• Microbiology and Biotechnology Letters
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• v.49 no.2
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• pp.239-248
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• 2021

The emergence of multidrug-resistant Acinetobacter baumannii has partly increased treatment failure and patient mortality. Class D β-lactamases is an important mechanism of resistance to beta-lactam antibiotics in this species. This study aimed to investigate the relationship between the presence oxacillinase gene and genetic fingerprints of A. baumannii isolates from the intensive care unit of an Egyptian tertiary care hospital. One hundred and twenty A. baumannii clinical isolates were collected. Multiplex PCR was performed to detect genes encoding oxacillinases (OXA-23, OXA-24, OXA-51, OXA-58 and OXA-143). Molecular typing of all collected isolates was performed using random amplified polymorphic DNA (RAPD)-PCR assay. Out of 120 examined isolates, 92, 88 and 84% were resistant to ertapenem, imipenem and meropenem, respectively. The species-specific, commonly present OXA-51 gene was found in all isolates while OXA-23 showed a high prevalence of 88% of isolates. OXA-24 and OXA-143 genes were detected in 3% and 1% of isolates, respectively. No OXA-58 gene was detected. Five clusters consisting of 19 genotypes were detected using RAPD-PCR. Genotype A was the most prevalent, it was observed in 62% of the isolates followed by genotype B (12%). These results revealed that genotypes A and B are common in the hospital. Results also demonstrate that RAPD-PCR is a rapid and reliable method for studying the clonal similarity among A. baumannii isolated from different clinical specimens.

• Genomics & Informatics
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• v.20 no.4
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• pp.47.1-47.13
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• 2022

Klebsiella pneumoniae is a gram-negative bacterium that is known for causing infection in nosocomial settings. As reported by the World Health Organization, carbapenem-resistant Enterobacteriaceae, a category that includes K. pneumoniae, are classified as an urgent threat, and the greatest concern is that these bacterial pathogens may acquire genetic traits that make them resistant towards antibiotics. The last class of antibiotics, carbapenems, are not able to combat these bacterial pathogens, allowing them to clonally expand antibiotic-resistant strains. Most antibiotics target essential pathways of bacterial cells; however, these targets are no longer susceptible to antibiotics. Hence, in our study, we focused on a hypothetical protein in K. pneumoniae that contains a DNA methylation protein domain, suggesting a new potential site as a drug target. DNA methylation regulates the attenuation of bacterial virulence. We integrated computational-aided drug design by using a bioinformatics approach to perform subtractive genomics, virtual screening, and fingerprint similarity search. We identified a new potential drug, koenimbine, which could be a novel antibiotic.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.4
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• pp.265-272
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• 2022

The emergence and dissemination of carbapenemase-producing Enterobacteriaceae (CPE), particularly the Klebsiella pneumoniae carbapenemase-2 (KPC-2) producing Klebsiella pneumoniae, has been rapidly increasing worldwide and is becoming a serious public health threat. Since the epidemiology and characteristics of these KPC-2-producing K. pneumoniae vary according to the region and period under consideration, this study investigated the prevalence of carbapenemases and the epidemiological relationship of 78 carbapenem-resistant K. pneumoniae (CRKP) isolated from a tertiary hospital in Daejeon, from March 2017 to December 2020. The antimicrobial susceptibility tests were identified using the disk-diffusion method. PCR and DNA sequencing were used to determine the carbapenemase genes. In addition, molecular epidemiology was performed by multilocus sequence typing (MLST). Among the 78 CRKP isolates, 35 isolates (44.9%) were carbapenemase-producing K. pneumoniae (CPKP) and the major carbapenemase type was KPC-2 (30 isolates, 85.7%). The New Delhi metallo-enzyme-1 (NDM-1) and NDM-5 were identified in 4 isolates (11.4%) and 1 isolate (2.9%), respectively. Multilocus sequence typing (MLST) analysis showed 10 sequence types (STs) and the most prevalent ST was ST307 (51.4%, 18/35). All the ST307 isolates were KPC-2-producing K. pneumoniae and were multidrug-resistant (MDR). In addition, ST307 has gradually emerged during a four-year period. These findings indicate that continuous monitoring and proper infection control are needed to prevent the spread of KPC-2-producing K. pneumoniae ST307.

• Microbiology and Biotechnology Letters
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• v.51 no.4
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• pp.517-525
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• 2023

The emergence and spread of multidrug-resistant Pseudomonas aeruginosa (MRPA) have become a serious problem worldwide. The involvement of metallo-β-lactamases (MBLs) in inducing carbapenem resistance is particularly acute. However, unlike other members of the Enterobacteriaceae genus, new clones of P. aeruginosa are constantly emerging and rapidly replacing previously prevalent dominant clones. Therefore, this study aimed to perform antimicrobial resistance gene analysis, integron gene cassette analysis using DNA sequencing, and plasmid transfer analysis by conjugation to investigate the antimicrobial resistance dynamics of 18 P. aeruginosa strains isolated from various medical samples at a general hospital in Busan from September 2017 to September 2019. All 18 strains showed extensively drug-resistant (XDR) phenotype and were resistant to most antibiotics, except colistin (100%) but were susceptible to aztreonam (22.2%) and ceftazidime (16.6%). Approximately 66.7% of the strains had Class 1 integrons showing various antimicrobial resistances. Notably, IMP-6 ST235 (66.7%), VIM-2 ST357 (16.7%), and IMP-1 ST446(16.7%) were identified. The identification of IMP-1-producing ST446, previously unreported in Korea, is noteworthy considering the emergence and prevalence of another MRPA high-risk clone.

• Biomedical Science Letters
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• v.22 no.2
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• pp.29-36
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• 2016

Among the several agents causing carbapenem resistance of Acinetobacter baumannii, the most common cause is OXA-23 ${\beta}$-lactamase, which is known to hydrolyze carbapenem. To effectively control dissemination of carbapenem-resistant Acinetobacter baumannii (CRAB), development of both rapid and easy-to-use detection methods are required. The aim of this study is to develop a novel immunochromatographic assay (ICA) for rapid detection of OXA-23 ${\beta}$-lactamase. Of the seven monoclonal antibodies (mAbs) screened by ELISA, four mAbs (4G6, 4H6, 6G4, 9A4) exhibited high reactivity. Of these four specific antibodies, the combination of 6G4/4G6 showed the greatest reactivity and this combination of mAbs (6G4/4G6 mAbs) was used to develop the OXA-23 ${\beta}$-lactamase ICA. Of 102 A. baumannii isolates tested, the OXA-23 ${\beta}$-lactamase ICA results were consistent with PCR analysis except one false positive and one false negative isolate. The overall sensitivity and specificity were 98.36% and 97.56%, respectively. In conclusion, to the best of our knowledge, we have developed the first specific antibody set to detect OXA-23 ${\beta}$-lactamase using an ICA kit. This novel ICA can be used as a reliable and easy-to-use immunological assay for detection of OXA-23 ${\beta}$-lactamase producing CRAB in clinical laboratories.

• Biomedical Science Letters
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• v.25 no.4
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• pp.321-330
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• 2019

Carbapenem is recently considered as the last resort of the therapeutics for gram negative bacterial infection. Increasing of organisms producing metallo-β-lactamase (MBL), we have difficulty in choosing the antimicrobial agents. Among 345 clinical isolates of Pseudomonas spp., 61 isolates (17.7%) were positive for the modified imipenem or meropenem-Hodge test and 55 isolates (15.9%) were positive for the imipenem-EDTA + SMA double disk synergy test (DDS). PCR and sequencing of bla_VIM-2-allele and bla_IMP-1-allele showed that 17 isolates of Pseudomonas aeruginosa, 9 isolates of Pseudomonas taiwnensis and 2 Pseudomonas plecoglossicida had bla_VIM-2, and 22 isolates of P. aeruginosa and one Pseudomonas otitidis had bla_IMP-6. These MBL genes were all in class 1 integron. The size of class 1 integron with bla_VIM-2 ranged from 3.5 kb to 5.5 kb in clinical isolates of Pseudomonas spp. including P. aeruginosa. bla_VIM-2 was most often located first in the class 1 integron, sometimes in the second or third position, and these integrons often had aacA4 or aadA1. Strict infection control measures are needed to more effectively prevent further spread of these MBL-producing Pseudomonas spp. In addition, MBL-producing Pseudomonas spp. is expected to continue to spread in various countries and regions.

• YAKHAK HOEJI
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• v.41 no.2
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• pp.233-240
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• 1997

The in vitro antibacterial activity of DWP20418 (1R, 5S, 6S)-6-[1-(R)-Hydroxyethyl)-l-methyl-2-[(2S,4S)-2-(piperazinylcarbonyl)-1-(R)-hydroxyethyl)pyrrolidine-4-thio]carb apen-2-em-3-carboxylic acid), a new carbapenem antibiotic, was compared with those of imipenem (IPM) and meropenem (MEPM). DWP20418 was comparable or slightly more superior to MEPM against gram-positive bacteria, and it showed more potent activity to IPM against gram-negative bacteria. DWP20418 was particularly active against MRSA, and its $MIC_{90}$ of methicillin-susceptible S. aureus, low methicillin-resistant S. aureus and high methicillin-resistant S. aureus were 0.391, 25 and 50 ${\mu}g/ml$, respectively. With a view of $MIC_{90}$, DWP20418 was comparable than the other carbapenems against P. aeruginosa and E. coli isolates. The activity of DWP20418 was not affected in the presence of $Mg^{2+},\;Ca^{2+}$ or horse serum. But inoculum size and alterations in pH of medium affected its antibacterial activity. DWP20418 showed rapidly bactericidal activity within 1h, and regrowth was not observed even incubation of 24hrs at the concentrations near the MIC.

• Pediatric Infection and Vaccine
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• v.16 no.1
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• pp.6-12
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• 2009

There are relatively few novel antimicrobial agents despite the dramatic increase in antimicrobial resistance and multiple drug resistance of clinical isolates worldwide. Vancomycin is still the most widely used antibiotic for treating resistant Gram-positive coccal infections in children, especially for methicillin-resistant Staphylococcus aureus. For children with Gram-positive coccal infections where vancomycin is not effective or older therapeutic agents cannot be tolerated, linezolid, quinupristin-dalfopristin or daptomycin may be useful in the appropriate clinical setting. For Gram-negative bacterial infections, new carbapenems await clinical application. Tebipenem pivoxil is a novel oral carbapenem undergoing clinical trials for acute otitis media in pediatric patients. Antiviral drug development is now progressing at the pace of antibiotic development 30 years ago. Newer antiviral agents used for the treatment of herpes viruses and hepatitis C virus infections in children are included in this review.

• Korean Journal of Clinical Pharmacy
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• v.22 no.2
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• pp.181-186
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• 2012

Objective: To report a fatal case of Multidrug-resistant Acinetobacter baumannii (MDR-AB) in a patient with interstitial lung disease (ILD) on high-dose glucocorticoids. Case Summary: A 66-year-old man with a history of coniosis was transferred to the hospital with progressive cough and sputum production. This patient has been diagnosed with pneumonia and ILD on admission, requires antimicrobial therapy and systemic immunosuppressants. He received high dose of methylprednisolone and cyclophosphamide for ILD as well as ceftriaxone and azithromycin for pneumonia. On day 7 in the intensive care units (ICUs), patient had fever and leukocytosis, thus antimicrobials were switched to piperacillin. After 13 days in the ICU, Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) were isolated on transtracheal aspirate (TTA) and meropenem was initiated. However, it was revealed a multidrug-resistant Acinetobacter baumannii (MDR-AB) species, resistant to carbapenem. Patient was administered colistin but expired due to septic shock on day 84. Discussion: Systemic immunosuppressive therapy can result in infections that may compromise patient's survival. MDR-AB has emerged as a serious cause of nosocomial infections in immunocompromised patients. MDR-AB is resistant to most standard antimicrobials and therapeutic options are limited. Conclusion: We report our recent experience with a fatal MDR-AB pneumonia in a patient with ILD, who had to be treated with high dose glucocorticoids and immunosuppressnts.

• Korean Journal of Microbiology
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• v.54 no.4
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• pp.442-444
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• 2018

Recently, we isolated a multidrug-resistant Escherichia coli strain KBN10P04869 from a patient with acute myeloid leukemia. We report the complete genome of this strain which consists of 5,104,264 bp with 4,457 protein-coding genes, 88 tRNAs, and 22 rRNAs, and the co-occurrence of multidrug- resistant genes including $^{bla}CMY-2$, $^{bla}TEM-1$, $^{bla}CTX-M-15$, $^{bla}NDM-5$, and $^{bla}OXA-18$.