Treatment of Skin and Soft Tissue Infections

CME REVIEW ARTICLE

Loren G. Yamamoto, MD, MPH, MBA

infection has great controversy in many aspects. Its history is infor- Abstract: Group A streptococcus and Staphylococcus aureus are the mative of these controversies. In the early 1980s, a treatment strat- most common bacterial etiologies of skin and soft tissue infections that egy that was used taught that although both organisms were range in virulence from very mild to limb/life threatening. Antibiotic cover- present, treating the GAS alone would be sufficient for clinical res- age recommendations are varying and subject to controversy. Antibiotic re- olution. Even at that time, S aureus was largely penicillin resistant; sistance patterns are evolving with many different biochemical mechanisms. thus, treating many patients with penicillin during this period did in Rapid bacterial identification using mass spectrometry is on the horizon. fact result in clinical cures despite S aureus' penicillin resistance. Therapeutic considerations should include cost and adherence issues. Impetigo was also successfully treated with amoxicillin, Key Words: skin infections, soft tissue infection, group A streptococcus, erythromycin, and the emerging new cephalosporin class at that Staphylococcus aureus, staph aureus, impetigo, toxic shock, time. Clindamycin was not used during this period because it necrotizing fasciitis, intertrigo, bacterial virulence, bacterial resistance, had developed a notorious reputation of pseudomembranous coli- antibiotics, antibiotic resistance tis. Even chloramphenicol was used more commonly than – clindamycin in the early 1980s. Methicillin (intravenous [IV]), (Pediatr Emer Care 2017;33: 49 57) nafcillin (IV) oxacillin (IV or orally [PO]), cloxacillin (PO), and dicloxacillin (PO) were subsequently used as the desire to treat TARGET AUDIENCE the Saureuscomponent increased, although the data supporting This CME article is intended for pediatric emergency medicine this change in practice are difficult to substantiate. These drugs physicians, emergency medicine physicians, pediatricians, nurse were known as penicillinase-resistant penicillins (a misnomer practitioners, nurses, physician assistants, and any other medical because their use was largely limited to S aureus, not other personnel involved in the care of children presenting with acute care penicillinase-producing organisms). The suspension forms of conditions that could present with skin and soft tissue infections. these drugs had a bitter metallic taste, which prompted most pediatricians to treat patients with cephalosporins instead. Methicillin- LEARNING OBJECTIVES resistant S aureus (MRSA) gradually became more common. After completion of this CME article, readers should have Methicillin resistance corresponded with cephalosporin resistance improved their knowledge of and enhanced their competence to: as well, rendering both drug classes ineffective in treating MRSA. As the MRSA frequency increased, practitioners changed their 1. Clinically distinguish the various types of skin and soft treatment to clindamycin and trimethoprim-sulfamethoxasole tissue infections. (TMP-SMX), which had better coverage of S aureus. Unfortu- 2. Identify the bacterial etiologies of skin and soft tissue infections. nately, whereas GAS was 100% sensitive to penicillins and ceph- 3. Initiate effective antibiotic strategies to treat skin and soft alosporins, there was some modest resistance to clindamycin and tissue infections. what was thought to be frequent resistance to TMP-SMX. The history is interesting here because the strategy in the 1980s was kin and soft tissue infections commonly present to the emer- to primarily treat the GAS component, but this gradually evolved S gency department (ED), urgent care, acute care, and primary to primarily treat the S aureus component. The data supporting care settings. Although most of these are not serious, treatment this change are lacking, yet the current practice is so pervasive that failure can result in the need for hospitalization. In addition, some no clinician would currently ignore the S aureus component. Currently, GAS is still universally sensitive to penicillin and patients can harbor uncommon and occult yet life-threatening 3,4 conditions that are essential for the clinician to diagnose and treat beta-lactams. The sensitivity of GAS to antibiotics other than immediately. The skin is a barrier to infection, but this can be beta-lactams is more difficult to determine. Most laboratories breached via glands, follicles, wounds, bug bites, and common do not run sensitivity tests for GAS because it is 100% penicillin skin conditions such as eczema.1,2 sensitive. In searching for antibiotic sensitivity in the literature, sensitivity to clindamycin seems to be fairly consistent at approx- imately 98%, but sensitivity to erythromycin ranges widely from Impetigo and Its Relatives 52% to 95%.3,5–7 In addition, many reports indicate that erythro- Impetigo is a common infection. Culturing impetigo lesions mycin sensitivity within a region can vary greatly during periods classically yields both Staphylococcus aureus and Streptococcus of high or low macrolide use. Thus, one should assume that GAS pyogenes (also known as a group A beta-hemolytic streptococcus, sensitivity to erythromycin is unpredictable. Staphylococcus group A streptococcus, GAS). This seemingly simple and common aureus has clearly evolved to a different organism, but it is unclear if the early recommendation of ignoring the S aureus in the treat- Professor of Pediatrics, University of Hawai‘i John A. Burns School of Medicine ment of impetigo is still correct. Organisms can vary in 2 basic and Kapi‘olani Medical Center for Women & Children, Honolulu, HI. The author and staff in a position to control the content of this CME activity ways that are often considered the same, but they are clearly dif- and their spouses/life partners (if any) have disclosed that they have no ferent: resistance and virulence. financial relationships with, or financial interest in, any commercial Resistance refers to difficulties encountered in the treatment organizations pertaining to this educational activity. of the organism, of which antibiotic resistance dominates. Reprints: Loren Yamamoto, MD, MPH, MBA, Department of Pediatrics, 1319 Punahou St, 7th Floor, Honolulu, HI 96826 (e‐mail: [email protected]). Methicillin-resistant S aureus refer to S aureus that are resistant Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. to methicillin (also resistant to cephalosporins and all the antistaph ISSN: 0749-5161 penicillins). Staphylococcus aureus is a penicillinase producer but

Pediatric Emergency Care • Volume 33, Number 1, January 2017 www.pec-online.com 49

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Yamamoto Pediatric Emergency Care • Volume 33, Number 1, January 2017 it possesses additional resistance factors rendering beta-lactamase remnants of an old blister. Does this mean that GAS has no role inhibitor additives, such as clavulanic acid, tazobactam, and in bullous impetigo? In other words, can the treatment of GAS sulbactam, useless most of the time. The MRSAs are not homoge- in such cases be completely ignored? Apparently not, since some neous. There are multiple known subtypes. Community-acquired patients presenting with poststreptococcal glomerulonephritis have MRSAs tend to be sensitive to clindamycin, whereas hospital- visible evidence of bullous impetigo. Thus, the clinical conse- acquired MRSAs are almost always clindamycin resistant. As quences of bullous versus nonbullous impetigo might not be very clindamycin use increases, it is likely that clindamycin resistance important with regard to therapeutic decisions because the current will increase. practice is to cover the S aureus component regardless. Virulence refers to the organism's ability to inflict substantial Both Saureusand GAS possess a unique type of resistance harm on the body. The best example of this is the classic observa- known as MLS (macrolide, lincosamide, streptogramin)-inducible tion by microbiologists in the early 1900s in which it was noted resistance.13–16 The most common interaction is between erythro- that mice died when injected with colonies of smooth pneumo- mycin and clindamycin. Figure 1 shows 2 antibiotic disks on a cocci (possessing a polysaccharide capsule), but the mice survived petri plate inoculated with S aureus. The disk on the left shows when injected with colonies of rough pneumococci (nonencap- no zone of inhibition (hence resistance) for the E (erythromycin) sulated). Encapsulated pneumococci are more virulent than non- disk and a large zone of inhibition (hence sensitive) for the C encapsulated pneumococci. The polysaccharide capsule is a (clindamycin) disk. The C disk on the right shows a D-shaped virulence factor that shields the organism from opsonization and zone of inhibition for clindamycin. This indicates that in the area other attempts by the immune system to neutralize the organism. between the erythromycin and clindamycin disks, the presence of We now know that pneumococcal vaccines target the polysaccha- erythromycin has induced resistance to clindamycin. In the ab- ride capsules of the most virulent strains. Nonencapsulated pneu- sence of erythromycin, the organism is sensitive to clindamycin. mococci often result in simple nasopharyngeal colonization, The presence of erythromycin promotes a clindamycin resistance sinusitis, and otitis media. Encapsulated pneumococci are the factor. Among S aureus, MLS-inducible resistance is present in strains most often associated with invasive pneumococcal disease roughly 10% to 25% of both MRSA and methicillin-sensitive such as pneumococcal meningitis. Similarly, Haemophilus S aureus community-acquired isolates, with some series showing influenzae type B has a polysaccharide capsule virulence factor, a higher frequency among MRSA and vice versa.13–16 It is advis- whereas nontypable Hinfluenzaeis less virulent. able to avoid using these 2 drugs together. In addition, because Staphylococcus aureus strains that produce toxic shock this type of resistance is inducible, conventional antibiotic suscep- toxin8 can kill a patient (ie, it is highly virulent), whereas an ordi- tibility testing to erythromycin and clindamycin might overesti- nary S aureus without this toxin might cause impetigo (ie, its vir- mate true susceptibility (underestimate resistance).13 Published ulence is low). Both virulent and nonvirulent S aureus can be susceptibility numbers are overly optimistic to some degree for MRSA or methicillin-sensitive S aureus; thus, resistance does the MLS group of antibiotics. not necessarily correlate with virulence. Other virulence factors Another type of resistance occurs when GAS is in close of S aureus are staphylococcal scalded skin syndrome (SSSS) proximity to another penicillinase-producing organism such as S epidermolytic toxin, exotoxins associated with septic shock, and aureus. The penicillinase creates tiny microenvironments that other factors that increase the invasiveness of the organism.8,9 are free of any penicillins, permitting GAS to survive.3,5 For example, consider these 2 cases: a patient with a simple bee Although there are published treatment guidelines17,18 for sting developed a modest cellulitis of the elbow. He shortly impetigo, controversy remains. The GAS remains penicillin sensi- thereafter developed staphylococcal pneumonia, empyema, tive, yet S aureus is almost always resistant. It is currently pneumothorax, and septic shock. Another patient presented with extensive impetigo and developed staphylococcal pneumonia, empyema, and septic shock. In considering why these patients developed invasive disease whereas most patients have infections limited to cellulitis and impetigo, this could be due to host immunity factors, the quantitative load of organisms, and/or the virulence of the organism. Other S aureus virulence factors include membrane-damaging toxins, cell wall–anchored proteins, clumping factors A and B, fibronectin-binding proteins, Panton-Valentine leucocidin, alpha-hemolysin, phenol-soluble modulins, arginine catabolic mobile element, etc.2,8,9 Similarly, the virulence of GAS ranges broadly from streptococcal pharyngitis that resolves without treatment to impetigo, severe tonsillitis, scarlet fever, sepsis, pneumonia, and necrotizing fasciitis (NF).4,10,11 Even with a relatively benign streptococcal sore throat, some strains are rheumatogenic, placing patients at risk for acute rheumatic fever. Some GAS strains are nephritogenic, placing patients at risk for acute poststreptococcal glomerulonephritis.10,11 Although all these strains are penicillin sensitive, their virulence varies tremendously. Concurrent varicella and nonste- FIGURE 1. MLS resistance. This is an agar plate of S aureus.Thereis roidal antiinflammatory drug12 use seem to be associated with se- no zone of inhibition around the E (erythromycin) disk on the left. vere GAS infections.11 There is a large zone of inhibition around the C (clindamycin) disk on the right, but in the area between the 2 disks, the clindamycin Some references describe differences in bullous and 1 zone of inhibition is smaller with visible colonies growing adjacent to nonbullous forms of impetigo. The common distinction is that the clindamycin disk. The presence of erythromycin has induced the bullous form more likely involves S aureus.Someofthese resistance to clindamycin in this area. This picture is known as the present clinically with thin bullae surrounding the lesions or bulla D-test because it results in a D-shaped zone of inhibition around that have lysed revealing a thin rim of epidermis similar to the the clindamycin disk.

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Pediatric Emergency Care • Volume 33, Number 1, January 2017 Skin and Soft Tissue Infections unthinkable to treat impetigo with penicillin, although this had GAS-associated condition such as impetigo, is most likely to be been done 30 years ago. Clindamycin is commonly used, yet there due to uncomplicated scarlet fever; however, some patients will is increasing resistance by both GAS and S aureus. The GAS is have early streptococcal or staphylococcal toxic shock syndrome cephalosporin sensitive; however, it will not cover MRSA. The (TSS). It is critically important to distinguish the two because scar- TMP-SMX is more reliable in covering Saureus, but its coverage let fever can usually be managed with oral antibiotics as an outpa- of GAS is thought to be poor based on older susceptibility studies. tient, whereas TSS requires intensive care unit management with In vitro GAS susceptibility to TMP-SMX is dependent on thymi- fluid resuscitation and, in some cases, with vasoactive inotrope in- dine present in the growth media because its presence bypasses fusions. If the patient is obviously exhibiting signs and symptoms the folate inhibition mechanism of action. When tested in non– of shock, then the patient clearly needs to be admitted to the inten- thymidine-containing media, GAS was found to be sensitive to sive care unit. However, most cases are not this obvious and, in TMP-SMX.19 However, this in vitro testing needs to be confirmed fact, most cases are scarlet fever and not TSS. Because there is to be valid in vivo because thymidine and other substrates are pres- no readily available diagnostic test to distinguish the two, it prob- ent in variable concentrations in the host as well. Table 1 shows ably is best to begin anti-GAS and anti-S aureus antibiotic treat- some theoretical coverage rates depending on resistance rates in ment in the ED and monitor the patient for several hours. your community. Other than using linezolid, the highest theoreti- Laboratory testing can help to provide reassuring or nonreassuring cal success rate is achieved with TMP-SMX (assuming that this information, yet these are not diagnostic. If the patient continues covers GAS), and cephalexin + clindamycin (which some might to improve during a prolonged ED observation, it is more likely feel is too much antibiotic treatment for a relatively minor prob- that the patient's erythroderma is due to scarlet fever, and the pa- lem). Although most practitioners use clindamycin to treat impe- tient can be discharged from the ED after confirming the presence tigo, as clindamycin resistance increases, this treatment strategy of reliable home observers and follow-up can be assured. If the pa- will become less effective. tient has TSS, it is more likely that signs and symptoms of shock Whereas oral antibiotic strategies have some controversy, will develop. These can be variable, but even though tachycardia topical treatment with mupirocin is highly effective for superficial is nonspecific, its persistence should raise concern. Other con- infections such as impetigo.17 If the number of lesions is limited, cerning symptoms include lightheadedness, irritability, lethargy, topical mupirocin is reasonably easy for a patient/parent to apply combativeness, behavior changes, muscle pain, vomiting, and/or and there are minimal systemic adverse effects. If the number of lower-than-expected urine output.12,20 If in doubt, extend the ED lesions is high, then topical treatment becomes extensive that observation period or admit the patient to the hospital. might prove to be difficult to apply or the patient/parent might not be willing to do this. Multiple tubes will be necessary increas- Cellulitis ing the cost of treatment, but many oral antibiotic strategies are Cellulitis can be caused by both GAS and S aureus.Itisdif- similarly expensive. Oral antibiotic dosing might be easier, but it ficult to confirm the causative organism with certainty. Surface has systemic absorption and adverse effects that could be avoided cultures can be misleading, blood cultures are most often negative, with topical therapy. and leading edge or other soft tissue cultures have not proven to be useful. Cellulitis due to S aureus is usually localized under a cuta- Impetigo With Febrile Erythroderma neous lesion, often with a small abscess or draining purulence. Some patients with impetigo will simultaneously present Cellulitis due to GAS is usually extensive with a central open le- with a febrile erythroderma. Fever alone can increase the perfu- sion, most commonly on the lower extremities, but sometimes sion of the skin giving the patient the appearance of a slight on the face. Its color is magenta, and the history is often that the erythroderma. A true erythroderma in conjunction with any large area of redness appeared in a relatively short period, which

TABLE 1. Antibiotic Sensitivity of GAS and Saureus. Theoretical Therapeutic Success Rate (Both Organisms Sensitive to the Antibiotic)

GAS Sensitivity S. aureus Sensitivity Theoretical Success Rate Penicillin 100% 0% 0% Amoxicillin 100% 0% 0% Amoxicillin/clavulinate 100% 70% 70% Cephalexin 100% 69% 69% Erythromycin3,5–7 70% 55% 39% Clindamycin3,5–7 98% 76% 74% Cephalexin + Clindamycin 100% 93% 93% Penicillin + Clindamycin 100% 76% 76% TMP-SMX (assumes GAS mod resistant) 50% 95% 48% TMP-SMX (assumes GAS sensitive) 100% 95% 95% Rifampicin3,5 100% 99% 99% Tetracycline3,5 70% 99% 70% Ciprofloxacin3,6 99% 82% 81% Linezolid3 100% 100% 100% Vancomycin3,5 100% 100% 100% Staphylococcus aureus sensitivity numbers are from the 2015 emergency department nonurine isolates from Kapi‘olani Medical Center for Women & Children. Presumably, these are mostly community acquired because they are ED patients (no inpatients in this group). Sensitivities vary between commu- nities. The GAS sensitivities are 100% for all beta-lactams and otherwise based on values from the literature (see citation numbers).

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Yamamoto Pediatric Emergency Care • Volume 33, Number 1, January 2017 raises concern that this could be an overwhelming infection. The Neck intertrigo tends to occur in infants because the neck is short term erysipelas can be used together (near synonyms) with GAS with poorly ventilated moist intertriginous skin folds that abut cellulitis,17 or when it is limited to the superficial epidermis1,12 against each other, similar to the perianal region. Other areas in- (as opposed to true cellulitis, which is a deeper infection), or when clude the popliteal fossa, perineal/inguinal skin folds, and vaginal associated with lymphangitis or lymphadenitis. Because GAS is skin folds. The appearance is described as “fiery red” and “beefy always sensitive to penicillin, one could treat this with penicillin, red”. A foul odor is often present. Especially in the neck and skin but it takes great fortitude and confidence to treat such a large folds, the skin is moist, macerated, and often denuded, which cellulitis with such a narrow-spectrum drug. It is useful to advise breaches the skin barrier. The borders are often well demarcated patients that after effective treatment has commenced, they between macerated and normal skin. This is often mistaken for should anticipate a darkening of the erythroderma and, often, candida infections that can also have a beefy red appearance. the formation of tiny blisters with eventual superficial desquama- However, intertrigo usually does not have satellite lesions, and it tion on the surface of the cellulitis. This can be alarming if the pa- tends to occur in these poorly ventilated areas such as the infant tient is not expecting it. The major reason for treatment failure is neck and the perianal region. Fever is usually not present. The the presence of an abscess that requires drainage. The GAS cel- GAS can be cultured from the surface.25–29 Rapid strep testing lulitis is diffuse and it forms more rapidly making the presence is usually positive.27,29 of an abscess less likely. Atypical factors such as more extensive swelling or pain might be suggestive of an abscess, but there are no good studies to confirm the reliability of these signs. In the Necrotizing Fasciitis emerging age of bedside ultrasound, it makes sense that clini- Associated with GAS in its most virulent form, this is per- cians should scan the cellulitis region with the high-resolution, haps the most dangerous condition discussed in this report. It re- high-frequency linear probe because it is likely that the depth sults in a severe threat to life and limb.30–34 The actual infection of an abscess would be less than 4 to 5 cm.21,22 Although tiny ab- is most often polymicrobial,34,35 yet GAS is frequently a dominant scesses might be difficult to confirm, these might not require pathogen.30 An early diagnosis is often missed because its exter- drainage. Ultrasonographic cobblestoning has been described nal appearance is often unimpressive. The classic triad includes with cellulitis,21,22 but this likely does not add to the diagnostic localized pain, swelling, and erythema,31 which are not specific certainty of cellulitis because this can be readily visualized with- enough for an obvious early diagnosis. Severe pain, bullae, skin out ultrasound. The main role of ultrasound is to identify necrosis (purple color), and crepitus are more specific signs when an abscess. present.34,35 Roughly 70% of cases are initially misdiagnosed, Cellulitis due to Saureusis more likely to have an associated most commonly as cellulitis or an abscess.33 Plain x-ray findings abscess. Because its size is smaller and localized, abscess identifi- are usually nondiagnostic. A computed tomography scan or mag- cation can usually be done clinically in most instances. However, netic resonance imaging scan may help to confirm the diagnosis applying a bedside ultrasound probe to the area will be more once the clinical suspicion is high enough, but neither modality reassuring. A questionable abscess finding can be followed by is highly sensitive or specific without clinical correlation.32,35 needle aspiration to determine if an abscess is present. This results in a delay in treatment often resulting in the necessity The presence of an abscess is often clinically apparent. The for more extensive soft tissue or muscle debridement or limb am- more superficial it is, the easier it is to identify. Deeper abscesses putation. Common locations tend to be the scrotum, perineum, ab- can be difficult to identify. Ultrasound can be very helpful.21,22 dominal wall, and the extremities.30,31 Immunocompromised The high-resolution linear probe is limited to superficial depth patients, diabetics, and IV drug abusers are at higher risk, but this penetration, but 4 to 5 cm is generally more than sufficient to iden- still occurs in healthy patients with small initial wounds or lesions tify most abscesses that will benefit from drainage in the ED. Even that are often characterized as trivial.30,33,34 Some early publica- in cases in which the abscess location seems to be obvious, it is of- tions suggested that tissue necrosis indicative of NF could be con- ten wise to ultrasound this area anyway. In some instances, an ab- firmed with the finger test in which a gloved finger, inserted scess is not present or it is present in a location that was not through a 2-cm incision overlying the site of infection, dissects expected. This practice avoids incising unnecessarily or incising into the tissues with minimal resistance.30,33 In current practice, in the wrong location. this test is not used because it has been supplanted by imaging In abscesses alone, in which there is no cellulitis, the or, in cases with a strong-enough clinical suspicion, immediate American College of Emergency Physicians recommends against treatment with surgical debridement and antibiotic therapy. the practice of culturing the abscess fluid and initiating antibiotics, In addition to GAS and S aureus, other organisms include citing evidence that these are not necessary, as part of their Clostridium perfringens (gas gangrene), Vibrio vulnificus (ma- “Choosing Wisely” campaign.23 However, a treatment guideline rine organism, injury by fish fins), Aeromonas hydrophilia document agrees with this approach only for mild abscesses.17 (water and soil organism) polymicrobial anaerobes, and Gram- This likely explains why nearly all drained abscesses get better de- negative organisms. These unusual organisms (eg, marine vibrio) spite moderate antibiotic resistance rates. Because most abscesses require additional antibiotic coverage (eg, doxycycline,18 quino- have some degree of cellulitis, antibiotic treatment might still be lones), thus the history of the wound can be important in antibi- necessary for moderate cellulitis, but the criteria defining when otic selection. Candida and fungal infections typically occur in to withhold and when to use antibiotics requires guidelines with immunocompromised hosts.31,33,35 greater clarity. One study of outpatient abscesses drained in the Bedside ultrasound has been described as a tool to facilitate ED comparing treatment with TMP-SMX versus no antibiotics af- the diagnosis,36–39 but these cases are few and far between, thus ter drainage found better clinical cures in the TMP-SMX group no clinician is likely to have sufficient experience with these cases (80.5% vs. 73.6%).24 to develop the pattern recognition for this. Clinicians will have to learn and remember the ultrasound appearance from previously published images so that it can be recognized when encountered. Intertrigo of the Neck and Perianal Area One report describes the “STAFF” sign, which is a series of ultra- This is a localized GAS infection that occurs most commonly sound findings that include positive subcutaneous thickening, air, in the intertriginous skin folds of the perianal and neck areas. and fascial fluid, spelling out STAFF.36

Necrotizing fasciitis requires immediate surgical debride- bacterial etiologies. These 2 organisms collectively result in a ment and broad-spectrum antibiotics that should include wide range of virulence, disease processes, antibiotic resistance clindamycin and penicillin.30,34 Because this is a polymicrobial patterns, and clinical treatment strategies. disease condition, broad-spectrum antibiotics, beta-lactamase in- Lemierre disease can present with tonsillitis and neck swell- hibitors, and metronidazole can be used to more effectively cover ing appearing to be a soft tissue infection of the neck. However, it these organisms.31 IV immune globulin and hyperbaric oxygen is a septic thrombophlebitis of the internal jugular vein most often therapy might have benefits as well4,11,30; however, a Cochrane due to Fusobacterium necrophorum requiring hospitalization.45 systematic review on hyperbaric oxygen concluded that no trials Although Lemierre disease is uncommon, in a cohort of college sufficiently met their criteria for review.40 students presenting with an acute sore throat versus asymptom- atic controls, F necrophorum was found in 20.5% of sore throats Rapid Organism Identification and 9.4% of controls, whereas GAS was found in 10.3% of sore throats and 1.1% of controls.46 Other publications suggest that The age of organism identification via mass spectrometry 47,48 (MS) has arrived. In the past, organisms were identified by grow- Fnecrophorumis prevalent, which suggests that it only rarely ing them on petri plates and identifying morphologic features by progresses to cause Lemierre disease. Gram stain light microscopy and metabolic features of the organ- Lugwig angina is an uncommon infection originating from the mouth that can present with swelling and redness of the neck ism (eg, coagulase, disaccharide metabolism enzymes). Matrix- 49 assisted laser desorption/ionization-time of flight mass spec- and submandibular region. Both Lemierre disease and Ludwig trometry (MALDI-TOF) MS analyzes a laser protein, lipid, and angina are generally discussed within the scope of head and neck infections, rather than skin and soft tissue infections. nucleic acid fingerprint of the organism, which can be compared 50 51 to a catalog of organisms to identify the organism rapidly.41–43 Organ- Skin and soft tissue infections by parasites and viruses ism subtypes can be determined in this fashion. These subtypes can are not covered in this report. Animal bites by domestic dogs have known virulence factors and antibiotic sensitivity patterns giving and cats have other controversies related to coverage of their unique organisms. Amoxicillin-clavulinate is commonly recom- clinicians this useful information at an earlier point in the patient's 17 clinical course. Proteins produced by organisms can be identified mended, yet this might not cover S aureus well. In addition, by MS, which can also enable antibiotic sensitivity (eg, beta- animal exposures and bites have other concerns such as rabies, lactamase or penicillin-binding proteins) and virulence (eg, SSSS cat-scratch disease, toxoplasmosis, tularemia, Lyme disease, toxin, Gram-negative endotoxin) determination. Because this Rocky Mountain spotted fever, and other unusual animal organ- methodology does not require repeated incubation cycles, identi- isms that are beyond the scope of this article. fication and sensitivity times can be reduced by eliminating the second incubation commonly used for final identification and antibiotic sensitivity. This time savings can be even more pro- Therapeutic Considerations nounced for fastidious or slow-growing organisms such as Clindamycin can be a very expensive pediatric drug. If one acid-fast bacilli. Most of the progress in MS has been with Gram- uses a dose of 30 mg/kg per day (10 mg/kg per dose, 3 times a negative organisms, but very soon, all organisms will be identified day for 10 days), Table 2 shows the dosing and the retail cost of and characterized in this fashion. Many clinical laboratories are the clindamycin.52 Because most children can swallow pills by already using these methods; however, these methods are 6 years, training them to do so can result in a substantial cost sav- evolving rapidly, and it will take time before MS methods for ings. In practice, many 6- to 12-year-old children are unwilling to organism identification and sensitivity will become routine. – swallow pills. Encouraging children to learn to swallow pills in the Nucleic acid based methods such as rapid polymerase chain 6- to 8-year age range is reasonable, which can result in tremen- reaction amplification of bacterial genomes, fluorescence in situ dous cost savings for the system. Emergency department nurses hybridization, and microarrays can provide similar information can frequently train children to do this by administering the first of bacterial identification, resistance, and virulence factors. These dose in the ED. This has the advantage of starting the treatment methods currently compete with MS methods as they develop to 44 immediately without resorting to the parenteral route, and it con- improve sampling, turnaround times, and accuracy. firms that the child can swallow pills/capsules, permitting the ED physician to prescribe it as such. If the trial fails, then a pre- Other Skin Soft Tissue Infections scription for the suspension/liquid form is provided instead. Sim- This topic is broad, and the focus of this report has largely ilarly, the cost for the suspension/liquid forms of cephalexin and been on GAS and Saureus. These are, by far, the most common amoxicillin are higher than the pill/capsule forms.

TABLE 2. Retail Cost of Oral Clindamycin at 30 mg/kg per Day Divided in 3 Doses (TID) for 10 Days. The Cost of the Liquid Forms Is Much Higher Than the Equivalent Dose of Capsules. Non-Generic Suspension Costs Are In Parentheses

Dose 150-mg Capsules 300-mg Capsules 75 mg/5 mL, Suspension 10-kg infant 100 mg TID $160 ($338) 20-kg 4 year old 200 mg TID $320 ($676) 30-kg 7 year old 300 mg TID $10 $15 $480 ($1014) 40-kg 12 year old 400 mg TID $640 ($1352) 75-kg teen/adult 600 mg TID $20 $31 $960 ($2028) Capsules: 150-mg capsules at $0.17 per capsule, 300-mg capsules at $0.51 per capsule.53 Suspension: generic 75 mg/5 mL, 100-mL bottle at $8052 (nongeneric retail price, $16953). TID indicates 3 times a day.

The taste of clindamycin can be poor. Earlier forms of significant roles in uncommon and more serious infections. Anti- clindamycin liquid are no longer on the market. In a more recent biotic strategies are controversial and evolving. Bacterial identifi- study comparing 3 forms of clindamycin suspension, 1 form cation methods are evolving and advancing rapidly. was better than the other 2 forms. The better tasting form was rated to taste just slightly poorer (but within overlapping 95% confidence intervals) than amoxicillin.52 A practitioner cannot deter- REFERENCES mine which form of clindamycin will be dispensed to the patient. 1. Ibrahim F, Khan T, Pujalte GG. Bacterial skin infections. Prim Care.2015; A pharmacist will not taste test the drug for the patient as a condi- 42:485–499. tion of purchase. The patient will get what the pharmacy dis- penses, and the patient will find out how it tastes after he or she 2. Lacey KA, Geoghegan JA, McLoughlin RM. 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