Typhus group Rickettsia community-acquired bacterial central nervous system infections: We must think outside the box!

Typhus group rickettsiosis (TGR), caused by Rickettsia typhi and Rickettsia prowazekii, are globally distributed vector-borne diseases with increasing cases. Diagnosis is usually clinical, confirmed by seroconversion of IgG antibodies. Human infection occurs in diverse geographic areas with some developing CNS infection characterized by fever, headache, meningismus, and/or focal signs - usually beyond the first week of initial symptomatology. Seizures and other CNS manifestations have been observed. When untreated, infection may result in neurologic sequelae and even death. This study presents a systematic review of all documented cases of Rickettsia typhi meningoencephalitis published since 2015 with the addition of five cases of TGR in South Coastal Texas, USA. This review followed the guidelines outlined in PRISMA. A schematic explanation of the pathophysiology is offered. CSF may present with high opening pressure, mild to moderate pleocytosis, mildly elevated protein levels, and low csf/serum glucose ratio, or normal findings. Meningeal enhancement, intracranial hypertension, and focal abnormalities have been described in imaging studies, but can be normal. Treatment with doxycycline leads to prompt resolution of symptoms. Failure to initiate early empiric treatment can lead to serious consequences. The study recommends routine testing for TGR in patients from endemic areas with classical symptoms when other diagnoses are inconclusive or in cases with atypical presentations. The authors advocate for incorporating empiric treatment for murine typhus into community-acquired bacterial meningitis guidelines in endemic areas; and stress the importance of enhancing laboratory diagnostic capabilities in public health entities world-wide. Further studies of community acquired mengingoencephalitis caused by TGR are highly encouraged.

A retrospective, multicentre evaluation of eravacycline utilisation in community and academic hospitals.

OBJECTIVES: Eravacycline is a novel, fully-synthetic tetracycline approved by the FDA for treatment of complicated intra-abdominal infections in August 2018. This study sought to characterise early clinical experience with this novel antibiotic. METHODS: Eravacycline utilisation for 66 patients was retrospectively evaluated. RESULTS: Eravacycline was used as monotherapy in 62.1% of cases. Mean duration of therapy was 13.1 ± 9.9 days. The majority (68.2%) of treatment was for off-label indications, including 34.8% for pulmonary and 28.8% for skin/soft tissue infections. A number of difficult-to-treat organisms were encountered: 50% of identified Gram-negative pathogens were resistant to carbapenems in vitro; and 48% of identified Gram-positive pathogens were resistant to vancomycin in vitro. The patient population had a high illness acuity, with 42.4% requiring ICU admission, 59.1% having ≥2 co-morbidities and 33.3% having ≥3 co-morbidities. Nevertheless, 95.5% experienced clinical improvement, with 86.4% achieving full infection resolution following eravacycline. Three patients who did not experience clinical improvement had an intra-abdominal source of infection without adequate source control. The remaining six who did not experience full infection resolution died from unrelated non-infectious causes during hospital admission. Adverse events were uncommon (4.5%), limited to nausea/vomiting, and not leading to eravacycline discontinuation. Although two patients had a history of Clostridioides difficile infection (CDI), no patients developed CDI while receiving eravacycline. CONCLUSION: These results illustrate the potential versatility of eravacycline with a broad activity spectrum, good safety and tolerability profile, flexibility for use in patients with renal injury or antibiotic allergies, and positive clinical outcomes in this real-world cohort.

Novel approaches in the treatment of Hansen's disease (Leprosy): a case series of multidrug therapy of monthly rifampin, moxifloxacin, and minocycline (RMM) in the United States.

The World Health Organization (WHO) recommends multidrug therapy (MDT) for the treatment of paucibacillary and multibacillary forms of leprosy, also known as Hansen's disease (HD). MDT combinations of dapsone, rifampin, and clofazimine have reduced the prevalence of the disease but are not without adverse effects impacting regimen adherence. Hence, an urgent need exists to consider alternative MDT regimens with an improved safety profile that promotes treatment adherence. Herein, we described a case series of 10 patients with HD (nine patients with multibacillary leprosy and one with pure neural leprosy) treated with monthly rifampin, moxifloxacin, and minocycline (RMM). The United States National Hansen's Disease Program (NHDP) diagnosed and treated patients across US institutions. All patients received a regimen of 12-24 months of RMM. We reviewed the clinical outcomes, adherence, rate of completion, and adverse events of patients treated with monthly RMM from January 2019 to August 2022. Nine patients had multibacillary leprosy, with some having type-2 reactions. One patient had pure neural leprosy with a reversal reaction. In this case series, we identified that all patients completed the RMM regimen without treatment interruptions. None of the patients experienced any skin hyperpigmentation or any significant side effects. All patients tolerated the monthly RMM regimen with rapid improvement of skin lesions and without logistic hurdles. Based on previous clinical evidence and the results of this case series, the NHDP and other programs should consider the RMM regimen as first-line therapy.

Impact of fluvoxamine on outpatient treatment of COVID-19 in Honduras in a prospective observational real-world study.

Background: The COVID-19 pandemic has impacted millions of lives globally. While COVID-19 did not discriminate against developed or developing nations, it has been a significant challenge for third world countries like Honduras to have widespread availability of advanced therapies. The concept of early treatment was almost unheard of when early outpatient treatments utilizing repurposed drugs in Latin American countries began showing promising results. One such drug is fluvoxamine, which has shown tremendous potential in two major studies. As a direct result, fluvoxamine was added to the standard of care in a major medical center outpatient COVID-19 clinic. Methods: This is a prospective observational study performed at the Hospital Centro Médico Sampedrano (CEMESA) in San Pedro Sula, Cortes, Honduras in the COVID-19 outpatient clinic. All patients were at least 15 years of age who had presented with mild or moderate signs and symptoms of COVID-19, and who also had a documented positive SARS-CoV-2 antigen or Reverse Transcription Polymerase Chain Reaction (RT-PCR) were included in the study. These patients then were all prescribed fluvoxamine. The cohort of patients who decided to take fluvoxamine were compared for primary endpoints of mortality and hospitalization risk to the cohort who did not take fluvoxamine. Patients were then monitored for 30 days with the first follow up at 7 days and the second follow up at 10-14 days of symptom onset. Categorical variables were compared by Pearson Chi-square test. The Relative risk was calculated using regression models. Continuous variables were compared by t-test and Wilcoxon rank-sum tests. Results: Out of total 657 COVID-19 cases, 594 patients took fluvoxamine and 63 did not take fluvoxamine. A total of five patients (0.76 percent) died, with only one death occurring in the fluvoxamine group. Patients who received fluvoxamine had a significantly lower relative risk of mortality (RR 0.06, p 0.011, 95% CI 0.007-0.516). There was a lower relative risk of hospitalization in the patients who in the fluvoxamine group. (-10 vs. 30 hospitalizations, RR 0.49, p = 0.035, 95% CI 0.26-0.95). There was 73 percent reduction in relative risk of requiring oxygen in the fluvoxamine group (RR 0.27, p < 0.001, 95% CI 0.14-0.54 Mean lymphocytes count on the first follow-up visit was significantly higher in the fluvoxamine group (1.72 vs. 1.38, Δ 0.33, p 0.007, CI 0.09-0.58). Conclusion: The results of our study suggest that fluvoxamine lowers the relative risk of death, hospitalization, and oxygen requirement in COVID 19 patients.

Improved economic and clinical outcomes with oritavancin versus a comparator group for treatment of acute bacterial skin and skin structure infections in a community hospital.

BACKGROUND: Oritavancin is a lipoglycopeptide antibiotic with in vitro bactericidal activity against gram-positive pathogens indicated for use in adults with acute bacterial skin and skin structure infections (ABSSSI). Its concentration-dependent activity and prolonged half-life provide a convenient single-dose alternative to multi-dose daily therapies for ABSSSI. This retrospective cohort study was conducted to quantify the clinical and economic advantages of using oritavancin compared to other antibiotic agents that have been historically effective for ABSSSI. METHODS: Seventy-nine patients received oritavancin who had failed previous outpatient antibiotic therapy (OPAT) for cellulitis or abscess and were subsequently readmitted to the hospital as an inpatient between 2016 and 2018. These patients were compared to a cohort of 28 patients receiving other antibiotics following OPAT failure and subsequent hospitalization for these two infection types. The primary clinical end point was average length of stay (aLOS) and secondary endpoints included readmission rates for the same indication at 30 and 90 days after discharge and the average hospital cost (aHC). RESULTS: A total of 107 patients were hospitalized for treatment of cellulitis or abscess. Demographic characteristics of both the oritavancin and comparator groups were similar except for the presence of diabetes. The primary clinical endpoint showed a non-significant decrease in aLOS between the oritavancin group versus comparator (2.12 days versus 2.59 days; p = 0.097). The secondary endpoints revealed lower readmission rates associated with oritavancin treatment at 30 and 90 days; the average hospital cost was 5.9% lower for patients that received oritavancin. CONCLUSION: The results of this study demonstrate that oritavancin provides not only a single-dose alternative to multi-day therapies for skin and skin structure infections, but also a clinical and economic advantage compared to other antibiotic agents.

A New Potential Strategy for Acute Non-Alcoholic Steatohepatitis (NASH).

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States, and 25% of patients with NAFLD progress to non-alcoholic steatohepatitis (NASH). NAFLD is predicted to be the most common indication for liver transplantation by 2030. Despite associated high morbidity and mortality, there is currently no approved therapy for NASH. PCSK9 inhibitors are approved for reducing LDL in patients who are statin-intolerant or need further LDL reduction. Increased LDL levels are independently associated with an elevated risk of NAFLD. CASE REPORT We present a case of a 39-year-old woman with acute NASH with familial hypercholesterolemia that was refractory to lifestyle modifications and HMG-CoA reductase inhibitors. An episode of rhabdomyolysis warranted a search for alternatives to statin therapy. Results of a liver biopsy showed microvesicular and macrovesicular steatosis with ballooning degeneration, indicating acute NASH. She was started on PCSK9 inhibitors as salvage therapy. Three monthly doses resulted in a more than an 80% reduction in ALT and AST and a 48% reduction in LDL levels. A liver biopsy done 8 months after the first biopsy showed normalization of liver histology. CONCLUSIONS The use of PCSK9 inhibitors showed a dramatic response in this patient who failed conventional therapies, and the encouraging results seen in this case merit further research into the use of PCSK9 inhibitors as first-line therapy for the acute phase of NASH.

Upper extremity Histoplasma capsulatum treatment with isavuconazole.

Extrapulmonary Histoplasma capsulatum infections in the immunocompetent population are rare and pose a diagnostic challenge. Upper extremity histoplasmosis without a primary lung infection is uncommon. It is possible to acquire it by inadvertent trauma with direct inoculation. Our case describes an immunocompetent patient with progressive swelling with minimal pain in the wrist associated with a small puncture wound on the left dorsal forearm. The initial workup failed to identify a specific etiology. For the following six weeks, the patient experienced progressive worsening of symptoms, warranting a referral to an orthopedic hand surgeon. Left lower extremity magnetic resonance imaging (MRI) findings were non-specific. The surgeon performed a surgical exploration and debridement with the excision of hypertrophic tissue. Initial stains showed a granulomatous tissue but did not reveal an organism; however, a month later, mold was identified on the growth medium. The patient was initiated in isavuconazole empiric therapy. Four weeks later, a matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) confirmed the diagnosis as Histoplasma capsulatum. The patient had clinical remission with isavuconazole used as the United States Food and Drug Administration (FDA) off label use.

A multi-mechanism approach reduces length of stay in the ICU for severe COVID-19 patients.

PURPOSE: COVID-19 pandemic has multifaceted presentations with rising evidence of immune-mediated mechanisms underplay. We sought to explore the outcomes of severe COVID-19 patients treated with a multi-mechanism approach (MMA) in addition to standard-of-care (SC) versus patients who only received SC treatment. MATERIALS AND METHODS: Data were collected retrospectively for patients admitted to the intensive care unit (ICU). This observational cohort study was performed at five institutions, 3 in the United States and 2 in Honduras. Patients were stratified for MMA vs. SC treatment during ICU stay. MMA treatment consists of widely available medications started immediately upon hospitalization. These interventions target immunomodulation, anticoagulation, viral suppression, and oxygenation. Primary outcomes included in-hospital mortality and length of stay (LOS) for the index hospitalization and were measured using logistic regression. RESULTS: Of 86 patients admitted, 65 (76%) who had severe COVID-19 were included in the study; 30 (46%) patients were in SC group, compared with 35 (54%) patients treated with MMA group. Twelve (40%) patients in the SC group died, compared with 5 (14%) in the MMA group (p-value = 0.01, Chi squared test). After adjustment for gender, age, treatment group, Q-SOFA score, the MMA group had a mean length of stay 8.15 days, when compared with SC group with 13.55 days. ICU length of stay was reduced by a mean of 5.4 days (adjusted for a mean age of 54 years, p-value 0.03) and up to 9 days (unadjusted for mean age), with no significant reduction in overall adjusted mortality rate, where the strongest predictor of mortality was the use of mechanical ventilation. CONCLUSION: The finding that MMA decreases the average ICU length of stay by 5.4 days and up to 9 days in older patients suggests that implementation of this treatment protocol could allow a healthcare system to manage 60% more COVID-19 patients with the same number of ICU beds.

Postoperative instrumented spine infections: a retrospective review.

BACKGROUND: Postoperative infection following posterior instrumentation of the spine is not uncommon and is a potentially catastrophic complication. Removal of the instrumentation is ideal for eradicating infection. However, removal is not always possible from a structural standpoint. An alternative is to treat the patient with antibiotics in combination with irrigation and debridement. MATERIALS AND METHODS: All patients undergoing posterior instrumentation of the thoracolumbar spine from a single institution between 1996 and 2004 that developed an infection were retrospectively reviewed. The goal of this study was to determine the effectiveness of treating postoperative spinal instrument infections with antibiotics and irrigation and debridement alone without removal of the hardware. RESULTS: Out of a total of 737 spinal surgeries, 26 cases of postoperative infection were found. Nineteen of the patients had early onset infection, and 7 were late onset. Seventeen (90%) of the 19 patients with early onset infections successfully received long term antibiotics with initial retention of instrumentation. Six out of the 7 patients with late onset infection required removal of instrumentation for cure. All patients were considered cured with at least 36 months follow up with one patient still on oral antibiotics using this approach. CONCLUSIONS: The management of infected spinal instrumentation is dependent on the time of onset. Early onset infections can be successfully treated without instrumentation removal and 4-6 weeks of IV antibiotics followed by a course of oral antibiotics of 4-12 weeks. Late onset infections require instrumentation removal.

Thymoma Causing Bilateral Upper Extremity Deep Vein Thrombosis.

A 38-year-old African American male presented with progressive pain, swelling, numbness, and warmth of the left upper extremity ten days before admission. A chest computerized tomography scan showed a large 8.3 cm × 6.1 cm x 9.9 cm anterior mediastinal mass with compression of the left brachiocephalic vein and superior vena cava. A venous doppler showed multiple occlusive venous thrombi in bilateral upper extremities, including the bilateral internal jugular and subclavian veins, as well as the left subclavian, axillary, cephalic, brachial and median cubital veins. Further laboratory workup came positive for acetylcholine receptor binding antibody suggesting myasthenia gravis, but the patient was asymptomatic for myasthenia gravis. A percutaneous core CT guided biopsy pathology resulted in a predominant T-cell population CD5 positive with few B cells; the immunophenotypic features suggested Type B2 thymoma. To the best of our knowledge, this case is the only reported thymoma presenting with bilateral deep vein thrombosis of the upper extremities. The deep vein thrombosis therapy was enoxaparin 1mg/kg subcutaneously every 12 hours and dexamethasone 4mg intravenously every 4 hours as an anti-inflammatory drug for thymoma related compression of the mediastinum. The patient was referred to a tertiary oncological medical center for a total thymectomy, chemotherapy, and adjuvant radiotherapy.

Successful treatment of a prosthetic hip infection due to Enterococcus faecalis with sequential dosing of oritavancin and prosthesis preservation without prosthetic joint surgical manipulation.

A patient with a prosthetic joint infection (PJI) complicated with deep surgical site infection due to vancomycin-susceptible Enterococcus faecalis. The initial treatment consisted of 10 days with daptomycin plus ampicillin. The hip prosthesis was retained and salvaged with six outpatient sequential doses of oritavancin 1200 mg every seven days without intra-articular irrigation or other surgical interventions. The patient was ambulating independently without symptoms after ten months of the last treatment of oritavancin.

Rickettsia typhi central nervous system infection.

A 39 year-old male was residing along the south coast of Texas, the USA, presented with fever, myalgias, headaches, and weight loss for ten days. Symptoms and manifestations progressed to include nuchal rigidity, photophobia, hyponatremia, thrombocytopenia, and transaminitis despite the intravenous administration of ceftriaxone and azithromycin. A lumbar puncture performed in the Emergency Department yielded pleocytosis and glucose cerebrospinal fluid/serum ratio of 0.35, suggestive of meningoencephalitis. Conglomerate data raised the suspicion of meningitis secondary to a zoonotic acquired infection, which was later confirmed to be Rickettsia typhi. Doxycycline is the drug of choice for the suspected Rickettsia disease. After doxycycline administration, the patient improved and was discharged home asymptomatic.

Nontyphoidal Salmonella purulent pericarditis presenting with pericardial tamponade in a patient on infliximab therapy.

Infection with nontyphoidal Salmonella is traditionally characterized by intestinal manifestations. However, extra-intestinal infections are known to occur, with purulent pericarditis associated with cardiac tamponade being rare. This case report is of a 57-year-old male with Crohn's disease initiated on infliximab therapy two months prior to presentation. He presented with recurrent chest pain and a single occurrence of fever. A Computed Tomography (CT) scan of the chest revealed a pericardial effusion. An echocardiogram confirmed the presence of the fluid with tamponade physiology, requiring immediate surgical decompression. The pericardial fluid culture grew Salmonella enterica, despite the patient having only a single episode of fever, disproportionate to the severity of the infection. Conceivably, the lack of systemic symptoms may be attributed to recent infliximab therapy. Upon conducting a literature review, immunosuppressive factors seem to play a significant role in nontyphoid Salmonella enterica pericardial effusion presenting with cardiac tamponade.

The CHROME Study, a Real-world Experience of Single- and Multiple-Dose Oritavancin for Treatment of Gram-Positive Infections.

BACKGROUND: Oritavancin (ORI) is a long-acting lipoglycopeptide indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSIs) caused or suspected to be caused by susceptible Gram-positive (GP) pathogens. METHODS: Data collected from a retrospective observational program (2014-2017), Clinical and Historic Registry and Orbactiv Medical Evaluation (CHROME), describe the utilization, outcomes, and adverse events (AEs) associated with ORI in 440 patients treated at 26 US sites for ABSSSI and other GP infections. RESULTS: Clinical success in evaluable patients receiving at least 1 dose of oritavancin was 88.1% (386/438). In a subgroup of patients who received ORI for skin and soft tissue infections (n = 401) and bacteremia (n = 7), clinical success was achieved in 89.0% and 100%, respectively. A cohort of 32 patients received 2-10 ORI doses separated by no more than 14 days for complicated GP infections. Clinical success was observed in 30 of 32 patients (93.8%), including 10 of 11 (90.9%) patients with bone and joint infections and 7 of 8 (87.5%) patients with osteomyelitis. In the safety evaluable population, the overall rate of AEs was 6.6%. CONCLUSIONS: We describe results from a real-world program that includes the largest multicenter, retrospective, observational study in patients who received at least 1 dose of ORI for the treatment of GP infections. This study confirms that ORI is an effective, well-tolerated antibiotic used in single and multiple doses for the treatment of ABSSSIs and complicated GP infections.

Cryptococcus laurentii meningitis in a non-HIV patient.

Cryptococcus species (other than Cryptococcus neoformans) have been labeled as saprophytic and nonpathogenic in immunocompetent individuals in the past. In recent years, infections caused by non-neoformans Cryptococcus species have been recognized. Cryptococcus laurentii is known to be a rare human pathogen. In this case report, we present a 59-year-old man who did not have HIV infection with meningoencephalitis caused by Cryptococcus laurentii. No significant underlying immunosuppressive disorder was found. The only identifiable risk factors were that the patient was a farmer with previous exposure to pigeon droppings. Here, we describe what we believe to be the fifth reported case of meningitis caused by Cryptococcus laurentii.

Rickettsia typhi infection presenting as severe ARDS.

Murine typhus, also known as endemic typhus, is a disease resulting from an infection caused by the gram-negative bacillus Rickettsia typhi. Murine typhus is identified worldwide, predominantly in tropical and subtropical geographic locations. Transmission occurs through direct inoculation by an arthropod vector, most commonly the rat flea, Xenopsylla cheopis. rickettsial infections are notorious for disseminated infections throughout the endothelial cells. The increase in permeability is an immediate consequence and has the potential of leading to non-cardiogenic pulmonary edema, otherwise known as acute respiratory distress syndrome (ARDS). Clinical manifestations are non-specific and initially mimic typical viral etiologies, obscuring early diagnosis. As a result, clinicians often do not include rickettsial infections in their differential diagnoses. Definitive diagnosis is based on clinical recognition, epidemiologic awareness, and serological testing. Here we present a confirmed case of murine typhus in a young non-immunocompromised patient who developed ARDS one week from the initial onset of symptoms.

A rationale for combination ampicillin and daptomycin in renal transplant patients with enterococcal infective endocarditis.

Treatment of enterococcal endocarditis in patients with history of renal transplantation is complicated. Treatment failure and/or drug toxicities are not uncommon. Treatment with ampicillin and daptomycin in a renal transplant patient has been rarely reported. Here we report a patient who was successfully treated with this novel combination.

Talaromyces marneffei infection in a non-HIV non-endemic population.

Introduction: Talaromyces marneffei infection is a systemic mycosis, caused by a dimorphic fungus, an opportunistic pathogen formerly known as Penicillium marneffei. This disease is endemic to Southeast Asia and common in human immunodeficiency virus (HIV) infected patients with low CD4 counts. Here we present a very rarely reported case of Talaromyces marneffei infection in an apparent non-immunosuppressed patient presenting decades later in a non-endemic setting (United States). Presentation of case: Our patient was a 75-year-old Caucasian Navy veteran, who served in Vietnam as a part of the Swift Boat service in 1966. He presented to his primary care provider with uncontrolled nonproductive cough and abnormal chest computerized tomography. Bronchoscopy specimens showed Talaromyces. He was empirically treated with itraconazole and then switched to voriconazole after confirmation of diagnosis but he later deteriorated was changed to liposomal amphotericin B and isavuconazole. Patient did well for the next 90 days on isavuconazole until the therapy was stopped. Soon after stopping the medication (isavuconazole) his symptoms recurred and ultimately patient expired. Discussion: Talaromycosis generally presents as pulmonary infection with manifestations similar with other endemic fungi. It is often seen HIV patients with travel to South east Asia. Very rarely this infection is seen and reported in non-immunosuppressed and in non-endemic areas. To date there are 4 well-documented cases among non-HIV, non-endemic population. Conclusion: Talaromyces can cause infection in non-HIV and non-endemic population and could be an underrecognized cause of pulmonary infections among veterans with even a remote history of exposure to the organism during deployment.

Clinical significance of Aerococcus urinae: a retrospective review.

A retrospective chart review was performed on 54 patients with positive urine cultures during a 1-year period to assess the clinical significance of Aerococcus urinae. Based on predetermined criteria, patients were classified into 2 groups: those with urinary tract infections (UTIs) and those who were considered colonized. The majority of the patients were > or =65 years old and were female. Only 31% of patients with UTI and 45% of colonized patients had A. urinae isolated in pure cultures. Both groups had significant but similar underlying medical conditions, with urologic conditions being predominant. Significantly more patients in the UTI group had urinary catheters (P < .01). No direct complications or invasive disease was recognized in either group regardless of whether patients were treated with antibiotics. Apparently, A. urinae is a relatively avirulent organism when cultured from urine.

Spectrum of pulmonary toxicity associated with the use of interferon therapy for hepatitis C: case report and review of the literature.

Hepatitis C is one of the leading causes of liver disease in the United States, and current recommendations for its treatment include the use of interferon (IFN). Pulmonary side effects, although uncommon, have been reported in association with the use of IFN. We report a case of interstitial granulomatous pneumonitis that occurred after therapy with IFN and ribavirin, and we review the literature concerning this entity and other forms of IFN-associated pulmonary toxicity in patients with hepatitis C. The purpose of the present study is to increase awareness of the unusually wide spectrum of pulmonary toxicities associated with the use of IFN and ribavirin, with the anticipation that IFN will be used more frequently in the future for the treatment of hepatitis C.