Springer Science and Business Media LLC

People who inject drugs represent an under-treated chronic hepatitis C virus (HCV)-infected patient population. INTEGRATE was a prospective, observational study investigating the effectiveness, safety, and adherence in routine clinical practice to telaprevir in combination with peg-interferon and ribavirin (Peg-IFN/RBV) in patients with history of injecting drug use chronically infected with genotype 1 HCV. A total of 46 patients were enrolled and included in the intent-to-treat (ITT) population. Among heroin and/or cocaine users (n = 37; 80%), 22% reported use in the past month; 74% (34/46) of patients were on opioid substitution therapy in the pre-treatment phase, and 43% (20/46) discontinued HCV treatment prematurely. Sustained virologic response rate was 54% (25/46) in the ITT population and 74% (25/34) in the per protocol (evaluable-for-effectiveness) population. The main reason for failure in the ITT analysis was loss to follow-up (n = 8; 17%). Adverse events occurred in 91% (42/46) of patients. Mean patient-reported adherence to study drugs was >89% at Week 4, Week 12 and end of treatment. Despite a high rate of treatment discontinuation (including loss to follow-up), self-reported adherence to treatment was good and virologic cure rates were similar to those reported in large real-world cohorts. Our findings suggest that people with a history of injecting drug use should be considered for treatment of chronic HCV infection, and highlight the need for improvements in patient support to boost retention in care and, in turn, help to prevent reinfection and transmission. Clinicaltrials.gov identifier, NCT01980290. Janssen Pharmaceuticals.

A potential drug-drug interaction exists between divalent and trivalent cations (Ca2+, Fe3+, Mg2+, Al3+, Zn2+) and HIV-1 integrase strand transfer inhibitors (INSTIs). There are limited case reports describing the clinical significance of this potential interaction and none to our knowledge identifying zinc co-administration with INSTIs. In this report we present a patient taking bictegravir/emtricitabine/tenofovir alafenamide who became viremic after ingesting zinc and calcium supplements and later was able to obtain virologic re-suppression after discontinuing supplements. This case represents a potential significant drug interaction between a commonly prescribed antiretroviral drug class and readily available over-the-counter divalent cation products.

Parasitological confirmation before administration of antimalarial treatment has been recommended by the World Health Organization in everyone presenting with symptoms suggestive of malaria at all levels of the health system. The authors assessed the performance of a histidine-rich protein 2-based malaria rapid diagnostic test used by community health workers in the context of an integrated approach to diagnosis and treatment for malaria and pneumonia. A total of 525 children below 5 years of age were recruited into the study. Children with fever/history of fever within the last 24 h were tested with the rapid diagnostic test (RDT) and a blood smear was obtained for delayed reading. Overall, the FirstSign™ Malaria Pf (Unimed International Inc, South San Francisco, USA) has shown a high sensitivity profile of 97.9% (95% CI 96.3–98.8), but a low specificity of 53.4% (95% CI 49.1–57.7). The specificity was significantly lower during the high transmission season at 25.4% (95% CI 20.5–31.0) compared to 63.7% (95% CI 57.6–69.4%) at the low transmission season. The negative predictive value (NPV) was 95.4% (95% CI 93.2–96.9) and positive predictive value was 71.7% (95% CI 67.7–75.4). The NPV was significantly higher during the low transmission season at 98.2% (95% CI 95.7–99.3) than compared to 80.0% (95% CI 74.7–84.4) at the high transmission season. With such a low specificity, caution should be exercised when using these RDTs for community case management of malaria.

Fidaxomicin is as effective as vancomycin in treating Clostridioides difficile infection (CDI) but more effective at preventing recurrence. However, because fidaxomicin is more costly than vancomycin, its overall value in managing CDI is not well understood. This study assessed the budget impact of introducing fidaxomicin versus vancomycin for the treatment of adults with CDI from a hospital perspective in the US. A cohort-based decision analytic model was developed over a 1-year horizon. A hospital with 10,000 annual hospitalizations was simulated. The model considered two adult populations: patients with no prior CDI episode and patients with one prior CDI episode. Two scenarios were assessed per population: 15% fidaxomicin/85% vancomycin use and 100% vancomycin use. Model inputs were obtained from published sources and expert opinion. Model outcomes included cost, payment, and revenue at the hospital level, per treated CDI patient, and per admitted patient. Budget impact was calculated as the difference in revenue between scenarios. One-way sensitivity analyses tested the effects of varying model inputs on the budget impact. In patients with no prior CDI episode, treatment with fidaxomicin resulted in potential savings over 1 year of $1105 at the hospital level, $14 per treated CDI patient, and $0.11 per admitted patient. In patients with one prior CDI episode, fidaxomicin use was associated with potential savings over 1 year of $1150 at the hospital level, $74 per treated CDI patient, and $0.12 per admitted patient. Savings were driven by a reduced rate of CDI recurrence with fidaxomicin treatment and uptake of fidaxomicin. Sensitivity analyses indicated savings when inputs were varied in most scenarios. Budgetary savings can be achieved with fidaxomicin due to reduced CDI recurrence as a result of a superior sustained clinical response. Our results support considering the broader benefits of fidaxomicin, beyond its cost, when making formulary inclusion decisions. Clostridioides difficile infection (CDI) is a common hospital-acquired infection that affects about half a million people in the US each year. In some patients who have already had CDI, it can recur. These recurrent infections can be difficult to treat, and they place a burden on the healthcare system. CDI is usually treated with the antibiotics fidaxomicin or vancomycin. Fidaxomicin is as effective as vancomycin for treating CDI but is even more effective than vancomycin at preventing CDI recurrence. However, fidaxomicin is more expensive. In this study, we estimated the impact of replacing vancomycin with fidaxomicin for treating CDI on the budget of a typical US hospital. We estimated that treating 15% of patients with CDI using fidaxomicin in place of vancomycin would save the hospital between $1105 and $1150 in a year. This means that despite the higher cost of fidaxomicin, treating as few as 15% of patients with CDI using fidaxomicin instead of vancomycin can be cost-saving for hospitals.

Lower respiratory tract infections (LRTIs) are a major cause of morbidity and death. Because of changes in how LRTIs are defined coupled with the increasing prevalence of drug resistance, there is a gap in knowledge regarding the current burden of antimicrobial use for Centers for Disease Control and Prevention (CDC)-defined LRTIs. We describe the infection characteristics, antibiotic consumption, and clinical and economic outcomes of patients with Gram-negative (GN) LRTIs treated in intensive care units (ICUs). This was a retrospective, observational, cross-sectional study of adult patients treated in ICUs at two large academic medical centers in metropolitan Detroit, Michigan, from October 2013 to October 2015. To meet the inclusion criteria, patients must have had CDC-defined LRTI caused by a GN pathogen during ICU stay. Microbiological assessment of available Pseudomonas aeruginosa isolates included minimum inhibitory concentrations for key antimicrobial agents. Four hundred and seventy-two patients, primarily from the community (346, 73.3%), were treated in medical ICUs (272, 57.6%). Clinically defined pneumonia was common (264, 55.9%). Six hundred and nineteen GN organisms were identified from index respiratory cultures: P. aeruginosa was common (224, 36.2%), with 21.6% of these isolates being multidrug resistant. Cefepime (213, 45.1%) and piperacillin/tazobactam (174, 36.8%) were the most frequent empiric GN therapies. Empiric GN therapy was inappropriate in 44.6% of cases. Lack of in vitro susceptibility (80.1%) was the most common reason for inappropriateness. Patients with inappropriate empiric GN therapy had longer overall stay, which translated to a median total cost of care of $79,800 (interquartile range $48,775 to $129,600) versus $68,000 (interquartile range $38,400 to $116,175), p = 0.013. Clinical failure (31.5% vs 30.0%, p = 0.912) and in-hospital all-cause mortality (26.4% vs 25.9%, p = 0.814) were not different. Drug-resistant pathogens were frequently found and empiric GN therapy was inappropriate in nearly 50% of cases. Inappropriate therapy led to increased lengths of stay and was associated with higher costs of care.

Bacterial infections that cause community-acquired urinary tract infections (CA-UTI) and upper respiratory tract infections (CA-URTI) are most frequently treated empirically. However, an increase in antimicrobial resistance has become a problem when treating outpatients. This study determined the in vitro activities of oral antibiotics among 1501 pathogens from outpatients with CA-UTI and CA-URTI in medical centers during 2012 and 2013 from Argentina, Mexico, Venezuela, Russia, and the Philippines. Minimal inhibitory concentrations (MICs) were determined using broth microdilution and susceptibility defined by Clinical Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) criteria. Ceftibuten (MIC50, ≤0.25 mg/L) was more potent in vitro compared to other β-lactams against Enterobacteriaceae from CA-UTI. Susceptibility to fluoroquinolones using CLSI criteria varied: Argentina and Mexico (50%), the Philippines (60%), Venezuela (70%), and Russia (80%). Fosfomycin susceptibility was >90% against Enterobacteriaceae in each country. Susceptibility among Enterobacteriaceae to trimethoprim-sulfamethoxazole was 30.6–75.6% and nitrofurantoin susceptibility also varied among the countries and was higher when EUCAST breakpoints were applied (65–>90%) compared to CLSI (52–84%). All Haemophilus influenzae isolates from CA-URTI were susceptible to ceftibuten, cefixime, cefpodoxime, and cefuroxime using CLSI breakpoint criteria. EUCAST criteria produced intermediate and resistant MIC values for these oral cephalosporins. Country-specific susceptibility variation for fluoroquinolones, macrolides, and trimethoprim-sulfamethoxazole was observed among Streptococcus pneumoniae and Streptococcus pyogenes from CA-URTI. This study demonstrated that antimicrobial susceptibility patterns varied in the five countries investigated among pathogens from CA-UTI and CA-URTI. Merck & Co. Inc., Kenilworth, New Jersey, USA.