37 Tigecycline (formerly GAR-936), a synthetic analogue of tetracycline, is the first member of a new class of antimicro- bial agents, the glycylcyclines, that inhibits bacterial protein biosynthesis blocking the attachment of amino-acyl tRNA to the A site of the ribosome and preventing the elongation of peptide chains (7). The drug manteins its activity even in pres- ence of mechanisms that otherwise confer tetracycline resist- ance (2, 6). In previous studies this new drug had demonstrat- ed significant antibacterial properties with an excellent in vitro activity against clinical and laboratory Gram-positive and - negative bacteria, anaerobic and atypical pathogens. Moreover the broad spectrum of tygecycline includes diffi- cult to treat methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), penicillin-resistant Streptococcus pneumoniae (PRSP) and extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae (3, 6-7). Tigecycline resistance is very infrequent and is also difficult to induce in laboratory, with a selection frequency lower than 10 -9 (3, 6). This study was undertaken to document the in vitro activity of tigecycline against clinical isolates collected in Italy from in-patient and out-patient populations. A total of 313 clinical isolates, 205 Gram-negative (50 Escherichia coli, 37 Klebsiella pneumoniae, 36 Pseudomonas aeruginosa, 21 Enterobacter cloacae, 21 Acinetobacter. bau- mannii, 14 Serratia marcescens, 13 Klebsiella oxytoca, 13 Haemophilus influenzae) and 108 Gram-positive (48 Staphylococcus aureus, 25 Streptococcus pneumoniae, 20 Streptococcus agalactiae, 15 Enterococcus faecalis), were col- lected and identified to the species level in Sezione di Microbiologia of University of Genova during 2007-2008. Minimum inhibitory concentrations (MICs) of the antimicro- bial agents were determined by the CLSI recommended broth microdilution testing method (1). Quality controls (QC) were performed using the following strains: E. coli ATCC 25922 and S. aureus ATCC 29213. Tigecycline was supplied by Wyeth Pharmaceuticals (Milano). On Gram-negative pathogens (Table 1), Tigecycline demon- strated excellent inhibitory activity. Tigecycline activity particulary on E. coli isolates, with a MIC90 of 1 mg/l, was comparable to more active agents (meropenem, levofloxacin and amikacin) and lower than beta- lactams, beta-lactam/beta-lactamase inhibitor combinations. Against other Enterobacteriaceae tigecycline’s MIC90 was minor or equal to 4 mg/l. This new agent, as the other tetra- cyclines, showed limited in vitro activity against P. aerugi- nosa, with MIC90 values more than 16 mg/l. Against H. influenzae (MIC50 0.25 mg/l and MIC90 0.5 mg/l), included beta-lactamase-producer strains, the new agent demonstratedan excellent inhibitory activity. In vitro tigecycline’s activity on Acinetobacter spp. (MIC50 0.5 mg/l and MIC90 1 mg/l) was superior to beta-lactams, beta-lactam/beta-lactamase inhibitor combinations, cephalosporins, aminoglycosides and levofloxacin. Tigecycline exhibited a potent in vitro activity even in Gram- positive pathogens (Table 2). The drug presented MIC90 of 0.25 mg/l against Enterococcus spp., regardless of susceptibility to vancomycin. This value was the lowest of all comparative agents, in particular in van- comycin-resistant E. faecium and E. faecalis was several folds lower than linezolid, minocycline and levofloxacin (Table 2). The drug has shown a potent inhibitory activity against S. aureus regardless of methicillin-resistant phenotype. Tigecycline, with MIC50 and MIC90 values of 0.25 and 0.5 mg/l, respectively, demonstrated in vitro activity comparable to linezolid and vancomycin and greater than levofloxacin against MRSA. In MSSA MIC50 and MIC90 had the same value of 0.25 mg/l (Table 2). Tigecycline demonstrated potent inhibitory activity against S. agalactiae and S. pneumoniae, even in penicillin-intermedi- ate or resistant strains (Table 2), with MIC90 values ≤ 1 mg/l. Resistance to currently available antibiotics and incidence of infection due to multidrug-resistant bacteria has dramatically increased worldwide during the last twenty years. In presence of a serius infection, appropriate empirical antibi- otic therapy can be life-saving and the choice of an antimi- crobial to which the pathogens are susceptible may be criti- cal. For these reasons, the development of new antimicrobial agents with expanded antibacterial spectrum (increased activity against Gram-negative as well as Gram-positive microrganisms) is more urgent than ever. (4). Tigecycline’s in vitro activity was comparable to or greater than most commonly prescribed antimicrobial against impor- tant clinical pathogens. Tigecycline, for example, demon- strated on methicillin-resistant S. aureus (MRSA) in vitro activ- ity comparable to linezolid and vancomycin, the antimicrobial agents currently used for the treatment of serious staphylococ- MICROBIOLOGIA MEDICA, Vol. 25 (1), 2010 IN VITRO ACTIVITY OF TIGECYCLINE In vitro activity of tigecycline against 313 Gram-positive and Gram-negative clinical isolates Elisabetta Maioli, Erika Coppo, Ramona Barbieri, Elisabetta Canepa, Laura Gualco, Carla Pruzzo, Eugenio A. Debbia, Anna Marchese Sezione di Microbiologia, DISCMIT, Università di Genova, Genova, Italia Key words: tigecycline, broad-spectrum activity, antibiotic-resistance Attività in vitro di tigeciclina su 313 ceppi Gram-positivi e Gram-negativi di isolamento clinico SUMMARY Objectives. In this study the in vitro activity of tigecycline, member of a new class of antimicrobial agents, the glycylcyclines, was evaluated against clinical isolates collected in Italy. Study Design. A total of 313 clinical pathogens were collected and identified in our Institution during 2007-2008. Minimum inhibitory con- centrations (MICs) of the antimicrobial agents were determined by the CLSI (2007) recommended broth microdilution method. Results. Globally 205 Gram-negative and 108 Gram-positive pathogens were evaluated.Tigecycline demonstrated excellent inhibitory activ- ity against Acinetobacter spp., H. influenzae, E. coli, Enterococcus spp., S. aureus, S. agalactiae and S. pneumoniae with MIC90 ≤1mg/l. Conclusion. Tigecycline exhibited potent in vitro antibacterial activity (comparable to or greater than most commonly employed antimicro- bials) against both Gram-positive and negative clinical pathogens.These data suggest that tigecycline, with an expanded broad-spectrum antimi- crobial activity,may be an effective empiric therapeutic option for the treatment of serious infections caused by clinically relevant pathogens. Corresponding author: Anna Marchese Sezione di Microbiologia - DISCMIT, Università di Genova. 16132 Genova, Italia, Largo Rosanna Benzi 10 - Tel. + 39-10-3537502; Fax +39-10-3537651; E-mail: anna.marchese@unige.it