Hindawi Publishing Corporation Infectious Diseases in Obstetrics and Gynecology Volume 2008, Article ID 491401, 5 pages doi:10.

1155/2008/491401

Case Report Necrotizing Pneumonia Caused by Panton-Valentine Leucocidin-Producing Staphylococcus aureus Originating from a Bartholins Abscess
N. Jung,1 C. Lehmann,1 M. Hellmann,1 H. Seifert,2 M. M. Valter,3 M. Hallek,1 G. Fatkenheuer,1 and M. Kochanek1
1 Department 2 Institute

I of Internal Medicine, University of Cologne, 50935 Cologne, Germany for Medical Microbiology, Immunology and Hygiene, University of Cologne, 50935 Cologne, Germany 3 Clinic for Gynecology, University of Cologne, 50935 Cologne, Germany Correspondence should be addressed to N. Jung, [email protected] Received 22 January 2008; Revised 9 April 2008; Accepted 11 June 2008 Recommended by Roberta Ness Background. Panton-Valentine leukocidin (PVL-)producing Staphylococcus aureus 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 Bartholins abcesses have been described but involvement of S. aureus is rare. Case report. We present a 23-year-old apparently healthy female patient without any typical predisposing ndings who developed severe sepsis with necrotizing pneumonia and multiple abscesses following incision of a Bartholins abscess. Methicillin-sensitive S. aureus harbouring Panton-Valentine leucocidin genes were cultured from the abscess uid, multiple blood cultures and a postoperative wound swab. Aggressive antibiotic therapy with ucloxacillin, rifampicin and clindamycin, drainage and intensive supportive care lead nally to recovery. Conclusions. S. aureus, in particular PVL-positive strains, should be considered when a young, immunocompetent person develops a fulminant necrotizing pneumonia. Minor infectionssuch as Bartholins abscesscan precede this life-threating syndrome. Bactericidal antistaphylococcal antibiotics are recommended for treatment, and surgical procedures may become necessary. Copyright 2008 N. Jung et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Panton-Valentine leucocidin (PVL) is a pore-forming cytotoxin of Staphylococcus aureus 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 [1]. S. aureus has the capacity to produce a wide array of virulence factors which are responsible for divergent clinical syndromes [2]. In the US, the most common circulating community-associated methicillin-resistant S. aureus strain USA 300 contains PVL, but most infections are skin and soft tissue infections, including boils, and are not life threatening [3]. Necrotizing pneumonia due to PVL-positive S. aureus is usually severe and often fatal, involves primarily young and healthy patients, and carries a mortality rate up to 75% despite intensive medical treatment [4].

To our knowledge, we present the rst case of necrotizing pneumonia following incision of a Bartholins abscess. In October 2006, a 23-year-old woman with no systemic signs of infection had a surgical incision of a Bartholins abscess (3 5 3 cm) without the installation of a drainage. The patient was discharged without antimicrobial therapy. The abscess uid was submitted for culture. 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. She presented with an inuenza-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

Infectious Diseases in Obstetrics and Gynecology Empirical intravenous antibiotic therapy with piperacillin/tazobactam and levooxacin was started immediately. On day 2, the initial abscess uid yielded S. aureus fully susceptible to antistaphylococcal agents with the exception of penicillin and tetracyclin. Therefore, piperacillin/tazobactam was changed to high-dose intravenous ucloxacillin 4 g tid and levooxacin was discontinued. On day 3, blood cultures and both wound and vaginal swab taken on admission also grew S. aureus. On day 4, rifampicin 600 mg Rifampicin 600 mg (once daily) was added as blood cultures continued to be positive and the patient still suered from high fever and severe dyspnoea. CT scans of the chest and abdomen showed newly emerged extensive bilateral pleural eusions. 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) amplication of the lukS-lukF genes was performed as described previously [5] and conrmed the presence of the PVL gene in all available S. aureus 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 eusions increased. Cultures of the pleural uid showed no growth. All S. aureus isolates from the abscess, the postoperative wound and multiple blood cultures had identical susceptibility proles. Minimal inhibitory concentrations (MICs) were <0.25 mg/l for oxacillin, <0.25 mg/l for clindamycin, and <0.5 mg/l for rifampicin. Pulsed-eld gel electrophoresis (PFGE) of SmaI digests of genomic DNA from all available S. aureus isolates showed identical patterns (data not shown). 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 ucloxacillin. Swabs of persons in close contact to the patient were taken but were negative for PVL-producing S. aureus. S. aureus 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. S. aureus is responsible for at least 10% of cases of nosocomial pneumonia but only for 2% of community-acquired pneumonia [6, 7]. Our patient was a young immunocompetent woman with no apparent risk factors who sustained severe community-onset necrotizing pneumonia, multiple abscesses, and extensive pleural eusions. These clinical features are characteristic for invasive infections with S. aureus exhibiting the putative virulence factor PVL. 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 methicillinsensitive S. aureus (MSSA), PVL is more often identied in community-acquired methicillin-resistant S. aureus (MRSA) [8].

Figure 1: CT scan revealed nodular opacities and diuse bilateral inltrates.

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 diuse 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. Admission laboratory data revealed an elevated leukocyte count of 13.6 109 /L, a very low platelet count of 24 109 /L, elevated inammatory markers including a C-reactive protein of 399 mg/L (reference range (RR) < 5 mg/L) and a procalcitonin level of 34 ng/L (RR < 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 inuenza season and rst occurence of the inuenza-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 deciency. Multiple blood cultures and swabs of the postoperative wound and the vagina were obtained and sumitted for culture. A computed tomography scan (CT) of the chest showed diuse bilateral alveolar inltrates and nodular opacities with cavity forming consistent with necrotising pneumonia (Figure 1). Transthoracal echocardiography on the day after admission showed no abnormal ndings, in particular no vegetations suggestive of infective endocarditis. Communityonset pneumonia and severe sepsis with coagulopathy was diagnosed.

N. Jung et al. PVL is a very virulent toxin expressed by S. aureus, which was rst characterized in 1932. Less than 5% of all S. aureus strains harbor PVL genes. PVL is a pore-forming toxin destroying the membrane of the host defence cells and erythrocytes [9]. Lina et al. [5] screened S. aureus isolates to correlate toxin production with disease manifestation. They found a denite association between the occurrence of PVL genes and furunculosis and community-onset pneumonia. Gillet et al. [4] compared the clinical features of PVL-positive pneumonia with PVL-negative pneumonia and found signicant dierences. PVL-positive patients were younger without risk factors for infection. They presented more often with haemoptysis, high fever, tachycardia, tachypnoea and developed diuse bilateral inltrates and pleural eusion. The mortality rate was signicantly higher with 75% in PVL-positive compared to 47% in PVL-negative infections. Other case series conrm the characteristics and severeness of the PVL-positive infections [1014]. The symptoms of our patient tted very well into this disease. Since PVL-positive S. aureus strains may spread between persons in close contact to the index patient [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 [16], but established public health recommendations do not exist. For the therapy of necrotizing pneumonia caused by PVL-positive S. aureus no specic guidelines have been published. Combination therapy is widely used empirically in life-threatening infections. Bactericidal antibiotics such as -lactam antibiotics are preferrd over bacteriostatic agents. For pneumonia, good penetration into the tissue has also to be considered. We added levooxacin empirically to piperacillin/tazobactam to treat potential atypical bacteria. As soon as cultures became positive for S. aureus the antibiotic regimen was changed from piperacillin/tazobactam to high-dose ucloxacillin, as this is the antibiotic of choice for -lactamase-positive S. aureus. As blood cultures remained continuously positive and the patients condition worsened, rifampicin, another very potent antistaphylococcal antibiotic, was added. The ecacy of rifampicin as an adjunctive drug in patients with life-threatening infections remains controversial. As soon as the S. aureus 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 [17, 18]. New in vitro data showed an augmentation of PVL toxin production by lactam antibiotics, but no in vivo data have supported these observations so far [19, 20]. Other in vitro data showed that the addition of rifampicin or clindamycin to oxacillin inhibits PVL production [21]. PVL-positive MRSA infection requires treatment with vancomycin as the rst-line agent. In severe S. aureus infections intravenous antibiotic therapy should be given for at least 4 weeks after the last blood culture positive for S. aureus . 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

3 might be sucient to cause pneumonia, it is not likely to be the only virulence determinant responsible for this syndrome [2, 22]. 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 [23]. In our patient, necrotizing pneumonia developed shortly after incision of a Bartholins abscess. Infection of the Bartholins gland is the most common infectious vulvar disease and develops in approximately 2% of all women [24]. Surgical intervention is considered the primary treatment, and controversy on the benet of antibiotics exists [25, 26]. Complication rates are very low, but cases of severe infections have been reported [2736]. S. aureus 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. Bartholins abscesses mostly contain a mixed ora of aerobic and predominantly anaerobic bacteria. The most frequently isolated aerobe is Escherichia coli, while S. aureus is only rarely detected [37, 38]. PVL-positive S. aureus infection should early be included in the dierential diagnosis when young immunocompetent persons develop necrotizing pneumonia. Various minor infectionssuch as Bartholins abscesscan precede this life threatening syndrome. Antibiotic treatment with bactericidal antistaphylococcal agents is recommended, and invasive surgical procedures may become necessary. REFERENCES
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