Descriptive Epidemiology and Outcomes of Nonventilated Hospital-Acquired, Ventilated Hospital-Acquired, and Ventilator-Associated Bacterial Pneumonia in the United States, 2012-2019.

OBJECTIVES: Multiple randomized controlled trials exploring the outcomes of patients with ventilator-associated bacterial pneumonia and hospital-acquired bacterial pneumonia have noted that hospital-acquired bacterial pneumonia patients who require subsequent ventilated hospital-acquired bacterial pneumonia suffered higher mortality than either those who did not (nonventilated hospital-acquired bacterial pneumonia) or had ventilator-associated bacterial pneumonia. We examined the epidemiology and outcomes of all three conditions in a large U.S. database. DESIGN: Retrospective cohort. SETTING: Two hundred fifty-three acute-care hospitals, United States, contributing data (including microbiology) to Premier database, 2012-2019. PATIENTS: Patients with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia identified based on a slightly modified previously published International Classification of Diseases, 9th Edition/International Classification of Diseases, 10th Edition-Clinical Modification algorithm. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 17,819 patients who met enrollment criteria, 26.5% had nonventilated hospital-acquired bacterial pneumonia, 25.6% vHAPB, and 47.9% ventilator-associated bacterial pneumonia. Ventilator-associated bacterial pneumonia predominated in the Northeastern United States and in large urban teaching hospitals. Patients with nonventilated hospital-acquired bacterial pneumonia were oldest (mean 66.7 ± 15.1 yr) and most likely White (76.9%), whereas those with ventilator-associated bacterial pneumonia were youngest (59.7 ± 16.6 yr) and least likely White (70.3%). Ventilated hospital-acquired bacterial pneumonia was associated with the highest comorbidity burden (mean Charlson score 4.1 ± 2.8) and ventilator-associated bacterial pneumonia with the lowest (3.2 ± 2.5). Similarly, hospital mortality was highest among patients with ventilated hospital-acquired bacterial pneumonia (29.2%) and lowest in nonventilated hospital-acquired bacterial pneumonia (11.7%), with ventilator-associated bacterial pneumonia in-between (21.3%). Among survivors, 24.5% of nonventilated hospital-acquired bacterial pneumonia required a rehospitalization within 30 days of discharge, compared with 22.5% among ventilated hospital-acquired bacterial pneumonia and 18.8% ventilator-associated bacterial pneumonia. Unadjusted hospital length of stay after infection onset was longest among ventilator-associated bacterial pneumonia and shortest among nonventilated hospital-acquired bacterial pneumonia patients. Median total hospital costs mirrored length of stay: ventilator-associated bacterial pneumonia $77,657, ventilated hospital-acquired bacterial pneumonia $62,464, and nonventilated hospital-acquired bacterial pneumonia $39,911. CONCLUSIONS: Both hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia remain associated with significant mortality and cost in the United States. Our analyses confirm that of all three conditions, ventilated hospital-acquired bacterial pneumonia carries the highest risk of death. In contrast, ventilator-associated bacterial pneumonia remains most costly. Nonventilated hospital-acquired bacterial pneumonia survivors were most likely to require a readmission within 30 days of discharge.

Research on the economic loss of hospital-acquired pneumonia caused by Klebsiella pneumonia base on propensity score matching.

BACKGROUND: Hospital-acquired pneumonia (HAP) caused by Klebsiella pneumonia (KP) is a common nosocomial infection (NI). However, the reports on the economic burden of hospital-acquired pneumonia caused by Klebsiella pneumonia (KP-HAP) were scarce. The study aims to study the direct economic loss caused by KP-HAP with the method of propensity score matching (PSM) to provide a basis for the cost accounting of NI and provide references for the formulation of infection control measures. METHODS: A retrospective investigation was conducted on the hospitalization information of all patients discharged from a tertiary group hospital in Shenzhen, Guangdong province, China, from June 2016 to August 2019. According to the inclusion and exclusion criteria, patients were divided into the HAP group and noninfection group, the extended-spectrum beta-lactamases (ESBLs) positive KP infection group, and the ESBLs-negative KP infection group. After the baselines of each group were balanced with the PSM, length of stay (LOS) and hospital cost of each group were compared. RESULTS: After the PSM, there were no differences in the baselines of each group. Compared with the noninfection group, the median LOS in the KP-HAP group increased by 15 days (2.14 times), and the median hospital costs increased by 7329 yuan (0.89 times). Compared with the ESBLs-negative KP-HAP group, the median LOS in the ESBLs-positive KP-HAP group increased by 7.5 days (0.39 times), and the median hospital costs increased by 22,424 yuan (1.90 times). CONCLUSION: KP-HAP prolonged LOS and increased hospital costs, and HAP caused by ESBLs-positive KP had more economic losses than ESBLs-negative, which deserves our attention and should be controlled by practical measures.

Cost-effectiveness Comparison of Ceftazidime/Avibactam Versus Meropenem in the Empirical Treatment of Hospital-acquired Pneumonia, Including Ventilator-associated Pneumonia, in Italy.

PURPOSE: Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose combination antibiotic approved in Europe and the United States for patients with hospital-acquired pneumonia, including ventilator-associated pneumonia (HAP/VAP). The economic benefits of a new drug such as CAZ-AVI are required to be assessed against those of available comparators, from the perspective of health care providers and payers, through cost-effectiveness and cost-utility analyses. The objective of this analysis was to compare the cost-effectiveness of CAZ-AVI versus meropenem in the empirical treatment of appropriate hospitalized patients with HAP/VAP caused by gram-negative pathogens, from the perspective of publicly funded health care in Italy (third-party perspective, based on the data from the REPROVE (Ceftazidime-Avibactam Versus Meropenem In Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia) clinical study; ClinicalTrials.gov NCT01808092). METHODS: A patient-level, sequential simulation model of the HAP/VAP clinical course was developed using spreadsheet software. The analysis focused on direct medical costs. The time horizon of the model selected was 5 years, with an annual discount rate of 3% on costs and quality-adjusted life-years (QALYs). Clinical inputs for treatment comparisons were mainly obtained from the REPROVE clinical study data. In addition to clinical outcomes observed in the trial, the model incorporated impact of resistance pathogens, based on data from published studies and expert opinion. Certain assumptions were made for some model parameters due to a lack of data. FINDINGS: The analysis demonstrated that the intervention sequence (CAZ-AVI followed by colistin + high-dose meropenem) versus the comparator sequence (meropenem followed by colistin + high-dose meropenem) provided a better clinical cure rate (+13.52%), which led to a shorter hospital stay (-0.40 days per patient), and gains in the number of life-years (+0.195) and QALYs (+0.350) per patient. The intervention sequence had an estimated net incremental total cost of €1254 ($1401) per patient, and the estimated incremental cost-effectiveness ratio was €3581 ($4000) per QALY gained, well below the willingness-to-pay threshold of €30,000 ($33,507) per QALY in Italy. IMPLICATIONS: The model results showed that CAZ-AVI is expected to provide clinical benefits in hospitalized patients with HAP/VAP in Italy at an acceptable cost compared to meropenem.

Effects of hospital-acquired pneumonia on long-term recovery and hospital resource utilization following moderate to severe traumatic brain injury.

BACKGROUND: Individuals with traumatic brain injury (TBI) have extended inpatient hospital stays that include prolonged mechanical ventilation, increasing risk for infections, including pneumonia. Studies show the negative short-term effects of hospital-acquired pneumonia (HAP) on hospital-based outcomes; however, little is known of its long-term effects. METHODS: A prospective cohort study was conducted. National Trauma Databank and Traumatic Brain Injury Model Systems were merged to derive a cohort of 3,717 adults with moderate-to-severe TBI. Exposure data were gathered from the National Trauma Databank, and outcomes were gathered from the Traumatic Brain Injury Model Systems. The primary outcome was the Glasgow Outcome Scale-Extended (GOS-E), which was collected at 1, 2, and 5 years postinjury. The GOS-E was categorized as favorable (>5) or unfavorable (≤5) outcomes. A generalized estimating equation model was fitted estimating the effects of HAP on GOS-E over the first 5 years post-TBI, adjusting for age, race, ventilation status, brain injury severity, injury severity score, thoracic Abbreviated Injury Scale score of 3 or greater, mechanism of injury, intraventricular hemorrhage, and subarachnoid hemorrhage. RESULTS: Individuals with HAP had a 34% (odds ratio, 1.34; 95% confidence interval, 1.15-1.56) increased odds for unfavorable GOS-E over the first 5 years post-TBI compared with individuals without HAP, after adjustment for covariates. There was a significant interaction between HAP and follow-up, such that the effect of HAP on GOS-E declined over time. Sensitivity analyses that weighted for nonresponse bias and adjusted for differences across trauma facilities did not appreciably change the results. Individuals with HAP spent 10.1 days longer in acute care and 4.8 days longer in inpatient rehabilitation and had less efficient functional improvement during inpatient rehabilitation. CONCLUSION: Individuals with HAP during acute hospitalization have worse long-term prognosis and greater hospital resource utilization. Preventing HAP may be cost-effective and improve long-term recovery for individuals with TBI. Future studies should compare the effectiveness of different prophylaxis methods to prevent HAP. LEVEL OF EVIDENCE: Prospective cohort study, level III.

A Novel Algorithm to Analyze Epidemiology and Outcomes of Carbapenem Resistance Among Patients With Hospital-Acquired and Ventilator-Associated Pneumonia: A Retrospective Cohort Study.

BACKGROUND: Carbapenem resistance is a growing concern. Applying a novel algorithm, we examined epidemiology and outcomes of carbapenem resistance among gram-negative pathogens in hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). METHODS: In a retrospective cohort design within the Premier Research database (2009-2016), all hospitalized adult patients with a gram-negative organism in a respiratory or blood culture specimen who fit criteria for HAP/VAP based on International Classification of Diseases, Ninth Revision, Clinical Modification, codes were included in the study. RESULTS: Among 8,969 patients with HAP/VAP, 1,059 isolates (11.8%) were carbapenem-resistant (CR) organisms. Patients with CR organisms were more likely female (41.4% vs 33.2%; P < .001) and medical admissions (33.8% vs 27.4%, P < .001) than those with carbapenem-susceptible (CS) organisms. Patients with carbapenem resistance had higher comorbidity burden than those with carbapenem susceptibility (median [interquartile range] Charlson Comorbidity Index score, 3 [1-4] vs 2 [1-4]; P < .001). Pseudomonas aeruginosa was the most common gram-negative pathogen overall (24.9%) and among CS organisms (23.5%), and was second to Stenotrophomonas maltophilia (44.0%) among CR organisms (35.3%). Acinetobacter baumannii accounted for 11.8% of CR organisms and 2.5% of CS organisms (P < .001). Patients with carbapenem resistance were more likely than those with carbapenem susceptibility to receive inappropriate empiric therapy (25.8% vs 10.0%; P < .001). Carbapenem resistance did not affect adjusted mortality (22.9% CR vs 21.6% CS) or postinfection length of stay (except among survivors of VAP), but it was associated with excess costs ($8,921; 95% CI, 3,864-13,977). CONCLUSIONS: Using administrative data, our novel algorithm identified patients with pneumonia at high risk for death, consistent with HAP/VAP. Among them, carbapenem resistance occurred in 12% of all cases and was associated with substantial excess in hospital costs.

The potential economic value of sputum culture use in patients with community-acquired pneumonia and healthcare-associated pneumonia.

OBJECTIVE: Despite numerous studies, the clinical value of sputum cultures in the management of pneumonia remains controversial; therefore, understanding the economic value of sputum cultures may help decision makers determine their appropriate use in patient management. METHODS: We developed a decision model to determine the economic and clinical value of using sputum cultures in the treatment of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) from the hospital perspective under various conditions. RESULTS: For both CAP and HCAP patients, obtaining sputum cultures resulted in similar costs compared to no culture, even if cultures cost $0. Given current clinical practices, obtaining cultures cost $539-631 more per CAP patient and $13-170 per HCAP patient compared to no culture use. However, cultures saved $8-202 per HCAP patient with a 40% probability the pathogen was the true cause (75% reduction in adverse outcomes, greater length of hospital stay (LOS) increase) to a 70% probability the pathogen was the true cause (25% reduction in outcomes and greater LOS increase and a 75% reduction in outcomes and all LOS increases). Additionally, obtaining sputum cultures had no impact on the number of adverse outcomes (i.e., adverse drug events, Clostridium difficile infection, pneumonia readmissions, additional hospitalization days). When all patients were treated with antibiotics empirically, obtaining cultures saved $4-342. CONCLUSIONS: Overall, obtaining sputum cultures does not provide significant clinical or economic benefits for CAP or HCAP patients; however, it can reduce costs and shorten overall LOS under some circumstances. Clinicians should consider their local conditions when making decisions about sputum culture use.

Reducing missed oral care opportunities to prevent non-ventilator associated hospital acquired pneumonia at the Department of Veterans Affairs.

Consistently delivered, effective oral care targets bacterial multiplication reducing the risk of non-ventilator associated hospital acquired pneumonia (NV-HAP). AIM: Determine the effect of a twice daily oral care initiative on the incidence and cost of NV-HAP. METHODS: This single arm intervention study used pre/post population data to determine the effectiveness of a universal, standardized oral care protocol vs. usual care in preventing NV-HAP. This phase followed a retrospective study of 14,396 patient days (2002-2012) that determined the pre-intervention levels of nursing care provided, and the overall disease prevalence. RESULTS: The pilot incidence rate on the geriatric units decreased from 105 to 8.3 cases per 1,000 patient days (by 92%) in the first year. The intervention yielded an estimated cost avoidance of $2.84 million and 13 lives saved in 19 months post-implementation. Expansion of this study as quality improvement is in progress at 8 VA hospitals with plans for national VA deployment. CONCLUSIONS: While oral care may seem deceptively simple in terms of base care provision, hospital and nursing services struggle to provide effective oral care delivery with high-reliability. Barriers to oral care include: (1) the perception that oral care is an optional daily care activity for patient's comfort, (2) hospitals supply inadequate, poorly designed oral care materials, and (3) hospitals are not required to monitor the incidence of NV-HAP. The impact of consistently delivered oral care is substantial in terms of Veteran health, quality of life, and well-being in addition to considerable cost avoidance.

Cost-effectiveness analysis of low versus high dose colistin in the treatment of multi-drug resistant pneumonia in Saudi Arabia.

Background Gram negative pathogens are increasingly resistant to commonly used first line antibiotics and colistin is in most cases the only medicine available. There is very limited information available comparing the effectiveness and costs of low versus high dose colistin with studies showing efficacy with both doses and with variable levels of adverse effects. The absence of a definite dosing strategy makes a model to compare low dose and high dose colistin invaluable in making decisions regarding the appropriate use of colistin. Objective This study was designed to evaluate the cost effectiveness of low versus high dose colistin in the treatment of Pneumonia caused by colistin-only sensitive gram negative bacteria from the perspective of a tertiary care hospital in Saudi Arabia. Setting 300-bed tertiary care hospital in Saudi Arabia. Method A retrospective review was conducted to compare the costs and outcomes of treatment of pneumonia with low versus high dose colistin. The model followed an average patient from initiation of treatment until clinical cure or failure. Main outcome measures The main outcomes were cure, nephrotoxicity, total direct costs per episode, cost per additional cure and cost per nephrotoxicity avoided. Results There was no significant difference between high and low dose colistin with regards to clinical cure (30% vs. 21%; p = 0.292). Significantly more patients experienced nephrotoxicity with high versus low dose colistin (30% vs. 8%; p = 0.004). With low dose colistin the incremental costs per nephrotoxicity avoided was SAR-3056.28. One-way sensitivity analyses did not change the overall results. Conclusion Low dose was not inferior to high dose colistin in terms of clinical cure and had a lower incidence of nephrotoxicity resulting in significant cost avoidance.

Epidemiology of ICU-acquired pneumonia.

PURPOSE OF REVIEW: Review of the epidemiology of ICU-acquired pneumonia, including both ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) in nonventilated ICU patients, with critical review of the most recent literature in this setting. RECENT FINDINGS: The incidence of ICU-acquired pneumonia, mainly VAP has decrease significantly in recent years possibly due to the generalized implementation of preventive bundles. However, the exact incidence of VAP is difficult to establish due to the diagnostic limitations and the methods employed to report rates. Incidence rates greatly vary based on the studied populations. Data in the literature strongly support the relevance of intubation, not ventilatory support, in the development of HAP in ICU patients, but also that the incidence of HAP in nonintubated patients is not negligible. Despite the fact of a high crude mortality associated with the development of VAP, the overall attributable mortality of this complication was estimated in 13%, with higher mortality rates in surgical patients and those with mid-range severity scores at admission. Mortality is consistently greatest in patients with HAP who require intubation, slightly less in VAP, and least for nonventilated HAP. The economic burden of ICU acquired pneumonia, particularly VAP, is important. The increased costs are mainly related to the longer periods of ventilatory assistance and ICU and hospital stays required by these patients. However, the different impact of VAP on economic burden among countries is largely dependent on the different costs associated with heath care. SUMMARY: VAP has significant impact on mortality mainly in surgical patients and those with mid-range severity scores at admission. The economic burden on ICU-acquired pneumonia depends mainly on the increased length of stay of these patients.

Could a risk-assessment tool prevent hospital-acquired pneumonia?

Hospital-acquired pneumonia (HAP) has been shown to be the second most common healthcare-acquired infection (HCAI) after urinary tract infection and linked to more than half of all deaths from HCAIs. Preventing the infection could potentially save many lives. The author therefore proposes that HAP could be prevented by the implementation of a risk-assessment tool. A hypothetical risk-assessment tool is discussed. Several potential risk factors are proposed; however, further research into these risk factors and the appropriate weighting to give these in developing such a tool is required.

The epidemiology of nonventilator hospital-acquired pneumonia in the United States.

BACKGROUND: Nonventilator hospital-acquired pneumonia (NV-HAP) is among the most common hospital-acquired infections. The purpose of our study was to quantify the incidence and influence of NV-HAP in the United States using a national dataset. METHODS: The 2012 US National Inpatient Sample dataset was used to compare an NV-HAP group to 4 additional group cohorts: pneumonia on admission, general hospital admissions, matched on mortality and disease severity, and ventilator-associated pneumonia (VAP). The main outcome was NV-HAP incidence. The secondary outcome was to compare hospital length of stay, total hospital charges, and mortality between the NV-HAP group and the 4 additional group cohorts. RESULTS: The overall incidence of NV-HAP was 1.6%, which represents a rate of 3.63 per 1,000 patient-days. NV-HAP was associated with increased total hospital charges, a longer hospital length of stay, and greater likelihood of death in comparison to all groups except patients with VAP. CONCLUSION: NV-HAP is an underappreciated and serious patient safety issue, resulting in significant increases in cost, length of stay, and mortality. Efforts toward prevention of NV-HAP should be raised to the same level of concern as VAP prevention.

Cost Drivers of a Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase 3 Clinical Trial.

Background: Studies indicate that the prevalence of multidrug-resistant infections, including hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), has been rising. There are many challenges associated with these disease conditions and the ability to develop new treatments. Additionally, HABP/VABP clinical trials are very costly to conduct given their complex protocol designs and the difficulty in recruiting and retaining patients. Methods: With input from clinicians, representatives from industry, and the US Food and Drug Administration, we conducted a study to (1) evaluate the drivers of HABP/VABP phase 3 direct and indirect clinical trial costs; (2) to identify opportunities to lower these costs; and (3) to compare (1) and (2) to endocrine and oncology clinical trials. Benchmark data were gathered from proprietary and commercial databases and used to create a model that calculates the fully loaded (direct and indirect) cost of typical phase 3 HABP/VABP endocrine and oncology clinical trials. Results: Results indicate that the cost per patient for a 200-site, 1000-patient phase 3 HABP/VABP study is $89600 per patient. The cost of screen failures and screen failure rates are the main cost drivers. Conclusions: Results indicate that biopharmaceutical companies and regulatory agencies should consider strategies to improve screening and recruitment to decrease HABP/VABP clinical trial costs.

Impact of Pneumococcal Vaccination on Pneumonia Hospitalizations and Related Costs in Ontario: A Population-Based Ecological Study.

Background: In Ontario, Canada, pneumococcal conjugate vaccine (PCV) was approved for infants in 2001 and became part of the publicly funded routine immunization schedule in 2005. We assessed the population-level impact of PCV on pneumonia hospitalizations and related costs. Methods: We used the difference-in-differences approach to evaluate the impact of pneumococcal vaccination on pneumonia hospitalizations and related costs, using nonpneumonia hospitalization as the control condition. We extracted monthly hospitalization costs, stratified by age group, from population-based health administrative data between April 1992 and March 2014. The study period was divided into 5 intervals: prevaccine period, availability of 7-valent PCV (PCV7) for private purchase, public funding for PCV7, replacement of PCV7 with 10-valent PCV (PCV10), and replacement of PCV10 with 13-valent PCV (PCV13). Results: A total of 1063700 pneumonia hospitalizations were recorded during the study period. In the vaccine-eligible age group, pneumonia hospitalizations declined by 34% (95% confidence interval, 32%-37%), 38% (32%-43%), and 45% (40%-51%) and hospitalization-related costs declined by 38% (25%-51%), 39% (33%-45%), and 46% (41%-52%) after public funding for PCV7, PCV10, and PCV13, respectively. Pneumonia hospitalizations and related costs also declined substantially for PCV-ineligible older children and elderly persons (aged >65 years). Conclusions: Our results suggest that the publicly funded PCV immunization program is responsible for substantial reductions in pneumonia hospitalizations and related healthcare costs, among both young children eligible for publicly funded vaccination and other age groups not included in the publicly funded program.