Analysis of Pathogen and Host Factors Related to Clinical Outcomes in Patients with Hospital-Acquired Pneumonia Due to Methicillin-Resistant Staphylococcus aureus

Abstract

dMethicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial pneumonia. To characterize pathogen-derived and host-related factors in intensive care unit (ICU) patients with MRSA pneumonia, we evaluated the Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) database. We performed multivariate regression analyses of 28-day mortality and clinical response using univariate analysis variables at a P level of <0.25. In isolates from 251 patients, the most common molecular characteristics were USA100 (55.0%) and USA300 (23.9%), SCCmec types II (64.1%) and IV (33.1%), and agr I (36.7%) and II (61.8%). Panton-Valentine leukocidin (PVL) was present in 21.9%, and vancomycin heteroresistance was present in 15.9%. Mortality occurred in 37.1% of patients; factors in the univariate analysis were age, APACHE II score, AIDS, cardiac disease, vascular disease, diabetes, SCCmec type II, PVL negativity, and higher vancomycin MIC (all P values were <0.05). In multivariate analysis, independent predictors were APACHE II score (odds ratio [OR], 1.090; 95% confidence interval [CI], 1.041 to 1.141; P < 0.001) and age (OR, 1.024; 95% CI, 1.003 to 1.046; P ‫؍‬ 0.02). Clinical failure occurred in 36.8% of 201 evaluable patients; the only independent predictor was APACHE II score (OR, 1.082; 95% CI, 1.031 to 1.136; P ‫؍‬ 0.002). In summary, APACHE II score (mortality, clinical failure) and age (mortality) were the only independent predictors, which is consistent with severity of illness in ICU patients with MRSA pneumonia. Interestingly, our univariate findings suggest that both pathogen and host factors influence outcomes. As the epidemiology of MRSA pneumonia continues to evolve, both pathogen-and host-related factors should be considered when describing epidemiological trends and outcomes of therapeutic interventions. Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired pneumonia (HAP), ventilatorassociated pneumonia (VAP), and health care-associated pneumonia (HCAP) (26). These infections are associated with significant morbidity, mortality, and cost burdens (3,20,25).While previous studies have attempted to identify risk factors for morbidity and mortality in patients with MRSA infections, they have typically focused on either the pathogen or the host. For example, severity of underlying illness, septic shock, age, comorbidities, and other selected host-related factors appear to be independent predictors of poor outcomes (5-7, 10, 14). MRSA features associated with poor prognosis in a variety of infection types include increases in vancomycin MIC, vancomycin heteroresistance, presence of Panton-Valentine leukocidin (PVL), agr group I, individual genes, and persistent colonization (1, 9, 11, 27). Because the outcomes of MRSA pneumonia are probably due to a combination of factors, studies are needed to evaluate the combined roles of MRSA-derived and host-related factors in a large sample of patients with HAP, VAP, or HCAP ...

Outcomes and Treatment of Chronic Methicillin-ResistantStaphylococcus aureusDiffers by Staphylococcal Cassette Chromosomemec(SCCmec) Type in Children With Cystic Fibrosis

“…In addition, outcomes observed here may be related to host characteristics rather than bacterial virulence. Observational studies of invasive MRSA infections in the United States have reported that the underlying disease severity of the infected individual, rather than the SCCmec type, was the main risk factor associated with mortality [17,32].…”

“…Studies evaluating the molecular epidemiology of MRSA in patients with CF in the United States have reported approximately two-thirds of MRSA strains were SCCmec II [13][14][15]. In non-CF MRSA disease, outcomes may be different based on SCCmec status [16,17]. However, outcomes associated with different SCCmec types have not been addressed in CF patients with chronic lung infections, and SCCmec status is not currently used in clinical care.…”

Predictors of Clinical Success Among a National Veterans Affairs Cohort With Methicillin-Resistant Staphylococcus aureus Pneumonia

“…35 Furthermore, we were unable to molecularly classify the MRSA isolates; molecular differences in MRSA strains have been shown to affect clinical results. [14][15][16] Susceptibility data and trough data were not available, and therefore it is not known if subjects reached therapeutic levels of the treatment agent.…”

“…For example, age, underlying comorbidities, severity of illness, multiple lobe involvement, and need for intensive care unit (ICU) admission have been associated with poor clinical outcomes. [9][10][11]13,14 There are multiple differences among MRSA strains on a molecular level, including staphylococcal cassette chromosome mec (SCCmec) type, presence of the toxin Panton-Valentine leukocidin, and minimum inhibitory concentration, which can affect clinical outcomes. [14][15][16] MRSA pneumonia is a complex disease associated with significant morbidity and mortality.…”

Rapid detection of methicillin-resistant Staphylococcus aureus and SCCmec types from nasal swabs by multiplex PCR

“…MRSA isolates present a staphylococcal cassette chromosome mec (SCCmec), and types II, III and IV are the most frequent [2,3,4]. Epidemiological studies conducted in recent years have shown that SCCmec IV isolates, mainly related to USA300 and European clones, are found in about 80% of MRSA isolates collected from community and hospital settings in Europe [2].…”