Improving antimicrobial treatment in terms of antimicrobial stewardship and health costs by an OPAT service.

PURPOSE: Outpatient parenteral antimicrobial therapy (OPAT) is a standard for antimicrobial therapy internationally. With this prospective cohort study, we aimed to assess the impact of an OPAT service as part of antimicrobial stewardship (AMS) and evaluate the safety and efficiency of the program while illuminating the financial benefit for the hospital. METHODS: Socio-demographic data, treatment regimen and outcomes were prospectively recorded for all patients assigned to the program of the OPAT unit of the University Hospital of Zurich between November 2018 and September 2022. RESULTS: In total, we recorded 303 OPAT assignments of which 260 resulted in effective OPAT episodes. The 260 OPAT episodes were further optimized toward the choice of antimicrobial agent (n = 18) and length of therapy (n = 6). Moreover, OPAT resulted in alteration of patient assessment and care led by AMS strategies in 247 of 260 episodes (95%). While the bed days saved per year increased consistently with time, a total of 3934 in-hospital treatment days were saved amounting to a cost saving of 9,835,000 CHF over 47 months. Adverse events were recorded in 46 cases whilst only two of these have been the reason for readmission during OPAT treatment. Clinical cure was noted in 77% (199/260) and was negatively associated with Charlson Comorbidity Index (CCI; OR per 1 unit higher 0.85 (95% CI 0.78-0.93)). CONCLUSION: This study demonstrates the impact of an OPAT service in the framework of AMS as well as its benefits for the hospital whilst preserving safety and efficacy for the patient's parenteral antimicrobial treatment.

Rapid antimicrobial susceptibility testing in patients with bacteraemia due to Enterobacterales: an implementation study.

AIMS OF THE STUDY: The goal of this descriptive study was to assess the performance as well as the extent of the clinical impact of rapid automated antimicrobial susceptibility testing in patients with bacteraemia due to Enterobacterales. We also aimed to analyse how rapid automated antimicrobial susceptibility testing influences clinical decision-making. METHODS: This single-centre study conducted at the University Hospital of Zurich included data from all consecutive patients with Enterobacterales bacteraemia from November 2019 to October 2020. There was no control group. The primary outcome was the effect of rapid automated antimicrobial susceptibility testing on antibiotic therapy (no adjustment, escalation to a broader-spectrum antibiotic or de-escalation to a narrower-spectrum antibiotic). Rapid automated antimicrobial susceptibility testing results were further compared to susceptibility tests using European Committee on Antimicrobial Susceptibility Testing (EUCAST) standard methods and erroneous results were noted. Additionally, we investigated turnaround times for rapid automated antimicrobial susceptibility testing and routine diagnostic testing. RESULTS: We analysed 106 patients with 116 episodes of bacteraemia due to Enterobacterales, with Escherichia coli and Klebsiella pneumoniae being the most frequent isolates. Almost 8% of pathogens were multidrug resistant. Rapid automated antimicrobial susceptibility testing showed category agreement in 98.4% of all interpretable cases. A significant reduction of more than 20 h in turnaround times could be achieved with rapid automated antimicrobial susceptibility testing compared to the routine diagnostic workflow. In the majority of cases, rapid automated antimicrobial susceptibility testing had no effect, given that the empirical therapy was already correct or circumstances did not allow for de-escalation. In 38.8% of cases, antimicrobial therapy was adjusted, whereas eight cases were de-escalated based on rapid automated antimicrobial susceptibility testing alone. CONCLUSIONS: Rapid automated antimicrobial susceptibility testing may be a valuable and safe way to accelerate diagnosis. In particular, time to suitable therapy can be shortened in cases of incorrect therapy. However, physicians are reluctant to de-escalate antibiotic therapy based on rapid automated antimicrobial susceptibility testing alone, limiting its impact in everyday clinics. To further explore the potential of rapid automated antimicrobial susceptibility testing, a stringent/compulsory antibiotic stewardship programme would be a valuable next step.

Intervertebral disc cell chondroptosis elicits neutrophil response in Staphylococcus aureus spondylodiscitis.

To understand the pathophysiology of spondylodiscitis due to Staphylococcus aureus, an emerging infectious disease of the intervertebral disc (IVD) and vertebral body with a high complication rate, we combined clinical insights and experimental approaches. Clinical data and histological material of nine patients suffering from S. aureus spondylodiscitis were retrospectively collected at a single center. To mirror the clinical findings experimentally, we developed a novel porcine ex vivo model mimicking acute S. aureus spondylodiscitis and assessed the interaction between S. aureus and IVD cells within their native environment. In addition, the inflammatory features underlying this interaction were assessed in primary human IVD cells. Finally, mirroring the clinical findings, we assessed primary human neutrophils for their ability to respond to secreted inflammatory modulators of IVD cells upon the S. aureus challenge. Acute S. aureus spondylodiscitis in patients was characterized by tissue necrosis and neutrophil infiltration. Additionally, the presence of empty IVD cells' lacunae was observed. This was mirrored in the ex vivo porcine model, where S. aureus induced extensive IVD cell death, leading to empty lacunae. Concomitant engagement of the apoptotic and pyroptotic cell death pathways was observed in primary human IVD cells, resulting in cytokine release. Among the released cytokines, functionally intact neutrophil-priming as well as broad pro- and anti-inflammatory cytokines which are known for their involvement in IVD degeneration were found. In patients as well as ex vivo in a novel porcine model, S. aureus IVD infection caused IVD cell death, resulting in empty lacunae, which was accompanied by the release of inflammatory markers and recruitment of neutrophils. These findings offer valuable insights into the important role of inflammatory IVD cell death during spondylodiscitis and potential future therapeutic approaches.

Quantification of within-patient Staphylococcus aureus phenotypic heterogeneity as a proxy for the presence of persisters across clinical presentations.

OBJECTIVES: Difficult-to-treat infections caused by antibiotic-susceptible strains have been linked to the occurrence of persisters, a subpopulation of dormant bacteria that tolerate antibiotic exposure despite lacking genetic resistance. These persisters can be identified phenotypically by plating on nutrient agar because of their altered growth dynamics, resulting in colony-size heterogeneity. The occurrence of within-patient bacterial phenotypic heterogeneity in various infections and clinical determinants of persister formation remains unknown. METHODS: We plated bacteria derived from 132 patient samples of difficult-to-treat infections directly on nutrient-rich agar and monitored colony growth by time-lapse imaging. We retained 36 Staphylococcus aureus monocultures for further analysis. We investigated clinical factors associated with increased colony growth-delay with regression analyses. We corroborated the clinical findings using in vitro grown static biofilms exposed to distinct antibiotics. RESULTS: The extent of phenotypic heterogeneity of patient-derived S. aureus varied substantially between patients (from no delay to a maximum of 57.6 hours). Increased heterogeneity coincided with increased median colony growth-delay. Multivariable regression showed that rifampicin treatment was significantly associated with increased median growth-delay (13.3 hours; 95% CI 7.13-19.6 hours; p < 0.001). S. aureus grown in biofilms and exposed to high concentrations of rifampicin or a combination of rifampicin with clindamycin or levofloxacin exhibited prolonged growth-delay (p < 0.05 for 11 of 12 comparisons), correlating with a strain-dependent increase in antibiotic tolerance. DISCUSSION: Colony-size heterogeneity upon direct sampling of difficult-to-treat S. aureus infections was frequently observed. Hence, future studies are needed to assess the potential benefit of phenotypic heterogeneity quantification for staphylococcal infection prognosis and treatment guidelines.

Management and outcome of spinal implant-associated surgical site infections in patients with posterior instrumentation: analysis of 176 cases.

PURPOSE: The management of implant-associated surgical site infections (SSI) in patients with posterior instrumentation is challenging. Evidence regarding the most appropriate treatment and the need for removal of implants is equivocal. We sought to evaluate the management and outcome of such patients at our institution. METHODS: We searched our prospectively documented databases for eligible patients with posterior spinal instrumentation, excluding the cervical spine (January 2008-June 2018). Patient files were reviewed, demographic data and treatment details were recorded. Patient-reported outcome (PRO) was assessed with the Core Outcome Measures Index (COMI) preoperatively and postoperatively at 3 and 12 months. RESULTS: A total of 170 patients underwent 210 revisions for 176 SSIs. Two-thirds presented within four weeks (105/176, 59.7%, median 22.5d, 7d-11.1y). The most common pathogens were Staphylococcus aureus (n = 79/210, 37.6%) and Staphylococcus epidermidis (n = 56/210, 26.7%). Debridement and implant retention was performed in 135/210 (64.3%) revisions and partial replacement in 62/210 (29.5%). In 28/176 SSI (15.9%), persistent infection required multiple revisions (≤ 4). Surgery was followed by intravenous and oral antimicrobial treatment (10-12w). In 139/176 SSIs (79%) with ≥ 1y follow-up, infection was cured in 115/139 (82.7%); relapse occurred in 9 (relapse rate: 5.1%). Two patients (1.4%) died. COMI decreased significantly (8.2 ± 1.5 vs. 4.8 ± 2.9, p < 0.0001) over 12 months. 72.7% of patients were (very) satisfied with their care. CONCLUSION: Patients with SSI after posterior (thoraco-)lumbo(-sacral) instrumentation can be successfully treated in most cases with surgical and specific antibiotic treatment. An interdisciplinary approach is recommended. Loose implants should be replaced. In some cases, multiple revisions may be necessary. Patient outcomes were satisfactory.

Impact of an electronic alert on prescription patterns of meropenem, voriconazole and caspofungin.

BACKGROUND: Antimicrobial stewardship programs promote the appropriate use of antimicrobial substances through the implementation of evidence-based, active and passive interventions. We analyzed the effect of a computer-assisted intervention on antimicrobial use in a tertiary care hospital. METHODS: Between 2011 and 2016 we introduced an electronic alert for patients being prescribed meropenem, voriconazole and caspofungin. At prescription and at day 3 of treatment, physicians were informed about the risk related to these antimicrobial substances by an electronic alert in the medical records. Physicians were invited to revoke or confirm the prescription and to contact the infectious disease (ID) team. Using interrupted time series regression, the days of therapy (DOTs) and the number of prescriptions before and after the intervention were compared. RESULTS: We counted 64,281 DOTs for 5549 prescriptions during 4100 hospital stays. Overall, the DOTs decreased continuously over time. An additional benefit of the alert could not be observed. Similarly, the number of prescriptions decreased over time, without significant effect of the intervention. When considering the three drugs separately, the alert impacted the duration (change in slope of DOTs/1000 bed days; P = 0.0017) as well as the number of prescriptions (change in slope of prescriptions/1000 bed days; P < 0.001) of voriconazole only. CONCLUSIONS: The introduction of the alert lowered prescriptions of voriconazole only. Thus, self-stewardship alone seems to have a limited impact on electronic prescriptions of anti-infective substances. Additional measures such as face-to-face prompting with ID physicians or audit and feedback are indispensable to optimize antimicrobial use.

Spectrum of antibiotic resistance in UTI caused by Escherichia coli among HIV-infected patients in Uganda: a cross-sectional study.

BACKGROUND: Antimicrobial drug resistance is one of the top ten threats to global health according to the World Health Organization. Urinary tract infections (UTIs) are among the most common bacterial infections and main reason for antibiotic prescription. The incidence of UTIs appears to be high among people living with HIV. We sought to determine the most common UTI pathogens among HIV infected patients and evaluate their susceptibility towards antibiotics. METHODS: We performed a cross-sectional study among HIV-infected patients aged ≥ 18 years presenting at an HIV care specialized clinic with symptoms suggestive of a urethritis. Urine cultures were subjected to antibiotic susceptibility testing according to Clinical Laboratory Standards Institute. The data was analyzed using STATA, we performed Pearson's Chi-square and Fisher's exact tests to compare differences between proportions. RESULTS: Out of the 200 patients, 123 (62%) were female. The median age was 41.9 years (IQR 34.7-49.3). Only 32 (16%) urine cultures showed bacterial growth. Escherichia coli was the most commonly isolated uropathogen (72%), followed by Klebsiella pneumoniae (9%). E. coli was completely resistant to cotrimoxazole and ampicillin; resistance to ciprofloxacin and ceftriaxone was 44% and 35% respectively; 9% to gentamicin; no resistance detected to nitrofurantoin and imipenem. CONCLUSIONS: Our findings are congruent with the Uganda national clinical guidelines which recommends nitrofurantoin as the first line antibiotic for uncomplicated UTI. Significant ciprofloxacin and ceftriaxone resistance was detected. In the era of emerging antibiotic resistance, understanding the local susceptibilities among sub-populations such as HIV infected patients is crucial. Further investigation is needed to address reasons for the low bacterial growth rate observed in the urine cultures.

Impact of PET/CT among patients with suspected mycotic aortic aneurysms.

PURPOSE: To determine the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) on clinical management in patients with suspected mycotic aortic aneurysms (MAA). MATERIALS AND METHODS: For this observational cohort study 101 PET/CT were acquired in 50 patients, thereof 50 for the initial diagnosis/baseline scan, 51 for follow-up. Impact on patient management was defined in three categories: PET/CT results were "confirmed" (by clinical follow-up), "suspected" (conclusive, not confirmed), or "misleading" (proven wrong by follow-up). For clinical follow-up patient data were recorded at the time of imaging, and at the latest recorded clinical visit. It included patient demographics, clinical information, laboratory data, results of microbiology and other diagnostic procedures, information about treatment, and patient's general health condition. RESULTS: In four patients (8%) no clinical follow-up was feasible, the other 46 patients were clinically followed for a median of 898 days (IQR 320-4105). The combined evaluation of all 101 PET/CT demonstrated an impact on patient management in 78,5% of cases (48,5% confirmed, 30% suspected). Results of 21,5% of the PET/CT examinations were misleading. Respective values at baseline and at follow-up were: impact on patient management in 82% and 74,5% (70% and 27.5% confirmed, and 12% and 47% suspected), misleading cases in 18% and 25.5%. CONCLUSION: In MAA, PET/CT has a high impact on patient management, which is more pronounced with baseline than with follow-up examinations. However, PET/CT results may be misleading in a smaller proportion of cases.

Open wounds and rifampicin therapy are associated with rifampicin resistance among staphylococcal vascular graft/endograft infections.

BACKGROUND: Optimal timing for rifampicin combination therapy in patients with staphylococcal vascular graft/endograft infection (S-VGEI) is unknown. Experts recommend adding rifampicin after lowering bacterial load by surgery and wound closure. OBJECTIVES: To assess predictors of rifampicin resistance among staphylococci isolated from patients in the Vascular Graft Infection Cohort Study. METHODS: We included prospective patients with S-VGEI diagnosis from 1 January 2002 to 30 June 2020. We retrospectively assessed determinants of rifampicin resistance using exact logistic regression and described survival with Kaplan-Meier curves. RESULTS: We analysed 513 Staphylococcus spp. among 143 predominantly male (82%) patients with a median age of 68 years (IQR 60-75). Thereof, 82 (57%) received a rifampicin combination therapy and 61 (43%) received an antimicrobial therapy without rifampicin. Among 82 patients with rifampicin, 26/26 patients with any rifampicin resistance had open wounds with a strong association of rifampicin resistance with rifampicin treatment while having open wounds (OR 37, 95% CI 6.1 to ∞). Among 75 patients with a rifampicin combination therapy and rifampicin-susceptible staphylococci at S-VGEI diagnosis, 12/12 patients with a secondary rifampicin-resistant isolate had an open wound (OR 14, 95% CI 2.1 to ∞). CONCLUSIONS: Rifampicin should be started after wound closure due to increased risk of rifampicin resistance observed while having open wounds or second-look surgeries among patients with S-VGEI.

Impact of unknown incidental findings in PET/CT examinations of patients with proven or suspected vascular graft or endograft infections.

Vascular graft or endograft Infections (VGEI) are rare but severe complications of vascular reconstructive surgery, and associated with significant mortality and morbidity risk. Positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (PET/CT) has been shown to have a high diagnostic accuracy in the detection of VGEI. In this single-center prospective cohort study, we assessed the rate and the impact on patient management of relevant unknown incidental findings in PET/CT of patients with proven or suspected VGEI, and clinical follow-up of all patients was performed. Our study results show a comparably high rate of relevant unknown incidental findings (181 in 502 examinations), with documented direct impact on patient management in 80 of 181 (44%) of all findings. PET/CT scan- and patient-based evaluation revealed impact on patient management in 76 of 502 (17%) of all PET/CT scans, and in 59 of 162 (36%) of all patients, respectively. Furthermore, PET/CT correctly identified the final diagnosis in 20 of 36 (56%) patients without VGEI. In conclusion, in proven and suspected VGEI, PET/CT detects a high rate of relevant unknown incidental findings with high impact on patient management.

PET/CT in therapy control of infective native aortic aneurysms.

Infective native aortic aneurysms (INAA) are aneurysms arising from infection of the aortic wall. Treatment is demanding with 5-year survival rates between 53 and 55%. The aim of our study was to evaluate the usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the long-term monitoring of patients with proven INAA. Fifty-three PET/CT were performed in 15 patients with INAA in this single-center retrospective cohort study and retrospective analysis of prospectively collected Vascular Graft Cohort Study (VASGRA) data. Median metabolic activity (as measured by maximum standardized uptake value, SUVmax) of the aneurysms at the initial PET/CT was high (6.8 (IQR 5.7-21.8)), and lower at the last PET/CT prior to the end of antimicrobial therapy (3.9 (IQR 2.7-6.8); n = 11) as well as in the first PET/CT after the end of the treatment (3.9 (IQR 3.0-4.4);n = 6). Compared to the course of C-reactive protein alone, PET/CT provided different (> 20% difference in trend) or altering (opposed trend) information on the course of disease in at least 14 comparisons (56%) in 11 patients (73%). The one-year and five-year freedom from all-cause lethality was 92% (95% confidence interval 57%-99%). As compared to the course of C-reactive protein, PET/CT provides different and occasionally altering information in therapy control of INAA.

Lymphocyte Subsets in HIV-Exposed Uninfected Infants: The Impact of Neonatal Postexposure Prophylaxis With Zidovudine.

HIV-exposed, uninfected (HEU) infants receiving neonatal postexposure prophylaxis with zidovudine showed nonsignificant trends of lower CD4 and CD8 T cells as well as CD19 B cells than those who did not, suggesting toxicity that might impact the overall health of HEU children.

Diagnostic Accuracy of PET/CT and Contrast Enhanced CT in Patients With Suspected Infected Aortic Aneurysms.

OBJECTIVE: Infected aortic aneurysms are highly lethal, and management is very demanding, requiring an early diagnosis. The aim of this study was to evaluate the diagnostic accuracy of positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (PET/CT) and contrast enhanced CT (CE-CT) in patients with suspected infected aortic aneurysms. METHODS: PET/CT was performed in patients with clinically suspected infected aortic aneurysms, and additional CE-CT was performed if feasible. Diagnostic accuracy was assessed by two independent readers using a four point grading score for both imaging modalities. Maximum standardised uptake values (SUVmax) were calculated for quantitative measurements of metabolic activity in PET/CT. The reference standard was a combination of clinical presentation, laboratory findings, and imaging. RESULTS: Ten patients were included prospectively in the study, 24 retrospectively; 16 patients (47%) prior to the start of antimicrobial treatment and all 34 patients prior to any vascular intervention. Thirteen of the 34 patients had an infected aortic aneurysm (38%). Proven infected aortic aneurysms were all metabolically active on PET/CT with a median SUVmax of 6.6 (interquartile range 4.7-21.8). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT for the diagnosis of infected aortic aneurysm was 100%, 71%, 68%, 100%, and 82%, for reader 1 and 85%, 71%, 65%, 88%, and 77%, for reader 2. Respective values for CE-CT, performed in 20 patients (59%), were 63%, 75%, 63%, 75%, and 70%, for reader 1 and 88%, 50%, 54%, 86%, and 65%, for reader 2. CONCLUSION: The diagnostic accuracy of PET/CT in the detection of infected aortic aneurysms (n = 13) is high, and higher than CE-CT. While PET/CT demonstrates an excellent sensitivity, its specificity is hampered because of false positive findings.

Deep infection with Mycobacterium marinum: successful treatment of a frequently misdiagnosed disease.

We report a rare yet typical presentation of a severe infection with Mycobacterium marinum that affected the deep structure of the hand and wrist of a 43-old fish breeder. A combination therapy of surgical debridement and antibiotic treatment with clarithromycin and ethambutol for 6 months led to a total resolution of the symptoms. Intensive rehabilitation completely restored the function of the hand.

Delayed Sputum Culture Conversion in Tuberculosis-Human Immunodeficiency Virus-Coinfected Patients With Low Isoniazid and Rifampicin Concentrations.

Background: The relationship between concentrations of antituberculosis drugs, sputum culture conversion, and treatment outcome remains unclear. We sought to determine the association between antituberculosis drug concentrations and sputum conversion among patients coinfected with tuberculosis and human immunodeficiency virus (HIV) and receiving first-line antituberculosis drugs. Methods: We enrolled HIV-infected Ugandans with pulmonary tuberculosis. Estimation of first-line antituberculosis drug concentrations was performed 1, 2, and 4 hours after drug intake at 2, 8, and 24 weeks of tuberculosis treatment. Serial sputum cultures were performed at each visit. Time-to-event analysis was used to determine factors associated with sputum culture conversion. Results: We enrolled 268 HIV-infected patients. Patients with low isoniazid and rifampicin concentrations were less likely to have sputum culture conversion before the end of tuberculosis treatment (hazard ratio, 0.54; 95% confidence interval, .37-.77; P = .001) or by the end of follow-up (0.61; .44-.85; P = .003). Patients in the highest quartile for area under the rifampicin and isoniazid concentration-time curves for were twice as likely to experience sputum conversion than those in the lowest quartile. Rifampicin and isoniazid concentrations below the thresholds and weight <55 kg were both risk factors for unfavorable tuberculosis treatment outcomes. Only 4.4% of the participants had treatment failure. Conclusion: Although low antituberculosis drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications for tuberculosis transmission. Clinical Trials Registration: NCT01782950.

A Lead-In with Silibinin Prior to Triple-Therapy Translates into Favorable Treatment Outcomes in Difficult-To-Treat HIV/Hepatitis C Coinfected Patients.

BACKGROUND: The efficacy of first-generation protease inhibitor based triple-therapy against hepatitis C virus (HCV) infection is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and non-response to previous peginterferon-ribavirin. These patients have a low chance of achieving a sustained virologic response (SVR) using first generation triple-therapy, with a success rate of only 20%. We investigated the efficacy and safety of lead-in therapy with intravenous silibinin followed by triple-therapy in this difficult-to-treat patient group. METHODOLOGY: Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented previous treatment failure on peginterferon-ribavirin. The intervention was a lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days, followed by triple-therapy (peginterferon-ribavirin and telaprevir) for 12 weeks, and peginterferon-ribavirin alone for 36 weeks. Outcome measurements were HCV-RNA after silibinin lead-in and during triple-therapy, SVR data at week 12, and safety and tolerability of silibinin. RESULTS: We examined sixteen HIV/HCV-coinfected patients with previous peginterferon-ribavirin failure, of whom 14 had a fibrosis grade METAVIR ≥F3. All were on successful antiretroviral therapy. Median (IQR) HCV-RNA decline after silibinin therapy was 2.65 (2.1-2.8) log10 copies/mL. Fifteen of sixteen patients (94%) had undetectable HCV RNA at weeks 4 and 12, eleven patients (69%) showed end-of-treatment response (i.e., undetectable HCV-RNA at week 48), and ten patients (63%) reached SVR at week 12 (SVR 12). Six of the sixteen patients (37%) did not reach SVR 12: One patient had rapid virologic response (RVR) (i.e., undetectable HCV-RNA at week 4) but stopped treatment at week 8 due to major depression. Five patients had RVR, but experienced viral breakthroughs at week 21, 22, 25, or 32, or a relapse at week 52. The HIV RNA remained below the limit of detection in all patients during the complete treatment period. No serious adverse events and no significant drug-drug interactions were associated with silibinin. CONCLUSION: A lead-in with silibinin before triple-therapy was safe and highly effective in difficult-to-treat HIV/HCV coinfected patients, with a pronounced HCV-RNA decline during the lead-in phase, which translates into 63% SVR. An add-on of intravenous silibinin to standard of care HCV treatment is worth further exploration in selected difficult-to-treat patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01816490.