Potency of Carbapenems for the Prevention of Carbapenem-Resistant Mutants of Pseudomonas aeruginosa

Sakyo, Shihomi; Tomita, Haruyoshi; Tanimoto, Koichi; Fujimoto, Shuhei; Ike, Yasuyoshi

doi:10.1038/ja.2006.31

Cited by 98 publications

(55 citation statements)

References 24 publications

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“…Only one isolate was resistant to carbapenems and didn't show crossresistance to other beta lactams so it can be imipenem-resistant P. aeruginosa mutant. 24 We investigated the relation between mexA, mexC, mexX, mexE genes and quinolones because they are substrates of four efflux system but we didn't find. We also found no relation between mexR gene that negatively regulates mexAB-oprM, and mexT gene that positively regulates mexCD-oprJ and the resistance against the antibiotics.…”

Section: Resultsmentioning

confidence: 99%

Efflux pump genes and antimicrobial resistance of Pseudomonas aeruginosa strains isolated from lower respiratory tract infections acquired in an intensive care unit

et al. 2011

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The aim of this study was to determine the antimicrobial resistance rates and the resistance genes associated with efflux pumps of Pseudomonas aeruginosa strains isolated from the patients who acquired lower respiratory tract infection (LRTI) in intensive care unit (ICU). Fifty P. aeruginosa strains isolated from the lower respiratory tract specimens of the patients who acquired LRTIs in ICU were included in this study. P. aeruginosa strains were isolated from tracheal aspirate (27), bronchoalveolar lavage (14) and sputum (9). The susceptibilities of the isolates were investigated by the disk diffusion method. Multiplex PCR assay was carried out for the detection of 13 antibiotic-resistance genes. Antimicrobial resistance rates of the isolates were found high and the highest resistance rate of the isolates studied was determined against to mezlocillin (50%) followed by norfloxacin (48%), ciprofloxacin (46%), meropenem (40%). Fourty-three isolates (86%) were determined to carry one and more resistance genes. NfxB gene was most often determined in the genes that were investigated. The significant relation between the resistance to cefepime, piperacilline/tazobactam and the mexC gene, that between the resistance to mezlocillin, piperacilline/tazobactam, ceftazidime, cefepime and ampC genes, and that between the resistance to ciprofloxacin, norfloxacin and oprJ, oprN and nfxB genes was identified. Resistance caused by genes for carbapenemases, aminoglycoside-modifying enzymes and other mechanisms were not identified in this study. Understanding the prevalence and mechanism of antimicrobial resistance in P. aeruginosa may help to select empirical therapy for nosocomial LRTIs due to P. aeruginosa in our ICU.

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Section: Resultsmentioning

confidence: 99%

Efflux pump genes and antimicrobial resistance of Pseudomonas aeruginosa strains isolated from lower respiratory tract infections acquired in an intensive care unit

et al. 2011

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“…15 Doripenem represents an attractive option among the carbapenems since (I) it has potent in vitro activity against many Gram-negative and -positive pathogens; 1,4,19,20 (II) lower propensity to select for resistance; [21][22][23] (III) safe tolerability profile with lower seizure potential than imipenem; 4,8,24 and (IV) extended solution stability at room temperature. 4,8,25 Sakyo et al 21 have shown that the potency of carbapenems in preventing the growth of the carbapenem-resistant P. aeruginosa mutants differed for doripenem, imipenem, and meropenem. Mutants were not selected on agar plates containing ½ or ¼ MIC doripenem at a frequency of greater than 10 -9 per cell per generation, whereas mutants of each P. aeruginosa strain were selected on agar containing meropenem or imipenem at frequencies of 10 -7 to 10 -9 per cell per generation.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial activity of doripenem against Gram-negative pathogens: results from INVITA-A-DORI Brazilian study

Gales¹,

Azevedo²,

Cereda³

et al. 2011

Braz J Infect Dis

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In vitro activity of doripenem and comparator antimicrobial agents was evaluated against Gram-negative bacilli recently isolated from Brazilian private hospitals that were enrolled in the INVITA-A-DORI Brazilian Study. A total of 805 unique Gram-negative bacilli were collected from patients hospitalized at 18 medical centers between May/08 and March/09. Each hospital was asked to submit 50 single Gram-negative bacilli isolated from blood, lower respiratory tract or intraabdominal secretions. Bacterial identification was confirmed and antimicrobial susceptibility testing was performed using Clinical Laboratory Standards Institute (CLSI) microdilution method at a central laboratory. CLSI M100-S21 (2011) or US-FDA package insert criteria (tigecycline) was used for interpretation of the antimicrobial susceptibility results. Doripenem was as active as meropenem and more active than imipenem against E. coli and K. pneumoniae isolates. A total of 50.0% of Enterobacter spp. isolates were resistant to ceftazidime but 85.7% of them were inhibited at doripenem MICs < 1 µg/mL. Polymyxin B was the only agent to show potent activity against Acinetobacter spp. (MIC50/90, < 0.5/1 µg/mL) and P. aeruginosa (MIC50/90, 1/2 µg/mL). Although high rates of imipenem (53.1%) and meropenem (44.5%) resistance were detected among P. aeruginosa, doripenem showed MIC50 of 16 µg/mL against imipenem-resistant P. aeruginosa and inhibited a greater number of imipenem-resistant P. aeruginosa (10.5%) at MIC values of < 4 µg/mL than did meropenem (0.0%). In this study, doripenem showed similar in vitro activity to that of meropenem and retained some activity against imipenem-resistant P. aeruginosa isolated from Brazilian medical centers

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“…In vivo, the proliferative inhibitory effect and maximal bactericidal action correlate with the time for which the drug concentration exceeds its minimum inhibitory concentration MIC ; T MIC . In the present study, we chose DRPM as the antibiotic to be evaluated for the following reasons : 1 DRPM is highly effective against aerobic Gram-negative and Gram-positive bacteria, as well as anaerobic bacteria, and it suppresses the growth of antimicrobial-resistant Pseudomonas aeruginosa ; 2 DRPM, MEPM, and IPM exhibit potent activity, with an MIC 90 of 4, 16, and 32 µg / ml, respectively, and DRPM is clinically effective against P. aeruginosa infection ; 3 DRPM does not show any cross-resistance with MEPM and IPM against P. aeruginosa ; 4 incompatibility between DRPM and protease inhibitors is low ; and 5 DRPM is a drug with little effect on the central nervous system [30][31][32][33][34][35][36] .…”

Section: Discussionmentioning

confidence: 99%

Usefulness of Continuous Regional Arterial Infusion with Doripenem and Protease Inhibitors for Severe Acute Pancreatitis

Yamamiya

Kitamura

Ishii

et al. 2015

Showa Univ J Med Sci

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: Doripenem DRPM is a relatively new drug belonging to the carbapenem antibiotic group. We hypothesized that the pharmacological characteristics of DRPM could make it useful in the treatment of severe acute pancreatitis SAP . We investigated the usefulness of continuous regional arterial infusion CRAI with DRPM and protease inhibitors for SAP. Two hundred and forty-two patients with SAP were admitted to Showa University Hospital between November 2002 and June 2013. Of these, 53 patients were treated with CRAI with carbapenem antibiotics and nafamostat mesilate NM , a serine protease inhibitor, via the celiac and superior mesenteric arteries. Clinical outcomes were evaluated retrospectively in 34 patients treated with DRPM and 19 patients undergoing non-DRPM therapy meropenem n 11, imipenem n 6 ; biapenem n 2 . The median time to commencement of oral intake was significantly shorter in the DRPM than non-DRPM group 9 vs 14 hospital days, respectively ; P 0.01 . In addition, the rate of walled-off necrosis in the DRPM group tended to be lower than in the non-DRPM group 37.5 vs 64.7 , respectively, P 0.069 . The results of the present study suggest that CRAI with DRPM and NM for SAP could have equivalent therapeutic effects to CRAI with other carbapenem antibiotics and NM.

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Potency of Carbapenems for the Prevention of Carbapenem-Resistant Mutants of Pseudomonas aeruginosa

Cited by 98 publications

References 24 publications

Efflux pump genes and antimicrobial resistance of Pseudomonas aeruginosa strains isolated from lower respiratory tract infections acquired in an intensive care unit

Efflux pump genes and antimicrobial resistance of Pseudomonas aeruginosa strains isolated from lower respiratory tract infections acquired in an intensive care unit

Antimicrobial activity of doripenem against Gram-negative pathogens: results from INVITA-A-DORI Brazilian study

Usefulness of Continuous Regional Arterial Infusion with Doripenem and Protease Inhibitors for Severe Acute Pancreatitis

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