H5N1

CIDRAP: Canada reports rising MRSA, VRE but drop in antibiotic use

Via CIDRAP, Chris Dall writes: Canada reports rising MRSA, VRE but drop in antibiotic use. Excerpt:

A new report from the Canadian Antimicrobial Resistance Surveillance System (CARSS) shows rising antibiotic resistance in two major healthcare-associated pathogens, along with noteworthy decreases in antibiotic use in humans and animals.  

The CARRS-2017 Report is the third published by the Public Health Agency of Canada (PHAC) and includes surveillance data on antimicrobial resistance and use, both in humans and animals, through 2016. The report is based on available surveillance data from the PHAC's nine surveillance systems and laboratory reference services. This year's report includes new data on antibiotic-resistant infections and antibiotic use in community settings.  

Worrisome trends 

The two pathogens of concern are methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The CARRS report shows that the overall rate of MRSA infection in sentinel hospitals in Canada increased from 2.84 cases to 3.13 cases per 10,000 patient-days from 2011 through 2016, with a decrease in healthcare-associated MRSA (HA-MRSA) cases (from 1.93 cases in 2011 to 1.69 in 2016) and an increase in community-associated cases (from 0.56 cases to 0.96 cases per 1,000 admissions).  

Most concerning was a fivefold increase in HA-MRSA bloodstream infections (BSIs) in the country's pediatric hospitals—from 0.08 to 0.43 cases per 10,000 patient-days between 2011 and 2016. 

The rate of VRE infections in Canada, meanwhile, rose from 0.41 cases per 10,000 patient-days in 2015 to 0.44 cases in 2016. While that's a reduction from a high of 0.61 cases in 2012, it still represents a significant rise since 2007, when the rate was 0.10 cases per 10,000 patient-days. 

In addition, the report shows that the rate of VRE BSI in sentinel adult hospitals more than doubled from 2011 to 2016, climbing from 0.12 cases per 10,000 patient-days to 0.26 cases. "This finding points to the need for ongoing monitoring of this microorganism in Canada," the authors of the report write.  

The report also found that drug-resistant gonorrhea is becoming an increasing problem in Canada, matching a trend that has been observed worldwide. From 2014 through 2015, the proportion of cultured Neisseria gonorrhea isolates that were resistant to at least one antibiotic rose from 52% to 60%, with increases observed in the proportion of isolates resistant to azithromycin (from 1.3% in 2010 to 4.7% in 2015) and in the proportion of isolates with decreased susceptibility to the cephalosporin antibiotics cefixime or ceftriaxone (from 1.1% and 2.7% in 2014, respectively, to 1.9% and 3.5% in 2015). 

Since 2001, the rate of gonorrhea infections in Canada has more than doubled. But the country has not yet reported any treatment failures resulting from resistance to azithromycin and decreased susceptibility to cephalosporins—the currently recommended dual therapy for gonorrhea. 

On a positive note, the CARSS-2017 Report showed that the rate of healthcare-associated Clostridium difficile infection (CDI) in Canada continued to decline, falling from 6.64 cases per 10,000 patient-days in 2015 to 4.05 cases in 2016. Surveillance of sentinel hospitals beginning in 2015 showed that 37% of all CDI reported in patients admitted to those hospitals was community-associated.

Multidrug-resistant Neisseria gonorrhoeae infection, Denmark, 2017

Via Eurosurveillance: Multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and intermediate resistance to azithromycin, Denmark, 2017. The abstract:

We describe a multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and azithromycin intermediate resistance in a heterosexual man in Denmark, 2017. Whole genome sequencing of the strain GK124 identified MSLT ST1903, NG-MAST ST1614 and all relevant resistance determinants including similar penA resistance mutations previously described in ceftriaxone-resistant gonococcal strains. 

Although treatment with ceftriaxone 0.5 g plus azithromycin 2 g was successful, increased awareness of spread of gonococcal strains threatening the recommended dual therapy is crucial.

UK: New class of antibiotic raises hopes for urgently-needed gonorrhea drug

Via The Guardian: New class of antibiotic raises hopes for urgently-needed gonorrhoea drug. Excerpt:

A new class of antibiotic has been found to work in the lab against the sexually transmitted infection gonorrhoea, which can cause infertility and damage to babies and is fast becoming resistant to all existing drugs. 

Although it is early days, because the antibiotic has yet to be tried in animals or humans, researchers say they are excited by its potential. The World Health Organisation has listed gonorrhoea as a high priority infection that poses a great threat to human health, estimating that there about about 78m gonorrhoea infections worldwide each year. In the UK, gonorrhoea is the second most common bacterial STI after chlamydia, with 35,000 cases in England in 2014 alone. New drugs are urgently needed.  

Closthioamide, which was discovered in 2010, has been tested in the lab against samples of the Neisseria gonorrhoeae bacterium causing the disease by researchers from Imperial College London and the London School of Hygiene and Tropical Medicine (LSHTM). 

They tested 149 samples of bacteria from hospital patients with infections in the throat, urethra, cervix and rectum. Very small amounts of the antibiotic were effective against 146 of the 149 samples. The drug was also effective against samples of the drug-resistant bacteria provided to the researchers by the World Health Organisation. Their results are published in the journal Antimicrobial Agents and Chemotherapy.

Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand

Via The Lancet, an encouraging report: Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: a retrospective case-control study. The summary:

Background 

Gonorrhoea is a major global public health problem that is exacerbated by drug resistance. Effective vaccine development has been unsuccessful, but surveillance data suggest that outer membrane vesicle meningococcal group B vaccines affect the incidence of gonorrhoea. We assessed vaccine effectiveness of the outer membrane vesicle meningococcal B vaccine (MeNZB) against gonorrhoea in young adults aged 15–30 years in New Zealand. 

Methods 

We did a retrospective case-control study of patients at sexual health clinics aged 15–30 years who were born between Jan 1, 1984, and Dec 31, 1998, eligible to receive MeNZB, and diagnosed with gonorrhoea or chlamydia, or both. Demographic data, sexual health clinic data, and National Immunisation Register data were linked via patients' unique personal identifier. For primary analysis, cases were confirmed by laboratory isolation or detection of Neisseria gonorrhoeae only from a clinical specimen, and controls were individuals with a positive chlamydia test only. We estimated odds ratios (ORs) comparing disease outcomes in vaccinated versus unvaccinated participants via multivariable logistic regression. Vaccine effectiveness was calculated as 100×(1–OR). 

Findings 

11 of 24 clinics nationally provided records. There were 14 730 cases and controls for analyses: 1241 incidences of gonorrhoea, 12 487 incidences of chlamydia, and 1002 incidences of co-infection. Vaccinated individuals were significantly less likely to be cases than controls (511 [41%] vs 6424 [51%]; adjusted OR 0·69 [95% CI 0·61–0·79]; p<0·0001). Estimate vaccine effectiveness of MeNZB against gonorrhoea after adjustment for ethnicity, deprivation, geographical area, and sex was 31% (95% CI 21–39). 

Interpretation 

Exposure to MeNZB was associated with reduced rates of gonorrhoea diagnosis, the first time a vaccine has shown any protection against gonorrhoea. These results provide a proof of principle that can inform prospective vaccine development not only for gonorrhoea but also for meningococcal vaccines.

See also this STAT report by Helen Branswell on the study.

Sexually transmitted infections: Challenges ahead

Via The Lancet Infectious Diseases, a report by The Lancet Infectious Diseases Commission: Sexually transmitted infections: challenges ahead. The summary:

WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. 

In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. 

The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. 

Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. 

STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. 

Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. 

Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.

WHO: Antibiotic-resistant gonorrhoea on the rise, new drugs needed

A news release from WHO: Antibiotic-resistant gonorrhoea on the rise, new drugs needed. Excerpt:

Data from 77 countries show that antibiotic resistance is making gonorrhoea – a common sexually-transmitted infection – much harder, and sometimes impossible, to treat.

"The bacteria that cause gonorrhoea are particularly smart. Every time we use a new class of antibiotics to treat the infection, the bacteria evolve to resist them," said Dr Teodora Wi, Medical Officer, Human Reproduction, at WHO.  

WHO reports widespread resistance to older and cheaper antibiotics. Some countries – particularly high-income ones, where surveillance is best – are finding cases of the infection that are untreatable by all known antibiotics. 

"These cases may just be the tip of the iceberg, since systems to diagnose and report untreatable infections are lacking in lower-income countries where gonorrhoea is actually more common," adds Dr Wi.  

Each year, an estimated 78 million people are infected with gonorrhoea. Gonorrhoea can infect the genitals, rectum, and throat. Complications of gonorrhoea disproportionally affect women, including pelvic inflammatory disease, ectopic pregnancy and infertility, as well as an increased risk of HIV.  

Decreasing condom use, increased urbanization and travel, poor infection detection rates, and inadequate or failed treatment all contribute to this increase. 

Monitoring drug resistance  

The WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP), monitors trends in drug-resistant gonorrhoea. WHO GASP data from 2009 to 2014 find widespread resistance to ciprofloxacin [97% of countries that reported data in that period found drug-resistant strains], increasing resistance to azithromycin [81%], and the emergence of resistance to the current last-resort treatment: the extended-spectrum cephalosporins (ESCs) oral cefixime or injectable ceftriaxone [66%]. 

Currently, in most countries, ESCs are the only single antibiotic that remain effective for treating gonorrhoea. But resistance to cefixime – and more rarely to ceftriaxone – has now been reported in more than 50 countries. As a result, WHO issued updated global treatment recommendations in 2016 advising doctors to give 2 antibiotics: ceftriaxone and azithromycin. 

Development of new drugs 

The R&D pipeline for gonorrhoea is relatively empty, with only 3 new candidate drugs in various stages of clinical development: solithromycin, for which a phase III trial has recently been completed; zoliflodacin, which has completed a phase II trial; and gepotidacin, which has also completed a phase II trial. 

The development of new antibiotics is not very attractive for commercial pharmaceutical companies. Treatments are taken only for short periods of time (unlike medicines for chronic diseases) and they become less effective as resistance develops, meaning that the supply of new drugs constantly needs to be replenished.

See also Helen Branswell's report on this statement.

WHO publishes list of bacteria for which new antibiotics are urgently needed

A news release: WHO publishes list of bacteria for which new antibiotics are urgently needed. Excerpt:

WHO today published its first ever list of antibiotic-resistant "priority pathogens" – a catalogue of 12 families of bacteria that pose the greatest threat to human health.  

The list was drawn up in a bid to guide and promote research and development (R&D) of new antibiotics, as part of WHO’s efforts to address growing global resistance to antimicrobial medicines.  

The list highlights in particular the threat of gram-negative bacteria that are resistant to multiple antibiotics. These bacteria have built-in abilities to find new ways to resist treatment and can pass along genetic material that allows other bacteria to become drug-resistant as well.  

"This list is a new tool to ensure R&D responds to urgent public health needs," says Dr Marie-Paule Kieny, WHO's Assistant Director-General for Health Systems and Innovation. "Antibiotic resistance is growing, and we are fast running out of treatment options. If we leave it to market forces alone, the new antibiotics we most urgently need are not going to be developed in time."  

The WHO list is divided into three categories according to the urgency of need for new antibiotics: critical, high and medium priority. 

The most critical group of all includes multidrug resistant bacteria that pose a particular threat in hospitals, nursing homes, and among patients whose care requires devices such as ventilators and blood catheters. They include Acinetobacter, Pseudomonas and various Enterobacteriaceae (including Klebsiella, E. coli, Serratia, and Proteus). They can cause severe and often deadly infections such as bloodstream infections and pneumonia.  

These bacteria have become resistant to a large number of antibiotics, including carbapenems and third generation cephalosporins – the best available antibiotics for treating multi-drug resistant bacteria. 

The second and third tiers in the list – the high and medium priority categories – contain other increasingly drug-resistant bacteria that cause more common diseases such as gonorrhoea and food poisoning caused by salmonella.

Canada: Risky behaviour not the only cause of syphilis outbreaks, new study proposes

Via CBC News British Columbia: Risky behaviour not only cause of syphilis outbreaks, new study proposes. Excerpt:

A new study from B.C. researchers is proposing a biological reason behind the "astounding" increase in syphilis cases, saying high-risk sexual behaviour doesn't explain the outbreaks that are happening. 

Syphilis outbreaks have been on the rise worldwide, including B.C. and many other locations in Canada — primarily among men who have sex with men, many of whom are taking antiretroviral drugs to treat HIV, the study states.  

Past research has speculated new, highly effective HIV treatments had encouraged more high-risk sexual behaviour. 

However, the study's lead author said that didn't make sense as a sole explanation,  because other sexually-transmitted disease such as chlamydia and gonorrhea weren't rising as quickly.  

"That led me to believe there must be something else going on," said Michael Rekert, clinical professor in the University of B.C.'s School of Population and Public Health, in a news release.

The study, published this week in the journal Sexually Transmitted Infections, proposes another possible cause — that the HIV therapy itself may make patients more vulnerable to syphilis. 

"What we are hypothesizing is there is an additional reason, besides behaviour, for why we are seeing this increase in syphilis cases," said Caroline Cameron, a University of Victoria microbiologist and co-author of the study.  

In B.C. for example, from 2005 to 2014, syphilis cases rose 90.6 per cent, much more than chlamydia (39.9 per cent) and gonorrhea (63.8 per cent). 

Biology vs. behaviour 

The paper hasn't demonstrated HIV therapy has this effect on syphilis but examines the case for it. 

One part of that is looking at the microbiology: whether there's a plausible biological mechanism for the HIV treatment, known as highly active anti-retroviral therapy, or HAART, to affect how the body responds to syphilis. 

"What we're hypothesizing is it's altering the immune response ... in a way that is increasing susceptibility to the pathogen," said Cameron. "It warrants further study." 

The authors are clear: HAART drugs are life-saving for people with HIV and shouldn't be stopped even if they make someone more vulnerable to syphilis.  

But it's important to explore the connection, with laboratory tests and other work, said Cameron.

ECDC: Five infectious diseases accounted for 75% of reported cases in EU

ECDC has published Five infectious diseases accounted for 75% of reported cases in EU - report. Click or tap through for related links.

Chlamydia infection, campylobacteriosis, salmonellosis, gonorrhoea and tuberculosis were the most commonly reported notifiable infectious diseases in the EU and EEA in 2014 according to the executive summary of ECDC’s Annual epidemiological report . These diseases accounted for over 850,000 cases, 75% of the 1.1 million cases of infectious diseases reported overall. Over 6,700 deaths were reported for tuberculosis, HIV/AIDS, invasive pneumococcal disease, Legionnaires’ disease and listeriosis. 

Antimicrobial resistance continues to increase in gram-negative bacteria, including multidrug resistance and resistance to last-line drugs like carbapenems and, in certain parts of Europe, polymyxins. 

“Reliable and correct surveillance data of infectious diseases are crucial sources of information that help policy makers and health experts in making informed decisions regarding public health actions,” says Dr Denis Coulombier, ECDC Head of Unit for Surveillance and Response Support. “It is therefore imperative that we continue to improve the timeliness and quality of surveillance data across the EU and EEA.”   

For the first time, the annual epidemiological report is available as web pages. Each disease or health topic under the Centre’s surveillance has or will have its own chapter which, in conjunction with the ECDC Surveillance Atlas of Infectious Diseases, provides a concise epidemiological overview and downloadable maps, tables and graphs.

UK: Super-gonorrhea outbreak could be out of control as attempts to stop spread fail

Via The Independent: Super-gonorrhoea outbreak could be out of control as attempts to stop spread fail. Excerpt:

An outbreak of super-gonorrhoea in the UK is out of control and efforts to stop it have been unsuccessful, health officials have warned.  

It is feared the sexually transmitted disease may be becoming increasingly resistant to treatment, prompting concerns further rapid spread could occur. 

In April, it emerged an outbreak of so-called ‘super-gonorrhoea’ had occurred in Leeds, with cases also noted in the West Midlands, London and southern-England. It began among heterosexual couples but has since been spread among men who have sex with men (MSM).   

In a report issued today by health agency Public Health England, the group warned: “The outbreak of HL-AziR gonorrhoea in England persists. There have been 17 cases of HL-AziR gonorrhoea reported to date in 2016 compared to 15 cases for the same time period in 2015. Between November 2014 and August 2016 there have been a total of 48 confirmed and two probable cases.  

“The potential for rapid spread of HL-AziR N. gonorrhoeae among high risk sexual networks including MSM is of particular concern.” 

The disease can result in serious discomfort, pelvic inflammatory disease and even infertility. Among 1 in 10 infected men and half of infected women, symptoms can go undetected. Symptoms include a green or yellow discharge from the genitals, discomfort urinating and irregular bleeding between periods.  

Chief Executive of sexual health charity FPA Natika H Halil told The Independent: “There should be statutory sex and relationships education, which the government has still not implemented, and easy access to sexual health services. With ever-shrinking public health budgets and increasing pressure on local authorities to meet people’s varied health needs, this is no longer a given and is a cause of real concern. 

“PHE’s report is a timely reminder, ahead of our Sexual Health Week focusing on STIs next week, how important it is for people to know how to protect themselves. It particularly highlights the importance of testing so that cases can be diagnosed early and as well as of partner notification to help limit infections being passed on."