Resistance or adaptation? How susceptible is a 'glutaraldehyde-resistant' Pseudomonas aeruginosa isolate in the absence of selection pressure?

The activities of glutaraldehyde solution and an instrument disinfectant based on glutaraldehyde on a Pseudomonas aeruginosa isolate with reduced susceptibility to glutaraldehyde after the first and fifth passages were determined using three concentrations and temperatures. No significant difference was found between the first and fifth passages so phenotypic adaptation is unlikely.

World Health Organization-recommended hand-rub formulations do not meet European efficacy requirements for surgical hand disinfection in five minutes.

The World Health Organization (WHO) has recommended two hand-rub formulations for local production based on 80% ethanol or 75% isopropanol (both v/v). We have looked at their efficacy according to EN 12791. Twenty-six subjects treated their hands with the reference procedure (n-propanol, 60%) for 3 min or with one of the two formulations for 1.5, 3 or 5 min (Latin square design). Post-values (immediate effect) were taken from one hand, the other hand was gloved for 3 h. After the glove had been taken off, the second post-value was taken (3 h effect). The mean log(10) reduction of each hand rub at all three application times was compared to Hodges and Lehmann's reference procedure for non-inferiority. In the first block the reference procedure reduced bacterial load by 2.43 log(10) (immediate effect) and 2.22 log(10) (3 h effect). The efficacy of the ethanol-based formulation (e.g. immediate efficacy of 1.41 log(10) at 5 min) was inferior to the reference procedure at all application times [lower 95% confidence interval (CI): less than -0.75]. In the second block the reference procedure reduced bacterial load by 2.72 log(10) (immediate effect) and 2.26 log(10) (3 h effect). The efficacy of the isopropanol-based formulation (e.g. immediate efficacy of 2.05 log(10) at 5 min) was also inferior to the reference procedure at all application times (lower 95% CI: less than -0.75). Both WHO-recommended hand-rub formulations failed to meet the EN 12791 efficacy requirements for surgical hand disinfection within 5 min. A higher concentration of the active ingredients may improve the efficacy.

A 1-minute hand wash does not impair the efficacy of a propanol-based hand rub in two consecutive surgical hand disinfection procedures.

We studied the effect of a 1-min hand wash on the bacterial hand flora in two consecutive surgical hand disinfection procedures. A propanol-based hand rub (PBHR; Sterillium) and n-propanol (60%, v/v) were tested in a Latin-square design according to EN 12791 in four variations. The reference alcohol was always applied for 3 min after a 1-min hand wash (variation 1). The PBHR was applied for 1.5 min (first application) or 0.5 min (second application). Variation 2 included a 1-min hand wash before both applications, variation 3 included the hand wash before application 1, in variation 4 hands were not washed at all before application. Pre- and post-values were obtained according to EN 12791. The reference disinfection reduced bacteria by 2.99 log(10) (immediate efficacy) and 2.22 log(10) after 3 h. The second reference disinfection reduced bacteria by 0.95 log(10) (immediate efficacy) and 0.68 log(10) after 3 h. The PBHR always yielded an equivalent reduction with and without a preceding hand wash (p > 0.05; Friedman test). A 1-min hand wash before application of the PBHR did not significantly change its efficacy for surgical hand disinfection in two consecutive surgical procedures of 3 h.

Comparative review of the test design Tentative Final Monograph (TFM) and EN 12791 for surgical hand disinfectants.

Preoperative antiseptic treatment of the hands of the surgical team is a standard procedure used worldwide in order to reduce the risk of surgical site infection. Two different types of antiseptics are available: alcohol-based hand rubs and antimicrobial liquid detergents ("soaps"). Standards have been developed to determine the antimicrobial efficacy of such preparations: the European norm EN 12971, finally issued in 2005, and the Tentative Final Monograph (TFM) for health care antiseptic products from 1994, which is the corresponding document in the USA. Although both methods use the reduction of resident hand flora as a quantitative parameter for antimicrobial efficacy, there are major differences concerning the test design. Whereas the European method is carried out following a randomized, reference-controlled crossover design, the US method can be characterized as a randomized, blinded parallel arm design. While both standards aim at immediate as well as sustained efficacy of the procedure, according to the EN the test product must not be significantly less effective than the reference procedure, whereas the TFM requires absolute reduction of > or = 1, > or = 2, and > or = 3 log10 per hand on days 1, 2, and 5, respectively. Results from various studies demonstrated that meeting the criteria defined by both standards may happen, but meeting the specifications of one standard does not necessarily mean that the same product will pass the requirements of the other. Missing accordance may be due to a number of considerable differences between both test methods. For a number of reasons the European method seems to be closer to clinical practice and to provide higher patient safety than the US method. However, available study data do neither allow for evaluation of the clinical impact of surgical hand disinfection as such nor of the effect of a particular product on postoperative wound infection rates.

Surgical hand disinfection with a propanol-based hand rub: equivalence of shorter application times.

The aim of this study was to determine the efficacy of a propanol-based hand rub at application times shorter than 3 min. The bacterial pre-value was obtained from the finger tips (prEN 12791). Subjects treated their hands with the reference procedure (n-propanol, 60%) for 3 min or the product (crossover design). Sterillium was applied for 3, 2, 1.5 and 1 min. Four other preparations were tested for 1 min. Post-values (immediate effect) were taken from one hand, and the other hand was gloved for 3h. After the gloves were removed, the second post-value was taken (sustained effect). Sterillium was more effective than the reference procedure at 3, 2 and 1.5 min (immediate and sustained effect). The immediate effect after 1 min was significantly lower [mean log(10) reduction factor (RF): 1.91+/-0.90 vs. 2.52+/-0.95; P=0.001], whereas the sustained effect was not (mean RF: 1.81+/-1.06 vs. 2.05+/-1.14; P=0.204). All other preparations failed the efficacy requirement at 1 min for both the immediate and sustained effect. Using 2 x 3 mL Sterillium for a total of 1.5 min for surgical hand disinfection was at least as effective as the 3-min reference disinfection.

Efficacy of alcohol-based gels compared with simple hand wash and hygienic hand disinfection.

A recent research letter on the limited efficacy of alcohol-based hand gels has alerted the global infection control community and raised the question of the true significance of data obtained according to EN 1500. It has been described that a 1 min simple hand wash reduces artificial contamination of hands by a log(10) reduction factor of 2.8 and a 1 min reference hand disinfection with 2-propanol (60%, v/v) by a factor of 4.6 steps. The EN 1500 gel data show that the 30 s efficacy of most gels is closer to a simple hand wash than to the reference hand disinfection. The 30 s efficacy of most alcohol-based liquid products and one gel, however, is almost identical to the reference hand disinfection. In many European countries alcohol-based liquid products have been established as a standard practice in hygienic hand disinfection for decades. Replacement of these products with most available gels would be a step backward in terms of efficacy and has still to be seen critically from the efficacy point of view.

Inter-laboratory reproducibility of the hand disinfection reference procedure of EN 1500.

Recent tests carried out using EN 1500 have suggested that most alcohol-based hand gels are significantly less effective than the reference alcohol [2-propanol, 60% (v/v)] whereas liquid alcohol-based hand rubs are not. However concerns about the accuracy and reproducibility of the test have been raised. We therefore analysed 41 experiments performed in four different laboratories using EN 1500 hand disinfection procedures with the reference alcohol, to analyse inter-laboratory reproducibility of the test. The mean reduction factors (difference of the log(10) of the pre-value and the post-value) from the four laboratories did not reveal a significant difference (P=0.059; analysis of variance), although the difference of the mean pre and post-values was highly significant (P<0.001). EN 1500 is a reproducible test method which leads to valid data.

Intra-laboratory reproducibility of the hand hygiene reference procedures of EN 1499 (hygienic handwash) and EN 1500 (hygienic hand disinfection).

The bactericidal efficacy of hand antiseptic products is determined in Europe using two norms--EN1499 (hygienic handwash), and EN 1500 (hygienic hand disinfection) based on reducing the counts of bacteria on artificially contaminated hands. Each requires 12-15 data sets per test and comparison with a reference procedure. Recent research using EN 1500 suggested that most alcohol-based hand gels are significantly less effective than the reference alcohol (2-propanol 60%), whereas liquid alcohol-based rubs are not. However concerns about the accuracy and reproducibility of the norm reference procedures have been raised. We therefore analysed 23 experiments carried out using EN 1500 representing 342 hand disinfection procedures, and 12 experiments using EN 1499 representing 178 handwashes, all performed in the same laboratory for reproducibility of the reference procedures. The reference alcohol gave a mean log(10) reduction factor (RF) of 4.64 +/- 0.93; only one data set gave a significantly higher result (5.14, P = 0.034), and one significantly lower (4.05; P = 0.034). Analysis of all 23 means revealed no significant difference (P = 0.188; ANOVA model). The reference soap gave a mean reduction of 2.82 +/- 0.49. Two data sets were significantly higher than this (3.35,P < 0.001; 3.12, P < 0.001) and two significantly lower (2.55, P = 0.031; 2.47,P = 0.004). Analysis of all the means did reveal a significant difference (P < 0.001, ANOVA model), which is probably explained by the smaller standard deviations of these results. Pre-values (bacteria recovered from fingers before a reference procedure) correlated significantly with RFs for both hand disinfection (correlation coefficient: 0.291;P = 0.01) and handwash (correlation coefficient: 0.372, P = 0.01). Overall both procedures gave accurate and reproducible results.