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Case 6: Discussion


Staphylococcus aureus is a gram-positive bacteria that grows in grape-like clusters (Figure 1). In the past decade, medical providers in the United States have witnessed an epidemic of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections. These infections have been predominantly caused by the highly virulent infectious strain of S. aureus known as the USA300 clone[1]. Although investigators identified MRSA more than 40 years ago, reports involving the USA300 MRSA clone first surfaced in the year 2000 in the United States and rapidly underwent clonal expansion. Community-acquired MRSA infections have predominantly consisted of skin and soft tissue infections, but other clinical manifestations have included pneumonia, bacteremia, and endocarditis. Among HIV-infected persons, community-acquired skin and soft tissue infections caused by MRSA have become a significant clinical problem[2]. Accordingly, the following discussion will focus on skin and soft tissue infections in HIV-infected individuals.

Epidemiology and Risk Factors

Among HIV-infected persons in the United States, MRSA now causes the majority of community-acquired skin and soft tissueinfections[3,4]. For example, in a study of cultures taken from HIV-infected persons who underwent incision and drainage of a skin abscess, 69 (74%) of 93 cultures grew MRSA[4]. The problem of in HIV-infected persons, MRSA skin and soft tissue infections emerged in most regions during the first half of the 2000 decade, as shown by the 6-fold increass in San Diego, California between 2000 and 2003[2] and the 4-fold increase in Cook County, Illinois[16] between the 2000 to 2003 period and 2004 to 2007 (Figure 2). In addition, available data suggest that HIV-infected individuals have markedly higher rates of MRSA infection than in the general population[5,6]and more than 50% of patients with MRSA skin and soft tissue infections develop a recurrence[7]. Most of the MRSA infections in HIV-infected patients have involved the USA300 clone[8]. In one study, risk factors identified for MRSA infections in HIV-infected persons consisted of male-to-male sexual contact, injection drug use, CD4 count less than 50 cells/mm3, high plasma HIV RNA levels, and non-use of trimethoprim-sulfamethoxazole (Bactrim, Septra)[2]. In a separate case-control study that involved HIV-infected men who have sex with men, investigators identified high-risk sex and drug use, but not immune status, as risk factors for MRSA skin infections[9]. A prospective study examining MRSA nasal colonization in HIV-infected individuals in an out-patient setting found that 15 (10.3%) of 146 were colonized with MRSA; risk factors associated with MRSA colonization included prior staphylococcal infection with either methicillin-sensitive S. aureus (MSSA) or MRSA, lower CD4 count, and no current or recent use of trimethoprim-sulfamethoxazole[10].

Mechanism of Staphylococcal Multi-Drug Resistance

In the past 50 years, S. aureus has evolved to possess an impressive array of resistance tools that provide defenses against multiple antimicrobial agents. In the early antimicrobial era, penicillin had reliable activity in treating S. aureus infections. Penicillin, as well as other beta-lactam antimicrobials (penicillins, cephalosporins, carbapenems, and monobactams), exert their mechanism of action by binding to the bacterial penicillin binding protein (and rendering it ineffective), thereby disrupting the penicillin binding protein's ability to cross-link the peptidoglycan components of the bacterial cell wall (Figure 3Role of Penicillin Binding ProteinBinding of Beta-Lactam to Penicillin Binding ProteinDegradation of Bacterial Cell Wall). In the early 1940's, researchers discovered that S. aureus acquired a plasmid (extra loop of DNA) that contained the blaZ gene; this blaZ gene encodes for beta-lactamase, an enzyme that destroys the penicillin beta-lactam ring (Figure 4). In 1959, the anti-staphylococcal antimicrobial methicillin was introduced as an new agent to treat penicillin-resistant S. aureus[11]. Shortly thereafter, in the early 1960's, investigators identified the first S. aureus strains with methicillin resistance. Staphylococcal methicillin resistance resulted from the acquisition of the mecA gene, which is part of a larger mobile genetic element known as the staphylococcal chromosomal cassette (SCCmec)--a genetic element that integrates into the staphylococcal chromosome. The mecA gene encodes for an altered penicillin binding protein known as penicillin binding protein 2a (Figure 5), which has reduced affinity for methicillin binding and thus confers resistance to methicillin and other similar beta-lactam agents. Although methicillin is no longer used, the term methicillin-resistant Staphylococcus aureus (MRSA) has persisted since methicillin was the most common anti-staphylococcal agent used when this resistance was discovered.

Clinical Findings

Patients with a MRSA skin and soft tissue infection most often present with a localized inflammatory abscess. The skin lesions often begin as a simple pimple or boil, but then typically expand into a larger erythematous, swollen, and painful lesion (Figure 6). The center of the lesion often has a yellow or white color (Figure 7), and usually softens as abscess formation progresses; spontaneous drainage of pus may occur. Some patients present with lesions that have marked induration, erythema, and tenderness, but without a detectable soft abscess The skin lesions can take on a punched-out necrotic look (Figure 8). Skin and soft tissue infections caused by MRSA can occur anywhere on the body, including the penis, scrotum, vulva, perianal region, extremities, and face (Figure 9). One study suggested a predilection for buttock or scrotal abscess formation[6]. Some patients state that they have recently suffered a "spider bite", though few have actually seen a spider. Indeed, this complaint should raise suspicion for a possible MRSA abscess. Among HIV-infected patients with MRSA skin and soft tissue infections, fewer than 10% develop bacteremia[2,3]. The role of MRSA in cellulitis without abscess formation remains unclear, since cultures are rarely obtained in this setting.


In most cases, the initial diagnosis is made on a clinical basis. Most clinicians have becomes familiar with the characteristic clinical appearance of MRSA skin abscesses. Any clinician who performs an incision and drainage of a skin lesion should send the abscess material for culture; the goal is to identify the causative organism, and if S. aureus, to determine the antimicrobial susceptibility. If the clinician is considering using clindamycin to treat the infection, it is important to ensure the laboratory performs a "D zone test" to rule out inducible clindamycin resistance.

Management: Incision and Drainage

When fluctuance is present (a fluid-filled cavity is palpable), incision and drainage should be performed. In the clinic setting, incision and drainage can typically be performed using local anesthesia. (See the instructional article and video Abscess Incision and Drainage[12].) Key principles outlined in this article regarding abscess incision and drainage are as follows[12]:

  • To minimize scar formation, make the incision along the patient's existing skin-tension lines
  • Extend the incision to a length sufficient to adequately drain the abscess; the opening should be large enough to allow insertion of a hemostat and packing material.
  • Obtain a culture from within the abscess.
  • Express additional material remaining from within the abscess that did not spontaneously drain after the incision.
  • Use a curved hemostat to perform blunt dissection to break up loculations and fully open the abscess cavity; the dissection should proceed in a circular direction around the abscess cavity.
  • Irrigate the wound with normal saline until the fluid becomes clear, making sure to use a splash shield during this process.
  • Pack the inside of the wound with a packing strip, but avoid packing the wound too tightly.
  • Clean the skin around the wound and then cover the wound with a sterile dressing.

Some patients initially present with a tense inflammatory lesion that does not contain a softer, fluid-filled region amenable to incision and drainage. On physical examination, it may be difficult to determine whether the skin lesion requires exploratory incision and drainage. If the benefit of incision and drainage is not clear, anesthetize a small region of the skin lesion and attempt to aspirate fluid with a 16- or 18-gauge needle attached to a syringe; obtaining purulent material would suggest proceeding to incision and drainage, whereas a "dry" aspirate indicates that incision and drainage is unlikely to yield a significant amount of purulent material.

Management: General Principles

In January 2011, the Infectious Diseases Society of America (IDSA) published guidelines on the managment of community-acquired skin and soft tissue infection in the current era of MRSA infections[17]. For a simple abscess or boil, incision and drainage is considered the primary treatment and often provides a good clinical response even without antimicrobial therapy. The 2011 IDSA guidelines recommend giving antimicrobial therapy (in addition to incision and drainage) in the following situations: (1) severe disease or multiple sites of infection, (2) rapid progression in the presence of associated cellulitis, (3) presence of signs and symptoms of systemic illness, (4) associated comorbidities or immunosuppression, (5) extremes of age, (6) location of an abscess in a region difficult to perform drainage (e.g face, hand, genital area), (7) presence of associated septic phlebitis, (8) failure to respond to incision and drainage alone[13]. There are insufficient data regarding the benfit of antimicrobial therapy following the incision and drainage of a simple abscess in HIV-infected individuals. For patients with purulent cellulitis (absence of a drainable abscess), empiric antimicirobial therapy should cover MRSA until culture results are known. Patients with a nonpurulent cellulitis (and absence of an abscess) often have infection with a streptococcal species, such as Streptococcus pyogenes (group A streptococcus); since incision and drainage is not an option in nonpurulent cellulitis, antimicrobial therapy is the primary therapy.

Management: Choice of Antimicrobial Therapy

When choosing antimicrobial therapy, clinicians should consider prior results from the same patient as well as local resistance data, if known. Most of the community-acquired MRSA isolates from HIV-infected patients have remained susceptible to trimethoprim-sulfamethoxazole, tetracyclines,and clindamycin, but not to fluoroquinolones or macrolides(Figure 10)[2]. When antimicrobial therapy for MSA is needed, the IDSA guidelines[17] recommended the following options for empiric coverage of MRSA: clindamycin, trimethoprim-sulfamethoxazole, a tetracycline (doxycycline or minocycline), and linezolid (Zyvox) (Figure 11). The empiric use of a fluoroquinolone or macrolide is not recommended. In this author's opinion, clindamycin is less preferable than trimethoprim-sulfamethoxazole or a tetracyline because of the required three times daily dosing, risk of developing Clostridium difficile-associated colitis, and potential for development of inducible clindamycin resistance.  In addition, this author notes that although linezolid is a highly effective agent against MRSA, it is extremely expensive and should be reserved for patients with severe infections or those who have antimicrobial allergies that prohibit them from taking first-line agents. Some clinicians have used rifampin as adjunct therapy in this setting, but the IDSA guidelines recommend against the use of rifampin, either as a single agent or as an adjunct agent for the treatment of a MRSA abscess or cellulitis. If additional coverage for group A streptococus is desired, the best options are to use clindamycin or linezolid alone, or to add a beta-lactam agent, such as amoxicillin (500 mg PO TID), to trimethoprim-sulfamethoxazole or a tetracycline. Oral antimicrobial therapy is usually sufficient in this setting, but patients with severe skin and soft tissue infections may require hospitalization and intravenous therapy; preferred options for intravenous therapy recommended in the IDSA guidelines include vancomycin, linezolid, daptomycin, and telavancin.

Management: Patients with Nonpurulent Cellulitis and no Abscess

In patients who have nonpurulent cellulitis (and no abscess), use of trimethoprim-sulfamethoxazole alone to target MRSA is problematic, since S. pyogenes is a common pathogen and this organism typically responds poorly to trimethoprim-sulfamethoxazole[13]. Thus, in patients who have nonpurulent cellulitis without abscess, the initial regimen should include an agent, such as amoxicillin, amoxicillin-clavulanic acid (Augmentin), dicloxacillin, or cephalexin (Keflex), that has good activity against streptococci. The frequency and role of MRSA in nonpurulent cellulitis remains poorly define; the use of antimicrobials to treat MRSA in this setting is recommended if a patient does not respond to treatment with a beta-lactam alone and initial empiric MRSA treatment should be considered in patients with systemic toxicity. The recommended treatment duration for nonpurulent cellulitis is usually 5 to 10 days.


Studies have identified colonization of MRSA on multiple body sites, most frequently the nares, axillae, and perineum(Figure 12)[14]. In one study from Dallas, 15 (10.3%) of 146 patients had MRSA nasal colonization[10]. Multiple strategies have been attempted to eradicate MRSA colonization, including topical nasal therapy, antiseptic body washes, and oral antimicrobial agents[13]. In a study that involved 76 HIV-infected patients with S. aureus nasal carriage, participants received nasal mupirocin (twice daily for 5 days in the anterior nares) or control. One week after treatment 12% of mupirocin-treated patients had positive nasal S. aureus cultures compared with 92% of placebo-treated patients (P<.001), but in the 10-week post-treatment period most of the mupirocin treated patients became recolonized with the pre-treatment strain of S. aureus(Figure 13)[15]. Although retapamulin (Altabax) has in vitro activity against MRSA, there are insufficient data to recommend its use for decontamination of MRSA. The IDSA guidelines recommend the following options for decontamination: (1) nasal decolonization with mupirocin twice daily x 5 to 10 days,or (2) nasal decolonization with mupirocin twice daily x 5 to 10 days plus topical body decolonization with a skin antispetic solution (e.g. chlorhexidine) for 5 to 14 days or dilute bleach baths (1 teaspoon of bleach per gallon of water or 1/4 cup per 1/4 tub of water) used for 15 minutes twice weakly x 3 months[17]. With the use of body washes, patients should be instructed to scrub in the axillae and perineal region. In general, decontamination strategies do not required the use of systemic antimicrobials, except in the presence of an active infection.

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    Figure 1. Scanning Electron Micrograph of Methicilin-Resistant <em>Staphylococcus aureus</em> (MRSA)

    This colorized scanning electron micrograph shows abundant clumps of MRSA. Magnification 4780x. Photo Credit: Centers for Disease Control and Prevention: Janice Carr and Jeff Hageman. 

    Figure 1
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    Figure 2. Incidence of Community-Acquired MRSA Skin and Soft Tissue Infections Among HIV-Infected Patients
    Source: Popovich KJ, et al. Clin Infect Dis. 2010;50:979-87.

    Figure 2
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    Figure 3: Mechanism of Action of Beta Lactam Antimicrobials. Image 1. Role of Penicillin Binding Protein in the Cross-Linking of Bacterial Cell Wall Subunits

    Figure 3
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    Figure 4. Inactivation of Beta-Lactam Antimicrobial by Beta-Lactamase

    Figure 4
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    Figure 5. Title
    Note: the altered penicillin binding protein (PBP2a) resists binding of beta-lactam antimicrobial, but maintains function of cross-lining bacterial cell wall components. Abbreviations: PBP = penicillin binding protein; SCC = staphylococcal chromosomal cassette

    Figure 5
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    Figure 6. MRSA Abscess and Surrounding Cellulitis in Right Arm of Patient with HIV Infection
    Image courtesy of Dr. Timothy Dellit.

    Figure 6
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    Figure 7. MRSA Abscess in Pubic Region (with Central Pustule) in HIV-Infected Patient

    Figure 7
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    Figure 8. MRSA Soft Tissue Infection of Left Hand in HIV-Infected Patient

    Figure 8
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    Figure 9. MRSA Soft Tissue Infection in Region Above Left Eye in HIV-Infected Patient

    Figure 9
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    Figure 10. Antibiotic Resistance in <em>Staphylococcus aureus</em>-Containing Cutaneous abscesses of Patients with HIV

    Source: Krucke GW, et al. Am J Emerg Med. 2009;27:344-7

    Figure 10
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    Figure 11. Antimicrobial Therapy for MRSA Skin and Soft Tissue Infections

    Figure 11
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    Figure 12. Body Sites for MRSA Colonization

    Figure 12
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    Figure 13. Efficacy of Mupirocin in Nasal Decolonization of MRSA
    Source: Martin JN, et al. J Infect Dis. 1999;180:860-9.

    Figure 13