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To derive and validate a model for risk of resistance to first-line community-acquired pneumonia (CAP) therapy.
We developed a logistic regression prediction model from a large multihospital discharge database and validated it versus the Drug Resistance in Pneumonia (DRIP) score in a holdout sample and another hospital system outside that database. Resistance to first-line CAP therapy (quinolone or third generation cephalosporin plus macrolide) was based on blood or respiratory cultures.
This study was conducted using data from 177 Premier Healthcare database hospitals and 11 Cleveland Clinic hospitals.
Adults hospitalized for CAP.
Risk factors for resistant infection.
Among 138,762 eligible patients in the Premier database, 12,181 (8.8%) had positive cultures and 5,200 (3.8%) had organisms resistant to CAP therapy. Infection with a resistant organism in the previous year was the strongest predictor of resistance; markers of acute illness (eg, receipt of mechanical ventilation or vasopressors) and chronic illness (eg, pressure ulcer, paralysis) were also associated with resistant infections. Our model outperformed the DRIP score with a C-statistic of 0.71 versus 0.63 for the DRIP score (P < .001) in the Premier holdout sample, and 0.65 versus 0.58 (P < .001) in Cleveland Clinic hospitals. Clinicians at Premier facilities used broad-spectrum antibiotics for 20%–30% of patients. In discriminating between patients with and without resistant infections, physician judgment slightly outperformed the DRIP instrument but not our model.
Our model predicting infection with a resistant pathogen outperformed both the DRIP score and physician practice in an external validation set. Its integration into practice could reduce unnecessary use of broad-spectrum antibiotics.
Clostridioides difficile infection (CDI) is the most common cause of gastroenteritis, and community-acquired pneumonia (CAP) is the most common infection treated in hospitals. American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) CAP guidelines recommend empiric therapy with a respiratory fluoroquinolone or cephalosporin plus macrolide combination, but the CDI risk of these regimens is unknown. We examined the association between each antibiotic regimen and the development of hospital-onset CDI.
We conducted a retrospective cohort study using data from 638 US hospitals contributing administrative including 177 also contributing microbiologic data to Premier, Inc. We included adults admitted with pneumonia and discharged from July 2010 through June 2015 with a pneumonia diagnosis code who received ≥3 days of either empiric regimen. Hospital-onset CDI was defined by a diagnosis code not present on admission and positive laboratory test on day 4 or later or readmission for CDI. Mixed propensity-weighted multiple logistic regression was used to estimate the associations of CDI with antibiotic regimens.
Our sample included 58,060 patients treated with either cephalosporin plus macrolide (36,796 patients) or a fluoroquinolone alone (21,264 patients) and with microbiological data; 127 (0.35%) patients who received cephalosporin plus macrolide and 65 (0.31%) who received a fluoroquinolone developed CDI. After adjustment for patient demographics, comorbidities, risk factors for antimicrobial resistance, and hospital characteristics, CDI risks were similar for fluoroquinolones versus cephalosporin plus macrolide (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.70–1.38).
Among patients with CAP at US hospitals, CDI was uncommon, occurring in ∼0.33% of patients. We did not detect a significant association between the choice of empiric guideline recommended antibiotic therapy and the development of CDI.
To explore whether microbiology profiles and the impact of inappropriate empiric treatment differ in the setting of hospital-acquired bacterial pneumonia that requires subsequent mechanical ventilation (vHABP) versus one that does not (nvHABP) versus ventilator-associated bacterial pneumonia (VABP).
Multicenter retrospective cohort study within Premier Research database, 2014–2019.
We identified cases based on a previously published International Classification of Disease, Ninth Revision/Tenth Revision Clinical Modification (ICD-9/ICD-10-CM) algorithm, and we compared the 3 groups with respect to the bacterial pathogens isolated from their blood, sputum, or lower airway samples, and their respective rates of exposure to inappropriate empiric treatment. Using regression modeling we computed the effect of inappropriate empiric treatment on outcomes.
Among 17,819 patients who met enrollment criteria, 26.5% had nvHABP, 25.6% vHAPB, and 47.9% VABP. S. aureus (majority methicillin-susceptible) was the most frequently isolated organism, followed P. aeruginosa, K. pneumoniae, and E. coli with variations across the conditions. Rates of carbapenem resistance were highest in VABP (9.1%) and to third-generation cephalosporins in vHABP (14.9%). Patients with nvHABP were most likely to receive inappropriate empiric treatment (8.5%). Although inappropriate empiric treatment was associated with an increase in adjusted postinfection-onset hospital length of stay (2.3 days) and cost ($12,142), its greatest magnitude was in the nvHABP group (4.9 days, $13,147).
Substantial microbiologic differences exist among populations who suffer nvHABP, vHABP, and VABP, and inappropriate empiric treatment significantly worsens utilization outcomes. Given the moderate rates of carbapenem resistance and third-generation cephalosporin resistance, all patients require empiric coverage for a range of bacteria, including those targeting extended-spectrum β-lactamase and carbapenem resistance where appropriate.
Evidence from pandemics suggests that influenza is often associated with bacterial coinfection. Among patients hospitalized for influenza pneumonia, we report the rate of coinfection and distribution of pathogens, and we compare outcomes of patients with and without bacterial coinfection.
We included adults admitted with community-acquired pneumonia (CAP) and tested for influenza from 2010 to 2015 at 179 US hospitals participating in the Premier database. Pneumonia was identified using an International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm. We used multiple logistic and gamma-generalized linear mixed models to assess the relationships between coinfection and inpatient mortality, intensive care unit (ICU) admission, length of stay, and cost.
Among 38,665 patients hospitalized with CAP and tested for influenza, 4,313 (11.2%) were positive. In the first 3 hospital days, patients with influenza were less likely than those without to have a positive culture (10.3% vs 16.2%; P < .001), and cultures were more likely to contain Staphylococcus aureus (34.2% vs 28.2%; P = .007) and less likely to contain Streptococcus pneumoniae (24.9% vs 31.0%; P = .008). Of S. aureus isolates, 42.8% were methicillin resistant among influenza patients versus 53.2% among those without influenza (P = .01). After hospital day 3, pathogens for both groups were similar. Bacterial coinfection was associated with increased odds of in-hospital mortality (aOR, 3.00; 95% CI, 2.17–4.16), late ICU transfer (aOR, 2.83; 95% CI, 1.98–4.04), and higher cost (risk-adjusted mean multiplier, 1.77; 95% CI, 1.59–1.96).
In a large US inpatient sample hospitalized with influenza and CAP, S. aureus was the most frequent cause of bacterial coinfection. Coinfection was associated with worse outcomes and higher costs.
Viruses are more common than bacteria in patients hospitalized with community-acquired pneumonia. Little is known, however, about the frequency of respiratory viral testing and its associations with antimicrobial utilization.
Retrospective cohort study.
The study included 179 US hospitals.
Adults admitted with pneumonia between July 2010 and June 2015.
We assessed the frequency of respiratory virus testing and compared antimicrobial utilization, mortality, length of stay, and costs between tested versus untested patients, and between virus-positive versus virus-negative patients.
Among 166,273 patients with pneumonia on admission, 40,787 patients (24.5%) were tested for respiratory viruses, 94.8% were tested for influenza, and 20.7% were tested for other viruses. Viral assays were positive in 5,133 of 40,787 tested patients (12.6%), typically for influenza and rhinovirus. Tested patients were younger and had fewer comorbidities than untested patients, but patients with positive viral assays were older and had more comorbidities than those with negative assays. Blood cultures were positive for bacterial pathogens in 2.7% of patients with positive viral assays versus 5.3% of patients with negative viral tests (P < .001). Antibacterial courses were shorter for virus-positive versus -negative patients overall (mean 5.5 vs 6.4 days; P < .001) but varied by bacterial testing: 8.1 versus 8.0 days (P = .60) if bacterial tests were positive; 5.3 versus 6.1 days (P < .001) if bacterial tests were negative; and 3.3 versus 5.2 days (P < .001) if bacterial tests were not obtained (interaction P < .001).
A minority of patients hospitalized with pneumonia were tested for respiratory viruses; only a fraction of potential viral pathogens were assayed; and patients with positive viral tests often received long antibacterial courses.
We developed a bedside instrument to predict carbapenem resistance in complicated urinary tract infections. A model assigning weighted points for admission from an extended care facility (1), history of weight loss (1), early mechanical ventilation (1), age <50 years (2), male gender (3), catheter-associated urinary tract infection (4), prior antibiotics treatment (4), and prior carbapenem-resistant infection (8) exhibited good discrimination (C statistic, 0.721).
To examine attributable mortality and costs of Clostridium difficile infection (CDI) in the Medicare population.
A population-based cohort study among US adults aged at least 65 years in the 2008–2010 Medicare 5% sample, with follow-up of 12 months.
Incident CDI episode was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification code of 008.45 and no other occurrences within the preceding 12 months. To quantify the adjusted mortality and costs we developed a 1:1 propensity-matched sample of CDI and non-CDI patients.
Among 1,165,165 patients included, 6,838 (0.6%) had a CDI episode in 2009 (82.5% healthcare-associated). Patients with CDI were older (mean [SD] age, 81.0±8.0 vs 77.0±7.7 years, P<.001), were more likely to come from the Northeast (27.4% vs 18.6%, P<.001), and had a higher comorbidity burden (Charlson score, 4.6±3.3 vs 1.7±2.1, P<.001). Hospitalizations (63.2% vs 6.0%, P<.001) and antibiotics (33.9% vs 12.5%, P<.001) within the prior 90 days were more common in the group with CDI. In the propensity-adjusted analysis, CDI was associated with near doubling of both mortality (42.6% vs 23.4%, P<.001) and total healthcare costs ($64,807±$66,480 vs $38,128±$46,485, P<.001).
Among elderly patients, CDI is associated with an increase in adjusted mortality and healthcare costs following a CDI episode. Nationwide annually this equals 240,000 patients with CDI, 46,000 potential deaths, and more than $6 billion in costs.
While incidence, mortality, morbidity, and recurrence rates of C. difficile infection (CDI) among the critically ill have been investigated, the impact of its recurrence on 30-day rehospitalization (ReAd), an important policy focus, has not been examined.
Secondary analysis of a multicenter retrospective cohort study
Adult critically ill patients who survived their index hospitalization complicated by CDI
CDI was defined by diarrhea or pseudomembranous colitis and a positive assay for C. difficile toxins A and/or B. CDI recurrence (rCDI) was defined as diarrhea, positive C. difficile toxin and need for retreatment after cessation of therapy. Descriptive statistics and a logistic regression examined ReAd rates and characteristics, and factors that impact it.
Among 287 hospital survivors, 76 (26.5%) required ReAd (ReAd+). At baseline, the ReAd+ group did not differ significantly from the ReAd– group based on demographics, comorbidities, APACHE II scores, or ICU type. ReAd+ patients were more likely to have hypotension at CDI onset (48.7% vs 34.1%, P=.025) and to require vasopressors (40.0% vs 27.1%, P=.038); they were less likely to require mechanical ventilation (56.0% vs 77.3%, P<.001). A far greater proportion of ReAd+ than ReAd– had developed a recurrence either during the index hospitalization or within 30 days after discharge (32.89% vs 2.84%, P<.001). In a logistic regression, rCDI was a strong predictor of ReAd+ (adjusted odd ratio, 15.33, 95% confidence interval, 5.68–41.40).
Greater than 25% of all survivors of critical illness complicated by CDI require readmission within 30 days of discharge. CDI recurrence is a strong predictor of such rehospitalizations.
Healthcare-associated pneumonia (HCAP) is an entity distinct from community-acquired pneumonia (CAP). HCAP has a higher case-fatality rate, due either to HCAP organisms or to the health status of HCAP patients. The contribution of HCAP criteria to case-fatality rate is unknown.
We conducted a retrospective review of adult patients admitted with a diagnosis of pneumonia from July 2007 through November 2011 to 491 US hospitals. HCAP was defined as having at least 1 of the following: prior hospitalization within 90 days, hemodialysis, admission from a skilled nursing facility, or immune suppression. We compared characteristics of patients with CAP and patients with HCAP and explored the contribution of HCAP criteria to case-fatality rate in a hierarchical generalized linear model.
Of 436,483 patients hospitalized with pneumonia, 149,963 (34.4%) had HCAP. Compared to CAP patients, HCAP patients were older, had more comorbidities, and were more likely to require intensive care unit (ICU) care. In-hospital case-fatality rate was higher among patients with HCAP, compared to those with CAP (11.1% vs 5.1%, P < .001). After adjustment for demographics, comorbidities, presence of other infections, early ICU admission, chronic and acute medications, early tests and therapies, and length of stay, HCAP remained associated with increased case-fatality rate (odds ratio [OR], 1.35 [95% confidence interval (CI), 1.32-1.39]); odds of death increased for each additional HCAP criterion (OR [95% CI]: 1 criterion, 1.27 [1.23-1.31], 2 criteria, 1.55 [1.49-1.62], and 3 or more criteria, 1.88 [1.72-2.06]).
After adjustment for differences in patient characteristics, HCAP was associated with greater case-fatality rate than CAP. This difference may be due to HCAP organisms or to HCAP criteria themselves.
Urinary tract infections (UTIs) are common among hospitalized patients. Selection of an appropriate antibiotic for this infection requires knowledge of both its general microbiology and the epidemiology of drug-resistant organisms. We sought to determine secular trends in UTI hospitalizations that involve gram-negative (GN) multidrug-resistant Pseudomonas aeruginosa (MDR-PA), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (EC) and Klebsiella pneumoniae(KP), and carbapenem-resistant Enterobacteriaceae (CRE).
Patients with UTI in US hospitals between 2000 and 2009.
We first derived the total number of UTI hospitalizations in the United States from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database years 2000–2009. Based on a literature review, we then determined what proportion of all UTIs arise due to each of the organisms of interest, irrespective of resistance pattern. Finally, we assessed the prevalence of resistance within each pathogen based on the Eurofins Surveillance Network database 2000–2009. Susceptibility patterns served as phenotypic surrogates for resistance.
Between 2000 and 2009, the frequency of UTI hospitalizations increased by approximately 50%, from 53 to 77 cases per 1,000 hospitalizations. Infections due to all GN bacteria followed a similar trajectory, whereas those caused by resistant GN pathogens increased by approximately 50% (MDR-PA) to approximately 300% (ESBL). CRE emerged and reached 0.5 cases per 1,000 hospitalizations in this 10-year period.
The epidemiology and microbiology of GN UTI hospitalizations has shifted over the past decade. The proportion of all hospitalizations involving this infection has climbed. Resistant GN bacteria are becoming more prevalent and are implicated in an increasing proportion of UTIs among hospitalized patients.
To determine the attributable in-hospital mortality, length of stay (LOS), and cost of hospital-onset Clostridium difficile infection (HO-CDI).
Propensity score matching.
Six Pennsylvania hospitals (2 academic centers, 1 community teaching facility, and 3 community nonteaching facilities) contributing data to a clinical research database.
Adult inpatients between 2007 and 2008.
We defined HO-CDI in adult inpatients as a positive C. difficile toxin assay result from a specimen collected more than 48 hours after admission and more than 8 weeks following any previous positive result. We developed an HO-CDI propensity model and matched cases with noncases by propensity score at a 1 : 3 ratio. We further restricted matching within the same hospital, within the same principal disease group, and within a similar length of lead time from admission to onset of HO-CDI.
Among 77,257 discharges, 282 HO-CDI cases were identified. The propensity score-matched rate was 90%. Compared with matched noncases, HO-CDI patients had higher mortality (11.8% vs 7.3%; P<.05), longer LOS (median [interquartile range (IQR)], 12 [9–21] vs 11 [8–17] days; P< .01), and higher cost (median [IQR], $20,804 [$ll,059-$38,429] vs $16,634 [$9,413–$30,319]; P< .01). The attributable effect of HO-CDI was 4.5% (95% confidence interval [CI], 0.2%–8.7%; P<.05) for mortality, 2.3 days (95% CI, 0.9–3.8; P<.01) for LOS, and $6,117 (95% CI, $1,659–$10,574; P<.01) for cost.
Patients with HO-CDI incur additional attributable mortality, LOS, and cost burden compared with patients with similar primary clinical condition, exposure risk, lead time of hospitalization, and baseline characteristics.
Expanding hospitalized patients' risk stratification for Clostridium difficile infection (CDI) is important for improving patient safety. We applied definitions for hospital-onset (HO) and community-onset (CO) CDI to electronic data from 85 hospitals between January 2007 and June 2008 to identify factors associated with higher HO CDI rates.
Nonrecurrent CDI cases were identified among adult (≥18-year-old) inpatients by a positive C. difficile toxin assay result more than 8 weeks after any previous positive result. Case categories included HO, CO-hospital associated (CO-HA), CO-indeterminate hospital association (CO-IN), and CO–non–hospital associated (CO-NHA). C. difficile testing intensity (CDTI) was defined as the total number of C. difficile tests performed, normalized to the number of patients with at least 1 C. difficile toxin test recorded. We calculated both the incidence density and the prevalence of CDI where appropriate. We fitted a multivariable Poisson model to identify factors associated with higher HO CDI rates.
Among 1,351,156 unique patients with 2,022,213 admissions, 9,803 cases of CDI were identified; of these, 50.6% were HO, 17.4% were CO-HA, 9.0% were CO-IN, and 23.0% were CO-NHA. The incidence density of HO was 6.3 per 10,000 patient-days. The prevalence of CO CDI on admission was, per 10,000 admissions, 8.4 for CO-HA, 4.4 for CO-IN, and 11.1 for CO-NHA. Factors associated (P< .0001) with higher HO CDI rates included older age, higher CO-NHA prevalence on admission, and increased CDTI.
Electronic health information can be leveraged to risk-stratify HO CDI rates by patient age and CO-NHA prevalence on admission. Hospitals should optimize diagnostic testing to improve patient care and measured CDI rates.
Healthcare-associated infections are likely to be caused by drug-resistant and possibly mixed organisms and to be treated with inappropriate antibiotics. Because prompt appropriate treatment is associated with better outcomes, we studied the epidemiology of healthcare-associated complicated skin and skin-structure infections (cSSSIs).
Persons hospitalized with cSSSI and a positive culture result.
We conducted a single-center retrospective cohort study from April 2006 through December 2007. We differentiated healthcare-associated from community-acquired cSSSIs by at least 1 of the following risk factors: (1) recent hospitalization, (2) recent antibiotics, (3) hemodialysis, and (4) transfer from a nursing home. Inappropriate treatment was defined as no antimicrobial therapy with activity against the offending pathogen(s) within 24 hours after collection of a culture specimen. Mixed infections were those caused by both a gram-positive and a gram-negative organism.
Among 717 hospitalized patients with cSSSI, 527 (73.5%) had healthcare-associated cSSSI. Gram-negative organisms were more common (relative risk, 1.24 [95% confidence interval, 1.14–1.35) and inappropriate treatment trended toward being more common (odds ratio, 1.29 [95% confidence interval, 0.85–1.95]) in healthcare-associated cSSSI than in community-acquired cSSSI. Mixed cSSSIs occurred in 10.6% of patients with healthcare-associated cSSSI and 6.3% of those with community-acquired cSSSI (P = .082) and were more likely to be treated inappropriately than to be nonmixed infections (odds ratio, 2.42 [95% confidence interval, 1.43–4.10]). Both median length of hospital stay (6.2 vs 2.9 days; P < .001) and mortality rate (6.6% vs 1.1%; P = .003) were significantly higher for healthcare-associated cSSSI than community-acquired cSSSI.
Healthcare-associated cSSSIs are common and are likely to be caused by gram-negative organisms. Mixed infections carry a <2-fold greater risk of inappropriate treatment. Healthcare-associated cSSSIs are associated with increased mortality and prolonged length of hospital stay, compared with community-acquired cSSSIs.
To conduct a cost-effectiveness analysis of the economic outcomes of ventilator-associated pneumonia (VAP) prevention associated with silver-coated endotracheal tubes versus uncoated endotracheal tubes.
We used a simple decision model based on a hypothetical 1,000-patient cohort intubated with silver-coated or uncoated endotracheal tubes. The primary end point was marginal hospital savings per case of VAP prevented (savings from using silver-coated endotracheal tubes minus acquisition cost divided by number of VAP cases prevented).
We followed each branch of the decision model to VAP or no VAP and conducted Monte Carlo simulations and sensitivity analyses. Inputs for VAP incidence, relative risk reduction, and hospital costs were derived from publicly available sources. Relative risk reduction was derived from the pivotal study of the silver-coated endotracheal tube.
In the base-case analysis, we reduced the pivotal study relative risk in incidence of microbiologically confirmed VAP in patients intubated ≥24 hours from 35.9% to 24%. Thus, 23 of 97 expected cases of VAP could be prevented with silver-coated endotracheal tubes. The savings per case of VAP prevented was $12,840 in the base case, with assumed marginal VAP cost of $16,620 and costs of $90.00 for coated and $2.00 for uncoated endotracheal tubes. Estimates were most sensitive to assumptions regarding VAP cost and relative risk reduction with silver-coated endotracheal tubes. Nonetheless, in multivariate sensitivity analyses, the silver-coated endotracheal tubes yielded persistent savings (95% confidence interval, $9,630-$16,356) per case of VAP prevented. With other base-case inputs held constant, breakeven cost for silver-coated endotracheal tubes was $388.
The silver-coated endotracheal tube represents a strategy for preventing VAP that may yield hospital savings.
Although the incidence of hospitalizations with infection due to vancomycin-resistant pathogens in the United States remained stable during 2000–2003, it increased from 4.60 to 9.48 hospitalizations per 100,000 population during 2003–2006. Hospitalizations with infection due to vancomycin-resistant pathogens also increased as a proportion of all US hospitalizations, from 3.16 to 6.51 hospitalizations with VRE infection per 10,000 total hospitalizations during 2003–2006. The number of hospitalizations with infection due to vancomycin-resistant pathogens is increasing in the United States. Because infection due to vancomycin-resistant organisms is associated with poor outcomes, the epidemiology of this trend needs further exploration.
In the United States, from January 1, 2000, through December 31, 2005, the incidence of candidemia-related hospitalization per 100,000 population rose by 52%, from 3.65 to 5.56 cases; and the incidence per 1,000 hospitalizations rose by 49%, from 0.28 to 0.42 cases. The proportion of all candidemia-related hospitalizations in which candidemia was the principal diagnosis remained stable at approximately 14%.
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