Burden of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay associated with bloodstream infections due to Escherichia coli resistant to third-generation cephalosporins.

OBJECTIVES: This study determined excess mortality and length of hospital stay (LOS) attributable to bloodstream infection (BSI) caused by third-generation-cephalosporin-resistant Escherichia coli in Europe. METHODS: A prospective parallel matched cohort design was used. Cohort I consisted of patients with third-generation-cephalosporin-resistant E. coli BSI (REC) and cohort II consisted of patients with third-generation-cephalosporin-susceptible E. coli BSI (SEC). Patients in both cohorts were matched for LOS before infection with patients free of the respective BSI. Thirteen European tertiary care centres participated between July 2007 and June 2008. RESULTS: Cohort I consisted of 111 REC patients and 204 controls and cohort II consisted of 1110 SEC patients and 2084 controls. REC patients had a higher mortality at 30 days (adjusted odds ratio = 4.6) and a higher hospital mortality (adjusted hazard ratio = 5.7) than their controls. LOS was increased by 8 days. For SEC patients, these figures were adjusted odds ratio = 1.9, adjusted hazard ratio = 2.0 and excess LOS = 3 days. A 2.5 times [95% confidence interval (95% CI) 0.9-6.8] increase in all-cause mortality at 30 days and a 2.9 times (95% CI 1.2-6.9) increase in mortality during entire hospital stay as well as an excess LOS of 5 days (95% CI 0.4-10.2) could be attributed to resistance to third-generation cephalosporins in E. coli BSI. CONCLUSIONS: Morbidity and mortality attributable to third-generation-cephalosporin-resistant E. coli BSI is significant. If prevailing resistance trends continue, high societal and economic costs can be expected. Better management of infections caused by resistant E. coli is becoming essential.

Streptococcus mutans, Streptococcus sobrinus and Candida albicans in oral samples from caries-free and caries-active children.

AIM: This was to examine the occurrence of S. mutans, S. sobrinus and C. albicans in dental plaque and saliva from caries-free and caries-active Greek children. METHODS: Saliva and dental plaque samples from 46 caries-free and 51 caries-active 3-to-13-year-old children were examined using selective media for the three microbes. Identification of isolated mutans streptococci (S. mutans and S. sobrinus) was performed with biochemical test and specific DNA probes. The salivary levels of mutans streptococci were additionally determined by a chair-side test (Dentocult® SM strips). RESULTS: The isolation frequencies of S. mutans, S. sobrinus and C. albicans were 66, 11 and 18 %, respectively. Caries-active children harboured more frequently and at significantly higher numbers the specific microbes than caries-free children. A similar pattern was observed with the Dentocult® SM strip scores. No correlation was found between the presence of these microbes and the age or gender of the children. CONCLUSIONS: Caries experience was statistically significantly related to the presence of all three microbes under study, both in dental plaque and saliva.

Efficacy of deoxycholate amphotericin B and unilamellar liposomal amphotericin B in prophylaxis of experimental Aspergillus fumigatus endocarditis.

OBJECTIVE: To evaluate and compare in vivo the protective efficacy of unilamellar liposomal amphotericin B (L-AmB) with that of deoxycholate amphotericin B (D-AmB) in experimental endocarditis. MATERIAL AND METHODS: In the rabbit model of experimental Aspergillus fumigatus endocarditis, two doses of each antifungal agent (1.5 mg/kg each) were administered intravenously at 4 hours and at 30 minutes before challenge with an inoculum of A. fumigatus. Three days later, the animals were sacrificed, and the aortic vegetations were analyzed. RESULTS: All 19 animals that did not receive chemoprophylaxis acquired endocarditis. In contrast, endocarditis developed in 2 of 10 animals pretreated with D-AmB (P < 0.01) and 3 of 8 animals pretreated with L-AmB (P < 0.01). Both D-AmB and L-AmB prevented the development of endocarditis due to A. fumigatus and decreased the concentration of fungi in the aortic vegetations by more than 1 log10. CONCLUSION: In the rabbit experimental model of Aspergillus endocarditis, D-AmB and L-AmB were equally effective in reducing the incidence of the infection and the tissue burden of fungi.

Comparative in vitro and in vivo efficacy of roxithromycin and erythromycin against a strain of methicillin-susceptible Staphylococcus epidermidis.

The in vitro and in vivo efficacy of roxithromycin was compared with that of erythromycin, against a methicillin-susceptible strain of Staphylococcus epidermidis. We performed standard in vitro testing (MIC, MBC, and time-kill kinetics) for roxithromycin, erythromycin, and rifampin. Both macrolides were bacteriostatic in vitro. There was no significant difference in microbial survival between erythromycin and roxithromycin groups in the time-kill kinetics (p = 0.3). For the in vivo experiments, using the rabbit experimental endocarditis model, roxithromycin was found to be inferior to erythromycin in decreasing the microbial burden of the endocardial vegetations (p < 0.05). Rifampin was highly effective, both in vitro and in vivo. In conclusion, the efficacy of roxithromycin was poor and inferior to erythromycin against a strain of methicillin-susceptible S. epidermidis.

Field trials to determine residues of chlozolinate in table grapes.

Chlozolinate (Serinal) is a dicarboximide fungicide used in southern European countries principally on grapes. Maximum residue levels have not yet been set by FAO/WHO and are under evaluation in the EU. Field trials have been carried out in Greece on two varieties of table grapes (Cardinal and Victoria) during two consecutive years to assess residues remaining after application according to good agricultural practice. Analysis using a multiresidue method with gas chromatography (ECD) showed that the parent compound decays with a first-order rate constant of 0.057 +/- 0.011 day(-)(1) and that residues had fallen below the proposed MRL of 5 mg/kg in all samples by 21 days postapplication (the proposed PHI). The contribution of the main metabolite, S1, to the total residue is generally <20%. Washing removes a substantial amount (up to 80%) of chlozolinate, which appears to be nonsystemic on grapes, thus reducing real consumer exposure to this pesticide.

A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies.

Invasive candidiasis is a life-threatening infection in patients with haematological malignancies. The objective of our study was to determine the incidence, microbiological characteristics and clinical outcome of candidaemia among hospitalized adult patients with haematological malignancies. This is a population-based, prospective, multicentre study of patients ≥ 18 years admitted to haematology and/or haematopoietic stem cell transplantation units of nine tertiary care Greek hospitals from January 2009 through to February 2012. Within this cohort, we conducted a nested case-control study to determine the risk factors for candidaemia. Stepwise logistic regression was used to identify independent predictors of 28-day mortality. Candidaemia was detected in 40 of 27,864 patients with haematological malignancies vs. 967 of 1,158,018 non-haematology patients for an incidence of 1.4 cases/1000 admissions vs. 0.83/1000 respectively (p <0.001). Candidaemia was caused predominantly (35/40, 87.5%) by non-Candida albicans species, particularly Candida parapsilosis (20/40, 50%). In vitro resistance to at least one antifungal agent was observed in 27% of Candida isolates. Twenty-one patients (53%) developed breakthrough candidaemia while receiving antifungal agents. Central venous catheters, hypogammaglobulinaemia and a high APACHE II score were independent risk factors for the development of candidaemia. Crude mortality at day 28 was greater in those with candidaemia than in control cases (18/40 (45%) vs. 9/80 (11%); p <0.0001). In conclusion, despite antifungal prophylaxis, candidaemia is a relatively frequent infection associated with high mortality caused by non-C. albicans spp., especially C. parapsilosis. Central venous catheters and hypogammaglobulinaemia are independent risk factors for candidaemia that provide potential targets for improving the outcome.

Conditional evaluation of broncho-alveolar lavage in mechanically ventilated patients with suspected unilateral lobar pneumonia.

OBJECTIVE: In an attempt to improve our ability to diagnose the cause of ventilator-associated pneumonia (VAP), we explore the usefulness of the conditional evaluation of bronchoalveolar lavage (BAL) samples from the involved and non-involved areas in patients with suspected unilateral lobar VAP (UL-VAP). DESIGN: Prospective study. SETTING: University teaching hospital intensive care unit. PATIENTS: We studied 19 consecutive patients with suspected UL-VAP. MEASUREMENTS AND MAIN RESULTS: Nine of the 12 patients (47%) developed UL-VAP. There was a significant difference between the involved and non-involved areas in UL-VAP patients (P < 0.001) in respect of the quantitative bacterial cultures (QBCs) of BAL samples for each micro-organism, whereas there was no difference in patients without UL-VAP. When we applied the criterion of usual BAL (one micro-organism in concentrations > 10(5) colony-forming units per millilitre) for UL-VAP diagnosis, the sensitivity was 100%, the specificity 70%, the positive predictive value 75%, and the negative predictive value 100%. When we used the conditional evaluation of the BAL results for UL-VAP diagnosis, in the involved and non-involved areas, the sensitivity was 78%, the specificity 90%, the positive predictive value 87.5% and the negative predictive value 82%. A statistically significant difference was found when we compared the difference in QBCs between the BAL samples for each micro-organism, between the involved and non-involved areas in patients with and without VAP (P < 0.001). CONCLUSION: These data suggest that utilisation of the conditional evaluation of the QBCs of BAL samples improves significantly our ability to diagnose the cause of UL-VAP.

The diagnostic value of gram stain of bronchoalveolar lavage samples in patients with suspected ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is one of the most common causes of morbidity and mortality in intensive care unit patients. However, the diagnosis is quite difficult. Gram stain (GS) of bronchoalveolar lavage (BAL) sample is a time-saving diagnostic method for VAP. However, its clinical significance has not been adequately investigated. The aim of this study was to determine its sensitivity and specificity for VAP diagnosis. We prospectively performed GS and quantitative bacterial cultures (QBC) of BAL samples, obtained through fiberoptic bronchoscope, in 75 consecutive postoperative and/or multiple trauma patients with suspected VAP. We considered BAL-GS as positive for VAP diagnosis when (i) polymorphonuclear neutrophils were > 25 per optic field at a magnification x 100 (p.o.f x 100); (ii) squamous epithelial cells were < 1% p.o.f x 100; and (iii) one or more microorganisms were seen p.o.f. at a magnification x 1,000 (p.o.f. x 1,000). VAP was diagnosed with criteria similar to those used in previous studies. Pneumonia was the final diagnosis in 22/75 (29%) patients. The BAL-GS was positive in 17/22 patients with VAP and in 7/53 patients without VAP. Accordingly, the sensitivity of BAL-GS for VAP diagnosis was 77%, the specificity 87%, the positive predictive value 71% and the negative predictive value 90%. Our data suggest that BAL-GS has good sensitivity and high specificity for VAP diagnosis. It could therefore constitute a useful complementary tool in the task of early diagnosis and treatment of VAP.