Bloodstream infections caused by multidrug-resistant Klebsiella pneumoniae producing the carbapenem-hydrolysing VIM-1 metallo-beta-lactamase: first Italian outbreak.

OBJECTIVES: To investigate the first Italian outbreak of bloodstream infections caused by multidrug-resistant (MDR) Klebsiella pneumoniae producing metallo-beta-lactamase (MBL), which occurred in three wards of one large tertiary-care hospital in Genoa, Italy, from September 2004 to March 2005. METHODS: MBL production was screened by an imipenem-EDTA disc synergy test and confirmed by a conventional hydrolysis test. Antibiotic susceptibility was determined by broth microdilution or disc diffusion. PFGE was used to study the genetic relatedness of isolates. PCR and sequencing were carried out to identify the beta-lactamase genes and to analyse the genetic context of the MBL gene. Outer membrane protein (OMP) profiles were analysed by SDS-PAGE. RESULTS: Nine cases of bloodstream infections caused by an MDR strain of K. pneumoniae producing the VIM-1 MBL and the SHV-5 extended-spectrum beta-lactamase (ESBL) were identified. The isolates exhibited various carbapenem resistance levels (imipenem MICs ranged from 4 to 64 mg/L) and were resistant to other beta-lactams, fluoroquinolones, trimethoprim/sulfamethoxazole and chloramphenicol. The isolate with the highest imipenem MIC also lacked the k36 OMP. The bla(VIM-1) gene cassette was part of the variable region of a class 1 integron that also included an aac(6')-IIc cassette. The ESBL and MBL genes were transferable by conjugation. CONCLUSIONS: This is the first report on the emergence of an MDR strain of K. pneumoniae producing the VIM-1 MBL, causing an outbreak of bloodstream infections in an Italian hospital. The strain evolved through OMP alterations generating a mutant with increased carbapenem resistance.

Microbiological rationale for the utilisation of prulifloxacin, a new fluoroquinolone, in the eradication of serious infections caused by Pseudomonas aeruginosa.

Minimal inhibitory concentrations (MICs) of prulifloxacin were evaluated in comparison with ciprofloxacin, levofloxacin and moxifloxacin against a large collection (N = 300) of Pseudomonas aeruginosa strains characterised according to the CLSI/NCCLS microdilution method. Additional in vitro tests (time-kill curves and mutant prevention concentration (MPC) determinations) were carried out. Assuming a susceptibility breakpoint for prulifloxacin identical to that of ciprofloxacin, the new fluoroquinolone emerged as the most potent antibiotic (72% of susceptible strains versus 65%, 61% and 23% for ciprofloxacin, levofloxacin and moxifloxacin, respectively). Time-kill tests at 4x MIC confirmed the pronounced bactericidal potency of the drug against P. aeruginosa. Amongst the members of the fluoroquinolone class assessed, prulifloxacin produced the lowest MPC values (< or = 4 mg/L). Our in vitro results indicate that prulifloxacin represents the most powerful antipseudomonal drug available today.

Pleiotropic effect of sodium arsenite on Escherichia coli.

The effects of sodium arsenite at a sub-MIC concentration (25 mg/l) upon different bacterial functions were studied. This compound reduced the killing activity of nalidixic acid, amikacin, and meropenem. It also promoted the loss of F'lac from bacterial hosts and increased the number of recombinants in conjugation and transduction experiments. Transposition of Tn9 was also enhanced by the salt. In addition, sodium arsenite abolished the lethal effect of temperature on thermosusceptible DNA synthesis mutants in a similar manner to that seen in an anaerobic environment. Finally at a low dose, it induced the SOS response, and the related production of recA-dependent enzymes was reduced as the sodium arsenite concentration increased. It has been suggested that arsenite primarily affects the uvrA gene product, influencing the other bacterial functions studied. The energetic depletion caused by this compound appears to play a role in the activity of autolytic enzymes.

In vitro activity of ABT773, a new ketolide derivative exhibiting innovative microbiological properties against well-characterised antibiotic resistant pathogens in Italy.

The in vitro activity of ABT773, a new ketolide, was assessed against a collection (518) of well-characterised Gram-positive and Gram-negative pathogens and compared with that of other appropriate drugs. ABT773 was active (MIC-90=0.03 mg/l) against the staphylococci tested which included macrolide-resistant but clindamycin susceptible organisms. Streptococcus pneumoniae, S. pyogenes and S. agalactiae were also inhibited (MIC-90 range: <0.0075-0.5mg/l) irrespective of their antibiotic resistance phenotype. Enterococcus faecalis was sensitive to ABT773 with the exception of VanA mutants. E. faecium showed poor susceptibility to ABT773. The activity of the new ketolide against Haemophilus influenzae and Moraxella catarrhalis was comparable with that of the most potent drugs tested. ABT773 displays the characteristics of a promising agent that deserves to be introduced as the empirical therapy of infections caused by the bacterial species tested here, even if they are multiply resistant.