Save Antibiotics: a call for action of the World Alliance Against Antibiotic Resistance (WAAAR)

International audienceResistance to antibiotics has recently increased dramatically worldwide. The pipeline of new classes of antibiotics is dry for at least the next few years. Therefore antibiotic resistance represents one of the most problematic public health issues of our time. Treatment failures already happen in increasing numbers for common community-acquired infections, such as urinary tract infections or intra-abdominal infections. This is due in particular to Enterobacteriaceae harboring extended-spectrum beta-lactamases (ESBL). Enterobacteriaceae harboring carbapenemases are also highly prevalent in many countries. In the future, difficult surgical procedures, transplants, and other immunosuppressive therapies may become very risky. Resistance is mainly due to an excessive usage of antibiotics, in both humans and animals, and to cross-transmission of resistant bacteria. Action is urgently needed. Therefore, a World Alliance Against Antibiotic Resistance (WAAAR) was created in 2011. It includes healthcare professionals, consumers, health managers, and politicians. We present here the main measures proposed by the Alliance, as a result of a strong consensus between the different stakeholders, including general practitioners and veterinarians

The PIRO Concept: O is for organ dysfunction

SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated pneumonia by inhibition of quorum sensing: a randomized controlled trial

Purpose: Anti-virulence strategies have not been evaluated for the prevention of bacterial infections. Prolonged colonization of intubated patients with Pseudomonas aeruginosa isolates producing high-levels of the quorum sensing (QS)-regulated virulence factor rhamnolipids has been associated with ventilator-associated pneumonia (VAP). In this pathogen, azithromycin reduces QS-regulated virulence. We aimed to assess whether azithromycin could prevent VAP in patients colonized by rhamnolipids producing isolates. Methods: In a randomized, double-blind, multicenter trial, intubated colonized patients received either 300mg/day azithromycin or placebo. Primary endpoint was the occurrence of P. aeruginosa VAP. We further identified those patients persistently colonized by isolates producing high-levels of rhamnolipids and therefore at the highest risk to develop VAP linked to this QS-dependent virulence factor. Results: Ninety-two patients were enrolled; 43 azithromycin-treated and 42 placebo patients were eligible for the per-protocol analysis. In the per-protocol population, the occurrence of P. aeruginosa VAP was reduced in the azithromycin group but without reaching statistical significance (4.7 vs. 14.3% VAP, p=0.156). QS-dependent virulence of colonizing isolates was similarly low in both study groups, and only five patients in each arm were persistently colonized by high-level rhamnolipids producing isolates. In this high-risk subgroup, the incidence of VAP was reduced fivefold in azithromycin versus placebo patients (1/5 vs. 5/5 VAP, p=0.048). Conclusions: There was a trend towards reduced incidence of VAP in colonized azithromycin-treated patients. In addition, azithromycin significantly prevented VAP in those patients at high risk of rhamnolipid-dependent VAP, suggesting that virulence inhibition is a promising anti-microbial strateg

Effect of previous antimicrobial therapy on the accuracy of the main procedures used to diagnose nosocomial pneumonia in patients who are using ventilation.

peer reviewedWe evaluated the effect of antibiotic treatment received before the suspicion of pneumonia on the diagnostic yield of protected specimen brush (PSB), direct examination (BAL D) and culture (BAL C) of lavage fluid on consecutive mechanically ventilated patients with suspected nosocomial pneumonia. Bronchoscopy was always performed before any treatment for suspected pneumonia. One hundred and sixty-one patients with suspected pneumonia underwent PSB and BAL before any institution or change in antibiotic therapy (AB). Sixty-five patients received AB for an earlier septic episode (ON AB group) and 96 patients did not (OFF AB group). All but two strains recovered were highly resistant to previous AB. Sensitivity and specificity of each test were not different between the ON AB and OFF AB groups as well as the percentage of complete agreement between the 3 procedures, 74 and 67% respectively. We conclude that previous AB received to treat an earlier septic episode unrelated to suspected pneumonia do not affect the diagnostic yield of PSB and BAL

Reappraisal of distal diagnostic testing in the diagnosis of ICU-acquired pneumonia.

peer reviewed[en] BACKGROUND: The thresholds of the diagnostic procedures performed to diagnose ICU-acquired pneumonia (IAP) are either speculated or incompletely tested. PURPOSE: To evaluate the best threshold of protected specimen brush (PSB), plugged telescoping catheter (PTC), BAL culture (BAL C), and direct examination of cytocentrifugated lavage fluid (BAL D) to diagnose IAP. Each mechanically ventilated patient with suspected IAP underwent bronchoscopy successively with PSB, PTC, and BAL in the lung segment identified radiographically. POPULATION: One hundred twenty-two episodes of suspected IAP (occurring in 26% of all mechanically ventilated patients) were studied. Forty-five patients had definite IAP, and 58 had no IAP. Diagnosis was uncertain in 19 cases. RESULTS: Using the classic thresholds, sensitivity was 67% for PSB, 54% for PTC, 59% for BAL D, and 77% for BAL C. Specificity was 88% for PSB, 77% for PTC, 98% for BAL D, and 77% for BAL C. We used receiver operating characteristics methods to reappraise thresholds. Decreasing the thresholds to 500 cfu/mL for PSB, 10(2) cfu/mL for PTC, 2% cells containing bacteria for BAL D, 4 x 10(3) cfu/mL for BAL C increased the sensitivities (plus 14%, 23%, 25%, 10%, respectively) and moderately decreased the specificities (minus 4%, 9%, 2%, 4%, respectively) of the four examinations. The association of PSB with a 500 cfu/mL threshold and BAL D with a 2% threshold recovered all but one episode of pneumonia (SE 96 +/- 4%) with a 84 +/- 10% specificity. For a similar ICU population, these "best" thresholds increased negative predictive value with a minimal decrease of positive predictive value. They need to be confirmed in multiple ICU settings in prospective fashion

Central vein catheter-related thrombosis in intensive care patients: incidence, risks factors, and relationship with catheter-related sepsis.

peer reviewed[en] OBJECTIVE: To evaluate the incidence and risk factors for catheter-related central vein thrombosis in ICU patients. DESIGN: Observational prospective multicenter study. SETTING: An 8-bed surgical ICU, a 10-bed surgical cardiovascular ICU, and a 10-bed medical-surgical ICU. PATIENTS: During an 18-month period, 265 internaljugular or subclavian catheters were included. Veins were explored by duplex scanning performed just before or < 24 h after catheter removal. Suspected risk factors of catheter-related central vein thrombosis were recorded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-seven catheters were excluded from the analysis. Therefore 208 catheters were analyzed. Mean age of patients was 64+/-15 years, simplified acute physiologic score was 12+/-5, organ system failure score at insertion was 1+/-1, and mean duration of catheterization was 9+/-5 days. A catheter-related internal jugular or subclavian vein thrombosis occurred in 33% of the cases (42% [95% confidence interval (CI), 34 to 49%] and 10% [95% CI, 3 to 18%], respectively). Thrombosis was limited in 8%, large in 22%, and occlusive in 3% of the cases. Internal jugular route (relative risk [RR], 4.13; 95% CI, 1.72 to 9.95), therapeutic heparinization (RR 0.47; 95% CI, 0.23 to 0.99), and age >64 years (RR, 2.44; 95% CI, 2.05 to 3.19) were independently associated with catheter-related thrombosis. Moreover, the risk of catheter-related sepsis was 2.62-fold higher when thrombosis occurred (p=0.011). CONCLUSIONS: Catheter-related central vein thrombosis is a frequent complication of central venous catheterization in ICU patients and is closely associated with catheter-related sepsis

Is protected specimen brush a reproducible method to diagnose ICU-acquired pneumonia?

peer reviewed[en] UNLABELLED: Protected specimen brush (PSB) is considered to be one of the standard methods for the diagnosis of ventilator-associated pneumonia, but to our knowledge, intraindividual variability in results has not been reported previously. PURPOSE: To compare the results of two PSB performed in the same subsegment on patients with suspected ICU-acquired pneumonia (IAP). STUDY DESIGN: Between October 1991 and April 1992, each mechanically ventilated patient with suspected IAP underwent bronchoscopy with two successive PSB in the lung segment identified as abnormal on radiographs. Results of the two PSB cultures were compared using 10(3) cfu/ml cutoff for a positive result. Four definite diagnoses were established during the follow up: definite pneumonia, probable pneumonia, excluded pneumonia, and uncertain pneumonia. POPULATION: Forty-two episodes in 26 patients were studied; 60 percent of patients received prior antibiotic therapy. Thirty-two microorganisms were isolated from 24 pairs of PSB. Definite diagnosis was definite pneumonia in 7, probable pneumonia in 8, excluded pneumonia in 17, and uncertain pneumonia in 10 cases. RESULTS: The PSB recovered the same microorganisms and argued for a good qualitative reproducibility. The distinction of positive and negative results on the basis of the 10(3) cfu/ml classic threshold was less reproducible. For 24 percent of the microorganisms recovered and in 16.7 percent of episodes of suspected IAP, the two consecutive samples gave results spread out on each side of the 10(3) cfu/ml cutoff. Discordance was higher when definite diagnosis was certain or probable than when diagnosis was excluded (p = 0.015). There was no statistical effect of the order of samples between the two specimens for bacterial index and microorganism concentrations. CONCLUSION: These findings argue for the poor repeatability of PSB in suspected IAP and question the yield of the 10(3) cfu/ml threshold. In attempting to diagnose IAP, the results of PSB must be interpreted with caution considering the intraindividual variability

Detecting Faults in Inner Product Masking Scheme - IPM-FD: IPM with Fault Detection (extended version∗)

Side-channel analysis and fault injection attacks are two typical threats to cryptographic implementations, especially in modern embedded devices. Thus there is an insistent demand for dual side-channel and fault injection protections. As it is known, masking is a kind of provable countermeasure against side-channel attacks. Recently, inner product masking (IPM) was proposed as a promising higher-order masking scheme against side-channel analysis, but not for fault injection attacks. In this paper, we devise a new masking scheme named IPM-FD. It is built on IPM, which enables fault detection. This novel masking scheme has three properties: the security orders in the word-level probing model, bit-level probing model, and the number of detected faults. IPM-FD is proven secure both in the word-level and in the bit-level probing models, and allows for end-to-end fault detection against fault injection attacks. Furthermore, we illustrate its security order by interpreting IPM-FD as a coding problem then linking it to one defining parameters of linear code, and show its implementation cost by applying IPM-FD to AES-128