Planning and executing a national point prevalence study: a blueprint for the future.

Healthcare-associated infections (HAIs) are a significant risk for patients and a burden on the health system. In 2021, the Te Tahu Hauora Health Quality & Safety Commission New Zealand Infection Prevention and Control Team undertook a national HAI point prevalence survey (PPS) across all 20 district health boards (DHBs). We describe the process that was undertaken to plan for and execute the PPS. The key stages of this project were planning, communication and engagement, piloting and then refining the process, training surveyors, delivering the full PPS, and finally, data analysis and reporting. Support for the PPS was received at a national level from clinical and non-clinical management. The sharing of this information may support other health provider groups to use similar methodology to better understand the epidemiology of both infectious and non-infectious diseases locally. It provides a useful planning strategy for those considering similar surveys.

Species distribution and susceptibility of Nocardia isolates in New Zealand 2002-2021.

The aim was to record the distribution and susceptibility of Nocardia species in New Zealand. Local and referred isolates were identified by an evolving approach over the study period including conventional phenotypic methods, susceptibility profiles, matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF) and molecular sequencing. Isolates previously identified as a Nocardia sp. or part of the N. asteroides complex were reidentified by MALDI-TOF and/or molecular methods. Antimicrobial susceptibility to eight antibiotics was performed by standard microbroth dilution. The site of isolation, susceptibility profiles and species distribution were analysed. A total of 383 isolates were tested: N. brasiliensis 23 (6%), N. cyriacigeorgica 42 (11%), N. farcinica 41 (11%), N. nova complex 226 (59%), and 51 (13%) other species/complexes. The respiratory tract was the most common site of infection (244, 64%), with skin and soft tissue the second most common site (104, 27%). All 23 N. brasiliensis isolates were from skin and soft tissue specimens. Almost all isolates (≥98%) were susceptible to amikacin, linezolid and trimethoprim-sulfamethoxazole; 35% and 77% were resistant to clarithromycin and quinolones, respectively. The expected susceptibility profiles of the four common species and complex were observed for most agent-organism parings. Multi-drug resistance was uncommon (3.4%). The spectrum of Nocardia species in New Zealand is similar to overseas reports and our most common group is the N. nova complex. While amikacin, linezolid and trimethoprim-sulfamethoxazole remain good empiric treatment choices, other agents should have their activity confirmed before use.

Complete Genome Sequence of a New Zealand Mycobacterium tuberculosis Strain Responsible for Ongoing Transmission over the Past 30 Years.

We report here the complete genome sequence of Mycobacterium tuberculosis strain Colonial S-type 1 (CS1), which has been responsible for ongoing outbreaks of tuberculosis in New Zealand over the past 30 years. CS1 appears to be highly transmissible, with greater rates of progression to active disease, compared to other circulating M. tuberculosis strains; therefore, comparison of its genomic content is of interest.

Sources of healthcare-associated Staphylococcus aureus bacteraemia in New Zealand acute hospitals.

AIM: The primary aim of this study was to identify the source of healthcare-associated Staphylococcus aureus bacteraemia (HA-SAB) in acute district health board (DHB) hospitals to inform future national quality improvement activities. METHOD: De-identified HA-SAB event source information was submitted to the Commission from all DHBs for the period 1 January 2017 to 30 June 2021. Data was categorised and analysed to identify trends and significant sources of infection. RESULTS: There were 1,867 HA-SAB events. Of the events where S. aureus susceptibility results were reported, 159 (10%) isolates were methicillin-resistant S. aureus. The principal sources of HA-SAB were medical devices (65%), surgical site infection (10%), and organ site (8%). Ninety-five percent of medical devices were for vascular access, primarily central venous catheters (50%) and peripheral intravenous catheters (45%). CONCLUSION: This study has identified intravascular devices as significant sources of HA-SAB. Ongoing surveillance for HA-SAB source is required to identify the major risk factors and to support quality improvement activities targeting infection prevention measures and best practice related to intravascular and other medical devices.

Risk factors differ for Gram-negative surgical site infection following hip and knee arthroplasty: an observational study from a national surveillance system.

AIM: To describe risk factors for surgical site infection (SSI) caused by aerobic Gram-negative organisms after hip and knee arthroplasty. METHOD: Publicly funded hip and knee arthroplasties (performed between 1 July 2013 and 31 December 2017) that developed SSIs were compared to those that did not. SSIs were grouped by causative organism: Gram-negative (Pseudomonas spp. or enteric Gram-negative bacilli) or staphylococcal (pure or mixed growth of Staphylococcus spp.). Independent risk factors in each group were identified. RESULTS: 24,842 (54%) hip and 20,993 (46%) knee arthroplasties were performed. There were 497 (1.1%) SSIs. Staphylococci were responsible for 233 SSIs (47%) and Gram-negatives were responsible for 73 (15%). Age, sex, body mass index ≥35kg/m2, smoking status, socioeconomic deprivation, American Society of Anesthesiologists classification, revision surgery and prophylactic antibiotic dose were all independent predictors of all-cause SSI. On subgroup analysis, socioeconomic deprivation and Pasifika ethnicity were independent risk factors for Gram-negative SSI, but not staphylococcal SSI. DISCUSSION: In this study, socioeconomic deprivation and ethnicity were independent and novel risk factors for Gram-negative SSI following arthroplasty. Some of the SSI risk factors can be modified before arthroplasty (e.g., appropriate timing of prophylactic antibiotics, smoking cessation, weight loss). Non-modifiable risk factors can help identify high-risk procedures where additional pre- and post-operative interventions may be warranted.

Comprehensive analysis of SARS-CoV-2 antibody dynamics in New Zealand.

OBJECTIVES: Circulating antibodies are important markers of previous infection and immunity. Questions remain with respect to the durability and functionality of SARS-CoV-2 antibodies. This study explored antibody responses in recovered COVID-19 patients in a setting where the probability of re-exposure is effectively nil, owing to New Zealand's successful elimination strategy. METHODS: A triplex bead-based assay that detects antibody isotype (IgG, IgM and IgA) and subclass (IgG1, IgG2, IgG3 and IgG4) responses against Nucleocapsid (N) protein, the receptor binding domain (RBD) and Spike (S) protein of SARS-CoV-2 was developed. After establishing baseline levels with pre-pandemic control sera (n = 113), samples from PCR-confirmed COVID-19 patients with mild-moderate disease (n = 189) collected up to 8 months post-infection were examined. The relationship between antigen-specific antibodies and neutralising antibodies (NAbs) was explored with a surrogate neutralisation assay that quantifies inhibition of the RBD/hACE-2 interaction. RESULTS: While most individuals had broad isotype and subclass responses to each antigen shortly after infection, only RBD and S protein IgG, as well as NAbs, were relatively stable over the study period, with 99%, 96% and 90% of samples, respectively, having responses over baseline 4-8 months post-infection. Anti-RBD antibodies were strongly correlated with NAbs at all time points (Pearson's r ≥ 0.87), and feasibility of using finger prick sampling to accurately measure anti-RBD IgG was demonstrated. CONCLUSION: Antibodies to SARS-CoV-2 persist for up to 8 months following mild-to-moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in our setting.

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.

Demographic and behavioural factors associated with antimicrobial susceptibility to azithromycin and ceftriaxone in Neisseria gonorrhoeae.

Antimicrobial resistance of Neisseria gonorrhoeae (NG) is of global public health concern. The aim of this study was to explore demographic and behavioural factors associated with antimicrobial susceptibility of NG to ceftriaxone and azithromycin. Gonococcal isolates (n = 391) from clients attending the Auckland Sexual Health Service, New Zealand, from July 2014 - June 2015 (n = 206), and July 2017 - June 2018 (n = 185), were tested for susceptibility to ceftriaxone and azithromycin. Laboratory data were linked with behavioural and demographic data. Geometric mean azithromycin MICs increased across the two time periods (0.239 mg/L in 2014/15 to 0.347 mg/L in 2017/18, p < 0.001), and ceftriaxone MICs decreased (0.007 mg/L in 2014/15 to 0.005 mg/L in 2017/18, p < 0.001). Demographic and behavioural factors were not associated with differences in ceftriaxone MICs; however azithromycin MICs were higher in men who have sex with men (0.356 mg/L) compared with the heterosexual study population (0.192 mg/L, p < 0.001) and were lower in Pacific peoples (0.201 mg/L, p < 0.001) and Maori (0.244 mg/L, p = 0.05) compared with those of European ethnicity (0.321 mg/L). Our findings show that azithromycin MICs increased in our region between 2014 and 2018; associations were seen with sexual orientation and ethnicity.

Collaborative networks enable the rapid establishment of serological assays for SARS-CoV-2 during nationwide lockdown in New Zealand.

BACKGROUND: Serological assays that detect antibodies to SARS-CoV-2 are critical for determining past infection and investigating immune responses in the COVID-19 pandemic. We established ELISA-based immunoassays using locally produced antigens when New Zealand went into a nationwide lockdown and the supply chain of diagnostic reagents was a widely held domestic concern. The relationship between serum antibody binding measured by ELISA and neutralising capacity was investigated using a surrogate viral neutralisation test (sVNT). METHODS: A pre-pandemic sera panel (n = 113), including respiratory infections with symptom overlap with COVID-19, was used to establish assay specificity. Sera from PCR­confirmed SARS-CoV-2 patients (n = 21), and PCR-negative patients with respiratory symptoms suggestive of COVID-19 (n = 82) that presented to the two largest hospitals in Auckland during the lockdown period were included. A two-step IgG ELISA based on the receptor binding domain (RBD) and spike protein was adapted to determine seropositivity, and neutralising antibodies that block the RBD/hACE­2 interaction were quantified by sVNT. RESULTS: The calculated cut-off (>0.2) in the two-step ELISA maximised specificity by classifying all pre-pandemic samples as negative. Sera from all PCR-confirmed COVID-19 patients were classified as seropositive by ELISA ≥7 days after symptom onset. There was 100% concordance between the two-step ELISA and the sVNT with all 7+ day sera from PCR­confirmed COVID-19 patients also classified as positive with respect to neutralising antibodies. Of the symptomatic PCR-negative cohort, one individual with notable travel history was classified as positive by two-step ELISA and sVNT, demonstrating the value of serology in detecting prior infection. CONCLUSIONS: These serological assays were established and assessed at a time when human activity was severely restricted in New Zealand. This was achieved by generous sharing of reagents and technical expertise by the international scientific community, and highly collaborative efforts of scientists and clinicians across the country. The assays have immediate utility in supporting clinical diagnostics, understanding transmission in high-risk cohorts and underpinning longer­term 'exit' strategies based on effective vaccines and therapeutics.

Circadian rhythm in negative affect: Implications for mood disorders.

In humans, there is an endogenous, near 24-h (i.e., circadian) variation in mood with the best mood occurring during the circadian day and the worst mood occurring during the circadian night. Only positive affect, and not negative affect, has been shown to contribute to this circadian rhythm. We discovered a sharp circadian peak in negative affect during the circadian night coincident with a circadian trough in positive affect. These findings may help explain the association of depression with insomnia, the increased risk of suicide with nocturnal wakefulness, and the correlation between circadian misalignment and symptom severity in Major Depressive Disorder.

Surgical site infection rate is higher following hip and knee arthroplasty when cefazolin is underdosed.

PURPOSE: While many guidelines recommend higher doses of cefazolin for patients with higher body weights, there are scant outcome data showing the benefit of higher doses. Surgical site infection (SSI) rates by dose of cefazolin used for surgical prophylaxis after hip or knee arthroplasty were analyzed. METHODS: Analysis of patient data entered into New Zealand's national, prospective, surveillance and quality improvement SSI Improvement Programme database for the period July 2013 through December 2017 was conducted. The US Centers for Disease Control and Prevention's National Healthcare Safety Network SSI definitions were used, and patients were followed for 90 days after surgery. Underdosing was defined as use of 1 g of cefazolin in patients weighing 80 kg or more or a cefazolin dose of <3 g in those weighing 120 kg or more. RESULTS: There were 38,288 procedures where cefazolin was used for prophylaxis; patient body weight was known for all these procedures. Of the 1,840 patients who received 1 g of cefazolin, 676 (37%) weighed 80 kg or more. Of the 2,011 patients weighing 120 kg or more, 1,464 (73%) were underdosed. After multivariable analysis, male gender, higher total surgical risk scores, performance of revision and hip arthroplasties, and cefazolin underdosing were associated with higher SSI rates. For the 2,106 underdosed patients, the odds ratio for SSI was 2.19 (95% confidence interval, 1.61-2.99; P < 0.0001). The number of higher-weight patients needed to treat to prevent 1 SSI was 83, with an estimated cost of 35 kg/m2 or >40 kg/m2) remains unanswered.

Aerococcus urinae Aortitis: A Case Report.

BACKGROUND: Aerococcus urinae is a Gram-positive coccus that is increasingly recognized as a urinary pathogen since the introduction of mass spectrometry for identification of bacteria. We report a case of abdominal aortitis (with aneurysm) caused by A urinae in a male with recurrent urinary tract infections and recently treated A urinae bacteremia. A 63-year-old gentleman with a history of A urinae urosepsis 7 weeks prior, presented to the Emergency Department with thoracolumbar back pain radiating bilaterally into the groin. Radiological and surgical findings were consistent with infective infrarenal aortitis with aneurysm. METHODS: The patient successfully underwent open surgical debridement and reconstruction of the infrarenal aorta with autologous vein graft. RESULTS: Aerococcus urinae was isolated from excised tissue. The patient completed a 4-week course of intravenous antimicrobial therapy. CONCLUSIONS: Aurinae is a urinary pathogen with the ability to cause severe invasive disease including endovascular infections.

Variability in Azithromycin Susceptibility Results for Neisseria gonorrhoeae Obtained Using Gradient MIC Strip and Agar Dilution Techniques.

Azithromycin is a component of empirical treatment regimens for Neisseria gonorrhoeae infections, but antimicrobial susceptibility testing for this agent is technically challenging. We compared the intertest variability, MIC values, and CLSI/EUCAST categorization of clinical and reference isolates of N. gonorrhoeae treated with azithromycin by testing 107 clinical isolates and nine reference isolates by agar dilution and in duplicates using MIC test strips (Liofilchem, Italy) and Etests (bioMérieux, France). Replicate isolate agreement within 1 log2 between duplicate tests was 87% for MIC test strips and 100% for Etests (P < 0.001). Essential agreement with the agar dilution method was higher for Etests (91%) than for MIC test strips (44%, P < 0.001). The geometric mean MIC was highest for MIC test strips (0.8 mg/liter) and significantly higher than both Etest (0.47 mg/liter, P < 0.001) and agar dilution (0.26 mg/liter, P < 0.001) methods. Etest MICs were higher than those obtained with agar dilution (P < 0.001). Agar dilution, MIC test strip, and Etest methods categorized 96%, 85%, and 95% (P = 0.003) of clinical isolates, respectively, as susceptible/wild type according to CLSI/EUCAST criteria. Our results illustrate the difficulties underlying azithromycin susceptibility testing for N. gonorrhoeae and demonstrate that results can vary using different methods. This variability could influence antimicrobial resistance reporting between laboratories involved in N. gonorrhoeae surveillance programs.

The burden of Legionnaires' disease in New Zealand (LegiNZ): a national surveillance study.

BACKGROUND: Legionnaires' disease is under-diagnosed because of inconsistent use of diagnostic tests and uncertainty about whom to test. We assessed the increase in case detection following large-scale introduction of routine PCR testing of respiratory specimens in New Zealand. METHODS: LegiNZ was a national surveillance study done over 1-year in which active case-finding was used to maximise the identification of cases of Legionnaires' disease in hospitals. Respiratory specimens from patients of any age with pneumonia, who could provide an eligible lower respiratory specimen, admitted to one of 20 participating hospitals, covering a catchment area of 96% of New Zealand's population, were routinely tested for legionella by PCR. Additional cases of Legionnaires' disease in hospital were identified through mandatory notification. FINDINGS: Between May 21, 2015, and May 20, 2016, 5622 eligible specimens from 4862 patients were tested by PCR. From these, 197 cases of Legionnaires' disease were detected. An additional 41 cases were identified from notification data, giving 238 cases requiring hospitalisation. The overall incidence of Legionnaires' disease cases in hospital in the study area was 5·4 per 100 000 people per year, and Legionella longbeachae was the predominant cause, found in 150 (63%) of 238 cases. INTERPRETATION: The rate of notified disease during the study period was three-times the average over the preceding 3 years. Active case-finding through systematic PCR testing better clarified the regional epidemiology of Legionnaires' disease and uncovered an otherwise hidden burden of disease. These data inform local Legionnaires' disease testing strategies, allow targeted antibiotic therapy, and help identify outbreaks and effective prevention strategies. The same approach might have similar benefits if applied elsewhere in the world. FUNDING: Health Research Council of New Zealand.

Group B Streptococcus in surgical site and non-invasive bacterial infections worldwide: A systematic review and meta-analysis.

OBJECTIVES: The epidemiology of disease caused by group B Streptococcus (GBS; Streptococcus agalactiae) outside pregnancy and the neonatal period is poorly characterized. The aim of this study was to quantify the role of GBS as a cause of surgical site and non-invasive infections at all ages. METHODS: A systematic review (PROSPERO CRD42017068914) and meta-analysis of GBS as a proportion (%) of bacterial isolates from surgical site infection (SSI), skin/soft tissue infection (SSTI), urinary tract infection (UTI), and respiratory tract infection (RTI) was conducted. RESULTS: Seventy-four studies and data sources were included, covering 67 countries. In orthopaedic surgery, GBS accounted for 0.37% (95% confidence interval (CI) 0.08-1.68%), 0.87% (95% CI 0.33-2.28%), and 1.46% (95% CI 0.49-4.29%) of superficial, deep, and organ/space SSI, respectively. GBS played a more significant role as a cause of post-caesarean section SSI, detected in 2.92% (95% CI 1.51-5.55%), 1.93% (95% CI 0.97-3.81%), and 9.69% (95% CI 6.72-13.8%) of superficial, deep, and organ/space SSI. Of the SSTI isolates, 1.89% (95% CI 1.16-3.05%) were GBS. The prevalence of GBS in community and hospital UTI isolates was 1.61% (1.13-2.30%) and 0.73% (0.43-1.23%), respectively. GBS was uncommonly associated with RTI, accounting for 0.35% (95% CI 0.19-0.63%) of community and 0.27% (95% CI 0.15-0.48%) of hospital RTI isolates. CONCLUSIONS: GBS is implicated in a small proportion of surgical site and non-invasive infections, but a substantial proportion of invasive SSI post-caesarean section.

Separate and interacting effects of the endogenous circadian system and behaviors on plasma aldosterone in humans.

Measurements of aldosterone for diagnosis of primary aldosteronism are usually made from blood sampled in the morning when aldosterone typically peaks. We tested the relative contributions and interacting influences of the circadian system, ongoing behaviors, and prior sleep to this morning peak in aldosterone. To determine circadian rhythmicity and separate effects of behaviors on aldosterone, 16 healthy participants completed a 5-day protocol in dim light while all behaviors ranging from sleep to exercise were standardized and scheduled evenly across the 24-h circadian period. In another experiment, to test the separate effects of prior nocturnal sleep or the inactivity that accompanies sleep on aldosterone, 10 healthy participants were studied across 2 nights: 1 with sleep and 1 with maintained wakefulness (randomized order). Plasma aldosterone was measured repeatedly in each experiment. Aldosterone had a significant endogenous rhythm ( P < 0.001), rising across the circadian night and peaking in the morning (~8 AM). Activity, including exercise, increased aldosterone, and different behaviors modulated aldosterone differently across the circadian cycle (circadian phase × behavior interaction; P < 0.001). In the second experiment, prior nocturnal sleep and prior rested wakefulness both increased plasma aldosterone ( P < 0.001) in the morning, to the same extent as the change in circadian phases between evening and morning. The morning increase in aldosterone is due to effects of the circadian system plus increased morning activities and not prior sleep or the inactivity accompanying sleep. These findings have implications for the time of and behaviors preceding measurement of aldosterone, especially under conditions of shift work and jet lag.

Dispersal of Mycobacterium tuberculosis Driven by Historical European Trade in the South Pacific.

Mycobacterium tuberculosis (Mtb) is a globally distributed bacterial pathogen whose population structure has largely been shaped by the activities of its obligate human host. Oceania was the last major global region to be reached by Europeans and is the last region for which the dispersal and evolution of Mtb remains largely unexplored. Here, we investigated the evolutionary history of the Euro-American L4.4 sublineage and its dispersal to the South Pacific. Using a phylodynamics approach and a dataset of 236 global Mtb L4.4 genomes we have traced the origins and dispersal of L4.4 strains to New Zealand. These strains are predominantly found in indigenous Maori and Pacific people and we identify a clade of European, likely French, origin that is prevalent in indigenous populations in both New Zealand and Canada. Molecular dating suggests the expansion of European trade networks in the early 19th century drove the dispersal of this clade to the South Pacific. We also identify historical and social factors within the region that have contributed to the local spread and expansion of these strains, including recent Pacific migrations to New Zealand and the rapid urbanization of Maori in the 20th century. Our results offer new insight into the expansion and dispersal of Mtb in the South Pacific and provide a striking example of the role of historical European migrations in the global dispersal of Mtb.

Utility of whole genome sequencing for multidrug resistant Mycobacterium tuberculosis isolates in a reference TB laboratory in New Zealand.

New Zealand has a low burden of multi-drug resistant TB (MDR-TB), but with increased mobility within the population, rapid detection and treatment of MDR-TB is a priority from the public health point of view. Mycobacterium Reference Laboratory in LabPLUS, Auckland City Hospital receives referred Mycobacterium tuberculosis complex (MTBC) isolates from all over New Zealand for second-line drug susceptibility testing (DST) and 24-loci MIRU VNTR genotyping. Between 2002 and 2013, 38 multidrug resistant Mycobacterium tuberculosis (MDR-TB) isolates were recorded by culture-based DST. A retrospective study revealed that in 12 of these 38 MDR-TB isolates (28%) there was a discrepancy between the genotypic and the phenotypic results. In order to address this, whole genome sequencing (WGS) was performed on the discrepant MDR-TB isolates. Reported here are the additional information on the drug resistant markers from WGS, which shed light on the discordance between results from the culture-based DST and the molecular diagnostic tests. These results underscore the utility of WGS in a reference mycobacterium laboratory in New Zealand to supplement other molecular tests and to assist in a rapid but accurate diagnosis and appropriate management of MDR-TB.