Spread of multidrug-resistant Proteus mirabilis isolates producing an AmpC-type β-lactamase: epidemiology and clinical management

Abstract

A remarkable increase in Proteus mirabilis strains producing acquired AmpC-type β-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 β-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.