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.

Coaching ward pharmacists in antimicrobial stewardship: A pilot study.

Background: Ward pharmacists are well-positioned to enhance the activities of hospital antimicrobial stewardship (AMS) programs by reviewing the appropriateness of antimicrobials and making recommendations to prescribers. However, recent studies have identified gaps in ward pharmacists' AMS practice, knowledge, skills, and confidence which suggests education and training programs are needed. Objectives: To describe, for the first time, an interactive educational activity - coaching in AMS - targeted at ward pharmacists and explore their perceptions of coaching as a mode of delivering education to improve AMS knowledge, skills, confidence, and practice. A secondary objective was to describe the type, frequency, and acceptance of AMS recommendations made by coached pharmacists. Methods: This was a descriptive pilot study with a qualitative evaluation of pharmacists' perceptions and experiences of coaching. AMS coaching was delivered over 2 months in 2019 to pharmacists providing clinical pharmacy services to general medical and surgical wards. A focus group was conducted one month after the coaching period to elicit pharmacists' perceptions of coaching as a mode of delivering AMS education and how it impacted their AMS knowledge, skills, confidence, and practice. AMS recommendations made by coached pharmacists were prospectively recorded, and the prescriber acceptance rate was determined. Results: Ward pharmacists reported positive experiences with AMS coaching and believed it helped them identify a range of recommendations to improve antimicrobial prescribing and increased their confidence to communicate recommendations to prescribers. Workload issues were identified as the main barrier to implementation. Suggestions were provided to improve coaching implementation feasibility. During coaching, 162 AMS recommendations were identified for a range of antimicrobials, and 69% (113/162) were accepted and implemented. Conclusions: Ward pharmacists believed coaching improved their AMS knowledge, skills, confidence, and practice, including their confidence to discuss recommendations with prescribers. These results can assist with the design and evaluation of future hospital-based AMS educational initiatives.

Exploring the practice, confidence and educational needs of hospital pharmacists in reviewing antimicrobial prescribing: a cross-sectional, nationwide survey.

BACKGROUND: Antimicrobial stewardship (AMS) programs are usually limited in resources and scope. Therefore, wider engagement of hospital pharmacists in reviewing antimicrobial orders is necessary to ensure appropriate prescribing. We assessed hospital pharmacists' self-reported practice and confidence in reviewing antimicrobial prescribing, and their knowledge in making AMS interventions. METHODS: We conducted an Australia-wide, cross-sectional survey in October 2017. A link to the online survey was emailed to hospital pharmacists via the Society of Hospital Pharmacists of Australia. Factors associated with higher knowledge scores were explored using linear regression models. RESULTS: There were 439 respondents, of whom 272 (61.7%) were from metropolitan public hospitals. Pharmacists were more likely to assess the appropriateness of intravenous, broad-spectrum or restricted antibiotics than narrow-spectrum, oral antibiotics within 24-72 h of prescription; p < 0.001. Fifty percent or fewer respondents were confident in identifying AMS interventions related to dose optimization based on infection-specific factors, bug-drug mismatch, and inappropriate lack of spectra of antimicrobial activity. The median knowledge score (correct answers to knowledge questions) was 6 out of 9 (interquartile range, 5-7); key gaps were noted in antimicrobials' anaerobic spectrum, beta-lactam allergy assessment and dosing in immunocompromised patients. Clinical practice in inpatient areas, registration for 3-5 years and receipt of recent AMS education were associated with higher knowledge scores. More interactive modes of education delivery were preferred over didactic modes; p ≤ 0.01. CONCLUSION: Gaps in practice, confidence and knowledge among hospital pharmacists were identified that could inform the design of educational strategies to help improve antimicrobial prescribing in Australian hospitals.

Evaluation of intravenous to oral antimicrobial switch at a hospital with a tightly regulated antimicrobial stewardship program.

Timely intravenous (IV) to oral antimicrobial switch (IV-oral-switch) is a key antimicrobial stewardship (AMS) strategy. We aimed to explore concordance with IV-oral-switch guidelines in the context of a long-standing, tightly regulated AMS program. Data was retrospectively collected for 107 adult general medical and surgical patients in an Australian hospital. Median duration of IV antimicrobial courses before switching to oral therapy was 3 days (interquartile range [IQR] 2.25-5.00). Timely IV-oral-switch occurred in 57% (n = 61) of patients. The median delay to switching was 0 days (IQR 0 to 1.25). In most courses (92/106, 86.8%), the choice of oral alternative after switching was appropriate. In 45% (47/105) of courses, total duration of therapy (IV plus oral) exceeded the recommended duration by >1.0 day. Excessive IV antimicrobial duration was uncommon at a hospital with a tightly regulated AMS program. Total duration of therapy was identified as an AMS target for improvement.

Cure of Limb-Threatening XDR Pseudomonas aeruginosa Infection: Combining Genome Sequencing, Therapeutic Drug Level Monitoring, and Surgical Debridement.

We describe a case of limb-threatening osteomyelitis and metalware infection with carbapenemase-producing extensively drug-resistant Pseudomonas aeruginosa successfully cured with aggressive surgical debridement and combined intravenous fosfomycin and colistin. Real-time therapeutic drug monitoring was used to maximize probability of efficacy and minimize potential for toxicity.

Outcomes of an electronic medical record (EMR)-driven intensive care unit (ICU)-antimicrobial stewardship (AMS) ward round: Assessing the "Five Moments of Antimicrobial Prescribing".

OBJECTIVE: The primary objective of this study was to examine the impact of an electronic medical record (EMR)-driven intensive care unit (ICU) antimicrobial stewardship (AMS) service on clinician compliance with face-to-face AMS recommendations. AMS recommendations were defined by an internally developed "5 Moments of Antimicrobial Prescribing" metric: (1) escalation, (2) de-escalation, (3) discontinuation, (4) switch, and (5) optimization. The secondary objectives included measuring the impact of this service on (1) antibiotic appropriateness, and (2) use of high-priority target antimicrobials. METHODS: A prospective review was undertaken of the implementation and compliance with a new ICU-AMS service that utilized EMR data coupled with face-to-face recommendations. Additional patient data were collected when an AMS recommendation was made. The impact of the ICU-AMS round on antimicrobial appropriateness was evaluated using point-prevalence survey data. RESULTS: For the 202 patients, 412 recommendations were made in accordance with the "5 Moments" metric. The most common recommendation made by the ICU-AMS team was moment 3 (discontinuation), which comprised 173 of 412 recommendations (42.0%), with an acceptance rate of 83.8% (145 of 173). Data collected for point-prevalence surveys showed an increase in prescribing appropriateness from 21 of 45 (46.7%) preintervention (October 2016) to 30 of 39 (76.9%) during the study period (September 2017). CONCLUSIONS: The integration of EMR with an ICU-AMS program allowed us to implement a new AMS service, which was associated with high clinician compliance with recommendations and improved antibiotic appropriateness. Our "5 Moments of Antimicrobial Prescribing" metric provides a framework for measuring AMS recommendation compliance.

Increasing tolerance of hospital Enterococcus faecium to handwash alcohols.

Alcohol-based disinfectants and particularly hand rubs are a key way to control hospital infections worldwide. Such disinfectants restrict transmission of pathogens, such as multidrug-resistant Staphylococcus aureus and Enterococcus faecium Despite this success, health care infections caused by E. faecium are increasing. We tested alcohol tolerance of 139 hospital isolates of E. faecium obtained between 1997 and 2015 and found that E. faecium isolates after 2010 were 10-fold more tolerant to killing by alcohol than were older isolates. Using a mouse gut colonization model of E. faecium transmission, we showed that alcohol-tolerant E. faecium resisted standard 70% isopropanol surface disinfection, resulting in greater mouse gut colonization compared to alcohol-sensitive E. faecium We next looked for bacterial genomic signatures of adaptation. Alcohol-tolerant E. faecium accumulated mutations in genes involved in carbohydrate uptake and metabolism. Mutagenesis confirmed the roles of these genes in the tolerance of E. faecium to isopropanol. These findings suggest that bacterial adaptation is complicating infection control recommendations, necessitating additional procedures to prevent E. faecium from spreading in hospital settings.

Vancomycin-resistant Enterococcus faecium sequence type 796 - rapid international dissemination of a new epidemic clone.

Background: Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably; it is uncertain how they spread despite improved infection control. We aimed to investigate the relatedness of a novel sequence type (ST) of vanB E. faecium - ST796 - very near its time of origin from hospitals in three Australian states and New Zealand. Methods: Following near-simultaneous outbreaks of ST796 in multiple institutions, we gathered then tested colonization and bloodstream infection isolates' antimicrobial resistance (AMR) phenotypes, and phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data was explored to trace the spread of ST796. Results: A novel clone of vanB E. faecium (ST796) was first detected at one Australian hospital in late 2011, then in two New Zealand hospitals linked by inter-hospital transfers from separate Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New South Wales and was responsible for at least one major colonization outbreak in a Neonatal Intensive Care Unit without identifiable links between centers. No exceptional AMR was detected in the isolates. While WGS analysis showed very limited diversity at the core genome, consistent with recent emergence of the clone, clustering by institution was observed. Conclusions: Evolution of new E. faecium clones, followed by recognized or unrecognized movement of colonized individuals then rapid intra-institutional cross-transmission best explain the multi-center, multistate and international outbreak we observed.

Evolutionary origins of the emergent ST796 clone of vancomycin resistant Enterococcus faecium.

From early 2012, a novel clone of vancomycin resistant Enterococcus faecium (assigned the multi locus sequence type ST796) was simultaneously isolated from geographically separate hospitals in south eastern Australia and New Zealand. Here we describe the complete genome sequence of Ef_aus0233, a representative ST796 E. faecium isolate. We used PacBio single molecule real-time sequencing to establish a high quality, fully assembled genome comprising a circular chromosome of 2,888,087 bp and five plasmids. Comparison of Ef_aus0233 to other E. faecium genomes shows Ef_aus0233 is a member of the epidemic hospital-adapted lineage and has evolved from an ST555-like ancestral progenitor by the accumulation or modification of five mosaic plasmids and five putative prophage, acquisition of two cryptic genomic islands, accrued chromosomal single nucleotide polymorphisms and a 80 kb region of recombination, also gaining Tn1549 and Tn916, transposons conferring resistance to vancomycin and tetracycline respectively. The genomic dissection of this new clone presented here underscores the propensity of the hospital E. faecium lineage to change, presumably in response to the specific conditions of hospital and healthcare environments.

Outbreak of vanB vancomycin-resistant Enterococcus faecium colonization in a neonatal service.

OBJECTIVE: To describe successful termination of an outbreak of vancomycin-resistant Enterococcus faecium (VREfm) colonization within a neonatal service. SETTING: Multisite neonatal intensive care unit and special care nurseries within a single health care service. PARTICIPANTS: Forty-four cases of VREfm-colonized neonatal inpatients-including 2 clinical isolates (eye swab and catheter-urine specimen) and 42 screening isolates. INTERVENTIONS: Active surveillance cultures, patient isolation, contact precautions, enhanced environment cleaning, and staff and parent education. Whole genome sequencing and multilocus sequence typing were used to characterize the outbreak and refine infection control procedures. RESULTS: Peak prevalence of VREfm colonization across all sites was 31% upon discovery of the outbreak. Subsequent to the intervention, transmission was halted within 8 weeks and no further isolates of the outbreak strain have been detected as of 12 months following outbreak cessation. Environmental swabs revealed VREfm colonization of baby-weighing scales, a baby bath, and a pharmacy refrigerator within the neonatal intensive care unit. All isolates were of a single multilocus sequence type (sequence type 796) and highly clonal at the core genome level. CONCLUSIONS: Bundled infection control interventions were effective in rapidly terminating a clonal outbreak of sequence type 796 VREfm colonization within a neonatal inpatient service. Strain-typing and active surveillance cultures were critical in guiding the management of this outbreak. The closed environment of a neonatal unit likely facilitated eradication of the patient and environment reservoirs of VREfm colonization.

Beyond injecting drug use: investigation of a Victorian cluster of hepatitis C among HIV-infected men who have sex with men.

OBJECTIVES: To examine increased notifications of hepatitis C virus (HCV) in men who have sex with men (MSM) infected with HIV in Victoria, and evaluate HCV transmission risk factors other than injecting drug use. DESIGN, SETTING AND PARTICIPANTS: Case series through retrospective review of all HCV cases in Victoria from 1 April 2010 to 30 June 2011, with clinical and laboratory data examined in likely MSM to identify a co-infected cohort. Patients with newly acquired HCV with HIV co-infection were invited to complete a questionnaire exploring novel risk factors for HCV transmission (non-injecting drug use, sexual practices with increased likelihood of trauma, and presence of genital ulcers). Sequencing was performed to determine the local molecular epidemiology of HCV co-infection. MAIN OUTCOME MEASURES: Demographics of newly co-infected MSM, traditional versus novel risk factors for HCV acquisition, prior knowledge of potential for sexual transmission of HCV, and association between viral sequences. RESULTS: Thirty-one patients with HIV were identified from 3365 notifications of hepatitis C. The median age was 42 years, and median time from HIV to HCV diagnosis was 22 months. Most patients were asymptomatic, with abnormal liver function tests prompting HCV testing. Interviews with 14 patients identified a high prevalence of novel risk factors and limited knowledge of HCV risk. Two clusters of matching viral sequences were identified. CONCLUSIONS: Novel HCV transmission routes have emerged in Victoria. These data reinforce the need for targeted testing and prevention strategies among HIV-infected MSM.

Successful treatment of Epstein-Barr virus encephalitis in the setting of HIV-associated neurocognitive disorder: a diagnostic and therapeutic challenge.

We report a challenging case of HIV-associated neurocognitive disorder with superimposed Epstein-Barr virus (EBV) encephalitis. The patient presented with an abnormal MRI brain scan, and EBV DNA that was detected in the cerebrospinal fluid and brain biopsy, which also demonstrated histopathological findings consistent with the diagnosis. This occurred on the background of a 12-month period of gradual cognitive decrease secondary to HIV-associated dementia. Invasive testing was required to reach the diagnosis in this case, highlighting the importance of thorough investigation of neurological impairment in HIV-positive patients. Clinicopathological recovery was achieved through optimization of antiretroviral therapy and use of valganciclovir.

Diagnosing swine flu: the inaccuracy of case definitions during the 2009 pandemic, an attempt at refinement, and the implications for future planning.

BACKGROUND: At the onset of the pandemic H1N1/09 influenza A outbreak in Australia, health authorities devised official clinical case definitions to guide testing and access to antiviral therapy. OBJECTIVES: To assess the diagnostic accuracy of these case definitions and to attempt to improve on them using a scoring system based on clinical findings at presentation. PATIENTS/METHODS: This study is a retrospective case-control study across three metropolitan Melbourne hospitals and one associated community-based clinic during the influenza season, 2009. Patients presenting with influenza-like illness who were tested for H1N1/09 influenza A were administered a standard questionnaire of symptomatology, comorbidities, and risk factors. Patients with a positive test were compared to those with a negative test. Logistic regression was performed to examine for correlation of clinical features with disease. A scoring system was devised and compared with case definitions used during the pandemic. The main outcome measures were the positive and negative predictive values of our scoring system, based on real-life data, versus the mandated case definitions'. RESULTS: Both the devised scoring system and the case definitions gave similar positive predictive values (38-58% using ascending score groups, against 39-44% using the various case definitions). Negative predictive values were also closely matched (ranging from 94% to 73% in the respective score groups against 83-84% for the case definitions). CONCLUSIONS: Accurate clinical diagnosis of H1N1/09 influenza A was difficult and not improved significantly by a structured scoring system. Investment in more widespread availability of rapid and sensitive diagnostic tests should be considered in future pandemic planning.