Carbapenemase-Producing Enterobacteriaceae (CPE) in the Pediatric Setting: Results from an 18-Month Survey

Abstract

The occurrence of carbapenemase-producing Enterobacteriaceae (CPE) at the Regina Margherita Children's Hospital, Turin, Italy, between 1 May 2012 and 31 October 2013, was evaluated. Patients from whom CPE strains had been isolated from any clinical specimens were included and prospectively investigated. Identification and susceptibility testing of the first isolate from each patient were performed. Enterobacteriaceae isolates with imipenem and/or meropenem MICs of 2 mg/litre or greater were tested for carbapenemase production. 15 patients (9 males) were identified as infected or colonized with CPE. The mean age was 10.6+or-5.84 years. All patients had been treated with antibiotics effective against Gram-negative bacteria for at least 20 days in the previous 3 months: 11 with carbapenems, 7 with quinolones, and 9 with aminoglycosides. CPE strains were isolated from urine specimens in 7 cases (47%), blood specimens in 4 (27%), urinary catheter tips in 2 (13%), and skin and nasal swab samples in one case each. The identified bacteria included Klebsiella pneumoniae (n=11; 73%) and Escherichia coli (n=4, 27%). 12 isolates (80%) produced K. pneumoniae carbapenemases (KPCs), 2 (13%) produced oxacillinase (OXA)-48-like carbapenemases, and one (7%) produced metallo- beta -lactamase. All strains showed resistance to amoxicillin-clavulanic acid, piperacillin-tazobactam, third- and fourth-generation cephalosporins, and trimethoprim-sulfamethoxazole. 11 isolates were resistant and 3 were intermediately resistant to imipenem, whereas the remaining one was susceptible to imipenem but resistant to meropenem. All isolates were sensitive to colistin. The susceptibility rates to other antibiotics tested were: nitrofurantoin, 100% (4 of 4 isolates); fosfomycin, 67% (4 of 6); amikacin, 67% (10 of 15); gentamicin, 27% (4 of 15); ciprofloxacin, 20% (3 of 15); and tigecycline, 20% (1 of 5). Six patients were infected with CPE. Four had bloodstream infection, with prescription of appropriate antibiotic regimen 3 days after the onset of bacteraemia. Among the antibiotic combinations prescribed were colistin plus meropenem and tigecycline, ciprofloxacin plus meropenem, and colistin plus meropenem. Two patients died, with CPE infection being identified as a contributing factor. The remaining 2 were successfully treated with intravenous antimicrobial therapy for a mean of 14+or-5.66 days. The last 2 patients had symptomatic urinary tract infection: one patient was treated with amikacin for 7 days and the second patient was treated empirically with ceftazidime. In both cases, complete recovery occurred within 5 days after disease onset. None of the patients developed reinfection. Nine patients were colonized with CPE. Four received appropriate antibiotic therapy based on antibiogram results; however, one patient remained colonized for more than one month after the first isolate was obtained, in addition to 2 untreated subjects. This study suggests that CPE infections represent a serious threat in the paediatric setting as well.