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

Researchers develop a rapid test for antibiotic susceptibility

Originally published by CIDRAP News Aug 10

A team of researchers in Sweden have developed a test that can determine antibiotic susceptibility in less than 30 minutes, according to a new study in Proceedings of the National Academy of Sciences.

The "fASTest" method, developed by researchers at Uppsala University, uses a microfluidic chip that captures bacterial cells in 2,000 parallel cell traps. Growth media containing antibiotics is loaded into the chip, and the growth rate of the individual bacterial cells in response to the antibiotic is monitored using microscopy and compared to the growth rate of cells exposed to growth media without antibiotics. The total time for testing, from loading of the bacterial sample to diagnostic readout, is less 30 minutes—fast enough to be used at the point of care.

For the study, the researchers tested urinary tract infections (UTIs) caused by Escherichia coli, the primary cause of infection in 85% of UTIs diagnosed in primary care. First, they determined the antibiotic response time of E coli to nine different antibiotics used to treat UTIs, and found that it was possible to detect changes in the growth rate of the bacteria within 3 to 11 minutes. In a test of 49 clinical uropathogenic E coli isolates in response to ciprofloxacin, all isolates were correctly classified as susceptible or resistant in less than 10 minutes, with similar sensitivity and specificity as traditional methods of antibiotic susceptibility tests.

Although the test is years away from clinical use, the findings are significant because traditional antibiotic susceptibility tests, which measure bacterial growth with and without antibiotics in liquid cultures or solid agar plates, typically take 1 to 2 days to produce results. As a result, clinicians often have to prescribe a broad-spectrum antibiotic in the early stages of an infection, or risk prescribing the incorrect antibiotic. A susceptibility test that could provide results in 30 minutes would enable clinicians to provide proper treatment more quickly.

"The hope is that, in the future, the method could be used in hospitals and health centers to quickly provide correct treatment and reduce unnecessary use of antibiotics," study co-author Dan Andersson, PhD, said in an Uppsala University news release.
Aug 8 Proc Natl Acad Sci study
Aug 8 Uppsala University news release

New antibiotic shows promise against gonorrhea in lab experiments

Originally published by CIDRAP News Aug 9

New early-stage research out of the United Kingdom has identified a potential antibiotic candidate for treatment of drug-resistant gonorrhea.

In a paper published in Antimicrobial Agents and Chemotherapy, scientists from the London School of Hygiene and Tropical Medicine and Imperial College London report that the novel antimicrobial closthioamide (CTA) inhibited the growth of 146 of 149 (98%) clinical Neisseria gonorrhea isolates at a minimum inhibitory concentration of 0.125mg/L or less, a low therapeutic dose that could reduce any potential toxicity. Furthermore, the in vitro tests showed CTA to be effective against N gonorrhea isolates that were resistant to ciprofloxacin and to the first-line antibiotics ceftriaxone and azithromycin.

CTA, discovered in 2010, is derived from the anaerobic bacterium Clostridium cellulolyticum. It has been shown to have high in vitro activity against other drug-resistant microorganisms, including multidrug-resistant (MDR) bacteria.

The emergence of gonorrhea strains that are resistant to azithromycin and ceftriaxone—the currently recommended treatments for the sexually transmitted infection—is a major concern for public health officials, since there are no other alternatives. Last month, the World Health Organization warned that widespread treatment failure is likely in the coming years unless new antibiotics are developed. Serious and permanent health problems, including pelvic inflammatory disease and infertility, can result if gonorrhea goes untreated.

The authors of the study say that while the initial laboratory results are intriguing, further research in animals and humans is needed to evaluate CTA's safety and effectiveness.

"Despite showing tremendous promise, it will be a number of years before, and if, we can use the drug in real life human cases," lead author John Heap, PhD, said in a news release from Imperial College London.
Aug 7 Antimicrob Agents Chemother abstract
Aug 7 Imperial College London news release

Rapid malaria diagnostic tests linked to increased antibiotic prescribing

Originally published by CIDRAP News Aug 8

A review of 10 linked studies yesterday in the American Journal of Tropical Medicine and Hygieneindicates that introduction of rapid diagnostic tests for malaria in Africa and Afghanistan curbed use of anti-malaria drugs but was also linked to increased antibiotic prescribing.

The 10 related studies, which analyzed drug prescriptions written from 2007 to 2013 for 562,368 patients in malaria-endemic regions of Africa (Ghana, Cameroon, Tanzania, Nigeria, and Uganda) and Afghanistan, were conducted by the ACT Consortium, a research partnership created to investigate delivery of artemisinin-based combination therapies (ACTs) for malaria treatment. The studies looked at the impact of malaria rapid diagnostic testing (mRDT) on fever case management across a range of clinical settings, and included a comparison group without mRDT intervention.

Overall, mRDTs were associated with lower ACT prescribing, with mRDT interventions in most settings (10 African settings, 4 Afghanistan settings) producing statistically significant reductions in ACT prescribing compared to scenarios without mRDT intervention. Lower prescribing was mostly due to malaria test-negative patients not receiving ACTs. However, mRDT interventions were also associated with significantly more systemic prescribing of antibiotics in seven settings (5 in Africa, 2 in Afghanistan), with antibiotics being prescribed to 40% to 80% of patients who tested negative.

Across most settings, either an antimalarial or an antimicrobial was prescribed for more than 75% of patients. The studies also showed that prescribing did not always adhere to malaria test results. In many settings, ACTs were prescribed to more than 30% of test-negative patients; in other settings, more than 20% of the patients who tested positive were not given ACTs.

The findings echo those from a Mar 29 BMJ analysis of nine of the studies, which found that the risk of antibiotic prescription was 21% higher in places where mRDT was introduced. The authors say the results "highlight issues that warrant particular attention in future work on point-of-care diagnosis and fever and malaria case management.
Aug 7 Am J Trop Med Hyg abstract
Related Mar 29 CIDRAP News story

Study: Carbapenem restriction reduces resistance in P aeruginosa

Originally published by CIDRAP News Aug 8

A new study in Clinical Infectious Diseases suggests that restricting carbapenem antibiotics, even for a short time, may be an effective strategy for managing carbapenem resistance in Pseudomonas aeruginosa.

In the study, researchers at King Saud Medical City, a public hospital in Riyadh, Saudi Arabia, conducted a two-phase retrospective study to investigate to compare the antimicrobial susceptibility pattern of P aeruginosa before and after implementation of a carbapenem restriction program. The program was in response to the identification of a new strain of P aeruginosa in the hospital's intensive care unit that was susceptible to many antipseudomonals but resistant to imipenem and meropenem.

The program restricted use of imipenem and meropenem except in three cases: culture-based carbapenem therapy, empirical carbapenem therapy after failure of other antibiotics, and carbapenem therapy prescribed by an infectious disease consultant. The first phase of the study was from May 2016 to July 2016 (before carbapenem restriction) and the second phase was September 2016 to November 2016 (after carbapenem restriction).

The results showed that after implementing carbapenem restriction, overall carbapenem consumption fell from 28.44 to 11.67 defined daily doses (DDD) per 1,000 patient days, and the percentage of P aeruginosa isolates that were resistant to imipenem and meropenem decreased significantly, from 76% to 38.5% (P=0.019) and from 74.1% to 30% (P=0.012), respectively. Susceptibility of P aeruginosa to other antibiotics was not affected by carbapenem restriction. The study did not investigate clinical outcomes before and after carbapenem restriction.

The authors write, "Although some investigatorsargued that a long period of time is required for a change in antibiotic prescribing practice to show an effect on the antimicrobial susceptibility pattern, the present study proved that even a short duration of change in antibiotic prescribing habits might cause a change in the antimicrobial susceptibility pattern."
Aug 4 Clin Infect Dis study

Study shows clinical impact of an educational ASP in Spain

Originally published by CIDRAP News Aug 8

A new study by researchers in Spain reports that an education-based antimicrobial stewardship program (ASP) at a large teaching hospital produced a sustained reduction in antibiotic use and decreased the incidence and mortality of hospital-acquired candidemia and multidrug-resistant bloodstream infections (MDR-BSI).

The quasi-experimental study, published yesterday in Clinical Infectious Diseases, investigated to impact of a multifaceted educational intervention at a tertiary-care teaching hospital in Sevilla, Spain, over a 5-year period. The main intervention was weekly peer-to-peer educational interviews, in which counselors selected one antibiotic prescription per week and interviewed the prescribers about the case. The researchers recorded data on antibiotic consumption over five years, calculated as DDD per 1,000 occupied bed days (OBD), and analyzed the incident density per 1,000 OBD of hospital-acquired BSI caused by the six most frequent microorganisms—E coli, Klebsiella pneumoniae, Acinetobacter baumannii, P aeruginosa, Staphylococcus aureus, and Candida SPP. They also assessed crude death rate per 1,000 OBD.

The results showed that implementation of the ASP was followed by a significant drop in antibiotic consumption that was sustained during the following years, with the median consumption dropping from 1,008 DDD/1,000 OBD in the first year to 774 DDD/1,000 OBD in the last year. The reduction was observed in all classes of antibiotics.

In addition, the incidence density and mortality of hospital-acquired candidemia and MDR-BSI decreased parallel to the reduction in antibiotic pressure. The increasing trend observed in the pre-intervention period for incidence of candidemia and MDR-BSI (+0.018 cases per 1,000 OBD per quarter) reverted toward a decreasing trend with a change in slope of -0.029 cases/1,000 OBD per quarter, while the increasing trend in the crude death rate in the pre-intervention period (+0.011 deaths/1,000 OBD per quarter) reverted toward a decreasing trend with a change in slope of -0.015deaths/1,000 OBD per quarter.

The authors of the study say they believe this is the first ASP to demonstrate that reducing antibiotic pressure can reduce the incidence and mortality of hospital-acquired MDR-BSI, an important finding given that the evidence supporting the clinical benefits of ASPs has to date been insufficient. "Our results prove that educational interventions can be successful when based on active learning targeted towards real clinical problems of interest to specialists of all departments," they write.
Aug 7 Clin Infect Dis abstract

Study: Macrolide-resistant M pneumoniae on the decline in Japan

Originally published by CIDRAP News Aug 7

A new study in Emerging Infectious Diseases reports that the prevalence of macrolide-resistant Mycoplasma pneumoniae in Japan was as high 82% in 2012 but has declined in the following years.

In the study, Japanese researchers investigated 1,448 nasopharyngeal swab samples and sputum samples from children who were treated for respiratory tract infections caused by M pneumoniae from January 2008 through December 2015. In general, M pneumoniae infection is a mild illness that is most common in young adults and school-aged children; outbreaks tend to occur mostly in crowded environments, like schools. An M pneumoniae pandemic occurred in Japan during 2010-2012, especially among children, and a rise in macrolide-resistant infections has been documented during that pandemic. The purpose of the study was to investigate macrolide resistance after the pandemic.

The researchers found that the overall prevalence rate of the macrolide-resistant M pneumoniae during the study period was 70.2% (1,016 of 1,448 samples). When divided into three time periods (pre-pandemic, pandemic, and post-pandemic), the overall rate of macrolide-resistant M pneumoniae was substantially lower in the post-pandemic period than in the pandemic period. After a peak of 81.6% in 2012, macrolide-resistant M pneumoniae decreased to 65.8% in 2013, 59.3% in 2014, and 43.6% in 2015.

By comparison, the prevalence of macrolide-resistant M pneumoniae infections is 13.2% in the United States, 8.3% in France, and 3.1% in Germany, which could reflect differences in macrolide prescribing among countries. The authors of the study say careful, continuous monitoring of macrolide-resistant M pneumoniae infection rates in Japan and other countries is needed.
Aug 4 Emerg Infect Dis dispatch