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Ventriculoperitoneal shunt infection caused by Staphylococcus lugdunensis

2001; Elsevier BV; Volume: 7; Issue: 7 Linguagem: Inglês

10.1046/j.1198-743x.2001.00268.x

1469-0691

Jonathan Sandoe, Christopher Longshaw,

Infective Endocarditis Diagnosis and Management

Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) with the capacity to cause opportunistic infections in humans. However, infections involving S. lugdunensis typically resemble those associated with S. aureus in terms of the virulence of the organism and the clinical course of infection, which is often highly destructive [1Vandenesch F Etienne J Reverdy ME et al.Endocarditis due to Staphylococcus lugdunensis. report of 11 cases and review.Clin Infect Dis. 1993; 17: 871Crossref PubMed Scopus (165) Google Scholar, 2Schnitzler N Meilicke R Conrads G et al.Staphylococcus lugdunensis: report of a case of peritonitis and an easy‐to‐perform screening strategy.J Clin Microbiol. 1998; 36: 812-813PubMed Google Scholar]. Clinical case reports of infection caused by this organism include native valve endocarditis, peritonitis, vertebral osteomyelitis and catheter-related infection but it has not previously been reported as a cause of ventriculoperitoneal (VP) shunt infection [1Vandenesch F Etienne J Reverdy ME et al.Endocarditis due to Staphylococcus lugdunensis. report of 11 cases and review.Clin Infect Dis. 1993; 17: 871Crossref PubMed Scopus (165) Google Scholar, 2Schnitzler N Meilicke R Conrads G et al.Staphylococcus lugdunensis: report of a case of peritonitis and an easy‐to‐perform screening strategy.J Clin Microbiol. 1998; 36: 812-813PubMed Google Scholar, 3Murdoch DR Everts RJ Chambers ST et al.Vertebral osteomyelitis due to Staphylococcus lugdunensis.J Clin Microbiol. 1996; 34: 993-994PubMed Google Scholar]. S. epidermidis is the most common cause of cerebrospinal fluid (CSF) shunt infections, causing more than 50% of cases in one series [4Bayston R Hydrocephalus shunt infections.J Antimicrob Chemother. 1994; 34: S75-S84Crossref PubMed Scopus (50) Google Scholar]. The affinity of S. epidermidis for medical devices, such as VP shunts, has been attributed to its ability to adhere to plastics, with the subsequent formation of biofilm which can reduce efficacy of treatment and cause persistence of infection [5Frebourg NB Lefebvre S Baert S et al.PCR‐based assay for discrimination between invasive and contaminating Staphylococcus epidermidis strains.J Clin Microbiol. 2000; 38: 877-880PubMed Google Scholar]. Biofilm formation is believed to be mediated via the intercellular adhesin gene cluster (tea), which is found more frequently in invasive S. epidermidis isolates than contaminating strains [5Frebourg NB Lefebvre S Baert S et al.PCR‐based assay for discrimination between invasive and contaminating Staphylococcus epidermidis strains.J Clin Microbiol. 2000; 38: 877-880PubMed Google Scholar, 6Von Eiff C Heilmann C Peters G New aspects in the molecular basis of polymer‐associated infections due to staphylococci.Eur J Clin Microbiol Infect Dis. 1999; 18: 843-846Crossref PubMed Scopus (102) Google Scholar]. This report describes a case of VP shunt infection caused by S. lugdunensis. In contrast to the usual indolent, subacute presentation of S. epidermidis VP shunt infection, this case presented acutely in a manner akin to a S. aureus infection. The association of S. lugdunensis with a VP shunt infection prompted a search for biofilm-forming ability which could be important for the pathogenicity of this organism. Since S. lugdunensis can cause aggressive infections, and shares some virulence factors with S. aureus, the causative strain was also investigated for hemolysin production and homologues of the global regulatory locus agr (accessory gene regulator) which regulates virulence factor production in S. aureus [7Novick RP Ross HF Projan SJ et al.Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule.EMBO J. 1993; 12: 3967-3975Crossref PubMed Scopus (791) Google Scholar]. A 74-year-old male was referred for management of normal pressure hydrocephalus. The patient had experienced increasing problems with walking, urinary incontinence, memory loss and loss of inhibition for 1 year prior to presentation. A computed tomography (CT) scan was performed and showed ventriculomegaly out of proportion to his cerebral atrophy. In 1996, the patient underwent insertion of a VP shunt and was discharged 7 days after the procedure, without any immediate postoperative problems. Seven days later the patient was readmitted with abdominal pain and sweating. The pain was right-sided, affecting the upper quadrant and was exacerbated by deep inspiration. On admission, the patient appeared ill and was pyrexic (37.9 °C). Peripheral white cell count was 17.5 × 109 /L. Intra-abdominal sepsis was suspected and a CT scan confirmed the presence of a small subphrenic collection and associated pleural effusion. The shunt was removed and the patient started empirically on intravenous vancomycin, cefuroxime and rifampicin. At the time of surgery, the scalp incision was opened first, and the ventricular tip and a specimen of CSF sent for microscopy and culture. The abdominal wound was then opened and, on removal of the peritoneal catheter, purulent fluid emerged from the abdominal cavity. Specimens of pus and the peritoneal catheter were sent for culture. Postoperatively, the patient made a good recovery and intravenous vancomycin with rifampicin was continued for 1 week. A further 1 week of oral ciprofloxacin and rifampicin was prescribed and the patient was discharged well. A penicillin was not prescribed because of a history of allergy. Initial microscopy and Gram stain of the CSF showed 6/mm3 red blood cells, 6/mm3 white blood cells and scanty Gram-positive cocci. The peritoneal pus contained >3000/mL red blood cells, > 3000/mL white blood cells but no organisms were seen. Cultures of CSF, intraperitoneal pus, ventricular catheter tip and peritoneal catheter tip subsequently grew a catalase-positive Gram-positive coccus which was clumping factor-positive, tube coagulase-negative (rabbit plasma) and DNAse-negative. The organism also demonstrated synergistic β-hemolysis when plated alongside S. aureus 8325 on sheep blood agar. The isolate was identified as S. lugdunensis by API 32 Staph identification kit (bioMerieux, Mary-l'Etoile, France) [API profile 467114600] and conventional tests. All four isolates were biochemically indistinguishable. The ability to adhere to plastic and subsequent biofilm formation was quantified using a microtitre plate assay. The optical density of S. lugdunensis biofilm at 590 nm was 0.245 compared with 0.458 shown by S. epidermidis S9 (a biofilm-producing strain), where values above 0.12 were considered to be positive for biofilm production. S. epidermidis and S. aureus adhesion to biomaterials and production of biofilm has been associated with production of extracellular polysaccharide adhesins PS/A and PIA, encoded by the intercellular adhesin (tea) locus [8Heilmann C Schweitzer O Gerke C et al.Molecular basis of intercellular adhesion in the biofilm‐forming Staphylococcus epidermidis.Mol Microbiol. 1996; 20: 1083-1091Crossref PubMed Scopus (714) Google Scholar, 9Ziebuhr W Heilmann C Götz F et al.Detection of the intercellular adhesion gene cluster (ica) and phase variation in Staphylococcus epidermidis blood culture strains and mucosal isolates.Infect Immun. 1997; 65: 890-896Crossref PubMed Google Scholar, 10Crampton SE Gerke C Schnell NF et al.The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation.Infect Immun. 1999; 67: 5427-5433PubMed Google Scholar]. Production of extracellular polysaccharide by the clinical isolate described here was initially indicated by production of black pigmented colonies when grown on Congo red agar (CRA). Because previous studies of S. epidermidis have shown an association between black pigmentation of colonies on CRA and a functional tea locus [9Ziebuhr W Heilmann C Götz F et al.Detection of the intercellular adhesion gene cluster (ica) and phase variation in Staphylococcus epidermidis blood culture strains and mucosal isolates.Infect Immun. 1997; 65: 890-896Crossref PubMed Google Scholar], it was decided to screen the genomic DNA of the isolate for the presence of a homolog of the icaA gene using PCR. Oligonucleotide primers: ICAP (GATGGAA-GTTCTGATAATAC) and ICAR (CCTCTGTCTGGGC-TTGACC), were designed towards regions of high sequence conservation between the icaA genes of S. epidermidis and S. aureus. Genomic DNA was prepared from S. lugdunensis and a PCR reaction using the above primers generated a single 973 (bp) DNA product. This correlated well with the expected size, predicted from the icaA sequence from S. epidermidis and S. aureus. The DNA product was subsequently sequenced from both DNA strands and was found to have high homology to the icaA genes of both S. epidermidis and S. aureus, with 80% and 92% identical residues, respectively. During infection, S. aureus produces a number of extracellular proteins that are important for the pathogenesis of the organism. Synthesis of many of these factors, including protein A, hemolysins, enterotoxins and toxic shock syndrome toxin − 1, is regulated by an untranslated mRNA molecule, RNAIII, whose expression level is modulated by the global regulatory locus, agr [11Morfeldt E Tegmark K Arvidson S Transcriptional control of the agr‐dependent virulence gene regulator, RNAIIIS, in Staphylococcus aureus.Mol Microbiol. 1996; 21: 1227-1237Crossref PubMed Scopus (137) Google Scholar]. agr-Related sequences have been demonstrated in S. lugdunensis previously and were investigated in this clinical isolate [12Vandenesch F Projan SJ Kreiswirth B et al.Agr‐related sequences in Staphylococcus lugdunensis.FEMS Microbiol Lett. 1993; 111: 115-122Crossref PubMed Google Scholar]. Oligonucleotide primers: RNAP (GACAGCT-TAGTGCCACATTT) and RNAR (GCCTAACTGTT-TAAT TCGCATA) were designed toward the S. lugdunensis RNAIII homologue using the published sequence (GenBank accession no. LI3334). PCR was carried out using S. lugdunensis genomic DNA and amplified a single 600 base pair (bp) DNA product which correlated with the expected size of 597 bp. The DNA product was subsequently identified as the S. lugdunensis RNAIII homolog by sequencing from both strands. CoNS are among the commonest causes of VP shunt infections [4Bayston R Hydrocephalus shunt infections.J Antimicrob Chemother. 1994; 34: S75-S84Crossref PubMed Scopus (50) Google Scholar]. It is the ability of these organisms to adhere to indwelling medical devices and form biofilms that allows them to colonize and persist on VP shunts. CoNS are usually low virulence pathogens and the VP shunt infections they cause are mostly indolent and subacute in presentation. In contrast, S. aureus shunt infections frequently manifest a systemic inflammatory response, signs of meningism and involve the shunt and surrounding tissues. The case described suggests that this strain of S. lugdunensis was able to adhere to shunt material and also cause an acute infection similar in clinical picture to S. aureus infection. This isolate of S. lugdunensis could adhere to plastic and form biofilms in vitro, and possessed pathogenicity factors homologous to those which are known to be important for similar infections in S. aureus. S. lugdunensis is usually susceptible to a wide range of antimicrobials, although treatment of CoNS VP shunt infections usually requires shunt removal in addition to antibiotics, as was necessary in this case, to achieve complete clearance of the infecting organism. Infections caused by this organism have been described as resembling those of S. aureus rather than the less virulent CoNS, and further evidence is provided here for the aggressive nature of S. lugdunensis and its significance as an opportunistic human pathogen [2Schnitzler N Meilicke R Conrads G et al.Staphylococcus lugdunensis: report of a case of peritonitis and an easy‐to‐perform screening strategy.J Clin Microbiol. 1998; 36: 812-813PubMed Google Scholar]. The ability of S. lugdunensis to cause infections of indwelling medical devices via biofilm formation and the presence of an icaA gene homolog warrants further investigation, as does the presence of an agr-related sequence whose role in this organism is unclear but which signifies the potential for coordinated virulence gene regulation. S. lugdunensis produces clumping factor but can readily be distinguished from S. aureus in the clinical diagnostic laboratory by negative tube coagulase and DNAse reactions. It is our opinion that isolation of S. lugdunensis should not be disregarded as a contaminant when recovered from a normally sterile body site and should prompt a rapid clinical evaluation by attending clinicians. Infections of VP shunts by S. lugdunensis can be added to the growing list of site-specific infections caused by this emerging opportunistic pathogen.