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Once more into the unknown

5/2/2015

 
“In a world of diminishing mystery, the unknown persists” well at least for the out-of-hours Primary Care Physician visiting an elderly care home. Imagine the scenario; it is 8 o’clock on a Saturday evening and you are oncall for your local primary care service. You’ve been asked to see an 85 year old lady who has become increasingly confused and incontinent of urine over the last 24 hours. You take as much history as you can and examine the lady. She has a temperature of 37.8 oC and a few crackles in her chest, but otherwise her examination is unremarkable. A urine dipstick is positive for leukocytes and nitrites so as you cannot exclude a urine infection you decide to treat for a urinary tract infection (UTI), sound familiar?
Having decided to treat for a UTI you now have a number of decisions to make:
  • What antibiotic are you going to use?
  • What dose and frequency are you going to use?
  • How long a course are you going to recommend?
  • What samples (if any) are you going to send to the microbiology laboratory?

This may sound obvious. There are national and local guidelines for antibiotics in primary care: 1st line Trimethoprim and 2nd line Nitrofurantoin. But perhaps it’s not easy as it first appears…
Picture
Does the patient have a problem with recurrent UTIs?
Many older patients get recurrent UTIs. Vaginal or cervical prolapsed and benign prostatic hypertrophy can obstruct urine flow from the bladder. Obstruction to urine outflow from the bladder leads to a degree of urinary retention, and this stale urine can become infected. The vulval and vaginal skin in older women also becomes increasingly fragile, which can lead to atrophic vaginitis, allowing gut bacteria to colonise the skin and ascend the urethra to cause UTIs more readily. In addition to these physiological reasons, it can also become harder for frail people to maintain personal hygiene, especially if they suffer from faecal incontinence, and this can also lead to more UTIs.

In the scenario of a patient with recurrent UTIs there is a high likelihood that past antibiotic treatments will have selected out more resistant bacteria within the patients normal bowel flora. It is therefore more likely that the causative bacterium will be resistant to the commonly used antibiotics e.g. Trimethoprim.

In an ideal world, primary care physicians seeing patients with suspected infections would have access to their previous laboratory results so that they can see whether they have had an antibiotic-resistant bacterium in the past. If they have, then it is essential to ensure that the antibiotic used to treat the current infection will also treat any previous resistant bacteria as these are likely to be the cause this time as well.

Are there any cautions and contraindications to the choice of antibiotic?
The decision about which antibiotic to use is often complicated by a number of patient related factors including:
  • Renal failure – it is often difficult to know what the true renal function of elderly patients is (60% of over 75 year olds have moderate to severe renal failure, CKD III-V), and many antibiotics should be used at reduced doses in renal failure. Estimated glomerular filtration rates (eGFR) from biochemistry laboratories do not take muscle mass into account and assume everyone is the same weight. If a patient has very little weight then the eGFR can significantly overestimate renal function e.g. an 85 year old lady with a creatinine of 65mmol/L who weighs 70kg has a calculated GFR of 62ml/min but if she only weighs 45kg the calculated GFR is only 40ml/min, whereas in both cases the eGFR will be >60ml/min. In my experience, the most common error with prescribing for UTIs in renal failure (a patient with a calculated GFR <60ml/min) is to use Nitrofurantoin. With PHE guidelines suggesting Nitrofurantoin 2nd line this is a very common oversight in the elderly. Not only will Nitrofurantoin not work in renal failure, but the patient will develop Nitrofurantoin toxicity with nausea, vomiting and increasing confusion, which can all lead to the false assumption that the patient is dying from their UTI. In my opinion, unless you know that the patient has a calculated GFR >60ml/min, Nitrofurantoin is best avoided in the elderly
  • Drug interactions – Many elderly patients are on lots of different medications, and these can potentially interact with the antibiotics often used to treat UTIs. The most serious interactions in my experience are with antibiotics such as Trimethoprim and Ciprofloxacin when given with Methotrexate. Trimethoprim works in a similar way to Methotrexate and Ciprofloxacin increases Methotrexate levels: both antibiotics can lead to bone marrow failure if given with Methotrexate and are therefore contraindicated. Trimethoprim and Ciprofloxacin also both increase Phenytoin levels in people with epilepsy, and Ciprofloxacin can also lower the threshold at which patients with epilepsy can have seizures. Trimethoprim and Ciprofloxacin should be avoided if possible in patients with epilepsy
  • Beta-lactam allergy – 1 in 20 people get a rash with penicillins and 1 in 2000 get a severe reaction such as anaphylaxis. Penicillins such as Amoxicillin and Co-amoxiclav should be avoided in all patients with a history of penicillin allergy, but if the allergic reaction is a rash then other beta-lactams such as the cephalosporins can still be used. If the allergic reaction is severe then all beta-lactams should be avoided

What duration of antibiotic treatment should be given?
The decision about how long to treat a patient with a UTI is dependent on whether the UTI is classified as uncomplicated, complicated or pyelonephritis. An uncomplicated UTI is an infection in women with a structurally and functionally normal urinary tract. A complicated UTI is an infection in men or a functionally or anatomically abnormal urinary tract. Pyelonephritis is an infection of the renal tissue.

The duration of treatment for each type of UTI is:
  • Uncomplicated - 3 days 
  • Complicated  - 7 days
  • Pyelonephritis – 7 days

Should a urine sample be sent to the microbiology laboratory?
It may not be necessary to send a urine sample to the microbiology laboratory for every patient with a suspected UTI, but a urine dipstick should be performed on them all as a negative urine dipstick is very good at excluding a UTI. For an earlier blog about diagnosing urine infections click here

A urine sample should always be sent to the laboratory for the following situations:
  • Failure of 1st line therapy
  • Recurrent UTIs
  • Previous UTIs due to bacteria resistant to commonly used antibiotics such as Trimethoprim, Nitrofurantoin and beta-lactams (including cephalosporins)
  • Unusual choice of intended antibiotic treatment e.g. Fosfomycin
 
If a urine sample is being sent to the laboratory it is essential to complete the request form accurately. Clinical details should be provided, and the recent and proposed antibiotic treatments given. This information allows the Microbiologist to adapt the laboratory report to the specific patient and release appropriate antibiotic sensitivities for current treatment. It also prevents you needing to call to check; microbiologists will not release sensitivities if you gave no information about what the patient had been treated with! My personal frustration is a request form stating “? UTI”; this is not a clinical detail but rather a blindingly obvious statement about a possible diagnosis - if a UTI wasn’t a possibility, surely a urine sample wouldn’t be being sent to the laboratory in the first place? Good clinical details might say: “nursing home resident with moderate renal failure, incontinence and confusion, failed treatment with Trimethoprim, proposed treatment with Nitrofurantoin”. This allows the microbiologist to release both Trimethoprim and Nitrofurantoin sensitivity and give alternatives for an elderly patient who might be in renal failure. It is also good practice to ensure that a copy of the report is directed to the patient’s own GP if you are seeing them in an oncall capacity.

Examples of empirical treatment strategies
In all of the scenarios below, unless you know that the patient has a calculated GFR >60ml/min, Nitrofurantoin is best avoided in the elderly.

Scenario 1 - 85 year old lady, unknown renal function, no allergies, uncomplicated UTI.
Treat with Trimethoprim for 3 days, no need for a sample to be sent to the laboratory. If recently failed treatment with Trimethoprim consider using Amoxicillin (as most UTIs are caused by E. coli which usually remains sensitive) and send a urine sample to the laboratory. Often cephalosporins are prescribed to this group but these can predispose to Clostridium difficile and should be avoided if possible. Advise the nursing home staff to contact the patient’s own GP if she fails to respond to treatment or becomes more unwell.

Scenario 2 - 85 year old lady with unknown renal function, beta-lactam allergy, uncomplicated UTI.
Treat with Trimethoprim for 3 days, no need for a sample to be sent to the laboratory. If recently failed treatment with Trimethoprim and beta-lactam allergy is non-severe then consider using a cephalosporin for 3 days e.g. Cefradine, Cefaclor or Cefalexin and send a urine sample to the laboratory. If beta-lactam allergy is severe then consider using either 3 days of Ciprofloxacin or a single dose of Fosfomycin and send a urine sample to the laboratory. Advise the nursing home staff to contact the patient’s own GP if she fails to respond to treatment or becomes more unwell, specifically warning them about the risk of Clostridium difficile if using cephalosporins or Ciprofloxacin.

Scenario 3 - 85 year old lady with unknown renal function, unknown allergies, uncomplicated UTI due to a resistant bacterium
Treat with an antibiotic to which the recent urine culture result is sensitive. It is increasingly common in primary care to see E. coli resistant to most oral antibiotics, as well as producing extended-spectrum beta-lactamases (ESBL). Ciprofloxacin for 3 days occasionally remains active but a more reliable choice would be a single dose of Fosfomycin which is almost always still active. In this circumstance it is essential to send a urine sample to the laboratory and advise the nursing home staff to contact the patient’s own GP if she fails to respond to treatment or becomes more unwell.

Key points
So what may appear to be a simple problem at first glance may not be so clear cut. The key questions that should be considered are:
  1. Does the patient have a problem with recurrent UTIs?
  2. Are there any cautions and contraindications to the choice of antibiotic?
  3. What duration of antibiotic treatment should be given?
  4. Should a urine sample be sent to the microbiology laboratory?
 
Whatever the outcome of these decisions it is important to make sure that the nursing home knows to call for a review if the patient doesn’t respond to treatment or becomes more unwell.


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    Blog Author:

    David Garner
    Consultant Microbiologist
    Surrey, UK

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