Brandon May

 (HCV) genotype 2 and genotype 3, treatment regimens comprised of daclatasvir plus sofosbuvir plus ribavirin (DCV+SOF±RBV) and velpatasvir/sofosbuvir (VEL/SOF) plus RBV confer similar efficacy profiles in terms of achieving a cure, according to a new study.

Predictors for sustained virologic response (SVR) in genotype 3 patients treated with these regimens, according to the researchers, include prior HCV treatment, FIB-4 >3.25, and history of decompensated liver disease.

“Given the size of the cohort, we were able to discern differences among these treatment regimens which are widely used throughout the world, particularly among treatment-experienced patients, thus providing germane information on their effectiveness in genotype 2 and genotype 3 populations to better inform HCV management strategies,” leading study author, Lisa Backus, MD, PhD, told 

®. “We believe these findings are relevant to an extensive audience, including environments where wide access to all regimens are not readily available.”

Backus noted that, while DCV+SOF is not widely used in the US, investigators found it is as effective as VEL/SOF in difficult-to-treat subgroups.

For this observational study, investigators evaluated the effectiveness of DCV+SOF±RBV or VEL/SOF±RBV between patients with genotype 2 and genotype 3 HCV patients receiving care at the Department of Veterans Affairs. Specified analyses were focused on patients receiving DCV+SOF (n = 255), VEL/SOF (n = 2230), DCV+SOF+RBV (n= 42), and VEL/SOF+RBV (n= 247).

In patients with HCV genotype 2, there were no differences in regard to SVRs in patients receiving DCV+SOF and VEL/SOF (94.5% vs 94.4%; 

= .94) or between DCV+SOF+RBV and VEL/SOF+RBV (88.1% vs 89.5%; 

= 1.00). Additionally, there were no differences among HCV genotype 3 patients in terms of the SVR between regimens comprised of DCV+SOF and VEL/SOF (90.8% vs 92.0%; 

= .50) or DCV+SOF+RBV and VEL/SOF+RBV (88.1% vs 86.4%, respectively; 

There was no significant predictive effect of any treatment regimen for predicting the odds of SVR in either genotype 2 or genotype 3 patients. In genotype 3 patients, however, significant predictors associated with a decreased SVR odds included prior HCV treatment (odds ratio [OR] 0.51; 95% CI: 0.36 - 0.72; 

< .001), FIB-4 >3.25 (OR 0.60; 95% CI: 0.43 - 0.84; 

= .002), and a history of decompensated liver disease (OR 0.68; 95% CI: 0.47 - 0.98; 

“Because of the timeframe of this study, some regimens that were used were not a part of current HCV guideline recommendations as guidelines were either not updated at the time these patients were initiating treatment (mid 2015 to early 2017) because of the rapidity of emerging data or because guideline recommendations have since changed,” Backus explained.

As such, he stressed the importance of remember real-world providers may make decisions to extend treatment, add ribavirin, or use non-approved combinations.

Backus added that future research studies should focus on evaluating such outcomes with non-traditional regimens as potential therapy alternatives, particularly given the limited HCV drug pipeline.

“As new data emerges with expanded use of HCV antiviral agents, it is important to consider real-world data when updating HCV treatment guidelines, recognizing that inevitably not all patients will be treated as recommended in guidelines,” Backus said.

The study, "Real-world Effectiveness of Daclatasvir plus Sofosbuvir and Velpatasvir/Sofosbuvir in Hepatitis C Genotype 2 and 3," was published online in the 

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Treatment regimens comprised of DCV+SOF±RBV and VEL/SOF+RBV offer similar cure rates among HCV patients with genotypes 2 and 3.

Daclatasvir-Sofosbuvir-Ribavirin Combination Similar to VEL/SOF Plus RBV for Hepatitis C Genotypes

Investigators have targeted a new source for hepatitis C (HCV) treatment analysis—a source with relevant data in the era of direct-acting antiviral (DAA) therapy.

The national Veterans Health Administration (VA) Corporate Data Warehouse (CDW) is a resource with accurate data on DAA use for chronic HCV treatment, making this data source a reliable base from which researchers can create retrospective analyses, according to a new study.

As a result, this observational data could serve an important role in pharmacoepidemiologic studies that would assess the overall benefit and risks of modern HCV therapies, investigators, led by Christopher T. Rentsch, MPH, noted. The CDW is a national source of documented prescriptions and pharmacy fills. In contrast, electronic data from each VA facility going through multiple extracts, transforms, and loads—meaning original data validity could be compromised.

Investigators retrospectively assessed HCV-infected patients treated with DAAs who were included in the Veterans Aging Cohort Study (VACS) at 5 different VA treatment sites (n = 501). All patients had pharmacy fill data available for analysis. The range of DAA agents or regimens prescribed in the cohort were as follows:

Ombitasvir/ paritaprevir/ ritonavir/ dasabuvir

The researchers also randomly selected patients with chronic HCV infection who were not treated for HCV during the 2-year study period. These patients underwent chart review. Study investigators calculated the positive predictive and negative predictive values overall and by VA treatment site.

Out of 2416 prescriptions recorded for the overall cohort, only 494 were validated based on data from the CDW approximately 6 months following the study period. This validation resulted in a positive predictive value of 98.6% (95% CI: 97.6 - 99.6). Across all 5 treatment sites, the positive predictive values featured a range of 96.7% to 100% (

In 100 HCV patients in the CDW who did not receive HCV treatment, approximately 97% (n = 97) had confirmation of non-treatment, whereas 3% (n = 3) did receive HCV treatment during the 2-year study period. These findings resulted in an overall negative predictive value of 97.0% (95% CI: 93.7 - 100), which were comparable across all treatment sites (

In data extraction 6 months after the main study period, only 1 out of 22 prescriptions were found for 3 patients who had no records of treatment recorded in the CDW. This finding yielded an updated positive predictive value of 98.6% (95% CI: 97.6 - 99.6) as well as a negative predictive value of 99.0% (95% CI: 97.1 - 100).

The analysis of patients attending only 5 VA sites may have resulted in findings that lack generalizability across all VA centers. Additionally, the retrospective nature of the study was a potential limitation of the analysis.

That said, observational data could still play an important role in safety- and efficacy-based assessments of modern HCV therapies.

“These findings provide assurance to researchers who use national VA CDW data for retrospective cohort studies that the CDW contains accurate information, particularly after a 6-month lag for data extraction, on HCV therapies in the modern treatment era, even for VA patients who obtained treatment from non-VA providers,” investigators wrote.

Assessing comparative effectiveness of several different DAA regimens, the importance of adverse effects (eg, acute liver injury or HBV reactivation), and the effect of alcohol abuse on DAA receipt with treatment outcomes may be an important future area of research, investigators concluded.

Provider verification of electronic health record receipt and nonreceipt of direct-acting antivirals for the treatment of hepatitis C virus infection

This observational data could serve an important role in pharmacoepidemiologic studies that would assess the overall benefit and risks of modern HCV therapies, namely direct-acting antivirals.

VA Corporate Data Proves To Accurate Source for HCV Treatment Assessment

Female sex, previous gastrointestinal comorbidity, and non-gastrointestinal comorbidity were independently associated with a higher risk of community-acquired 

 infection in patients with urinary tract infection (UTI), according to a study published in 

“The findings from our study of particularly interest for primary care physicians, infectious disease physicians, as well as urologists and urogynecologists in an age where we are seeing the various repercussions of our increasing antibiotic use,” Ivy Ge, PharmD, of Kaiser Permanente South San Francisco, told 

®. “This research is also especially important due to the prevalence of UTI, especially in female population. We hope this study will provide greater insight for physicians who treat patients with UTI and co-occurring [community acquired 

Researchers from Kaiser Permanente Northern California performed a nested case-control study of adult patients who received ≥1 antibiotic prescription for acute uncomplicated UTI between 2007-2010. Cases reported loose stools and had a positive test for 

 for ≥3 days following the start of an antibiotic regimen and <90 days following stopping their antibiotic regimen (n = 68). Each case was matched with a total of 2 randomly selected age-matched controls who had antibiotic-treated UTI but no diagnosis of 

The investigators classified antibiotics as low risk (eg, nitrofurantoin and sulfamethoxazole/trimethoprim), moderate risk, high risk (eg, cefpodoxime, ceftriaxone, and clindamycin), and most common (eg, ciprofloxacin) for 

infection. The primary measurement of interest was the association between antibiotic treatment of uncomplicated UTI and history of gastrointestinal comorbidity with community-acquired 

 infection risk. Gastrointestinal comorbidities included gastrointestinal diagnoses, procedures, and gastric acid suppression treatment.

In the adjusted analysis, factors associated with 

 risk included past gastrointestinal comorbidities (OR 2.3; 95% CI 1.1-4.8) and Charlson comorbidity (OR 2.8; CI 1.4-5.6). Additionally, non-gastrointestinal comorbidities were associated with community-acquired 

 (prevalence 6%; OR 2.8; 95% CI 1.4-5.6). Treatment with ciprofloxacin (OR 2.7; 95% CI 1.0-7.2), moderate-risk antibiotics (OR 3.6; 95% CI 1.2-11), and high-risk antibiotics (OR 11.2; 95% CI 2.4-52) compared with low-risk antibiotics.

Compared with men, women presented with a 6.3-fold greater risk for 

 (95% CI 1.7-24). A subgroup analysis in women demonstrated that there was an association between a higher risk for 

 and the use of ciprofloxacin (OR 2.9; 95% CI 1.1-8.0), moderate risk (OR 3.7; 95% CI 1.2-11), and high risk (OR 8.0; 95% CI 1.8037) compared with low-risk agents. Additionally, women had a higher risk if they had a history of Charlson comorbidity (OR 2.2; 95% CI 1.0-4.9) and gastrointestinal comorbidities (OR 3.0; 95% CI 1.5-6.2).

Limitations of this study include its relatively small sample size, inclusion of patients from a single center, and the high prevalence of female patients in the overall cohort.

“Since many clinicians are able to identify at-risk patients by examining their medical histories, they should have the ability to switch these patients to lower-risk options, particularly with this high-risk cohort,” Ge added. “Additional research, in addition to public health efforts to promote improved hygiene, sexual practices, and health behaviors among girls and women, is needed to further reduce the morbidity associated with UTIs and antibiotic use for UTI treatment.”

Reducing risk of Clostridium difficile infection and overall use of antibiotic in the outpatient treatment of urinary tract infection

Female sex, previous gastrointestinal, and non-gastrointestinal comorbidities are associated with C difficile infection in women with UTIs, study finds.

Gastrointestinal Comorbidities Increase Risk of C Difficile for Patients with UTIs

A behavioral approach consisting of in-person discussions with nurses and prescribers regarding 

management recommendations was associated with self-sustained practice changes and significant improvements in specific suboptimal 

Optimizing testing and infection management remain substantial challenges in caring for patients with 

infections. Inappropriate testing, as well as inaccurate documentation of bowel movements (BMs), can result in overdiagnosis of 

“CD Action Team’s (CDAT) face-to-face interaction with providers led to significant improvement in BM documentation, antibiotic use for concomitant non-

 infections, and proton pump inhibitor (PPI) use,” investigators, led by Valeria Fabre, MD, of the Johns Hopkins University School of Medicine, wrote. “For some 

 antibiotic therapy and BM documentation), we observed a cumulative effect after a second intervention, suggesting a potential long-term benefit of repetitive interventions.”

Fabre and colleagues prospectively reviewed medical charts of adult patients who were hospitalized with positive 

 tests (n = 96). Using these data, they developed management recommendations for these patients. Two interventions were implemented during the 11-month study, both of which used an in-person, real-time, case-based education and discussion with the patient by a CDAT.

The CDAT comprised 3 infectious disease physicians, 2 infection preventionists, and 3 pharmacists. Case evaluations occurred within a 24-hour period of a patient receiving a positive 

 test, whereas management was assessed within a 48-hour period following CDAT delivery of recommendations during the intervention periods.

Primary outcomes of the analysis included CDAT-prompted changes as well as CDAT-independent changes. In the CDAT-prompted change outcome, investigators compared the percentage of patients receiving optimized 

 management within a 48-hour period following CDAT with the percentage of patients who received optimized management of 

The CDAT-independent changes were evaluated by comparing the percentage of patients who received optimized management of 

 during both the observation period as well as before intervention, with the percentage of patients who received optimized 

At least 1 opportunity to improve the management of 

 was identified by the CDAT in 84 patients. During the intervention periods, the CDAT provided recommendations for a total of 76 cases. There were significant improvements in the response to CDAT-led direct interventions for patients with BM documentation, showing that suboptimal BM documentation decreased by 68% and 92% during the first intervention and second intervention, respectively; 

Additionally, suboptimal antibiotic use was reduced by 57% during the first intervention and 76% during the second intervention (

<.01 for both). Finally, the investigators observed a 63% decrease in inappropriate PPI use during both interventions (

Clinical acceptance of the practice change recommendations was fairly similar among categories, including recommendations to stop unnecessary PPI use (52% of cases), stop laxatives (53%), improve BM documentation (57%), change or stop 

 therapy (58%), and change or stop antibiotics for non-

The relatively small sample size, the lack of a comparator or control intervention (ie, sham intervention), and the specificity of these findings to only 

 management represent the primary limitations of the analysis.

“Our results add to the emerging literature supporting a role for nurses in antibiotic and diagnostic stewardship efforts.” the investigators added. “Nurses perform many antibiotic functions in their daily practice (eg, they review and administer antibiotics and other medications that can impact the course of an infection, they obtain specimens for microbiology testing); however, [many times] these activities are not formally aligned with antibiotic stewardship efforts.”

Impact of Case-Specific Education and Face-to-Face Feedback to Prescribers and Nurses in the Management of Hospitalized Patients with a Positive Clostridium difficile Test

A face-to-face, case-specific education intervention improved the management practices among nurses who cared for hospitalized patients with C difficile infections.

Brandon May

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