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The panelists discuss the importance of appropriate culturing and how their antibiotic regimen for treating diabetic foot infections has evolved over the years.
Dr. Armstrong: How and when should we culture wounds?
Dr. Lavery: The most important point is when not to culture wounds. I see a lot of medical students and podiatrists, as well as some residents who rotate throughout the wound clinic, and their knee-jerk response is to culture everything. They want to swab every wound on a person’s body. This is another reason the IDSA classification is a nice teaching tool.
Again, it goes back to what one sees clinically. If there is a clinical infection, one may have a reason to culture the wound. However, if there is no clinical infection, then one would not culture. Otherwise, one is creating an unnecessary expense and generating information that probably will not impact treatment. When a wound is infected and the clinician is looking for underlying pathogens, one should prep the wound, debride it and get some tissue, preferably deep tissue, for a culture. Generally, I don’t prefer to swab them.
|  | | “A recent study shows that clinicians will be wrong a third of the time if they use superficial swabs for cultures.”
— Dr. Lipsky |
Dr. Lipsky: I agree with Dr. Lavery entirely. We have been saying this for a long time and we have cited several studies that were done in the past decade. I have come across a more recent study that Slater, et. al., published in Diabetic Medicine in 2004.15 The authors of this study looked at 60 infected diabetic foot wounds and did a superficial swab before debridement, which is unfortunately the way wounds are frequently cultured in clinical practice, and then obtained a deep tissue specimen by a curettage type of method post-debridement.
Culture results from the superficial swab showed a mean of almost 2.7 isolates compared with 2.5 isolates per culture from the deep tissue specimen. In comparing these two, they found the results were identical in only 62 percent of patients. There was an additional organism on the swab that was not present in the deep tissue in 25 percent of cases. The swab missed the organism that was present on the deep tissue in 18 percent of the cases. Superficial wound swabs were particularly poor when it came to wounds that went deep to bone, where they recovered all the isolates only 55 percent of the time.15
This paper shows that clinicians are going to be wrong at least a third of the time if they rely on a superficial swab compared to what a better specimen would show. Wrong culture results lead to wrong antibiotic choices with either over- or undertreating of the true pathogens.
Dr. Joseph: In 1978, in the Journal of the American Medical Association, Mackowiak wrote there was very little correlation between sinus tract cultures and cultures from bone in osteomyelitis with the exception of Staph aureus.16 If Staph aureus grew from the sinus tract, one could be pretty certain that Staph aureus was in the bone. Dr. Lipsky, was there any sort of finding in this paper you just referenced that is similar in that regard, showing for instance that Staph is common in both?
Dr. Lipsky: They did not specifically mention this. It is interesting, however, in the Mackowiak study to think about the fact that there are two common events, Staph aureus isolated from bone and from a sinus tract. Since Staph was the most commonly isolated pathogen in both sites, it is not surprising that there would be a correlation between the two different culture specimens for that organism. It may be a statistical aberration and I would like to see someone redo that study. I think there is a need to look again at the issue of whether culturing sinus tracts helps in trying to determine the etiologic agent in osteomyelitis.
Exploring The Evolution Of Antibiotic Regimens For Diabetic Foot Infections
Dr. Armstrong: In your clinic, what is your current antibiotic treatment regimen for diabetic foot infections and how has it changed over the years?
Dr. Joseph: The antibiotic selection has changed a little bit. In regard to the mild infections, we know we can treat these with oral antibiotics. For years in podiatric practice, amoxicillin/clavulanic acid was the number one most commonly used drug because of this impression that this is a broad-spectrum drug. It offers anaerobic coverage, has some gram negative coverage and some Enterococcus coverage. This was sort of an all-in-one drug that could be used in cases of mild diabetic foot infections.
|  | | Here one can see a clean, non-infected ulcer after debridement. One should not culture wounds that have no clinical signs of infection, according to Dr. Lavery. (Photo courtesy of Warren Joseph, DPM) |
Now we are a little more cognizant of the fact that the aerobic gram positive cocci are the most common organisms in diabetic foot infections so we can probably treat these infections with drugs such as cephalexin or any of the other anti-staphylococcal oral cephalosporins such as cefdinir. When patients are truly allergic to beta-lactams, we may use clindamycin, which has some anaerobic spectrum but no gram negative spectrum.
For the more severe infections, we still see a lot of use of the beta-lactam and beta-lactamase inhibitor compounds such as piperacillin/tazobactam or ampicillin/ sulbactam. In our center, piperacillin/tazobactam is still probably the most commonly used antibiotic to treat severe diabetic foot infections. I believe there is a move now to consider drugs such as ertapenem, a new type 1 carbapenem.17 Certainly, ertapenem is a more convenient option for outpatients and presents a new opportunity for outpatient parenteral antimicrobial therapy. It is probably less expensive for inpatients due to the once-a-day dosing.18 The SIDESTEP study shows the efficacy of ertapenem was at least as good as piperacillin/tazobactam, if not potentially superior at a 10-day follow-up.19-23
Overall, there has been a little bit of shift there. We are now emphasizing the singular aerobic gram positive aspects when it comes to treating mild to moderate diabetic foot infections. For more severe infections, we are looking at broader spectrum drugs for more severe infections that may be easier to use due to reduced dosing.
Dr. Lavery: I agree with what Dr. Joseph said. I find myself using clindamycin and, in some cases, trimethoprim/sulfamethoxazole more than I did five or six years ago without regret.
Dr. Joseph: I am a little concerned. Trimethoprim/sulfamethoxazole is a good drug, especially in patients who are allergic to penicillin. My concerns are allergy and potential interaction with the sulfonylureas. Also, if there is some decreased renal function, one has to make sure the patient is really hydrated because of crystalluria problems. Overall, though, we are using drugs with a narrower spectrum for the mild infections.
Dr. Lipsky: Unfortunately, trimethoprim/sulfamethoxazole is one of the few drugs that has not been tested in clinical trials of diabetic foot infections. On the other hand, it is active against many community-acquired strains of MRSA. It is one of the few oral agents that is inexpensive and available for that purpose. Trimethoprim/sulfamethoxazole and perhaps doxycycline are the agents that we are going to use more frequently because they are inexpensive and do cover perhaps 60 to 70 percent of the MRSA strains in the community.24
Dr. Joseph: Clinical Infectious Diseases recently published a very compelling paper.25 It was one of the first papers that I am aware of that looked at the newer generation of tetracyclines for complicated skin-skin structure infections. It was a retrospective study of only 24 patients but it was really the first study with any numbers at all that showed four complicated skin-skin structure infections caused by MRSA. Doxycycline or minocycline was actually effective.
Dr. Lipsky: With the MRSA coverage issues, I think we must bring up the point made in a recent New England Journal of Medicine article.26 These authors found that while MRSA is a more frequent and sometimes very virulent pathogen in community acquired infections, providing specific coverage for that organism in one study did not appear to make much difference in the patients who had MRSA infection. The explanation for that was not entirely clear but patients who received coverage against MRSA did not do any better than those who did not, even though these were serious infections.
|  | | When it comes to mild diabetic foot infections (as shown with the above photo of a cellulitic hallux paronychia), Dr. Joseph emphasizes the singular aerobic gram positive coverage when choosing an antibiotic. (Photo courtesy of Warren Joseph, DPM) |
This raises the issue of how important the correct selection of antimicrobial agent is in relation to a variety of other things we do, such as caring for the wound, optimizing glycemic control, offloading the foot and other aspects of care, in treating those with diabetic foot infections. Certainly, treating an MRSA infection with an antibiotic active against that organism is appropriate in most instances.
Discussing The Emergence Of More Specific Indications For Antibiotics
Dr. Armstrong: What are some of the emerging antibiotics that show some promise in the diabetic foot that you are aware of that may be available now or may be coming out over the next couple of years?
Dr. Joseph: It is really interesting to see what is happening in the world of diabetic foot antibiotics. Diabetic foot infection has always been kind of the poor stepsister of the infectious disease world. I remember doing two “Meet the Professor” sessions with Dr. Lipsky at the IDSA meeting seven or eight years ago. I think that was the first time in the history of IDSA that they ever had talks on the diabetic foot.
The emerging interest in this subject translated into interest within the pharmaceutical industry. If you look at the history of all antibiotics, there are only a couple of drugs, piperacillin/tazobactam and linezolid, that actually have a specific indication for complicated skin-skin structure infections including diabetic foot infections. Of course, linezolid is usually reserved only for those complicated diabetic foot infections that have MRSA.
The pharmaceutical industry is starting to recognize that diabetic foot infection is a viable condition to get an indication for these new antibiotics. The makers of ertapenem have filed for the indication and we may see this occur with some of the other emerging drugs such as tigecycline and dalbavancin. |
