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OBJECTIVES: To assess clinical outcomes and identify risk factors for mortality in older adults with Staphylococcus aureus bloodstream infection (SAB).
DESIGN: Retrospective review.
SETTING: University of Michigan Health System, Ann Arbor.
PARTICIPANTS: All patients aged 80 and older with SAB between January 2004 and July 2008.
MEASUREMENTS: Clinical data, including comorbid conditions, SAB source, echocardiography results, Charlson Comorbidity Index, mortality (in-hospital and 6-month), and need for rehospitalization or chronic care after discharge.
RESULTS: Seventy-six patients aged 80 and older (mean 85.5 ± 4.2) with SAB were identified. Infection sources included 14 (18.4%) vascular catheter associated, 16 (21.1%) wound related, seven (9.2%) endocarditis, five (6.6%) intravascular, and 19 (25%) with unknown source; 46 (60.5%) patients had methicillin-resistant strains. Twenty-two (28.9%) patients underwent surgery or device placement within 30 days of developing SAB; 10 of these 22 had SAB associated with surgical site infection (SSI). Twenty two (28.9%) patients died in the hospital or were discharged to hospice care; at least 43 (56.6%) patients died within 6 months of presentation, and eight were lost to follow-up. Unknown source of bacteremia (odds ratio=5.2, P=.008) was independently associated with in-hospital death. Echocardiography was not pursued in 45% of patients. Of surviving patients, 40 (74.1%) required skilled care after discharge; eight (20%) required rehospitalization.
CONCLUSION: SAB was associated with high mortality rates in patients aged 80 and older. The observed association between SAB and SSI may direct preventive strategies such as perioperative decolonization or antimicrobial prophylaxis. Interventions to optimize clinical care practices in elderly patients with SAB are essential given the associated morbidity and mortality.
The continued expansion of the geriatric population has been associated with an increase in the number of serious infections in older adults, including bloodstream infections.1–4Staphylococcus aureus bloodstream infection (SAB) represents a significant burden in terms of morbidity and mortality for older adults. Major risk factors associated with the development of SAB includes the presence of comorbid illnesses, such as congestive heart failure, chronic kidney disease, and diabetes mellitus, and the use of medical devices.5–10 The overall rates of SAB also increase with age, as does mortality and attributable mortality, which is twice as high in patients aged 65 and older as in younger patients.5,8,9
Recent work has suggested that the odds of death within 6 months of SAB doubles for every decade increase in age, and four of seven (57%) patients aged 80 older died within 6 months.5 Based on these observations, it was decided to specifically review the records of a different and larger cohort of older patients (≥80) to better define risk factors for mortality and identify potential areas for intervention. The clinical course of SAB in the oldest old (≥80) and risk factors for in-hospital mortality were examined.
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The preceding results provide further evidence that SAB results in substantial mortality in older adults. This patient population experienced 28.9% in-hospital and at least 56.6% 6-month mortality. Risk factors for death included unknown source of bacteremia, lack of echocardiography evaluation, acute renal insufficiency, and high Charlson WIC (Table 3). Unknown source of infection remained independently associated with in-hospital mortality on multivariable analysis (Table 4).
Table 4. Multivariate Analysis of the Association Between Select Patient Characteristics and In-Hospital Mortality in Patients Aged ≥80 with Staphylococcus aureus Bloodstream Infections
|Characteristic||OR (95% CI) P-Value|
|MRSA||2.1 (0.7–6.3) .16||2.1 (0.6–7.2) .22|
|Unknown cause infection||5.8 (1.9–17.7) .001||5.2 (1.5–18.0) .008|
|Acute renal insufficiency||2.9 (1.1–8.3) .03||1.7 (0.5–5.7) .37|
|Charlson weighted index||1.3 (1.03–1.6) .03||1.2 (1.0–1.6) .10|
The reasons for the association between unknown cause of bacteremia and in-hospital mortality remains unclear. One possible explanation is that extensive diagnostic efforts to identify a source were not pursued, and therefore a source was not identified. Review of patient records suggests that this was the case for some of the patients with unknown source because clinicians caring for these individuals documented that the overall prognosis was poor. Several patients with unknown source of infection died soon after admission or were quickly discharged to hospice care. Review of the medical chart suggests that aggressive medical examination was not pursued in part because of a presumed poor prognosis. The duration of bacteremia was shorter in patients with unknown source than in patients with an identifiable source (1.4 ± 0.8 days vs 4.1 ± 6.0 days, P=.05). This finding probably reflects that several patients with unknown source died soon after admission or were discharged to hospice care—so these patients did not have an opportunity to have extended bacteremia.
Of the 19 patients with unknown source, 14 did not have echocardiography evaluation. The lack of echocardiography may have confounded these results, because several patients with unknown source could have had occult endocarditis, an infection associated with higher mortality than simple SAB, particularly in older adults.13,14 Ten (52.6%) of the 19 patients with unknown source were community dwelling before admission, which probably increases the possibility of occult endocarditis.13,14 The microbiology in patients with unknown source did not differ from the overall cohort; 12 (63.2%) of the 19 had MRSA (vs 60.5% overall). Regardless of possible misclassification bias, the observed association between unknown source of SAB and greater mortality warrants further investigation in larger, prospective studies.
Perhaps more importantly, the diagnostic approach to older adults with SAB should be examined critically. Forty-five percent of patients did not undergo any type of echocardiography in the setting of SAB. In general, transesophageal echocardiography (TEE) is recommended for patients with any blood culture positive for S. aureus to excluded occult endocarditis,15 but TEE is an invasive procedure that requires sedation, anesthesia, or both, and some clinicians may have perceived this testing as too aggressive in this older cohort, particularly for patients who were felt to have a poor prognosis overall. Alternatively, clinicians may have had similar feelings in patients with short durations of SAB with a clearly identifiable source. Both of these scenarios were noted in the patients who did not receive TEEs. Low rates of transthoracic echo testing, which unlike TEE, is a noninvasive test, were also observed.
Prospective evaluation should consider clinicians' reasons for ordering or not ordering TEE for older adults in the setting of SAB. It remains unclear whether confirmation of a diagnosis of endocarditis would affect clinical outcomes, because definitive treatment with valve replacement surgery also has significant operative risk.16 Elderly patients with infective endocarditis have been noted to have lower rates of surgical treatment and higher mortality than younger patients.13 Alternatively, by excluding endocarditis, TEE results might help clinicians select shorter durations of parenteral antimicrobial therapy with confidence, thus decreasing the risk of adverse events related to extended courses of antistaphylococcal therapy and the extended need for intravenous access. Although the reasons for not obtaining echocardiography remains unclear, the results may offer important prognostic information and thus help establish overall goals of care in a population with a high incidence of adverse events (including mortality).
The association of SAB with prior surgery or other invasive procedures before SAB is another important observation. In these patients, the surgical intervention was the source of SAB almost half of the time. Interventions to decrease S. aureus–related surgical site infections (SSIs) include preoperative screening and decolonization efforts.17,18 Although larger studies have failed to show consistent benefits of this strategy, older patients may benefit with a modified version of this approach. Recent work has demonstrated a strong association between ADL impairment and MRSA SSIs.19 Although functional status is generally not considered an absolute contraindication for surgery, the observation that even modest impairment in ADLs can result in significant risk of MRSA SSI (and consequently SAB) is notable.19 The association between SSI and SAB presents another important area for future investigation, particularly with regard to preventative strategies.20,21
Although MRSA is well recognized as an important risk factor for death in patients with SAB,6,7,22,23 the results of the current study failed to show such an association. The lack of association probably reflects the large portion of patients who had MRSA, the high rates of overall mortality, or simply a Type II error due to a relatively small sample size. Although no association was observed between baseline functional status (independent vs requiring assistance with ADLs) and mortality, earlier studies have clearly demonstrated the relationship between poor functional status and infection-related mortality.24,25 Detailed measures of functional status should be recorded in future studies of SAB to help further define the relationship between debility and infection outcomes.
Although its retrospective design and small sample size limited the present study, the results show significant in-hospital and 6-month mortality in elderly patients with SAB. There is also a possible association with recent surgeries or implantation of medical devices. The reasons why clinicians did not pursue echocardiography evaluation in this patient cohort are unclear but may reflect a belief that the risks of TEE are perceived as too high in older adults. Future investigation of SAB in older adults should focus on preventative strategies, as well as diagnostic and treatment paradigms, given the high morbidity and mortality associated with this infection.
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Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper.
This work was supported in part by the Veterans Affairs Ann Arbor Healthcare System, Geriatric Research Education and Clinical Center. This work was presented in part at the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America 46th Annual Meeting, Washington, DC, October 25 to 28, 2008.
Author Contributions: Big: study design, data collection, manuscript preparation. Malani: study design, analysis and interpretation of data, manuscript preparation.