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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
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.
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
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
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(2005) Coagulase-negative staphylococcal meningitis in adults: clinical
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and clinical significance of this pathogen. Katayama Y, Ito T, Hiramatsu K (2001) Genetic organization of the
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Acknowledgments in mecA-carrying, low-level methicillin-resistant Staphylococcus hae-
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