So where does bone cement fit into this story? Since the 1940s, bone cement has been used, well, to cement bones back together (sorry it’s so obvious!). The bone cement I am discussing here is one of the most commonly used, a polymer called polymethylmethacrylate (PMMA). One of the first applications of PMMA was in cranioplasties (to repair cracks in skulls) in the 1940s. Since then, PMMA has become a widely used material across the field of orthopaedics, and especially in arthroplasties, where it is used to fix the prosthetic joint to the remaining bone. It is a material that stays in place after the surgery, as new bone tissue will eventually use the cement as a scaffold (known as osteointegration).
Because of the high frequency with which bone cement is used, and the lack of a need to remove it (disturbing a healing wound), it really does make an ideal candidate for antibiotic loading. Which is why: antibiotic loaded bone cement was used in 86% of total knee and 45% of total hip replacements in the UK in 2012; and antibiotics such as gentamicin are pre-mixed into bone cement powder. Although as with most things, considerations have to be made!
When added to the cement, an antibiotic becomes incorporated into the polymer. However it has very minimal use and benefit if it stays stuck in the cement. Likewise it is useless if the cement or curing process (over 80°C in PMMA) alters the antibiotic’s chemical structure. Therefore it is essential that the antibiotics can get back out (elute) from the cement and enter the surgical cavity once inside the patient – at a clinically relevant dose and retaining their antimicrobial activity.
The antibiotic also cannot have an effect on the structure of the cement, which need to maintain its mechanical and structural integrity. For example, the antibiotic rifampicin stops PMMA from curing and therefore hardening, rendering the resulting cement useless. In the case of adding multiple antibiotics to the cement – to tackle multi-drug-resistant bacteria, or to protect against infections from different bacterial species – all the antibiotics have to elute from the cement, again at the correct dose and with their antimicrobial activity.
In addition to the PMMA specific issues, a possible issue with prophylactic antibiotics is that you could be the tiny minority that acquires pathogenic bacteria that don’t cause SSIs as often, or even worse, a strain that is resistant to the antibiotics that have been prescribed. Bacteria acquired from healthcare environments are known as ‘nosocomial pathogens’, and due to their environment can be more resistant to more drugs and even cleaning products, and produce worse symptoms in infections they cause. There are two reasons why prophylaxis isn’t an issue often. Surgeons are more frequently prescribing ‘multi-drug-cocktails’. This is a brilliant tactic because, two antibiotics are more likely to kill more bacteria than one – the bacteria are less likely to be resistant to two antibiotics, and because less bacteria should survive there is a smaller chance of antibiotic resistance developing. The second reason is that a lot of data is collected on the species that cause SSIs, both generally and in orthopaedics. This data is used to inform the decisions that surgeons make when prophylactically prescribing antibiotics.
For the unlucky percentage that do get a SSI after an arthroplasty, I have been informed that it is very unpleasant. It can be weeks before the patient differentiates the feeling of recovery from the surgery and an infection. For the even more unlucky, the infection can progress into the bone marrow and essentially hollow-out the bone. Which is why prophylaxis in surgery (not just orthopaedics) is important. Comparing the usage of antibiotic loaded cement (86% of total knee and 45% of total hip replacements), to the low rates of orthopaedic SSIs here in the UK, it is clear that this method is highly effective. However it must be used wisely, as with all antibiotics, because their overuse leads to bacteria developing resistance.
If these obstacles can be overcome, then a method is available to prophylactically prevent infections by multi-drug-resistant pathogens, by a range of pathogens, without disturbing the surgical site. Because of the efforts of orthopaedic surgeons, and microbiologists (including myself!), the risk of getting a SSI from an arthroplasty is very small, and will hopefully stay that way for the foreseeable future.
In part 3, I am going to talk about how my first piece of research, as an undergraduate, helped contribute to the current range of antibiotic loaded bone cements.
Thanks for reading!