Skip Navigation

Risk Factors For Hematogenous Complications of Intravascular Catheter—Associated Staphylococcus aureus Bacteremia

  1. Vance G. Fowler Jr.1,3,
  2. Anita Justice4,
  3. Catrin Moore4,
  4. Daniel K. Benjamin Jr.2,3,
  5. Christopher W. Woods1,
  6. Steven Campbell1,
  7. L. Barth Reller1,
  8. G. Ralph Corey1,
  9. Nicholas P. J. Day4, and
  10. Sharon J. Peacock4
  1. 1Departments of Medicine, Duke University Medical Center, Durham, North Carolina
  2. 2Departments of Pediatrics, Duke University Medical Center, Durham, North Carolina
  3. 3Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
  4. 4Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom
  1. Reprints or correspondence: Dr. Vance G. Fowler, Jr., Box 3281, Div. of Infectious Diseases, Duke Univ. Medical Center, Durham, NC 27710 (vance.fowler{at}duke.edu).
 
Next Section

Abstract

Background. The role of both host and pathogen characteristics in hematogenous seeding following Staphylococcus aureus bacteremia is incompletely understood.

Methods. Consecutive patients with intravascular catheter—associated Staphylococcus aureus bacteremia were prospectively recruited over a 91-month period. The corresponding bloodstream isolates were examined for the presence of 35 putative virulence determinants. Patient and bacterial characteristics associated with the development of hematogenous complications (HCs) (i.e., septic arthritis, vertebral osteomyelitis, or endocarditis) were defined.

Results. HC occurred in 42 (13%) of 324 patients. Patient characteristics at diagnosis that were associated with HC included community onset (relative risk [RR], 2.25; 95% confidence interval [CI], 1.24–4.07; P = .007), increased symptom duration (odds ratio for each day, 1.14; 95% CI, 1.06–1.2; P < .001), presence of a long-term intravascular catheter or noncatheter prosthesis (RR, 4.02; 95% CI, 1.74–9.27; P < .001), hemodialysis dependence (RR, 3.84; 95% CI, 2.08–7.10; P < .001), and higher APACHE II score (P = .02). Bacterial characteristics included sea (RR, 2.03; 95% CI, 1.16–3.55; P = .011) and methicillin-resistant S. aureus (MRSA) (RR, 2.09; 95% CI, 1.19–3.67; P = .015). Subsequent failure to remove a catheter was also associated with HC (RR, 2.28; 95% CI, 1.22–4.27; P = .011). On multivariable analysis, symptom duration, hemodialysis dependence, presence of a long-term intravascular catheter or a noncatheter device, and infection with MRSA remained significantly associated with HC.

Conclusions. This investigation identifies 4 host- and pathogen-related risk factors for hematogenous bacterial seeding and reaffirms the importance of prompt catheter removal.

Intravascular catheter—associated Staphylococcus aureus bacteremia (SAB) is an epidemic disease encountered in modern medical practice. Clinicians treating this infection must estimate the risk for hematogenous seeding of host tissues by S. aureus. This bedside judgment forms the basis for a variety of management decisions that have important implications for the patient and for health care costs.

Bacterial seeding is likely to be determined by a combination of host and bacterial factors. Several bacterial factors, including toxins, secreted exoproteins, and cell wall—associated adhesins, have been associated with bacterial invasion of host tissues [1–4]. For example, genes encoding 7 determinants (fnbA, cna, sdrE, sej, eta, hlg, and ica) are significantly more common among invasive S. aureus isolates than among nasal-carriage control isolates, and they appear to contribute cumulatively to virulence [5]. Host factors are also likely to influence the likelihood of bacterial seeding [6]. Therefore, the purpose of the present investigation was to examine the significance of both host and bacterial risk factors for hematogenous seeding, specifically in relation to catheter-associated SAB.

Previous SectionNext Section

Patients and Methods

Clinical characteristics of the patients. The study was approved by the internal review board of Duke University Medical Center (DUMC) (Durham, North Carolina). The research guidelines of Duke University and the University of Oxford were followed in conducting the clinical research reported here. Daily reports were received from the microbiology laboratory documenting all patients at DUMC with clinical evidence of infection and ⩾1 blood culture positive for S. aureus. Clinical data were collected at the time of the first positive blood culture result. Exclusion criteria included being an outpatient, being <18 years old, the presence of polymicrobial infection, an absolute neutrophil count of <1.0 × 109 cells/L, or death before evaluation. Outcomes for all study patients were obtained 12 weeks after the initial positive blood culture results were obtained. Only data from the initial episode of bacteremia for each patient was included in this investigation.

Isolation and characterization of isolates. Bloodstream isolates from consecutive patients with SAB caused by an infected intravascular catheter from September 1994 through March 2001 were included in the current analysis. S. aureus isolates were stored at -70°C from the time of identification until they were tested in the current investigation.

Study definitions. The duration of symptoms was defined as the interval between the patient-reported onset of symptoms and the date of the initial blood culture positive for S. aureus. Time to effective antibiotic therapy was defined as the time, in days, from the initial blood culture positive for S. aureus to the initiation of effective parenteral therapy. Health care—associated bacteremia was defined according to standard definitions [7, 8]; community-acquisition was defined as catheter-associated bacteremia acquired by patients living in their own home. An intravascular catheter was considered to be the portal of entry if inflammation was present around the catheter insertion site or if a catheter-tip culture was positive for S. aureus and no other source was evident [9]. Patients were further defined as having either hematogenous complications (HCs) or uncomplicated bacteremia. HC was defined as the presence of infective endocarditis (IE), septic arthritis, or vertebral osteomyelitis caused by hematogenous seeding of the infected site, either at the time of initial hospitalization or during the 12 weeks after the initial positive blood culture result. All HCs were independently confirmed by radiologic imaging, culture of S. aureus from a normally sterile site, or the use of the Duke diagnostic criteria for IE [10]. Uncomplicated bacteremia was defined as catheter-associated bacteremia without any of the above complications for 12 weeks after the initial positive blood culture result. Two types of permanent foreign bodies were defined in the population studied: first, long-term intravascular catheters (e.g., tunneled cuffed intravascular catheter or subcutaneous port catheter), and second, noncatheter devices (including pacemakers and/or defibrillators, prosthetic heart valves, orthopedic devices, and other permanent implants).

Evaluation of bacterial factors. A total of 35 determinants were evaluated by investigators blinded to any clinical or patient information. Of these determinants, 30 were evaluated using PCR and 5 (α-toxin, β-toxin, δ-toxin, coagulase, and methicillin resistance) were assessed using phenotypic tests, as described elsewhere [5]. Methicillin susceptibility was determined using the oxacillin disk test, performed as specified by NCCLS and confirmed by MIC testing using frozen reference panels (Trek Diagnostics). The presence of the gene encoding chemotaxis inhibitory protein (i.e., the chp gene) was determined using primers designed using GenBank accession number AF285146 (forward primer, 5′-TTTTTAACGGCAGGAATC-3′; reverse primer, 5′-TTGGCAAGTTATGAAATGTCT-3′). PCR cycling conditions were 34 cycles at 96°C for 1 min, 58°C for 1 min, and 72°C for 2 min. PCR was otherwise performed using primers and conditions described elsewhere [5].

Statistical methods. Stata software, version 8.1 (StataCorp) was used for all statistical analyses. Continuous variables were compared between groups by use of the Student's t test or the Kruskal-Wallis H test, as indicated, with an OR per unit derived using bivariable logistic regression analysis. Contingency tables were used to compare proportions between groups, with a relative risk (RR) and 95% CI calculated for the effect of each explanatory variable. Summary statistics were generated for each strain, consisting of the sum of putative bacterial virulence factors and bacterial factors previously shown to be associated with virulence. These were compared between groups by use of the Kruskal-Wallis H test. Logistic regression analysis was used to model the effects of multiple explanatory variables on our primary outcome of interest (i.e., HCs) and to explore their independence. The initial multivariable model included variables that were associated with the outcome and that had P values of <.1 on bivariable analysis. Variables were removed in a stepwise manner, and final associations were recorded as ORs with 95% CIs. The significance of factors and interactions between factors was investigated using likelihood ratio tests to compare the differences in log likelihoods between models with and without each factor.

Previous SectionNext Section

Results

Patient characteristics. Catheter-associated SAB was found in 324 consecutive patients over the 91-month period. The source of bacteremia was presumed to be a tunneled cuffed intravascular catheter (e.g., Permcath or Hickman catheter) in 144 patients (44.4%), a temporary central venous catheter in 83 patients (25.6%), a peripheral vascular catheter in 46 patients (14.2%), a peripherally inserted central catheter in 19 patients (5.9%), a subcutaneous port catheter in 17 patients (5.2%), an intraaortic balloon pump in 8 patients (2.5%), and an arterial catheter in 7 patients (2.2%). By definition [7], all 324 patients had health care—associated bacteremia; 180 bloodstream isolates (56%) were associated with hospital- or nursing home—acquired infections. Forty-two patients (13%) had HCs; 31 patients had endocarditis, 11 had septic arthritis, and 7 had vertebral osteomyelitis. More than 1 of these complications were present in 6 patients. The mean duration (±SD) of antibiotic therapy was 18.3 (±11.5) days for patients with uncomplicated bacteremia and 36.3 (±29.2) days for patients with HC. Of the 324 patients in the study, 235 (72.5%) underwent echocardiographic examination (transthoracic examination only in 105 patients, transesophageal examination only in 23 patients, and both transthoracic and transesophageal examination in 107 patients).

Host factors. The presence of a permanent foreign body carried a significant risk of HC (RR, 4.02; 95% CI, 1.74–9.27) (table 1). This association persisted when the presence of either a long-term vascular catheter (included in the definition of a permanent foreign body) (RR, 2.85; 95% CI, 1.49–5.48) or a noncatheter device (RR, 2.38; 95% CI, 1.30–4.37) were considered separately. The interval between onset of symptoms and diagnosis was also significantly associated with HC (OR, 1.14 per day; 95% CI, 1.06–1.2). Other host characteristics associated with HC included hemodialysis dependence (RR, 3.84; 95% CI, 2.08–7.10), community onset of infection (RR, 2.25; 95% CI, 1.24–4.07), diabetes (RR, 1.85; 95% CI, 1.05–3.26; P = .04), and a higher mean APACHE II score (18.0 vs. 15.5; P = .02). Treatment-related variables associated with HC were failure to remove a catheter (RR, 2.28; 95% CI, 1.22–4.27) and, among patients for whom the catheter was removed, an increasing mean duration from onset of symptoms to catheter removal (5 days vs. 2 days; P < .001).

Table 1
View larger version:
Table 1

Characteristics of 324 patients with intravascular catheter—associated Staphylococcus aureus bacteremia.

Bacterial factors: methicillin resistance. A total of 119 isolates (36.7%) were methicillin-resistant S. aureus (MRSA) according to both oxacillin disk testing and MIC testing. Of these 119 isolates, 46 were associated with community-acquired infections in patients with extensive health care contact. The mean time to appropriate antibiotic therapy was similar for MRSA- and methicillin-susceptible S. aureus–infected patients (0.38 days vs. 0.28 days, respectively; P = .53). Methicillin-resistance was associated with HC (RR, 2.09; 95% CI, 1.19–3.67); 54.8% of the 42 isolates associated with HC were methicillin resistant, compared with 34.0% of the 282 isolates associated with uncomplicated bacteremia (P = .015 by Fisher's exact test).

Bacterial virulence factors. The presence of 34 other putative virulence determinants is shown in table 2. Although 2 factors (sea and tst) were associated with HC in bivariable analysis, the statistical significance of these associations was lost after applying a Bonferroni correction for multiple comparisons. On stepwise logistic regression including all of the bacterial virulence factors, only sea remained associated with HC (OR, 2.4; 95% CI, 1.2–4.6). When the analysis was repeated for all of the bacterial factors plus methicillin resistance, only MRSA remained significantly associated with HC (OR, 2.50; 95% CI, 1.28–4.87). A cumulative effect of putative virulence determinants on outcome was not demonstrated for the 34 putative virulence determinants (excluding agr types, which are not binary) (P = .16, by the Kruskal-Wallis H test) or for the 7 genes previously shown [5] to be associated with virulence (P = .71). The gene sea was associated with MRSA; 66% of MRSA isolates (but only 16% of MSSA isolates) were positive for this gene (P < .0001).

Table 2
View larger version:
Table 2

Presence of putative virulence determinants in Staphylococcus aureus strains isolated from blood samples obtained from patients with uncomplicated and complicated catheter-associated bacteremia.

Multivariable analysis of host and bacterial factors present at the time of initial bacteremia and associated with HC. On the basis of their association on bivariable analysis, the following host and bacterial characteristics were included as initial independent variables in a multivariable model in which the dependent variable was the presence of HC: presence of permanent foreign body, duration of symptoms before diagnosis, community onset, hemodialysis dependence, APACHE II score, methicillin resistance, and presence of diabetes. A significant positive association was noted between hemodialysis dependence and the presence of a foreign body. Because a significant statistical interaction in relation to outcome was also noted between the 2 variables, an interaction term was included in the multivariable analysis. With use of backward stepwise elimination, the presence of diabetes, community onset, and APACHE II score were dropped from the model. In the final multivariable model (table 3), the duration of symptoms before diagnosis, the presence of a permanent foreign body, hemodialysis dependence, methicillin resistance, and the interaction term of concurrent permanent foreign body and hemodialysis dependence remained independently associated with HC. The area under the receiver operating characteristic curve for this final model was 0.81.

Table 3
View larger version:
Table 3

Final multivariable analysis of patient and bacterial characteristics associated with hematogenous complications of intravascular catheter—associated Staphylococcus aureus bacteremia.

Two types of permanent foreign bodies existed in the population studied: first, long-term catheters serving as portals of entry (in 161 patients), and second, noncatheter devices at risk for hematogenous seeding (in 42 patients). When the multivariate model was repeated with the variable “permanent foreign body” divided into these 2 separate device-associated variables, both long-term catheter (OR, 4.50; 95% CI, 1.16–17.5; P = .03) and noncatheter prosthesis (OR, 6.22; 95% CI, 2.16–19.9; P = .001) were independently associated with HC.

Multivariable analysis of HC: addition of treatment-related variables. A further multivariable analysis was performed to account for the potential impact of treatment-related variables on the risk for HC. In this analysis, we added the following variables to the initial multivariable analysis: time to effective antibiotic therapy, failure to remove catheter after positive blood culture result, and the interaction term “methicillin resistance and failure to remove a catheter” (because the 2 variables were positively associated). All significant variables from the original model remained significant when these additional treatment-related variables were added to the initial model. Although the time to effective therapy and the interaction term were not significant, failure to remove the catheter remained a significant risk for hematogenous spread (RR, 8.99; 95% CI, 2.15–37.5; P = .003).

The multivariable analysis also identified a patient population at low risk for complications. Among patients with intravascular catheter—associated SAB with neither hemodialysis nor a permanent foreign body (i.e., long-term catheter or noncatheter prosthesis), the rate of HC was 2.4% (range, 0.5%–6.9%).

Previous SectionNext Section

Discussion

The clinical severity and outcome of S. aureus infection in a given individual is likely to be dictated by a complex interplay between host and pathogen. The study of bacterial pathogenesis is further complicated by the heterogeneity of S. aureus infections. This study of consecutive patients with a single type of S. aureus infection addresses such issues and has highlighted several risk factors for HC in patients with catheter-associated SAB.

Methicillin resistance, present in more than one-third of the isolates cultured from blood specimens in this study, was independently associated with an increased risk for HC. This association persisted even after adjustment for patient comorbid conditions with use of APACHE II scores. This finding is consistent with some prior clinical reports [11–16] but is not consistent with others [17–20]. There are several potential explanations for this observation. The genetic complement of MRSA isolates, and in particular the accessory genes, may produce a more virulent phenotype in cases of catheter-associated bacteremia. Consistent with this explanation are our findings that MRSA isolates associated with infection contained a distinct genetic virulence repertoire (e.g., had higher carriage of sea) and were more clonally restricted than were MSSA isolates, according to PFGE analysis (data not shown). Earlier in vitro studies have demonstrated no difference in virulence between MRSA and MSSA [21–25]. However, the current investigation is the first to simultaneously consider both patient and bacterial factors in a large collection of S. aureus isolates associated with a single infection type, making this study more reflective of the clinical interactions leading to HC than others. It is also possible that MRSA-infected patients had higher rates of HC because of treatment with vancomycin, which has been associated with high rates of clinical failure [26], prolonged bacteremia [27], and relapse [28–30]. These findings support additional studies to define the role of alternatives to vancomycin (e.g., daptomycin or linezolid) in the empirical treatment of infection due to S. aureus.

The presence of a permanent foreign body was also an independent predictor of HC in this study. This was true independently for both long-term catheters (which are potential portals of entry into the blood stream for infecting bacteria) and noncatheter devices (which can serve as a focus for hematogenous spread). This observation is consistent with prior reports documenting high rates of seeding by S. aureus in a variety of noncatheter devices [31–34]. However, the current investigation is the first to document the high risk of HC among patients with long-term indwelling catheters, even when compared with patients with SAB caused by other types of vascular catheters. This finding may be explained in part by the diagnostic and therapeutic delay associated with the patient's community residence and/or with reluctance to remove the long-term vascular access. The high rate of foreign body infection in this study may also be explained in part by the fact that bacterial characteristics involved in catheter-associated sepsis are also integral determinants of other forms of device-associated infection. For example, rates of cna and icaA in the current study were significantly higher than in our previous study [5], which primarily involved isolates that were not associated with catheter infection.

Although previous studies have reported high rates of complications among hemodialysis -dependent patients [35], before the current investigation, it was unclear whether this was related to the presence of chronic intravascular access or to the direct effects of hemodialysis on host susceptibility to staphylococcal infection. The current investigation demonstrates that hemodialysis dependence is an independent risk factor for HC, even among patients with catheter-associated SAB. This elevated risk may be related to the impact of hemodialysis on host immunity, including uremia-associated phagocyte dysfunction [36] and iron overload [37, 38].

The current investigation also documents that the failure to remove or the delay in removal of an infected catheter is an independent risk factor for HC. These findings are consistent with published guidelines for the treatment of catheter-associated infections [39, 40] and emphasize the importance of prompt removal if such catheters are believed to be the source of an episode of SAB.

The current investigation supports the use of microarray technology to further pursue the impact of bacterial characteristics on disease severity, because it is possible that the bacterial factors influencing the risk for hematogenous seeding have simply not yet been characterized. For example, DNA microarray analysis of 36 clonally diverse S. aureus strains identified 10 large regions of difference with numerous genes encoding previously unknown putative virulence factors [41]. In addition, the genome of an isolate of community-acquired MRSA (i.e., MW2) was shown to have 18 toxins not present within any of 5 S. aureus genomes with which it was compared [42]. The combination of genetic diversity and rapid genetic exchange could give rise to particular S. aureus phenotypes that are better equipped than others for invasion of the human host. Indeed, the increased risk for hematogenous seeding found among the study patients with MRSA bacteremia suggests that as-yet-unidentified factors can enhance the virulence properties of these clonal strains.

Our investigation had limitations. We were unable to evaluate the impact of conditions such as necrotic bone and osteoarthritis, because these conditions were not systematically sought (e.g., by diagnostic imaging) in all study patients by the treating physicians, potentially biasing the recognition of these conditions. In addition, our sample size limited our ability to fully evaluate multiple host characteristics that were unrelated to the intravascular catheter. Finally, the study was conducted at a single tertiary care center. Thus, confirmation of these findings with use of geographically diverse patients and isolates is required.

In conclusion, SAB associated with intravascular devices is a serious, common complication of medical progress. This study has defined 4 clinically relevant factors for HC of catheter-associated SAB and has provided evidence suggesting heightened virulence among MRSA strains isolated from the bloodstream. Further investigations are required to clarify the impact of virulence characteristics of individual S. aureus strains on the outcome of infection.

Previous SectionNext Section

Acknowledgments

We thank Kasia Stepniewska, for statistical advice, and Dr. Robert D. Arbeit, for reviewing the manuscript.

Financial support. Wellcome Trust of Great Britain (grants to N.P.J.D. and S.J.P. and a Wellcome Trust Career Development Award in Clinical Tropical Medicine to S.J.P.) and the National Institutes of Health (1R01 AI059111 to V.G.F.).

Potential conflicts of interest. All authors: no conflicts.

  • Received August 30, 2004.
  • Accepted October 22, 2004.
Previous Section
 

References

  1. ↵
    1. Tristan A,
    2. Ying L,
    3. Bes M,
    4. Etienne J,
    5. Vandenesch F,
    6. Lina G
    . Use of multiplex PCR to identify Staphylococcus aureus adhesins involved in human hematogenous infections. J Clin Microbiol 2003;41:4465-7.
    Abstract/FREE Full Text
    1. Vandenesch F,
    2. Naimi T,
    3. Enright MC,
    4. et al
    . Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis 2003;9:978-84.
    MedlineWeb of Science
    1. Gillet Y,
    2. Issartel B,
    3. Vanhems P,
    4. et al
    . Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet 2002;359:753-9.
    CrossRefMedlineWeb of Science
  4. ↵
    1. Jarraud S,
    2. Mougel C,
    3. Thioulouse J,
    4. et al
    . Relationships between Staphylococcus aureus genetic background, virulence factors, agr groups (alleles), and human disease. Infect Immun 2002;70:631-41.
    Abstract/FREE Full Text
  5. ↵
    1. Peacock SJ,
    2. Moore CE,
    3. Justice A,
    4. et al
    . Virulent combinations of adhesin and toxin genes in natural populations of Staphylococcus aureus. Infect Immun 2002;70:4987-96.
    Abstract/FREE Full Text
  6. ↵
    1. Fowler VG Jr,
    2. Olsen MK,
    3. Corey GR,
    4. et al
    . Clinical identifiers of complicated Staphylococcus aureus bacteremia. Arch Intern Med 2003;163:2066-72.
    Abstract/FREE Full Text
  7. ↵
    1. Friedman ND,
    2. Kaye KS,
    3. Stout JE,
    4. et al
    . Health care-associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 2002;137:791-7.
    Abstract/FREE Full Text
  8. ↵
    1. Naimi TS,
    2. LeDell KH,
    3. Como-Sabetti K,
    4. et al
    . Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA 2003;290:2976-84.
    Abstract/FREE Full Text
  9. ↵
    1. Libman H,
    2. Arbeit RD
    . Complications associated with Staphylococcus aureus bacteremia. Arch Intern Med 1984;144:541-5.
    Abstract/FREE Full Text
  10. ↵
    1. Durack DT,
    2. Lukes AS,
    3. Bright DK
    . New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Am J Med 1994;96:200-9.
    CrossRefMedlineWeb of Science
  11. ↵
    1. Blot SI,
    2. Vandewoude KH,
    3. Hoste EA,
    4. Colardyn FA
    . Outcome and attributable mortality in critically ill patients with bacteremia involving methicillin-susceptible and methicillin-resistant Staphylococcus aureus. Arch Intern Med 2002;162:2229-35.
    Abstract/FREE Full Text
    1. Conterno LO,
    2. Wey SB,
    3. Castelo A
    . Risk factors for mortality in Staphylococcus aureus bacteremia. Infect Control Hosp Epidemiol 1998;19:32-7.
    MedlineWeb of Science
    1. Cosgrove SE,
    2. Sakoulas G,
    3. Perencevich EN,
    4. Schwaber MJ,
    5. Karchmer AW,
    6. Carmeli Y
    . Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 2003;36:53-9.
    Abstract/FREE Full Text
    1. Engemann JJ,
    2. Carmeli Y,
    3. Cosgrove SE,
    4. et al
    . Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection. Clin Infect Dis 2003;36:592-8.
    Abstract/FREE Full Text
    1. Mekontso-Dessap A,
    2. Kirsch M,
    3. Brun-Buisson C,
    4. Loisance D
    . Poststernotomy mediastinitis due to Staphylococcus aureus: comparison of methicillin-resistant and methicillin-susceptible cases. Clin Infect Dis 2001;32:877-83.
    Abstract/FREE Full Text
  16. ↵
    1. Melzer MES
    . Is methicillin-resistant Staphylococcus aureus more virulent than methicillin-susceptible S. aureus? A comparative cohort study of British patients with nosocomial infection and bacteremia. Clin Infect Dis 2003;37:1453-60.
    Abstract/FREE Full Text
  17. ↵
    1. Harbarth S,
    2. Rutschmann O,
    3. Sudre P,
    4. Pittet D
    . Impact of methicillin resistance on the outcome of patients with bacteremia caused by Staphylococcus aureus. Arch Intern Med 1998;158:182-9.
    Abstract/FREE Full Text
    1. Mylotte JM,
    2. Tayara A
    . Staphylococcus aureus bacteremia: predictors of 30-day mortality in a large cohort. Clin Infect Dis 2000;31:1170-4.
    Abstract/FREE Full Text
    1. Soriano A,
    2. Martinez JA,
    3. Mensa J,
    4. et al
    . Pathogenic significance of methicillin resistance for patients with Staphylococcus aureus bacteremia. Clin Infect Dis 2000;30:368-73.
    Abstract/FREE Full Text
  20. ↵
    1. Wisplinghoff H,
    2. Seifert H,
    3. Coimbra M,
    4. Wenzel RP,
    5. Edmond MB
    . Systemic inflammatory response syndrome in adult patients with nosocomial bloodstream infection due to Staphylococcus aureus. Clin Infect Dis 2001;33:733-6.
    Abstract/FREE Full Text
  21. ↵
    1. Schmitz FJ,
    2. MacKenzie CR,
    3. Geisel R,
    4. et al
    . Enterotoxin and toxic shock syndrome toxin-1 production of methicillin resistant and methicillin sensitive Staphylococcus aureus strains. Eur J Epidemiol 1997;13:699-708.
    CrossRefMedlineWeb of Science
    1. Duckworth GJ,
    2. Jordens JZ
    . Adherence and survival properties of an epidemic methicillin-resistant strain of Staphylococcus aureus compared with those of methicillin-sensitive strains. J Med Microbiol 1990;32:195-200.
    Abstract/FREE Full Text
    1. Jordens JZ,
    2. Duckworth GJ,
    3. Williams RJ
    . Production of “virulence factors” by “epidemic” methicillin-resistant Staphylococcus aureus in vitro. J Med Microbiol 1989;30:245-52.
    Abstract/FREE Full Text
    1. Peacock JE Jr,
    2. Moorman DR,
    3. Wenzel RP,
    4. Mandell GL
    . Methicillin-resistant Staphylococcus aureus: microbiologic characteristics, antimicrobial susceptibilities, and assessment of virulence of an epidemic strain. J Infect Dis 1981;144:575-82.
    Abstract/FREE Full Text
  25. ↵
    1. Cutler RR
    . Relationship between antibiotic resistance, the production of “virulence factors,” and virulence for experimental animals in Staphylococcus aureus. J Med Microbiol 1979;12:55-62.
    Abstract/FREE Full Text
  26. ↵
    1. Small PM,
    2. Chambers HF
    . Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users. Antimicrob Agents Chemother 1990;34:1227-31.
    Abstract/FREE Full Text
  27. ↵
    1. Levine DP,
    2. Fromm BS,
    3. Reddy BR
    . Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med 1991;115:674-80.
    Abstract/FREE Full Text
  28. ↵
    1. Chang FY,
    2. Peacock JE Jr,
    3. Musher DM,
    4. et al
    . Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine 2003;82:333-9.
    Medline
    1. Fowler VGJ,
    2. Kong LK,
    3. Corey GR,
    4. et al
    . Recurrent Staphylococcus aureus bacteremia: pulsed-field gel electrophoresis findings in 29 patients. J Infect Dis 1999;179:1157-61.
    Abstract/FREE Full Text
  30. ↵
    1. Hartstein AI,
    2. Mulligan ME,
    3. Morthland VH,
    4. Kwok RY
    . Recurrent Staphylococcus aureus bacteremia. J Clin Microbiol 1992;30:670-4.
    Abstract/FREE Full Text
  31. ↵
    1. Chamis AL,
    2. Peterson GE,
    3. Cabell CH,
    4. et al
    . Staphylococcus aureus bacteremia in patients with permanent pacemakers or implantable cardioverter-defibrillators. Circulation 2001;104:1029-33.
    Abstract/FREE Full Text
    1. Murdoch D,
    2. Roberts S,
    3. Fowler VG Jr,
    4. et al
    . Infection of orthopedic prostheses after Staphylococcus aureus bacteremia. Clin Infect Dis 2001;32:647-9.
    Abstract/FREE Full Text
    1. Chang FY,
    2. MacDonald BB,
    3. Peacock JE Jr,
    4. et al
    . A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Medicine 2003;82:322-32.
    Medline
  34. ↵
    1. Fang G,
    2. Keys TF,
    3. Gentry LO,
    4. et al
    . Prosthetic valve endocarditis resulting from nosocomial bacteremia: a prospective, multicenter study. Ann Intern Med 1993;119:560-7.
    Abstract/FREE Full Text
  35. ↵
    1. Marr KA,
    2. Kong L,
    3. Fowler VG,
    4. et al
    . Incidence and outcome of Staphylococcus aureus bacteremia in hemodialysis patients. Kidney Int 1998;54:1684-9.
    CrossRefMedlineWeb of Science
  36. ↵
    1. Vanholder R,
    2. De Smet R,
    3. Jacobs V,
    4. et al
    . Uraemic toxic retention solutes depress polymorphonuclear response to phagocytosis. Nephrol Dial Transplant 1994;9:1271-8.
    Abstract/FREE Full Text
  37. ↵
    1. Boelaert JR,
    2. Daneels RF,
    3. Schurgers ML,
    4. Matthys EG,
    5. Gordts BZ,
    6. Van Landuyt HW
    . Iron overload in haemodialysis patients increases the risk of bacteraemia: a prospective study. Nephrol Dial Transplant 1990;5:130-4.
    Abstract/FREE Full Text
  38. ↵
    1. Hoen B,
    2. Paul-Dauphin A,
    3. Hestin D,
    4. Kessler M
    . EPIBACDIAL: a multicenter prospective study of risk factors for bacteremia in chronic hemodialysis patients. J Am Soc Nephrol 1998;9:869-76.
    Abstract
  39. ↵
    1. Fowler VGJ,
    2. Sanders LL,
    3. Sexton DJ,
    4. et al
    . Outcome of Staphylococcus aureus bacteremia according to compliance with recommendations of infectious diseases specialists: experience with 244 patients. Clin Infect Dis 1998;27:478-86.
    Abstract/FREE Full Text
  40. ↵
    1. Mermel LA,
    2. Farr BM,
    3. Sherertz RJ,
    4. et al
    . Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 2001;32:1249-72.
    FREE Full Text
  41. ↵
    1. Fitzgerald JR,
    2. Sturdevant DE,
    3. Mackie SM,
    4. Gill SR,
    5. Musser JM
    . Evolutionary genomics of Staphylococcus aureus: insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic. Proc Natl Acad Sci USA 2001;98:8821-6.
    Abstract/FREE Full Text
  42. ↵
    1. Baba T,
    2. Takeuchi F,
    3. Kuroda M,
    4. et al
    . Genome and virulence determinants of high virulence community-acquired MRSA. Lancet 2002;359:1819-27.
    CrossRefMedlineWeb of Science
    1. Greene C,
    2. McDevitt D,
    3. Francois P,
    4. Vaudaux PE,
    5. Lew DP,
    6. Foster TJ
    . Adhesion properties of mutants of Staphylococcus aureus defective in fibronectin-binding proteins and studies on the expression of fnb genes. Mol Microbiol 1995;17:1143-52.
    CrossRefMedlineWeb of Science
    1. Wann ER,
    2. Gurusiddappa S,
    3. Hook M
    . The fibronectin-binding MSCRAMM FnbpA of Staphylococcus aureus is a bifunctional protein that also binds to fibrinogen. J Biol Chem 2000;275:13863-71.
    Abstract/FREE Full Text
    1. Ni Eidhin D,
    2. Perkins S,
    3. Francois P,
    4. Vaudaux P,
    5. Hook M,
    6. Foster TJ
    . Clumping factor B (ClfB), a new surface-located fibrinogen-binding adhesin of Staphylococcus aureus. Mol Microbiol 1998;30:245-57.
    CrossRefMedlineWeb of Science
    1. O'Brien L,
    2. Kerrigan SW,
    3. Kaw G,
    4. et al
    . Multiple mechanisms for the activation of human platelet aggregation by Staphylococcus aureus: roles for the clumping factors ClfA and ClfB, the serine-aspartate repeat protein SdrE and protein A. Mol Microbiol 2002;44:1033-44.
    CrossRefMedlineWeb of Science
    1. O'Brien LM,
    2. Walsh EJ,
    3. Massey RC,
    4. Peacock SJ,
    5. Foster TJ
    . Staphylococcus aureus clumping factor B (ClfB) promotes adherence to human type I cytokeratin 10: implications for nasal colonization. Cell Microbiol 2002;4:759-70.
    CrossRefMedlineWeb of Science
    1. Patti JM,
    2. Jonsson H,
    3. Guss B,
    4. et al
    . Molecular characterization and expression of a gene encoding a Staphylococcus aureus collagen adhesin. J Biol Chem 1992;267:4766-72.
    Abstract/FREE Full Text
    1. Hartleib J,
    2. Kohler N,
    3. Dickinson RB,
    4. et al
    . Protein A is the von Willebrand factor binding protein on Staphylococcus aureus. Blood 2000;96:2149-56.
    Abstract/FREE Full Text
    1. Josefsson E,
    2. McCrea KW,
    3. Ni Eidhin D,
    4. et al
    . Three new members of the serine-aspartate repeat protein multigene family of Staphylococcus aureus. Microbiology 1998;144:3387-95.
    Abstract/FREE Full Text
    1. Tung H,
    2. Guss B,
    3. Hellman U,
    4. Persson L,
    5. Rubin K,
    6. Ryden C
    . A bone sialoprotein-binding protein from Staphylococcus aureus: a member of the staphylococcal Sdr family. Biochem J 2000;345:611-9.
    CrossRefMedline
    1. Downer R,
    2. Roche F,
    3. Park PW,
    4. Mecham RP,
    5. Foster TJ
    . The elastin-binding protein of Staphylococcus aureus (EbpS) is expressed at the cell surface as an integral membrane protein and not as a cell wall-associated protein. J Biol Chem 2002;277:243-50.
    Abstract/FREE Full Text
    1. Palma M,
    2. Haggar A,
    3. Flock JI
    . Adherence of Staphylococcus aureus is enhanced by an endogenous secreted protein with broad binding activity. J Bacteriol 1999;181:2840-5.
    Abstract/FREE Full Text
    1. Haggar A,
    2. Hussain M,
    3. Lonnies H,
    4. Herrmann M,
    5. Norrby-Teglund A,
    6. Flock JI
    . Extracellular adherence protein from Staphylococcus aureus enhances internalization into eukaryotic cells. Infect Immun 2003;71:2310-7.
    Abstract/FREE Full Text
    1. Chavakis T,
    2. Hussain M,
    3. Kanse SM,
    4. et al
    . Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes. Nature Med 2002;8:687-93.
    CrossRefMedlineWeb of Science
    1. Bohach GA,
    2. Fast DJ,
    3. Nelson RD,
    4. Schlievert PM
    . Staphylococcal and streptococcal pyrogenic toxins involved in toxic shock syndrome and related illnesses. Crit Rev Microbiol 1990;17:251-72.
    MedlineWeb of Science
    1. Betley MJ,
    2. Borst DW,
    3. Regassa LB
    . Staphylococcal enterotoxins, toxic shock syndrome toxin and streptococcal pyrogenic exotoxins: a comparative study of their molecular biology. Chem Immunol 1992;55:1-35.
    MedlineWeb of Science
    1. Prevost G,
    2. Cribier B,
    3. Couppie P,
    4. et al
    . Panton-Valentine leucocidin and gamma-hemolysin from Staphylococcus aureus ATCC 49775 are encoded by distinct genetic loci and have different biological activities. Infect Immun 1995;63:4121-9.
    Abstract/FREE Full Text
    1. Supersac G,
    2. Prevost G,
    3. Piemont Y
    . Sequencing of leucocidin R from Staphylococcus aureus P83 suggests that staphylococcal leucocidins and gamma-hemolysin are members of a single, two-component family of toxins. Infect Immun 1993;61:580-7.
    Abstract/FREE Full Text
    1. Bhakdi S,
    2. Tranum-Jensen J
    . Alpha-toxin of Staphylococcus aureus. Microbiol Rev 1991;55:733-51.
    Abstract/FREE Full Text
    1. Cohen P,
    2. van Heyningen S
    1. Arbuthnott JP
    . Bacterial cytolysins (membrane-damaging toxins). In: Cohen P, van Heyningen S, editors. Molecular action of toxins and viruses. Amsterdam: Elsevier Biomedical Press; 1982. p. 107-29.
    1. Hemker HC,
    2. Bas BM,
    3. Muller AD
    . Activation of a pro-enzyme by a stoichiometric reaction with another protein: the reaction between prothrombin and staphylocoagulase. Biochim Biophys Acta 1975;379:180-8.
    Medline
    1. Kawabata S,
    2. Morita T,
    3. Iwanaga S,
    4. Igarashi H
    . Enzymatic properties of staphylothrombin, an active molecular complex formed between staphylocoagulase and human prothrombin. J Biochem 1985;98:1603-14.
    Abstract/FREE Full Text
    1. Boden MK,
    2. Flock JI
    . Cloning and characterization of a gene for a 19 kDa fibrinogen-binding protein from Staphylococcus aureus. Mol Microbiol 1994;12:599-606.
    CrossRefMedlineWeb of Science
    1. Cramton SE,
    2. Gerke C,
    3. Schnell NF,
    4. Nichols WW,
    5. Gotz F
    . The intercellular adhesion (ica) locus is present in Staphylococcus aureus and is required for biofilm formation. Infect Immun 1999;67:5427-33.
    Abstract/FREE Full Text
    1. Haas P,
    2. de Haas CJC,
    3. Kleibeuker KPM,
    4. van Kessel KPM,
    5. Verhoef J,
    6. van Strijp JAG
    . Program and abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology; 2003. Two separate chemokine-receptor-modulating regions within the chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) [abstract B-1517]; p. 63.
    1. Drapeau GR,
    2. Boily Y,
    3. Houmard J
    . Purification and properties of an extracellular protease of Staphylococcus aureus. J Biol Chem 1972;247:6720-6.
    Abstract/FREE Full Text
    1. Jarraud S,
    2. Lyon GJ,
    3. Figueiredo AM,
    4. et al
    . Exfoliatin-producing strains define a fourth agr specificity group in Staphylococcus aureus. J Bacteriol 2000;182:6517-22.
    Abstract/FREE Full Text
    1. Ji G,
    2. Beavis R,
    3. Novick RP
    . Bacterial interference caused by autoinducing peptide variants. Science 1997;276:2027-30.
    Abstract/FREE Full Text
| Table of Contents

This Article

  1. Clin Infect Dis. (2005) 40 (5): 695-703. doi: 10.1086/427806
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 54 (5)
  1. Clinical Infectious Diseases
  1. Alert me to new issues

Most