Prediction accuracy of commonly used pneumonia severity scores in Aboriginal patients with severe community-acquired pneumonia: a retrospective study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is highly prevalent in the Aboriginal population. Few pneumonia severity scores are validated in this population. AIMS: To assess the prediction accuracy of pneumonia severity scores in Aboriginal patients with SCAP and to identify risk factors for poor prognosis. METHODS: Retrospective cohort study examining Aboriginal patients admitted to the intensive care unit with confirmed SCAP between January 2011 and December 2014. Severity scores were calculated for SMARTCOP (systolic blood pressure, multi-lobar, albumin, respiratory rate, tachycardia, confusion, oxygenation and arterial pH), SMARTACOP (systolic blood pressure, multi-lobar, albumin, respiratory rate, tachycardia, Aboriginal status, confusion, oxygenation and arterial pH), CURB-65 (confusion, urea, respiratory rate, blood pressure and age ≥65 years), pneumonia severity index, Infectious Diseases Society of America and American Thoracic Society SCAP, and Acute Physiology and Chronic Health Evaluation (APACHE) II/III using medical records. Prediction accuracy of 30-day mortality and requirement for intensive respiratory and/or vasoactive support (IRVS) were assessed using logistic regression and the area under the receiver operating characteristic curve (AUROC). Multivariate analysis was used to test associations between poor prognosis and demographic/clinical variables. RESULTS: A total of 203 cases (49% women) was identified. Thirty-day mortality was 6.4% (n = 13), and 53% (n = 107) required IRVS. None of the tested pneumonia severity scores accurately predicted mortality. SMARTCOP and SMARTACOP predicted IRVS requirement with the highest diagnostic accuracy, but only achieved acceptable discrimination (P <0.001 and <0.001; AUROC = 0.74 and 0.75 respectively). APACHE II/III predicted both mortality (P = 0.003 and 0.001; AUROC = 0.74 and 0.73 respectively) and IRVS requirement (P <0.001 and <0.001; AUROC = 0.72 and 0.73 respectively). Multivariate analysis associated mortality with male gender, cirrhosis, immunosuppression and acidaemia, and IRVS requirement with multi-lobar pneumonia, hypotension and tachypnoea. Multivariate analysis for mortality and IRVS requirement achieved an AUROC of 0.93 and 0.87 respectively. CONCLUSION: None of the pneumonia severity scores accurately predicted mortality. We recommend SMARTACOP to predict IRVS requirement in Aboriginal patients with SCAP. Given Aboriginal patients are over-represented in Australian intensive care units, a new score is warranted for this understudied population.

Epidemiology and microbiology of severe community-acquired pneumonia in Central Australia: a retrospective study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) has high mortality and morbidity. AIMS: To describe the epidemiology and microbiology of SCAP in Central Australia. METHODS: A retrospective epidemiological study describing the characteristics, incidence rates (IR) and microbiological aetiology of SCAP in Central Australia. Adult patients admitted to Alice Springs Hospital Intensive Care Unit (ICU) between 2011 and 2014 that fitted the Infectious Diseases Society of America and American Thoracic Society definition of SCAP were included. Medical records were reviewed and compared between indigenous and non-indigenous patients. Primary outcomes were incidence rate and microbiological aetiology of SCAP. Secondary outcomes were 30-day mortality, and ICU and hospital length of stay (LoS). RESULTS: A total of 185 patents were included (156 indigenous; 29 non-indigenous). The overall SCAP IR per 1000 person-years was 3.24 (3.75 indigenous; 1.87 non-indigenous) with an IR difference of 2.71 after adjustment (P < 0.001). Those aged ≥50 years had an IR 74.8% higher than those younger. Male IR was 50% higher than females. There was a significant difference between indigenous and non-indigenous groups for age (48 vs 64 years), but not for 30-day mortality (7.7% vs 10.3%), ICU LoS (4.8 vs 4.6 days) and hospital LoS (10.9 vs 15.1 days) respectively. Likely causative pathogen(s) were identified in 117 patients; Streptococcus pneumoniae was the most common pathogen (28.2%), followed by Haemophilus influenzae (19.7%), Influenza A/B (16.2%) and Staphylococcus aureus (14.5%). CONCLUSION: A high incidence of SCAP was observed in Central Australia, disproportionately affecting the indigenous population. Prevention strategies are imperative, as well as early identification of SCAP and appropriate empiric antibiotic regimens.

Enterococcus faecalis infective endocarditis arising from chronic rectal prolapse in the setting of spinal cord injury.

A 45-year-old man had recurrent presentations with pleuritic chest pain and shortness of breath. Four months prior, he had developed cauda equina syndrome from a spinal epidural abscess in the setting of intravenous drug use, complicated by lasting neurological deficits and a rectal prolapse. On his final presentation, blood cultures taken in the absence of antibiotics grew Enterococcus faecalis from multiple sets. A transoesophageal echocardiogram confirmed tricuspid valve endocarditis. He recovered well post-targeted long-term antibiotics. Endoscopy confirmed a chronic rectal prolapse with multiple ulcers and was hypothesised as the source of bacteraemia. He subsequently underwent perineal rectosigmoidectomy. This uncommon sequela of rectal prolapse highlights several issues, including the management of neurogenic bowel dysfunction following spinal cord injury and the importance of early prolapse recognition and management. Finally, appropriate collection of blood cultures and correct use of echocardiography are critical steps in investigating infective endocarditis.

High burden of complicated skin and soft tissue infections in the Indigenous population of Central Australia due to dominant Panton Valentine leucocidin clones ST93-MRSA and CC121-MSSA.

BACKGROUND: Superficial skin and soft tissue infections (SSTIs) are common among the Indigenous population of the desert regions of Central Australia. However, the overall burden of disease and molecular epidemiology of Staphylococcus aureus complicated SSTIs has yet to be described in this unique population. METHODS: Alice Springs Hospital (ASH) admission data was interrogated to establish the population incidence of SSTIs. A prospective observational study was conducted on a subset of S. aureus complicated SSTIs (carbuncles and furuncles requiring surgical intervention) presenting during a one month period to further characterize the clinical and molecular epidemiology. High resolution melting analysis was used for clonal complex discrimination. Real-time polymerase chain reaction identifying the lukF component of the Panton Valentine leucocidin (pvl) gene determined pvl status. Clinical and outcome data was obtained from the ASH medical and Northern Territory shared electronic health records. RESULTS: SSTIs represented 2.1% of ASH admissions during 2014. 82.6% occurred in Indigenous patients (n = 382) with an estimated incidence of 18.9 per 1, 000 people years compared to the non-Indigenous population of 2.9 per 1000, with an incident rate ratio of 6.6 (95% confidence interval 5.1-8.5). Clinical and molecular analysis was performed on 50 isolates from 47 patients. Community-associated methicillin-resistant S. aureus (CA-MRSA) predominated (57% of isolates). The high burden of SSTIs is partly explained by the prevalence of pvl positive strains of S. aureus (90% isolates) for both CA-MRSA and methicillin-susceptible S. aureus (MSSA). ST93-MRSA and CC121-MSSA were the most prevalent clones. SSTIs due to ST93-MRSA were more likely to require further debridement (p = 0.039), however they also more frequently received inactive antimicrobial therapy (p < 0.001). CONCLUSIONS: ST93-MRSA and CC121-MSSA are the dominant causes of carbuncles and furuncles in Central Australia. Both of these virulent clones harbor pvl but the impact on clinical outcomes remains uncertain. The high prevalence of CA-MRSA supports empiric vancomycin use in this population when antimicrobial therapy is indicated. Prompt surgical intervention remains the cornerstone of treatment.

Optimising meropenem dosing in critically ill Australian Indigenous patients with severe sepsis.

Currently there are no pharmacokinetic (PK) data to guide antibiotic dosing in critically ill Australian Indigenous patients with severe sepsis. This study aimed to determine whether the population pharmacokinetics of meropenem were different between critically ill Australian Indigenous and critically ill Caucasian patients. Serial plasma and urine samples as well as clinical and demographic data were collected over two dosing intervals from critically ill Australian Indigenous patients. Plasma meropenem concentrations were assayed by validated chromatography. Concentration-time data were analysed with data from a previous PK study in critically ill Caucasian patients using Pmetrics. The population PK model was subsequently used for Monte Carlo dosing simulations to describe optimal doses for these patients. Six Indigenous and five Caucasian subjects were included. A two-compartment model described the data adequately, with meropenem clearance and volume of distribution of the central compartment described by creatinine clearance (CLCr) and patient weight, respectively. Patient ethnicity was not supported as a covariate in the final model. Significant differences were observed for meropenem clearance between the Indigenous and Caucasian groups [median 11.0 (range 3.0-14.1) L/h vs. 17.4 (4.3-30.3) L/h, respectively; P <0.01]. Standard dosing regimens (1 g intravenous every 8 h as a 30-min infusion) consistently achieved target exposures at the minimum inhibitory concentration breakpoint in the absence of augmented renal clearance. No significant interethnic differences in meropenem pharmacokinetics between the Indigenous and Caucasian groups were detected and CLCr was found to be the strongest determinant of appropriate dosing regimens.

Total and unbound ceftriaxone pharmacokinetics in critically ill Australian Indigenous patients with severe sepsis.

In the absence of specific data to guide optimal dosing, this study aimed to describe the pharmacokinetics of ceftriaxone in severely septic Australian Indigenous patients and to assess achievement of the pharmacodynamic target of the regimens prescribed. A pharmacokinetic study was conducted in a remote hospital intensive care unit in patients receiving ceftriaxone dosing of 1 g every 12 h (q12h). Serial blood and urine samples were collected over one dosing interval on two consecutive days. Samples were assayed using a validated chromatography method for total and unbound concentrations. Concentration-time data collected were analysed with a non-compartmental approach. A total of 100 plasma samples were collected from five subjects. Ceftriaxone clearance, volume of distribution at steady-state, elimination half-life and elimination rate constant estimates were 0.9 (0.6-1.5) L/h, 11.2 (7.6-13.4) L, 9.5 (3.2-10.2) h and 0.07 (0.07-0.21) h-1, respectively. The unbound fraction of ceftriaxone ranged between 14% and 43%, with a higher unbound fraction present at higher total concentrations. The unbound concentrations at 720 min from the initiation of infusion for the first and second dosing intervals were 7.2 (4.8-10.7) mg/L and 7.8 (4.7-12.1) mg/L respectively, which exceeds the minimum inhibitory concentration of all typical target pathogens. In conclusion, the regimen of ceftriaxone 1 g q12h is adequate for critically ill Australian Indigenous patients with severe sepsis caused by non-resistant pathogens.

Pharmacokinetics of Piperacillin in Critically Ill Australian Indigenous Patients with Severe Sepsis.

There are no available pharmacokinetic data to guide piperacillin dosing in critically ill Australian Indigenous patients despite numerous reported physiological differences. This study aimed to describe the population pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis. A population pharmacokinetic study of Indigenous patients with severe sepsis was conducted in a remote hospital intensive care unit. Plasma samples were collected over two dosing intervals and assayed by validated chromatography. Population pharmacokinetic modeling was conducted using Pmetrics. Nine patients were recruited, and a two-compartment model adequately described the data. The piperacillin clearance (CL), volume of distribution of the central compartment (Vc), and distribution rate constants from the central to the peripheral compartment and from the peripheral to the central compartment were 5.6 ± 3.2 liters/h, 14.5 ± 6.6 liters, 1.5 ± 0.4 h-1, and 1.8 ± 0.9 h-1, respectively, where CL and Vc were found to be described by creatinine clearance (CLCR) and total body weight, respectively. In this patient population, piperacillin demonstrated high interindividual pharmacokinetic variability. CLCR was found to be the most important determinant of piperacillin pharmacokinetics.

Influenza epidemiology, vaccine coverage and vaccine effectiveness in children admitted to sentinel Australian hospitals in 2014: the Influenza Complications Alert Network (FluCAN).

The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance programme operating in all states and territories in Australia. We summarise the epidemiology of children hospitalised with laboratory-confirmed influenza in 2014 and reports on the effectiveness of inactivated trivalent inactivated vaccine (TIV) in children. In this observational study, cases were defined as children admitted with acute respiratory illness (ARI) with influenza confirmed by PCR. Controls were hospitalised children with ARI testing negative for influenza. Vaccine effectiveness (VE) was estimated as 1 minus the odds ratio of vaccination in influenza positive cases compared with test-negative controls using conditional logistic regression models. From April until October 2014, 402 children were admitted with PCR-confirmed influenza. Of these, 28% were aged < 1 year, 16% were Indigenous, and 39% had underlying conditions predisposing to severe influenza. Influenza A was detected in 90% of cases of influenza; influenza A(H1N1)pdm09 was the most frequent subtype (109/141 of subtyped cases) followed by A(H3N2) (32/141). Only 15% of children with influenza received antiviral therapy. The adjusted VE of one or more doses of TIV for preventing hospitalised influenza was estimated at 55.5% (95% confidence intervals (CI): 11.6-77.6%). Effectiveness against influenza A(H1N1)pdm09 was high (91.6% , 95% CI: 36.0-98.9%) yet appeared poor against H3N2. In summary, the 2014 southern hemisphere TIV was moderately effective against severe influenza in children. Significant VE was observed against influenza A(H1N1)pdm09.

Influenza epidemiology in adults admitted to sentinel Australian hospitals in 2014: the Influenza Complications Alert Network (FluCAN).

The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2014 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals with an acute respiratory illness with influenza confirmed by nucleic acid detection. During the period 3 April to 31 October 2014 (the 2014 influenza season), 1,692 adult patients (>16 years) were admitted with confirmed influenza to one of 15 of 17 FluCAN sentinel hospitals (excluding 2 paediatric hospitals). Of these, 47% were over 65 years of age, 10% were Indigenous Australians, 3.3% were pregnant and 85% had chronic co-morbidities. The majority of cases were due to influenza A. Influenza B was detected in 7% of patients. There were a large number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2014. These are estimated to represent a national annual burden of around 15,000 admissions and almost 100,000 bed-days nationally.

Endemic melioidosis in residents of desert region after atypically intense rainfall in central Australia, 2011.

After heavy rains and flooding during early 2011 in the normally arid interior of Australia, melioidosis was diagnosed in 6 persons over a 4-month period. Although the precise global distribution of the causal bacterium Burkholderia pseudomallei remains to be determined, this organism can clearly survive in harsh and even desert environments outside the wet tropics.

Influenza epidemiology, vaccine coverage and vaccine effectiveness in sentinel Australian hospitals in 2013: the Influenza Complications Alert Network.

The National Influenza Program aims to reduce serious morbidity and mortality from influenza by providing public funding for vaccination to at-risk groups. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 14 sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with confirmed influenza, estimates vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2013 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals, with influenza confirmed by nucleic acid testing. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 5 April to 31 October 2012, 631 patients were admitted with confirmed influenza at the 14 FluCAN sentinel hospitals. Of these, 31% were more than 65 years of age, 9.5% were Indigenous Australians, 4.3% were pregnant and 77% had chronic co-morbidities. Influenza B was detected in 30% of patients. Vaccination coverage was estimated at 81% in patients more than 65 years of age but only 49% in patients aged less than 65 years with chronic comorbidities. Vaccination effectiveness against hospitalisation with influenza was estimated at 50% (95% confidence interval: 33%, 63%, P<0.001). We detected a significant number of hospital admissions with confirmed influenza in a national observational study. Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. Our results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza in the 2013 season.

Utility of exercise electrocardiography testing for the diagnosis of coronary artery disease in a remote Australian setting.

OBJECTIVE: To determine the utility of exercise electrocardiography testing (EET) in evaluating suspected coronary artery disease in a remote Australian setting where a significant proportion of patients are Indigenous Australians. DESIGN: Retrospective cohort study with grouping based on EET results. PATIENTS AND SETTING: 268 patients with suspected coronary artery disease who underwent EET at Alice Springs Hospital--a specialist teaching hospital in Central Australia with no resident specialist cardiology service--in the period 1 June 2009 to 31 May 2010. MAIN OUTCOME MEASURES: Diagnosis of coronary artery disease, based on coronary angiography and/or admission with acute coronary syndrome, in the 24 months after EET. RESULTS: Indigenous patients were younger, more likely to be women and were twice as likely as non-Indigenous patients to have a chronic disease. Indigenous patients and those with a chronic disease had a higher proportion of inconclusive results. Completed EET had a positive predictive value of 48.1% (95% CI, 28.7%-68.1%) and a negative predictive value of 96.5% (95% CI, 93.2%-98.5%). Similar results were seen among Indigenous and non-Indigenous patients. CONCLUSIONS: In regional and remote Australian settings, EET remains an important tool for the diagnosis of coronary artery disease. It is useful, and is reassuring to patients and clinicians if the result is negative, particularly in a remote Indigenous Australian population with a significant burden of cardiovascular risk.

Influenza epidemiology, vaccine coverage and vaccine effectiveness in sentinel Australian hospitals in 2012: the Influenza Complications Alert Network (FluCAN).

Influenza is mostly a mild, self-limiting infection and severe infection requiring hospitalisation is uncommon. Immunisation aims to reduce serious morbidity and mortality. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 15 sites across all states and territories in Australia. This study reports on the epidemiology of hospitalisation with confirmed influenza, estimate vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2012 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals with influenza confirmed by nucleic acid detection. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 9 April to 31 October 2012, 1,231 patients were admitted with confirmed influenza at the 15 FluCAN sentinel hospitals. Of these, 47% were more than 65 years of age, 8% were Indigenous Australians, 3% were pregnant and 76% had chronic co-morbidities. Influenza A was detected in 83% of patients. Vaccination coverage was calculated from the vaccination status of 1,216 test negative controls and was estimated at 77% in patients 65 years or over and 61% in patients with chronic comorbidities. Vaccination effectiveness was estimated at 41% (95% CI: 28%, 51%, P<0.001). Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. The study results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza during the 2012 season.

Hospitalised adult patients with pandemic (H1N1) 2009 influenza in Melbourne, Australia.

OBJECTIVE: To describe the case characteristics and outcomes of patients hospitalised with pandemic (H1N1) 2009 influenza infection during the first 2 months of the epidemic. DESIGN, PARTICIPANTS AND SETTING: Prospective case series of 112 patients admitted to seven hospitals in Melbourne with laboratory-confirmed pandemic (H1N1) 2009 influenza between 1 May and 17 July 2009. MAIN OUTCOME MEASURES: Details of case characteristics, risk factors for severe disease, treatment and clinical course. RESULTS: Of 112 hospitalised patients, most presented with cough (88%) and/or fever (82%), but several (4%) had neither symptom. A quarter of female patients (15) were pregnant or in the post-partum period. Patients presenting with multifocal changes on chest x-ray had significantly longer hospital lengths of stay, and were more likely to require intensive care unit admission. Thirty patients required admission to an intensive care unit, and three died during their acute illness. The median length of intensive care admission was 10.5 days (interquartile range, 5-16 days). CONCLUSIONS: This study highlights risk factors for severe disease, particularly pregnancy. Clinical and public health planning for upcoming influenza seasons should take into account the spectrum and severity of clinical infection demonstrated in this report, and the need to concentrate resources effectively in high-risk patient groups.

2009 H1N1 influenza A and pregnancy outcomes in Victoria, Australia.

BACKGROUND: Pregnant women have been identified as a group at risk of increased morbidity and mortality associated with the pandemic H1N1 influenza A 2009 (H1N1/09) outbreak. METHODS: Six hospitals in the state of Victoria, Australia, contributed retrospective and prospective demographic and clinical data, reason for admission data, and maternal and fetal outcome data for women with laboratory-confirmed H1N1/09 admitted to the hospital from 20 May 2009 through 31 July 2009. RESULTS: Forty-three cases were reported during the study period, including 8 intensive care unit admissions, 1 maternal death, 2 fetal deaths, and 1 neonatal death. The most common reason for admission was uncomplicated influenza-like illness. Patients hospitalized for uncomplicated influenza-like illness had a length of stay significantly less than those with confirmed pneumonia. Thirty-six percent of women delivered during the hospitalization. Of the women delivering before 37 weeks' gestation, almost all had pneumonia. Almost half of our case series had no other comorbidity, a large proportion (77%) of women received antivirals, and 56% received antibiotics. The incidence of hospitalization was estimated at 0.46% (95% confidence interval, 0.31%-0.66%) of all 6094 pregnant women in the third trimester during the 3-month study period. The incidence of hospitalization in the second trimester was estimated at 0.21% (95% confidence interval, 0.11%-0.36%). CONCLUSIONS: This case series confirms a high number of complications in pregnant women due to pandemic H1N1/09. Many of these women had comorbidities, although almost 50% of the women in this case series who required hospitalization did not have an additional risk factor other than being pregnant.

Melting muscles: novel H1N1 influenza A associated rhabdomyolysis.

We report the first case of myositis and rhabdomyolysis after infection with novel influenza A (H1N1/09) virus. The case demonstrates the novel virus' capacity for causing significant disease. Myositis and the possibility of rhabdomyolysis should be considered in any individual presenting with influenza-like symptoms in which severe myalgia or muscle weakness is apparent. It is likely that we will see severe clinical manifestations of infection with this novel influenza virus in the coming respiratory virus season.