Skin and soft tissue infections and current antimicrobial prescribing practices in Australian aged care residents.

To determine the burden of skin and soft tissue infections (SSTI), the nature of antimicrobial prescribing and factors contributing to inappropriate prescribing for SSTIs in Australian aged care facilities, SSTI and antimicrobial prescribing data were collected via a standardised national survey. The proportion of residents prescribed ⩾1 antimicrobial for presumed SSTI and the proportion whose infections met McGeer et al. surveillance definitions were determined. Antimicrobial choice was compared to national prescribing guidelines and prescription duration analysed using a negative binomial mixed-effects regression model. Of 12 319 surveyed residents, 452 (3.7%) were prescribed an antimicrobial for a SSTI and 29% of these residents had confirmed infection. Topical clotrimazole was most frequently prescribed, often for unspecified indications. Where an indication was documented, antimicrobial choice was generally aligned with recommendations. Duration of prescribing (in days) was associated with use of an agent for prophylaxis (rate ratio (RR) 1.63, 95% confidence interval (CI) 1.08-2.52), PRN orders (RR 2.10, 95% CI 1.42-3.11) and prescription of a topical agent (RR 1.47, 95% CI 1.08-2.02), while documentation of a review or stop date was associated with reduced duration of prescribing (RR 0.33, 95% CI 0.25-0.43). Antimicrobial prescribing for SSTI is frequent in aged care facilities in Australia. Methods to enhance appropriate prescribing, including clinician documentation, are required.

Epidemiology of Exobasidium Leaf and Fruit Spot of Rabbiteye Blueberry: Pathogen Overwintering, Primary Infection, and Disease Progression on Leaves and Fruit.

Epidemiological field studies utilizing disease monitoring, spore trapping, and trap plants were conducted on rabbiteye blueberry (Vaccinium virgatum) between 2014 and 2017 to shed light on the epidemiology of Exobasidium leaf and fruit spot, an emerging disease in the southeastern United States caused by the fungus Exobasidium maculosum. Wash plating of field-collected blueberry tissue from the late dormant season through bud expansion showed that the pathogen overwintered epiphytically on blueberry plants in the field, most likely in its yeast-like conidial stage. Agrichemical applications during the dormant season altered epiphytic populations of the pathogen, which correlated directly with leaf spot incidence later in the spring. Disease monitoring of field plants and weekly exposure of potted trap plants revealed that young leaves at the mouse-ear stage were most susceptible to infection, that disease incidence on leaves progressed monocyclically, and that infection periods were associated with rainfall variables such as the number of days per week with ≥1.0 mm of rain or cumulative weekly rainfall. Weekly spore trapping with an Andersen sampler showed that airborne inoculum was detected only after sporulating leaf lesions producing basidiospores were present in the field, suggesting that the primary inoculum is not airborne. The first symptoms on young, green fruit were observed soon after petal fall (requiring removal of the waxy fruit layer to visualize lesions), and visible disease progress on fruit was delayed by 1 to 3 weeks relative to that on leaves. Fruit infection of field plants and trap plants occurred before airborne propagules were detected by spore trapping and before sporulating leaf lesions were present in the field. Hence, this study showed that fruit infections are initiated by the same initial inoculum as leaf infections but it was not possible to conclusively exclude the possibility of a contribution of basidiospore inoculum from leaf lesions to disease progress on later developing fruit. This is one of only a few studies addressing the epidemiology and disease cycle of an Exobasidium sp. in a pathosystem where artificial inoculation has not been possible to date.

Enteric fever in the Pacific: a regional retrospective study from Auckland, New Zealand.

BACKGROUND: There are limited clinical data on enteric fever in the Pacific and New Zealand (NZ) compared with the Indian subcontinent (ISC) and South-East Asia (SEA). Our objective was to describe enteric fever in Auckland - a large Pacific city, focusing on disease acquired in these regions. METHODS: We reviewed enteric fever cases hospitalised in Auckland from January 2005 to December 2010. RESULTS: Microbiologically confirmed EF was identified in 162 patients. Travel regions: Pacific, 40 cases (25%) (Samoa, 38; Fiji, two), ISC, 72 (44%), SEA, seven (4%), other, three (2%), no travel, 40 (25%). Enteric fever rates for Auckland resident travellers were: India 50.3/100 000; Samoa 19.7/100 000.All Pacific cases were Salmonella Typhi. Of local isolates (without travel history), 38 were S. Typhi (36 fully susceptible, one multi-drug resistant (MDR) + nalidixic acid resistant (NAR), one unknown) and two S. Paratyphi (both NAR). Of non-Pacific travel, 56/82 (69%) isolates were S. Typhi, the remainder S. Paratyphi (15 isolates were fully susceptible, only 1% were MDR). Significant associations of serotype and antibiotic resistance with different travel regions and similarity of phage types (local and Pacific) were observed. Headache, vomiting and acute kidney injuries were more frequent with Pacific travel, while abdominal distension and cholecystitis with local disease. Shorter duration of treatment in the Pacific group was seen despite length of stay in hospital not being reduced. Local cases were associated with longer hospital admissions. CONCLUSIONS: One half of cases in Auckland are acquired either from Pacific or locally. Similarities mean that disease acquired locally is likely of Pacific origin.

Helicobacter pylori downregulates expression of human ß-defensin 1 in the gastric mucosa in a type IV secretion-dependent fashion.

Helicobacter pylori establishes a chronic lifelong infection in the human gastric mucosa, which may lead to peptic ulcer disease or gastric adenocarcinoma. The human beta-defensins (hßDs) are antimicrobial peptides, hßD1 being constitutively expressed in the human stomach. We hypothesized that H. pylori may persist, in part, by downregulating gastric hßD1 expression. We measured hßD1 and hßD2 expression in vivo in relation to the presence, density and severity of H. pylori infection, investigated differential effects of H. pylori virulence factors, and studied underlying signalling mechanisms in vitro. Significantly lower hßD1 and higher hßD2 mRNA and protein concentrations were present in gastric biopsies from infected patients. Those patients with higher-level bacterial colonization and inflammation had significantly lower hßD1 expression, but there were no differences in hßD2. H. pylori infection of human gastric epithelial cell lines also downregulated hßD1. Using wild-type strains and isogenic mutants, we showed that a functional cag pathogenicity island-encoded type IV secretion system induced this downregulation. Treatment with chemical inhibitors or siRNA revealed that H. pylori usurped NF-κB signalling to modulate hßD1 expression. These data indicate that H. pylori downregulates hßD1 expression via NF-κB signalling, and suggest that this may promote bacterial survival and persistence in the gastric niche.

Sticking to minimum standards: implementing antibiotic stewardship in intensive care.

BACKGROUND: In Australia, antimicrobial stewardship programmes are a compulsory component of hospital accreditation. Good documentation around anti-microbial prescribing aids communication and can improve prescribing practice in environments with multiple decision makers. AIM: This study aims to develop and implement an intervention to improve antimicrobial prescribing practice in a 24-bed intensive care unit in a tertiary referral adult hospital. METHODS: We conducted a four-phase (observation, reflection, implementation, evaluation) prospective collaborative before-after quality improvement study. Baseline audits and surveys of antimicrobial prescribing practices identified barriers to and enablers of good prescribing practice. A customised intervention was then implemented over 6 weeks and included a yellow medication record sticker, quarterly education sessions and intensive care unit-specific empiric antimicrobial prescribing guidelines. Post-implementation, the effects were monitored by serial antimicrobial prescribing audits for 1 year. The primary outcomes were clear documentation of the start date, the planned stop date or review date and the indication for an antibiotic. These were all considered the 'minimum standards' for an antimicrobial prescription on the medication record. RESULTS: Documentation of minimum standards specifically addressed by the sticker improved (start date (72% to 90%, P < 0.001), stop date (16% to 63%, P < 0.001), antimicrobial indication documented on medication chart (58% to 83%, P < 0.01)). Overall, adherence to all three minimum standards (start date, stop date and indication) improved from 41/306 (13%) to 306/492 (63%) (P < 0.001). One-year post-implementation, the yellow sticker had become embedded into daily practice. CONCLUSION: A systematic approach to quality improvement combined with the implementation of a tailored, multi-faceted intervention can improve antimicrobial prescribing practices.

Exposure to anthrax toxin alters human leucocyte expression of anthrax toxin receptor 1.

Anthrax is a toxin-mediated disease, the lethal effects of which are initiated by the binding of protective antigen (PA) with one of three reported cell surface toxin receptors (ANTXR). Receptor binding has been shown to influence host susceptibility to the toxins. Despite this crucial role for ANTXR in the outcome of disease, and the reported immunomodulatory consequence of the anthrax toxins during infection, little is known about ANTXR expression on human leucocytes. We characterized the expression levels of ANTXR1 (TEM8) on human leucocytes using flow cytometry. In order to assess the effect of prior toxin exposure on ANTXR1 expression levels, leucocytes from individuals with no known exposure, those exposed to toxin through vaccination and convalescent individuals were analysed. Donors could be defined as either 'low' or 'high' expressers based on the percentage of ANTXR1-positive monocytes detected. Previous exposure to toxins appears to modulate ANTXR1 expression, exposure through active infection being associated with lower receptor expression. A significant correlation between low receptor expression and high anthrax toxin-specific interferon (IFN)-γ responses was observed in previously infected individuals. We propose that there is an attenuation of ANTXR1 expression post-infection which may be a protective mechanism that has evolved to prevent reinfection.

Good outcome in HIV-infected refugees after resettlement in New Zealand: population study.

BACKGROUND: The aims of this study were to determine the clinical characteristics on arrival and the subsequent clinical outcome of HIV-infected UN quota refugees who settled in New Zealand during the last 11 years and to estimate their rate of HIV transmission. METHODS: A population study was conducted. Data were provided by the Mangere Refugee Resettlement Centre, the infectious disease physicians caring for the subjects, the New Zealand AIDS Epidemiology Group and laboratories carrying out HIV viral load assays. RESULTS: One hundred of 7732 (1.3%) UN quota refugees were HIV positive; mean age 30 years, 56% were men, median initial CD4 count was 320 (range 20-1358). HIV infection was most commonly acquired by heterosexual intercourse (74%). The median follow up was 5.0 years (range 1 month to 9.7 years). Five died and 15 subjects had 16 AIDS-defining illnesses, most commonly tuberculosis (n = 10). Sixty subjects commenced highly active antiretroviral therapy of whom 36/59 (61%) had an undetectable HIV viral load after 1 year of treatment. None of the six children born to HIV-infected women in New Zealand were infected. There were two known cases of horizontal transmission of HIV infection. CONCLUSION: Although HIV-infected quota refugees often have to overcome severe social, cultural and financial handicaps, their clinical outcome is generally very good, with response rates to highly active antiretroviral therapy that are similar to other patient groups. Furthermore, they have not been a significant source of transmission of HIV infection after resettlement in New Zealand.

A secretory leukocyte protease inhibitor variant with improved activity against lung infection.

Secretory leukocyte protease inhibitor (SLPI) is an important respiratory tract host defense protein, which is proteolytically inactivated by excessive neutrophil elastase (NE) during chronic Pseudomonas infection in the cystic fibrosis (CF) lung. We generated two putative NE-resistant variants of SLPI by site-directed mutagenesis, SLPI-A16G and SLPI-S15G-A16G, with a view to improving SLPI's proteolytic stability. Both variants showed enhanced resistance to degradation in the presence of excess NE as well as CF patient sputum compared with SLPI-wild type (SLPI-WT). The ability of both variants to bind bacterial lipopolysaccharides and interact with nuclear factor-κB DNA binding sites was also preserved. Finally, we demonstrate increased anti-inflammatory activity of the SLPI-A16G protein compared with SLPI-WT in a murine model of pulmonary Pseudomonas infection. This study demonstrates the increased stability of these SLPI variants compared with SLPI-WT and their therapeutic potential as a putative anti-inflammatory treatment for CF lung disease.

Dimethicone barrier cream prevents infection of human skin by schistosome cercariae: evidence from Franz cell studies.

One approach to the prevention of schistosomiasis is the use of topical formulations to inhibit cercarial penetration of skin. A number of formulations containing either cercaricidal ingredients or components designed to inhibit penetration have been studied, but with variable results. Such studies have rarely considered the persistence of inhibitory effects through time, and to date, there have been no systematic investigations of barrier formulations. The aim of this study was to use Franz cells to investigate the effect of such barrier creams on the penetration of S. mansoni cercariae into human skin. The results show that a single application of a barrier cream based on dimethicone offers a high level of protection against penetration that is sustained for at least 48 hr.

Outpatient treatment of pneumonia.

In children, pneumonia must be differentiated from bronchiolitis and asthma. Pneumonia is the only one of these three conditions for which antibiotics are indicated. Clinical signs are more useful than radiological or laboratory investigations for differentiating pneumonia from bronchiolitis and asthma. A child has pneumonia if s/he has tachypnoea or indrawing and is not wheezing. The child's age and the severity of the illness episode predict the aetiology of the pneumonia. The majority of children with community-acquired pneumonia can be managed in primary care. The antibiotic of choice for children < or = 5 years of age is oral amoxycillin and for older children and adolescents is oral erythromycin. Antibiotics will not prevent pneumonia in a child with an upper respiratory tract infection. Up to 80% of adults with pneumonia can be managed as outpatients. Indicators of morbidity and mortality from pneumonia are well described. Clinical features and radiology do not reliably predict the causative agent in adults with pneumonia, thus initial treatment is empirical. Streptococcus pneumoniae is the most common cause of pneumonia in all studies. The initial antibiotic treatment should be active against this organism. Penicillin oramoxycillin or erythromycin are all suitable. Erythromycin has the advantage of being active against Mycoplasma pneumoniae and Legionella species. Follow-up of patients is important to decide whether they are responding to the empirical treatment.

Experience with pneumocystis carinii pneumonia in patients with AIDS.

We have reviewed admission data, some diagnostic tests, treatment and outcome of 31 male homosexual patients infected with the human immunodeficiency virus with 37 consecutive episodes of presumptive Pneumocystis carinii pneumonia treated at the infectious disease unit, Auckland Hospital, between 1985 and 30 June 1988. The median age was 39 years. Eight episodes were proven Pneumocystis carinii pneumonia, 18 satisfied Centres for Disease Control criteria for presumptive Pneumocystis carinii pneumonia and 11 lacked one Centres for Disease Control criterion. Patients began intravenous or oral cotrimoxazole in 32 episodes, initially 20 mg/k/d of trimethoprim component, but since early 1988 10 mg/k/d. In nine episodes treatment was changed to intravenous pentamidine because of side effects or failure to respond while five received pentamidine as their only drug. Cotrimoxazole caused side effects in 20 of 32 episodes (rash in 11) and pentamidine in 10 of 14 (renal impairment in nine). Two patients died (ie, a 5% mortality for all 37 episodes or 8% for 26 proven and Centres for Disease Control presumptive episodes). Median hospital stay for survivors was 11 days. Fourteen other patients have subsequently died a median eight months after the initial episode. Pneumocystis carinii pneumonia is an important infection in patients infected with the human immunodeficiency virus.

Cryptococcal meningitis in Auckland 1969-89.

Twenty-six patients with cryptococcal meningitis were seen in Auckland between 1969 and 1989. The incidence of cryptococcal meningitis in Auckland residents was 0.12 cases/100,000/year. Ten (38%) of the patients were Maori or Pacific Island Polynesians. Nineteen (73%) had a predisposing cause, including immunosuppressive therapy in nine and the acquired immunodeficiency syndrome (AIDS) in seven. The most common presenting syndrome was a subacute or chronic meningitis. Other clinical syndromes included a slowly progressive ataxia, polyradiculopathy, and headache with vomiting. In two patients, the symptoms of meningitis were overshadowed by those of systemic cryptococcal infection. Delay in making the diagnosis was common. The most sensitive method for diagnosing cryptococcal meningitis was the cerebrospinal fluid cryptococcal antigen test. Antifungal therapy cured 17 of the 25 (68%) treated patients overall, 15 of the 19 (79%) without AIDS and six of the seven with no underlying disease.

Endocarditis due to Neisseria mucosa: two case reports and review.

Two cases of endocarditis caused by Neisseria mucosa are reported, and the literature on N. mucosa endocarditis is reviewed. N. mucosa is a rare but serious cause of endocarditis that is associated with a high rate of embolic complications and high mortality and is not always highly sensitive to benzylpenicillin. Most patients with N. mucosa endocarditis have been treated with combined therapy with penicillin and an aminoglycoside, although the optimal regimen has not been defined.

A placebo controlled evaluation of lomefloxacin in the treatment of bacterial diarrhoea in the community.

We compared 40 patients taking lomefloxacin 400 mg once daily for 5 days in a double blind trial with 44 placebo takers with proven community acquired bacterial diarrhoea (85% due to Campylobacter spp.). Lomefloxacin eradicated Campylobacter spp. in 75% but did not alter clinical outcome. Twenty-eight per cent of the campylobacter isolates developed resistance. Thirty-three per cent developed side-effects. Lomefloxacin is not recommended for community-acquired bacterial diarrhoea when Campylobacter spp. predominate.

Management and outcome of pneumothoraces in patients infected with human immunodeficiency virus.

To better understand the natural history, management, and outcome of pneumothoraces in HIV-infected patients, we reviewed hospital charts and chest radiographs of HIV-infected adults discharged from the University of Maryland Medical Center over a 6-year period. Sixty pneumothoraces occurred in 39 patients. Twenty-three pneumothoraces resulted from trauma and 37 were spontaneous. Thirty-two (86%) of the spontaneous pneumothoraces occurred in patients with Pneumocystis carinii pneumonia (PCP). Eight percent of the traumatic pneumothoraces in patients who did not have PCP resolved. Patients who had pneumothorax as well as PCP were more difficult to manage and had a poorer outcome (50% mortality) than those who did not have PCP (25% mortality).

Penetration of human skin by the cercariae of Schistosoma mansoni: an investigation of the effect of multiple cercarial applications.

It has previously been postulated that L-arginine emitted by penetrating Schistosoma mansoni cercariae serves as an intraspecific signal guiding other cercariae to the penetration site. It was suggested that penetrating in groups offers a selective advantage. If this hypothesis is correct and group penetration at one site on the host offers an advantage, it would follow that at such a site, successive groups of cercariae would be able to penetrate skin in either greater numbers or at a faster rate. This prediction was tested by the use of an in vitro model of cercarial penetration based on the Franz cell and using human skin. It was demonstrated that there was no increase in the percentage of cercariae able to penetrate the skin with subsequent exposures. Consequently, it seems unlikely that the release of L-arginine by cercariae during penetration could have evolved as a specific orientation system based on a selective advantage offered by group penetration.