Tigecycline MIC Research Articles

Antimicrobial susceptibility of clinical isolates of Bacteroides fragilis group organisms recovered from 2009 to 2012 in a Korean hospital.

BackgroundPeriodic monitoring of antimicrobial resistance trends of clinically important anaerobic bacteria such as Bacteroides fragilis group organisms is required. We determined the antimicrobial susceptibilities of clinical isolates of B. fragilis group organisms recovered from 2009 to 2012 in a tertiary-care hospital in Korea.MethodsA total of 180 nonduplicate clinical isolates of B. fragilis group organisms were collected in a tertiary care hospital. The species were identified by conventional methods: the ATB 32A rapid identification system (bioMérieux, France) and the Vitek MS matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (bioMérieux). Antimicrobial susceptibility was determined by the CLSI agar dilution method.ResultsImipenem and meropenem resistance rates were 0-6% for B. fragilis group isolates. The rate of resistance to piperacillin-tazobactam was 2% for B. fragilis and 0% for other Bacteroides species, but 17% for B. thetaiotaomicron isolates. High resistance rates to piperacillin (72% and 69%), cefotetan (89% and 58%), and clindamycin (83% and 69%) were observed for B. thetaiotaomicron and other Bacteroides spp. The moxifloxacin resistance rate was 27% for other Bacteroides spp. The MIC50 and MIC90 of tigecycline were 2-4 µg/mL and 8-16 µg/mL, respectively. No isolates were resistant to chloramphenicol or metronidazole.ConclusionsImipenem, meropenem, chloramphenicol, and metronidazole remain active against B. fragilis group isolates. Moxifloxacin and tigecycline resistance rates are 2-27% and 8-15% for B. fragilis group isolates, respectively.

IS5 element integration, a novel mechanism for rapid in vivo emergence of tigecycline nonsusceptibility in Klebsiella pneumoniae.

Tigecycline nonsusceptibility is concerning because tigecycline is increasingly relied upon to treat carbapenem- or colistin-resistant organisms. In Enterobacteriaceae, tigecycline nonsusceptibility is mediated by the AcrAB-TolC efflux pump, among others, and pump activity is often a downstream effect of mutations in their transcriptional regulators, cognate repressor genes, or noncoding regions, as demonstrated in Enterobacteriaceae and Acinetobacter isolates. Here, we report the emergence of tigecycline nonsusceptibility in a longitudinal series of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Klebsiella pneumoniae isolates collected during tigecycline therapy and the elucidation of its resistance mechanisms. Clinical isolates were recovered prior to and during tigecycline therapy of a 2.5-month-old Honduran neonate. Antimicrobial susceptibility tests to tigecycline determined that the MIC increased from 1 to 4 μg/ml prior to the completion of tigecycline therapy. Unlike other studies, we did not find increased expression of ramA, ramR, oqxA, acrB, marA, or rarA genes by reverse transcription-quantitative PCR (qRT-PCR). Whole-genome sequencing revealed an IS5 insertion element in nonsusceptible isolates 85 bp upstream of a putative efflux pump operon, here named kpgABC, previously unknown to be involved in resistance. Introduction of the kpgABC genes in a non-kpgABC background increased the MIC of tigecycline 4-fold and is independent of a functional AcrAB-TolC pump. This is the first report to propose a function for kpgABC and identify an insertion element whose presence correlated with the in vivo development of tigecycline nonsusceptibility in K. pneumoniae.

In vitro activity of tigecycline and comparators against carbapenem-resistant Enterobacteriaceae in Africa-Middle East countries: TEST 2007-2012.

Multidrug-resistant (MDR) Enterobacteriaceae are an emerging concern for healthcare providers. Infections caused by MDR pathogens are associated with increased costs, length of hospital stay, and morbidity and mortality rates. Carbapenem-resistant Enterobacteriaceae (CRE) continue to increase, and infections with these organisms are observed worldwide not only as hospital-acquired infections but also as community-acquired infections. Increasing antimicrobial resistance dictates the need for continued surveillance studies of common and MDR pathogens. The Tigecycline Evaluation Surveillance Trial (TEST) examined the susceptibility of pathogens isolated in Africa and the Middle East from 2007 to 2012. A total of 4155 Enterobacteriaceae isolates were evaluated to determine the in vitro activity and changes in resistance patterns for tigecycline and comparators. Carbapenem resistance was found in 191 (4.6%) of the isolates tested. Klebsiella pneumoniae was the most common CRE (64.9%), followed by Enterobacter cloacae (14.1%) and Escherichia coli (9.9%). Tigecycline MIC90 values (minimum inhibitory concentration required to inhibit 90% of the isolates) were 2μg/mL against all of these enteric species, with susceptibility rates of 96.8%, 92.6% and 100%, respectively. Tigecycline had in vitro activity against CRE, with a 95.3% susceptibility rate.

Colistin, Polymyxin B and Tigecycline Suspectibility to Metallo Betalactamase Producing <i>Acinetobacter Baumannii</i> Isolated From Tertiary Health Care Hospital

Acinetobacter baumannii have emerged as important nosocomical pathogens especially in intensive care patients. Carbapenems are the choice of drug for their treatment but they started developing resistance to carbapenems predominatantly by producing Metallo beta-lactamases (MBL). Treatment of such carbapenem resistant Acinetobacter has led to reintroduction of polymyxins like colistin, polymyxin B and newer tetracycline group of drugs like tigecycline. As there were limited studies in on Minimum inhibitory concentrations (MIC) of MBL producing Acinetobacter to polymyxins and tigecyclines from india, the present study was undertaken. MBL detection was done by combined disc test with imipenem and EDTA. MIC of the drugs was determined by Agar dilution method. MIC50 and MIC90 of tigecycline were found to be 0.5 μg/ml and 1 μg/ml respectively. Suseptibility MIC ranges for tigecycline were found to be 0.5 to 2 μg/ml. Resistance rates for tigecycline were found to be 6%. MIC50 and MIC90 of colistin was found to be 2 μg/ml. Susceptibility MIC ranges for colistin were found to be 0.25 to 1 μg/ml. MIC50 and MIC90 of polymyxinB were found to be 1 μg/ml and 2 μg/ml respectively. Susceptibility MIC ranges for polymyxin B were found to be between 0.5 to 2ug/ml. The susceptibility rates with colistin and polymyxin B were found to be 99.2% and 100% respectively. Polymyxin B and colistin are very good drugs of choice for treatment of MBL producing Acinetobacter baumannii with 0.8% and 0% resistance rates. Though good sensitivity was noticed with tigecycline, we found 6% resistance rate.

Major Variation in MICs of Tigecycline in Gram-Negative Bacilli as a Function of Testing Method

Tigecycline is one of the few remaining therapeutic options for extensively drug-resistant (XDR) Gram-negative bacilli (GNB). MICs of tigecycline to Acinetobacter baumannii have been reported to be elevated when determined by the Etest compared to determinations by the broth microdilution (BMD) method. The study aim was to compare the susceptibility of GNB to tigecycline by four different testing methods. GNB were collected from six health care systems (25 hospitals) in southeast Michigan from January 2010 to September 2011. Tigecycline MICs among A. baumannii, carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, and susceptible Enterobacteriaceae isolates were determined by Etest, BMD, Vitek-2, and MicroScan. Nonsusceptibility was categorized as a tigecycline MIC of ≥4 μg/ml for both A. baumannii and Enterobacteriaceae. The study included 4,427 isolates: 2,065 ESBL-producing Enterobacteriaceae, 1,105 A. baumannii, 888 susceptible Enterobacteriaceae, and 369 CRE isolates. Tigecycline nonsusceptibility among A. baumannii isolates was significantly more common as determined by Etest compared to that determined by BMD (odds ratio [OR], 10.3; P<0.001), MicroScan (OR, 12.4; P<0.001), or Vitek-2 (OR, 9.4; P<0.001). These differences were not evident with the other pathogens. Tigecycline MICs varied greatly according to the in vitro testing methods among A. baumannii isolates. Etest should probably not be used by laboratories for tigecycline MIC testing of A. baumannii isolates, since MICs are significantly elevated with Etest compared to those determined by the three other methods.

In vitro activity of tigecycline against isolates collected from complicated skin and skin structure infections and intra-abdominal infections in Africa and Middle East countries: TEST 2007–2012

Complicated skin and skin structure infections (cSSSIs) and intra-abdominal infections (IAIs) are problematic due to decreasing therapeutic options available against multidrug-resistant pathogens common among these types of infections. A total of 2245 isolates from African and the Middle Eastern (AfME) countries were collected to determine in vitro activity for tigecycline and comparators during 2007–2012 as part of the Tigecycline Evaluation Surveillance Trial program. Tigecycline was launched in the AfME in 2007 and remains active against a wide range of targeted pathogens worldwide. Isolates were recovered from cSSSI (1990) and IAI (255) from 38 sites in 11 AfME countries. Staphylococcus aureus was the most common species from cSSSI (27.9%), and the methicillin-resistant S. aureus rate was 25%. Enterococcus spp. (7.1%) and Streptococcus agalactiae (2.9%) were other common Gram-positive pathogens represented. Enterobacter spp. (14.5%), Pseudomonas aeruginosa (13.9%), Escherichia coli (11.4%), Klebsiella spp. (10.9%), and Acinetobacter spp. (7.2 %) were the most common Gram-negative species collected. Tigecycline MIC90 values were 0.25 μg/mL against S. aureus. E. coli and Enterobacter spp. had tigecycline MIC90 values of 1 and 2 μg/mL, respectively. E. coli was the most frequently collected species from IAI (28.3%), followed by Klebsiella spp. (20.8%), Enterococcus spp. (11.8%), and Stenotrophomonas maltophilia (6.3%). Isolates collected from IAI had the following tigecycline MIC90 values: E. coli (1 μg/mL), Klebsiella spp. and other Enterobacteriaceae (2 μg/mL), Enterococcus spp. (0.25 μg/mL), and S. maltophilia (1 μg/mL). Tigecycline in vitro activity was observed against a broad spectrum of bacterial species, including strains resistant to other antimicrobial classes.

Effect of Proton Pump Inhibitors on In Vitro Activity of Tigecycline against Several Common Clinical Pathogens

In this study, we evaluated the effect of proton pump inhibitors (PPIs) on in vitro antimicrobial activity of tigecycline against several species of clinical pathogens. Clinical non-duplicate isolates of Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis and three species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumonia and Enterobacter cloacae) were collected from a tertiary hospital and their MICs of tigecycline alone and in combination with PPIs (omeprazole, lansoprazole and pantoprazole) were determined. With one randomly selected isolate of each bacterial species, an in vitro time–kill study was performed for the confirmation of the effect of PPIs on tigecycline activity. The MIC changes after PPIs addition correlated with the PPIs concentrations in the test media. Compared with tigecycline alone, the addition of 5 mg/L PPIs could increase the MICs of tigecycline by 0 to 2-fold and the addition of 50 mg/L PPIs could increase the MICs of tigecycline by 4 to >128-fold. The time–kill study confirmed that the addition of PPIs could affect the in vitro activity of tigecycline. Even at low concentration (5 mg/L) of omeprazole and pantoprazole, antagonistic effect could be observed in E. cloacae and E. faecalis strains. We conclude that In vitro activity of tigecycline can be influenced by the presence of PPIs in a concentration-dependent manner.

Clinical and microbiological characteristics of tigecycline non-susceptible Klebsiella pneumoniaebacteremia in Taiwan

BackgroundResistance among Klebsiella pneumoniae to most antibiotics is on the rise. Tigecycline has been considered as one of the few therapeutic options available to treat multidrug-resistant bacteria. We investigated the clinical and microbiological characteristics of tigecycline non-susceptible K. pneumoniae bacteremia.MethodsAdult patients with tigecycline non-susceptible K. pneumoniae bacteremia at a medical center in Taiwan over a 3-year period were enrolled. K. pneumoniae isolates were identified by the E-test using criteria set by the US Food and Drug Administration (FDA). Data on the clinical features of patients were collected from medical records. Genes for β-lactamases, antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE) results were determined for all isolates.ResultsOf 36 patients, 27 had nosocomial bacteremia. Overall 28-day mortality was 38.9%. The MIC50 and MIC90 of tigecycline were 6 and 8 mg/L, respectively. No carbapenemase was detected among the 36 isolates. Twenty isolates carried extended spectrum β-lactamases and/or DHA-1 genes. No major cluster of isolates was found among the 36 isolates by PFGE. Intensive care unit onset of tigecycline non-susceptible Klebsiella pneumoniae bacteremia was the only independent risk factor for 28-day mortality.ConclusionsThe high mortality of patients with tigecycline non-susceptible K. pneumoniae bacteremia may suggest a critical problem. Further study to identify the possible risk factors for its development and further investigation of this type of bacteremia is necessary.

Genetic and antibiotic susceptibility profiles of drug-resistant Acinetobacter baumannii from various parts of Lebanon

Objectives. To determine the population structure and antimicrobial sensitivity profile of carbapenem-resistant A. baumannii isolates from different hospitals of Lebanon. Methods. Thirty-two isolates of A. baumannii were collected between Jan-June 2011 from three distant hospitals in Lebanon. Molecular identification was done by partial rpoB sequencing. The antibiotic susceptibility testing was determined by agar disc diffusion. MICs for imipenem, meropenem, colistin, tigecycline and sulbactam were also determined for imipenem resistant strains. Genetic testing was per- formed using MLST. Results. Thirty isolates were identified as A. baumannii according to the molecular identification test, of these 24 exhibited imipenem re - sistance. Susceptibility profiles (susceptible vs. intermediate vs. resis - tant) of these isolates were 0% vs.12.5% vs.87.5% for meropenem, 8.3%vs.54.2%vs.37.5% for tigecycline and 8.3%vs.8.3%vs83.4% for sulbactam, respectively. All isolates (100%) were sensitive to colistin. All isolates (except one) belonged to international clone 2. Conclusion. High prevalence of drug resistant of A. baumannii pauses a major risk for patients in Lebanon. Therefore, an effective antimi- crobial treatment, strict infection control measurements and rational antibiotic use over in Lebanon are mandatory to control further ag- gravation of the antibiotic resistance organisms in this country.

Decreased susceptibility to tigecycline in Acinetobacter baumannii mediated by a mutation in trm encoding SAM-dependent methyltransferase

Acinetobacter baumannii is an important opportunistic pathogen and multidrug-resistant isolate. Although tigecycline is a potent antibiotic for treating infections with multidrug-resistant isolates, resistance is becoming a problem. This study aimed to explore the mechanism of tigecycline resistance in A. baumannii. A serial passage experiment was performed to collect isolates selected by tigecycline. The expression of efflux pumps was quantified in the final selected isolate, 19606-T8. The whole genome of 19606-T8 was sequenced and the putative mutations were confirmed using PCR and Sanger sequencing. A complementation experiment was performed to evaluate the contribution of the mutations to decreased susceptibility to tigecycline. The significance of a deletion mutation was further investigated in terms of growth rate and antibiotic susceptibilities. We collected serial isolates by selective pressure of tigecycline, and designated them 19606-T1 to 19606-T8. The efflux pumps AdeABC, AdeFGH and AdeIJK were not overexpressed in 19606-T8, which had decreased susceptibility to tigecycline. Isolate 19606-T8 carried one deletion mutation in trm and three non-synonymous substitutions in msbA (A84V), lolA (P91L) and filC (N168K). The deletion mutation in trm (encoding S-adenosyl-L-methionine-dependent methyltransferase) resulted in decreased susceptibility to tigecycline as well as to minocycline and doxycycline. In complementation experiments, the MICs of tigecycline, minocycline and doxycycline in a tigecycline-resistant isolate were restored by complementation with wild-type trm. Given that the deletion mutation in trm was associated with decreased susceptibility to tigecycline and that a wild-type trm plasmid could restore the susceptibility, trm is considered to play an important role in decreased susceptibility to tigecycline in A. baumannii.

Bacterial Peritonitis Due to Acinetobacter baumannii Sequence Type 25 with Plasmid-Borne New Delhi Metallo-β-Lactamase in Honduras

A carbapenem-resistant Acinetobacter baumannii strain was isolated from the peritoneal fluid of a patient with complicated intra-abdominal infection and evaluated at the Multidrug-resistant Organism Repository and Surveillance Network by whole-genome sequencing and real-time PCR. The isolate was sequence type 25 and susceptible to colistin and minocycline, with low MICs of tigecycline. blaNDM-1 was located on a plasmid with >99% homology to pNDM-BJ02. The isolate carried numerous other antibiotic resistance genes, including the 16S methylase gene, armA.

P2.089 Antimicrobial Susceptibility Profile of Neisseria Gonorrhoeae Isolates in the Province of Québec: 2012

BackgroundSince 1988, the LSPQ (Laboratoire de santé publique du Québec) coordinates the Neisseria gonorrhoeae antimicrobial resistance programme,to support treatment guidelines updates. In the context of decreasing susceptibilities to 3rd generation...

P330 Antibiotic combination therapy and clinical outcome for multidrug-resistant Pseudomonas aeruginosa infections

globally, tigecyclinewas consideredas the last resort to treat pandrugresistant bacteria. Though tigecycline non-susceptible K. pneumoniae isolates have been identified increasingly in recent years, the clinical information regarding bloodstream infection due to tigecycline nonsusceptible K. pneumoniae has never been reported. Objectives: The aim of this cohort study is to investigate the clinical and microbiological characteristics of tigecycline non-susceptible Klebsiella pneumoniae bacteremia in adult patients from a medical center in Taiwan. Methods: Patients with tigecycline non-susceptible K. pneumoniae bacteremia identified by E-test using FDA criteria were analyzed at a medical center in Taiwan between January 2010 and December 2012. Data on clinical features, therapy and outcomes of patients were collected from medical records. Genes for cabapenemases, plasmidic ampC -type, and extended-spectrum b-lactamases (EBSLs) were analyzed by polymerase chain reaction. Antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE) results were determined among all the isolates. Results: A total of 36 patients with tigecycline non-susceptible K. pneumoniae bacteremia were identified. 29 patients had nosocomial bacteremia and 4patients had healthcare-associated bacteremia. Only 13 patients had the exposure to tigecycline in the past 30 days. The overall 28-day mortality rate was 36.1%. The MIC50 and MIC90 of tigecycline were 6 and 8mg/L, respectively. 8 isolates were ertapenem non-susceptible K. pneumoniae , including 2 isolates not susceptible to imipenem. 19 isolates were ESBL producers, and DHA-1 was detected in 18 isolates. No carbapenemase was detected among the 36 isolates. PFGE demonstrated that most isolates were epidemiologically unrelated. Conclusion: This study for the first time showed the distinct features of tigecycline non-susceptible K. pneumoniae causing bacteremia and the associated poor prognosis. More studies focusing on the risk factor and the resistance mechanisms of tigecycline non-susceptible K. pneumoniae bacteremia are necessary in Taiwan.

RND-Type Efflux Pumps in Multidrug-Resistant Clinical Isolates of Acinetobacter baumannii: Major Role for AdeABC Overexpression and AdeRS Mutations

Increased expression of chromosomal genes for resistance-nodulation-cell division (RND)-type efflux systems plays a major role in the multidrug resistance (MDR) of Acinetobacter baumannii. However, the relative contributions of the three most prevalent pumps, AdeABC, AdeFGH, and AdeIJK, have not been evaluated in clinical settings. We have screened 14 MDR clinical isolates shown to be distinct on the basis of multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) for the presence and overexpression of the three Ade efflux systems and analyzed the sequences of the regulators AdeRS, a two-component system, for AdeABC and AdeL, a LysR-type regulator, for AdeFGH. Gene adeB was detected in 13 of 14 isolates, and adeG and the intrinsic adeJ gene were detected in all strains. Significant overexpression of adeB was observed in 10 strains, whereas only 7 had moderately increased levels of expression of AdeFGH, and none overexpressed AdeIJK. Thirteen strains had reduced susceptibility to tigecycline, but there was no correlation between tigecycline MICs and the levels of AdeABC expression, suggesting the presence of other mechanisms for tigecycline resistance. No mutations were found in the highly conserved LysR regulator of the nine strains expressing AdeFGH. In contrast, functional mutations were found in conserved domains of AdeRS in all the strains that overexpressed AdeABC with two mutational hot spots, one in AdeS near histidine 149 suggesting convergent evolution and the other in the DNA binding domain of AdeR compatible with horizontal gene transfer. This report outlines the high incidence of AdeABC efflux pump overexpression in MDR A. baumannii as a result of a variety of single mutations in the corresponding two-component regulatory system.

Alternatives to carbapenems in ESBL-producing Escherichia coli infections

ObjectivesThe authors had for objective to assess the activity of a wide panel of antibiotics on extended-spectrum-β-lactamase producing Escherichia coli isolates (ESBL-Ec), because of the sharp increase of their frequency, leading to an increased use of carbapenems. Material and methodsWe selected 100 ESBL-Ec in which ESBLs were identified by PCR and sequencing, between 2009 and 2010. We determined the MICs of amoxicillin-clavulanate, piperacillin-tazobactam, temocillin, mecillinam, cefoxitin, cefotaxime, ceftazidime, aztreonam, tigecycline, nitrofurantoin, and fosfomycin using reference methods. The susceptibility profiles were defined according to EUCAST 2012 recommendations. ResultsFosfomycin, nitrofurantoin, and pivmecillinam were active against more than 90% of isolates and remain excellent choices for the oral treatment of urinary tract infections (UTIs). Temocillin and piperacillin-tazobactam are also good candidates for the treatment of pyelonephritis or bloodstream infections. Only 27, 23, and 8% of isolates were susceptible to ceftazidime, cefepime, and cefotaxime, respectively. ConclusionOur study results prove that in many cases, there are non-carbapenem alternatives for the treatment of ESBL-Ec infections.

Tigecycline susceptibility in Klebsiella pneumoniae and Escherichia coli causing neonatal septicaemia (2007–10) and role of an efflux pump in tigecycline non-susceptibility

To investigate the trend of tigecycline susceptibility and mechanisms behind tigecycline non-susceptibility in Klebsiella pneumoniae and Escherichia coli isolates causing neonatal septicaemia (2007-10). MICs of tigecycline for the isolates were determined. The isolates were evaluated for β-lactamases and carbapenemases. Molecular typing of the tigecycline-resistant isolates was performed. Expression of efflux pump genes (acrA, acrB and tolC) and regulators (soxS and ramA) was examined by real-time RT-PCR and western blotting. Sequencing of the ramA and ramR genes was carried out to identify mutations within these genes. Tigecycline susceptibility was evaluated in all K. pneumoniae (n = 57) and E. coli (n = 19) blood isolates. The prevalence of extended-spectrum β-lactamase (ESBL)-producing organisms was high, but tigecycline non-susceptibility remained low in these isolates. Though MIC values of tigecycline remained in the susceptible range, there was a 2-fold increase in the value of MIC90 from 2007 to 2010. Over the 4 year period K. pneumoniae showed higher MIC values of tigecycline in comparison with E. coli. Tigecycline non-susceptibility was not observed among carbapenem-resistant isolates. Only two ESBL-producing clonally distinct K. pneumoniae isolates showed tigecycline resistance with overexpression of ramA and the AcrAB-TolC pump. No mutations were present within the ramA and ramR genes that might enhance the expression of the pump. The study showed for the first time the trend of tigecycline susceptibility in E. coli and K. pneumoniae causing neonatal septicaemia. Tigecycline still has potent antimicrobial effects against most ESBL- or carbapenemase-producing K. pneumoniae and E. coli, but the increasing MIC values make it essential to be vigilant.

Acinetobacter baumannii extensively drug resistant lineages in Buenos Aires hospitals differ from the international clones I–III

As a way to contribute to the assessment of Acinetobacter baumannii clinical population structure, multi-locus sequence typing (MLST) was performed in a collection of 93 isolates from Buenos Aires (1983–2012) and Rosario (2006–2009) hospitals. Sequence types (STs) were achieved by Bartual (B) and Institut Pasteur (P) schemes. PFGE typing, antimicrobial susceptibility assays, and the amplification of the OXA carbapenemase genes most prevalent in our region, were also performed.e-Burst clustered the 25 STsB (15 novels) into 5 clonal complexes (CC) and 5 singletons, and grouped the 18 STsP (12 novels) into 3 CC and 4 singletons. Bartual scheme divided the CC79P into two groups. CC113B/CC79P prevailed in Buenos Aires at least in 1992–2009, being responsible for epidemic and for endemic infections and acquiring the XDR (extensively drug-resistant) pattern throughout the years. While, CC119B/CC79P was apparently present before the CC113B/CC79Pdomain. CC103B/CC15P was the second most prevalent CC. Interestingly, CC110B/ST25P apparently increased over the last years. Conversely, CC109B/CC1P (international clone I) predominated in Rosario, although the presence of CC113B/CC79P, CC103B/CC15P and CC110B/ST25P was observed. Nineteen novel STs clustered in CC79P, CC15P, CC113B, CC109B and CC103B, suggesting their clonal expansion during persistence. PFGE typing proved transmission of strains intra- and inter-hospitals in each city. Except for one, all the recent isolates (2007–2012) harboured the blaOXA-23-like. All isolates were susceptible to colistin. Tigecycline MIC90 was 1mg/L and the rifampicin MIC>512mg/l was found among isolates in three hospitals.In conclusion, the international clone II (CC92B/CC2P) was not found among our isolates. CC113B/CC79P, CC103B/CC15P, and ST25P, suggested also as major components in the A. baumannii population together with the international clone I, were present in Buenos Aires and Rosario with different prevalence rate. Their recent isolates showed high distribution of the blaOXA-23-like as well as the XDR pattern.

In vitro susceptibility of multidrug-resistant Enterobacteriaceae clinical isolates to tigecycline

To assess the in vitro susceptibility of multidrug-resistant Enterobacteriaceae (MDRE) isolates to tigecycline. Clinical isolates of MDRE tested in this study were obtained from 91 hospitals in Belgium during the period January 2010 to April 2010. MICs of tigecycline were determined by Vitek 2 (VTK) and by the reference broth microdilution (BMD) method, and the results were interpreted based on the 2011 MIC interpretative criteria recommended by EUCAST. A total of 501 non-duplicate MDRE isolates were tested. These comprised 284 isolates of Escherichia coli [255 (89.7%) were extended-spectrum β-lactamase (ESBL)-producing isolates], 72 isolates of Klebsiella pneumoniae [53 (73.6%) were ESBL-producing isolates], 72 isolates of Enterobacter aerogenes, 33 isolates of Enterobacter cloacae, 19 isolates of Klebsiella oxytoca and 21 miscellaneous others. The MIC(90) values of tigecycline for E. coli and non-E. coli ESBL-producing Enterobacteriaceae isolates were 0.5 and 2 mg/L by BMD, and 0.5 and 8 mg/L by VTK, respectively. The highest essential and categorical agreement rates between VTK and BMD results using EUCAST breakpoints were observed in E. coli isolates (97.2%), while lower and unacceptable essential and categorical agreement rates were obtained for isolates belonging to species other than E. coli (81.1% and 59.4%, respectively). VTK appears to be a suitable method for routine susceptibility testing of tigecycline only for E. coli isolates, while BMD should be preferred for other Enterobacteriaceae species isolates.

In vitro activity of tigecycline and comparators against organisms associated with intra-abdominal infections collected as part of TEST (2004–2009)

As part of the Tigecycline Evaluation and Surveillance Trial (TEST), bacterial isolates were collected consecutively from centers globally between 2004 and 2009. MICs were determined locally using Clinical and Laboratory Standards Institute broth microdilution methodology. A total of 3114 anaerobic and 99,256 aerobic isolates were included in this study. The most active agents against Gram-negative anaerobes were metronidazole and meropenem (resistance ranges 0.0–0.5% and 0.0–0.9%, respectively); piperacillin–tazobactam was also active (resistance range 0.5–9.4%). Among Gram-positive anaerobes, resistance rates were lowest for meropenem, piperacillin–tazobactam, and metronidazole (ranges 0.0–0.5%, 0.0–1.8%, and 0.0–3.2% respectively). Tigecycline MIC90 values for anaerobes ranged from 0.12 to 2 μg/mL. The most active antimicrobial agent against Gram-negative aerobes (excluding Pseudomonas aeruginosa) was tigecycline, with resistance ranging from <0.01% to 1.4%. Resistance was also low for imipenem (0.3–9.4%) and meropenem (0.7–15.1%). Extended-spectrum beta-lactamases were produced by 12.2% and 19.7% of E. coli and K. pneumoniae isolates, respectively.

Effect of Manganese in Test Media on In Vitro Susceptibility of Enterobacteriaceae and Acinetobacter baumannii to Tigecycline

We assessed the effect of increasing manganese concentrations in test media (0.001 to 1,024 mg/liter) on MICs of tigecycline. For both broth microdilution (BMD) and Etests, this effect was negligible for physiological concentrations, but MICs increased when concentrations exceeded 8 mg/liter. Susceptibility testing should be performed on media with standardized low manganese content.