VRE acquisition in hospital and its association with hospital antimicrobial usage -a non-linear analysis of an extended time series.

BACKGROUND: Vancomycin resistant enterococci (VRE) have become endemic pathogens in many Australian hospitals causing significant morbidity. There are few observational studies that have evaluated the effect of antibiotic usage on VRE acquisition. This study examined VRE acquisition and its association with antimicrobial use. The setting was a NSW tertiary hospital with 800 beds over a 63 month period up to March 2020, straddling piperacillin-tazobactam (PT) shortages that occurred from in September 2017. METHODS: The primary outcome was monthly inpatient hospital onset Vancomycin-resistant Enterococci (VRE) acquisitions. Multivariate adaptive regression splines (MARS) were used to estimate hypothetical thresholds, where antimicrobial use above threshold is associated with increased incidence of hospital onset VRE acquisition. Specific antimicrobials and categorised usage (broad, less broad and narrow spectrum) were modelled. RESULTS: There were 846 hospital onset VRE detections over the study period. Hospital onset vanB and vanA VRE acquisitions fell significantly by 64% and 36% respectively after the PT shortage. MARS modelling indicated that PT usage was the only antibiotic found to exhibit a meaningful threshold. PT usage greater than 17.4 defined daily doses/1000 occupied bed-days (95%C I: 13.4, 20.5) was associated with higher onset of hospital VRE. CONCLUSIONS: This paper highlights the large, sustained impact that reduced broad spectrum antimicrobial use had on VRE acquisition and showed that PT use in particular was a major driver with a relatively low threshold. It raises the question as to whether hospitals should be determining local antimicrobial usage targets based on direct evidence from local data analysed with non-linear methods.

Cefazolin susceptibility of coagulase-negative staphylococci (CoNS) causing late-onset neonatal bacteraemia.

BACKGROUND: CoNS bacteraemia causes significant neonatal morbidity. Previous work has suggested that ß-lactam antibiotics vary in their binding affinity to PBP2a (produced by the mecA gene) present in most CoNS. OBJECTIVES: We evaluated cefazolin MICs for CoNS isolated in an Australian neonatal ICU (NICU) and correlated them with isolate genotype and phenotype. METHODS: Significant blood isolates from 2009 to 2017 were speciated and underwent broth microdilution testing for cefazolin, cefoxitin, oxacillin and flucloxacillin. Correlation with mecA presence and PBP2a expression was evaluated. A selection of Staphylococcus capitis isolates underwent WGS. RESULTS: The CoNS (n = 99) isolates were confirmed as S. capitis (n = 57), Staphylococcus epidermidis (n = 32), Staphylococcus haemolyticus (n = 2) and Staphylococcus warneri (n = 8). The MIC of cefazolin was ≤2 mg/L for 30% of isolates and 75% had an MIC of ≤8 mg/L (MIC90 = 16 mg/L). This contrasted with MIC90s of cefoxitin, oxacillin and flucloxacillin, which were all ≥32 mg/L. WGS found a number of S. capitis isolates closely related to the globally established NRCS-A clone. CONCLUSIONS: CoNS displayed distinctly lower MIC values of cefazolin than of other agents tested. MIC variation may be related to binding affinity of PBP2a or regulation of expression of mecA by mecR1-mecI functional genes. Further, NRCS-A S. capitis strains were present in this Australian NICU before and after the unit underwent physical relocation, which raised questions about a common environmental source. It is considered justified to conduct a randomized clinical trial that assesses cefazolin versus vancomycin for management of late-onset neonatal sepsis.

How accurately is hospital acquired pneumonia documented for the correct assignment of a hospital acquired complication (HAC)?

BACKGROUND: In 2016, the Australian Commission on Safety and Quality in Healthcare (ACSQHC) released a list of 16 categories of potentially preventable, high impact hospital-acquired complications (HAC) identified by using administrative coded data (ACD). An important category are hospital-acquired infections (HAI). Within this category, hospital-acquired pneumonia (HAP) is among the most frequent complications documented. There are no published studies concerning the current ACSQHC approach to HAI surveillance using ACD and no pneumonia-specific ACD studies reported from Australia. Published work indicates that ACD detection of HAP has low a sensitivity and positive predictive value (PPV). The current study was designed to examine whether coders correctly reflected the documentation of HAP that was present in the medical record and also evaluated the medical documentation that was present. METHODS: One hundred patients with ACD encoded HAP were selected for review, drawn from admissions to 2 Hunter New England Health hospitals during 2017. Patient records and the eMR were reviewed by two medical officers to assess medical and radiological documentation of pneumonia. The district coding manager reviewed the accuracy of coding of a subset of 23 cases where medical review had not located documented evidence of HAP. RESULTS: Of the 100 reviewed cases, the median patient age was 75 years (range 0-95 years) with 3% under 16 years of age. Twenty one were intensive care-associated of which 13 were associated with ventilation. In 23 cases the documentation was disputed and a secondary review took place - the coding manager confirmed coding changes in 14 of these 23 cases. CONCLUSIONS: This study found that administrative coded data of HAP, utilizing the ACSQHC method reliably reflected the available documentation with a PPV of 86% (95% binomial exact confidence interval 77-92%), much higher than documented by previous ACD studies. The actual documentation of pneumonia by medical staff frequently used the non-specific term 'lower respiratory infection (LRTI)' which we recommend to be avoided. Radiological confirmation was absent in one third of cases. We recommend the adoption of a medical note template checklist for HAP to prompt clinicians with the accepted diagnostic criteria. We also recommend documenting a reason as to why any antibiotic has been commenced in a hospitalized patient in accord with the ACSQHC Antimicrobial Stewardship Clinical Care Standard.

Measuring environmental contamination in critical care using dilute hydrogen peroxide (DHP) technology: An observational cross-over study.

BACKGROUND: The environment has an important role in the transmission of healthcare associated infections. This has encouraged interest in novel methods to improve hygiene in hospitals. One such technology is the use of hydrogen peroxide to decontaminate rooms and equipment; there are, however, few studies that have investigated the effect of continuous dilute hydrogen peroxide (DHP) in the clinical environment. The aim of this study was to examine the use of dilute hydrogen peroxide (DHP) in a critical care unit and measure the microbiological impact on surface contamination. METHODS: We conducted a prospective observational cross-over study in a ten-bed critical care unit in one rural Australian hospital. Selected high-touch sites were screened using dipslides across three study phases: baseline; continuous DHP; and no DHP (control). Quantitative aerobic colony counts (ACC) were assessed against a benchmark standard of ACC >2.5 cfu/cm2 to indicate hygiene failure. RESULTS: There were low levels of microbial contamination in the unit for baseline; DHP; and no DHP phases: 2.2% (95% CI 0.7-5.4%) vs 7.7% (95% CI 4.3-13.0%) vs 6% (95% CI 3.2-10.4%) hygiene failures, respectively. Significant reduction in ACCs did not occur when the DHP was operating compared with baseline and control phases. CONCLUSION: Further work is needed to determine whether continuous DHP technology has a role in decontamination for healthcare settings.

Gram negative anaerobe susceptibility testing in clinical isolates using Sensititre and Etest methods.

Gram negative anaerobic organisms are important pathogens in a range of clinical infections, and susceptibility testing is not commonly performed in the microbiology laboratory. We performed anaerobic susceptibility testing on 70 clinically relevant Gram negative anaerobes isolated from routine cultures in a busy diagnostic laboratory which were identified by MALDI-TOF mass spectrometry (MALDI-TOF MS). The susceptibility testing was performed by two methods: Sensititre trays (ThermoFisher Scientific) against 15 different antibiotics, and Etests (bioMérieux) against five clinically relevant antibiotics (metronidazole, piperacillin-tazobactam, amoxicillin-clavulanate, meropenem and clindamycin). We found that all isolates were susceptible to metronidazole, and overall susceptibility to commonly used antibiotics such as piperacillin-tazobactam and amoxicillin-clavulanate was high (93-100% and 89-100%, respectively). Two isolates of Bacteroides fragilis were resistant to both broad spectrum ß-lactams and carbapenems. Comparing the two methods, using Sensititre broth microdilution as gold standard, there was high categorical agreement (92-100%). Antibiograms provide useful information for clinicians when choosing antimicrobials for infections caused by anaerobic organisms. This study has shown that in our area, use of metronidazole as a broad spectrum anti-anaerobic agent remains appropriate. Anaerobic susceptibility testing is also important to perform in individual clinical isolates, especially from sterile sites or in pure culture. The emergence of broad spectrum ß-lactam and carbapenem resistance in clinical isolates of Bacteroides fragilis is of concern and will require further monitoring. The Etest method was considered superior to Sensititre trays given that the higher inoculum used may allow demonstration of heteroresistance, anaerobiasis can be maintained during setup, lower failure rates, and the ability to select only the antibiotics required.

A predictive model of days from infection to discharge in patients with healthcare-associated urinary tract infections: a structural equation modelling approach.

BACKGROUND: Length of stay (LOS) in hospital is an important component of describing how costs change in relation to healthcare-associated infection and this variable underpins models used to evaluate cost. It this therefore imperative that estimations of LOS associated with infections are performed accurately. AIM: To test the relationships between the size of hospital, age, and patient comorbidity on days from admission to infection and days from infection to discharge in patients with a healthcare-associated urinary tract infection (HAUTI), using structural equation modelling (SEM). METHODS: A non-current cohort study in eight hospitals in New South Wales, Australia. All patients admitted to the hospital for >48 h and who acquired a HAUTI were included. FINDINGS: From the 162,503 eligible patient admissions, 2821 (1.73%) acquired a HAUTI. SEM showed that the proposed model had acceptable fit indices for the combined sample (GFI = 1.00; AGFI = 1.00; NFI = 1.00; CFI = 1.00; RMSEA = 0.000). The main findings showed that age of patient had a direct association with days from admission to infection and with days from infection to discharge. Patient comorbidity had direct links to the variables days from admission to infection and days from infection to discharge. Multi-group analysis indicated that the age of male patients was more influential on the factor days from admission to infection when compared to female patients. Furthermore, the number of comorbidities was significantly more influential on days from admission to infection in male patients than in female patients. CONCLUSION: As the first published study to use SEM to explore a healthcare-associated infection and the predictors of days from infection to discharge in hospital, we can confirm that accounting for the timing of infection during hospitalization is important and that patient comorbidity influences the timing of infection.

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.

Length of stay and mortality associated with healthcare-associated urinary tract infections: a multi-state model.

BACKGROUND: The emergence of antimicrobial resistance is of particular concern with respect to urinary tract infections, since the majority of causative agents are Gram-negative bacteria. Healthcare-associated urinary tract infections (HAUTIs) are frequently associated with instrumentation of the urinary tract, specifically with indwelling catheters. AIM: To evaluate the current incidence, mortality, and length of hospital stay associated with HAUTIs. METHODS: A non-concurrent cohort study design was used, conducted between January 1st, 2010 and June 30th, 2014. All patients admitted to one of the eight participating Australian hospitals and who were hospitalized for more than two days were included. The primary outcome measures were the incidence, mortality, and excess length of stay associated with HAUTIs. FINDINGS: From 162,503 patient admissions, 1.73% [95% confidence interval (CI): 1.67-1.80] of admitted patients acquired a HAUTI. Using a multi-state model, the expected extra length of stay due to HAUTI was four days (95% CI: 3.1-5.0 days). Using a Cox regression model, infection significantly reduced the rate of discharge (hazard ratio: 0.78; 95% CI: 0.73-0.83). Women were less likely to die (0.71; 0.66-0.75), whereas older patients were more likely to die (1.40; 1.38-1.43). Death was rarer in a tertiary referral hospital compared to other hospitals, after adjusting for age and sex (0.74; 0.69-0.78). CONCLUSION: This study is the first to explore the burden of HAUTIs in hospitals using appropriate statistical methods in a developed country. Our study indicates that the incidence of HAUTI, in addition to its associated extra length of stay in hospital, presents a burden to the hospital system. With increasing incidence of UTI due to antimicrobial-resistant organisms, surveillance and interventions to reduce the incidence of HAUTI are required.

Antibiotic therapy for inducible AmpC ß-lactamase-producing Gram-negative bacilli: what are the alternatives to carbapenems, quinolones and aminoglycosides?

Some bacteria that possess chromosomally determined AmpC ß-lactamases may express these enzymes at a high level following exposure to ß-lactams, either by induction or selection for derepressed mutants. This may lead to clinical failure even if an isolate initially tests susceptible in vitro, a phenomenon best characterised by third-generation cephalosporin therapy for Enterobacter bacteraemia or meningitis. Several other Enterobacteriaceae, such as Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (often termed the 'ESCPM' group), may also express high levels of AmpC. However, the risk of clinical failure with ß-lactams that test susceptible in vitro is less clear in these species than for Enterobacter. Laboratories frequently do not report ß-lactam or ß-lactamase inhibitor combination drug susceptibilities for ESCPM organisms, encouraging alternative therapy with quinolones, aminoglycosides or carbapenems. However, quinolones and carbapenems present problems with selective pressure for multiresistant organisms, and aminoglycosides with potential toxicity. The risk of emergent AmpC-mediated resistance for non-Enterobacter spp. appears rare in clinical studies. Piperacillin/tazobactam may remain effective and may be less selective for AmpC derepressed mutants than cephalosporins. The potential roles for agents such as cefepime or trimethoprim/sulfamethoxazole are also discussed. Clinical studies that better define optimal treatment for this group of bacteria are required.

Preventing healthcare-associated infection: risks, healthcare systems and behaviour.

More than 177 000 potentially preventable healthcare-associated infections (HAIs) occur per annum in Australia with sizable attributable mortality. Organizational systems to protect against HAI in hospitals in Australia are relatively poorly developed. Awareness and practice of infection control by medical and other healthcare staff are often poor. These lapses in practice create significant risk for patients and staff from HAI. Excessive patient exposure to antimicrobials is another key factor in the emergence of antibiotic-resistant bacteria and Clostridium difficile infection. Physicians must ensure that their interactions with patients are safe from the infection prevention standpoint. The critical preventative practice is hand hygiene in accord with the World Health Organization 5 moments model. Improving the use of antimicrobials, asepsis and immunization also has great importance. Hospitals should measure and feed back HAI rates to clinical teams. Physicians as leaders, role models and educators play an important part in promoting adherence to safe practices by other staff and students. They are also potentially effective system engineers who can embed safer practices in all elements of patient care and promote essential structural and organizational change. Patients and the public in general are becoming increasingly aware of the risk of infection when entering a hospital and expect their carers to adhere to safe practice. Poor infection control practice will be regarded in a negative light by patients and their families, regardless of any other manifest skills of the practitioner.

Pulsed-field gel electrophoresis is a useful tool in the monitoring of methicillin-resistant Staphylococcus aureus epidemic outbreaks in the intensive care unit.

We wished to determine how pulsed-field gel electrophoresis may be of use in monitoring methicillin-resistant Staphylococcus aureus (MRSA) outbreaks in the intensive care unit (ICU). A retrospective epidemiological analysis was conducted. All 27 ICU patients and 11 patients from other hospital wards from whom MRSA was isolated over a one year period were included in the study. Seventeen of the 27 ICU MRSA isolates were analysed by pulsed-field gel electrophoresis for clonality and compared with the 11 other hospital isolates genotypes over the same period. During three MRSA outbreaks, five MRSA genotypes were identified in ICU whilst the same five genotypes and three additional were found in the rest of the hospital. Pulsed-field gel electrophoresis analysis was useful in identifying clonality of ICU MRSA infections and establishing that they were imported from hospital wards, rather than arising de novo in ICU. We were further able to identify clonal clusters within the unit linked by temporal and geographical proximity, suggestive of cross-infection. Pulsed-field gel electrophoresis typing might be additionally useful in tracing the source of human and/or environmental factors if a genotype were persistently identified.

A population-based study of children with cerebral tuberculosis in New South Wales.

OBJECTIVE: To determine the incidence of childhood cerebral tuberculosis (tuberculous meningitis [TBM] and tuberculoma) in a defined population. DESIGN: Retrospective, population-based study. SETTING AND PARTICIPANTS: All resident children aged up to 14 years in New South Wales diagnosed with cerebral tuberculosis, from 1982 to 1996. MAIN OUTCOME MEASURE: Population-based incidence of childhood TBM. RESULTS: 10 children with TBM and one with tuberculoma were identified in the 15 years. The incidence of TBM was 0.053 (95% CI, 0.025-0.097) per 100,000. Eight of the 10 TBM patients were born in Australia and five were of white European origin. Only one had been vaccinated with BCG vaccine. Three of the children died. CONCLUSIONS: The incidence of childhood TBM in New South Wales is low, and comparable with that in other First World countries.

Progressive vaccinia treated with ribavirin and vaccinia immune globulin.

A 67-year-old man with metastatic melanoma and chronic lymphocytic leukemia was inadvertently given a vaccinia melanoma oncolysate vaccination. He developed progressive vaccinia at the site of inoculation. The lesion started to heal only when he was treated with ribavirin. Vaccinia immune globulin was administered and appeared to help control the initial lesion and limit the development of satellite lesions.

Primary cryptococcal cellulitis caused by Cryptococcus neoformans var. gattii in an immunocompetent host.

Primary cutaneous cryptococcal infection is uncommon. The cutaneous manifestations are most often the result of dissemination from the central nervous system or lung, usually in an immunocompromised host; cellulitis is regarded as the rarest cutaneous form. Primary cutaneous cryptococcosis has occasionally been reported in the immunocompetent, the causative organism being Cryptococcus neoformans var. neoformans. We present a case of cellulitis of the right arm in a 75-year-old man caused by Cryptococcus neoformans var. gattii, a fungus which is endemic in Australia and an important cause of infection in the immunocompetent. This is the first case described of a primary cutaneous infection due to Cryptococcus neoformans var. gattii. The interesting ecology of this organism is discussed.

Risk-stratified nosocomial infection surveillance in a neonatal intensive care unit: report on 24 months of surveillance.

OBJECTIVE: To document the nosocomial infection rate in a single neonatal intensive care unit (NICU) in terms of patient workload and device utilization. METHODOLOGY: Nosocomial infections have been identified and documented by the methodology described by the National Nosocomial Infection Surveillance System (NNIS), Centres for Disease Control, Atlanta. In addition, antibiotic usage has been surveyed in the NICU and standardized measures of patient exposure to antibiotics stratified by birthweight and gestational age have been described. RESULTS: Overall nosocomial infection rates compared favourably with the published NNIS figures at 6.2 infections per 100 admissions or 4.8 per 1000 patient days. Infection rates were significantly higher in lower birthweight groups. Device-related infection rates in each birthweight cohort were also very close to published figures and varied less with birthweight group. Antibiotic exposure averaged 12% of total admission days, less than previously published data. CONCLUSIONS: The NNIS system is applicable to Australian NICU and provides an effective tool for monitoring infection episodes.

Prospective study of diarrhoeal outbreaks in child long-daycare centres in western Sydney.

OBJECTIVE: To investigate outbreaks of diarrhoeal illness in children attending long-daycare centres (LDCs), to characterise parasitic, bacterial and viral isolates from the children's faeces and to identify individual and LDC risk factors for diarrhoea. DESIGN: Eleven-month prospective case-control study of diarrhoeal outbreaks among children in LDCs. SUBJECTS: 2368 children attending 35 LDCs in the western Sydney area. MAIN OUTCOME MEASURES: Frequency of diarrhoeal outbreaks, rate of attack and spread to family members; pathogens isolated from stools; and individual and LDC risk factors. RESULTS: The overall incidence of diarrhoeal disease was low (0.28 outbreaks per centre per year and 0.056 outbreak-associated cases per child-year). Attack rates during outbreaks varied widely (4%-55%; mean, 15%), as did secondary spread rates to family members (1%-15%; mean, 9%). Pathogens were isolated from 7% of symptomatic children and 7% of controls; no outbreak was shown to be caused by a recognised pathogen. Children with outbreak-associated diarrhoeal illness were more likely to have suffered vomiting, poor appetite, lack of energy, fever and to have taken antibiotics in the previous week than other children. Hygiene practices varied widely among centres. CONCLUSIONS: We found low incidence and morbidity from diarrhoeal illness in Australian urban LDCs. Diarrhoea in children in LDCs may be caused predominantly by non-infectious factors such as diet and antibiotic exposure. Current hygiene measures in LDCs seem adequate to prevent and contain outbreaks of infectious diarrhoea.