ASP Scan (Weekly) for Dec 01, 2017

New TB molecular test
HIV drug resistance
Antibiotics and babies' gut microbiome
Stewardship metrics guide
Ambulance antibiotics for sepsis
Protecting the gut from antibiotics
Cost of C diff in kids
MDR-TB in Europe

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Updated molecular TB test found to be more sensitive, less specific

An international team of researchers has found that a re-engineered rapid molecular test for detection of tuberculosis (TB) is more sensitive than the current test but less specific, according to a study yesterday in The Lancet Infectious Diseases.

The primary objectives of the prospective multicenter study were to estimate and compare the sensitivity and specificity of Xpert MTB/RIF Ultra (Xpert Ultra) with the original test (Xpert) for detection of smear-negative TB and rifampicin resistance. Xpert, an automated, cartridge-based molecular assay, is used in TB programs in more than 120 countries and has helped increase detection of TB and drug-resistant TB globally, but its sensitivity is inadequate when few bacilli are present in a clinical specimen, which limits its usefulness in children and patients with HIV. Xpert Ultra was developed to overcome this limitation.

Overall, 1,753 participants from eight high-incidence countries participated in the study, with 1,439 in the case detection group and 314 in the multidrug-resistance group. The results showed that the sensitivity of Xpert Ultra was superior to Xpert for TB detection in all patients with culture-positive TB (88% vs. 83%), with the difference being pronounced in patients with smear-negative sputum (63% vs. 46%) and in patients co-infected with HIV (90% vs. 77%).

But the specificity of Xpert Ultra was 2 percentage points lower than Xpert overall (96% vs. 98%) and 5 percentage points lower in patients who had a history of TB (93% vs. 98%), which means more false-positive results. The two assays performed similarly in detecting rifampicin resistance.

The authors of the study say that, in clinical practice, the high sensitivity of Xpert Ultra could facilitate diagnosis of TB at earlier stages of the disease, especially for patients with HIV, resulting in more evidence-based treatment decisions. Further research is needed, they add, to clarify the implications of the trade-off between increased sensitivity and decreased specificity.

Based on these findings, the World Health Organization (WHO) has concluded that Xpert Ultra can be used as an alternative to Xpert for initial testing in adults with signs or symptoms of TB, the authors said.
Nov 30 Lancet Infect Dis study


HIV drug-resistance on the rise, large meta-analysis finds

In another study yesterday in The Lancet Infectious Diseases, an international team of researchers report that the prevalence of pretreatment HIV drug resistance is rising in many lower- and middle-income countries (LMICs).

The study, a systematic review and meta-regression analysis of screened publications and unpublished datasets, aimed to assess the prevalence of pretreatment drug resistance in people starting or about to start antiretroviral therapy (ART) in LMICs. Although some degree of HIV drug resistance has been anticipated, the concern is that a substantial rise in resistance could endanger the WHO's efforts to end the AIDS epidemic. To achieve that goal, the WHO has set a milestone of ensuring treatment achieves virus suppression in 90% of all people with HIV infection by 2020.

The researchers identified 358 datasets from 2001 to 2016, representing 56,044 adults in 63 countries. They found substantial yearly increases in pretreatment resistance to non-nucleotide transcriptase inhibitors (NNRTIs)—a component of first-line ART—in all regions. The yearly increases in the odds of pretreatment NNRTI resistance were 23% in southern Africa, 17% in eastern Africa, 17% in western and central Africa, 11% in Latin America and the Caribbean, and 11% in Asia. Modelled prevalence estimates of pretreatment resistance in 2016 were 11% in southern Africa, 10.1% in eastern Africa, 7.2% in western and central Africa, 9.4% in Latin America and the Caribbean, and 3.2% in Asia.

The researchers also found that previous exposure to ART was found to be associated with substantially higher NNRTI resistance and significantly greater risk of treatment failure.

According to the study, modeling suggests that HIV drug resistance in excess of 10% could result in 890,000 AIDS deaths and 450,000 new infections in sub-Saharan Africa alone by 2030. The WHO's guidelines on pre-treatment HIV drug resistance recommend that countries switch their first-line treatment when resistance levels reach 10%.

"Our findings show the importance of improving how we monitor drug resistance, and suggest we should review which drugs are included in first-line therapies," lead author Ravindra Gupta, MPH, of University College London said in a university press release.
Nov 30 Lancet Infect Dis study
Nov 30 University College London news release


Antibiotics given to moms during labor might affect babies' microbiomes

Originally published by CIDRAP News Nov 29

Antibiotics administered to mothers during labor to prevent group B Streptococcus infections appear to alter the gut microbiome of newborns, according to a small study yesterday in Scientific Reports.

The effects appeared to resolve within 12 weeks.

Researchers from McMaster University in Hamilton, Ont., compared "bacterial community succession," or the growth of gut bacteria in 53 infants with no antibiotic exposure with 14 infants whose mothers received the preventive antibiotics during delivery. The team tested the development of the infants' gut microbiome at 3 days, 10 days, 6 weeks, and 12 weeks from birth.

"Our research indicates there is a delay in the expansion of the dominant infant gut colonizer, called Bifidobacterium, when infants are exposed to antibiotics," said Jennifer Stearns, PhD, the study's lead author, in a McMaster news release. The bacterial differences between the two groups all but disappeared by 12 weeks.

"It's a good sign that bacterial groups recover by 12 weeks but it's still unclear what these findings mean for infant health, especially since early infancy is such an important developmental time," Stearns said.

About a fourth to a third of pregnant women test positive for group B Streptococcus during routine screening, and most receive antibiotics during labor to prevent transmitting the bacterium to their infants at birth, according to the release.
Nov 28 Sci Rep study
Nov 28 McMaster University 
press release


Duke publishes guide for gathering key ASP data

Originally published by CIDRAP News Nov 29

Duke University has published a metrics guide on developing patient outcome measures and measurement tools for antibiotic stewardship programs (ASPs), the Duke Antimicrobial Stewardship Outreach Network (DASON) said in a Nov 27 news release.

The guide, produced through a partnership with the US Centers for Disease Control and Prevention Foundation and Merck, aims to address a need for strong stewardship metrics "that reflect the impact of ASPs on patient safety and optimized care," DASON said. Despite the importance of data to drive decision making, most facilities have limited access to local data and thus limited ability to assess the impact of ASPs, the center said.

DASON convened a panel of experts to assess metrics used or proposed in the medical literature, as well as unpublished data. The panel then identified the best metrics to (1) improve antimicrobial prescribing practices, (2) improve patient care, and (3) aid in targeting ASP efforts, as well as those that can be feasibly monitored in any hospital that has an electronic health record. Scientists then tested the candidate metrics at five pilot sites.

"Working closely with these pilot partner sites, the feasibility of data capture and analysis as well as the utility of each candidate metric to guide local stewardship activities was assessed during on-site visits, frequent communication with the stewardship teams, and formal survey techniques," DASON said. "This Guide reflects the outcome from this development and feasibility project."

The guide includes a technical manual, a report tool, data table guidelines, sample feedback reports, and other resources.
Nov 27 DASON news release
Nov 27 DASON 
ASP metrics guide


Study shows EMS-administered antibiotics don't help with sepsis

Originally published by CIDRAP News Nov 29

Having emergency medical services (EMS) personnel administer antibiotics to suspected sepsis patients in the ambulance en route to the hospital did not improve survival, regardless of illness severity, Dutch researchers reported yesterday in The Lancet Respiratory Medicine.

After training EMS personnel to recognize sepsis, the investigators conducted a randomized controlled open-label trial involving 10 large regional ambulance services serving 34 secondary and tertiary care hospitals in the Netherlands. They compared the effects of early administration of the antibiotic ceftriaxone in the ambulance with usual care (the control group).

The study involved 2,672 patients, 1,535 in the intervention group and 1,137 in the control group. Patients in the intervention group received antibiotics a median of 26 minutes before arriving at the hospital emergency department.

At day 28, 120 patients (8%) had died in the intervention group and 93 (8%) in the control group. In addition, 102 patients (7%) in the intervention group and 119 (10%) in the control group were readmitted to a hospital within 28 days, but the difference was not statistically significant. The researchers reported seven mild allergic reactions that could not be attributed to ceftriaxone.

The authors conclude, "In patients with varying severity of sepsis, EMS personnel training improved early recognition and care in the whole acute care chain. However, giving antibiotics in the ambulance did not lead to improved survival, regardless of illness severity."

An accompanying commentary suggests that researchers should perform a randomized controlled trial involving only the most severe cases, and antibiotics with a narrower mechanism of action be used.
Nov 28 Lancet Respir Med study
Nov 28 Lancet Respir Med 


Activated charcoal may help protect gut microbiome from antibiotics

Originally published by CIDRAP News Nov 27

The results of a small phase 1 clinical trial show that an activated charcoal product helped protect the gut microbiome in volunteers treated with moxifloxacin, French researchers report in the Journal of Infectious Diseases.

The product, called DAV132, was developed as a potential strategy to protect the gut microbiome from the deleterious effects of non-absorbed antibiotics, which can wipe out beneficial bacteria in the gut and result in Clostridium difficile infection and the selection of antibiotic-resistant bacteria. It contains 5.11 grams of activated charcoal as the active absorbing ingredient. A previous phase 1 trial had shown that DAV132 could deliver a powerful non-specific absorbent to the late ileum of healthy volunteers and did not affect the plasma pharmacokinetics of the antibiotic amoxicillin.

For the randomized controlled trial, investigators recruited 28 healthy volunteers and randomized them to receive moxifloxacin alone or with DAV132 for 5 days. Two control groups of 8 volunteers, each receiving either DAV132 alone or a non-active substitute, were added. The primary objective was to evaluate the influence of DAV132 on free fecal moxifloxacin concentrations.

The investigators found that the combination of moxifloxacin and DAV132 reduced free moxifloxacin fecal concentrations by 99% compared with moxifloxacin alone, without affecting the plasma pharmacokinetics of the antibiotic or causing serious adverse effects. In addition, co-administration of DAV132 largely protected the richness and composition of the intestinal microbiota of the moxifloxacin-treated volunteers. DAV132 also showed it could absorb a wide range of antibiotics in ex vivo tests.

The authors conclude, "DAV132 may constitute a breakthrough product to prevent short- and long-term detrimental effects of antibiotic treatments." They say further studies are under way to evaluate DAV132's clinical potential.
Nov 23 J Infect Dis abstract


US pediatric C diff cases in hospitals cost thousands, study finds

Originally published by CIDRAP News Nov 27

Using a large US pediatrics database, researchers determined that the cost of a C difficile infection (CDI) in a hospitalized child ranged from almost $2,000 to over $8,000, depending on the length of stay, according to a study today in Infection Control and Hospital Epidemiology.

The investigators used a logistic regression model to predict CDI during hospitalization based on data from 8,527 pediatric hospitalizations with a diagnosis of CDI and 1,597,513 discharges of patients who did not have a CDI diagnosis. They found that that the cost attributed to CDI ranged from $1,917 to $8,317, depending on whether the team used a model adjusted for length of stay or not. The average hospital stay for CDI was about 4 days.

The authors concluded, "Clostridium difficile infection in hospitalized children is associated with an economic burden similar to adult estimates. This finding supports a continued focus on preventing CDI in children as a priority."
Nov 27 Infect Control Hosp Epidemiol abstract


Report finds MDR-TB burden low in European children

Originally published by CIDRAP News Nov 27

European scientists reported late last week in Eurosurveillance that the burden of multidrug-resistant tuberculosis (MDR-TB) appears to be low in European children but could be underestimated because of challenges with lab confirmation.

From surveillance data from 2007 through 2015, the researchers reported 18,826 pediatric TB cases, of which 4,129 (21.9%) were lab-confirmed. Of the 3,378 cases for which drug-susceptibility data were available, 249 (7.4%) were single-drug-resistant TB, 64 (1.9%) were poly-resistant TB, 90 (2.7%) were MDR-TB, and 8 (0.2%) were extensively drug-resistant.

Children with a foreign background had almost double the risk of MDR-TB, while those with previous TB treatment had a more than sixfold-higher risk. Successful treatment outcome was reported for 58 (78.4%) of 74 pediatric MDR-TB cases that had outcome information available. Children aged 5 to 9 years old were the only group significantly associated with unsuccessful treatment outcome.

The authors concluded, "The burden of MDR TB in children in the EU/EEA appears low, but may be underestimated owing to challenges in laboratory confirmation. Diagnostic improvements are needed for early detection and adequate treatment of MDR TB."
Nov 23 Eurosurveill study

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