Oritavancin in vitro activity against Gram-positive organisms from European medical centers: a 10-year longitudinal overview from the SENTRY Antimicrobial Surveillance Program (2010-2019).

To assess oritavancin in vitro activity against clinically relevant Gram-positive pathogens in European (EU) hospitals, a total of 51,531 consecutive and unique clinical isolates collected in 2010-2019 were evaluated. All isolates were tested by CLSI broth microdilution methods. The key resistance phenotypes differed considerably between Eastern Europe (E-EU) and Western Europe (W-EU), respectively: methicillin-resistant (MR) Staphylococcus aureus 27.7%/22.9%; multidrug resistant (MDR) S. aureus, 19.7%/15.2%; MR coagulase-negative staphylococci, 77.3%/61.9%; vancomycin-resistant enterococci (E. faecium), 44.2%/20.9%; and MDR E. faecium, 63.8%/55.4%. There were no substantive differences in oritavancin minimum inhibitory concentration (MIC) values for the different species/organism groups over time or by EU region. Oritavancin inhibited 99.9% and 99.1% of all S. aureus and coagulase-negative staphylococci at 0.12 mg/L, respectively, and all isolates of E. faecalis and E. faecium at ≤0.5 mg/L. Oritavancin susceptibility rates against ß-hemolytic and Viridans group streptococci isolates were 98.1% and 99.4%, respectively. Oritavancin had potent activity in vitro against this contemporary collection of European Gram-positive isolates from 2010 to 2019.

Activity of Aztreonam in Combination with Avibactam, Clavulanate, Relebactam, and Vaborbactam against Multidrug-Resistant Stenotrophomonas maltophilia.

The intrinsic L1 metallo- and L2 serine-ß-lactamases in Stenotrophomonas maltophilia make it naturally multidrug resistant and difficult to treat. There is a need to identify novel treatment strategies for this pathogen, especially against isolates resistant to first-line agents. Aztreonam in combination with avibactam has demonstrated potential, although data on other aztreonam-ß-lactamase inhibitor (BLI) combinations are lacking. Additionally, molecular mechanisms for reduced susceptibility to these combinations have not been explored. The objectives of this study were to evaluate and compare the in vitro activities and to understand the mechanisms of resistance to aztreonam in combination with avibactam, clavulanate, relebactam, and vaborbactam against S. maltophilia A panel of 47 clinical S. maltophilia strains nonsusceptible to levofloxacin and/or trimethoprim-sulfamethoxazole were tested against each aztreonam-BLI combination via broth microdilution, and 6 isolates were then evaluated in time-kill analyses. Three isolates with various aztreonam-BLI MICs were subjected to whole-genome sequencing and quantitative reverse transcriptase PCR. Avibactam restored aztreonam susceptibility in 98% of aztreonam-resistant isolates, compared to 61, 71, and 15% with clavulanate, relebactam, and vaborbactam, respectively. The addition of avibactam to aztreonam resulted in a ≥2-log10-CFU/ml decrease at 24 h versus aztreonam alone against 5/6 isolates compared to 1/6 with clavulanate, 4/6 with relebactam, and 2/6 with vaborbactam. Molecular analyses revealed that decreased susceptibility to aztreonam-avibactam was associated with increased expression of genes encoding L1 and L2, as well as the efflux pump (smeABC). Aztreonam-avibactam is the most promising BLI-combination against multidrug-resistant S. maltophilia Decreased susceptibility may be due to the combination of overexpressed ß-lactamases and efflux pumps. Further studies evaluating this combination against S. maltophilia are warranted.

Activity of Cefiderocol Alone and in Combination with Levofloxacin, Minocycline, Polymyxin B, or Trimethoprim-Sulfamethoxazole against Multidrug-Resistant Stenotrophomonas maltophilia.

The production of an L1 metallo-ß-lactamase and an L2 serine active-site ß-lactamase precludes the use of ß-lactams for the treatment of Stenotrophomonas maltophilia infections. Preclinical data suggest that cefiderocol is the first approved ß-lactam with reliable activity against S. maltophilia, but data on strains resistant to current first-line agents are limited, and no studies have assessed cefiderocol-based combinations. The objective of this study was to evaluate and compare the in vitro activity of cefiderocol alone and in combination with levofloxacin, minocycline, polymyxin B, or trimethoprim-sulfamethoxazole (TMP-SMZ) against a collection of highly resistant clinical S. maltophilia isolates. For this purpose, the MICs of cefiderocol, ceftazidime, levofloxacin, minocycline, polymyxin B, and TMP-SMZ for 37 S. maltophilia isolates not susceptible to levofloxacin and/or TMP-SMZ were determined. Nine strains with various cefiderocol MICs were then tested in time-kill experiments with cefiderocol alone and in combination with comparators. The only agents for which susceptibility rates exceeded 40% were cefiderocol (100%) and minocycline (97.3%). Cefiderocol displayed the lowest MIC50 and MIC90 values (0.125 and 0.5 mg/liter, respectively). In time-kill experiments, synergy was observed when cefiderocol was combined with levofloxacin, minocycline, polymyxin B, or TMP-SMZ against 4/9 (44.4%), 6/9 (66.7%), 5/9 (55.5%), and 6/9 (66.7%) isolates, respectively. These data suggest that cefiderocol displays potent in vitro activity against S. maltophilia, including strains resistant to currently preferred agents. Future dynamic and in vivo studies of cefiderocol alone and in combination are warranted to further define cefiderocol's synergistic capabilities and its place in therapy for S. maltophilia infections.

Immunization with the recombinant myosin regulatory light chain (FhrMRLC) in Adjuplex® adjuvant elicits a Th1-biased immune response and a reduction of parasite burden in Fasciola hepatica infected rats.

The aim of this study was to assess the immune response and the protective efficacy elicited by the vaccination with the recombinant Fasciola hepatica myosin regulatory light chain (FhrMRLC) in Adjuplex® adjuvant against the infection with F. hepatica in rats. Four groups of 15 animals each were used for the study, one group was immunized with the recombinant F. hepatica MRLC in Adjuplex® adjuvant and the other groups remained as adjuvant, positive and negative control groups. The parasitological study showed that a statistically significant reduction of 65.1% and 82.1% in fluke burden and fecal egg count, respectively, was detected in vaccinated animals. In addition, vaccination with FhrMRLC induced a well-defined humoral and cellular immune response characterized by a significant production of specific IgG and IL-2, IL-12, TNF-α and IFN-γ; which confirms the immunogenic capacity of the FhrMRLC.

Activity of Potential Alternative Treatment Agents for Stenotrophomonas maltophilia Isolates Nonsusceptible to Levofloxacin and/or Trimethoprim-Sulfamethoxazole.

Stenotrophomonas maltophilia is difficult to treat due to the production of multiple intrinsic and acquired mechanisms of resistance. Trimethoprim-sulfamethoxazole (TMP-SMZ) and the fluoroquinolones have traditionally been considered the drugs of choice but are plagued by increasing resistance and adverse drug effects. The objective of this study was to evaluate the in vitro activities of 12 clinically relevant antimicrobials against clinical S. maltophilia isolates nonsusceptible to levofloxacin and/or TMP-SMZ. A diverse panel of 41 clinical S. maltophilia isolates collected through the SENTRY Antimicrobial Surveillance Program from 2008 to 2018 was evaluated against ceftazidime, ceftazidime-avibactam, chloramphenicol, delafloxacin, levofloxacin, moxifloxacin, eravacycline, minocycline, omadacycline, polymyxin B, and tigecycline. MICs were determined in triplicate via reference broth microdilution and interpreted according to CLSI guidelines where available. MIC distributions and susceptibilities were also compared across infection type, acquisition setting, and geographic origin. Susceptibilities to levofloxacin and TMP-SMZ were 29.3% and 36.6%, respectively. Minocycline displayed the highest susceptibility rate overall (92.7%) and the lowest MIC90 value (4 mg/liter) of any of the 12 agents tested. Only 3 isolates were resistant to levofloxacin, TMP-SMZ, and minocycline. Polymyxin B and tigecycline were the second most active agents. No significant differences were observed in MIC distributions across the 3 strata evaluated. These data demonstrate that few antimicrobials, old or new, maintain reliable activity against resistant S. maltophilia The role of minocycline in the treatment of infections due to S. maltophilia warrants further clinical investigation given its potent in vitro activity and favorable adverse effect profile.

Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects.

The ex vivo bactericidal activity and pharmacodynamics of fosfomycin in urine were evaluated in 18 healthy subjects. Subjects received 3 g every other day (QOD) for 3 doses and then every day (QD) for 7 doses or vice versa. Serial urine samples were collected before and up to 24 h after dosing on days 1 and 5. Eight bacterial strains with various genotypic and phenotypic susceptibilities to fosfomycin were used for all experiments (5 Escherichia coli, 2 Klebsiella pneumoniae, and 1 Proteus mirabilis). MICs were performed via agar dilution. Urinary bactericidal titers (UBTs) were performed via modified Schlichter test using participant's drug-free urine as the diluent. Urinary time-kill analyses were performed on pooled 24-h urine aliquots from days 1 and 5. All experiments were performed in triplicate with and without the addition of 25 mg/liter of glucose-6-phosphate (G6P). Mean 24-h urine concentrations of fosfomycin ranged from 324.7 to 434.6 mg/liter regardless of study day or dosing regimen. The urinary antibacterial activity of fosfomycin was also similar across study days and dosing regimens. UBT values did not correlate with MICs determined in the presence of G6P. Fosfomycin was reliably bactericidal in urine only against the 5 E. coli strains, regardless of genotype or MIC value. Together, these data do not support the use of oral fosfomycin tromethamine for pathogens other than E. coli or at a dosing frequency higher than QOD. Fosfomycin MICs determined in the presence of G6P may not accurately reflect the in vivo activity given the lack of G6P in human urine. (This study has been registered at ClinicalTrials.gov under identifier NCT02570074.).

Evolving oxazolidinone resistance mechanisms in a worldwide collection of enterococcal clinical isolates: results from the SENTRY Antimicrobial Surveillance Program.

Objectives: This study evaluated the oxazolidinone resistance mechanisms among a global collection of enterococcal clinical isolates. The epidemiology of optrA-carrying isolates and the optrA genetic context were determined. Methods: Enterococcal isolates (26 648) from the SENTRY Antimicrobial Surveillance Program (2008-16) were identified by MALDI-TOF MS and MICs were determined by broth microdilution. Isolates with linezolid MICs of ≥4 mg/L were screened for resistance mechanisms. Isolates carrying optrA had their genome sequenced for genetic context and epidemiology information. Results: Thirty-six Enterococcus faecalis and 66 Enterococcus faecium had linezolid MICs of ≥4 mg/L (0.38% of surveillance enterococci). E. faecalis had a linezolid MIC range of 4-16 mg/L, while E. faecium displayed higher values (4-64 mg/L). Nine E. faecalis had G2576T mutations and optrA was detected in 26 (72.2%) isolates from the Asia-Pacific region, North America, Latin America and Europe; 3 isolates also produced Cfr [Thailand (1)] or Cfr(B) [Panama (2)]. All E. faecium isolates had G2576T alterations, while three isolates from the USA had concomitant presence of cfr(B). The optrA gene was plasmid- and chromosome-located in 22 and 3 E. faecalis, respectively. One isolate signalled hybridization on plasmid and chromosome. The genetic context of optrA varied. E. faecalis belonging to the same clonal complex were detected in distinct geographical regions. Also, genetically distinct isolates from Ireland had an identical optrA context, indicating plasmid dissemination. Conclusions: Alterations in 23S rRNA remained the main oxazolidinone resistance mechanism in E. faecium, while optrA prevailed in E. faecalis. These results demonstrate global dissemination of optrA and warrant surveillance for monitoring.

Relationship between day 1 and day 2 Vancomycin area under the curve values and emergence of heterogeneous Vancomycin-intermediate Staphylococcus aureus (hVISA) by Etest® macromethod among patients with MRSA bloodstream infections: a pilot study.

BACKGROUND: In vitro data suggests that suboptimal initial vancomycin exposure may select for heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections. However, no clinical studies have evaluated the relationship between initial vancomycin exposure and emergence of hVISA. This pilot study seeks to assess the relationship between day 1 and day 2 vancomycin area under the curve (AUC) and emergence of hVISA bloodstream infections (BSIs) by Etest® macromethod among patients with a non-hVISA BSI at baseline. METHODS: This was a retrospective cohort study of patients with methicillin-resistant Staphylococcus aureus (MRSA) BSIs at Albany Medical Center Hospital (AMCH) between January 2005 and June 2009. The vancomycin AUC exposure variables on day 1 (AUC0-24h) and day 2 (AUC24-48h) were estimated using the maximal a posteriori probability (MAP) procedure in ADAPT 5. RESULTS: There were 238 unique episodes of MRSA BSIs during the study period, 119 of which met inclusion criteria. Overall, hVISA emerged in 7/119 (5.9%) of patients. All 7 cases of hVISA involved patients who did not achieve area under the curve over broth microdilution minimum inhibitory concentration (AUC0-24h/MICBMD) ratio of 521 or an AUC24-48h/MICBMD ratio of 650. No associations between other day 1 and day 2 AUC variables and emergence of hVISA were noted. CONCLUSIONS: Although more data are needed to draw definitive conclusions, these findings suggest that hVISA emergence among patients with non-hVISA MRSA BSIs at baseline may be partially explained by suboptimal exposure to vancomycin in the first 1 to 2 days of therapy. At a minimum, these findings support further study of the relationship between initial vancomycin exposure and hVISA emergence among patients with MRSA BSIs in a well-powered, multi-center, prospective trial.

Antimicrobial activity of tigecycline and cefoperazone/sulbactam tested against 18,386 Gram-negative organisms from Europe and the Asia-Pacific region (2013-2014).

A total of 18,386 organisms, including 13,224 Enterobacteriaceae, 3536 Pseudomonas aeruginosa, 1254 Acinetobacter spp., and 372Stenotrophomonas maltophilia were collected from Western Europe (WEU; n=10,021), Eastern Europe (EEU; n=4957), and the Asia-Pacific region (APAC; n=3408 [1052 from China]) in 2013-2014 as part of the SENTRY Antimicrobial Surveillance Program and tested by a reference broth microdilution method for susceptibility against tigecycline, cefoperazone/sulbactam, and comparator agents. Overall, 95.3% of Enterobacteriaceae were susceptible (≤1µg/mL; EUCAST) to tigecycline (MIC50/90, 0.12/1µg/mL) with regional EUCAST susceptibility rates of 94.8-97.8% (98.9-99.6% inhibited at ≤2µg/mL [US FDA]). Among Acinetobacter spp., 66.1% (EEU) and 79.5% (WEU) were inhibited at ≤1µg/mL of tigecycline (94.9% and 97.3% inhibited at ≤2µg/mL; pan-European MIC50/90, 1/2µg/mL). For S. maltophilia, 65.4% (China) to 88.9% (EEU) of the isolates were inhibited at ≤1µg/mL of tigecycline. Cefoperazone/sulbactam inhibited 94.6/83.5/91.5% of Enterobacteriaceae at ≤16µg/mL in WEU/EEU/APAC, respectively.

Update of the activity of telavancin against a global collection of Staphylococcus aureus causing bacteremia, including endocarditis (2011-2014).

The efficacy and safety of telavancin is under evaluation for the treatment of subjects with complicated Staphylococcus aureus bacteremia and S. aureus right-sided infective endocarditis. This study evaluated the telavancin activity against a global collection of S. aureus causing bloodstream infections (BSI), including endocarditis, to support the development of bacteremia/endocarditis clinical indications. This study included a total of 4191 S. aureus [1490 methicillin-resistant S. aureus (MRSA)], which were unique (one per patient) clinical isolates recovered from blood samples collected during 2011-2014 in a global network of hospitals. All isolates were deemed responsible for BSI, including endocarditis, by local guidelines. Isolates were tested for susceptibility by broth microdilution. Telavancin (MIC50/90, 0.03/0.06 µg/ml) inhibited all S. aureus at ≤0.12 µg/ml, the breakpoint for susceptibility. Equivalent minimum inhibitory concentration (MIC) values (MIC50/90, 0.03/0.06 µg/ml) were obtained for telavancin against methicillin-susceptible S. aureus (MSSA) and MRSA isolates, as well as MRSA from community and healthcare origins. Similar telavancin activities (MIC50, 0.03 µg/ml) were observed against MRSA subsets from North America and Europe, while isolates from the Asia-Pacific (APAC) and Latin America regions had MIC50 values of 0.06 µg/ml. MRSA with vancomycin MIC values of 2-4 µg/ml and the multidrug resistance (MDR) subset had telavancin MIC50 results of 0.06 µg/ml, although the MIC100 result obtained against these subsets remained identical to those of MSSA (MIC100, 0.12 µg/ml, respectively). This study updates the telavancin in vitro activity, which continues to demonstrate great potency against invasive S. aureus, regardless of the susceptibility phenotype or demographic characteristics (100.0% susceptible), and supports the sought-after subsequent indications.

Oxidative stress in dairy cows naturally infected with the lungworm Dictyocaulus viviparus (Nematoda: Trichostrongyloidea).

The aim of this study was to analyse the oxidative and anti-oxidant status in serum samples from dairy cows naturally infected by Dictyocaulus viviparus and its relation with pathological analyses. The diagnosis of the disease was confirmed by necropsy of one dairy cow with heavy infection by the parasite in the lungs and bronchi. Later, blood and faeces were collected from another 22 cows from the same farm to measure reactive oxygen species (ROS) levels, thiobarbituric acid-reactive substances (TBARS), catalase (CAT) and superoxide dismutase (SOD) activities on day 0 (pre-treatment) and day 10 (post-treatment with eprinomectin). Faecal examination confirmed the infection in all lactating cows. However, the number of D. viviparus larvae per gram of faeces varied between animals. Cows showed different degrees of severity according to respiratory clinical signs of the disease (cough and nasal secretion). Further, they were classified and divided into two groups: those with mild (n = 10) and severe disease (n = 12). Increased levels of TBARS (P < 0.001), ROS (P = 0.002) and SOD activity (P < 0.001), as well as reduced CAT activity (P < 0.001) were observed in cows with severe clinical signs of the disease compared to those with mild clinical signs. Eprinomectin treatment (day 10) caused a reduction of ROS levels (P = 0.006) and SOD activity (P < 0.001), and an increase of CAT activity (P = 0.05) compared to day 0 (pre-treatment). TBARS levels did not differ with treatment (P = 0.11). In summary, increased ROS production and lipid peroxidation altered CAT and SOD activities, as an adaptive response against D. viviparus infection, contributing to the occurrence of oxidative stress and severity of the disease. Treatment with eprinomectin eliminated the infection, and thus minimized oxidative stress in dairy cows.

Relationship Between Pathological Findings and Cholinesterase Activity and Nitric Oxide Levels in Cattle Infected Naturally by Eurytrema coelomaticum.

The aim of this study was to evaluate the role of butyrylcholinesterase (BChE) (in the serum and pancreas), acetylcholinesterase (AChE) (in the whole blood and pancreas) and nitric oxide (NO) (in the serum and pancreas) in cattle infected naturally by Eurytrema coelomaticum. Fifty-one cattle were studied, including 33 infected by E. coelomaticum and 18 uninfected animals. Significantly greater AChE activity was found in the pancreas of infected animals (P <0.01); however, these cattle had lower AChE activity in whole blood. BChE activity was greater in the sera of infected animals (P = 0.05), but was less in pancreatic samples. NO levels were significantly higher in the sera (P <0.05) and pancreas (P <0.001) of infected cattle compared with uninfected animals. A positive correlation was found between AChE activity in the pancreas and parasite load, but there was negative correlation between pancreatic BChE activity and parasitic load. Expression of AChE, BChE and NO is therefore linked to the inflammation caused by E. coelomaticum in cattle.

Antimicrobial activity of solithromycin against serotyped macrolide-resistant Streptococcus pneumoniae isolates collected from U.S. medical centers in 2012.

Solithromycin, a next-generation macrolide and novel fluoroketolide, was tested against a 2012 collection of serotyped U.S. macrolide-resistant Streptococcus pneumoniae isolates associated with community-acquired bacterial pneumonia (CABP). Against all 272 isolates, solithromycin demonstrated high potency (MIC50/90, 0.06/0.25 µg/ml), and it inhibited all strains at MICs of ≤0.5 µg/ml, including the two most prevalent macrolide-resistant serotypes (19A and 35B). These data support the continued clinical development of solithromycin for the treatment of multidrug-resistant CABP.

Timpanismo ruminal crônico secundário à hipoplasia de pregas de omaso em dois bovinos / Chronic ruminal bloat secondary to omasal laminae hypoplasia in two cattle

Um novilho normando e outro charolês apresentando distensão abdominal, diarreia intermitente e timpanismo ruminal crônico, que iniciaram após desmame, foram enviados para necropsia. Observou-se ausência de pregas omasais associada à hipoplasia do órgão, assim como redução de tamanho das papilas ruminais e reticulares. Com base nas lesões e histórico, conclui-se que o timpanismo ruminal foi ocasionado pela falha no desenvolvimento do omaso...

Two emaciated juvenile steers, one Normande and one Charolaise breed with abdominal distension, intermittent diarrhea and chronic ruminal bloat that had begun at weaning were necropsied. Absence of the omasal laminae with omasal hypoplasia were found together with loss of ruminal papillae and reticular folds. Based on the lesions and history we concluded that the ruminal bloat was due to a development failure of the omasum...

Quantifying the matrix of relationships between reduced vancomycin susceptibility phenotypes and outcomes among patients with MRSA bloodstream infections treated with vancomycin .

OBJECTIVES: Several phenotypic characteristics of Staphylococcus aureus have been identified as aetiological factors responsible for adverse outcomes among patients receiving vancomycin. However, characterization of the outcomes associated with these reduced vancomycin susceptibility phenotypes (rVSPs) remains largely incomplete and it is unknown if these features contribute to deleterious treatment outcomes alone or in concert. This study described the interrelationship between rVSPs and assessed their individual and combined effects on outcomes among patients who received vancomycin for a methicillin-resistant S. aureus (MRSA) bloodstream infection. METHODS: An observational study of adult, hospitalized patients with MRSA bloodstream infections who were treated with vancomycin between January 2005 and June 2009 was performed. The rVSPs evaluated included the following: (i) Etest MIC; (ii) broth microdilution MIC; (iii) MBC : MIC ratio; and (iv) heteroresistance to vancomycin by the Etest macromethod. Failure was defined as any of the following: (i) 30 day mortality; (ii) bacteraemia ≥ 7 days on therapy; or (iii) recurrence of MRSA bacteraemia within 60 days of therapy discontinuation. RESULTS: During the study period, 184 cases met the study criteria and 41.3% met the failure criteria. There was a clear linear exposure-response relationship between the number of these phenotypic markers and outcomes. As the number of phenotypes escalated, the incidence of overall failure increased incrementally by 10%-18%. CONCLUSIONS: The data suggest that rVSPs contribute to deleterious treatment outcomes in concert.

Humoral immune response in goats immunised with cathepsin L1, peroxiredoxin and Sm14 antigen and experimentally challenged with Fasciola hepatica.

The humoral immune response was analysed in goats immunised with FhCL1, FhPrx, Sm14, and experimentally challenged with Fasciola hepatica. All immunised animals developed significant levels of anti-fluke specific antibodies and those immunised with FhCL1 showed the highest antibody titre. After experimental infection, an increase in the antibody level was detected only in goats immunised with FhCL1. In the adjuvant-control animals, the experimental challenge induced significant production of specific antibodies against FhCL1, FhPrx and Sm14. While liver fluke specific humoral responses were seen in all groups, no significant protection in any of the vaccinated groups was found.

Doença granulomatosa sistêmica em bovinos no estado de Santa Catarina associada ao pastoreio de ervilhaca peluda (Vicia villosa) / Systemic granulomatous disease in cattle in Santa Catarina, Brazil, associated with grazing of vetch (Vicia villosa)

Spontaneous intoxication in three dairy cows grazing pasture contaminated with Vicia villosa in two different farms was reported. Hyperthermia, skin alopecia and pruritus were the main clinical signs. Macroscopically, gray to white up to 5cm nodules were detected, especially in kidney and lymph nodes, which correspond to mild to severe multifocal granulomatous infiltrate. This is the first report of systemic granulomatous disease due to consumption of hairy vetch in the State of Santa Catarina, Brazil.

Eight-year (2002-2009) summary of the linezolid (Zyvox® Annual Appraisal of Potency and Spectrum; ZAAPS) program in European countries.

The linezolid surveillance network (ZAAPS program) has been monitoring linezolid activity and susceptibility rates for eight years (2002-2009) in european medical centers. Samples from 12-24 sites annually in 11 countries were monitored by a central laboratory design using reference MIC methods with international and regional interpretations (EUCAST). A total of 13,404 gram-positive pathogens were tested from 6 pathogen groups. Linezolid remained without documented resistance from 2002 through 2005, but beginning in 2006 resistant strains emerged at very low rates among Staphylococcus aureus (G2576T mutant in ireland, 2007), coagulase-negative staphylococci (CoNS; usually Staphylococcus epidermidis, France and Italy in 2006-2009) and enterococci (Enterococcus faecium in Germany [2006, 2008, 2009] and E. faecalis in Sweden [2008], United Kingdom [2008] and Germany [2009]); all but one strain having a target mutation. A mobile cfr was detected in an italian CoNS strain (2008 and 2009), and clonal spread was noted for linezolid-resistant strains (PFGE results). Overall the linezolid susceptibility rates were >99.9, 99.7 and 99.6% for S. aureus, CoNS and enterococci, respectively; and all streptococcal strains were susceptible (MIC(90), 1 mg/l). In conclusion, the ZAAPS program surveillance confirmed high, sustained levels of linezolid activity from 2002-2009 and without evidence of MIC creep or escalating resistance in gram-positive pathogens across monitored european nations.

Telavancin Activity against gram-positive bacteria isolated from patients with skin and skin-structure infections.

Telavancin is approved in the United States and Canada for the treatment of complicated skin and skin structure infections (cSSSI) in adults caused by susceptible Gram-positive organisms. The antimicrobial activity of telavancin and comparators was evaluated against 5,027 (2007-2008) Gram-positive bacteria responsible for SSSI in medical centers in Asia-Pacific, European, Latin American, and North American regions. Telavancin was active against Staphylococcus aureus (MIC50(/)90, 0.12/0.25 mg/l; 100.0% susceptible) and coagulase-negative staphylococci (MIC50(/)90, 0.12/0.25 mg/l). telavancin inhibited all Enterococcus faecalis, including four strains displaying a VanB phenotype, at ≤ 1 mg/L (MIC50(/)90, 0.25/0.5 mg/l), except for two isolates with a VanA phenotype (MIC, >2 mg/l). Vancomycin-susceptible and VanB vancomycin-resistant E. faecium were inhibited by telavancin at ≤ 0.25 mg/L, while this drug exhibited elevated MIC values (≥ 0.5 mg/l) against E. faecium of VanA phenotype (MIC50(/)90, 2/>2 mg/l). Telavancin was potent against ß-haemolytic streptococci (MIC50(/)90, 0.03/0.12 mg/l; 100.0% susceptible) and viridans group streptococci (MIC50(/)90, 0.03/0.06 mg/l; 100.0% susceptible). These in vitro data document the activity of telavancin against contemporary Gram-positive isolates and support its clinical use for the treatment of cSSSI caused by the indicated pathogens.

Evaluation of hepatic damage and local immune response in goats immunized with native glutathione S-transferase of Fasciola hepatica.

Worm burden, hepatic damage and local cellular and humoral immune responses were assessed in goats immunized with glutathione-S-transferase and challenged with Fasciola hepatica. Infected but unimmunized and uninfected control groups were also studied. Hepatic damage was evaluated grossly and microscopically. Local immune response was evaluated by (1) microscopical examination of hepatic lymph nodes (HLNs); (2) analysis of the distribution of CD2(+), CD4(+), CD8(+), T-cell receptor gammadelta(+) lymphocytes and immunoglobulin (Ig) G(+) plasma cells; and (3) investigation of the distribution of cells expressing interleukin (IL)-4 and interferon (IFN)-gamma in the hepatic inflammatory infiltrates and HLNs. Immunized animals did not have significant reduction in fluke number, but there was significant (P<0.05) reduction of fluke size relative to the control groups. The lesions in the two infected groups were similar and consisted of fibrous perihepatitis and white tortuous tracts, mainly involving the left hepatic lobe. Microscopical lesions were similar in both infected groups and were typical of chronic fascioliosis. These included portal fibrosis, inflammatory infiltration with plasma cells, formation of lymphoid follicles, accumulation of haemosiderin-laden macrophages and granulomatous foci. Both infected groups had a marked local immune response characterized by infiltration of CD2(+), CD4(+) and CD8(+) T lymphocytes, and IgG(+) plasma cells in hepatic lesions and in HLNs. There was no expression of IL-4 or INF-gamma by cells in the hepatic inflammatory infiltrate, but expression of INF-gamma in HLNs was much lower than that of IL-4, suggesting an immune response dominated by T helper 2 cells.