A large retrospective assessment of voriconazole exposure in patients treated with extracorporeal membrane oxygenation

Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population. Methods: Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit’s binding sites over time. Results: Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO (p = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2–4.7) mg/L under ECMO and 2.5 (1.4–3.9) mg/L without ECMO (p = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure. Conclusions: No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations

Phylogenetic Analysis of Staphylococcus aureus CC398 Reveals a Sub-Lineage Epidemiologically Associated with Infections in Horses

In the early 2000s, a particular MRSA clonal complex (CC398) was found mainly in pigs and pig farmers in Europe. Since then, CC398 has been detected among a wide variety of animal species worldwide. We investigated the population structure of CC398 through mutation discovery at 97 genetic housekeeping loci, which are distributed along the CC398 chromosome within 195 CC398 isolates, collected from various countries and host species, including humans. Most of the isolates in this collection were received from collaborating microbiologists, who had preserved them over years. We discovered 96 bi-allelic polymorphisms, and phylogenetic analyses revealed that an epidemic sub-clone within CC398 (dubbed 'clade (C)') has spread within and between equine hospitals, where it causes nosocomial infections in horses and colonises the personnel. While clade (C) was strongly associated with S. aureus from horses in veterinary-care settings (p = 2 × 10(-7)), it remained extremely rare among S. aureus isolates from human infections

The utility of the PCR method to study aacA gene heterogeneity in Serratia marcescens36656

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Comparative in vitro activity of cefepime and four extended-spectrum beta-lactams on 1,251 aminoglycoside-resistant gram-negative hospital strains36644

Cefepime was the most active compound on the Enterobacteriaceae with a MIC90 of 0.26 microgram/ml and a resistance rate of 0.1%. Ceftazidime was the most active drug on the non-fermenting bacilli (MIC90 9.65 micrograms/ml; resistance rate 3%). Amikacin- and gentamicin-resistant strains showed a decreased susceptibility to the beta-lactams, though the Enterobacteriaceae and the non-fermenters remained fairly sensitive to cefepime and ceftazidime, respectively. Aminoglycoside-3-N-acetyltransferase was the most prevalent enzyme and was often associated with intermediate resistance or resistance to beta-lactams. Non-fermenters showing aminoglycoside impermeability were very often intermediately resistant or resistant to beta-lactams</p

Antibacterial activity of carumonam and cefpirome on hospital strains resistant to gentamicin and cephalothin: comparison with other beta-lactam antibiotics, new fluoroquinolones, aminoglycosides and other antibiotics

&lt;p&gt;The antibacterial in vitro activity of carumonam, a new monobactam, and cefpirome, a new cephalosporin, was studied on 483 hospital strains resistant to gentamicin and cephalothin, in comparison with amikacin, azlocillin, aztreonam, cefmenoxim, cefoperazone, cefotaxim, cefsulodin (for Pseudomonas), ceftazidime, ceftriaxone, cefuroxim, chloramphenicol, ciprofloxacin, doxycycline, enoxacin, netilmicin, norfloxacin, pefloxacin, piperacillin, rifampicin, tobramycin and trimethoprim. In general the two compounds have a very good in vito activity on Enterobacteriaceae but are less active on non-fermenting microorganisms. For the Enterobacteriaceae the minimal inhibitory concentrations 90% for carumonam was less than or equal to 1.1 mg/l excepted for Enterobacter spp. (43,6 mg/l) and M. morganii (56.8 mg/l) . All the Enterobacteriaceae are susceptible to cefpirome (minimal inhibitory concentrations 90% less than or equal to 5.3 mg/l). The activity of carumonam and cefpirome on Enterobacteriaceae is comparable with that of the third generation cephalosporins. Carumonam is more active than cefpirome and other beta-lactams, ceftazidime excepted, on Pseudomonas aeruginosa and Pseudomonas spp. On the other hand, both compounds reveal to have only a low activity on the other non-fermenters which minimal inhibitory concentrations 90% values of 115.4 mg/l for carumonam and 32.0 mg/l for cefpirome&lt;/p&gt;</p

Contribution of two molecular assays as compared to selective culture for MRSA screening in a low MRSA prevalence population

BACKGROUND: As the prompt detection of methicillin-resistant Staphylococcus aureus (MRSA) carriers upon admission is fundamental in the MRSA prevention strategy of our hospital, the infection control team is eagerly seeking the most sensitive and rapid screening method. The aim of this study was to compare the performance of two molecular techniques with a conventional MRSA-selective culture test (Bio-Rad chromogenic MRSASelect) in order to elucidate the suitability of the assays specifically in an expected low MRSA prevalence population. PATIENTS AND METHODS: The anterior nares and throat of 500 patients and visitors attending the emergency department of Sint-Jan General Hospital between May and June 2007 were sampled, and MRSA carriage was determined by selective culture after enrichment and the BD GeneOhm StaphSR and the Cepheid Xpert MRSA assays. RESULTS: Eight MRSA carriers were detected by selective culture (1.6% prevalence). The sensitivity, specificity, positive [corrected] predictive value, and negative [corrected] predictive value were 62.5, 99.0, 50.0, and 99.4% for BD GeneOhm StaphSR and 62.5, 97.7, 31.3, and 99.4% for Cepheid Xpert MRSA, respectively. CONCLUSIONS: We conclude that MRSA rapid screening techniques must be interpreted cautiously in a low-prevalence population, as the sensitivity is lower than in selected high-risk populations. MRSA carriers detected with molecular techniques must be confirmed by conventional culture methods for follow-up. The specificity and negative predictive value indicate that molecular rapid methods are worthwhile to be considered in MRSA-preventive strategies

The comparative activity of pefloxacin, enoxacin, ciprofloxacin and 13 other antimicrobial agents against enteropathogenic microorganisms36622

In this study, we compared the activity of pefloxacin, enoxacin and ciprofloxacin against 269 enteropathogenic strains (Campylobacter jejuni, enteropathogenic Escherichia coli, Salmonella typhi, Shigella spp., Vibrio cholerae and Yersinia enterocolitica) with that of rosoxacin, flumequin, nifuroxazide, erythromycin, chloramphenicol, ampicillin, cefotaxime, tetracycline, amikacin, netilmicin, sulfamethoxazole, trimethoprim and co-trimoxazole. Pefloxacin, enoxacin and ciprofloxacin were always among the most active compounds. Furthermore, resistant strains or strains with elevated MIC values were not found. The MIC90 value for these three compounds was less than or equal to 0.25 mg/l, except for C. jejuni where it was 0.3 mg/l and 1.4 mg/l for pefloxacin and enoxacin, respectively</p

Activity of cefotiam in combination with beta-lactam antibiotics on enterobacterial hospital strains36636

By using checkerboard titrations the effect of cefotiam combined with different beta-lactam antibiotics on fifty strains of Enterobacteriaceae moderately susceptible (minimal inhibiting concentration greater than or equal to 8 mg/l) or resistant (minimal inhibiting concentration greater than or equal to 64 mg/l) to cefotiam was evaluated. The following compounds were tested: cefamandole, cefazolin, cefmenoxime, cefotaxime, cefotiam, ceftazidime, cefuroxime, mecillinam and piperacillin. The synergistic effect varied markedly. The combination cefotiam-mecillinam showed the highest rate of synergistic activity. Antagonism was found in 1% of the combinations</p

Serotypes and extended spectrum beta-lactam resistance in aminoglycoside resistant Pseudomonas aeruginosa isolates from two Belgian general hospitals: a seven year study36650

A total of 1896 isolates of Pseudomonas aeruginosa resistant to aminoglycosides and isolated during the period 1983-1989 in two Belgian general hospitals were included in this study. The most frequently encountered O serotypes were O4, O11, O12 and non-typable isolates. The majority of the isolates showed resistance to extended spectrum beta-lactam antibiotics (cefotaxime, ceftriaxone and cefepime). However, a low degree of resistance was found for ceftazidime. By contrast, amikacin and isepamicin, remained active on a significant number of aminoglycoside resistant isolates. In both hospitals, impermeability and AAC(3)II enzyme production were the most prevalent aminoglycoside resistance mechanisms. There were marked differences between the two hospitals with regard to the distribution of the O-serotypes and resistance profiles</p