Understanding antibiotic resistance
Understanding antibiotic resistance

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Understanding antibiotic resistance

8 Case study: Neisseria gonorrhoeae

In this week’s case study, you will look at how Neisseria gonorrhoeae, which causes gonorrhoea, is evolving into a superbug. Third-generation cephalosporins, also known as extended spectrum cephalosporins (ESCs), are the lynchpin of current therapy for gonorrhoea. But resistance to ESCs is emerging.

The next activity will give you an overview of this topic.

Activity 7 Antibiotic-resistant N. gonorrhoeae in the USA

Allow about 10 minutes

First, watch the following video about the emergence of antibiotic-resistant gonorrhoea in the USA. The video was produced by the USA’s foremost health protection agency – the Centers for Disease Control and Prevention (CDC).

Download this video clip.Video player: Video 5
Skip transcript: Video 5 Drug-resistant gonorrhoea: an urgent public health issue.

Transcript: Video 5 Drug-resistant gonorrhoea: an urgent public health issue.

NARRATOR:
Gonorrhoea is a major public health concern in the United States. More than 800000 new infections occur each year. But because many people don't have symptoms, fewer than half are detected and reported to CDC. Untreated gonorrhoea can cause serious health problems. For women, it can increase their risk for a life-threatening ectopic pregnancy. And for men and women, the infection can cause conditions that can lead to infertility. It can also increase a person's risk of getting or giving HIV.
Medication to treat gonorrhoea has been around for decades, but the bacteria has grown resistant to nearly every drug ever used to treat it. In the 1980s, resistance to penicillin and tetracycline grows, and they are no longer recommended to treat gonorrhoea. Fluoroquinolones are the leading drugs to treat gonorrhoea in the 1990s, but the bacteria was adapting to the drugs. By the 2000s, resistance to fluoroquinolones steadily takes hold. CDC modifies treatment recommendations throughout much of the decade to keep pace.
In 2000, the drug is no longer recommended to treat people infected in Asia or the Pacific Islands. By 2002, this recommendation extends to California. By 2004, CDC no longer recommends it for men who have sex with men in the United States. By 2007, resistance is so widespread that CDC no longer recommends fluoroquinolones to anyone in the US to treat gonorrhoea.
Only one class of antibiotics, known as cephalosporins, remains to treat the infection. There are two main cephalosporins to treat gonorrhoea-- the oral drugs Cefixime and the injection Ceftriaxone. In 2010, CDC takes additional measures to combat resistance, recommending dual treatment with either Cefixime or an increased dose of Ceftriaxone and Azithromycin or Doxycycline. But just two years later, in 2012, CDC updates treatment recommendations again in response to data suggesting the oral cephalosporin Cefixime is becoming less effective. And Gonorrhoea has become harder and harder to treat.
Today, we are down to one last recommended treatment option-- dual treatment with an injection of Ceftriaxone and an oral dose of Azithromycin. Little now stands between us and untreatable Gonorrhoea. There are already troubling signs with the last recommended treatment. Abroad, infections resistant to Ceftriaxone have been detected in several countries. And within the US, while not common, resistance to Azithromycin has been found.
The US hasn't seen treatment failure when using these two drugs together, but drug resistance is rising, and the pipeline for new drugs is shrinking. Our last treatment option won't last forever. We must keep drug-resistant Gonorrhoea as a leading priority.
Learn more at cdc.gov/std/Gonorrhoea/arg.
End transcript: Video 5 Drug-resistant gonorrhoea: an urgent public health issue.
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Video 5 Drug-resistant gonorrhoea: an urgent public health issue.
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Now answer the following questions, based on the video.

  1. Which two cephalosporins were introduced in the 2000s to treat gonorrhoea?
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  1. When were cephalosporin-resistant N. gonorrhoeae first detected?
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  1. In 2018, only one therapy was recommended for gonorrhoea. What was it?
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  1. Why does the narrator predict that the last treatment option ‘won’t last forever’?
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Answer

  1. Cefixime and ceftriaxone.
  2. In 2012.
  3. Dual treatment with ceftriaxone and azithromycin – a macrolide antibiotic.
  4. N. gonorrhoeae has developed resistance to every antibiotic used to treat gonorrhoea. Reports of isolates resistant to ceftriaxone or azithromycin are expected to become more frequent.

ESC-resistant gonorrhoea has been reported in many other countries, as you will see in the next activity.

Activity 8 ESC-resistant gonorrhoea

Allow about 5 minutes

WHO recommends not using an antibiotic in cases where resistance levels are 5% or higher and the bacterial pathogen is unknown. Would this apply to any countries in Figure 12?

Described image
Figure 12 Percentage of isolates with resistance to cefixime and/or ceftriaxone. Data from WHO-GASP (2014 for most countries but 2011–2013 for a few countries) (Wi et al., 2017).

Answer

Yes. ESC-resistance is at least 5% in over 20 countries. Using ESCs in these circumstances increases the likelihood of resistance developing and spreading.

Although resistance to ESCs is low level and emerging, resistance to azithromycin is widespread. Gonorrhoea superbugs, which are resistant to ESCs and azithromycin, have already been isolated from Japan, France and Spain.

(WHO, 2017c).

In the final activity this week, you will look at the scale of the problem and the challenges faced in trying to bring the situation under control.

Activity 9 The rise of antibiotic-resistant gonorrhoea

Allow about 15 minutes

First, read the article below about the global challenge of treating gonorrhoea effectively because of antibiotic resistance.

Article 1: The world is running out of antibiotics, WHO report confirms (WHO, 2017c). [Tip: hold Ctrl and click a link to open it in a new tab. (Hide tip)]

Now answer the following questions, based on the article.

  1. How many people become infected with gonorrhoea each year?
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  1. Why is this probably an underestimate?
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  1. What percentage of N. gonorrhoeae isolates are ESC-resistant?
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  1. How many countries have reported resistance to cefixime or ceftriaxone?
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  1. Why might antibiotic resistance increase in the absence of suitable diagnostics?
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  1. How many new drugs are currently being developed to treat gonorrhoea?
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Answer

  1. About 78 million people worldwide.
  2. LICs, where gonorrhoea is thought to be more common, do not have reliable diagnostic and reporting systems.
  3. 66%
  4. Over 50 countries have reported ESC resistance.
  5. Asymptomatic cases are undiagnosed and untreated, and the infection spreads. Conversely, patients presenting with gonorrhoea-like symptoms may be presumed to have the disease and be prescribed unnecessary or incorrect antibiotics.
  6. Only three drugs are in clinical development.

Globally, gonorrhoea is becoming increasingly difficult to treat as a result of antibiotic resistance. High infection rates result in high rates of antibiotic use. Inadequate diagnostics and poor monitoring and surveillance of AMR encourage the misuse and overuse of antibiotics. New antibiotics are urgently needed. The threat that gonorrhoea may again become impossible to treat is very real.

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