Central-line associated bloodstream infections in intensive care units before and after implementation of daily antiseptic bathing with chlorhexidine or octenidine: a post-hoc analysis of a cluster-randomised controlled trial.

BACKGROUNDS: Antiseptic bathing did not reduce central-line (CL) associated bloodstream infection (CLABSI) rates in intensive care units (ICU) according to a recent cluster randomised controlled trial (cRCT). However, this analysis did not consider baseline infection rates. Our post-hoc analysis of this cRCT aimed to use a before-after comparison to examine the effect of daily bathing with chlorhexidine, octenidine or water and soap (control) on ICU-attributable CLABSI rates. METHODS: A post-hoc analysis of a multi-center cRCT was done. ICUs that did not yet perform routine antiseptic bathing were randomly assigned to one of three study groups applying daily bathing with 2% chlorhexidine-impregnated cloths, 0.08% octenidine wash mitts or water and soap (control) for 12 months. Baseline data was assessed 12 months before the intervention started when all ICUs routinely used water and soap. Poisson regression and generalised estimating equation models were applied to identify changes of CLABSI rates per 1000 CL days between intervention and baseline periods in each study group. RESULTS: The cRCT was conducted in 72 ICUs (24 per study group) including 76,139 patients in the baseline and 76,815 patients in the intervention period. In the chlorhexidine group, incidence density of CLABSI was reduced from 1.48 to 0.90 CLABSI per 1000 CL days comparing baseline versus intervention period (P = 0.0085). No reduction was observed in the octenidine group (1.26 versus 1.47 CLABSI per 1000 CL days, P = 0.8735) and the control group (1.20 versus 1.17, P = 0.3298). Adjusted incidence rate ratios (intervention versus baseline) were 0.63 (95%CI 0.46-0.87, P = 0.0172) in the chlorhexidine, 1.17 (95% CI 0.79-1.72, P = 0.5111) in the octenidine and 0.98 (95% CI 0.60-1.58, P = 0.9190) in the control group. Chlorhexidine bathing reduced CLABSI with gram-positive bacteria, mainly coagulase-negative staphylococci (CoNS). CONCLUSIONS: In this post-hoc analysis of a cRCT, the application of 2% chlorhexidine-impregnated cloths reduced ICU-attributable CLABSI. This preventive effect of chlorhexidine was restricted to CLABSI caused by gram-positive pathogens (CoNS). In contrast, 0.08% octenidine wash mitts did not reduce CLABSI rates in ICUs. Trial registration Registration number DRKS00010475, registration date August 18, 2016.

Chlorhexidine and octenidine susceptibility of bacterial isolates from clinical samples in a three-armed cluster randomised decolonisation trial.

BACKGROUND: Routine use of chlorhexidine or octenidine for antiseptic bathing may have unintended consequences. Our analysis aimed to assess the phenotypic susceptibility of bacterial isolates from clinical samples to chlorhexidine and octenidine collected from intensive care units (ICU) that routinely used 2% chlorhexidine-impregnated wash cloths or 0.08% octenidine wash mitts (intervention) or water and soap (control) for daily patient care. METHODS: This study was conducted within the context of a three armed cluster-randomised controlled decolonisation trial (Registration number DRKS00010475, registration date August 18, 2016). Bacterial isolates were collected prior to and at the end of a 12-month-intervention period from patients with ≥ 3 days length of stay at an ICU assigned to one of two intervention groups or the control group. Phenotypic susceptibility to chlorhexidine and octenidine was assessed by an accredited contract research laboratory determining minimal inhibitory concentrations (MIC) as percentage of extraction solutions used. MIC were reported as estimated concentrations in µg/ml derived from the chlorhexidine and octenidine extraction solutions. Statistical analyses including generalized estimating equation models were applied. RESULTS: In total, 790 ICU-attributable bacterial isolates from clinical samples (e.g. blood, urine, tracheal aspirate) were eligible for all analyses. Pathogens included were Staphylococcus aureus (n = 155), coagulase-negative staphylococci (CoNS, n = 122), Escherichia coli (n = 227), Klebsiella spp. (n = 150) and Pseudomonas aeruginosa (n = 136). For all species, chlorhexidine and octenidine MIC did not increase from baseline to intervention period in the antiseptic bathing groups. For proportions of bacterial isolates with elevated chlorhexidine / octenidine MIC (≥ species-specific chlorhexidine / octenidine MIC50), adjusted incidence rate ratios (aIRR) showed no differences between the intervention groups and the control group (intervention period). CONCLUSION: We found no evidence for reduced phenotypic susceptibilities of bacterial isolates from clinical samples to chlorhexidine or octenidine in ICUs 12 months after implementation of routine antiseptic bathing with the respective substances.

Effect of antiseptic bathing with chlorhexidine or octenidine on central line-associated bloodstream infections in intensive care patients: a cluster-randomized controlled trial.

OBJECTIVES: Our study aimed to compare the effect of daily bathing with chlorhexidine, octenidine, or water and soap (routine care = control) on central line (CL)-associated bloodstream infection (CLABSI) rates in intensive care units (ICUs). METHODS: A multicentre cluster-randomized controlled trial was done with a 12-month intervention period from February 1, 2017 to January 31, 2018 (octenidine and routine care group) or from June 1, 2017 to May 31, 2018 (chlorhexidine group). Wards were randomly assigned to one of two decolonization regimes or routine care (control). Intervention included daily bathing with 2% chlorhexidine-impregnated cloths or 0.08% octenidine wash mitts for 12 months, whereas the control group used water and soap (routine care). The primary outcome was incidence density of CLABSI per 1000 CL days. Poisson regression and generalized estimating equation models were applied. RESULTS: A total of 72 ICUs with 76 815 patients (22 897 patients in the chlorhexidine group, 25 127 in the octenidine group, and 28 791 in the routine care group) were included. Incidence densities were 0.90 CLABSI per 1000 CL days (95% CI 0.67-1.19) in the chlorhexidine group, 1.47 (95% CI 1.17-1.81) in the octenidine group, and 1.17 (95% CI 0.93-1.45) in the routine care group. Adjusted incidence rate ratios of CLABSI were 0.69 (95% CI 0.37-1.22, p = 0.28) in the chlorhexidine group and 1.22 (95% CI 0.54-2.75, p = 0.65) in the octenidine group (compared with routine care). DISCUSSION: Antiseptic bathing with 2% chlorhexidine-impregnated cloths and 0.08% octenidine wash mitts lacks a significant preventive effect on CLABSI rates in ICUs. However, our trial has a high likelihood of being underpowered because CLABSI rates in the routine care group were approximately 40% lower than initially assumed.

Contact isolation versus standard precautions to decrease acquisition of extended-spectrum ß-lactamase-producing Enterobacterales in non-critical care wards: a cluster-randomised crossover trial.

BACKGROUND: The effectiveness of contact isolation for decreasing the spread of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) has been questioned. The aim of this study was to establish the benefits of contact isolation over standard precautions for reducing the incidence density of ESBL-E colonisation and infection in adult medical and surgical wards with an active surveillance culture programme. METHODS: We did a cluster-randomised crossover trial in adult wards in four European university hospitals. Medical, surgical, or combined medical-surgical wards without critical care were randomised to continue standard precautions alone or implement contact isolation alongside standard precautions for 12 months, followed by a 1 month washout period and 12 months of the alternate strategy. Randomisation was done via a computer-generated sequence, with a block size of two consecutive wards. Only laboratory technicians and data analysts were masked to allocation. Patients were screened for ESBL-E carriage within 3 days of admission, once a week thereafter, and on discharge. The primary outcome was the incidence density of ESBL-E, defined as the acquisition rate per 1000 patient-days at risk at the ward level and assessed in the per-protocol population, which included all patients screened at least twice with a length of stay of more than 1 week for each intervention period. No specific safety measures were assessed given the minimal risk of adverse events. The trial is registered, ISRCTN57648070. FINDINGS: We enrolled 20 wards from four hospitals in Germany (eight wards), the Netherlands (four wards), Spain (four wards), and Switzerland (four wards). Between Jan 6, 2014, and Aug 31, 2016, 38 357 patients were admitted to these wards. Among 15 184 patients with a length of stay of more than 1 week, 11 368 patients (75%) were screened at least twice. The incidence density of ward-acquired ESBL-E was 6·0 events per 1000 patient-days at risk (95% CI 5·4-6·7) during periods of contact isolation and 6·1 (5·5-6·7) during periods of standard precautions (p=0·9710). Multivariable analysis adjusted for length of stay, percentage of patients screened, and prevalence in first screening cultures yielded an incidence rate ratio of 0·99 (95% CI 0·80-1·22; p=0·9177) for care under contact isolation compared with standard precautions. INTERPRETATION: Contact isolation showed no benefit when added to standard precautions for controlling the spread of ESBL-E on non-critical care wards with extensive surveillance screening. FUNDING: European Commission.

Transforming growth factor ß1 polymorphisms and progression of graft fibrosis after liver transplantation for hepatitis C virus--induced liver disease.

Re-infection with the hepatitis C virus (HCV) is an important development after liver transplantation (LT); it can lead to graft fibrosis. The aim of this study was to assess the role of transforming growth factor ß1 (TGF-ß1) polymorphisms in the development of HCV-related graft disease by evaluating protocol liver biopsies. A total of 192 patients with a recurrence of HCV infection after LT were genotyped for TGF-ß1 codon 10 (C→T) and codon 25 (G→C) using the polymerase chain reaction. Histological evaluation of 614 protocol liver biopsies obtained from these patients was undertaken using the classification of Desmet and Scheuer to stage the degree of fibrosis. Mild stages of fibrosis (0-2) were compared to advanced stages of fibrosis (3-4) that developed during the period of infection with the virus. Correlations between the prevalence of TGF-ß1 genotypes and the different degrees of fibrosis that developed were determined. No statistically significant differences were found for genotype distributions (codons 10 and 25) with respect to recipient age, donor sex, occurrence of acute cellular rejection, and response to antiviral therapy. However, the C allele at codon 25 was significantly less frequent in the group with advanced fibrosis (P = 0.001). Furthermore, a positive association was found between progression of fibrosis and male recipient sex (P = 0.024), donor age (P = 0.041), and viral genotype 1b (P = 0.002). In conclusion, this study, in which the evolution of hepatic fibrosis was assessed histologically in a large cohort of patients with HCV re-infection after LT, has demonstrated that the C allele at codon 25 of the TGF-ß1 gene is a marker for the development of graft fibrosis.