In vitro activity of apramycin (EBL-1003) in combination with colistin, meropenem, minocycline or sulbactam against XDR/PDR Acinetobacter baumannii isolates from Greece.

OBJECTIVES: To evaluate the in vitro activity of the combination of apramycin with colistin, meropenem, minocycline or sulbactam, against some well-characterized XDR Acinetobacter baumannii clinical isolates from Greece, to understand how apramycin can be best incorporated into clinical practice and optimize effectiveness. METHODS: In vitro interactions of apramycin (0.5×, 1× and 2× the MIC value) with colistin (2 mg/L), meropenem (30 mg/L), minocycline (3.5 mg/L) or sulbactam (24 mg/L) were tested using time-kill methodology. Twenty-one clinical A. baumannii isolates were chosen, exhibiting apramycin MICs of 4-16 mg/L, which were at or below the apramycin preliminary epidemiological cut-off value of 16 mg/L. These isolates were selected for a range of colistin (4-32 mg/L), meropenem (16-256 mg/L), minocycline (8-32 mg/L) and sulbactam (8-32 mg/L) MICs across the resistant range. Synergy was defined as a ≥2 log10 cfu/mL reduction compared with the most active agent. RESULTS: The combination of apramycin with colistin, meropenem, minocycline or sulbactam was synergistic, at least at one of the concentrations of apramycin (0.5×, 1× or 2× MIC), against 83.3%, 90.5%, 90.9% or 92.3% of the tested isolates, respectively. Apramycin alone was bactericidal at 24 h against 9.5% and 33.3% of the tested isolates at concentrations equal to 1× and 2× MIC, while the combination of apramycin at 2× MIC with colistin, meropenem or sulbactam was bactericidal against all isolates tested (100%). The apramycin 2× MIC/minocycline combination had bactericidal activity against 90.9% of the tested isolates. CONCLUSIONS: Apramycin combinations may have potential as a treatment option for XDR/pandrug-resistant (PDR) A. baumannii infections and warrant validation in the clinical setting, when this new aminoglycoside is available for clinical use.

Characterisation of macrolide-non-susceptible Streptococcus pneumoniae colonising children attending day-care centres in Athens, Greece during 2000 and 2003.

Nasopharyngeal Streptococcus pneumoniae isolates colonising young children are representative of isolates causing clinical disease. This study determined the frequency of macrolide-non-susceptible pneumococci, as well as their phenotypic and genotypic characteristics, among pneumococci collected during two cross-sectional surveillance studies of the nasopharynx of 2847 children attending day-care centres in the Athens metropolitan area during 2000 and 2003. In total, 227 macrolide-non-susceptible pneumococcal isolates were studied. Increases in macrolide non-susceptibility, from 23% to 30.3% (p <0.05), and in macrolide and penicillin co-resistance, from 3.4% to 48.6% (p <0.001), were identified during the study period. The M resistance phenotype, associated with the presence of the mef(A)/(E) gene, predominated in both surveys, and isolates carrying both mef(A)/(E) and erm(AM) were identified, for the first time in Greece, among the isolates from the 2003 survey. Pulsed-field gel electrophoresis analysis of the isolates from the 2000 survey indicated the spread of a macrolide- and penicillin-resistant clone among day-care centres. The serogroups identified most commonly in the study were 19F, 6A, 6B, 14 and 23F, suggesting that the theoretical protection of the seven-valent conjugate vaccine against macrolide-non-susceptible isolates was c. 85% during both study periods.

First identification of an Escherichia coli clinical isolate producing both metallo-beta-lactamase VIM-2 and extended-spectrum beta-lactamase IBC-1.

An Escherichia coli strain with decreased susceptibility to carbapenems was isolated from a hospitalised patient in Athens, Greece. The strain was resistant to all beta-lactams, including aztreonam, whereas the MIC of imipenem and meropenem was 0.5 mg/L. A positive EDTA-disk synergy test suggested the production of a metallo-beta-lactamase. PCR experiments revealed the presence of the bla(VIM-2), bla(IBC-1), and bla(TEM-1) genes. Resistance to beta-lactams was not transferable by conjugation. This is the first report of a clinical isolate of E. coli producing VIM-2, and the first report of the coexistence of bla(VIM-2) and bla(IBC-1) in a single clinical isolate.