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Original Research: PNEUMONIA |

Relationship of Vancomycin Minimum Inhibitory Concentration to Mortality in Patients With Methicillin-Resistant Staphylococcus aureus Hospital-Acquired, Ventilator-Associated, or Health-care-Associated Pneumonia FREE TO VIEW

Nadia Z. Haque, PharmD; Lizbeth Cahuayme Zuniga, MD; Paula Peyrani, MD; Katherine Reyes, MD; Lois Lamerato, PhD; Carol L. Moore, PharmD; Shruti Patel, MD; Marty Allen, MD; Edward Peterson, PhD; Timothy Wiemken, MPH; Ennie Cano, PharmD; Julie E. Mangino, MD; Daniel H. Kett, MD; Julio A. Ramirez, MD; Marcus J. Zervos, MD; the Improving Medicine through Pathway Assessment of Critical Therapy of Hospital-Acquired Pneumonia (IMPACT-HAP) Investigators
Author and Funding Information

From the Henry Ford Health System (Drs Haque, Cahuayme Zuniga, Reyes, Lamerato, Moore, Patel, Peterson, and Zervos), and the School of Medicine (Dr Zervos), Wayne State University, Detroit, MI; the University of Louisville (Drs Peyrani, Allen, and Ramirez and Mr Wiemken), Louisville, KY; the Ohio State University (Dr Mangino), Columbus, OH; and the University of Miami Miller School of Medicine and Jackson Memorial Hospital (Drs Cano and Kett), Miami, FL.

Correspondence to: Marcus J. Zervos, MD, Infectious Diseases, Wayne State University School of Medicine, Henry Ford Health System, 2799 West Grand Blvd, Detroit, MI 48202; e-mail: mzervos1@hfhs.org


Part of this article was published previously in abstract form (Haque NZ, Cahuayme Zuniga L, Osaki Kiyan P, et al; IMPACT-HAP Study Group. Relationship of MIC to vancomycin on outcome of methicillin-resistant Staphylococcus aureus health care-associated and hospital-acquired pneumonia. In: 48th Annual ICAAC/IDSA 46th Annual Meeting; October 25-28, 2008; Washington, DC. Abstract K-531).

Funding/Support: This work was supported by a grant from Pfizer Inc US Medical.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(6):1356-1362. doi:10.1378/chest.09-2453
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Background:  Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health-care-associated pneumonia (HCAP). These infections are associated with significant morbidity, mortality, and cost. The impact of vancomycin minimum inhibitory concentration (MIC) on mortality for patients with MRSA pneumonia has not been determined.

Methods:  Adult patients in ICUs with a diagnosis of MRSA HAP, VAP, or HCAP were entered in the study. Clinical and laboratory information were prospectively collected. Vancomycin MIC and heteroresistance were determined for each MRSA isolate. Data were collected from February 2006 through August 2007. The primary outcome variable was all-cause mortality at day 28. A propensity score approach was used to adjust for confounding variables.

Results:  The study sample consisted of 158 patients. All-cause mortality at day 28 was 32.3%. The majority of MRSA isolates had a vancomycin MIC ≥ 1.5 mg/mL (115/158, 72.8%). Propensity score analysis demonstrated an increase in 28-day mortality as vancomycin MIC increased from 0.75 to 3 mg/mL (P ≤ .001). Heteroresistance to vancomycin, demonstrated in 21.5% isolates, was not associated with mortality.

Conclusions:  Mortality in patients with MRSA HAP, VAP, and HCAP increases as a function of the vancomycin MIC, even for strains with MIC values within the susceptible range. Evaluation of vancomycin MICs should be contemplated at the institutional level and for individual cases of MRSA pneumonia. The use of vancomycin therapy in patients with MRSA pneumonia caused by isolates with MICs between 1 and 2 mg/mL should be undertaken with caution, and alternative therapies should be considered.

Figures in this Article

Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as a major cause of nosocomial and health-care-associated pneumonia (HCAP).1 The prevalence of MRSA infections is increasing, and these infections are associated with significant morbidity, mortality, and cost of medical care.2-4 Vancomycin has been the cornerstone of therapy for serious MRSA infections, and its use has increased dramatically worldwide since the mid-1980s, largely as a result of both empirical and directed therapy against the increasing number of MRSA infections.5

This increasing use of vancomycin contributes to the growing problem of nonsusceptible strains in both community and hospital settings.6 Although cases of vancomycin-intermediate Saureus with minimum inhibitory concentrations (MIC) of 4 to 8 μg/mL and vancomycin-resistant strains (MIC ≥ 16 μg/mL) have been reported in the literature, they still remain rare.5,7 However, cases of vancomycin treatment failure despite apparent in vitro susceptibility have increasingly been reported, particularly for strains with vancomycin MICs of 1 to 2 μg/mL, well within the susceptible range.8,9

Most of the information on the possible relationship of vancomycin MICs to treatment outcome has been described in patients with MRSA bacteremia9-11 and patients with a variety of other infections caused by MRSA.12 However, to our knowledge, no clinical studies have specifically assessed the relationship of vancomycin MICs to treatment outcomes in patients with MRSA hospital-acquired pneumonia (HAP), including HCAP and ventilator-associated pneumonia (VAP). Information specific for this particular group of patients is critical because several studies have consistently reported clinical failure rates of 40% or greater for vancomycin in patients with nosocomial pneumonia, including patients in ICUs and mechanically ventilated patients.13-15

The objective of this study was to describe the relationship between vancomycin MIC and mortality in patients diagnosed with MRSA HAP (including VAP and HCAP). Patients were treated at four different centers in the United States using a treatment algorithm derived from the 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines for the treatment of adults with HAP, VAP, and HCAP.16

Study Design

We performed an analysis of the Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) database. The IMPACT-HAP is a prospective, multicenter study of patients in ICUs with HAP, VAP, and HCAP who were treated in four academic institutions: the University of Louisville (Louisville, Kentucky), the Ohio State University Medical Center (Columbus, Ohio), the Henry Ford Health System (Detroit, Michigan), and the University of Miami/Jackson Memorial Hospital (Miami, Florida). Investigators from these four centers created a performance-improvement project with the intention to improve the care of patients in ICUs with HAP, VAP, and HCAP. A consensus diagnostic and treatment algorithm derived from the 2005 ATS/IDSA guidelines was developed and implemented at each institution.17 The algorithm included major principles from the ATS/IDSA guidelines for the treatment of adults with HAP, VAP, and HCAP,16 yet allowed for customization based on local epidemiology. Data were collected from February 2006 through August 2007. Nonconsecutive adult patients in ICUs who met the ATS/IDSA definitions for HAP, VAP, and HCAP16 were entered into our database. For each case, investigators completed a case report form that was transferred via the Internet to the IMPACT-HAP coordinating center at the University of Louisville. Validation of data quality was performed at the coordinating center before the case was entered into the database. The study was approved by the institutional review board at each participating center.

Patient Identification

Eligible patients were those who met the ATS/IDSA definitions for HAP, VAP, or HCAP16 and had at least one positive MRSA culture isolated from blood or a respiratory site. Availability of the MRSA isolate for additional testing was required, as well as knowledge of the patient’s vital status (alive, dead) at day 28 after admission into the IMPACT-HAP study. Patients were excluded if they received ≤ 1 day of therapy, were in hospice care, were felt to be colonized with MRSA, had septic emboli in association with endocarditis, or if the isolate was not available for analysis.

Study Variables

As part of the IMPACT-HAP protocol, we collected data related to demographic characteristics, comorbidities, physical examination, laboratory results, and chest radiograph findings. The variables selected for this analysis included age, sex, weight, race, place of residence (home vs nursing home) before the index infection, comorbid conditions, mean vancomycin serum trough concentration for each patient (vancomycin was dosed per pharmacokinetic protocol at each institution to attain a trough of 15-20 μg/mL), clinical response (14-day and 28-day), and all-cause mortality at day 28. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score was calculated for all patients at the time of admission into the study to assess the severity of the underlying illness. Patient comorbidity information collected included data on end-stage renal disease, end-stage liver disease, cardiac disease (systolic or diastolic heart failure), renal disease (defined as a history of chronic renal disease or abnormal BUN and creatinine concentrations), cardiovascular disease (history of peripheral or central vascular disease), diabetes, COPD, presence of malignancies, and AIDS. Data on previous hospitalizations in the last 90 days, nursing home residence, receipt of home IV infusion treatment and home wound-care treatment, and outpatient hemodialysis were also gathered.

Laboratory Analysis

Initial identification of isolates and in vitro susceptibilities was determined using clinical microbiology laboratory tests with automated susceptibility testing methods at each participating institution. Isolates were then stored and shipped to our study’s microbiology reference laboratory at Henry Ford Hospital for further evaluation. Isolates were screened for inducible clindamycin resistance using d-test methodology.18 Vancomycin MICs were determined using the standard Etest method (AB bioMérieux; Solna, Sweden). The Etest macromethod that uses a higher inoculum to detect the presence of a less susceptible subpopulation was used to screen for heteroresistance.19

Statistical Analysis

All-cause mortality was defined as any death that occurred during the next 28 days after the initial diagnosis of pneumonia. Baseline characteristics of survivors and nonsurvivors at day 28 were compared using a generalized estimating equation (GEE) approach adjusting for the clustering by institution. Categorical variables, all yes/no except for gender, were analyzed using a GEE logistic regression routine. The variable for AIDS did not have sufficient occurrences for this approach and was examined using a Fisher exact test. The two continuous variables, age and APACHE II score, were analyzed using a GEE approach with a normal distribution and an identity link. The GEE approach adjusts the analysis for possible correlations within the institutions.

To control for possible confounding variables in the relationship between vancomycin MIC and 28-day mortality, a propensity approach was used20. The propensity score was derived from a regression model predicting vancomycin MIC using all study variables listed in Table 1 for this analysis. The propensity score was then categorized into quintiles and used to adjust the effect of vancomycin MIC on mortality at day 28 using a GEE logistic model.21

Table Graphic Jump Location
Table 1 —Characteristics of Patients with MRSA, HAP, VAP, and HCAP, Stratified by Mortality

Data are No. (%) of patients, unless otherwise indicated. A generalized estimating equations approach was used for all variables except AIDS, which had too few cases; in that case, a Fisher exact test was used. For t value, a normal distribution with an identity link function was used. The χ2 value indicates a binomial distribution with a logit link function. The class variable was the institution, with four levels. The sample size varied for patients with cardiac conditions and COPD, with 106 28-day survivors; previous hospitalization, with 105 28-day survivors; and malignancy, with 106 28-day survivors and 50 28-day nonsurvivors. APACHE = Acute Physiology and Chronic Health Evaluation; HAP = hospital-acquired pneumonia; HCAP = health-care-associated pneumonia; MRSA = methicillin-resistant Staphylococcus aureus; VAP = ventilator-associated pneumonia.

There were 163 patients with MRSA HAP, VAP, and HCAP identified during the study period. Of these, 28-day survival and mortality information was available for 159 patients, and isolate information was available in 158 of those patients, who were included in the final analysis. All-cause mortality at day 28 was documented in 51 of the 158 patients (32.3%), with 107 patients (67.7%) found alive up to that time point. Eleven patients (7%) had concomitant MRSA bacteremia. Mortality at day 28 was documented in five (45%) of those patients and was not increased as compared with patients without bacteremia (the P value was not significant). All but 11 patients received vancomycin therapy initially; of those 11 patients, 10 received linezolid and one received clindamycin.

Table 1 presents baseline characteristics for the study population, stratified by mortality. Nonsurvivors were older (68.3 vs 56.1 years of age; P < .001) and had a higher APACHE II score (24.4 vs 18.5; P < .001). In addition, nonsurvivors were statistically more likely to present with comorbidities like diabetes (P = .015), heart failure (P = .012), and vascular disease (P = .001). Furthermore, nonsurvivors were more likely to reside in a nursing home (P = .012) and to have received home-based IV infusion therapy (P = .049) prior to the index infection. Table 2 presents baseline characteristics for the study population, stratified by MIC group.

Table Graphic Jump Location
Table 2 —Propensity-Adjusted Risk of Mortality With MRSA HAP, VAP, and HCAP for Vancomycin MIC Value (mg/mL), Adjusted for Institution

EST = estimate; MIC = minimum inhibitory concentration; SE = standard error. See Table 1 for expansion of other abbreviations.

Results of susceptibility testing performed on MRSA isolates are depicted in Figure 1. The majority of isolates had a vancomycin MIC ≥ 1.5 μg/mL (115/158, 72.8%). There was no increase of MIC to vancomycin over the study period. We observed a significant association between 28-day mortality and vancomycin values (Table 2), with the unadjusted OR of death being 3.73 (P = .007) for an increase of 1 μg/mL. The relationship between the predicted risk of mortality and the vancomycin MIC value as determined using a propensity-adjusted GEE logistic regression model was statistically significant (P < .038) (Table 2). The OR of death was 2.97 for an increase of 1μg/mL of vancomycin MIC.

Figure Jump LinkFigure 1. Vancomycin MIC distribution of methicillin-resistant Staphylococcus aureus isolates with corresponding percentage of heteroresistant isolates from 158 patients with hospital-acquired pneumonia (including ventilator-associated pneumonia and health-care-associated pneumonia). P value calculated from logistic regression adjusted for the institution. MIC = minimum inhibitory concentration.Grahic Jump Location

Heteroresistance to vancomycin was demonstrated in 34 of the 158 isolates (21.5%), and all of them had a vancomycin MIC between 1 and 2 μg/mL. The mean vancomycin MIC for heteroresistant MRSA strains was 1.544 μg/mL, and for nonheteroresistant strains was 1.441 μg/mL (the P value was not significant). MRSA isolates that demonstrated heteroresistance to vancomycin were not associated with increased mortality when compared with MRSA isolates that did not exhibit heteroresistance (10/34, 29.4% vs 41/124, 33.1%; P = .687).

The median and mean vancomycin troughs in our patient population were 14 μg/mL and 15.57 ± 6.35 μg/mL, respectively. Forty-five percent of the patients had vancomycin troughs ≥ 15 μg/mL, and 79% had troughs > 10 μg/mL. Mean vancomycin troughs did not differ among the groups with an MIC ≤ 1, 1.5, or ≥ 2 (15.63 ± 6.48 μg/mL, 15.07 ± 6.61 μg/mL, 17.67 ± 5.27 μg/mL, respectively, P = .312).

This study shows that an increase in vancomycin MIC is associated with an increased risk for 28-day mortality in patients with MRSA HAP, VAP and HCAP, including isolates that would otherwise be considered within the susceptible range. HAP, VAP, and HCAP remain significant causes of morbidity and mortality despite advances in antimicrobial therapy, supportive care, and preventive measures.16Staphylococcus aureus, and in particular MRSA, has emerged as a leading bacterial cause for these infections in the United States,22 with MRSA responsible for 20% and up to 55% of HAP and VAP cases, respectively.23 MRSA pneumonia is recognized as a difficult-to-treat infection, and while vancomycin has been considered the foundation of therapy for serious MRSA infections,24 studies have consistently reported clinical failure rates of 40% or greater in patients with pneumonia.13-15 Our patients had an all-cause mortality rate of 32.3%, reflecting the fact that mortality associated with these infections is high despite the use of active antimicrobial agents,25-27 which highlights the need to generate data specific to patients with MRSA HAP, VAP, and HCAP. The present study is one of the largest series describing the clinical impact of vancomycin MICs in this critical group of patients.

Treatment failures of vancomycin for MRSA infections have been increasingly reported despite apparent in vitro susceptibility. This discordance between in vitro susceptibility and in vivo treatment outcomes has been attributed to various causes, including inappropriate vancomycin dosing with the subsequent inability of achieving optimal pharmacodynamic targets, limited vancomycin penetration into lung tissue and epithelial lining fluid,28-30 heteroresistance to vancomycin,31 and subtle but significant increases in vancomycin MIC over time, also referred as “MIC creep.”5. Our study demonstrates that in cases of MRSA HAP, VAP, and HCAP, the risk for increased mortality begins to emerge with increasing vancomycin MICs that are well within the susceptible range.

Whereas previous studies have suggested the possibility of clinical failure of vancomycin therapy in patients with MRSA infections in which the isolates have increased MICs but are still in the susceptible range, most of the information comes from patients with bacteremia9-11 and patients with a mixture of infections caused by MRSA.12 To our knowledge, no clinical studies have specifically assessed the relationship of vancomycin MICs to mortality in patients with MRSA HAP. The present study extends the findings of past investigations and is to our knowledge the first to report an association between vancomycin MIC and mortality exclusively in patients in ICUs with MRSA HAP, VAP, and HCAP.

The 2005 ATS/IDSA guidelines for the treatment of adults with HAP, VAP, and HCAP16 suggest that trough levels for vancomycin should be 15 to 20 μg/mL, based on the potential to improve tissue penetration, increase the probability of optimal target serum vancomycin concentrations, and improve clinical outcomes for complicated infections. Although this approach is not currently supported by evidence from large, randomized clinical trials, many physicians have tried to achieve trough concentrations ≥ 15 μg/mL when treating patients with HAP. Our patients received care at four different institutions using a treatment algorithm derived from the 2005 guidelines, and high vancomycin troughs were achieved in our patients (mean vancomycin trough 15.57 ± 6.35 μg/mL, 79% with troughs > 10 μg/mL). These results make inappropriate vancomycin dosing an unlikely reason for our findings.

Similarly, heteroresistance to vancomycin, as documented in 21.5% of the MRSA isolates in our study, was not associated with increased mortality when compared with infections caused by MRSA isolates that did not exhibit heteroresistance, and the finding for this was undetermined. Again, these results make heteroresistance an improbable explanation for our findings.

Our study has possible limitations worth noting. While we observed patients prospectively, we followed a nonrandomized design, enrolling nonconsecutive patients at each center. We also failed to collect information on the number of patients who qualified for the study but were not enrolled. The identification of respiratory isolates was based on qualitative rather than quantitative cultures, however all positive cultures were reviewed by the investigators at each site and categorized as pathogenic vs colonization. Vancomycin MICs were determined using the standard Etest method, and while the various susceptibility test methods commonly used in the clinical microbiology laboratory can give a variation in vancomycin MIC values, Etest MIC results appear to be more precise and predictive of treatment response to vancomycin.32 We also want to underscore several strengths of the data, including the use of predefined clinical criteria for the diagnosis and classification of pneumonia, the enrollment of patients representing different geographic areas in the United States, and the use of a well-characterized group of patients with clinical and laboratory information available for analysis. To date, this is the largest study describing the clinical impact of vancomycin MIC specific to patients with MRSA HAP, VAP, and HCAP.

In conclusion, the results of this study provide evidence that mortality in patients with MRSA HAP, VAP, and HCAP treated with vancomycin will increase as a function of the vancomycin MIC, even for MRSA strains with MICs within the susceptible range. Since different hospital centers can have diverse antibiotic use patterns, the assessment of increasing vancomycin MICs should be considered at the institutional level and for individual cases of MRSA pneumonia. Laboratories should consider in vitro susceptibility testing on all MRSA pneumonias with cutoff values enumerated. The selection of vancomycin for the treatment of patients with documented MRSA pneumonia caused by isolates with vancomycin MICs between 1 and 2 μg/mL should be undertaken with caution, vancomycin should be dosed to achieve serum trough levels of 15 to 20 μg/mL until further comparative information is available, and alternative therapies should be contemplated.

Author contributions:Dr Haque: designed the study, analyzed and interpreted data, wrote the manuscript, and was the coordinator for the Henry Ford Hospital site.

Dr Cahuayme Zuniga: collected and analyzed data, and read and approved the final manuscript.

Dr Peyrani: collected and analyzed data, and read and approved the final manuscript.

Dr Reyes: collected and analyzed data, and read and approved the final manuscript.

Dr Lamerato: provided statistical expertise, and read and approved the final manuscript.

Dr Moore: provided assistance in the study design and data analysis, and read and approved the final manuscript.

Dr Patel: collected and analyzed data, and read and approved the final manuscript.

Dr Allen: read and approved the final manuscript.

Dr Peterson: provided statistical expertise, and read and approved the final manuscript.

Mr Wiemken: provided statistical expertise, and read and approved the final manuscript.

Dr Cano: contributed to the study design and data analysis, and read and approved the final manuscript.

Dr Mangino: conceived and designed the study, analyzed and interpreted the data, provided important critical revisions of the article, and read and approved the final manuscript.

Dr Kett: conceived and designed the study, analyzed and interpreted the data, provided important critical revisions of the article, and read and approved the final manuscript.

Dr Ramirez: conceived and designed the study, analyzed and interpreted the data, provided important critical revisions of the article, and read and approved the final manuscript.

Dr Zervos: conceived and designed the study, analyzed and interpreted the data, and provided important critical revisions of the article.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Lamerato has received research money paid directly to Henry Ford Hospital System by pharmaceutic and analytic corporations, including Novartis, Johnson & Johnson, Pfizer, GlaxoSmithKline, Amgen, Policy Analysis Inc, the Centers for Disease Control and Prevention, and the National Institutes of Health. Dr Allen has received research support from Ortho-McNeil and also honoraria from lectures for Pfizer. Dr Mangino has received monies from Madcat Healthcare, Pfizer, Astellas, and Merck, and educational grants from Fallon Medica LLC. Dr Kett has received research support and served as a consultant to and is on the speakers’ bureau of Pfizer. Dr Ramirez has received research support from Pfizer, is a consultant for Pfizer, and has received honoraria from Pfizer, Merck, and Wyeth for lectures. Dr Zervos has received research support from Astellas, Cubist, Pfizer, and Johnson & Johnson, and is on the speaker bureaus of Astellas and Cubist. Drs Haque, Cahuayme Zuniga, Peyrani, Reyes, Moore, Patel, Peterson, Cano, and Mr Wiemken have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: The Improving Medicine through Pathway Assessment of Critical Therapy of Hospital-Acquired Pneumonia (IMPACT-HAP) Investigators are Forest Arnold, DO, and Raul Nakamatsu, MD (University of Louisville, Louisville, KY); Paola Osaki Kiyan, MD, Mary Beth Perri, MT, and Susan Donabedian, MPH (Henry Ford Health System, Detroit, MI); Carol Myers, RN, David Taylor, PhD, Kari Mount, PharmD, and Lindsay Pell, PharmD (Ohio State University, Columbus, OH); Galo Fernando Cubillos, MD, and Andreas S. Castelblanco, MD (University of Miami Miller School of Medicine and Jackson Memorial Hospital, Miami, FL), and Kimbal D. Ford, PharmD, and Ernesto G. Scerpella (Pfizer Inc, New York, NY). They all participated in discussions leading to the study design and data analysis, and in the writing of the manuscript. This study was performed at the following institutions: University of Louisville (Louisville, KY), The Ohio State University Medical Center (Columbus, OH), the Henry Ford Health System (Detroit, MI), and the University of Miami/Jackson Memorial Hospital (Miami, FL).

APACHE

Acute Physiology and Chronic Health Evaluation

ATS/IDSA

American Thoracic Society/Infectious Diseases Society of America

GEE

generalized estimating equation

HAP

hospital-acquired pneumonia

HCAP

health-care-associated pneumonia

IMPACT-HAP

Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia

MIC

minimum inhibitory concentration

MRSA

methicillin-resistant Staphylococcus aureus

VAP

ventilator-associated pneumonia

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Lamer C, de Beco V, Soler P, et al. Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients. Antimicrob Agents Chemother. 1993;372:281-286. [CrossRef] [PubMed]
 
Liu C, Chambers HF. Staphylococcus aureuswith heterogeneous resistance to vancomycin: epidemiology, clinical significance, and critical assessment of diagnostic methods. Antimicrob Agents Chemother. 2003;4710:3040-3045. [CrossRef] [PubMed]
 
Hsu DI, Hidayat LK, Quist R, et al. Comparison of method-specific vancomycin minimum inhibitory concentration values and their predictability for treatment outcome of methicillin-resistantStaphylococcus aureus(MRSA) infections. Int J Antimicrob Agents. 2008;325:378-385. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Vancomycin MIC distribution of methicillin-resistant Staphylococcus aureus isolates with corresponding percentage of heteroresistant isolates from 158 patients with hospital-acquired pneumonia (including ventilator-associated pneumonia and health-care-associated pneumonia). P value calculated from logistic regression adjusted for the institution. MIC = minimum inhibitory concentration.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Characteristics of Patients with MRSA, HAP, VAP, and HCAP, Stratified by Mortality

Data are No. (%) of patients, unless otherwise indicated. A generalized estimating equations approach was used for all variables except AIDS, which had too few cases; in that case, a Fisher exact test was used. For t value, a normal distribution with an identity link function was used. The χ2 value indicates a binomial distribution with a logit link function. The class variable was the institution, with four levels. The sample size varied for patients with cardiac conditions and COPD, with 106 28-day survivors; previous hospitalization, with 105 28-day survivors; and malignancy, with 106 28-day survivors and 50 28-day nonsurvivors. APACHE = Acute Physiology and Chronic Health Evaluation; HAP = hospital-acquired pneumonia; HCAP = health-care-associated pneumonia; MRSA = methicillin-resistant Staphylococcus aureus; VAP = ventilator-associated pneumonia.

Table Graphic Jump Location
Table 2 —Propensity-Adjusted Risk of Mortality With MRSA HAP, VAP, and HCAP for Vancomycin MIC Value (mg/mL), Adjusted for Institution

EST = estimate; MIC = minimum inhibitory concentration; SE = standard error. See Table 1 for expansion of other abbreviations.

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Liu C, Chambers HF. Staphylococcus aureuswith heterogeneous resistance to vancomycin: epidemiology, clinical significance, and critical assessment of diagnostic methods. Antimicrob Agents Chemother. 2003;4710:3040-3045. [CrossRef] [PubMed]
 
Hsu DI, Hidayat LK, Quist R, et al. Comparison of method-specific vancomycin minimum inhibitory concentration values and their predictability for treatment outcome of methicillin-resistantStaphylococcus aureus(MRSA) infections. Int J Antimicrob Agents. 2008;325:378-385. [CrossRef] [PubMed]
 
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