Pseudomonas aeruginosa (Pa) is commonly responsible for nosocomial infections, including surgical site infection, urinary tract infection, pneumonia, and bloodstream infection (BSI) [1, 2]. In particular, this organism is responsible for 3–7% BSI cases [1, 3–5]. Notably, high morbidity and mortality rates (range 27% to 48%) have been observed in critically ill patients [5, 6].
Resistance to multiple drugs is a common feature of hospital-acquired Pa strains [4, 7, 8]. Low permeability of the outer membrane proteins (OMPs), production of the inducible AmpC chromosomal β-lactamase, and multi-drug efflux systems contribute to the intrinsic resistance of this species . Thus, drugs suitable against Pa infections are limited to aminoglycosides (e.g., gentamicin, amikacin), fluoroquinolones (ciprofloxacin remains the most active), selected β-lactams (e.g., ceftazidime, carbapenems), and one β-lactam/β-lactamase inhibitor combination (piperacillin/tazobactam) [4, 5, 7, 8]. Unfortunately, acquired resistance to different categories of the anti-pseudomonal agents is also possible and has been widely illustrated . In particular, resistance to β-lactams is very common and is due to mutations amplifying intrinsic resistance mechanisms (i.e., AmpC), and/or acquisition of additional β-lactamase genes by horizontal transfer [7, 8].
Acquired β-lactamases found in Pa isolates can be classified into three different groups: i) narrow-spectrum enzymes (e.g., PSE-1/4) that efficiently degrade penicillins and cefoperazone; ii) extended-spectrum β-lactamases (ESBL) (e.g., PER-1, VEB-1, GES-1/2) that also degrade cephems and monobactams; iii) metallo-β-lactamases (MBL) (e.g., IMP-, VIM-type) that efficiently degrade all anti-pseudomonal β-lactams with the exception of monobactams [7, 8].
The PER-1 ESBL is a class A enzyme conferring high-level of resistance to anti-pseudomonal β-lactams and is one of the most frequently ESBL detected in Pa [9–11]. PER-1 was first detected in a urinary Pa isolate in a Turkish patient in 1991 [9, 12]. Subsequently, it was frequently recognized in Pa and Acinetobacter spp. isolates [13, 14]. In 1997, our group was the first to detect PER-1-positive Pa (PER-1-Pa) isolates outside the geographical area of origin . To date, the PER-1 ESBL has been reported also from other areas of Europe and Asia [16–19], and in different genera and species (i.e., Alcaligenes faecalis, Salmonella tiphymurium, P. mirabilis, Providencia spp.) [20–24].
Risk factors, empirical treatment and treatment outcome of BSI due to Pa have been investigated by different authors [25–28]. Particular emphasis has been posed on clinical differences observed between multi-drug resistant (MDR) and susceptible Pa isolates . In contrast, the clinical features of BSI caused by ESBL-positive Pa strains have not been investigated.
We had the opportunity of studying 26 cases of BSI caused by ceftazidime-resistant Pa (CAZ-R-Pa) of which 9 were caused by PER-1-Pa strains. Microbiological and clinical data have been compared to those of 17 BSI cases due to ESBL-negative Pa isolates (ESBL-N-Pa). The impact of PER-1 expression on risk factors and treatment outcome was evaluated.