In March, 2018, a strain of gonorrhoea isolated from a heterosexual man in the UK that was resistant to ceftriaxone (minimum inhibitory concentration MIC 0·5 mg/L) and azithromycin (high-level MIC ...>256 mg/L) was reported.2 This strain was the first to be reported resistant to both agents, and raised grave concerns for the future management of gonorrhoea. Two similar N gonorrhoeae clinical isolates have subsequently been observed in Australia,3 with both being resistant to ceftriaxone (MIC 0·25–0·5 mg/L) and exhibiting high-level resistance to azithromycin (MIC ≥256 mg/L; appendix). Clinicians should be made aware of the emergence of these resistant strains, so they can request culture and susceptibility testing (where possible), perform test-of-cures, capture travel history, and ensure contact tracing, partner notification, and treatment.
Ceftriaxone remains a first-line treatment for patients infected by Neisseria gonorrhoeae in most settings. We investigated the possible spread of a ceftriaxone-resistant FC428 N. gonorrhoeae clone ...in Japan after recent isolation of similar strains in Denmark (GK124) and Canada (47707). We report 2 instances of the FC428 clone in Australia in heterosexual men traveling from Asia. Our bioinformatic analyses included core single-nucleotide variation phylogeny and in silico molecular typing; phylogenetic analysis showed close genetic relatedness among all 5 isolates. Results showed multilocus sequence type 1903; N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) 233; and harboring of mosaic penA allele encoding alterations A311V and T483S (penA-60.001), associated with ceftriaxone resistance. Our results provide further evidence of international transmission of ceftriaxone-resistant N. gonorrhoeae. We recommend increasing awareness of international spread of this drug-resistant strain, strengthening surveillance to include identifying treatment failures and contacts, and strengthening international sharing of data.
A young woman with a vaginal discharge was found by means of sensitivity testing and genetic analysis to have ceftriaxone-resistant
Neisseria gonorrhoeae
. The infection did not respond to ...ceftriaxone but was treated successfully with ceftriaxone plus azithromycin.
To the Editor:
In 2013, the Centers for Disease Control and Prevention identified
Neisseria gonorrhoeae
antimicrobial resistance as being an urgent threat. Ceftriaxone monotherapy or dual therapy with azithromycin is now the mainstay of treatment for gonorrhea, and no ideal alternatives have been identified. There have been three sporadic reports of two ceftriaxone-resistant strains of
N. gonorrhoeae
in the past 5 years: H041 and F89 (Table 1).
1
–
3
H041 was identified in only a single case involving a female sex worker in Japan in 2009.
1
F89 was initially reported in France in 2010 in a man who has sex with . . .
Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a serious public health problem, compromising the management and control of gonorrhoea globally. Resistance in N. gonorrhoeae to ...ceftriaxone, the last option for first-line empirical monotherapy of gonorrhoea, has been reported from many countries globally, and sporadic failures to cure especially pharyngeal gonorrhoea with ceftriaxone monotherapy and dual antimicrobial therapies (ceftriaxone plus azithromycin or doxycycline) have been confirmed in several countries. In 2018, the first gonococcal isolates with ceftriaxone resistance plus high-level azithromycin resistance were identified in England and Australia. The World Health Organization (WHO) Global Gonococcal Antimicrobial Surveillance Program (GASP) is essential to monitor AMR trends, identify emerging AMR and provide evidence for refinements of treatment guidelines and public health policy globally. Herein we describe the WHO GASP data from 67 countries in 2015-16, confirmed gonorrhoea treatment failures with ceftriaxone with or without azithromycin or doxycycline, and international collaborative actions and research efforts essential for the effective management and control of gonorrhoea. In most countries, resistance to ciprofloxacin is exceedingly high, azithromycin resistance is present and decreased susceptibility or resistance to ceftriaxone has emerged. Enhanced global collaborative actions are crucial for the control of gonorrhoea, including improved prevention, early diagnosis, treatment of index patient and partner (including test-of-cure), improved and expanded AMR surveillance (including surveillance of antimicrobial use and treatment failures), increased knowledge of correct antimicrobial use and the pharmacokinetics and pharmacodynamics of antimicrobials and effective drug regulations and prescription policies (including antimicrobial stewardship). Ultimately, rapid, accurate and affordable point-of-care diagnostic tests (ideally also predicting AMR and/or susceptibility), new therapeutic antimicrobials and, the only sustainable solution, gonococcal vaccine(s) are imperative.
Gonorrhoea and MDR Neisseria gonorrhoeae remain public health concerns globally. Enhanced, quality-assured, gonococcal antimicrobial resistance (AMR) surveillance is essential worldwide. The WHO ...global Gonococcal Antimicrobial Surveillance Programme (GASP) was relaunched in 2009. We describe the phenotypic, genetic and reference genome characteristics of the 2016 WHO gonococcal reference strains intended for quality assurance in the WHO global GASP, other GASPs, diagnostics and research worldwide.
The 2016 WHO reference strains (n = 14) constitute the eight 2008 WHO reference strains and six novel strains. The novel strains represent low-level to high-level cephalosporin resistance, high-level azithromycin resistance and a porA mutant. All strains were comprehensively characterized for antibiogram (n = 23), serovar, prolyliminopeptidase, plasmid types, molecular AMR determinants, N. gonorrhoeae multiantigen sequence typing STs and MLST STs. Complete reference genomes were produced using single-molecule PacBio sequencing.
The reference strains represented all available phenotypes, susceptible and resistant, to antimicrobials previously and currently used or considered for future use in gonorrhoea treatment. All corresponding resistance genotypes and molecular epidemiological types were described. Fully characterized, annotated and finished references genomes (n = 14) were presented.
The 2016 WHO gonococcal reference strains are intended for internal and external quality assurance and quality control in laboratory investigations, particularly in the WHO global GASP and other GASPs, but also in phenotypic (e.g. culture, species determination) and molecular diagnostics, molecular AMR detection, molecular epidemiology and as fully characterized, annotated and finished reference genomes in WGS analysis, transcriptomics, proteomics and other molecular technologies and data analysis.
Between February and April 2018, three ceftriaxone-resistant and high-level azithromycin-resistant
cases were identified; one in the United Kingdom and two in Australia. Whole genome sequencing was ...used to show that the isolates from these cases belong to a single gonococcal clone, which we name the A2543 clone.
Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major health concerns globally. Increased global surveillance of gonococcal AMR is essential. We aimed to describe the ...2017–18 data from WHO's global gonococcal AMR surveillance, and to discuss priorities essential for the effective management and control of gonorrhoea.
We did a retrospective observational study of the AMR data of gonococcal isolates reported to WHO by 73 countries in 2017–18. WHO recommends that each country collects at least 100 gonococcal isolates per year, and that quantitative methods to determine the minimum inhibitory concentration of antimicrobials, interpreted by internationally standardised resistance breakpoints, are used.
In 2017–18, 73 countries provided AMR data for one or more drug. Decreased susceptibility or resistance to ceftriaxone was reported by 21 (31%) of 68 reporting countries and to cefixime by 24 (47%) of 51 reporting countries. Resistance to azithromycin was reported by 51 (84%) of 61 reporting countries and to ciprofloxacin by all 70 (100%) reporting countries. The annual proportion of decreased susceptibility or resistance across countries was 0–21% to ceftriaxone and 0–22% to cefixime, and that of resistance was 0–60% to azithromycin and 0–100% to ciprofloxacin. The number of countries reporting gonococcal AMR and resistant isolates, and the number of examined isolates, have increased since 2015–16. Surveillance remains scarce in central America and the Caribbean and eastern Europe, and in the WHO African, Eastern Mediterranean, and South-East Asian regions.
In many countries, ciprofloxacin resistance was exceedingly high, azithromycin resistance was increasing, and decreased susceptibility or resistance to ceftriaxone and cefixime continued to emerge. WHO's global surveillance of gonococcal AMR needs to expand internationally to provide imperative data for national and international management guidelines and public health policies. Improved prevention, early diagnosis, treatment of index patients and partners, enhanced surveillance (eg, infection, AMR, treatment failures, and antimicrobial use or misuse), and increased knowledge on antimicrobial selection, stewardship, and pharmacokinetics or pharmacodynamics are essential. The development of rapid, accurate, and affordable point-of-care gonococcal diagnostic tests, new antimicrobials, and gonococcal vaccines is imperative.
None.
OBJECTIVE To determine the impact of intrauterine inflammation of maternal (chorioamnionitis) and fetal (umbilical vasculitis) origin and neonatal sepsis on the development of neonatal chronic lung ...disease in preterm infants.
This study was conducted at Royal Prince Alfred Hospital in Sydney, Australia. All infants born at <30 weeks' gestation, admitted to the NICU, and surviving to 36 weeks' corrected gestation during 1992-2004 were eligible. Infants with major congenital abnormalities and those without placental examination were excluded. Antenatal and perinatal data extracted from hospital databases were correlated with the independent, central neonatal database and diagnostic laboratory reports. Neonatal sepsis was categorized according to blood culture isolates into 3 groups: coagulase-negative staphylococci, other bacteria, and Candida species.
There were 798 eligible infants born during the study period, and 761 (95.4%) had placental examination. The mean gestational age was 27.4 +/- 1.5 weeks. Antenatal maternal steroids were given to 94.4%. Regression analysis showed that chorioamnionitis with umbilical vasculitis and increasing gestation were associated with reduced odds of chronic lung disease. Chorioamnionitis without umbilical vasculitis showed a trend to reduced odds of chronic lung disease. Birth weight at <3rd percentile and neonatal sepsis were associated with increased odds of chronic lung disease.
A fetal inflammatory response is protective for chronic lung disease. Neonatal sepsis is strongly associated with chronic lung disease, and the infecting organism is important. Coagulase-negative staphylococcal infection confers a risk for chronic lung disease similar to that of other bacteremias. Candidemia confers the greatest risk of chronic lung disease.
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