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?

​The patient was in her fifties and had a history of long-standing myelodysplasia for which she received fortnightly blood transfusions. She had been neutropaenic for many months and had a number of admissions to hospital with febrile neutropaenia for which she was treated with antibiotics. On this occasion she had developed pain in her right eye followed by redness of the surrounding skin. On examination she had a marked proptosis (bulging eyeball) and an area of black mucosa was noted on her palate. She was started on antibiotics for orbital cellulitis but worsened overnight and so was discussed with the Microbiologist.
 
The Microbiologist noted that she was iron overloaded as a result of her frequent blood transfusions and given her clinical presentation of cellulitis unresponsive to antibacterials, proptosis and black palate made a provisional diagnosis of mucormycosis. An urgent MRI showed oedema of the orbital tissues and nasal sinus involvement. Posaconazole was added to her treatment and it was strongly advised that she have surgical decompression and resection of the infected material in her orbit.

Patient A is immunocompromised from leukaemia and has a cough and severe shortness of breath not responding to antibacterials, patient B is on chemotherapy for melanoma and has a headache and proptosis (bulging eyeball) and patient C is HIV positive and has meningitis. All these patients have one thing in common; they have an invasive fungal infection. These infections are often hard to diagnose, difficult to treat and delayed management leads to a poor outcome for the patients. Invasive fungal infections are a particular problem for immunocompromised patients, those on critical care units or those with long-term disorders such as chronic lung diseases.
 
Many patients have to start empirical treatment with antifungals whilst awaiting results from reference laboratories as there is often a lack of locally available diagnostic tests. This results in a lot of unnecessary treatment of patients with potentially toxic and expensive drugs. In fact, antifungals are often the most expensive drugs used within hospitals; using better diagnostics could produce significant cost savings. To give you an idea, the listed drug costs in the BNF for one day of antifungal treatment for a 70kg patient are:

• IV AmBisome (5mg/kg OD) = £700
• IV Caspofungin (50mg OD) = £330
• IV Voriconazole (4-6mg/kg BD) = £300