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

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.