2% chlorhexidine gluconate aqueous versus 2% chlorhexidine gluconate in 70% isopropyl alcohol for skin disinfection prior to percutaneous central venous catheterisation: the ARCTIC randomised controlled feasibility trial.

OBJECTIVE: Catheter-related sepsis (CRS) is a major complication with significant morbidity and mortality. Evidence is lacking regarding the most appropriate antiseptic for skin disinfection before percutaneous central venous catheter (PCVC) insertion in preterm neonates. To inform the feasibility and design of a definitive randomised controlled trial (RCT) of two antiseptic formulations, we conducted the Antiseptic Randomised Controlled Trial for Insertion of Catheters (ARCTIC) feasibility study to assess catheter colonisation, sepsis, and skin morbidity. DESIGN: Feasibility RCT. SETTING: Two UK tertiary-level neonatal intensive care units. PATIENTS: Preterm infants born <34 weeks' gestation scheduled to undergo PCVC insertion. INTERVENTIONS: Skin disinfection with either 2% chlorhexidine gluconate (CHG)-aqueous or 2% CHG-70% isopropyl alcohol (IPA) before PCVC insertion and at removal. PRIMARY OUTCOME: Proportion in the 2% CHG-70% IPA arm with a colonised catheter at removal. MAIN FEASIBILITY OUTCOMES: Rates of: (1) CRS, catheter-associated sepsis (CAS), and CRS/CAS per 1,000 PCVC days; (2) recruitment and retention; (3) data completeness. SAFETY OUTCOMES: Daily skin morbidity scores recorded from catheter insertion until 48 hours post-removal. RESULTS: 116 babies were randomised. Primary outcome incidence was 4.1% (95% confidence interval: 0.9% to 11.5%). Overall catheter colonisation rate was 5.2% (5/97); CRS 2.3/1000 catheter days; CAS 14.8/1000 catheter days. Recruitment, retention and data completeness were good. No major antiseptic-related skin injury was reported. CONCLUSIONS: A definitive comparative efficacy trial is feasible, but the very low catheter colonisation rate would make a large-scale RCT challenging due to the very large sample size required. ARCTIC provides preliminary reassurance supporting potential safe use of 2% CHG-70% IPA and 2% CHG-aqueous in preterm neonates. TRIAL REGISTRATION NUMBER: ISRCTN82571474.

Characterisation of neonatal Staphylococcus capitis NRCS-A isolates compared with non NRCS-A Staphylococcus capitis from neonates and adults.

Staphylococcus capitis is a frequent cause of late-onset sepsis in neonates admitted to Neonatal Intensive Care Units (NICU). One clone of S. capitis, NRCS-A has been isolated from NICUs globally although the reasons for the global success of this clone are not well understood.We analysed a collection of S. capitis colonising babies admitted to two NICUs, one in the UK and one in Germany as well as corresponding pathological clinical isolates. Genome analysis identified a population structure of three groups; non-NRCS-A isolates, NRCS-A isolates, and a group of 'proto NRCS-A' - isolates closely related to NRCS-A but not associated with neonatal infection. All bloodstream isolates belonged to the NRCS-A group and were indistinguishable from strains carried on the skin or in the gut. NRCS-A isolates showed increased tolerance to chlorhexidine and antibiotics relative to the other S. capitis as well as enhanced ability to grow at higher pH values. Analysis of the pangenome of 138 isolates identified characteristic nsr and tarJ genes in both the NRCS-A and proto groups. A CRISPR-cas system was only seen in NRCS-A isolates which also showed enrichment of genes for metal acquisition and transport.We found evidence for transmission of S. capitis NRCS-A within NICU, with related isolates shared between babies and multiple acquisitions by some babies. Our data show NRCS-A strains commonly colonise uninfected babies in NICU representing a potential reservoir for potential infection. This work provides more evidence that adaptation to survive in the gut and on skin facilitates spread of NRCS-A, and that metal acquisition and tolerance may be important to the biology of NRCS-A. Understanding how NRCS-A survives in NICUs can help develop infection control procedures against this clone.

Bifidobacterium bacteraemia is rare with routine probiotics use in preterm infants: A further case report with literature review.

Prophylactic administration of oral probiotics is associated with significant reductions in the morbidity and mortality of necrotising enterocolitis in preterm infants. We document the first case of Bifidobacterium longum subsp. infantis sub-clinical bacteraemia, in an extremely low birth weight preterm infant, since introduction of routine probiotic treatment at the Norfolk and Norwich University Hospital 10 years ago. Whole genome comparisons confirmed the isolated strain likely originated from the probiotic product.

Sensorineural hearing loss after neonatal meningitis: a single-centre retrospective study.

Babies in intensive care are at higher risk for meningitis and sensorineural hearing loss (SNHL). We reviewed the rate of SNHL among definite cases of bacterial/fungal meningitis in our neonatal intensive care unit over a 16-year period (2006-2021). We identified 16 confirmed meningitis cases among 16 070 admissions: 8 of 10 surviving infants with available diagnostic audiology had normal/satisfactory hearing while 2 of 10 had SNHL. Both infants with permanent hearing loss had been born extremely preterm and received potentially ototoxic antimicrobials. Larger studies are needed to clarify whether SNHL occurs mainly due to meningitis itself or to its antimicrobial drug treatment.

Safety and efficacy of 2% chlorhexidine gluconate aqueous versus 2% chlorhexidine gluconate in 70% isopropyl alcohol for skin disinfection prior to percutaneous central venous catheter insertion in preterm neonates: the ARCTIC randomised-controlled feasibility trial protocol.

INTRODUCTION: Catheter-related sepsis is one of the most dangerous complications of neonatal intensive care and is associated with significant morbidity and mortality. Use of catheter-care 'bundles' has reduced the incidence of catheter-related sepsis, although individual components have not been well studied. Better evidence is needed to guide selection of the most appropriate antiseptic solution for skin disinfection in preterm neonates. This study will inform the feasibility and design of the first randomised controlled trial to examine the safety and efficacy of alcohol-based versus aqueous-based chlorhexidine antiseptic formulations for skin disinfection prior to percutaneous central venous catheterisation in preterm neonates. The antiseptics to be compared are 2% chlorhexidine gluconate (CHG) aqueous and 2% CHG in 70% isopropyl alcohol. METHODS AND ANALYSIS: The Antiseptic Randomised Controlled Trial for Insertion of Catheters (ARCTIC) is a two-centre randomised-controlled feasibility trial. At least 100 preterm infants born at <34 weeks' gestation and due to undergo percutaneous insertion of a central venous catheter will be randomly allocated to receive prior skin disinfection with one of the two antiseptic solutions. Outcomes include: i) recruitment and retention rates; ii) completeness of data collection; iii) numbers of enrolled infants meeting case definitions for definite catheter-related sepsis, catheter-associated sepsis and catheter colonisation and iv) safety outcomes of skin morbidity scores recorded daily from catheter insertion until 48 hours post removal. The key feasibility metrics will be reported as proportions with 95% CIs. Estimated prevalence of catheter colonisation will allow calculation of sample size for the large-scale trial. The data will inform whether it will be feasible to progress to a large-scale trial. ETHICS AND DISSEMINATION: ARCTIC has been approved by the National Health Service Health Research Authority National Research Ethics Service Committee East of England (Cambridge South) (IRAS ID 163868), was adopted onto the National Institute of Health Research Clinical Research Network portfolio (CPMS ID 19899) and is registered with an International Standard Randomised Control Trials Number (ISRCTN: 82571474; Pre-results) and European Clinical Trials Database number 2015-000874-36. Dissemination plans include presentations at scientific conferences, scientific publications and sharing of the findings with parents via the support of Bliss baby charity. TRIAL REGISTRATION NUMBER: ISRCTN82571474; Pre-results.

Prevalence of ciprofloxacin-resistant Enterobacteriaceae in the intestinal flora of patients undergoing transrectal prostate biopsy in Norwich, UK.

OBJECTIVE: To determine the efficacy of fluoroquinolone prophylaxis in patients undergoing transrectal ultrasonography (TRUS)-guided biopsy of the prostate in the Norwich population, and its correlation with ciprofloxacin resistance in the faecal flora. We also aimed to determine the usefulness of a pre-biopsy rectal screen for resistant bacteria in these patients. PATIENTS AND METHODS: The incidence and microbiology of sepsis after TRUS-guided prostate biopsies between 2007 and 2011 was audited retrospectively. Subsequently, in 2012, a prospective study was performed, collecting the same data but also culturing rectal swabs from all patients undergoing TRUS-guided biopsy, with a post-biopsy follow-up period of 6 months. All patients were given prophylactic oral ciprofloxacin, as per Trust policy (750 mg 1 h before biopsy, followed by 250 mg twice daily for 3 subsequent days). RESULTS: Between 2007 and 2011, 3600 patients underwent TRUS-guided biopsy. Among these, 11 (0.3%) were admitted to hospital for post-biopsy related sepsis but only 4 (0.1%) had ciprofloxacin-resistant Escherichia coli confirmed from blood cultures: three had ciprofloxacin-susceptible Enterobacteriaceae, and four had no ciprofloxacin susceptibility data. In 2012, 10 (3.7%) of 267 patients sampled before biopsy had ciprofloxacin-resistant E. coli recovered on rectal swab culture but none of these men presented with post-biopsy sepsis; during the 6-month follow-up period, seven patients were diagnosed with urinary tract infections. CONCLUSION: Ciprofloxacin-resistant Enterobacteriaceae remains rare in the intestinal flora of the Norwich TRUS population, meaning that the drug remains adequate as prophylaxis. Pre-biopsy rectal swabs may be useful for individual departments to periodically assess their own populations and to ensure their antibiotic policy remains valid. In populations where resistance is known to be highly prevalent, pre-biopsy rectal swabs can help guide addition of further antibiotics to prevent post-biopsy septicaemia.

Skin colonisation at the catheter exit site is strongly associated with catheter colonisation and catheter-related sepsis.

AIM: The commonest mode of catheter colonisation is via the extraluminal route with skin bacteria. Catheter-related sepsis causes significant mortality and morbidity in neonates. Our aim was to study the relationships between culture-positive catheter exit site skin swabs, percutaneous central venous catheter segments and blood to determine the magnitude of associations between exit site skin colonisation, catheter colonisation and catheter-related sepsis. METHODS: In a prospective study, an exit site skin swab and three formerly in vivo catheter segments (proximal, middle and tip) were taken for culture at catheter removal. In those neonates who were clinically unwell at catheter removal, a peripheral blood culture was also collected. Univariate and multivariate analyses were used to study associations. RESULTS: Skin swabs were culture positive in 39 (21%) of 187 catheter removals. With a culture-positive skin swab, the risk of associated catheter colonisation was nearly eight times higher (OR: 7.84, 95% CI: 3.59-17.15) and the risk of definite catheter-related sepsis with the same organism was nearly 10 times higher (OR 9.86, 95% CI: 3.13-31.00). CONCLUSION: Culture-positive skin swabs from the catheter exit site were strongly associated with catheter colonisation and with definite catheter-related sepsis with the same organism. These data provide further evidence supporting catheter colonisation via the extraluminal route and highlight the importance of optimising skin disinfection before catheter insertion.

Segmental percutaneous central venous line cultures for diagnosis of catheter-related sepsis.

OBJECTIVE: Culture of percutaneous central venous line (PCVL) segments may assist the diagnosis of line colonisation and catheter-related sepsis (CRS). The authors aimed to determine if the diagnosis of CRS and colonisation of PCVLs in neonates is improved by the culture of the proximal and middle segments of the line in addition to the tip. PATIENTS AND METHODS: In a prospective study, proximal, middle and tip segments of PCVLs indwelling for more than 24 h in term and preterm infants were sent for culture at line removal. Definite CRS was considered as a positive peripheral blood culture plus any line segment growing the same organism in an infant with clinical signs of sepsis. RESULTS: 189 lines were removed from 143 neonates: 142 (75%) were from well infants and 47 (25%) were from neonates with suspected clinical sepsis. The overall CRS rate was 7.9% (15 of 189 line episodes). In well infants, bacterial colonisation rates were significantly higher for proximal segments than for tips (p=0.004). Comparative rates of segmental culture positivity and their positive predictive values for definite CRS were similar for all segments. The diagnosis of CRS was not improved beyond a sole line tip culture by additional middle or proximal segmental cultures or by combinations of the three segments. CONCLUSION: In well infants, the proximal segments of PCVLs were more often colonised than line tips, but in clinically septic infants preferential culture of proximal or middle segments or combinations of the three segments did not permit better prediction of definite CRS than the culture of the line tip alone. Further studies prior to antibiotic therapy are indicated in babies with suspected CRS.

Infective endocarditis caused by Moraxella nonliquefaciens in a percutaneous aortic valve replacement.

First case of infective endocarditis on a percutaneous aortic valve replacement due to Moraxalla nonliquefaciens in 64 year old woman. It was successfully treated medically with antibiotics. She had not suitable for surgical aortic valve replacement due to 3 sternotomies for thymoma resection and subsequent radiotherapy with blocked major thoracic veins. Due to her azathioprine immunosuppresion (myasthenia) she may have been at increased endocarditis risk. We suggest prophylactic antibiotics at implant for this group in future.

Late-onset sepsis in a preterm twin may harbinger life-threatening sepsis for the asymptomatic co-twin.

We report extremely preterm twins who developed late-onset Escherichia coli sepsis in the second postnatal week within a short time of each other. The asymptomatic twin was not treated initially, and within 2 days developed life-threatening septicemia and meningitis, followed by other serious morbidity. Occurrence of late-onset sepsis in a twin should prompt concurrent investigation and consideration of presumptive treatment of the apparently asymptomatic co-twin.