Catheter-related infections in patients with acute type II intestinal failure admitted to a national centre: Incidence and outcomes.

INTRODUCTION: The management of intestinal failure (IF) requires safe and sustained delivery of parenteral nutrition (PN). The long-term maintenance of central venous catheter (CVC) access is therefore vital, with meticulous catheter care and salvage of infected CVCs being of prime importance. CVC-related infection and loss of intravenous access are important causes of morbidity and mortality in IF. Avoidance, prompt recognition and appropriate management of CVC-related infections are crucial components of IF care. However, there are few, if any, data on the occurrence of CVC-related infections in patients with acute, type 2, IF managed on a dedicated IF unit and no data on the salvage outcomes of infected CVCs in this group of patients. METHODS: This is a retrospective observational study conducted between January 2011 and July 2017. All patients with acute, type 2 IF newly admitted to a national U.K. IF unit (IFU) during these dates were included. All patients admitted to the unit with a CVC in place underwent immediate 'screening' paired central and peripheral blood cultures on arrival before the CVC was used for any infusate. A prospectively maintained database was used to record all confirmed catheter-related blood stream infections (BSI)/colonisations, demographic and clinical data. Diagnosis of catheter-related BSI/colonisation was based on quantitative and qualitative analysis of paired central and peripheral blood cultures. A standardized 10-14-day catheter salvage treatment protocol involving antibiotic and urokinase CVC locks and systemic antibiotic administration was used to salvage any infected or colonised CVCs, as appropriate. The CVC was not used for PN until successful salvage had been confirmed by negative blood cultures drawn 48 h after antibiotic completion. The development of a subsequent catheter-related BSI was recorded for all patients, both during the remaining in-patient stay on the IFU and after discharge home on PN. RESULTS: Of the 509 patients with type 2 IF admitted to the IFU during the study period, 341 (54% female; mean age 54.6 (range 16-86 years)) had an indwelling CVC that had been placed in the referring hospital. Surgical complications and mesenteric ischaemia were the most common underlying disease aetiologies. Sixty-five of 341 (19.1%) patients had an infected/colonised CVC on the initial screening set of blood cultures. A successful CVC salvage rate of 91% was achieved in this cohort after antibiotic therapy. The subsequent in-patient catheter-related BSI rate for those admitted with a CVC (n = 341) on the IFU was 0.042 per 1000 catheter days, over a total of 23,548 in-patient catheter days. Two hundred and seventy nine of 341 patients were discharged on home PN (HPN); with a subsequent catheter-related BSI rate on HPN of 0.22 per 1000 catheter days (mean duration of HPN = 778 catheter days (range:)) over a follow-up period of 216,944 out-patient catheter days. There was no increased risk of HPN-related catheter-related BSI (p = 0.09) or mortality (p = 0.4) in those admitted with an infected CVC. CONCLUSION: This is the first study to report catheter-related BSI/colonisation rates and salvage outcomes in patients with type 2 IF newly admitted to a dedicated IF Unit. We report that nearly one-fifth of all patients were referred with evidence of a catheter related BSI/colonisation; despite this, successful catheter salvage is possible and, with stringent CVC care, an extremely low subsequent catheter related BSI rates can be achieved and maintained during in-patient stay on a dedicated IF Unit and after discharge on HPN. These data provide novel evidence to support ESPEN recommendations that patients with type 2 IF are managed on a dedicated IF Unit.

Assessing the impact of quality improvement measures on catheter related blood stream infections and catheter salvage: Experience from a national intestinal failure unit.

BACKGROUND & AIMS: Prevention of catheter related blood stream infections (CRBSI) and salvage of infected central venous catheters (CVC) are vital to maintaining long term venous access in patients needing home parenteral nutrition (HPN). It remains unclear as to whether patients are best trained for catheter care at home or in hospital or whether CRBSIs are lower if the patient self-cares for the CVC. Furthermore, there is minimal data on the longer term outcome following salvage of infected catheter and limited consensus on agreed protocols for catheter salvage. METHOD: We conducted a retrospective 5-year evaluation of CRBSI occurrence and CVC salvage outcomes in adult patients requiring HPN managed at a national UK Intestinal Failure Unit from 2012 to 2016. Prior to 2012, patients were primarily trained to administer PN in hospital; thereafter, patients underwent training at home. RESULTS: A total of 134 CRBSI were recorded in 92 patients (62 patients with a single CRBSI and 30 patients with more than 1 CRBSI) in a cohort of 559 HPN patients, with a total of 1163 HPN years. The overall CRBSI rate was 0.31 per 1000 catheter days. CNS were the most common isolates (41/134 (30.5%)), followed by polymicrobial infections (14/134 (10.4%)), Klebsiella spp. (16/134 (11.9%)) and methicillin - sensitive Staphylococcus aureus (MSSA) 5/134 ((3.7%)). Salvage was not attempted in 34 cases due to methicillin - resistant (MRSA) infection (1/34), fungal infection (13/34) or clinical instability due to sepsis (20/34). Of the 100 cases where salvage was attempted, 67% were successful. 82.8% of CNS salvage attempts were successful; there was no difference in salvage rates between CNS CRBSIs salvaged with a 10-day (22/26) or 14-day protocol (7/9) (p = 0.4). CRBSI rate, in those cared for by trained home care nurses was the lowest at 0.270 (self care: 0.342 and non-medical carer (e.g. family member): 0.320) (p = 0.03). CONCLUSION: We previously reported a sustained very low CRBSI rate in a large cohort of HPN patients in a national unit; we now further report that this is not influenced by training patients at home rather than in hospital but is influenced by the individual managing the catheter at home. CNS remains the primary cause of CRBSIs and can be successfully salvaged with a reduced duration of antibiotic therapy compared to our previous experience.

Dapsone-induced methemoglobinemia in renal transplant recipients: more prevalent than previously thought.

BACKGROUND: After an outbreak of Pneumocystis pneumonia (PCP) in our nephrology unit, dapsone was used as the second-line chemoprophylactic agent. Dapsone is the most common cause of drug-induced methemoglobinemia (MHb). Its prevalence is poorly described in the renal transplant population. Because dapsone is excreted by the kidneys, we hypothesized that the rate of MHb in these patients would be higher than previously reported. We aimed to describe the demographics, risk factors, and presenting features of MHb in these renal transplant patients. METHODS: Twenty-six transplant recipients commenced on dapsone for chemoprophylaxis against PCP from February to September 2011. All patients had normal glucose-6-phosphate dehydrogenase levels before treatment. Characteristics of patients with MHb were compared with those of the rest of the cohort to determine potential risk factors. RESULTS: Twelve (46%) patients developed MHb (levels 6.4 ± 4.1%). Six (50%) of the patients with MHb were asymptomatic on presentation. Cases had a mean drop in hemoglobin of 19 ± 7%. MHb led to five admissions (median length of stay 5 days, range 1-10 days). MHb level showed a strong correlation with the length of stay (correlation coefficient 0.762, P = 0.002). CONCLUSION: This is the highest reported prevalence of MHb, to our knowledge, in patients receiving dapsone, and its use led to significant hospitalization in this population. This study raises concerns about the use of dapsone as chemoprophylaxis in renal transplant recipients.

Investigation of a cluster of cutaneous aspergillosis in a neonatal intensive care unit.

Between December 2007 and July 2008, three neonates in a neonatal intensive care unit (NICU) in Salford, UK, were diagnosed with primary cutaneous aspergillosis (PCA) due to Aspergillus fumigatus. The first PCA case, in December 2007, developed multi-organ failure leading to death within a short time frame: the other two cases survived after treatment with intravenous antifungal therapy followed by oral posaconazole. Air, surface, and water samples were collected within the NICU and from the incubators that were occupied by the neonates. All recovered fungal isolates were confirmed as A. fumigatus by sequencing the beta-tubulin region. Microsatellite strain typing demonstrated genotypically related A. fumigatus isolates from the neonates and the humidity chambers (HCs) of the neonates' incubators, suggesting that the source of the infection may have been the HCs/incubators used in the NICU. Aspergillus strain typing may be a useful tool in clinical outbreak settings to help understand the source of exposure and to design targeted environmental interventions to prevent future infections.

Methicillin-resistant Staphylococcus aureus bacteraemia and mortality in a teaching hospital.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for more than 40% of S. aureus bacteraemias in the UK and is associated with considerable morbidity and mortality. This retrospective audit examined the epidemiology of MRSA bacteraemia (MRSAB) at our institution, where the MRSAB rate has been high. A retrospective case note review was undertaken of all patients dying within 90 days of an episode of MRSAB during a 12-month period. A clinical panel classified deaths as having MRSAB as the main cause, contributing cause or having no bearing on the death. Sixty-two patients had one or more episodes of MRSAB and 30 died within 90 days. The mean age of those dying was 72 (43-96) years and of those surviving was 57 (21-87) years. MRSAB was judged to be the main or contributing cause of death in 24 cases, giving an associated mortality of 39%. All-cause mortality at 7, 30 and 90 days was 19, 40 and 48%, respectively. We investigated the minimum inhibitory contribution (MIC) to vancomycin for 79 MRSAB isolates, of which 70.8% of isolates had an MIC value of 2 mg/l. None of the isolates expressed heteroresistance to vancomycin. Five out of seven patients in whom MRSAB was the main cause of death had community onset of infection. It is unlikely that efforts to reduce delays in delivering effective antimicrobial therapy will have a major impact on mortality. Efforts to reduce the burden of MRSAB should focus on the primary prevention of bacteraemia.

Best practice in primary care pathology: review 10.

This tenth best practice review examines four series of common primary care questions in laboratory medicine: (i) antenatal testing in pregnant women; (ii) estimated glomerular filtration rate calculation; (iii) safety testing for methotrexate; and (iv) blood glucose measurement in diabetes. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence-based. They will be updated periodically to take account of new information.

Glutamine deprivation facilitates tumour necrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate.

BACKGROUND AND AIMS: Factors that induce luminal bacteria to cross the intestinal epithelium following injury remain poorly defined. The aim of this study was to investigate the interaction between glutamine metabolism, energy supply, and inflammatory mediators in determining the translocation of non-pathogenic bacteria across cultured enterocytes. METHODS: The effect of tumour necrosis factor alpha (TNF-alpha) on translocation of Escherichia coli C25 across Caco-2 epithelial monolayers was studied in the presence of products and inhibitors of glutamine metabolism. Simultaneous measurements of transepithelial electrical resistance (TEER) and flux of lucifer yellow were used to assess effects on the paracellular pathway. Lactate dehydrogenase release was used to monitor enterocyte integrity. Imaging of monolayers in these experimental conditions was undertaken with transmission electron microscopy. RESULTS: Exposure to basolateral TNF-alpha (20 ng/ml) for six hours induced translocation of E coli across Caco-2 but only if accompanied by simultaneous glutamine depletion (p<0.01). Translocation was inhibited by addition of glutamine for two hours (p<0.01) but not by an isonitrogenous mixture of non-glutamine containing amino acids. Inhibition of glutamine conversion to alpha-ketoglutarate, but not blockade of glutathione or polyamine synthesis, also induced translocation in the presence of TNF-alpha. Manipulations that induced bacterial translocation were associated with a marked reduction in enterocyte ATP levels. No effect of these treatments on paracellular permeability or lactate dehydrogenase release was observed. Conditions in which translocation occurred were associated with the presence of bacteria within enterocyte vacuoles but not the paracellular space. CONCLUSIONS: In inflammatory conditions, the availability of glutamine as an enterocyte fuel substrate is essential for the preservation of a functional barrier to microorganisms. In conditions of acute glutamine depletion, cytokine mediated bacterial translocation appears to be primarily a transcellular process.

Increased stool sampling during a waterborne outbreak of cryptosporidiosis does not increase the detection of other faecal pathogens.

AIMS: To ascertain the effect of enhanced surveillance following an outbreak of waterborne cryptosporidiosis on the number of faecal specimens submitted to the local microbiology laboratory and the number positive for common enteric pathogens. The outbreak provided an opportunity to estimate the extent of routine under ascertainment of common enteric pathogens. METHOD: Retrospective search of the computerised microbiology system database for details of faecal examination requests for the period 26 April to 6 June in 1998 and 1999 (period of outbreak). RESULTS: Specimens were received from 378 community patients during the six week period 26 April to 6 June 1999. This was double that for the same period in 1998 (a non-outbreak year). Oocysts of Cryptosporidium parvum were detected in 59 patients, an eightfold increase compared with the same period in 1998. Despite the greater number of patients tested, the detection of other pathogens in patients with gastroenteritis was not altered when compared with the same period in the previous year. CONCLUSION: This study found no evidence of under ascertainment of gastrointestinal infection (common bacterial pathogens and rotavirus) by local general practitioners.

Management of hospital outbreaks of gastro-enteritis due to small roundstructured viruses.

Small round structured viruses (SRSVs, Norwalk-like viruses, NLVs) are the most common cause of outbreaks of gastro-enteritis in hospitals and also cause outbreaks in other settings such as schools, hotels, nursing homes and cruise ships. Hospital outbreaks often lead to ward closure and major disruption in hospital activity. Outbreaks usually affect both patients and staff, sometimes with attack rates in excess of 50%. For this reason, staff shortages can be severe, particularly if several wards are involved at the same time. SRSVs may be spread by several routes: faecal-oral; vomiting/aerosols; food and water. Viruses may be introduced into the ward environment by any of these routes and then propagated by person-to-person spread. In an outbreak setting, the diagnosis can usually be made rapidly and confidently on clinical and epidemiological grounds, particularly if vomiting is a prominent symptom. By the time an SRSV outbreak has been recognized at ward level, most susceptible individuals will have been exposed to the virus and infection control efforts must prioritize the prevention of spread of infection to other clinical areas bycontainment of infected/exposed individuals (especially the prevention of patient and staff movements to other areas), hand-hygiene and effective environmental decontamination. This report of the Public Health Laboratory Service Viral Gastro-enteritis Working Group reviews the epidemiology of outbreaks of infection due to SRSVs and makes recommendations for their management in the hospital setting. The basic principles which underpin these recommendations will also be applicable to the management of some community-based institutional outbreaks.

Preventing pancreatic infection in acute pancreatitis.

In acute pancreatitis, pancreatic inflammation may be complicated by the development of pancreatic infection with a high associated mortality. Pancreatic infection is related to the extent of pancreatic inflammation and necrosis and typically occurs in the second or third week of severe disease. It may be associated with a wide range of Gram-positive and Gram-negative bacteria, notably enterobacteria and also with Candida spp. Current surgical practice in the UK is to use prophylactic antimicrobial therapy in patients with severe disease, with the aim of preventing secondary pancreatic infection. Experimental evidence demonstrates that prophylactic antibacterial therapy prevents pancreatic infection and reduces mortality. Furthermore, studies of antibacterial prophylaxis in patients with acute pancreatitis suggest that prophylactic antibacterial therapy is associated with a reduction in mortality, particularly in those with severe disease. In general, broad-spectrum antibiotics have been used in animal and human studies. However, current evidence does not allow comparisons to be made between different antimicrobial agents. Nutritional strategies may also be important in the prevention of pancreatic infection. Enteral, rather than parenteral, nutrition has been associated with an improved clinical outcome in severe pancreatitis.

A study of infection in elderly nursing/residential home and community-based residents.

It is commonly believed that patients admitted to hospital from nursing homes/residential homes (NHRH) with infections are less likely to respond to treatment and have a higher fatality rate than counterparts admitted from their own homes ('the Community'). It is also believed that NHRH's harbour a reservoir of unusual and resistant organisms. These preconceptions may influence how these patients are managed. A database of 10593 sequential admissions to a Geriatric Medical unit over a three-year period was used to identify NHRH and community populations with a principal diagnosis of infection. They were investigated using the Department of Microbiology's database. The admission rate in the NHRH group was twice that of the community group. There were no significant differences in length of stay (LOS) [16 +/- 2 vs 17 +/- 2 days (s.e.m.)], or mean survival time (ST)(61 days (37-84) vs 48 days (25-72): 95% confidence intervals) between the two groups. Subgroups of the NHRH group did have significantly different survival times. Fatality rate was not significantly different between the NHRH (40%) or Community (35%) groups. Both the NHRH and community group underwent very similar levels of investigation (189 vs 200 investigations performed). The types and frequencies of pathogen seen in the two groups were very similar.

Detection of glycopeptide-resistant enterococci in routine diagnostic faeces specimens.

Faeces received in a diagnostic laboratory were screened for glycopeptide-resistant enterococci (GRE) on modified Lewisham medium, with and without enrichment in Enterococcosel broth. Colonization by GRE was detected in 102/838 patients (12.2%). In 74 (73%) of colonized patients GRE were detected by both methods and in 28 (27%) they were detected only after enrichment. The carriage rate in hospitalized patients was 32% (93/289) compared with 2.3% (11/425) in the community (GP patients and food-handlers). Carriage of GRE increased with age. Clostridium difficile isolation was associated with GRE colonization, odds ratio 6.76 (P<0.001). Fifty-nine percent (60/102) of the GRE had the VanA phenotype and 41% (42/102) had the VanB phenotype. In the community VanA predominated (91%), whereas 64% (57/89) of the isolates from hospitalised patients were of the VanB phenotype.