Antimicrobial stewardship audit and feedback rounds: the impact of electronic systems and moving beyond the restricted antibiotic list.

BACKGROUND: Current methods of antimicrobial usage surveillance have limited efficacy in changing practice due to delayed reporting to clinicians and the inability to stratify by medical specialty. This study was undertaken in a tertiary teaching hospital with a well established antimicrobial stewardship (AMS) programme and electronic medicines management (eMM) system in Sydney, Australia. AIMS: To describe and analyse the implementation of a novel AMS audit and feedback method, in the context of an eMM system. METHODS: The AMS team conducted the audit weekly, and the study design was a prospective, observational study. All acute, adult inpatients were included in this intervention. All active systemic antimicrobial prescriptions on the day of the rounds were included. RESULTS: The prevalence of patients on antimicrobial therapy was 37%. The median time taken per round was 44 min for eMM compared to 58 min for paper. All key performance indicators improved over the study period. Appropriateness compared to guidelines increased from 55% to 71%, and documentation of an indication increased from 75% to 98%. There were 1413 recommendations made, with the most common being to cease an antimicrobial agent. The recommendation uptake rate was 47% at 24 h post-round. CONCLUSIONS: AMS rounds are an effective tool for auditing and providing feedback on antimicrobial use and should include all antimicrobials rather than solely 'restricted' agents. These rounds had a high uptake rate, improvements in the appropriateness of antimicrobial use, and a planned duration or review date. A benefit of eMM was improvement in the documentation of indication for antimicrobial agents, and reduced time taken to audit.

The Hospital Water Environment as a Reservoir for Carbapenem-Resistant Organisms Causing Hospital-Acquired Infections-A Systematic Review of the Literature.

Over the last 20 years there have been 32 reports of carbapenem-resistant organisms in the hospital water environment, with half of these occurring since 2010. The majority of these reports have described associated clinical outbreaks in the intensive care setting, affecting the critically ill and the immunocompromised. Drains, sinks, and faucets were most frequently colonized, and Pseudomonas aeruginosa the predominant organism. Imipenemase (IMP), Klebsiella pneumoniae carbapenemase (KPC), and Verona integron-encoded metallo-ß-lactamase (VIM) were the most common carbapenemases found. Molecular typing was performed in almost all studies, with pulse field gel electrophoresis being most commonly used. Seventy-two percent of studies reported controlling outbreaks, of which just more than one-third eliminated the organism from the water environment. A combination of interventions seems to be most successful, including reinforcement of general infection control measures, alongside chemical disinfection. The most appropriate disinfection method remains unclear, however, and it is likely that replacement of colonized water reservoirs may be required for long-term clearance.

Changing epidemiology of candidaemia in Australia.

Objectives: Knowledge of contemporary epidemiology of candidaemia is essential. We aimed to identify changes since 2004 in incidence, species epidemiology and antifungal susceptibilities of Candida spp. causing candidaemia in Australia. Methods: These data were collected from nationwide active laboratory-based surveillance for candidaemia over 1 year (within 2014-2015). Isolate identification was by MALDI-TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed using Sensititre YeastOne™. Results: A total of 527 candidaemia episodes (yielding 548 isolates) were evaluable. The mean annual incidence was 2.41/105 population. The median patient age was 63 years (56% of cases occurred in males). Of 498 isolates with confirmed species identity, Candida albicans was the most common (44.4%) followed by Candida glabrata complex (26.7%) and Candida parapsilosis complex (16.5%). Uncommon Candida species comprised 25 (5%) isolates. Overall, C. albicans (>99%) and C. parapsilosis (98.8%) were fluconazole susceptible. However, 16.7% (4 of 24) of Candida tropicalis were fluconazole- and voriconazole-resistant and were non-WT to posaconazole. Of C. glabrata isolates, 6.8% were resistant/non-WT to azoles; only one isolate was classed as resistant to caspofungin (MIC of 0.5 mg/L) by CLSI criteria, but was micafungin and anidulafungin susceptible. There was no azole/echinocandin co-resistance. Conclusions: We report an almost 1.7-fold proportional increase in C. glabrata candidaemia (26.7% versus 16% in 2004) in Australia. Antifungal resistance was generally uncommon, but azole resistance (16.7% of isolates) amongst C. tropicalis may be emerging.

Clostridium difficile infection in the Lao People's Democratic Republic: first isolation and review of the literature.

BACKGROUND: Current knowledge of the epidemiology of Clostridium difficile infection in Asia, and in particular the Greater Mekong Subregion, is very limited. Only a few studies from Thailand and Vietnam have been reported from the region with variable testing methods and results, and no studies from Lao People's Democratic Republic (PDR). Therefore we investigated the presence of C. difficile in a single centre in the Lao PDR and determined the ribotypes present. METHOD: Seventy unformed stool samples from hospital inpatients at Mahosot Hospital, Vientiane, were tested for the presence of C. difficile using selective differential agar and confirmed by latex agglutination. C. difficile isolates were further characterised by ribotyping and toxin gene detection. RESULTS: C. difficile was isolated from five of the 70 patients, and five different ribotypes were identified (014, 017, 020, QX 107 and QX 574). CONCLUSION: This is the first isolation of C. difficile from human stool samples in the Lao PDR. These results will add to the limited amount of data on C. difficile in the region. In addition, we hope this information will alert clinicians to the presence of C. difficile in the country and will help inform future investigations into the epidemiology and diagnosis of C. difficile in Lao PDR.

Nocardia Septic Arthritis Complicating an Anterior Cruciate Ligament Repair.

Nocardia infection following anterior cruciate ligament (ACL) allograft reconstruction is a rare occurrence. We report a case of Nocardia infection of an allograft ACL reconstruction and septic arthritis of the knee joint due to an organism most similar to the novel Nocardia species Nocardia aobensis.

Anncaliia algerae microsporidial myositis.

The insect microsporidian Anncaliia algerae was first described in 2004 as a cause of fatal myositis in an immunosuppressed person from Pennsylvania, USA. Two cases were subsequently reported, and we detail 2 additional cases, including the only nonfatal case. We reviewed all 5 case histories with respect to clinical characteristics, diagnosis, and management and summarized organism life cycle and epidemiology. Before infection, all case-patients were using immunosuppressive medications for rheumatoid arthritis or solid-organ transplantation. Four of the 5 case-patients were from Australia. All diagnoses were confirmed by skeletal muscle biopsy; however, peripheral nerves and other tissues may be infected. The surviving patient received albendazole and had a reduction of immunosuppressive medications and measures to prevent complications. Although insects are the natural hosts for A. algerae, human contact with water contaminated by spores may be a mode of transmission. A. algerae has emerged as a cause of myositis, particularly in coastal Australia.

Dientamoeba fragilis: a family cluster of disease associated with marked peripheral eosinophilia.

Dientamoeba fragilis has emerged as an important and underrecognized cause of gastrointestinal illness. We report a familial cluster of D. fragilis associated with marked peripheral eosinophilia and gastrointestinal symptoms. Dientamoeba fragilis infection should be considered in the setting of unexplained eosinophilia. If confirmed, screening of household members should be considered.

Phylogenomic analysis of a global collection of Escherichia coli ST38: evidence of interspecies and environmental transmission?

IMPORTANCE: Extraintestinal pathogenic Escherichia coli (ExPEC) sequence type (ST) 38 is one of the top 10 human pandemic lineages. Although a major cause of urinary tract and blood stream infections, ST38 has been poorly characterized from a global phylogenomic perspective. A comprehensive genome-scale analysis of 925 ST38 isolate genomes identified two broad ancestral clades and linkage of discrete ST38 clusters with specific bla CTX-M variants. In addition, the clades and clusters carry important virulence genes, with diverse but poorly characterized plasmids. Numerous putative interhost and environment transmission events were identified here by the presence of ST38 clones (defined as isolates with ≤35 SNPs) within humans, companion animals, food sources, urban birds, wildlife, and the environment. A small cluster of international ST38 clones from diverse sources, likely representing progenitors of a hospital outbreak that occurred in Brisbane, Australia, in 2017, was also identified. Our study emphasizes the importance of characterizing isolate genomes derived from nonhuman sources and geographical locations, without any selection bias.

Refractory Mycobacterium genavense infection secondary to thymoma-associated endogenous IL-12 inhibitor.

Case: A 39-year-old man with thymoma-associated acetylcholine receptor antibody myasthenia gravis (MG) presented with fevers, night sweats, abdominal pain and weight loss. Marked splenomegaly and intra-abdominal lymphadenopathy were found. Biopsies confirmed disseminated Mycobacterium genavense infection. Despite antimicrobials and reduced immunosuppressive medications, he worsened. We suspected a thymoma-associated cytokine inhibitory antibody. The addition of subcutaneous interferon-gamma (IFN-γ) induced clinical and radiological improvement. His antimicrobials were able to be ceased. MG remained stable. Subsequent testing demonstrated an endogenous interleukin-12 (IL-12) inhibitor, likely inhibiting the IL-12/IFN-γ axis crucial for defence against mycobacterial infections. Discussion: This case illustrates the autoimmune manifestations that can occur with thymoma. It illustrates the benefit of exogenous IFN-γ in overcoming the immune deficit. In this case, its use did not exacerbate existing autoimmune disease or trigger others. We raise awareness of the need to consider cytokine pathway defects as a contributing factor to refractory atypical infections in patients with thymoma-associated MG.

Reusable venesection tourniquets: a potential source of hospital transmission of multiresistant organisms.

OBJECTIVE: To determine the prevalence of multiresistant organism (MRO) colonisation of reusable venesection tourniquets. DESIGN AND SETTING: A prospective study in a tertiary hospital to collect and analyse reusable venesection tourniquets for the presence of MROs - methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and extended-spectrum ß-lactamase and metallo-ß-lactamase-producing Enterobacteriaceae - using a sensitive enrichment method. Tourniquets were collected and tested during a 10-week period between September and November 2010. MAIN OUTCOME MEASURE: Prevalence of MRO colonisation of tourniquets. RESULTS: The overall colonisation rate of 100 tourniquets randomly collected from general wards, ambulatory care areas and critical care areas was 78%. MROs were isolated from 25 tourniquets collected from a variety of hospital locations, including general wards, the intensive care unit, burns unit and anaesthetic bay. MRSA was isolated from 14 tourniquets and VRE from 19; both MRSA and VRE were isolated from nine tourniquets. There were no microorganisms isolated from 22 tourniquets. CONCLUSION: Reusable tourniquets can be colonised with MROs and may be a potential source of transmission of MROs to hospitalised patients.

Efficacy of aerosolized hydrogen peroxide (Deprox) cleaning compared to physical cleaning in a Burns Unit.

BACKGROUND: The performance of Deprox aerosolized hydrogen peroxide (aHP) has not been extensively studied in real-world clinical settings. A comparative study of aHP terminal disinfection was conducted in a Burns Unit and its performance compared to physical cleaning alone. METHODS: Environmental surfaces were sampled pre-cleaning, post-cleaning and post-aHP disinfection. Samples were cultured for MRSA, VRE, Gram-negative multi-resistant organisms and other Gram-negative bacilli. RESULTS: 310 sites were sampled. There was a reduction in the rates of contaminated surfaces post-aHP, though pathogens were still recoverable in most cases, except for VRE. There was a marked reduction in MRSA contamination of soft surfaces (12% post-clean vs 6% post-aHP), and patient room surfaces (8.3% post-clean vs 2.8% post-aHP). It does not work as well for MRSA in bathrooms: 7% of surfaces were positive post-clean, and 9% post-aHP. There was a reduction in multiresistant Gram-negative bacteria (7%-3%), mostly due to drains (33%-13%). CONCLUSION: aHP is a useful method of environmental disinfection, especially for Gram-negative pathogens in drains and MRSA on hard and soft surfaces. Where ongoing acquisition of MRSA is a problem, an adjunctive method of terminal disinfection in bathrooms could be considered.

Use of Infliximab to Treat Paradoxical Tuberculous Meningitis Reactions.

We documented dramatic responses to infliximab in 4 tuberculous meningitis cases with severe paradoxical reactions after effective antibacterial treatment, despite high-dose steroids. In every instance, infliximab was used as a last resort after all other options were exhausted, resulting in delayed initiation that may have adversely affected patient outcomes.

Hospital MRSA outbreaks: Multiplex PCR-reverse line blot binary typing as a screening method for WGS, and the role of the environment in transmission.

BACKGROUND: Whole-genome sequencing (WGS) can provide useful information on methicillin-resistant Staphylococcus aureus (MRSA) transmission in hospitals. However, it is expensive and laborious, especially for environmental screening programs which generate large numbers of isolates. Multiplex PCR-reverse line blot binary typing (mPCR-RLB BT) is a rapid, high throughput, inexpensive typing method which could be useful to screen isolates for WGS. This study assessed the strategy of screening isolates with mPCR-RLB BT to reduce the need for WGS; and to assess the role of the environment in transmission. METHODS: MRSA transmission in a Burns Unit and its related Intensive Care Unit was studied. mPCR-RLB BT was performed on 238 isolates; this, combined with epidemiological data, was used to choose 97 isolates for WGS. RESULTS: Relationships between isolates by WGS demonstrated several outbreaks. There was a significant contribution of environmental isolates to transmission, and several problem areas were identified. There was a substantial cost saving from screening isolates with mPCR-RLB BT. CONCLUSIONS: The use of an inexpensive, rapid screening method for MRSA typing is useful to reduce expenditure and time spent on hospital infection control programs, and reductions are likely to be even more considerable in a non-outbreak setting. Environmental screening and WGS are useful to determine exact sources of transmission to focus mitigation strategies.

Genomic profiling of Escherichia coli isolates from bacteraemia patients: a 3-year cohort study of isolates collected at a Sydney teaching hospital.

This study sought to assess the genetic variability of Escherichia coli isolated from bloodstream infections (BSIs) presenting at Concord Hospital, Sydney during 2013-2016. Whole-genome sequencing was used to characterize 81 E. coli isolates sourced from community-onset (CO) and hospital-onset (HO) BSIs. The cohort comprised 64 CO and 17 HO isolates, including 35 multidrug-resistant (MDR) isolates exhibiting phenotypic resistance to three or more antibiotic classes. Phylogenetic analysis identified two major ancestral clades. One was genetically diverse with 25 isolates distributed in 16 different sequence types (STs) representing phylogroups A, B1, B2, C and F, while the other comprised phylogroup B2 isolates in subclades representing the ST131, ST73 and ST95 lineages. Forty-seven isolates contained a class 1 integron, of which 14 carried blaCTX -M-gene. Isolates with a class 1 integron carried more antibiotic resistance genes than isolates without an integron and, in most instances, resistance genes were localized within complex resistance loci (CRL). Resistance to fluoroquinolones could be attributed to point mutations in chromosomal parC and gyrB genes and, in addition, two isolates carried a plasmid-associated qnrB4 gene. Co-resistance to fluoroquinolone and broad-spectrum beta-lactam antibiotics was associated with ST131 (HO and CO), ST38 (HO), ST393 (CO), ST2003 (CO) and ST8196 (CO and HO), a novel ST identified in this study. Notably, 10/81 (12.3 %) isolates with ST95 (5 isolates), ST131 (2 isolates), ST88 (2 isolates) and a ST540 likely carry IncFII-IncFIB plasmid replicons with a full spectrum of virulence genes consistent with the carriage of ColV-like plasmids. Our data indicate that IncF plasmids play an important role in shaping virulence and resistance gene carriage in BSI E. coli in Australia.

Escherichia coli ST8196 is a novel, locally evolved, and extensively drug resistant pathogenic lineage within the ST131 clonal complex.

The H30Rx subclade of Escherichia coli ST131 is a clinically important, globally dispersed pathogenic lineage that typically displays resistance to fluoroquinolones and extended spectrum ß-lactams. Isolates EC233 and EC234, variants of ST131-H30Rx with a novel sequence type (ST) 8196, isolated from unrelated patients presenting with bacteraemia at a Sydney Hospital in 2014 are characterised here. EC233 and EC234 are phylogroup B2, serotype O25:H4A, and resistant to ampicillin, amoxicillin, cefoxitin, ceftazidime, ceftriaxone, ciprofloxacin, norfloxacin and gentamicin and are likely clonal. Both harbour an IncFII_2 plasmid (pSPRC_Ec234-FII) that carries most of the resistance genes on an IS26 associated translocatable unit, two small plasmids and a novel IncI1 plasmid (pSPRC_Ec234-I). SNP-based phylogenetic analysis of the core genome of representatives within the ST131 clonal complex places both isolates in a subclade with three clinical Australian ST131-H30Rx clade-C isolates. A MrBayes phylogeny analysis of EC233 and EC234 indicates ST8196 share a most recent common ancestor with ST131-H30Rx strain EC70 isolated from the same hospital in 2013. Our study identified genomic hallmarks that define the ST131-H30Rx subclade in the ST8196 isolates and highlights a need for unbiased genomic surveillance approaches to identify novel high-risk MDR E. coli pathogens that impact healthcare facilities.

Tocilizumab for severe COVID-19 pneumonia: Case series of 5 Australian patients.

AIM: To describe the first Australian cases of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) disease (COVID-19) pneumonia treated with the interleukin-6 receptor antagonist tocilizumab. METHODS: Retrospective, open-label, real-world, uncontrolled, single-arm case series conducted in 2 tertiary hospitals in NSW, Australia and 1 tertiary hospital in Victoria, Australia. Five adult male patients aged between 46 and 74 years with type 1 respiratory failure due to COVID-19 pneumonia requiring intensive care unit (ICU) admission and biochemical evidence of systemic hyperinflammation (C-reactive protein greater than 100 mg/L; ferritin greater than 700 µg/L) were administered variable-dose tocilizumab. RESULTS: At between 13 and 26 days follow-up, all patients are alive and have been discharged from ICU. Two patients have been discharged home. Two patients avoided endotracheal intubation. Oxygen therapy has been ceased in three patients. Four adverse events potentially associated with tocilizumab therapy occurred in three patients: ventilator-associated pneumonia, bacteremia associated with central venous catheterization, myositis and hepatitis. All patients received broad-spectrum antibiotics, 4 received corticosteroids and 2 received both lopinavir/ritonavir and hydroxychloroquine. The time from first tocilizumab administration to improvement in ventilation, defined as a 25% reduction in fraction of inspired oxygen required to maintain peripheral oxygen saturation greater than 92%, ranged from 7 hours to 4.6 days. CONCLUSIONS: Tocilizumab use was associated with favorable clinical outcome in our patients. We recommend tocilizumab be included in randomized controlled trials of treatment for patients with severe COVID-19 pneumonia, and be considered for compassionate use in such patients pending the results of these trials.

Tn6060, a transposon from a genomic island in a Pseudomonas aeruginosa clinical isolate that includes two class 1 integrons.

A 25,441-bp transposon was recovered from a Pseudomonas aeruginosa clinical isolate. While the transposition module was >99% identical to sequence of Tn1403, the element had been subject to rearrangements, with two In70.2-like class 1 integrons inserted into it in an unusual "tail-to-tail" configuration. One cassette array was the same as that in In70.2; however, the second was different, generating a transposon that collectively includes six resistance cassettes.