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CME/CE

Bacteremia Due to Staphylococcus aureus: Acquisition, Methicillin Resistance, and Treatment Issues

  • Authors: Faculty: Andrew F. Shorr, MD, MPH; William L. Jackson, MD
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Target Audience and Goal Statement

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:

  1. Discuss the impact of Staphylococcus aureus bacteremia on patient morbidity and mortality and on overall healthcare costs.
  2. Define and discuss the differences in nosocomial, healthcare-related, and community-acquired infections.
  3. Describe the importance of appropriate antimicrobial therapy in relation to patient morbidity and mortality.
  4. Identify concerns with traditional treatment options for patients with MRSA bacteremia.


Disclosures

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.


Author(s)

  • Andrew F. Shorr, MD, MPH

    Uniformed Services University of the Health Sciences, Bethesda, Maryland

    Disclosures

    Disclosure: Grants/Research Support: Pfizer Inc.

    Dr. Shorr intends to discuss unapproved, investigative uses of a commercial product.

  • William L. Jackson, MD

    Critical Care Medicine Service, Department of Surgery, Walter Reed Army Medical Center

    Disclosures

    Disclosure: Dr. Jackson declares no significant financial interest or other relationships with the manufacturers of any commercial products or services discussed in this educational presentation or with the commercial supporter of this educational activity.

    Dr. Jackson does not intend to discuss unapproved, investigative uses of a commercial product.


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  • AKH Inc. is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

    AKH Inc. designates this educational activity for a maximum of 1.0 category 1 credit toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.

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    For Nurses

  • AKH Inc. is accredited as a provider of continuing education in nursing by the American Nurses Credentialing Center (ANCC) and through the boards of nursing in CA#: CEP12070 and IA#: 277. This course is designed to meet the criteria for all state boards of nursing requiring continuing education.

    This educational activity is for 1.2 contact hours (0.12 CEU).

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  • AKH Inc. is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This program has been assigned the Universal Program Number UPN# 077-999-04-031-H01 and is acceptable for 1.0 contact hours (0.1 CEUs) in states that recognize ACPE-approved providers.

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For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]


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CME/CE

Bacteremia Due to Staphylococcus aureus: Acquisition, Methicillin Resistance, and Treatment Issues

Authors: Faculty: Andrew F. Shorr, MD, MPH; William L. Jackson, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

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Bacteremia Due to Staphylococcus aureus: Acquisition, Methicillin Resistance, and Treatment Issues, Presented by Andrew F. Shorr, MD, MPH; William L. Jackson, MD

Introduction

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]

Evolving Importance of Methicillin Resistance

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.

Healthcare-Related S aureus Bacteremia: A Unique Disease

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]

  • In a prospective cohort study of 504 patients with bacteremia, Friedman and colleagues[9] used specific criteria to categorize each case as nosocomial, healthcare related, or community acquired (Figure 1). Bacteremia was nosocomial in 175 patients (35%), healthcare related in 186 (37%), and community acquired in 143 (28%).[9] Of the 186 patients with healthcare-related bacteremia, 117 (63%) had been hospitalized in the preceding 90 days, 78 (42%) had received intravenous therapy or dialysis in the home or clinic, 64 (34%) had received home healthcare, and 29 (16%) were nursing home residents.

    S aureus was the most common pathogen in patients with healthcare-related or nosocomial bacteremia.[9] In contrast, Escherichia coli and Streptococcus pneumoniae were the most frequent organisms in patients with community-acquired bacteremia. Methicillin-resistant S aureus was isolated more often in patients with healthcare-related (35 of 186, 19%) or nosocomial bacteremia (35 of 175, 20%) than in those with community-acquired bacteremia (3 of 143, 2%).

  • Figure 1. Categories of bacteremia.

    Figure 1.

    Categories of bacteremia.

    (Enlarge Slide)
  • Sources of bacteremia and types of comorbid conditions differed between the groups.[9] Bacteremia associated with gastrointestinal tract infection was more common in the healthcare-related (17%) and nosocomial (13%) groups than in the community-acquired (4%) cohort. In contrast, the investigators reported that bacteremia secondary to urinary tract infection was documented more often in patients with community-acquired (46%) infection than in patients with healthcare-related (17%) or nosocomial (18%) disease. The incidence of bacteremia associated with intravascular devices was similar in the healthcare-related (42%) and nosocomial (52%) groups, highlighting the shared characteristics of healthcare-related and nosocomial infections. The distribution of comorbid illnesses varied on the basis of type of infection (Figure 2).

  • Figure 2. Comorbid conditions in nosocomial, healthcare-related, and community-acquired bacteremia.

    Figure 2.

    Comorbid conditions in nosocomial, healthcare-related, and community-acquired bacteremia.

    (Enlarge Slide)
  • Not surprisingly, outcomes differed among the 3 groups.[9] The median length of hospital stay was greater in patients with nosocomial bacteremia (23 days; interquartile range [IQR], 13.5 to 45 days) than in those with healthcare-related (7 days; IQR, 4 to 15 days) or community-acquired (6 days; IQR, 4 to 8.5 days) bacteremia. In-hospital mortality rates were significantly higher in the nosocomial group but did not differ significantly between the healthcare-related and community-acquired groups (P = .15) (Figure 3). Mortality rates 3 to 6 months after hospitalization were greater in the healthcare-related and nosocomial groups than in the community-acquired group (Figure 3). These results suggest that healthcare-related infection is a unique category, sharing characteristics with both community-acquired and nosocomial infections but lying somewhere between the two.

    Tacconelli and coworkers[10] obtained additional data about healthcare-related infections in a case-control study of 127 patients with bacteremia due to MRSA. In this study, a case was considered healthcare related if MRSA isolates were identified in blood cultures obtained within 24 hours of admission and the patient had recently been exposed to a healthcare setting or intervention. The criteria for recent exposure were similar to those used by Friedman and colleagues,[9] except that the window for recent hospitalization was expanded from 3 to 6 months.[10] Controls were matched for exposure to a healthcare setting or intervention but did not have MRSA recovered from blood cultures.

    No cases of community-acquired MRSA bacteremia were identified during the 5.5-year study period.[10] Cases that traditionally would have been considered community acquired were in fact healthcare related. Logistic regression analysis identified 4 risk factors independently associated with healthcare-related MRSA bacteremia: history of colonization or infection with MRSA (odds ratio [OR], 17.04; 95% confidence interval [CI], 4.98 to 58.27; P < .001), presence of a central venous catheter (OR, 3.30; 95% CI, 1.71 to 6.38; P < .001), and skin ulcers (OR, 3.12; 95% CI, 1.37 to 7.11; P = .007) or cellulitis (OR, 4.27; 95% CI, 1.52 to 11.94; P = .006) at admission. When history of colonization or infection with MRSA was excluded from the analysis, the presence of a central venous catheter remained a risk factor (OR, 3.24; 95% CI, 1.76 to 5.97; P < .001), but 3 other independent risk factors became apparent: hospitalization in the previous 6 months (OR, 2.01; 95% CI, 1.11 to 3.65; P = .02), quinolone use in the previous 30 days (OR, 1.99; 95% CI, 1.07 to 3.69; P = .02), and diabetes mellitus (OR, 1.84; 95% CI, 1.05 to 3.22; P = .03).

    The results of both studies support the concept of healthcare-related bacteremia as a distinct phenomenon. Although healthcare-related bacteremia is similar to nosocomial bacteremia in some ways (eg, incidence of cases due to S aureus and MRSA, source of infection, frequency of occurrence in patients with HIV or cancer, mortality rates at follow-up), it is also similar to community-acquired bacteremia (eg, length of hospital stay, in-hospital mortality rates).[9] Most importantly, recent hospitalization is a risk factor for healthcare-related bacteremia[10] and distinguishes this category of infection from both nosocomial and community-acquired infections.

  • Figure 3. Mortality due to nosocomial, healthcare-related, and community-acquired bacteremia.

    Figure 3.

    Mortality due to nosocomial, healthcare-related, and community-acquired bacteremia.

    (Enlarge Slide)

Is Methicillin-Resistant S Aureus Infection Worse?

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).

  • Those infected with MRSA faced worse outcomes: ICU stay was longer (37 vs 18 days; P < .001), durations of ventilator dependency was longer (29 vs 9 days; P < .001), and the mortality rate was significantly higher (Table 1).[13] On multivariate analysis, independent predictors of hospital mortality were methicillin resistance (hazard ratio [HR], 1.93; 95% CI, 1.18 to 3.18; P = .009), acute renal failure (HR, 4.13; 95% CI, 1.99 to 5.58; P < .001), and duration of mechanical ventilation (HR, 1.02; 95% CI, 1.00 to 1.03; P = .01). As in the Melzer and colleagues study,[12] attributable mortality was significantly higher among patients infected with MRSA (23.4% vs 1.3%; difference, 22.1%; 95% CI, 8.8% to 35.3%).[13]

  • Table 1. Mortality Rates in Patients With Bacteremia Caused by Staphylococcus aureus

    Table 1.

    Mortality Rates in Patients With Bacteremia Caused by Staphylococcus aureus

    (Enlarge Slide)
  • To summarize the emerging data on MRSA and outcomes and to better estimate the mortality associated with MRSA infection, Cosgrove and colleagues[14] conducted a meta-analysis of 31 S aureus bacteremia studies published from January 1980 through December 2000[15-45] (Figure 4). Of the 3963 patients described in the studies, 1360 (34.3%) had MRSA infections, and 2603 (65.7%) had MSSA infections. All-cause mortality was significantly higher in the MRSA group (pooled OR, 1.93; 95% CI, 1.54 to 2.42; P < .001). There was significant heterogeneity among the results of the studies (P = .03). However, when the researchers analyzed the results of the 11 studies that adjusted for potential confounding factors, mortality rates were again higher in patients infected with MRSA (pooled OR, 1.88; 95% CI, 1.33 to 2.69; P < .001); there was no heterogeneity among the results of these studies (P = .16). Analysis of the 6 studies that assessed attributable mortality revealed that infection with MRSA doubled the risk of death (pooled OR, 2.2; 95% CI, 1.2 to 3.8; P = .007).

    The economic impact of bacteremia due to MRSA is substantial. In a study of patients with primary nosocomial S aureus bacteremia who were hospitalized between December 1993 and March 1995, the median attributable total cost for bacteremia caused by MRSA was $27,083, compared with $9661 for bacteremia caused by MSSA (P = .043).[46] The mean attributable variable direct cost for MRSA bacteremia was $14,783, compared with $4989 for MSSA bacteremia (P = .043). Put simply, despite any controversy about mortality attributable to MRSA, the data clearly indicate that with the current treatment alternatives, costs are significantly higher for MRSA infection, whatever the source, than for MSSA infection.

  • Figure 4. Summary of unadjusted results of 31 studies included in meta-analysis.

    Figure 4.

    Summary of unadjusted results of 31 studies included in meta-analysis.

    (Enlarge Slide)

New Issues in Treatment

  • Endocarditis is a dreaded but unfortunately common complication of S aureus bacteremia. Over the last 5 years, several important trials have improved our understanding of this condition. Chang and colleagues[3] reported that 64 (13%) of the 505 patients with S aureus bacteremia in their study developed endocarditis; of these 64 patients, 20 (31%) were infected with MRSA. The severity of illness at diagnosis did not differ between the MRSA and MSSA groups (APACHE III score, 60.3 vs 51.9). But patients with endocarditis related to MRSA infection were more likely to have persistent bacteremia (65% vs 9%; P = .0001); in addition, mortality rates were significantly higher among these patients (Table 2).

    Unfortunately, clinical criteria alone are seldom adequate for identifying patients with endocarditis due to S aureus.[47] In cases of S aureus bacteremia, most experts generally recommend early use of transesophageal echocardiography. Fowler and colleagues[48] attempted to address this issue through a prospective, observational cohort study. From September 1994 through December 1999, 724 hospitalized patients with S aureus bacteremia were monitored for 12 weeks after the initial positive blood culture. S aureus bacteremia was community acquired in 124 (17%), healthcare related in 272 (38%), and nosocomial in 328 (45%).

    Complicated S aureus bacteremia occurred in 310 patients (43%): 228 (74%) had a complicated infection at the time of initial hospitalization, 86 (28%) died of S aureus bacteremia, 70 (23%) had recurrent S aureus infection, and 18 (6%) had embolic stroke.[48] Of the 228 patients with a complicated infection, 89 (39%) had endocarditis.

  • Table 2. Mortality Rates in Patients With Endocarditis Caused by Staphylococcus aureus

    Table 2.

    Mortality Rates in Patients With Endocarditis Caused by Staphylococcus aureus

    (Enlarge Slide)
  • In a model based on analysis of the 711 patients for whom data were available, 4 variables were significantly associated with complicated S aureus bacteremia.[48] By assigning points to these variables, the researchers created a risk-scoring system that relies on readily available clinical information to identify complicated S aureus bacteremia (Table 3).

  • Table 3. Variables Associated With Complicated S aureus Bacteremia and Their Assigned Points

    Table 3.

    Variables Associated With Complicated S aureus Bacteremia and Their Assigned Points

    (Enlarge Slide)
  • The risk of complications was 16% for patients who had none of the 4 risk factors and increased as the number of risk factors increased (Figure 5).

  • Figure 5. Association between the Staphylococcus aureus bacteremia score and probability of

    Figure 5.

    Association between the Staphylococcus aureus bacteremia score and probability of complicated Staphylococcus aureus bacteremia.

    (Enlarge Slide)
  • As noted earlier, adequacy of initial antibiotic treatment has emerged as an important aspect of our approach to bacteremia. To more precisely estimate the risks associated with inadequate treatment, Ibrahim and colleagues[27] investigated predictors of mortality in 492 patients with bacteremia. Unadjusted mortality rates were more than twice as high in patients receiving inadequate antimicrobial therapy (Table 4). In multivariate analysis, inadequate antimicrobial therapy represented the strongest independent predictor of hospital mortality (adjusted OR, 6.86; 95% CI, 5.09 to 9.24; P < .001). In this cohort of subjects, MRSA was the third most common pathogen that physicians treated inadequately. Among the patients with bacteremia due to MRSA, 33% received inadequate therapy, and the mortality rate was 37%; in contrast, fewer than 5% of patients with bacteremia due to MSSA received inadequate therapy. Reflecting this difference in the frequency of inadequate therapy was the lower (25%) mortality rate among patients with bacteremia due to MSSA.

    Valles and colleagues[1] further demonstrated the consequences of inadequate antimicrobial therapy. In their study, inadequate empiric antibiotic therapy at ICU admission was the most important independent predictor of death (OR, 4.11; 95% CI, 2.03 to 8.32). These investigators also identified 2 other independent predictors of a poor prognosis: septic shock (OR, 3.22; 95% CI, 1.69 to 6.13) and an APACHE II score of 15 or greater at ICU admission (OR, 2.42; 95% CI, 1.30 to 4.51). It is important to note that of the 3 variables, only the selection of antibiotic therapy is within the clinician's control.

    In the study by Valles and colleagues,[1] the mortality rate was 69.4% among patients who received inadequate therapy as opposed to 37.0% among those given adequate therapy (P < .05). Although S aureus was the third most common pathogen overall, it was the most common pathogen in patients who received inadequate therapy. Of the 46 patients with S aureus bacteremia, 15 (32.6%) received inadequate treatment, and 27 (58.7%) died (P < .05 vs patients who survived).

    An emerging concept is that vancomycin is a less-than-adequate antibiotic to treat S aureus bacteremia. To evaluate the effectiveness of vancomycin, Chang and colleagues[49] studied 444 patients with bacteremia caused by S aureus and explored outcomes as a function of resistance to methicillin. Methicillin-susceptible S aureus was identified in 298 subjects (67%), and therapy failed in 59% of the 70 patients treated with vancomycin despite the in vitro efficacy of this agent against MSSA. Methicillin-resistant S aureus accounted for 146 isolates (33%); treatment failed in 21 (25%) of the 83 patients who were treated with vancomycin. These findings suggest a disconnect between in vitro susceptibility and clinical response. The poor penetration of vancomycin and other glycopeptides into certain parts of the body, particularly the lung, may explain this observation. Difficulty in proper dosing probably also contributes to suboptimal outcomes with vancomycin, even in cases in which this agent should be efficacious. In this study, only treatment with vancomycin (OR, 6.5; 95% CI, 1.0 to 52.8; P < .048) and the development of endocarditis (OR, 7.6; 95% CI, 2.5 to 22.8; P < .009) predicted relapse among patients with bacteremia due to MSSA.

    Other trials support the hypothesis that vancomycin may be a suboptimal treatment option for S aureus bacteremia. Gonzalez and coworkers[50] prospectively studied patients with bacteremic pneumonia due to S aureus. Eighteen (56.3%) of 32 patients with MRSA and 22 (40.7%) of 54 patients with MSSA died because of the infection. In patients treated with vancomycin, mortality rates were equally high whether the pathogen was MRSA or MSSA (50% and 47%, respectively). As reported by Chang and colleagues,[49] treatment with vancomycin independently correlated with poor outcomes in MSSA: Mortality was 14.5-fold greater in patients who received vancomycin (OR, 14.5; 95% CI, 1.43 to 145.64).[50]

  • Table 4. Mortality and Adequacy of Therapy in Patients With Bacteremia

    Table 4.

    Mortality and Adequacy of Therapy in Patients With Bacteremia

    (Enlarge Slide)

Conclusions

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.