltext Characterization and Transcriptome Studies of Autoinducer Synthase Gene from Multidrug Resistant Acinetobacter baumannii Strain 863

Ng CK, How KY, Tee KK, Chan KG

Genes (Basel), 2019 04 08;10(4).
PMID: 30965610 DOI: 10.3390/genes10040282

Quorum sensing (QS) is a cell-to-cell communication system that uses autoinducers as signaling molecules to enable inter-species and intra-species interactions in response to external stimuli according to the population density. QS allows bacteria such as Acinetobacter baumannii to react rapidly in response to environmental changes and hence, increase the chances of survival. A. baumannii is one of the causative agents in hospital-acquired infections and the number of cases has increased remarkably in the past decade. In this study, A. baumannii strain 863, a multidrug-resistant pathogen, was found to exhibit QS activity by producing N-acyl homoserine lactone. We identified the autoinducer synthase gene, which we named abaI, by performing whole genome sequencing analysis of A. baumannii strain 863. Using high resolution tandem triple quadrupole mass spectrometry, we reported that abaI of A. baumannii strain 863 produced 3-hydroxy-dodecanoyl-homoserine lactone. A gene deletion mutant was constructed, which confirmed the functionality of abaI. A growth defect was observed in the QS-deficient mutant strain. Transcriptome profiling was performed to determine the possible genes regulated by QS. Four groups of genes that showed differential expression were discovered, namely those involved in carbon source metabolism, energy production, stress response and the translation process.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Fulltext Invasive Salmonella infections among children in Bintulu, Sarawak, Malaysian Borneo: a 6-year retrospective review

Mohan A, Munusamy C, Tan YC, Muthuvelu S, Hashim R, Chien SL, et al.

BMC Infect Dis, 2019 Apr 18;19(1):330.
PMID: 30999894 DOI: 10.1186/s12879-019-3963-x

BACKGROUND: Invasive Salmonella infections result in significant morbidity and mortality in developing countries. In Asia, typhoid and paratyphoid fever are reported to be the major invasive Salmonella infections, while invasive non-typhoidal Salmonella (iNTS) infections are believed to be uncommon. Data from Sarawak, in Malaysian Borneo, are limited.
METHODS: A retrospective study identifying all children aged drug resistant, nearly all other isolates were susceptible to most antimicrobials, including ampicillin.
CONCLUSIONS: Bintulu Division in Sarawak observed a very high incidence of childhood iNTS infections. Enteric fever was uncommon. The epidemiology of invasive Salmonella infections in Malaysian Borneo differs considerably from that of neighbouring countries in Asia.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Genomic analysis revealing the resistance mechanisms of extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolated from pig and humans in Malaysia

Mobasseri G, Thong KL, Teh CSJ

Int Microbiol, 2021 May;24(2):243-250.
PMID: 33469786 DOI: 10.1007/s10123-021-00161-5

Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae has been associated with a wide range of infections in humans and animals. The objective of this study was to determine the genomic characteristics of two multiple drug resistant, ESBLs-producing K. pneumoniae strains isolated from a swine in 2013 (KP2013Z28) and a hospitalized patient in 2014 (KP2014C46) in Malaysia. Genomic analyses of the two K. pneumoniae strains indicated the presence of various antimicrobial resistance genes associated with resistance to β-lactams, aminoglycosides, colistin, fluoroquinolones, phenicols, tetracycline, sulfonamides, and trimethoprim, corresponding to the antimicrobial susceptibility profiles of the strains. KP2013Z28 (ST25) and KP2014C46 (ST929) harbored 5 and 2 genomic plasmids, respectively. The phylogenomics of these two Malaysian K. pneumoniae, with other 19 strains around the world was determined based on SNPs analysis. Overall, the strains were resolved into five clusters that comprised of strains with different resistance determinants. This study provided a better understanding of the resistance mechanisms and phylogenetic relatedness of the Malaysian strains with 19 strains isolated worldwide. This study also highlighted the needs to monitor the usage of antibiotics in hospital settings, animal husbandry, and agricultural practices due to the increase of β-lactam, aminoglycosides, tetracycline, and colistin resistance among pathogenic bacteria for better infection control.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Anti-bacterial activity of inorganic nanomaterials and their antimicrobial peptide conjugates against resistant and non-resistant pathogens

Pardhi DM, Şen Karaman D, Timonen J, Wu W, Zhang Q, Satija S, et al.

Int J Pharm, 2020 Aug 30;586:119531.
PMID: 32540348 DOI: 10.1016/j.ijpharm.2020.119531

This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial
A Systematic Review of the Burden of Multidrug-Resistant Healthcare-Associated Infections Among Intensive Care Unit Patients in Southeast Asia: The Rise of Multidrug-Resistant Acinetobacter baumannii

Teerawattanapong N, Panich P, Kulpokin D, Na Ranong S, Kongpakwattana K, Saksinanon A, et al.

Infect Control Hosp Epidemiol, 2018 05;39(5):525-533.
PMID: 29580299 DOI: 10.1017/ice.2018.58

OBJECTIVETo summarize the clinical burden (cumulative incidence, prevalence, case fatality rate and length of stay) and economic burden (healthcare cost) of healthcare-associated infections (HAIs) due to multidrug-resistant organisms (MDROs) among patients in intensive care units (ICUs) in Southeast Asia.DESIGNSystematic review.METHODSWe conducted a comprehensive literature search in PubMed, EMBASE, CINAHL, EconLit, and the Cochrane Library databases from their inception through September 30, 2016. Clinical and economic burdens and study quality were assessed for each included study.RESULTSIn total, 41 studies met our inclusion criteria; together, 22,876 ICU patients from 7 Southeast Asian countries were included. The cumulative incidence of HAI caused by A. baumannii (AB) in Southeast Asia is substantially higher than has been reported in other regions, especially carbapenem-resistant AB (CRAB; 64.91%) and multidrug-resistant AB (MDR-AB) (58.51%). Evidence of a dose-response relationship between different degrees of drug resistance and excess mortality due to AB infections was observed. Adjusted odds ratios were 1.23 (95% confidence interval [CI], 0.51-3.00) for MDR-AB, 1.72 (95% CI, 0.77-3.80) for extensively drug-resistant AB (XDR-AB), and 1.82 (95% CI, 0.55-6.00) for pandrug-resistant AB (PDR-AB). There is, however, a paucity of published data on additional length of stay and costs attributable to MDROs.CONCLUSIONSThis review highlights the challenges in addressing MDROs in Southeast Asia, where HAIs caused by MDR gram-negative bacteria are abundant and have a strong impact on society. With our findings, we hope to draw the attention of clinicians and policy makers to the problem of antibiotic resistance and to issue a call for action in the management of MDROs.Infect Control Hosp Epidemiol 2018;39:525-533.

Matched MeSH terms: Drug Resistance, Multiple, Bacterial

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