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Group A Streptococcus (GAS) pharyngitis is a key initiator of acute rheumatic fever (ARF). In New Zealand, ARF cases occur more frequently among persons of certain ethnic and socioeconomic groups. We compared GAS pharyngitis estimates (1,257,058 throat swab samples) with ARF incidence (792 hospitalizations) in Auckland during 2010–2016. Among children 5–14 years of age in primary healthcare clinics, GAS pharyngitis was detected in similar proportions across ethnic groups (≈19%). Relative risk for GAS pharyngitis was moderately elevated among children of Pacific Islander and Māori ethnicities compared with those of European/other ethnicities, but risk for ARF was highly elevated for children of Pacific Islander and Māori ethnicity compared with those of European/other ethnicity. That ethnic disparities are much higher among children with ARF than among those with GAS pharyngitis implies that ARF is driven by factors other than rate of GAS pharyngitis alone.

SummaryDuring the first wave of SARS-CoV-2 infection in New Zealand a cohort of 78 PCR-confirmed COVID-19 cases was recruited in the Southern District Health Board region. Here we report on this unique cohort nearly 1-year after infection. There was no known community transmission in the region over the study period due to New Zealand’s elimination status at the time, nor had any participants received a COVID-19 vaccine. In the absence of re-exposure, antibody reactivity to the viral spike protein, as well as neutralising antibodies to both the ancestral strain and the delta variant remained relatively stable between 8 and 11 months post-infection. This suggests long-lived antibody responses can be generated from a single natural infection event. However, given the risks of serious disease associated with SARS-CoV-2 infection, vaccination is still strongly recommended.

Testing and treatment for Mycoplasma genitalium (MG) infections has recently been facilitated by the increasing availability of molecular tests, but the role of testing in community-based populations is not established. Between 15 May 2017 and 22 November 2017, we tested 561 samples from 547 individuals presenting to primary care in Auckland, New Zealand, requesting investigation for sexually transmitted infections, with concurrent sterile pyuria, using the Aptima MG assay (Hologic, San Diego, CA, USA) in order to establish the prevalence of MG in this group, rates of macrolide resistance and audit primary care’s capacity to manage infections in line with international guidelines. MG was detected in 55 (10%) samples, and co-pathogens were detected in 24 (44%) MG-positive samples. Macrolide resistance mutations were detected in 22/36 (61%) samples subsequently tested using PlexPCR M. genitalium ResistancePlus (Speedx Pvt Ltd., Sydney, Australia). Empiric azithromycin treatment was given to 18 (33%) patients, and test of cure was performed in 15 (27%) patients. Our pilot study demonstrates that sterile pyuria can be a useful marker to direct testing resources in community settings, but highlights important barriers to management of MG in primary care, including clinician knowledge, high prevalence of macrolide resistance and poor completion rates for test of cure.

BackgroundDuring New Zealand’s first outbreak in early 2020 the Southern Region had the highest per capita SARS-CoV-2 infection rate. PCR testing was initially limited by a narrow case definition and limited laboratory capacity, so cases may have been missed.ObjectivesTo evaluate the Abbott® SARS-CoV-2 IgG nucleocapsid assay, alongside spike-based assays, and to determine the frequency of antibodies among PCR-confirmed and probable cases, contacts, and higher risk individuals in the Southern Region of NZ.Study designPre-pandemic sera (n=300) were used to establish assay specificity and sera from PCR-confirmed SARS-CoV-2 patients (n=78) to establish sensitivity. For prevalence analysis, all samples (n=1214) were tested on the Abbott assay, and all PCR-confirmed cases (n=78), probable cases (n=9), and higher risk individuals with grey-zone (n=14) or positive results (n=11) were tested on four additional SARS-CoV-2 serological assays.ResultsThe median time from infection onset to serum collection for PCR-confirmed cases was 14 weeks (range 11-17 weeks). The Abbott assay demonstrated a specificity of 99.7% (95% CI, 98.2%-99.99%) and a sensitivity of 76.9% (95% CI, 66.0%-85.7%). Spike-based assays demonstrated superior sensitivity ranging 89.7-94.9%. Nine previously undiagnosed sero-positive individuals were identified, and all had epidemiological risk factors.ConclusionsSpike-based assays demonstrated higher sensitivity than the Abbott IgG assay, likely due to temporal differences in antibody persistence. No unexpected SARS-CoV-2 infections were found in the Southern region of NZ, supporting the elimination status of the country at the time this study was conducted.

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., This study shows that 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 New Zealand. The figure was created with BioRender.com.

ObjectivesCirculating 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.MethodsA triplex bead-based assay that detects antibody isotype (IgG, IgM and IgA) and subclass (IgG1, IgG2, IgG3, IgG4) responses against Nucleocapsid (N) protein, 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 eight 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.ResultsWhile 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 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.ConclusionAntibodies to SARS-CoV-2 persist for up to eight 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.

Streptococcal serology is a cornerstone in the diagnosis of acute rheumatic fever (ARF), a postinfectious sequela associated with group A Streptococcus infection. Current tests that measure anti-streptolysin O (ASO) and anti-DNaseB (ADB) titers require parallel processing, with their predictive value limited by the low rate of decay in antibody response. Accordingly, our objective was to develop and assess the diagnostic potential of a triplex bead-based assay, which simultaneously quantifies ASO and ADB together with titers for a third antigen, SpnA. Our previous cytometric bead assay was transferred to the clinically appropriate Luminex platform by coupling streptolysin O, DNaseB, and SpnA to spectrally unique magnetic beads. Sera from more than 350 subjects, including 97 ARF patients, were used to validate the assay and explore immunokinetics. Operating parameters demonstrate that the triplex assay produces accurate and reproducible antibody titers which, for ASO and ADB, are highly correlative with existing assay methodology. When ARF patients were stratified by time (days following hospital admission), there was no difference in ASO and ADB between

To assess whether trimethoprim remains an appropriate empiric treatment for uncomplicated cystitis in women 15-55 years old.General practitioners in Auckland, Nelson-Marlborough, Otago and Southland were invited to participate in this audit of current practice. Participating general practitioners were asked to submit urine to the laboratory for microscopy and culture from any woman aged 15-55 years presenting with uncomplicated cystitis. Urine samples submitted as part of the audit were identified by a "copy to" code. Data on laboratory results were extracted from the laboratory information system.Data were collected from June 2016 to August 2018. Four hundred and eighty-one samples were submitted, of which 340 (70.7%) met the inclusion criteria of the audit. A urinary pathogen was identified in 181 (53.2%) specimens, of which 148 (81.8%) were E. coli, 13 (7.2%) other coliforms and 20 (11.0%) Staphylococcus saprophyticus. Of the E. coli isolates, 109 of 148 (73.6%, 95% CI 66.6-80.7) were susceptible to trimethoprim, 144 of 144 (100%, 95% CI 100-100) to nitrofurantoin and 143 of 148 (96.6%, 95% CI 93.7-99.5) to cefalexin. Of the urinary pathogens, 139 of 185 (75.1%, 95% CI 68.9-81.4) were susceptible to trimethoprim, 164 of 177 tested (92.7%, 95% CI 88.8-96.5) to nitrofurantoin and 166 of 178 tested (93.3%, 95% CI 89.6-96.9) to cefalexin. Overall, a uropathogen resistant to trimethoprim was detected in 13.5%, to nitrofurantoin in 3.8%, and to cefalexin in 3.5% of samples tested.Similar rates of resistance to trimethoprim were seen in women 15-55 years old presenting with cystitis compared with unselected samples submitted from the general community. Given the high rates of resistance, trimethoprim is no longer appropriate as an empiric treatment option for cystitis in this group. Nitrofurantoin or cefalexin are appropriate alternative empiric treatment options. Given the current recommendation that a urine sample should not be submitted to the laboratory from women with uncomplicated cystitis, ongoing audits will be required to ensure that empiric treatment recommendations remain appropriate.

Background Warfarin remains a commonly used anticoagulant for the treatment and prevention of thrombosis. To balance the risks and benefits of therapy, monitoring of the international normalised ratio (INR) is necessary. Patients derive most benefit from warfarin when they spend ≥65% of time in the therapeutic range (INR 2-3). We performed an analysis of INR monitoring for the Auckland and Northland regions of New Zealand in order to estimate anticoagulation control and appropriateness of testing at the population level. Methods INR test results and patient demographics (age and sex) were extracted from the laboratory information system of Labtests and Northland Pathology Laboratories for the period of 1 January 2016 to 27 July 2016. Results We included 126 184 INR results from 10 922 patients. The median age of patients represented was 74 years and 57% were male. The overall mean time in therapeutic range was 63%, with a mean interval between INR tests of 14 days. Conclusion Our results indicate that anticoagulant control in our communities could be improved, and that inappropriately frequent INR testing should be redressed. Appropriate interventions could lead to net clinical benefits and reduce resource misallocation.

BACKGROUND The relentless emergence and spread of strains of Neisseria gonorrhoeae that are resistant to many antimicrobial agents has led to frequent changes in treatment guidelines, with a consequent risk that prescribers may not be aware of current guidelines. AIM To determine the proportion of patients with gonorrhoea who were treated with a regimen consistent with the New Zealand Sexual Health Society (NZSHS) guidelines. METHODS We audited the treatment given to adult patients with laboratory-proven gonorrhoea in Auckland, New Zealand, during the first 6 months of 2015. RESULTS Treatment compliant with the current NZSHS guidelines was administered in only 65% (458/706) episodes overall. Guideline-compliant treatment was much more likely to be prescribed for patients who presented to a sexual health clinic (89%) than for patients who presented to either a general practice or other community clinic (52%) or to a hospital (56%) (P

Streptococcal serology is a cornerstone in the diagnosis of acute rheumatic fever (ARF), a postinfectious sequela associated with group A Streptococcus infection. Current tests that measure anti-streptolysin O (ASO) and anti-DNaseB (ADB) titers require parallel processing, with their predictive value limited by the low rate of decay in antibody response. Accordingly, our objective was to develop and assess the diagnostic potential of a triplex bead-based assay, which simultaneously quantifies ASO and ADB together with titers for a third antigen, SpnA. Our previous cytometric bead assay was transferred to the clinically appropriate Luminex platform by coupling streptolysin O, DNaseB, and SpnA to spectrally unique magnetic beads. Sera from more than 350 subjects, including 97 ARF patients, were used to validate the assay and explore immunokinetics. Operating parameters demonstrate that the triplex assay produces accurate and reproducible antibody titers which, for ASO and ADB, are highly correlative with existing assay methodology. When ARF patients were stratified by time (days following hospital admission), there was no difference in ASO and ADB between

Molecular screening has increased detection of Shiga-toxin producing Escherichia coli (STEC). However, it is difficult to isolate the organism for epidemiological typing. We applied a molecular method for direct detection of nine O types from 110 stx positive faeces samples and compared the results with conventional isolate based methods. Using conventional methods 55/110 (50%) samples were O typed. Using the molecular method, 72/110 (65%) were O typed, including 23/38 (61%) culture negative samples. Combining both techniques typed 88/110 (80%) of samples. Molecular typing increased detection of O128 (2-25%, p

Background Group A Streptococcus (GAS) can trigger an immune-mediated response resulting in acute rheumatic fever (ARF). Historically, ARF has been considered a consequence of preceding GAS pharyngitis, but increasing evidence suggests that GAS skin infections may be a driver. Data on the primary care burden of GAS skin infection are limited. This paper aims to describe and compare the prevalence and distribution of GAS detection in skin swabs and ARF rates in the Auckland population. Methods This cross-sectional study used all laboratory skin swab data from people who had a skin swab taken as a result of a consultation with a health professional in the Auckland region (2010–2016). Initial primary hospitalisations for ARF were identified and all data were linked using unique patient identifiers to patient's age, prioritised ethnicity, sex, and socio-economic status. Findings 377,410 skin swabs from 239,494 individuals were included. 12·8% of swabs were GAS positive, an annual incidence of 4·8 per 1,000 person-years. Māori and Pacific Peoples under 20 years of age had markedly higher GAS detection in skin swabs (RR 4·0; 95% CI 3·9–4·2: RR 6·8; 95% CI 6·6–7·0) and significantly higher ARF rates (RR 30·3; 95% CI 19·5–46·9: RR 69·7 95% CI 45·8–106·1) compared with European/Other ethnicities. Interpretation The observation that GAS detection was markedly higher in Māori and Pacific Peoples provides a potential explanation for the marked ethnic differences in ARF. These findings support a greater focus on addressing the burden of skin infection in NZ, including as ARF prevention. Funding The first author received a training stipend from the New Zealand College of Public Health Medicine (NZCPHM) during her Masters of Public Health.

BACKGROUND:The anterior nares are regarded as the primary site for Staphylococcus aureus colonization, although studies have highlighted the potential importance of colonization at extra-nasal sites, including the oropharynx. Accordingly, the aims of this study were to assess the prevalence, persistence and molecular epidemiology of S. aureus colonization in the nares and oropharynx of Māori and Pacific children, a population with strikingly high rates of S. aureus infection.METHODS:A cross-sectional study of predominantly Māori and Pacific school-aged children in Auckland, New Zealand was performed in October 2013, and swabs were taken from the nares and oropharynx. Sampling was repeated from the same schools in October 2014. All S. aureus isolates underwent antimicrobial susceptibility testing and spa typing.RESULTS:Overall, 506/893 (56.7%) children were colonized with S. aureus, and the colonization prevalence was significantly higher in the oropharynx than nares (41.1% vs. 31.5%; P < 0.001). Longitudinal colonization was significantly higher in the oropharynx than the nares, and children with longitudinal oropharyngeal colonization were more likely to be colonized with the same spa type than those colonized in the nares (67.6% vs. 37.0%; P = 0.01). Approximately 40% of children had discordant spa types at the nares and oropharynx.CONCLUSIONS:Oropharyngeal S. aureus colonization represents a significant reservoir of S. aureus and it is possible that the oropharynx may represent a protected anatomical niche, enabling persistent colonization with the same S. aureus strain. Future study should attempt to better understand the determinants of oropharyngeal carriage.

ABSTRACT INTRODUCTION The faecal immunochemical test (FIT) detects small quantities of human haemoglobin in faeces. This test has increasingly become the screening tool of choice in bowel cancer screening programmes worldwide, including New Zealand’s upcoming national screening programme. AIM This study audited the appropriate use of faecal immunochemical tests (FIT) in general practice as current recommendations discourage the use of FIT outside the National Bowel Screening Programme. METHODS Data on all FIT requested by a multiclinic general practice serving 16000 patients from May 2017 to May 2018 were extracted from clinical records. Patient characteristics, results of tests, clinical rationale for the test, number of referrals and results and the completeness of clinical evaluation were recorded. RESULTS In all, 184 patients received an FIT, with 13 (7.1%) positive and 145 (78.8%) negative tests, and 26 (14.1%) tests declined by the laboratory. Nine patients (69.2%) with a positive FIT, 12 patients (8.1%) with a negative FIT and one patient (3.8%) with a declined test were referred to gastroenterology services. Seven colorectal cancers were detected, all in patients with a positive FIT who were aged between 67 and 91 years. FIT was requested most for changes in bowel habit (53%) and blood in stool (15%); 10% of tests were ordered for reassurance and 9% did not record an indication for the test. Two general practitioners (of 17 in the practice) accounted for over half of all tests requested. CONCLUSIONS Because FIT is only a screening tool for colorectal cancer, direct referral is recommended for symptomatic patients. Although cancers were detected only in patients with positive FITs, these patients would have qualified for direct referral for definitive investigation, and a referral was made concurrently. Awaiting test results may also delay necessary referrals and a negative FIT may produce false reassurance.

Group A streptococcal (GAS) pharyngitis is a particularly important condition in areas of New Zealand where the incidence of acute rheumatic fever remains unacceptably high. Prompt diagnosis and treatment of GAS pharyngitis are cornerstones of the Rheumatic Fever Prevention Programme, but these are hindered by the turnaround time of culture. Tests with excellent performance and rapid turnaround times are needed. For this study, throat swabs (Copan ESwabs) were collected from schoolchildren self-identifying with a sore throat. Samples were tested by routine culture and the illumigene GAS assay using loop-mediated isothermal amplification. Discrepant results were resolved by retesting of the same specimen by an alternative molecular assay. Seven hundred fifty-seven throat swab specimens were tested by both methods. The performance characteristics of the illumigene assay using culture on blood agar as the “gold standard” and following discrepancy analysis were as follows: sensitivity, 82% and 87%, respectively; specificity, 93% and 98%, respectively; positive predictive value, 61% and 88%, respectively; and negative predictive value, 97% and 97%, respectively. In our unique setting of a school-based throat swabbing program, the illumigene assay did not perform quite as well as described in previous reports. Despite this, its improved sensitivity and rapid turnaround time compared with those of culture are appealing.

Trichomonas vaginalis (TV) prevalence varies among different communities and peoples. The availability of robust molecular platforms for the detection of TV has advanced diagnosis; however, molecular tests are more costly than phenotypic methodologies, and testing all urogenital samples is costly. We recently replaced culture methods with the Aptima Trichomonas vaginalis nucleic acid amplification test on specific request and as reflex testing by the laboratory, and have audited this change.Data were collected from August 2015 (microbroth culture and microscopy) and August 2016 (Aptima TV assay) including referrer, testing volumes, results and test cost estimates.In August 2015, 10,299 vaginal swabs, and in August 2016, 2,189 specimens (urogenital swabs and urines), were tested. The positivity rate went from 0.9% to 5.3%, and overall more TV infections were detected in 2016. The number needed to test and cost for one positive TV result respectively was 111 and $902.55 in 2015, and 19 and $368.92 in 2016. Request volumes and positivity rates differed among referrers.The methodology change was associated with higher overall detection of TV, and reductions in the numbers needed to test/cost for one TV diagnosis. Our audit suggests that there is room for improvement with TV test requesting in our community.

Our aim was to assess national prescribing trends and determine longitudinal resistance patterns for topical antimicrobials in New Zealand. We observed a dramatic increase in fusidic acid (FA) resistance, and clonal expansion of FA-resistant Staphylococcus aureus. This increase was concurrent with a significant national increase in topical FA dispensing.

The relentless emergence and spread of strains of Neisseria gonorrhoeae that are resistant to many antimicrobial agents has led to frequent changes in treatment guidelines, with a consequent risk that prescribers may not be aware of current guidelines.To determine the proportion of patients with gonorrhoea who were treated with a regimen consistent with the New Zealand Sexual Health Society (NZSHS) guidelines.We audited the treatment given to adult patients with laboratory-proven gonorrhoea in Auckland, New Zealand, during the first 6 months of 2015.Treatment compliant with the current NZSHS guidelines was administered in only 65% (458/706) episodes overall. Guideline-compliant treatment was much more likely to be prescribed for patients who presented to a sexual health clinic (89%) than for patients who presented to either a general practice or other community clinic (52%) or to a hospital (56%) (P 0.0001). Overall, 52 of 706 (7%) episodes were not treated with any antimicrobial regimen by the service that diagnosed the patients' gonorrhoea, 13 of 62 (21%) episodes in patients who presented to a hospital, 34 of 403 (8%) episodes in patients who presented to a general practice or other community clinic and 5 of 241 (2%) episodes in patients who presented to a sexual health clinic (P 0.0001).Low levels of compliance with treatment guidelines increase the risk that antibiotic-resistant strains of N. gonorrhoeae will spread within the Auckland region. Improved compliance with treatment guidelines, particularly in patients who present either to general practice or to hospitals, is necessary to maintain the efficacy of current treatment regimens.

We sought to verify the performance of the EntericBio real-time Gastro Panel 2 (GP2; Serosep, Ireland) assay targeting Salmonella, Shigella, Campylobacter, verotoxin producing E. coli (VTEC), Giardia, and Cryptosporidium in a high-throughput diagnostic laboratory. Following a technical verification period where 237 faecal samples were tested in parallel, guided culture and discrepancy analysis were performed. A total of 13,223 faecal samples were screened by the GP2 assay. During technical verification, sensitivity, specificity, negative and positive predictive value of the GP2 assay compared with conventional methods were 100% (83-100%), 98% (96.7-98.2%), 100% (98.5-100%), and 82.6% (69-83%), respectively. With guided culture, specificity (99.4-100%) and positive predictive value (15-100%) varied by target. Challenges with interpretation of results, particularly for VTEC, Shigella and Salmonella, are discussed.

We report a case of disseminated isoniazid-resistant tuberculosis in an immunocompromised patient with evolution of rifampin (rifampicin) resistance in the central nervous system. This was cured with intraventricular and oral treatment but was followed by a late relapse of the original infection in a prosthetic hip joint. We provide drug levels in cerebrospinal fluid and serum.

Invasive fungal infections are now a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT) [1-3]. After the introduction of fluconazole prophylaxis in the 1990s, the incidence of candidemia decreased, coinciding with the emergence of invasive mold infections (IMIs), particularly invasive aspergillosis (IA) [1, 4]. The epidemiology of IMI continues to evolve; recently, the emergence of non-Aspergillus molds, such as Zygomycetes, Fusarium species, and Scedosporium species, has been noted [5-8]. Although the clinical risk factors associated with IA (e.g., underlying disease and graft-versus-host disease [GVHD]) during different periods after HSCT have been described, we have little understanding of the biological basis of clinical associations [1, 6, 9-11]. For instance, results of more-recent studies suggest that at least some of the variables associated with specific underlying diseases and other conditions, such as severe GVHD, surpass pharmacological immune suppression and include quantifiable “biological factors” that might impact immunity, such as iron overload, diabetes, and malnutrition [12-14]. These risk factors are recognized by laboratory tests and, therefore, may enable development of more-tailored preventative strategies. Specific goals of this study were (1) to analyze risk factors associated with the development of IMI after allogeneic HSCT, including risk factors for the development of infection due to non-Aspergillus molds; (2) to differentiate risk factors for early IMI from risk factors for late IMI; and (3) to evaluate the impact of biological risk factors on the development of IMI after HSCT.

New Zealand has unenviably high rates of bacterial resistance to topical antimicrobials. In this Viewpoint, we review the history and usage of topical antimicrobials in New Zealand, and suggest some strategies to mitigate further increases in antimicrobial resistance to topical agents.

In a previous study comparing fluconazole and itraconazole administered as antifungal prophylaxis in hematopoietic cell transplant (HCT) recipients, we found that fluconazole administration concurrent with cyclophosphamide (CY)-based conditioning was associated with fewer early toxicities compared to itraconazole. Fluconazole inhibits cytochrome P450 2C9, which is involved with the activation of CY, and so might provide protection from CY-related toxicities. To investigate this further, we compared CY and CY-metabolite data from patients who received fluconazole (n = 56) concurrent with CY-containing conditioning and in patients who did not (n = 17). The fluconazole group had greater exposure to CY, and lower peak serum concentration of CY-metabolite 4-hydroxycyclophosphamide. In a separate cohort, we examined outcomes in patients randomized to receive either fluconazole (n = 152) or placebo (n = 147) concurrent with CY-containing conditioning in a prior randomized trial. Patients who received fluconazole experienced less hepatic and renal toxicity, and had lower mortality. No difference in relapsed malignancy was apparent. These data support the hypothesis that fluconazole, when coadministered with CY, decreases CY-related toxicities by inhibiting cytochrome P450 2C9 metabolism.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by Chlamydia trachomatis. Five laboratory confirmed cases of LGV were detected in MSM (men who have sex with men) in the upper North Island; four in Auckland between September and December 2013 and a fifth case was detected in Waikato in June 2014. The absence of a recent travel history for four cases supports the likelihood of local transmission of this uncommon infection.

To describe colonisation patterns of Staphylococcus aureus (S. aureus) and Streptococcus pyogenes (S. pyogenes) among pre-school children in New Zealand.Anterior nasal, oropharyngeal, and antecubital fossa swabs were collected from a diverse sample of 139 New Zealand children aged 4 years. Swabs were cultured for S. aureus and S. pyogenes. S. aureus isolates were tested for antibiotic susceptibility.S. aureus colonisation was more prevalent than S. pyogenes colonisation; 54% of the children were colonised with S. aureus whereas only 16% were colonised with S. pyogenes, at one or more sampling sites (P0.0001). S. aureus was present in a larger proportion of swabs obtained from the anterior nasal (39%, P0.0001) or oropharynx (32%, P=0.0002) than from the antecubital fossa (14%). S. pyogenes was present in a larger proportion of swabs obtained from the oropharynx (16%) than either the anterior nasal (4%, P=0.001) or the antecubital fossa (2%, P0.0001).S. aureus and S. pyogenes are prevalent at superficial sites in preschool children in NZ, with S. aureus colonisation more prevalent than S. pyogenes colonisation. Colonisation frequency varies by site for both pathogens; S. aureus is more prevalent in the anterior nares and oropharynx while S. pyogenes is more prevalent in the oropharynx.

Background: The reported rate of post-sternotomy mediastinitis is between 0.8 and 2.3%, with up to 79% of cases caused by staphylococci. Mediastinitis is associated with significant morbidity and mortality. Obesity and diabetes are the only risk factors consistently identified. The aims of the present study were to determine the incidence and risk factors for staphylococci post-sternotomy mediastinitis and to audit its management. Methods: The clinical records of patients with staphylococcal post-sternotomy mediastinitis between 1 January 1998 and 31 May 2003 were retrospectively reviewed. Information collected included patient demographics, comorbidities, operation type, microbiology findings, surgical and medical management, and outcome. Data collected on cases were compared with data collected in a prospective database of all patients undergoing cardiac surgery. Results: The incidence of staphylococcal post-sternotomy mediastinitis was 1.2% (60 cases in 5176 median sternotomies). Staphylococcus aureus was isolated in 49 (82%) cases and coagulase-negative staphylococci in 11 (18%) cases. Eight (16%) S. aureus isolates were methicillin-resistant. Risk factors associated with mediastinitis were ethnicity, diabetes mellitus, emergency surgery, ejection fraction and length of preoperative hospital stay. In-hospital mortality was 15%. Eighteen per cent of cases were not cured by initial therapy. Conclusion: Staphylococcal mediastinitis is a serious complication with significant rates of relapse and mortality. This audit has lead to an evaluation of our clinical pathways to ensure that prevention and management of surgical site infection is optimized.

To analyse the culture results of heart valves removed following streptococcal endocarditis in order to gain insight into the duration of treatment required for valve sterilization.Retrospective review of 131 episodes of streptococcal endocarditis: 94 due to alpha-haemolytic streptococci; 15 due to beta-haemolytic streptococci; 10 due to nutritionally deficient streptococci; eight due to the Streptococcus anginosus group and four due to Streptococcus pneumoniae. Patients had their valves removed during antimicrobial treatment. Culture results were analysed with respect to duration of treatment before surgery.For alpha-haemolytic streptococci, 17 (18%) valves were culture-positive and 77 (82%) culture-negative after a median (range) of 4 (1-20) and 16 (4-58) days of treatment, respectively, P0.001. For beta-haemolytic streptococci, two valves (13%) were culture-positive; both patients had receivedor = 4 days of treatment. Four patients (40%) with nutritionally deficient streptococci were culture-positive, and had receivedor = 8 days of treatment. For the S. anginosus group, two valves (25%) were culture-positive; both patients had receivedor = 4 days of treatment before operation. Overall, only one of 131 (0.8%) valves was culture-positive after 14 days of treatment. All valves infected with beta-haemolytic streptococci, nutritionally deficient streptococci and the S. anginosus group, who were treated for more than 8 days before surgery, were culture-negative.Our findings support current treatment guidelines for endocarditis caused by alpha-haemolytic streptococci. We suggest that the recommended duration of treatment for endocarditis resulting from other streptococci may be excessive and treatment trials evaluating 2 and 4 week regimens are justified.

Background This study sought to determine community prevalence, epidemiology and testing patterns for sexually transmissible infections (STI) in northern New Zealand. Methods: A total of 2643 samples submitted for STI testing between 26 November 2015 and 7 December 2015 underwent analysis by Aptima Combo 2 (Hologic, San Diego, CA, USA), Trichomonas vaginalis (TV), and Mycoplasma genitalium (MG) assays. Results were analysed by patient demographics. Results: Four hundred and eleven pathogens were detected from 359 patients, with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), TV, and MG detected in 178 (6.7%), 19 (0.7%), 80 (3%) and 134 (5.1%) samples respectively. With the exception of TV, STI prevalence was highest in people

SummaryAims: To describe the molecular basis of pyrazinamide (PZA) resistance among Mycobacterium tuberculosis in New Zealand, and to compare the pncA gene sequence among isolates with phenotypic (Bactec 960 and Wayne's assay) evidence of PZA resistance.Methods: The pncA gene of 26 clinical isolates of M. tuberculosis found to be PZA resistant by phenotypic methods was sequenced. Phenotypic and genotypic data were compared.Results: Mutations were detected in 11 isolates, predominantely among isolates with a multi-drug resistance phenotype. While the mutations were dispersed along the pncA gene, a clustering of mutations were found at amino acid Ser18–His57 and His82–Val128 regions. Seven of the identified mutations have not been described previously.Conclusions: A high diversity of pncA gene mutation was seen among PZA resistant strains of M. tuberculosis. The Bactec 960 phenotypic test may over report PZA resistance.

A retrospective review was conducted of patients with external ventricular drains (EVDs) in situ in order to ascertain the utility of daily cerebrospinal fluid (CSF) analysis in such patients. All laboratory requests for CSF analysis, which were sent to the Microbiology Department, Auckland City Hospital, New Zealand, were reviewed to identify patients with EVDs in situ. The patients' clinical records were reviewed and information was obtained regarding their age, ethnicity, indication for EVD, duration of EVD, CSF analysis results, daily temperatures, Glasgow Coma Scale (GCS) and the presence of other infections. For CSF samples that grew organisms, the patients' notes were reviewed to ascertain whether the organism was a contaminant or was representative of EVD-associated ventriculitis. A total of 454 CSF specimens from 60 patients were reviewed. Of the 56 CSF specimens that were culture-positive, 40 (71 %) were found to reflect clinical infection. Routine CSF analysis identified nine episodes of EVD-associated ventriculitis. Coagulase-negative staphylococci and Staphylococcus epidermidis were the most common isolates and were associated with ventriculitis approximately half of the time. Gram-negative isolates were less frequently isolated, but, when present, were always associated with ventriculitis. This study found that patient temperature and GCS did not allow early prediction of EVD-associated ventriculitis.

To describe the molecular epidemiology of emm types associated with circulating pharyngeal group A streptococcus (GAS) isolates in Auckland, New Zealand.GAS isolates were collected over a 10-day period from a community pathology provider in Auckland. PCR analysis and sequencing of the emm gene was performed at the Institute of Environmental Science and Research.A total of 52 emm types were identified from 278 GAS isolates. The three most common emm types were emm1, emm89 and emm12. Overall, the experimental 30-valent GAS M protein vaccine covered 19 / 52 (37%) of emm types in our study.Our study provides baseline data on the circulating pharyngeal GAS emm types in Auckland. Future clinical and molecular surveillance of GAS pharyngitis is essential in the context of ongoing GAS vaccine development.

Summary Aims Streptococcus pyogenes or group A streptococcus (GAS) is a common cause of vulvo-vaginitis in pre-pubertal females but is uncommonly isolated from the vaginal swabs of adult females. We aimed to describe the clinical and laboratory findings of adult females with GAS isolated from vaginal swabs in a community and hospital laboratory. Methods Over a 19 week period the two laboratories identified females ≥15 years of age with GAS isolated from vaginal swabs. At least 2 weeks after reporting, the referring doctor or midwife was telephoned by the authors for clinical information or the clinical notes were reviewed. Laboratory data were also collected. Results One hundred adult females with GAS isolated from vaginal swabs were identified from approximately 4500-5000 community laboratory, and 20 from approximately 2000 hospital laboratory swabs. Community patients were more likely to have presented with vaginal symptoms such as discharge, while hospital patients were more likely to have ascending infection related to pregnancy/recent delivery. Of the community patients, 15% were asymptomatic compared with 5% of the hospital patients. Review of Gram stain and culture quantification was not found to be particularly useful for discriminating between clinical infection and asymptomatic colonisation. Conclusions Isolation of GAS from the vaginal swabs of adult females is uncommon. In the community setting it may represent infection with vulvo-vaginitis or asymptomatic colonisation. In the hospital setting, its isolation is frequently associated with pregnancy-related infectious complications.

The Roche cobas 4800 CT/NG assay is a commonly used commercial system for screening for Neisseria gonorrhoeae infection, and previous studies have shown the method to be highly sensitive and specific for urogenital samples. We present the first confirmed clinical N. gonorrhoeae false-positive result using the cobas 4800 NG assay, obtained from testing a pharyngeal swab sample and caused by cross-reaction with a commensal Neisseria strain.

Background: Chronic toxoplasmosis has been shown to be strongly associated with a range of neuropsychiatric effects including schizophrenia and suicide. However there have not been any prospective, community-based studies of the neuropsychiatric effects of acute toxoplasmosis in adult immunocompetent patients. Methods: Adult patients with a positive serum IgM anti-Toxoplasma gondii test result, in the context of an acute illness with lymphadenopathy, were invited to complete a questionnaire seeking information relating to the nature, severity, and duration of symptoms in the months following the diagnosis of acute toxoplasmosis. Results: Laboratory testing identifi ed a total of 187 adults who had a positive serum IgM anti-T. gondii test result between 1 January and 30 November 2011. Consent to contact 108/187 (58%) patients was provided by their family doctor; 37 (34%) of these 108 patients completed and returned the questionnaire. Questionnaires from the 31/108 (29%) patients who reported swollen lymph nodes during their illness were included in the study. Fatigue (90%), headache (74%), diffi culty concentrating (52%), and muscle aches (52%) were the most commonly reported symptoms. These symptoms commonly persisted for at least 4 weeks. Twenty-seven of 31 (87%) subjects reported a moderate or severe reduction in their overall physical and mental health during the fi rst 2 months of illness. Conclusions: Acute toxoplasmosis in immunocompetent adults commonly causes moderately severe neuropsychiatric symptoms that might result from replication of the organism in the central nervous system with consequent effects on brain function. Patients should be advised that such symptoms are common and reassured that they usually resolve completely within a few months.

We introduced polymerase chain reaction (PCR) testing for Neisseria gonorrhoeae (NG) on the Cobas 4800 CT/NG assay for all samples received with a Chlamdyia trachomatis request in March 2012. From 1 March 2012 to 30 June 2012, all PCR-positive/culture-negative specimens had additional testing at another assay. A total of 40053 tests were performed. The estimated specificity and positive predictive value were 99.9% and 97.1%, respectively; thus routine additional testing is not required.