this retrospective cohort study included pediatric and adult patients admitted to the university of iowa hospitals and clinics ( iowa city , ia , usa ) or to the university of maryland medical center ( baltimore , maryland , usa ) during 20032009 . first , we used codes from the international classification of diseases , ninth revision , clinical modification ( icd-9-cm ) , to identify patients with influenza - like illness ( ili ) ( 5 ) . this criterion was part of an initial study investigating influenza - like illness and s. aureus pneumonia ( j.s . patients were included in the study if they had respiratory cultures ( sputum , bronchial specimen , or tracheal aspirate ) that grew s. aureus and were tested for influenza before or during their admissions . if a patient was admitted > 1 time , only the admission with the first s. aureus positive respiratory culture was included . the primary outcome of interest , 30-day in - hospital mortality , was defined as death occurring in the hospital within 30 days of the first culture that grew s. aureus . the adapted charlson comorbidity index served as an aggregate score for co - occurring conditions ( 6 ) . the year of each patient s first positive s. aureus culture was dichotomized : 20032007 and 20082009 . we conducted bivariable analyses using either the  test or the fisher exact test for categorical variables and the student t - test or wilcoxon rank - sum test for continuous variables . we used logistic regression to identify associations between potential predictor variables and 30-day mortality rates . variables associated with death ( p<0.25 ) in the bivariable regression analysis were examined for fit within the multivariable model and were retained if statistically significant ( p<0.05 ) . the year of each patient s first positive s. aureus culture was forced into the model . we analyzed data using sas software version 9.3 ( sas institute , cary , nc , usa ) . a total of 195 patients had > 1 respiratory culture that grew s. aureus and were also tested for influenza . sputum samples ( 115 , 59% ) and bronchial washes ( 50 , 26% ) were the most common respiratory specimens . respiratory or blood samples of 109 ( 56% ) patients grew methicillin - resistant s. aureus ( mrsa ) . most patients ( 166 , 85% ) were admitted to the university of maryland medical center ; 116 ( 59% ) were male , and median age was 42 ( interquartile range 559 ) years .   of the 195 patients , 32 ( 16% ) had positive influenza test results . patients who had a positive influenza test were more likely to receive quinolones ( odds ratio [ or ] 3.30 , 95% ci 1.517.21 ) than were patients whose influenza tests were negative ( table 1 ) . patients who had a positive influenza test were significantly more likely to have the positive s. aureus respiratory culture collected < 2 days after hospital admission than were the patients whose influenza tests were negative ( or 3.27 , 95% ci 1.397.70 ) . of the 32 influenza - positive patients , 9 ( 28% ) died ; of the 163 influenza - negative patients , 18 ( 11% ) died ( or 3.15 , 95% ci 1.277.86 ; p = 0.021 ) ( table 2 ) . of the 9 influenza - positive patients who died , 5 had mrsa . among the 27 patients who died , those with a positive influenza test were more likely to have diabetes than those who had a negative influenza test ( 33% vs. 0% ; p = 0.029 ) . the multivariable logistic regression model found that , after statistically adjusting for year and time from admission to collection of s. aureus culture samples , patients whose influenza tests were positive had > 4-fold increased odds of death compared with patients whose influenza tests were negative ( or 4.31 , 95% ci 1.5711.83 ; p<0.005 ) ( table 2 ) . * defined as death occurring in the hospital within 30 d of the first respiratory culture that grew s. aureus . other investigators reported poor outcomes among patients who were co - infected with influenza viruses and s. aureus ( 3,4,7 ) . kallen et al . found a statistically significant increased risk for death among patients who had positive influenza test results and community - acquired s. aureus pneumonia , compared with patients who had negative influenza test results and community - acquired s. aureus pneumonia ( 7 ) . study included patients who had either mrsa or methicillin  susceptible s. aureus pneumonia ( 7 ) but evaluated only 47 patients . the sample size for our study was much larger than previously performed studies , and we were able to examine mortality rates among patients who had a respiratory culture that grew either mrsa or methicillin - susceptible s. aureus . additionally , co - infection with influenza and s. aureus has been examined in animal models to identify mechanisms that cause poor outcomes ( 812 ) . severity of illness related to co - infection has been associated with a dysfunctional cell repair system and an altered immunologic response such as suppression of macrophage function , inhibition in phagocytic bacterial clearance , and cell damage to the airway system ( 812 ) . investigators have hypothesized that influenza damages epithelial cells in the respiratory system , providing opportunity for enhanced bacterial attachment ( 8,11 ) . once bacteria invade , cell destruction and fluid cause dysfunction of the airway system ( 8,11 ) . first , the investigation might have excluded patients who were tested for influenza at other facilities or who did not have laboratory - confirmed influenza . second , we could not determine whether the respiratory cultures that grew s. aureus represented infections or colonization . however , the information we describe remains clinically relevant because often clinicians do not know whether patients with positive s. aureus cultures are infected or colonized . diagnosing s. aureus pneumonia is challenging , and acquiring a lower respiratory culture such as a bronchial specimen or tracheal aspirate can be invasive and difficult to collect . therefore , if s. aureus pneumonia is suspected ( e.g. , symptoms and positive sputum culture ) , patients may be treated without a confirmed positive lower respiratory culture . third , our dataset did not include information about variables such as influenza vaccination status , mechanical ventilation , co - infection with organisms other than influenza and s. aureus , and whether the pneumonia was necrotizing . patients with a negative influenza test may be misclassified since we were unable to determine the time interval between the onset of ili symptoms and the collection of the influenza sample . last , influenza - like illness icd-9-cm codes were used to identify the cohort because the patients initially were included in a study of influenza - like illness and s. aureus pneumonia ( j.s . therefore , patients may have been missed if they had a respiratory infection with s. aureus and the condition or symptoms were not captured through an icd-9-cm code . in conclusion , among patients whose respiratory cultures grew s. aureus , patients with influenza were significantly more likely to die than were patients whose influenza tests were negative . interventions that increase influenza vaccination rates among patients at high risk for s. aureus respiratory infections may prevent both co - infection and death .
we retrospectively analyzed data for 195 respiratory infection patients who had positive staphyloccocus aureus cultures and who were hospitalized in 2 hospitals in iowa and maryland , usa , during 20032009 . 
 odds for death for patients who also had influenza - positive test results were > 4 times higher than for those who had negative influenza test results .