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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
Spread of multidrug-resistant Proteus mirabilis isolates producing an AmpC-type beta-lactamase: epidemiology and
Francesco Luzzaro1, Gioconda Brigante, Marco Maria D'Andrea
1Laboratory of Medical Microbiology, Ospedale di Circolo, University of Insubria, Varese, Italy.
Abstract:
A remarkable increase in Proteus mirabilis strains producing acquired AmpC-type beta-lactamases (CBLs) has been observed at Ospedale di Circolo e Fondazione Macchi (Varese, Italy) over the last few years. The epidemiology and treatment outcome of infections associated with this unprecedented spread are reported. From 2004-2006, 2070 P. mirabilis isolates were investigated. Extended-spectrum beta-lactamases (ESBLs) and CBL resistance determinants were identified by gene amplification and direct sequencing. Clonal relatedness was evaluated by macrorestriction analysis. Overall, 43 CBL-positive isolates were obtained from hospitalised (n=22) and non-hospitalised (n=21) patients (median age 78.8 years). The prevalence of CBL-positive isolates increased from 0.3% in 2004 to 4.6% in 2006, whereas that of ESBL-positive isolates remained constant (ca. 10%). CBL-positive isolates were multidrug-resistant and carried the CMY-16 determinant. All but two isolates were genetically identical or closely related. Retrospective analysis of clinical records revealed that the majority of CMY-16-positive isolates were associated with urinary tract infections. Treatment with amikacin or carbapenems was consistently effective, whereas piperacillin/tazobactam produced a clinical response in seven of nine cases. This is the first report of a rapid spread of CBL-positive P. mirabilis strains endowed with remarkable antimicrobial resistance. Practical methods for CBL detection are needed for the appropriate management of related infections.
Insights
A rise in Proteus mirabilis infections resistant to AmpC-type beta-lactamases (CBLs) was observed. These multidrug-resistant strains, primarily causing urinary tract infections, require new detection methods for effective treatment.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- An increase in acquired AmpC-type beta-lactamase (CBL)-producing Proteus mirabilis strains was noted in Varese, Italy.
- This spread of multidrug-resistant bacteria poses a significant public health challenge.
Purpose of the Study:
- To investigate the epidemiology and treatment outcomes of infections caused by CBL-positive P. mirabilis.
- To characterize the resistance determinants and clonal relatedness of these isolates.
Main Methods:
- Analysis of 2070 P. mirabilis isolates collected between 2004-2006.
- Identification of resistance genes (ESBLs, CBLs) using gene amplification and direct sequencing.
- Evaluation of clonal relatedness via macrorestriction analysis.
Main Results:
- Prevalence of CBL-positive P. mirabilis increased from 0.3% to 4.6% between 2004 and 2006.
- All CBL-positive isolates were multidrug-resistant, carried the CMY-16 determinant, and were genetically related.
- Urinary tract infections were the most common clinical manifestation.
Conclusions:
- This study reports the first rapid spread of CBL-positive P. mirabilis with high antimicrobial resistance.
- Amikacin and carbapenems showed consistent efficacy, while piperacillin/tazobactam had a partial response rate.
- Development of practical CBL detection methods is crucial for managing these infections.
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