Scandinavian Journal of Infectious Diseases, 2006; 38: 192/234

CASE REPORTS

Panton-Valentine -producing infections: Report of 4 French cases

CARINE SALLIOT1, VALERIE ZELLER1, XAVIER PUECHAL2, VERONIQUE MANCERON3, STEPHANE SIRE4, NICOLAS VARACHE2, JEROME ETIENNE5, NICOLE DESPLACES6 & JEAN-MARC ZIZA1

From the 1Service de Me´decine Interne et Rhumatologie et 6Laboratoire de Microbiologie, Groupe Hospitalier Diaconesses- La Croix-Saint Simon, Paris, 2Service de Rhumatologie, Centre Hospitalier du Mans, Le Mans, 3Service de Me´decine Interne, Centre Hospitalo-Universitaire Louis Mourier, Colombes, 4Service des Maladies Infectieuses, Hoˆpital Jean Rougier, Cahors, and 5Centre National de Re´fe´rence de Toxe´mies Staphylococciques, Faculte´ de Me´decine, Lyon, France

Abstract We report 4 cases of community-acquired infections due to Staphylococcus aureus producing Panton-Valentin leukocidin (SA-PVL) with uncommon multivisceral localizations. These cases highlight the need to screen for PVL in patients with serious staphylococcal infections. All patients were cured. Two of them received intravenous immunoglobulins in addition to antibiotics.

Introduction (PCR), are found in 93% of 172 clinical SA strains associated with furunculosis. They are also detected Panton-Valentine leukocidin (PVL), produced by in 55% of strains associated with cellulites, in 50% less than 5% of Staphylococcus aureus (SA) strains, associated with cutaneous abscesses, rarely in strains is a bi-component pore-forming that has a associated with felons and bacteraemia, never in specific lytic activity on human polymorphonuclear strains responsive of other skin infections such as cells and monocytes [1]. The sequential and syner- post-surgery infections, impetigo, folliculitis, nor gistic interaction of the 2 components (LukS-PV with endocarditis, mediastinitis, enterocolitis and and LukF-PV) on surface cells induces the open- urinary tract infections [4]. The prevalence of ing of calcium channels, the formation of pores PVL-producing SA in nasopharyngal colonization through the membrane and the lysis of these cells is variable according to the studies: 0 to 98% [5,6]. [2]. It releases also proinflammatory mediators such PVL-positive staphylococcal pneumonias are necro- as leukotriene B4, interleukin-8 [3] and vasodilatat- tic and haemorrhagic and occur in healthy children ing factors (prostaglandins, histamine) that induce and young adults (median age, 15 y old). Despite severe inflammatory lesions. The toxin receptor anti-staphylococcal therapy, the mortality rate is might belong to a cytokine receptor family [1]. very high (75%) because of a toxic syndrome and LukS-PV and LukF-PV are encoded by 2 contiguous multivisceral failure [4,7,8]. An influenza-like syn- and co-transcripted open reading frames carried drome precedes pneumonia in 75% of the cases on a bacteriophage that can infect SA not produ- and median leukocytes count is low at day 1 (7). cing PVL. Bronchial damage could be explained by the binding PVL-producing SA is associated with community- of SA producing PVL on exposed collagen (type I acquired infections such as chronic pyodermitis and IV) and laminin. Previous viral airway infection and serious necrotizing pneumonias. Genes encod- may permit exposition of these extracellular matrix ing PVL, detected by polymerase chain reaction proteins [9].

Correspondence: C. Salliot, Medecine Interne-Rheumatologie, Paris, France. E-mail: [email protected]

(Received 6 August 2005; accepted 30 September 2005) ISSN 0036-5548 print/ISSN 1651-1980 online # 2006 Taylor & Francis DOI: 10.1080/00365540500388776 Case Reports 193

We review 4 cases of such infections in different condition improved slowly, but fever and inflamma- regions of France. tion persisted after 6 weeks of antibiotherapy. There- fore intravenous immunoglobulins (IVIG, 2 g per kg over 4 consecutive days) were administered and the Cases report infection was cured. The 4 observations are summarized in Table I. Patient 2 had a past history of chronic furunculosis Patient 1 was a healthy young male hospitalized and hydradenitis treated on several occasions by for lumbar pain, fever, right psoas weakness, confu- surgery. She was admitted for idiopathic epilepsy sion and dyspnoea that occurred a few days after a and developed fever, skin rash with bullous eruption, lumbar furonculosis. Staphylococcal septicaemia pneumonia and lymphocytic meningo-encephalitis with multiple localizations (pneumonia, meningitis, diagnosed as drug rash with eosinophilia and sys- lumbar epidural abscesses, right sacroiliitis, thigh temic symptoms syndrome (DRESS syndrome) cellulitis and muscular abscesses) (Figure 1) was attributed to phenobarbitol. Treatment with high diagnosed. He was treated initially with intravenous doses of steroids was initiated (80 mg per d of cefotaxime and fosfomycin, but cefotaxime was prednisolone for 3 days, followed by prednisone at changed for fusidic acid and pefloxacin because 50 mg per d), with improvement of the hypersensi- of severe neutropenia. This triple association (fosfo- tivity reaction. However, this treatment was followed mycin, fusidic acid and pefloxacin) was given for by serious inguinal and axillae furunculosis asso- 3 months and pefloxacin and fusidic acid was ciated with staphylococcal enterocolitis. She was administered for 3 further months. The patient’s treated with oral vibramycin for 6 months (because

Table I. Clinical and bacterial features of 4 patients with community-acquired PVL-producing Staphylococcus aureus infection.

Patient 1 2 3 4 Age (y) 19 34 26 29 Gender M W W M Ethnic group Caucasian From Maghreb Caucasian From Maghreb Chronic furonculosis No Yes No Yes SA infectious localizations Meningitis, epidural Enterocolitis, furunculosis Pneumonia with Shoulder cellulitis, abscess, sacro-iliitis, pleural effusion septicaemia muscular abscesses, cellulitis, pneumonia, septicaemia, SA-PVL sites Blood, skin, cerebro-spinal Skin, stool, nose, catheter Expectoration Blood, skin fluid Route of entry Sacral furuncles Inguinal and axillary None Arm and leg furuncles furuncles Leucocytes count at 22,0/337 16, 5/83 14, 6/354 13, 4/297 admission (x 109/l)/ CRP(mg/l) Immunodepression NSAID Steroids None None HIV status Negative Negative Negative Negative Other virulence factors B, M, O, Enterotoxins A, M, O, None Exfoliatin D G, I, N G, I, N Enterotoxins M, O, G, I, N, D, J

Resistance to anti- None None None OXA/KAN/TET/fusidic staphylococcal antibio- acid tics

Antibiotic treatment CFX/FOS, Fusidic Vibramycine (6 months) AMX/OFX VAN/GEN, RIF/OFX (total duration) acid/pefloxacin/FOS (10 d) (1 month) (6 months) Surgery None Drainage of axillary and None None inguinal abscesses IV IG (dose) Yes (0.5 g per kg for 4 d) Yes (0.5 grams per kg No No during 5 days) Outcome Cured Cured Cured Cured

SA: Staphylococcus aureus; M: man; W: woman; SA-PVL: Panton-Valentin leukocidin-producing Staphylococcus aureus; CRP: C reactive protein; NF: not found; NSAID: non-steroid anti-inflammatory drug; CFX: cefotaxime; AMX: amoxicillin; OXA: oxacillin; FOS: fosfomycin; KAN: kanamycin; TET: tetracycline; VAN: vancomycin; GEN: gentamicin; RIF: rifampicin; OFX: ofloxacin; IVIG: intravenous immunoglobulins; kg: kilogram. 194 Case Reports

Figure 1. Magnetic resonance image in T1 sequence shows multiple abscesses of the right tight (black arrows). of previous Quincke’s disease with penicillin), surgi- nation. Furunculosis was the route of entry cal drainage of abscesses and IVIG (2 g per kg over of infection for 3 patients (1,2 and 4). SA strains 5 consecutive days). carried other such as enterotoxins and The third patient was a young female who had exfoliatin in 3 patients that may have enhanced staphylococcal pneumonia without systemic and the severity of the infection. Indeed, patient 3, whose respiratory failures. strain did not produce other toxins, had the The fourth patient, with a past history of chronic less serious infection. Patient 4 harboured a MRSA furunculosis of arms and legs, had staphylococcal (mecA gene) also resistant to other antistaphylo- shoulder cellulitis complicating a septicaemia. coccal drugs. All patients have now fully recovered. In contrast to the literature, these observations For all strains, virulence factors production was highlight the variability of the clinical presentation of studied by the Centre National de Re´fe´rence such infection with unexpected multivisceral locali- de Toxe´mies Staphylococciques (Lyon, France). zations, especially involvement of the central nervous PVL production was characterized by polymerase system, bowel, muscles and joints. Nevertheless, a chain reaction (PCR) method using 2 primers [5] recent report described uncommon localizations (primer A3: 5 -AGTCAGCCAC-3 and primer ? ? such as tendosynovitis of the hand in a female 217D2: 5?-GCCCCCAGGGGCACAGT-3?). with Sezary syndrome [10]. Miller et al. reported Apart from the strain of patient 3, all strains 14 cases of necrotizing fasciitis caused by MRSA carried PVL genes with other virulence factors, such carrying PVL in Los Angeles [11]. An Australian as several enterotoxins (M, O, G, I, N), exfoliatin, study described 2 cases of osteomyelitis, 1 of Edin (A-C) and agr3 allele (up-regulator of the expression of toxin genes). One strain (patient 4) septic arthritis, 1 of psoas and 1 of paraspinal was a community-acquired methicillin resistant SA abscesses [12]. (CA-MRSA), also resistant to kanamycin, tetracy- Previously, SA-producing PVL was mostly sus- cline and fusidic acid. ceptible to methicillin; nevertheless a worldwide emergence since a few years of 5 clones of commu- nity-acquired MRSA, carrying type IV SCCmec and Discussion PVL genes, is becoming a public health problem In the present observations, SA producing PVL [13/16]. 70 to 90% of CA-MRSA strains, respon- infections were all community-acquired and oc- sive to skin and soft tissue infections, harbour this curred in immunocompetent young adults (mean leukocidin [17,18]. In Europe, a clone with a age 27.5 y, gender ratio/1). Nevertheless, patient 1 particular profile of resistance (kanamycin, cipro- received a non-steroid anti-inflammatory drug floxacin, tetracycline and fusidic acid) has emerged (NSAID) for lumbar pains and patient 2 was treated recently [13,14,16]. The MRSA strain of patient 3 with high doses of steroids for DRESS syndrome, exhibited this profile of resistance. Physicians should which may have facilitated staphylococcal dissemi- be attentive to this epidemiological aspect when Case Reports 195 confronted with serious SA infections resistant to a eus strain causing infantile pneumonia. J Clin Microbiol first line of antistaphylococcal drugs. 2001;39:/ 728/ /9. [9] De Bentzmann S, Tristan A, Etienne J, Brousse N, Vande- Two of our patients with persistent fever and nesch F, Lina G. Staphylococcus aureus isolates associated inflammation despite active antibiotherapy, received with necrotizing pneumonia bind to basement membrane

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