ASP Scan (Weekly) for Jul 13, 2018

Stewardship nudge
;
MDR-TB in kids
;
Mycoplasma genitalium guidelines
;
Fluoroquinolone safety update
;
Kids' fever and antibiotics
;
Resistant Klebsiella in Europe
;
Ceftolozane-tazobactam against E coli
;
UK competition for AMR innovation
;
Funding for new gonorrhea drug
;
Antibiotic course for pneumonia
;
CRE reduction in Israel
;
Southeast Asian neonatal infections

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

Study: Intervention reduces unnecessary antibiotic use for pneumonia

Originally published by CIDRAP News Jul 12

A new study by researchers with a health system in Detroit indicates that a small, behavioral "nudge" in microbiology reporting increased de-escalation and discontinuation of unnecessary broad-spectrum antibiotics in pneumonia patients. The results were reported in Open Forum Infectious Diseases.

In the study, researchers with the Henry Ford Health System evaluated antibiotic de-escalation and discontinuation in 210 patients treated with anti–methicillin-resistant Staphylococcus aureus (MRSA) and antipseudomonal antibiotics for respiratory infections. The quasi-experimental study was conducted over two periods: a 6-month period before implementation of an intervention to improve the clarity of microbiology results, and a corresponding 6-month period following the intervention.

In the intervention, respiratory cultures with no dominant organism growth and no Pseudomonas or S aureus were reported as "commensal respiratory flora only: No S aureus/MRSA or P. Aeruginosa." Prior to the intervention, these were reported as "commensal respiratory flora."

The researchers found that de-escalation/discontinuation was more commonly found in the intervention group than in the pre-intervention group (73% vs. 39%, P < 0.001). After adjusting for severity of illness and comorbidities, the intervention comment was associated with a 5.5-fold increased odds of de-escalation. Acute kidney injury was also reduced in the intervention group (14% vs. 31%, P = 0.003). No statistically significant difference in all-cause mortality was detected between the two groups (18% vs. 30%, P = 0.052).

"Our study demonstrates that a simple behavioral intervention to more clearly communicate respiratory culture results for normal flora can impact prescribing, and may reduce patient harm," the authors write.
Jul 10 Open Forum Infect Dis abstract

 

Meta-analysis finds 2nd-line therapy effective against MDR-TB in children

Originally published by CIDRAP News Jul 12

A meta-analysis of 28 studies involving children with multidrug-resistant tuberculosis (MDR-TB) determined that, in general, second-line MDR-TB antibiotics work well in this age-group, despite a high burden of severe disease, according to a study yesterday in PLoS Medicine.

The researchers analyzed data on 975 children from 18 countries; 731 (75%) had bacteriologically confirmed and 244 (25%) had clinically diagnosed MDR-TB. The median age was 7.1 years, and 39% were infected with HIV. When compared with clinically diagnosed patients, children with confirmed MDR-TB were more likely to be older, to be infected with HIV, to be malnourished, and to have severe TB on chest radiograph (P < 0.001 for all traits).

Overall, 764 of 975 (78%) had a successful treatment outcome at the conclusion of second-line therapy—75% among confirmed and 89% among clinically diagnosed children. Success dropped to 56%, however, among HIV-positive children who had bacteriologically confirmed TB and did not receive any antiretroviral treatment during MDR-TB therapy, compared with 82% in those who received ART.

In children with confirmed MDR-TB, the use of second-line injectable agents and high-dose isoniazid were associated with treatment success (adjusted odds ratio, 2.9 and 5.9, respectively), but the authors say the findings for high-dose isoniazid may have been skewed by site effect, as most of these patients came from Cape Town.
Jul 11 PLoS Med study

 

British group offers guidance to combat resistant Mycoplasma genitalium

Originally published by CIDRAP News Jul 12

The British Association for Sexual Health and HIV (BASHH) this week released new guidelines for managing infections with Mycoplasma genitalium, which is becoming increasingly antibiotic-resistant. The guidelines emphasize comprehensive testing, including for macrolide-resistance mutations, and point out that many clinics don't have such tests but should.

M genitalium infection is most often asymptomatic, but when they do occur they can mimic other sexually transmitted diseases like chlamydia and gonorrhea.

The highest-level recommendations in the guidance including testing all male patients who have non-gonococcal urinary tract infections, as well as all patients who have signs and symptoms of pelvic inflammatory disease. "Nucleic acid amplification tests (NAATs) that detect M. genitalium specific DNA or RNA in clinical specimens are the only useful diagnostic method," the guidelines state. "Several CE marked commercial tests are available, although none are currently FDA approved."

The authors also advise that, when possible, all M genitalium–positive specimens be tested for macrolide-resistance mediating mutations.

They state, "Whilst the guideline sets out recommendations for best practice according to current evidence, it is acknowledged that not all clinics will have access to M. genitalium testing at the time of guideline publication. The objective of this guideline is therefore also to assist clinics and laboratories in making the case for funding towards M. genitalium testing by underlining the importance of testing in relevant populations."

BASHH has opened the guidelines to feedback until Sep 1.
Jul 8 BASHH guidelines 

 

FDA updates safety labels for fluoroquinolones

Originally published by CIDRAP News Jul 11

The US Food and Drug Administration (FDA) yesterday announced that it is updating the labels for fluoroquinolone antibiotics to strengthen warnings about the risk of mental health side effects and reduced blood sugar.

The mental health side effects to be included in the updated labels for all systemic fluoroquinolones include disturbances in attention, disorientation, agitation, nervousness, memory impairment, and delirium. In addition, a subsection of the labeling on blood sugar disturbances will now be required to warn that low blood sugar levels can lead to hypoglycemic coma, particularly in older patients and patients with diabetes who are also taking drugs to reduce blood sugar. The changes were based on a comprehensive review of the FDA's adverse events reports and case reports in the medical literature.

This is not the first time the FDA has had to strengthen warnings about fluoroquinolones. In 2008, the agency added a Boxed Warning for increased risk of tendonitis and tendon rupture, and in 2016 enhanced warnings about the association of fluoroquinolones with disabling and potentially permanent side effects involving tendons, muscles, joints, nerves, and the central nervous system. Warnings about the risk of worsening symptoms for patients with myasthenia gravis have also been added to the labels.

"The FDA remains committed to keeping the risk information about these products current and comprehensive to ensure that health care providers and patients consider the risks and benefits of fluoroquinolones and make an informed decision about their use," Edward Cox, MD, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research, said in a news release.

FDA-approved fluoroquinolones include levofloxacin (Levaquin), ciprofloxacin (Cipro), ciprofloxacin extended-release tablets, moxifloxacin (Avelox), ofloxacin, gemifloxacin (Factive) and delafloxacin (Baxdela). There are more than 60 generic versions. 
Jul 10 FDA news release

 

Booklet may help reduce antibiotic prescribing for kids' fevers if used

Originally published by CIDRAP News Jul 11

Dutch investigators reporting in the current issue of Annals of Family Medicine say the availability of a parent-focused booklet on childhood fevers in doctors' offices didn't affect antibiotic prescribing, but it decreased prescribing if physicians actually used the booklet.

As part of a two-armed cluster-randomized trial involving 25,355 children at 20 after-hours primary care clinics in the Netherlands, family physicians in the intervention group had access to a booklet on children's fever. The booklet, designed for discussion with parents, provided advice on when to consult a physician, self-management strategies, and the duration of common childhood infections.

The researchers found that antibiotic prescribing was not significantly different in the intervention and control groups, but after they adjusted for use of the booklet, they found a statistically significant 17% reduction in antibiotic prescribing in children managed by the 3,407 family physicians who used the booklet compared with the control group. Children in the intervention group were also less likely to receive a prescription for any drug.

Though the reduction in antibiotic prescribing was modest, the authors suggest in a news release from the American Academy of Family Physicians (AAFP), which publishes the journal, that the study provides evidence of the likely "real world" benefits of the booklet. "Insight into reasons for use and nonuse may inform future interventions of this type," the authors conclude.
Jul/Aug Ann Fam Med abstract
Jul 10 AAFP news release

 

Carbapenemase-producing K pneumoniae detected in Nordic travelers

Originally published by CIDRAP News Jul 11

The European Centre for Disease Prevention and Control (ECDC) today issued a rapid risk assessment on a cluster of travelers from Sweden and Norway who carried or were infected with carbapenemase (OXA-48)–producing Klebsiella pneumoniae ST392 after being hospitalized in the Canary Islands.

The 13 patients, 4 of whom had infections, were all hospitalized in Gran Canaria in 2018; 9 of them were treated in the same hospital. Isolates from the patients all expressed the same multidrug resistance profile and contained the blaCTX-M-15 extended-spectrum beta-lactamase (ESBL) gene in addition to the blaOXA-48 carbapenemase gene. Whole-genome sequencing found that all the isolates were tightly clustered, indicating a common place of acquisition.

The report also includes four possible cases (two from Sweden and two from Finland) that were detected in 2015 and 2016 in patients with a history of travel to the Canary Islands.

Since OXA-48-producing K pneumoniae was first detected in a patient in Turkey in 2001, strains of the pathogen have caused outbreaks worldwide, with sporadic cases or outbreaks being reported in most European countries. Hospitalization abroad and cross-border transfer of patients are well-known modes of introducing carbapenemase-producing Enterobacteriaceae (CPE) from countries with high prevalence into those with a lower prevalence.

While the risk for travelers of acquiring OXA-48–producing K pneumoniae ST392 without healthcare contact is low, the concern is that if patients are colonized or infected with this cluster and subsequently admitted to a hospital in their country of origin, there is a high risk of transmission or outbreaks, especially if the pathogen goes undetected and the hospital has inadequate infection prevention and control measures.

The report recommends that European Union/European Economic Area countries should consider taking a detailed history of travels and hospitalizations for every patient, and should also perform preemptive isolation and screening for carriage of CPE in patients who were directly transferred from or hospitalized in countries with a high CPE prevalence.
Jul 11 ECDC rapid risk assessment

 

Ceftolozane-tazobactam shown effective against VA E coli isolates

Originally published by CIDRAP News Jul 11

University of Minnesota researchers have determined that ceftolozane-tazobactam (C/T), a new beta-lactamase inhibitor/antibiotic combination drug, was effective against Escherichia coli ST131 isolates from veterans—even resistant isolates—and should prove useful as a carbapenem-sparing therapy for multidrug-resistant E coli.

Writing yesterday in PLoS One, the scientists said they determined broth microdilution minimum inhibitory concentrations (MICs) for C/T and five comparators—piperacillin-tazobactam, levofloxacin, gentamicin, ceftazidime, and meropenem—for 595 clinical E coli isolates collected in 2011 from 24 Veterans Affairs Medical Centers across the United States.

They found that the prevalence of resistance was 0% for meropenem and 6% for C/T, whereas it ranged from 8% for piperacillin-tazobactam to 59% for levofloxacin. Also, except for meropenem, only a minority of comparator-resistant isolates were C/T-resistant (ranging from 9% to 38%).

The authors concluded, "C/T was broadly active against Ecoli clinical isolates from veterans, notwithstanding significant variation by resistance category and ST131-H30R1/H30Rx status, outperforming all non-carbapenem comparators. C/T should prove useful as a carbapenem-sparing therapy for multidrug-resistant Ecoli ST131 infections, including in veterans."
Jul 10 PLoS One study

 

UK launches research competition for AMR innovation

Originally published by CIDRAP News Jul 10

The UK Department of Health and Social Care (DHSC) yesterday announced the launch of a £10 million ($13 million) research competition to fund innovative efforts to combat antimicrobial resistance (AMR).

The money will be made available in research grants funded through a small business research initiative and will fund projects that focus on infection prevention and the development of new vaccines and antimicrobials effective against bacterial and fungal infections. The projects must describe their relevance to AMR, the anticipated clinical application, and the anticipated medical benefit and value. Funding will not be provided for projects that address tuberculosis and HIV.

DHSC will evaluate projects in two simultaneous competition strands. In strand 1, up to £5 million is available for projects that explore the scientific and technical feasibility of innovative solutions through proof-of-concept studies. Strand 2 projects should be more advanced, with possible demonstration of effectiveness in humans.

"More research is critical, which is why the UK government is calling on some of the country's brightest minds to come up with new ways to prevent, control and combat these infections in the future," Dame Sally Davies, chief medical officer for England, said in a department press release.

The competition opens on Jul 16.
Jul 9 DHSC press release

 

CARB-X to fund development of new gonorrhea treatment

Originally published by CIDRAP News Jul 10

CARB-X today announced funding to support the development of a new class of antibiotics to treat gonorrhea.

The award of $2 million will go to UK-based Summit Therapeutics plc, which has identified a series of novel class/novel target compounds that have shown high potency against Neisseria gonorrhoeae strains, including those that are multidrug-resistant. The money will support selection of a preclinical candidate from the lead series. Summit could receive an additional $2.5 million from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) based on achievement of certain project milestones.

"This CARB-X collaboration and funding is important to us as we aim to pioneer a new era in antibiotic innovation and allows us to accelerate the development of our first series of new mechanism of action gonorrhoea compounds," Glyn Edwards, chief executive officer of Summit, said in a CARB-X news release.

The World Health Organization has deemed gonorrhea a high priority for antibiotic research and development. According to the agency, more than 78 million new cases of gonorrhea occur each year, making it one of the most common sexually transmitted infections in the world. Furthermore, there has been an emergence in recent years of N gonorrhoeae strains that are increasingly resistant to the only remaining antibiotics that can cure the infection. Untreated gonorrhea can result in serious and permanent health problems, including pelvic inflammatory disease and infertility.

CARB-X is currently supporting 34 research and development projects for new antibiotics, diagnostics, and alternative treatments for drug-resistant pathogens, including 10 novel antibiotic classes. Since CARB-X was established in 2016, it has announced awards totaling $89.4 million, plus an additional $120.7 million if project milestones are met.
Jul 10 CARB-X news release

 

Short course of antibiotics shown effective against pneumonia

Originally published by CIDRAP News Jul 10

A meta-analysis published yesterday in Antimicrobial Agents and Chemotherapy found that, for community-acquired pneumonia (CAP) in adults, a short course of antibiotics is equally effective and potentially superior—in terms of mortality and serious adverse events—compared with a longer course.

The researchers, from Brown University in Providence, R.I., included 21 clinical trials that included 4,861 evaluable CAP patients. Nineteen of the trials were randomized. The authors considered antibiotic treatment of 6 days or less to be a short course.

They found that clinical cure rates were similar in patients taking a short course of antibiotics versus a longer course, irrespective of disease severity or patient setting. In addition, a short course was tied to almost half the mortality rate, 27% fewer serious adverse events, and a lower relapse rate.
Jul 9 Antimicrob Agents Chemother abstract

 

Israeli program sees CRE rates cut in half during 7-year period

Originally published by CIDRAP News Jul 9

Israeli long-term care facilities (LTCFs) saw a 50% reduction in carbapenem-resistant Enterobacteriaceae (CRE) during a 7-year national intervention program, according to a study today in Clinical Infectious Diseases.

The Israeli National Center for Infection Control (NCIC) led the program, which included implementation of population-tailored contact precautions, and early detection of carriers. NCIC started the program and enhanced surveillance in 2008, 2 years after the introduction of CRE into Israeli hospitals.

The program targeted Israel's 15 post-acute care hospitals (PACHs), 15 skilled nursing facilities (SNFs), and 300 nursing homes (NHs). Within 3 years of launching the program CRE acquisition rates dropped steadily, reaching 50% of baseline values by 2015. The incidence of CRE acquisition declined between 2009 and 2015 in all facility types, as expressed by an incidence rate ratio (IRR) of less than 1 per year (PACHs, 0.90; SNFs, 0.87; NHs, 0.93).

The number of these LTCFs reporting 5 or more CRE acquisitions annually (defined by the authors as an outbreak) decreased from 35 to 11 from 2012 to 2015, as well.

"We demonstrated that a comprehensive, multimodal, nationwide strategy effort focusing on improved infection control, early carrier detection and contact isolation succeeded in reducing CRE incidence in LTCFs by over 50%, and almost eliminating CRE prevalence 8 years into implementation," the authors concluded. 
Jul 9 Clin Infect Dis study

 

Study: Many neonatal infections have no known cause

Originally published by CIDRAP News Jul 9

Late last week The Lancet published the findings of the Aetiology of Neonatal Infection in South Asia (ANISA) study, which surveyed neonatal possible serious bacterial infections (pSBIs) among pregnant women in India, Bangladesh, and Pakistan, and noted a possible antibiotic stewardship connection.

The prospective study included 6,022 pSBI episodes among 63,114 babies, identified by community health care workers from 2011 to 2014 between days 0 through 59 post-birth. The workers found that 28% of episodes (16% bacterial and 12% viral) could be attributed to a known pathogen. Mean incidence of bacterial infections was 13.2 (95% credible interval [CrI], 11.2-15.6) per 1,000 livebirths and of viral infections was 10.1 (9.4-11.6) per 1,000 livebirths.

According to the study, among fatal infections, causes were attributed in 46% of pSBI episodes, among which 92% were bacterial. The vast majority (83%) of 102 blood culture isolates were susceptible to penicillin, ampicillin, gentamicin, or a combination of these drugs.

Respiratory syncytial virus (RSV) was the most commonly identified pathogen, represented in 5.4 per 1,000 livebirths. 

The lack of a cause in a high proportion of cases suggests that pSBI episodes might not be due to bacterial infection, and subsequently, antibiotics may be overused in this patient population. 

In an accompanying commentary, Anna Seale, MD, and Ramesh Agarwal, PhD, write, "Of 6,022 pSBI episodes, only 16% had attributed bacterial causes, and 102 (2%) of 4859 tested blood samples had clinically significant pathogens isolated by culture." Seal and Argawal said this information should shape antibiotic use among this patient population. 
Jul 6 Lancet study
Jul 6 Lancet commentary

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