Unusually virulent coagulase-negative Staphylococcus lugdunensis is frequently associated with infective endocarditis: a Waikato series of patients

Staphylococcus lugdunensis, a species of coagulase-negative staphylococcus (CoNS), was first described by Freney et al in 1988.1 This organism is a rare contaminant in culture and commonly found on human skin. In addition this pathogen is associated with a wide variety of infections ranging from mild skin and soft tissue infections to serious infections such as brain abscess, septicaemia, chronic osteomyelitis and infective endocarditis.2-4Case reviews have demonstrated that S. lugdunensis infective endocarditis is associated with a high mortality and early operation is often advised.4-7 A positive blood culture for this pathogen is frequently an indication of invasive infection.We report a case series of S. lugdunensis bacteraemia and clinical management and outcomes from our institution.Methods All blood cultures reported positive for S. lugdunensis at Waikato Hospital between March 2006 to April 2011 were retrospectively reviewed. Patient's presenting complaints, diagnosis, duration of antibiotics therapy and longer term outcomes were assessed. Microbiological data were retrieved from the laboratory database and antimicrobial susceptibility was recorded. All cases of infective endocarditis fulfilled the modified Duke's Criteria.8 Results Eleven consecutive cases of S. lugdunensis bacteraemia were identified from our microbiology laboratory. The cases are summarised in Table 1. Overall, 3 (27%) patients had infective endocarditis, 1 (9%) patient had deep tissue infection, 1 (9%) had necrotizing fasciitis, 1 (9%) patient had multiple organism sepsis, 2 (18.5%) had skin infection, 1 (9%) had post-pacemaker insertion bacteraemia, and 2 (18.5%) had a diagnosis of fever of unknown origin. Transthoracic or transoesophageal echocardiography was performed in 6 (55%) of the patients. All isolates were susceptible to Flucloxacillin and Vancomycin. The majority of patients were successfully managed with Flucloxacillin alone. Cephalosporin (intravenous Cefazolin and oral Cefaclor) were used successfully in one case where the patient had penicillin allergy. All but one (91%) patient survived the acute presentation of bacteraemia. Mortality occurred in the patient who had nosocomial sepsis following pelvic radiotherapy, this patient progressed rapidly to multiorgan failure on the background of terminal metastatic prostate carcinoma. During the median follow-up period of 10 months, the cumulative mortality was 45%. Case synopses Endocarditis—Three cases (Case 4, 9, 11) of infective endocarditis related to S. lugdunensiswere identified in our series. One patient had native aortic valve involvement, one had mechanical mitral valve involvement and the third case had native mitral valve vegetation identified on a long standing prolapsing mitral valve leaflet. An 80-year-old woman (Case 4) who presented with fever, general malaise and rigors, subsequently had native aortic valve infective endocarditis associated with severe aortic regurgitation diagnosed. She was successfully managed with high dose intravenous Flucloxacillin for a total duration of 6 weeks. The presence of severe aortic regurgitation led to deterioration in cardiac function (ejection fraction). Surgical intervention was not recommended due to general frailty and co-morbidities. She died 9 months post admission due to cardiac failure. A second case of endocarditis case was diagnosed in a 70-year-old man (Case 9) with a previous St Jude mitral valve replacement who presented with several days of fever. He was aggressively managed with intravenous Flucloxacillin (6 weeks), Gentamicin (2 weeks) and oral Rifampicin (6 weeks). He had good response to the medical treatment and transoesophageal echocardiography did not demonstrate significant valvular or para-valvular dysfunction. This patient died 4 months later due to an unrelated subarachnoid haemorrhage; computed tomography of the head did not show features to suggest mycotic aneurysm. The final case of infective endocarditis was in a 56-year-old man (Case 11) with known mitral valve prolapse, associated with moderate mitral regurgitation under regular cardiology follow-up. He presented to the hospital 2 weeks prior with recent onset of fever and malaise which settled spontaneously. On that admission there was documented left hemiplegia, which resolved completely within several hours. A computed tomography scan of the brain did not reveal any acute lesions. A diagnosis of transient ischaemic attack (TIA) was made. On that particular admission, only a single blood culture was taken, and it grew a CoNS, which was not further identified at that time. Thus, based on the resolution of fever, it was believed that CoNS was a contaminant. He subsequently returned to hospital with intermittent fever, rigors and abdominal pain; the working diagnosis communicated to the laboratory was suspected appendicitis or diverticulitis. This time, the first blood culture set grew two CoNS, one of which was identified as S. lugdunensis. A third set, taken 2 days later, grew only the S. lugdunensis. An urgent transthoracic echocardiography revealed a vegetation on the anterior mitral leaflet associated with severe mitral regurgitation which was confirmed on transoesophageal echocardiography. This patient underwent urgent mitral valve replacement surgery and a 6 week course of intravenous Flucloxacillin. Other infections—A number of other infections including deep tissue infection, necrotising fasciitis, severe nosocomial systemic sepsis, superficial skin infection, post-pacemaker implantation bacteraemia, and fever of unknown origin have also been associated with S. lugdunensis. The patient characteristics, diagnosis, antibiotics regime, duration, echocardiographic investigations and outcomes were summarized in Table 1. Flucloxacillin, Vancomycin, Amoxycillin-Clavulanate, second and third-generation of Cephalosporin monotherapy or combination had been used in treatment. Two of these eight patients died in the follow-up with associated comorbidities that resulted immunosuppression (Case 2 & 6, Table 1). One patient with end stage prostate cancer died in hospital due to nosocomial infection which progressed to multiorgan failure (Case 8, Table 1). Discussion S. lugdunensis infection, unlike sepsis due to other species of CoNS, is frequently aggressive and life threatening in nature.9 In our single centre report of 11 patients with S. lugdunensisbacteraemia presenting over a 5-years period, this organism was associated with serious clinical infection in almost half of the cases. This observation is similar to other published experience, where S. lugdunensis is reported as a virulent pathogen, causing invasive infection similar toStaphyloccocus aureus, particularly in the setting of infective endocarditis.4,10-12 In our series, 3 (27%) cases of S. lugdunensis bacteraemia were due to infective endocarditis which merits further discussion. The incidence of endocarditis in patients with S. lugdunensisbacteraemia is not well established. It is reported as high as 46% by Zinkernagel et al.11 Other studies report a much lower incidence of infective endocarditis with S. lugdunensis bacteremia from 0 -7%.12-14 Of note, in the presence of multiple positive blood cultures, systemic inflammatory response syndrome, sepsis or septic shock, the incidence of endocarditis was considerably higher in most series; 1 (17%) of 6 by Ebright et al and 4 (27%) of 15 by Choi et al.12,14 In our series, both native and prosthetic valves proved susceptible to infection which is in concordance with other series. In addition, pacemaker lead infection, as described in our series, can result in infective endocarditis, which was not clinically suspected in our patient, although no echocardiography was undertaken. Our series revealed that only 6 (55%) patients had echocardiogram performed with 4 (66%) of this cohort also undergoing transoesophageal echocardiography. The 2009 European Society of Cardiology (ESC) guidelines on the prevention, diagnosis and treatment of infective endocarditis recommends echocardiography in cases where infective endocarditis were highly suspected and\/or in patients with S. aureus bacteriaemia.15 Recommendation of echocardiography in patients with S. lugdunenesis bacteraemia, however, is not clear. Due to its aggressive nature and high association with infective endocarditis and devastating effects once intracardiac infection is established, we support, as a minimum, routine transthoracic echocardiography in this group of patients. S. lugdunensis endocarditis is associated with a high mortality rate with frequent surgical intervention considered necessary. Anguera et al, in a series of 912 consecutive endocarditis, reported the overall mortality of S. lugdunensis, S. aureus and Staphylococcus epidermidis as 50%, 14.5% and 20% respectively; surgery was performed in 70%, 36.9% and 60% respectively. Although S. lugdunensis accounts for 1.1% cases of endocarditis in this series, the high mortality rate highlights the aggressive nature of this particular CoNS in the setting of endocarditis.4 Liu et al, in their recent review of 67 cases of S. lugdunensis infective endocarditis from 1988 to 2008, documented that 82.5% of cases were left-sided valvular endocarditis, 78.7% occurred in native valves, with surgery performed in 66.7% of cases and a mortality rate of 38.8%.5 Unlike most of the CoNS, S. lugdunensis appears susceptible to a wide range of antibiotics including Penicillin, Cefazolin, Linezolid, Moxifloxacin, Nafcillin, Quinupristin-Dalfopristin, Rifampicin, Tetracycline, Trimethoprim-Sulfamethoxazole, and Vancomycin, using standard in vitro methods.16 However, Linezolid and Vancomycin were not bactericidal. In a biofilm model, the activity of most antibiotics was severely reduced and Nafcillin (a congener of the Flucloxacillin used in our case series) increased the production of biofilm.16 The 2009 European Society of Cardiology guidelines on the prevention, diagnosis and treatment of infective endocarditis has acknowledged the aggressive nature of S. lugdunensis and the recommended treatment is the same for Staphylococcus species which involves 4-6 weeks of Flucloxacillin (or Oxacillin) with 3-5 days of Gentamicin for native valve infection. For patients with prosthetic valve infection or Methicillin-resistant strains, addition of Rifampicin or the use of Vancomycin may be considered.15 All isolates in our series were susceptible to Flucloxacillin and Vancomycin. Oral treatment with Cephalosporin (Cefuroxime & Cefaclor) in simple soft-tissue infection appeared to be effective in our case series. The high rate of susceptibility to beta-lactams in our series is in concordance with available data.4,10,11 Multiple antibiotics resistance is rare in the literature and was not observed in our study. One of the described cases of infective endocarditis had CoNS identified on the admission blood culture which was initially considered to be a contaminant. As a consequence, no further identification was carried out. It is recommended that three sets of blood cultures are performed in cases of suspected endocarditis as continuous bacteraemia occurs. Contamination usually only affects one sample. This particular patient presented as fever and transient ischaemia attack which retrospectively may have represented an embolic event secondary to infective endocarditis. On the second presentation to the hospital 2 weeks later, three sets of blood cultures demonstrated S. lugdunensis and the initial culture was then re-studied and confirmed to be the same organism. Reliable methods for identification of of S. lugdunensishave been well described.1,17,18 S. lugdunensis colonies usually appear similar to other CoNS after 24 hrs incubation: small, white and non haemolytic. After 48 hrs, a faint yellow colour is often visible and they may resemble S. aureus. A high degree of skill and awareness is required for prompt recognition. Many laboratories use slide and rapid latex agglutination tests to distinguish S. aureus from CoNS but these kits do not detect staphylococcal coagulase itself. S. lugdunensis can be falsely identified as S. aureus due to the presence of clumping factor. In an experienced hand, phenotypic characteristics such as colony pleomorphism and beta-haemolysis are useful in detecting S. lugdunensis, in contrast to clumping and synergistic haemolysis, which characterize several CoNS species.19 Bocher et al in their study found that,S. lugdunensis has a prominent beta-haemolysis and characteristic Eikenella-like odour 2 days after incubation on Columbia agar with 5% sheep blood; by combining with these features and colony pleomorphism they were able to increase the yield of S. lugdunensis identification by 11-fold in all types of cultures.20 Conclusion S. lugdunensis bacteraemia is associated with infective endocarditis in one in three patients. Investigation for suspected endocarditis should include at least three sets of blood cultures, to distinguish contamination or transient bacteraemia from the continuous bacteraemia of endocarditis. Assessment for the presence of endocarditis with echocardiography should be considered strongly in all cases of S. lugdunensis bacteraemia.