Comparative analysis of antimicrobial susceptibility among organisms from France, Germany, Italy, Spain and the UK as part of the tigecycline evaluation and surveillance trial.

As part of the tigecycline evaluation and surveillance trial (TEST), bacterial isolates were collected from 39 centres in France, Germany, Italy, Spain and the UK between January 2004 and August 2006. Antimicrobial susceptibilities were determined according to CLSI guidelines. Italy had the highest rate of methicillin-resistant Staphylococcus aureus (36.4%), and was the only country to report vancomycin-resistant Enterococcus faecalis (8.6%). Tigecycline was the only agent to which all Gram-positive isolates were susceptible. For many of the Gram-negative organisms collected, antimicrobial susceptibilities were lowest among isolates from Italy and highest among isolates from Spain. The notable exception was Acinetobacter baumannii, where the poorest susceptibility profile was among isolates from Spain. For A. baumannii, MIC(90)s of imipenem varied from 1 mg/L for isolates in France and Germany to > or =32 mg/L for isolates from Italy and Spain. Tigecycline was the only agent to maintain an MIC(90) of < or =1 mg/L against isolates from all five countries. The in-vitro activity of tigecycline against both Gram-positive and Gram-negative isolates may make it valuable in the treatment of hospital infections, including those caused by otherwise antimicrobial-resistant organisms.     

Resistance trends and in vitro activity of tigecycline and 17 other antimicrobial agents against Gram-positive and Gram-negative organisms,including multidrug-resistant pathogens,in Germany

To document the development of resistance to tigecycline in comparison with 17 other antimicrobials, the susceptibilities of 2,741 isolates comprising 16 bacterial species recovered from hospitalised patients in 15 German centres in 2009 were assessed. The results were compared with those of previous trials (German Tigecycline Evaluation Surveillance Trial, G-TEST I and II, performed in 2005 and 2007, respectively) conducted prior to and shortly after the introduction of tigecycline in Germany. Moreover, the in vitro activities of tigecycline against the subset of multidrug-resistant (MDR) pathogens recovered within all three sampling periods (n = 4,988) were evaluated in comparison to the corresponding non-MDR isolates. All susceptibility tests were performed by broth microdilution. Between 2005 and 2009, tigecycline retained its high activity against Gram-positive and Gram-negative organisms, including MDR pathogens. By contrast, an in part marked increase in resistance to broad-spectrum beta-lactams and fluoroquinolones was observed for many Enterobacteriaceae and for non-fermenting Gram-negative bacteria. Against a background of a steadily increasing number of multiresistant pathogens, the activity of tigecycline remained unaltered. With the exception of Acinetobacter isolates with decreased susceptibility to carbapenems, tigecycline’s activity profile was not notably affected by organisms resistant to other drug classes and, thus, holds promise as an important therapeutic agent, particularly for situations in which MDR organisms are suspected.     

Susceptibility of clinical isolates of frequently encountered bacterial species to tigecycline one year after the introduction of this new class of antibiotics: results of the second multicentre surveillance trial in Germany (G-TEST II, 2007)

Tigecycline, a broad-spectrum antibiotic for parenteral use, was introduced in Germany in May 2006. In the G-TEST-II trial, the susceptibility of isolates, recovered in 2007 from hospitalised patients in 15 centres, was assessed against tigecycline and comparators. Susceptibility tests were performed by the microdilution procedure. This study reports on the susceptibility of the isolates of 16 bacterial species and compares the results with those of a trial (G-TEST I) conducted prior to the introduction of tigecycline. Between 2005 and 2007, tigecycline retained activity against Gram-positive and Gram-negative organisms. By contrast, the rate of vancomycin-resistant strains among Enterococcus faecium isolates almost doubled. Moreover, an increase in resistance to broad-spectrum beta-lactams and fluoroquinolones was observed for members of the family Enterobacteriaceae. Against a background of a steadily rising number of pathogens that are resistant to various antibiotic classes, tigecycline represents an important treatment option.     

In vitro activities of moxifloxacin and tigecycline against bacterial isolates associated with intraabdominal infections at a medical center in Taiwan, 2001–2006

A total of 569 nonduplicate isolates recovered from patients with community-onset or hospital-onset intraabdominal infections (IAIs) from 2001 to 2006 were studied. These included 28 Staphylococcus aureus and 541 Gram-negative isolates (33.6% Escherichia coli, 29.0% Klebsiella pneumoniae, 8.1% Acinetobacter baumannii, and 6.3% Pseudomonas aeruginosa). Minimum inhibitory concentrations (MICs) of the isolates to moxifloxacin, imipenem, and ciprofloxacin were determined using the agar dilution method and to tigecycline using the broth microdilution method. Extended-spectrum β-lactamase (ESBL) producers were found in 15.5% (29 out of 182) of E. coli, 15.3% (24 out of 157) of K. pneumoniae, and 15.4% (2 out of 13) of K. oxytoca isolates. More than 85% of Enterobacteriaceae were susceptible to moxifloxacin, but this percentage was lower among E. coli (78%). The percentage of E. coli (K. pneumoniae) isolates that were not susceptible to moxifloxacin was 6% (0%) in 2001, 39% (17%) in 2003, and 21% (14%) in 2006. Tigecycline exhibited good in vitro activities against all S. aureus and >95% of all Enterobacteriaceae tested. Among the 24 isolates of ESBL-producing K. pneumoniae, 4 had tigecycline MICs ≥2 μg/ml. Eighty percent of A. baumannii isolates exhibited tigecycline MICs of ≤2 μg/ml. This study found that moxifloxacin and tigecycline exhibited good in vitro activity against bacterial isolates causing IAIs.     

In vitro activity of tigecycline against methicillin-resistant Staphylococcus aureus, including livestock-associated strains

The in vitro activity of tigecycline was determined using a well-defined collection of methicillin-resistant Staphylococcus aureus (MRSA) isolates (n = 202), including 33 livestock-associated strains. Susceptibility testing was performed using the Etest system. Among the 202 MRSA strains, three (1.5%) had a minimum inhibitory concentration (MIC) value for tigecycline greater than 0.5 mg/l, which are considered to be resistant. When these strains were tested using Iso-Sensitest medium, the MICs were substantially lower and no resistance was found. This discrepancy warrants further investigations into the preferred test conditions for tigecycline. In conclusion, tigecycline showed good activity against MRSA strains in vitro.     

Synergy of fosfomycin with carbapenems, colistin, netilmicin, and tigecycline against multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates

Fosfomycin represents a potential last-resort treatment option for infections with certain multidrug-resistant (MDR) Gram-negative pathogens. We evaluated double-drug combinations of fosfomycin with imipenem, meropenem, doripenem, colistin, netilmicin, and tigecycline for in vitro synergy against 100 MDR Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates, using the Etest method. Synergy was defined as a fractional inhibitory concentration index ≤0.5. The isolates were consecutively collected at a university hospital in Greece from various clinical specimens. Against 50 serine carbapenemase-producing K. pneumoniae isolates, synergy of fosfomycin with imipenem, meropenem, doripenem, colistin, netilmicin, and tigecycline was observed for 74.0%, 70.0%, 74.0%, 36.0%, 42.0%, and 30.0% of the isolates, respectively. Against 14 extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae isolates, synergy of fosfomycin with imipenem, meropenem, doripenem, colistin, netilmicin, and tigecycline was observed for 78.6%, 42.9%, 42.9%, 7.1%, 42.9%, and 21.4%, respectively; for 20 ESBL-producing E. coli isolates, the corresponding values were 55.0%, 25.0%, 30.0%, 15.0%, 25.0%, and 25.0%; and for 15 MDR P. aeruginosa isolates, the corresponding values were 46.7%, 53.3%, 73.3%, 13.3% , 13.3%, and 13.3%. Antagonism was not observed for any of the combinations tested. Further studies are needed in order to confirm the clinical relevance of the above findings.     

Klebsiella pneumoniae: development of a mixed population of carbapenem and tigecycline resistance during antimicrobial therapy in a kidney transplant patient

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.     

In vitro activity and in vivo efficacy of tigecycline alone and in combination with daptomycin and rifampin against Gram-positive cocci isolated from surgical wound infection

The aim of this work was to determine the in vitro activity of tigecycline and its bactericidal effect for a large number of Gram-positive cocci, as well as to investigate its in vitro interaction with six clinically used antibiotics. In vivo, a wound model was established through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 10(7) colony-forming units (CFU) of Staphylococcus aureus or Enterococcus faecalis. For each bacterial strain, the study included an infected or non-infected group that did not receive any treatment, three groups singly treated with tigecycline, rifampin, and daptomycin, and two groups that received tigecycline treatment plus rifampin or daptomycin. In the in vitro studies, tigecycline, daptomycin, and teicoplanin were active against all of the 48 Gram-positive isolates. The combination of tigecycline with rifampicin and daptomycin was synergistic against S. aureus and Enterococcus spp. In the in vivo studies, all groups treated with single drugs showed statistically significant results compared to the control group. The two groups treated with a combination of drugs showed the highest antimicrobial efficacy. In conclusion, our results suggested a strong activity of tigecycline alone and in combination with other antimicrobial agents against multi-resistant Gram-positive organisms isolated from wound infections.     

Tigecycline use in the outpatient parenteral antibiotic therapy setting

In the context of globally increasing antimicrobial resistance, tigecycline appears to be a useful therapeutic option. The need for prolonged courses for complex infections has prompted consideration of its use via outpatient parenteral antibiotic therapy (OPAT) programmes, although clinical outcomes when used in this setting remain unknown. We retrospectively reviewed the patient characteristics and outcomes of 11 patients who received tigecycline, most commonly delivered as 100 mg once daily, via OPAT at three tertiary Australian hospitals. Rates of co-morbidity and prior antibiotic use were high. Patients had a wide range of infections including bone and/or joint (n?=?5), intra-abdominal (n?=?3), lower respiratory tract (n?=?2) and parapharyngeal abscess (n?=?1). Mycobacterial species (n?=?5) were the most frequent pathogen, and multi-resistant organisms were common (n?=?4). The median OPAT duration was 14 days (IQR 6–30). Nausea was encountered in 45 % of cases. At completion of OPAT, 1 patient (9 %) was cured, 2 (18 %) had improved and 8 (73 %) failed therapy. Failure occurred due to either progression or non-response of infection (n?=?4), re-admission (n?=?3), premature cessation of tigecycline due to nausea (n?=?3) or death (n?=?1). Whilst OPAT delivery of tigecycline is a therapeutic option, when used as second-line therapy for complex, often multi-resistant infections in patients with multiple comorbidities, high rates of clinical failure, readmissions and adverse effects, especially nausea, should be anticipated.     

Epidemiology of bacteremia episodes in a single center: increase in Gram-negative isolates, antibiotics resistance, and patient age

Increased resistance among isolates causing bacteremia constitutes a major challenge to medical practitioners and institutions. Variability between institutes is substantial, and requires the individual analysis of local trends. An eight-year (1997–2004) surveillance study of episodes of bacteremia was conducted in an 850-bed university hospital in central Israel. Trends of incidence, resistance, age, and mortality were analyzed. We studied 6,096 patient-unique episodes of bacteremia, of which, 2,722 (45.3%) were nosocomial and 523 (9.2%) involved children less than 18 years of age. The overall incidence of bacteremia episodes has increased over the study years by 39% and the patient mean age by 7.5 years. Gram-negative organisms accounted for 72% of hospital-acquired cases and 69% of community-acquired cases. There was a substantial increase in the incidence of nosocomial episodes, predominantly due to Gram-negative isolates, mainly Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli. Increased resistance to broad-spectrum antibiotics was noted among Gram-negative organisms, including quinolones (in K. pneumoniae), imipenem (A. baumannii and P. aeruginosa), piperacillin-tazobactam (K. pneumoniae), and amikacin (A. baumannii and P. aeruginosa). Increased resistance to oxacillin among coagulase-negative staphylococci was also noted. The all-cause mortality rates showed a significant rise. The patient age, intensive care unit (ICU) stay, and hospital acquisition were independently associated with mortality. We describe an increase in the incidence and resistance of Gram-negative organisms causing bacteremia and concomitant ageing of the patients with bacteremia. Similar patterns have been reported from other localities, and are of real concern.     

In vitro activity of FK-037, a novel parenteral cephalosporin,against bacterial isolates from neutropenic cancer patients

The in vitro activity of FK-037, a novel parenteral cephalosporin, was compared to that of ceftazidime, aztreonam and piperacillin (agents often used in empiric regimens in cancer patients) against recent bacterial isolates from patients with cancer. FK-037 was either equal to or 2 to 16-fold more active than the comparative agents against members of theEnterobacteriaceae. It was also active againstAcinetobacter spp.,Aeromonas spp.,Pseudomonas aeruginosa, and otherPseudomonas spp.Xanthomonas maltophilia andAlcaligenes denitrificans were relatively resistant to all four agents. FK-037 was also 4 to 16-fold more active against most gram-positive organisms (including some methicillin-resistant staphylococci) than was ceftazidime.Enterococcus spp.,Listeria monocytogenes andStaphylococcus haemolyticus were relatively resistant to FK-037 and ceftazidime. Overall, FK-037 has a broad antimicrobial spectrum that includes the majority of gram-positive and gram-negative isolates.     

Antimicrobial activity of some Australian plant species from the genus Eremophila

Plant species of the genus Eremophila (Myoporaceae) are native to Australia and are known to produce a diverse range of unusual secondary compounds. The purpose of this research was to examine the antimicrobial activity of 72 Eremophila species most of which had not been the subject of any previous pharmacological testing. Organic extracts of Eremophila species were screened for antimicrobial activity against Gram-positive and Gram-negative bacteria and yeasts of medical importance. Extracts of a number of Eremophila species showed selective activity against Gram-positive bacteria with MICs for the most active species in the range of 16 to 62 microg/ml for Streptococcus species, and 62 to 250 microg/ml for standard strains of Staphylococcus aureus. Extracts with the greatest activity against standard strains were tested against 68 clinical isolates of multi-resistant methicillin-resistant S. aureus (mMRSA). The majority of the clinical isolates were susceptible to concentrations below 62.5 microg/ml for the extracts of E. drummondii, E. linearis, E. serrulata, E. acrida, E. neglecta, E. virens and a new undescribed species affiliated with E. prolata. The extract of E. virens inhibited growth of all 68 clinical mMRSA isolates at the minimum tested concentration of 31 microg/ml. This study has shown for the first time that a number of different Eremophila species manifest selective antibacterial activity against Gram-positive organisms which are important causes of human disease. It shows that there are several Eremophila species possessing interesting antibacterial activity besides those that have published traditional use. These may yield novel antibacterial compounds with potential to be used in biomedical applications.     

Antimicrobial susceptibility pattern of Stenotrophomonas species isolated from Mexico

BackgroundStenotrophomonas species are multi-resistant bacteria with ability to cause opportunistic infectionsObjectiveWe isolated 45 Stenotrophomonas species from soil, sewage and the clinic with the aim of investigating their susceptibility to commonly used antimicrobial agents.MethodologyThe identities of isolates were confirmed with 16S rRNA gene sequence and MALDI-TOF analysis. Anti-microbial resistance, biofilm production and clonal diversity were also evaluated. The minimum inhibitory concentration technique as described by Clinical & Laboratory Standards Institute: CLSI Guidelines (CLSI) was employed for the evaluation of isolate susceptibility to antibiotics.ResultForty-five Stenotrophomonas species which include 36 environmental strains and 9 clinical strains of S. maltophilia were considered in this study. 32 (88.9 %) environmental strains were identified to be S. maltophilia, 2 (5.6 %) were Stenotrophomonas nitritireducens, and 2 (5.6 %) cluster as Stenotrophomonas spp. Stenotrophomonas isolates were resistant to at least six of the antibiotics tested, including Trimethoprim/Sulfamethoxazole (SXT).ConclusionEnvironmental isolates from this study were resistant to SXT which is commonly used for the treatment of S. maltophilia infections. This informs the need for good public hygiene as the environment could be a reservoir of multi-resistant bacteria. It also buttresses the importance of surveillance study in the management of bacterial resistance.     

Comparative in vitro activity of A-56268 (TE-031), a new macrolide antibiotic

The in vitro activity of A-56268 (TE-031) was determined by either standard agar dilution or macrobroth tube dilution and comapred with erythromycin and other antimicrobial agents against 329 clinical aerobic and anaerobic bacterial isolates. A-56268 showed good to excellent in vitro activity against methicillin-sensitiveStaphylococcus aureus,Neisseria meningitidis, and most anaerobes tested with the exception ofBacteroides fragilis isolates. A-56268 had relatively poor activity against coagulase-negative staphylococci and methicillin-resistantStaphylococcus aureus. Except forHaemo philus spp., the activity of A-56268 was similar to or more potent than erythromycin against all other isolates tested. A-56268 did not have significant bactericidal activity against any of the isolates examined.     

In vitro activity of tigecycline against gram-positive and gram-negative pathogens as evaluated by broth microdilution and Etest

The current surveillance establishes the activity profile of tigecycline against recent clinical U.S. isolates of target pathogens. Findings from a distributed surveillance that utilized Etest yielded a tigecycline activity profile that varied from that observed in a separate centralized broth microdilution (BMD) surveillance (D. C. Draghi et al., Poster D-0701, 46th Intersci. Conf. Antimicrob. Agents Chemother., San Francisco, CA). Differences were noted among Acinetobacter spp. and Serratia marcescens and, to a lesser extent, with Streptococcus pyogenes. To address whether these differences were due to discordance in testing methodology or to variations among the analyzed populations, isolates from the current surveillance were concurrently tested by BMD and Etest. In all, 1,800 Staphylococcus aureus, 259 S. pyogenes, 226 Streptococcus pneumoniae, 93 Enterococcus faecalis, 1,356 Enterobacteriaceae, and 227 Acinetobacter baumannii strains were evaluated. Tigecycline had potent activity by BMD, with >99.6% susceptibility (%S) observed for all pathogens with interpretive criteria, excluding Enterobacter cloacae (98.3% S) and E. faecalis (86.0% S), and MIC₉₀s ranged from 0.03 μg/ml (S. pyogenes/S. pneumoniae) to 1 μg/ml (Enterobacteriaceae/A. baumannii). Similar profiles were observed by Etest, with the exception of A. baumannii, although for most evaluated pathogens Etest MICs trended one doubling-dilution higher than BMD MICs. Major or very major errors were infrequent, and a high degree of essential agreement was observed, excluding A. baumannii, S. marcescens, and S. pneumoniae, for which ≥4-fold differences in MICs were observed for 29, 27.1, and 34% of the isolates, respectively. Further analysis regarding the suitability of the tigecycline Etest for testing S. marcescens, Acinetobacter spp., and S. pneumoniae is warranted.     

In vitro activity of tigecycline against multidrug-resistant <Emphasis Type="Italic">Enterobacteriaceae</Emphasis> isolates from a Belgian hospital

Bacterial resistance among Gram-negative pathogens is a challenging clinical problem. Tigecycline has been developed specifically to overcome resistance. The aim of this study was to assess the in vitro activity of tigecycline against ESBL-producing Escherichia coli, ESBL-producing Klebsiella spp., and multidrug-resistant Enterobacter spp. Between May 2007 and March 2008, 26 strains of ESBL-producing Escherichia coli, 10 strains of ESBL-producing Klebsiella spp., and 27 strains of multidrug-resistant Enterobacter spp. were isolated consecutively from inpatients with a documented infection in which the collected isolate was identified as the probable causative organism. The in vitro susceptibility against tigecycline was measured by the E-test method. MIC₅₀ values were 1 μg/ml, 2 μg/ml, and 3 μg/ml respectively. MIC₉₀ values were respectively 1.5 μg/ml, 4 μg/ml, and 12 μg/ml. Nonsusceptibility rates of 35%, 100%, and 96% respectively were found using EUCAST breakpoints. Despite the limited number of strains tested, our in vitro data suggest that tigecycline is unsuitable for the treatment of infections with multidrug-resistant Enterobacteriaceae in our setting. Therefore, we suggest that larger multicenter studies should be conducted to reconsider the value of tigecycline for the treatment of infections with multidrug-resistant, Gram-negative bacteria.     

Prevalence and antibiotic sensitivity of Danish versus other European bacterial isolates from intensive care and hematology/oncology units

The prevalence and antibiotic sensitivity patterns of bacteria collected consecutively from medical and surgical intensive care units (ICUs) and from hematology/oncology units in nine hospitals in Denmark were determined and compared to data collected simultaneously in 12 other European countries. Bacterial isolates from 794 Danish patients were tested and compared to 8,625 isolates from European patients. The minimal inhibitory concentrations of eight different antibiotics were determined using a microdilution plate. Similar to findings in European countries, the most common source of bacterial isolates in Danish units was the respiratory tract (49 %), followed by blood (18 %), urinary tract (14 %) and surgical wounds (10 %).Staphylococcus aureus was the most prevalent respiratory organism in Danish units, whereasEnterobacteriaceae andPseudomonas aeruginosa dominated in other countries. In blood,Escherichia coli was most prevalent in Denmark while coagulase-negative staphylococci were predominant in other countries. Urinary tract isolates were dominated byEscherichia coli in both Denmark and the other countries, butEnterococcus faecalis andPseudomonas aeruginosa were more frequently isolated in the other countries.Staphylococcus aureus was the most frequent wound isolate in Denmark, whileEnterobacteriaceae other thanEscherichia coli dominated in other European countries. Thus, in DenmarkEscherichia coli andStaphylococcus aureus, followed byPseudomonas aeruginosa andKlebsiella spp. (from ICUs) orEnterococcus spp. andKlebsiella spp. (from hematology/oncology units), are the most prominent pathogens in these units today. Indicator organisms of antibotic consumption (Pseudomonas aeruginosa and methicillin-resistant coagulase-negative staphylococci andStaphylococcus aureus) were more frequent in other European countries than Denmark. In general, the Danish isolates were more sensitive to antibiotics than the European isolates. Thus, the sensitivity of all organisms to third-generation cephalosporins was about 10 % higher in Denmark as compared to Europe, and for many frequent pathogens, the sensitivity matched the fourth-generation cephalosporin, cefpirome. A lower total antibiotic consumption and the infrequent use of broad-spectrum cephalosporins in Denmark may contribute to these differences.