Of Pseudomonas, porins, pumps and carbapenems

Livermore, David M.

doi:10.1093/jac/47.3.247

Cited by 326 publications

(225 citation statements)

References 24 publications

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“…It confers almost the same level of resistance as is seen in the altered OprD-derivative [19,21]. This type of mutant is predominantly selected by carbenicillin or CAZ [19].…”

Section: Discussionmentioning

confidence: 90%

“…The anti-pseudomonas activities of carbapenems are affected by carbapenem-specific porin OprD not IPM, are also decreased by the increased production of the efflux protein MexAB-OprM [16,17,19,21], although this mechanism rarely confers outright nor does it confer high level resistance. It confers almost the same level of resistance as is seen in the altered OprD-derivative [19,21].…”

Section: Discussionmentioning

confidence: 99%

“…This type of mutant has been isolated by selection of a MEPM-resistant mutant from a OprD deficient derivative on agar containing MEPM [23]. This type of double mutant would not be selected readily during carbapenem therapy [19,21,23,24]. The MIC 90 values of DRPM for P. aeruginosa strains were one dilution lower than those of MEPM and eight dilutions lower than IPM, indicating that the MICs of IPM were the highest of the three carbapenems [9,12,19].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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The potencies of the carbapenems; doripenem (DRPM), meropenem (MEPM) and imipenem (IPM) in preventing the emergence of carbapenem-resistant mutants were examined in Pseudomonas aeruginosa strains. The carbapenems predominantly selected carbapenem-resistant mutants or carbapenem mutants with reduced susceptibilities that were specifically resistant to carbapenems and had arisen as a result of the reduced level of expression of the outer membrane protein with a molecular weight of about 48,000 (OprD). The potency of carbapenems in preventing the growth of the mutants differed for DRPM, MEPM and IPM. The isolation frequency of the mutant was examined on agar plates containing each of the carbapenems at a concentration of 1/2 or 1/4 MIC of each carbapenem for that mutant. Mutants were not selected on agar containing DRPM at a frequency of greater than 10 Ϫ9 per cell per generation, whereas mutants of each strain were selected on agar containing MEPM or IPM at frequencies of 10 Ϫ7 to 10 Ϫ9 per cell per generation. The drug concentrations and the drug concentration range for the selective increase of carbapenem resistant mutants in the broth culture containing each carbapenem differed for each carbapenem. DRPM exhibited both the lowest drug concentration and the narrowest range of drug concentration for selection of the carbapenem-resistant mutants. The results shown in this report indicated that DRPM exhibited the greatest ability to prevent the emergence of the mutant.

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“…It confers almost the same level of resistance as is seen in the altered OprD-derivative [19,21]. This type of mutant is predominantly selected by carbenicillin or CAZ [19].…”

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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“…Carbapenems are the most potent β-lactams against P. aeruginosa because its strong affinity to penicillin binding proteins, stability against most serine β-lactamases and high permeability across the outer membrane (7,8). However, intensive use of the carbapenems facilitated the emergence of carbapenem-resistant P. aeruginosa.…”

mentioning

confidence: 99%

Molecular Characterization of Imipenem‐Resistant Pseudomonas aeruginosa in Hiroshima, Japan

Ohara

Kouda

Onodera

et al. 2007

Microbiology and Immunology

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Nosocomial infections by Pseudomonas aeruginosa continue to be a widespread problem in Asia, North and South America, and Europe. Carbapenems are the most potent β-lactams against P. aeruginosa because its strong affinity to penicillin binding proteins, stability against most serine β-lactamases and high permeability across the outer membrane (7,8). However, intensive use of the carbapenems facilitated the emergence of carbapenem-resistant P. aeruginosa. Low level resistance to imipenem (MIC, 8 to 32 µg/ml) in P. aeruginosa is mostly due to reduced uptake of the drug as a result of loss of the porin OprD (8). This mechanism correlates with continued expression of AmpC β-lactamase. Resistance to meropenem but not imipenem may also arise via overexpression of the MexA-MexBOprM efflux pump (14). High level resistance to carbapenems (MICϾ32 µg/ml) can be caused by the presence of metallo-β-lactamase, which exhibits a broadspectrum resistance to β-lactams including carbapenems. Metallo-β-lactamase-producing P. aeruginosa Abstract: Pseudomonas aeruginosa showing resistance to imipenem were found in 100 of 1,058 strains (9.5%) from six hospitals (a-f) in Hiroshima City, Japan. Of the 100 strains, 14 (14%) were double disk synergy test positive using sodium mercaptoacetic acid disks, and 18 (18%) were bla IMP-1 or blaVIM-2 allele positive by polymerase chain reaction (PCR). Among 100 imipenem-resistant strains, 32 were categorized into multi-drug resistant strains, in which 13 were positive for the metallo-␤-lactamase gene. Fifty-one strains (51%) among the 100 imipenem-resistant strains had elevated RND efflux pump activity against levofloxacin. But only 6 of 51 strains were classified as multi-drug resistant strains. The pulsed field gel electrophoresis analysis of the SpeI-digested DNA from the 100 isolates suggested not only clonal spread but spread of heterogeneous clones started to contribute to the prevalence of metallo-␤-lactamase producing P. aeruginosa strains in Japanese hospitals.

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“…These infections are often difficult to treat because the bacteria is sensitive to few antibiotics, and also can produce multiple resistance to other antibiotics during the infection treatment [4,5]. Using several classes of antibiotics to treat infections caused by this bacterium can lead to the emergence of new mutant strains, which have a high level of resistance to many antibiotics [6].…”

Section: Pseudomonas Aeruginosa: Microbiological Clinical and Epidemmentioning

confidence: 99%

A New Treatment Choice against Multi-Drug Resistant Pseudomonas aeruginosa: Doripenem

Barrios¹,

Oliver²

2014

J Bacteriol Parasitol

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Pseudomonas aeruginosa is a Gram-negative strict aerobic Bacillus that causes around 10% of nosocomial infections. This bacillus can become resistant to multiple antibiotics, and it has been described mainly in inmuno compromised patients. The prevalence of multidrug resistant Pseudomonas has been increasing over the last few years. Currently we have new agents to treat this type of infection. Doripenem is the new B-lactam from the carbapenem family, which has demonstrated in vitro the best activity against multidrug resistant Pseudomonas aeruginosa in different studies. Its mechanism of action consists of the inactivation of penicillin-binding proteins in the cell wall. This agent has been indicated in the treatment of several infections, such as complicated intraabdominal infections, complicated urinary tract infections and nosocomial pneumonia. The principal difference between doripenem and the other carbapenems, is the capacity of preventing the generation of resistant strains of Pseudomonas aeruginosa, so it is especially useful for severe infections caused by multidrug resistant Pseudomonas aeruginosa. But this situation may change if we don't use antibiotics properly. Promoting rationale use of antibiotics to treat infections caused by Pseudomonas aeruginosa may be critical to make the emergence of multidrug resistant strains difficult. The present review describes the main features of doripenem and its potential role in managing infections due to multi-drug resistant Pseudomonas aeruginosa.Keywords: Doripenem; Carbapenems; Pseudomonas aeruginosa; Multidrug-resistance; Nosocomial infection Pseudomonas aeruginosa: Microbiological, Clinical and Epidemiological FeaturesPseudomonas aeruginosa is a Gram-negative aerobic and facultative anaerobic bacillus which belongs to the Pseudomonadaceae family. It is a small microorganism, straight or slightly curved, non-fermenting glucose and not sporulated. It has motility due to a single polar flagellum and twitching. Its identification in the laboratory is simple, because the germ grows easily in a wide variety of media and the requirements for its identification are scarce. Most cultures of this bacteria produce a blue-green pigment pyocyanin; it is useful for identification of the microorganism, and because of the characteristic color of copper oxide, the bacteria is named aeruginosa [1].This germ is typically associated with nosocomial infections, causing about 10% of infections acquired in the hospital, but community-acquired infections also contributes to a substantial number of cases [2,3]. Pseudomonas causes a variety of infections, mainly urinary tract infections, respiratory infections, ocular infections, endocarditis, bone and joint infections, burn infections and other skin infections, such as ecthyma gangrenosum or cellulitis.These infections are often difficult to treat because the bacteria is sensitive to few antibiotics, and also can produce multiple resistance to other antibiotics during the infection treatment [4,5]. Using several classes of ...

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Of Pseudomonas, porins, pumps and carbapenems

Cited by 326 publications

References 24 publications

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

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

Molecular Characterization of Imipenem‐Resistant Pseudomonas aeruginosa in Hiroshima, Japan

A New Treatment Choice against Multi-Drug Resistant Pseudomonas aeruginosa: Doripenem

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