Therapeutic Phage Monitoring: A Review.

With the global rise in antimicrobial resistance, there has been a renewed interest in the application of therapeutic phages to treat bacterial infections. Therapeutic phage monitoring (TPM) is proposed as an essential element of phage therapy (PT) protocols to generate data and fill knowledge gaps regarding the in vivo efficacy of therapeutic phages, patients' immune responses to PT, and the wider ecological effects of PT. By monitoring phage concentrations in blood and tissues, together with immune responses and possible ecological changes during PT, TPM may enable the optimization of dosing and the implementation of precision medicine approaches. Furthermore, TPM can validate diagnostic surrogates of efficacy, direct research efforts, and establish quality assurance indicators for therapeutic phage products. Thus, TPM holds great potential for enhancing our understanding of the multidirectional phage-bacteria-host interactions and advancing "best practice" PT, ultimately improving patient care.

A systematic review of optimal pharmacokinetic/pharmacodynamic parameters for beta-lactam therapy in infective endocarditis.

BACKGROUND: Beta-lactam antibiotics are the mainstay of therapy for most bacterial causes of infective endocarditis (IE). Traditionally considered as agents with a broad therapeutic index, there is increasing recognition that standard doses may be subtherapeutic or toxic in critically ill patients. Optimizing therapy for efficacy requires a defined pharmacokinetic (PK)/pharmacodynamic (PD) target associated with clinical and microbiological cure. OBJECTIVES: To elucidate the factors that influence beta-lactam PK and PD variability in IE and to examine optimal PK/PD target parameters for therapy. METHODS: The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical and laboratory in vivo animal or human studies examining PK and/or PD of beta-lactam antibiotics in IE were eligible. Ovid MEDLINE, Embase and Cochrane Central Registry were searched using defined terms. The Office of Health Assessment and Translation (OHAT) tool was used for assessing risk of bias. RESULTS: From 2677 abstracts, 62 articles were selected for review and synthesis, comprising: 45 animal studies investigating the broad categories of beta-lactam diffusion into vegetations, PK/PD determinants of outcome, mode of antibiotic delivery and synergistic impact of agents; and 17 human studies totalling 347 participants. Findings supported the importance of time-dependent killing for beta-lactams but heterogeneous data limited the determination of an optimal PK/PD target for IE treatment. CONCLUSION: Beta-lactam PK and PD in endocarditis are variable and specific to the particular antibiotic-organism combination. Time-dependent killing is important, consistent with non-endocarditis studies, but there is little agreement on optimal drug exposure. Clinical studies examining PK/PD targets in endocarditis are required to further inform drug selection and dosing.

International survey of antibiotic dosing and monitoring in adult intensive care units.

BACKGROUND: In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time. METHODS: A cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing, administration and monitoring of vancomycin, piperacillin/tazobactam, meropenem and aminoglycosides. RESULTS: A total of 538 respondents (71% physicians and 29% pharmacists) from 409 hospitals in 45 countries completed the survey. Vancomycin was mostly administered as an intermittent infusion, and loading doses were used by 74% of respondents with 25 mg/kg and 20 mg/kg the most favoured doses for intermittent and continuous infusions, respectively. Piperacillin/tazobactam and meropenem were most frequently administered as an extended infusion (42% and 51%, respectively). Therapeutic drug monitoring was undertaken by 90%, 82%, 43%, and 39% of respondents for vancomycin, aminoglycosides, piperacillin/tazobactam, and meropenem, respectively, and was more frequently performed in high-income countries. Respondents rarely used dosing software to guide therapy in clinical practice and was most frequently used with vancomycin (11%). CONCLUSIONS: We observed numerous changes in practice since the ADMIN-ICU 2015 survey was conducted. Beta-lactams are more commonly administered as extended infusions, and therapeutic drug monitoring use has increased, which align with emerging evidence.

Personalized tobramycin dosing in children with cystic fibrosis: a comparative clinical evaluation of log-linear and Bayesian methods.

BACKGROUND: Children with cystic fibrosis (CF) pulmonary exacerbations receive IV tobramycin therapy, with dosing guided by either log-linear regression (LLR) or Bayesian forecasting (BF). OBJECTIVES: To compare clinical and performance outcomes for LLR and BF. PATIENTS AND METHODS: A quasi-experimental intervention study was conducted at a tertiary children's hospital. Electronic medical records were extracted (from January 2015 to September 2021) to establish a database consisting of pre-intervention (LLR) and post-intervention (BF) patient admissions and relevant outcomes. All consecutive patients treated with IV tobramycin for CF pulmonary exacerbations guided by either LLR or BF were eligible. RESULTS: A total of 376 hospital admissions (LLR = 248, BF = 128) for CF pulmonary exacerbations were included. Patient demographics were similar between cohorts. There were no significant differences found in overall hospital length of stay, rates of re-admission within 1 month of discharge or change in forced expiratory volume in the first second (Δ FEV1) at the end of tobramycin treatment. Patients treated with LLR on average had twice the number of therapeutic drug monitoring (TDM) blood samples collected during a single hospital admission. The timeframe for blood sampling was more flexible with BF, with TDM samples collected up to 16 h post-tobramycin dose compared with 10 h for LLR. The tobramycin AUC0-24 target of ≥100 mg/L·h was more frequently attained using BF (72%; 92/128) compared with LLR (50%; 124/248) (P < 0.001). Incidence of acute kidney injury was rare in both groups. CONCLUSIONS: LLR and BF result in comparable clinical outcomes. However, BF can significantly reduce the number of blood collections required during each admission, improve dosing accuracy, and provide more reliable target concentration attainment in CF children.

Emerging therapeutic drug monitoring of anti-infective agents in Australian hospitals: Availability, performance and barriers to implementation.

AIMS: The purpose of the study was to assess the status of emerging therapeutic drug monitoring (TDM) of anti-infective agents in Australian hospitals. METHODS: A nationwide cross-sectional survey of all Australian hospitals operating in the public and private health sector was conducted between August and September 2019. The survey consisted of questions regarding institutional TDM practice for anti-infective agents and clinical vignettes specific to ß-lactam antibiotics. RESULTS: Responses were received from 82 unique institutions, representing all Australian states and territories. All 29 (100%) of principal referral (major) hospitals in Australia participated. Five surveys were partially complete. Only 25% (20/80) of hospitals had TDM testing available on-site for any of the eight emerging TDM candidates considered: ß-lactam antibiotics, anti-tuberculous agents, flucytosine, fluoroquinolones, ganciclovir, human immunodeficiency virus (HIV) drugs, linezolid and teicoplanin. A considerable time lag was noted between TDM sampling and reporting of results. With respect to ß-lactam antibiotic TDM, variable indications, pharmacodynamic targets and sampling times were identified. The three greatest barriers to local TDM performance were found to be (1) lack of timely assays/results, (2) lack of institutional-wide expertise and/or training and (3) lack of guidelines to inform ordering of TDM and interpretation of results. The majority of respondents favoured establishing national TDM guidelines and increasing access to dose prediction software, at rates of 89% and 96%, respectively. CONCLUSION: Translating emerging TDM evidence into daily clinical practice is slow. Concerted efforts are required to address the barriers identified and facilitate the implementation of standardised practice.

Understanding the Pharmacokinetics of Antibiotics in Pregnancy: Is There a Role for Therapeutic Drug Monitoring? A Narrative Review.

PURPOSE: Antibiotics are commonly used during pregnancy. However, physiological changes during pregnancy can affect the pharmacokinetics of drugs, including antibiotics, used during this period. Pharmacokinetic evaluations have shed light on how antibiotics are affected during pregnancy and have influenced dosing recommendations in this context. METHODS: A narrative review was conducted and included reports providing data reflecting drug distribution and exposure in the context of pregnancy. RESULTS: Pharmacokinetic parameters of antibiotics in pregnancy and transplacental passage of antibiotics are comprehensively presented. CONCLUSIONS: Knowledge about the impact on pharmacokinetics and fetal exposure is especially helpful for complicated or severe infections, including intra-amniotic infection and sepsis in pregnancy, where both mother and fetus are at risk. Further studies are warranted to consolidate the role of therapeutic drug monitoring in complicated or severe infections in pregnant patients.

Optimal Practice for Vancomycin Therapeutic Drug Monitoring: Position Statement From the Anti-infectives Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.

ABSTRACT: Individualization of vancomycin dosing based on therapeutic drug monitoring (TDM) data is known to improve patient outcomes compared with fixed or empirical dosing strategies. There is increasing evidence to support area-under-the-curve (AUC24)-guided TDM to inform vancomycin dosing decisions for patients receiving therapy for more than 48 hours. It is acknowledged that there may be institutional barriers to the implementation of AUC24-guided dosing, and additional effort is required to enable the transition from trough-based to AUC24-based strategies. Adequate documentation of sampling, correct storage and transport, accurate laboratory analysis, and pertinent data reporting are required to ensure appropriate interpretation of TDM data to guide vancomycin dosing recommendations. Ultimately, TDM data in the clinical context of the patient and their response to treatment should guide vancomycin therapy. Endorsed by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology, the IATDMCT Anti-Infectives Committee, provides recommendations with respect to best clinical practice for vancomycin TDM.

Model-Optimized Fluconazole Dose Selection for Critically Ill Patients Improves Early Pharmacodynamic Target Attainment without the Need for Therapeutic Drug Monitoring.

Fluconazole has been associated with higher mortality compared with the echinocandins in patients treated for invasive candida infections. Underexposure from current fluconazole dosing regimens may contribute to these worse outcomes, so alternative dosing strategies require study. The objective of this study was to evaluate fluconazole drug exposure in critically ill patients comparing a novel model-optimized dose selection method with established approaches over a standard 14-day (336-h) treatment course. Target attainment was evaluated in a representative population of 1,000 critically ill adult patients for (i) guideline dosing (800-mg loading and 400-mg maintenance dosing adjusted to renal function), (ii) guideline dosing followed by therapeutic drug monitoring (TDM)-guided dose adjustment, and (iii) model-optimized dose selection based on patient factors (without TDM). Assuming a MIC of 2 mg/liter, free fluconazole 24-h area under the curve (fAUC24) targets of ≥200 mg · h/liter and <800 mg · h/liter were used for assessment of target attainment. Guideline dosing resulted in underexposure in 21% of patients at 48 h and in 23% of patients at 336 h. The TDM-guided strategy did not influence 0- to 48-h target attainment due to inherent procedural delays but resulted in 37% of patients being underexposed at 336 h. Model-optimized dosing resulted in ≥98% of patients meeting efficacy targets throughout the treatment course, while resulting in less overexposure compared with guideline dosing (7% versus 14%) at 336 h. Model-optimized dose selection enables fluconazole dose individualization in critical illness from the outset of therapy and should enable reevaluation of the comparative effectiveness of this drug in patients with severe fungal infections.

Are vancomycin dosing guidelines followed? A mixed methods study of vancomycin prescribing practices.

AIMS: Despite the availability of international consensus guidelines, vancomycin dosing and therapeutic drug monitoring (TDM) remain suboptimal. This study aimed to assess concordance of vancomycin dosing and TDM with institutional guidelines and to identify factors taken into consideration by clinicians when prescribing vancomycin. METHODS: A retrospective audit of 163 patients receiving vancomycin therapy (≥48 hours) was undertaken. Data collected included patient characteristics, dosing history and plasma vancomycin and creatinine concentrations. Concordance of dosing and TDM with institutional guidelines was evaluated. Semi-structured interviews, including simulated prescribing scenarios, were undertaken with prescribers (n = 17) and transcripts analysed. RESULTS: Plasma vancomycin concentrations (n = 1043) were collected during 179 courses of therapy. Only 24% of courses commenced with a loading dose with 72% lower than recommended. The initial maintenance dose was concordant in 42% of courses with 34% lower than recommended. Only 14% of TDM samples were trough vancomycin concentrations. Dose was not adjusted for 60% (21/35) of subtherapeutic and 43% (18/42) of supratherapeutic trough vancomycin concentrations, respectively. Interview participants reported that patient characteristics (including renal function), vancomycin concentrations, guidelines and expert advice influenced vancomycin prescribing decisions. Despite referring to guidelines when completing simulated prescribing scenarios, only 37% of prescribing decisions aligned with guideline recommendations. CONCLUSION: Poor compliance with institutional vancomycin guidelines was observed, despite prescriber awareness of available guidelines. Multifaceted strategies to support prescriber decision-making are required to improve vancomycin dosing and monitoring.

Current fluconazole treatment regimens result in under-dosing of critically ill adults during early therapy.

PURPOSE: To evaluate current fluconazole treatment regimens in critically ill adults over the typical treatment course. METHODS: Data from critically ill adults treated with fluconazole (n=30) were used to develop a population pharmacokinetic model. Probability of target attainment (PTA) (fAUC24/MIC >100) was determined from simulations for four previously proposed treatment regimens: (i) 400 mg once daily, (ii) an 800 mg loading dose followed by 400 mg once daily, (iii) 400 mg twice daily, and (iv) a 12 mg/kg loading dose followed by 6 mg/kg once daily. The effect of body weight (40, 70, 120 kg) and renal function (continuous renal replacement therapy (CRRT); 20, 60, 120, 180 mL/min creatinine clearance) on PTA was assessed. RESULTS: Early (0-48 h) fluconazole target attainment for infections with a minimum inhibitory concentration (MIC) of 2 mg/L was highly variable. PTA was highest with an 800 mg loading dose for underweight (40 kg) patients and with a 12 mg/kg loading dose for the remainder. End-of-treatment PTA was highest with the 400 mg twice daily maintenance dosing for patients who were under- or normal weight and 6 mg/kg maintenance dosing for overweight (120 kg) patients. None of the fluconazole regimens reliably attained early targets for MICs of ≥4 mg/L. CONCLUSION: Current fluconazole dosing regimens do not achieve adequate early target attainment in critically ill adults, particularly in those who are overweight, have higher creatinine clearance, or are undergoing CRRT. Current fluconazole dosing strategies are generally inadequate to treat organisms with an MIC of ≥4 mg/L.

Phage therapy for severe bacterial infections: a narrative review.

Bacteriophage (phage) therapy is re-emerging a century after it began. Activity against antibiotic-resistant pathogens and a lack of serious side effects make phage therapy an attractive treatment option in refractory bacterial infections. Phages are highly specific for their bacterial targets, but the relationship between in vitro activity and in vivo efficacy remains to be rigorously evaluated. Pharmacokinetic and pharmacodynamic principles of phage therapy are generally based on the classic predator-prey relationship, but numerous other factors contribute to phage clearance and optimal dosing strategies remain unclear. Combinations of fully characterised, exclusively lytic phages prepared under good manufacturing practice are limited in their availability. Safety has been demonstrated but randomised controlled trials are needed to evaluate efficacy.

An evaluation of the user-friendliness of Bayesian forecasting programs in a clinical setting.

AIMS: To evaluate 3 Bayesian forecasting (BF) programs-TDMx, InsightRx and DoseMe-on their user-friendliness and common liked and disliked features through a survey of hospital pharmacists. METHODS: Clinical pharmacists across 3 Australian hospitals that did not use a BF program were invited to a BF workshop and complete a survey on programs they trialled. Participants were given 4 case scenarios to work through and asked to complete a 5-point Likert scale survey evaluating the program's user-friendliness. Liked and disliked features of each program were ascertained through written responses to open-ended questions. Survey results were compared using a χ2 test of equal or given proportions to identify significant differences in response. RESULTS: Twenty-seven pharmacists, from hospitals, participated. BF programs were rated overall as user-friendly with 70%, 41% and 37% (P = .02) of participants recording a Likert score of 4 or 5 for DoseMe, TDMx and InsightRx, respectively. Participants found it easy to access all required information to use the programs, understood dosing recommendations and visualisations given by each program, and thought programs supported decision-making with >50% of participants scoring a 4 or 5 across the programs in these categories. Common liked features across all programs were the graphical displays and ease of data entry, while common disliked features were related to the units, layout and information display. CONCLUSION: Although differences exist between programs, all 3 programs were most commonly rated as user-friendly across all themes evaluated, which provides useful information for healthcare facilities wanting to implement a BF program.

An evaluation of risk factors to predict target concentration non-attainment in critically ill patients prior to empiric ß-lactam therapy.

To determine whether target concentration non-attainment can be anticipated in critically ill patients prior to initiating empiric ß-lactam antibiotic therapy based on readily available clinical factors. Retrospective review of consecutive patients treated with piperacillin or meropenem and who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015 was performed. Predefined subgroups were patients who received continuous renal replacement therapy (CRRT) and those who did not (non-CRRT). Potential risk factors were evaluated by correlation with ß-lactam antibiotic trough concentrations (Cmin) lower than or equal to targeted minimum inhibitory concentration (MIC). Only the first drug concentration after initiation of the antibiotic treatment was included to reflect empirical dose selection. A total of n = 249 patients (piperacillin, n = 169; meropenem, n = 80) were investigated. For non-CRRT patients (n = 210), multivariate analysis demonstrated the following: male gender (p = 0.006); younger age (p = 0.015); prescribed daily antibiotic dose less than 1.5 times the product information recommendations (p = 0.004); lack of positive microbiology (p = 0.006); lower overall illness severity (p = 0.005); and estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2 (p < 0.001), to be associated with Cmin ≤ MIC. No predictor variable was found to be significantly associated with Cmin ≤ MIC for the CRRT cohort. Evaluating the risk of target concentration non-attainment using simple clinical factors is possible at the bedside for non-CRRT patients prior to empiric antibiotic initiation. Clinicians should be wary of selecting doses based on the product information especially when treating younger male patients with apparently 'normal' renal function.

Barriers and facilitators of appropriate vancomycin use: prescribing context is key.

PURPOSE: Audit studies reveal frequent non-compliance with dosing and monitoring guidelines for vancomycin. This study aimed to qualitatively explore the barriers and facilitators of compliance with vancomycin dosing and monitoring guidelines. METHODS: Interviews were conducted with 16 prescribers in a large tertiary teaching hospital in Sydney, Australia. Questions explored knowledge, attitudes, and perceived complexities associated with vancomycin use. Interviews were analysed using thematic analysis. RESULTS: Prescribers reported utilising vancomycin guidelines, citing familiarity with guidelines, a positive perception of guidelines, awareness of poor guideline compliance, and assistance from specialist staff as facilitators of the uptake of guideline recommendations. Barriers existing within the prescribing environment such as the prescribing culture, a lack of time, and poor communication and coordination of therapeutic drug monitoring processes were identified as hindrances to guideline compliance. CONCLUSIONS: The provision of guidelines may not be sufficient in ensuring appropriate prescribing and monitoring of vancomycin when barriers relating to the prescribing environment exist. Developing interventions targeted toward these barriers, such as having dedicated phlebotomists for vancomycin blood sampling, fostering better handover processes, and educating staff on poorly understood aspects of guidelines, is likely to improve the uptake of guideline recommendations for vancomycin and other medications requiring therapeutic drug monitoring.

Too much of a good thing: a retrospective study of ß-lactam concentration-toxicity relationships.

Objectives: To determine the existence of concentration-toxicity relationships for common ß-lactam antibiotic adverse effects and define thresholds above which toxicity is more likely. Patients and methods: Retrospective review of consecutive patients treated with piperacillin, meropenem or flucloxacillin who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015. Adverse events investigated included neurotoxicity, nephrotoxicity, hepatotoxicity and opportunistic Clostridium difficile infection. Toxicity was measured using observational grading criteria, clinical assessment and relevant serum biomarkers. These findings were correlated with trough TDM measurements at the time of toxicity presentation. Results: TDM results from 378 patients (piperacillin = 223, meropenem = 94 and flucloxacillin = 61) were investigated. There was no difference in baseline patient characteristics across antibiotic groups. A statistically significant elevation in mean serum trough concentrations (Cmin) was found in patients diagnosed with neurotoxicity (piperacillin, P < 0.01; meropenem, P = 0.04; flucloxacillin, P = 0.01) and those who developed nephrotoxicity whilst being treated with piperacillin (P < 0.01) or meropenem (P < 0.01). Incidence of hepatotoxicity and C. difficile was not related to Cmin. Threshold concentrations for which there is 50% risk of developing a neurotoxicity event (piperacillin, Cmin >361.4 mg/L; meropenem, Cmin >64.2 mg/L; flucloxacillin, Cmin >125.1 mg/L) or nephrotoxicity (piperacillin, Cmin >452.65 mg/L; meropenem, Cmin >44.45 mg/L) varied across antibiotics. Conclusions: Our data reveal an association between toxic concentrations for a number of ß-lactam agents and neurotoxic/nephrotoxic effects. We have defined threshold concentrations above which these toxicities become more likely. Clinicians should balance concerns for therapeutic efficacy with potential toxicity when considering aggressive therapy.

Serum levels, safety and tolerability of new formulation SUBA-itraconazole prophylaxis in patients with haematological malignancy or undergoing allogeneic stem cell transplantation.

OBJECTIVES: To assess therapeutic levels, safety and tolerability of a novel formulation SUBA-itraconazole (where SUBA stands for SUper BioAvailability) when compared with conventional itraconazole liquid when used as antifungal prophylaxis in patients undergoing allogeneic HSCT or in haematological malignancy patients with an intermediate/high risk of invasive fungal infection (IFI). METHODS: This was a single-institution, prospective cohort study using a historical control group as the comparator. RESULTS: A total of 57 patients were assessed: 27 in the SUBA-itraconazole cohort and 30 in the liquid itraconazole cohort. Therapeutic concentrations were achieved significantly more quickly in the SUBA-itraconazole group: median of 6 (95% CI 5-11) days versus 14 (95% CI 12-21) days in the liquid itraconazole group (P < 0.0001). At day 10, therapeutic concentrations were achieved in 69% (95% CI 44%-81%) of the SUBA-itraconazole group versus 21% (95% CI 7%-33%) of the liquid itraconazole group (P < 0.0001). The mean trough serum concentrations at steady-state of SUBA-itraconazole were significantly higher, with less interpatient variability [1577 ng/mL, coefficient of variation (CV) 35%] versus liquid itraconazole (1218 ng/mL, CV 60%) (P < 0.001). There were two (7.4%) treatment failures in the SUBA-itraconazole group, both due to cessation of therapy for mucositis, compared with seven (23.3%) treatment failures in the liquid itraconazole group, due to subtherapeutic levels (five), mucositis (one) and gastrointestinal intolerance (one) (P = 0.096). CONCLUSIONS: The use of the SUBA-itraconazole formulation was associated with more rapid attainment of therapeutic levels with less interpatient variability compared with conventional liquid itraconazole when used as IFI prophylaxis in allogeneic HSCT or intermediate-/high-IFI risk haematological malignancy patients.

Angiostrongylus cantonensis: a review of its distribution, molecular biology and clinical significance as a human pathogen.

Angiostrongylus cantonensis is a metastrongyloid nematode found widely in the Asia-Pacific region, and the aetiological agent of angiostrongyliasis; a disease characterized by eosinophilic meningitis. Rattus rats are definitive hosts of A. cantonensis, while intermediate hosts include terrestrial and aquatic molluscs. Humans are dead-end hosts that usually become infected upon ingestion of infected molluscs. A presumptive diagnosis is often made based on clinical features, a history of mollusc consumption, eosinophilic pleocytosis in cerebral spinal fluid, and advanced imaging such as computed tomography. Serological tests are available for angiostrongyliasis, though many tests are still under development. While there is no treatment consensus, therapy often includes a combination of anthelmintics and corticosteroids. Angiostrongyliasis is relatively rare, but is often associated with morbidity and sometimes mortality. Recent reports suggest the parasites' range is increasing, leading to fatalities in regions previously considered Angiostrongylus-free, and sometimes, delayed diagnosis in newly invaded regions. Increased awareness of angiostrongyliasis would facilitate rapid diagnosis and improved clinical outcomes. This paper summarizes knowledge on the parasites' life cycle, clinical aspects and epidemiology. The molecular biology of Angiostrongylus spp. is also discussed. Attention is paid to the significance of angiostrongyliasis in Australia, given the recent severe cases reported from the Sydney region.