Current Epidemiology and Clinical Features of Cryptococcus Infection in Patients Without Human Immunodeficiency Virus: A Multicenter Study in 46 Hospitals in Australia and New Zealand.

BACKGROUND: Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. METHODS: We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. RESULTS: Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89). CONCLUSIONS: Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

Human Neural Larva Migrans Caused by Ophidascaris robertsi Ascarid.

We describe a case in Australia of human neural larva migrans caused by the ascarid Ophidascaris robertsi, for which Australian carpet pythons are definitive hosts. We made the diagnosis after a live nematode was removed from the brain of a 64-year-old woman who was immunosuppressed for a hypereosinophilic syndrome diagnosed 12 months earlier.

Campylobacter-associated hospitalisations in an Australian provincial setting.

BACKGROUND: Campylobacter spp. infections are a globally important cause of enterocolitis, causing substantial morbidity. Capturing accurate information on hospitalisations is challenging and limited population-level data exist to describe the clinico-epidemiological characteristics of hospitalised cases. METHODS: Hospital administrative and laboratory datasets were linked to identify Campylobacter-associated hospitalisations between 2004 and 2013. Accuracy of morbidity coding was assessed using laboratory diagnosis as a gold standard, with health department surveillance data used to calculate population-based rates. Additional patient-level data were collected via review of medical records. Descriptive statistics were used to assess changes in rates and proportions and to assess relationships between key variables including age, length of stay, comorbidity and complications. RESULTS: In total 685 Campylobacter-associated hospital admissions were identified, with the sensitivity of morbidity coding 52.8% (95% CI 48.9-56.7%). The mean annual rate of hospitalisation was 13.6%. Hospitalisation rates were higher for females across most age-groups, while for both genders marked increases were observed for those aged ≥60 years. Median admission age was 39.5 years, with an average length of stay of 3.5 days. Comorbidities were present in 34.5% (237/685) of admissions, with these patients more likely to develop electrolyte disturbances, hypotension, renal impairment or acute confusion (all p < 0.001). Bacteraemia and acute kidney injury were observed in 4.1% (28/685) and 3.6% (23/685) of admissions, respectively. Inpatient mortality was low (0.15%). CONCLUSION: Under reporting of Campylobacter-associated hospitalisations is substantial but can be improved through data linkage. We observed demographic differences among those hospitalised but further work is needed to determine risk factors and predictors for hospitalisation.

Bacteraemia, antimicrobial susceptibility and treatment among Campylobacter-associated hospitalisations in the Australian Capital Territory: a review.

BACKGROUND: Campylobacter spp. cause mostly self-limiting enterocolitis, although a significant proportion of cases require hospitalisation highlighting potential for severe disease. Among people admitted, blood culture specimens are frequently collected and antibiotic treatment is initiated. We sought to understand clinical and host factors associated with bacteraemia, antibiotic treatment and isolate non-susceptibility among Campylobacter-associated hospitalisations. METHODS: Using linked hospital microbiology and administrative data we identified and reviewed Campylobacter-associated hospitalisations between 2004 and 2013. We calculated population-level incidence for Campylobacter bacteraemia and used logistic regression to examine factors associated with bacteraemia, antibiotic treatment and isolate non-susceptibility among Campylobacter-associated hospitalisations. RESULTS: Among 685 Campylobacter-associated hospitalisations, we identified 25 admissions for bacteraemia, an estimated incidence of 0.71 cases per 100,000 population per year. Around half of hospitalisations (333/685) had blood culturing performed. Factors associated with bacteraemia included underlying liver disease (aOR 48.89, 95% CI 7.03-340.22, p < 0.001), Haematology unit admission (aOR 14.67, 95% CI 2.99-72.07, p = 0.001) and age 70-79 years (aOR 4.93, 95% CI 1.57-15.49). Approximately one-third (219/685) of admissions received antibiotics with treatment rates increasing significantly over time (p < 0.05). Factors associated with antibiotic treatment included Gastroenterology unit admission (aOR 3.75, 95% CI 1.95-7.20, p < 0.001), having blood cultures taken (aOR 2.76, 95% CI 1.79-4.26, p < 0.001) and age 40-49 years (aOR 2.34, 95% CI 1.14-4.79, p = 0.02). Non-susceptibility of isolates to standard antimicrobials increased significantly over time (p = 0.01) and was associated with overseas travel (aOR 11.80 95% CI 3.18-43.83, p < 0.001) and negatively associated with tachycardia (aOR 0.48, 95%CI 0.26-0.88, p = 0.02), suggesting a healthy traveller effect. CONCLUSIONS: Campylobacter infections result in considerable hospital burden. Among those admitted to hospital, an interplay of factors involving clinical presentation, presence of underlying comorbidities, complications and increasing age influence how a case is investigated and managed.

Epidemiology of non-typhoid Salmonella infection in the Australian Capital Territory over a 10-year period.

AIM: To describe the epidemiology of non-typhoid Salmonella (NTS) infection in the Australian Capital Territory (ACT), including factors associated with hospitalisation. METHODS: This was a retrospective descriptive and observational study of culture-confirmed NTS infections using data collected from ACT public health, public pathology and hospital services in the period 2003-2012. Outcome measures include incidence and NTS serotype for total reported and hospitalised cases and focus of infection, complications and antibiotic susceptibility for hospitalised cases. RESULTS: In total, 1469 cases of NTS infection were reported, with the crude annual incidence increasing from 24.4 to 61.3 cases per 100 000 population; 14% were hospitalised, representing an incidence of 5.9 hospitalisations per 100 000 population, without significant change over time. Hospitalisation incidence peaked at the extremes of age. Comorbid disease and age ≥ 80 years were associated with complications during hospitalisation. Salmonella serotype Typhimurium was the most common serotype, accounting for 64% of NTS. Independent risk factors for invasive disease included non-S. Typhimurium serotype (aRR 5.46, 95%CI 1.69-17.65 P = 0.005), ischaemic heart disease (aRR 4.18, 95%CI 1.20-14.60 P = 0.025) and haematological malignancy (aRR 6.93, 95%CI 2.54-18.94 P < 0.001). Among hospitalised patients, resistance to ampicillin, ceftriaxone, trimethoprim-sulfamethoxazole and quinolones was 9.9%, 0%, 4.4% and 2.5% respectively. CONCLUSIONS: NTS notifications in the ACT have increased over time, with outbreaks of food-borne disease contributing to this increase. Crude age-specific incidence is highest in the very young, while rates of hospitalisation are highest in the elderly. Comorbid disease and infection with a non-S. Typhimurium serotype were associated with complicated NTS disease course. Antimicrobial resistance in NTS is low and has not increased over time.

First case report of myopericarditis linked to Campylobacter coli enterocolitis.

BACKGROUND: Campylobacter spp. are a common cause of mostly self-limiting enterocolitis. Although rare, pericarditis and myopericarditis have been increasingly documented as complications following campylobacteriosis. Such cases have occurred predominantly in younger males, and involved a single causative species, namely Campylobacter jejuni. We report the first case of myopericarditis following Campylobacter coli enterocolitis, with illness occurring in an immunocompetent middle-aged female. CASE PRESENTATION: A 51-yo female was admitted to a cardiology unit with a 3-days history of chest pain. The woman had no significant medical history or risk factors for cardiac disease, nor did she report any recent overseas travel. Four days prior to the commencement of chest pain the woman had reported onset of an acute gastrointestinal illness, passing 3-4 loose stools daily, a situation that persisted at the time of presentation. Physical examination showed the woman's vital signs to be essentially stable, although she was noted to be mildly tachycardic. Laboratory testing showed mildly elevated C-reactive protein and a raised troponin I in the absence of elevation of the serum creatinine kinase. Electrocardiography (ECG) demonstrated concave ST segment elevations, and PR elevation in aVR and depression in lead II. Transthoracic echocardiogram (TTE) revealed normal biventricular size and function with no significant valvular abnormalities. There were no left ventricular regional wall motion abnormalities. No pericardial effusion was present but the pericardium appeared echodense. A diagnosis of myopericarditis was made on the basis of chest pain, typical ECG changes and troponin rise. The chest pain resolved and she was discharged from hospital after 2-days of observation, but with ongoing diarrhoea. Following discharge, a faecal sample taken during the admission, cultured Campylobacter spp. Matrix assisted laser desorption ionization time-of-flight (Bruker) confirmed the cultured isolate as C. coli. CONCLUSION: We report the first case of myopericarditis with a suggested link to an antecedent Campylobacter coli enterocolitis. Although rare, myopericarditis is becoming increasingly regarded as a complication following campylobacteriosis. Our report highlights potential for pericardial disease beyond that attributed to Campylobacter jejuni. However uncertainty regarding pathogenesis, coupled with a paucity of population level data continues to restrict conclusions regarding the strength of this apparent association.

Increasing incidence of Clostridium difficile infection, Australia, 2011-2012.

OBJECTIVES: To report the quarterly incidence of hospital-identified Clostridium difficile infection (HI-CDI) in Australia, and to estimate the burden ascribed to hospital-associated (HA) and community-associated (CA) infections. DESIGN, SETTING AND PATIENTS: Prospective surveillance of all cases of CDI diagnosed in hospital patients from 1 January 2011 to 31 December 2012 in 450 public hospitals in all Australian states and the Australian Capital Territory. All patients admitted to inpatient wards or units in acute public hospitals, including psychiatry, rehabilitation and aged care, were included, as well as those attending emergency departments and outpatient clinics. MAIN OUTCOME MEASURES: Incidence of HI-CDI (primary outcome); proportion and incidence of HA-CDI and CA-CDI (secondary outcomes). RESULTS: The annual incidence of HI-CDI increased from 3.25/10 000 patient-days (PD) in 2011 to 4.03/10 000 PD in 2012. Poisson regression modelling demonstrated a 29% increase (95% CI, 25% to 34%) per quarter between April and December 2011, with a peak of 4.49/10 000 PD in the October-December quarter. The incidence plateaued in January-March 2012 and then declined by 8% (95% CI, - 11% to - 5%) per quarter to 3.76/10 000 PD in July-September 2012, after which the rate rose again by 11% (95% CI, 4% to 19%) per quarter to 4.09/10 000 PD in October-December 2012. Trends were similar for HA-CDI and CA-CDI. A subgroup analysis determined that 26% of cases were CA-CDI. CONCLUSIONS: A significant increase in both HA-CDI and CA-CDI identified through hospital surveillance occurred in Australia during 2011-2012. Studies are required to further characterise the epidemiology of CDI in Australia.

Antibiotic stability in commercial peritoneal dialysis solutions: influence of formulation, storage and duration.

BACKGROUND: Peritoneal dialysis (PD)-associated peritonitis is treated by administration of antibiotics mixed with the PD solution. Data on antibiotic stability for solutions in current use are limited. The aim of this study was to determine the stability of cefepime, cephazolin and ampicillin in three commercial PD solutions. METHODS: Antibiotics were added to the non-glucose compartment of the Gambro (Gambrosol®) and Fresenius (Balance®) multi-compartment systems and Baxter (Dianeal®) single-compartment (glucose 2.5%) PD solutions in a sterile suite. Antibiotic stability over 3 weeks was determined using both a bioassay of bacterial inhibition and antibiotic concentrations. The influence on stability and sterility of storage conditions was determined. RESULTS: The bioassay demonstrated the stability of all antibiotics for 9 days at room temperature and 3 weeks when refrigerated, except ampicillin in the Gambro solution, which displayed no bioactivity after 4 days. However, a ceiling effect in bacterial inhibition at higher antibiotic concentrations limited the ability of the bioassay to detect antibiotic degradation at relevant concentrations. Antibiotic concentrations varied with time but were comparable to the bioassay and supported stability in refrigerated solutions, except ampicillin in the Gambro solution. No bacterial contamination, marked colour change or precipitation occurred. CONCLUSIONS: This study supports the stability of cephazolin and cefepime in all three PD solutions and ampicillin in only the Baxter and Fresenius PD solutions. Antibiotic stability studies should ideally be conducted prior to registration and marketing of new PD solutions.

Salmonella enterica bacteraemia: a multi-national population-based cohort study.

BACKGROUND: Salmonella enterica is an important emerging cause of invasive infections worldwide. However, population-based data are limited. The objective of this study was to define the occurrence of S. enterica bacteremia in a large international population and to evaluate temporal and regional differences. METHODS: We conducted population-based laboratory surveillance for all salmonella bacteremias in six regions (annual population at risk 7.7 million residents) in Finland, Australia, Denmark, and Canada during 2000-2007. RESULTS: A total of 622 cases were identified for an annual incidence of 1.02 per 100,000 population. The incidence of typhoidal (serotypes Typhi and Paratyphi) and non-typhoidal (other serotypes) disease was 0.21 and 0.81 per 100,000/year. There was major regional and moderate seasonal and year to year variability with an increased incidence observed in the latter years of the study related principally to increasing rates of non-typhoidal salmonella bacteremias. Advancing age and male gender were significant risk factors for acquiring non-typhoidal salmonella bacteremia. In contrast, typhoidal salmonella bacteremia showed a decreasing incidence with advancing age and no gender-related excess risk. CONCLUSIONS: Salmonella enterica is an important emerging pathogen and regional determinants of risk merits further investigation.

Mycoplasma hominis-associated parapharyngeal abscess following acute Epstein-Barr virus infection in a previously immunocompetent adult.

Mycoplasma hominis most frequently causes diseases of the genitourinary tract. Extragenital infections are uncommon, with almost all occurring in immunosuppressed persons or those predisposed due to trauma or surgery. We present the case of a previously well man who developed an M. hominis-associated parapharyngeal abscess following acute Epstein-Barr virus infection.

A cluster of nocardial brain abscesses.

BACKGROUND: Nocardia species are aerobic Gram-positive bacteria that are ubiquitous in the environment. Infection usually occurs through inhalation or direct cutaneous inoculation of the organism. It has been reported that infection is more common in warm, dry climates. Cerebral nocardiosis is an uncommon clinical entity, representing only 2% of all cerebral abscesses. It is an illness associated with significant morbidity and mortality. CASE DESCRIPTIONS: We report 4 cases of nocardial brain abscesses presenting to TCH, Australia, within a 1-year period. All 4 cases occurred in men without any significant underlying immunocompromise. In 3 of the cases, the diagnosis was only established after craniotomy. All cases were given prolonged antimicrobial therapy. After more than 8 months of follow-up, there have been no deaths or treatment failures. There has been only one other case of nocardial brain abscess at TCH over the past 15 years. We review the current literature on cerebral nocardiosis. CONCLUSION: Nocardial brain abscesses are uncommonly encountered at our institution. This cluster of 4 cases over a 1-year period has therefore led us to postulate that the severe drought may be aiding in the transmission of the bacteria. The cases also emphasize the propensity of nocardial infections to mimic other conditions, particularly malignancy, which may lead to delays in appropriate surgical treatment and antimicrobial therapy. The diagnosis requires a high clinical index of suspicion, with early tissue and microbiological diagnosis. Prolonged antimicrobial therapy is required to prevent relapse of the infection.

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance.

Candida glabrata can rapidly acquire mutations that result in drug resistance, especially to azoles and echinocandins. Identification of genetic mutations is essential, as resistance detected in vitro can often be correlated with clinical failure. We examined the feasibility of using whole genome sequencing (WGS) for genome-wide analysis of antifungal drug resistance in C. glabrata. The aim was torecognize enablers and barriers in the implementation WGS and measure its effectiveness. This paper outlines the key quality control checkpoints and essential components of WGS methodology to investigate genetic markers associated with reduced susceptibility to antifungal agents. It also estimates the accuracy of data analysis and turn-around-time of testing. Phenotypic susceptibility of 12 clinical, and one ATCC strain of C. glabrata was determined through antifungal susceptibility testing. These included three isolate pairs, from three patients, that developed rise in drug minimum inhibitory concentrations. In two pairs, the second isolate of each pair developed resistance to echinocandins. The second isolate of the third pair developed resistance to 5-flucytosine. The remaining comprised of susceptible and azole resistant isolates. Single nucleotide polymorphisms (SNPs) in genes linked to echinocandin, azole and 5-flucytosine resistance were confirmed in resistant isolates through WGS using the next generation sequencing. Non-synonymous SNPs in antifungal resistance genes such as FKS1, FKS2, CgPDR1, CgCDR1 and FCY2 were identified. Overall, an average of 98% of the WGS reads of C. glabrata isolates mapped to the reference genome with about 75-fold read depth coverage. The turnaround time and cost were comparable to Sanger sequencing. In conclusion, WGS of C. glabrata was feasible in revealing clinically significant gene mutations involved in resistance to different antifungal drug classes without the need for multiple PCR/DNA sequencing reactions. This represents a positive step towards establishing WGS capability in the clinical laboratory for simultaneous detection of antifungal resistance conferring substitutions.

The changing epidemiology of group B streptococcus bloodstream infection: a multi-national population-based assessment.

BACKGROUND: Population-based studies conducted in single regions or countries have identified significant changes in the epidemiology of invasive group B streptococcus (GBS) infection. However, no studies have concurrently compared the epidemiology of GBS infections among multiple different regions and countries over time. The study objectives were to define the contemporary incidence and determinants of GBS bloodstream infection (BSI) and assess temporal changes in a multi-national population. METHODS: Population-based surveillance for GBS BSI was conducted in nine regions in Australia, Canada, Denmark, Sweden, Finland and the UK during 2000-2010. Incidence rates were age- and gender-standardised to the EU population. RESULTS: During 114 million patient-years of observation, 3464 cases of GBS BSI were identified for an overall annual incidence of 3.4 patients per 100,000 persons. There were marked differences in the overall (range = 1.8-4.1 per 100,000 person-year) and neonatal (range = 0.19-0.83 per 1000 live births) incidences of GBS BSI observed among the study regions. The overall incidence significantly (p = 0.05) increased. Rates of neonatal disease were stable, while the incidence in individuals older than 60 years doubled (p = 0.003). In patients with detailed data (n = 1018), the most common co-morbidity was diabetes (25%). During the study period, the proportion of cases associated with diabetes increased. CONCLUSIONS: While marked variability in the incidence of GBS BSI was observed among these regions, it was consistently found that rates increased among older adults, especially in association with diabetes. The burden of this infection may be expected to continue to increase in ageing populations worldwide.

Antifungal susceptibilities of non-Aspergillus filamentous fungi causing invasive infection in Australia: support for current antifungal guideline recommendations.

Antifungal susceptibilities of non-Aspergillus filamentous fungal pathogens cannot always be inferred from their identification. Here we determined, using the Sensititre(®) YeastOne(®) YO10 panel, the in vitro activities of nine antifungal agents against 52 clinical isolates of emergent non-Aspergillus moulds representing 17 fungal groups in Australia. Isolates comprised Mucorales (n = 14), Scedosporium/Lomentospora spp. (n = 18) and a range of hyaline hyphomycetes (n = 9) and other dematiaceous fungi (n = 11). Excluding Verruconis gallopava, echinocandins demonstrated poor activity (MICs generally >8 mg/L) against these moulds. Lomentospora prolificans (n = 4) and Fusarium spp. (n = 6) demonstrated raised MICs to all antifungal drugs tested, with the lowest being to voriconazole and amphotericin B (AmB), respectively (geometric mean MICs of 3.4 mg/L and 2.2 mg/L, respectively). All Scedosporium apiospermum complex isolates (n = 14) were inhibited by voriconazole concentrations of ≤0.25 mg/L, followed by posaconazole and itraconazole at ≤1 mg/L. Posaconazole and AmB were the most active agents against the Mucorales, with MIC90 values of 1 mg/L and 2 mg/L, respectively, for Rhizopus spp. For dematiaceous fungi, all isolates were inhibited by itraconazole and posaconazole concentrations of ≤0.5 mg/L (MIC90, 0.12 mg/L and 0.25 mg/L, respectively), but voriconazole and AmB also had in vitro activity (MIC90, 0.5 mg/L and 1 mg/L, respectively). Differences in antifungal susceptibility within species and between species within genera support the need for testing individual patient isolates to guide therapy. The Sensititre(®) YeastOne(®) offers a practical alternative to the reference methodology for susceptibility testing of moulds.

Clinical impact of reducing routine blood culture incubation time from 7 to 5 days.

The aim of this study was to determine the clinical impact of reducing the blood culture incubation protocol from 7 to 5 days.A laboratory data extraction identified positive blood cultures occurring after 5 or more days of incubation at Canberra Hospital, Australia between 1 January 2001 and 31 August 2011. Isolates were identified as clinically significant using a pre-existing prospective bacteraemia database. Medical records review determined whether the positive result affected clinical management.Positive blood cultures after 5 or more days of incubation accounted for 2.65% (423/15979) of all positive blood cultures, although the majority were false positives or contaminants. Eighty-five were significant/indeterminate, representing an average of eight cases per year or 0.47% (85/15979) of all positive blood cultures sets. Forty-three were isolated for the first time, representing 1.1% of all significant/indeterminate blood culture episodes. Fungi and anaerobic bacteria compromised over 50% of isolates. In 26 cases (2.4 cases per year), the culture result led to a change in patient management.A 7 day incubation protocol is preferable due to late isolation of organisms; however, if space is required to accommodate increasing blood culture numbers, reducing to a 5 or 6 day protocol would miss only a small percentage of clinically significant isolates.

Scedosporium apiospermum brain abscesses in an immunocompetent man with silicosis.

We report a case of Scedosporium apiosporum brain abscesses in an immunocompetent 69-year-old man with a history of silicosis. Delayed diagnosis and institution of antifungal therapy was associated with neurological impairment, with subsequent complications resulting in death, highlighting the need for early diagnostic aspiration of brain abscesses non-responsive to antibiotics. We propose that, in the absence of identifiable immunosuppression, silicosis may have been a contributing factor to the development of central nervous system infection.

Epidemiology of Haemophilus influenzae bacteremia: a multi-national population-based assessment.

OBJECTIVES: Haemophilus influenzae is an important cause of invasive infection but contemporary data in non-selected populations is limited. METHODS: Population-based surveillance for Haemophilus influenzae bacteremia was conducted in seven regions in Australia, Canada, and Denmark during 2000-2008. RESULTS: The overall annual incidence rate was 1.31 per 100,000 population and type specific rates were 0.08 for H. influenzae serotype b (Hib), 0.22 for H. influenzae serotypes a, c-f (Hiac-f), and 0.98 per 100,000 for non-typeable H. influenzae (NTHi). Very young and old patients were at highest risk. The serotypes causing disease varied according to age with nearly all cases in the elderly due to NTHi. The presence of comorbid medical illness was common with 14%, 16%, and 29% patients having Charlson comorbidity scores of 1, 2, and ≥ 3, respectively. The 30-day all-cause case-fatality rate was 18%. Factors independently associated with death at 30-days in logistic regression analysis included male gender, hospital-onset disease, older age, and lower respiratory tract, central nervous system, or unknown focus of infection. CONCLUSIONS: Haemophilus influenzae is an important cause of morbidity and mortality particularly with NTHi in the elderly. These data serve as a baseline to assess the future effectiveness of new preventative interventions.