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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.)

Introduction: Escherichia coli is the most important uropathogen. The appearance of extended- spectrum beta-lactamase (ESBL)-producing E.coli in urinary tract infections (UTI) constitutes an important therapeutic challenge that requires the study of its evolution throughout time in order to establish a suitable empirical treatment. Our aim was to determine the prevalence of ESBL-producing E. coli urinary isolates in 2005, 2009 and 2011. We also determined the antimicrobial coresistance to several agents, including fosfomycin., Methods: We analyzed 5053, 6324 and 6644 E. coli isolates obtained from urine cultures in 2005, 2009 and 2011 respectively. Duplicate isolates were excluded. Antimicrobial susceptibility was determined by the Wider microdilution system (Soria Melguizo S.A.) and the phenotypic pattern of resistance that indicated a BLEE-producing E.coli was selected (CLSI 2009)., Results: 3.9% of strains (198) were ESBL producers in 2005, 7.3% (463) in 2009 and 8.7% (584) in 2011. Resistance to carbapenems was detected in 2009, they inhibited more than the 95% of strains in 2011. Among the non-beta-lactams, colistin was the most active antibiotic followed by nitrofurantoin. Ciprofloxacin and sulfamethoxazole-trimethoprim were not effective with 80% and 60% resistant isolates, respectively. An increasing resistance trend, from 0% to 9.3% in 2009 and 14.4% in 2011 was observed for fosfomycin., Conclusions: From 2005 our institution had an increasing prevalence of ESBL-producing E. coli rising to 8.7% in 2011. Carbapenems are still the most active agents. The increase of resistance was significant for fosfomycin.

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.)

From July 2007 to June 2009, all pneumococci causing invasive pneumococcal disease in our hospital were serotyped. Antimicrobial susceptibility was determined by microdilution. Molecular typing was performed by pulsed-field gel electrophoresis and by multilocus sequence typing. Among 251 invasive pneumococci, serotype 8 was the most frequent (13.5%). All serotype 8 strains were susceptible to penicillin; however, 61.8% (21/34) were co-resistant to erythromycin, levofloxacin and tetracycline and identical to the Sweden(15A) -ST63 clone. Serotype 8 was significantly more frequent among human immunodeficiency virus (HIV)-infected patients (36.5%). The high prevalence of this non-conjugate vaccine multiresistant serotype 8 is a cause for concern mainly in HIV-infected patients., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)

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.

Introduction: The objective of the study was to know the current situation of the antimicrobial sensitivity patterns of the main multi-resistant bacteria and to analyze any possible changes with respect to the VIRA study carried out in 2001., Methods: The 40 participating hospitals sent a total of 1,425 microorganisms isolated in February 2004, distributed as follows: penicillin-resistant Streptococcus pneumoniae (139), methicillin-resistant Staphylococcus aureus (289), clinically significant coagulase-negative staphylococci (158), ampicillin-resistant Enterococcus faecium (89) and Enterococcus faecalis (2), ampicillin-resistant Haemophilus influenzae (85), ciprofloxacin-resistant Escherichia coli (346), Pseudomonas aeruginosa (187), and Acinetobacter baumannii (130). The hospitals provided epidemiological data on these microorganisms. Sensitivity was determined by the broth microdilution method., Results: The number of highly penicillin-resistant pneumococci fell significantly (p < 0.0001) compared with the previous study (from 59.8% to 30.2%). Global methicillin-resistance in S. aureus was 31.2%, which represents a significant increase (p < 0.001) compared with the year 2001 (24.8%). 11.3% of the E. coli strains were extended-spectrum beta -lactamase-producers and came from 24 hospitals. One P. aeruginosa isolate gave a positive result in the E-test MBL assay, suggesting the presence of metallo-beta -lactamases. The strains of imipenem-resistant A. baumannii presented cross-resistance with several antibiotics., Conclusion: These results show how the multi-resistant bacteria included in the study represent a growing problem in our hospitals. This emphasizes the importance of resistance surveillance systems and the correct use of antimicrobial agents.

Introduction: Resistance to antimicrobial drugs has increased in recent years. The aim of this multicenter study was to determine the current situation in Spain regarding the resistance patterns of the most common infectious agents to antimicrobial drugs., Material and Methods: A total 1,475 strains isolated in 38 hospitals in October 2001 were studied. These included 294 methicillin-resistant Staphylococcus aureus (MRSA), 149 clinically significant coagulase-negative staphylococci (CNS), 96 Enterococcus faecium, 1 ampicillin-resistant Enterococcus faecalis, 204 penicillin-resistant Streptococcus pneumoniae, 100 ampicillin-resistant Haemophilus influenzae, 361 ciprofloxacin-resistant Escherichia coli, 160 Pseudomonas aeruginosa, and 110 Acinetobacter baumannii. Sensitivity to various antibiotics was studied by a broth microdilution method. Additionally, an epidemiologic survey was conducted in the participating hospitals to determine the incidence of these multi-drug resistant microorganisms., Results: Overall incidence of ciprofloxacin-resistant E. coli and MRSA strains was 24% in both cases. The pneumococci were resistant to several antibiotics. Telithromycin showed excellent activity against all the pneumococci, including those resistant to macrolides. Most MRSA isolates were resistant to quinolones and macrolides. All the staphylococci were susceptible to linezolid and quinupristin-dalfopristin. Only 50% of A. baumannii strains were susceptible to imipenem., Conclusion: The results of this study evidence increasing multi-drug resistance among various microorganisms, such as MRSA, CNS, ampicillin-resistant enterococci, and penicillin-resistant pneumococci, and underline the need for surveillance programs to gain information on this significant therapeutic problem.

The increase in the use of the fluoroquinolones, including for the treatment of lower respiratory tract infections, seems to be associated with a parallel increase in bacterial resistance. We studied the activity of penicillin and six fluoroquinolones against 101 viridans group streptococci isolated from blood (58 erythromycin-susceptible and 43 erythromycin-resistant). The percentage of strains not susceptible to penicillin was 35% and there were statistically significant differences in the percentages of penicillin resistance between erythromycin-susceptible and -resistant strains. The fluoroquinolones studied showed good activity against our viridans group streptococci independent of their susceptibility to erythromycin. The norfloxacin MIC(50) and MIC(90) were 8 and 16 mg/l, respectively. Ofloxacin and ciprofloxacin showed the same activity (MIC(50) 1 mg/l and MIC(90) 2 mg/l); levofloxacin was similar with MIC(50) and MIC(90) of 1 mg/l. The fluoroquinolones with enhanced activity were moxifloxacin and trovafloxacin (MIC(50) 0.12 mg/l and MIC(90) 0.25 mg/l). However, we found two strains resistant to trovafloxacin (MIC = 4 mg/l) that showed reduced susceptibility to all the fluoroquinolones tested, including moxifloxacin (MIC = 2 mg/l). Mutations in the topoisomerase genes parC and gyrA have been shown to occur in strains with reduced susceptibility; therefore, ongoing surveillance for the development of fluoroquinolone resistance in viridans streptococci is necessary.