Mixing Metronidazole Solution in Grafting Material?

I usually use tetracycline ,(half a cpsule of 250mg per gram of allograft), with nice results... not a single infection in years. best of luck

do u give systemic antibiotics as well, or u just go with the tetracylin local application?

The TCN is used to inhibit collagen break down during the healing process formation and not for the antibiotic properties.

Dear Dr W, I guess you are referring to my lecture given two weeks ago in Vancouver...Using Metronidazole in sinus lifts is not a new treatment modality and was advocated by a french group(Choukroun et al) a couple of years ago.An article using this method was submitted by our group for publication recently. 2ml of this 0,5% solution are containing only 10mg of metronidazole, i.e. 1/20 of a standard 200mg oral tablet. This is just enough to limit the contamination of the biomaterial, and to protect the early phases of bone construction from infection and the related inflammatory reaction.

As Dr.Mazor has mentioned, mixing of antibiotics with graft particularly in dead space of antrum is not new at all.I have seen and learned from pioneers of max. sinus grafts Dr.Hilt Tatum many years ago.You can even mix amoxicillin provided patient is not hypersensitive to it.Few drops of sterile gentamycin eye drops can be used too.

apparently there is a lot in practice. the main question is: r any of these agents evidence based? or is it anecdotal findings only? is their a comparison to group got placebo? if any can prove whats he using, this will be more scientific for others to consider.

Adding metronidazole to the grafting material does not seem to be a very wise idea.First, experience has shown that local usage of an antibiotic may result in development of systemic hypersensivity or drug allergy to that chemotherapeutic agent in the future.Second,metronidazole has a Disulfiram-like effect which means that when it is consumed in combination with Ethanol, the patient should be anticipating serious consequences.If the route of administration is oral or parenteral, then, one can avoid those interaction complications by simply stopping the drug consumption. However, if it is planted inside the body of the patient as a bulk, then its gradual absorption would be out of control.Third, metronidazole is a kind of drug that its topical application or usage near the eyes is absolutely forbidden, so its local storage inside the maxillary sinuses (even in low cocentrations) which are in close proximity to the eyes and share common vasculature and lymphatic drainage, does not seem to be quite safe for the patient.

I totally disagree with the previous statement that metronidazole is a bad idea.An article was submitted recently regarding it's use in sinus lifts. The local use of a very small quantity of metronidazole (equivalent to only 1/20 of a common 200mg oral tablet) could provide more security when performing sinus-lift procedures and an improved quality of the graft. This protocol should not be considered as an antibiotic therapy, but only as way to limit the initial contamination of bone graft. Analysis of tomodensitometric controls following sinus grafts clearly demonstrates systematic lack of homogeneity. Sinus contamination by anaerobic bacteria seems almost unavoidable during bone graft surgery, and this problem may jeopardize the healing process. The aim of this study was to characterize in a systematic way the non homogeneities observed at 1, 2 or 3 months postsurgery within allogenous sinus grafts, and to assess the possible influence of a 0,5 % sterile solution of metronidazole incorporated in the sinus bone graft.The 12 grafts performed without metronidazole showed significant non homogeneities at 1, 2 or 3 months. Moreover, when a CT-scan is performed at 10 days ,the presence of air bubbles in the graft is confirmed. The tomodensitometric aspects of all grafts treated with metronidazole in this series were absolutely identical : they showed a high degree of homogeneity

Dr Ziv, are u adding metronidazole to you sainus grafts? did that change you waiting period of implant plaecement? how long do oyu wait?

I would like some input on incorporating Clindamycin into an allograft. I was informed by a very astute clinician that he mixed this in with his allografts and I began to do so. It makes perfect sense to me and the larger the graft, the more prone I am to use it. I am incorporating 300mg/2ml into 1cc of MFDB. I am not sure of the improved quality of bone but as mentioned, it isn't for that primarily but as a deterrent to an untoward event. I certainly make sure the med hx does not indicate sensitivity. I was just curious if anyone has had experience with it. As far as Metronidazole, I can see both sides of the issue here. With TCN, I have strayed away from that from being informed that it chelated the good stuff that was forming. Yet many people use it. I just haven't. Don makes a great point about it, though, that has to do with repair and collagen. And he it literature-driven. Bill.

I just had two extractions at UCLA and asked the doc if he would add antibiotic to the bio-oss graft material....he said no and i wished he had.

When adding antibiotics to graft materials, there is an additional area of concern. If you are using an antibiotic whose mode of action or breakdown products are acidic (i.e. tetracycline hydrochloride), the lowering of pH has a profound effect on osteoblastic activity. Osteoblasts release vascular endothelial growth factor (VEGF) which is responsible for early angiogenesis. Even a slight drop in pH from 7.4 to 7.1 is enough to totally deactivate DNA synthesis within the osteoblast and this will continue until pH becomes neutral. This prevents the synthesis of type I human collagen; the precursor to early bone matrix formation. It should be obvious that this will significantly delay new bone formation and the timing of implant placement. If you add antibiotics to grafts, you should be aware of the mode of action and then time your cases accordingly. RJM

Dear Asri, Adding antibiotics doesn't change my waiting period for the sinus grafts which is 6 months.It helps me control possible anaerobic infections.I usually reconstitute my grafting material with the 0.5% solution.It is non acidic compared to Tetracycline that was previously mentioned.

thank you for the replies...the reason I felt I needed the antibiotic treatment was because I have had so much infection above/near the root, failed apicos. Plus we only removed 2 and I thought it would be extra and good precaution to use some topical and then add bio-oss. I do realize that bloodflow is a key factor and I wouldn't want to inhibit the new bone growth/graft. And...for you doctors to know...the pain was very severe during the first 3 days of healing. The apicos were very difficult to remove. Can anyone tell me the best way to make a flipper for missing tooth #12 and #10, and a pretty comprimised #13 not a great candidate to hold anything.???

To Dr.s Miller, Mazor and Jafari and Dr. , are there any studies evaluating the incorporation of ABX into the grafts? And if so, are there any comparative studies on ABX used? When I went to the AAID Maxicourse under Dr. Ed Mills, opinions of ABX were all over the board, even oral prophylaxis regimens ranging from none to many. My positions has always been to "prevent" an anarobic disaster, but you make a great point about the specific activity and breakdown products. With that in mind, I could see how you could postpone the disaster by killing all the anaerobes on the front end, only to kill the graft with metabolites and thed a late failure produces the very event you didnt want in the first place. I suppose that another factor to consider is what might even be happening to the autogenous bone if that were being used as well. And would it effect PRP or fibrin glue? Like I stated before, the larger the graft, the more likely I am to incorporate ABX into the graft. Now there is something else for me to think about. Thank you for any insight in this. Bill

Dr. Woods, I use clindamycin routinely in my grafts for sinus augmentation. I previously used ampicillin but have switched to clindamycin because of the small group of patients that have sensitivity to penicillin-like Abx. I have found no difference in success between the two Abx or even without but I was trained to use it. I actually soak my membrane in Abx as well and have found no deleterious effects. I stay away from TCN due to the acidity and filler that is commonly added. I must say it is interesting to read differing opinions on this since it probably has little overall effect.

Reading these two articles are recommended to those who are looking for more scientific data: 1) A randomized prospective controlled trial of antibiotic prophylaxis in intraoral bone-grafting procedures: preoperative single-dose penicillin versus preoperative single-dose clindamycin: J.A. Lindeboom, , J.W. Frenken, J.G. Tuk and F.H. Kroon International Journal of Oral and Maxillofacial Surgery, May 2006, Pages 433-436 2) A prospective placebo-controlled double-blind trial of antibiotic prophylaxis in intraoral bone grafting procedures: a pilot study,Jerome A. H. Lindeboom and Hans P. van den Akker,Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology & Endodontics, Volume 96, Issue 6, December 2003, Pages 669-672

Dr. Jafari, Thank you for referencing these articles as they are a reminder that Abx may not be necessary after surgery. However, these articles are not in line with the discussion as I understand it. These studies discuss systemic use with onlay bone grafting procedures and we are focused on Abx mixed in grafts for sinus augmentation specifically. Perhaps it is also unnecessary to mix Abx with the bone graft material but I feel the sinus requires added coverage against anaerobes.

As for the wisdom of using antibiotics incorporated in grafts, particularly in sinus augmentation should be at clinician's discretion until a peer review study comparing the the results and difference in waiting period between graft w/ and w/o antibiotics and even effects of antibiotics in different graft materials is available. At NYU we do not use antibiotics in grafts, but we give systemic antibiotics,mostly amoxicillin or clindamycin. In my practice I do use amoxicillin or clindamycin without any undesirable effects on grafts.

Thank you very much for the references and comments. Sorry about my spelling disaster, it was late and I didnt have my reading glasses...and I cant type - a deadly trifecta! Bill

Dr. Katranji That is exactly my point.If a practitioner has decided to provide an atibiotic coverage for his/her graft, then it better be via a systemic route rather than mixing with, or soaking into the chemical agent.As Dr. Miller has wisely reminded us,the chain of chemical actions and reactions that happen during the local absorption and systemic metabolism of that agent (and even if not the drug itself), may be very harmful to the grafting cells' survival.Incidentally, I feel that it is necessary to stress on a clinical fact about metronidazole.Many clinicians strongly believe that any topical application or usage of any form of metronidazole in the vicinity of the patients' eyes is totally unsafe.

Dr. Jafari, Mixing antibiotics is a common practice, taught by the leaders and pioneers of the technique, and has shown no delayed effects on the graft. I understand your point on metronidazole and the eye but I maintain that the local delivery and systemic use of antibiotics possess individual and different advantages specific to the sinus lift procedure. The articles you present are not relevant to this argument. I don't think adding abx to the graft is the only way, but it is the way that has shown high success in my hands.

I think it is clear from the comments on this thread that mixing antibiotics with graft material for sinus grafts is an empirical paradigm. I cannot recall any controlled, double-blinded studies on this procedure. While there are countless case reports in the literature, the efficacy of adding ABX to grafts is suspect. Add to that the dramatic increase in concentration for the formulations stated as compared to the oral route and it is difficult to come to a logical conclusion. But if we accept the fact that it is anaerobic contamination that we are concerned with, where do these anaerobes reside? Certainly not betwwen the Schneiderian membrane and osseous sinus floor. And I assume that we are using graft materials that are sterile. So if the anaerobes are in the sinus, the only way that they will enter the surgical area is through a sinus perforation. A good antibiotic regimen, timed just before sinus surgery, should be as effective as mixing it with the graft material. Unless you understand the biochemistry of antibiotic breakdown and it's effect on bone physiology, I would not recommend that we add this to our grafts. RJM

As I already have mentioned before, I am Not absolutely for or against use of antibiotic in grafts. Though I have one concern. It is very difficult to have absolute sterile surgical field when we deal with any intra-oral surgical procedure specially in dentulous patient.

I agree, absolute sterile conditions are difficult to achieve and verify. Thankfully I understand the biochemistry of Abx and their breakdown and feel comfortable using them in my graft and membrane.

End of my commentary: teh control without matronidazole are not homogeneous because the are many bubles of gas, traduction of anaerobic contagion. I repeat it's not a local Antibiotherapy..

It's not a local antibiotherapy! It's usually impossible to realize a sterile surgery in the mouth: the contagion of the graft is absolutely obligatory. And the most common bacteria in the mouth are Anaerobes.. My idea is only to prevent the contagion of the graft during the surgery, during the manipulation with the contaminated instruments... And for this I proposed to add to the allogenc graft a very small quantity of metronidazole solution (2ml): only to hydrate the biomaterial and prevent the contagion. The CT control after 1 week show a very homogeneous graft after using metronadazole, and a non homogeneous graft without metronidazole.

What about the possibility of possible teratogenic influence for metronidazol in the long term prognosis?

I heard from Antonio Scarano (a researcher from Chieti University, Italy) that mixing any chemioteraopic such as metronidazole or others would impair platelets' adhesion to the granules of graft material. In Scarano's opinion, the only presence of blood clot would be advisable.

Just use Ampicillin , I personally use that in sinus grafts and work out well, its not acidic. and it works well.

Asri, we usually start our patients on a combo of a systemic antibiotic, a dexametasone and a non steroidal antimflamatory strting 2 days beore the surgery and it has given great results for us.

I love this website - heaps of new ideas and techniques for a novice like me to learn from and the occasional drama of feuding minds. One small point though which always dictates my use of a loading dose of ABX an hour before any implant surgery (followed by a weeks further ABX), is that at best even after a thorough clean and pre-procedural rinsing with a CHX mouthwash, the oral environment remains bug laden - the achievement of absolute sterility is IMPOSSIBLE not difficult to achieve. The wonder of oral implantology is that despite this bug load, we routinely achieve excellent results.

I agree to use an antibiotic in a sinus lift. What I want to know is what is your choice of graft material and where can I purchase it. thanks in advance .Leo

(Mombelli et al): BRG did better when u give Metronidazole. ( Demolon et al ): BRG with system. Augmentin did not do better (Machtei et al): BRG with syst. TTC did not do better (Yukna et al): FDBA+TTC w/ systemic TTC in LJP did better, showed Algain,Bnfill, PPD reduction. (Drury et al): FDBA+TTC did better than FDBA alone(Baboons) TTC was always used as a mean to accelerate FDBA demineralization and never examined to my knowledge under the prism of its p[ossible local decontamination effect. I think that the rationale of mixing your graft or membrane with an antibiotic is solid but it is important to understand the properties of the agent used, the BRG used, the pt's background/MedHx etc. NO magic recipie being good for every single case.

Homeostasis, if we remember our physiology is the innate power of the body to bring any imbalance of our body to a proper balance. We should not underestimate the power of our bodys' cells and tissues to overcome any local conditions eg. acidity, alkalinity, bacteria, foreign bodies etc. in order to fulfill its normal duties. Any antibiotic, if the patient is not allergic, and if added in sensible amounts will locally kill or inhibit bacteria growth and should be useful if one wants to have additional guarantees against infection. Most localized insults if not too excessive will be overcome and bone will form, especially if most pathogens are eliminated locally. Whatever is left will be insufficient to mount an infective attack. My measured opinion is that it is okay to use localized insite antibiotics. And that is why we manage to get away with a lot of dubious treatments, not because our technique is foolproof, but because the body is supersmart.

I just want to ask about: 1- your opinion in the use of PRF ( Platelets rich fibrin ) membrans put beneath the lifted sinus membrane ( external sinus lift) & held in place by the Implants fixed in place at the same time of the sinus lift without any bonegraft even if we have only 2-3 mm of crestal bone as long as we are capable to have a good implant primary stability ? 2- What are the specifications of the machine centrifuging the blood to prepare the PRF ( spin/mn?-fixed rotor or swing out rotor?-

Flagyl is a graft material. Sounds good but flagyl is a sulfa and sulfas are very allergenic. Be careful. Try clindamycin.

Where/how do you get the 0.5% metronidazole soln?

Flagyl, (the tradename for metronidazole), is not a sulphonamide, (a "sulfa"!), it is an imidazole and allergy to it it relatively unusual (unlike to sulphonamides). Kind Regards, Bill Schaeffer

I will usually add a little Clinda solution to my sinus grafts and use Metronidazole solution (purchased at a hospital pharmacy) to flush out the sinus after I've opened it up. The CT study quoted above definitely lends evidence to the use of ABs in sinus grafts. The French group showed better results. Also, it costs next to nothing! As far as concerns about the sinus being close to the eye, the mouth is close to the eye and the patient can still take a Flagyl pill. The sinus is far removed from the eye anatomically.

PURPOSE: The purpose of the study is to investigate the efficacy of metronidazole topical gel in the treatment of ocular rosacea. METHODS: Ten patients with ocular rosacea were treated prospectively with lid hygiene and topical metronidazole applied to the lid margin in one eye and lid hygiene alone in the fellow eye. The treatment period was 12 weeks. A masked observer graded the ocular findings at the initial visit and at the conclusion of the treatment period. Pretreatment scores were compared with post-treatment scores with respect to ocular surface, eyelid margin, and combined eyelid plus ocular surface. RESULTS: Eight of ten treated eyes improved, whereas only five of ten control eyes improved. There was a statistically significant improvement in the eyelid score in both the treated and control groups (P = 0.003, P = 0.025, respectively), but no significant improvement in the ocular surface score in either group. When the pretreatment and post-treatment eyelid and ocular surface scores were combined, there was a significant improvement in the treated eyes but not in the control eyes (P = 0.022, P = 0.10, respectively). No adverse effects of the metronidazole treatment were encountered in this study. CONCLUSION: Metronidazole topical gel may be a safe and effective means of treating rosacea blepharitis SEEMS THESE GUYS WERE PUTTING METRONIDAZOLE GEL .75% A LOT CLOSER TO THE EYE THEN IN THE SINUS!

Sir, but you have forgotten to mention the name of the article, its authors, date and place of publication etc. In that case, the readers will be able to read the whole story and judge by themselves.