The role of management on costs and efficiency in HIV prevention interventions for female sex workers in Nigeria: a cluster-randomized control trial.

BACKGROUND: While the world has made much global progress toward the reduction of new HIV infections, HIV continues to be an important public health problem. In the face of constantly constrained resources, donors and grantees alike must seek to optimize resources and deliver HIV services as efficiently as possible. While there is evidence that management practices can affect efficiency, this has yet to be rigorously tested in the context of HIV service delivery. METHODS: The present protocol describes the design of a cluster-randomized control trial to estimate the effect of management practices on efficiency. Specifically, we will evaluate the impact of an intervention focused on improving management practices among community-based organizations (CBOs), on the costs of HIV prevention services for female sex workers (FSW) in Nigeria. To design the intervention, we used a qualitative, design thinking-informed methodology that allowed us to understand management in its organizational context better and to develop a user-centered solution. After designing the suite of management tools, we randomly assigned 16 CBOs to the intervention group, and 15 CBOs to the control group. The intervention consisted of a comprehensive management training and a management "toolkit" to support better planning and organization of their work and better communication between CBOs and community volunteers. Both treatment and control groups received training to record data on efficiency-inputs used, and outputs produced. Both groups will be prospectively followed through to the end of the study, at which point we will compare the average unit cost per FSW served between the two groups using a quasi-experimental "difference-in-differences" (DiD) strategy. This approach identifies the effect of the intervention by examining differences between treatment and control groups, before and after the intervention thus accounting for time-constant differences between groups. Despite the rigorous randomization procedure, the small sample size and diversity in the country may still cause unobservable characteristics linked to efficiency to unbalanced between treatment and control groups at baseline. In anticipation of this possibility, using the quasi-experimental DiD approach allows any baseline differences to be "differenced out" when measuring the effect. DISCUSSION: This study design will uniquely add to the literature around management practices by building rigorous evidence on the relationship between management skills and practices and service delivery efficiency. We expect that management will positively affect efficiency. This study will produce valuable evidence that we will disseminate to key stakeholders, including those integral to the Nigerian HIV response.Trial registration This trial has been registered in Clinical Trials (NCT03371914). Registered 13 December 2018.

Real-world use of fidaxomicin in a large UK tertiary hospital: how effective is it for treating recurrent disease?

All courses of fidaxomicin use in the study hospital were reviewed. It was used for first recurrence (six times), second recurrence (eight times) and one case of third recurrence. One patients received fidaxomicin as first-line treatment. Eight patients initially responded to therapy; of these, three patients were asymptomatic at 90 days, three patients remained asymptomatic at 30 days, and two patients had recurrences five and nine days after stopping therapy. Four patients failed to respond; of these, two patients required faecal transplantation and one patient required a colectomy. Two patients deteriorated and two patients died. Fidaxomicin was well tolerated. These findings suggest that the utility of fidaxomicin at this stage of infection is unclear.

Candida growth in urine cultures: a contemporary analysis of species and antifungal susceptibility profiles.

BACKGROUND: Recent publications suggest the distribution of Candida species causing candiduria may vary geographically, which has implications for the continued efficacy of antifungal therapy and emerging resistance. AIM: To investigate the incidence of Candiduria at a university hospital in the UK. Further, to assess the distribution of species and the accompanying antifungal susceptibility profile, in order to monitor the clinical utility of current antifungal treatment guidelines for candiduria so that patients receive the best possible outcomes from the most up to date care. DESIGN: Retrospective audit. METHODS: From 1st January 2005 to 31st October 2014, we retrospectively reviewed 37 538 positive urine cultures recorded in a computerized laboratory results database. Identification and susceptibility testing was performed using the VITEK® 2 fungal susceptibility card (bioMérieux, Marcy d'Etoile, France). RESULTS: In total, 96 cultures were positive for Candida species, of which 69 (72%) were C.albicans, which translates to a prevalence of 2.6 per 1000 positive urine cultures. Candiduria was more common in younger patients, males and catheterized females. We report 94 and 73% of isolates of C.albicans and other non-C.albicans Candida species were susceptible to fluconazole. All isolates were susceptible to amphotericin B. CONCLUSIONS: Our results add weight to the evidence supporting current European and North American guidelines recommending fluconazole or amphotericin B for treatment of candiduria, if antifungal treatment is clinically indicated.

Pseudomonas aeruginosa meningitis/ventriculitis in a UK tertiary referral hospital.

BACKGROUND: Pseudomonas aeruginosa is a rare cause of meningitis and ventriculitis but is generally associated with significant morbidity and mortality. AIM: We sought to determine the epidemiology, risk factors and outcome of meningitis and ventriculitis due to P. aeruginosa at our institution in order to inform preventive strategies and treatment guidelines. METHODS: Retrospective study of all patients with a positive cerebrospinal fluid (CSF) culture admitted to a tertiary care hospital over 18 years. Clinical details, demographic, microbiological and antibiotic data were obtained from laboratory and medical records. RESULTS: Twenty-four episodes occurred in 21 patients over 18 years. Pyrexia (75%), fluctuating mental status (50%) and headache (41%) were the most frequent presenting symptoms. Nineteen of the 21 patients had previously undergone a neurosurgical procedure and seven had extra-ventricular devices in situ. Twelve (57%) patients had P. aeruginosa isolated from another site prior to their episode. Most (89%) CSF samples demonstrated a neutrophilia; the CSF protein, when measured, was raised in all cases. Gram-negative bacilli were visible on CSF microscopy in only three isolates. There were relatively low rates of resistance to most antimicrobials tested and combination treatment of intravenous with intrathecal antibiotics was often used. No patients died within 28 days. CONCLUSION: Pseudomonas aeruginosa meningitis and ventriculitis are predominantly nosocomial and related to prior neurosurgery. It can be difficult to diagnose as CSF Gram-film and meningism are insensitive markers. Appropriate empirical treatment, neurosurgical prophylaxis and surveillance can aid in managing this infection.

Impact of routine bedside infectious disease consultation on clinical management and outcome of Staphylococcus aureus bacteraemia in adults.

Staphylococcus aureus bacteraemia (SAB) is a common, serious infection that is associated with high rates of morbidity and mortality. Evidence suggests that infectious disease consultation (IDC) improves clinical management in patients with SAB. We examined whether the introduction of a routine bedside IDC service for adults with SAB improved clinical management and outcomes compared to telephone consultation. We conducted an observational cohort study of 571 adults with SAB at a teaching hospital in the United Kingdom between July 2006 and December 2012. A telephone consultation was provided on the day of positive blood culture in all cases, but an additional bedside IDC was provided after November 2009 (routine IDC group). Compared to patients in the pre-IDC group, those in the routine IDC group were more likely to have a removable focus of infection identified, echocardiography performed and follow-up blood cultures performed. They also received longer courses of antimicrobial therapy, were more likely to receive combination antimicrobial therapy and were more likely to have SAB recorded in the hospital discharge summary. There was a trend towards lower mortality at 30 days in the routine IDC group compared to the pre-IDC group (12% vs. 22%, p 0.07). Our findings suggest that routine bedside IDC should become the standard of care for adults with SAB.

Introduction of an antifungal stewardship programme targeting high-cost antifungals at a tertiary hospital in Cambridge, England.

BACKGROUND: Antifungal stewardship aims to promote the optimal use of antifungals through the careful selection of agents based on patient profile, target organism, toxicity, costs and the likelihood of emergence and spread of resistance. METHODS: We report on an observational prospective 12 month study conducted by an antifungal stewardship team targeting the use of echinocandins (caspofungin and micafungin), voriconazole and liposomal amphotericin B in a tertiary referral hospital in the UK. RESULTS: One-hundred-and-seventy-three patients were reviewed on 294 occasions. Clinical advice was given and implemented during review of 45 (88.2%) of micafungin prescriptions, 70 (78.7%) of those receiving voriconazole, 78 (62.4%) of those receiving liposomal amphotericin B and 3 (27.3%) of those receiving caspofungin. Except for voriconazole, nearly half of all treatments reviewed were stopped or changed. This study found that a crude cost saving of ∼£180 000 in antifungal drugs was generated compared with the previous year. CONCLUSIONS: Using a multidisciplinary team, antifungal stewardship can achieve significant improvements in patient management and it may reduce costs.

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.

An audit of acute bacterial meningitis in a large teaching hospital 2005-10.

BACKGROUND: Acute bacterial meningitis (ABM) is a rare disease associated with severe neurological sequelae and death. Clinical features on admission may be subtle and thus delay recognition. Previous studies have shown association between early administration of antibiotics and favourable outcomes. AIM: To examine the presenting clinical features of patients aged >15 years with ABM admitted to a University teaching hospital. To audit investigations and treatment including lumbar puncture (LP), computed tomography (CT) and antibiotics against British Infection Association guidelines. DESIGN: Retrospective observational audit. METHODS: Hospital records were reviewed for presenting clinical features and timing of CT scan, LP and antibiotics. RESULTS: Records of 39 patients with ABM were reviewed. The classical triad of fever, neck stiffness and altered mental state was present on admission in only 21% of cases. LP was contraindicated in 69% of cases. Immediate LP was carried out in only 17% of those who had no contraindication. Antibiotics were administered after a median of 79 min (interquartile range 24-213 min); 65% were given within 3 h after arrival. Eighty-five percent of patients had antibiotics in accordance with local guidelines. CONCLUSION: In patients with ABM, the classical clinical features are uncommon on arrival to hospital and frequently evolve following admission. The majority of patients have contraindications to immediate LP. Efforts should be made to facilitate immediate LP performed in the Emergency Department when there are no contraindications. Earlier administration of antibiotics in cases of suspected ABM and close review following admission is recommended.

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.

Bacteraemia and subsequent vertebral osteomyelitis: a retrospective review of 125 patients.

BACKGROUND: Vertebral osteomyelitis (VO) is associated with considerable morbidity and its incidence seems to be increasing. Haematogenous spread is an important aetiological factor. AIM: The objective was to describe a series of patients with VO and to search for a relationship between preceding bacteraemia and subsequent VO with the same pathogen. DESIGN AND METHODS: A retrospective study of all treated cases of VO in a tertiary hospital over a 10-year period. RESULTS: There were 129 cases of VO (involving 125 patients) that received antimicrobial treatment. Eighty-three (66%) were male and the mean age was 59.5 years (range 1 month to 87 years). The vertebral level involved was lumbar in 66 (53%) cases and thoracic in 35 (28%) cases. Seventy-four cases (59%) had a microbiologically confirmed aetiology. The diagnostic yield from procedures was 46 and 36% from blood culture and bone biopsy, respectively. Staphylococcus aureus was the most common pathogen [38 of 74 (51%) cases]. Nine of 38 (24%) cases of Staphylococcus aureus VO had a preceding bacteraemia with the same pathogen in the previous year. CONCLUSION: Staphylococcus aureus is an important pathogen causing bacteraemia with the ability to cause metastatic complications including VO. The high proportion of cases developing VO following a documented bacteraemia, sometimes many months previously, reinforce the importance of adequate aggressive treatment for bacteraemia. VO must be considered in all patients presenting with back pain up to a year after bacteraemia. Previous bacteraemias with relevant pathogens can help guide antibiotic treatment at presentation of VO and if biopsy cannot be obtained.

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.

Role of interferon-gamma release assays in healthcare workers.

The advent of interferon-gamma release assays (IGRAs) provides new options for detection of latent tuberculosis infection (LTBI). This is particularly relevant to healthcare workers (HCWs), who are at higher risk of infection, but who have often also been vaccinated. In this article, we discuss the role of IGRAs for the diagnosis of LTBI in various healthcare settings. A search was performed for studies that reported data on IGRAs in HCWs in the last 18 years. Twenty-two studies met the inclusion criteria. IGRAs showed poor agreement with the tuberculin skin test (TST), except in countries with high incidences of tuberculosis (TB), but generally correlated better with markers of exposure to TB including during contact investigation. The T-SPOT.TB assay has not been adequately assessed in HCWs; the few studies available showed enhanced specificity of T-SPOT.TB when compared to TST. This review confirms the utility of IGRAs as important tools in the prevention and control of tuberculosis in healthcare settings.

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.

Detection of Mycobacterium avium subspecies paratuberculosis from patients with Crohn's disease using nucleic acid-based techniques: a systematic review and meta-analysis.

This study is a systematic review and meta-analysis of studies using nucleic acid-based techniques to detect Mycobacterium avium paratuberculosis (MAP) in patients with Crohn's disease (CD) compared with controls. Database searches were conducted and risk difference estimates were calculated using meta-analysis. Fifty-eight studies were reviewed, 47 of which were included in the analysis. The pooled estimate of risk difference from all studies was 0.23 (95% confidence interval [CI], 0.14-0.32) using a random effects model. Similarly, MAP was detected more frequently from patients with CD compared with those with ulcerative colitis (risk difference 0.19, 95% CI, 0.10-0.28). Year of study, assay type, and inclusion of children explained some but not all of the observed heterogeneity. The data confirms the observation that MAP is detected more frequently among CD patients compared with controls. However, the pathogenic role of this bacterium in the gut remains uncertain. Our analysis demonstrates that there is an association between MAP and CD, across many sites, by many investigators, and controlling for a number of factors; however, this association remains controversial and inconclusive. Future studies should determine whether there is a pathogenic role.