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Carbapenemase-producing Enterobacteriaceae (CPE) cause serious infections and are associated with high mortality in part due to limited treatment options. The in vitro activities of the new aminoglycoside plazomicin and comparators were evaluated against a collection of 164 CPE (VIM-1, n=125; KPC-2, n=34; OXA-48, n=4; and IMP-22, n=1). MIC90 values of gentamicin, tobramycin and amikacin were 256, 64 and 16 mg/L, respectively. Plazomicin exhibited an MIC range of 0.12-4 mg/L with MIC50 and MIC90 values of 0.25 and 1 mg/L. The MICs of plazomicin did not correlate with the other aminoglycoside MICs, with the resistance phenotype or with the carbapenemase harboured. Chequerboard experiments against 10 carbapenemase-producing Klebsiella pneumoniae isolates showed that combinations of plazomicin with colistin yielded synergy against 60% of the strains. Synergy of plazomicin with meropenem or fosfomycin was detected against 20% and 25% of the isolates, respectively. Using time-kill methodology, the interactions of plazomicin at 2×, 1× and 0.5× MIC with meropenem, colistin, fosfomycin or tigecycline at steady-state concentrations against two K. pneumoniae carrying the VIM-1 enzyme were investigated. Bactericidal activity was evident for both isolates at 2× MIC of plazomicin. Synergy was observed when plazomicin was combined with meropenem, colistin or fosfomycin against both isolates, whilst the combination with tigecycline resulted in indifference. Antagonism was not observed for any of the combinations tested. The results of this study suggest that plazomicin may address the need for new therapeutic options for the treatment of infections due to CPE., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Nine isolates of Klebsiella pneumoniae were isolated from a renal transplant patient suffering from recurrent urosepsis over a period of 4 months. Imipenem resistance was detected after imipenem-ertapenem therapy. When treatment was switched to tigecycline the K. pneumoniae developed resistance to tigecycline (MIC = 8 mg/L). The nine isolates were tested by determination of agar dilution MICs, phenotypic carbapenemase, extended-spectrum beta-lactamases and metallo-beta-lactamase (MBL) testing and pulsed-field gel electrophoresis. Polymerase chain reaction and sequencing analysis were employed for identification of bla genes and mapping of the integron carrying the MBL gene. The nine isolates were clonally related and all produced the SHV-12 enzyme. Five MBL-producing isolates showed imipenem MICs ranging from 2 to 64 mg/L and all were detected by testing with imipenem and EDTA. The five isolates harboured the bla(VIM-1) gene. Three isolates showed increased tigecycline MICs (4-8 mg/L). Serial blood cultures obtained on the same day resulted in a VIM-positive/tigecycline-susceptible and a VIM-negative/tigecycline-resistant K. pneumoniae isolate. No isolate developed concurrent imipenem and tigecycline resistance. The patient had a persistent urinary tract infection and recurrent bacteraemia caused by a mixed population of Klebesiella pneumoniae isolates adapting to the selective pressure of antimicrobial therapy at the time. The present study is a worrisome example of what could happen when an immunocompromised host is subjected to the pressures of antimicrobial therapy. In addition, we report the first treatment-emergent MIC increase of tigecycline from 0.5 to 8 mg/L in K. pneumoniae., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 1102 bacterial isolates from 20 centers in Spain. The MIC of tigecycline at which 90% (MIC(90)) of the pneumococci tested were inhibited was the lowest (0.06 microg/mL) of all the antibiotics tested. The MICs of tigecycline against enterococci ranged from 0.03 to 0.125 microg/mL. All staphylococci were inhibited by < or =0.25 microg/mL of tigecycline, and 99.6% of Enterobacteriaceae isolates were inhibited by < or =2 microg/mL of tigecycline. Tigecycline demonstrated good activity against Bacteroides fragilis group organisms with an MIC(90) of 4 microg/mL. The results of this study confirm the excellent activity of tigecycline against multiresistant Gram-positive and Gram-negative pathogens.

During 2003 in our hospital, 236 clinical faecal Campylobacter spp. were isolated, of which 166 (70%) were resistant to tetracycline and 199 (84%) were resistant to ciprofloxacin by the disk diffusion method. Resistance to both antimicrobial agents was found in 146 isolates (62%). The in vitro activity of tigecycline was compared with that of erythromycin, clindamycin and amoxicillin/clavulanic acid using the agar dilution method against 116 selected Campylobacter spp. that were resistant to both tetracycline and ciprofloxacin. The minimum inhibitory concentration at which 90% of the isolates were inhibited (MIC90) was 0.06 mg/L for tigecycline and 4, 2 and 1 microg/mL for amoxicillin/clavulanic acid, erythromycin and clindamycin, respectively. The high in vitro activity of tigecycline against tetracycline- and ciprofloxacin-resistant strains suggests a potential therapeutic role in the treatment of infections that involve Campylobacter spp.

Objectives: To ascertain the current susceptibility patterns of members of the Bacteroides fragilis group in our hospital and to assess the in vitro activity of tigecycline against these organisms., Methods: A total of 400 non-duplicate clinical isolates of the B. fragilis group collected from 2000 to 2002 were studied. Susceptibility testing was performed according to the reference agar dilution method described by the NCCLS. The following antimicrobials were tested: tigecycline, clindamycin, metronidazole, chloramphenicol, cefoxitin, imipenem, amoxicillin-clavulanate and piperacillin-tazobactam., Results: All strains were susceptible to metronidazole and chloramphenicol. For clindamycin and cefoxitin, the overall susceptibility rates were 59.5% and 83%, respectively. Imipenem and piperacillin-tazobactam were the most active beta-lactam agents tested. Tigecycline inhibited 89.8% of the strains at a concentration of 8 mg/L with an MIC range of 16 mg/L. By comparing the MIC50 and MIC90 values of tigecycline among the various species of the group, B. fragilis, Bacteroides thetaiotaomicron and Bacteroides vulgatus were the most susceptible (MIC50/MIC90s of 0.5-1/8 mg/L)., Conclusions: Tigecycline exhibited activity against most isolates of the B. fragilis group tested. These results indicate that tigecycline may be useful in the treatment and prophylaxis of infections involving these organisms.

The activity of tigecycline was tested against erythromycin-resistant streptococci (107 Streptococcus pyogenes and 98 Streptococcus agalactiae strains). The presence of erythromycin and tetracycline resistance genes was determined by PCR. Among S. pyogenes strains the most prevalent gene was mef(A) (91.6%). The erm(B) gene was the most prevalent (65.3%) among S. agalactiae strains. Tigecycline proved to be very active against all the isolates tested (MIC at which 90% of the isolates tested were inhibited, 0.06 micro g/ml), including those resistant to tetracycline.

The antimicrobial activities of tigecycline (GAR-936) were compared with those of other agents against 1,087 strains recently isolated in 12 Spanish medical centers. Tigecycline showed activity against a wide spectrum of aerobic and anaerobic bacteria, including strains such as methicillin-resistant Staphylococcus aureus, coagulase-negative staphylococci, penicillin-resistant Streptococcus pneumoniae, Enterococcus faecium, Acinetobacter baumannii, and Stenotrophomonas maltophilia.