H5N1

ECDC: Surveillance of antimicrobial resistance in Europe 2018

ECDC has published Surveillance of antimicrobial resistance in Europe 2018. Excerpt from the executive summary: 

As in previous years, the AMR situation in Europe displays wide variations depending on bacterial species, antimicrobial group and geographical region. For several bacterial species–antimicrobial group combinations, a north-to-south and west-to-east gradient is evident. In general, lower resistance percentages were reported by countries in the north while higher percentages were reported in the south and east of Europe. The high variability in AMR across EU/EEA countries reinforces the scope for significant reductions through investments to strengthen current best practice.   

In 2018, more than half of the Escherichia  coli isolates reported to EARS-Net and more than a third of the Klebsiella pneumoniae isolates were resistant to at least one antimicrobial group under regular surveillance, and combined resistance to several antimicrobial groups was frequent. Resistance percentages were generally higher in K. pneumoniae than in E. coli. While carbapenem resistance remained rare in E. coli, several countries reported carbapenem resistance percentages above 10% for K. pneumoniae. 

Carbapenem resistance was also common in Pseudomonas  aeruginosa and Acinetobacter species, and at higher percentages compared with K. pneumoniae. For all four gram-negative bacteria, the countries reporting the highest carbapenem resistance percentages were also among the countries reporting the highest resistance percentages for other antimicrobial groups. For most gram-negative bacterial species–antimicrobial group combinations, changes in resistance percentages between 2015 and 2018 were moderate, and resistance remained at previously reported high levels.  

For Streptococcus pneumoniae, the resistance situation appeared stable, but with large inter-country variations. For Staphylococcus aureus, the decline in the percentage of methicillin-resistant (i.e. MRSA) isolates reported in previous years continued in 2018. Nevertheless, MRSA remains an important pathogen in the EU/EEA, as the levels of MRSA were still high in several countries, and combined resistance to other antimicrobial groups was common. 

International travel as source of a hospital outbreak with an unusual methicillin-resistant Staphylococcus aureus clonal complex 398, Denmark, 2016

Eurosurveillance has published International travel as source of a hospital outbreak with an unusual meticillin-resistant Staphylococcus aureus clonal complex 398, Denmark, 2016. The abstract:

In May 2016, an unusual outbreak with the Panton-Valentine leukocidin-positive human variant of methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 occurred among mothers and infants in the maternity unit of a Danish hospital. MRSA sharing genotypic and phenotypic characteristics was confirmed in 36 cases, including 26 patients, nine household members and a healthcare worker (HCW) who had contact with all the patients. The national MRSA database contained 37 seemingly unlinked MRSA cases whose isolates shared the same genotypic and phenotypic characteristics as the outbreak strain. 

Whole genome sequencing showed that three of these isolates clustered together with the 36 outbreak isolates, suggesting spread outside the hospital. The HCW and 21 of 37 cases from the national MRSA database had links to south-eastern Asia, where the outbreak strain is endemic. These findings suggest that the HCW acquired the outbreak strain while travelling in south-eastern Asia and then introduced it into the hospital; from there, it spread within the patients’ households and into the community. 

Screening of travellers returning from countries with high levels of MRSA could be an important intervention to prevent spread of these bacteria into hospitals via patients or HCWs.

Climate change and antibiotic resistance

Via bioRxiv: Rates of increase of antibiotic resistance and ambient temperature in Europe: a cross-national analysis of 28 countries between 2000-2016. The abstract:

Background. 

Widely recognized as a major public health threat globally, the rapid increase of antibiotic resistance in bacteria could soon render our most effective method to combat infections obsolete. Factors influencing the burden of resistance in human populations remain poorly described, though temperature is known to play an important role in mechanisms at the bacterial level. 

Methods. 

We performed an ecologic analysis of country level antibiotic resistance prevalence in 3 common bacterial pathogens across 28 countries in Europe, and used multivariable models to evaluate associations with minimum temperature and other predictors over a 17-year period (2000-2016). We quantified the effects of minimum temperature, population density, and antibiotic consumption on the rate of change of antibiotic resistance across geographies. Findings. 

For three common bacterial pathogens and four classes of antibiotics, we found evidence of a long-term effect of ambient minimum temperature on rates of increase of antibiotic resistance across 28 countries in Europe between 2000-2016. 

Specifically, we show that across all antibiotic classes for the pathogens E. coli and K. pneumoniae, European countries with 10°C warmer ambient temperatures have experienced more rapid increases in antibiotic resistance over the 17-year period, ranging between 0.33%/year (95% CI 0.2, 0.5) and 1.2%/year (0.4, 1.9), even after accounting for recognized drivers of resistance including antibiotic consumption and population density. 

We found a decreasing relationship for S. aureus and methicillin of -0.4%/year (95% CI -0.7, 0.0), reflecting widespread declines in MRSA across Europe over the study period. 

Interpretation. 

Ambient temperature may be an important modulator of the rate of change of antibiotic resistance. Our findings suggest that rising temperatures globally may hasten the spread of resistance and complicate efforts to mitigate it.

Bacteria becoming resistant to hospital disinfectants, warn scientists

Via The Guardian: Bacteria becoming resistant to hospital disinfectants, warn scientists. Excerpt:

Hospitals will need to use new strategies to tackle bacteria experts have warned, after finding a type of hospital superbug is becoming increasingly tolerant of alcohol – the key component of current disinfectant hand rubs. 

Handwashes based on alcohols such as isopropanol have become commonplace as a method of infection control. But while the move has been linked to benefits, including a fall in rates of hospital infections of methicillin-resistant Staphylococcus aureus (MRSA), new research suggests it might also have had unexpected consequences. 

Scientists say they have discovered that superbugs known as vancomycin-resistant enterococci, or VRE, appear to be becoming more tolerant to alcohol.  

“This is a wake-up call to infection control hospital teams around the world that if you want to control the emergence of VRE you need to do more than just rely on your alcohol-based disinfectants,” said Prof Timothy Stinear, co-author of the research from the University of Melbourne, noting that these could include improved adherence to current regimens – such as thorough cleaning with alcohol hand rubs – the use of other disinfectants like chlorine-based products, and greater screening of patients for infections. 

One of the most common species of VRE is Enterococcus faecium, with infections on the rise in England and Australia. VRE infections, said Stinear, can be serious and sometimes even prove deadly. “The problem with VRE is that it can colonise the gut and then go into patients’ bloodstream and cause sepsis, bloodstream infection, and it is very difficult to get rid of because it is resistant to almost all antibiotics,” he said. Among the problems, Stinear added, is that it can lodge in heart valves and prosthetic device implants.

“It only impacts the most susceptible people – so healthy people do not get VRE infections,” Stinear said, noting that people receiving chemotherapy, organ transplants or who undergo dialysis are among those at risk. 

Writing in the journal Science Translational Medicine, Stinear and colleagues report how they took Enterococcus faecium bacteria recovered from patients – so-called “isolates” – and exposed these in the lab to an isopropanol-based solution for five minutes. In total 139 such samples were used, collected from two hospitals in Melbourne between 1997 and 2015. Alcohol-based handrubs were systematically introduced in Australia from the early 2000s, with the volume used increasing tenfold by 2015. 

The results reveal that Enterococcus faecium bacteria have become more tolerant to alcohol over that time.

The bugs are winning

Via The New York Review of Books, a review of Superbugs: An Arms Race Against Bacteria, by William Hall, Anthony McDonnell, and Jim O'Neill: The Bugs Are Winning. Excerpt:

Superbugs only briefly reviews the science of bacterial resistance; its focus is on the societal consequences. While there are no exact data on the total number of people dying each year from resistant microbes, the authors calculate it to be at least 1.5 million. This number outstrips deaths from road accidents (1.2 million) and approximates the number of deaths from diabetes (1.5 million).

The economic burden on our health care systems is considerable. People with resistant infections spend more time in the hospital, require more care from doctors and nurses, are treated with more expensive drugs, and often have to be isolated from other patients. In the United States, it costs an average of $16,000 to treat a patient with Staphylococcus aureus that is susceptible to the antibiotic methicillin, with an 11.5 percent chance of death; if the bacteria are resistant, the cost jumps to $35,000 and the chance of the patient dying more than doubles. A study from the European Medicines Agency in the European Union, which includes England, estimated the cost to EU health care systems at €900 million ($1.06 billion). 

The impact of bacterial resistance on economic productivity is also significant. The Centers for Disease Control and Prevention in the United States have estimated that resistance costs the American health care system about $20 billion per year, to which productivity losses add a further $35 billion. Using the American estimates, the authors of Superbugs extrapolate the total costs of antimicrobial resistance worldwide to about $57 billion for health systems, with the reduction in world productivity valued at $174 billion. 

Based on these economic calculations, Superbugs provides a set of policy prescriptions, framed in pragmatic terms meant to motivate self-interested politicians:  

"Governments might not want to invest in solutions, but they will ultimately pay either way. Any money not spent now will result in substantial costs in the future—not to mention many lost lives. Serious damage to economic productivity (which by extension threatens governments’ tax incomes) coupled with the higher costs of health care (which is largely government funded) should provide the impetus to deal with this crisis now."

A new class of synthetic retinoid antibiotics effective against bacterial persisters

Via Nature: A new class of synthetic retinoid antibiotics effective against bacterial persisters. The abstract:

A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant ‘persister’ subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. 

Here we used a Caenorhabditis elegans–MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. 

Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.

See also this report in The Guardian on the study.

Antimicrobial resistance in zoonotic bacteria still high in humans, animals and food, say ECDC and EFSA

A news release from ECDC: Antimicrobial resistance in zoonotic bacteria still high in humans, animals and food, say ECDC and EFSA. Excerpt:

Bacteria from humans and animals continue to show resistance to antimicrobials, according to a new report published today by the European Food Safety Authority (EFSA) and the European Centre for Disease Prevention and Control (ECDC). The report highlights some emerging issues and confirms antimicrobial resistance (AMR) as one of the biggest threats to public health. AMR reduces the effectiveness of treatment options. 

Vytenis Andriukaitis, European Commissioner for Health and Food Safety reaffirmed his commitment to tackle AMR: “Levels of antimicrobial resistance still differ significantly from one EU country to another. To win the fight, we need to join our efforts and implement stringent policies on the use of antibiotics across sectors. It is vital that we all renew our commitment to fight antimicrobial resistance by focusing on the key areas set out in the EU One Health Action Plan against antimicrobial resistance.”  

Among the new findings, based on data from 2016, are detection of resistance to carbapenems in poultry, an antibiotic which is not authorised for use in animals, and of ESBL-producing Salmonella Kentucky with high resistance to ciprofloxacin in humans, which was reported for the first time in four countries.  

Mike Catchpole, ECDC’s chief scientist, commented on the results: “We are concerned to see that Salmonella and Campylobacter bacteria in humans show high levels of antimicrobial resistance. The fact that we keep detecting multidrug-resistant bacteria means that the situation is not improving. We need to investigate the origins and prevent the spread of highly resistant strains, such as ESBL-producing Salmonella Kentucky”.  

Marta Hugas, EFSA’s chief scientist said: “The detection of resistance to carbapenems in poultry and to linezolid in methicillin-resistant Staphylococcus aureus in pigs is alarming because these antibiotics are used in humans to treat serious infections. It is important that risk managers follow-up on these findings.”

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.

Hong Kong urged to tackle superbug problem by making hospitals disclose infection and drug data

Via the South China Morning Post: Hong Kong urged to tackle superbug problem by making hospitals disclose infection and drug data. Excerpt and then a comment:

A leading microbiologist warns Hong Kong is “lagging behind” combating the spread of superbugs and says pressure should be put on public hospitals by making them disclose the number of cases and their use of antibiotics. 

Hospital chiefs would then be obliged to tackle the problem, linked to doctors who too freely hand out the drugs. 

Professor Yuen Kwok-yung said when this was done in Britain, cases of methicillin-resistant Staphylococcus aureus (MRSA) fell by about 90 per cent within 10 years. The superbug can infect different parts of the body and has been under World Health Organisation surveillance.  

The recommendation by Yuen, chair of infectious diseases at the University of Hong Kong and a government adviser on the issue, comes ahead of a meeting late this month by the government’s steering committee on antimicrobial resistance, headed by health minister Dr Ko Wing-man, to discuss expert proposals. 

Yuen said hospitals would only adopt more stringent measures if the prescription of antibiotics and the number of infections were under public scrutiny. 

“Pressure could be exerted only if hospitals are named. Hospital heads would then take action [to tackle the problem],” he said. 

The use of large amounts of antibiotics might indicate abuse of the drugs, which could kill both the bad and good germs in the body and promote the growth of antibiotic-resistant bacteria. 

In 2014 in Britain, 11 per cent of Staphylococcus aureus cases were MRSA, in contrast to 48 per cent in Hong Kong. 

The city also recorded a 47 per cent rate of Acinetobacter cases that were resistant to carbapenem, another superbug given a “critical” priority by the WHO, compared with just 2 per cent in Britain.

“I’m not very optimistic [about resolving the problem quickly]. It is way too severe,” Yuen said.

I'm currently reading Michael Osterholm's excellent new book Deadliest Enemy: Our War Against Killer Germs, in which he points out that US hospitals were horrified at being made to report their antibiotic-resistant cases

"This is going to ruin us!" doctors and administrators moaned.  But it got results: serious infection control and a drop in antibiotic usage.

The problem is worldwide, however, and few nations are doing as much about it as the US, Canada, and the Europeans. Osterholm cites one prediction that antimicrobial resistance will cause 300 million deaths and cost the world's economy $100 trillion by the year 2050.

Enhanced terminal room disinfection and acquisition and infection caused by multidrug-resistant organisms and Clostridium difficile

Via The Lancet: Enhanced terminal room disinfection and acquisition and infection caused by multidrug-resistant organisms and Clostridium difficile (the Benefits of Enhanced Terminal Room Disinfection study): a cluster-randomised, multicentre, crossover study. The summary:

Background 

Patients admitted to hospital can acquire multidrug-resistant organisms and Clostridium difficile from inadequately disinfected environmental surfaces. We determined the effect of three enhanced strategies for terminal room disinfection (disinfection of a room between occupying patients) on acquisition and infection due to meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, C difficile, and multidrug-resistant Acinetobacter. 

Methods 

We did a pragmatic, cluster-randomised, crossover trial at nine hospitals in the southeastern USA. Rooms from which a patient with infection or colonisation with a target organism was discharged were terminally disinfected with one of four strategies: reference (quaternary ammonium disinfectant except for C difficile, for which bleach was used); UV (quaternary ammonium disinfectant and disinfecting ultraviolet [UV-C] light except for C difficile, for which bleach and UV-C were used); bleach; and bleach and UV-C. The next patient admitted to the targeted room was considered exposed. 

Every strategy was used at each hospital in four consecutive 7-month periods. We randomly assigned the sequence of strategies for each hospital (1:1:1:1). The primary outcomes were the incidence of infection or colonisation with all target organisms among exposed patients and the incidence of C difficile infection among exposed patients in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01579370.  

Findings 

31 226 patients were exposed; 21 395 (69%) met all inclusion criteria, including 4916 in the reference group, 5178 in the UV group, 5438 in the bleach group, and 5863 in the bleach and UV group. 115 patients had the primary outcome during 22 426 exposure days in the reference group (51·3 per 10 000 exposure days). 

The incidence of target organisms among exposed patients was significantly lower after adding UV to standard cleaning strategies (n=76; 33·9 cases per 10 000 exposure days; relative risk [RR] 0·70, 95% CI 0·50–0·98; p=0·036). The primary outcome was not statistically lower with bleach (n=101; 41·6 cases per 10 000 exposure days; RR 0·85, 95% CI 0·69–1·04; p=0·116), or bleach and UV (n=131; 45·6 cases per 10 000 exposure days; RR 0·91, 95% CI 0·76–1·09; p=0·303) among exposed patients. 

Similarly, the incidence of C difficile infection among exposed patients was not changed after adding UV to cleaning with bleach (n=38 vs 36; 30·4 cases vs 31·6 cases per 10 000 exposure days; RR 1·0, 95% CI 0·57–1·75; p=0·997). 

Interpretation 

A contaminated health-care environment is an important source for acquisition of pathogens; enhanced terminal room disinfection decreases this risk.