Stewardship / Resistance Scan for Oct 31, 2018

Antibiotics for COPD
MCR resistance genes in Vietnam
Cefto-tazo for MDR Pseudomonas

COPD reviews highlight some benefits to antibiotics but also precautions

Two Cochrane reviews this week covered the use of antibiotics for chronic obstructive pulmonary disease (COPD), which found benefits in some instances but overall precautions about prescribing them judiciously.

The first review, published Oct 29, focused on COPD flare-ups (exacerbations) and included 2,663 study participants across 19 trials, 11 involving outpatients, 7 with inpatients, and 1 with intensive care unit (ICU) patients.

"Researchers have found that antibiotics have some effect on inpatients and outpatients, but these effects are small, and they are inconsistent for some outcomes (treatment failure) and absent for other outcomes (mortality, length of hospital stay)," the Cochrane reviewers concluded. The study in ICU patients, however, showed a strong beneficial effect of antibiotics.

"These inconsistent effects," the reviewers add, "call for research into clinical signs and biomarkers that can help identify patients who would benefit from antibiotics, while sparing antibiotics for patients who are unlikely to experience benefit and for whom downsides of antibiotics (side effects, costs, and multi-resistance) should be avoided."

The second review, posted yesterday, included 14 studies on prophylactic (preventive) antibiotics for COPD. The studies collectively involved 3,932 patients, mostly frequent exacerbators with at least moderate COPD. Also, the mean age ranged from 65 to 72 years.

The review found that continuous and intermittent prophylactic macrolides reduced COPD exacerbations, while the impact of pulsed antibiotics remains uncertain. The reviewers warn, "Because of concerns about antibiotic resistance and specific adverse effects, consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse."
Oct 29 Cochrane review on COPD flare-ups
Oct 30 Cochrane review on prophylactic therapy


Study notes high MCR rates in healthy villagers in Vietnam

More than 80% of Escherichia coli–positive stool specimens collected from healthy people in a village in Vietnam contained the colistin-resistance MCR gene, according to a research letter today in the Journal of Antimicrobial Chemotherapy.

Researchers collected one stool sample each from 98 people living in one of 36 households in a village in Thai Binh province along the northern Vietnamese coast. The villagers ranged in age from 2 to 81 years, with a median of 46.

Of the 98 samples, 88 (89.8%) were positive by culture assay for any pathogen, and 83 (84.7%) were positive for E coli. Of the 83 E coli isolates, 69 (83.1%) tested positive for colistin resistance, 68 of which (81.9%) contained MCR genes. Of that total, 64 were MCR-1, 3 were MCR-3, and one was MCR-1/3. Also, 29 of the 36 households (80.6%) had at least one person harboring an MCR gene.

Colistin is one of the most commonly used antibiotics in chickens and pigs in Vietnam, the authors note. "Such a high amount of colistin consumption by animals in Vietnam may facilitate the wide dissemination of [colistin-resistant E coli] in residents of rural communities," they postulate.

Colistin is considered an antibiotic of last resort for multidrug-resistant infections.
Oct 31 J Antimicrob Chemother letter


Benefits noted for ceftolozane-tazobactam for treating MDR Pseudomonas

Ceftolozane-tazobactam for patients with multidrug-resistant (MDR) Pseudomonas aeruginosa illness, known for being a hard-to-treat hospital-acquired infection, is effective, especially when used early, researchers who studied use of the therapy in a multicenter study reported today in Open Forum Infectious Diseases.

For their retrospective study, the investigators collected information on US adults from 20 hospitals who received ceftolozane-tazobactam treatment for MDR Pseudomonas infections from any source for at least 24 hours. Of 205 patients included in the analysis, severe illness and high levels of other medical conditions were common—59% had pneumonia. The team found that delayed treatment was common, with therapy beginning at a median of 9 days after culture collection.

Susceptibility testing found that 125 of 139 (89.9%) of isolates were susceptible to the drug combination. Deaths occurred in 39 (19%) of patients, with clinical success and microbiological cure numbers at 151 (73.7%) and 145 (70.7%), respectively.

Being started on ceftolozane-tazobactam treatment within 4 days of culture collection was associated with survival, clinical success, and microbiological cure.

The researchers said their study is the largest they know of so far to evaluate the treatment combo for MDR Pseudomonas infections. They highlighted the fact that no positive results were seen for concomitant intravenous antibiotics or high-dose ceftolozane-tazobactam treatment, though both practices were common, hinting that monotherapy may be enough for treating susceptible Pseudomonas infections.

They also said the benefit of earlier treatment initiation was significant. "Antimicrobial stewardship programs and individual practitioners alike need to strike a difficult balance between early use of agents such as ceftolozane-tazobactam in appropriate patients who may benefit from it with the economic and microbiological consequences of overuse," they wrote, acknowledging that rapid tests and scoring systems for MDR may help flag patients who could benefit from earlier treatment.
Oct 31 Open Forum Infect Dis abstract

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