Investigation of the effect of the adsorbent DAV131A on the propensity of moxifloxacin to induce simulated Clostridioides (Clostridium) difficile infection (CDI) in an in vitro human gut model.

BACKGROUND: Clostridioides difficile infection (CDI) remains a high burden worldwide. DAV131A, a novel adsorbent, reduces residual gut antimicrobial levels, reducing CDI risk in animal models. OBJECTIVES: We used a validated human gut model to investigate the efficacy of DAV131A in preventing moxifloxacin-induced CDI. METHODS: C. difficile (CD) spores were inoculated into two models populated with pooled human faeces. Moxifloxacin was instilled (43 mg/L, once daily, 7 days) alongside DAV131A (5 g in 18 mL PBS, three times daily, 14 days, Model A), or PBS (18 mL, three times daily, 14 days, Model B). Selected gut microbiota populations, CD total counts, spore counts, cytotoxin titre and antimicrobial concentrations (HPLC) were monitored daily. We monitored for reduced susceptibility of CD to moxifloxacin. Growth of CD in faecal filtrate and medium in the presence/absence of DAV131A, or in medium pre-treated with DAV131A, was also investigated. RESULTS: DAV131A instillation reduced active moxifloxacin levels to below the limit of detection (50 ng/mL), and prevented microbiota disruption, excepting Bacteroides fragilis group populations, which declined by ∼3 log10 cfu/mL. DAV131A delayed onset of simulated CDI by ∼2 weeks, but did not prevent CD germination and toxin production. DAV131A prevented emergence of reduced susceptibility of CD to moxifloxacin. In batch culture, DAV131A had minor effects on CD vegetative growth, but significantly reduced toxin/spores (P < 0.005). CONCLUSIONS: DAV131A reduced moxifloxacin-induced microbiota disruption and emergence of antibiotic-resistant CD. Delayed onset of CD germination and toxin production indicates further investigations are warranted to understand the clinical benefits of DAV131A in CDI prevention.

European survey on the current surveillance practices, management guidelines, treatment pathways and heterogeneity of testing of Clostridioides difficile, 2018-2019: results from The Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI).

BACKGROUND: Awareness and compliance with international guidelines for diagnosis and clinical management of Clostridioides difficile infection (CDI) are unknown. AIM: To compare the awareness and compliance with the recommended strategies for diagnosis and clinical management of CDI across Europe in 2018-2019. METHODS: Hospital sites and their associated community practices across 12 European countries completed an online survey in 2018-2019, to report on their practices in terms of surveillance, prevention, diagnosis, and treatment of CDI. Responses were collected from 105 hospitals and 39 community general practitioners (GPs). FINDINGS: Hospital sites of 11 countries reported participation in national surveillance schemes compared with six countries for international schemes. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID)-recommended CDI testing methodologies were used by 82% (86/105) of hospitals, however countries reporting the highest incidence of CDI used non-recommended tests. Over 75% (80/105) of hospitals were aware of the most recent European CDI treatment guidelines at the time of this survey compared with only 26% (10/39) of surveyed GPs. However, up to 15% (16/105) of hospitals reported using the non-recommended metronidazole for recurrent CDI cases, sites in countries with lower awareness of CDI treatment guidelines. Only 37% (39/105) of hospitals adopted contact isolation precautions in case of suspected CDI. CONCLUSION: Good awareness of guidelines for the management of CDI was observed across the surveyed European hospital sites. However, low compliance with diagnostic testing guidelines, infection control measures for suspected CDI, and insufficient awareness of treatment guidelines continued to be reported in some countries.

Guidance document for prevention of Clostridium difficile infection in acute healthcare settings.

SCOPE: Clostridium difficile infection (CDI) is the most important infective cause of healthcare-associated diarrhoea in high income countries and one of the most important healthcare-associated pathogens in both Europe and the United States. It is associated with high morbidity and mortality resulting in both societal and financial burden. A significant proportion of this burden is potentially preventable by a combination of targeted infection prevention and control measures and antimicrobial stewardship. The aim of this guidance document is to provide an update on recommendations for prevention of CDI in acute care settings to provide guidance to those responsible for institutional infection prevention and control programmes. METHODS: An expert group was set up by the European society of clinical microbiology and infectious diseases (ESCMID) Study Group for C. difficile (ESGCD), which performed a systematic review of the literature on prevention of CDI in adults hospitalized in acute care settings and derived respective recommendations according to the GRADE approach. Recommendations are stratified for both outbreak and endemic settings. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: This guidance document provides thirty-six statements on strategies to prevent CDI in acute care settings, including 18 strong recommendations. No recommendation was provided for three questions.

The potential of alcohol release doorplates to reduce surface contamination during hand contact.

BACKGROUND: Optimal hand hygiene may be compromised by contact with contaminated environmental surfaces. AIM: To investigate the in-vitro efficacy of a novel alcohol-release doorplate to reduce surface contamination during hand contact. METHODS: Prototype, horizontally held, Surfaceskins, alcohol gel-impregnated and control (aluminium) doorplates were challenged (N = 72 per micro-organism) with Staphylococcus aureus-, Eschericia coli-, Enterococcus faecalis-, or Clostridium difficile-contaminated fingers. S. aureus and E. faecalis were used for challenges (90 per micro-organism) of vertical (modified design) doorplates, on days 0, 3, 4, 6, and 7. Surface contamination was measured pre and immediately post challenges using agar contact plates. FINDINGS: Horizontal test, but not control, doorplates demonstrated bacterial killing of S. aureus, E. faecalis and E. coli, but not of C. difficile; hence, only testing of S. aureus and E. faecalis was continued. Vertical Surfaceskins, but not control, doorplates demonstrated rapid killing of S. aureus over seven days. There were significant reductions (>90% up to day 6; P ≤ 0.01) of surface bacterial colony counts compared with controls immediately post challenge. There were also significant reductions in Surfaceskins doorplate enterococcal colony counts compared with controls on every day of testing (P ≤ 0.004). There was no evidence that bacterial recovery was greater from the tops of Surfaceskins doorplates (i.e. due to pooling of contents). CONCLUSION: Surfaceskins doorplates were efficient at reducing surface contamination by S. aureus, E. faecalis, and E. coli. Reducing microbial contamination of frequently touched door surfaces, and so bacterial transfer via hands, could feasibly reduce the risk of healthcare-associated and other infections.

Subcutaneous fluid administration--better than the intravenous approach?

Hypodermoclysis is a method of subcutaneous fluid administration particularly useful in elderly patients and in palliative care settings where intravenous access may be difficult. Subcutaneous fluid delivery is an effective method of rehydration and of opioid administration, and can prevent the need for intravenous catheterization and consequently hospitalization. It is a simple procedure to initiate, safe, less distressing to the patient, and does not predispose to intravascular related infections. The reported incidence of infection at the delivery site is extremely low. However, local guidelines should be agreed so that a standardized protocol is operated and risks of localized infection are minimized.

Early experience with linezolid for infections in orthopaedics.

In infections following orthopaedic surgery, isolated staphylococci are reported to be methicillin resistant (MRSA) in up to 50% of cases. Linezolid, the first in a new class of antibiotics, has excellent efficacy against gram positive organisms that are resistant to other therapies and is 100% orally bioavailable. We report early results of its use for the treatment of resistant infections in orthopaedic practice. Infections were characterised according to the UK Nosocomial Infections National Surveillance Service classification of surgical infections as superficial, deep or organ/space. Osteomyelitis, joint sepsis and deep infection involving orthopaedic implants were included into the final category. Outcome was recorded as clinical, microbiological and blood parameter cure or fail. Over the 12-month study period, 54 patients received linezolid therapy, 41% of these had significant co-morbidity that might affect their ability to fight infection. Sixty-seven percent of infections were in association with implanted metal work. The majority of patients were treated with vancomycin for a short period before linezolid was used as oral 'switch' therapy for longer-term administration, allowing early discharge in all cases. MRSA was isolated in 87% of the patients treated. The mean length of linezolid therapy was 39 days (2-151). Clinical success was achieved in 90% of patients overall. Though there were no life-threatening complications, adverse event rates were significantly higher than those recorded in the literature, with 19% of patients needing to cease therapy. Linezolid offers an alternative to traditional treatments for resistant infections and can facilitate early discharge. Patients need to be monitored closely, particularly where long-term therapy is planned.

Subdural empyema due to Enterococcus faecalis.

Central nervous system infections due to Enterococcus species are uncommon. We report the first case of subdural empyema due to Enterococcus faecalis. Following partial treatment of a middle ear infection due to Enterococcus species and mixed coliforms, the patient developed signs of meningeal involvement. A lumbar puncture showed a raised polymorph cell count, but was sterile on culture; broad-spectrum antimicrobial therapy with cefotaxime, flucloxacillin and metronidazole was commenced. Following development of focal neurological signs, a CT scan revealed a subdural collection. Drainage and culture of the pus yielded a pure growth of Enterococcus faecalis. This case demonstrates the need to remain aware of the ability of the Enterococcus to cause serious infections and to direct specific antimicrobial therapy accordingly.