Rubor, dolor, calor and tumor (the name of my Medscape blog, oddly enough) of the skin and soft tissues aka erysipelas aka diffuse erythroderma.
There are many processes that can mimic cellulitis (PubMed).
And at least 30% of the time the diagnosis of cellulitis is wrong (PubMed). As was noted by JRR Tolkien, all that glitters is not gold, all legs that are red, hot and swollen are not cellulitis.
There was one study that measured CRAP and procalcitonin for cellulitis, each 4 times over 5 days. In my institution that would be at least a grand in extra testing. They suggested "Thus, a biomarker-guided prescribing strategy as an adjunct to clinical decision-making could reduce unnecessarily broad-spectrum and prolonged antibiotic regimens and warrants further study (PubMed)." I cannot help think that the only thing you need to manage cellulitis in the vast majority of cases is a fever curve and a look at the (elevated) leg every day. If you need to use biomarkers, it is time to pack it in and find another career, 'cause medicine ain't for you.
Trauma, often minor.
Chronic edema for any reason, but classically from lymph node dissection, leads to recurrent group A streptococcal infections. And ONLY streptococcal infections. It isn't osteomyelitis and it sure as hell isn't MRSA. It's recurrent STREPTOCOCCAL cellulitis in an edematous extremity.
Warm weather is a risk (PubMed) for cellulitis and wound infections.
Any chronic skin disease. Patients with psoriasis or atopic dermatitis usually are colonized with (PubMed). Diabetic foot infection is discussed here. Necrotizing fasciitis is discussed here. Carbuncles are discussed here.
Warm weather. Sweaty skin is an all you eat buffet for bacteria (PubMed). Another disease to increase with global warming.
The vast majority of cellulitis (diffuse erythroderma, no pus, no boil, are due to Streptococci (Group A and group G more often than the others)(PubMed) and S. aureus is a very distant third and for erysipelas, diffuse erythroderma, the S. aureus is never ever ever never MRSA in cellulitis. Never. Ever (PubMed). So stop with the damn MRSA treatments. It is stoopid.
MRSA is way overrated as a cause of cellulitis (a diffuse erythroderma with no abscess): "Results of this large, prospective study show that diffuse, nonculturable cellulitis is still mainly caused by BHS, despite the MRSA epidemic, and that for this infection type, treatment with beta-lactam antibiotics is still effective. (PubMed)". When there is an abscess, then, and only then worry about MRSA.
Diabetics? Same. For non-necrotizing/dead meat infections diabetics have the same causal bacteria for their cellulitis: Streptococci and S. aureus. (PubMed). Unless they have a necrotizing fasciitis all they need is cefazolin.
Staphylococcus pseudointermedius is a cause of skin disease in dogs and cats and can be spread to their masters to cause cellulitis (Pubmed). Well, cats (aka the other white meat) don't have masters.
For bacteremic cellulitis (PubMed):
"For erysipelas, 4.6% of 607 patients had positive blood cultures, of which 46% were Streptococcus pyogenes, 29% were other β-hemolytic streptococci, 14% were Staphylococcus aureus, and 11% were Gram-negative organisms. For cellulitis, 7.9% of 1578 patients had positive blood cultures of which 19% were Streptococcus pyogenes, 38% were other β-hemolytic streptococci, 14% were Staphylococcus aureus, and 28% were Gram-negative organisms."
In normal people gram negative rods do not cause cellulitis, gram negative rods cause necrotizing infections: dead meat that needs debridin'. There are exceptions such as Aeromonas (PubMed) and I have seen three Pseudomonal cellulitis cases in the morbidly obese. So stop with the zosin as well.
Anaerobes only infect dead meat and dead meat is also treated with debridement.
Helicobacter-like organism (H. cinaedi) can cause bacteremia and cellulitis. Blood cultures take 6–12 days to become positive (PubMed). Normal people can get an erysipelas that is due to Helicobacter (PubMed) but it can be difficult to grow requiring PCR to diagnose.
Atypical mycobacteria, including Mycobacterium abscessus, Mycobacterium fortuitum, Mycobacterium peregrinum and Mycobacterium mageritense can appear after a delay of 20–105 days (median, 60 days) after tsunami related trauma, often with concomitant subcutaneous infections due to other microorganisms, including Burkholderia pseudomallei and Cladophialophora bantiana (PubMed).
For outpatients with uncomplicated soft tissue infections (cellulitis without abscess), cephalexin OR dicloxacillin is all that is needed. Or even amoxicillin since the majority of cases are due to Streptococci. If you do not like the patient give Augmentin: since streptococci do not make a beta lactamase all Augmentin adds over amoxicillin is cost and diarrhea.
For inpateints? For classic cellulitis aka erysipelas aka diffuse erythroderma, cefazolin is all that is needed, assuming the history does not suggest an odd exposure. For severe disease, ICU bound, cefazolin PLUS clindamycin. Why? The Eagle effect, where high inoculum of Group A Strep are resistant to pencillin and patients do better on clindamycin (PubMed). Plus I do have an affinity for screwing with bacterial virulence factors aka proteins.
For inpatients usually IV cefazolin OR vancomycin (only if MRSA risk, pus or boils) or po cephalexin OR dicloxacillin alone along with elevation should suffice, 10 to 14 days of combined iv and/or po therapy is the tradition, 5 days total will probably suffice in patients who are doing well clinically.
Note: gram negative rods and anaerobes do not cause cellulitis unless a good exposure history or there is dead tissue.
If there is an abscess and only if there is an abscess, then and only then worry about MRSA. TMP/Sulfa and clindamycin have equal efficacy (PubMed) if there is an abscess. And don't forget to drain the pus. No I&D, no cure. Know I&D, know cure. If there is an MRSA boil, besides I&D, antibiotics will decrease new lesions and relapse (PubMed).
"Among patients diagnosed with cellulitis without abscess, the addition of trimethoprim-sulfamethoxazole to cephalexin did not improve outcomes, overall or by subgroup in two trials (PubMed)(PubMed)."
Adding clindamycin for outpatient cellulitis also adds nothing. (PubMed). So stop with the combo therapy already.
If for some reason your can't use a beta-lactam or you are worried about MRSA, try doxycycline = TMP/Sulfa = clindamycin (too much S. aureus resistance, still expensive, and drives C. difficile). I was always taught that S. pyogenes was resistant to sulfa, but that may be an artifact of testing (PubMed) and TMP/Sulfa will work as MONOTHERAPY for cellulitis (PubMed).
The use of combination oral therapy for cellulitis that seems popular is a waste of time, is steer manure and and suggests the prescriber doesn't know a burrow (hole in the ground) from a burro (an ass) about cellulitis.
In one meta-analysis, penicillin or cephalosporin were the equal to a macrolide or clindamycin in the treatment of cellulitis or erysipelas (Pubmed). That's because it is all Streptococci (Reference) all the way down and we can still kill streptococci.
Linezolid is not inferior to vancomycin (PubMed), but is one hell of a lot more expensive. Tedizolid was approved for 5 days instead of 10 days for linezolid (PubMed). I suspect that was just smart marketing; it is rare that anyone needs more than 5 days of antibiotics for cellulitis and 10 days of linezolid is likely 5 days too many.
How long to treat? Until they are cured. But we cannot use that as endpoint, so we give durations that are mostly based on the number of fingers (10 in most people) or days in the week (7,14,21). If we had cartoon fingers we would be given a lot less antibiotics. I suspect, but do know know, that 5 days is fine if the fever and WBC normalize.
Recurrent cellulitis is ALWAYS due to Group A streptococci, almost always in people with chronic edema. Get the edema under control and work on hygiene. It can be treated with daily penicillin or monthly IM benzathine penicillin. 250 mg PenVK bid, massively under-dosed for the BMI is the study, decreased recurrence from 37 to 22% compared to placebo (PubMed). I usually go with 875 bid . Better, I hope, for those with large volumes of distribution. In a meta-analysis (PubMed), "Antibiotic prophylaxis significantly reduced the number of patients having recurrent cellulitis, with a risk ratio (RR) of 0.46 (95% CI 0.26-0.79)."
If you have to use a quinolone, and you shouldn't, give moxifloxacin.
And the new long acting and horrifically expensive antibiotics like dalvabancin, telavancin and oritavancin. If you are resorting to these agents to kill what is usually Group A streptococcus, you really haven't a clue as to how to treat cellulitis. Give the penicillin to the patient and then burn a pile of 4500 dollar bills. Same result.
Prednisone 40 mg/d x 7 days in the non-diabetic gets a moderate vote in the guidelines. I have yet to do it. For me, giving steroids for infections is performing an unnatural act.
2 grams cefazolin iv q 24 hours PLUS probenecid is often enough to treat outpatients if you need a long acting beta-lactam.
Cephalexin or dicloxacillin can be given at 1 gram po qid with good blood levels and can be used instead of parenteral therapy. IV nafcillin / oxacillin should also be fine, but is hard on peripheral veins.
When to worry about an abscess: them what drink too much and those that have a delay in therapy (PubMed). As far as I can tell, cellulitis never results in a contiguous osteomyelitis if not trauma.
My non-referenced rules of thumb:
1) When you start treatment, the cellulitis worsens for a day, stabilizes for a day, then starts to improve.
Some patients are just slow to respond and you need patience. Who will be slow to respond? "Female sex, cardiovascular disease, higher body mass index, shorter duration of symptoms, and cellulitis other than typical erysipelas(Pubmed)." It is not the antibiotic (which had better be cefazolin) but the patient. Don't be changing to vancomycin or adding piperacillin/tazobactam when the patient isn't all better at day 2.
Outpatient failure of therapy, defined in this study as "any of the following events within 90 days of their initial visit: (1) need for a new course or change in antibiotic therapy for SSTI, (2) additional incision and drainage, (3) SSTI at a new site, (4) SSTI at the same site, (5) emergency department visit, or (6) hospital admission", is usually due to delay in seeking care and a large area infection (PubMed).
2) You cannot tell what the cellulitis is doing if the leg is not elevated above the heart. Active infection (rubor, dolor, calor, tumor) will not fade with elevation, redness etc from post-infectious edema will fade with elevation. I have cured many a chronic cellulitis with elevation.
3) For every 50 lbs overweight add a day to the resolution time.
4) The fever curve is more important the how the cellulitis looks. And look at the skin carefully. Often a lot of the redness is subcutaneous bleeding.
5) The first manifestation of Group A streptococcal cellulitis (occurring before the fever, chills and redness) can be groin pain, probably due to lymphadenitis. I want this referred to as Crislip's sign. Get to work. And there is an anatomical explanation for Crislip's sign: S. pyogenes "can rapidly access the lymphatic system and local lymph nodes via a hitherto unrecognized but specific interaction between its hyaluronan capsule, and the lymphatic endothelial receptor LYVE-1 (Pubmed)."
There is no such thing as chronic cellulitis or bilateral cellulitis, I cure each and every one by elevating the leg higher than the heart for 5 minutes. The rubor, dolor, calor and tumor of cellulitis does not fade with elevation; the rubor, dolor, calor and tumor of stasis, which is the cause of ALL 'bilateral' and/or 'chronic' cellulitis, does fade with elevation. Lets pretend you are now in college. The final is a 500 word essay; compare and contrast the rubor, dolor, calor and tumor of cellulitis and stasis.
Relevant links to my Medscape blog
Last Update: 06/05/18.