Sunday, May 28, 2023
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Uniformed Services University of the Health Sciences, Bethesda, Maryland
This CME offering is intended for physicians, physician assistants, pharmacists, nurse practitioners, and nurses.
A review of the literature, suggestions from thought leaders in the field of treatment of gram-positive infections, and comments from previous CME offerings indicate that physicians and other healthcare providers need up-to-date information on adequate treatment for bacteremia caused by S aureus, particularly MRSA . Therefore, this CME activity reviews current evidence in the treatment of S aureus bacteremia to help providers make appropriate choices for effective treatment of their patients with S aureus bacteremia.
Upon completion of this activity, participants will be able to:
It is the policy of AKH Inc. to ensure independence, balance, objectivity, scientific rigor, and integrity in all of their
continuing education activities. The faculty must disclose to the participants any significant relationships with the commercial
companies whose products or devices may be mentioned in the program or with the commercial supporter of this continuing education
activity. The information is for participant information only; it is not assumed that these relationships will have a negative
impact on the content of the activity.
AKH Inc. and its shareholders have no significant financial relationships with the manufacturers of medical or pharmaceutical products, nor with the providers of non-educational medical services.
This program is designed solely to provide the healthcare professional with information to assist in his/her practice and
professional development. The program is researched thoroughly utilizing current literature and includes practical experiences.
This program is not to be considered a diagnostic tool to replace professional advice or treatment. The program serves as
a general guide to the healthcare professional, and therefore, cannot be considered as giving legal, nursing, medical, or
other professional advice in specific cases. The faculty specifically disclaim responsibility for any adverse consequences
resulting directly or indirectly from information in the course. AKH further disclaims any responsibility for undetected error,
or from through participant's misunderstanding of the course. No part of this program may be reproduced, stored in a retrieval
system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise without
the prior written permission of AKH Inc.
Uniformed Services University of the Health Sciences, Bethesda, Maryland
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Staphylococcus aureus is increasingly recognized as a common and serious cause of bacteremia. Valles and colleagues[1] reported that S aureus was the third most frequent cause of community-acquired bacteremia in a European multicenter study, accounting for 13.6% of cases. Of 46 patients with S aureus bacteremia, 26 (56.5%) had septic shock, and 27 (58.7%) died. Mylotte and colleagues,[2] focusing on a different setting, studied 166 nursing home residents with bacteremia. In this study, S aureus was the second most common pathogen, causing approximately 1 in 5 cases of bacteremia. To better understand the epidemiology of S aureus bacteremia, Chang and colleagues[3] identified 505 patients with community-acquired, nosocomial, or nursing home-related S aureus bacteremia as part of a cooperative, multicenter, prospective observational project. Among individuals with S aureus bacteremia, the 30-day mortality rate was 31% in patients who had endocarditis and 21% in patients who had bacteremia not complicated by endocarditis.
Bacteremia due to S aureus also remains common in certain special populations, such as patients with human immunodeficiency virus (HIV) infection. In a study of men with community-acquired or nosocomial S aureus bacteremia, Senthilkumar and colleagues[4] found that HIV infection increased the risk of S aureus bacteremia nearly 17-fold. In a study of 109 episodes of endocarditis in 101 patients, S aureus was the most commonly isolated pathogen (45%), particularly among those with HIV infection.[5]
The continuing increase in the incidence of infections caused by methicillin-resistant S aureus (MRSA) complicates the approach to treating S aureus bacteremia. The National Nosocomial Infections Surveillance System of the Centers for Disease Control and Prevention[6] estimates that the prevalence of methicillin resistance among S aureus strains causing nosocomial infections in patients in the intensive care unit (ICU) reached 57% in 2002, an absolute increase of 13% over the 44% prevalence in the previous 5-year period. Among the more than 82,000 blood culture isolates reported in hospitalized patients in the United States in 2002, S aureus was the second most common pathogen, and 49% of S aureus isolates were methicillin resistant.[7] In addition, MRSA is no longer a pathogen found primarily in ICUs. Methicillin resistance was present in 52% of S aureus isolates from ICU patients and 49% of S aureus isolates from non-ICU patients. In other words, the assumption that MRSA is a problem confined to severely ill patients in the ICU is no longer valid.
Investigators have noted evidence of the increasing burden of MRSA in analyses distinct from reviews of large surveillance networks. The study by Valles and colleagues,[1] for example, confirmed a rise in the prevalence of infections due to MRSA, with 10 of the 46 cases of S aureus bacteremia (22%) caused by methicillin-resistant strains. The most common resistant organism in the study by Mylotte and colleagues[2] was MRSA, occurring in 12 of the 41 cases of S aureus bacteremia (29%). Finally, Chang and colleagues[3] noted that MRSA was the causative pathogen in 154 of the 441 cases of S aureus bacteremia without endocarditis (35%) and in 20 of the 64 cases with endocarditis (31%).
Efforts to identify clinical variables that identify patients likely to be infected with MRSA as opposed to methicillin-susceptible S aureus (MSSA) have been frustrating. Johnson and colleagues[8] investigated the changing epidemiology of nonnosocomial bacteremia caused by MRSA or MSSA. Patients infected with MRSA were more likely to reside in a long-term care facility (27% vs 4%, P = .05) and to have had multiple hospitalizations (46% vs 15%, P = .03). Other risk factors for MRSA infection (eg, dialysis, presence of a central venous catheter) failed to distinguish MRSA from MSSA. In a 1980 outbreak of MRSA infections in the same community, a single clone predominated. However, Johnson and colleagues[8] observed 14 unique strains among the 26 patients with nonnosocomial MRSA bacteremia. Several of these strains were identical to those isolated from patients with nosocomial MRSA bacteremia. These findings suggest that nonnosocomial spread of MRSA is often related to contact with the healthcare system.
Bacteremia has traditionally been categorized as nosocomial or community acquired. Nosocomial refers to an infection that originates in the hospital, is not present or incubating before admission, and generally develops within 72 hours after admission. By default, community-acquired bacteremia has included infections that are not nosocomial. Recent evidence supports the existence of a third category, healthcare-related bacteremia, for infections that are present at admission or develop within the first 48 hours after hospitalization in patients who have had recent exposure to healthcare outside the hospital (eg, home or clinic intravenous therapy), who were hospitalized for 2 or more days in the previous 90 days, or who live in a nursing home or other long-term care facility.[9]
The debate about the burden of MRSA infection with respect to both morbidity and mortality continues. Recent reports show convincingly that MRSA infections are associated with increased costs and longer lengths of hospitalization. For mortality, the question remains clouded by issues related to the adequacy of initial antibiotic therapy. Osmon and colleagues,[11] for example, conducted a study of hospital mortality among patients with nosocomial, healthcare-related, or community-acquired bacteremia. Of the 265 patients with S aureus bacteremia, 148 (56%) were infected with MRSA and 117 (44%) with MSSA. Patients with MRSA infection had higher incidences of chronic obstructive pulmonary disease (20.3% vs 6.0%; P = .001) and congestive heart failure (45.3% vs 28.2%; P = .004). Prior antibiotic use was more common in patients with MRSA infections (31.8% vs 15.4%; P = .002).
Patients with bacteremia caused by MRSA used more healthcare resources than those with bacteremia due to MSSA.[11] Patients with MRSA bacteremia also required more days of antibiotic treatment (9.9 vs 6.2; P = .001); had greater use of vancomycin (8.4 days vs 4.4 days; P < .001); and spent more time in the hospital (22.1 vs 13.2 days; P = .001), in the ICU (15.9 vs 9.1 days; P = .017), and on mechanical ventilation (21.4 vs 7.4 days; P = .001).
Although patients in the MRSA and MSSA groups had similar responses to initial treatment (83.1% and 88.9%, respectively; P = .182) and similar hospital mortality rates (13.5% and 16.2%, respectively; P = .534), these similarities may have been related to an institutional practice of treating patients with vancomycin when bacteremia is suspected and MRSA has not yet been excluded.[11] The failure to note a difference in mortality suggests that MRSA is not more virulent per se. Rather, the key issue is the adequacy of initial therapy. In other words, if patients infected with MRSA receive an agent active against MRSA as part of their initial antibiotic regimen, they do not necessarily face an increased risk of death. For the clinician practicing at an institution where MRSA is a problem pathogen, this means that use of anti-MRSA agents must increase if one hopes to avoid the risk of mortality associated with delaying antibiotic treatment until culture results are available.
In a 6-year study of 815 patients with nosocomial or healthcare-related S aureus bacteremia, Melzer and colleagues[12] examined the risk of death attributable to MRSA. Methicillin-resistant S aureus was present in 382 patients (46.9%), and MSSA was present in 433 (53.1%). Patients infected with MRSA were older, more often in the ICU when the first episode of bacteremia developed, more likely to have wounds (classified as sternal or nonsternal), and less likely to be dependent on dialysis or to have a primary infection at the site of access for a peripheral vascular catheter. Attributable mortality was significantly higher among patients infected with MRSA (11.8% vs 5.1%; OR, 2.49; 95% CI, 1.46 to 4.24; P < .001). Even after adjustment for host variables (eg, age, primary site of infection), attributable mortality remained higher for patients with MRSA infections (OR, 1.72; 95% CI, 0.92 to 3.20; P = .09). These investigators, however, did not control for the appropriateness of initial antibiotic therapy.
Blot and colleagues[13] performed a similar investigation to describe the clinical characteristics and outcomes of patients with bacteremia due to MRSA. Studying 47 patients infected with MRSA and 38 infected with MSSA, they found that patients with MRSA infections were more severely ill. Before they developed bacteremia, these patients had more instances of acute renal failure (26% vs 0%; P < .001) and hemodynamic instability (62% vs 32%; P = .01), were hospitalized longer (29 vs 10 days; P < .001), and spent more time in the ICU (20 vs 8 days; P = .001). They also were more severely ill as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system (23 vs 17; P = .001).
Compared with MSSA, MRSA is associated with worse outcomes, including longer hospital and ICU stays, longer durations of mechanical ventilation, and higher mortality rates. In addition, the cost of treating patients with bacteremia due to MRSA is higher. Inadequate antibiotic therapy is common, is associated with significant mortality, and perhaps explains why outcomes in MRSA infection are so poor. Emerging data suggest that therapy with vancomycin is less than optimal; treatment failure and mortality rates are substantial whether the cause of bacteremia is MRSA or MSSA. Because MRSA is far more common in healthcare-related or nosocomial bacteremia than in community-acquired bacteremia, empiric antibiotic therapy for patients with healthcare-related bacteremia should include coverage for MRSA.
