You are on page 1of 7

Diagnostic Microbiology and Infectious Disease 57 (2007) 325 331

www.elsevier.com/locate/diagmicrobio
Case report
Staphylococcus haemolyticus endocarditis:
clinical and microbiologic analysis of 4 cases
Marco Falconea, Floriana Campanileb, Maddalena Giannellaa,
Sonia Borboneb, Stefania Stefanib, Mario Vendittia,4
a
Department of Clinical Medicine, Policlinico Umberto I, University of Rome bLa SapienzaQ, 00185 Rome, Italy
b
Department of Microbiology, University of Catania, 95124 Catania, Italy
Received 24 June 2006; accepted 28 August 2006

Abstract

Only 3 cases of infective endocarditis (IE) due to methicillin-resistant Staphylococcus haemolyticus (MRSH) have been reported in
English literature. Here we report 4 cases of IE due to MRSH encountered in a single university hospital. Population analysis of the strains
was performed to assess the presence of vancomycin/teicoplanin heteroresistant subpopulations. Pulsed-field gel electrophoresis was used for
molecular typing of isolates. IE was defined in 3 cases as health care associated, and in 1 case, as community acquired. A causative strain was
lost. Two strains were heteroresistant to teicoplanin, and 1 also to vancomycin. Genome macrorestriction profile studies demonstrated that
2 MRSH isolates belonged to clones A and E, possessing a class C1 mecDNA, whereas 1 clone was sporadic. All patients were treated with
vancomycin plus rifampin. Two patients were cured with antibiotic therapy alone, 1 patient needed surgery, and 1 patient died. Methicillin-
resistant multiresistant S. haemolyticus may represent a difficult-to-treat cause of both community and nosocomially acquired IE.
D 2007 Elsevier Inc. All right reserved.
Keywords: Staphylococcus haemolyticus; Infective endocarditis; Teicoplanin; Vancomycin; Heteroresistance; Molecular epidemiology

1. Introduction islands conferring a large variation to the combination of


virulence and resistance genes not only intraspecies but also
Coagulase-negative staphylococci (CoNS) have been
interstaphylococcal species (Baba et al., 2004; Tackeuchi
considered to be low-virulent pathogens, but during the last
et al., 2005).
decades, they have emerged as a major cause of infection,
Among CoNS, Staphylococcus haemolyticus is of increas-
particularly in hospitalized patients with implanted devices
ing importance as a cause of nosocomial infections (Santos
(Viale and Stefani, 2006). CoNS are a leading cause of
Sanchez et al., 2000; Falcone et al., 2004, 2006; Raponi et al.,
prosthetic valve endocarditis (PVE), but recent evidence has
2005), and today, it represents the 3rd most common organism
indicated that they are an emerging cause of native valve
among clinical isolates of methicillin-resistant staphylococci
endocarditis (NVE) (Chu et al., 2004). These infections are
(Santos Sanchez et al., 2000). In addition, S. haemolyticus is
associated with high rates of heart failure, valvular surgery,
frequently resistant to multiple antibiotics, and, unique among
and mortality (Anguera et al., 2005).
staphylococcal species, it is predisposed to develop resistance
The increased recognition of the role of CoNS as
pathogens is not only the result of medical progress: in to glycopeptides (Billot-Klein et al., 1996; Campanile et al.,
fact, it is becoming more evident that various staphylococcal 2006). Some recent reports have recognized S. haemolyticus as
species express proteins that were until recently thought to the cause of severe infections, including meningitis, skin or
belong exclusively to Staphylococcus aureus. Furthermore, soft tissue infections, prosthetic joint infections, or bacteremia
comparative genome analyses revealed that many staphylo- (Falcone et al., 2004, 2006; Raponi et al., 2005; Huang et al.,
coccal genes involved in pathogenicity and drug resistance 2005; Shittu et al., 2004). However, infective endocarditis (IE)
are localized on mobile genetic elements or genomic caused by S. haemolyticus is a very rare infectious process, not
specifically examined in English medical literature (Rocha
4 Corresponding author. Tel.: +39-649972083; fax: +39-64940421. et al., 1999; Louagie et al., 1998; Krcmery et al., 2003). In
E-mail address: mario.venditti@uniroma1.it (M. Venditti). fact, the International Collaboration on Endocarditis Merged
0732-8893/$ see front matter D 2007 Elsevier Inc. All right reserved.
doi:10.1016/j.diagmicrobio.2006.08.019
326 M. Falcone et al. / Diagnostic Microbiology and Infectious Disease 57 (2007) 325 331

Database (ICE-MD) investigation, involving 99 episodes of 2.3.2. In vitro susceptibility testing


native valve IE due to CoNS (the largest study to date), did A panel of antibiotics (i.e., oxacillin, erythromycin,
not find any case caused by this organism (Chu et al., 2004). cotrimoxazole, clindamycin, ciprofloxacin, gentamicin, ri-
We report 4 cases of methicillin-resistant S. haemolyticus fampin, vancomycin, teicoplanin, and linezolid) was tested
(MRSH) IE (1 NVE and 3 PVE), encountered during a by the broth microdilution method to determine the MIC
period of 2 years (20032004) in a single university following the Clinical Laboratory Standard Institute (2005)
hospital, and describe some salient clinical and microbio- guidelines. Methicillin resistance was detected by standard
logic features and outcomes of these infections. methods and confirmed by PCR for the presence of the
mecA gene (de Lencastre et al., 1994).
To assess the presence of vancomycin-heteroresistant
2. Methods
subpopulations, population analysis of the strains from the
2.1. Setting infected patients and control strains was performed according
to the method previously described (Hiramatsu et al., 1997).
The study was conducted in the Policlinico Umberto I,
Briefly, serial dilutions of an overnight culture in Mueller-
University of Rome, Rome, Italy (1), during the period
Hinton broth (Oxoid, Milan, Italy) were plated (100 AL) on
of 2004 to 2005 in which CoNS bacteremia was care-
Brain Heart Infusion (BHI) agar plates (Oxoid, Milan, Italy)
fully monitored. Microorganisms primarily identified as
containing the following concentrations of vancomycin: 0, 1,
S. haemolyticus were sent to the Department of Microbiol-
2, 4, 6, 8, or 10 mg/L. Heteroresistance was defined as the
ogy, University of Catania, Catania, Italy (2), for identifica-
presence of vancomycin-resistant colonies at a frequency of
tion, confirmation, and further molecular characterizations.
1  10 6 or higher.
Unfortunately, 1 isolate (case 3) was lost.
Furthermore, inducible resistance to clindamycin was
2.2. Case definitions tested for all strains susceptible to the drug by disk
approximation test with erythromycin as formerly described
IE was diagnosed on the basis of modified Duke criteria
(Schreckenberger et al., 2004).
(Li et al., 2000). Health-careassociated IE was defined as
either nosocomial infection or nonnosocomial health-care
2.3.3. Molecular typing
associated infection. Nosocomial infection was defined as
Pulsed-field gel electrophoresis (PFGE) was used for
IE developing in a patient hospitalized for more than 48 h
molecular typing of all isolates. SmaI restriction analysis was
before the onset of signs/symptoms consistent with IE. Non-
carried out in a CHEF-DR II apparatus (Bio Rad, Hercules,
nosocomial health-careassociated infection was defined as
CA), after running conditions already described (Mato et al.,
IE diagnosed within 48 h of admission of an outpatient with
2004). The restriction profiles of the 3 IE isolates were
extensive health care contact as reflected by any of the
compared with other bloodstream S. haemolyticus strains
following criteria: 1) received intravenous therapy, wound
isolated in the same hospital (European Congress on Clinical
care, or specialized nursing care at home within 30 days
Microbiology and Infectious Diseases [ECCMID], Campa-
before the onset of IE; 2) attended a hospital or hemodial-
nile et al., 2006). Similarities among SmaI restriction patterns
ysis clinic or received intravenous chemotherapy within
were identified according to established criteria (Tenover
30 days before onset of IE; 3) was hospitalized in an acute
et al., 1995). Isolates were considered to be clonal when they
care hospital for 2 days or more in the 90 days before the
showed identical PFGE profiles and were then assigned to the
onset of IE; or 4) resided in a nursing home or long-term
same PFGE type, or differed by V 3 bands, and were then
care facility. Community-acquired IE was defined as IE
assigned to different subtypes of the same PFGE type.
diagnosed at the time of admission (or within 48 h of
admission) in a patient not fulfilling the criteria for health-
2.3.4. PCR analysis of the mec complex structure
careassociated infection (Fowler et al., 2005).
In the strains tested, the molecular analysis of the mec
2.3. Microbiologic detection and characterization of complex was performed by extracting whole genomic DNA,
S. haemolyticus as previously described (Pitcher et al., 1989). The PCR
amplification for the characterization of the complex was
2.3.1. S. haemolyticus strains performed in a Biometra Personal Cyclerk Gottingen,
All S. haemolyticus isolated from the 4 cases of IE in the Germany after a procedure previously described (Katayama
study were collected and reconfirmed for their identification et al., 2001).
by biochemical tests (API-staph system, BioMerieux, Marcy
LEtoile, France) and on the basis of molecular identifica-
tion by polymerase chain reaction (PCR) and sequencing 3. Results
of a variable region of the 16S rRNA gene, by using
3.1. Case reports
oligonucleotides previously published (Skow et al., 2005).
All strains were kept at 80 8C until their use for further Description of patients and clinical features of the 4 cases
molecular characterizations. of S. haemolyticus IE are summarized in Table 1.
M. Falcone et al. / Diagnostic Microbiology and Infectious Disease 57 (2007) 325 331 327

Table 1
Clinical features of 4 cases of S. haemolyticus endocarditis
No. Age/sex Risk factors Clinical presentation No. of Location and Antibiotic Surgery Complications 12-month
positive blood maximum a (cm) therapy follow-up
cultures/total of vegetations on
echocardiography
1 70/F Hepatitis C virus Dyspnea, cardiac 4/5 NV (aortic), 0.8 Vanco Yes Heart failure Cured
infection, joint murmur, low-grade plus rifa
prosthesis, recent fever, leukocytosis
hospitalization
2 72/M PV, CAD Fever, peripheral 4/4 PV, 0.7 Vanco plus No Peripheral Improved, C. albicans
embolism, rifa plus embolism PVE 7 months
leukocytosis genta (radial artery) after antibiotic
discontinuation
3 77/M PV Fever, sweating, 3/3 PV, 0.6 Vanco No Improved, lost
leukocytosis plus rifa after a 3-month
follow-up
4 65/M PV, diabetes Fever, neurologic 4/5 Vanco No Cerebral mycotic
mellitus symptoms, plus rifa aneurysm,
leukocytosis rupture, death
a = diameter; NV = native valve; PV = prosthetic valve; CAD = coronary artery disease; Vanco = vancomycin; rifa = rifampin; genta = gentamicin.

3.1.1. Case 1 positive cocci. The patient completed an 8-week course of


A 70-year-old woman was admitted to hospital with a antibiotic therapy with vancomycin and rifampin, com-
10-day history of progressive dyspnea, sweating, and bined with gentamicin during the initial 2 weeks of
bilateral leg edema. She did not report fever in the previous therapy. A transesophageal echocardiography performed
days. Nine months previously, she had undergone left hip after 47 days of antibiotic therapy revealed the disappear-
replacement. Twenty-five days before admission, she was ance of the aortic vegetation. Seven months after antibiotic
hospitalized for an episode of acute gastrointestinal bleed- discontinuation, the patient developed a new episode of IE
ing. On admission, the patient had low-grade fever, symp- (caused by Candida albicans) and underwent a new aortic
toms, and signs of congestive heart failure, and a grade IV valve replacement.
diastolic murmur was present. As soon as 3 of 4 blood
culture sets grew CoNS, therapy with teicoplanin (7 mg/kg 3.1.3. Case 3
every 24 h) was started. On day 3 of teicoplanin therapy, a On day 19 after aortic valve replacement, a 77-year-old
new blood culture set grew CoNS. All the CoNS isolates male patient developed fever up to 39 8C. A set of 3 blood
were recognized as MRSH. A transthoracic and trans- cultures grew CoNS, eventually identified as MRSH, and a
esophageal echocardiography revealed 1 large (8 mm) and transesophageal echocardiogram demonstrated a 6-mm
some smaller vegetations on the aortic valve, severe aortic vegetation on the aortic prosthetic valve. Empiric therapy
insufficiency, and moderate mitral regurgitation. Antibio- with vancomycin and rifampin was promptly started. The
tic therapy was shifted to vancomycin plus rifampin with day after, 1 additional blood culture yielded an MRSH, but
clearance of S. haemolyticus bacteremia. After a 6-week on subsequent days, the patient progressively improved with
antibiotic treatment, the patient underwent aortic valve clearance of bacteremia. The patient completed an 8-week
replacement; cultures of the removed valve did not yield course of vancomycin plus rifampin treatment in another
microbial growth. No relapse was observed during a hospital closer to his home, but he was lost to follow-up
12-month follow-up. 3 months after antibiotic discontinuation.

3.1.2. Case 2 3.1.4. Case 4


A 72-year-old man was readmitted to the cardiosurgery A 65-year-old man was admitted to the neurosurgery
unit of our hospital for the onset of fever, chills, dyspnea, intensive care unit for the sudden onset of headache and
and acute pain of the left thumb and finger index. Ten aphasia rapidly progressing to coma. The patient had a
months earlier, he had undergone coronary bypass surgery history of aortic valve replacement 5 years earlier for aortic
and aortic valve replacement for severe aortic stenosis. At stenosis. He had no recent history of fever. At admission,
admission, a Doppler ultrasonography revealed an embolus the patient was febrile. Physical examination revealed finger
in the distal radial artery. Immediate therapy included a clubbing and Janeway lesions; laboratory studies showed a
selective surgical embolectomy of the distal radial artery marked increase of his white cell count (17 300/mm3)
followed by a local intra-arterial lysis. Four blood cultures with neutrophilia (88%). Magnetic resonance imaging
grew an MRSH. A transesophageal echocardiography showed a subarachnoid hemorrhage localized in the right
showed a 7-mm vegetation on the prosthetic aortic valve. left temporoparietal region. Four blood cultures grew a
Histology examination of the embolus demonstrated Gram- teicoplanin-susceptible MRSH strain. Cerebral angiography
328 M. Falcone et al. / Diagnostic Microbiology and Infectious Disease 57 (2007) 325 331

Table 2
Microbiologic studies
Strains Identification Origin PFGE Mec DNA Susceptible to Resistant to DD test Vanco Teico
heteroresistance heteroresistance
Case 1 S. haemolyticus HCA Clone A Class C1 Vanco, rif, clinda, Teico, ery, No No
M /MR (nonnosocomial) clor, tetra, lin cotri, cipro, genta induction
6 6
Case 2 S. haemolyticus HCA Clone E Class C1 Rif, clinda, cotri, Ery, cipro, genta No 10 10
M+/MR (nosocomial) clor, tetra, lin induction
Case 3 S. haemolyticus HCA Not Vanco, rif, clinda, Teico, cotri,
M+/MR (nosocomial) performed clor, tetra, lin ery, cipro, genta
5
Case 4 S. haemolyticus CA Sporadic Class C1 Vanco, rif, genta, Ery, cotri, cipro Yes No 10
M /MR clone clinda, clor, tetra, lin
In case 3, the causative strain was lost for further microbiologic investigation.
M /MR = mannitol nonfermenter/methicillin resistant; M+/MR = mannitol fermenter/methicillin resistant; HCA = health-care associated; Vanco =
vancomycin; teico = teicoplanin; rif = rifampin; clinda = clindamycin; clor = cloramphenicol; tetra = tetracycline; lin = linezolid; ery = erythromycin;
cotri = cotrimoxazole; cipro = ciprofloxacin; genta = gentamicin.

demonstrated a cerebral, probably mycotic, aneurysm at the et al., 2006). The strain was resistant to teicoplanin and
right communicans posterior artery. Although the transtho- many other antibiotics (Table 2). Clone A is 1 of the most
racic echocardiography did not show vegetations, a diag- diffused clones in the hospital (accounting for approximate-
nosis of IE was made on the basis of a modified Duke ly 30% of S. haemolyticus isolates) and is a multiresistant
criteria (Li et al., 2000). He was treated with vancomycin clone (Fig. 1).
plus rifampin. Despite clearance of MRSH bacteremia, the The hospital-acquired MRSH mannitol fermenter isolate
patients general conditions worsened, and he died after in case 2 was identified as the clone E, less diffused with
9 days in a deep coma. Autopsy was not performed. respect to clone A, and was circulating in the hospital in
2004. This multiresistant clone was susceptible to rifampin,
3.2. Microbiologic characterization
clindamycin, cotrimoxazole, chloramphenicol, and tetracy-
Isolates from 3 of the 4 cases of S. haemolyticus were cline. The strain showed induction of clindamycin resist-
available for molecular studies. Details of their character- ance by erythromycin and showed heteroresistance at the
ization are shown in Table 2 and Figs. 1 and 2. frequency of 10 6 to both glycopeptides at the concentration
The genotypic features of the MRSH strains in the study of z 8 mg/L. In spite of the presence of subpopulations
were compared by PFGE analysis. The SmaI patterns were resistant to vancomycin, the association between vancomy-
correlated with those of other bloodstream S. haemolyticus cin and rifampin was effective and synergic, as demonstrat-
strains isolated in the same hospital. The results showed that ed by the in vitro timekill experiment in which a reduction
in 2 of the 3 cases (1 and 2), the PFGE profiles of N3 log10 CFU was seen.
corresponded to those of the multiresistant MRSH clones From the 4 blood cultures of case 4, a mannitol
that were widespread in the hospital (A and E) (Fig. 1). nonfermenter community-associated (CA) MRSH strain
The MRSH strain isolated in case 1 was genotypically was isolated. The strain, genotypically characterized as a
characterized as belonging to the methicillin-resistant sporadic clone, was susceptible to vancomycin, rifampin,
mannitol nonfermenter clone A, circulating in the hospital clindamycin, cloramphenicol, and tetracycline, and resistant
in 2000; this clone, after a period of disappearance, persisted to erythromycin, cotrimoxazole, and ciprofloxacin. This
in the same hospital environment until 2005 (Campanile strain showed clindamycin induction of resistance by

Fig. 2. (A) Amplification with IS431F-mecA (A and C1), IS431R-


Fig. 1. (A) PFGE profiles of a sample of MRSH strains spread in the mecA (C2), and IS1272-mecA (B). (B) mec complex A was confirmed
hospital (Campanile et al., 2006); the PFGE types of the strains in study (in by mecI PCR. All the MRSH strains in the study showed a mec complex
bold) are already shown in panel B. of class C1.
M. Falcone et al. / Diagnostic Microbiology and Infectious Disease 57 (2007) 325 331 329

erythromycin and was heteroresistant to teicoplanin at the laboratories, which mainly receives clinical specimens from
frequency of 10 5 at the concentration of z 8 mg/L. posttrauma/postsurgery and posttransplantation intensive
care unit, found that S. haemolyticus was the 2nd most
3.3. mecA complex
common cause of CoNS bacteremia (after Staphylococcus
In each MRSH isolate, methicillin resistance was due to epidermidis), accounting for 22% to 24% of central nervous
the presence of the mecA gene. To define the structural system isolates annually (Raponi et al., 2005). Similar
diversity of the mec complex of the MRSH strains, we results were found analyzing the annual incidence of CoNS
characterized this region by PCR; the sequences of primers bacteremia in patients with hematologic malignancies
were selected to overlap the IS431 insertion sequence (Falcone et al., 2004). The large use of teicoplanin in our
(in the 2 different orientations) and the mecA gene. All the hospital was postulated to be a factor leading to the noso-
S. haemolyticus strains in the study showed a copy of IS431 comial spread of S. haemolyticus (Falcone et al., 2006).
upstream, and in the same orientation of the mecA gene, However, the clinical significance of MRSH bacteremia
confirming a mec-complex structure of class C1 (Fig. 2). remained uncertain, and our data showed that isolation of
MRSH from bacteremic patients with hematologic malig-
nancies was associated with negligible morbidity/mortality
4. Discussion
rates (Falcone et al., 2004). On the contrary, the present
Although S. haemolyticus is frequently considered a study demonstrates that MRSH IE may be associated
contaminant when isolated from normally sterile body with left-sided valvular disruption, embolic complications,
fluids, the 4 cases presented here show the potential of and death.
S. haemolyticus to cause complicated NVE and PVE. To our It is interesting to note that community-acquisition of
knowledge, the present study represents the largest series of MRSH infection was suggested in 1 patient of our series
IE due to S. haemolyticus observed in a single institution. who had no risk factors for health-careassociated staphy-
A Medline search of the English-language medical literature lococcal infection. Molecular studies confirmed this hy-
conducted using the terms S. haemolyticus and endocarditis pothesis because the causative strain was characterized as a
revealed only 2 cases in hemodialysis patients (Rocha et al., sporadic clone not previously isolated in our hospital. To
1999; Louagie et al., 1998) and 1 case among a total number our knowledge, severe community-acquired infections
of 339 IE observed in the Slovak Republic (Krcmery et al., caused by S. haemolyticus have not been previously
2003). The rarity of this infection is confirmed by the data reported. On the other hand, we would like to stress that
of the ICE-MD investigation, which did not identify any MRSH was also the cause of both nosocomial and
case of NVE caused by this organism (Chu et al., 2004). nonnosocomial health-careassociated IE.
The real incidence of multidrug-resistant CoNS infec- As observed in cases of endocarditis due to other CoNS,
tions could be underrecognized or underreported for at least patients with S. haemolyticus IE share high rates of
2 reasons: i) because of the lack of identification at the predisposing comorbid conditions, including advanced age
species level of this group of microorganisms (many lab- and requiring frequent hospitalization. These clinical fea-
oratories identify at the species level only S. aureus), or ii) tures might have affected the clinical presentation of MRSH
when identification is carried out through conventional IE, which was rather insidious in 2 patients (cases 1 and 4),
methods and commercial identification kits are used, there is who were unaware of their fever, and sought medical
a risk of misidentification because the biochemical traits of attention for severe complications such as heart failure or
the species are similar and many clinical isolates show cerebral hemorrhage due to ruptured mycotic aneurysm. As
intermediate traits (Kawamura et al, 1998). suggested by previous reports (Terpenning et al., 1987;
Full and accurate identification of CoNS isolates is Werner et al., 1996), elderly patients are less likely to
important for clinical and epidemiologic interest to clinicians complain of fever or chills than young and middle-aged
because particular species are also associated with distinct patients. On the other hand, the indolent clinical course of
patterns of antimicrobial susceptibility (Kloos and Banner- IE due to MRSH might also be explained by the low
man, 1994): misidentification can limit treatment options, virulence of our isolates, which allowed a slow progression
causing severe consequences for patients. For these reasons, of infection.
DNA-based assays for the identification of staphylococci As already reported (Raponi et al., 2005; Campanile et al.,
isolated from clinical specimens are necessary for improving 2006), MRSH isolates were frequently heteroresistant to
the accuracy of the diagnosis of staphylococcal infections. glycopeptides, especially to teicoplanin. This phenomenon
The role of S. haemolyticus as a cause of nosocomial seems to be clinically relevant, because we observed a poor
infections is not surprising, because over the last few years, clinical response in case 1, where the patient remained
it has been isolated with increasing frequency from patients bacteremic under teicoplanin therapy and improved only
admitted to our hospital, particularly those at high risk of after the introduction of vancomycin in combination with
infection such as hematologic patients (Falcone et al., 2004) rifampin. Vice versa, bactericidal synergism between vanco-
or intensive care unit patients (Raponi et al., 2005). During mycin and rifampin, documented by the timekill curve
the period 2000 to 2003, 1 of the hospital microbiology study, might have favored the microbiologic eradication of
330 M. Falcone et al. / Diagnostic Microbiology and Infectious Disease 57 (2007) 325 331

PVE caused by the vancomycin heteroresistant MRSH JT, Elliott TS, Levine DP, Bayer AS, ICE investigators (2005)
in case 2. Staphylococcus aureus endocarditis. A consequence of medical
progress. JAMA 293:3012 3021.
In conclusion, our series suggests that MRSH may Hiramatsu K, Aritaka N, Hanaki H, Kawasaki S, Hosoda Y, Hori S,
represent a cause of IE. The associated glycopeptide Fukuchi Y, Kobayashi I (1997) Dissemination in Japanese hospitals of
heteroresistance is alarming and stresses the importance of Staphylococcus aureus strains heterogeneously resistant to vancomycin.
new antibiotics with bactericidal activity against this Lancet 350:1670 1673.
organism. Further studies on clinical and molecular charac- Huang CR, Lu CH, Wu JJ, Chang HW, Chien CC, Lei CB, Chang WN
(2005) Coagulase-negative staphylococcal meningitis in adults: clinical
teristics of MRSH are needed to clarify the epidemiology characteristics and therapeutic outcomes. Infection 33:56 60.
and clinical significance of this pathogen. Katayama Y, Ito T, Hiramatsu K (2001) Genetic organization of the
chromosome region surrounding mecA in clinical staphylococcal
strains: role of IS431-mediated mecI deletion in expression of resistance
Acknowledgments in mecA-carrying, low-level methicillin-resistant Staphylococcus hae-
molyticus. Antimicrob Agents Chemother 45:1955 1963.
This work was supported by a grant from the Italian Kawamura Y, Hou X, Sultana G, Hirose F, Miyake K, Shu M, Ezaki SE
Ministry of Education, University and Scientific Research (1998) Distribution of Staphylococcus species among human clinical
(MIUR). specimens and emended description of Staphylococcus caprae. J Clin
Microbiol 36:2038 2042.
Kloos WE, Bannerman TL (1994) Update on clinical significance of
References coagulase-negative staphylococci. Clin Microbiol Rev 7:117 140.
Krcmery V, Gogova M, Ondrusova A, Buckova E, Doczeova A, Mrazova
Anguera I, Miro JM, Cabell CH, Abrutyn E, Fowler Jr VG, Hoen B, M, Hricak V, Fischer V, Marks P, Slovak Endocarditis Study Group
Olaison L, Pappas PA, de Lazzari E, Eykyn S, Habib G, Pare C, Wang (2003) Etiology and risk factors of 339 cases of infective endocarditis:
A, Corey R, ICE-MD investigators (2005) Clinical characteristics and report from a 10-year national prospective survey in the Slovak
outcome of aortic endocarditis with periannular abscess in the Republic. J Chemother 15:579 583.
International Collaboration on Endocarditis Merged Database. Am J Li JS, Sexton DJ, Mick N, Nettles R, Fowler Jr VG, Ryan T, Bashore T,
Cardiol 96:976 981. Corey GR (2000) Proposed modifications to the Duke criteria for the
Baba T, Takeuchi F, Kuroda M (2004) The Staphylococcus aureus genome. diagnosis of infective endocarditis. Clin Infect Dis 30:633 638.
In Staphylococcus aureus Molecular and Clinical Aspects. Eds, D Louagie H, Struelens M, De Ryck R, Claeys G, Verschraegen G, Vogelaers
Aladeen and K Hiramatsu. Chichester, UK7 Harwood Publishing D, Lameire N, Vaneechoutte M (1998) Problems in diagnosis and
Limited, pp 66 153. treatment of Staphylococcus haemolyticus endocarditis in a hemodial-
Billot-Klein D, Gutmann L, Byant D, Bell D, Van Heijenoort J, Grewal J, ysis patient. Clin Microbiol Infect 4:44 48.
Shlaes DM (1996) Peptidoglycan synthesis and structure in Staphylo- Mato R, Campanile F, Stefani S, Crisostomo MI, Santagati M, Sanches SI,
coccus haemolyticus expressing increasing levels of resistance to de Lancastre H (2004) Clonal types and multidrug resistance patterns of
glycopeptide antibiotics. J Bacteriol 178:4696 4703. methicillin-resistant Staphylococcus aureus (MRSA) recovered in Italy
Campanile F, Venditti M, Borbone S, Buongiorno D, Penni A, Stefani S during the 1990s. Microb Drug Resist 10:106 113.
(2006) Daptomycin activity against multi-resistant Staphylococcus Pitcher DG, Sanders NA, Owen RJ (1989) Rapid extraction of
haemolyticus bloodstream isolates from severe infections. Poster n. bacterial genomic DNA with guanidine thiocyanate. Lett Appl Microbiol
1585. Berlin/Heidelberg: Springer. 16th ECCMID-Nice, p 131. 8:151 156.
Chu VH, Cabell VH, Abrutyn E, Corey GR, Hoen B, Miro JM, Olaison L, Raponi G, Ghezzi MC, Ghepardi G, Dicuonzo G, Caputo D, Venditti M,
Stryjewski ME, Pappas PA, Anstrom KJ, Eykyn S, Habib G, Benito N, Rocco M, Micozzi A, Mancini C (2005) Antimicrobial susceptibility,
Fowler Jr VG, and the International Collaboration on Endocarditis biochemical and genetic profiles of Staphylococcus haemolyticus
Merged Database Study Group (2004) Native valve endocarditis due to strains isolated from the bloodstream of patients hospitalized in Critical
coagulase-negative staphylococci: report of 99 episodes from the Care Units. J Chemother 17:264 269.
International Collaboration on Endocarditis Merged Database. Clin Rocha JL, Gonzalez-Roncero F, Lopez-Hidalgo R, Gomez-Garcia L,
Infect Dis 39:1527 1530. Martin-Herrera C, Rodriguez-Puras MJ, Navarro M, Castilla JJ (1999)
Clinical and Laboratory Standard Institute (2005) Performance Standard Inverse paradoxical embolism in a patient on chronic hemodialysis with
for Antimicrobial Susceptibility Testing. CLSI M7-A6. Wayne, PA7 aortic bacterial endocarditis. Am J Kidney Dis 34:338 340.
CLSI. Santos Sanches I, Mato R, de Lancastre H, Tomasz A, CEM/NET
de Lencastre H, Couto I, Melo-Cristino J, Torres-Pereire A, Tomasz A Collaborators and the International Collaborators (2000) Patterns of
(1994) Methicillin-resistant Staphylococcus aureus disease in a multidrug resistance among methicillin-resistant hospital isolates of
Portuguese hospital: characterization of clonal types by a combina- coagulase-positive and coagulase-negative staphylococci collected in
tion of DNA typing methods. Eur J Clin Microbiol Infect Dis 13: the international multicenter study RESIST in 1997 and 1998. Microb
64 73. Drug Resist 6:199 211.
Falcone M, Micozzi A, Pompeo ME, Baiocchi P, Fabi F, Penni A, Schreckenberger PC, Ilendo E, Ristow KL (2004) Incidence of constitutive
Martino P, Venditti M (2004) Methicillin-resistant staphylococcal and inducible clindamycin resistance in Staphylococcus aureus and
bacteremia in patients with hematologic malignancies: clinical and coagulase-negative staphylococci in a community and a tertiary care
microbiological retrospective comparative analysis of Staphylococcus hospital. J Clin Microbiol 42:2777 2779.
haemolyticus, Staphylococcus epidermidis, and Staphylococcus aure- Shittu A, Lin J, Morrison D, Kolawole D (2004) Isolation and molecular
us. J Chemother 16:540 548. characterization of multiresistant Staphylococcus sciuri and Staphylo-
Falcone M, Giannella M, Raponi G, Mancini C, Venditti M (2006) coccus haemolyticus associated with skin and soft-tissue infections.
Teicoplanin use and emergence of Staphylococcus haemolyticus: is J Med Microbiol 53:51 55.
there a link? Clin Microbiol Infect 12:96 97. Skow A, Mangold KA, Tajuddin M, Huntington A, Fritz B, Thomson Jr
Fowler VG, Miro JM, Hoen B, Cabell CH, Abrutyn E, Rubinstein E, RB, Kaul KL (2005) Species-level identification of staphylococcal
Corey GR, Spelman D, Bradley SF, Barsic B, Pappas PA, Anstrom isolates by real-time PCR and melt curve analysis. J Clin Microbiol
KJ, Wray D, Fortes CQ, Anguera I, Athan E, Jones P, van der Meer 43:2876 2880.
M. Falcone et al. / Diagnostic Microbiology and Infectious Disease 57 (2007) 325 331 331

Takeuchi F, Watanabe S, Baba T, Yuzawa H, Ito T, Morimoto Y, Kuroda M, Terpenning MS, Buggy BP, Kauffman CA (1987) Infective endo-
Cui L, Takahashi M, Ankai A, Baba S, Fukui S, Lee JC, Hiramatsu K carditis: clinical features in young and elderly patients. Am J Med
(2005) Whole-genome sequencing of Staphylococcus haemolyticus 83:626 634.
uncovers the extreme plasticity of its genome and the evolution of Viale P, Stefani S (2006) Vascular catheter associated infections:
human-colonizing staphylococcal species. J Bacteriol 187:7292 7308. a microbiological and therapeutic update. J Chemother 18:14 28.
Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing Werner GS, Schulz R, Fuchs JB, Andreas S, Prange H, Ruschewski W,
DH, Swaminathan B (1995) Interpreting chromosomal DNA restriction Kreuzer H (1996) Infective endocarditis in the elderly in the era of
patterns produced by pulsed-field gel electrophoresis: criteria for transesophageal echocardiography: clinical features and prognosis
bacterial strain typing. J Clin Microbiol 33:2233 2239. compared with younger patients. Am J Med 100:90 97.

You might also like