Karl T. Clebak, MD, MHA, FAAFP; Alexis Reedy-Cooper, MD, MPH; A guide to the Tx of cellulitis Michael T. Partin, MD; Christopher R. Davis, MD Penn State Health Milton and other soft-tissue infections S. Hershey Medical Center, Hershey (Drs. Clebak, Partin, and Davis); Penn State Diagnostic and therapeutic priorities vary for the 8 types Health St. Joseph Medical Center, Reading (Dr. Reedy- of infection reviewed. Cooper). kclebak@ pennstatehealth.psu.edu kin and soft-tissue infections, frequently encountered in PRACTICE The authors reported no primary care, range from the uncomplicated erysipelas potential conflict of interest RECOMMENDATIONS relevant to this article. to the life-threatening necrotizing fasciitis. This review ❯ Start trimethoprim- S draws from the latest evidence and guidelines to help guide doi: 10.12788/jfp.0198 sulfamethoxazole, clindamycin, doxycycline, the care you provide to patients with cellulitis, orbital cellulitis, minocycline, or a third- erysipelas, folliculitis, furuncles, carbuncles, abscesses, and or fourth-generation necrotizing fasciitis. fluoroquinolone for patients with cellulitis likely caused by community Cellulitis acquired methicillin- Cellulitis, an infection of the deep dermal and subcutaneous resistant Staphylococcus layers of the skin, has become increasingly common in recent aureus (MRSA). A years, with both incidence and hospitalization rates rising.1 ❯ Consider culturing for Cellulitis occurs when pathogens enter the dermis through MRSA and treating with oral breaks in the skin barrier due to cutaneous fungal infections, doxycycline or trimethoprim- trauma, pressure sores, venous stasis, or inflammation. The sulfamethoxazole for resistant diagnosis is often made clinically based on characteristic cases of folliculitis. C skin findings—classically an acute, poorly demarcated area ❯ Perform complete of erythema, warmth, swelling, and tenderness. Lymphangitic surgical debridement streaking and local lymphadenopathy may also be present. In- promptly if necrotizing fection often occurs on an extremity (although it can be found fasciitis is suspected. C on other areas of the body) and is usually unilateral. Fever may ❯ Prescribe broad-spectrum or may not be present.2 antibiotics for necrotizing ❚ Likely responsible microorganisms. Staphylococcus au- fasciitis, covering both reus and Group A streptococci (often Streptococcus pyogenes) anaerobes and aerobes are common culprits. One systematic review that examined including MRSA. C cultures taken of intact skin in cellulitis patients found S aureus Strength of recommendation (SOR) to be about twice as common as S pyogenes, with both bacte- A Good-quality patient-oriented ria accounting for a little more than 70% of cases. Of the re- evidence maining positive cultures, the most common organisms were B Inconsistent or limited-quality patient-oriented evidence alpha- hemolytic streptococcus, group B streptococcus, Pseu- C Consensus, usual practice, domonas aeruginosa, Clostridium perfringens, Escherichia opinion, disease-oriented 3 evidence, case series coli, Pasteurella multocida, and Proteus mirabilis. Similarly, a systematic review of bacteremia in patients with cellulitis and erysipelas found that S pyogenes, other beta-hemolytic strep, and S aureus account for about 70% of cases (although S au- reus was responsible for just 14%), with the remainder of cases 214 THE JOURNAL OF FAMILY PRACTICE | JUNE 2021 | VOL 70, NO 5 caused by gram-negative organisms such as posterior to the orbital septum.6,7 Periorbital, E coli and P aeruginosa.4 or preseptal, cellulitis occurs anterior to the ❚ Treatment considerations. Strict orbital septum and is the more common of treatment guidelines for cellulitis are lack- the 2 infections—84% compared with 16% for ing, but general consensus encourages the orbital cellulitis.6 However, orbital cellulitis, use of antibiotics and occasionally surgery. which affects mainly children at a median age For mild and moderate cases of cellulitis, of 7 years,6 must be detected and treated early prescribe oral and parenteral antibiotics due to the potential for serious complications to cover for streptococci and methicillin- such as cavernous sinus thrombosis, men- susceptible S aureus, respectively. Expand ingitis, intracranial abscess, and vision loss.7 coverage to include vancomycin if nasal Chemosis (conjunctival edema) and diplopia colonization shows methicillin-resistant are more commonly associated with orbital S aureus (MRSA) or if you otherwise sus- cellulitis and are seldom seen with preseptal pect prior MRSA exposure. Expanded cov- cellulitis. erage will also be needed if there is severe ❚ Predominant causative organisms are nonpurulent infection associated with S pneumoniae, Moraxella catarrhalis, non- penetrating trauma or a history of intrave- typeable Haemophilus influenzae, and group nous drug use, or the patient meets criteria A streptococcus. The most common mecha- for systemic inflammatory response syn- nism of infection is tracking from periorbital drome. If patients are severely compromised structures (eg, paranasal and ethmoid sinus- For orbital (eg, neutropenic), it is reasonable to further itis). Other causes include orbital trauma/ cellulitis, choose add broad-spectrum coverage (eg, intrave- fracture, periorbital surgery, and bacterial antibiotics nous piperacillin- tazobactam or carbape- endocarditis. Clinically, patients present with effective against nem). Typical duration of treatment is 5 to limited ocular motility and proptosis associ- sinusitis-related 7 days, although this should be extended if ated with inflamed conjunctiva, orbital pain, pathogens (eg, there is no clinical improvement. headache, malaise, fever, eyelid edema, and S pneumoniae, Generally, cellulitis can be managed in possible decrease in visual acuity. The diag- H influenzae, the outpatient setting, although hospitaliza- nosis is often made clinically and confirmed M catarrhalis), tion is recommended if there are concerns for with orbital computed tomography (CT) with S aureus, and deep or necrotizing infection, if patients are contrast, which can assist in ruling out intra- anaerobes. nonadherent to therapy or are immunocom- cranial involvement such as abscess. promised, or if outpatient therapy has failed.5 ❚ Antibiotic therapy, generally admin- Furthermore, in an observational study of istered intravenously, is recommended for 606 adult patients, prior episodes of cellulitis, at least 3 days or until orbital symptoms venous insufficiency, and immunosuppres- begin to resolve. Choose antibiotics effec- sion were all independently associated with tive against sinusitis-related pathogens poorer clinical outcomes.2 Also treat underly- (eg, S pneumoniae, H influenzae, M catarrha- ing predisposing factors such as edema, obe- lis), S aureus, and anaerobes.8 For instance, a sity, eczema, venous insufficiency, and toe regimen may include vancomycin for MRSA web abnormalities such as fissures, scaling, coverage, a third-generation cephalosporin, or maceration.5 Consider the use of prophy- or metronidazole for anaerobic coverage if lactic antibiotics for patients who have had there is concern about intracranial involve- 3 to 4 episodes of cellulitis despite attempts ment. Surgical intervention is often reserved to treat predisposing conditions. Prophylac- for patients with inadequate response to tic antibiotic regimens include penicillin or antibiotic therapy, necessitating biopsy for erythromycin orally and penicillin G benza- pathogen identification, as well as drainage thine intramuscularly.5 Antibiotic regimens of large abscesses refractory to antibiotics. are summarized in the TABLE.5 Erysipelas Orbital cellulitis Erysipelas, a related yet distinct form of cellu- Orbital cellulitis is an infection of the tissues litis, is a bacterial infection of the superficial MDEDGE.COM/FAMILYMEDICINE VOL 70, NO 5 | JUNE 2021 | THE JOURNAL OF FAMILY PRACTICE 215 TABLE Antibiotic regimens for skin and soft-tissue infections5 ANTIBIOTIC ADULT DOSAGE Mild infection: Treat 5-7 days; extend if clinical improvement is insufficient Penicillin V 250-500 mg po q6h Amoxicillin 500 mg po tid, or 875 mg po bid Cephalexin 500 mg po q6h Dicloxacillin 500 mg po q6h Ciprofloxacin 500 mg po bid Clindamycin* 300 po qid, or 450 mg po tid Doxycycline* 100 mg po bid Trimethoprim-sulfamethoxazole* 1-2 DS tablets po bid Minocycline* 100 mg po daily Moderate systemic infection: Treat until there is clinical improvement and the patient is able to take oral antibiotics Penicillin G 2-4 million units IV q4-6h Ceftriaxone 1-2 g IV daily When clinical Vancomycin* 15 mg/kg IV bid exam alone is inconclusive Linezolid* 600 mg po bid when evaluating Daptomycin* 4 mg/kg IV q24h skin and soft- Ceftaroline* 600 mg IV bid tissue infections Severe systemic infection: Treat until there is clinical improvement in children and Vancomycin + piperacillin-tazobactam 15 mg/kg IV bid + 4.5 g IV q8h adolescents, Vancomycin + imipenem-cilastatin 15 mg/kg IV bid + 500 mg IV q6h or 1 g q8h IV for consider using fully susceptible organisms ultrasound Recurrent infections: Treat 4-52 weeks or as long as predisposing risk factors are present to improve Penicillin V 250-500 mg po q6h diagnostic accuracy. Benzathine penicillin 1.2 million units IM q2-4 weeks Erythromycin 250 mg po bid * Coverage for suspected MRSA. bid, twice a day; DS, double strength; IM, intramuscularly; IV, intravenously; MRSA, methicillin-resistant Staphylococcus aureus; po, by mouth; qid, 4 times a day; q6h, every