At the clinic visit the patient’s respiratory function had once again deteriorated, and both he and his physician were understandably frustrated by this turn of events. The Physician called the Microbiologist for advice about what to do next.
When confronted with a patient failing to respond to treatment I believe it is important to adopt a structured approach to trying to work out why. The structured approach allows all possible reasons to be explored and also means that if an action to correct the problem doesn’t work then it is easy to continue down the list of potential reasons and try something else without going around in circles trying the same things over and over again.
Questions to ask:
- Has the antibiotic been given for long enough to assess for failed response? Few infections respond in <24-48 hours
- Is the diagnosis correct? Review the clinical history and investigations. If diagnosis incorrect initiate treatment for correct diagnosis
- Is the antibiotic choice correct for the diagnosis and common causative microorganisms? If incorrect antibiotic choice prescribe correct treatment
- Does the patient have a new problem or secondary infection? Examples: cannula site infections, bacterial infections following viral chest infections. If patient has new problem then commence new treatment
- Is the patient compliant with treatment? If patient refusing antibiotics then educate patient or prescribe more acceptable treatment
- Is the patient actually being given the antibiotic? Review the drug chart for missing doses. If the patient is not being given the antibiotic then correct the reasons why e.g. IV antibiotics are not being given due to lack of IV access. Therefore gain IV access
- If patient on oral antibiotics is the patient able to swallow and absorb oral medication? If patient unable to take oral antibiotics, or absorb from the gastrointestinal tract, consider converting to IV
- Is the dose of antibiotic appropriate for the patient? Does the patient weigh more than 70kg? If patient overweight, dose of antibiotic may need increasing (discuss with the ward Pharmacist or Microbiologist)
- Is the patient on any drugs that might interact with the antibiotics e.g. folic acid and Trimethoprim? If uncertain then check with the BNF or discuss with the ward Pharmacist. Consider stopping drug that is interacting or change antibiotic
- Does the patient have prosthetic material that needs to be removed before the antibiotics will be effective? e.g. IV lines in cannula site infections. Remove prosthetic material and continue current treatment
- Does the patient have an infection with a microorganism resistant to antibiotics e.g. MRSA, GRE, ESBL or AmpC producer, Pseudomonas spp.? Prescribe an antibiotic with activity against the resistant bacteria
So let’s consider our patient above.
Has the antibiotic been given for long enough to assess for failed response?
The patient has had at least 3 weeks of antibiotics. An exacerbation of COPD should have responded by now.
Is the diagnosis correct?
The clinical features and assessment by the Respiratory Physician is very clear, this patient has an exacerbation of COPD. There is no other possible diagnosis at this stage.
Is the antibiotic choice correct for the diagnosis and common causative micoorganisms?
Clarithromycin, Doxycycline and Levofloxacin are all appropriate choices of antibiotics for the treatment of exacerbation of COPD which is often caused by Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus or Moraxella catarrhalis. Whilst the Haemophilus influenzae isolated from his sputum sample is resistant to Clarithromycin, it is sensitive to Doxycycline and Levofloxacin so these should have treated this bacterium. Viruses can also cause exacerbations of COPD but there is evidence that the cause is Haemophilus influenzae and anyway viruses would have resolved by this stage.
Does the patient have a new problem or secondary infection?
The Respiratory Physician has been unable to find any secondary problems, and on specific questioning there are no complications of the antibiotic courses such as drug allergy.
Is the patient compliant with treatment?
The Respiratory Physician is confident that the patient has taken his medication.
If patient on oral antibiotics is the patient able to swallow and absorb oral medication?
The patient is able to swallow his tablets and capsules and has no bowel problem such as inflammatory bowel disease or malabsorption which might prevent him from absorbing his antibiotics.
Is the dose of antibiotic appropriate for the patient?
The patient was prescribed the correct doses of antibiotics for exacerbation of COPD. He weighs 85kg which whilst making him overweight is unlikely to be enough to make the doses of antibiotics prescribed too low.
Is the patient on any drugs that might interact with the antibiotics?
The Respiratory Physician ran through the list of other medications the patient was taking, and within this were antacids for the management of recurrent gastritis. So could these be interacting with his antibiotics?
Antacids can interfere with the oral absorption of some antibiotics and in particular both Doxycycline and Levofloxacin which were given to this patient. They do this by binding to the antibiotic within the bowel lumen thereby preventing it from being absorbed. This would also explain why this patient responded to IV antibiotics but then when given the same antibiotic orally they got worse again. Essentially the patient received the entire IV antibiotic but almost none of the PO antibiotic which would have stayed inside the gastrointestinal tract.
Does the patient have prosthetic material that needs to be removed before the antibiotics will be effective?
The patient has no prosthetic material that might prevent them from responding to the antibiotics.
Does the patient have an infection with a microorganism resistant to antibiotics e.g. MRSA, GRE, ESBL or AmpC producer, Pseudomonas spp.?
There is no evidence that the patient has a resistant bacterium causing this infection. They have never grown any bacteria such as Pseudomonas spp. which might be resistant to either the Doxycycline or Levofloxacin.
So where are we up to with our review of why this patient may not be responding to the antibiotics prescribed for his exacerbation of COPD? The only explanation we have been able to identify is that the antacids he is on are likely to be preventing him from absorbing the oral antibiotics.
So what advice would you now give to the Respiratory Physician about how to resolve this issue?
The options are:
1. Treat the patient with IV antibiotics for the duration of his treatment which will be at least 7 days. This seems a bit extreme as it would necessitate the patient being admitted to hospital for a week just so he can be given his antibiotics.
2. Stop the antacids whilst his exacerbation of COPD is being treated. There is a risk of a flare up of the patient’s gastritis during this time.
In the end the Respiratory Physician discussed the two options with the patient and they decided to stop his antacids whilst he was on treatment. After a week of oral Levofloxacin he was back to his normal baseline respiratory function. His gastritis had been fine and so it was decided not to restart the antacids but to see how he got on without them.