Carbapenem-resistant Acinetobacter spp. are considered priority drug-resistant human-pathogenic bacteria. The genomes of two carbapenem-resistant Acinetobacter spp. clinical isolates obtained from the same tertiary hospital in Terengganu, Malaysia, namely, A. baumannii AC1633 and A. nosocomialis AC1530, were sequenced. Both isolates were found to harbor the carbapenemase genes blaNDM-1 and blaOXA-58 in a large (ca. 170 kb) plasmid designated pAC1633-1 and pAC1530, respectively, that also encodes genes that confer resistance to aminoglycosides, sulfonamides, and macrolides. The two plasmids were almost identical except for the insertion of ISAba11 and an IS4 family element in pAC1633-1, and ISAba11 along with relBE toxin-antitoxin genes flanked by inversely orientated pdif (XerC/XerD) recombination sites in pAC1530. The blaNDM-1 gene was encoded in a Tn125 composite transposon structure flanked by ISAba125, whereas blaOXA-58 was flanked by ISAba11 and ISAba3 downstream and a partial ISAba3 element upstream within a pdif module. The presence of conjugative genes in plasmids pAC1633-1/pAC1530 and their discovery in two distinct species of Acinetobacter from the same hospital are suggestive of conjugative transfer, but mating experiments failed to demonstrate transmissibility under standard laboratory conditions. Comparative sequence analysis strongly inferred that pAC1633-1/pAC1530 was derived from two separate plasmids in an IS1006-mediated recombination or transposition event. A. baumannii AC1633 also harbored three other plasmids designated pAC1633-2, pAC1633-3, and pAC1633-4. Both pAC1633-3 and pAC1633-4 are cryptic plasmids, whereas pAC1633-2 is a 12,651-bp plasmid of the GR8/GR23 Rep3-superfamily group that encodes the tetA(39) tetracycline resistance determinant in a pdif module.IMPORTANCE Bacteria of the genus Acinetobacter are important hospital-acquired pathogens, with carbapenem-resistant A. baumannii listed by the World Health Organization as the one of the top priority pathogens. Whole-genome sequencing of carbapenem-resistant A. baumannii AC1633 and A. nosocomialis AC1530, which were isolated from the main tertiary hospital in Terengganu, Malaysia, led to the discovery of a large, ca. 170-kb plasmid that harbored genes encoding the New Delhi metallo-β-lactamase-1 (NDM-1) and OXA-58 carbapenemases alongside genes that conferred resistance to aminoglycosides, macrolides, and sulfonamides. The plasmid was a patchwork of multiple mobile genetic elements and comparative sequence analysis indicated that it may have been derived from two separate plasmids through an IS1006-mediated recombination or transposition event. The presence of such a potentially transmissible plasmid encoding resistance to multiple antimicrobials warrants vigilance, as its spread to susceptible strains would lead to increasing incidences of antimicrobial resistance.
Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics
Resistance to chemotherapy agents is a major challenge infront of cancer patient treatment and researchers. It is known that several factors, such as multidrug resistance proteins and ATP-binding cassette families, are cell membrane transporters that can efflux several substrates such as chemotherapy agents from the cell cytoplasm. To reduce the adverse effects of chemotherapy agents, various targeted-based cancer therapy (TBCT) agents have been developed. TBCT has revolutionized cancer treatment, and several agents have shown more specific effects on tumor cells than chemotherapies. Small molecule inhibitors and monoclonal antibodies are specific agents that mostly target tumor cells but have low side effects on normal cells. Although these agents have been very useful for cancer treatment, however, the presence of natural and acquired resistance has blunted the advantages of targeted therapies. Therefore, development of new options might be necessary. A better understanding of tumor cell resistance mechanisms to current treatment agents may provide an appropriate platform for developing and improving new treatment modalities. Therefore, in this review, different mechanisms of tumor cell resistance to chemotherapy drugs and current targeted therapies have been described.
Multidrug-resistant tuberculosis (MDR-TB) is one of the causes of morbidity and mortality, among tuberculosis (TB) patients in Malaysia. The purpose of this study was to determine the contributing risk factors to the prevalence of (MDR-TB). Based on systematic review of the literatures, the prevalence of (MDR-TB) and associated risk factors in Malaysia were studied. A comprehensive search of Scopus, Science direct, PubMed, DOAJ, CINAHL Plus, MyJournal, BIREME, BMC Public Health, Medline, CAB, and WoS databases were done among the articles published from 31st January 2009 to 31st December 2018, by using medical subject heading (MeSH) key terms. In conducting this study, a total of 121 papers were reviewed and 23 research papers were chosen, because, they met the specific inclusion criteria. In this study, gender, age, marital status, ethnicity, homeless status, living in urban area and history of imprisonment were evaluated as demographic factors, while educational level and employment were evaluated as socioeconomic factors. Smoking, diabetes mellitus, drug abuse and alcohol consumption were evaluated as behavioral and co-morbidities factors. All the studies chosen as eligible to be included in this study were found to be significantly associated with the risk factors for the prevalence of (MDR-TB). It was also discovered that, lack of adequate knowledge among the community and (TB) patients might increase the progression of (MDR-TB) infection in Malaysia. Thus, carried out a systematic review provided a comprehensive assessment of the (MDR-TB) which might be useful for policy makers, health experts and researchers to implement appropriate strategies for (TB) infected population in Malaysia.
Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
Multidrug-resistant (MDR) or extensively drug-resistant (XDR) Tuberculosis (TB) is a major challenge to global TB control. Therefore, accurate tracing of in-country MDR-TB transmission are crucial for the development of optimal TB management strategies. This study aimed to investigate the diversity of MTBC in Nigeria. The lineage and drug-resistance patterns of the clinical MTBC isolates of TB patients in Southwestern region of Nigeria were determined using the WGS approach. The phenotypic DST of the isolates was determined for nine anti-TB drugs. The sequencing achieved average genome coverage of 65.99X. The most represented lineages were L4 (n = 52, 83%), L1 (n = 8, 12%), L2 (n = 2, 3%) and L5 (n = 1, 2%), suggesting a diversified MTB population. In term of detection of M/XDR-TB, while mutations in katG and rpoB genes are the strong predictors for the presence of M/XDR-TB, the current study also found the lack of good genetic markers for drug resistance amongst the MTBC in Nigeria which may pose greater problems on local tuberculosis management efforts. This high-resolution molecular epidemiological data provides valuable insights into the mechanistic for M/XDR TB in Lagos, Nigeria.
Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics
Antimicrobial activities of plants have long been evaluated for their promising use as antimicrobial agent and in minimizing the unwanted resistance effects of microorganisms. The study was conducted to evaluate the antibacterial activity of Quercus infectoria gall crude extracts against multidrug resistant (MDR) bacteria in vitro. The screening test was determined by disc diffusion technique using sterile filter paper discs impregnated with 1 mg/ disc (50 mg/ml) aqueous and ethanol extracts of Q. infectoria galls tested on five selected MDR bacterial strains. The minimum inhibitory concentration (MIC) was determined using the twofold serial micro dilution technique at concentration ranging from 5.00 mg/ml to 0.01 mg/ml. The minimum bactericidal concentration (MBC) was determined by sub culturing the microtitre wells showing no turbidity on the agar plate to obtain the MBC value. Both extracts showed substantial inhibitory effects against methicillin resistant coagulase negative Staphylococcus (MRCoNS) and methicillin resistant Staphylococcus aureus (MRSA). A slightly reduced inhibitory zone diameter was observed with MDR Acinetobacter sp. while no inhibitory effect was displayed among the extended spectrum beta lactamases (ESBL) K. pneumoniae and ESBL E. coli isolates. A significant difference in the zone sizes between both extracts was only observed in MRSA (p < 0.05). The MIC values ranged from 0.08 mg/ml to 0.63 mg/ml for aqueous and ethanol extracts against MRSA, MRCoNS and MDR Acinetobacter sp. while their MBC to MIC ratio values were 2 and less. The Q. infectoria gall extracts have shown very promising in vitro antibacterial activities and may be considered as a potentially good source of antimicrobial agent especially against MDR Gram positive bacteria.
Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
Prior to the implementation of Haemophilus influenzae type b vaccination worldwide, H. influenzae has been one of the main causative agents of community acquired pneumonia and meningitis in children. Due to the lack of information on the characteristics of the H. influenzae isolates that have previously been collected in Malaysia, the H. influenzae were assessed of their microbial susceptibility to commonly used antibiotics. Emphasis was made on strains that were resistance to co-trimoxazole (SXT) and their mode of transfer of the antibiotic resistance determinants were examined. A collection of 34 H. influenzae isolates was serotyped and antimicrobial susceptibility tests were performed to 11 antibiotics. To the isolates that were found to be resistant to co-trimoxazole, minimum inhibition concentration (MIC) to SXT was performed using Etest while agar dilution method was used to measure the individual MICs of trimethoprim (TMP) and sulfamethoxazole (SUL). These isolates were also examined for presence of plasmid by PCR and isolation method. Conjugal transfers of SXT-resistant genes to SXT-susceptible hosts were performed to determine their rate of transfer. Result showed that 20.6% of the total number of isolates was serotype B while the remaining was non-typeable. Antimicrobial susceptibility profile of all the isolates revealed that 58.8% was resistant to at least one antibiotic. Majority of these isolates were equally resistant to ampicillin and tetracycline (29.4% each), followed by resistance to SXT (26.5%). From nine isolates that were found to be SXT-resistant, five contained plasmid/s. Conjugal transfer experiment showed that these five isolates with plasmid transferred SXT-resistance determinants at a higher frequency than those without. From these observations, it is postulated that plasmid is not involved in the transfer of SXT-resistance genes but presence of plasmid facilitates their transfer. The information obtained from this study provides some basic knowledge on the antimicrobial susceptibility pattern of the H. influenzae isolates and their mode of transfer of SXT-resistance genes.
Matched MeSH terms: Drug Resistance, Multiple, Bacterial
The objectives of this study were to determine the occurrence of Campylobacter spp. in live chickens sold at wet markets in Selangor, Malaysia and the multidrug resistance (MDR) profiles of the isolates. Cloacal swabs were taken from the chickens before slaughter and their caecal mucosae were swabbed after slaughter. Of the 90 chickens examined, 68 (75.6%) were positive for Campylobacter. Campylobacter were recovered from caecal swabs (53/90) and cloacal swabs (34/90) and Campylobacter coli (46 isolates) were identified slightly more than Campylobacter jejuni (41 isolates), but these differences were not significant (p<0.05). The most frequently observed resistance was to cephalothin (95.5%), followed by tetracycline (80.8%), erythromycin (51.4%), enrofloxacin (42.4%) and gentamicin (24.4%). Multidrug resistance (resistant to four or more antibiotics) was detected in 35.3% isolates. Campylobacter jejuni showed nine resistance profiles and the most common was to gentamicin-eryhtromycin-enrofloxacin-cephalothin-tetracycline (32.4%) combination while C. coli showed six profiles, with cephalothin-tetracycline (32.2%) combination being most common.
Matched MeSH terms: Drug Resistance, Multiple, Bacterial*
Methicillin-resistant Staphylococcus aureus (MRSA) is known to cause nosocomial infections and is now becoming an emerging problem in veterinary medicine. The objective of the study was to determine the presence of MRSA in 100 cats and dogs sampled between November 2007 and April 2008 at the University Veterinary Hospital, Universiti Putra Malaysia. MRSA was detected in 8% of pets sampled. Ten percent (5/50) and 6% (3/50) of the isolates were from dogs and cats, respectively. All MRSA isolates possessed the mecA gene and were found to be resistant to at least three antimicrobials with a minimum of Oxacillin MIC of 8 μg/mL. One isolate (CT04) had an extremely high MIC of >256 μg/mL. The MLST type ST59 found in this study have been reported earlier from Singapore and other countries as a strain from animal and community-associated MRSA respectively. Pulsed-field gel electrophoresis revealed five pulsotypes. Two isolates from cats (CT27 and CT33) and three isolates from dogs (DG16, DG20, and DG49) were respectively assigned to pulsotypes B and D. The study suggests that cats and dogs in Malaysia are potential reservoirs for MRSA.
Matched MeSH terms: Drug Resistance, Multiple, Bacterial
The present study aims to explore the possible mechanisms underlying the multidrug resistance characteristic of Cryptosporidium parvum by detecting the presence of ATP-binding cassette (ABC) protein encoding genes, especially one that shows high similarity to members belonging to the multidrug resistance protein (MDR) and multidrug resistance associated protein (MRP) subfamilies. PCR using ABC-specific degenerate primers successfully amplified two unique fragments, designated Cpnbd1 and Cpnbd2, from C. parvum genomic DNA. Cpnbd1 exhibited high degree of homology (99-100%) with the nucleotide- binding domains (NBDs) at the NH2 -terminal halves of two previously reported ABC proteins (CpABC and CpABC1) of human and bovine origin C. parvum isolates. It is likely that CpABC, CpABC1 and Cpnbd1 were encoded by homologous genes of a type of ABC transporter protein found in different C. parvum isolates. However, Cpnbd2 showed moderate levels of similarities (28-49%) to the NBDs of four ABC proteins characterised in C. parvum to date. Therefore, Cpnbd2 could be a novel member of an ABC superfamily of proteins in C. parvum. Phylogenetic analyses on a list of ABC transporters known to associate with MDR phenotype has significantly linked Cpnbd1 and Cpnbd2 to these transporters, thus suggesting that Cpnbd1 and Cpnbd2 proteins may contribute to the intrinsic multidrug resistance phenotype of C. parvum.
Matched MeSH terms: Drug Resistance, Multiple/genetics*
Antimicrobial resistance is a worldwide public health concern. Rise in the number of antimicrobial resistant organisms, such as extended spectrum β-lactamase- (ESBL) and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae, continue to burden millions of people worldwide. E. coli and K. pneumoniae were isolated and collected for four months from a teaching hospital in the Philippines. All isolates were subjected to ESBL and carbapenemase testing using the double disk synergy test and modified Hodge test, respectively. Their pattern of resistance among different classes of antimicrobial agents was also investigated using the Kirby-Bauer disk diffusion test. Among the 32 clinical isolates tested, 28.1% were positive for ESBL production and 6.3% were positive for carbapenemase production. Species-specific classification showed that E. coli (44.4%) has the highest rate of ESBL production whereas both E. coli (5.6%) and K. pneumoniae (7.1%) showed almost similar rates of carbapenemase production. Antimicrobial resistance pattern of drug resistant isolates showed that all organisms were resistant to ampicillin, and majority showed resistance towards ciprofloxacin, cefotaxime, ceftriaxone, and sulfamethoxazole/trimethoprim. ESBL production is seen highest among E. coli isolates while similar rates of carbapenemase production was observed to both E. coli and K. pneumoniae isolates. Overall, antimicrobial resistance continues to rise and poses a huge threat in public health worldwide. Efforts should be made in developing rapid tests for antimicrobial resistance and to search for effective treatment from infections caused by multidrug resistant organisms.
Matched MeSH terms: Drug Resistance, Multiple, Bacterial
Anthelmintic resistance in nematode parasites of sheep and goats on a government farm in north Malaysia was monitored over a 3-year period (1997-2000). The faecal egg count reduction test (FECRT) was conducted on young sheep at the beginning and end of this period. Changes in management, designed to reduce the selection pressure for the development of anthelmintic resistance, were also implemented during this time. By far the most important parasite problem was Haemonchus contortus. In 1997, this nematode was found to be resistant to levamisole, with suspected resistance to closantel and moxidectin. However, when the FECRT was repeated 3 years later, its resistance status had become much more severe, with resistance to benzimidazole, levamisole and ivermectin, and suspected resistance to moxidectin. This rapid evolution to multiple anthelmintic resistance is a major concern that needs to be arrested. There is an urgent need to evaluate other control strategies that incorporate livestock management, the 'smart' use of drugs and non-chemotherapeutic approaches, such as biological control agents.
The prevalence of resistance to rifampicin and fusidic acid among Malaysian strains of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. This study aimed to determine the mechanisms of rifampicin and fusidic acid resistance and the genetic diversity of MRSA strains from a Malaysian tertiary hospital.
Matched MeSH terms: Drug Resistance, Multiple, Bacterial/genetics*
Uncomplicated falciparum malaria patients were randomly assigned to receive either 25 mg/kg chloroquine (CHL) over 3 d or a statim dose of 25 mg/kg sulfadoxine (SDX) plus 1.25 mg/kg pyrimethamine (PYR). Patients were followed up for 28 d and the parasite response graded according to World Health Organization criteria. Overall resistance to CHL was 63.3% and 47.4% to SDX/PYR. RI, RII and RIII rates were 9.1%, 42.4% and 12.1% for CHL and 10.5%, 21.1% and 15.8% for SDX/PYR, respectively. Degree and rates of resistance to CHL were significantly correlated with pre-treatment parasite density, but not those to SDX/PYR. Plasma CHL and SDX/PYR levels were within the reported ranges and were not significantly different in patients with sensitive and resistant responses.
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*
Many Proteobacteria communicate via production followed by response of quorum sensing molecules, namely, N-acyl homoserine lactones (AHLs). These molecules consist of a lactone moiety with N-acyl side chain with various chain lengths and degrees of saturation at C-3 position. AHL-dependent QS is often associated with regulation of diverse bacterial phenotypes including the expression of virulence factors. With the use of biosensor and high resolution liquid chromatography tandem mass spectrometry, the AHL production of clinical isolate A. baumannii 4KT was studied. Production of short chain AHL, namely, N-hexanoyl-homoserine lactone (C6-HSL) and N-octanoyl-homoserine lactone (C8-HSL), was detected.
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
Abstract. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a pathogen recognized to be distinct in both phenotype and genotype from hospital-acquired MRSA. We have identified CA-MRSA cases in Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia, including their antibiotic susceptibility patterns and genotypic characteristics. Cases were identified during January to December 2009 from routine clinical specimens, where culture and antibiotic susceptibility results yielded pauci-resistant MRSA isolates suspected as being CA-MRSA. The patients' clinical data were collected and their specimens were sent for molecular confirmation and analysis. Five cases of CA-MRSA were identified, which had a multi-sensitive pattern on antibiotic susceptibility tests and were resistant to only penicillin and oxacillin. All cases were skin and soft-tissue infections, including diabetic foot with gangrene, infected scalp hematoma, philtrum abscess in a healthcare worker, thrombophlebitis complicated with abscess and infected bedsore. All five cases were confirmed MRSA by detection of mecA. SCCmec typing (ccr and mec complex) revealed SCCmec type IV for all cases except the infected bedsore case. Panton-Valentine leukocidin gene was positive in all isolates. As clinical features among methicillin-sensitive Staphylococcus aureus, CA-MRSA and "nosocomial CA-MRSA" are indistinct, early recognition is necessary in order to initiate appropriate antibiotics and infection control measures. Continual surveillance of pauci-resistant MRSA and molecular analysis are necessary in order to identify emerging strains as well as their epidemiology and transmission, both in the community and in healthcare setting.
Matched MeSH terms: Drug Resistance, Multiple, Bacterial
This study was conducted to determine the antibiotic susceptibility pattern and distribution of exoU and exoS among 44 clinical isolates of P. aeruginosa collected from different patients over a 3-month period in 2010 at a major Malaysian hospital. Susceptibility data by disk diffusion method for cefepime (30 microg), ceftazidime (30 microg), gentamicin (10 microg), piperacillin-tazobactam (100/10 microg) and ciprofloxacin (5 microg) were available for 38 isolates. Resistance to ceftazidime and piperacillin-tazobactam was the most common (74%) with five isolates not susceptible to three or more different antibiotics. PCR detection of exoU and exoS of all 44 isolates showed the former gene to be present in 18 and exoS in 41. In analyzing the two genes together, 17 isolates were detected for exoU and exoS with only two being negative for both genes. Only one isolate was detected for exoU alone whereas 24 for exoS alone. Distribution of the genes in relation to antibiotic susceptibility was inapplicable due to the majority of the isolates having similar susceptibility patterns, but the tendency of exoU-carrying isolates to be present in male patients (83%) and respiratory sites (61%) was observed (p < 0.050). The finding warrants further investigation in a larger sample of isolates.\
Study site: Hospital Kuala Lumpur (HKL)
Matched MeSH terms: Drug Resistance, Multiple, Bacterial