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.

Refractory Helicobacter pylori infection in Australia: updated multicentre antimicrobial resistance.

BACKGROUND AND AIM: Helicobacter pylori infection is responsible for considerable morbidity and mortality worldwide and eradication rates are falling globally because of increasing antimicrobial resistance. However, there is a paucity of local data to guide the choice of eradication therapy in Australia. This study aimed to evaluate current Australian rates of H. pylori antibiotic resistance in patients who had failed prior eradication therapy. METHODS: A retrospective analysis of routine culture and antibiotic susceptibility data from two pathology laboratories servicing multiple tertiary referral hospitals in Western Australia (WA) and South Australia (SA), between 2018 and 2022, was performed. Rates of antimicrobial resistance and prevalence of multiresistant isolates in both SA and WA were calculated and comparison of temporal trends and differences between the two states was conducted. RESULTS: A total of 796 H. pylori isolates revealed a clarithromycin resistance rate of 82%, metronidazole 68%, amoxicillin 4.4% and tetracycline 0.5%. Resistance to levofloxacin was observed in 22% and rifampicin 14%. Rates of resistance to clarithromycin were lower in SA compared with WA (incidence rate ratio [IRR]: 0.69, P = 0.0001). Multiresistant isolates were discovered in 63% of patients, with lower rates in SA compared with WA (IRR: 0.74, P = 0.002). CONCLUSION: This first multicentre, multistate study of H. pylori resistance in Australian patients exposed to prior therapy demonstrated high rates of antimicrobial resistance, including levofloxacin (>20%). This raises concern about recommending levofloxacin in empirical second-line therapies. Increased monitoring and awareness of current H. pylori resistance rates in Australia are needed to guide local eradication practices.

Omadacycline therapy for Mycobacterium abscessus species infections.

BACKGROUND: Antimicrobial resistance and therapy-related adverse effects make Mycobacterium abscessus treatment challenging. Omadacycline is a novel, bioavailable aminomethylcycline with favourable in vitro activity against M. abscessus. AIMS: To describe a case report and review the published literature describing outcomes for M. abscessus infections treated with omadacycline. METHODS: Systematic literature review. RESULTS: We identified three articles that, in addition to our case report, describe 18 patients. Pulmonary infections were most frequent. Minimum inhibitory concentrations were reported for two isolates (0.25 and 0.5 mg/L). Despite half the patients starting omadacycline because of failure of prior therapy, 15 (83%) had a favourable outcome, defined as 'cure', 'improvement' or 'clinical success' as determined by the primary study authors. One patient (6%) discontinued omadacycline because of gastrointestinal intolerance. CONCLUSIONS: Although the limited observational data and in vitro susceptibility results are encouraging, randomised control trials are required to determine the role of omadacycline as part of combination therapy for this most difficult-to-treat pathogen.

Antifungal use via outpatient parenteral antimicrobial therapy.

BACKGROUND: Antifungal administration via outpatient parenteral antimicrobial therapy (OPAT) is infrequent. As patients with invasive fungal infections (IFIs) receiving OPAT are at high risk of readmissions, careful, risk-based patient selection and monitoring is important. OBJECTIVES: To describe our experience managing IFIs via OPAT, including assessment of risk factors associated with unplanned readmissions. PATIENTS AND METHODS: A retrospective cohort study of outpatients from two tertiary hospitals in Western Australia managed with parenteral antifungals for the treatment of IFIs from 2012 to 2020. Outcomes assessed were unplanned OPAT-related readmissions; adverse events and achievement of treatment aim at the completion of OPAT. RESULTS: Forty-six patients were included, encompassing 696 OPAT days. Twenty-three (50%) patients received intravenous (IV) liposomal amphotericin B (L-AmB), 23 (50%) received IV echinocandins and one (2%) patient received IV fluconazole. One patient received both IV L-AmB and an echinocandin. Unplanned OPAT-related readmissions occurred in 13 (28%) patients and any adverse event occurred in 19 (41%), most commonly nephrotoxicity amongst patients receiving L-AmB. On univariate analysis, unplanned OPAT-related readmissions were more common in Mucorales infection, L-AmB doses of ≥5 mg/kg and otorhinolaryngologic (ENT) infections. At the completion of OPAT, attainment of treatment aims occurred in 28 (61%) patients. CONCLUSIONS: Patients receiving parenteral antifungals via OPAT experience high rates of unplanned readmissions and adverse events. Risk factor identification may facilitate optimal patient selection and establishment of treatment aims.

Antibiotic allergy labels and optimal antimicrobial stewardship.

BACKGROUND: Although common, antimicrobial allergy labels (AAL) rarely reflect immunologically-mediated hypersensitivity and can lead to poorer outcomes from alternative antimicrobial agents. Antimicrobial stewardship programs are ideally placed to assess AAL early as a means of improving antimicrobial use. AIMS: To quantify the prevalence of AAL in patients referred for antimicrobial stewardship review and assess their impact on antibiotic prescribing, patient mortality, hospital length of stay, readmission and rates of multidrug-resistant infections. METHODS: We conducted a retrospective analysis of adult patients referred for inpatient antimicrobial prospective audit and feedback rounds (PAFR) through an electronic referral system (eReferrals) over a 12-month period in 2015. Outcome data were collected for a period of 36 months following the initial review. RESULTS: Of the 639 patient records reviewed, 630 met inclusion criteria; 103 (16%) had an AAL, of which 82 (13%) had reported allergies to ß-lactam antibiotics. Those with AAL were significantly less likely to be receiving guideline-recommended antimicrobial therapy (50% vs 64%, P = 0.0311); however, there were no significant difference in mortality, hospital length of stay, readmission or increased incidence of multidrug-resistant infections. CONCLUSIONS: Our cohort demonstrated that AAL was associated with reduced adherence to antibiotic guidelines. The lack of association with adverse outcomes may reflect limitations within the study including retrospective cohort study numbers and observational nature, further skewed by high rates of poor documentation. A clear opportunity exists for antimicrobial stewardship programs to incorporate allergy assessment, de-labelling, challenge and referral into these rounds.

Risk factors for catheter related thrombosis during outpatient parenteral antimicrobial therapy.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) delivery using peripherally inserted central catheters is associated with a risk of catheter related thrombosis (CRT). Individualised preventative interventions may reduce this occurrence, however patient selection is hampered by a lack of understanding of risk factors. We aimed to identify patient, infection or treatment related risk factors for CRT in the OPAT setting. METHODS: Retrospective case control study (1:3 matching) within OPAT services at two tertiary hospitals within Australia. RESULTS: Over a 2 year period, encompassing OPAT delivery to 1803 patients, there were 19 cases of CRT, giving a prevalence of 1.1% and incidence of 0.58/1000 catheter days. Amongst the cases of CRT, there were nine (47%) unplanned readmissions and two (11%) pulmonary emboli. Compared to controls, cases had a higher frequency of malposition of the catheter tip (4/19 (21%) vs 0/57 (0%), p = 0.003) and complicated catheter insertion (3/19 (16%) vs 1/57 (2%), p = 0.046). CONCLUSIONS: Although CRTs during OPAT are infrequent, they often have clinically significant sequelae. Identification of modifiable vascular access related predictors of CRT should assist with patient risk stratification and guide risk reduction strategies.

Subcutaneous ertapenem delivered by an Australian outpatient parenteral antimicrobial therapy service: a retrospective comparative efficacy study.

Subcutaneous (SC) administration of ertapenem in outpatient parenteral antimicrobial therapy (OPAT) services may be a practical alternative to intravenous delivery for complicated infections. The clinical features and outcomes according to route of administration were compared from a large Australian OPAT service. Chronic renal impairment was more common in the SC group, reflecting an opportunity for route of administration as a vein preservation strategy. Adverse events were uncommon and successful outcomes were not different between the groups.

A clinical and in vitro assessment of outpatient parenteral benzylpenicillin and ceftriaxone combination therapy for enterococcal endovascular infections.

BACKGROUND: Amoxicillin plus ceftriaxone combination therapy is now standard of care for enterococcal endocarditis. Due to amoxicillin instability in infusion devices, benzylpenicillin plus ceftriaxone may be substituted to facilitate outpatient parenteral antimicrobial therapy (OPAT) delivery, despite lack of guideline endorsement. OBJECTIVES: To assess the clinical efficacy of benzylpenicillin plus ceftriaxone for the management of enterococcal endovascular infections, in addition to assessing this combination's in vitro synergy. PATIENTS AND METHODS: Retrospective cohort study assessing unplanned readmissions, relapses and mortality for 20 patients with endovascular Enterococcus faecalis infections treated with benzylpenicillin plus ceftriaxone delivered via OPAT. For a subset of isolates, synergism for both amoxicillin and benzylpenicillin in combination with ceftriaxone was calculated using a chequerboard method. RESULTS: Patients had endovascular infections of native cardiac valves (n = 11), mechanical or bioprosthetic cardiac valves (n = 7), pacemaker leads (n = 1) or left ventricular assistant devices (n = 1). The median duration of OPAT was 22 days, and the most frequent antimicrobial regimen was benzylpenicillin 14 g/day via continuous infusion and ceftriaxone 4 g once daily via short infusion. Rates of unplanned readmissions were high (30%), although rates of relapsed bacteraemia (5%) and 1 year mortality (15%) were comparable to the published literature. Benzylpenicillin less frequently displayed a synergistic interaction with ceftriaxone when compared with amoxicillin (3 versus 4 out of 6 isolates). CONCLUSIONS: Lower rates of synergistic antimicrobial interaction and a significant proportion of unplanned readmissions suggest clinicians should exercise caution when treating enterococcal endovascular infection utilizing a combination of benzylpenicillin and ceftriaxone via OPAT.

Laboratory and clinical impacts of an overnight laboratory service.

Delayed initiation of effective antimicrobial therapy for sepsis is associated with increased mortality. Whilst automated blood culture machines operate continuously, this does not align with conventional staff working hours and so turn-around-times (TAT) for reporting gram stains to clinicians are 3-7 times longer for blood cultures that flag positive overnight. We retrospectively compared laboratory TATs and clinical outcomes for blood cultures from 183 patients that flagged positive overnight during a 4-month period before and after the implementation of an overnight laboratory service. Enterobacterales and urinary tract infections were the most frequent pathogens and clinical syndrome respectively, and the prevalence of multi-resistant organisms was 15%. Compared with the pre-implementation period, the post-implementation period was associated with shorter median time from blood culture positivity to gram stain (7.4 vs 1.2 h), first genus level identification (7.2 vs 5.8 h) and first antimicrobial susceptibility result (24.1 vs 7.9 h). Similarly, the median time from blood culture positivity to clinicians first being informed was significantly shorter (9.2 vs 1.3 h). After removal of likely contaminants, 78% of patients were on effective empiric antimicrobials and for patients on ineffective empiric antimicrobials, effective therapy was initiated a median of 3.2 h sooner during the post-implementation period, without impact on mortality. Implementation of an overnight laboratory service was associated with significantly faster TAT for reporting blood culture results and more prompt initiation of effective antimicrobials for patients receiving ineffective empiric therapy, improving attainment of sepsis management goals.

Needles in a haystack: Extremely rare invasive fungal infections reported in FungiScopeⓇ-Global Registry for Emerging Fungal Infections.

OBJECTIVES: Emerging invasive fungal infections (IFI) have become a notable challenge. Apart from the more frequently described fusariosis, lomentosporiosis, mucormycosis, scedosporiosis, and certain dematiaceae or yeasts, little is known about extremely rare IFI. METHODS: Extremely rare IFI collected in the FungiScopeⓇ registry were grouped as Dematiaceae, Hypocreales, Saccharomycetales, Eurotiales, Dermatomycetes, Agaricales, and Mucorales. RESULTS: Between 2003 and June 2019, 186 extremely rare IFI were documented in FungiScopeⓇ. Dematiaceae (35.5%), Hypocreales (23.1%), Mucorales (11.8%), and Saccharomycetales (11.3%) caused most IFI. Most patients had an underlying malignancy (38.7%) with acute leukemia accounting for 50% of cancers. Dissemination was observed in 26.9% of the patients. Complete or partial clinical response rate was 68.3%, being highest in Eurotiales (82.4%) and in Agaricales (80.0%). Overall mortality rate was 29.3%, ranging from 11.8% in Eurotiales to 50.0% in Mucorales. CONCLUSIONS: Physicians are confronted with a complex variety of fungal pathogens, for which treatment recommendations are lacking and successful outcome might be incidental. Through an international consortium of physicians and scientists, these cases of extremely rare IFI can be collected to further investigate their epidemiology and eventually identify effective treatment regimens.

Impact of adherence to surgical and non-surgical components of infective endocarditis guidelines and recommendations.

BACKGROUND: Infective endocarditis (IE) is associated with significant morbidity and mortality. Non-adherence to IE guidelines and recommendations is frequent, and may adversely impact patient outcomes. AIM: To assess the impact of non-adherence to components of existing IE guidelines and recommendations on a composite outcome consisting of any of the following: mortality, unplanned cardiac surgery, embolic event or relapse of positive blood culture within six months of diagnosis. METHODS: A single centre, retrospective cohort study. RESULTS: Amongst 157 patients, there was inconsistent adherence to: initial diagnosis of an infective condition (87%), timely administration of antimicrobial therapy (82%), appropriateness of predominant antimicrobial regime (94%), appropriate management of the portal of entry (86%), multidisciplinary input (75%), end of antimicrobial therapy repeat echocardiography (60%) and adherence to indications for surgery (76%). Inpatient mortality was 12.1% (n = 19) and the composite adverse outcome occurred in 36 (22.9%) patients. In multivariate logistic regression analysis, infection of prosthetic device (adjusted odds ratio [95% confidence interval]; 2.43 [1.07-5.50]) and non-adherence to surgical guidelines (aOR 3.67 [1.60-8.47]) were significantly associated with an adverse outcome. CONCLUSIONS: Our data suggests that adherence to differing components of IE management guidelines and recommendations varies and that non-adherence to surgical aspects of guidelines has the biggest impact in determining outcomes.

Non-adherence to antimicrobial stewardship prospective audit and feedback advice: Risk factors and clinical consequences.

Amongst 325 patients receiving restricted antimicrobials whose management was subject to antimicrobial stewardship prospective audit and feedback, adherence to advice was 78%. Non-adherence was associated with diabetic patients, giving more than 1 piece of advice and receipt of piperacillin/tazobactam therapy, and was inversely associated with liver disease. Adherence to advice was associated with a one third reduction in duration of antimicrobial use without adversely impacting other infection-related patient outcomes.

Managing diabetic foot infections: a survey of Australasian infectious diseases clinicians.

BACKGROUND: Diabetic foot infections (DFI) present a major morbidity, mortality and economic challenge for the tertiary health sector. However, lack of high quality evidence for specific treatment regimens for patients with DFIs may result in inconsistent management. This study aimed to identify DFI caseload proportion and patterns of clinical practice of Infectious Diseases (ID) Physicians and Trainees within Australia and New Zealand. METHODS: A cross-sectional online survey of Australian and New Zealand ID Physicians and Trainees was undertaken, to estimate the overall ID caseload devoted to patients with DFIs and assess clinicians' management practices of patients with DFIs. RESULTS: Approximately 28% (142/499) of ID Physicians and Trainees from Australia and New Zealand responded to the survey. DFI made up 19.2% of all ID consultations. Involvement in multidisciplinary teams (MDT) was common as 77.5% (93/120) of those responding indicated their patients had access to an inpatient or outpatient MDT. Significant heterogeneity of antimicrobial treatments was reported, with 82 unique treatment regimens used by 102 respondents in one scenario and 76 unique treatment regimens used by 101 respondents in the second scenario. The duration of therapy and the choice of antibiotics for microorganisms isolated from superficial swabs also varied widely. CONCLUSIONS: Patients with DFIs represent a significant proportion of an ID clinician's caseload. This should be reflected in the ID training program. Large heterogeneity in practice between clinicians reflects a lack of evidence from well-designed clinical trials for patients with DFI and highlights the need for management guidelines informed by future trials.

Optimizing adherence to advice from antimicrobial stewardship audit and feedback rounds.

We examined adherence to antimicrobial stewardship prospective audit and feedback rounds in a rehabilitation service compared with the remainder of the acute hospital, and explored the reasons for this. Between October 2014 and December 2015, we retrospectively assessed the rate of non-adherence to advice from antimicrobial stewardship prospective audit and feedback rounds between the rehabilitation service and the acute hospital, along with the source of the patient referral. Compared with the rehabilitation service, acute hospital medical staff were almost twice as likely to not adhere to advice provided on antimicrobial stewardship prospective audit and feedback rounds (13.8% vs. 7.6%, p < 0.0001, relative risk 1.8 [95% confidence interval 1.3, 2.5]). In the rehabilitation service, referrals were more likely to come from medical staff (61.9% vs. 16.3%, p < 0.0001). These findings may be explained by regular, direct engagement of the antimicrobial stewardship team with the rehabilitation service clinical team, a model potentially applicable to other settings.

Successful outpatient parenteral antibiotic therapy delivery via telemedicine.

Objectives: Most outpatient parenteral antimicrobial therapy (OPAT) services use a hospital-based model of care in which patients remain in proximity to large hospitals facilitating clinical review. We aimed to evaluate clinical outcomes and complication rates for patients living in geographically isolated locations managed by telemedicine-supported OPAT. Methods: This was a retrospective cohort study. Results: Between 2011 and 2015, we delivered 88 episodes of care involving 83 adult patients resulting in 2261 days of OPAT. The median age was 56 years, 8 of 83 (10%) were indigenous Australian and the median Charlson comorbidity index score was 2 (IQR 1-4). The median distance of patients' residence from our hospital was 288 km (IQR 201-715) and the median duration on the programme was 26 days (IQR 14-34). Bone and joint infections accounted for 75% of infections treated. Favourable clinical outcomes (improvement or cure) were achieved in 87% of patients and the unplanned, OPAT-related readmission rate was 8%. Nineteen percent and 10% of patients had drug-related and line-related adverse effects, respectively. Conclusions: Despite a complex case mix, our adverse event and readmission rates are similar to the published literature describing a non-telemedicine model to deliver OPAT. High rates of favourable clinical outcomes and likely cost benefits suggest that telemedicine-supported OPAT is an efficacious and safe substitute for inpatient care in our setting.

Phylogenetic diversity, antimicrobial susceptibility and virulence characteristics of phylogroup F Escherichia coli in Australia.

Unlike Escherichia coli strains belonging to phylogroup B2, the clinical significance of strains belonging to phylogroup F is not well understood. Here we report on a collection of phylogroup F strains recovered in Australia from faeces and extra-intestinal sites from humans, companion animals and native animals, as well as from poultry meat and water samples. The distribution of sequence types was clearly non-random with respect to isolate source. The antimicrobial resistance and virulence trait profiles also varied with the sequence type of the isolate. Phylogroup F strains tended to lack the virulence traits typically associated with phylogroup B2 strains responsible for extra-intestinal infection in humans. Resistance to fluoroquinolones and/or expanded-spectrum cephalosporins was common within ST648, ST354 and ST3711. Although ST354 and ST3711 are part of the same clonal complex, the ST3711 isolates were only recovered from native birds being cared for in a single wildlife rehabilitation centre, whereas the ST354 isolates were from faeces and extra-intestinal sites of dogs and humans, as well as from poultry meat. Although ST354 isolates from chicken meat in Western Australia were distinct from all other ST354 isolates, those from poultry meat samples collected in eastern Australia shared many similarities with other ST354 isolates from humans and companion animals.

Temporal flux in ß-lactam resistance among Klebsiella pneumoniae in Western Australia.

Our aim was to identify long-term ß-lactam resistance trends in local Klebsiella pneumoniae isolates, which are a common cause of sepsis in Western Australia. We studied three collections of K. pneumoniae isolates from Western Australia between 1977 and 2015 comprising contemporary blood culture (n = 98), multiresistant (n = 21) and historical (n = 50) isolates. Antimicrobial resistance was determined by Clinical and Laboratory Standards Institute agar dilution methods. PCR DNA sequencing identified ß-lactamase variants and porin mutations contributing to ß-lactam resistance. Isolates were genotyped by PFGE, multilocus sequence typing and a variable number tandem repeat method. From 1989 onwards, we detected the SHV-2a extended-spectrum ß-lactamase (ESBL) in ceftriaxone-resistant isolates, and in ceftazidime- and aztreonam-resistant isolates from 1993. Ceftriaxone, ceftazidime and aztreonam resistance persisted, with blaCTX-M types becoming the dominant ESBLs by 2010. CTX-M-15 was encountered in both multiresistant and blood culture isolates. Meropenem resistance was detected for the first time in 2011 in a locally isolated blaIMP-4-positive K. pneumoniae. We found sequence types ST23 and ST86 that occurred in multiple isolates from invasive infections. ST86 was the most common and maintained a high degree (90 %) of similarity by PFGE since 1977. Ceftazidime-resistant K. pneumoniae sequence types have caused invasive infections in Western Australia since 1993. Invasive isolates producing CTX-M-14 and CTX-M-15 appeared in Western Australia during the last decade, before the appearance of carbapenemases. The diversity of ß-lactam resistance and ß-lactamase resistance mechanisms in Western Australian K. pneumoniae has increased since ESBLs were first described locally.