26 Rifampin induces the metabolism of multiple other

agents (e.g., warfarin, anticonvulsants, azole antifungals); therefore, a thorough

review of A.T.’s medication profile is critical. A.T.’s baseline liver function should

also be evaluated and rechecked at least monthly while she is taking

rifampin.

27Additionally, weekly assessment of A.T.’s complete blood count and renal

function along with periodic vancomycin trough serum concentrations should be

performed.

28

SEPTIC ARTHRITIS

Septic arthritis or infectious arthritis is usually acquired hematogenously. The highly

vascular synovium of the joint allows easy passage of bacteria from blood into the

synovial space. Bacteremia, secondary to Neisseria gonorrhoeae or S. aureus in

particular, often is associated with joint infections. Septic arthritis also can develop

secondary to inoculation of pathogens due to trauma, including puncture (e.g., animal

bites, nail) or surgery, as well as via contiguous spread from osteomyelitis.

29

Several factors predispose patients to the development of infectious arthritis.

Patients with abnormal joint structure, including rheumatoid arthritis (RA), prosthetic

joints, or recent joint surgery, are more susceptible to the development of infection.

Patients with age greater than 80 years, diabetes mellitus, and chronic illnesses such

as malignancy and chronic renal failure are also at an increased risk. Gonococcal

arthritis may occur in those who have been exposed to or are infected with N.

gonorrhoeae.

29

Clinical Presentation of Nongonococcal Arthritis

CASE 73-6

QUESTION 1: C.H., a 45-year-old man, is referred to the rheumatology clinic for left knee swelling. Two

days ago, his left knee became painful and swollen, and he is unable to flex the joint. He also recorded

temperatures at home of 100.7°F to 102°F for at least 4 days. In clinic, a joint effusion is noted, and fluid is

aspirated for cell count, Gram stain, and culture. His medical history is unremarkable. C.H.’s WBC count is

16,000/μL, and his ESR is 42 mm/hour. The synovial fluid from his right knee contains 30,000 WBC/μL with

90% neutrophils, and the Gram stain shows gram-positive cocci in clusters. Culture results are pending. His

temperature is 38.5°C. What findings in C.H. are consistent with septic arthritis?

C.H. has an acute onset of monoarticular joint pain and swelling, with reduced

range of motion and fever. These findings are classic for septic, nongonococcal

arthritis. The joint effusion shows a predominance of neutrophils, which confirms the

diagnosis. C.H.’s knee has been infected hematogenously from a distant,

unrecognized, source of infection. The knee is infected

p. 1542

p. 1543

most frequently, and the most common causative pathogens are Gram-positive,

including Staphylococcus, Streptococcus, and Enterococcus species.

A single joint is infected in 80% to 90% of nongonococcal arthritis cases. Other

possible sites of infectious arthritis in adults besides the knee include the hip,

shoulder, sternoclavicular, sacroiliac, and ankle joints.

29 Patients commonly present

with fever, pain, swelling, redness, and decreased mobility of the involved joint.

As illustrated by C.H., most patients have joint effusion on physical examination.

When evaluating a patient with possible septic arthritis, any purulent joint effusion

should be considered septic until proven otherwise. Alternatively, noninfectious

conditions may be present, such as single joint involvement with synovial effusions

in acute RA, gout, or chondrocalcinosis.

29

Aspirated joint fluid should be cultured because isolation of bacteria is the only

definitive diagnostic test for bacterial arthritis. C.H.’s joint fluid picture is typical.

The leukocyte count in the synovial fluid usually is elevated significantly, with counts

above 50,000/μL with a predominance of neutrophils (>75%). Blood cultures are

positive in 25% to 70% of patients.

Another laboratory finding in C.H. consistent with infectious arthritis is the

elevated ESR and peripheral WBC count. CRP is frequently elevated as well,

although both ESR and CRP are nonspecific markers of inflammation and can be

elevated due to causes other than infectious arthritis.

The patient’s age impacts the most common bacterial cause of infection. In adults

older than 30 years of age such as C.H., and in children older than 2 years of age, S.

aureus is the most common bacterial source. In sexually active young adults, N.

gonorrhoeae is more likely to be the causative agent. Streptococci, such as group A

β-hemolytic streptococci, can cause infection in children and adults. Other

organisms, such as group B streptococci, anaerobic streptococci, and gram-negative

bacteria, can also cause infection. Gram-negative bacilli are responsible for

approximately 5% to 20% of cases and often infect multiple joints. Infections with

gram-negative bacteria usually are associated with predisposing factors, such as RA,

osteoarthritis, history of joint surgery, intra-articular injections, or intravenous drug

use. An organism commonly isolated from patients with bacterial arthritis who have

a history of IV drug use is P. aeruginosa.

29

,

30

Initial Antimicrobial Therapy

CASE 73-6, QUESTION 2: How should C.H. be treated, and for how long? How should the efficacy of

treatment be monitored?

Treatment of nongonococcal arthritis includes drainage of purulent joint fluid (by

needle aspiration or surgery) and appropriate antibiotic therapy. Because of the

increasing frequency of community-acquired MRSA causing infection, initial empiric

therapy with vancomycin (15 mg/kg/dose IV every 12 hours, goal serum trough

concentration 15–20 mg/L) should be initiated to provide coverage for this and

streptococci in C.H. Daptomycin and linezolid are typically reserved for patients

with vancomycin intermediate-susceptible or resistant gram-positive organisms or

those patients with intolerance or allergy to vancomycin. Vancomycin can be changed

on the basis of sensitivity testing to oxacillin, nafcillin, or cefazolin if the isolated

organism is susceptible.

29

,

30

DURATION OF THERAPY

No high-quality studies have been performed to determine the optimal duration of

therapy for bacterial arthritis.

30 Previous recommendations based on early clinical

trials recommended treating for 2 to 3 weeks.

31 However, current recommendations

are to initiate therapy with at least 2 weeks of IV antibiotics, followed by oral

antibiotics (if possible based on susceptibilities) for at least 4 more weeks.

29

,

30

C.H. should be treated for at least 4 weeks.

29

,

30 His response to therapy should be

monitored clinically (resolution of symptoms, fever, and falling ESR, CRP, or both)

as well as by periodic evaluation of joint fluid. Frequent aspirations of joint fluid via

closed-needle aspiration or following arthroscopic lavage, and debridement and

insertion of drains will permit daily evaluation of cell count and fluid culture.

Effective therapy should result in a decreasing WBC count in the joint fluid and

negative cultures, usually within 3 to 4 days of treatment.

29

Joint inflammation and other symptoms also should diminish during the first week

of treatment. The duration of articular symptoms before antibiotic therapy begun

correlates with the subsequent time required to sterilize the synovial fluid. Therefore,

delay in initiating antibiotic treatment may necessitate a longer course of therapy.

Similar to hematogenous osteomyelitis, oral antibiotics have been used in septic

arthritis to complete treatment if the initial response to IV therapy is adequate for

some pathogens and in patients at lower risk for recurrent infection.

29

,

30 C.H. should

be advised that parenteral treatment with vancomycin, which can be accomplished at

home, would be the most effective mode of treatment if his cultures grow MRSA,

because this pathogen typically requires 4 weeks of IV antibiotics. Finally, injections

of antibiotics into the joint space are of no value. Most systemic antibiotics readily

penetrate the joint space and enter the synovial fluid.

Gonococcal Arthritis

Polyarticular arthritis in a young, sexually active adult is caused most commonly by

N. gonorrhoeae. Arthritis in multiple joints is a common feature of disseminated

gonococcal infection (DGI). Unlike nongonococcal arthritis, which is almost

exclusively monoarticular, gonococcal arthritis involves multiple joints in

approximately 50% of cases. Women have a four-fold increased risk of developing

gonococcal arthritis as compared with men, often due to delays in diagnosis of

genital infection.

29

,

32 Clinically, patients present with a migratory polyarthralgia often

with fever, dermatitis, and tenosynovitis. Skin lesions are an important clue to the

diagnosis of DGI and often begin as tiny erythematous papules and develop into

larger vesicles. As in hematogenously acquired nongonococcal arthritis, the synovial

fluid leukocyte count usually is elevated, but often to a lesser degree. N. gonorrhoeae

is recovered in approximately 50% of purulent joint effusions, but is detected using

polymerase chain reaction (PCR) assays that have approximately 96% specificity

and 80% sensitivity. These laboratory studies, coupled with the patient’s clinical

presentation, can be used to make a definitive diagnosis.

29

,

32

CLINICAL PRESENTATION OF GONOCOCCAL ARTHRITIS

CASE 73-7

QUESTION 1: E.D, a 21-year-old woman, presents to the walk-in clinic with right knee and right shoulder

pain, nausea, and vomiting. On physical examination, her right knee is swollen and she has decreased range of

motion of her right shoulder. Several erythematous, papular skin lesions are noted on both hands. She also has a

vaginal discharge. Her temperature is 38.2°C, and her WBC count is 15,000/μL. She gives a history of having

two recent sexual partners. Cultures of blood, joint fluid, and vaginal discharge are obtained; a joint fluid Gram

stain shows 4+ PMNs, but no organisms are seen. Why is E.D. considered to have gonococcal arthritis?

p. 1543

p. 1544

E.D. has systemic signs of infection (fever, nausea, vomiting, leukocytosis), skin

lesions, and multiple joint involvement, which are classic for DGI. Her history of

recent sexual activity and the presence of a vaginal discharge are consistent with

gonococcal infection, although evidence of mucosal infection with N. gonorrhoeae is

not necessary for disseminated infection to occur.

29

,

32

PATIENT WORKUP AND TREATMENT IN THE CLINIC

CASE 73-7, QUESTION 2: What additional workup should be done in E.D.? Can she be treated immediately

in the clinic?

E.D. should be evaluated for other sexually transmitted diseases, specifically

syphilis and HIV infection. Serologic testing for syphilis (rapid plasma reagent

[RPR] or venereal disease research laboratory [VDRL] testing) and for antibody to

HIV should be obtained. In addition, she should have a pregnancy test because some

of the antibiotics that may be used are contraindicated during pregnancy, including

doxycycline.

Because of possible penicillinase production by N. gonorrhoeae, recommended

therapy is with ceftriaxone (1 g intramuscularly or IV every 24 hours) for at least 7

days. E.D. should receive her first dose of ceftriaxone in the clinic today. Conversion

to oral antibiotics should be guided by antimicrobial susceptibility testing following

24 to 48 hours of clinical improvement by the patient.

33

E.D.’s sexual partners should also be evaluated and treated for relevant sexually

transmitted diseases. She should also be counseled on utilization of barrier methods

(e.g., condoms) to prevent sexually transmitted infections.

FULL COURSE OF THERAPY

CASE 73-7, QUESTION 3: Results of RPR and pregnancy testing in E.D. are negative. How should she

complete her course of therapy?

E.D.’s DGI should be treated for at least 7 days. E.D. also should begin treatment

with azithromycin (1 g orally once) or doxycycline (100 mg orally twice daily for 7

days) for the possibility of concomitant chlamydial infection. Azithromycin is

preferred because of increasing resistance with tetracyclines.

34 Treatment guidelines

for DGI are also included in the gonorrhea section of Chapter 72, Sexually

Transmitted Diseases.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and website for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

Key References

Berbari EF et al. Osteomyelitis. In: Mandell GL et al., eds. Mandell, Douglas, and Bennett’s Principles and

Practice of Infectious Diseases. 8th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2015:1318. (1)

Conterno LO, Turchi MD. Antibiotics for treating chronic osteomyelitis in adults (review). Cochrane Database

Syst Rev. 2013;9:CD004439. (20)

Forrest GN, Tamura K. Rifampin combination therapy for nonmycobacterial infections. Clin Microbiol Rev.

2010;23(1):14. (25)

Keren R et al. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute

osteomyelitis in children. JAMA Pediatr. 2015;169(2):120–128. (12)

Lipsky BA et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and

treatment of diabetic foot infections. Clin Infect Dis. 2012;54(12):e132–e173. (15)

Liu C et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of

methicillin-resistant Staphylococcus Aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18–

e55. (9)

Osmon DR et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the

Infectious Diseases Society of America. Clin Infect Dis. 2013;56(1):e1. (23)

Spellberg B, Lipsky BA. Systemic antibiotic therapy for chronic osteomyelitis in adults. Clin Infect Dis.

2012;54(3):393–407. (19)

Zimmerli W, Sendi P. Orthopedic implant-associated infections. In: Bennett JE et al., eds. Mandell, Douglas, and

Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, PA: Elsevier Churchill

Livingstone; 2015:1328. (22)

Additional Reference

Berbari EF et al. 2015 Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis

and treatment of native vertebral osteomyelitis in adults. Clin Infect Dis. 2015;61(6):e26–e46.

Key Websites

Centers for Disease Control and Prevention, Sexually Transmitted Diseases Treatment Guidelines, 2015.

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htm. Accessed December 2, 2015.

COMPLETE REFERENCES CHAPTER 73 OSTEOMYELITIS

AND SEPTIC ARTHRITIS

Berbari EF et al. Osteomyelitis. In: Mandell GL et al., eds. Mandell, Douglas, and Bennett’s Principles and

Practice of Infectious Diseases. 8th ed. Philadelphia, PA: Elsevier Churchill Livingstone; 2015:1318.

Petolta H, Paakkonen M. Acute osteomyelitis in children. N EnglJ Med. 2014;370:352–360.

Eid AJ, Berbari EF. Osteomyelitis: review of pathophysiology, diagnostic modalities and therapeutic options. J Med

Liban. 2012;60:51–60.

Krogstad P. Osteomyelitis. In: Feigin RD et al., eds. Textbook of Pediatric Infectious Diseases. 7th ed.

Philadelphia, PA: WB Saunders; 2014:711.

Mantadakis E et al. Deep venous thrombosis in children with musculoskeletal infections: the clinical evidence. Int J

Infect Dis. 2012;16(4):e236–e243.

Kaplan SL. Recent lessons for the management of bone and joint infections. J Infect. 2014;68:S51–S56.

Thomsen I, Creech CB. Advances in the diagnosis and management of pediatric osteomyelitis. Curr Infect Dis

Rep. 2011;13(5):451–460.

Dubnov-Raz G et al. Invasive pediatric Kingella kingae infections: a nationwide collaborative study. Pediatr Infect

Dis J. 2010;29(7):639–643.

Liu C et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of

methicillin-resistant Staphylococcus Aureus infections in adults and children. Clin Infect Dis. 2011;52(3):e18–

e55.

Garcia C, McCracken GH. Antibacterial therapeutic agents. In: Feigin RD et al., eds. Textbook of Pediatric

Infectious Diseases. 7th ed. Philadelphia, PA: WB Saunders; 2014:3182.

Landersdorfer CB et al. Penetration of antibacterials into bone: pharmacokinetic, pharmacodynamics and

bioanalytical considerations. Clin Pharmacokinet. 2009;48(2):89–124.

Keren R et al. Comparative effectiveness of intravenous vs oral antibiotics for postdischarge treatment of acute

osteomyelitis in children. JAMA Pediatr. 2015;169(2):120–128.

MajewskiJ et al. Route and length of acute uncomplicated hematogenous osteomyelitis: do we have the answers

yet? Hosp Pediatr. 2014;4(1):44–47.

Howard-Jones AR, Isaacs D. Systematic review of duration and choice of systemic antibiotic therapy for acute

haematogenous bacterial osteomyelitis in children. J Paediatr Child Health. 2013;49(9):760–768.

Lipsky BA et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and

treatment of diabetic foot infections. Clin Infect Dis. 2012;54(12):e132–e173.

Senneville E et al. Needle puncture and transcutaneous bone biopsy cultures are inconsistent in patients with

diabetes and suspected osteomyelitis of the foot [published correction appears in Clin Infect Dis.

2009;49(3):489]. Clin Infect Dis. 2009;48(7):888–893.

Falagas ME et al. Linezolid for the treatment of adults with bone and joint infections. Int J Antimicrob Agents.

2007;29(3):233–239.

Ware JK et al. Chronic osteomyelitis. In: Skeletal Trauma: Basic science, management, and reconstruction. 5th

ed. Philadelphia PA, Saunders; 2015;609–635.

Spellberg B, Lipsky BA. Systemic antibiotic therapy for chronic osteomyelitis in adults. Clin Infect Dis.

2012;54(3):393–407.

Conterno LO, Turchi MD. Antibiotics for treating chronic osteomyelitis in adults (review). Cochrane Database

Syst Rev. 2013;9:CD004439.

Soundrapandian C et al. Drug-eluting implants for osteomyelitis. Crit Rev Ther Drug Carrier Syst.

2007;24(6):493–545.

Zimmerli W, Sendi P. Orthopedic implant-associated infections. In: Bennett JE et al., eds. Mandell, Douglas, and

Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, PA: Elsevier Churchill

Livingstone; 2015:1328.

Osmon DR et al. Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the

Infectious Diseases Society of America. Clin Infect Dis. 2013;56(1):e1–e25.

Lamp KC et al. Clinical experience with daptomycin for the treatment of patients with osteomyelitis. Am J Med.

2007;120(10 Suppl 1):S13–S20.

Forrest GN, Tamura K. Rifampin combination therapy for nonmycobacterial infections. Clin Microbiol Rev.

2010;23(1):14–34.

Perlroth J et al. Adjunctive use of rifampin for the treatment of Staphylococcus aureus infections: a systematic

review of the literature. Arch Intern Med. 2008;168(8):805–819.

Zimmerli W et al. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a

randomized controlled trial. Foreign-Body Infection (FBI) Study Group. JAMA. 1998;279(19):1537–1541.

Tice AD et al. Practice guidelines for outpatient antimicrobial therapy. IDSA guidelines. Clin Infect Dis.

2004;38:1651–1672.

Ohl CA, Forster D. Infectious arthritis of native joints. In: Mandell GL et al., eds. Mandell, Douglas, and

Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, PA: Elsevier Churchill

Livingstone; 2015:1302.

Sharff KA et al. Clinical management of septic arthritis. Curr Rheumatol Rep. 2013;15:332.

Syrogiannopoulos GA, Nelson JD. Duration of antimicrobial therapy for acute suppurative osteoarticular

infections. Lancet. 1988;1(8575–8576):37–40.

Garcia-Arias M et al. Septic arthritis. Best Prac Res Clin Rheumatol. 2011;25:407–421.

Centers for Disease Control and Prevention, Sexually Transmitted Diseases Treatment Guidelines, 2015.

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htm. Accessed December 2, 2015.

Centers for Disease Control and Prevention, Update to CDC’s Sexually Transmitted Diseases Treatment

Guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infrections.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6131a3.htm. Accessed June 15, 2015.

p. 1544

SKIN AND SOFT TISSUE INFECTIONS

Cellulitis (an acute inflammation of the skin and subcutaneous fat) is

characterized by local tenderness, pain, swelling, warmth, and erythema

with or without a definite entry point.

Case 74-1 (Question 1)

Cellulitis is most often caused by group A β-hemolytic streptococci

(Streptococcus pyogenes) and, less often, Staphylococcus aureus.

Case 74-1 (Question 1),

Table 74-1

Community-acquired methicillin-resistant S. aureus (CA-MRSA) may be

a causative pathogen, especially in high-risk patients (children,

competitive athletes, prisoners, soldiers, selected ethnic populations,

Native Americans/Alaska Natives, Pacific Islanders, intravenous drug

users, men who have sex with men), and empiric treatment should have

activity against CA-MRSA.

Case 74-1 (Question 1)

For most cases of cellulitis requiring antibiotics, the least expensive of

dicloxacillin or cephalexin should be chosen. Cases of cellulitis as

evidenced by signs of systemic infection require parenteral antibiotics.

The duration of therapy should be at least 5 days.

Case 74-1 (Questions 1, 4)

Case 74-2 (Question 1)

Conversion to oral antibiotic therapy should be considered when patients

show signs of clinical improvement and are afebrile for at least 24

hours.

Case 74-2 (Questions 3, 4)

Abscesses, furuncles, and carbuncles are commonly caused by S.

aureus and should be managed with incision and drainage. Antibiotic

therapy is warranted when systemic inflammatory response syndrome is

present.

Case 74-3 (Questions 2, 3),

Table 74-1

ERYSIPELAS

Oral or parenteral penicillins, with activity against group A streptococci,

are the drugs of choice for treatment.

Case 74-4 (Question 1),

Table 74-1

SKIN AND SOFT TISSUE INFECTIONS IN DIABETIC

PATIENTS

Skin and soft tissue infections are very common in diabetic patients with Case 74-5 (Question 1)

approximately 25% of patients reporting a history of skin and soft tissue

infection.

Mild infections in diabetics can be treated similar to cellulitis (Grampositive coverage), whereas moderate-to-severe infections require

broad-spectrum coverage.

Case 74-5 (Questions 1, 2)

Table 74-1

NECROTIZING SOFT TISSUE INFECTIONS

Necrotizing soft tissue infections can progress rapidly to cause local

(e.g., necrosis and loss of skin sensation) and severe systemic effects

(e.g., hypotension, shock).

Case 74-6 (Question 1)

Initial treatment of necrotizing soft tissue infections involves extensive

debridement to remove all necrotic tissue, fluid resuscitation, and broadspectrum antibiotics.

Case 74-6 (Question 1),

Table 74-1

p. 1545

p. 1546

ANIMAL BITES

The oral flora of animals (cats, dogs) necessitates irrigation to reduce

risk of infection and may include aerobic or anaerobic organisms.

Amoxicillin/clavulanate is the preferred first-line agent.

Case 74-7 (Questions 1, 2)

Table 74-1

HUMAN BITES

Treating a human bite is similar to any other laceration, including

cleansing, irrigating, exploring, debriding, draining, excising, and suturing,

as required. Human-bite infections can be caused by aerobic and

anaerobic organisms and should be treated with amoxicillin/clavulanate

or ampicillin/sulbactam, or ertapenem.

Case 74-8 (Question 1),

Table 74-1

Skin and soft tissue infections may involve any or all layers of the skin (epidermis,

dermis), subcutaneous fat, fascia, or muscle. Many terms or classifications are used

to describe various skin and soft tissue infections, and these often are based on the

site of infection and causative organism(s).

1 This chapter focuses on skin and soft

tissue infections that are primarily the result of a break in the skin after an abrasion,

skin puncture, ulceration, surgical wound, intentional or unintentional insertion of a

foreign body, or blunt soft tissue contusion. Treatment of skin and soft tissue

infections often is empiric and based on the severity and site of infection, presence of

purulence, the patient’s underlying immunocompetence, and the triggering event (e.g.,

abrasion, bite, insertion of a foreign object) because attempts to isolate the causative

organism often are futile.

SKIN AND SOFT TISSUE INFECTIONS

Cellulitis (an acute inflammation of the skin and subcutaneous fat) is characterized by

local tenderness, pain, swelling, warmth, and erythema with or without a definite

entry point. Cellulitis is usually secondary to trauma or an underlying skin lesion that

allows bacterial penetration into the skin and underlying tissues. Cellulitis is most

often caused by group A β-hemolytic streptococci (Streptococcus pyogenes) and

other streptococcus species (B, C, F, or G), and less often, Staphylococcus aureus

(Table 74-1).

2 However, if the patient presents with abscess, purulence, or

penetrating trauma, coverage of S. aureus is indicated.

2 Coverage for communityacquired methicillin-resistant S. aureus (CA-MRSA) may be warranted because the

incidence has been increasing.

3 Gram-negative organisms (e.g., Escherichia coli,

Pseudomonas aeruginosa, Klebsiella pneumoniae) also can cause cellulitis, but

should be suspected only in immunocompromised patients or in patients who fail to

respond to antibiotics that have activity limited to Gram-positive organisms. Wound

cultures often are negative and fail to identify the causative organism.

Severity of infection is based upon presence of systemic signs of infection, failure

of oral antibiotics, and immunocompetence. Cases of mild cellulitis without signs of

systemic infection often require treatment with antibiotics active against streptococci.

Patients with evidence of a systemic infection, suggesting a moderate-to-severe

infection, will require intravenous [IV] antibiotics, in addition to local wound care.

Severe infections occur in patients who have failed oral antibiotic therapy or those

that are immunocompromised. Antibiotic selection is based on the suspected etiology

as well as severity of infection.

In addition to cellulitis, skin and soft tissue infections include abscesses, furuncles,

and carbuncles. A skin abscess is an infection and results in a collection of pus

within the dermis and deep skin tissues.

2 Furuncles are abscesses that initiate in the

hair follicle and penetrate into the surrounding subcutaneous tissue, whereas

carbuncles are a coalescence of furuncles.

Table 74-1

Potential Organisms Causing Skin and Soft Tissue Infections

Gram Positive Gram Negative Anaerobes

Staphylococcal Streptococcal

Escherichia

coli,

Klebsiella

species,

Proteus

Species

Pasteurella

multocida

Eikenella

corrodens

Oral

Anaerobes

Clostridium

Species

Cellulitis X X

Diabetic

soft tissue

X X X

Necrotizing

infections

X X X X X

Erysipelas X

Animal

bites

X X X X X

Human

bites

X X X X X

X, organisms that should be covered empirically with appropriate antibiotic therapy.

p. 1546

p. 1547

CASE 74-1

QUESTION 1: N.P., a 25-year-old woman, presents to her family doctor with a 2- to 3-day history of

worsening pain, redness, and swelling on her left leg after an abrasion that occurred after falling while jogging in

the park. The area is red, painful, nonpurulent, and warm to the touch. During the past 24 to 36 hours, the leg

has become increasingly painful and “tight.” N.P. denies having fever or chills. The presumptive diagnosis is a

mild cellulitis, and dicloxacillin is prescribed. Why is dicloxacillin appropriate empiric treatment for N.P.?

Oral dicloxacillin is appropriate empiric therapy for cellulitis in an otherwise

healthy individual with no signs or symptoms of systemic infection, regardless of

presence of purulence. Dicloxacillin has predictable activity against streptococcus

and methicillin-sensitive staphylococcus organisms and is better tolerated than

erythromycin or clindamycin. Because the patient presents with nonpurulent

cellulitis, penicillin VK is also an option; however, it lacks coverage against

staphylococcus. If the cellulitis is well demarcated and nonpurulent, penicillin alone

can be appropriate because the causative organism is likely to be Streptococcus.

Many other available antibiotics that have activity against staphylococcus and

streptococcus organisms have been evaluated for effectiveness in skin and soft tissue

infections. A recent review concluded that the available evidence does not allow

specific recommendations for the best antibiotic regimen for cellulitis.

3

,

4 Cephalexin

is probably as effective and as well tolerated as dicloxacillin and is comparable in

cost. However, the Gram-negative activity of cephalexin (not present with

dicloxacillin) is not required for most cases of cellulitis in otherwise healthy

patients. In this case, antibiotic treatment is required, and N.P. can receive

dicloxacillin or cephalexin.

In geographic areas where the incidence of CA-MRSA has become clinically

important (>10% of isolates), particularly with additional risk factors (children,

competitive athletes, prisoners, soldiers, selected ethnic populations, Native

Americans/Alaska Natives, Pacific Islanders, IV drug users, men who have sex with

men), empiric treatment should include antibiotics with activity against CA-MRSA.

5

In cases in which there is an abscess without signs of systemic infection, drainage is

often all that is needed because antibiotic therapy has been shown to be no better than

placebo for uncomplicated skin abscesses in a population at risk for CA-MRSA

infection.

6 At present, most CA-MRSA are still susceptible to trimethoprimsulfamethoxazole, clindamycin, and doxycycline.

2 Although trimethoprimsulfamethoxazole has good activity against S. aureus, its activity against S. pyogenes,

that is group A streptococci, is weak, making this antibiotic undesirable alone as

empiric therapy. If these agents are used, a reasonable suggestion would be to reevaluate (by the patient if they are competent) within 24 to 48 hours to verify that an

improvement is occurring. Some clinicians avoid the use of clindamycin because of

concerns of inducible resistance. In areas with a clinically important incidence of

CA-MRSA, laboratories should test for inducible clindamycin resistance. If N.P. is

from an area of high CA-MRSA prevalence and has associated risk factors, the

combination of trimethoprim-sulfamethoxazole or doxycycline with beta-lactam

(penicillin, cephalexin, amoxicillin) would provide therapy for the anticipated

pathogens. However, even in areas of high CA-MRSA prevalence, some

investigations have found cephalexin to be as effective as therapy specifically

targeted for CA-MRSA, although this has not been supported in all studies.

7–9

If CAMRSA does not require antibacterial coverage, this practice may reduce

antibacterial selection pressure and expense.

10

CASE 74-1, QUESTION 2: What agents could be chosen if N.P. is allergic to penicillin?

Clindamycin could be chosen for patients with a documented history of penicillin

or cephalosporin allergy.

2

In certain geographic areas, group A streptococci

macrolide resistance approaches 15% to 20%, decreasing the potential value of this

agent. Clindamycin is superior to macrolides with respect to group A streptococcal

coverage; however, it causes diarrhea in 20% of patients and is one of the main

agents responsible for antibiotic-associated colitis. Moxifloxacin and levofloxacin

are potential alternatives that have the convenience of once-daily dosing.

CASE 74-1, QUESTION 3: What dose should be prescribed for N.P.?

The recommended dosage of dicloxacillin is 500 mg orally every 6 hours. The

dosage for penicillin V is 250 to 500 mg orally every 6 hours; for oral clindamycin,

the dosage is 300 to 450 mg every 6 hours. Because dicloxacillin is the drug chosen

for N.P., a dosage of 500 mg orally every 6 hours is appropriate. The dose for

doxycycline is 100 mg orally every 12 hours, and the dose for trimethoprimsulfamethoxazole is one to two double-strength tablets orally every 12 hours. The

recommended dose for moxifloxacin is 400 mg orally every 24 hours and 500 mg

orally every 24 hours for levofloxacin.

CASE 74-1, QUESTION 4: What is the appropriate duration of therapy for N.P.?

Although the recommended duration of therapy for cellulitis is 5 days, treatment

may be extended if clinical improvement is not seen.

2 A reasonable recommendation

to the patient would be to continue oral antibiotics for 2 to 3 days after the patient has

become afebrile and has clinically improved. N.P. should be counseled to expect a

response within 1 to 2 days after therapy begins (although erythema may persist

longer). In addition, she should be instructed to return for re-evaluation if the

condition does not improve or worsens during the next few days.

CASE 74-1, QUESTION 5: What further diagnostic evaluation should be undertaken for N.P.?

In otherwise healthy individuals, identification of the causative organism in cases

of mild cellulitis is unnecessary. Needle aspiration, fine-needle aspiration biopsy,

and punch biopsy identify the causative organism in only 20% to 30% of patients.

2

Appropriate empiric treatment is effective in most patients, and an attempt to isolate

the organism does not improve success of treatment and adds significantly to the cost

of care. However, patients with moderate-to-severe purulent infection, patients who

failed initial empiric therapy, immunocompromised patients, patients with potential

joint or tendon damage, or patients with life-threatening infections requiring

hospitalization may benefit from additional cultures. In these cases, a swab of the

primary wound and a needle aspiration or punch biopsy of the leading edge of the

cellulitis should be obtained for Gram stain and culture before initiating

antimicrobial therapy. Blood and wound cultures should be drawn in these patients.

Anaerobic cultures need to be drawn only when the wound contains necrotic tissue,

the wound is foul smelling, or crepitus is present. Even if wound and blood cultures

are obtained, many infections will be culture negative (74%). Blood culture results

are positive in less than 5% of cellulitis cases. Culture information, in conjunction

with clinical course, can be used to modify subsequent treatment. Because N.P. has

only a mild cellulitis, cultures are not required and therapy should be given

empirically. In addition to systemic therapy, N.P. should be instructed to keep the

area clean

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with soap and water (if an open wound is present) and to protect the area.

Treatment of cellulitis should also include rest, immobilization and elevation of the

infected area, and surgical drainage or debridement, as required. The wound should

be assessed daily for local tenderness, pain, erythema, swelling, ulceration, necrosis,

and wound drainage.

CASE 74-1, QUESTION 6: Could topical antibiotics be used to treat N.P.’s cellulitis?

The value of topical antibiotics in treating skin infections is questionable.

11 Most

topical antibiotics have not been evaluated in appropriately designed trials. Although

mupirocin is superior to placebo in treating some types of wound infections, its value

in more severe disease is uncertain. In patients with moderate-to-severe infections,

mupirocin, or any topical antibiotics (neomycin, bacitracin, polymyxin B) should not

be used to replace or augment systemic antibiotics. Topical antibiotics likely do little

but add to the cost of therapy, and they occasionally cause a contact dermatitis.

Therefore, N.P. should not be treated with topical antibiotics because her cellulitis

should be managed adequately by her systemic antimicrobial therapy.

CASE 74-2

QUESTION 1: O.A., a 49-year-old man, presents to the ED with a 3- to 4-day history of increasing pain

around his left hip, secondary to an injury he received falling on the sidewalk. In addition, he has a fever and

feels weak, lethargic, and nauseated. Examination reveals a swollen, warm, and extremely tender hip. O.A. has

a temperature of 39.8°C and appears quite ill. A diagnosis of moderate-to-severe cellulitis is made, and O.A. is

hospitalized because of the severity of the infection. O.A. has no other underlying medical problems. What

empiric antibiotic regimen would be reasonable for O.A.?

In moderate-to-severe ill patients, when hospitalization is required, antibiotics

should be administered parenterally. The parenteral agent of choice is nafcillin or

oxacillin.

2 Cefazolin (1–2 g IV every 8 hours) would be an appropriate alternative if

it is less expensive than nafcillin. Second- and third-generation cephalosporins

(cefuroxime, cefoxitin, ceftriaxone, cefotaxime) and some quinolones may be as

effective as nafcillin, but provide no clinical advantages for most cellulitis. Patients

with risk factors for MRSA (penetrating trauma, history of MRSA, nasal

colonization, IV drug abuse, presence of systemic inflammatory response syndrome)

should be treated with vancomycin or agents with activity against Streptococci and

MRSA. One potential option is linezolid, but is limited by potential for drug

interactions with serotonergic agents. Other agents include daptomycin, telavancin,

dalbavancin, oritavancin, and ceftaroline. Although these agents are as effective in

severe cellulitis, they are not used as commonly as vancomycin because of cost and

formulary availability.

Therefore, O.A. should receive either nafcillin, oxacillin, or cefazolin, whichever

is less expensive and more tolerable for the patient. Once O.A. has become afebrile

and has evidence of clinical improvement, the parenteral antibiotic should be

discontinued and appropriate oral therapy should be initiated to complete at least a

5-day course (or until clinical improvement).

CASE 74-2, QUESTION 2: Two days after starting therapy, O.A. develops a maculopapular skin rash. What

alternative therapy should be chosen?

Regardless of when during the course of therapy a drug rash occurs (early or late),

the precipitant drug should be discontinued because there is a chance, although small,

that the reaction could worsen. In patients who have a penicillin allergy and who still

require parenteral therapy, clindamycin, vancomycin, linezolid, moxifloxacin, or

levofloxacin could be chosen. Because all of these agents are equally effective, the

choice should be based on cost and dosing convenience and presence of risk factors

for MRSA.

CASE 74-2, QUESTION 3: After 48 hours of therapy, culture and sensitivity results are available. What

changes, if any, should be made in O.A.’s treatment?

If cultures show only streptococcus species in a patient who is not allergic to

penicillin, therapy should be deescalated to penicillin because it is effective, well

tolerated, and less expensive than nafcillin. If cultures grow staphylococcus species

(S. aureus) that are sensitive to methicillin/oxacillin, the initial empiric therapy

should be continued. If the organisms are resistant to methicillin/oxacillin, therapy

should be switched to vancomycin 15 mg/kg IV every 12 hours or alternative agent as

previously described. Because O.A. has a presumed penicillin allergy (due to

maculopapular rash) and does not require therapy for MRSA, he should continue

with clindamycin or vancomycin. Cefazolin may also be an option for penicillinallergic patients who do not experience severe allergic reactions, such as urticaria

and anaphylaxis.

CASE 74-2, QUESTION 4: After 72 hours of therapy, O.A. has improved considerably and has been

afebrile for 24 hours. Can he be switched to oral therapy?

Once O.A. has been afebrile for at least 24 hours and is significantly improved, he

can be switched to oral therapy, if tolerated. Clinicians should select the oral agent

on the basis of culture results (if available), anticipated pathogens (if no culture

results), convenience, and cost.

CASE 74-2, QUESTION 5: What is the role of anti-inflammatory agents as adjunctive treatment of cellulitis?

Anti-inflammatory agents, such as nonsteroidal anti-inflammatory agents and

corticosteroids, have been shown to decrease time to resolution of cellulitis when

given in conjunction with antibiotics to patients without diabetes.

2 Although

supporting evidence is weak, a significantly quicker resolution of symptoms in

patients on prednisolone 5 to 30 mg/day has been seen.

2

,

12

,

13

CASE 74-3

QUESTION 1: M.C. is a 22-year-old college football player who presents to the ED with a 3- to 4-day history

of pain in his left thigh. On examination, he has a swollen, erythematous, and purulent 2 × 3 cm abscess in the

inner left thigh. The area is warm and tender to the touch. M.C. is afebrile with no signs of lymphangitis. What

tests are needed to confirm the diagnosis?

In patients with abscesses, large furuncles (superficial skin abscess), and

carbuncles (clusters of furuncles), Gram stain and culture of pus is recommended.

2

Though, typically cases may be adequately treated without further testing. M.C. has

risk factors for CA-MRSA (competitive athlete); if CA-MRSA is identified,

infection control measures should be implemented to prevent outbreak.

14

In febrile

patients, blood cultures should be drawn before antibiotics are started to maximize

the ability to isolate the pathogen.

CASE 74-3, QUESTION 2: Are the suspected organisms similar to those found in other patients with

cellulitis?

Abscess, furuncles, and carbuncles are most commonly caused by staphylococci,

predominately S. aureus.

2

,

6 Abscesses may also be polymicrobial. For patients who

are IV drug abusers and present with abscess or cellulitis, the infecting bacteria are

similar to those found in normal hosts. Intravenous drug use is also a risk factor for

infection with CA-MRSA and should be particularly considered

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if the patient has had recurrent infections or has failed to respond to MSSAdirected antibiotic therapy.

14 Although Staphylococcus epidermidis, Gram-negative

organisms, including P. aeruginosa, and anaerobes are rarely pathogens, they may be

present and should be considered in patients who do not respond to initial therapy.

CASE 74-3, QUESTION 3: What is the appropriate empiric therapy?

Antibiotic therapy is often not required. Incision and drainage should be performed

for all abscesses, large furuncles, and carbuncles.

2 Antibiotics may be considered as

adjunct to incision and drainage when systemic inflammatory response syndrome is

present, but has not been shown to improve cure rates in patients with cutaneous

abscess. Antibiotic therapy should be directed toward CA-MRSA and based on

severity of infection. Mild-to-moderate infection can be adequately treated with

doxycycline or sulfamethoxazole/trimethoprim, whereas more severe disease should

be empirically treated with vancomycin, daptomycin, linezolid, telavancin, or

ceftaroline.

2

,

14

If treatment does not result in some resolution of inflammation within

48 hours, antimicrobial coverage should be expanded to cover Gram-negative

organisms and resistant streptococci.

ERYSIPELAS

Erysipelas is a superficial skin infection caused by streptococci, predominantly

group A, although groups C and G (and group B in children) also may cause the

infection.

15

,

16 This skin infection affects approximately 1 in 1,000 persons/year and is

associated with diabetes mellitus, chronic venous insufficiency, and cardiovascular

disease.

16 Erysipelas is diagnosed based on characteristics of the skin lesion and

concurrent systemic symptoms.

15 The lesion is a continuous, indurated, edematous

area, with a clearly defined raised edge.

16 Early in the course, the lesion is bright

red, but it may turn to brown as the lesion ages or grows. The lesion spreads

peripherally with no islands of unaffected tissue. The initial lesion results from a

small break in the skin that becomes infected, although signs of the initial wound

often are not evident. Aspiration of the lesion or a superficial swab is not

recommended because this has not been shown useful in detecting the pathogen.

15

Patients with erysipelas have associated systemic symptoms of high fever, chills,

frequent history of rigors, and general malaise. This constellation of systemic

symptoms differentiates erysipelas from other local skin disorders.

CASE 74-4

QUESTION 1: D.D., a 70-year-old man, presents to the ED with a red, swollen face. He describes the area

as “a swollen red spot” that has appeared during the past 2 days. He also describes feeling unwell for the

previous 3 days and having a fever. On examination, D.D. has a bright red, shiny, edematous lesion on his right

cheek that is 0.4 cm wide. It is a continuous lesion with a clearly demarcated border. What antibiotic therapy

should be initiated for D.D.?

Erysipelas will respond promptly to antibiotics with activity against group A

streptococci.

17 Oral penicillin V 250 to 500 mg every 6 hours and for severe cases

and parenteral penicillin G (2–4 million units IV every 6 hours) generally reduce the

systemic symptoms (e.g., fever, malaise) within 24 to 48 hours

17

; however, it will

take several more days for the skin lesion to resolve. If D.D.’s condition does not

improve within 72 hours after initiation of antibiotics, he should be instructed to

return for reassessment. If D.D. has an allergy to penicillins, then a macrolide,

clindamycin, or an oral fluoroquinolone, such as moxifloxacin, is an alternative.

15

,

17

Ceftriaxone may also be an alternative in Penicillin allergic patients (without

anaphylaxis) due to low (<1%) cross sensitivity risk. If the community has increased

macrolide resistance to group A streptococci, these agents should not be part of

empiric therapy. Antibiotic therapy should be continued for 10 days even if signs and

symptoms resolve quickly to avoid a relapse, which could lead to chronic infection

or scarring.

SKIN AND SOFT TISSUE INFECTIONS IN

DIABETIC PATIENTS

Skin and soft tissue infections are common in patients with diabetes mellitus.

Approximately 25% of diabetic patients report a history of skin and soft tissue

infections, and 5% to 15% of diabetic patients may undergo limb amputation.

18

In

addition to the cost associated with treating skin and soft tissue infections, functional

disability may occur, which can significantly decrease the patient’s quality of life.

Diabetic patients are at particular risk for foot problems, primarily because of the

neuropathies and peripheral vascular diseases associated with long-standing

diabetes. The decreased pain sensation allows the patient to continue to bear weight

in the presence of skin damage, thereby promoting the formation of an ulcer. In

addition, minor trauma (e.g., cuts, foreign body insertion) can go unnoticed and, when

left untreated, can become infected and extensive. Although these infections are

common, preventive measures should reduce the frequency of amputations. Mild

infections can be treated empirically with those agents used for soft tissue infections

in nondiabetic patients because these are commonly caused by aerobic Grampositive cocci. In moderate-to-severe infections, antibiotic coverage should be

expanded because multiple organisms may be responsible for the infection. Although

it is often difficult to determine colonizers from true pathogens, an average of two to

six organisms are cultured from foot ulcers in patients with diabetes.

19

,

20 The

following organisms (in no particular order) have been isolated in more than 20% of

wounds in patients with diabetes: S. aureus, S. epidermidis, Enterococcus faecalis,

other streptococci, Proteus species, E. coli, Klebsiella species, Peptococcus species,

Peptostreptococcus species, and Bacteroides species.

20 These infections are often

polymicrobic, but treatment can be effective even if not all cultured pathogens are

covered.

19 To determine the pathogens most accurately, a specimen of infected deep

tissue should be obtained after the wound has been cleaned. If this is not possible,

cultures of purulent exudate or curettage should be obtained, versus superficial swab,

to determine the true pathogens in the wound.

18 Although antibiotics have an

important role, drainage and surgical debridement to remove necrotic tissue are

essential and may be the mainstay of treatment.

19 Cultures of the affected areas may

not be useful unless bone is infected. Although anaerobic organisms often are

difficult to culture, they must be considered if an abscess or devitalized, necrotic,

foul-smelling tissue is present or the wound is a result of abdominal surgery.

CASE 74-5

QUESTION 1: T.U. is a 67-year-old man with diabetes presenting to his general practitioner for a routine

checkup and has no specific complaints. T.U. has a 15-year history of poorly controlled type 2 diabetes and a 3-

year history of recurrent foot ulcers. On examination, the physician observes that an ulcer on the underside of

the foot, which had previously healed over, is open and inflamed; purulent fluid can be expressed from the

wound. T.U. reports no pain around the area and was unaware that the ulcer had worsened. He is currently

febrile, and physical examination reveals mild lymphadenopathy and elevated white blood cell count. Does T.U.

have an active infection, and is antibiotic therapy required?

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All open wounds, in diabetic and nondiabetic patients, will become colonized

with bacteria, but only infected wounds should be treated with antibiotic therapy.

19

,

20

Often it is difficult to determine whether an open wound is infected, but signs and

symptoms (e.g., purulent drainage, erythema, pain, and swelling around the area) are

suggestive of infection. Based on his symptoms, T.U. has an infection that requires

treatment.

CASE 74-5, QUESTION 2: What treatment should T.U. receive?

Prior to initiating antibiotic therapy, the presence of a clinically infected wound

must first be confirmed as often diabetic wounds may not be infected and thus do not

require antimicrobial therapy. When determining appropriate antibiotic therapy for

infected wounds, clinicians must consider the severity of infection (mild versus

moderate to severe), whether the patient has risk factors for MRSA or P. aeruginosa

or whether the patient has received any antibiotics within the past month. Mild

diabetic foot infections should not be treated with topical antibiotic preparations

because the evidence of efficacy is limited; the preparations do not allow sufficient

penetration of antibiotic into the tissues; many preparations are detrimental to wound

healing.

21 Mild infections can be treated empirically in a similar way to other soft

tissue infections because these are commonly caused by aerobic Gram-positive

cocci.