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Antibiotics

Skin and soft tissue infections. Uncomplicated cellulitis in patients with normal host defenses. The sorts of things that you see most of the time in your practice. The two leading causes of cellulitis are Staphylococcus aureus and group A streptococci. You really need to cover those two organisms, and you can still do that with an oral anti-staphylococcal penicillin. Ampicillin/clavulanic, will do that.

Bite wounds, be they human or animal bites, here you really need to cover two things. There is the issue of prophylactic coverage and then there’s the issue of therapeutic coverage. I am primarily talking about infected bite wounds now. The issue of prophylactic coverage is actually talked about in the guide itself, remains somewhat controversial but for severe bites I think most people in the emergency room would cover those. Some people would call it preemptive rather than prophylactic therapy because the presumption is that organisms have been introduced into those wounds.

For puncture wounds in the feet, occurring in the summertime, often in kids wearing sneakers who step on nails and things like that, you worry about organisms that are on the skin, like staph aureus, and you worry about organisms that grow in wet, dark places like sneaker soles. The organism there that classically does that is Pseudomonas serisinosa. So kids who have puncture wounds of the feet are at high risk of developing soft tissue.

Pharyngitis tonsillitis. I am going to spend a minute talking about this because this shows you some of the issues, this and of deciding optimal antimicrobial therapy, based on clinical studies. There are a lot of organisms that cause sore throats that we can’t treat. In fact, the majority of sore throats are caused by viruses and we can’t do anything about that. We are getting increasing evidence that Mycoplasma and Chlamydia pneumoniae also cause pharyngitis and cause sore throats and we could potentially treat those.

Virtually every oral antimicrobial agent that has gram-positive activity has been tested against group A streptococcal pharyngitis because it’s so easy to do these clinical studies. What I am going to show you on the next slide are a couple of what I call a pseudo meta-analyses. They are not true meta-analyses. But they are studies comparing the standard regimen, i.e. oral penicillin, versus one of these new oral cephalosporins.

As an alternative you could use erythromycin or azithromycin. Fortunately in the United States we have not seen a huge increase in macrolide resistance in group A streptococci. That has occurred in many parts of the world. In Japan, for instance, in the 1970’s, 70% of group A strep because resistant to erythromycin. So far in the United States it is less than 1%. So these are reasonable alternatives. Or you could use an oral cephalosporin in that setting. But most people still start with penicillin. It’s cost effective and the differences between the cure rates with that and the cure rates with the other agents here are such that it still really remains the drug of choice. But if the patient relapses or if for some reason doesn’t respond, then the alternative drugs can be used.

Sinusitis. Otis media. I put them together because even though the occur in very different settings - most of the otitis media is in children, the majority of sinusitis in adults - there is a crossover. Obviously you can occasionally see otitis media in adults and occasionally sinusitis in kids. But the reason for putting them together is that the bacteriologic flora that causes these two conditions is virtually identical. So the treatment should be, or at least the considerations for treatment, should be quite similar. Now what you are going to see though is that when I come down to the final recommendations, the recommendations are slightly different in these two settings. I’ll tell you why that is as we go through it. These are the organisms that cause sinusitis in adults. I chose this study, which is now about 10 or 11 years old from Finland, because it points out the importance of Hemophilus influenzae in this disease. Fifty-percent of these were caused by H. flu. The pneumococcus 20%, group A strep 5% and - it was Branhamella - it is now Moraxella catarrhalis - only 2%. And I show you that because there has been a lot said.

Let’s move out of the respiratory tract to the urinary tract for a minute. Acute community-acquired UTI’s. Most of these are in young, sexually active women. The organism that causes it almost invariably is E. coli. So the question in managing these, are there two questions? One, how long to treat, and two - before that - what is the susceptibility of the organism to standard agents? Currently about 40% of community-acquired E. coli around the country are resistant to ampicillin or amoxicillin. So we no longer use that as the drug of first choice. Trimethoprim sulfa has generally been the considered the drug of first choice. However, the incidence of resistance to that is increasing.

How about gonorrhea? Gonococcal infections? Well, we know that we are seeing more and more resistance to penicillin in gonococci because of beta-lactamase production. For that reason we no longer can use penicillin or ampicillin as first line therapy. The CDC actually has just redone these recommendations but they are essentially similar to what I have here. For uncomplicated gonorrhea ceftriaxone, single dose, or a number of oral regimens, and these are listed by the CDC but there are other regimens as well that work in single dose for uncomplicated gonorrhea. Now what’s given the CDC some problems when they put together the most recent guidelines.

For genital Chlamydial infections, the problem here is that we only have one regimen for single dose therapy. None of the fluoroquinolones which have activity work in single doses. So if you are treating genital Chlamydial infections you can either use the drugs of choice that are listed here: doxycycline 100 mg p.o. b.i.d x 7 days, or azithromycin 1 gram, single dose. That does work. Now the issue about using azithromycin in single dose therapy for genital Chlamydial infections is that the 1 gram dose is not effective for gonococci as you would like. You can go up to 2 grams and the Europeans do this and it’s approved in Europe, a single 2 gram dose. That will cover both GC and Chlamydia. The problem is there is an awful lot of GI toxicity with that dose and a lot of patient don’t tolerate it very well.

These are some alternative regimens here that you can use in that setting. Note that ofloxacin has to be given for seven days. Ofloxacin is the most effective of the currently approved fluoroquinolones in that setting. Trovafloxacin was better and trovafloxacin was approved for a five day regimen but once again, that is off the market.

For PID there are a number of regimens. For inpatient therapy still the cefoxy-doxy regimen, cefoxitin and doxycycline is considered important. Basically you are trying to cover an amount of gonococci and C. trachomatis plus or minus anaerobes in that setting. For outpatient therapy this has just been recently updated by the CDC, just at the end of last year. What they now recommend as optimal treatment for outpatient therapy is ceftriaxone 250 mg IM plus probenecid. Or another third generation cephalosporin plus doxycycline and now they add metronidazole if bacterial vaginosis is present. That’s the change in the recommendations from the CDC. Then now say that if the patient has either documented bacterial vaginosis or a history of bacterial vaginosis, add a regimen that covers the flora that causes bacterial vaginosis, anaerobes and Gardnerella. The only way to do that is with metronidazole. So that is new and that is a change. The alternative oral regimen that they recommend right now is ofloxacin 400 mg p.o. b.i.d. x 14 days, plus metronidazole or clindamycin for 14 days.