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Primary Care Corner with Geoffrey Modest MD: Treatment of skin infections in era of MRSA

30 Mar, 15 | by EBM

By: Dr. Geoffrey Modest

A study done in 4 centers (Univ of Chicago, San Francisco General Hosp, Harbor-UCLA , and Vanderbilt Univ Med Ctr) looked at the efficacy of clindamycin vs trimethoprim-sulfamethoxazole (TMP-SMX) for uncomplicated skin infections (see N Engl J Med 2015;372:1093-1103​). The question was: which medication is preferred in the current era of community-acquired methicillin-resistant Staph aureus (MRSA), which seems to be extremely common around the country?



–524 patients, including 155 children. 30.5% with abscess (>5cm, in adults), 53.4% with cellulitis, 15.6% with both; the patients were 52.3% male, 53.2% Black, 40.3% White, 28.6% Hispanic. Mean age 27.1. 29.6% children.

–patients were randomized to clindamycin (adults at 300mg tid) or TMP-SMX (on double-strength tablet bid), all for 10 days. Pediatric doses adjusted by body weight

— of those with positive cultures (n=277), 217 had s. aureus [167 with MRSA, 77.0% of the staph infections, with 21 (12.4%) resistant to clinda and 1 resistant to TMP-SMX; 52 were methicillin sensitive]; 32 were strep of different varieties; 10 were proteus, 38 coagulase-negative staph, 15 diphteroids, and a smattering of others. Note: all of the cultures were from those with abscesses, not cellulitis (cellulitis being 53.4% of the skin infections)

–no difference in outcomes between these medications: 80.3% were cured with clindamycin, 77.7% with TMP-SMX in intention-to-treat analysis, but in the 466 evaluable patients, it was 89.5% with clindamycin and 88.2% with TMP-SMX.

–no difference in children vs adults, in those with abscesses vs cellulitis. also no difference in subgroups infected with s. aureus, MRSA, or MSSA. of the 15 patients with clindamycin-resistant staph, 11 were cured (73.3%) vs 91.7% of those sensitive to clinda

–adverse events: similar: 18.9% with TMP-SMX​  and 18.6% with clindamycin, with both antibiotics associated with diarrhea in about 10%, nausea 2.5%, pruritus in 1.5%, rash in 1%. no cases of clindamycin-associated c. diff infections.

So, a few points:

–It is pretty remarkable how well TMP-SMX did, since a reasonable percentage of the patients had strep which is felt not to be sensitive to TMP-SMX. And, it is generally held that cellulitis is much more likely than abscesses to be caused by strep (though we cannot really culture cellulitis), yet the cure rate with TMP-SMX was the same for cellulitis and abscesses. there is some literature suggesting that the way sensitivity testing is done may underestimate TMP-SMX sensitivity. [As a general point, agar-plate antibiotic resistance is not always an accurate reflection of what happens in the body. For example, many organisms causing urinary tract infections seemingly resistant to antibiotics may in fact respond, perhaps related to the high concentration of antibiotics in the urine]

–Several studies have found that antibiotics do not add much to the primary treatment of abscesses (which is: incision and drainage, I&D), so the high cure rate with any antibiotic may not be surprising. So, for example, 73.3% of those with clindamycin-resistant staph in the above study “responded” to antibiotics, but these bacterial isolates were from abscesses and may not have needed antibiotics. But I should add that the literature on this is really all over the place. Some studies suggest that abscesses> 5cm (as in the above study) do better with antibiotics in addition to I&D. Some find that MRSA infections in particular respond better when antibiotics are added. but there are studies to the contrary.

–There have been studies finding that cephalosporins or other b-lactam antibiotics with anti-strep activity work somewhat better than TMP-SMX for skin infections, though given the very high prevalence of MRSA that we find at our health center, we have been mostly using TMP-SMX as the primary agent and with good results​ (again, we only culture those with abscesses). I had a patient with morbid obesity and diabetes a few years ago who had a very large inner thigh abscess and surrounding cellulitis from documented MRSA, sent home from the hospital on linezolid, but I was unable to get the required prior approval and switched him to TMP-SMX​, and he had a great result… In general, we do usually add antibiotics for skin infections because of the articles suggesting benefit in MRSA, and there was even an article suggesting less likely recurrences if use TMP-SMX​.

Note: I have several other articles in the BMJ online blogs on MRSA, including the use of bleach baths, the new Infectious Disease Society guidelines on treatment of skin infections, and skin abscess treatment. See here. ​

Primary Care Corner with Geoffrey Modest MD: Choosing wisely — infectious disease society recommendations

3 Mar, 15 | by EBM

By: Dr. Geoffrey Modest

Will pass along the infectious disease society “choosing-wisely” recommendations for decreasing antibiotic use. Although none of these are new or surprising, data suggest that antibiotics are still being prescribed for these conditions unwisely….  (see here)

  1. Don’t treat asymptomatic bacteruria with antibiotics. (except pregnant patients, those undergoing invasive urological surgery including prostate surgery, or those within 1 year of kidney or kidney pancreas transplant)
  2. Avoid antibiotics for upper respiratory infections. most are viral. But one should treat group A strep and pertussis
  3. Don’t use antibiotics for stasis dermatitis of lower extremities. Use leg elevation and compression. [in my experience, this can be a difficult call: stasis dermatitis can really look like cellulitis with bright red, well-demarcated erythema, though with less induration than cellulitis. And i would add that topical steroids do work quickly with stasis dermatitis]
  4. Don’t test for clostridium difficile infection in the absence of diarrhea. Except if ileus from c. difficile is suspected. In general​, c. diff carriage should not be treated so shouldn’t be looked for
  5. Don’t use prophylactic antibiotics for treatment of mitral valve prolapse as a means to prevent endocarditis.

So, just a reminder.

Primary Care Corner with Geoffrey Modest MD: Soft Tissue Infection Guidelines

7 Oct, 14 | by EBM

​The Infectious Diseases Society of America just updated their 2005 guidelines for treatment of skin and soft tissue infections (see DOI: 10.1093/cid/ciu296). The guideline deals with minor infections and up to life threatening ones, but I will focus on ones seen/treated in primary care (there is also an algorithm for wound infections, which I will leave to you to investigate).

-Mild nonpurulent infections (cellulitis, erysipelas): Where mild infection is defined as skin infection without systemic signs of infection (>38 deg C, tachycardia >90, tachypnea >24,or WBC >12K or <400, or immunocompromized):

–Blood culture/biopsies etc. only if patient is immunocompromized (and these patients should be admitted/get IV antibiotics)

–Should use antibiotic with anti-strep activity for 5 days, then extend if necessary after further evaluation. They do note that many clinicians (which includes me) like to cover methicillin-sensitive staph (MSSA). Also, consider covering methicillin-resistant (MRSA) if severe infection, nasal colonization with MRSA, injection drug use.

–In lower extremity cellulitis, examine interdigital toe spaces to look for fissuring, scaling, maceration which could lead to recurrent cellulitis  (I’ve had a couple of patients with recurrent lower extremity cellulitis and bad fungal infections of toenails or interdigitally, who did not have further cellultitis when those were treated. I would also add that patients with venous insufficiency and recurrent cellulitis seem to do better with compression stockings.) Consider prophylactic antibiotics in patients with recurrent infections (3-4 episodes/yr) , e.g. with oral penicillin or erythromycin for 4-52 weeks or benzathine penicillin IM 2.4M units ​every 2-4 weeks.

–Dog/cat bites — give preemptive therapy for 3-5 days in those with more severe bites or immunocompromized (they note that patients with relatively minor dog bites, not involving the face, hand, or foot found a pretty low incidence of infection — 16% — and may not justify routine antibiotic administration, esp if there is good followup available.  Give amox-clavulanate 875/125 bid. for human bites, always give antibiotics). Give Td or Tdap if not given within past 10 years, consider rabies prophylaxis, do not generally close wounds except on face, and give azithro if concerned about cat scratch disease.

–In terms of general treatment, MRSA is unusual cause of cellulitis (study in cellulitis patients at a medical center with high incidence of other MRSA-related skin infections found that cefazolin or oxacillin was successful in 96% of the patients. Another recent study not referenced in this article found greater efficacy of cephalexin to TMP/SMX,  and, I would add, some of the agents used to treat MRSA, esp TMP-SMX and doxycycline, are less active against strep).

–Antibiotic recommendations: pen VK (I do not use this since by inspection cannot rule-out staph infection), cephalosporin, dicloxacillin, or clindamycin orally — see doses under impetigo/ecthyma

–Impetigo/ecthyma (ecthyma is deeper infection, lesions usually begin as vesicles which rupture, then get circular erythematous ulcer with adherent crusts, and typically leaves a scar

–Gram stain and culture pus or exudates to see if staph or strep, but treatment without this is reasonable in typical cases

–Bullous or nonbullous impetigo: can use oral therapy or topical, though oral therapy preferred if multiple lesions

–Therapies: topical — use either mupirocin or retapamulin bid for 5 days; oral — 7 days of therapy active against staph (unless culture shows strep alone), with MSSA agent (dicloxacillin 250 qid,  cephalexin 250 qid, though I usually use 500 bid with good effect, amox-clav 875/125 bid), or if MRSA suspected can use doxycycline 100 bid , clindamycin 300-400 qid, or TMP/SMX 1-2 DS tabs bid.

–Purulent skin infections/abscesses

–Gram stain and culture are recommended (though not for inflamed epidermoid cysts).

–I&D is recommended for inflamed epidermoid cysts, and abscesses (including carbuncles, large furuncles).

–Use of antibiotics should be based on presence or absence of systemic inflammatory response (T>38C or <36C, tachypnea>24, tachycardia >90, WBC>12000 or <400)

–Antibiotic for MRSA is recommended in those who fail initial antibiotic treatment or have impaired host defenses. Also for those with systemic symptoms as above.

–For those with recurrent abscesses, look for local causes (eg pilonidal cyst, hidradenitis or foreign body), drain and culture, then treat with 5 to 10 days of an active antibiotic. Consider 5-day decolonization regimen (e.g., intranasal mupirocin, daily chlorhexidene washes, daily decontamination of personal items) and evaluate for neutrophil disorders if recurrent abscesses began in childhood. They do mention bleach baths (1/4-1/2 cup of bleach per full bath) — see here for a previous blog that promots bleach baths and I have had a few people email me with very positive stories. Data is not great for the 5-day decolonization regimens they cite. I would also add that I have seen a patient with apparent recurrent abscesses on his hands, which turned out to be a herpetic whitlow.

​–Choice of antibiotics for empiric therapy: TMP/SMX 1-2 DS tabs bid or doxycycline/minocycline 100mg bid. For culture-guided therapy: dicloxacillin 500 qid or cephalexin 500 qid (they did not include clindamycin in the empiric therapy. Not sure why. I have certainly had much success with that and it covers strep if needed.)


Primary Care Corner with Geoffrey Modest MD: Bleach baths to decrease recurrent skin infections

2 Apr, 14 | by EBM

1000 healthy kids aged 3 months to 18 yrs with probable community-associated staph aureus skin/soft tissue (SSTI) or invasive infection randomized to daily hygiene vs that with 2x/week bleach baths for 3 months (see DOI: 10.1093/cid/cit764). basically,

–recurrence of SSTI common: about 50%
–bleach bath consisted of adding 5ml of bleach (regular bleach, 6.0% hypochlorite) to every gallon of bath water, and bathing in that for 15 min 2x/week, for 3 months. 12-month followup. dilute bleach solutions known to kill staph.
–colonization cultures were obtained from nares, pharynx, groin. 56% were colonized with s. aureus at minimum of 1 site (most common = groin in 38%, nares 22%, throat 17%). MRSA (methicillin-resistant) more common in groin and throat, MSSA (methicillin-sensitive) in nose. more colonization in younger ages, esp <2yo
–rate of “medically-attended” recurrent infection: 17% with bleach bath and 20.9% with regular hygiene (not significant, but arguably too small a trial: needed around 1000 kids to detect 50% reduction with 90% power). no diff between MRSA and MSSA infections (though most infections were MRSA). higher rates of infection with more colonization sites culture-positive
–not adverse effects found, other than dry skin in a few kids and burning eyes in 1 patient only.

 so, obviously a small study at least in terms of outcomes, only with kids, short-term (3 months of baths, with 12 month follow-up) and not powered to get significant results. but, besides that, pretty intriguing… recurrent staph infections really common in kids and adults. seems like a pretty benign therapy (esp given the alternatives of recurrent courses of antibiotics, need for frequent ER visits, etc — ie alternatives not great). and by my quick and dirty (?) measurements in my bathtub, 6″deep water would require 4 ounces of bleach. so, might be reasonable to try in people with documented recurrent infections???? i checked out the Am Acad of Dermatology website for hidradenitis, and they suggested bleach bath as one approach (1/2 cup non-scented bleach to 1/2 full bathtub of water), noting that it works sometimes.


Primary Care Corner with Geoffrey Modest MD: Skin Abscesses Treatment

25 Mar, 14 | by EBM

review article in new england journal last week on management of skin abscesses in era of methicillin-resistant staph aureaus MRSA (see DOI: 10.1056/NEJMra1212788). both the incidence of skin abscesses overall and the % of MRSA have increased over time. a few comments:

–diagnostic accuracy is not great: eg, a study of 126 adults with cellulitis where ER MD felt abscess not evident, ultrasound found abscess in 50%
–treatment of abscess is primarily I&D
–there may be more rapid healing if the I&D incision is closed vs leaving it open (studies mostly in the anogenital area, showing half the healing time and no diff in recurrences). should consider primary closure if incision >2cm. [goes against conventional wisdom that needs to be open to continue draining]
–no data as to whether to irrigate the wound, and data on whether packing helps is unclear (a couple of very small studies done, one in adults showing more pain but no outcome difference, one in kids found more frequent subsequent drainage and antibiotic treatment in those not packed)
–antibiotics. in 2008, 63% of abscesses were from community-associated MRSA. 15% in MSSA, 2% b-hemolytic strep, 20% other. but cure rates for just I&D alone are in the 85% range. a study in kids found no diff if give tmp/smx vs placebo after I&D, though some decrease in new lesion development. so, Infectious Diseases Society of America recommends systemic antibiotics for patients with extensive disease (multiple sites), rapidly progressive dz, signs/symptoms of systemic illness, immunosuppression, very young or old, abscess in difficult area to drain, associated septic phlebitis, or drained abscess not responding just to I&D.
–empirical antibiotic therapy when chosen should cover MRSA, ie first choice of tmp/smx 1-2 DS tabs bid. some resistance to clinda and tetras, but can do clindamycin 300-450 tid, doxycylcine 100 bid or minocycline 200, then 100 q12h.
–if cellulitis alone, more likely to be strep (difficult to really know the organism if just cellulitis, though), and TMP/SMX and tetracyclines less active. clinda may be better choice. and my experience is that TMP/SMX, which has limited activity against strep, typically works well with cellulitis (though i never do ultrasound to rule-out small abscess…). if severe cellulitis, might cover with TMP/SMX plus cephalexin. there are no great data for these suggestions from clinical trials, and some trials are currently ongoing.

so, this brings up a few issues. even though it is commonly incorrect to conclude that an abscess is not present without the aid of an ultrasound, those of us in the community cannot typically get an ultrasound easily. unless the patient has severe infection needing hospitalization, we treat them by I&D if there is an evident abscess present, will occasionally needle it if not sure (though sometimes purulent collections can be quite viscous and can be missed with a needle), and (probably more often than is necessary) prescribe antibiotics. my experience is that small abscesses/collections often resorb with heat and antibiotics without I&D.


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