Antifungal susceptibility of clinical mould isolates in New Zealand, 2001-2019.

The objective of this study was to review the antifungal susceptibility of clinical mould isolates performed by the New Zealand Mycology Reference Laboratory. Isolates were either local or referred for testing from other New Zealand laboratories. All isolates were tested by the broth colorimetric microdilution method, Sensititre YeastOne (SYO). Epidemiological cut-off values (ECVs) derived from either the Clinical and Laboratory Standards Institute (CLSI) method or SYO were used to determine the proportion of non-wild type (non-WT) isolates, i.e., those with an increased likelihood to harbour acquired mechanisms of resistance. A total of 614 isolates were tested. Most isolates (55%) were from the respiratory tract followed by musculoskeletal tissue (17%), eye (10%) and abdomen (5%). The azoles had similar activity except for voriconazole which was less active against the Mucorales. The echinocandins had good activity against Aspergillus spp., other hyaline moulds and dematiaceous isolates but were inactive against Fusarium spp., Lomentospora prolificans and the Mucorales. Amphotericin B had best activity against the Mucorales. The two least susceptible groups were Fusarium spp. and L. prolificans isolates. Three Aspergillus isolates were non-WT for amphotericin B, and four non-WT for azoles. Non-WT were not encountered for caspofungin. Non-Aspergillus isolates in New Zealand have susceptibility patterns similar to those reported elsewhere. In contrast to a growing number of other countries, azole resistance was rare in A. fumigatus sensu stricto. Non-WT isolates were uncommon. The results provide a baseline for monitoring emerging antifungal resistance in New Zealand and support current Australasian treatment guidelines for invasive fungal infections.

Point prevalence surveys of antimicrobial use in adult inpatients at Canterbury District Health Board Hospitals.

AIMS: To determine the nature and appropriateness of antimicrobial prescribing in adult inpatients at Canterbury District Health Board (CDHB). METHODS: Multidisciplinary teams collected clinical details for all adult inpatients on antimicrobial therapy at three CDHB facilities (~1,100 beds) and made standardised assessments based on the Australian National Antimicrobial Prescribing Survey (http://naps.org.au) against local guidelines and national funding criteria. RESULTS: Antimicrobial therapy was prescribed to 42% of inpatients (322/760), usually to treat infections [377/480 prescriptions (79%)], with amoxicillin+clavulanic acid the agent most commonly prescribed [72/480 prescriptions (15%)]. Of assessable prescriptions, 74% (205/278) were guideline compliant, 98% (469/480) were funding criteria compliant, and 83% (375/451) were appropriate clinically. Prescriptions for the most common indications-surgical prophylaxis [66/480 (14%)] and community-acquired pneumonia [56/480 (12%)]-were often non-compliant with guidelines (32% and 41%, respectively) and inappropriate (18% and 21%, respectively). Overall, the indication was documented in 353/480 (74%) prescriptions, the review/stop date documented in 145/480 (30%) prescriptions, and surgical prophylaxis stopped within 24 hours in 53/66 (80%) prescriptions. CONCLUSIONS: Most antimicrobial prescriptions were appropriate and complied with guidelines. Compliance with key quality indicators (indication documented, review/stop date documented, and surgical prophylaxis ceased within 24 hours) were well below target (>95%) and needs improvement.

Population-level exposures associated with MRSA and ESBL-E. coli infection across district health boards in Aotearoa New Zealand: an ecological study.

AIMS: National responses to antimicrobial resistance (AMR) require an understanding of the factors driving its development and spread. Research to date has primarily focused on determining individual-level risk factors for AMR-associated infections. However, additional insights may be gained by investigating exposures associated with AMR variation at the population level. METHODS: We used an ecological study design to describe the association between the incidence rate of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase producing Escherichia coli (ESBL-E. coli) infection and population-level variables among 18 geographically distinct populations, defined by district health boards, in Aotearoa New Zealand. Associations were described using Spearman's correlational analysis. RESULTS: Positive correlations were found between the incidence of both MRSA and ESBL-E. coli infection and household crowding and community antimicrobial use. Positive correlations were also observed between MRSA and socioeconomic deprivation; age <5 years; Maori ethnicity; and Pacific ethnicity. For ESBL-E. coli, positive correlations were also observed with Asian ethnicity; Pacific ethnicity; and overseas-born new arrivals. European ethnicity was negatively correlated with both MRSA and ESBL-E. coli infection. CONCLUSIONS: These findings provide insight into the potential contribution of population-level exposures to MRSA and ESBL-E. coli infection in New Zealand. Exposures such as household crowding, community antimicrobial use and socioeconomic deprivation, are in principle modifiable and may present potentially novel opportunities to reduce the burden of AMR.

Inappropriate prescribing of antibiotics following discharge after major surgery: an area for improvement.

AIM: This study aims to determine the indications for antibiotic use in patients discharged following major surgery at Auckland City Hospital (ACH); to determine if the indications were appropriate and to identify opportunities where antimicrobial stewardship interventions would be beneficial. METHODS: This was a retrospective study of adult patients who were dispensed an antibiotic within the first two days of discharge after major surgery at ACH between 1 January 2013 and 31 December 2013. The indication for antibiotic use was determined and subsequently classified as either 'appropriate', 'not assessable' or 'inappropriate'. RESULTS: Among the 378 patients analysed, an indication for antibiotic use was not documented in 52 patients (13.8%). Antibiotics were prescribed for an established infection in 172 patients (45.5%), as empiric therapy in 100 patients (26.4%), and as prolonged surgical antimicrobial prophylaxis in 41 patients (10.8%). Overall, nearly half of the antibiotic courses dispensed (48.7%) were either 'inappropriate' or the indication was 'not assessable'. CONCLUSIONS: This study demonstrates that a significant proportion of antibiotics prescribed in patients discharged following surgery are inappropriate and there is need for enhanced antimicrobial stewardship in this area.

Antifungal susceptibility testing results of New Zealand yeast isolates, 2001-2015: Impact of recent CLSI breakpoints and epidemiological cut-off values for Candida and other yeast species.

OBJECTIVES: We reviewed the antifungal susceptibility testing results of local yeast isolates (2001-2015) to record the impact of recently updated interpretive criteria and epidemiological cut-off values (ECVs) for yeast species. METHODS: Susceptibility testing was performed using Sensititre® YeastOne®. The results were interpreted following CLSI criteria or YeastOne-derived ECVs. RESULTS: A total of 2345 isolates were tested; 62.0% were from sterile body sites or tissue. Application of new CLSI interpretative criteria for fluconazole increased the proportion of non-susceptible isolates of Candida parapsilosis, Candida tropicalis and Candida glabrata (P≤0.03 for all species). For voriconazole, the greatest increase was for C. tropicalis (P<0.0001). Application of new CLSI interpretive criteria for caspofungin increased the proportion of non-susceptible isolates for C. glabrata and Pichia kudriavzevii (P<0.0001 for both). The new amphotericin ECV (≤2mg/L) did not reveal any non-wild-type (non-WT) isolates in the five species covered. YeastOne itraconazole ECVs detected 2%, 5% and 6% non-WT isolates for P. kudriavzevii, C. tropicalis and C. glabrata, respectively. No itraconazole non-WT isolates of Clavispora lusitaniae were detected. CONCLUSIONS: Whilst most results are similar to other large surveys of fungal susceptibility, the new CLSI interpretive criteria significantly altered the proportion of non-susceptible isolates to fluconazole, voriconazole and caspofungin for several Candida spp. Application of CLSI and YeastOne-derived ECVs revealed the presence of a low proportion of non-WT isolates for many species. The results serve as a baseline to monitor the susceptibility of Candida and other yeast species in New Zealand over time.

Hospital-Onset MRSA Bacteremia Rates Are Significantly Correlated With Sociodemographic Factors: A Step Toward Risk Adjustment.

The correlations between census-derived sociodemographic variables and hospital-onset methicillin-resistant Staphylococcus aureus bacteremia (HO-MRSAB) rates were examined at the US state level. On multivariable analysis, only percent African American remained statistically significant. This finding highlights an important disparity and suggests that risk adjustment is needed when comparing HO-MRSAB rates among US states. Infect Control Hosp Epidemiol 2018;39:479-481.

Household transmission of NDM-producing E. coli in New Zealand.

This report describes the introduction of an extensively antibiotic-resistant carbapenemase-producing Escherichia coli into a hospital in Auckland, New Zealand, by a patient who was a household contact of recent travellers to the Indian subcontinent. The carbapenemase was identified as New Delhi metallo-ß-lactamase (NDM) and reflects probable household transmission in the context of a recent upsurge in NDM-producing Enterobacteriaceae isolation in New Zealand. The observations in this report suggest that hospital screening practices to identify carbapenemase-producing Enterobacteriaceae (CPE) colonised patients may need to be extended to include travellers to high-risk countries who were not hospitalised during their trip, and possibly also their close contacts.

Draft Genome Sequence of a Drug-Susceptible New Zealand Isolate of Mycobacterium tuberculosis Lineage 3.

We report here the draft whole-genome sequence of a drug-susceptible lineage 3 (East-African Indian) isolate of Mycobacterium tuberculosis from New Zealand (NZ3DS1) and compare it to a multidrug-resistant lineage 3 isolate (NZ3MDR1) with an identical 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat profile.

Sequence type 131 fimH30 and fimH41 subclones amongst Escherichia coli isolates in Australia and New Zealand.

The clonal composition of Escherichia coli causing extra-intestinal infections includes ST131 and other common uropathogenic clones. Drivers for the spread of these clones and risks for their acquisition have been difficult to define. In this study, molecular epidemiology was combined with clinical data from 182 patients enrolled in a case-control study of community-onset expanded-spectrum cephalosporin-resistant E. coli (ESC-R-EC) in Australia and New Zealand. Genetic analysis included antimicrobial resistance mechanisms, clonality by DiversiLab (rep-PCR) and multilocus sequence typing (MLST), and subtyping of ST131 by identification of polymorphisms in the fimH gene. The clonal composition of expanded-spectrum cephalosporin-susceptible E. coli and ESC-R-EC isolates differed, with six MLST clusters amongst susceptible isolates (median 7 isolates/cluster) and three clusters amongst resistant isolates, including 40 (45%) ST131 isolates. Population estimates indicate that ST131 comprises 8% of all E. coli within our population; the fluoroquinolone-susceptible H41 subclone comprised 4.5% and the H30 subclone comprised 3.5%. The H30 subclone comprised 39% of all ESC-R-EC and 41% of all fluoroquinolone-resistant E. coli within our population. Patients with ST131 were also more likely than those with non-ST131 isolates to present with an upper than lower urinary tract infection (RR=1.8, 95% CI 1.01-3.1). ST131 and the H30 subclone were predominant amongst ESC-R-EC but were infrequent amongst susceptible isolates where the H41 subclone was more prevalent. Within our population, the proportional contribution of ST131 to fluoroquinolone resistance is comparable with that of other regions. In contrast, the overall burden of ST131 is low by global standards.

Differences in risk-factor profiles between patients with ESBL-producing Escherichia coli and Klebsiella pneumoniae: a multicentre case-case comparison study.

BACKGROUND: Generic epidemiological differences between extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP), are poorly defined. Nonetheless, defining such differences and understanding their basis could have strategic implications for infection control policy and practice. METHODS: Between 2009 and 2011 patients with bacteraemia due to ESBL-EC or ESBL-KP across all three acute hospitals in the city of Auckland, New Zealand, were eligible for inclusion. Recognised risk factors for ESBL bacteraemia were compared between species in a retrospective case-case study design using multivariate logistic regression. Representative isolates underwent ESBL gene characterisation and molecular typing. RESULTS: 170 patients and 176 isolates were included in the study (92 patients with ESBL-EC, 78 with ESBL-KP). 92.6% had CTX-Ms. 39% of EC were ST131 while 51% of KP belonged to 3 different STs (i.e. ST20, ST48 & ST1087). Specific sequence types were associated with specific hospitals for ESBL-KP but not ESBL-EC. Variables positively associated with ESBL-EC on multivariate analysis were: community acquired infection (odds ratio [OR] 7.9; 95% CI: 2.6-23.9); chronic pulmonary disease (OR 5.5; 95% CI: 1.5-20.1); and high prevalence country of origin (OR 4.3; 95% CI: 1.6-11.6). Variables negatively associated with ESBL-EC were previous transplant (OR 0.06; 95% CI: 0.007-0.6); Hospital 2 (OR 0.3; 95% CI: 0.1-0.7) and recent ICU admission (OR 0.3; 95% CI: 0.07-0.9). CONCLUSIONS: Differences in risk profiles between patients with ESBL-EC and ESBL-KP suggest fundamental differences in transmission dynamics. Understanding the biological basis for these differences could have implications for infection control practice. Tailoring of infection control measures according to ESBL species may be indicated in some instances.

Draft Genome Sequence of the First Isolate of Extensively Drug-Resistant Mycobacterium tuberculosis in New Zealand.

Extensively drug-resistant (XDR) tuberculosis has now been described in >90 countries worldwide. The first case of XDR tuberculosis (XDR-TB) in New Zealand was recorded in 2010. We report the draft whole-genome sequence of the New Zealand isolate, NZXDR1, and describe a number of single-nucleotide polymorphisms that relate to drug resistance.

Predictors of hospital surface contamination with Extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae: patient and organism factors.

BACKGROUND: The role of the hospital environment in transmission of ESBL-Klebsiella pneumoniae (ESBL-KP) and ESBL-Escherichia coli (ESBL-EC) is poorly defined. Recent data however suggest that in the hospital setting, ESBL-KP is more transmissible than ESBL-EC. We sought therefore to measure the difference in hospital contamination rates between the two species and to identify key risk factors for contamination of the hospital environment with these organisms. METHODS: We systematically sampled 8 surfaces in the rooms and bathrooms of adult patients colonized or infected with ESBL-EC or ESBL-KP throughout their hospital stay. Data were collected on factors potentially affecting contamination rates. Environmental contamination was defined as recovery of an ESBL-producing organism matching the source patient's isolate. Multivariate logistic regression analysis was performed at the level of the patient visit using generalized estimating equations to identify independent predictors of environmental contamination. RESULTS: 24 patients (11 with ESBL-KP, 11 ESBL-EC and 2 with both organisms) had 1104 swabs collected during 138 visits. The overall contamination rate was 3.4% (38/1104) and was significantly higher for ESBL-KP than ESBL-EC (5.4% versus 0.4%; p < 0.0001). After multivariate analysis, environmental contamination was found to be negatively associated with carbapenem exposure (OR 0.06 [95% CI 0.01-0.61]; p = 0.017) and positively associated with the presence of an indwelling urinary catheter (OR 6.12 [95% CI 1.23-30.37]; p = 0.027) and ESBL-KP in the source patient (OR 26.23 [95% CI 2.70-254.67]; p = 0.005). CONCLUSIONS: Contamination of the hospital environment with ESBL-producing Enterobacteriaceae (ESBL-E) is inversely associated with carbapenem exposure. Predictors of hospital contamination with ESBL-E include: indwelling urinary catheters and ESBL-KP. Rooms of patients with ESBL-KP have substantially higher contamination rates than those with ESBL-EC. This finding may help explain the apparently higher transmissibility of ESBL-KP in the hospital setting.

Community-onset Escherichia coli infection resistant to expanded-spectrum cephalosporins in low-prevalence countries.

By global standards, the prevalence of community-onset expanded-spectrum-cephalosporin-resistant (ESC-R) Escherichia coli remains low in Australia and New Zealand. Of concern, our countries are in a unique position, with high extramural resistance pressure from close population and trade links to Asia-Pacific neighbors with high ESC-R E. coli rates. We aimed to characterize the risks and dynamics of community-onset ESC-R E. coli infection in our low-prevalence region. A case-control methodology was used. Patients with ESC-R E. coli or ESC-susceptible E. coli isolated from blood or urine were recruited at six geographically dispersed tertiary care hospitals in Australia and New Zealand. Epidemiological data were prospectively collected, and bacteria were retained for analysis. In total, 182 patients (91 cases and 91 controls) were recruited. Multivariate logistic regression identified risk factors for ESC-R among E. coli strains, including birth on the Indian subcontinent (odds ratio [OR]=11.13, 95% confidence interval [95% CI]=2.17 to 56.98, P=0.003), urinary tract infection in the past year (per-infection OR=1.430, 95% CI=1.13 to 1.82, P=0.003), travel to southeast Asia, China, the Indian subcontinent, Africa, and the Middle East (OR=3.089, 95% CI=1.29 to 7.38, P=0.011), prior exposure to trimethoprim with or without sulfamethoxazole and with or without an expanded-spectrum cephalosporin (OR=3.665, 95% CI=1.30 to 10.35, P=0.014), and health care exposure in the previous 6 months (OR=3.16, 95% CI=1.54 to 6.46, P=0.02). Among our ESC-R E. coli strains, the blaCTX-M ESBLs were dominant (83% of ESC-R E. coli strains), and the worldwide pandemic ST-131 clone was frequent (45% of ESC-R E. coli strains). In our low-prevalence setting, ESC-R among community-onset E. coli strains may be associated with both "export" from health care facilities into the community and direct "import" into the community from high-prevalence regions.

The Mark Coventry Award: Higher tissue concentrations of vancomycin with low-dose intraosseous regional versus systemic prophylaxis in TKA: a randomized trial.

BACKGROUND: In response to increasing antibiotic resistance, vancomycin has been proposed as an alternative prophylactic agent in TKA. However, vancomycin requires a prolonged administration time, risks promoting further antibiotic resistance, and can cause systemic toxicity. Intraosseous regional administration (IORA) is known to achieve markedly higher antibiotic concentrations than systemic administration and may allow the use of a lower vancomycin dose. QUESTIONS/PURPOSES: We assessed whether low-dose IORA vancomycin can achieve tissue concentrations equal or superior to those of systemic administration in TKA and compared complications between patients treated with IORA and intravenous vancomycin. METHODS: We randomized 30 patients undergoing primary TKA to receive 250 or 500 mg vancomycin via IORA or 1 g via systemic administration. IORA was performed as a bolus injection into a tibial intraosseous cannula below an inflated thigh tourniquet immediately before skin incision. Subcutaneous fat and bone samples were taken during the procedure and antibiotic concentrations measured. RESULTS: The overall mean tissue concentration of vancomycin in subcutaneous fat was 14 µg/g in the 250-mg IORA group, 44 µg/g in the 500-mg IORA group, and 3.2 µg/g in the systemic group. Mean concentrations in bone were 16 µg/g in the 250-mg IORA group, 38 µg/g in the 500-mg IORA group, and 4.0 µg/g in the systemic group. One patient in the systemic group developed red man syndrome during infusion. CONCLUSIONS: Low-dose IORA vancomycin results in tissue concentrations equal or superior to those of systemic administration. IORA optimizes timing of vancomycin administration, and the lower dose may reduce the risk of systemic side effects while providing equal or enhanced prophylaxis in TKA.

Bacteroides fragilis concealed in an infant with Escherichia coli meningitis.

Anaerobic meningitis in infants is rare, therefore a high index of clinical suspicion is essential as routine methods for processing cerebrospinal fluid (CSF) do not detect anaerobes and specific antimicrobial therapy is required. We present an infant with Escherichia coli meningitis where treatment-resistance developed in association with culture negative purulent CSF. These features should have alerted us to the presence of anaerobes, prompting a search for the causes of polymicrobial meningitis in infants.

Widespread dissemination of CTX-M-15 genotype extended-spectrum-ß-lactamase-producing enterobacteriaceae among patients presenting to community hospitals in the southeastern United States.

Extended-spectrum-ß-lactamase (ESBL)-producing organisms are increasingly prevalent. We determined the characteristics of 66 consecutive ESBL-producing isolates from six community hospitals in North Carolina and Virginia from 2010 to 2012. Fifty-three (80%) ESBL-producing isolates contained CTX-M enzymes; CTX-M-15 was found in 68% of Escherichia coli and 73% of Klebsiella isolates. Sequence type 131 (ST131) was the commonest type of E. coli, accounting for 48% of CTX-M-15-producing and 66% of CTX-M-14-producing isolates. In conclusion, the CTX-M genotype and ST131 E. coli were common among ESBL isolates from U.S. community hospitals.

Severe Clostridium difficile infection in New Zealand associated with an emerging strain, PCR-ribotype 244.

AIM: To compare disease severity and clinical outcome of Clostridium difficile infection (CDI) due to PCR-ribotype (RT) 244 with CDI due to other strains present in Auckland. METHOD: A retrospective, case-control study was conducted. Ten cases with CDI due to RT 244 were compared with 20 controls infected with other C. difficile strains. RT 244 isolates were further analysed for antimicrobial susceptibility, binary toxin genes and mutations in the tcdC gene. RESULTS: Cases were significantly more likely to have severe disease than controls (OR 9.33; p=0.015). 50% of cases had community-associated CDI compared with 15% of controls (p=0.078). All RT 244 isolates produced binary toxin and had a single-base pair deletion in tcdC at position 117. CONCLUSION: C. difficile RT 244 is a newly recognised strain in New Zealand. It shares several features that characterise RT 027. Given its propensity to cause severe community-associated disease, a heightened awareness of this strain is needed to ensure early testing in patients admitted from the community with identified risk factors for CDI.