Care pathways of sepsis survivors: sequelae, mortality and use of healthcare services in France, 2015-2018.

BACKGROUND: Individuals who survive sepsis are at high risk of chronic sequelae, resulting in significant health-economic costs. Several studies have focused on aspects of healthcare pathways of sepsis survivors but comprehensive, longitudinal overview of their pathways of care are scarce. The aim of this retrospective, longitudinal cohort study is to identify sepsis survivor profiles based on their healthcare pathways and describe their healthcare consumption and costs over the 3 years following their index hospitalization. METHODS: The data were extracted from the French National Hospital Discharge Database. The study population included all patients above 15 years old, with bacterial sepsis, who survived an incident hospitalization in an acute care facility in 2015. To identify survivor profiles, state sequence and clustering analyses were conducted over the year following the index hospitalization. For each profile, patient characteristics and their index hospital stay and sequelae were described, as well as use of care and its associated monetary costs, both pre- and post-sepsis. RESULTS: New medical (79.2%), psychological (26.9%) and cognitive (18.5%) impairments were identified post-sepsis, and 65.3% of survivors were rehospitalized in acute care. Cumulative mortality reached 36.6% by 3 years post-sepsis. The total medical cost increased by 856 million € in the year post-sepsis. Five patient clusters were identified: home (65.6% of patients), early death (12.9%), late death (6.8%), short-term rehabilitation (11.3%) and long-term rehabilitation (3.3%). Survivors with early and late death clusters had high rates of cancer and primary bacteremia and experienced more hospital-at-home care post-sepsis. Survivors in short- or long-term rehabilitation clusters were older, with higher percentage of septic shock than those coming back home, and had high rates of multiple site infections and higher rates of new psychological and cognitive impairment. CONCLUSIONS: Over three years post-sepsis, different profiles of sepsis survivors were identified with different mortality rates, sequels and healthcare services usage and cost. This study confirmed the importance of sepsis burden and suggests that strategies of post-discharge care, in accordance with patient profile, should be further tested in order to reduce sepsis burden.

Antibiotic prescriptions and risk factors for antimicrobial resistance in patients hospitalized with urinary tract infection: a matched case-control study using the French health insurance database (SNDS).

BACKGROUND: Antibiotic resistance is increasing among urinary pathogens, resulting in worse clinical and economic outcomes. We analysed factors associated with antibiotic-resistant bacteria (ARB) in patients hospitalized for urinary tract infection, using the comprehensive French national claims database. METHODS: Hospitalized urinary tract infections were identified from 2015 to 2017. Cases (due to ARB) were matched to controls (without ARB) according to year, age, sex, infection, and bacterium. Healthcare-associated (HCAI) and community-acquired (CAI) infections were analysed separately; logistic regressions were stratified by sex. RESULTS: From 9460 cases identified, 6468 CAIs and 2855 HCAIs were matched with controls. Over a 12-months window, the risk increased when exposure occurred within the last 3 months. The following risk factors were identified: antibiotic exposure, with an OR reaching 3.6 [2.8-4.5] for men with CAI, mostly associated with broad-spectrum antibiotics; surgical procedure on urinary tract (OR 2.0 [1.5-2.6] for women with HCAI and 1.3 [1.1-1.6] for men with CAI); stay in intensive care unit > 7 days (OR 1.7 [1.2-2.6] for men with HCAI). Studied co-morbidities had no impact on ARB. CONCLUSIONS: This study points out the critical window of 3 months for antibiotic exposure, confirms the impact of broad-spectrum antibiotic consumption on ARB, and supports the importance of prevention during urological procedures, and long intensive care unit stays.

Costs and Outcomes of 1-year post-discharge care trajectories of patients admitted with infection due to antibiotic-resistant bacteria.

BACKGROUND: The impact of antibiotic resistance (AMR) on initial hospital management has been extensively studied but its consequences after hospital discharge remain largely unknown. We aimed to analyze hospital care trajectories, cumulative length of hospital stays (c-LOS) and associated costs of care over a 1-year period after hospitalization with incident AMR infection. METHOD: All incident bacterial infection-related hospitalizations occurring from January 1, 2015, to December 31, 2015 and recorded in the French national health data information system were extracted. Bacterial resistance ICD-10 codes determined six infection status. Inpatient and outpatient care consumption and associated costs were studied. The impact of resistance on c-LOS was estimated using a Poisson regression. A sequence analysis through optimal matching method was conducted to identify hospital trajectories along with an extrapolation. FINDING: Of the 73,244 patients selected, 15.9% had AMR infection, thus providing 58,286 incident AMR infections after extrapolation. c-LOS was significantly longer for infections with resistant bacteria, reaching 20.4 days and 2.9 additional days IC95%[2.6; 3.2] for skin and soft tissue infections. An estimated 29,793 (51.1%) patients had hospital readmission within the following year, for a total cost of €675 million. Five post-discharge trajectories were identified: Post-hospitalization mainly at home (68.4% of patients); Transition to home from rehabilitation care (12.3%); Early death (<3 months) (9.7%); Late death (7.4%), and Long-term hospitalization (2.2%). INTERPRETATION: AMR has an impact on patients' c-LOS stay beyond the initial hospitalization. Half of patients hospitalized due to AMR are readmitted to hospital within the ensuing year, along five different trajectories. FUNDING: French Ministry of health.

A Payer Perspective of the Hospital Inpatient Additional Care Costs of Antimicrobial Resistance in France: A Matched Case-Control Study.

BACKGROUND AND OBJECTIVE: Antimicrobial resistance (AMR) has become one of the biggest threats to global public health given its association with mortality, morbidity and cost of health care. However, little is known on the economic burden of hospitalization attributable to AMR from a public health insurance perspective. We assessed the excess costs to the French public health insurance system attributable to AMR infections in hospitals. METHODS: Bacterial infectious disease-related hospitalizations were extracted from the National health data information system for all stays occurring in 2015. Bacterial infections, strains, and microbial resistance were identified by specific French ICD-10 codes. Information about health care expenditure, co-morbidities and demographic characteristics (i.e. gender, age) are provided. We used a matched case-control approach to determine the excess of reimbursements paid to stays with AMR compared to stays with an infection without resistance. Cases and controls were matched on gender, age, Charlson comorbidity index, category of infection, infection as principal diagnosis (two classes), microorganism and hospital status. The overall AMR cost was extrapolated to stays with AMR and excluded from the sample (multiple infections), and a second extrapolation was performed to consider stays with unknown resistance status. RESULTS: The final sample included 52,921 matched-pairs (98.2% cases). Our results suggest that AMR overall cost reached EUR109.3 million in France with a mean of EUR1103 per stay; extrapolation to the entire database shows that the overall cost could potentially reach EUR287.1 million if all cases would be identified. The mean excess length of hospital stay attributable to AMR was estimated at 1.6 days. CONCLUSION: AMR causes substantial cost burden in France for the public health insurance. Our study confirms the need to reinforce programs to prevent AMR infection and thereby reduce their economic burden.

Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial.

PURPOSE: Microbiological diagnosis (MD) of infections remains insufficient. The resulting empirical antimicrobial therapy leads to multidrug resistance and inappropriate treatments. We therefore evaluated the cost-effectiveness of direct molecular detection of pathogens in blood for patients with severe sepsis (SES), febrile neutropenia (FN) and suspected infective endocarditis (SIE). METHODS: Patients were enrolled in a multicentre, open-label, cluster-randomised crossover trial conducted during two consecutive periods, randomly assigned as control period (CP; standard diagnostic workup) or intervention period (IP; additional testing with LightCycler®SeptiFast). Multilevel models used to account for clustering were stratified by clinical setting (SES, FN, SIE). RESULTS: A total of 1416 patients (907 SES, 440 FN, 69 SIE) were evaluated for the primary endpoint (rate of blood MD). For SES patients, the MD rate was higher during IP than during CP [42.6% (198/465) vs. 28.1% (125/442), odds ratio (OR) 1.89, 95% confidence interval (CI) 1.43-2.50; P < 0.001], with an absolute increase of 14.5% (95% CI 8.4-20.7). A trend towards an association was observed for SIE [35.4% (17/48) vs. 9.5% (2/21); OR 6.22 (0.98-39.6)], but not for FN [32.1% (70/218) vs. 30.2% (67/222), P = 0.66]. Overall, turn-around time was shorter during IP than during CP (22.9 vs. 49.5 h, P < 0.001) and hospital costs were similar (median, mean ± SD: IP €14,826, €18,118 ± 17,775; CP €17,828, €18,653 ± 15,966). Bootstrap analysis of the incremental cost-effectiveness ratio showed weak dominance of intervention in SES patients. CONCLUSION: Addition of molecular detection to standard care improves MD and thus efficiency of healthcare resource usage in patients with SES. ClinicalTrials.gov registration number: NCT00709358.

Improving antibiotic use in the hospital: Focusing on positive blood cultures is an effective option.

OBJECTIVES: The unsolicited and systematic evaluation of positive blood cultures (pBC) after laboratory report by a single infectious disease specialist (IDS) was evaluated during one year, using a computer-generated alert by the laboratory. The main objectives of IDS counselling were to improve antibiotic use for bloodstream infection (i.e., initiating or modifying therapy) and to stop unjustified therapy for contaminated pBC. METHODS: During the first part of the study (4 months), all pBC in patients from ICUs, medical and surgical wards were analyzed. After an interim analysis, only pBC from medical and surgical wards were evaluated during the second part (8 months). RESULTS: Overall, 1090 episodes of pBC (representing 866 patients) were evaluated and classified as bloodstream infection (65.5%), contamination (29%) or undetermined (5.5%). Forty-three percent of episodes prompted IDS counselling, including initiation (5%), modification (27.5%), withdrawal (3.5%) and diagnosis workup (5%). Restricting the evaluation to medical and surgical wards increased the rate of counselling (61.2% vs. 27.7%, P<0.0001), notably for de-escalating (20% vs. 8%, P<0.0001), initiating (9% vs. 2%, P<0.0001), oral switch (6% vs. 2%, P<0.0001), withdrawing (5% vs. 2%, P=0.002) or reducing the duration of therapy (5% vs. 2%, P=0.002). DISCUSSION AND CONCLUSIONS: In complement to the laboratory report, a computer-generated alert used by the IDS was useful for the management of pBC in hospital. The impact of IDS counselling was more effective when the evaluation was restricted to medical and surgical wards.

Inappropriate prescribing of aminoglycosides: risk factors and impact of an antibiotic control team.

OBJECTIVES: Many factors are involved in the appropriate use of aminoglycosides, such as modalities of administration, drug levels monitoring and duration of treatment. We assessed prospectively the impact of an antibiotic control team on the appropriateness of prescriptions. METHODS: After a first observational audit assessing the appropriateness of prescriptions, and issuing updated recommendations, we performed an interventional audit, where an antibiotic control team provided counselling when prescriptions were considered inappropriate. Appropriateness of prescriptions, clinical outcomes of patients and medical costs were compared between the two periods. RESULTS: One hundred consecutive prescriptions were analysed in each period, and 32% of prescriptions were modified by the control team. As compared with the observational period, prescriptions in the intervention period were more appropriate with regard to treatment duration (73% versus 56%, P = 0.01) and drug levels monitoring (61% versus 40%, P = 0.05), and the median treatment duration was shorter (4 versus 6 days, P = 0.0002). Independent factors associated with appropriate treatment duration were hospitalization in intensive care unit [adjusted odds ratio (aOR), 4.46; 95% confidence interval (CI), 1.60-12.46], polymicrobial infection (aOR, 3.97; 1.32-11.92) and antibiotic control team intervention (aOR, 2.49; 1.27-4.87). The intervention period was associated with lower rate of nephrotoxicity (15% versus 4%, P = 0.01) and lower direct medical costs (4,039.4 Euros per 100 persons treated). CONCLUSIONS: Aminoglycoside use was frequently associated with excessive treatment duration and incorrect drug level monitoring. Reinforcing practice guidelines through direct counselling improved the appropriateness of prescriptions.

The costs of septic syndromes in the intensive care unit and influence of hospital-acquired sepsis.

OBJECTIVE: To document the costs and outcomes of the various forms of the septic syndromes [systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock), particularly those associated with infection acquired in an intensive care unit (ICU). DESIGN: Prospective data collection for all septic patients admitted to a medical ICU during a 1-year period. Costs were computed from the viewpoint of the hospital. RESULTS: Mean total hospital costs were Euro 26,256, Euro 35,185, and Euro 27,083 for patients with sepsis, severe sepsis, and septic shock, respectively. Total costs varied slightly according to the site of infection and the severity of sepsis but were influenced mostly by its mode of acquisition: patients having sepsis associated with ICU-acquired infection incurred total costs about three times those of patients presenting with infection and sepsis on ICU admission (from Euro 39,908 in patients with ICU acquired sepsis to Euro 44,851 in patients with ICU-acquired septic shock). Stratifying patients by the presence of ICU-acquired infection also showed that a first episode of infection complicated by ICU-acquired sepsis incurred at least 2.5 times more costs than a single episode of sepsis. CONCLUSIONS: In this series the medical costs of sepsis were not markedly influenced by its severity but by its mode of acquisition. Due to wide variations in ICU costs cost-effectiveness analyses of treatments for sepsis should document the case-mix of patients and the contribution to this of nosocomial infections.