Stewardship / Resistance Scan for Sep 30, 2019

News brief

Targeted stewardship may reduce post-discharge fluoroquinolones

Researchers conducting a Veterans Health Administration (VHA) study involving 122 hospitals have determined that a targeted inpatient fluoroquinolone stewardship program (ASP) is tied to improved fluoroquinolone prescribing at hospital discharge, with urinary tract infections (UTIs) and chronic obstructive pulmonary disease (COPD) most often associated with inappropriate prescribing of the drugs, according to findings published in Clinical Infectious Diseases.

The researchers analyzed data on more than 1.7 million patients from 2014 through 2016 among the VHA hospitals and on 1.73 million fluoroquinolone days of therapy (DOTs). Of that total, 39% of DOTs were prescribed for inpatients, and the rest were for use post-discharge.

The team also assessed two ASP approaches for optimizing fluoroquinolone prescribing— prospective audit-and-feedback (PAF) and restrictive policies (RP)—as well as no strategy. They assessed the three approaches in three hospitals each, and assessed 125 patients in each hospital.

The authors used risk-adjusted analysis to determine that post-discharge fluoroquinolone exposure differed significantly only between RP and no-strategy sites (3.8% vs 9.3%, P = 0.012). They found no significant difference in fluoroquinolone exposure between PAF and no-strategy hospitals. About 31% of all post-discharge fluoroquinolones were prescribed for patients who did not receive them while an inpatient, and most common diagnoses among those prescribed the antibiotics at discharge were UTI (18.7%) and COPD (14.5%).

The investigators also report that post-discharge fluoroquinolone prescription was deemed inappropriate by selection or duration in 154 (41.1%) of 375 patients, with the rate varying from 35.2% in hospitals with a targeted ASP versus 52.8% in no-strategy hospitals. The scientists report that the difference between PAF (29.6%) and RP (40.8%) hospitals did not reach statistical significance (P =0.06). Inappropriate post-discharge fluoroquinolones were flagged for 23 (79.3%) of 29 COPD patients and for 32 (55.2%) of 58 UTI patients.

The authors conclude, "Our findings suggest that stewardship efforts to minimize and improve fluoroquinolone-prescribing should also focus on antimicrobial-prescribing at hospital discharge."

An accompanying commentary adds, "Successful implementation of [antibiotic stewardship] at this critical transition point will need to leverage and engage frontline providers, staff, pharmacists, case management, nurses, and the entire care team."
Sep 28 Clin Infect Dis study
Sep 28 Clin Infect Dis commentary

Phase 3 trial for new gonorrhea antibiotic to launch

Biopharmaceutical company Entasis Therapeutics and the nonprofit Global Antibiotic Research and Development Partnership (GARDP) today announced the initiation of a global phase 3 clinical trial for zoliflodacin, a new antibiotic for treating uncomplicated gonorrhea.

The trial aims to enroll approximately 1,000 patients with urogenital gonorrhea from sites in the United States, Netherlands, Thailand, and South Africa. Patients will be randomized 2:1 to receive either zoliflodacin or a combination of ceftriaxone and azithromycin, the current first-line treatments for uncomplicated gonorrhea.

Developed by Entasis, of Waltham, Massachusetts, zoliflodacin is a single-dose oral antibiotic with a mechanism of action that differs from current therapies. In a phase 2 trial involving 179 patients from sexual health clinics in Louisiana, Alabama, Indiana, North Carolina, and Washington, the drug was found to be highly effective in treating urogenital and rectal gonorrhea and was well-tolerated. But it was much less effective in treating pharyngeal gonorrhea.

The trial is critical, because the World Health Organization (WHO) has warned that rising resistance to ceftriaxone and azithromycin threatens the ability to treat the sexually transmitted infection, and that failure to develop new drugs could result in widespread treatment failure. Untreated gonorrhea can lead to pelvic inflammatory disease, ectopic pregnancy, infertility, and increased HIV risk.

Under the agreement with Entasis, GARDP is responsible for the phase 3 trial and pharmaceutical development activities to support regulatory approval and market availability, and has commercial rights to zoliflodacin in up to 168 low- and middle-income countries.

"The initiation of the phase 3 trial of zoliflodacin is an important milestone and brings hope for people affected by this disease. Our partnership with Entasis is critical for preventing the dire scenario of untreatable gonorrhoea and controlling this infection," GARDP Executive Director Manica Balasegaram, MRCP, MSc, said in a GARDP press release. "The global nature of the trial, across four continents, represents our commitment to ensuring this treatment is available to anyone who needs it, wherever they live."

The WHO estimates that 87 million new gonorrhea cases occur each year, and the rate is rising.
Sep 30 GARDP press release

Rapid viral testing fails to reduce antibiotics, hospital stays in Finnish trial

The results of a randomized controlled clinical trial conducted in Finland show that rapid viral testing did not reduce antibiotic consumption or shorten hospital stays in acutely ill adults, Finnish researchers report in Clinical Microbiology and Infection.

The single-center study involved patients with respiratory symptoms, fever, chest pain, or poor general condition in the emergency unit of a tertiary hospital in Finland who were randomized 1:1 into two groups: a rapid viral diagnostics group (the intervention group) and a delayed viral diagnostics group (the control group). The attending physician received the viral results for the intervention group within 24 hours and the results from the control group within 7 days. Nasal swab samples were analyzed using a multiplex real-time polymerase chain reaction (PCR) detection method. The primary outcomes were duration of hospitalization and antibiotic consumption.

Of the 998 randomized patients, 841 (84%) had respiratory symptoms at study entry. A respiratory virus was detected in 175 patients—94 (19%) in the intervention group and 81 (16%) in the control group.

Among the 684 patients admitted to the hospital, the mean duration of hospitalization was 4.2 days (standard deviation [SD], 5.4) in the intervention group and 4.1 days (SD, 4.9) in the control group (difference, 0.1 days; 95% confidence interval [CI], -0.5 to 0.6, P = 0.810). Among the 639 patients who received antibiotic treatment, the mean days on antibiotics were 11.3 days (SD 12.6) in the intervention group and 10.4 days (SD, 11.4) in the control group (difference 0.9; 95% CI, -0.6 to 2.4, P = 0.235). There was no statistically significant difference between the two groups.

The researchers note that the results are in line with several other randomized studies conducted in recent years that have tested whether improved diagnostics could reduce antibiotic consumption in adult patients with respiratory illness. They suggest that one of the reasons these interventions have failed in that aim may be clinicians' anxiety in the face of poor outcomes, especially in older patients and other high-risk groups.
Sep 28 Clin Microbiol Infect study

News Scan for Sep 30, 2019

News brief

Saudi Arabia officials confirm another MERS case

Saudi Arabia's Ministry of Health (MOH) today reported another MERS-CoV case, the fourth case in September.

The new MERS-CoV (Middle East respiratory syndrome coronavirus) case involves a 39-year-old man from Al Hofuf in the eastern part of the country. The man had contact with a camel, the most common primary risk factor associated with contracting MERS.

As of Sep 19, the WHO's Eastern Mediterranean regional office said that, since 2012 there have been 2,468 MERS cases, at least 850 of them fatal. The vast majority of cases have been in Saudi Araba.
Sep 30 Saudi MOH report

With 2 more cases, US measles outbreak grows to 1,243

The Centers for Disease Control and Prevention (CDC) today said it has recorded 2 more measles cases in the past week, raising 2019's total to 1,243 cases, the most in any year since 1992 and since the disease was declared eliminated from the United States in 2000.

Thirty-one states have confirmed measles cases, but more than 75% of this year's cases have been in New York state.

As of last week, a measles outbreak in Rockland County, New York, with 312 cases, was declared over; Rockland County's outbreak needed to end before Oct 2 to avoid losing the country's measles-free status. The CDC said that today marks 42 days since the last case was identified, which represents two transmission cycles without any new cases.

The CDC is tracking another measles outbreak in New York, unrelated to the one in Rockland County. The outbreak—the only one still ongoing—is identified only as New York State #2 in today's update.
Sep 30 CDC update

More evidence rotavirus vaccine protects kids from severe illness

A new study in JAMA Network Open offers more evidence that the rotavirus vaccine reduces emergency room visits and hospitalizations among US children.

Researchers conducted a case-control study that included 1,193 children under the age of 5 years who had lab-confirmed rotavirus infections paired with 9,620 controls who had acute gastroenteritis; all children were seen in seven hospitals from Nov 1, 2009, through Jun 30, 2016. Medical records were used to determine rotavirus vaccine status for patients, and stool specimens confirmed rotavirus diagnosis.

"Of the 1,193 rotavirus cases in our analysis, 711 (60.0%) had received at least 1 dose of rotavirus vaccine. Of the 9,620 controls, 8,484 (88.2%) had been similarly vaccinated," the authors said.

At least one dose of rotavirus vaccine was 82% protective against rotavirus-associated inpatient visits and 75% protective against rotavirus-associated emergency department visits. The vaccine was most protective against severe illnesses, which the authors called a gradation in vaccine effectiveness by severity. In the combined clinical setting, any dose of rotavirus vaccine was 65% effective against mild infections, 81% against moderate infections, and 91% against severe infections, they said.

"Our vaccine effectiveness assessment supports that RV5 and RV1 rotavirus vaccines continue to perform well in the United States and are associated with the prevention of inpatient visits, severe infections, and among younger children," the authors concluded.
Sep 27 JAMA Netw Open study

Study: Shorter rabies post-exposure vaccine course stacks up well

A shortened rabies post-exposure prophylaxis based on a regimen used for decades by the Thai Red Cross provides as strong of an immune response as the longer regimen, researchers based at the Pasteur Institute in Cambodia reported late last week in The Lancet Infectious Diseases.

The group studied the shorter regimen to assess if it might be a way to improve timely access to the vaccine, especially in light of a global goal to eradicate canine-related rabies in humans by 2030.

For the observational cohort study, the scientists measured rabies virus neutralizing antibody titers in 116 people bitten by dogs who had lab-confirmed rabies from April 2016 to February 2018 and 20 controls. The patients were referred to a rabies prevention clinic at the Pasteur Institute, where they received two intradermal injections of post-exposure prophylaxis on days 0, 3, 7, and 28, with or without rabies immunoglobulin.

No significant difference in neutralizing antibody concentration in people bitten by rabies-positive dogs were seen between days 28 and 42, after titers had reached a plateau. The titers reached didn't seem affected by immunoglobulin use, age, sex, nutrition status, body mass index in adults, or dog infection status. Titers did not increase in the 2 weeks after the last injection, and all patients were alive after 1 year.

The researchers concluded that the fourth vaccine session on day 28 provided no additional benefit and that prophylaxis can be streamlined to a two-dose, three-session 1-week regimen to boost post-exposure prophylaxis coverage at no risk to patients.

In a related commentary in the same issue, a US and South African expert wrote that the compelling data help identify the best use of post-exposure prophylaxis. They said as rabies vaccines have improved in potency and safety, the intradermal route has become a strategy to explore immunogenicity, dose-sparing, and the economic benefits of both pre- and post-exposure prophylaxis, particularly in low- and middle-income countries.
Sep 27 Lancet Infect Dis abstract
Sep 27 Lancet Infect Dis commentary