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  1. Fulltext Carbapenem resistance gene crisis in A. baumannii: a computational analysis
    Zahra N, Zeshan B, Ishaq M
    BMC Microbiol, 2022 Dec 03;22(1):290.
    PMID: 36463105 DOI: 10.1186/s12866-022-02706-8
    Acinetobacter baumannii (A. baumannii) is one of the members of ESKAPE bacteria which is considered multidrug resistant globally. The objective of this study is to determine the protein docking of different antibiotic resistance gene (ARGs) in A. baumannii. In silico analysis of antibiotic resistance genes against carbapenem are the blaOXA-51, blaOXA-23, blaOXA-58, blaOXA-24, blaOXA-143, NMD-1 and IMP-1 in A. baumannii. The doripenem, imipenem and meropenem were docked to blaOXA-51 and blaOXA-23 using PyRx. The top docking energy was -5.5 kcal/mol by imipenem and doripenem and meropenem showed a binding score of -5. 2 kcal/mol each and blaOXA-23 energy was -4.3 kcal/mol by imipenem and meropenem showed a binding score of -2.3 kcal/mol, while doripenem showed the binding score of -3.4 kcal/mol. Similarly, doripenem imipenem and meropenem were docked to blaOXA-58, IMP-1, Rec A and blaOXA-143, with docking energy was -8.8 kcal/mol by doripenem and meropenem each while imipenem showed a binding score of -4.2 kcal/mol and with IMP-1 demonstrated their binding energies. was -5.7 kcal/mol by meropenem and doripenem showed a binding score of -5.3 kcal/mol, while imipenem showed a binding score of -4.5 kcal/mol. And docking energy was -4.9 kcal/mol by imipenem and meropenem showed binding energy of -3.6 kcal/mol each while doripenem showed a binding score of -3.9 kcal/mol in RecA and with blaOXA-143 docking energy was -3.0 kcal/mol by imipenem and meropenem showed a binding score of -1.9 kcal/mol, while doripenem showed the binding score of -2.5 kcal/mol respectively. Doripenem, imipenem, and meropenem docking findings with blaOXA-24 confirmed their binding energies. Doripenem had the highest docking energy of -5.5 kcal/mol, meropenem had a binding score of -4.0 kcal/mol, and imipenem had a binding score of -3.9 kcal/mol. PyRx was used to dock the doripenem, imipenem, and meropenem to NMD-1. Docking energies for doripenem were all - 4.0 kcal/mol, whereas meropenem had docking energy of -3.3 kcal/mol and imipenem was -1.50 kcal/mol. To the best of our knowledge the underlying mechanism of phenotypic with genotypic resistance molecular docking regarding carbapenem resistance A. baumannii is unclear. Our molecular docking finds the possible protein targeting mechanism for carbapenem-resistant A.baumannii.
    Matched MeSH terms: Imipenem/pharmacology
  2. Computational modelling of potential Zn-sensitive non-β-lactam inhibitors of imipenemase-1 (IMP-1)
    Ayipo YO, Ahmad I, Alananzeh W, Lawal A, Patel H, Mordi MN
    J Biomol Struct Dyn, 2023 Nov;41(19):10096-10116.
    PMID: 36476097 DOI: 10.1080/07391102.2022.2153168
    Antibiotic resistance (AR) remains one of the leading global health challenges, mostly implicated in disease-related deaths. The Enterobacteriaceae-producing metallo-β-lactamases (MBLs) are critically involved in AR pathogenesis through Zn-dependent catalytic destruction of β-lactam antibiotics, yet with limited successful clinical inhibitors. The efficacy of relevant broad-spectrum β-lactams including imipenem and meropenem are seriously challenged by their susceptibility to the Zn-dependent carbapenemase hydrolysis, as such, searching for alternatives remains imperative. In this study, computational molecular modelling and virtual screening methods were extensively applied to identify new putative Zn-sensitive broad-spectrum inhibitors of MBLs, specifically imipenemase-1 (IMP-1) from the IBScreen database. Three ligands, STOCK3S-30154, STOCK3S-30418 and STOCK3S-30514 selectively displayed stronger binding interactions with the enzymes compared to reference inhibitors, imipenem and meropenem. For instance, the ligands showed molecular docking scores of -9.450, -8.005 and -10.159 kcal/mol, and MM-GBSA values of -40.404, -31.902 and -33.680 kcal/mol respectively against the IMP-1. Whereas, imipenem and meropenem showed docking scores of -9.038 and -10.875 kcal/mol, and MM-GBSA of -31.184 and -32.330 kcal/mol respectively against the enzyme. The ligands demonstrated good thermodynamic stability and compactness in complexes with IMP-1 throughout the 100 ns molecular dynamics (MD) trajectories. Interestingly, their binding affinities and stabilities were significantly affected in contacts with the remodelled Zn-deficient IMP-1, indicating sensitivity to the carbapenemase active Zn site, however, with non-β-lactam scaffolds, tenable to resist catalytic hydrolysis. They displayed ideal drug-like ADMET properties, thus, representing putative Zn-sensitive non-β-lactam inhibitors of IMP-1 amenable for further experimental studies.
    Matched MeSH terms: Imipenem/pharmacology
  3. An unusual neurological complication from a garden-variety organism: post-melioidosis parkinsonism
    Ng CS, Azmin S, Law ZK, Sahathevan R, Wan Yahya WN, Remli R, et al.
    Med J Aust, 2015 Apr 06;202(6):333-4.
    PMID: 25832163
    Matched MeSH terms: Imipenem/administration & dosage; Imipenem/therapeutic use*
  4. Distribution of extended spectrum beta-lactamase resistance genes among nosocomial imipenem resistant A. Baumannii strains harboring BLAoxa-23 carbapenemases isolated from Ilam and Tehran
    Taherikalani M, Sekawi Z, Azizi-Jalilian F, Keshavarz B, Soroush S, Akbari M, et al.
    J Biol Regul Homeost Agents, 2013 Jul-Sep;27(3):883-9.
    PMID: 24152853
    Antimicrobial susceptibility and ESBLs genes of 42 imipenem resistant A. baumannii carried out by DDST and PCR. The most antimicrobial agents against A. baumannii strains, harboring blaOXA-23-like carbapenemases, were meropenem (33.4 percent), piperacillin-tazobactam (23.9 percent), ceftazidime (14.3 percent) and gatifoxacin (19.1 percent), respectively. All the 42 isolates harbored the blaTEM gene, but the bla SHV and VEB genes were not present among all the isolates. With the exception of seven isolates, all the A. baumannii strains harbor blaTEM showed ESBL positivity in DDST. The result of this study show that resistance against antimicrobial agents, especially carbapenems, has increased and that blaTEM harboring A. baumannii strains can be help the blaOXA-like carbapenemase genes to code for resistance against carbapenem antibiotics.
    Matched MeSH terms: Imipenem/pharmacology*
  5. Imipenem for the treatment of melioidosis
    Minassian MA, Gage A, Price E, Sefton AM
    Int J Antimicrob Agents, 1999 Aug;12(3):263-5.
    PMID: 10461846
    Melioidosis is a protean disease caused by Burkholderia pseudomallei. It is rare in the UK and is generally only seen in patients with a travel history to endemic areas such as Thailand, Singapore and Malaysia. Cases may present with disseminated bacteraemic, non-disseminated bacteraemic, multi-focal bacteraemic or localized disease. Subclinical infections also occur. Following acquisition of the organism a patient may remain asymptomatic for several years before infection becomes clinically apparent. Factors such as diabetes, renal failure or other causes for a decrease in host immunity may precipitate the appearance of overt disease. The current treatment choice for severe melioidosis is parenteral ceftazidime followed by oral amoxycillin-clavulanic acid or a combination of co-trimoxazole, doxycycline and chloramphenicol. We report a case of melioidosis in a 59-year-old male diabetic from Bangladesh who initially responded to piperacillin-tazobactam but was changed to ceftazidime when a definitive diagnosis was made. His condition deteriorated on the latter antibiotic. He subsequently responded to imipenem. The patient's long-term outcome is still not known.
    Matched MeSH terms: Imipenem/therapeutic use*
  6. Fulltext Imipenem Treatment Induces Expression of Important Genes and Phenotypes in a Resistant Acinetobacter baumannii Isolate
    Dhabaan GN, AbuBakar S, Cerqueira GM, Al-Haroni M, Pang SP, Hassan H
    Antimicrob Agents Chemother, 2015 Dec 14;60(3):1370-6.
    PMID: 26666943 DOI: 10.1128/AAC.01696-15
    Acinetobacter baumannii has emerged as a notorious multidrug-resistant pathogen, and development of novel control measures is of the utmost importance. Understanding the factors that play a role in drug resistance may contribute to the identification of novel therapeutic targets. Pili are essential for A. baumannii adherence to and biofilm formation on abiotic surfaces as well as virulence. In the present study, we found that biofilm formation was significantly induced in an imipenem-resistant (Imp(r)) strain treated with a subinhibitory concentration of antibiotic compared to that in an untreated control and an imipenem-susceptible (Imp(s)) isolate. Using microarray and quantitative PCR analyses, we observed that several genes responsible for the synthesis of type IV pili were significantly upregulated in the Imp(r) but not in the Imp(s) isolate. Notably, this finding is corroborated by an increase in the motility of the Imp(r) strain. Our results suggest that the ability to overproduce colonization factors in response to imipenem treatment confers biological advantage to A. baumannii and may contribute to clinical success.
    Matched MeSH terms: Imipenem/administration & dosage; Imipenem/pharmacology*
  7. Fulltext Prevalence and antimicrobial susceptibility of Vibrio parahaemolyticus isolated from retail shrimps in Malaysia
    Letchumanan V, Yin WF, Lee LH, Chan KG
    Front Microbiol, 2015;6:33.
    PMID: 25688239 DOI: 10.3389/fmicb.2015.00033
    Vibrio parahaemolyticus is a marine and estuarine bacterium that has been the leading cause of foodborne outbreaks which leads to a significant threat to human health worldwide. Consumption of seafood contaminated with V. parahaemolyticus causes acute gastroenteritis in individuals. The bacterium poses two main virulence factor including the thermostable direct hemolysin (tdh) which is a pore-forming protein that contributes to the invasiveness of the bacterium in humans and TDH-related hemolysin (trh), which plays a similar role as tdh in the disease pathogenesis. This study aimed to investigate the antimicrobial resistance V. parahaemolyticus strains in shrimps purchased from wetmarkets and supermarkets. The toxR-based PCR assay indicated that a total of 57.8% (185/320) isolates were positive for V. parahaemolyticus. Only 10% (19/185) toxR-positive isolate exhibit the trh gene and none of the isolates were tested positive for tdh. The MAR index was measured for 14 common antimicrobial agents. The results indicated 98% of the isolates were highly susceptible to imipenem, ampicillin sulbactam (96%), chloramphenicol (95%), trimethoprim-sulfamethoxazole (93%), gentamicin (85%), levofloxacin (83%), and tetracycline (82%). The chloramphenicol (catA2) and kanamycin (aphA-3) resistance genes were detected in the resistant V. parahaemolyticus isolates. Our results demonstrate that shrimps are contaminated with V. parahaemolyticus, some of which carry the trh-gene thus being potential to cause food borne illness. The occurrence of multidrug resistance strains in the environment could be an indication of excessive usage of antibiotics in agriculture and aquaculture fields.
    Matched MeSH terms: Imipenem
  8. Fulltext Melioidosis: a case report
    Barman P, Sidhwa H, Shirkhande PA
    J Glob Infect Dis, 2011 Apr;3(2):183-6.
    PMID: 21731307 DOI: 10.4103/0974-777X.81697
    Burkhloderia pseudomallei has recently gained importance as an emerging pathogen in India. It causes various clinical manifestations like pneumoniae, septicaemia, arthritis, abscess etc. Cases have been reported from Southeast Asia mainly Thailand, Malaysia, Vietnam, etc. In India, few cases have been reported mainly from the southern part of the country. Patient was a 65-year-old male and presented with fever 1 month back, cough and breathlessness for same period, swelling on both ankles from 7 days. B. pseudomallei was isolated from endotracheal secretions, blood cultures, leg wound. He was successfully treated with Imipenem and Doxycycline and put on maintenance therapy now, and is currently doing well.
    Matched MeSH terms: Imipenem
  9. Fulltext An Inactivated Antibiotic-Exposed Whole-Cell Vaccine Enhances Bactericidal Activities Against Multidrug-Resistant Acinetobacter baumannii
    Shu MH, MatRahim N, NorAmdan N, Pang SP, Hashim SH, Phoon WH, et al.
    Sci Rep, 2016;6:22332.
    PMID: 26923424 DOI: 10.1038/srep22332
    Vaccination may be an alternative treatment for infection with multidrug-resistance (MDR) Acinetobacter baumannii. The study reported here evaluated the bactericidal antibody responses following immunization of mice using an inactivated whole-cell vaccine derived from antibiotic-exposed MDR A. baumannii (I-M28-47-114). Mice inoculated with I-M28-47 (non-antibiotic-exposed control) and I-M28-47-114 showed a high IgG antibody response by day 5 post-inoculation. Sera from mice inoculated with I-M28-47-114 collected on day 30 resulted in 80.7 ± 12.0% complement-mediated bacteriolysis in vitro of the test MDR A. baumannii treated with imipenem, which was a higher level of bacteriolysis over sera from mice inoculated with I-M28-47. Macrophage-like U937 cells eliminated 49.3 ± 11.6% of the test MDR A. baumannii treated with imipenem when opsonized with sera from mice inoculated with I-M28-47-114, which was a higher level of elimination than observed for test MDR A. baumannii opsonized with sera from mice inoculated with I-M28-47. These results suggest that vaccination with I-M28-47-114 stimulated antibody responses capable of mounting high bactericidal killing of MDR A. baumannii. Therefore, the inactivated antibiotic-exposed whole-cell vaccine (I-M28-47-114) has potential for development as a candidate vaccine for broad clearance and protection against MDR A. baumannii infections.
    Matched MeSH terms: Imipenem
  10. Fulltext Molecular Characterization of Carbapenem Resistant Klebsiella pneumoniae in Malaysia Hospital
    Lau MY, Teng FE, Chua KH, Ponnampalavanar S, Chong CW, Abdul Jabar K, et al.
    Pathogens, 2021 Mar 02;10(3).
    PMID: 33801250 DOI: 10.3390/pathogens10030279
    The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great concern, as carbapenems are the last-line therapy for multidrug-resistant Gram-negative bacteria infections. This study aims to report the epidemiology of CRKP in a teaching hospital in Malaysia based on the molecular genotypic and clinical characteristics of the isolates. Sixty-three CRKP strains were isolated from a tertiary teaching hospital from January 2016 until August 2017. Carbapenemase genes were detected in 55 isolates, with blaOXA-48 (63.5%) as the predominant carbapenemase gene, followed by blaNDM (36.5%). At least one porin loss was detected in nine isolates. Overall, 63 isolates were divided into 30 clusters at similarity of 80% with PFGE analysis. Statistical analysis showed that in-hospital mortality was significantly associated with the usage of central venous catheter, infection or colonization by CRKP, particularly NDM-producers. In comparison, survival analysis using Cox proportional hazards regression identified a higher hazard ratio for patients with a stoma and patients treated with imipenem but a lower hazard ratio for patients with NDM-producing CRKP. OXA-48 carbapenemase gene was the predominant carbapenemase gene in this study. As CRKP infection could lead to a high rate of in-hospital mortality, early detection of the isolates was important to reduce their dissemination.
    Matched MeSH terms: Imipenem
  11. Fulltext Antibiotic resistance and biosafety of Vibrio cholerae and Vibrio parahaemolyticus from freshwater fish at retail level
    International Food Research Journal, 2011;18(4):1523-1530.
    MyJurnal
    A total of 49 isolates of V. parahaemolyticus and 8 isolates of V. cholerae isolated from freshwater fish of patin (Pangasius hypopthalmus) and red tilapia (Oreochromis sp.) were purchased from different retail level in Selangor, Malaysia. All of the isolates showed a multiple resistances towards all 15 antibiotics tested. Some of the isolates show a high resistance to different antibiotics including bacitracin, vancomycin, tetracycline, furazididone, cephalothin and erythromycin. However, both species was susceptible towards imipenem. Overall antibiotics resistance patterns of all isolates were resistant from 2 to 14 resistance patterns with multiple antibiotic resistance (MAR) index ranging from 0.13 to 0.93 respectively. As the results obtained in the dendrogram produced from both species had indicates that these antibiotics were intensively used whether in the aquaculture farm through feeds during culture or at the hatchery production of seed. Thus, this study will provides an essential information of the MAR index and also the clustering analysis in order to determine the biosafety of Vibrio spp. in freshwater aquaculture fish sold at different retail level in Malaysia.
    Matched MeSH terms: Imipenem
  12. Fulltext Prevalence and Antimicrobial Susceptibility of Vibrio parahaemolyticus Isolated from Short Mackerels (Rastrelliger brachysoma) in Malaysia
    Tan CW, Malcolm TTH, Kuan CH, Thung TY, Chang WS, Loo YY, et al.
    Front Microbiol, 2017;8:1087.
    PMID: 28659901 DOI: 10.3389/fmicb.2017.01087
    Numerous prevalence studies and outbreaks of Vibrio parahaemolyticus infection have been extensively reported in shellfish and crustaceans. Information on the quantitative detection of V. parahaemolyticus in finfish species is limited. In this study, short mackerels (Rastrelliger brachysoma) obtained from different retail marketplaces were monitored with the presence of total and pathogenic strains of V. parahaemolyticus. Out of 130 short mackerel samples, 116 (89.2%) were detected with the presence of total V. parahaemolyticus and microbial loads of total V. parahaemolyticus ranging from <3 to >10(5) MPN/g. Prevalence of total V. parahaemolyticus was found highest in wet markets (95.2%) followed by minimarkets (89.1%) and hypermarkets (83.3%). Pathogenic V. parahaemolyticus strains (tdh+ and/or trh+) were detected in 16.2% (21 of 130) of short mackerel samples. The density of tdh+ V. parahaemolyticus strains were examined ranging from 3.6 to >10(5) MPN/g and microbial loads of V. parahaemolyticus strains positive for both tdh and trh were found ranging from 300 to 740 MPN/g. On the other hand, antibiotic susceptibility profiles of V. parahaemolyticus strains isolated from short mackerels were determined through disc diffusion method in this study. Assessment of antimicrobial susceptibility profile of V. parahaemolyticus revealed majority of the isolates were highly susceptible to ampicillin sulbactam, meropenem, ceftazidime, and imipenem, but resistant to penicillin G and ampicillin. Two isolates (2.99%) exhibited the highest multiple antibiotic resistance (MAR) index value of 0.41 which shown resistance to 7 antibiotics. Results of the present study demonstrated that the occurrence of pathogenic V. parahaemolyticus strains in short mackerels and multidrug resistance of V. parahaemolyticus isolates could be a potential public health concerns to the consumer. Furthermore, prevalence data attained from the current study can be further used to develop a microbial risk assessment model to estimate health risks associated with the consumption of short mackerels contaminated with pathogenic V. parahaemolyticus.
    Matched MeSH terms: Imipenem
  13. Fulltext Antimicrobial susceptibility and virulence genes of clinical and environmental isolates of Pseudomonas aeruginosa
    Liew SM, Rajasekaram G, Puthucheary SA, Chua KH
    PeerJ, 2019;7:e6217.
    PMID: 30697478 DOI: 10.7717/peerj.6217
    Background: Pseudomonas aeruginosa is ubiquitous, has intrinsic antibiotic resistance mechanisms, and is associated with serious hospital-associated infections. It has evolved from being a burn wound infection into a major nosocomial threat. In this study, we compared and correlated the antimicrobial resistance, virulence traits and clonal relatedness between clinical and fresh water environmental isolates of P. aeruginosa.

    Methods: 219 P. aeruginosa isolates were studied: (a) 105 clinical isolates from 1977 to 1985 (n = 52) and 2015 (n = 53), and (b) 114 environmental isolates from different fresh water sources. All isolates were subjected to ERIC-PCR typing, antimicrobial susceptibility testing and virulence factor genes screening.

    Results: Clinical and environmental isolates of P. aeruginosa were genetically heterogenous, with only four clinical isolates showing 100% identical ERIC-PCR patterns to seven environmental isolates. Most of the clinical and environmental isolates were sensitive to almost all of the antipseudomonal drugs, except for ticarcillin/clavulanic acid. Increased resistant isolates was seen in 2015 compared to that of the archived isolates; four MDR strains were detected and all were retrieved in 2015. All clinical isolates retrieved from 1977 to 1985 were susceptible to ceftazidime and ciprofloxacin; but in comparison, the clinical isolates recovered in 2015 exhibited 9.4% resistance to ceftazidime and 5.7% to ciprofloxacin; a rise in resistance to imipenem (3.8% to 7.5%), piperacillin (9.6% to 11.3%) and amikacin (1.9% to 5.7%) and a slight drop in resistance rates to piperacillin/tazobactam (7.7% to 7.5%), ticarcillin/clavulanic acid (19.2% to 18.9%), meropenem (15.4% to 7.5%), doripenem (11.5% to 7.5%), gentamicin (7.7% to 7.5%) and netilmicin (7.7% to 7.5%). Environmental isolates were resistant to piperacillin/tazobactam (1.8%), ciprofloxacin (1.8%), piperacillin (4.4%) and carbapenems (doripenem 11.4%, meropenem 8.8% and imipenem 2.6%). Both clinical and environmental isolates showed high prevalence of virulence factor genes, but none were detected in 10 (9.5%) clinical and 18 (15.8%) environmental isolates. The exoT gene was not detected in any of the clinical isolates. Resistance to carbapenems (meropenem, doripenem and imipenem), β-lactamase inhibitors (ticarcillin/clavulanic acid and piperacillin/tazobactam), piperacillin, ceftazidime and ciprofloxacin was observed in some of the isolates without virulence factor genes. Five virulence-negative isolates were susceptible to all of the antimicrobials. Only one MDR strain harbored none of the virulence factor genes.

    Conclusion: Over a period of 30 years, a rise in antipseudomonal drug resistance particularly to ceftazidime and ciprofloxacin was observed in two hospitals in Malaysia. The occurrence of resistant environmental isolates from densely populated areas is relevant and gives rise to collective anxiety to the community at large.

    Matched MeSH terms: Imipenem
  14. Fulltext Antimicrobial susceptibility of clinical isolates of Pseudomonas aeruginosa from a Malaysian Hospital
    Pathmanathan SG, Samat NA, Mohamed R
    Malays J Med Sci, 2009 Apr;16(2):27-32.
    PMID: 22589655 MyJurnal
    Ongoing surveillance of Pseudomonas aeruginosa resistance against antimicrobial agents is fundamental to monitor trends in susceptibility patterns and to appropriately guide clinicians in choosing empirical or directed therapy. The in vitro activity level of eight antimicrobial drugs was assessed against 97 clinical isolates of P. aeruginosa collected consecutively for three months in 2007 from a Malaysian hospital. Antimicrobial susceptibility was determined using the E-test method in addition to the hospital's routine diagnostic testing by the disk diffusion method. Respiratory and wound swab isolates were the most frequently encountered isolates. The E-test and disk diffusion methods showed high concordance in determining the in vitro activity of the antimicrobial agents against the E isolates. Piperacillin-tazobactam was the most active antimicrobial agent with 91.8% susceptibility, followed by the aminoglycosides (amikacin, 86.6% and gentamicin, 84.5%), the quinolone (ciprofloxacin, 83.5%) and the beta-lactams (cefepime, 80.4%, ceftazidime, 80.4%, imipenem, 79.4% and meropenem, 77.3%). Incidence of multidrug resistance was 19.6% (19 out of 97 isolates). Periodic antibiotic resistance surveillance is fundamental to monitor changes in susceptibility patterns in a hospital setting.

    Study site: Hospital Kuala Lumpur
    Matched MeSH terms: Imipenem
  15. Fulltext Phenotypic detection of metallo-β-lactamase in imipenem-resistant Pseudomonas aeruginosa
    Khosravi Y, Loke MF, Chua EG, Tay ST, Vadivelu J
    ScientificWorldJournal, 2012;2012:654939.
    PMID: 22792048 DOI: 10.1100/2012/654939
    Carbapenems are the primary choice of treatment for severe Pseudomonas aeruginosa infection. However, the emergence of carbapenem resistance due to the production of metallo-β-lactamases (MBLs) is of global concern. In this study, 90 imipenem- (IPM- or IP-) resistant P. aeruginosa (IRPA) isolates, including 32 previously tested positive and genotyped for MBL genes by PCR, were subjected to double-disk synergy test (DDST), combined disk test (CDT), and imipenem/imipenem-inhibitor (IP/IPI) E-test to evaluate their MBLs detection capability. All three methods were shown to have a sensitivity of 100%. However, DDST was the most specific of the three (96.6%), followed by IP/IPI E-test interpreted based on the single criteria of IP/IPI ≥8 as positive (62.1%), and CDT was the least specific (43.1%). Based on the data from this evaluation, we propose that only IRPA with IP MIC >16 μg/mL and IP/IPI ≥8 by IP/IPI E-test should be taken as positive for MBL activity. With the new dual interpretation criteria, the MBL IP/IPI E-test was shown to achieve 100% sensitivity as well as specificity for the IRPA in this study. Therefore, the IP/IPI E-test is a viable alternative phenotypic assay to detect MBL production in IRPA in our population in circumstances where PCR detection is not a feasible option.
    Matched MeSH terms: Imipenem/pharmacology*
  16. Fulltext First isolation of Burkholderia tropica from a neonatal patient successfully treated with imipenem
    Deris ZZ, Van Rostenberghe H, Habsah H, Noraida R, Tan GC, Chan YY, et al.
    Int J Infect Dis, 2010 Jan;14(1):e73-4.
    PMID: 19482535 DOI: 10.1016/j.ijid.2009.03.005
    We report the first case of a human Burkholderia tropica infection. The patient was a premature neonate who had necrotizing enterocolitis with bowel perforation requiring surgical intervention. The stoma care and difficulties in feeding were a chronic problem. At the age of almost 4 months he developed septicemia due to B. tropica. Three consecutive blood cultures grew this organism. The organism was cleared from the blood after a course of imipenem and resolution of post-operative ileus. Our case suggests that environmental and plant pathogens can cause human infection especially in those in an immunocompromised condition.
    Matched MeSH terms: Imipenem/therapeutic use*
  17. Burkholderia pseudomallei: in vitro susceptibility to some new and old antimicrobials
    Karunakaran R, Puthucheary SD
    Scand. J. Infect. Dis., 2007;39(10):858-61.
    PMID: 17852912
    The treatment of melioidosis currently involves the use of antimicrobials such as ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate and doxycycline. Evaluation of other antimicrobials with activity against the organism continues to be pursued, however, as the causative organism, B. pseudomallei, may not always be susceptible to the above antimicrobials. This study aimed to test the susceptibility of Malaysian isolates of B. pseudomallei against imipenem, meropenem, ertapenem, moxifloxacin and azithromycin. 80 previously stocked clinical isolates collected between 1978 and 2003 from the UMMC, Kuala Lumpur were tested for in vitro susceptibility to these antimicrobials using the E-test minimum inhibitory concentration method. 100% of isolates were sensitive to imipenem and meropenem, 97.5% were sensitive to trimethoprim-sulfamethozaxole, 37.5% to moxifloxacin, and only a minority was sensitive to ertapenem (7.5%). Using breakpoints for Staphylococcus and Haemophilus, 5.0%-6.3% of isolates were sensitive to azithromycin. In conclusion, our findings support the in vitro efficacy of imipenem, meropenem and trimethoprim-sulfamethoxazole against B. pseudomallei. Moxifloxacin, ertapenem and azithromycin cannot be recommended for the treatment of melioidosis; however, further studies are needed to test the efficacy of azithromycin in combination with quinolones.
    Matched MeSH terms: Imipenem/pharmacology*
  18. Interaction of LysM BON family protein domain with carbapenems: A putative mechanism of carbapenem resistance
    Ali A, Kumar R, Khan A, Khan AU
    Int J Biol Macromol, 2020 Oct 01;160:212-223.
    PMID: 32464197 DOI: 10.1016/j.ijbiomac.2020.05.172
    Carbapenem resistance in Gram-negative pathogens has become a global concern for health workers worldwide. In one of our earlier studies, a Klebsiella pneumoniae-carbapenemase-2 producing strain was induced with meropenem to explore differentially expressed proteins under induced and uninduced conditions. There is, LysM domain BON family protein, was found over 12-fold expressed under the induced state. A hypothesis was proposed that LysM domain protein might have an affinity towards carbapenem antibiotics making them unavailable to bind with their target. Hence, we initiated a study to understand the binding mode of carbapenem with LysM domain protein. MICs of imipenem and meropenem against LysM clone were increased by several folds as compared to NP-6 clinical strain as well as DH5 α (PET-28a KPC-2) clone. This study further revealed a strong binding of both antibiotics to LysM domain protein. Molecular simulation studies of LysM domain protein with meropenem and imipenem for 80 ns has also showed stable structure. We concluded that overexpressed LysM domain under induced condition interacted with carbapenems, leading to enhanced resistance as proved by high MIC values. Hence, the study proved the proposed hypothesis that the LysM domain plays a significant role in the putative mechanism of antibiotics resistance.
    Matched MeSH terms: Imipenem/pharmacology
  19. Susceptibility patterns of anaerobes isolated from clinical specimens in tertiary Hospital, Malaysia
    Ishak N, Abdul Wahab Z, Amin Nordin S, Ibrahim R
    Malays J Pathol, 2020 Aug;42(2):245-252.
    PMID: 32860377
    INTRODUCTION: The susceptibility patterns of anaerobes are becoming less predictable due to the emergence of anaerobic resistance trends to antibiotics; hence increasing the importance of the isolation and antimicrobial susceptibility testing of anaerobes.

    MATERIALS AND METHODS: This study investigated the isolation of anaerobes from the clinical specimens of Hospital Sungai Buloh, Malaysia, from January 2015 to December 2015. All isolates were identified using the API 20A system (bioMérieux, France). Antimicrobial susceptibility testing was performed using the E-test (bioMérieux, France).

    RESULTS: The proportion of obligate anaerobes isolated from the clinical specimens was 0.83%. The Gram-positive anaerobes were most susceptible to vancomycin and imipenem, showing 100% sensitivity to these antimicrobials, followed by clindamycin (86.3%), penicillin (76.7%), and metronidazole (48.9%). Meanwhile, Gram-negative anaerobes were most susceptible to metronidazole (96%) followed by imipenem (89%), clindamycin (79%), and ampicillin (32%). The present study also showed that 3 out of 12 Bacteroides fragilis isolates were resistant to imipenem.

    CONCLUSION: This study demonstrated the differences in the susceptibility patterns of anaerobes towards commonly used antimicrobials for the treatment of anaerobic infections. In summary, continuous monitoring of antimicrobial resistance trends among anaerobes is needed to ensure the appropriateness of treatment.

    Matched MeSH terms: Imipenem/pharmacology
  20. Carbapenem-resistant Pseudomonas aeruginosa in malaysia producing IMP-7 beta-lactamase
    Ho SE, Subramaniam G, Palasubramaniam S, Navaratnam P
    Antimicrob Agents Chemother, 2002 Oct;46(10):3286-7.
    PMID: 12234862
    We have isolated and identified a carbapenem-resistant Pseudomonas aeruginosa strain from Malaysia that produces an IMP-7 metallo-beta-lactamase. This isolate showed high-level resistance to meropenem and imipenem, the MICs of which were 256 and 128 micro g/ml, respectively. Isoelectric focusing analyses revealed pI values of >9.0, 8.2, and 7.8, which indicated the possible presence of IMP and OXA. DNA sequencing confirmed the identity of the IMP-7 determinant.
    Matched MeSH terms: Imipenem/pharmacology
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