Activity of meropenem against antibiotic-resistant or infrequently encountered gram-negative bacilli

Jorgensen, James H.; Maher, Louise; Howell, A W

doi:10.1128/aac.35.11.2410

Cited by 33 publications

(18 citation statements)

References 6 publications

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“…In vitro, meropenem is more active than imipenem against members of the family Enterobacteriaceae and most oxidasepositive and/or glucose-nonfermenting gram-negative bacilli (3,8). The marked discordance between meropenem and imipenem susceptibility that we describe has not to our knowledge been observed in other gram-negative bacilli.…”

Section: Discordant Carbapenem Susceptibility In Methylobacterium Specontrasting

confidence: 37%

Discordant Carbapenem Susceptibility in Methylobacterium Species and Its Application as a Method for Phenotypic Identification

2001

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Section: Discordant Carbapenem Susceptibility In Methylobacterium Specontrasting

confidence: 37%

Discordant Carbapenem Susceptibility in Methylobacterium Species and Its Application as a Method for Phenotypic Identification

2001

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“…In addition, given the possibility of horizontal gene transfer, it is advisable to always perform susceptibility testing with large inocula or to analyze all strains of cphA-negative species with a cphA-specific probe. Since imipenem was the sole carbapenem tested in the present study, the considerations given above could not apply to other carbapenems such as meropenem which, in comparison with imipenem, usually has lower MICs for Aeromonas strains of cphApositive species (10,16) and also appears to be hydrolyzed somewhat less efficiently by the CphA enzyme (23). However, the facts that the CphA enzyme is also active against meropenem (14,23), that the mutation leading to constitutive highlevel expression of the Aeromonas carbapenemase results in resistance to both imipenem and meropenem (22), and that the inoculum size effect is observed for both imipenem and meropenem with clinical A. hydrophila and A. veronii bv.…”

Section: Discussionmentioning

confidence: 98%

Distribution of cphA or related carbapenemase-encoding genes and production of carbapenemase activity in members of the genus Aeromonas

Rossolini

Zanchi

Chiesurin

et al. 1995

Antimicrob Agents Chemother

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The prevalence of the cphA gene or related carbapenemase-encoding genes was investigated in 114 Aeromonas strains belonging to the six species of major clinical interest. A species-related distribution of cphA-related sequences was observed. Similar sequences were found in A. hydrophila, A. veronii bv. sobria, A. veronii bv. veronii, and A. jandaei, but not in A. caviae, A. trota, or A. schubertii. However, a single A. caviae strain (of 62 tested) was found carrying cphA-related sequences, suggesting the possibility of the horizontal transfer of this gene to species which normally do not carry it. Production of carbapenemase activity was detectable in 83% of the hybridization-positive strains but in none of the hybridization-negative ones. When it was present, carbapenemase activity was always inhibitable by EDTA. Either carbapenemase-producing or not, Aeromonas strains appeared to be susceptible to imipenem when in vitro susceptibility testing was performed with inocula of conventional size (10 5 CFU), for which MICs were always Յ1 g/ml. With a larger inoculum (10 8 CFU), the MICs for carbapenemase-negative strains always remained Յ1 g/ml, while those for carbapenemase-producing strains were always Ն4 g/ml, being usually higher than the breakpoint for susceptibility. The present results indicate that the production of metallocarbapenemase activity, apparently encoded by cphA homologs, is widespread among some of the Aeromonas species of clinical interest (A. hydrophila, A. veronii bv. sobria, A. veronii bv. veronii, and A. jandaei) and that imipenem MICs for carbapenemase-producing strains are subjected to a relevant inoculum size effect.Carbapenem compounds are ␤-lactam antibiotics of great therapeutic potential owing to their broad spectra of activity and resistance to most bacterial ␤-lactamases. However, enzymes able to inactivate the carbapenem molecule by hydrolysis of the ␤-lactam ring (carbapenemases) are produced by some microbial species and can cause microbial resistance to these compounds (11,12,18). Most of the carbapenemases thus far described are metalloenzymes which use a zinc ioncontaining active site (11), and all of the metallocarbapenemases thus far characterized at the sequence level belong to the same molecular class (class B), suggesting a common phylogeny (6,7,14,17,25).Members of the genus Aeromonas, which in the last decade have been the objects of increasing interest as human and animal pathogens (9), are among the few microorganisms that can produce metallocarbapenemase activities (1, 8, 24). The CphA metallo-␤-lactamase of A. hydrophila is one of the most active carbapenemases known, showing also, in comparison with other class B enzymes, a very specific substrate profile (5, 6, 23). The production of carbapenemase activity has previously been investigated in Aeromonas strains belonging to different species (1,8,24). However, recent developments in the field of Aeromonas taxonomy have led to a redefinition of some of the old species and to the description of new species (9) in which...

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“…Meropenem is highly active against these strains (16,17) and has been demonstrated to be effective in cases of meningitis caused by Pseudomonas aeruginosa (5,8), including one case following unsuccessful management with ceftazidime or ciprofloxacin plus amikacin (8).…”

Section: Discussionmentioning

confidence: 99%

Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Meropenem Meningitis Study Group

Klugman

Dagan

1995

Antimicrob Agents Chemother

159

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Broad-spectrum cephalosporins are drugs of choice for the treatment of meningitis in communities which can afford them. The emergence of cephalosporin-resistant pneumococci demands the clinical trial of alternate agents. Carbapenems are active against the bacteria causing meningitis, but the use of imipenem-cilastatin was frustrated by drug-associated seizures. The safety and efficacy of meropenem, a new carbapenem, were compared to those of cefotaxime in a prospective randomized trial of 190 children with bacterial meningitis. Seizures occurred within 24 h before antibiotic therapy in 16 of 98 patients (16%) randomized to receive meropenem and in 6 of 92 patients (7%) randomized to receive cefotaxime. In patients without seizures before therapy, seizures occurred during therapy in 5 of 82 patients (6%) receiving meropenem and in 1 of 86 patients (1%) receiving cefotaxime (95% confidence interval: ؊0.7%, 10.6%). None were thought to be drug related. Twenty-four meropenem-treated patients (24%) and 11 cefotaxime-treated patients (12%) had neurological abnormalities before therapy. In patients without pretherapy neurological abnormalities, these abnormalities were present after treatment in 4 of 74 meropenem-treated patients (5%) and in 2 of 81 cefotaxime-treated patients (2%) (95% confidence interval: ؊3.2%, 9.1%). Of 75 meropenem-treated and 64 cefotaxime-treated patients with pretherapy positive cerebrospinal-fluid cultures, 68 and 59, respectively, had repeat lumbar punctures. Bacterial eradication was found to be 100% in both groups. Our data suggest that meropenem may be a carbapenem agent that is well tolerated and effective in the treatment of bacterial meningitis.

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Activity of meropenem against antibiotic-resistant or infrequently encountered gram-negative bacilli

Cited by 33 publications

References 6 publications

Discordant Carbapenem Susceptibility in Methylobacterium Species and Its Application as a Method for Phenotypic Identification

Discordant Carbapenem Susceptibility in Methylobacterium Species and Its Application as a Method for Phenotypic Identification

Distribution of cphA or related carbapenemase-encoding genes and production of carbapenemase activity in members of the genus Aeromonas

Randomized comparison of meropenem with cefotaxime for treatment of bacterial meningitis. Meropenem Meningitis Study Group

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