Sometimes you come across an idea so brilliant and yet so simple that you think to yourself “I wish I’d thought of that!” Well that’s what happened to me at the Federation of Infection Societies annual conference at the beginning of December.
 
I guess I should start by saying I have no affiliation to, or sponsorship from, any company, pharmaceutical or otherwise. I can therefore say I am totally objective, but I was impressed!
 
So what was it I was so impressed by? Well, it’s a beta-lactamase… What, a beta-lactamase!?! But they’re bad, they breakdown antibiotics and stop them working, how can they be a good thing? Well, before we consider the beta-lactamase let’s think about why antibiotics can be bad for you.

On the ward round a patient reported to the doctor that she had developed diarrhoea on the antibiotics that had been given for her community acquired pneumonia (CAP). She had already had 5 days of antibiotics and other than the diarrhoea was feeling much better. The doctor noted the patient was afebrile and looked at the blood tests which showed the white blood cell count and C-reactive protein had reduced considerably. Knowing that the hospital antibiotic guidelines said the treatment for CAP was seven days the doctor decided to call the Microbiologist for advice.
 
The Microbiologist went through the story and the said “okay, you can stop the antibiotics”.
 
“But the guidelines say we should give seven days”, replied the doctor.

​“Yes, but the patient is better” replied the Microbiologist.
 
“So why do the guidelines say seven days then” persisted the doctor.
 
Good point thought the Microbiologist…
 
So why do we have defined durations for courses of antibiotics? Why do these appear to be carved in stone so that no doctor or patient dares to deviate from the principal of “you must finish the course of antibiotics”? Surely the correct length of course is whatever makes the patient feel better?

You are busy reading the culture plates in the laboratory when you come across a sample from the Genitourinary Medicine (GUM) clinic growing a Neisseria gonorrhoeae reported as resistant to Ceftriaxone, Azithromycin, Doxycycline, Cefixime and Ciprofloxacin. What would you do? Would you authorise this as normal or would you do anything else? Hopefully this type of resistance pattern would ring alarm bells and prompt further work, but why?
 
The rising incidence of STIs
In 2015 there were about 435,000 Sexually Transmitted Infections (STIs) diagnosed in the UK. The majority of these were chlamydia at about 200,000. Worryingly the number of cases of gonorrhoea were over 41,200 (an increase of 53% since 2012) and syphilis 5,300 (76% increase since 2012). A lot of the increase is in men who have sex with men (MSM); 80% of gonorrhoea and 90% of syphilis has been in MSMs.

My last blog was about the impending doom of the post-antibiotic era and one of the points raised by readers was “what about phages”? Well it’s such a good question that this is going to be the topic of this week’s blog!
 
Bacteriophages, or “phages” as they are commonly known, are viruses that infect bacterial cells. They attach to the outside of bacterial cells and inject genes into the bacterium which causes lysis and destroys the infecting bacteria. To me they look a bit like the lunar module that NASA launched into space back in the 1960s. 

Perhaps one of the most important and worrying studies into antibiotic resistance has just been published in The Lancet. It heralds the end of the antibiotic era…yes yes there has been talk of it for a while but it is NOW HERE...I see you think I’m being melodramatic so read on…
 
Imagine the scenario of a thirty year old lady with pyelonephritis. Over the past few days she has had worsening loin pain and is now septic with a high fever and rigors. On admission she is fluid resuscitated, started on IV Piptazobactam and given a stat dose of IV Gentamicin as per the hospital empirical antibiotic guidelines. Despite this she remains septic so she is changed to IV Meropenem. The next day the Microbiologists start to get anxious; her blood cultures grow a Meropenem resistant Escherichia coli. The Microbiologist recommends changing the patient to the last line of antibiotics: IV Colistin PLUS IV Amikacin. Despite all of the doctors best efforts this young lady, who has never been in hospital before, dies the following day from uncontrolled sepsis. Later the E. coli from her blood cultures is shown to be resistant to every antibiotic tested! There was simply no effective antibiotic treatment available. Does this sound like an unlikely doomsday scenario? Maybe we need to think again?

Infections due to Pseudomonas aeruginosa, a Gram-negative
aerobic bacterium, can be very difficult to treat because they are often resistant to a number of antibiotics (see earlier blog). Let me illustrate with a recent patient of mine...

The news section of the current BMJ (BMJ 2014;349:g5238) runs the headline “GPs feel pressurised to prescribe unneeded antibiotics”. The article states that:    
• 55% of GPs felt pressurised by patients to prescribe an antibiotic (10% of patients expected antibiotics every time and a further 13% expected antibiotics most of the time)
• 44% admitted to prescribing antibiotics to get a patient out of the surgery
• 28% of GPs were not sure of the medical necessity of their prescription
• 24% of GPs felt there was a lack of easy to use diagnostic tools

It’s no wonder that antibiotic resistance is increasing!

In April of this year the World Health Organisation released a sobering report on the state of antibiotic resistance internationally. This is the latest in a long line of reports since the Department of Health published “The Path of Least Resistance” in 1998, which made the following key points:
• Antibiotics have enabled huge advances in medicine
• Antibiotic use selects for resistant bacteria
• Resistant bacteria accumulate and spread
• Resistance increases clinical complications, lengthens
hospital stay and adds cost
• Development of new antibiotics is slow, expensive and
cannot be guaranteed
• With more resistance and few new antimicrobial agents,
modern medicine is threatened

I have recently had the pleasure of interviewing for new Consultant colleagues and I thought it would be good to ask them “what infection  keeps you awake at night?” Their answers where all the same: carbapenemases.