Ebook Cases in medical microbiology and infectious diseases Part 2

SECTION
FOUR

SKIN AND SOFT
TISSUE INFECTIONS

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256 Skin and Soft Tissue Infections

I N T ROD UC T I O N T O S E C T I ON IV
The resistance of skin to infection is due to the integrity of the keratinized skin, the presence of inhibitory fatty acids produced by sebaceous glands, the dryness of the skin, and
the inhibitory effect of the resident normal skin microbiota. Skin and soft tissue infections
can be caused by either direct penetration of a pathogen through the skin or hematogenous spread of the pathogen to the site. The normal skin microbiota includes organisms
that may cause infection in the setting of a disruption in the integrity of the skin (such as
the presence of a surgical suture or an insect bite). In the setting of severe damage to the
skin, as occurs with burns, even normally innocuous organisms, including endogenous
bacteria, can cause severe disease. Similarly, when the skin is no longer dry, as may occur
in moist intertriginous spaces or when occlusive dressings are present, the patient is at
increased risk of infection.
Cutaneous manifestations of systemic disease are common. Rocky Mountain spotted
fever, meningococcemia, enteroviral infection, and toxic shock syndrome can all present
with fever and a diffuse erythematous macular rash. Other systemic infections that can
present with a diffuse rash include scarlet fever, measles, and German measles. The characteristic rash of Lyme disease, erythema migrans, is specific enough to establish the
diagnosis. The nature of the lesion (macular, papular, vesicular, pustular, or bullous) may
help to narrow the differential diagnosis. For example, varicella-zoster virus infection
typically results in vesicular skin lesions. The rash of secondary syphilis, on the other hand,
may present clinically as macular, papular, maculopapular, or pustular skin lesions but does

not present as a vesicular rash.
Skin and soft tissue infections can be classified on the basis of the anatomic level at
which infection occurs. The more superficial infections, such as folliculitis caused by
Staphylococcus aureus or cellulitis caused by Streptococcus pyogenes, are important to treat at
an early stage. Delay in treatment may result in invasion of the deeper structures, as in
necrotizing fasciitis, which has a high mortality rate.
Damage to the skin and soft tissues, as occurs in traumatic injuries, may allow the
entry into the wound of soil organisms such as Clostridium perfringens, an anaerobic,
Gram-positive rod. Under favorable conditions, potentially fatal soft tissue infections
(myositis, gas gangrene) may occur.
New technologies such as 16S rRNA gene sequencing and matrix-assisted laser
desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) allow us to
identify to the species level Gram-positive bacilli recovered from soft tissue infections.
Rapidly growing mycobacteria including Mycobacterium abscessus, Mycobacterium chelonae,
and Mycobacterium fortuitum have been found to cause infection secondary to cosmetic
surgery and pedicures. Other environmental mycobacteria such as Mycobacterium marinum
have been associated with soft tissue infection following traumatic injury involving water
exposure. Cornyebacterium kroppenstedtii has been associated with mastitis. Three species of
Actinomyces—A. neuii, A. radingae, and A. turicensis—are now recognized to cause skin and
soft tissue infections. These three organisms are also indigenous flora on skin, so the find-

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Skin and Soft Tissue Infections 257

ing of these organisms in clinical specimens should be accompanied by evidence of inflammation such as the presence of white blood cells on direct Gram stain of the patient’s
specimen.
Important agents of skin and soft tissue infection are listed in Table 4. The presence
of ectoparasites, such as lice and bedbugs, is not designated an infection but rather an
infestation. Ectoparasites are, however, included for completeness.
TABLE IV  ​S ELECTED SKIN AND SOFT TISSUE PATHOGENS
GENERAL
CHARACTERISTICS

SOURCE OF INFECTION

DISEASE MANIFESTATION

Actinomyces neuii

Short, Gram-positive
bacillus

Endogenous (skin
flora)

Cellulitis, skin abscess,
superficial wound
infections

Actinomyces radingae

Short, Gram-positive
bacillus

Endogenous (skin
flora)

Cellulitis, skin abscess,
superficial wound
infections

Actinomyces turicensis

Short, Gram-positive
bacillus

Endogenous (skin
flora)

Cellulitis, skin abscess,
superficial wound
infections

Bacillus anthracis

Spore-forming, aerobic, Exogenous; livestock
Gram-positive bacillus
or animal products;
bioterrorism agent

Cutaneous, gastrointestinal,
and inhalation anthrax;
meningitis; bacteremia

Bartonella henselae

Fastidious, Gramnegative bacillus

Exogenous; cats
appear to be primary
host

Cat scratch disease,
bacillary angiomatosis (in
immunocompromised
individuals)

Borrelia burgdorferi

Spirochete

Tick-borne

Lyme disease; rash,
arthritis, nervous system
and cardiac manifestations

Clostridium
perfringens

Anaerobic, Grampositive bacillus

Exogenous (wounds);
endogenous (bowel

flora)

Gas gangrene, bacteremia,
food poisoning,
emphysematous
cholecystitis

Clostridium tetani

Anaerobic, Grampositive bacillus

Exogenous (wounds)

Tetanus

Corynebacterium
diphtheriae

Aerobic, Gram-positive
bacillus

Exogenous

Diphtheria (pharyngeal)
and wound diphtheria

Corynebacterium
kroppenstedtii

Aerobic, Gram-positive

bacillus

Endogenous (skin
flora)

Mastitis, breast abscess

Group A
streptococci
(Streptococcus
pyogenes)

Catalase-negative,
Gram-positive cocci

Endogenous;
exogenous

Cellulitis, bacteremia,
scarlet fever, necrotizing
fasciitis, pharyngitis,
pneumonia, rheumatic
fever, poststreptococcal
glomerulonephritis

ORGANISM

Bacteria

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258 Skin and Soft Tissue Infections

TABLE IV  ​S ELECTED SKIN AND SOFT TISSUE PATHOGENS (continued)
ORGANISM

GENERAL
CHARACTERISTICS

SOURCE OF INFECTION

DISEASE MANIFESTATION

Group B
streptococci
(Streptococcus
agalactiae)

Catalase-negative,
Gram-positive cocci

Endogenous

Cellulitis, sepsis,
meningitis, UTIa

(diabetics)

Mycobacterium
abscessus

Acid-fast bacillus,
environmental

Exogenous (water)

Surgical wounds, chronic
lung infections in cystic
fibrosis patients, linerelated sepsis

Mycobacterium
chelonae

Acid-fast bacillus,
environmental

Exogenous (water)

Surgical wounds, linerelated sepsis, post-LASIK
keratitis

Mycobacterium
fortuitum

Acid-fast bacillus,
environmental

Exogenous (water)

Surgical wounds; linerelated sepsis; traumatic,
chronic wounds

Mycobacterium
marinum

Acid-fast bacillus,
environmental

Exogenous (fresh,
brackish, and salt
water)

Traumatic wounds, septic
arthritis, cellulitis

Neisseria gonorrhoeae

Oxidase-positive,
Gram-negative
diplococcus

Direct sexual contact;
vertical, mother to
child

Genital tract involvement,

pharyngeal infection,
ocular infection,
bacteremia, arthritis with
dermatitis

Neisseria meningitidis

Oxidase-positive,
Gram-negative
diplococcus

Endogenous (from
colonization)

Meningitis, bacteremia,
pneumonia

Pasteurella multocida

Oxidase-positive,
Gram-negative bacillus

Zoonosis (often
animal bite or scratch)

Cellulitis, bacteremia,
osteomyelitis, meningitis,
pneumonia

Pseudomonas

aeruginosa

Lactose-nonfermenting, Exogenous
oxidase-positive, Gramnegative bacillus

Skin infections in burn
patients, community and
health care-associated UTI,
health care-associated
pneumonia, health careassociated bacteremia,
ecthyma gangrenosum

Staphylococcus aureus

Catalase-positive,
coagulase-positive,
Gram-positive coccus

Endogenous

Cellulitis, bacteremia,
endocarditis, septic
arthritis, abscesses,
pneumonia

Treponema pallidum

Spirochete (does not
Gram stain)

Direct sexual contact;
vertical, mother to
child

Primary (painless chancre),
secondary (diffuse rash),
latent, and late syphilis; can
affect any organ

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Skin and Soft Tissue Infections 259



TABLE IV  ​S ELECTED SKIN AND SOFT TISSUE PATHOGENS (continued)
GENERAL
CHARACTERISTICS

SOURCE OF INFECTION

DISEASE MANIFESTATION

Blastomyces
dermatitidis

Dimorphic mold

Exogenous

Cutaneous infection,
pneumonia, meningitis,
bone infection

Candida albicans

Yeast, often germ tube
positive

Endogenous

Thrush, vaginal yeast
infection, diaper rash,
esophagitis, health careassociated UTI, health
care-associated
bloodstream infection

Candida spp., nonalbicans

Yeasts, germ tube
negative

Endogenous

Thrush, vaginal yeast
infection, health careassociated UTI, health
care-associated

bloodstream infection

Cryptococcus
neoformans

Encapsulated yeast

Exogenous
(environmental, rarely
zoonotic)

Meningitis, pneumonia,
bloodstream infection,
cellulitis

Epidermophyton
floccosum

KOH-positive skin
lesions; club-shaped
macroconidia, absent
microconidia

Anthropophilic

Dermatophyte infection of
keratinized tissue (rarely
nails)

Microsporum spp.

KOH-positive skin
lesions; fluoresce
yellow-green under
Wood’s light

May be zoophilic (e.g., Dermatophyte infection of
keratinized tissue (rarely
M. canis), geophilic
nails)
(e.g., M. gypseum), or
anthropophilic (e.g.,
M. audouinii)

Trichophyton spp.

KOH-positive skin
lesions

May be zoophilic (e.g., Dermatophyte infection of
keratinized tissue
T. mentagrophytes) or
anthropophilic (e.g., T. (including nails)
schoenleinii)

Ancylostoma
braziliense

Hookworm of dog

Exogenous

Cutaneous larva migrans

Ancylostoma caninum

Hookworm of dog

Exogenous

Cutaneous larva migrans

Cimex lectularius

Ectoparasite

Exogenous

Bedbug; itching skin
lesions

Leishmania tropica,
Leishmania
braziliensis

Protozoans

Exogenous (sand fly)

Ulcerative skin lesions

Pediculus spp.

Ectoparasites

Exogenous

Body lice

Phthirus pubis

Ectoparasite

Exogenous

Crab louse

ORGANISM

Fungi

Parasites

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260 Skin and Soft Tissue Infections

TABLE IV  ​S ELECTED SKIN AND SOFT TISSUE PATHOGENS (continued)
ORGANISM

GENERAL
CHARACTERISTICS

Sarcoptes scabiei

SOURCE OF INFECTION

DISEASE MANIFESTATION

Ectoparasite

Exogenous; zoonotic
varieties less common
than human varieties

Scabies infestation

Nonenveloped, ssRNAb

Usually fecal-oral

Aseptic meningitis, rash,
myocarditis

Herpes simplex virus Enveloped, dsDNAc

1 and 2

Person to person;
reactivation of latent
infection; during
passage of the neonate
through the birth
canal

Genital ulcers; oral, ocular
infections; encephalitis;
neonatal infection;
esophagitis
(immunocompromised
individuals)

HIV

Enveloped RNA
retrovirus

Blood-borne and
sexual transmission;
vertical, mother to
child

AIDS, mononucleosis-like
syndrome with rash in
primary infection

Human herpesvirus
6

Enveloped, dsDNA

Person to person

Exanthema subitum
(roseola)

Rubella virus
(German measles)

Enveloped, ssRNA

Vertical, mother to
child

Inapparent or subclinical
infection in adults; birth
defects in infants

Rubeola virus
(measles)

Enveloped, ssRNA

Respiratory spread

Measles, pneumonia,

encephalomyelitis, subacute
sclerosing panencephalitis

Papillomavirus

Nonenveloped, dsDNA

Person to person

Warts

Varicella-zoster virus Enveloped, dsDNA

Respiratory spread

Chicken pox; zoster (may
disseminate)

Variola virus

Person to person,
respiratory spread;
bioterrorism agent

Smallpox; vesicular,
pustular, hemorrhagic rash

Viruses
Enteroviruses

Enveloped, dsDNA

a

 UTI, urinary tract infection.

b

 ssRNA, single-stranded RNA.

c

 dsDNA, double-stranded DNA.

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261

CASE

The patient was a 45-year-old male who was in his usual state
of good health when he awoke at 3 a.m. with pain in the lateral
aspect of his left calf. He looked at his calf and thought that the
pain was due to an ingrown hair and went back to sleep. At 10
a.m., he expressed a small amount of pus from the ingrown hair.
Over the next 8 hours, the patient developed an area of cellulitis on the lateral
aspect of the calf of approximately 5 by 10 cm. At that time, a small amount of pus

was again expressed from the area of the ingrown hair. The next morning, the area
of cellulitis extended from just below the knee to just above the ankle. The patient
visited his physician. His vital signs at that visit, including pulse, respirations,
blood pressure, and temperature, were all within normal limits. Physical exam was
significant for an area of cellulitis as described that was red and warm to the touch
but with no area of obvious fluctuance. No lymphadenopathy was observed. The
central area of the cellulitis, near the area that the patient described as where the
ingrown hair had been, was punctured three times with a 20-gauge needle but no
pus was drained. The patient was referred to the surgery service. The surgeons
examined the patient and said they would follow him. The patient was given 2 g
of ceftriaxone intramuscularly and begun on oral cephalexin.
The patient returned to the surgical clinic 48 hours later with an obvious area of
fluctuance in the center of the area of cellulitis. Over the preceding 48 hours, the
patient reported low-grade fevers. Approximately 1 ml of pus was aspirated and was
sent for Gram stain and culture (Fig.
36.1 and 36.2). When pus was aspirated
from the lesion, the surgeon decided to
excise and drain the lesion (Fig. 36.3).

36

1. Describe what you observed in
Fig. 36.1 and 36.2. The organism is catalase and coagulase
positive. What organism was
causing his infection?

2. Why were incision and drain-

Figure 36.1

age necessary to treat this
infection? Why would antimicrobial agents alone not be
effective in treatment of this
infection?

3. Susceptibility results for this
organism are seen in Fig. 36.4.
How do you interpret these
susceptibility results? Explain

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Figure 36.2

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262

Skin and Soft Tissue Infections

the likely reasons for the results seen with drugs 2 and 4. How do results
of the testing of drug 2 explain the progression of his infection despite a
large intramuscular dose of ceftriaxone followed by oral cephalexin?
Also explain the findings for drugs 7 and 8. How should the isolate
infecting this patient be treated?

4. What test is being used to test vancomycin (drug 5)? Why is this test
being used and what does it show?

5. What virulence factor is particularly associated with skin and soft tissue
infections (SSTIs)? Explain its mechanism of action. This virulence factor and this type of antibiogram are associated with a particular strain of
this organism. Briefly discuss the evolving epidemiology of this strain.

6 What infection control precautions would be necessary for this patient?
What are some of the potential unintended consequences of hospitalized patients who are colonized with this organism?

7. Why are these organisms viewed as a global threat?

Figure 36.3

Figure 36.4 Disk diffusion susceptibility test of patient’s isolate.

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Case 36 263

CASE DISCUSSION

CASE

1. The finding of Gram-positive cocci in clusters on Gram stain is

36

consistent with staphylococci. The finding of a yellowish colony that is
beta-hemolytic on 5% sheep blood agar is consistent with Staphylococcus

aureus. The staphylococci are divided into two groups based on the biochemical test
called the coagulase test; S. aureus is positive, while a group of >30 other staphylococcal
species are negative. This group of organisms is referred to as the coagulase-negative
staphylococci (CoNS). Three of the CoNS species are frequently encountered clinically. Staphylococcus epidermidis can infect implanted foreign bodies, such as pacemakers, cerebrospinal fluid shunts used to treat hydrocephalus, intravascular catheters,
and artificial joints. Staphylococcus lugdunensis has been associated with skin and soft
tissue infections (SSTIs) as well as native valve endocarditis. Although S. lugdunensis
can cause SSTIs, it is less common than S. aureus. The other frequently encountered
CoNS species is Staphylococcus saprophyticus, which causes urinary infections primarily
in young, sexually active women. The isolate recovered from this patient was coagulase positive and was identified as S. aureus.
The patient’s infection began as a folliculitis at the site of the ingrown hair, progressed to a cellulitis, and ultimately evolved into an abscess. Approximately 20% of
adults are chronic nasal carriers of S. aureus, while an additional 60% may carry the
organism intermittently. From the nose, the skin can become colonized. Studies have
shown intermittent skin carriage rates as high as 40%, although most studies target the
skin carriage rate at 10 to 15%. In all likelihood this individual’s initial folliculitis was a
result of the infecting S. aureus coming from skin colonization. Manipulation of the skin
resulted in the spread of the organism to the dermis, leading to cellulitis and abscess
formation.

2. The standard of care for an abscess is 2-fold: incision and drainage (Fig. 36.3) and
antimicrobial therapy. The reason why antibiotics alone would not be sufficient is that
abscess formation results in a loss of blood flow to the center of the infected area (the
abscess). As a result, antibiotic levels in the center of the abscess would be low or, in a
large abscess, completely absent, allowing the survival of the infecting organisms present there. Incision and drainage removes a large number of organisms and reduces the
infected area, making penetration of much higher levels of antimicrobial agents to the
infected tissue and killing of the infecting organism more likely.

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264 Skin and Soft Tissue Infections

3.  The susceptibility test that was performed on this patient is a disk diffusion test for
seven drugs and an E-test for one drug. The basis for disk diffusion susceptibility testing
is described in the introductory chapter of this text, and the reader is referred there for
further details. The antibiogram for this organism is as follows:
Drug 1: trimethoprim-sulfamethoxazole, to which the organism is susceptible
Drug 2: cefoxitin, to which the organism is resistant
Drug 3: doxycycline, to which the organism is susceptible
Drug 4: penicillin G, to which the organism is resistant
Drug 5: vancomycin with an MIC of 2 μg/ml by E-test (see answer 3 for more details)
Drug 6: gentamicin, to which the organism is susceptible
Drug 7: clindamycin, to which the organism is susceptible
Drug 8: erythromycin, to which the organism is resistant
This S. aureus strain is expressing two different resistance mechanisms against the β-lactam
drugs. One is evidenced by its resistance to penicillin G. This resistance is due to the
organism’s ability to produce an enzyme, β-lactamase, that degrades the β-lactam ring of
penicillin G, rendering this and the related widely used antimicrobials ampicillin,
amoxicillin, and piperacillin inactive. Approximately 90 to 95% of S. aureus strains
produce a β-lactamase that is encoded on the bacterial chromosome. Almost as soon
as penicillin G was put into widespread therapeutic use, recognition of S. aureus
strains resistant to penicillin G by virtue of β-lactamase production emerged. New
agents including penicillinase-stable penicillins (oxacillin, nafcillin, and the oral agent
dicloxacillin); first-, second-, and third-generation cephalosporins; and carbapenems were
developed over the following decades. A characteristic all these drugs shared was that they
were relatively stable in the presence of β-lactamase-producing S. aureus. However, a second resistance mechanism to β-lactam drugs soon emerged. The presence of this resistance is predicted by the cefoxitin result. Although cefoxitin is not a drug that is used to
treat S. aureus infections, S. aureus strains expressing cefoxitin resistance predictably have
alteration of a specific penicillin-binding protein, PBP2. The altered penicillin-binding
protein, PBP2a, is encoded by mecA. All β-lactam antimicrobials have significantly reduced

affinity for PBP2a relative to PBP2. This altered affinity is the basis for what we call methicillin resistance in S. aureus. This term is obviously a bit of a misnomer since this PBP
alteration confers resistance to all β-lactam drugs, just not methicillin. The reason the
term “methicillin-resistant S. aureus,” or MRSA, became widespread is that methicillin
was the drug used to treat serious S. aureus infections when this resistance was first
encountered. It is critical to remember that no β-lactam antimicrobial has clinical efficacy
against MRSA with the exception of a newly developed cephalosporin, ceftaroline,
although some β-lactams may appear to have activity against S. aureus in vitro.
The only other antimicrobial to which this isolate is resistant is erythromycin. If the
placements of the clindamycin (disk 7) and erythromycin (disk 8) disks are closely examined, it should be noted that they are closer together than the other disks in order to
determine whether there is formation of a D-shaped zone of inhibition around the clin-

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Case 36 265

damycin. The D-zone occurs when erythromycin induces the production of an rRNA
methylase encoded by the erm gene. Expression of this methylase can be either constitutive (always on) or inducible (on only in the presence of an inducer such as erythromycin).
erm-specific methylation of the rRNA results in both erythromycin and clindamycin
resistance. The D-zone test is assessing whether the inducible form of erm is present. The
bacteria growing closest to the erythromycin disk are in the presence of an inducer, and
therefore will be resistant to clindamycin; this resistance causes a “flattening” of the zone
of inhibition in the area between the two disks, creating a characteristic D-shaped zone
around the clindamycin disk (Fig. 36.3). If the constitutive form of erm was present, the
organism would test as resistant to clindamycin independent of the presence of erythromycin. Clinical failures of clindamycin therapy for infections due to S. aureus strains with
inducible erm genes are well documented in the literature. Mild SSTIs can be treated with

oral antimicrobials. Because his isolate was resistant by virtue of altered PBPs to both of
the drugs he was given initially, ceftriaxone and cephalexin (an oral cephalosporin), this
patient next was given oral clindamycin. Some studies suggest that incision and drainage
is all that is necessary to clear the infection, but the physician was being cautious.

4.  Vancomycin is a key drug in treating MRSA infections, particularly severe ones as
seen in this patient. Vancomycin (drug 5) is being tested using a special antimicrobialimpregnated strip called an E-test. The strip is designed to release a gradient of a specific
antimicrobial agent into the agar. The point where the elliptical zone of bacterial growth
inhibition (thus the name “E-test”) meets the strip determines the MIC of the antimicrobial for the organism being tested. The vancomycin MIC is 2 μg/ml, which is at the upper
level of susceptibility for this organism. Strains with vancomycin MICs of 4 or 8 μg/ml are
referred to as vancomycin-intermediate S. aureus, or VISA, and are more likely to result
in treatment failures. VISA strains are not reliably detected by disk diffusion techniques;
thus the need for a MIC technique. The reduced susceptibility of VISA isolates is due to
a thickening of the cell wall, resulting in “trapping” of vancomycin, a large, highly charged
molecule. VISA strains should not be confused with vancomycin-resistant S. aureus, or
VRSA. VRSA strains are still quite rare worldwide. Their resistance is due to the acquisition of the vanA gene from Enterococcus faecium. VRSA strains have high-level vancomycin
resistance (MICs of 16 to ≥128 μg/ml).

5.  Panton-Valentine leukocidin is a virulence factor that is specifically associated with
SSTIs. It is a cytolytic pore-forming hexameric protein that can lyse a variety of cell types.
It has particular affinity for polymorphonuclear cells and macrophages (thus the name
“leukocidin”). With increasing frequency, S. aureus strains with a specific molecular signature have been documented to be responsible for significant SSTIs causing individuals to
seek care in emergency departments. These strains are called community-associated MRSA,
or CA-MRSA. CA-MRSA strains carry the lukS-PV and lukF-PV genes encoding PantonValentin leukocidin and a small staphylococcal chromosomal cassette (SCCmec type IV) that
harbors mecA. Among CA-MRSA isolates, a specific pulsed-field gel electrophoresis pattern

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266 Skin and Soft Tissue Infections

called USA300 predominates. Infections with this strain have attracted significant attention in the popular media because of outbreaks among a variety of athletic teams, day care
centers, schools, and military units. More ominously, severe cases of pneumonia are being
documented with increasing frequency. Cases of CA-MRSA necrotizing pneumonia have
significant morbidity and mortality. One of the interesting things about CA-MRSA is that
it remains susceptible to a variety of oral agents, in this case, clindamycin, doxycycline, and
trimethoprim-sulfamethoxazole. This is in stark contrast to another group of MRSA
strains that are classified as health care-associated MRSA, or HA-MRSA. Typically
acquired in a health care setting, these strains are often resistant to oral agents and aminoglycosides, making vancomycin the primary therapeutic option, while three newer
agents, daptomycin, linezolid, and ceftaroline, are important second-line drugs. For
HA-MRSA, linezolid is often the only susceptible oral drug, and it is poorly tolerated and
expensive. Thus, serious HA-MRSA infections are almost always treated with intravenous
vancomycin. Because of its oto- and nephrotoxicity, vancomycin is complicated to give,
since drug levels must be monitored to ensure that toxic levels are not accumulating.

6.  MRSA, vancomycin-resistant enterococci, and Clostridium difficile are the most important bacterial causes of health care-associated infections. Patients who are colonized with
MRSA are more likely to develop serious HA-MRSA infections, including postoperative
wound infections, central venous catheter-related bacteremia, and ventilator-associated
pneumonia. They may also spread MRSA to other patients directly or via common caregivers. A number of strategies have been advocated for preventing HA-MRSA infections, although evidence to support some of them is often contradictory. Strict adherence
to hand washing is essential in preventing the spread of all health care-associated pathogens. Isolation and contact precautions for patients colonized or infected with MRSA is
standard practice. Contact precautions include wearing gloves and gowns when entering
the rooms of MRSA-colonized or -infected patients. Proper disposal of gloves and
gowns coupled with hand hygiene is essential. One of the areas of controversy in the
prevention of HA-MRSA infections is who should be screened for MRSA carriage and
what laboratory method should be used for screening. This discussion is quite complex
and is in a state of flux, so we will not attempt to cover it here. However, patients who
are in isolation and on contact precautions often do not get the same level of care as
patients who are not. This translates into fewer visits from health care providers, missed

medicine doses, fewer assessments of vital signs, increased risks of falls, and not surprisingly, poorer satisfaction with health care. Additionally, patients who are admitted from
long-term health care facilities may get “stuck” in the hospital if they are colonized with
MRSA or vancomycin-resistant enterococci because a particular facility may not accept
individuals with these multidrug-resistant infections.
Another issue of note is decolonization of MRSA-colonized individuals. Decolonization
is done by applying a topical antimicrobial, mupirocin, to the nares to eliminate nasal
carriage and bathing in either dilute solutions of chlorhexidine or bleach to decrease skin
colonization, including inguinal sites.

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Case 36 267

In the community, CA-MRSA has been associated with a variety of sports activities.
Most of the evidence to date suggests that this organism is spread from person to person
either by direct contact (as in the case of football players, wrestlers, and fencers) or via
fomites such as by sharing towels with colonized/infected individuals or by contact with
training equipment that has been previously used by CA-MRSA carriers. Strict attention
to personal hygiene, including good hand-washing practices, not sharing towels, and wiping down exercise equipment with disinfectant following use, could help reduce these
infections.

7. CA-MRSA is now recognized as an important emerging human pathogen. A recent
report in JAMA indicates that in the United States, MRSA is a more important cause of
mortality than HIV. CA-MRSA has made a significant contribution to this mortality, and
its importance as a human pathogen appears to be increasing. This strain’s predilection to

cause serious pulmonary infections made this organism of particular concern because it
was feared that secondary bacterial superinfection due to CA-MRSA would greatly
increase morbidity and mortality during any future influenza pandemic. CA-MRSA was
found to be widespread in the United States by the early 2000s. Importantly, there is currently no evidence to suggest that increased numbers of secondary CA-MRSA pneumonia
occurred during the influenza A/H1N1 pandemic of 2009 to 2011.

REFE R E N C E S
1. Daum RS. 2007. Clinical practice. Skin and soft-tissue infections caused by methicillinresistant Staphylococcus aureus. N Engl J Med 357:380–390.
2. Deresinski S. 2012. Methicillin-resistant Staphylococcus aureus and vancomycin: minimum
inhibitory concentration matters. Clin Infect Dis 54:772–774.
3. Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH,
Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK,
Carey RB, Fridkin SK; Active Bacterial Core surveillance (ABCs) MRSA Investigators.
2007. Invasive methicillin-resistant Staphylococcus aureus infections in the United States.
JAMA 298:1763–1771.
4. Platt R. Time for a culture change? N Engl J Med 364:1464–1465.
5. Smith TL, Pearson ML, Wilcox KR, Cruz C, Lancaster MV, Robinson-Dunn B,
Tenover FC, Zervos MJ, Band JD, White E, Jarvis WR; Glycopeptide-Intermediate
Staphylococcus aureus Working Group. 1999. Emergence of vancomycin resistance in
Staphylococcus aureus. N Engl J Med 340:493–501.

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268

CASE

This 65-year-old woman was bitten by her cat on the dorsal
aspect of the right middle finger at 8:00 a.m. She rinsed the bite
with water, and at 4:30 p.m. she noted pain and swelling in the
finger and the dorsum of the right hand. She then noted pain in
the axilla, red streaking up the forearm, and chills. On examination
she had a temperature of 38°C and her right upper extremity was notable for
swelling, erythema, warmth, and tenderness on the dorsum of the hand. Two small
puncture wounds were seen on the proximal phalanx of the long finger, and erythema was visible over the extensor surface of the forearm. Axillary tenderness was
also noted. Laboratory studies demonstrated an elevated white blood cell count of
12,000/μl with a left shift (the presence of immature neutrophils in the peripheral
blood). Aspiration of an abscess on her finger was sent for culture, and the patient
was taken to the operating room for incision and drainage of the abscess. A Gram
stain of the organism causing this woman’s infection is seen in Fig. 37.1, and Fig.
37.2 shows cultures on sheep blood and chocolate agars. The organism failed to
grow on MacConkey agar, and spot tests from the blood agar plate were oxidase
and spot indole positive.

37

1. Which organism was isolated on culture of the abscess? If this had been
a human bite, what organisms might cause an infection?

2. What is the reservoir of this organism? How do humans most commonly become infected by this organism?

3. How can infection with this organism be prevented?
4. What other clinical syndromes can be caused by this organism?
5. If this patient had been scratched by a young cat rather than bitten and
had subsequently developed regional lymphadenitis, what would be the
likely organism?

Figure 37.1

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Case 37

269

6. Domestic animals such as cats and dogs are vaccinated against what
pathogen in order to protect humans? When should humans be vaccinated against this pathogen?

Figure 37.2

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270 Skin and Soft Tissue Infections

CASE

CASE DISCUSSION

37

1. Two organisms associated with domestic animal bites that are oxidasepositive, Gram-negative bacilli and fail to grow on MacConkey agar are

Pasteurella multocida and Capnocytophaga canimorsus. The organism that was
isolated from this patient’s abscess was P. multocida. P. multocida can be differentiated from
C. canimorsus on the basis of two characteristics. First, P. multocida is a Gram-negative
coccobacillus, while C. canimorsus is a long, thin bacillus. Additionally, P. multocida is spot
indole positive, while C. canimorsus is negative. A key feature of this case, which is typical
of P. multocida, was the rapid onset of clinical signs of infection following the animal bite.
One point worth emphasizing is that infections following cat and dog bites are commonly
polymicrobial, often including both aerobic and anaerobic bacteria, with a median of five
different bacterial isolates per culture when appropriate techniques are employed for the
isolation of anaerobes.
Like those from cat and dog bites, human bite wound infections are typically due to
a mixture of aerobic and anaerobic organisms that are part of the oral microbiota. Key
organisms include facultative Gram-positive cocci in the Streptococcus anginosus group, the
facultative Gram-negative bacillus Eikenella corrodens, and anaerobic Gram-negative
bacilli within the genera Prevotella and Fusobacterium. Another important organism is
Staphylococcus aureus, which likely arises from the skin microbiota of the injured individual.
The emergence of community-associated methicillin-resistant S. aureus (MRSA) infections means that these infections must also be considered when choosing antimicrobials.
Interestingly, facultative Gram-negative bacilli such as Pasteurella and C. canimorsus are not
present in human bite wounds.
2. P. multocida is widely distributed throughout nature and is part of the normal flora in
the nasopharynx of many mammals (both wild and domestic) and birds. Human infection
is most likely to be associated with cat bites or scratches and less likely (though still quite
commonly) to be caused by dog bites. Infections following bites by other members of the
cat family, including lions, have been reported to cause P. multocida wound infections. In a
minority of human infections, the patients have had no known animal exposure. Particular
organisms are often associated with bites from specific animals. For example, C. canimorsus
(cani = “dog”; morsus = “bite”) infection may be transmitted by dog bites, and both
Streptobacillus moniliformis and Spirillum minus are transmitted by rat bites. It is important
to note that bites of domestic animals are responsible for hundreds of thousands of emergency department visits annually in the United States.

3. Infection can be prevented by limiting contact with cats and dogs. If a person is bitten or scratched by a cat or dog, the wound should be thoroughly cleaned as soon as
possible. The animal should also be observed for sign of rabies, especially if rabies vaccination is not well documented.

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Case 37 271

4.  In addition to soft tissue infection with rapid onset, other clinical syndromes seen
with this organism following animal bites include osteomyelitis, tenosynovitis, abscess
formation, and arthritis. Serious infections are more frequent after cat bites than after dog
bites. It is speculated that the cat tooth, which is long and narrow, is more likely to cause
puncture wounds that penetrate the tendon sheath (causing tenosynovitis) or periosteum
(causing osteomyelitis). These infections are particularly problematic because they often
occur on the hands and wrists. Because of the extraordinarily complex anatomy involved,
infections of the hand and wrist, if neglected, can require complicated surgical debridement and loss of important motor function for the patient, either temporarily or permanently. Other uncommon complications include bacteremia with septic shock, meningitis,
brain abscess, and peritonitis. Interestingly, there have been a fair number of reported
cases of peritonitis due to P. multocida in which a cat bit into the tubing that was being used
during peritoneal dialysis. Pneumonia due to cat exposure, rather than a bite, occurs as
well.

5.  Cat scratch disease is characterized by the development of a small lesion 1 to 2 weeks
after a cat scratch, usually on the hand, wrist, or forearm. This lesion is followed 1 to 3
weeks later by regional lymphadenopathy, typically of a single or multiple nodes, most
commonly in the axilla but sometimes in the cervical or epitrochlear region. Multiple sites
are infrequently involved. The nodes may remain enlarged for several months and then

resolve without treatment. The etiologic agent is a fastidious Gram-negative bacillus,
Bartonella henselae. Although this organism can be grown from the blood of cats, it is rarely
if ever recovered from the tissue of infected individuals. Diagnosis is likely to be sought in
order to rule out other potential causes of lymphadenopathy such as malignancy. There
are limited diagnostic tools clinically available to diagnose cat scratch disease. Although
the antibodies that are tested for when using serology cross-react with similar organisms,
the detection of a 4-fold rise in titer from acute- to convalescent-phase sera is diagnostic
in the appropriate clinical setting. However, serology only provides a retrospective diagnosis. Multiple nucleic acid amplification tests have been described in the literature, but
sensitive detection from human tissue often requires culture enrichment prior to molecular amplification, and this technique remains a research tool. Although the organism can
be visualized in lymph node tissue with silver staining early in the disease course, this
method is nonspecific and its sensitivity is unknown.

6.  Both dogs and cats should be vaccinated against the neurotropic, single-strandedRNA, enveloped virus rabies. Rabies is transmitted by the bite of a mammal, typically a
dog. However, in the United States, cats are more likely to have rabies than dogs. This is
probably because rabies vaccination is a requirement for dog licensure, and this licensure
is required in most locales in the United States. On the other hand, only one state, Rhode
Island, requires cat licensure, suggesting that cats are much less likely to receive rabies
vaccination.

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272 Skin and Soft Tissue Infections

Rabies is endemic in many regions of the world, with travelers to Africa, South Asia,
India, and certain regions of South and Central America at greatest risk of exposure.
Rabies vaccination is recommended for individuals who are traveling to these regions and
are likely to come in contact with dogs. More than 95% of cases that are imported into

Europe and North America are due to dog bites. Of the small number of cases in the
United States that are acquired in the absence of foreign travel, bats are often the source
of the infection. In particular, parents are encouraged to have their children vaccinated if
they may be exposed to dogs during their travels since they may be less careful about
approaching these animals. Only 12% of travelers to regions where rabies is endemic are
vaccinated. The reason for this low rate is thought to be the expense of the human rabies
vaccine. The importance of this vaccine is illustrated by a case of rabies obtained by a U.S.
soldier serving in Afghanistan who was bitten by a dog, was not offered postexposure prophylaxis, and developed rabies several months later and died. Unvaccinated people visiting
countries where rabies is endemic should have a plan to get postexposure prophylaxis
consisting of rabies immune globulin and vaccine if bitten by a dog, cat, monkey, bat, wolf,
fox, or other mammal. This may include traveling to a place where such treatment is available. In the industrialized world, there is not as great a need to start postexposure prophylaxis immediately, since this risk is lower, especially if the animal responsible for the
exposure can be observed or tested for the presence of rabies.

REF EREN C E S
1. Centers for Disease Control and Prevention (CDC). 2012. Imported human rabies in
U.S. Army soldier—New York, 2011. MMWR Morb Mortal Wkly Rep 61:302–305.
2. Chomel BB, Boulouis HJ, Maruyama S, Breitschwerdt EB. 2006. Bartonella spp. in
pets and effect on human health. Emerg Infect Dis 12:389–394.
3. Gautret P, Parola P. 2012. Rabies vaccination for international travelers. Vaccine 30:126–
133.
4. Talan DA, Abrahamian FM, Moran GJ, Citron DM, Tan JO, Goldstein EJ; Emergency
Medicine Human Bite Infection Study Group. 2003. Clinical presentation and bacteriologic analysis of infected human bites in patients presenting to emergency departments.
Clin Infect Dis 37:1481–1489.
5. Talan DA, Citron DM, Abrahamian FM, Moran GJ, Goldstein EJ; Emergency
Medicine Animal Bite Infection Study Group. 1999. Bacteriologic analysis of infected
dog and cat bites. N Engl J Med 340:85–92.
6. Weber DJ, Wolfson JS, Swartz MN, Hooper DC. 1984. Pasteurella multocida infections.
Report of 34 cases and review of the literature. Medicine (Baltimore) 63:133–154.

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273

CASE

An 18-month-old female presented to the emergency department with fever, a diffuse rash (onset 5 days before), and a
swollen right hand. On examination she was irritable but alert.
Her temperature was 39°C and her heart rate was increased at
180 beats/min. She had diffuse vesiculopustular lesions over her
entire body (Fig. 38.1), with some areas showing older, crusted lesions. She had
cellulitis of the right hand manifested by marked erythema, swelling, and tenderness. There were no mouth lesions, the lungs were clear, and the liver and spleen
were not enlarged. Laboratory data were significant only for leukocytosis with a
white blood cell count of 15,800/μl with 88% neutrophils. The chest radiograph
was clear. A radiograph of the right hand showed only soft tissue swelling. The
patient was treated with intravenous cefazolin. Improvement in the condition of
her right hand was notable within 48 hours. This patient had a systemic viral
infection with a complication of bacterial superinfection (cellulitis).

38

1. This patient had a characteristic rash (Fig. 38.1) at various stages of
evolution. What was her underlying viral illness? What other causes of
her skin rash should be considered in the differential diagnosis?

2. How is the diagnosis of infection with this pathogen made?
3. Describe the epidemiology of this viral infection and how it has changed
since 1995.

4. What complications other than bacterial superinfection (as seen in this
case) can occur as a result of this viral infection?

5. After acute primary infection with this virus, latent infection develops.
What illness may occur years later as a result of viral reactivation? How
do the clinical manifestations of this reactivation infection differ from
those of primary infection?

6. What specific antiviral therapy has been shown to be efficacious? Are
there any concerns about resistance?

7. What are the infection control
issues related to this patient’s
illness?

8. Two different vaccines exist
against this agent. How do they
differ in terms of vaccine composition, target population, and
efficacy?

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Figure 38.1

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274 Skin and Soft Tissue Infections

CASE

CASE DISCUSSION

38

1. The patient’s underlying viral illness was varicella (chicken pox). This
illness is due to primary infection with varicella-zoster virus (VZV), which
is a member of the herpesvirus family. These are enveloped, double-stranded
DNA viruses. Varicella lesions develop in “crops” such that lesions can be seen in various
stages of evolution, including vesicular, pustular, and crusted.
The differential diagnosis in this case includes impetigo (group A streptococcal infection), disseminated enteroviral infection, and disseminated herpes simplex virus infection
in a child with underlying skin disease (e.g., eczema). This child had no history of a preexisting dermatologic disorder. Other viruses that cause “pox”-like lesions are in the
Poxviridae family and include the orthopoxviruses and molluscum contagiosum virus.
Molluscum contagiosum was unlikely in this case; in immunocompetent individuals, it
remains localized and does not cause a sudden-onset systemic infection. However, the
orthopoxviruses are important to consider, including monkeypox and smallpox. Although
monkeypox is endemic in Central and West Africa and is rarely seen in the United States,
there was an outbreak of monkeypox in the Midwest in 2003. This outbreak affected 72
individuals, all of whom had exposure to prairie dogs that had been housed at the same
facility with imported, monkeypox-infected Gambian rats. Because of concerns about
bioterrorism, the specter of smallpox must also be considered. Smallpox lesions, unlike
those of chicken pox, are all at the same stage of development, whereas this patient’s
lesions simultaneously included vesicular, pustular, and crusted lesions. Smallpox lesions
often occur on the palms and soles of the feet and are most concentrated on the face and
extremities. This is in contrast to chicken pox lesions, which are rarely on the palms and
soles and are more concentrated on the torso. If the patient had recently been vaccinated
against smallpox, then disseminated vaccinia should also be in the differential. Noninfectious
causes of skin rashes that may be confused with varicella include contact dermatitis, drug
reactions, and insect bites.

2. In immunocompetent children, the
diagnosis of chicken pox is often made on the
basis of clinical findings alone. For adults and
immunocompromised children, laboratory
confirmation of VZV infection is frequently
sought. A method that combines rapidity
with sensitivity is direct fluorescent-antibody
staining of scrapings taken from vesicular
lesions. Culture techniques for detection of
VZV include rapid centrifugation culture
(i.e., shell vial) (Fig. 38.2) and standard tissue
culture. Shell vial cultures, which take 2 to 4

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Figure 38.2

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Case 38 275

days, are both more rapid and more sensitive than standard tissue culture, which may
take as long as 3 weeks to recover VZV. Nucleic acid amplification tests have also been
developed, including quantitative assays. A recent study compared the sensitivity of
direct fluorescent-antibody assay, shell vial culture, and two PCR assays and demonstrated 87.8, 46.3, and 97.6 and 100% sensitivity, respectively. Although highly sensitive
and relatively rapid, nucleic acid amplification tests have not been approved by the FDA
and therefore have limited availability.

3.  VZV has a worldwide distribution. Disease is more common in temperate regions,
with annual epidemics in the late winter and spring in areas with low vaccination rates.
The virus is spread by the respiratory route and is highly infectious, with ~90% of nonimmune household contacts and 10 to 35% of nonimmune classroom contacts becoming
infected. VZV can also be spread by direct contact with skin lesions and fomites. In 1995,
a live attenuated vaccine was approved in the United States for prevention of primary
varicella. In the prevaccine era, there were ~4 million cases of varicella annually in the
United States, which translates to 15 to 16 cases per 1,000. In the first 5 years after introduction of the vaccine, the incidence dropped 76 to 87% in the United States.

4.  In general, varicella causes much more severe illness in adults than in children.
Immunocompromised children and nonimmune, pregnant women also are more prone to
complications with this virus than is the general population. The severe illness seen with
VZV in these patient populations is due in large part to the significant morbidity and
mortality associated with varicella pneumonia. Other complications include hepatitis,
arthritis, glomerulonephritis, myocarditis, pericarditis, pancreatitis, encephalitis, and cerebellar ataxia. Multiorgan involvement is associated with high mortality. Primary varicella
during pregnancy can also cause intrauterine infection leading to fetal loss or an infant
born with congenital varicella syndrome, which may include dermatomal scarring, limb
hypoplasia, ocular defects, low birth weight, and mental retardation.
In addition, secondary bacterial infections of the skin lesions, as was seen in this case
(cellulitis of the right hand), can also occur. These bacterial infections are most commonly
caused by Streptococcus pyogenes and Staphylococcus aureus. VZV infections are associated
with S. pyogenes-induced necrotizing fasciitis, as VZV skin lesions have been well recognized as an important portal of entry for S. pyogenes. Reye’s syndrome, with encephalopathy, elevated transaminase levels, and elevated serum ammonia levels, can occur in children
with varicella or influenza who take aspirin. It should be remembered that patients with
VZV infection can have a prodrome characterized by fever, malaise, headache, and
abdominal pain that is indistinguishable from many other viral illnesses. Therefore,
infants and children with febrile illnesses should not be given aspirin.

5.  Herpes zoster (shingles) is a reactivation of a latent VZV infection. The dorsal root
ganglia are latently infected following primary infections. Cell-mediated immunity (CMI),

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276 Skin and Soft Tissue Infections

and not VZV antibody, is necessary to maintain latency. A loss in CMI, as is seen with
increasing age, is associated with reactivation. Other risk factors for reactivation include
CMI dysfunction (transplant, hematologic malignancies, HIV), diabetes, and even recent
physiologic stress.
In herpes zoster, skin lesions appear in a single dermatomal distribution innervated by
the specific dorsal root or extramedullary cranial ganglia where VZV had been latent.
There are four groups of herpes zoster complications—cutaneous, visceral, neurological,
and ocular. Perhaps the most debilitating complication is the persistent pain that can occur
with the rash and persist even after the lesions heal. This persistent pain is called postherpetic neuralgia.
Rarely, skin lesions disseminate beyond the primary dermatome involved. In immunosuppressed patients, however, complicating viremia can occur, with dissemination to
extradermatomal skin sites, lungs, liver, and the central nervous system. This condition,
with extradermatomal sites of infection, is called disseminated herpes zoster. Patients with
zoster are also infectious, although apparently not as infectious as patients with varicella.

6.  Acyclovir is beneficial in treating VZV (both varicella and herpes zoster). In immunocompetent adults ≥50 years of age, treatment with both analgesics and antivirals is
recommended, particularly in patients with ocular involvement. In immunocompetent
patients <50 years old, antivirals are not necessary but can shorten the duration of illness.
Because of its cost, acyclovir is often not used in uncomplicated cases. Thymidine kinase
mutations in VZV conferring resistance to acyclovir have been described, though almost
exclusively in immunocompromised patients. In one report, 27% of hematopoietic stem
cell transplant recipients with persistent VZV infection had mutations possibly associated
with resistance. Interestingly, in patients with disseminated disease, all infected sites may
not harbor the resistant virus. Therefore, it is prudent to test multiple specimen types

when screening for resistance mutations. Acyclovir-resistant VZV in immunocompetent
patients appears to be rare, but has been reported.

7.  Patients with varicella are very contagious. Secondary cases are frequently more
severe. The increased severity is believed to be due to high viral inoculum. Hospitalized
patients with varicella must be placed in respiratory isolation (airborne precautions), and
strict infection control measures regarding skin contact (hand washing, use of gloves and
gowns, etc.) must be implemented (contact precautions). Precautions must remain in place
until lesions are dry and crusted. Only individuals who are nonimmune, including health
care personnel, need to wear a mask. Ideally, nonimmune health care personnel should not
care for a VZV-infected patient. Seronegative health care personnel who do come in contact with these infected patients should not have contact with other patients, especially
immunocompromised ones, for a minimum of 2 weeks after exposure, the incubation
period of this viral infection.

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Case 38 277

There are also infection control considerations when a nonimmune person has been
exposed to VZV. Postexposure vaccine should be administered within 120 hours of exposure. For exposed individuals who cannot receive the live vaccine, a varicella-zoster
immune globulin preparation (i.e., VariZIG) should be administered within 96 hours. This
would apply to immunocompromised individuals, infants, and pregnant women.

8.  There are two VZV vaccines—one to prevent varicella and one to prevent herpes
zoster. Both are live, attenuated vaccines made from the same vaccine strain, but the difference is the titer of the virus in each vaccine. The herpes zoster vaccine has a much

higher titer than that of the varicella vaccine (~14 times higher). A higher titer is needed
to provide an immune booster to prevent herpes zoster reactivation or at least decrease
the severity of disease. Because these are live virus vaccines, they should not be used in
immunocompromised individuals, including those with a hematologic malignancy, congenital immunodeficiency, or symptomatic HIV infection. Persons receiving high-dose
immunosuppressive drugs and pregnant women should also not receive these live vaccines.
The varicella vaccine is licensed for use in the United States for all children >12
months of age. Current recommendations call for the vaccine to be given in two doses—
the first dose at 12 to 15 months of age and the second dose at 4 to 6 years of age.
Adolescents and adults with no previous evidence of disease should receive two doses of
the vaccine 4 to 8 weeks apart. The vaccine is very efficacious, vaccine failures are rare, and
it has been shown to be particularly effective at preventing severe VZV disease.
Postlicensure vaccine safety surveillance using the Vaccine Adverse Event Reporting
System of the Centers for Disease Control and Prevention has shown the vaccine to be
remarkably safe. Both vaccine-associated and natural infections have been noted postvaccination. Serious infections and deaths due to infection caused by the vaccine strain have
been observed but are quite rare (1 death/1,000,000 doses of vaccine administered).
The herpes zoster vaccine is licensed for individuals ≥50 years of age and only requires
one dose. The target population for vaccination is individuals ≥60 years of age due to the
higher rate of herpes zoster and its complications in this population. The initial clinical
trial data (≥60-year-olds) showed that the vaccine reduced the incidence of herpes zoster
by 51% and the incidence of postherpetic neuralgia by 67%.
Two questions remain unanswered concerning the effect of these vaccines on the natural progression of disease. First, will individuals who receive the varicella vaccine be at
risk for herpes zoster due to the vaccine strain later in life? Limited data suggest that they
may, but that the rates and severity of herpes zoster are reduced compared with those in
individuals who have natural disease. Second, will immunity wane in adults who received
the varicella vaccine as a child? As natural disease declines, this could result in an at-risk
population. Since adults are most vulnerable to severe varicella disease, this is a legitimate
concern. Twenty-year follow-up data suggest that immunity persists, but these studies

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278 Skin and Soft Tissue Infections

were done in settings where natural disease continues to be common, offering the opportunity for immunized individuals to receive a “booster” effect from exposure to infected
individuals.

REF EREN C E S
1. Gershon AA, Gershon MD, Breuer J, Levin MJ, Oaklander AL, Griffiths PD. 2010.
Advances in the understanding of the pathogenesis and epidemiology of herpes zoster.
J Clin Virol 48:S2–S7.
2. van der Beek MT, Vermont CL, Bredius RG, Marijt EW, van der Blij-de Brouwer
CS, Kroes AC, Claas EC, Vossen AC. 2013. Persistence and antiviral resistance of varicella zoster virus in hematological patients. Clin Infect Dis 56:335–343.
3. Wilson DA, Yen-Lieberman B, Schindler S, Asamoto K, Schold JD, Procop GW.
2012. Should varicella-zoster virus culture be eliminated? A comparison of direct immunofluorescence antigen detection, culture, and PCR, with a historical review. J Clin Microbiol
50:4120–4122.
4. Wise RP, Salive ME, Braun MM, Mootrey GT, Seward JF, Rider LG, Krause PR.
2000. Postlicensure safety surveillance for varicella vaccine. JAMA 284:1271–1279.

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279

CASE

A 44-year-old female was transferred to the hospital by air

ambulance after suffering a respiratory arrest in her doctor’s
office. She arrived intubated after being resuscitated. Her past
medical history was significant for her having suffered a dislocated left thumb 3 days previously at work while assisting a patient
into a wheelchair. When she got home from work, a family member reduced the
dislocation. Over the next 2 days she had gradually increasing ascending pain and
swelling in her left arm. She visited her local emergency department on each of
those 2 days. Both times she was given analgesics and sent home. On her third day
of illness, she was visiting her primary care physician, where she had a cardiopulmonary arrest.
On physical examination she had a temperature of 39.1°C, heart rate of 197
beats/min, and blood pressure of 95/45 mm Hg. Her white blood cell count was
4,700/μl, her hemoglobin was 11.7 g/dl, and she had a creatinine of 1.9 mg/dl, a
blood urea nitrogen of 32 mg/dl, and a creatine kinase of 3,307 units/liter.
Physical examination of her left arm was consistent with a nonperfused extremity
including a cold, cyanotic hand, blisters with skin necrosis between the wrist and
elbow, and arm warm to the touch at the elbow and above.
She was begun on clindamycin and penicillin G and taken to the operating
room, where an incision was made over her left humerus, which revealed necrotic
tissue and dishwater fluid between tissue planes at the fascial level. Her arm was
amputated at the shoulder. She had additional chest wall debridement down to the
pectoralis major. Tissue Gram stain showed 4+ Gram-positive cocci in pairs and
short chains (Fig. 39.1). Postoperatively the patient became increasingly hemodynamically unstable, had a cardiac arrest, and could not be resuscitated. It was
subsequently learned that the individual with whom the patient was working
when she suffered the thumb dislocation had been admitted with septic shock to
another hospital. The organism recovered from the patient is shown in Fig. 39.2.

39

1. What organism caused this patient’s infection?
2. What syndrome did this patient have? How does it explain the physical
finding of a cold, cyanotic extremity on admission? What virulence factors does this organism produce that played a role in her clinical disease

course? What is the typical outcome of this infection? What might have
been done to make her case less severe?

3. How did this patient become infected? How can this be proven?
4. Two other individuals in the community had a similar illness to the case
patient in the same week. There was no direct epidemiologic link among
the three. How do you explain this observation?

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