Stewardship / Resistance Scan for Sep 18, 2017

Resistant E coli clone in kids
New pneumonia antibiotic
UK strep guidelines

Study finds subclone is prominent in resistant E coli infections in kids

Researchers at the University of Washington report in Clinical Infectious Diseases that a subclone of the emerging global pathogen Escherichia coli sequence type (ST) 131 is not as prevalent in children as adults but is nearly as dominant in drug-resistant E coli infections in children.

E coli ST131-H30 has been recognized as a clone of significant public health importance, comprising 10% to 20% of all extra-intestinal E coli infections among US adults. But data about its epidemiology in children are lacking. To quantify the burden and identify clinical and demographic correlates of infection with E coli ST131-H30 in children, the researchers prospectively collected all extended-spectrum cephalosporin-resistant (ESC-R) E coli isolates from urine or other sterile sites identified at four US children's hospitals from 2009 to 2013, along with demographic and clinical data. For each resistant isolate, researchers collected three extended-spectrum cephalosporin-susceptible (ESC-S) isolates.

A total of 339 ESC-R isolates from 278 patients and 1,008 ESC-S isolates from 1,008 patients were available for analyses. The estimated prevalence of H30 among all clinical E coli isolates at all hospitals was 5.3%. However, H30 was the most common subclone identified among the ESC-R isolates in the study, accounting for 29.9% of all ESC-R isolates and 43.3% of all extended-spectrum beta-lactamase (ESBL)–producing isolates—a proportion close to what has been observed in US adults (about 50%).

The researchers also found that patient age was associated with infection due to H30, although the nature of the association contrasted between ESC-R and ESC-S infections. In patients with ESC-R infections, H30 was associated with younger age (0 to 5 years); in patients with ESC-S infections, H30 was associated with older age (6 to 21 years) and underlying health conditions.

The authors of the study suggest the low overall prevalence of H30 in children could be the result of low fluoroquinolone use in pediatrics. They conclude, "More densely sampled studies are needed to elucidate the reservoirs and transmission dynamics of this difficult-to-treat pathogen in a pediatric population."
Sep 15 Clin Infect Dis abstract

New antibiotic shows promise against community-acquired pneumonia

Initial results from a phase 3 clinical trial show that the antibiotic lefamulin compares favorably to standard therapy in patients with moderate-to-severe community-acquired bacterial pneumonia (CABP), according to a news release today from Nabriva Therapeutics, the drug's maker.

In the lefamulin evaluation against pneumonia (LEAP 1) trial, the first of two phase 3 trials for the drug, intravenous to oral lefamulin met the Food and Drug Administration (FDA) primary end point of non-inferiority (NI, 12.5% margin) compared with moxifloxacin with or without adjunctive linezolid, according to Nabriva, which is based in Dublin. Early clinical response (ECR) rates assessed 72 to 120 hours following initiation of therapy were 87.3% for lefamulin and 90.2% for moxifloxacin with or without linezolid.

The drug also met the primary end points for non-inferiority established by the European Medicines Agency (NI, 10% margin). In addition, ECR by pathogen was similar to overall response rates and was comparable between treatment arms.

The trial enrolled 551 CABP patients, with 276 and 275 randomly assigned to the lefamulin arm and the moxifloxacin with or without linezolid arm, respectively. Individuals aged 65 or older represented 47.8% of the patients in the lefamulin arm, compared with 39.3 % of the patients in the moxifloxacin arm. Linezolid was added to moxifloxacin if an investigator suspected that a patient had been infected with methicillin-resistant Staphylococcus aureus prior to randomization.

A similar rate of treatment-emergent adverse events (TEAEs) was observed in both arms—38.1% in the lefamulin patients and 37.7% in the moxifloxacin with or without linezolid patients. TEAEs occurring in more than 2% of patients included hypokalemia, nausea, insomnia, infusion-site pain, infusion-site phlebitis, alanine aminotransminase increase, and hypertension. While no cases of Clostridium difficile were reported in either treatment group, diarrhea was observed in 7.7% of patients in the moxifloxacin group, compared with 0.7% of the lefamulin group.

"These Phase 3 data provide strong evidence of the potential of lefamulin to treat adults with CABP and provide an alternative to a current gold standard treatment regimen," Nabriva Therapeutics CEO Colin Broom, MBBS, said in the release. "Due to lefamulin's flexible dosing and targeted spectrum of activity against the pathogens most commonly associated with CABP, including multidrug-resistant strains, we believe that lefamulin is well suited to be a first-line empiric monotherapy."
Sep 18 Nabriva Therapeutics press release


UK: Women in preterm labor to be offered anti-Streptococcus antibiotics

Women who begin labor before 37 weeks of pregnancy should be offered antibiotics to prevent a group B Streptococcus (GBS) infections in newborns, according to guidance from the Royal College of Obstetricians and Gynaecologists (RCOG) updated last week.

GBS is the most frequent cause of severe early-onset infection in newborns, occurs naturally in the lower vaginal tract of women, and can be passed on to the babies, RCOG said in a news release. The vast majority of infants will suffer no ill effects, but a small percentage will develop an infection and fall seriously ill.

Incidence of early-onset GBS appears to be rising in the UK and around 500 babies developed the condition in 2015, RCOG said. With prompt treatment, 17 of 20 diagnosed babies will fully recover, but 2 in 20 will recover with some disability, and 1 in 20 will die. Women are at higher risk of passing GBS to their baby if they go into preterm labor, and the risk of dying from GBS can be 10 times higher in preterm babies compared with those born at full term.

For these reasons, the RCOG guidelines now recommend all women who go into preterm labor, regardless of whether their waters have broken, receive intravenous antibiotics during labor. The guidance, which has now been updated three times, the most recent in 2012, also advises that women who were known GBS carriers in a previous pregnancy can be offered a test at 35 to 37 week to see whether they are still a carrier.

The guidance does not recommend universal bacteriological screening for GBS, in line with recommendations by the UK National Screening Committee. The experts who produced the RCOG guidelines found no clear evidence to show routine testing would do more good than harm.
Sep 13 RCOG guidance
Sep 13 RCOG
news release

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