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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.

The activity of plazomicin and clinically relevant aminoglycosides was tested against 346 extended-spectrum-␤-lactamase/AmpC-producing Escherichia coli urinary isolates, and the results were correlated with the presence of aminoglycoside-modifying enzymes (AMEs). Data showed that plazomicin was very active against all ESBL/AmpCproducing E. coli urinary isolates. Its activity was not related to the AME genes studied.KEYWORDS AMEs, ESBL, Escherichia coli, plazomicin, aminoglycosides E scherichia coli strains producing extended-spectrum ␤-lactamases (ESBLs) have emerged as major global pathogens, primarily associated with urinary tract infections (1). These strains possess plasmids that carry genes conferring resistance to multiple antibiotic classes (2). As a result, therapeutic options against these ␤-lactamresistant E. coli infections are extremely limited.Aminoglycoside resistance in Gram-negatives is mainly conferred by production of aminoglycoside-modifying enzymes (AMEs) (3). Genes encoding AMEs are located on mobile genetic elements along with other resistance determinants, resulting in multidrug-resistant (MDR) isolates (3). Plazomicin is a next-generation aminoglycoside modified to evade AMEs. The compound is currently under clinical development for the treatment of complicated urinary tract infections (cUTIs) and acute pyelonephritis as a single agent (4,5).In this study, we evaluated the activity of plazomicin and clinically relevant aminoglycosides against 346 ESBL/AmpC-producing E. coli urinary isolates. The presence of four AME genes was also investigated, and the relationship between the AME genes detected and the resistance phenotype found was determined.The isolates were obtained prospectively during 2013 at the Hospital Clínico San Carlos (Madrid, Spain). Only one isolate per patient was included. PCR characterization (6, 7) showed 302 ESBL producers and 44 AmpC producers.MICs of gentamicin, tobramycin, amikacin, and plazomicin were determined by the agar dilution method. MICs of plazomicin were also determined by the broth microdilution method (8). Antimicrobial agents were obtained from their respective manufacturers. Plazomicin was supplied from Achaogen (South San Francisco, CA). The results were interpreted according the guidelines of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (9).All isolates resistant to at least one of the aminoglycosides studied were tested by PCR for the presence of AME genes. Sets of primers for the following genes were

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A total of 94 clinical isolates of the Bacteroides fragilis group was tested for susceptibility to metronidazole, chloramphenicol, clindamycin, cefoxitin, cefotetan, cefmetazole, moxalactam, mezlocillin, amoxicllin-clavulanic acid, and imipenem. All the strains tested were susceptible to imipenem, metronidazole, amoxicillinclavulanic acid, and chloramphenicol. The rate of resistance to clindamycin was 21%. The results of this study demonstrate a difference in resistance rates from one species of the B. fragilis group to another.During the last few years, anaerobic bacteria have shown an increase in resistance to most of the traditionally used antimicrobial agents and some of the newer beta-lactam agents (8,12,14,24 Tables 1 and 2. ,B-Lactamase production was detected in 95% of strains.All the strains tested were susceptible to metronidazole and chloramphenicol. Imipenem and amoxicillin-clavulanic acid were the most active beta-lactam drugs and had similar activities against all species of the B. fragilis group. No resistance was found.Mezlocillin showed good activity with low resistance rates for the entire group (3%) as well as for the individual species. The inhibitory activity of mezlocillin was found to be lowest against B. ovatus, with a resistance rate of 10%.The resistance rate of the B. fragilis group to clindamycin was 21%. Clindamycin-resistant strains occurred at rates of 50, 30, and 33% in B. thetaiotaomicron, B. ovatus, and B. distasonis, respectively, whereas in B. fragilis the resistance rate was lower (12%) ( Table 2). All the B. vulgatus strains tested were susceptible to clindamycin.The activities of cefoxitin, cefotetan, and moxalactam were comparable for the B. fragilis group, with MICs for 90% of the strains of 16, 32, and 16 ,ug/ml, respectively. Cefmetazole was less active; the MIC for 90% of the strains was 64 p,g/ml. As reported previously (3,8,16, 26) (Table 2).The results of this study indicate that several of the new beta-lactam agents are effective in vitro against the B. fragilis group. As expected, chloramphenicol and metronidazole were uniformly effective against all 94 isolates. Imipenem was the most effective beta-lactam drug in this study; the MIC for 90% of the strains was 0.5 ,ug/ml, and we detected no resistance, which was in accordance with the 671