Nocardia species distribution and antimicrobial susceptibility within Australia.

BACKGROUND: Nocardia is a ubiquitous saprophyte capable of causing human disease. Disease is primarily respiratory or cutaneous, usually acquired via inhalation or inoculation. Under the influence of environmental and host factors, Nocardia incidence and species distribution demonstrate geographical variation. AIMS: To examine for differences in Nocardia incidence within Western Australia (WA) and analyse species distribution in the context of prior published studies. To analyse antibiogram data from a nationwide passive antimicrobial resistance surveillance program. METHODS: Retrospective extraction of laboratory data for Western Australian Nocardia isolates over a 21-year period. Analysis of Nocardia antimicrobial susceptibility testing data submitted to the Australian Passive Antimicrobial Resistance Surveillance (APAS) program between 2005 and 2022. RESULTS: Nine hundred sixty WA isolates were identified, giving an annual incidence of 3.03 per 100 000 population with apparent latitudinal variation. The four most common species identified within WA and amongst APAS isolates were N. nova, N. cyriacigeorgica, N. brasiliensis and N. farcinica. APAS data demonstrated that all species exhibited high rates of susceptibility to linezolid (100%) and trimethoprim-sulfamethoxazole (98%). Amikacin (>90% susceptibility for all species except N. transvalensis) was the next most active parenteral agent, superior to both carbapenems and third-generation cephalosporins. Susceptibility to oral antimicrobials (other than linezolid) demonstrated significant interspecies variation. CONCLUSIONS: We demonstrate geographical variation in the distribution of Nocardia incidence. Four species predominate in the Australian setting, and nationwide data confirm a high in vitro susceptibility to trimethoprim-sulphamethoxazole and linezolid, justifying their ongoing role as part of first-line empiric therapy.

Comparison of contemporary invasive and non-invasive Streptococcus pneumoniae isolates reveals new insights into circulating anti-microbial resistance determinants.

Streptococcus pneumoniae is a major human pathogen with a high burden of disease. Non-invasive isolates (those found in non-sterile sites) are thought to be a key source of invasive isolates (those found in sterile sites) and a reservoir of anti-microbial resistance (AMR) determinants. Despite this, pneumococcal surveillance has almost exclusively focused on invasive isolates. We aimed to compare contemporaneous invasive and non-invasive isolate populations to understand how they interact and identify differences in AMR gene distribution. We used a combination of whole-genome sequencing and phenotypic anti-microbial susceptibility testing and a data set of invasive (n = 1,288) and non-invasive (n = 186) pneumococcal isolates, collected in Victoria, Australia, between 2018 and 2022. The non-invasive population had increased levels of antibiotic resistance to multiple classes of antibiotics including beta-lactam antibiotics penicillin and ceftriaxone. We identified genomic intersections between the invasive and non-invasive populations and no distinct phylogenetic clustering of the two populations. However, this analysis revealed sub-populations overrepresented in each population. The sub-populations that had high levels of AMR were overrepresented in the non-invasive population. We determined that WamR-Pneumo was the most accurate in silico tool for predicting resistance to the antibiotics tested. This tool was then used to assess the allelic diversity of the penicillin-binding protein genes, which acquire mutations leading to beta-lactam antibiotic resistance, and found that they were highly conserved (≥80% shared) between the two populations. These findings show the potential of non-invasive isolates to serve as reservoirs of AMR determinants.

Long-term antibiotic prescribing in the community: 6 years of Australian national data.

BACKGROUND: Prolonged or indefinite courses of antibiotics are sometimes prescribed for suppression of chronic infection, prophylaxis, and noninfective indications. Little is known about long-term prescribing practices in the community. In Australia, 75% of outpatient prescribing is funded through the Pharmaceutical Benefits Scheme (PBS), a government program for subsidized medications. OBJECTIVES: To describe the landscape of outpatient prescribing of long-term antibiotics in Australia. METHODS: We descriptively analyzed a randomized 10% sample of PBS prescription data from 2014 to 2020. "Long term" was defined as continuous prescribing 12 months or more. Patients were identified using a rolling window algorithm with 12-month look-back from each script provided. RESULTS: Prolonged continuous antibiotics (> 12 months) were prescribed to 339/100,000 population; 50% of patients were aged more than 65 years and prescribing increased with age (1440/100,000 population in patients > 75 years). Frequently prescribed antibiotic classes were tetracyclines (43% of all long-term antibiotics), sulfonamides/trimethoprim (21%, predominantly cotrimoxazole), cephalosporins (15%, predominantly cefalexin), and penicillins (13%). Prophylaxis of infection and immunomodulatory indications were most common. Patients were co-prescribed analgesics (30%), antidepressants (30%), corticosteroids (20%), and immunosuppressive drugs (6%). CONCLUSION: Prolonged community prescribing of antibiotics is an important target for antibiotic stewardship, particularly in older adults.

Outcomes in Medicare-ineligible people living with human immunodeficiency virus in a large healthcare network in Melbourne 2004-2019.

Australia has approximately 1.6 million Medicare-ineligible residents, of whom around 450 are living with human immunodeficiency virus (PLHIV). We examined the outcomes in a cohort of 50 Medicare-ineligible patients presenting to our hospital network over a 15-year period: 31 women (62%) and 19 men. Twenty-four were newly diagnosed. Sixteen of 24 remained in Australia more than 1 year after diagnosis. Although the mean CD4 count at initial contact was 353 cells/mm3 (range 3-2228; standard deviation (SD) = 452.88), 13 people required treatment for opportunistic infections and 21 people required hospital admissions related to HIV, incurring total estimated hospital costs of $886 310. The mean number of contact years spent with the service was 2.2 (range 0-12; SD = 2.6) and 20 people remain under care. Twenty-seven PLHIV remain in Australia, seven have transferred care within Australia, two people are known to have died and eight are lost to follow up. The median number of admissions was 0 (range 0-4; SD = 1) and median length of admission was 5 days (range 0-73; SD = 19). Many people leave Australia shortly after a diagnosis of HIV, but most Medicare-ineligible PLHIV remain. Delays in diagnosing HIV and acquiring Medicare status are associated with a significant burden of disease and cost. Keeping people well, on therapy and out of hospital is likely to be cost-saving in addition to good clinical practice.

Trichomoniasis among men presenting to a sexual health clinic in Melbourne, Australia.

In response to the report by Abraham et al ., we present our observations of Trichomonas vaginalis (TV) detection in men tested at a public hospital laboratory in Melbourne, Australia, using a multiplex PCR. These studies provide valuable information about TV prevalence in urban communities.

Under-utilisation of cardioprotective glucose-lowering medication in diabetics living with HIV.

Diabetes is an increasingly common co-morbidity in people living with HIV (PLWH). Given new evidence demonstrating cardiovascular benefits of sodium glucose transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) in diabetic patients, we reviewed medical charts of 262 PLWH at Monash Health through a 1-year retrospective cohort study to determine the rates of their use. Prevalence of diabetes was 13.4% (35) and 60% (21) had microvascular and macrovascular complications. Only 4% (95% CI 0.1%-19.6%) of diabetic patients were receiving SGLT2i and 19% (95% CI 6%-39.4%) were receiving GLP1RA. Prescribers should carefully consider their choice of glucose-lowering medication when treating PLWH.

Viral Genomics to Inform Infection-control Response in Occupational Coronavirus Disease 2019 (COVID-19) Transmission.

Healthcare workers are at increased risk of occupational transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report 2 instances of healthcare workers contracting SARS-CoV-2 despite no known breach of personal protective equipment. Additional specific equipment cleaning was initiated. Viral genomic sequencing supported this transmission hypothesis and our subsequent response.

Antimicrobial resistance surveillance of Clostridioides difficile in Australia, 2015-18.

BACKGROUND: Clostridioides difficile was listed as an urgent antimicrobial resistance (AMR) threat in a report by the CDC in 2019. AMR drives the evolution of C. difficile and facilitates its emergence and spread. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is nationwide longitudinal surveillance of C. difficile infection (CDI) in Australia. OBJECTIVES: To determine the antimicrobial susceptibility of C. difficile isolated in Australia between 2015 and 2018. METHODS: A total of 1091 strains of C. difficile were collected over a 3 year period by a network of 10 diagnostic microbiology laboratories in five Australian states. These strains were tested for their susceptibility to nine antimicrobials using the CLSI agar incorporation method. RESULTS: All strains were susceptible to metronidazole, fidaxomicin, rifaximin and amoxicillin/clavulanate and low numbers of resistant strains were observed for meropenem (0.1%; 1/1091), moxifloxacin (3.5%; 38/1091) and vancomycin (5.7%; 62/1091). Resistance to clindamycin was common (85.2%; 929/1091), followed by resistance to ceftriaxone (18.8%; 205/1091). The in vitro activity of fidaxomicin [geometric mean MIC (GM) = 0.101 mg/L] was superior to that of vancomycin (1.700 mg/L) and metronidazole (0.229 mg/L). The prevalence of MDR C. difficile, as defined by resistance to ≥3 antimicrobial classes, was low (1.7%; 19/1091). CONCLUSIONS: The majority of C. difficile isolated in Australia did not show reduced susceptibility to antimicrobials recommended for treatment of CDI (vancomycin, metronidazole and fidaxomicin). Resistance to carbapenems and fluoroquinolones was low and MDR was uncommon; however, clindamycin resistance was frequent. One fluoroquinolone-resistant ribotype 027 strain was detected.

COVID-19 in Australia: our national response to the first cases of SARS-CoV-2 infection during the early biocontainment phase.

BACKGROUND: On 31 December 2019, the World Health Organization recognised clusters of pneumonia-like cases due to a novel coronavirus disease (COVID-19). COVID-19 became a pandemic 71 days later. AIM: To report the clinical and epidemiological features, laboratory data and outcomes of the first group of 11 returned travellers with COVID-19 in Australia. METHODS: This is a retrospective, multi-centre case series. All patients with confirmed COVID-19 infection were admitted to tertiary referral hospitals in New South Wales, Queensland, Victoria and South Australia. RESULTS: The median age of the patient cohort was 42 years (interquartile range (IQR), 24-53 years) with six men and five women. Eight (72.7%) patients had returned from Wuhan, one from Shenzhen, one from Japan and one from Europe. Possible human-to-human transmission from close family contacts in gatherings overseas occurred in two cases. Symptoms on admission were fever, cough and sore throat (n = 9, 81.8%). Co-morbidities included hypertension (n = 3, 27.3%) and hypercholesterolaemia (n = 2, 18.2%). No patients developed severe acute respiratory distress nor required intensive care unit admission or mechanical ventilation. After a median hospital stay of 14.5 days (IQR, 6.75-21), all patients were discharged. CONCLUSIONS: This is a historical record of the first COVID-19 cases in Australia during the early biocontainment phase of the national response. These findings were invaluable for establishing early inpatient and outpatient COVID-19 models of care and informing the management of COVID-19 over time as the outbreak evolved. Future research should extend this Australian case series to examine global epidemiological variation of this novel infection.

Laboratory-Based Surveillance of Clostridium difficile Infection in Australian Health Care and Community Settings, 2013 to 2018.

In the early 2000s, a binary toxin (CDT)-producing strain of Clostridium difficile, ribotype 027 (RT027), caused extensive outbreaks of diarrheal disease in North America and Europe. This strain has not become established in Australia, and there is a markedly different repertoire of circulating strains there compared to other regions of the world. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is a nationwide longitudinal surveillance study of C. difficile infection (CDI) in Australia. Here, we describe the molecular epidemiology of CDI in Australian health care and community settings over the first 5 years of the study, 2013 to 2018. Between 2013 and 2018, 10 diagnostic microbiology laboratories from five states in Australia participated in the CDARS study. From each of five states, one private (representing community) and one public (representing hospitals) laboratory submitted isolates of C. difficile or PCR-positive stool samples during two collection periods per year, February-March (summer/autumn) and August-September (winter/spring). C. difficile was characterized by toxin gene profiling and ribotyping. A total of 1,523 isolates of C. difficile were studied. PCR ribotyping yielded 203 different RTs, the most prevalent being RT014/020 (n = 449; 29.5%). The epidemic CDT+ RT027 (n = 2) and RT078 (n = 6), and the recently described RT251 (n = 10) and RT244 (n = 6) were not common, while RT126 (n = 17) was the most prevalent CDT+ type. A heterogeneous C. difficile population was identified. C. difficile RT014/020 was the most prevalent type found in humans with CDI. Continued surveillance of CDI in Australia remains critical for the detection of emerging strain lineages.

Isolation and rapid sharing of the 2019 novel coronavirus (SARS-CoV-2) from the first patient diagnosed with COVID-19 in Australia.

OBJECTIVES: To describe the first isolation and sequencing of SARS-CoV-2 in Australia and rapid sharing of the isolate. SETTING: SARS-CoV-2 was isolated from a 58-year-old man from Wuhan, China who arrived in Melbourne on 19 January 2020 and was admitted to the Monash Medical Centre, Melbourne from the emergency department on 24 January 2020 with fever, cough, and progressive dyspnoea. MAJOR OUTCOMES: Clinical course and laboratory features of the first reported case of COVID-19 (the illness caused by SARS-CoV-2) in Australia; isolation, whole genome sequencing, imaging, and rapid sharing of virus from the patient. RESULTS: A nasopharyngeal swab and sputum collected when the patient presented to hospital were each positive for SARS-CoV-2 (reverse transcription polymerase chain reaction). Inoculation of Vero/hSLAM cells with material from the nasopharyngeal swab led to the isolation of SARS-CoV-2 virus in culture. Electron microscopy of the supernatant confirmed the presence of virus particles with morphology characteristic of viruses of the family Coronaviridae. Whole genome sequencing of the viral isolate and phylogenetic analysis indicated the isolate exhibited greater than 99.99% sequence identity with other publicly available SARS-CoV-2 genomes. Within 24 hours of isolation, the first Australian SARS-CoV-2 isolate was shared with local and overseas reference laboratories and major North American and European culture collections. CONCLUSIONS: The ability to rapidly identify, propagate, and internationally share our SARS-CoV-2 isolate is an important step in collaborative scientific efforts to deal effectively with this international public health emergency by developing better diagnostic procedures, vaccine candidates, and antiviral agents.

Review of HIV testing recommendations in Australian specialty guidelines for HIV indicator conditions: a missed opportunity for recommending testing?

BACKGROUND: Australian National human immunodeficiency virus (HIV) Testing policy recommends HIV indicator condition-based testing, adapted from the European AIDS Clinical Society (EACS) guidelines. AIM: To evaluate the extent that Australian non-HIV specialty guidelines mention and recommend HIV testing in HIV indicator conditions. METHODS: EACS guidelines were reviewed to produce a list of 24 AIDS-defining conditions (ADC) and 31 indicator conditions (IC) where HIV prevalence >0.1%, and 5 IC where HIV non-diagnosis would have adverse effect on patients' management. Australian guidelines for these conditions were identified from websites of specialty societies, electronic Therapeutic Guidelines, National Health and Medical Research Council (NHMRC), state governments, MEDLINE and Google searches. We identified eight key IC as that were part of the HIDES I study. RESULTS: Overall, 51 ADC and IC had Australian guidelines: 24/51(47%) mention association with HIV and 14/51 (27%) recommend HIV testing. Twenty-five out of 51 (49%) Australian guidelines were for ADC: 18/25(72%) mention association with HIV and 5/25 (20%) recommend testing. Twenty-five out of 51 (49%) were guidelines IC with HIV prevalence of 0.1%: 6/25 (24%) mention HIV association and 8/25 (32%) recommend HIV testing. Two of eight (25%) key IC had no Australian guidelines and 3/8 (38%) do not mention HIV association or recommend HIV testing. CONCLUSIONS: Although almost half of HIV non-HIV guidelines for ADC and IC mention HIV association, only 27% specifically recommend HIV testing. This suggests partnership with guideline development and specialist groups may be useful to ensure patients diagnosed with ADC/IC are tested for HIV.

Burden of infective endocarditis in an Australian cohort of people who inject drugs.

BACKGROUND: Infective endocarditis (IE) results in substantial morbidity and mortality in people who inject drugs (PWID). AIMS: To describe the burden of IE and its outcomes in PWID. METHODS: Retrospective cohort study of adults admitted to a tertiary referral centre in Melbourne, Australia, with IE due to injection drug use from 1997 to 2015. RESULTS: Ninety-seven PWID with 127 episodes of IE were identified with a median acute inpatient stay of 37 days (1-84). Admission to an intensive care unit was required in 67/127 (53%) episodes. Twenty-seven percent (34/127) of episodes occurred in patients with a previous episode of endocarditis. One third (43/127, 34%) of episodes involved left-sided cardiac valves. Antimicrobial treatment was completed in 88 (70%) episodes. Valve surgery was performed in 25/127 (20%) episodes. Predictors of surgery in univariable analysis were left-sided cardiac involvement (risk ratio (RR) 6.0), severe valvular regurgitation (RR 2.6) and cardiac failure (RR 2.2) (all P < 0.005). Twenty (16%) episodes resulted in death. Predictors of mortality on univariable analysis were left-sided cardiac involvement (RR 6.4), and not completing treatment (RR 0.12; both P < 0.001). The average estimated cost per episode was AU$74 168. CONCLUSIONS: IE causes a considerable burden of disease in PWID, with significant healthcare utilisation and cost. Surgery and death are not infrequent complications. In addition to ensuring completion of antimicrobial therapy, strategies such as opioid maintenance programmes may be useful in improving health outcomes for PWID.

Anti-Helicobacter pylori activity of ethoxzolamide.

Ethoxzolamide (EZA), acetazolamide, and methazolamide are clinically used sulphonamide drugs designed to treat non-bacteria-related illnesses (e.g. glaucoma), but they also show antimicrobial activity against the gastric pathogen Helicobacter pylori. EZA showed the highest activity, and was effective against clinical isolates resistant to metronidazole, clarithromycin, and/or amoxicillin, suggesting that EZA kills H. pylori via mechanisms different from that of these antibiotics. The frequency of single-step spontaneous resistance acquisition by H. pylori was less than 5 × 10-9, showing that resistance to EZA does not develop easily. Resistance was associated with mutations in three genes, including the one that encodes undecaprenyl pyrophosphate synthase, a known target of sulphonamides. The data indicate that EZA impacts multiple targets in killing H. pylori. Our findings suggest that developing the approved anti-glaucoma drug EZA into a more effective anti-H. pylori agent may offer a faster and cost-effective route towards new antimicrobials with a novel mechanism of action.

Management of gonorrhoea in a hospital network: are we following best practice?

Background Gonorrhoea is usually managed in community sexual health or general practice, but a proportion of cases present to hospital settings. In this study, we examined how gonorrhoea was managed through a large hospital network and what the implications may be for public health management. METHODS: A retrospective chart review was performed of the management of patients with Neisseria gonorrhoeae infection diagnosed at a large Australian healthcare network from January 2015 to May 2018. Documentation rates of five parameters of care were assessed: (1) the presence (or absence) of previous sexually transmissible infections (STIs); (2) recent travel; (3) discussion of HIV testing; (4) contact tracing; and (5) public health notification. RESULTS: In all, 110 cases (48 male, 62 female) were analysed. Most cases were in the 15-39 years age group; 98 cases (89%) were symptomatic, and 12 (11%) were screening tests. The most common presenting syndromes were pelvic inflammatory disease (32%; 31/98 symptomatic cases), urethritis (26%; 25/98) and epididymo-orchitis (13%; 13/98). None of the five parameters assessed were documented in most cases. Documentation was most likely to occur in patients admitted to hospital. When HIV testing was performed, no new cases of HIV were identified. CONCLUSION: Infections with gonorrhoea present on a regular basis to hospital practice, but overall management is suboptimal. Automated prompts for other recommended tests, including HIV testing when testing for other sexually transmissible diseases is ordered, may improve management. Better awareness of best practice is needed, which can be facilitated with ongoing education. However, the greatest benefit is likely achieved by linking patients back to community-based services, which are best placed to provide ongoing long-term care.

Life-long antimicrobial therapy: where is the evidence?

The decision to prescribe long-term or 'life-long' antibiotics in patients requires careful consideration by the treating clinician. While several guidelines exist to help assist in this decision, the long-term consequences are yet to be well studied. In this review, we aim to provide a summary of the available evidence for patient populations where long-term antibiotic therapy is currently recommended in clinical practice. We will also discuss the pitfalls of this approach, including medication adverse effects, economic cost and any possible contribution to the emerging epidemic of microbial resistance.

Morbidity from in-hospital complications is greater than treatment failure in patients with Staphylococcus aureus bacteraemia.

BACKGROUND: Various studies have identified numerous factors associated with poor clinical outcomes in patients with Staphylococcus aureus bacteraemia (SAB). A new study was created to provide deeper insight into in-hospital complications and risk factors for treatment failure. METHODS: Adult patients hospitalised with Staphylococcus aureus bacteraemia (SAB) were recruited prospectively into a multi-centre cohort. The primary outcome was treatment failure at 30 days (composite of all-cause mortality, persistent bacteraemia, or recurrent bacteraemia), and secondary measures included in-hospital complications and mortality at 6- and 12-months. Data were available for 222 patients recruited from February 2011 to December 2012. RESULTS: Treatment failure at 30-days was recorded in 14.4% of patients (30-day mortality 9.5%). Multivariable analysis predictors of treatment failure included age > 70 years, Pitt bacteraemia score ≥ 2, CRP at onset of SAB > 250 mg/L, and persistent fevers after SAB onset; serum albumin at onset of SAB, receipt of appropriate empiric treatment, recent healthcare attendance, and performing echocardiography were protective. 6-month and 12-month mortality were 19.1% and 24.2% respectively. 45% experienced at least one in-hospital complication, including nephrotoxicity in 19.5%. CONCLUSIONS: This study demonstrates significant improvements in 30-day outcomes in SAB in Australia. However, we have identified important areas to improve outcomes from SAB, particularly reducing renal dysfunction and in-hospital treatment-related complications.