Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Central venous catheter associated blood stream infections (CVC-BSIs) in the non-intensive care settings: Epidemiology, microbiology and outcomes.

BACKGROUND: Most studies have examined central venous catheter associated blood stream infections (CVC-BSIs) in Intensive Care Units (ICUs) but information on CVC-BSIs in non-ICU settings is sparse. This study aimed to determine the burden, microbiologic patterns, and associations of CVC-BSIs in non-ICU settings in a tertiary regional centre, University Hospital Geelong (UHG), Victoria, Australia. METHODS: A retrospective study was conducted in the UHG from October 2016 to April 2018. Based on the National Healthcare Safety Network definition, 23 CVC-BSIs occurred in non-ICU settings. Data analysed using SPSS-v25 with a P value < 0.05 was deemed as significant. RESULTS: The incidence rate was 1.2 per 10,000 bed-days. The mean age of patients was 57.22 ± 18 years. 43.5% of patients had Charlson index score of ≥5 and 78% received appropriate empiric antibiotics. The 90-day mortality rate was zero. In total, 26 microorganisms were isolated. Gram-negative bacilli were more common than Gram-positive cocci. The mean catheter duration was 45.22 ± 8.99 days. Hickman lines contributed to 52.2% of BSIs. Within the first two weeks of line insertion, 53.84% of CVC-BSIs occurred with 76.92% of CVC-Gram-negative bacteraemia and 71.4% of BSIs were related to Hickman lines. Also, 69.2% of CVC-BSIs occurred within ≤4 weeks of line insertion including 84.6% of CVC-Gram-negative bacteraemia. CONCLUSION: CVC-BSIs constitute a significant burden on high risk patients in non-ICU settings, with Gram negative bacilli predominating. A prospective surveillance program for all patients with CVC in the non-ICU setting may improve CVC management processes and influence educational measures.

The changing epidemiology worldwide of Mycobacterium ulcerans.

Mycobacterium ulcerans is recognised as the third most common mycobacterial infection worldwide. It causes necrotising infections of skin and soft tissue and is classified as a neglected tropical disease by the World Health Organization (WHO). However, despite extensive research, the environmental reservoir of the organism and mode of transmission of the infection to humans remain unknown. This limits the ability to design and implement public health interventions to effectively and consistently prevent the spread and reduce the incidence of this disease. In recent years, the epidemiology of the disease has changed. In most endemic regions of the world, the number of cases reported to the WHO are reducing, with a 64% reduction in cases reported worldwide in the last 9 years. Conversely, in a smaller number of countries including Australia and Nigeria, reported cases are increasing at a rapid rate, new endemic areas continue to appear, and in Australia cases are becoming more severe. The reasons for this changing epidemiology are unknown. We review the epidemiology of M. ulcerans disease worldwide, and document recent changes. We also outline and discuss the current state of knowledge on the ecology of M. ulcerans, possible transmission mechanisms to humans and what may be enabling the spread of M. ulcerans into new endemic areas.

Aiming for elimination: Outcomes of a consultation pathway supporting regional general practitioners to prescribe direct-acting antiviral therapy for hepatitis C.

To increase access to treatment, the Australian government enabled general practitioners (GPs) to prescribe direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV)-in consultation with a specialist if inexperienced in HCV management. This study describes the establishment and outcomes of a remote consultation pathway supporting GPs to treat HCV. Key stakeholders from primary and tertiary healthcare services in the Barwon South Western region developed and implemented an HCV remote consultation pathway. Pharmaceutical Benefits Schedule prescription data were used to evaluate GP DAA prescription 12 months pre-and post- pathway implementation. A retrospective review of patients referred for remote consultation for 12 months post- pathway inception was undertaken to determine the care cascade. HCV treatment initiation by GPs increased after implementation of the remote consultation pathway. In the 12-month study period, 74 GPs referred 169 people for remote consultation; 114 (67%) were approved for GP DAA treatment; 48 (28%) were referred for specialist assessment. In total, 119 (71%) patients commenced DAA; 69 were eligible for SVR12 assessment. Post-treatment HCV RNA data were available for 52 (75%) people; 37 achieved SVR12; 15 achieved SVR ranging from week 5 to 11 post-treatment. No treatment failure was detected. Collaborative development and implementation of a remote consultation pathway has engaged regional GPs in managing HCV. Follow-up post-treatment could be improved; however, no treatment failure has been documented. To eliminate HCV as a public health threat, it is vital that specialists support GPs to prescribe DAA.

The rise of methicillin resistant Staphylococcus aureus: now the dominant cause of skin and soft tissue infection in Central Australia.

This study aimed to examine the epidemiology and treatment outcomes of community-onset purulent staphylococcal skin and soft tissue infections (SSTI) in Central Australia. We performed a prospective observational study of patients hospitalised with community-onset purulent staphylococcal SSTI (n = 160). Indigenous patients accounted for 78% of cases. Patients were predominantly young adults; however, there were high rates of co-morbid disease. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was the dominant phenotype, accounting for 60% of cases. Hospitalisation during the preceding 6 months, and haemodialysis dependence were significant predictors of CA-MRSA infection on univariate analysis. Clinical presentation and treatment outcomes were found to be comparable for methicillin-susceptible S. aureus (MSSA) and methicillin-resistant cases. All MRSA isolates were characterised as non-multi-resistant, with this term used interchangeably with CA-MRSA in this analysis. We did not find an association between receipt of an active antimicrobial agent within the first 48 h, and progression of infection; need for further surgical debridement; unplanned General Practitioner or hospital re-presentation; or need for further antibiotics. At least one adverse outcome was experienced by 39% of patients. Clindamycin resistance was common, while rates of trimethoprim-sulfamethoxazole resistance were low. This study suggested the possibility of healthcare-associated transmission of CA-MRSA. This is the first Australian report of CA-MRSA superseding MSSA as the cause of community onset staphylococcal SSTI.

Australasian Society of Infectious Diseases updated guidelines for the management of Clostridium difficile infection in adults and children in Australia and New Zealand.

The incidence of Clostridium difficile infection (CDI) continues to rise, whilst treatment remains problematic due to recurrent, refractory and potentially severe nature of disease. The treatment of C. difficile is a challenge for community and hospital-based clinicians. With the advent of an expanding therapeutic arsenal against C. difficile since the last published Australasian guidelines, an update on CDI treatment recommendations for Australasian clinicians was required. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children.

Mucormycosis in Australia: contemporary epidemiology and outcomes.

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p <0.001). Disseminated infection was common (39.2%). Apophysomyces spp. and Saksenaea spp. caused infection in immuno-competent hosts, most frequently associated with trauma and affected sites other than lung and sinuses. The 180-day mortality was 56.7%. The strongest predictors of mortality were rheumatological/autoimmune disorder (OR = 24.0, p 0.038 95% CI 1.2-481.4), haematological malignancy (OR = 7.7, p 0.001, 95% CI 2.3-25.2) and admission to intensive care unit (OR = 4.2, p 0.02, 95% CI 1.3-13.8). Most deaths occurred within one month. Thereafter we observed divergence in survival between the haematological and non-haematological populations (p 0.006). The mortality of mucormycosis remains particularly high in the immuno-compromised host. Underlying rheumatological/autoimmune disorders are a previously under-appreciated risk for infection and poor outcome.

One Health approach to controlling a Q fever outbreak on an Australian goat farm.

A recent outbreak of Q fever was linked to an intensive goat and sheep dairy farm in Victoria, Australia, 2012-2014. Seventeen employees and one family member were confirmed with Q fever over a 28-month period, including two culture-positive cases. The outbreak investigation and management involved a One Health approach with representation from human, animal, environmental and public health. Seroprevalence in non-pregnant milking goats was 15% [95% confidence interval (CI) 7-27]; active infection was confirmed by positive quantitative PCR on several animal specimens. Genotyping of Coxiella burnetii DNA obtained from goat and human specimens was identical by two typing methods. A number of farming practices probably contributed to the outbreak, with similar precipitating factors to the Netherlands outbreak, 2007-2012. Compared to workers in a high-efficiency particulate arrestance (HEPA) filtered factory, administrative staff in an unfiltered adjoining office and those regularly handling goats and kids had 5·49 (95% CI 1·29-23·4) and 5·65 (95% CI 1·09-29·3) times the risk of infection, respectively; suggesting factory workers were protected from windborne spread of organisms. Reduction in the incidence of human cases was achieved through an intensive human vaccination programme plus environmental and biosecurity interventions. Subsequent non-occupational acquisition of Q fever in the spouse of an employee, indicates that infection remains endemic in the goat herd, and remains a challenge to manage without source control.

Survey of infection control and antimicrobial stewardship practices in Australian residential aged-care facilities.

This study assessed infection prevention and antimicrobial stewardship (AMS) practices in Australian residential aged-care facilities (RACF). Two hundred and sixty-five surveys (15.6%) were completed with all states represented and the majority (177 (67.3%)) privately run. Only 30.6% RACF had infection control trained staff on site. Few facilities had AMS policies, only 14% had antimicrobial prescribing restrictions. Most facilities offered vaccination to residents (influenza vaccination rates >75% in 73% of facilities), but pneumococcal vaccination was poor.

Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality.

The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes; mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%); antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p <0.01); 61 (37.7%) of cases affected patients without HMs or transplantation. Antifungal therapy was administered to 93.2% of patients (median 68 days, interquartile range 19-275), and adjunctive surgery was performed in 58.6%. The all-cause 90-day mortality was 44.4%; HMs and intensive-care admission were the strongest predictors of death (both p <0.001). Survival varied by fungal group, with the risk of death being significantly lower in patients with dematiaceous mould infections than in patients with other non-Aspergillus mould infections. Non-Aspergillus IFD affected diverse patient groups, including non-immunocompromised hosts and those outside traditional risk groups; therefore, definitions of IFD in these patients are required. Given the high mortality, increased recognition of infections and accurate identification of the causative agent are required.

Consensus guidelines for implementation of quality processes to prevent invasive fungal disease and enhanced surveillance measures during hospital building works, 2014.

Healthcare-associated fungal outbreaks impose a substantial economic burden on the health system and typically result in high patient morbidity and mortality, particularly in the immunocompromised host. As the population at risk of invasive fungal infection continues to grow due to the increased burden of cancer and related factors, the need for hospitals to employ preventative measures has become increasingly important. These guidelines outline the standard quality processes hospitals need to accommodate into everyday practice and at times of healthcare-associated outbreak, including the role of antifungal stewardship programmes and best practice environmental sampling. Specific recommendations are also provided to help guide the planning and implementation of quality processes and enhanced surveillance before, during and after high-risk activities, such as hospital building works. Areas in which information is still lacking and further research is required are also highlighted.

Enterococcal endocarditis in the beginning of the 21st century: analysis from the International Collaboration on Endocarditis-Prospective Cohort Study.

Enterococci are reportedly the third most common group of endocarditis-causing pathogens but data on enterococcal infective endocarditis (IE) are limited. The aim of this study was to analyse the characteristics and prognostic factors of enterococcal IE within the International Collaboration on Endocarditis. In this multicentre, prospective observational cohort study of 4974 adults with definite IE recorded from June 2000 to September 2006, 500 patients had enterococcal IE. Their characteristics were described and compared with those of oral and group D streptococcal IE. Prognostic factors for enterococcal IE were analysed using multivariable Cox regression models. The patients' mean age was 65 years and 361/500 were male. Twenty-three per cent (117/500) of cases were healthcare related. Enterococcal IE were more frequent than oral and group D streptococcal IE in North America. The 1-year mortality rate was 28.9% (144/500). E. faecalis accounted for 90% (453/500) of enterococcal IE. Resistance to vancomycin was observed in 12 strains, eight of which were observed in North America, where they accounted for 10% (8/79) of enterococcal strains, and was more frequent in E. faecium than in E. faecalis (3/16 vs. 7/364 , p 0.01). Variables significantly associated with 1-year mortality were heart failure (HR 2.4, 95% CI 1.7--3.5, p <0.0001), stroke (HR 1.9, 95% CI 1.3--2.8, p 0.001) and age (HR 1.02 per 1-year increment, 95% CI 1.01--1.04, p 0.002). Surgery was not associated with better outcome. Enterococci are an important cause of IE, with a high mortality rate. Healthcare association and vancomycin resistance are common in particular in North America.

Staphylococcus aureus bacteraemia: evaluation of the role of transoesophageal echocardiography in identifying clinically unsuspected endocarditis.

Staphylococcus aureus bacteraemia (SAB) is an important cause of community and nosocomial sepsis, with a significant mortality rate. Infective endocarditis (IE) is a serious complication, occurring in up to 25 % of cases. Transoesophageal echocardiography (TOE) significantly improves the sensitivity of diagnosis. We compared the sensitivity and specificity of clinical evaluation alone in diagnosing IE. We evaluated all adult patients with SAB at our centre from 1998 to 2006 in order to determine what proportion of clinically unsuspected cases were diagnosed with IE on TOE. IE was defined according to modified Duke criteria. The median age of the patients was 68 years, 77 % were male and the majority of cases did not have a known pre-existing condition. Twenty-one percent were methicillin-resistant Staphylococcus aureus (MRSA). Intravascular device was the most common cause of bacteraemia. TOE was performed in 144 (100 %) of the cases. IE was suspected clinically in 15 % of cases, and the overall prevalence of possible or definite IE on TOE-inclusive Duke criteria was 29 % (n = 41). Following TOE, 22 (15 %) cases were reclassified as either possible or definite endocarditis. TOE detected a vegetation in 37 (90 %) of the 41 cases of IE. Nineteen (46 %) were not suspected clinically by Duke criteria. Sensitivity improved in the presence of pre-existing valve lesion or community acquisition. The overall in-hospital mortality was 10 %. There is a high incidence of endocarditis in SAB and a large percentage of cases are not evident on clinical grounds. TOE evaluation is indicated for all medically suitable adult patients with SAB in order to improve the detection of endocarditis.

Outpatient parenteral antimicrobial therapy is safe and effective for the treatment of infective endocarditis: a retrospective cohort study.

BACKGROUND: Outpatient parenteral antibiotic therapy has been shown to be efficacious, safe and cost-effective for a variety of infections. The data from managing infective endocarditis (IE) with hospital in the home (HITH) are limited. We evaluated the safety and outcomes of patients with IE treated with HITH at our centre. AIMS: To evaluate the safety, efficacy and 1-year outcomes of patients with IE treated under HITH at our centre over 9 years. METHOD: A retrospective analysis of the clinical outcomes of all cases of IE treated with HITH at a tertiary referral centre was undertaken for patients treated between June 2002 and July 2011 (9 years). Outcome measures included clinical cure, readmission rate, relapses and 1-year mortality. RESULTS: Sixty-eight cases of IE were treated with HITH over the study period, including 29 native valve infections, 24 prosthetic valve infections, 12 pacemaker lead infections, 1 defibrillator lead infection, 1 myocardial wall infection and 1 aortic graft infection. Thirteen cases had valve replacement surgery and 12 cases had removal of infected pacemaker leads. Staphylococcus aureus (18 cases), Coagulase-negative staphylococcus (10 cases) and viridians-group streptococcus (18 cases) were the most common pathogens. Median duration of antimicrobial therapy with HITH was 24 days (range 4 to 42 days). There were three readmissions during antimicrobial therapy with HITH. Two patients relapsed. There were two deaths and one patient was lost to follow up. One-year survival was 96% (65/68). CONCLUSION: Outpatient antimicrobial therapy with HITH is safe and effective in carefully selected cases of IE.

Preventing invasive fungal infection during hospital building works.

Hospital building works increase the risk of invasive fungal infections. Nosocomial outbreaks have been reported. A pre-emptive strategy for planned building works is paramount. The roles of HEPA filtration, air-sampling and modulation of 'routine' antifungal prophylaxis practice are discussed in the context of pre-emptive planning and outbreak management.

Successful control of an outbreak of invasive aspergillosis in a regional haematology unit during hospital construction works.

We report the successful control of an outbreak of six cases of nosocomial invasive aspergillosis (IA) in our haematology unit coinciding with major hospital construction works. Infection control changes included unit relocation, impermeable barriers at construction site, face-masking and voriconazole prophylaxis of 18 further high-risk patients, none of which developed breakthrough IA. A multi-faceted pre-emptive approach involving clinicians, hospital management, engineering and building departments is essential in preventing nosocomial IA outbreaks.

Candida infective endocarditis.

Candida infective endocarditis (IE) is uncommon but often fatal. Most epidemiologic data are derived from small case series or case reports. This study was conducted to explore the epidemiology, treatment patterns, and outcomes of patients with Candida IE. We compared 33 Candida IE cases to 2,716 patients with non-fungal IE in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS). Patients were enrolled and the data collected from June 2000 until August 2005. We noted that patients with Candida IE were more likely to have prosthetic valves (p < 0.001), short-term indwelling catheters (p < 0.0001), and have healthcare-associated infections (p < 0.001). The reasons for surgery differed between the two groups: myocardial abscess (46.7% vs. 22.2%, p = 0.026) and persistent positive blood cultures (33.3% vs. 9.9%, p = 0.003) were more common among those with Candida IE. Mortality at discharge was higher in patients with Candida IE (30.3%) when compared to non-fungal cases (17%, p = 0.046). Among Candida patients, mortality was similar in patients who received combination surgical and antifungal therapy versus antifungal therapy alone (33.3% vs. 27.8%, p = 0.26). New antifungal drugs, particularly echinocandins, were used frequently. These multi-center data suggest distinct epidemiologic features of Candida IE when compared to non-fungal cases. Indications for surgical intervention are different and mortality is increased. Newer antifungal treatment options are increasingly used. Large, multi-center studies are needed to help better define Candida IE.

Prevalence of multiresistant Gram-negative organisms in a surgical hospital in Ho Chi Minh City, Vietnam.

OBJECTIVE: To determine resistance patterns of multiresistant Gram-negative organisms at a surgical hospital in Ho Chi Minh City, Vietnam, in order to guide appropriate antibiotic prescribing and improve infection control procedures. METHOD: All samples sent in for microbiological analysis over a 3-month period were included. A resource neutral double disc-diffusion test was introduced to detect the presence of extended-spectrum beta-lactamase (ESBL) production. RESULTS: We obtained 350 bacterial isolates from clinical specimens; 87.4% were Gram-negative bacteria (GNB). Of these, 88.9% were Enterobacteriaceae, of which 14.7% produced ESBL. Fifteen (37.5%) of these were isolated within 48 h of admission. Resistance to gentamicin and ciprofloxacin occurred in 70.0% and 72.5% of those organisms that produced ESBL and in 39.5% and 38.7% of those that did not. Resistance to third-generation cephalosporins was common: 36.7% of all GNB were resistant to ceftriaxone, 34.0% to cefotaxime, 19.6% to ceftazidime and 36.7% to cefoperazone. CONCLUSION: Multiresistant Gram-negative organisms are common and pose a challenge to antibiotic therapy. Successful implementation of a simple test to detect ESBL production allowed reporting of these organisms, appropriate antibiotic prescribing and infection control interventions. Development of antibiotic-prescribing guidelines must take into account these resistance patterns.

Candida glabrata prosthetic valve endocarditis treated successfully with fluconazole plus caspofungin without surgery: a case report and literature review.

Reported here is the case of a 72-year-old man who was diagnosed with Candida glabrata prosthetic mitral valve endocarditis and treated successfully with fluconazole plus caspofungin after he refused and was determined unfit for surgery. Initial treatment with intravenous amphotericin B resulted in acute renal impairment. Despite 8 days of intravenous fluconazole therapy, he remained fungemic. Caspofungin was added to the treatment regimen with subsequent sterilisation of blood culture. The patient was treated for 34 days with caspofungin and 41 days with fluconazole. He continued oral fluconazole after hospital discharge and remained well at follow-up 11 months later. The role of fluconazole and caspofungin in the treatment of Candida endocarditis is discussed.