Stewardship / Resistance Scan for Nov 12, 2019

News brief

Study: Pre-surgical antibiotic prescriptions often inappropriate

A new study that surveyed 22.5% of Australia's hospitals from January 2016 through June 2018 found that surgical antimicrobial prophylaxis (SAP) was often inappropriate, because of both incorrect timing and overly long treatment. The study appears in JAMA Network Open.

A total of 15,395 prescriptions (10,740 procedural and 4,655 postprocedural) were audited for appropriateness by pharmacists, nurses, and infectious disease physicians who were trained in study methodology. They found that only 48.7% of all total prescriptions were appropriate. Appropriateness varied among types of surgeries: Only 33.7% (95% confidence interval [CI], 26.3%-41.2%) of dentoalveolar surgical SAP prescriptions were appropriate, while 68.9% of neurosurgey prescriptions were appropriate.

"The adjusted appropriateness of postprocedural prescriptions was also low, ranging from 21.5% (95% CI, 13.4%-29.7%) for breast surgery to 58.7% (95% CI, 47.9%-69.4%) for ophthalmological procedures. The most common reason for inappropriate procedural SAP was incorrect timing (44.9%), while duration greater than 24 hours was the most common reason for inappropriate postprocedural SAP (54.3%)," the authors wrote.

Among procedural prescriptions, 11.7% were prescribed when procedural SAP was not deemed to be required, the authors said.

In a commentary on the study, two researchers said the study was well-designed, but ultimately the audits were too time-consuming. Instead they suggested conducting smaller-scale audits more frequently, and using antibiotic consumption data to assess SAP.
Nov 8 JAMA Netw Open study
Nov 8 JAMA Netw Open commentary

Highly deadly Klebsiella pneumoniae strain identified in Brazilian hospital

A retrospective analysis of adult bloodstream infections involving carbapenemase-producing Klebsiella pneumoniae (KPC-KP) at a Brazilian teaching hospital identified an emerging strain linked to high mortality rates. A team from Brazil and Cardiff University in the United Kingdom reported its findings today in Clinical Infectious Diseases.

For the study, the researchers looked at cases from January 2014 to December 2016 to assess the molecular epidemiology and impact on 30-day all-cause mortality. Of 165 KPC-KP cases, the endemic CC258 group was predominant (66%), followed by ST16 (12%). Though the overall 30-day mortality rate was 60%, it was much higher for ST16, for which 95% of the cases were fatal.

The team found no differences in patient severity scores and baseline clinical variables, but they did find that risk factors for fatal outcomes were presence of ST16 and septic shock.

Further investigation found that the ST16 clone carried up to 14 resistance genes and was highly pathogenic in moth larvae. "Our results suggest that even in endemic settings, highly virulent clones can rapidly emerge demanding constant monitoring," they wrote.
Nov 12 Clin Infect Dis abstract

Review: FDA guidance often touts indirect end points for antimicrobial trials

A systematic review today of 27 US Food and Drug Administration (FDA) guidance documents on developing new anti-infective agents has determined that the documents frequently recommend as study end points indirect measures of patient benefit—rather than direct measures, such as symptom resolution or survival—raising questions about whether the FDA is following its own standards when it comes to new antimicrobial drugs such as antibiotics.

For the study, published in JAMA Internal Medicine, Harvard University scientists included 22 guidance in their review. The documents included recommendations for primary end points in 27 "pivotal" clinical trials for drugs designed to combat infectious diseases. An end point is an event or outcome that can be objectively measured to see if the drug benefits patients.

The investigators found that 21 of 27 indications recommended surrogate—or indirect—outcomes as either the sole primary end point or as one or more components. What's more, none of the recommendations for the use of surrogate end points matched the regulatory and scientific conditions favoring indirect outcomes in place of clinical outcomes, the authors reported.

The authors conclude, "Existing guidance documents should be updated and revised to recommend appropriate clinical outcomes consistent with general scientific and regulatory parameters."

A related commentary in the same journal, however, notes that surrogate end points are not necessarily bad, such as with uncomplicated gonorrhea, for which the primary end point is microbiological cure. "This surrogate measure of microbiological cure meets none of the 3 criteria previously listed for surrogate trial end points," write the commentary authors, Paul Volberding, MD, and Henry Chambers, MD. "Nonetheless, both clinically and from a public health perspective, eradication of the organism is the important outcome."

The commentators, from the University of California San Francisco, add, "The true debate is not whether to use surrogate markers. Rather, the debate is about when surrogate markers are meaningful."
Nov 11 JAMA Intern Med systematic review
Nov 11 JAMA Intern Med commentary

News Scan for Nov 12, 2019

News brief

Saudi Arabia tracks 8th MERS case this month

In an update today, Saudi Arabia's Ministry of Health (MOH) reported one new MERS-CoV case, in a man from Riyadh. The case is Saudi Arabia's eighth this month.

The patient is a 31-year-old man from the country's capital city, and his contact with camels isn't known. He is not a health worker, and his exposure is listed as primary, meaning he probably didn't contract MERS-CoV (Middle East respiratory syndrome coronavirus) from another patient.

The World Health Organization (WHO) said in a recent update that since the virus was first detected in humans in 2012, it has received reports of 2,470 MERS cases as of early October, at least 851 of them fatal. About 84% are from Saudi Arabia.
Nov 12 MOH report

Flu shows signs of rise in some parts of Northern Hemisphere

Flu levels continue to increase in the Arabian Peninsula, and, in other Northern Hemisphere developments, respiratory illness markers increased in parts of Europe, eastern Asia, and North America but are still below seasonal thresholds, the WHO said yesterday in a global flu update.

As of late September, other areas experiencing flu increases include some countries in the Americas, such as Cuba, Jamaica, El Salvador, and Nicaragua.

Elsewhere, flu levels are on the rise in Iran and southern Asia and are still elevated in some West African countries, including Ivory Coast and Ghana. In Southeast Asia, flu is still elevated in Laos and is on the rise in Malaysia.

In the Southern Hemisphere, flu activity has declined to interseasonal levels in most countries, except for Chile, where mainly influenza B continues to be reported, though at decreasing levels.

Globally, testing at WHO-affiliated flu labs in the last half of October revealed that nearly 70% of positive specimens were influenza A. Of subtyped influenza A viruses, 42.7% were 2009 H1N1 and 57.3% were H3N2. Of the characterized B viruses, 95.2% belonged to the Victoria lineage.
Nov 11 WHO global flu update

CDC reports 11 new measles cases, national total at 1,261

In its monthly update, the US Centers for Disease Control and Prevention (CDC) reported 11 more measles cases, lifting the national number for the year to 1,261, the most in any year since 1992. The number of affected states remained the same, at 31.

The CDC's total reflects cases through Nov 7. The number of monthly cases is slightly higher than 7 new cases reported in its last monthly update on Oct 11. Overall, the pace of new infections has steadily declined since 300 cases reported in both March and April.

The report showed no ongoing outbreaks, which are defined as three more related cases.

So far, 123 people infected with measles this year were hospitalized, and 61 experienced complications such as pneumonia and encephalitis.

A dramatic spike in cases this year, most linked to large outbreaks in and around New York City, threatened but ultimately did not change the nation's measles elimination status. US outbreaks this year have been linked to outbreaks in foreign countries.
Nov 12 CDC update

DRC measles outbreak grows by 53,000 cases in past 2 months

Officials tracking a massive measles outbreak in the Democratic Republic of the Congo (DRC) recorded 53,860 additional cases since Sep 15, according to the latest update from the WHO African regional office.

From Jan 1 to Oct 27, a cumulative 233,337 suspected measles cases with 4,723 deaths (case-fatality rate [CFR] of 2%) have been reported. The outbreak is occurring throughout the country, the WHO said, with 44% of health zones in an epidemic.

"Cases continue to be reported from Ituri and North-Kivu provinces, concomitantly affected by the ongoing Ebola outbreak, with 9,809 cases (CFR 0.6%) and 4,777 cases (CFR 0.3%) reported respectively, between January and October 2019," the WHO said.

A vaccination campaign that began on Oct 30 is still ongoing, and officials have moved up a campaign planned for February 2020 to next month. As in the ongoing Ebola outbreak, vaccination campaigns have been hindered by violent conflicts in the country's eastern provinces.
Nov 10 WHO regional update