Pediatric Invasive Meningococcal Disease, Auckland, New Zealand (Aotearoa), 2004-2020.

New Zealand (Aotearoa) experienced a Neisseria meningitidis serogroup B epidemic during 1991-2006, and incidence remains twice that of other high-income countries. We reviewed clinical, laboratory, and immunization data for children <15 years of age with laboratory-confirmed invasive meningococcal disease in Auckland, New Zealand, during January 1, 2004-December 31, 2020. Of 319 cases in 318 children, 4.1% died, and 23.6% with follow-up data experienced sequelae. Children of Maori and Pacific ethnicity and those living in the most deprived areas were overrepresented. Eighty-one percent were positive for N. meningitidis serogroup B, 8.6% for serogroup W, 6.3% for serogroup C, and 3.7% for serogroup Y. Seventy-nine percent had bacteremia, and 63.9% had meningitis. In New Zealand, Maori and Pacific children are disproportionately affected by this preventable disease. N. meningitidis serogroup B vaccine should be included in the New Zealand National Immunization Schedule to address this persistent health inequity.

Outcomes of adults with invasive meningococcal disease with reduced penicillin susceptibility in Auckland 2004-2017.

PURPOSE: The purpose of this study was to assess the clinical outcomes of adults with invasive meningococcal disease (IMD) and to compare the outcomes of patients with IMD caused by a penicillin susceptible isolate (minimum inhibitory concentration (MIC) ≤ 0.06 mg/L) with patients with IMD caused by an isolate with reduced penicillin susceptibility (MIC > 0.06 mg/L). We also assessed the outcomes of patients with IMD caused by an isolate with reduced penicillin susceptibility who were treated exclusively with intravenous (IV) benzylpenicillin. METHODS: Retrospective study of all culture positive IMD in adult patients (age ≥ 15 years) in the Auckland region from 2004 to 2017. RESULTS: One hundred and thirty-nine patients were included; 94 had penicillin susceptible isolates (88 cured, 6 died), and 45 had an isolate with reduced penicillin susceptibility (41 cured, 1 possible relapse, 3 died). The median benzylpenicillin/ceftriaxone treatment duration was 3 days for both groups. There was no difference in the patient outcomes of both groups. Eighteen patients with IMD caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone and were cured. CONCLUSIONS: This study provides further support to existing data that has shown that short duration IV beta-lactam treatment is effective for IMD in adults. Only a small number of patients with meningitis caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone, limiting its evaluation. For Neisseria meningitidis meningitis, we recommend ceftriaxone as empiric treatment and as definitive treatment when this is caused by an isolate with reduced penicillin susceptibility.

Genomic Analysis of Multiresistant Staphylococcus capitis Associated with Neonatal Sepsis.

Coagulase-negative staphylococci (CoNS), such as Staphylococcus capitis, are major causes of bloodstream infections in neonatal intensive care units (NICUs). Recently, a distinct clone of S. capitis (designated S. capitis NRCS-A) has emerged as an important pathogen in NICUs internationally. Here, 122 S. capitis isolates from New Zealand (NZ) underwent whole-genome sequencing (WGS), and these data were supplemented with publicly available S. capitis sequence reads. Phylogenetic and comparative genomic analyses were performed, as were phenotypic assessments of antimicrobial resistance, biofilm formation, and plasmid segregational stability on representative isolates. A distinct lineage of S. capitis was identified in NZ associated with neonates and the NICU environment. Isolates from this lineage produced increased levels of biofilm, displayed higher levels of tolerance to chlorhexidine, and were multidrug resistant. Although similar to globally circulating NICU-associated S. capitis strains at a core-genome level, NZ NICU S. capitis isolates carried a novel stably maintained multidrug-resistant plasmid that was not present in non-NICU isolates. Neonatal blood culture isolates were indistinguishable from environmental S. capitis isolates found on fomites, such as stethoscopes and neonatal incubators, but were generally distinct from those isolates carried by NICU staff. This work implicates the NICU environment as a potential reservoir for neonatal sepsis caused by S. capitis and highlights the capacity of genomics-based tracking and surveillance to inform future hospital infection control practices aimed at containing the spread of this important neonatal pathogen.

Topical Antibiotic Use Coselects for the Carriage of Mobile Genetic Elements Conferring Resistance to Unrelated Antimicrobials in Staphylococcus aureus.

Topical antibiotics, such as mupirocin and fusidic acid, are commonly used in the prevention and treatment of skin infections, particularly those caused by staphylococci. However, the widespread use of these agents is associated with increased resistance to these agents, potentially limiting their efficacy. Of particular concern is the observation that resistance to topical antibiotics is often associated with multidrug resistance, suggesting that topical antibiotics may play a role in the emergence of multidrug-resistant (MDR) strains. New Zealand (NZ) has some of the highest globally recorded rates of topical antibiotic usage and resistance. Using a combination of Pacific Biosciences single-molecule real-time (SMRT) whole-genome sequencing, Illumina short-read sequencing, and Bayesian phylogenomic modeling on 118 new multilocus sequence type 1 (ST1) community Staphylococcus aureus isolates from New Zealand and 61 publically available international ST1 genome sequences, we demonstrate a strong correlation between the clinical introduction of topical antibiotics and the emergence of MDR ST1 S. aureus We also provide in vitro experimental evidence showing that exposure to topical antibiotics can lead to the rapid selection of MDR S. aureus isolates carrying plasmids that confer resistance to multiple unrelated antibiotics, from within a mixed population of competitor strains. These findings have important implications regarding the impact of the indiscriminate use of topical antibiotics.

Genomic epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in New Zealand.

Background: Antimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health. No studies to date have examined the genomic epidemiology of gonorrhoea in the Western Pacific Region, where the incidence of gonorrhoea is particularly high. Methods: A population-level study of N. gonorrhoeae in New Zealand (October 2014 to May 2015). Comprehensive susceptibility testing and WGS data were obtained for 398 isolates. Relatedness was inferred using phylogenetic trees, and pairwise core SNPs. Mutations and genes known to be associated with resistance were identified, and correlated with phenotype. Results: Eleven clusters were identified. In six of these clusters, >25% of isolates were from females, while in eight of them, >15% of isolates were from females. Drug resistance was common; 98%, 32% and 68% of isolates were non-susceptible to penicillin, ciprofloxacin and tetracycline, respectively. Elevated MICs to extended-spectrum cephalosporins (ESCs) were observed in 3.5% of isolates (cefixime MICs ≥ 0.12 mg/L, ceftriaxone MICs ≥ 0.06 mg/L). Only nine isolates had penA XXXIV genotypes, three of which had decreased susceptibility to ESCs (MIC = 0.12 mg/L). Azithromycin non-susceptibility was identified in 43 isolates (10.8%); two of these isolates had 23S mutations (C2611T, 4/4 alleles), while all had mutations in mtrR or its promoter. Conclusions: The high proportion of females in clusters suggests transmission is not exclusively among MSM in New Zealand; re-assessment of risk factors for transmission may be warranted in this context. As elevated MICs of ESCs and/or azithromycin were found in closely related strains, targeted public health interventions to halt transmission are urgently needed.

Neonatal invasive pneumococcal disease: New Zealand experience in the era of pneumococcal vaccination.

BACKGROUND: Invasive pneumococcal disease (IPD) became a notifiable disease in New Zealand in 2008, and in the same year pneumococcal conjugate vaccine (PCV) was added to the childhood immunisation schedule. DESIGN: This was a retrospective study of IPD in infants aged <90 days reported to the national notifiable disease database, EpiSurv, from 1 January 2009 to 31 December 2013. All cases had Streptococcus pneumoniae isolated from a normally sterile site. MAIN OUTCOME MEASURES: IPD incidence was calculated for babies aged <90 and <30 days using the number of national IPD cases with a denominator of annual infant live births. Clinical, demographic and outcome data were reviewed for infants aged less than seven days (early onset). RESULTS: There were 29 cases of IPD in infants aged <90 days and 19 cases in infants aged <30 days. Of the nine early-onset cases, six occurred within the first 48 h. Six of the early-onset cases were infants of NZ Maori ethnicity. One infant died six hours after birth. Three infants developed long-term neurological or respiratory sequelae. Isolates from five of the early-onset cases were S. pneumoniae serotypes not covered by the PCV in use at the time of infection. Maternal vaccination with 23-valent pneumococcal vaccine would have covered 84% (16 of 19) of serotypes responsible for the cases in infants <30 days old. CONCLUSION: Strategies such as maternal vaccination or accelerated neonatal vaccination may be beneficial to protect neonates at high risk of IPD.

Rapid Emergence and Evolution of Staphylococcus aureus Clones Harboring fusC-Containing Staphylococcal Cassette Chromosome Elements.

The prevalence of fusidic acid (FA) resistance amongStaphylococcus aureusstrains in New Zealand (NZ) is among the highest reported globally, with a recent study describing a resistance rate of approximately 28%. Three FA-resistantS. aureusclones (ST5 MRSA, ST1 MSSA, and ST1 MRSA) have emerged over the past decade and now predominate in NZ, and in all three clones FA resistance is mediated by thefusCgene. In particular, ST5 MRSA has rapidly become the dominant MRSA clone in NZ, although the origin of FA-resistant ST5 MRSA has not been explored, and the genetic context offusCin FA-resistant NZ isolates is unknown. To better understand the rapid emergence of FA-resistantS. aureus, we used population-based comparative genomics to characterize a collection of FA-resistant and FA-susceptible isolates from NZ. FA-resistant NZ ST5 MRSA displayed minimal genetic diversity and represented a phylogenetically distinct clade within a global population model of clonal complex 5 (CC5)S. aureus In all lineages,fusCwas invariably located within staphylococcal cassette chromosome (SCC) elements, suggesting that SCC-mediated horizontal transfer is the primary mechanism offusCdissemination. The genotypic association offusCwithmecAhas important implications for the emergence of MRSA clones in populations with high usage of fusidic acid. In addition, we found thatfusCwas colocated with a recently described virulence factor (tirS) in dominant NZS. aureusclones, suggesting a fitness advantage. This study points to the likely molecular mechanisms responsible for the successful emergence and spread of FA-resistantS. aureus.

High usage of topical fusidic acid and rapid clonal expansion of fusidic acid-resistant Staphylococcus aureus: a cautionary tale.

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.

Methicillin-resistant Staphylococcus aureus, Samoa, 2007-2008.

Little is known about the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in most Pacific Island nations. Relatively high rates of MRSA have been reported in Polynesian people living outside the Pacific Islands. To determine the prevalence and characteristics of MRSA, we assessed wound swabs from 399 persons with skin and soft tissue infection living in Samoa. MRSA was isolated from 9% of study participants; 34 of the 196 S. aureus isolates were MRSA. Five MRSA genotypes were identified; the 3 most common were USA300, the Queensland clone, and a sequence type 1 MRSA strain that shares <85% homology with the sequence type 1 MRSA strain common in the region (WA MRSA-1). The Southwest Pacific MRSA clone was identified but accounted for only 12% of MRSA isolates. The high prevalence of MRSA in Samoa provides impetus for initiatives to improve antimicrobial drug resistance surveillance, infection control, and antimicrobial drug use in Pacific Island nations.

Variation in erythromycin and clindamycin resistance patterns between New Zealand and Australian group B streptococcus isolates.

BACKGROUND: Intrapartum chemoprophylaxis for group B streptococcus (GBS) carriers reduces the risk of early-onset neonatal GBS infection. For women with ß-lactam allergy, either erythromycin or clindamycin are administered. Recent reports worldwide suggest that GBS resistance to these antibiotics is increasing. AIMS: To compare erythromycin and clindamycin resistance phenotypes in invasive neonatal GBS isolates across New Zealand and Australia over the past two decades and to determine whether regional variation in resistance patterns exist. METHOD: Invasive neonatal GBS isolates were collected from laboratories across New Zealand (n=107) and Australia (n=74) over two time periods (1992-1994 and 2002-2004 in New Zealand; 1982-2001 and 2002-2006 in Australia) and subjected to standard antibiotic susceptibility testing. A nested sub-study in New Zealand examined antibiotic susceptibilities of 112 maternal colonising GBS isolates during 2003-2004. RESULTS: Erythromycin resistance among invasive neonatal GBS isolates increased across both countries over the past decade, with similar rates of resistance in New Zealand (9%) and Australia (6%) in recent years. New Zealand erythromycin-resistant GBS isolates commonly displayed cross-resistance to clindamycin. Also, there were significantly higher rates of isolated clindamycin resistance in GBS isolates from New Zealand than Australia (P=0.034). Maternal GBS isolates from New Zealand showed similar resistance patterns to neonatal isolates. CONCLUSION: Erythromycin and clindamycin resistance among invasive neonatal GBS isolates has emerged in both New Zealand and Australia over the past decade and is consistent with global trends in GBS resistance patterns. Although regional variations exist, these findings should be considered when implementing intrapartum GBS prevention strategies.

Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent.

The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere.IMPORTANCE The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in the region. ST772 progressively acquired specific resistance elements at limited cost to its fitness and continues to be exported globally, resulting in small-scale community and health care outbreaks. The Bengal Bay clone therefore combines the virulence potential and epidemiology of community-associated clones with the multidrug resistance of health care-associated S. aureus lineages. This study demonstrates the importance of whole-genome sequencing for the surveillance of highly antibiotic-resistant pathogens, which may emerge in the community setting of regions with poor antibiotic stewardship and rapidly spread into hospitals and communities across the world.

Community-onset genitourinary tract infection due to CTX-M-15-Producing Escherichia coli among travelers to the Indian subcontinent in New Zealand.

A series of patients are described who presented to a New Zealand hospital with genitourinary tract infection due to CTX-M-15-producing Escherichia coli. All had a history of travel to the Indian subcontinent and lacked traditional risk factors for urinary tract infection due to a multidrug-resistant organism.

Antimicrobial resistance among Shigella in New Zealand.

AIM: We undertook a national survey to provide current information on antimicrobial resistance among Shigella isolated in New Zealand. METHODS: Diagnostic laboratories are requested to refer all Shigella isolates to the Institute of Environmental Science and Research (ESR) for epidemiological typing as part of the national surveillance of shigellosis. The antimicrobial susceptibility of 263 non-duplicate Shigella isolates referred to ESR in 2015 and 2016 was tested. RESULTS: The 263 Shigella comprised 141 (53.6%) S. sonnei, 113 (43.0%) S. flexneri, 7 (2.7%) S. boydii and 2 (0.8%) S. dysenteriae. Among the 141 S. sonnei, the majority were either biotype g (90) or biotype a (50). Rates of resistance to the two currently recommended first-line antibiotics, co-trimoxazole and fluoroquinolones, were relatively high at 56.7% and 22.8%, respectively. Azithromycin is considered a second-line treatment option, but 11.0% of Shigella were categorised as having a non-wildtype (NWT) azithromycin phenotype (ie, having some mechanism of azithromycin resistance although not necessarily clinically resistant). There were several significant differences in resistance between the two most prevalent S. sonnei biotypes, with resistance being significantly more prevalent among biotype g isolates. Shigella from patients who had not travelled overseas were significantly more likely to be azithromycin NWT than isolates from patients who had recently travelled (20.7 vs 5.6%). Azithromycin NWT was more prevalent among Shigella from males than females (13.9 vs 7.7%). CONCLUSIONS: These results suggest there is an immediate need to revise the currently recommended first-line treatment for shigellosis, especially when treatment is given on an empirical basis. Equally concerning is the fact that resistance to the second-line antibiotic for shigellosis, azithromycin, appears to be emerging in New Zealand. As diagnostic laboratories increase their use of culture-independent testing, it is recommended that they should continue to culture specimens from all shigellosis cases so that isolates are available for susceptibility testing and epidemiological typing.

Vancomycin-resistant Enterococcus faecium sequence type 796 - rapid international dissemination of a new epidemic clone.

Background: Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably; it is uncertain how they spread despite improved infection control. We aimed to investigate the relatedness of a novel sequence type (ST) of vanB E. faecium - ST796 - very near its time of origin from hospitals in three Australian states and New Zealand. Methods: Following near-simultaneous outbreaks of ST796 in multiple institutions, we gathered then tested colonization and bloodstream infection isolates' antimicrobial resistance (AMR) phenotypes, and phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data was explored to trace the spread of ST796. Results: A novel clone of vanB E. faecium (ST796) was first detected at one Australian hospital in late 2011, then in two New Zealand hospitals linked by inter-hospital transfers from separate Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New South Wales and was responsible for at least one major colonization outbreak in a Neonatal Intensive Care Unit without identifiable links between centers. No exceptional AMR was detected in the isolates. While WGS analysis showed very limited diversity at the core genome, consistent with recent emergence of the clone, clustering by institution was observed. Conclusions: Evolution of new E. faecium clones, followed by recognized or unrecognized movement of colonized individuals then rapid intra-institutional cross-transmission best explain the multi-center, multistate and international outbreak we observed.

Global Scale Dissemination of ST93: A Divergent Staphylococcus aureus Epidemic Lineage That Has Recently Emerged From Remote Northern Australia.

Background: In Australia, community-associated methicillin-resistant Staphylococcus aureus (MRSA) lineage sequence type (ST) 93 has rapidly risen to dominance since being described in the early 1990s. We examined 459 ST93 genome sequences from Australia, New Zealand, Samoa, and Europe to investigate the evolutionary history of ST93, its emergence in Australia and subsequent spread overseas. Results: Comparisons with other S. aureus genomes indicate that ST93 is an early diverging and recombinant lineage, comprising of segments from the ST59/ST121 lineage and from a divergent but currently unsampled Staphylococcal population. However, within extant ST93 strains limited genetic diversity was apparent with the most recent common ancestor dated to 1977 (95% highest posterior density 1973-1981). An epidemic ST93 population arose from a methicillin-susceptible progenitor in remote Northern Australia, which has a proportionally large Indigenous population, with documented overcrowded housing and a high burden of skin infection. Methicillin-resistance was acquired three times in these regions, with a clade harboring a staphylococcal cassette chromosome mec (SCCmec) IVa expanding and spreading to Australia's east coast by 2000. We observed sporadic and non-sustained introductions of ST93-MRSA-IVa to the United Kingdom. In contrast, in New Zealand, ST93-MRSA-IVa was sustainably transmitted with clonal expansion within the Pacific Islander population, who experience similar disadvantages as Australian Indigenous populations. Conclusion: ST93 has a highly recombinant genome including portions derived from an early diverging S. aureus population. Our findings highlight the need to understand host population factors in the emergence and spread of antimicrobial resistant community pathogens.

The clear and present danger of carbapenemase-producing Enterobacteriaceae (CPE) in New Zealand: time for a national response plan.

Antimicrobial resistance (AMR) in general poses a threat to the sustainability of modern healthcare, but a particularly urgent and serious threat is posed by a specific group of antibiotic-resistant bacteria known as carbapenemase-producing Enterobacteriaceae (CPE). CPE are resistant to nearly all antibiotics and include common pathogens such as Escherichia coli and Klebsiella pneumoniae. In New Zealand, the incidence of CPE has increased from three isolates in 2012 to 45 in 2016. The current epidemiology of CPE in New Zealand has similarities with the extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) epidemic in the early 2000s (just before ESBL-PE underwent a non-linear increase in incidence). Although to date in New Zealand, nearly all CPE have been imported from overseas, this situation appears to be changing, with evidence of secondary spread in both households and healthcare facilities over the last year. In this article, we argue that CPE should be regarded as the foremost AMR threat currently facing New Zealand, and highlight the need for a comprehensive national response plan, analogous to plans for other emerging transmissible infections, such as pandemic influenza and Ebola. We also make recommendations about the components of such a plan and advocate that CPE should be recognised as a key priority in New Zealand's national AMR strategy, due to be published in May 2017.