P1689 Antimicrobial activity of tigecycline and daptomycin against Gram-positive cocci: a multicentre study in Greek hospitals

P1689 Antimicrobial activity of tigecycline and daptomycin against Gram-positive cocci: a multicentre study in Greek hospitals

S478 sent for hVISA confirmation by PAP-analysis. Among the MRSA strains we found following sequence types (ST): ST228 (30%), ST8 (29%), ST22 (15%), ST...

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S478 sent for hVISA confirmation by PAP-analysis. Among the MRSA strains we found following sequence types (ST): ST228 (30%), ST8 (29%), ST22 (15%), ST5 (12%), and other types under 3% each. Conclusions: In comparison with resistance data up to 2003 from Upper Austria we observed an increase in G and T resistance, a decrease in FOS resistance and a stable resistance rate to LC and FU. All strains were susceptible to L and TG. The ST distribution was more diverse in Vienna and Salzburg and with strong dominant types in Carynthia and Lower Austria were the resistance rate was also higher. P1687 Marked tigecycline and colistin synergistic bactericidal effect against a nosocomial epidemic carbapenemase (VIM-1) producing Klebsiella pneumoniae clone M.I. Morosini, M. Garc´ıa-Castillo, M. Tato, V. Pintado, F. Baquero, J. Cobo, R. Cant´on (Madrid, ES) Tigecycline, a new available glycylcycline derivative, is one of the few alternatives for the treatment of Gram negative bacilli harbouring extended-spectrum b-lactamases and its role against carbapenemaseproducing strains is also advocated. Colistin comprises another option in these cases. Objectives: The activity of tigecycline and colistin, alone or in combination, was assessed in time-kill studies against a multiresitant VIM-1-producing Klebsiella pneumoniae epidemic clone recovered in Madrid (Spain) in 2005. Methods: Tigecycline and colistin sulphate MICs were determined by the standard broth macrodilution method (CLSI). Duplicate killing curves (Lorian, 1991) with each compound alone or in combination at 1xMIC and 2xMIC and at the serum peak concentration achievable after standard dosing regimens (1 mg/L for tigecycline and 4 mg/L for colistin) were performed. Results: MICs were 0.5 mg/L for tigecycline and 1 mg/L for colistin. Tigecycline was bacteriostatic at all tested concentrations whereas colistin exhibited concentration-dependent bactericidal activity. Tigecycline and colistin combinations were markedly synergistic at 3 hours (106 drop in CFU per mL). Moreover, consistent regrowth at 6 hours observed with single-colistin exposure with all tested concentrations was delayed with tigecycline until 12 hours, even with the lowest tigecycline concentration. Conclusion: Tigecycline and colistin act synergistically rendering complete killing of a VIM-1 producing K. pneumoniae epidemic clone at 3 hours. Tigecycline abolishes consistent regrowth observed with singlecolistin exposure. In vitro synergistic activity of both compounds gives support to the possible treatment of infections caused by carbapenemaseproducing isolates. Addition of tigecycline may allow reducing colistin doses lowering secondary toxicity. Optimal regimens remain to be determined. P1688 In vitro activity of tigecycline and other antimicrobial agents against extended-spectrum b-lactamase E. coli producers C. Rodriguez-Avial, O. L´opez, I. Rodriguez-Avial, E. Hernandez, J. Picazo (Madrid, ES) Objective: Tigecycline is likely to have a role in the treatment of infections due to multirresistant pathogens. ESBL-producing E. coli are being recognized as an increasing problem. When they are isolated from patients with urinary tract infections (UTI), they leave few therapeutical options. We sought to determine the incidence and susceptibility patterns of ESBL-E. coli isolated in urine samples in our laboratory in 2005. Methods: A total of 5.053 E. coli were isolated from urine samples. The MICs of the b-lactamic agents: cefotaxime, ceftazidime, aztreonam and cefepime, with and without clavulanic acid, amoxycillin-clavulanate, cefoxitin, imipenen (I) and ertapenem (E), and the non b-lactamic: ciprofloxacin (CIP), tetracycline (T), tigecycline (TY), gentamycin (G) and nitrofurantoin (N) were determined by agar dilution method (CLSI guidelines), fosfomycin (F) and co-trimoxazol (SXT) were tested by Etest method. The origin (hospital or community) was also determined.

17th ECCMID / 25th ICC, Posters Results: Of the 5.053 E. coli isolates, 216 (4, 2%) were ESBL producers (CLSI Confirmatory test). ESBL-E. coli (n = 192, one isolate per patient) showed also elevated resistance percentages to non-b-lactamic agents: CIP 83%, T 69%, SXT 58% and G 15%. Resistance was low for N 3% (MIC90 : 64 mg/L), and F 3, 7% (MIC90 : 16 mg/L). No resistance was found to the b-lactamic agents I (MIC90 : 0.25 mg/L) and E (MIC90 : 0.12 mg/L) and to TY (MIC90 : 2 mg/L). We observed a greater proportion (67%) of ESBL-E. coli isolates from non-hospitalised patients. Conclusions: F and N showed good activity against ESBL-E. coli, and are options for the treatment of uncomplicated UTI in the greater proportion of ESBL-E. coli isolated in non-hospitalised patients. I and E showed very high activity, making carbapenems a good option for the treatment of complicated UTI. TY was very active against our ESBLE. coli producers. Tigecycline is likely to have a role in the treatment of infections due to multirresistant pathogens including ESBL-E. coli producers. P1689 Antimicrobial activity of tigecycline and daptomycin against Gram-positive cocci: a multicentre study in Greek hospitals F. Kolonitsiou, A. Pratti, I. Spiliopoulou, M. Karanika, S. Alexiou-Daniel, D. Bakola, M. Vergi, M. Oeconomou, C. Koutsia-Karouzou, H. Malamou-Lada, L. Zerva, E. Petinaki (Patras, Larissa, Thessaloniki, Lamia, Athens, GR) Objectives: During the last decades, the emergence of Gram-positive strains resistant to different antimicrobial agents has become a serious medical problem. New compounds that are effective against infections caused by multi-resistant Gram-positive cocci are urgently needed. In the present study we tested the activity of tigecycline and daptomycin against a large number of recent Gram-positive cocci, collected in seven Greek hospitals located in different regions Methods: From January 2005 to August 2006 a total of 3,160 Grampositive cocci (870 Staphylococcus aureus, 700 coagulase-negative staphylococci, 400 Enterococcus faecalis, 320 Enterococcus faecium, 200 Streptococcus pneumoniae, 200 Streptococcus agalactiae, 300 Streptococcus pyogenes and 170 viridans streptococci) were isolated in seven different Greek hospitals, from clinically significant specimens (blood, pus, pleural fluid, etc). MICs to tigecycline and daptomycin were determined by the E-test. Susceptibility for tigecycline and daptomycin was defined as approved by US-FDA. Results: Table 1 summarises the MICs modal, MIC50 and MIC90 of the isolates tested. According to the US-FDA criteria, six MSSA were not susceptible to tigecycline, having MICs 0.75 mg/L; on the other hand among E. faecalis, twelve isolates had MICs greater than the breakpoints proposed (four with MICs 0.5 mg/L, five with MICs 0.75 mg/L and three with MICs 1 mg/L). Among E. faecium, 30 isolates had MICs greater than 0.25 mg/L, while among coagulase-negative staphylococci 35 isolates had MIC greater than 0.5 mg/L. Based on the FDA breakpoints for daptomycin, all S. pyogenes, S. agalactiae, and E. faecalis were susceptible to daptomycin. However, 52 MRSA and 59 MSSA had MICs greater than 1 mg/L. Table 1. MICs of isolates tested against tigecycline and daptomycin Tigecycline

Daptomycin

Isolates

No

MICmodal

Range

MIC50

MIC90

MICmodal

Range

MIC50

MIC90

MRSA MSSA E. faecalis E. faecium CoNS-ME CoNS-MR S. pneumoniae S. agalactiae S. pyogenes S. viridans

348 522 400 320 120 580 200 200 300 170

0.125 0.133 0.311 0.26 0.187 0.215 0.185 0.137 0.157 0.123

0.016−0.5 0.064–0.38 0.047−1 0.064−1.5 0.064–0.75 0.094−1.5 0.094−0.5 0.047−0.5 0.047−0.5 0.015–0.38

0.069 0.077 0.16 0.118 0.104 0.076 0.125 0.073 0.082 0.114

0.109 0.112 0.255 0.204 0.141 0.151 0.155 0.103 0.132 0.120

0.909 0.8 1.49 2.17 0.317 0.57 0.78 0.15 0.148 0.86

0.125−3 0.19−3 0.19−3 0.5−4 0.023−1.5 0.125−5 0.125−1 0.064–0.75 0.125−1 0.06−1

0.438 0.234 1.005 1.36 0.123 0.244 0.5 0.089 0.125 0.5

0.791 0.624 1.363 1.905 0.241 0.436 0.62 0.118 0.35 0.7

Conclusions: This is the first multi-centre study in Greece, confirming the good in vitro activity of tigecycline and daptomycin against a range of Gram-positive pathogens.