Risk factors for mortality in patients with diabetic foot infections: a prospective cohort study.

BACKGROUND: An increasing prevalence of diabetes mellitus has led to a high risk of diabetic foot infections (DFI) and associated morbidity. However, little is known about the relationship between DFI and mortality. AIM: To investigate the risk of mortality and associated factors in patients with DFI in an Australian context. METHODS: A prospective cohort study of inpatients with DFI between May 2012 and October 2016 was done at Royal Darwin Hospital, a tertiary referral hospital for the Top End of the Northern Territory. Primary outcome was 1-year mortality with Cox regression analysis undertaken to assess risk factors for mortality. RESULTS: Four hundred and thirteen consecutive adult diabetic patients with 737 admissions were referred to the High-Risk Foot Service for DFI. Cumulative risk of mortality at 1 year was 8.9% (95% confidence interval (CI) 6.4-12.2). On univariable analysis, mortality was associated with older age (hazard ratio (HR) per year increase 1.08, 95% CI 1.06-1.11, P = 0.001), haemodialysis (HR 3.64, 1.74-7.62, P < 0.001), isolation of Pseudomonas aeruginosa (HR 2.32, 1.05-5.12, P = 0.04) and ischaemic heart disease (HR 2.05, 1.04-4.07, P = 0.04), while indigenous status (HR 0.48, 0.25-0.95, P = 0.04) and HbA1c > 7% (HR 0.45, 0.20-0.99, P < 0.05) were protective. After adjusting for confounders, independent risk factors for mortality were haemodialysis (adjusted HR 5.76, 95% CI 2.28-14.59, P < 0.001) and older age (adjusted HR 1.09, 1.06-1.13, P < 0.001). Patients on haemodialysis had a cumulative risk of mortality of 24.5% (95% CI 14.0-40.8) at 1 year. CONCLUSION: There is a high risk of mortality associated with DFI, substantially increased in patients undergoing haemodialysis, highlighting the importance of early and dedicated interventions targeted at this high-risk group.

Outcomes of multisite antimicrobial stewardship programme implementation with a shared clinical decision support system.

Background: Studies evaluating antimicrobial stewardship programmes (ASPs) supported by computerized clinical decision support systems (CDSSs) have predominantly been conducted in single site metropolitan hospitals. Objectives: To examine outcomes of multisite ASP implementation supported by a centrally deployed CDSS. Methods: An interrupted time series study was conducted across five hospitals in New South Wales, Australia, from 2010 to 2014. Outcomes analysed were: effect of the intervention on targeted antimicrobial use, antimicrobial costs and healthcare-associated Clostridium difficile infection (HCA-CDI) rates. Infection-related length of stay (LOS) and standardized mortality ratios (SMRs) were also assessed. Results: Post-intervention, antimicrobials targeted for increased use rose from 223 to 293 defined daily doses (DDDs)/1000 occupied bed days (OBDs)/month (+32%, P < 0.01). Conversely, antimicrobials targeted for decreased use fell from 254 to 196 DDDs/1000 OBDs/month (-23%; P < 0.01). These effects diminished over time. Antimicrobial costs decreased initially (-AUD$64551/month; P < 0.01), then increased (+AUD$7273/month; P < 0.01). HCA-CDI rates decreased post-intervention (-0.2 cases/10 000 OBDs/month; P < 0.01). Proportional LOS reductions for key infections (respiratory from 4.8 to 4.3 days, P < 0.01; septicaemia 6.8 to 6.1 days, P < 0.01) were similar to background LOS reductions (2.1 to 1.9 days). Similarly, infection-related SMRs (observed/expected deaths) decreased (respiratory from 1.1 to 0.75; septicaemia 1.25 to 0.8; background rate 1.19 to 0.90. Conclusions: Implementation of a collaborative multisite ASP supported by a centrally deployed CDSS was associated with changes in targeted antimicrobial use, decreased antimicrobial costs, decreased HCA-CDI rates, and no observable increase in LOS or mortality. Ongoing targeted interventions are suggested to promote sustainability.

Staphylococcus aureus Prostatic abscess: a clinical case report and a review of the literature.

BACKGROUND: Prostatic abscess is a rare complication of acute bacterial prostatitis and is most commonly caused by Enterobacteriaceae. We report on a case of prostatic abscess caused by Staphylococcus aureus and conduct a review of the literature. CASE PRESENTATIVE: We present a case of S. aureus prostatic abscess that was successfully treated with a combination of antibiotic and surgical therapy. The isolate was non­multidrug-resistant, methicillin-resistant Staphylococcus aureus and was genotyped as clonal complex 5, an emerging regional clone that is trimethoprim resistant and Panton-Valentine leukocidin positive. This current case report is the first to describe the use of clindamycin step-down therapy. A literature review identified a further 39 cases of S. aureus prostatic abscesses, of which 26 were methicillin resistant. CONCLUSION: S. aureus is an uncommon cause of prostatic abscess. Optimal management includes both antibiotic therapy and surgical drainage. Our use of clindamycin as step-down therapy was guided by its excellent prostatic penetration.

Impact of an antimicrobial stewardship intervention on appropriateness of prescribing for community-acquired pneumonia in an Australian regional hospital.

Community-acquired pneumonia (CAP) is the second commonest indication for antibiotic use in Australian hospitals and is therefore a frequent target for antimicrobial stewardship. A single-centre prospective study was conducted in a regional referral hospital comparing management of adult patients with CAP before and after an educational intervention. We demonstrated a reduction in duration of therapy and reduced inappropriate use of ceftriaxone-based regimens for non-severe CAP.

Nocardia Septic Arthritis Complicating an Anterior Cruciate Ligament Repair.

Nocardia infection following anterior cruciate ligament (ACL) allograft reconstruction is a rare occurrence. We report a case of Nocardia infection of an allograft ACL reconstruction and septic arthritis of the knee joint due to an organism most similar to the novel Nocardia species Nocardia aobensis.

Yersinia intussusception: case report and review.

Intussusception is a recognised paediatric presentation in emergency department and primary care settings. The aetiology of intussusception is multifactorial and largely unknown but includes infection in some cases. Yersinia has been the most frequently cited bacterial association in children. Identifying Yersinia affects the role and choice of antibiotics in a child's treatment regimen. This article reports on Australia's first proven case of Yersinia enterocolitica intussusception, and reviews the clinical epidemiology of all known reported cases world-wide.

Clinical correlates of Panton-Valentine leukocidin (PVL), PVL isoforms, and clonal complex in the Staphylococcus aureus population of Northern Australia.

BACKGROUND: Regional differences in the prevalence of Panton-Valentine leukocidin (PVL) and PVL isoform-harboring strains as well as in the local population structure of Staphylococcus aureus may influence the clinical spectrum of S. aureus infections. METHODS: Using a prospective collection of S. aureus isolates from northern Australia, we determined differences between infections caused by (1) PVL(+) and PVL(-) isolates, (2) PVL histidine (H) isoform- and PVL arginine (R) isoform-harboring isolates, and (3) different lineages, including the genetically divergent clonal complex (CC) 75 and the PVL(+) CC93. RESULTS: PVL(+) isolates comprised 54% (128/239) of community-associated methicillin-resistant isolates and 40% (95/239) of methicillin-susceptible S. aureus (MSSA) isolates. There were 113 H isoform- and 110 R isoform-harboring isolates. PVL was associated with truly community-acquired disease, younger age, and presentation with sepsis. We found no differences in infections due to H isoform-harboring isolates, compared with R isoform-harboring isolates. CC93 was the most prevalent lineage. The genetically divergent CC75 caused clinical disease similar to that of other S. aureus clones. CONCLUSIONS: PVL(+) and PVL(-) infections are clearly distinct. MSSA contributes a large but underrecognized burden of PVL(+) disease. Compared with elsewhere in the world, there is a relative abundance of the clade that contains CC93 and CC121 in both northern Australia and Asia.

Discontinuation of peri-operative gentamicin use for indwelling urinary catheter manipulation in orthopaedic surgery.

BACKGROUND: Gentamicin has historically been used prior to insertion and removal of indwelling urinary catheters (IDCs) around elective joint replacement surgery to prevent infection; however, this indication is not recognized in the Australian Therapeutic Guidelines: Antibiotic and the paradigm for safe use of gentamicin has shifted. METHODS: The antimicrobial stewardship team of a 500 bed tertiary regional hospital performed a retrospective clinical study of gentamicin IDC prophylaxis around total hip and knee arthroplasties. Results were presented to the orthopaedic surgeons. A literature review identified no guidelines to support gentamicin prophylaxis and only a very low risk of bacteraemia associated with IDC insertion/removal in patients with established bacteriuria. Consensus was reached with the surgeons to discontinue this practice. Subsequent prospective data collection was commenced to determine effectiveness, with weekly feedback to the Department Head of Orthopaedics. RESULTS: Data from 137 operations pre-intervention (6 months) were compared with 205 operations post-intervention (12 months). The median patient age was 72 years in both groups. Following the intervention, reductions in gentamicin use were demonstrated for IDC insertion (59/137 (42%) to 4/205 (2%), P < 0.01) and removal (39/137 (28%) to 6/205 (3%), P < 0.01). No gentamicin use was observed during the final 40 weeks of the post-intervention period. There were no significant differences between the groups for pre-operative bacteriuria, surgical site infections or acute kidney injury. CONCLUSION: A collaborative approach using quality improvement methodology can lead to an evidence-based reappraisal of established practice. Regular rolling audits and timely feedback were useful in sustaining change.

Malaria tolerance--for whom the cell tolls?

How is it that individuals exposed to intense malaria transmission can tolerate the presence of malaria parasites in their blood at levels that would produce fever in others? In light of evidence discounting a role for nitric oxide or antibodies to plasmodial glycosylphosphatidylinositols in maintaining this tolerant state, refractoriness to toxin-induced Toll-like receptor-mediated signalling has emerged as a likely explanation that links malarial and bacterial endotoxin tolerance. Understanding the mechanisms underlying tolerance and the potential for cross-tolerization has significant implications for understanding the potential for antitoxic vaccine strategies, as well as interactions between different malaria species and between malaria and other human parasites.

Candida costochondritis associated with recent intravenous drug use.

Candida osteoarticular infections are being reported with increasing frequency, possibly due to an expanding population at risk. However, Candida costochondritis is uncommon. We report two cases of Candida costochondritis in patients who presented with subacute-onset chest wall swelling and whose only identifiable risk factor was a history of recent intravenous drug use.

Antibody reactivity to linear epitopes of Plasmodium falciparum cytoadherence-linked asexual gene 9 in asymptomatic children and adults from papua new Guinea.

The cytoadherence-linked asexual gene 9 (clag 9) of Plasmodium falciparum has been implicated in the cytoadherence of infected erythrocytes. To determine the immunogenicity of the clag 9 gene product (CLAG 9 protein) in humans, we measured antibody responses to 11 synthetic CLAG 9 peptides in a group of 177 asymptomatic children and adults subject to intense malaria exposure in Madang, Papua New Guinea. The CLAG 9 peptides were immunogenic in adults and children. Antibody responses to peptides 4 and 10 were high across all age groups and detectable in a majority of children less than five years of age. While CLAG 9 peptides are immunogenic in humans, longitudinal studies will be required to determine the longevity of antibody responses to CLAG 9 and their role in protection from disease.

Supraglottitis due to group B streptococcus in an adult with IgG4 and C2 deficiency: a case report and review of the literature.

Acute supraglottitis is a medical emergency as it can rapidly lead to airway compromise. With routine pediatric immunization for Hemophilus influenzae serotype b, supraglottitis is now more prevalent in adults, with a shift in the causative organisms and a change in the natural history of this disease. Here, we present a case of supraglottitis due to group B streptococcus that occurred in an adult with previously undetected immunoglobulin 4 (IgG4) and complement protein C2 deficiency.

Inducible nitric oxide synthase (NOS2) promoter CCTTT repeat polymorphism: relationship to in vivo nitric oxide production/NOS activity in an asymptomatic malaria-endemic population.

Polymorphisms in the inducible nitric oxide synthase gene (NOS2) promoter have been associated with clinical outcome from malaria. These include a CCTTT repeat (CCTTTn) 2.5 kilobases upstream from the NOS2 transcription start site, and two single nucleotide substitutions: G-->C at position -954 (G-954C), and C-->T at position -1173 (C-1173T). Although hypothesized to influence NO production in vivo, the functional relevance of (CCTTT)n and G-954C is uncertain because disease association studies have yielded inconsistent results. This study found no association between CCTTT repeat number and levels of plasma NO metabolites or peripheral blood mononuclear cell NOS activity in a cohort of asymptomatic malaria-exposed coastal Papua New Guineans 1-60 years old. This suggests that (CCTTT)n does not independently influence NOS2 transcription in vivo. Neither the G-954C nor the C-1173T polymorphisms were identified in this population, indicating the variability and complexity of selection for NOS2 promoter polymorphisms in different malaria-endemic populations.

Community-associated strains of methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus in indigenous Northern Australia: epidemiology and outcomes.

BACKGROUND: Some strains of non-multidrug-resistant, methicillin-resistant Staphylococcus aureus (nmMRSA) in Australia are likely to have emerged from strains of methicillin-susceptible S. aureus (MSSA) in remote Aboriginal communities. OBJECTIVE: To describe the clinical epidemiology of infection due to community-associated MRSA strains in an Australian tropical hospital setting with a significant Aboriginal population and to compare infections caused by community-associated strains of MRSA, health-care-associated strains of MRSA, and MSSA strains with respect to demographic risk factors and clinical outcomes. Methods. We queried the microbiology database for the Top End of the Northern Territory, Australia, to determine population incidences for S. aureus infection and conducted a prospective matched case-control study to compare infection due to nmMRSA, MSSA, or multidrug-resistant MRSA at the Royal Darwin Hospital. RESULTS: The annual incidence of S. aureus bacteremia was 65 cases per 100,000 population, but in the Aboriginal population the incidence was 172 cases per 100,000 population (odds ratio [OR] compared with non-Aboriginal population, 5.8 [95% confidence interval {CI}, 3.8-8.9). Female sex (adjusted OR [aOR], 1.5 [95% CI, 1.1-2.0) and remote residence (aOR, 1.8 [95% CI, 1.2-2.5]) were associated with the isolation of nmMRSA rather than MSSA, but disease spectrum and outcomes were similar. Among those from whom nmMRSA was isolated, Aboriginal patients were younger (aOR for each additional year, 0.94 [95% CI, 0.92-0.96]), more likely to be female (aOR, 3.8 [95% CI, 1.7-8.5]), and more likely to reside in a remote community (aOR, 29 [95% CI, 8.9-94]) than non-Aboriginal patients. The presence of Panton-Valentine leukocidin in nmMRSA was associated with double the odds of sepsis (aOR, 2.2 [95% CI, 1.1-4.6]). CONCLUSIONS: The association of nmMRSA infection with female sex and remote residence supports the hypothesis that nmMRSA arose from MSSA strains in remote Aboriginal communities where staphylococcal disease is highly prevalent. The similar clinical spectrum and outcomes for nmMRSA infection and MSSA infection suggest that virulence is not correlated with resistance phenotype.

Flinders Island spotted fever rickettsioses caused by "marmionii" strain of Rickettsia honei, Eastern Australia.

Australia has 4 rickettsial diseases: murine typhus, Queensland tick typhus, Flinders Island spotted fever, and scrub typhus. We describe 7 cases of a rickettsiosis with an acute onset and symptoms of fever (100%), headache (71%), arthralgia (43%), myalgia (43%), cough (43%), maculopapular/petechial rash (43%), nausea (29%), pharyngitis (29%), lymphadenopathy (29%), and eschar (29%). Cases were most prevalent in autumn and from eastern Australia, including Queensland, Tasmania, and South Australia. One patient had a history of tick bite (Haemaphysalis novaeguineae). An isolate shared 99.2%, 99.8%, 99.8%, 99.9%, and 100% homology with the 17 kDa, ompA, gltA, 16S rRNA, and Sca4 genes, respectively, of Rickettsia honei. This Australian rickettsiosis has similar symptoms to Flinders Island spotted fever, and the strain is genetically related to R. honei. It has been designated the "marmionii" strain of R. honei, in honor of Australian physician and scientist Barrie Marmion.

Elevated plasma phenylalanine in severe malaria and implications for pathophysiology of neurological complications.

Cerebral malaria is associated with decreased production of nitric oxide and decreased levels of its precursor, l-arginine. Abnormal amino acid metabolism may thus be an important factor in malaria pathogenesis. We sought to determine if other amino acid abnormalities are associated with disease severity in falciparum malaria. Subjects were enrolled in Dar es Salaam, Tanzania (children) (n = 126), and Papua, Indonesia (adults) (n = 156), in two separate studies. Plasma samples were collected from subjects with WHO-defined cerebral malaria (children), all forms of severe malaria (adults), and uncomplicated malaria (children and adults). Healthy children and adults without fever or illness served as controls. Plasma amino acids were measured using reverse-phase high-performance liquid chromatography with fluorescence detection. Several plasma amino acids were significantly lower in the clinical malaria groups than in healthy controls. Despite the differences, phenylalanine was the only amino acid with mean levels outside the normal range (40 to 84 microM) and was markedly elevated in children with cerebral malaria (median [95% confidence interval], 163 [134 to 193] microM; P < 0.0001) and adults with all forms of severe malaria (median [95% confidence interval], 129 [111 to 155] microM; P < 0.0001). In adults who survived severe malaria, phenylalanine levels returned to normal, with clinical improvement (P = 0.0002). Maintenance of plasma phenylalanine homeostasis is disrupted in severe malaria, leading to significant hyperphenylalaninemia. This is likely a result of an acquired abnormality in the function of the liver enzyme phenylalanine hydroxylase. Determination of the mechanism of this abnormality may contribute to the understanding of neurological complications in malaria.

Nitric oxide production and nitric oxide synthase activity in malaria-exposed Papua New Guinean children and adults show longitudinal stability and no association with parasitemia.

Individuals in areas of intense malaria transmission exhibit resistance (or tolerance) to levels of parasitemia in their blood that would normally be associated with febrile illness in malaria-naive subjects. The resulting level of parasitemia associated with illness (the pyrogenic threshold) is highest in childhood and lowest in adulthood. Clinical parallels between malarial and bacterial endotoxin tolerance have led to the supposition that both share common physiological processes, with nitric oxide (NO) proposed as a candidate mediator. The hypotheses that NO mediates tolerance and blood stage parasite killing in vivo were tested by determining its relationship to age and parasitemia cross-sectionally and longitudinally in a population of 195 children and adults from Papua New Guinea encountering intense malaria exposure. Despite pharmacological clearance of asymptomatic parasitemia, NO production and mononuclear cell NO synthase (NOS) activity were remarkably stable within individuals over time, were not influenced by parasitemia, and varied little with age. These results contrast with previous smaller cross-sectional studies. Baseline NO production and NOS activity did not protect against recurrent parasitemia, consistent with previous data suggesting that NO does not have antiparasitic effects against blood stage infection in vivo. The NO indices studied were markedly higher in specimens from study subjects than in samples from Australian controls, and NOS activity was significantly associated with plasma immunoglobulin E levels, consistent with induction of NO by chronic exposure to other infections and/or host genetic factors. These results suggest that NO is unlikely to mediate killing of blood stage parasites in this setting and is unlikely to be the primary mediator in the acquisition or maintenance of malarial tolerance.