7.1 Quantity measures: antimicrobial consumption

DDD is ‘defined daily doses’, and the main purpose of this DDD system is a tool for presenting drug utilisation statistics with the aim of improving drug use. It’s a WHO tool that was developed, and it is defined as the assumed average maintenance dose per day for a drug for its main indication in adults, assuming that compliance is there. So it’s a technical drug metric system that measures drugs consumption. And we can use it to standardise comparison with drug use between different drugs, between different [inaudible], between countries.

Like I said, it does not really – it’s a unit of measurement, but it does not reflect the prescribed daily dose. It’s not the same thing. They are different. They are different. So we can’t – you know, you can use it to calculate the drug consumption, cost of drugs, and also to study adverse – the frequency of adverse drug reaction.

In addition to what I said, DDD can be used to collect utilisation data in various settings. You can use it to collect sales data from the wholesale, dispensing data from the pharmacy with electronic or manual. You can use it to collect patient and contact-based data, patient survey data, health facility data, and so on and so forth we should note that DDDs are used to measure antibiotic use over time and are probably used by AMS team to monitor the trends within the ward, within the hospital, or a primary care setting. This allows the team to identify areas of other investigations and use audits and quality improvement methods to address such.

Quantity measures is the measures of the aggregate antimicrobial use. And it’s the most common metrics for the ASP. And they are often expressed as a rate x divided by y, as we mentioned before. By using a standard approach to recalculations, antimicrobial stewards are in a better position to make meaningful comparisons across locations where antibiotics are used: hospital, wards, patients.

There are many numerators that we can use, like defined daily dose, days of therapy, length of therapy, prescribed daily dose, and others. What's the difference between days of therapy and length of therapy? Days of therapy are the number of days that a patient is on antibiotic, regardless of the dose. And it’s applicable for paediatrics – that’s a good point. For example, if we have a patient who is on two antimicrobials: he started his first antimicrobials on Day 1 and Day 2, then stopped. While from Day 2 to Day 5, he used another antimicrobial, which is Antimicrobial 2. So the days of therapy for the first antimicrobial for this patient are two days of therapy. While for the second are only four. So the total days of therapy of antimicrobials for this patient are six days of therapy. But what about length of stay? Length of stay are the duration when he started his first antimicrobial regimen till the end of the last antimicrobial drug used. Here, the length of therapy are five days.

Days of therapy can be used to target the consumption of certain antimicrobial, meropenem, or certain class, like carbapenems, or even certain formulation. And it depends on your goal. Defined daily dose can be used too. But days of therapy can be measures also to assess some ASP strategy’s implementation, such as unnecessary double coverage, such as redundant anaerobic coverage of ertapenem and metronidazole, or compliance to antimicrobial duration therapy. And this can be clear from days of therapy. So days of therapy are used to assess some prescribing habits for wards or institutions as well. It’s advisable to review resources attached for further details on antimicrobial use metrics.

What’s a prescribed daily dose? It’s average prescribed dose in the main indication defined locally at ward, or hospital, or even a group of hospital level, but it does not allow inter-hospital comparisons. What about the defined daily dose? The defined daily dose is assumed average maintenance dose per day for a drug used for its main indication in adults. Which means that, for example, the paracetamol defined daily dose is 3 g. That means that the average maintenance dose (not the loading one) used for an adult patient who weighs 70 kg of paracetamol used as an antipyretic is 3 g daily.

A defined daily dose will only be assigned for drugs that already have an ATC code. ATC code consists of many items – a letter, the number, then another letter, then another letter, then another number – that we’ll see in a few seconds. But it should be emphasised that the defined daily dose is a unit of measurement and does not necessarily reflect the recommended or prescribed daily dose. Doses for individual patients and patient groups will often differ from the defined daily dose, and will necessarily have to be based on individual characteristics – age, weight and so on – and also pharmacokinetic considerations.

Defined daily dose are not established for topical products, sera, vaccines, antineoplastic, allergens extract, general and local anaesthesia, and also contrast media. So now, I will show you briefly how to navigate and get a specific DDD for a given drug formulation.

When you first opened the website for the WHO ATC/DDD, you will have a page like this. When you click ‘DDD’ on your left, you will have more information about the defined daily dose. When you click the ‘ATC/DDD index’, you will have this page where you can search for the DDD by the ATC code or the drug name. Obviously, searching by scientific name is much easier.

So we type, for example, ciprofloxacin. We will have all ciprofloxacin available. The code J is for systematic use of drugs; the number 1 is for antimicrobial class; the letter M is for quinolones; the letter A is for fluoroquinolones; finally, the number 2 is for the ciprofloxacin itself. That’s used as an anti-infective systemically without any combination.

We will choose the first one. We will have the following. As we see, the defined daily dose for oral cipro is 1 g, while that for parenteral use is 0.5. So we have to be very careful. Finally, don’t forget that the DDD is updated annually. And the last update is written below.

How to calculate defined daily dose? First step is to determine the number of DDDs of each antibiotic, which will be by the total grams dispensed, number of packages multiplied by a number of units per pack multiplied by concentration divided by the DDD defined by the WHO collaborating. This is the numerator data. Then you have to divide by a denominator data, as we mentioned before.

Some examples: you can see here ciprofloxacin, 500 mg tab, 20 per tab, 100 packages. So the number of grams are 100 packages multiplied by 20 tablets per pack multiplied by 0.5 g per tab, which is equal to 1000 g. Then the number of DDDs equals 1000 divided by 1, which is the DDD defined by WHO collaborating centre. So the total DDDs for ciprofloxacin to be taken orally are 1000 DDDs for this example.

What are advantages? Advantages are that they are independent from price and package size, easy, allow for comparisons, and it can define that one day treatment receives approximately equal weight, whatever the drug is. For example, 0.24 g gentamicin is approximately equal to 4 g cefotaxime, approximately equal to 14 g piperacillin.

But limitations: it is not suitable for paediatrics and patients with organ dysfunctions; it’s updated annually – we have to keep an eye on it; and the total DDDs is strongly influenced by formula mix.