An enzyme-responsive controlled release system based on a dual-functional peptide.

A new controlled release system was developed by loading a dual-functional peptide (DFP) on a mesoporous silica material. One-pot synthesis produced a DFP that was stimuli responsive, releasing a therapeutic peptide by protease cleavage. The design provides new steps towards smart biomaterials.

Co-infection as a confounder for the role of Clostridium difficile infection in children with diarrhoea: a summary of the literature.

Although Clostridium difficile is a major cause of antibiotic-associated diarrhoea in adults, the incidence and severity of C. difficile infection (CDI) in children is unclear. One complicating factor in assessing the role of CDI in children is the possibility of co-infection with other gastrointestinal pathogens. In this review, we summarise the literature concerning C. difficile co-infections in young children, in an attempt to discuss the rate of co-infections and their potential role in the severity of CDI clinical presentation. We identified 31 studies where co-infections were analysed, comprising 1,718 patients with positive C. difficile tests. The pooled percentage of reported co-infections was 20.7% (range 0-100%). Viral co-infections were most commonly reported (46%), with bacteria and parasites accounting for 14.9% and 0.01% of cases, respectively. However, the panel of co-infections tested for varied considerably among studies and 38% of stated co-infections did not have a pathogen reported. Substantial variation in how and when tests for gastrointestinal co-infections are carried out, small sample sizes and a lack of clear CDI case definitions preclude meaningful conclusions on the true rate of co-infections in this patient population. This review suggests that co-infections may be common in children with diarrhoea who tested positive for C. difficile. Given a lack of CDI case definitions, especially in young children under the age of 5 years, a broad panel of pathogens should be tested for to exclude other microbiological causes. However, the summarised poor quality of the available literature on this subject highlights a need for further studies.

Micafungin for the treatment of invasive aspergillosis.

Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients, particularly those with neutropenia and those undergoing bone marrow or stem cell transplants. Micafungin is an echinocandin antifungal drug with activity against all major Candida spp. Currently, micafungin is indicated for treatment of invasive candidiasis, oesophageal candidiasis and prophylaxis of Candida infection in patients undergoing allogeneic haematopoietic stem cell transplantation or patients who are expected to have neutropenia. Micafungin demonstrates in vitro and in vivo activity against Aspergillus spp. It is currently not licensed to treat Aspergillus infections in the UK or USA. This review summarises the current evidence base surrounding the clinical use of micafungin in the treatment of invasive aspergillosis to consider the potential role of micafungin in these patients. There are currently no randomised studies comparing micafungin with standard antifungal therapy. Prospective non-randomised clinical studies, predominantly performed in Japan, involving 492 patients with aspergillosis and 455 febrile patients with chemotherapy-induced neutropenia suggest that micafungin may be as effective as comparator antifungal agents. Other clinical evidence is limited to case reports. Further experience in the form of randomised controlled trials is required to establish the exact role of micafungin in the context of currently available broad-spectrum antifungal agents.

Epidemiology of extended-spectrum beta-lactamase-producing Enterobacteriaceae in a UK district hospital; an observational study.

BACKGROUND: Extended-spectrum beta-lactamases (ESBLs) are an increasingly important cause of resistance in Gram-negative bacteria throughout the world. AIM: We investigated the clinical and molecular epidemiology of infections caused by ESBL-producing Enterobacteriaceae in a UK hospital, to identify the types of ESBL produced and risk factors for acquisition. METHODS: Between July 2008 and June 2009, all patients yielding ESBL-producing Enterobacteriaceae from any clinical specimen were prospectively investigated using a questionnaire. API20E was used for bacterial identification; susceptibility testing and ESBL production were assessed by BSAC disc diffusion and cefpodoxime-clavulanate synergy tests, respectively. Polymerase chain reaction was used to screen a subset of isolates for bla(CTX-M) genes, to assign Escherichia coli isolates to their phylogenetic groups, and to identify members of the uropathogenic ST131 lineage. RESULTS: The overall prevalence of ESBL producers among clinical samples yielding Enterobacteriaceae was 1%; ESBL producers, obtained from 124 patients, were E. coli (N = 105), Klebsiella pneumoniae (N = 12), and others (N = 7). The main risk factors identified include recent antibiotic use (93%) and presence of a urinary catheter (24%). CTX-M group 1 ESBLs dominated (in 59 of 78, 76%, isolates studied). Most E. coli (35 of 56 tested) were phylogroup B2; of these, 23 belonged to the ST131 clone, 12 were phylogroup D, and four each belonged to phylogroups A and B1. CONCLUSION: ESBLs are an uncommon but significant problem in north-west Cambridgeshire. CTX-M-type enzymes were found in 75% of ESBL-positive isolates. All but two patients had at least one recognized risk factor. This study supports the requirement for interventions to reduce inappropriate urinary catheterization and antibiotic prescribing.

Campylobacter gastroenteritis associated with Sweet's syndrome.

Sweet's syndrome or acute febrile neutrophilic dermatosis has been associated with underlying infection, malignancy, inflammatory disease and certain medications. The infection agents associated with this include Streptococcus species, Yersinia species, Chlamydia species, Salmonella species and Helicobacter pylori. We report a case of Sweet's syndrome in a 73-year-old woman following a 2 week course of severe gastroenteritis caused by Campylobacter species. Histological examination of skin lesions showed marked inflammatory infiltrate throughout the dermis, composed of neutrophils and histiocytes. The patient was successfully treated with topical and systemic steroids. To date, this is the first case of Sweet's syndrome to be reported linked to Campylobacter species to our knowledge.

MRSA surveillance in a UK district hospital: measuring clinical isolates with MRSA is more useful than measuring MRSA bacteraemias.

The introduction of mandatory surveillance of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemias and targets in England has led to reductions in most hospitals. However, reductions were difficult to demonstrate at Peterborough & Stamford Hospitals NHS Foundation Trust as MRSA bacteraemia was already an uncommon event. The authors questioned the efficacy of monitoring bacteraemias in a low-prevalence hospital, and this study sought to determine the accuracy of measuring bacteraemias compared with all clinical isolates (excluding bacteraemias; e.g. wound, sputa, urine) to assess the effectiveness of interventions. Over the six-year study period, a significant reduction was seen in MRSA in clinical specimens and new MRSA carriers identified by screening, whereas the MRSA bacteraemia rate remained at low levels. The measurement of clinical isolates may be more useful for assessment of the effectiveness of interventions now that MRSA bacteraemia rates have fallen to low levels almost universally across the UK.

Posaconazole for the treatment of mucormycosis.

Posaconazole (PCZ) is an orally administered, extended-spectrum triazole antifungal agent with activity against the Mucorales. This article describes the clinical and laboratory data supporting its use against this rare group of pathogens. To date, PCZ has been mostly used for salvage therapy and at present there is no strong published clinical evidence to support its role as a single agent in the treatment of mucormycosis. Further studies are required to explore its role as a single agent and in combination therapy for the management of these infections.

Outcome for Gram-negative bacteraemia when following restrictive empirical antibiotic guidelines.

INTRODUCTION: Restrictions in prescribing broad spectrum antimicrobials have been part of a strategy to reduce Clostridium difficile cases in the UK in recent years. However, there has been little work on assessing the safety of alternative antimicrobial agents. METHODS: We performed an uncontrolled prospective observational survey over a 1-year period to determine the effectiveness and safety of a new antimicrobial stewardship programme in a district hospital in the UK. RESULTS: In total, 227 Gram-negative bacteraemias (203 episodes) occurred in the study period. Guidelines were adequate in 194 of 203 (95%) episodes and 163 episodes (80.2%) received adequate therapy. Patients in the inadequate therapy group had >2-fold increased likelihood of death [odds ratio (OR) = 2.63, 95% confidence interval (CI) = 1.09-6.34] within 30 days and >6-fold increased risk of death (OR = 6.40, 95% CI = 2.22-18.45) within 1 week when compared to patients in the adequate therapy group. Failure to administer gentamicin was the principal reason for not following the guidelines (18 episodes). Eight of these 18 episodes were susceptible to cefuroxime and two of these patients died. DISCUSSION: Adherence to the guidelines was associated with a correct empirical antibiotic choice and reduced mortality. This study also demonstrates the importance of adopting guidelines based on local susceptibility patterns.

A review of mortality due to Clostridium difficile infection.

SUMMARY: In this review we examine published literature to ascertain mortality in relation to Clostridium difficile infection (CDI) and the factors associated with mortality. In the 27 studies that had sufficient data, there were 10975 cases of CDI with great heterogeneity in the methods for reporting mortality. We calculated the overall associated mortality to be at least 5.99% within 3 months of diagnosis. The most important finding is that higher mortality is associated with advanced age, being 13.5% in patients over 80 years. Studies performed after 2000 had a significantly higher mortality than those before this date. We propose minimum standards for reporting mortality in future studies.

Relapse of enterococcal prosthetic valve endocarditis with aortic root abscess following treatment with daptomycin in a patient not fit for surgery.

Daptomycin is a novel lipopeptide with activity against Gram-positive organisms including enterococci. It is licensed for the treatment of Staphylococcus aureus bacteraemia and right-sided endocarditis, but not endocarditis due to Enterococcus spp. We report a case of enterococcal prosthetic valve endocarditis with an aortic root abscess in an elderly patient who was not fit for surgery. The patient's endocarditis relapsed 9 weeks after a 6 week course of daptomycin.

Random meticillin-resistant Staphylococcus aureus carrier surveillance at a district hospital and the impact of interventions to reduce endemic carriage.

Colonisation with meticillin-resistant Staphylococcus aureus (MRSA) has previously been described as a risk factor for subsequent infection. MRSA colonisation reached endemic proportions in most healthcare institutions in the UK during the 1990s. Bacteraemia due to MRSA is associated with increased mortality and morbidity compared with meticillin-susceptible S. aureus and national targets have been set for reduction. We present our findings of regular random colonisation surveillance and systematic decolonisation of MRSA carriers over a five-year period with the aim of reducing the pool of carriers and number of MRSA bacteraemia cases. Interventions to reduce the rate of colonisation included assurance of decolonisation and follow up, targeting wards with the highest carriage rates using enhanced screening and education, and screening all admissions aged >65 years. There was a statistically significant reduction in the proportion of patients colonised from 14.6% to 7.0% (P<0.001) and the total number of bacteraemia cases from 42 to 22 (P=0.012) in the initial 24 months of surveillance compared to the most recent 24 months. Regular surveillance of MRSA carriage is useful for monitoring the effects of control measures on MRSA carriage among inpatients. Interventions to reduce carriage are able to reduce the pool of MRSA carriers, thereby reducing cases of bacteraemia.

Oral antimicrobial options for the treatment of skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in the UK.

This review outlines the oral treatment options available for treating skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus (MRSA) in the community and discusses the evidence supporting their use.

Meticillin-resistant Staphylococcus aureus carriage among district nurse patients and medical admissions in a UK district.

We studied the prevalence of meticillin-resistant Staphylococcus aureus (MRSA) carriage in two defined community populations and assessed risk factors associated with MRSA colonization. The study was designed as a population prevalence survey and was carried out in the medical assessment unit (MAU) of the local hospital and the district nurse patient (DNP) population in Huntingdonshire. In all, 162 participants were recruited, 91 were from MAU and 71 from the DNP population. MRSA was found in 21.1% [confidence interval (CI): 11.6-30.4] of the DNP study population and 6.6% (CI 1.5-11.7) of the MAU study population. Factors found to be significantly associated with MRSA colonization were age (76.6 years, P=0.008), presence of wound/ulcer (P=0.012), hospital admission in the past year (P=0.017), past history of MRSA (P<0.001), and antibiotic use in the preceding six months (P=0.016). The only independent predictor for MRSA colonization was found to be past history of MRSA (adjusted odds ratio: 8.53; CI: 2.11-34.43; P=0.003). The DNP population are a significant reservoir for MRSA in the community and policies on screening high-risk patients need to reflect this.

The catalase reaction of Shigella species and its use in rapid screening for epidemic Shigella dysenteriae type 1.

As epidemic dysentery caused by Shigella dysenteriae type 1 is associated with high mortality, early identification of outbreaks is important. Since S. dysenteriae type 1 differs from most of the Enterobacteriaceae in that it does not produce catalase, a test for catalase may provide a useful screening method. The ability of a catalase test to provide rapid identification of S. dysenteriae type 1 has now been assessed, using isolates of this pathogen from five continents, Shigella of other species, and entero-invasive (EIEC) and Shiga-toxin-producing Escherichia coli (STEC). All of the isolates of S. dysenteriae type 1, as well as S. dysenteriae of types 3, 4, 6, 9, 11 and 12 and S. boydii of type 12, were found catalase-negative. All the other bacteria tested were positive for catalase. In an epidemic setting in South Africa, 406 xylose-negative and lysine-decarboxylase-negative isolates, collected from xylose-lysine-deoxycholate (XLD) agar, were tested for catalase. All 356 of the catalase-negative isolates were confirmed to be of S. dysenteriae type 1. None of the catalase-positive isolates were of S. dysenteriae type 1. The catalase test is useful in the rapid, presumptive identification of S. dysenteriae type 1, from appropriate culture media, because of its high predictive value, simplicity and speed. It would be particularly useful during dysentery outbreaks, when other Shigella would be uncommon. There was no association between the absence of catalase activity and the production of Shiga toxin.

Two cases of parotid gland infection with bacteraemia due to meticillin-resistant Staphylococcus aureus.

Parotid gland infection as a source of meticillin-resistant Staphylococcus aureus bacteraemia has been rarely reported. It is predominantly a disease of the elderly and is associated with significant mortality. Two cases are described here that presented over a 6 month history at a district general hospital. Many cases may be preventable with adequate hydration and good oral hygiene, combined with effective infection control.