JSTOR

Methods

Study patients. All patients with SAB were identified by review of the results of blood cultures performed between January 2003 and December 2004 at the microbiology laboratories of 2 tertiary teaching medical centers. All patients who were 60 years or older and had 1 or more blood cultures positive for S. aureus were included in the study. If the same patient developed SAB due to the same strain more than once, the first episode was included in the study and further episodes were excluded from the data analysis. Patients were followed up until discharge from the hospital or death once included in the study. The study was approved by the human subjects committee and the institutional review board of the respective institutions.

Design. This cohort study was a retrospective analysis of data collected from the medical records of older adults with SAB. The collected data included age, race, sex, underlying medical condition, Charlson WIC score, length of hospital stay, Simplified Acute Physiology Score (SAPS) II on the day of SAB onset, evidence of secondary metastatic foci of infection, and outcome. Microbiological data included the strain type of the S. aureus isolate, the time of onset of SAB after hospital admission, and the presence of other bacteremia.

Definitions. SAB was defined as the presence of at least 1 blood culture positive for S. aureus and signs and symptoms of infection. The day of onset of SAB was defined as the date when the first S. aureus–positive blood culture result was obtained. SAB was considered nosocomial if it developed more than 48 hours after hospital admission in the absence of clinical evidence of infection on admission. A localized focus of staphylococcal infection was considered the source of SAB if symptoms and signs of infection antedated the onset of bacteremia, and the focus of infection was confirmed, if necessary, by laboratory and radiological findings. An intravascular catheter was considered the source of SAB if there was evidence of inflammation at the catheter insertion site, purulent drainage from the insertion site that on culture yielded S. aureus, a catheter‐tip culture positive for S. aureus, or if there was no evidence of another source of SAB in the presence of an intravascular catheter. Soft tissue was considered the source of SAB if clinical signs of a soft‐tissue infection antedated the onset of SAB. A pulmonary source of SAB was considered if there was evidence of an infiltrate on a chest radiograph, S. aureus was cultured from sputum or an endotracheal aspirate specimen, and no other portal of entry was identified. A secondary metastatic focus of infection due to SAB was defined as presence of a blood culture positive for S. aureus along with documentation of infection in internal organs by both imaging and culture. Infective endocarditis was defined using Duke criteria.

The Charlson WIC was developed in 1987 based on 1‐year mortality data from internal medicine patients admitted to a single New York hospital and was initially validated in a cohort of breast cancer patients. The index encompasses 19 medical conditions, weighted on a scale of 1 to 6, with total scores ranging from 0 to 37 (Appendix Table A1).¹¹

SAPS II includes physiology variables (heart rate; systolic blood pressure; temperature; 24‐hour urine output; Pao₂/Fio₂ value; white blood cell count; and sodium, potassium, bicarbonate, urea, and bilirubin levels), age, type of admission (scheduled surgical, unscheduled surgical, or medical), Glasgow Coma Scale score, and underlying disease variables (acquired immunodeficiency syndrome, metastatic cancer, and hematologic malignancy). It quantifies the severity of illness and the corresponding probability of in‐hospital mortality on the basis of the most abnormal data from the first 24 hours after admission.¹² The primary outcome measure was whether the patient was dead or alive 7 days after the onset of SAB (7‐day mortality).

Statistical analysis. Descriptive statistics were used to summarize the data. Categorical variables were analyzed using the χ² test or Fisher exact test, whereas continuous variables were analyzed by Wilcoxon rank sum test. To determine the predictors of 7‐day mortality among older adults with SAB and whether comorbid conditions measured by Charlson WIC have an impact on the 7‐day mortality, a stepwise logistic regression analysis was performed. The model was verified by forward and backward variable insertion. Multiple variables were considered as possible predictors of mortality among older adults with SAB. These variables were selected on the basis of their clinical and statistical importance. The variables were as follows: SAPS II greater than 45 on the day of SAB onset, nosocomial SAB, the type of S. aureus strain, Charlson WIC score greater than 5, altered mental status on the day of SAB onset, the source of SAB, and previous hospitalization in the past 3 months.

To determine the predictors of MRSA colonization and infection among older adults with SAB, another stepwise logistic regression analysis was performed. The selected variables in the model were previous hospitalization in the past 3 months, altered mental status on the day of SAB onset, the day of onset of SAB, and whether the patient was admitted from the community or a long‐term care facility. A P value of less than .05 was considered statistically significant, and all P values were 2‐sided. Statistical analysis was performed using SAS statistical software, version 8.2 (SAS Institute).

Results

From January 2003 through December 2004, we identified 249 patients with SAB, 142 of whom were aged 60 years or older. Seven patients were not included in the study because of inability to locate and review their medical records. A total of 135 patients were included in the study and final analysis. The demographic and clinical characteristics of older adults with SAB are given in Table 1.

Table 1.  Demographic and Clinical Characteristics of Older Adults With Staphylococcus aureus Bacteremia (SAB), Stratified by Survival at 7 Days After the Onset of Bacteremia

Open New Window

The mean age (±SD) of the study patients was years. Diabetes mellitus was the most common underlying condition (in 46% of patients), followed by congestive heart failure (in 34.8%), chronic lung diseases (in 34.8%), and chronic renal failure (in 34.8%).

The source of SAB was unknown in 40 patients (29.6%). The known sources of SAB were as follows: intravascular catheters, in 32.6% of patients; soft‐tissue, joint, and bone infections, 14.1%; urine, 11.1%; lung, 7.4%; and prosthetic devices, 5.2%. Fifty‐eight patients (43.0%) had intravascular catheter at the time of SAB. The intravascular catheter was removed after the onset of SAB for 48 patients (82.8%), and only 24 (50.0%) of them had a catheter tip culture that yielded the same S. aureus strain type that grew in the blood culture. Forty‐two patients (31.1%) had bacteremia other than SAB during the same hospitalization; coagulase‐negative Staphylococcus was the most common isolate (in 23 [54.8%] of the 42 patients), followed by enterococcus species (in 11 [26.2%]).

Of the 135 patients with SAB, 65 (48.2%) underwent evaluation for secondary metastatic infections by transthoracic or transesophageal echocardiography and imaging at the time of onset of SAB. Of these, 19 patients (29.2%) had evidence of secondary metastatic foci of infection. Sixteen (36%) of 45 patients with community‐onset SAB who underwent evaluation for metastatic infection had evidence of secondary metastatic infections, whereas 3 (15%) of 20 patients with hospital‐acquired SAB had evidence of secondary metastatic infections. Nine (26%) of 35 patients with MRSA bacteremia had evidence of secondary metastasis, whereas 10 (33%) of 30 patients with methicillin‐sensitive S. aureus (MSSA) bacteremia had evidence of secondary metastasis. Four patients with evidence of secondary metastatic infection died; 3 of them had infective endocarditis. The types of metastatic infection were as follows: endocarditis (in 5 patients), osteomyelitis (in 2), epidural abscess (in 1), osteomyelitis with epidural abscess (in 5), septic arthritis (in 4), scrotal abscess (in 1), and endocarditis with endophthalmitis (in 1).

During the follow‐up period from admission to discharge, 36 patients (26.7%) had died. However, the 7‐day mortality rate was 15.6% (21 of 135 patients). Table 1 gives the results of the univariate analysis for identification of predictors of 7‐day mortality.

The mortality rate was 22.5% (11 of 49 patients) among patients with nosocomial SAB, compared with 11.6% (10 of 86 patients) among patients with community‐onset SAB. All patients with community‐onset SAB who died within 7 days after the onset of SAB had been previously hospitalized in the past 3 months. Nine patients (81.8%) with hospital‐acquired SAB who died within 7 days after the onset of SAB had been previously hospitalized in the past 3 months. Patients who died were more likely to have MRSA bacteremia ( ), an unknown source of SAB ( ), more comorbid conditions ( ), and altered mental status at the time of onset of SAB ( ) than were patients who survived.

A multivariate analysis with a stepwise logistic regression model was used to identify risk factors associated with 7‐day mortality in elderly patients with SAB. A P value of less than .20 was considered significant for covariate inclusion in the model, and a P value of less than .05 was used for retention in the model. A Charlson WIC score greater than 5, previous hospitalization in the past 3 months, and altered mental status at the onset of SAB were the most important predictors of 7‐day mortality (Table 2).

Table 2.  Risk Factors Associated with Mortality at 7 Days Among Older Adults With Staphylococcus aureus Bacteremia (SAB)

Open New Window

Of the 135 patients with SAB, 74 (56.1%) had MRSA bacteremia, and 58 (43.9%) had MSSA bacteremia. The percentage of cases of SAB due to MRSA increased during the study period from 53.2% in 2003 to 58.6% in 2004. Factors associated with MRSA bacteremia by univariate analysis were chronic lung disease ( ), residence in a long‐term care facility ( ), altered mental status at the onset of SAB ( 1), previous hospitalization in the past 3 months ( ), and SAPS II greater than 45 at the time of onset of SAB ( ) (Table 3). The 7‐day mortality rate was 20.3% (15 of 74 patients) among patients with MRSA bacteremia and 5.2% (3 of 58 patients) among patients with MSSA bacteremia ( ). No significant differences were found in the 2 groups with respect to Charlson WIC score.

Table 3.  Risk Factors Associated With Bacteremia Due to a Methicillin‐Resistant Strain Among Older Adults With Staphylococcus aureus Bacteremia (SAB)

Open New Window

Forty‐three (50%) of the 86 cases of community‐acquired SAB were due to MRSA, whereas 31 (63%) of 49 cases of hospital‐acquired SAB were due to MRSA ( ). Thirty (70%) of the 43 patients with community‐onset MRSA bacteremia had been previously hospitalized in the past 3 months, whereas 19 (61%) of the 31 patients with hospital‐acquired MRSA bacteremia had been previously hospitalized in the past 3 months. Multivariate analysis indicated that the most common predictors of MRSA bacteremia among older adults were previous hospitalization in the past 3 months, residence in a long‐term care facility, and altered mental status at the onset of SAB (Table 4).

Table 4.  Results of Multivariate Analysis of Methicillin Resistance Among Older Adults With Staphylococcus aureus Bacteremia (SAB)

Open New Window

Discussion

This is the first study, to our knowledge, to determine 7‐day mortality and its predictors among older adults with SAB after adjustment for comorbid conditions using the Charlson WIC scoring system. A Charlson WIC score greater than 5, previous hospitalization in the past 3 months, and altered mental status at the onset of SAB were independent predictors of death among older adults with SAB. Our findings verify those of a previous study that demonstrated that comorbid conditions measured by the Charlson WIC scoring system are an important predictor of mortality in patients with SAB.⁸ However, in that previous study, a score of 3 or more was a significant predictor of mortality. This difference might be due to variation in the study population. The previous study included patients who were 18 years and older, and the mean age of the study population was 65 years.⁸ Our study included patients who were aged 60 years and older, and the mean age of the patients was 73 years.

Adults older than 65 years are more likely to have chronic conditions, compared with patients in other age categories. Other studies have used the McCabe and Jackson classification to control for comorbidity and found it a significant predictor of mortality in patients with SAB.^7,13 The McCabe and Jackson classification has been criticized for being subjective and not accounting for the seriousness and the combination of comorbid diseases (Appendix, Table A2).¹⁴

The Charlson WIC is a simple, objective scoring system that accounts for the severity and combination of underlying diseases.¹¹ However, there are several disadvantages to using the Charlson WIC score as a predictor of mortality among older adults with SAB. First, the comorbidities included in the scoring system may not include all comorbid conditions (such as immobility) that are associated with increased mortality in patients with SAB. Second, some comorbid conditions included in the scoring system may either have no association with the increased mortality due to SAB or be inappropriately weighted in the calculated scores. For example, we are not aware of any study that found an association between peptic ulcer diseases or dementia and increased mortality in patients with SAB. Third, the Charlson WIC system does not account for the significance of acute events, such as myocardial infarction, trauma, and surgical complications. We have compensated for this deficiency by using SAPS II to adjust for the severity of acute conditions. Finally, the Charlson WIC score also does not account for the improved prognosis for patients with comorbid conditions since the introduction of new therapeutic methods.^11,15,16

In our study, comorbidity measured by the Charlson WIC was not a significant predictor of the presence of MRSA bacteremia among older adults with SAB. McGregor et al.¹⁶ found in a case‐control study that comorbidity measured by either the Charlson WIC score or the chronic disease score was not a good predictor of MRSA‐associated nosocomial bloodstream infection.

Previous hospitalization in the past 3 months was associated with both increased mortality due to SAB and isolation of MRSA. All patients with community‐onset SAB who died within 7 days after the onset of SAB had previously been hospitalized in the past 3 months, whereas more than 80% of patients with hospital‐acquired SAB had previously been hospitalized in the past 3 months. Most patients with community‐onset MRSA bacteremia had previously been hospitalized in the past 3 months. Previous hospitalization is a known risk factor for colonization with MRSA that may persist for months to years.^17,18 Several studies found that most cases of community‐onset MRSA bacteremia were healthcare related and had been preceded by a previous hospitalization.^18‐21 Morin and Hadler¹⁹ found that only 16% of patients with healthcare‐associated SAB were infected with MRSA, whereas Freidman et al.²⁰ found that 51% of their patients with healthcare‐associated SAB had MRSA infection. In our study, 49 (64%) of 76 previously hospitalized older adults with SAB had MRSA infection. This difference might be a reflection of a higher prevalence of MRSA infection among older adults.^4,9 Since most MRSA among older adult patients is acquired through contact with the healthcare system, it may be prevented by intensively applied infection control measures. The mortality was also greater in patients with healthcare‐associated infection who had been hospitalized in the 3 months before their bloodstream infection (29% vs 16%; ) than in patients with true community‐acquired infection.²⁰

This study has several limitations. The size of our sample of older adults with SAB was small and was predominantly male. We did not study the effect on mortality of different available treatment options for SAB. Previous studies have not found a significant difference in mortality associated with treatment with vancomycin, a β‐lactam, or other antibiotics or with a delay in treatment for 48 hours.^6,22 We had no information on antibiotics received previously and their impact on the percentage of our patients with MRSA bacteremia. Previous use of antimicrobial agents has been associated with the isolation of MRSA from patients with SAB.²³

Several important conclusions can be drawn from this study. First, comorbidity measured by the Charlson WIC is a good predictor of mortality among older adults with SAB, and it should be used to control for comorbidity in studies that investigate the risk factors of mortality among older adults with SAB. Second, older adults are more likely to be infected with MRSA. Therefore, vancomycin should be considered for empirical therapy, pending the results of susceptibility testing. This is particularly important for patients who reside in a long‐term care facility, present with altered mental status at the onset of SAB, or have been previously hospitalized in the past 3 months. However, an initial delay of 2 days in the use vancomycin before the preliminary susceptibility testing did not adversely affect outcomes among patients with MRSA bacteremia.²⁴ Third, both altered mental status at the onset of SAB and previous hospitalization in the past 3 months are predictors of increased mortality and the isolation of MRSA among older patients with SAB. Infection control measures, such as identification of patients for isolation or performance of surveillance cultures, should be considered for such patients, in addition to patients who reside in a long‐term care facility.