Stewardship / Resistance Scan for Aug 21, 2019

News brief

UK study details high inappropriate antibiotic prescribing in primary care

An analysis of the electronic health records of more than 1.6 million UK patients revealed that doctors don't always prescribe antibiotics according to guidelines, especially for upper respiratory tract infections (URTI) and otitis externa (outer ear passage infection), according to a study yesterday in the Journal of Antimicrobial Chemotherapy.

The main goal of the study was to look at how antibiotic prescribing deviated from national guidelines released in 2017. The research group focused on prescriptions after 2010 when Public Health England published its first guidelines for managing infections in primary care. The data they used cover about 8% of the UK population and were collected from January 2010 through June 2015.

The investigators found that the highest levels of prescribing not in accord with guidelines were for otitis externa (67.3%) and URTI (38.7%). Levels were relatively low for otitis media (3.4%), sinusitis (2.2%), lower respiratory tractions infections (LRTI) (1.5%), and urinary tract infection (UTI) in adults (2.3%), and UTI in children (0.7%).

Though not recommended for the conditions, amoxicillin was the most common drug prescribed for all respiratory tract infections except for URTI. Small variations in inappropriate prescribing was linked to the clustering effect at the practice level, and the group also found that patients with underlying health conditions were more likely to receive inappropriate antibiotics for URTI, LRTI, and UTI in adults.

The researchers concluded that future studies should examine how individuals' characteristics vary between practices and that future antibiotic stewardship activities should focus on urging primary care providers to cut back on amoxicillin use in favor of narrow-spectrum antibiotics.
Aug 20 J Antimicrob Chemother abstract

Combination drug for complicated UTIs shows promise in phase 3 trial

The results of a randomized non-inferiority trial conducted in India suggest a novel combination of two antibiotics and an antibiotic adjuvant could be a potential alternative to carbapenems for patients who have complicated urinary tract infections (cUTIs) caused by multidrug-resistant gram-negative pathogens.

In the phase 3 trial, published today in Open Forum Infectious Diseases, 230 adults at 17 sites with a diagnosis of cUTI, including acute pyelonephritis, were randomized 1:1 to receive either intravenous ceftriaxone, sulbactam, and disbodium EDTA (CSE) or intravenous meropenem. The addition sulbactam and disbodium EDTA (a known metal chelator) has been shown to expand the in vitro activity of ceftriaxone against beta-lactamase producing bacteria, and CSE has demonstrated efficacy in animal infection models. The primary objective of the trial was to show the noninferiority of CSE to meropenem in the microbiologic modified intent-to-treat (mMITT) population at the test-of-cure visit, with a non-inferiority margin of 10 percentage points.

The mMITT population consisted of 143 patients, with 74 receiving CSE and 69 receiving meropenem. Ceftriaxone non-susceptible pathogens were identified in 140 patients (97.9%), extended-spectrum beta-lactamase-producing pathogens in 119 (83.2%), and multidrug-resistant pathogens in 100 (69.9%).

Noninferiority of CRE to meropenem was demonstrated for both of the US Food and Drug Administration–defined co-primary end points. Seventy-one of 74 patients (95.9%) in the CSE group showed symptomatic resolution at test-of-cure, compared with 62 of 69 patients (89.9%) in the meropenem group (treatment difference, 6 percentage points; 95% confidence interval [CI], -2.6 to 16), and 70 of 74 patients (94.6%) in the CSE group showed both symptomatic resolution and microbiologic eradication at test-of-cure, compared with 60 of 69 (87.0%) patients (treatment difference, 7.6 percentage points; 95% CI, -2 to 18.4). Non-inferiority was also demonstrated for the European Medicine Agency primary end point (microbiologic eradication at test-of-cure). The safety profile of CSE was consistent with that of ceftriaxone alone.

"The results support the use of CSE as a potential alternative to carbapenems in the treatment of patients with cUTI or acute pyelonephritis, including infections caused by extended-spectrum beta-lactamase-producing gram-negative bacteria," the authors of the study conclude.

The study was supported by CSE developer Venus Remedies Limited, and three of the six authors are employees of the company.
Aug 21 Open Forum Infect Dis abstract

News Scan for Aug 21, 2019

News brief

US Customs has no plan to vaccinate migrant detainees against flu

US Customs and Border Protection (CBP) said it will not vaccinate migrants, despite concerns some have raised about infectious disease spread, particularly the deaths of three children who died after falling ill with flu while in US custody, according to media reports.

In response to queries, the CBP issued a statement saying it nor its medical contractor administers vaccines because of the short-term nature of CBP holding, CNN reported yesterday. According to the report, migrants are supposed to be held by CBP for 72 hours or less, but are often held longer.

Children without parents held by CBP are handled by the Department of Health and Human Services (HHS), which does distribute flu vaccine, Evelyn Stauffer, a spokeswoman for the Office of Refugee Resettlement told CNN.

In responding to the CBP stance, public health experts contacted by CNN said short-term detention should not be an obstacle to vaccinating migrants.

In a related development, on Aug 5 two lawmakers wrote a letter to the Department of Homeland Security (DHS) and HHS raising concerns about infectious disease spread, following their Jul 15 visit to a DHS detention facility, according to the CNN report. The members of Congress who wrote the letter are Reps Rosa DeLauro and Lucille Roybal-Allard, both California Democrats.
Aug 20 CNN story

CDC records 3,700 more hepatitis A cases in widespread outbreaks

Earlier this week the Centers for Disease Control and Prevention (CDC) updated information regarding a 3-year hepatitis A outbreak, and said 24,280 cases, including 236 deaths have been recorded in 30 states.

This case total represents an increase of 3,768 cases since late June, when the CDC recorded 20,512 cases of hepatitis A virus (HAV). Sixty percent of all cases have required hospitalization, the CDC said.

A total of 28 states still have ongoing, active outbreaks, with Kentucky, Ohio, Florida, and West Virginia reporting the most cases since August 2016. Drug users, the homeless, men who have sex with men, people currently or recently incarcerated, and those with chronic liver disease are the most heavily affected in these outbreaks, the CDC said.

"One dose of single-antigen hepatitis A vaccine has been shown to control outbreaks of hepatitis A and provides up to 95% seroprotection in healthy individuals for up to 11 years," the CDC said. "Postexposure prophylaxis (PEP) is recommended for unvaccinated people who have been exposed to hepatitis A virus (HAV) in the last 2 weeks; those with evidence of previous vaccination do not require PEP."
Aug 19 CDC update
Jun 24 CIDRAP News Scan "CDC: 24 hepatitis A outbreaks in US since 2016 total 20,500 cases"

Nigeria reaches wild poliovirus eradication benchmark

The World Health Organization (WHO) today said Nigeria has reached a major milestone in its efforts to eradicate wild poliovirus by reaching 3 years with no new cases.

In a WHO statement, Faisal Shuaib, MD, DrPH, executive director of the National Primary Health Care Development Agency, said Nigeria's accomplishment is a step toward certifying the whole African region as free of wild poliovirus. And he added that the achievement is very fragile, "one which we must delicately manage with cautious euphoria."

He commended novel strategies used in the fight against the disease and the strong domestic and global financing of the efforts. Remaining challenges are low immunization rates in some areas that have led to outbreaks of vaccine-derived polio and the difficulty that immunization campaigns have in reaching children in some inaccessible areas.

Following Nigeria's recent achievement, the African Regional Commission for Certification of Polio Eradication will start a rigorous effort to confirm that each African region country is free of wild poliovirus, and Nigeria will submit its final data for evaluation in March 2020, if there are no new cases. The whole region could be certified as wild polio–free as soon as the middle of 2020, leaving only one region of the world as endemic: the Eastern Mediterranean.
Aug 21 WHO Africa regional office statement