<p>Recommended by Roberta Ness</p> <p>
<italic>Background</italic>. Panton-Valentine leukocidin (PVL-)producing <italic>Staphylococcus aureus</italic> is emerging as a serious problem worldwide. There has been an increase in the incidence of necrotizing lung infections in otherwise healthy young people with a very high mortality associated with these strains. Sporadic severe infectious complications after incision of Bartholin's abcesses have been described but involvement of <italic>S. aureus</italic> is rare.
<italic>Case report</italic>. We present a 23-year-old apparently healthy female patient without any typical predisposing findings who developed severe sepsis with necrotizing pneumonia and multiple abscesses following incision of a Bartholin's abscess. Methicillin-sensitive <italic>S. aureus</italic> harbouring Panton-Valentine leucocidin genes were cultured from the abscess fluid, multiple blood cultures and a postoperative wound swab. Aggressive antibiotic therapy with flucloxacillin, rifampicin and clindamycin, drainage and intensive supportive care lead finally to recovery.
<italic>Conclusions</italic>. <italic>S. aureus</italic>, in particular PVL-positive strains, should be considered when a young, immunocompetent person develops a fulminant necrotizing pneumonia. Minor infections—such as Bartholin's abscess—can precede this life-threating syndrome. Bactericidal antistaphylococcal antibiotics are recommended for treatment, and surgical procedures may become necessary.</p>
<p>Panton-Valentine leucocidin (PVL) is
a pore-forming cytotoxin of <italic>Staphylococcus aureus</italic> inducing leukocyte
lysis. It has been associated with diverse clinical syndromes, including
primary and secondary skin infections such as furunculosis and abscesses and
deep seated infections such as necrotizing pneumonia. Its role and regulation
are still under investigation [##REF##18190315##1##]. <italic>S. aureus</italic> has the capacity
to produce a wide array of virulence factors which are responsible for
divergent clinical syndromes [##REF##15854883##2##]. 
In the US, the most common circulating community-associated
methicillin-resistant <italic>S. aureus</italic> strain USA 300 contains PVL, 
but most 
infections are skin and soft tissue infections, including boils, and are not life 
threatening [##REF##16390957##3##].</p> <p>Necrotizing pneumonia due to
PVL-positive <italic>S. aureus</italic> is usually severe and often fatal, involves primarily
young and healthy patients, and carries a mortality rate up to 75% despite
intensive medical treatment [##UREF##0##4##].</p> <p>To our knowledge, we present the
first case of necrotizing pneumonia following incision of a Bartholin's
abscess. In October 2006, a 23-year-old woman with no systemic signs of
infection had a surgical incision of a Bartholin's abscess (3 × 5 × 3 cm) without
the installation of a drainage. The patient was discharged without antimicrobial
therapy. The abscess fluid was submitted for culture.</p> <p>24 hours later, the woman developed
fever and her state of health worsened continuously, so she was admitted to a
local hospital 4 days after surgery. Community-acquired pneumonia was diagnosed
and a macrolide was administered. One day later, the patient became critically
ill and was transferred to our tertiary care hospital and immediately admitted
to the intensive care unit.</p> <p>She presented with an influenza-like
illness with severe muscle pain in all extremities, spiking fever up to 40°C, dry cough but no sore
throat. She showed ortho- and tachypnoea
with a respiratory rate of 30 breaths/minute, oxygen saturation was 96% with
the supply of 31/minute of oxygen but no need for intubation. Her blood
pressure was 100/60 mmHg and her heart rate 140/minute. Physical examination revealed
crackles in the inferior and middle parts of both lungs, a diffuse tenderness
of the abdomen, and severe
pain in the muscles. Auscultation
of the heart was unremarkable. Vaginal examination revealed a postoperative
wound without any signs of infection. She denied ever having used illicit
drugs.</p> <p>Admission laboratory data revealed an
elevated leukocyte count of 13.6 × 10<sup>9</sup>/L, a very low platelet count
of 24 × 10<sup>9</sup>/L, elevated inflammatory markers including a 
C-reactive
protein of 399 mg/L (reference range (RR) &lt; 5 mg/L) and a
procalcitonin level of 34 ng/L (RR &lt; 0.1 ng/L), and an elevated creatinine of
1.27 mg/dl. Her hemoglobin was
only slightly reduced with 11.5 g/dl. As the patient did not present during the influenza season and first occurence of the influenza-like symptoms
was parallel with the positive blood cultures, testing was not performed. Testing for HIV was
negative and fasting glucose was normal. As the patient had no increased rate
of infections in the past, we did not test for complement of IgG deficiency. Multiple
blood cultures and swabs of the postoperative wound and the vagina were obtained
and sumitted for culture.</p> <p>A computed tomography scan (CT) of
the chest showed diffuse bilateral alveolar infiltrates and nodular opacities
with cavity forming consistent with necrotising pneumonia (##FIG##0##Figure 1##).</p> <p>Transthoracal echocardiography on the day after
admission showed no abnormal findings, in particular no vegetations suggestive
of infective endocarditis. Community-onset pneumonia and severe
sepsis with coagulopathy was diagnosed.</p> <p>Empirical intravenous antibiotic
therapy with piperacillin/tazobactam and levofloxacin was started immediately. On
day 2, the initial abscess fluid yielded <italic>S. aureus</italic> fully susceptible to
antistaphylococcal agents with the exception of penicillin and tetracyclin.
Therefore, piperacillin/tazobactam was changed to high-dose intravenous flucloxacillin
4 g tid and levofloxacin was discontinued. On day 3, blood cultures and both
wound and vaginal swab taken on admission also grew <italic>S. aureus.</italic> On day 4,
rifampicin 600 mg Rifampicin 600 mg (once daily) was added as
blood cultures continued to be positive and the patient still suffered from
high fever and severe dyspnoea. CT scans of the chest and abdomen showed newly
emerged extensive bilateral pleural effusions. In addition, multiple abscesses
had evolved in the pectoralis, supraspinatus, and gluteus muscle. A reevaluation
of the heart valves by transesophagal
echocardiography revealed no abnormalities. On day 6, polymerase chain reaction
(PCR) amplification of the <italic>lukS-lukF</italic> genes was performed as described previously [##REF##10524952##5##] and confirmed the presence of the PVL gene in all available <italic>S. aureus</italic> isolates. Subsequently, clindamyin 600 mg
tid was added on day 7. With this treatment, blood cultures became negative on
day 8. On day 11, bilateral pleural drainage tubes had to be inserted as
effusions increased. Cultures of the pleural fluid showed no growth. All <italic>S.
aureus</italic> isolates from the abscess, the postoperative wound and multiple blood
cultures had identical susceptibility profiles. Minimal inhibitory
concentrations (MICs) were &lt;0.25 mg/l for oxacillin, &lt;0.25 mg/l for
clindamycin, and &lt;0.5 mg/l for rifampicin. Pulsed-field gel electrophoresis
(PFGE) of <italic>Sma</italic>I digests of genomic DNA
from all available <italic>S. aureus</italic> isolates
showed identical patterns (data not shown).</p> <p>The patient recovered very slowly
with a 3 weeks stay at the intensive care unit with maximal supportive care.
Respiratory support and vasopressors had not been necessary. Subsequently, the
patient stayed for another 8 weeks on a regular ward until recovery.
Antibiotics were continued for a total treatment duration of 5 weeks for
rifampicin and clindamycin and of 8 weeks for flucloxacillin.</p> <p>Swabs of persons in close contact to
the patient were taken but were negative for PVL-producing <italic>S. aureus.</italic>
</p> <p>
<italic>S. aureus</italic> is a major cause of respiratory,
skin, bone, joint, and endovascular infections. Mostly these infections occur
in persons with known risk factors such as cardiovascular disease, malignancy,
or diabetes mellitus. <italic>S. aureus</italic> is responsible for at least 10% of cases
of nosocomial pneumonia but only for 2% of community-acquired pneumonia [##REF##8041242##6##, ##REF##9709046##7##].</p> <p>Our patient was a young
immunocompetent woman with no apparent risk factors who sustained severe
community-onset necrotizing pneumonia, multiple abscesses, and extensive pleural
effusions. These clinical features are characteristic for invasive infections
with <italic>S. aureus</italic> exhibiting the
putative virulence factor PVL.</p> <p>The true incidence of PVL-associated
pneumonia is unknown, since the number of cases published is likely to be an 
underestimate. Besides its occurence in methicillin-sensitive <italic>S. aureus</italic> (MSSA), PVL is more often identified in
community-acquired methicillin-resistant <italic>S.
aureus</italic> (MRSA) [##REF##15614698##8##].</p> <p>PVL is a very virulent toxin
expressed by <italic>S. aureus</italic>, which was first
characterized in 1932. Less than 5% of all <italic>S. aureus</italic> strains harbor PVL genes. PVL
is a pore-forming toxin destroying the membrane of the host defence cells and
erythrocytes [##REF##7707330##9##]. Lina et al. [##REF##10524952##5##] screened <italic>S. aureus</italic> isolates to correlate toxin production with disease manifestation.
They found a definite association between the occurrence of PVL genes and furunculosis and
community-onset pneumonia. Gillet et al. [##UREF##0##4##] compared the clinical features of
PVL-positive pneumonia with PVL-negative pneumonia and found significant
differences. PVL-positive patients were younger without risk factors for
infection. They presented more often with haemoptysis, high fever, tachycardia,
tachypnoea and developed diffuse bilateral infiltrates and pleural effusion.
The mortality rate was significantly higher with 75% in PVL-positive compared
to 47% in PVL-negative infections. Other case series confirm the
characteristics and severeness of the PVL-positive infections [##REF##17366043##10##–##REF##16012013##14##]. The symptoms of our patient fitted
very well into this disease.</p> <p>Since PVL-positive <italic>S. aureus</italic> strains may spread between persons in close contact to the index patient [##REF##12477329##15##], swabs should be taken to prevent further
spreading. In a report from Germany, control of a furunculosis outbreak involving
PVL-positive MSSA in a rural village was achieved by stringent decolonization of
carriers [##REF##17479931##16##], but established public health
recommendations do not exist.</p> <p>For the therapy of necrotizing pneumonia
caused by PVL-positive <italic>S. aureus</italic> no
specific guidelines have been published. Combination therapy is widely used
empirically in life-threatening infections. Bactericidal antibiotics such as <italic>β</italic>-lactam
antibiotics are preferrd over bacteriostatic agents. For pneumonia, good
penetration into the tissue has also to be considered. We added levofloxacin
empirically to piperacillin/tazobactam to treat potential atypical bacteria. As
soon as cultures became positive for <italic>S.
aureus</italic> the antibiotic regimen was changed from piperacillin/tazobactam to
high-dose flucloxacillin, as this is the antibiotic of choice for <italic>β</italic>-lactamase-positive <italic>S. aureus.</italic> As blood cultures remained
continuously positive and the patient's condition worsened, rifampicin, another
very potent antistaphylococcal antibiotic, was added. The efficacy of
rifampicin as an adjunctive drug in patients with life-threatening infections
remains controversial. As soon as the <italic>S. aureus</italic> isolates turned out to
be PVL-positive, clindamycin was added. Several authors recommend the addition
of clindamycin to the treatment of toxin-producing grampositive bacteria as it
targets the bacterial ribosomes thereby potentially blocking the toxin
production [##REF##11691576##17##, ##REF##16210260##18##]. New in vitro data showed an augmentation of PVL toxin production by
<italic>β</italic>-lactam antibiotics, but no in vivo
data have supported these observations so far [##REF##17629464##19##, ##REF##17191165##20##]. Other in vitro data showed that the addition of rifampicin or
clindamycin to oxacillin inhibits PVL production [##REF##18261123##21##]. PVL-positive MRSA infection
requires treatment with vancomycin as the first-line agent. In severe <italic>S.
aureus</italic> infections intravenous antibiotic therapy should be given for at
least 4 weeks after the last blood culture positive for <italic>S. aureus</italic> . Although PVL plays
a key role in the pathogenesis of necrotising pneumonia and Labandeira-Rey et
al. could show in a mouse model that the PVL toxin alone might be sufficient to
cause pneumonia, it is not likely to be the only virulence determinant
responsible for this syndrome [##REF##15854883##2##, ##REF##17234914##22##].</p> <p>The outcome of patients with
necrotizing pneumonia may be poor in many cases even if appropriate antibiotics
are administered. In addition, intensive supportive care is crucial for improving
the outcome in these severe infections [##REF##18295681##23##].</p> <p>In our patient, necrotizing
pneumonia developed shortly after incision of a Bartholin's abscess. Infection
of the Bartholin's gland is the most common infectious vulvar disease and
develops in approximately 2% of all women [##REF##12962350##24##]. Surgical intervention is
considered the primary treatment, and controversy on the benefit of antibiotics
exists [##REF##9556648##25##, ##REF##12887119##26##]. Complication rates are very low,
but cases of severe infections have been reported [##REF##11725737##27##–##REF##6270397##36##]. <italic>S.
aureus</italic> appears to be only very
rarely involved in these cases. Clinical complications have included septic
shock, toxic-like-syndrome, necrotizing fasciitis, myocarditis, and gangrene
but pneumonia has not been reported.</p> <p>Bartholin's abscesses mostly contain
a mixed flora of aerobic and predominantly anaerobic bacteria. The most
frequently isolated aerobe is <italic>Escherichia
coli</italic>, while <italic>S. aureus</italic> is only rarely detected [##UREF##4##37##, ##UREF##5##38##].</p> <p>PVL-positive <italic>S. aureus</italic> infection should early be
included in the differential diagnosis when young immunocompetent persons
develop necrotizing pneumonia. Various minor infections—such as
Bartholin's abscess—can precede this
life threatening syndrome. Antibiotic
treatment with bactericidal antistaphylococcal
agents is recommended, and invasive surgical procedures may become necessary.</p>
<fig id="fig1" position="float"><label>Figure 1</label><caption><p> CT scan revealed nodular opacities and diffuse
bilateral infiltrates.</p></caption></fig>
<graphic xlink:href="IDOG2008-491401.001"/>
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Infect Dis Obstet Gynecol. 2008 Jul 29; 2008:491401