Efficacy of a novel patient-focused intervention aimed at increasing adherence to guideline-based preventive measures in asplenic patients: the PrePSS trial.

PURPOSE: To determine whether a novel intervention improves the adherence to guideline-based preventive measures in asplenic patients at risk of post-splenectomy sepsis (PSS). METHODS: We used a prospective controlled, two-armed historical control group design to compare a novel, health action process approach (HAPA)-based telephonic intervention involving both patients and their general practitioners to usual care. Eligible patients were identified in cooperation with the insurance provider AOK Baden-Wuerttemberg, Germany. Patients with anatomic asplenia (n = 106) were prospectively enrolled and compared to a historical control group (n = 113). Comparisons were done using a propensity-score-based overlap-weighting model. Adherence to preventive measures was quantified by the study-specific 'Preventing PSS score' (PrePSS score) which includes pneumococcal and meningococcal vaccination status, the availability of a stand-by antibiotic and a medical alert card. RESULTS: At six months after the intervention, we estimated an effect of 3.96 (95% CI 3.68-4.24) points on the PrePSS score scale (range 0-10) with mean PrePSS scores of 3.73 and 7.70 in control and intervention group, respectively. Substantial improvement was seen in all subcategories of the PrePSS score with the highest absolute gains in the availability of stand-by antibiotics. We graded the degree of participation by the general practitioner (no contact, short contact, full intervention) and noted that the observed effect was only marginally influenced by the degree of physician participation. CONCLUSIONS: Patients who had received the intervention exhibited a significantly higher adherence to guideline-based preventive measures compared to the control group. These data suggest that widespread adoption of this pragmatic intervention may improve management of asplenic patients. Health insurance provider-initiated identification of at-risk patients combined with a patient-focused intervention may serve as a blueprint for a wide range of other preventive efforts leading to patient empowerment and ultimately to better adherence to standards of care.

Impact of Immunosuppressive Agents on Clinical Manifestations and Outcome of Staphylococcus aureus Bloodstream Infection: A Propensity Score-Matched Analysis in 2 Large, Prospectively Evaluated Cohorts.

BACKGROUND: Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection. The impact of immunosuppressive agents on the outcome of patients with SAB is incompletely understood. METHODS: Data from 2 large prospective, international, multicenter cohort studies (Invasive Staphylococcus aureus Infections Cohort [INSTINCT] and International Staphylococcus aureus Collaboration [ISAC]) between 2006 and 2015 were analyzed. Patients receiving immunosuppressive agents were identified and a 1:1 propensity score-matched analysis was performed to adjust for baseline characteristics of patients. Overall survival and time to SAB-related late complications (SAB relapse, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed by Cox regression and competing risk analyses, respectively. This approach was then repeated for specific immunosuppressive agents (corticosteroid monotherapy and immunosuppressive agents other than steroids [IMOTS]). RESULTS: Of 3188 analyzed patients, 309 were receiving immunosuppressive treatment according to our definitions and were matched to 309 nonimmunosuppressed patients. After propensity score matching, baseline characteristics were well balanced. In the Cox regression analysis, we observed no significant difference in survival between the 2 groups (death during follow-up: 105/309 [33.9%] immunosuppressed vs 94/309 [30.4%] nonimmunosuppressed; hazard ratio [HR], 1.20 [95% confidence interval {CI}, .84-1.71]). Competing risk analysis showed a cause-specific HR of 1.81 (95% CI, .85-3.87) for SAB-related late complications in patients receiving immunosuppressive agents. The cause-specific HR was higher in patients taking IMOTS (3.69 [95% CI, 1.41-9.68]). CONCLUSIONS: Immunosuppressive agents were not associated with an overall higher mortality. The risk for SAB-related late complications in patients receiving specific immunosuppressive agents such as IMOTS warrants further investigations.

Limited Multidrug Resistance Efflux Pump Overexpression among Multidrug-Resistant Escherichia coli Strains of ST131.

Gram-negative bacteria partly rely on efflux pumps to facilitate growth under stressful conditions and to increase resistance to a wide variety of commonly used drugs. In recent years, Escherichia coli sequence type 131 (ST131) has emerged as a major cause of extraintestinal infection frequently exhibiting a multidrug resistance (MDR) phenotype. The contribution of efflux to MDR in emerging E. coli MDR clones, however, is not well studied. We characterized strains from an international collection of clinical MDR E. coli isolates by MIC testing with and without the addition of the AcrAB-TolC efflux inhibitor 1-(1-naphthylmethyl)-piperazine (NMP). MIC data for 6 antimicrobial agents and their reversion by NMP were analyzed by principal-component analysis (PCA). PCA revealed a group of 17 MDR E. coli isolates (n = 34) exhibiting increased susceptibility to treatment with NMP, suggesting an enhanced contribution of efflux pumps to antimicrobial resistance in these strains (termed enhanced efflux phenotype [EEP] strains). Only 1/17 EEP strains versus 12/17 non-EEP MDR strains belonged to the ST131 clonal group. Whole-genome sequencing revealed marked differences in efflux-related genes between EEP and control strains, with the majority of notable amino acid substitutions occurring in AcrR, MarR, and SoxR. Quantitative reverse transcription-PCR (qRT-PCR) of multiple efflux-related genes showed significant overexpression of the AcrAB-TolC system in EEP strains, whereas in the remaining strains, we found enhanced expression of alternative efflux proteins. We conclude that a proportion of MDR E. coli strains exhibit an EEP, which is linked to an overexpression of the AcrAB-TolC efflux pump and a distinct array of genomic variations. Members of ST131, although highly successful, are less likely to exhibit the EEP.

Combination therapy with rifampicin or fosfomycin in patients with Staphylococcus aureus bloodstream infection at high risk for complications or relapse: results of a large prospective observational cohort.

OBJECTIVES: To investigate whether Staphylococcus aureus bloodstream infection (SAB) patients at high risk for complications or relapse benefit from combination therapy with adjunctive rifampicin or fosfomycin. METHODS: In this post hoc analysis, SAB patients with native valve infective endocarditis, osteoarticular infections or implanted foreign devices were included. The co-primary endpoints were all-cause 90 day mortality and death or SAB-related late complications within 180 days. To overcome treatment selection bias and account for its time dependence, inverse probability of treatment weights were calculated and included in marginal structural Cox proportional hazard models (MSCMs). RESULTS: A total of 578 patients were included in the analysis, of which 313 (54%) received combination therapy with either rifampicin (n = 242) or fosfomycin (n = 58). In the multivariable MSCM, combination therapy was associated with a better outcome, that is, a lower rate of death or SAB-related late complications within 180 days (HR 0.65, 95% CI 0.46-0.92). This beneficial effect was primarily seen in patients with implanted foreign devices, in which combination therapy was associated with a lower rate of death or SAB-related late complications within 180 days (HR 0.53, 95% CI 0.35-0.79) and a lower 90 day mortality (HR 0.57, 95% CI 0.36-0.91). Upon agent-specific stratification, we found no significant differences in outcomes between combination therapy containing rifampicin and fosfomycin; however, the number of patients in most subgroups was not large enough to draw firm conclusions. CONCLUSIONS: In patients with implanted foreign devices, combination therapy was associated with a better long-term outcome. Larger prospective studies are needed to validate these findings.

Prevention of post-splenectomy sepsis in patients with asplenia - a study protocol of a controlled trial.

BACKGROUND: Patients with asplenia have a significantly increased lifelong risk of severe invasive infections, particular post-splenectomy sepsis (PSS). Clear preventive measures have been described in the literature, but previous studies found poor implementation of prevention recommendations. Aim of the study is to improve the adherence to guideline-based preventive measures and thereby reduce the incidence of PSS by a novel telephone-delivered intervention that involves both patients and their physicians. METHODS: A prospective controlled, two-armed historical control group design is used to evaluate the new intervention compared to usual care. The intervention for patients includes both educational aspects and, building on the Health Action Process Approach (HAPA), intervention components that promote motivation and planning of preventive measures. For physicians the intervention is primarily information-based. The primary outcome, the adherence to preventative measures, is indicated by a study-specific 'Preventing PSS-score' (PrePSS-score), which is assessed at baseline and at 6-months follow-up. Secondary outcomes include, amongst others, patient self-efficacy and action-planning, asplenia-specific health literacy, general self-management and asplenia-specific self-management. In a process-evaluating part of the study interview-data on patients' and physicians' evaluation of the intervention will be gathered. DISCUSSION: This trial will provide evidence about the effectiveness of the novel prevention intervention for asplenic patients. If demonstrated beneficial, the intervention manual will be made publicly available to enable implementation in practice. The experience gained within this trial may also be valuable for prevention strategies in patients with other diseases. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00015238; Trial registration date 07. December 2018.

Diagnostic accuracy of detection and quantification of HBV-DNA and HCV-RNA using dried blood spot (DBS) samples - a systematic review and meta-analysis.

BACKGROUND: The detection and quantification of hepatitis B (HBV) DNA and hepatitis C (HCV) RNA in whole blood collected on dried blood spots (DBS) may facilitate access to diagnosis and treatment of HBV and HCV infection in resource-poor settings. We evaluated the diagnostic performance of DBS compared to venous blood samples for detection and quantification of HBV-DNA and HCV-RNA in two systematic reviews and meta-analyses on the diagnostic accuracy of HBV DNA and HCV RNA from DBS compared to venous blood samples. METHODS: We searched MEDLINE, Embase, Global Health, Web of Science, LILAC and Cochrane library for studies that assessed diagnostic accuracy with DBS. Heterogeneity was assessed and where appropriate pooled estimates of sensitivity and specificity were generated using bivariate analyses with maximum likelihood estimates and 95% confidence intervals. We also conducted a narrative review on the impact of varying storage conditions or different cut-offs for detection from studies that undertook this in a subset of samples. The QUADAS-2 tool was used to assess risk of bias. RESULTS: In the quantitative synthesis for diagnostic accuracy of HBV-DNA using DBS, 521 citations were identified, and 12 studies met the inclusion criteria. Overall quality of studies was rated as low. The pooled estimate of sensitivity and specificity for HBV-DNA was 95% (95% CI: 83-99) and 99% (95% CI: 53-100), respectively. In the two studies that reported on cut-offs and limit of detection (LoD) - one reported a sensitivity of 98% for a cut-off of ≥2000 IU/ml and another reported a LoD of 914 IU/ml using a commercial assay. Varying storage conditions for individual samples did not result in a significant variation of results. In the synthesis for diagnostic accuracy of HCV-RNA using DBS, 15 studies met the inclusion criteria, and this included six additional studies to a previously published review. The pooled sensitivity and specificity was 98% (95% CI:95-99) and 98% (95% CI:95-99.0), respectively. Varying storage conditions resulted in a decrease in accuracy for quantification but not for reported positivity. CONCLUSIONS: These findings show a high level of diagnostic performance for the use of DBS for HBV-DNA and HCV-RNA detection. However, this was based on a limited number and quality of studies. There is a need for development of standardized protocols by manufacturers on the use of DBS with their assays, as well as for larger studies on use of DBS conducted in different settings and with varying storage conditions.

Diagnostic accuracy of serological diagnosis of hepatitis C and B using dried blood spot samples (DBS): two systematic reviews and meta-analyses.

BACKGROUND: Dried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV. METHODS: We conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias. RESULTS: For the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%-99%) and 100% (95%CI:99-100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95-99) and 99% (CI95%:98-100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews. CONCLUSION: HCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.

In Which Patients Do the 2023 Duke-ISCVID Criteria for Infective Endocarditis Increase the Diagnosis of "Definite Endocarditis"?-A Preliminary Analysis in the Prospectively Evaluated DERIVE Cohort.

Background/Objectives: Recently, an update of the Duke criteria for the diagnosis of infectious endocarditis has been published: the 2023 Duke-ISCVID criteria. To gain an insight into which proportion of patients are affected by the new criteria, and which criteria might be the most relevant for the expected increase in sensitivity, we analysed data from a registry of cardiovascular infections. Methods: The 2023 Duke-ISCVID criteria were applied to patients who were diagnosed with and treated for endocarditis after having been classified as "possible" endocarditis according to the 2015 ESC Modified Duke criteria. In patients thus newly classified as "definite endocarditis", diagnostic factors leading to this reclassification were described. Results: Of 397 patients, 48 (12%) did not fulfil the definition "definite infectious endocarditis" according to the 2015 ESC Modified Duke criteria. Of these, six (13%) fulfilled the definition when the 2023 Duke-ISCVID criteria were applied. A main factor triggering this reclassification was the consideration of microorganisms identified using valve PCR. Conclusions: As expected, the sensitivity of the new 2023 Duke-ISCVID criteria is increased in this cohort, mainly through the incorporation of new diagnostic methods in the criteria. Further studies are required to assess the effect on specificity in detail.

Health care utilisation of asylum seekers and refugees in the South-West of Germany.

BACKGROUND: Limited evidence on utilisation of health care by recently arrived asylum seekers and refugees in high-income countries is available. This study aims to describe the implementation of an integrated care facility (ICF) in an initial reception centre and measure the utilisation of care and the influence of operational parameters. METHODS: In a retrospective cohort study design, using medical records, we followed inhabitants of a reception centre in Germany between 11.10.2015 and 30.05.2018. We assessed frequency of visits and revisits to a newly established integrated care facility (ICF), and the effects of the ICF on visits to the local emergency department (LED) in the regional tertiary hospital using survival analysis and time series regression. We also explore the influence of operational parameters on the different implementation phases; phase 1: provisional clinic with 1-2 hours of physician presence daily, phase 2: implementation of ICF with 2-4 hours of care by a team of doctors and nurses daily, phase 3: routine running of ICF with daily operational hours of 10am-2pm with care provided by an interdisciplinary team of doctors and nurses. RESULTS: 14,419 total medical visits were recorded from 1,883 persons seeking health care in the ICF. The absolute number of visits per day remained similar over the study period (19·9/day), yet the relative number of visits changed from 2·2 to 15 per 100 inhabitants from phase 2 to 3, respectively. Most visits were due to respiratory infections (612/3080, 20%), and trauma and musculoskeletal conditions (441/3080, 14%). The rate of revisits to ICF was 2·9 per person per month (95%CI 2·9-3), more for those older, female, from North Africa and those with a translator present. The ratio of visits to the LED changed from 0·3/100 inhabitants per day to 0·14/100 inhabitants after implementation of the ICF and back to 0·3/100 inhabitants during the routine running. CONCLUSIONS: Though seasonal variation and referral practices must be considered, a high rate of revisits to the ICF were recorded. While visits to the LED decreased after the implementation of the ICF, visits returned to the pre-ICF levels during the routine running of the ICF. The results show that AS&R require reliable access to health care, yet the needs of specific groups of migrants may be different, especially those with language barriers, minority groups or those from certain regions. As such, care should be migrant sensitive and adapt to the changing needs of the population. Though more research is required to better understand the differing needs of migrants, this study may help to inform guidelines surrounding migrant sensitive standards of care in Germany.

Effects of a health psychology-based intervention for patients with asplenia on psychological determinants of preventive behaviour: A propensity score analysis.

OBJECTIVE: Patients with asplenia have an increased lifelong risk of severe infections especially post splenectomy sepsis with hospital mortality rates of 30-50%. Adherence to existing guidelines for preventive measures is low. Objective of the study is the evaluation of a novel intervention to increase health psychological outcomes in patients with asplenia resulting in better adherence to preventive measures. METHODS: The intervention was evaluated by conducting a prospective, two-armed historical control group design via propensity score analysis. Focus are health-psychological outcomes: self-efficacy, intention, risk perception, behaviour planning, self-management, health literacy, patient involvement and disease-knowledge. RESULTS: Patients in the intervention group (N = 110) showed a higher increase in almost all outcomes compared to a historical control group (N = 115). The strongest increase was observed in "asplenia-specific self-management" (average treatment effect: ATE 1.14 [95% CI 0.91-1.36] p < .001) and "asplenia-specific health-literacy" (ATE 1.42 [95% CI 1.18-1.65] p < .001). Significant intervention effects were also found in behaviour planning, perceived involvement and disease-knowledge. CONCLUSION: The patient-focused intervention is effective in improving health-psychological outcomes in patients with asplenia. PRACTICE IMPLICATIONS: The implementation of the intervention can make an important contribution to care and lead to an improvement of health-psychological outcomes that may result in a higher adherence to prevention measures.

Patients' with asplenia and doctors' experiences in implementing preventative measures following a novel educational intervention: a qualitative analysis.

OBJECTIVE: To explore patients' with asplenia and general practitioners' (GPs) (1) perceptions of a novel, Health Action Process Approach (HAPA)-based, educational intervention which targets to increase adherence to post-splenectomy sepsis (PSS) prevention measures and (2) their experience in implementing prevention measures following this intervention. DESIGN: A process evaluation conducted on average 3.5 (for patients) and 3.8 (for GPs) months after the intervention between January 2020 and April 2021 individually by means of semi-structured guideline-based telephone interviews. Data was analysed using qualitative content analysis. PARTICIPANTS: Volunteer subsample of N=25 patients with asplenia and N=8 GPs who received the intervention. Inclusion criteria were met by prior participation in the intervention (German-speaking, of full age and insured by the cooperating health insurance). Patient selection was done by purposeful selection aiming at maximum variability in terms of adherence to preventative measures prior to intervention participation. Participating GPs are a non-purposeful selected convenience sample. For reasons of data protection, no personal data was collected. RESULTS: The intervention was positively evaluated and its personal relevancy for patients and for the GPs' professional work became apparent. The intervention promoted risk awareness, intention to action, action planning and subsequently, improved adherence to preventative measures. Helpful factors for implementation among the patients were social support by relatives and GPs. Barriers to adherence identified in both groups can be divided into patient-attributed (eg, comorbidities), doctor-related (eg, lack of knowledge or support) as well as contextual factors (eg, vaccine supply constraints). CONCLUSIONS: Our findings indicate a patient and GP perceived benefit of the intervention, but still identify prevailing barriers to implementation. In a further step, a quantitative evaluation of the intervention will be conducted and recommendations for integrating the intervention in usual care will be made. TRIAL REGISTRATION NUMBER: DRKS00015238.

Impact of neutropenia on clinical manifestations and outcome of Staphylococcus aureus bloodstream infection: a propensity score-based overlap weight analysis in two large, prospectively evaluated cohorts.

OBJECTIVES: This study aimed to investigate whether neutropenia influenced mortality and long-term outcomes of Staphylococcus aureus bloodstream (SAB) infection. METHODS: Data from two prospective, multicentre cohort studies (INSTINCT and ISAC) conducted at 20 tertiary care hospitals in six countries between 2006 and 2015 were analyzed. Neutropenic and severely neutropenic patients (defined by proxy of total white blood cell count <1000/µl and <500/µl, respectively, at onset of SAB infection) were compared with a control group using a propensity score model and overlapping weights to adjust for baseline characteristics. Overall survival and time to SAB infection-related late complications (SAB infection recurrence, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed with Cox regression and competing risk analyses, respectively. RESULTS: Of the 3187 included patients, 102 were neutropenic and 70 severely neutropenic at the time of SAB infection onset. Applying overlap weights yielded two groups of 83 neutropenic and 220 nonneutropenic patients, respectively. The baseline characteristics of these groups were exactly balanced. In the Cox regression analysis, we observed no significant difference in survival between the two groups (death during follow up: 36.1% in neutropenic vs. 30.6% in nonneutropenic patients; hazard ratio (HR): 1.21; 95% CI, 0.79-1.83). This finding remained unchanged when we considered severely neutropenic patients (HR: 1.08; 95% CI, 0.60-1.94). A competing risk analysis showed a cause-specific HR of 0.39 (95% CI, 0.11-1.39) for SAB infection-related late complications in neutropenic patients. DISCUSSION: Neutropenia was not associated with a higher survival rate during follow up. The lower rate of SAB infection-related late complications in neutropenic patients should be validated in other cohorts.

Detection of High-Level Rifaximin Resistance in Enteric Bacteria by Agar Screen.

Objectives: This study aimed at determining the prevalence of rifaximin resistance in a large collection of Enterobacterales resistant to third-generation cephalosporins. A simple agar screen was developed to detect high-level resistance. Methods: A total of 401 isolates nonsusceptible to third-generation cephalosporins (including 342 Escherichia coli and 39 Klebsiella spp. and 20 Enterobacter spp.) were tested by microdilution for their MICs of rifaximin and rifampicin. Isolates with a confirmed rifaximin minimal inhibitory concentration (MIC) of >64 mg/L and a number of high-level resistant, and susceptible control isolates were tested for growth on Mueller-Hinton agar supplemented with rifaximin or rifampicin at a concentration of 256 mg/L. Amino acid mutations in rpoB and the presence of rifaximin resistance-associated genes arabidopsis response regulator (arr) 2/3 were investigated. Results: Microdilution assays identified rifaximin resistance in nine E. coli and three Klebsiella spp. isolates with complete cross-resistance to rifampicin (MICs of both >64 mg/L). The rifaximin agar screen correctly identified 9/9 clinical E. coli isolates, 2/2 E. coli controls, and 3/3 Klebsiella spp. with high-level rifaximin resistance, and was negative in 45 control clinical isolates with rifaximin MICs ranging between 2 and 32 mg/L according to broth microdilution. All nine high-level rifaximin agar screen-positive E. coli clinical isolates (vs. none of the tested controls) had rpoB mutations or carried arr2/3. Conclusions: Our agar screen test has the potential to detect high-level rifaximin-resistant Enterobacterales. Such strains remain rare among extended spectrum beta-lactamase (ESBL)-positive enteric bacteria, but may emerge among patients receiving rifaximin for prevention of hepatic encephalopathy and spontaneous bacterial peritonitis or among patients receiving rifaximin for other indications.

[Health care of refugees - A short review with focus on infectious diseases]. / Gesundheitsversorgung geflüchteter Menschen.

Few guidelines for health care of refugees exist in Germany. Screening as a part of initial health checks as well as general organisation of early health care for refugees is very heterogenous across different regions. Current experience will be relevant to develop integrated health care models. Prevention and care of infectious diseases are an important part of early health care for refugees, even if non-communicable diseases and mental health conditions should also be considered in every effort to design early health care models. We are presenting a pragmatic review of current evidence for prevention and care of tuberculosis, HIV, chronic viral hepatitis and other infectious diseases. More evidence is needed to assess morbidity and efficacy of early health care interventions and integrated care models in refugees.