A wide variety of treatments have been suggested for simple, non-bullous impetigo, ranging from observation to systemic antibiotics. A Cochrane systematic literature review was recently performed on the treatment for impetigo.129 It showed that topical mupirocin and fusidic acid (which is not commercially available in the United States) are either as effective as or more effective than systemic antibiotics with less side effects. Interestingly, bacitracinseems to be inferior to mupirocin and fusidic acid. No evidence exists to support the use of disinfectants, such as chlorhexidine, in the treatment of0 impetigo.130,131
Simple Abscesses And Cellulitis
A mainstay of therapy in the treatment of soft tissue abscesses is incision and drainage (I&D) of the fluid collection. Controversy has existed for some time as to the efficacy of I&D alone in the treatment of simple soft tissue abscesses. In the pre-MRSA era, a number of trials demonstrated that I&D by itself was equivalent to I&D plus oral antibiotics in the management of soft-tissue infections.132-134 However, there have been no comparable studies in the CA-MRSA era. With the associated increase in virulence often seen in strains of MRSA, many are hesitant to treat abscesses that may be infected with MRSA solely with I&D for fear of inadequately treating a highly virulent pathogen. A number of studies, however, have illustrated that many physicians are treating skin abscesses which eventually grow MRSA with first and second generation cephalosporins.3,135,136 In these cases, no adverse outcomes have been reported despite the pathogen's resistance to the prescribed antibiotics.
Some have therefore proposed that this is adequate evidence that small (< 5 cm) abscesses without surrounding cellulitis in immunocompetent children may be treated with I&D alone and without antibiotics.135 The lack of a definitive study confirming this hypothesis, however, means that adequate patient follow-up must be assured prior to discharging patients after draining abscesses without antibiotic prescription.
Controversy also continues to exist regarding antibiotic choice in the treatment of skin and soft tissue infections. Rates of MRSA have grown exponentially over the past 10 years. Despite this, many practitioners have continued to treat patients with cephalosporins, which should in theory not adequately treat these infections. Yet there has not been a documented concomitant increase in complications from skin and soft tissue infections. In one study comparing cefdinir versus cephalexin, (two cephalosporins to which CA-MRSA should be resistant) in a variety of skin and soft tissue infections in immunocompetent patients, clinical cure rates were 93% and 91% for the two antibiotics when treating MSSA, but also 91% and 90% when treating CAMRSA.137 Even in infections that were treated without incision and drainage, there existed in another study no significant difference in need for follow up visits, subsequent incision and drainage, or antibiotic change in patients prescribed either active or inactive therapy.3 It is unclear whether or not this is due to the self-limited nature of most simple skin and soft tissue infections or some partial in vivo efficacy of cephalosporins in treating CA-MRSA despite its resistance pattern in vitro.
Without the existence of studies treating cellulitis with observation only, cellulitis of any significance still merits systemic antibiotic therapy. Phillips et al recently did a cost analysis of empiric antimicrobial strategies for cellulitis in adults in the MRSA era based on medication costs, MRSA prevalence, and probabilities for treatment failure.138 The authors concluded that for what they considered the base prevalence for MRSA (27%), cephalexin was the most cost-effective antimicrobial therapy. The major flaw with this study, however, is that it underestimates the ever increasing prevalence of MRSA in the community. While some authors are still reporting recent base prevalences of MRSA at around 20%,3 many others are reporting rates up to 37%,139 51%,140 and 74%.21 In the ED-based study by Moran et al, 9 of 11 communities have MRSA base prevalence rates of 50% or greater.21 Additionally, the Phillips et al study used only a 37% likelihood that cellulitis is caused by S. aureus.138 While this figure may be appropriate in adults, it is not applicable in children, where the likelihood of S.aureus being the etiologic agent in skin infections is much higher (> 70%)4,6 than 37%. After adjusting the likelihood of S. aureus to 70%, as appropriate for children, and the base prevalence of MRSA to a more realistic 50%, the model employed by Phillips et al would make empiric treatment with clindamycin more cost effective than cephalexin for cellulitis. That, along with the intrinsic sense it makes to use an antibiotic that MRSA is sensitive to in vitro to treat cellulitis, makes a non-beta-lactam antibiotic the preferable therapy for skin and soft tissue infections in children.
Of the non-beta-lactam antibiotics available, clindamycin has many advantages for empiric treatment. It is active against both aerobic gram-positive (including GAS and S. aureus) and anaerobic bacteria.19 Clindamycin is highly active against CAMRSA, with susceptibilities ranging from 83% to 97%.3,136,141-143 It does have a few down sides, though. Dosing is every six to eight hours, and the liquid formulation has a poor taste that may affect compliance in children. Additionally, a proportion of CA-MRSA that are resistant to erythromycin have inducible clindamycin resistance. In these bacteria, the mutation that causes erythromycin resistance may evolve to also cause clindamycin resistance during clindamycin therapy.144 To exclude inducible clindamycin resistance, the double-disk diffusion test (D test) should be performed on all clindamycin isolates that are resistant to erythromycin to exclude this inducible resistance.145 There exists a wide variation in reported rates of inducible resistance to clindamycin in erythromycin-resistant MRSA, with some studies having rates below 10%,141,142,146 while others had rates that were significantly higher.147-149
Trimethoprim-sulfamethoxazole (TMP-SMX) also has high activity against CA-MRSA, with susceptibilities between 83% and 99% at different sites.3,136,141-143 TMP-SMX, unlike clindamycin, is not active against GAS. Therefore, it should not be used as monotherapy when GAS infection is in the differential diagnosis. Rifampin is another antibiotic to which CA-MRSA is highly susceptible.3,142,143
It is potentially hepatotoxic,19 however, and may induce resistance if used as monotherapy.150 CAMRSA is also usually susceptible to tetracycline and doxycycline, with susceptibilities in CA-MRSA ranging from 55% to 92%.3,136,143 However, tetracycline antibiotics are contraindicated in pediatric patients under eight years of age, due to concerns for tooth staining and decreased bone growth. CAMRSA is highly resistant to erythromycin,3,141-143 and it should not be used in the treatment of skin and soft tissue infections. Likewise, rising GAS resistance to erythromycin has been reported.151
Orbital And Periorbital Cellulitis
Treatment of periorbital cellulitis may vary depending on the source and severity of infection. Most cases of periorbital cellulitis can be safely managed in the outpatient setting with oral antibiotics such as amoxicillin-clavulanate, cephalosporins, or clindamycin. If the source of the cellulitis is clearly local trauma, then the antibiotic regimen should cover gram-positive organisms.90 If the patient is systemically ill, however, the causative organism is very likely Streptococcus, and both GAS and Streptococcus pneumoniae should be empirically covered in the inpatient setting with intravenous antibiotics such as ceftriaxone, ampicillin-sulbactam, or clindamycin.152
Orbital cellulitis, on the other hand, is a much more serious condition and requires more aggressive inpatient treatment. Orbital cellulitis originates almost uniformly from sinusitis; for this reason, antibiotics that cover S. pneumoniae and other organisms found in the sinuses are indicated. Typical choices for empiric intravenous therapy include ampicillin-sulbactam or ceftriaxone, either alone or with the addition of clindamycin. Since orbital cellulitis often requires surgical intervention, immediate consultation with pediatric ophthalmology and otolaryngology should be sought.153 While the therapeutic approach to orbital cellulitis in the past had been mostly surgical, conservative medical management with broad spectrum antibiotic therapy is being increasingly used with good success,91 with one small study showing successful outcomes in 9 of 10 patients treated with medical therapy alone.
Severe Skin And Soft Tissue Infections
Patients with vital sign abnormalities, mental status changes, lethargy, rapidly progressing disease, fever, chills, or any other concerning symptoms should be treated aggressively with parenteral antibiotics.50 Also, children with significant comorbidities, such as asplenia or immunocompromised status, should be treated with IV antibiotics as well. Patients who have concerning infections but otherwise do not appear septic may be treated with IV antibiotics and observed for disease improvement. Intravenous clindamycin is often given empirically in this setting not only for its excellent coverage of GAS and CAMRSA infection, but also for its ability to inhibit protein toxin production.
Those patients who do appear septic, however, should be treated with antibiotics to which grampositive bacteria are highly susceptible. Intravenous vancomycin has traditionally been the mainstay of therapy for empiric treatment of serious life- or limb-threatening skin and soft tissue infections. Concern continues to grow, however, about the development of vancomycin-resistant S. aureus (VRSA). At least three cases of VRSA have been reported in the literature in the United States so far.154-156 Additionally, vancomycin has been shown to be less effective than beta-lactams in the treatment of MSSA endocarditis.157 Therefore, the addition of rifampin or gentamicin should be considered for synergistic effect in treating serious infections thought to be secondary to S. aureus.19
Linezolid is another option in the treatment of serious skin and soft tissue infections. It has activity against MRSA, GAS, S. pneumoniae, vancomycinresistant enterococcus (VRE), anaerobic bacteria, and some activity against rapidly growing mycobacteria.12 Linezolid comes in both oral and parenteral forms. There exists mixed evidence on the comparative effectiveness of vancomycin and linezolid in the treatment of serious soft tissue infections. Two studies showed linezolid to be significantly superior to vancomycin in seven day cure rates of surgical site infections158 and complicated skin and soft tissue infections159 in adults. Other studies, however, have shown no significant difference between linezolid and vancomycin in the treatment of soft tissue infections in children160 or adults.161 Some theorize that there exists intermediate resistance to vancomycin in some MRSA isolates, and this explains the apparent superior efficacy of linezolid in the treatment of MRSA infections in some studies.162
Other antibiotics have been used in the treatment of serious MRSA infections as well. Quinupristin-dalfopristin is bacteriocidal against gram-positive bacteria, including MRSA and VRE. It is approved for treatment of complicated skin and soft tissue infections and right-sided bacterial endocarditis in adults.163 Its use in children, however, has been highly limited.164 Another potentially useful antibiotic is tigecycline. It is also active against gram-positive bacteria, including MRSA and VRE, as well as gram-negative, anaerobic, and atypical bacteria. There is currently no data supporting its use in children under 18 years of age.19 No matter what therapy is chosen, it is important to obtain emergent infectious disease consultation prior to initiating any of these therapies in severe infections.
Patients with necrotizing fasciitis often deteriorate extremely rapidly. Morbidity and mortality rates in necrotizing fasciitis remain extremely high, with on recent study reporting a 17% mortality rate, with limb loss occurring in an additional 26% of adult patients.165 A recent pediatric series reported similar data, with mortality at 18%.61 Immediate stabilization begins with circulatory support with vasopressors in addition to crystalloid infusions if the patient presents in shock.166 Once hemodynamically stabilized, the patient should be taken to the operating room as soon as possible for surgical debridement of affected tissue. One study demonstrated a doubling of adult patient mortality when surgical debridement was delayed for more than 24 hours.167
Antibiotics have little effect prior to surgical debridement, secondary to the poor vascular supply reaching necrotic tissue.168 If antibiotics are initiated in the emergency department, however, they should cover gram-positive organisms and gram-negative aerobes and anaerobes. For many years, a broad spectrum beta-lactam antibiotic along with clindamycin was thought to be adequate therapy; however, with the reported emergence of MRSA as a causative pathogen of necrotizing fasciitis,96 it is no longer so. A regimen consisting of vancomycin, clindamycin, and a broad spectrum antibiotic covering gram-negative and anaerobic organisms would be appropriate therapy. Clindamycin is added for "the Eagle effect:" its ability to control toxin production in slowly metabolizing bacteria.169 Hyperbaric oxygen therapy has also been used to treat necrotizing fasciitis, but its efficacy is controversial.170
The primary treatment for staphylococcal scalded skin syndrome (SSSS) is medical pharmacotherapy. Most children without extensive skin involvement can be managed with outpatient oral antibiotics. While multi-drug resistance is rare in the staphylococcal strains causing SSSS,171 there have been multiple reports of MRSA causing SSSS.172-174 Therefore, if a cephalosporin or anti-staphylococcal penicillin is used to treat SSSS, careful follow-up must be assured. New lesions may appear 24-48 hours after the initiation of therapy, but should not be observed thereafter.102 Blisters from the rash should be kept intact; areas where blisters have erupted may be dressed with petroleumimpregnated gauze.171 More severely affected patients may need to be admitted for parenteral antibiotics as well as pain, temperature, fluid, electrolyte, and nutritional management. Very badly affected patients may require admission to a burn unit for further management.175
In toxic shock syndrome (TSS), the first priority of therapy is establishing hemodynamic stability in patients. Patients are often in profound shock secondary to capillary leakage and require multiple boluses of crystalloid or colloid.103 Vasopressors may also be indicated. Possible sources of infection must be investigated and addressed. A vaginal examination should be performed on all female patients to ensure a foreign body is not the nidus of infection. Areas of necrotizing fasciitis or abscess should be urgently debrided or incised and drained.105 Clindamycin is a mainstay of therapy for TSS whether caused by GAS or staphylococcus. Since clindamycin works by reducing protein synthesis, it acts to halt toxin production, thereby limiting disease.176 If GAS is known to be the cause of TSS in a patient, clindamycin may be used along with parenteral penicillin in treatment. In patients in whom S. aureus associated TSS is suspected, vancomycin should be added to clindamycin in areas where MRSA infections are common;177 otherwise, a beta-lactamase resistant anti-staphylococcal antibiotic may be used.
The vast majority of these pathogens will be difficult to identify in a busy emergency department. Consultation with an infectious disease specialist is recommended prior to initiating treatment. Nevertheless, knowledge of the treatments of these pathogens may be helpful both in initiating new therapy and treating patients who have already begun therapy but have returned to the emergency department for further treatment.
Actinomyces causes the chronic presence of "wooden" appearing, suppurative nodules in skin and soft tissues. It may be identified by either the "sulfur granule" like material that it drains or by culture.178 Treatment is high dose intravenous penicillin for two to six weeks, followed by oral penicillin for an additional 6-12 months.53 Similarly, Nocardia can cause a chronic, suppurative cellulitis or pyoderma that may be cultured on simple media. Treatment is with sulfonamides, such as TMP-SMX, for one to three months.53 Subcutaneous infection from Sporothrix schenckii causes sporotrichosis, characterized by either a solitary nodule or group of nodules along the local lymphatic track. It may be treated with either itraconazole or saturated solution of potassium iodide, with treatment lasting three to six months.179
Anaerobic infections are often associated with abscesses or necrotizing fasciitis, so drainage or surgical debridement of affected areas is essential. For many years, penicillins were the treatment of choice for anaerobic infections, but resistance to these antibiotics is increasing.60 Treatment for most anaerobic skin and soft tissue infections should also cover aerobic gram-positive bacteria, since they are often concomitant pathogens. Simple infections may be treated with clindamycin, with optional addition of a second or third generation cephalosporin for additional gram-negative coverage. Ertapenem is a newer class I carbapenem with good coverage against both aerobic and anaerobic organisms180 and may be used as well. Other options include penicillin-beta-lactamase-inhibitor combinations (such as ampicillin-sulbactam, piperacillin-tazobactam, or ticarcillin-clavulanate) and linezolid for severe infections.66
Pseudomonas infections require treatment with antibiotics with anti-pseudomonal activity. Ill children with ecthyma gangrenosum should be recognized immediately as having a potentially lifethreatening condition and should be treated aggressively,181 particularly in immunocompromised children. For severe or systemic infections, an aminoglycoside, such as tobramycin, amikacin, or gentamicin, plus an anti-pseudomonal cephalosporin, such as ceftazidime or cefepime, as indicated.182 For more localized infections, topical antibiotics or hot compresses with 2% acetic acid may be used.183 In patients age 18 or over, ciprofloxacin is a useful antibiotic as well, as it is available in both oral and intravenous formulations.
Salt water wounds infected with Vibrio species must be treated aggressively because even superficial wounds can progress to necrotizing soft-tissue infections.68 Wounds exposed to seawater demonstrating a rapidly progressing cellulitis should be treated as Vibrio infectious until proven otherwise.67 Immediate surgical debridement should be undertaken, and patients should be treated with parenteral antibiotics. In children eight years of age or greater, the recommended antibiotic regimen is a tetracycline, typically doxycycline, and ceftazidime.67 In children under this age, treatment decisions are more difficult. While Vibrio is sensitive to all third-generation cephalosporins,184 the severity of patient illness may dictate using a tetracycline as well. In at least one case report, doxycycline was used in this manner.185 Aeromonas hydrophila infected wounds can also develop rapidly progressive cellulitis or myonecrosis.28 Rapidly progressing wounds exposed to freshwater in children should be treated with a third or fourth generation cephalosporin that also covers Pseudomonas.186
Treatment for atypical mycobacterial infections varies based on the species identified. No specific treatment regimen has been established for Mycobacterium marinum infections. Examples of regimens that have been used in clinical practice include tetracyclines, TMP-SMX, and rifampin plus ethambutol.70 Other non-pulmonary mycobacterial infections are treated on the basis on antimicrobial susceptibility testing, but regimens often include amikacin and clarithromycin.187