ASP Scan (Weekly) for Mar 01, 2019

News brief

CDC study links reduced antibiotic use with decrease in C difficile rates

Researchers with the US Centers for Disease Control and Prevention (CDC) reported today in Clinical Infectious Diseases that reductions in antibiotic use, particularly fluoroquinolones and third- and fourth-generation cephalosporins, was associated with a decrease in Clostridioides difficile rates in US acute care hospitals.

To examine cross-sectional and temporal associations between levels of antibiotic use and incidence of hospital-onset C difficile infection (HO-CDI), the researchers conducted an ecological analysis using data from 549 US hospitals from 2006 to 2012. Cross-sectional associations between annual rates of antibiotic use and HO-CDI were examined using multivariable generalized estimating equation models, and temporal trends in HO-CDI and antibiotic use rates were assessed through analysis of monthly rates of HO-CDI, total antibiotic use, and use of antibiotic classes for which significant cross-sectional associations with HO-CDI were observed.

During 2006-2012, the unadjusted annual rates of HO-CDI and total antibiotic use were 7.3 per 10,000 patient-days (PD) and 811 days of therapy (DOT)/1,000 PD, respectively. In the cross-sectional analysis, for every 50 DOT/1,000 PD increase in total antibiotic use, there was a 4.4% increase in HO-CDI. In particular, higher use of third- and fourth-generation cephalosporins and carbapenems was associated with increases in HO-CDI.

In the time-series analysis, hospitals that reduced total antibiotic use by 10% or lower experienced a 3% decrease in annual HO-CDI rates, and the 6 acute care hospitals with a decrease in total antibiotic use of 30% or more had a 33% decrease in HO-CDI. In addition, acute care hospitals with a decrease in fluoroquinolone or third- and fourth-generation cephalosporin use of 20% or more had a corresponding decrease in HO-CDI of 8% and 13%, respectively.

"These findings support the evidence that effective antibiotic stewardship programs can have major impact on HO-CDI in the U.S.," the authors of the study write.
Mar 1 Clin Infect Dis abstract

 

Carbapenem-producing Enterobacteriaceae activity increasing in Europe

Only 14 of 37 European countries have national action plans to address carbapenem-producing Enterobacteriaceae (CPE), while 11 nations report a worsening CPE situation, researchers from the Public Health Agency of Sweden and the European Centre for Disease Prevention and Control (ECDC) reported yesterday in Eurosurveillance.

The investigators conducted a survey on the epidemiological situation, surveillance, and containment activities for CPE in European countries in 2018. All 37 participating nations reported cases, but since 2015, CPE activity has increased in 11 countries. The authors also found that 33 countries have reference laboratory capability, 27 have dedicated surveillance efforts, but only 14 have a specific national containment plan.

The researchers ranked CPE epidemiologic activity from stage 0 (no cases reported) to stage 5 (endemic situation), with Greece, Italy, Malta, and Turkey reaching stage 5. In 2010, Greece was the only country with endemic CPE. Eleven countries were at stage 4—inter-regional spread, compared with only two in 2010.

"These results do not provide information on the factors driving the apparent increasing dissemination of CPE in Europe, which would require further investigations," the authors concluded.
Feb 28 Eurosurveill report

 

Surveillance data show gonorrhea resistance levels stable in Europe

Originally published by CIDRAP News Feb 28

The latest data from the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) reveal stable levels of resistance to the currently recommended antibiotics for Neisseria gonorrhoeae, according to a report today from the ECDC. But high resistance to azithromycin threatens the effectiveness of the treatment regimen, ECDC officials warn.

Testing of 3,248 N gonorrhoeae isolates collected from 27 European Union/European Economic Area countries in 2017 shows that resistance to cefixime and azithromycin (1.9% and 7.5%, respectively) remained stable compared with 2016 (2.1% and 7.5%). In addition, no isolates with resistance to ceftriaxone were detected for the second year in a row. But the number of countries reporting resistant isolates for both antibiotics increased, with the number of countries reporting cefixime-resistant isolates climbing to 15 (from 14 in 2016 and 9 in 2015) and the number of countries reporting azithromycin-resistant isolates rising to 23 (from 21 in 2016 and 18 in 2015).

"The fact that we have not seen ceftriaxone resistance among the tested isolates for two consecutive years is promising," ECDC expert Gianfranco Spinaldi, MD, MPH, said in a press release. "But at the same time, the persistent level of resistance to azithromycin across Europe is a major concern for us because it compromises the recommended dual therapy with ceftriaxone and azithromycin."

The ECDC also notes that the recent reports of extensively drug-resistant gonorrhea strains, particularly the cases with ceftriaxone resistance and high-level azithromycin resistance identified in the United Kingdom and Australia in 2018, highlight the need to understand what is driving changes in resistance prevalence.

The ECDC will publish a revised version of its multidrug-resistant gonorrhea response plan later this year.
Feb 28 ECDC Euro-GASP report
Feb 28 ECDC press release

 

UTI study ties risks of infection, death to no or delayed antibiotics in seniors

Originally published by CIDRAP News Feb 28

A study yesterday in the British Medical Journal (BMJ) found that, in elderly patients with a diagnosed urinary tract infection (UTI), receiving no antibiotics or delayed antibiotics was associated with an increased risk of bloodstream infection or death within 60 days

The retrospective study looked at primary care records from 157,264 adults aged 65 years and older in England who presented to a general practitioner with at least one UTI symptom from November 2007 to June 2015. The main outcome measures were bloodstream infection, hospital admission, and all-cause mortality within 60 days after the index UTI diagnosis.

Among the 312,896 UTI episodes recorded, 7.2% did not have a record of antibiotics being prescribed, and 6.2% showed a delay in prescribing. Overall, 1,539 episodes of bloodstream infection were recorded after the initial UTI. The rate of bloodstream infection significantly increased when patients were not prescribed an antibiotic (2.9% vs 0.2% for immediate antibiotics) and when antibiotics were deferred (2.2% vs 0.2%). After adjusting for covariates, patients were significantly more likely to experience a bloodstream infection in the no antibiotics group (adjusted odds ratio [aOR], 8.08; 95% confidence interval [CI], 7.12 to 9.16) and the deferred antibiotics group (aOR, 7.12; 95% CI, 6.22 to 8.14).

In addition, the results showed that the proportion of patients admitted to the hospital was nearly two times higher for those in the no antibiotics group (27%) and the deferred antibiotics group (26.8%) compared with the immediate antibiotics group (14.8%), and the risk of all-cause mortality within 60 days was significantly higher with no antibiotics (aOR, 2.18; 95% CI, 2.04 to 2.33) and deferred antibiotics (aOR, 1.16; 95% CI, 1.06 to 1.27). Men older than 85 were particularly at risk for both bloodstream infection and 60-day all-cause mortality.

The authors of the study say the findings are particularly noteworthy given the rising incidence of gram-negative bloodstream infections in England.

"Our study suggests the early initiation of antibiotics for UTI in older high risk adult populations (especially men over aged >85 years) should be recommended to prevent serious complications," they conclude.
Feb 27 BMJ study

 

Study examines deaths from XDR gram-negative infections

Originally published by CIDRAP News Feb 28

A study from a large healthcare database estimated that deaths from extensively drug-resistant (XDR) gram-negative infections was 12.6% and that hospitalization for an XDR infection costs more than $35,000. A team led by the National Institutes of Health (NIH) reported their findings yesterday in the American Journal of Infection Control.

The database they used from Vizent, Inc., contained clinical information, including claim codes and specific medication charges, from 120 academic medical centers and 300 affiliated hospitals. For the study, researchers looked at inpatient encounters between January of 2010 and December of 2013. And they used a tracer antibiotic algorithm as a surrogate marker to investigate and estimate mortality related to XDR gram-negative infections.

Over the study period, 232,834 gram-negative infections were reported from 79 hospitals, of which 1,023 per 3,350 (30.5%) who were prescribed colistin died and 9,188 per 105,641 (8.7%) who were on beta lactams died. Patients who received 4 or more consecutive days of intravenous colistin or died within 4 days of starting the treatment had an excess mortality of 12.6% compared to those who received noncarbapenem beta-lactams that targeted gram-negative bacteria.

The team also found that mortality for the XDR gram-negative infections varied by infection site, onset, and severity. For example, infections coded for sepsis had 3-fold higher mortality and severe sepsis or septic shock had 9-fold higher mortality, which the authors said could suggest that a higher baseline risk of death could amplify the impact of XDR on clinical outcome.

They noted that the healthcare cost of the infections falls within earlier estimates for multi-drug resistant infections, but may be a conservative estimate, because discharge factors such as rehabilitation costs and productivity loss weren't factored in.

Though the prevalence of XDR phenotypes among gram-negative infections is relatively now, documenting their high mortality, role in outbreaks, and global spread are important for raising awareness, the group wrote, adding that new tools for analyzing information from large databases and electronic medical record repositories will help guide antibiotic use and development, as well as other control measures, such as new rapid diagnostics.
Feb 27 Am J Infect Control abstract

 

Joint Commission, Pfizer fund grants to boost stewardship in Asia-Pacific

Originally published by CIDRAP News Feb 28

The Joint Commission and drug company Pfizer this week announced the selection of six quality improvement projects to receive funding as part of a 2-year grant to improve antimicrobial stewardship in the Asia-Pacific region, according to a Joint Commission news release.

Grant recipients range from establishing a unit-based safety program in India to developing a primary care stewardship model in China to building an international network in India, Micronesia, Nepal, and the Philippines. The projects are anticipated to be completed by early 2022.

Scott Williams, PsyD, director of research with the Joint Commission, said, "We believe the projects can help accelerate the development and adoption of evidence-based approaches that have the capacity to prevent or contain antimicrobial resistance and support the appropriate use of antimicrobial agents."

The Joint Commission did not specify a dollar amount for the grants.
Feb 26 Joint Commission news release

 

Study analyzes patterns of movement of CRE infections in Atlanta

Originally published by CIDRAP News Feb 28

Using regional surveillance data, researchers from the CDC, the Atlanta Veterans Affairs Medical Center, and Emory University have determined that patients with carbapenem-resistant Enterobacteriaceae (CRE) infections in the Atlanta metro area transfer between healthcare facilities in similar patterns as Medicare patients, with the exception of a handful of nursing homes.

In a study today in Clinical Infectious Diseases, the researchers used surveillance data from the Georgia Emerging Infections program to identify all positive CRE cultures from urine or a sterile body site collected in 2016 in Georgia's Health District 3, an eight-county portion of the Atlanta metro area.

To construct a patient transfer network, each CRE was attributed to an acute care hospital (ACH), long-term acute care hospital (LTACH), or skilled nursing facility (SNF) based on timing of culture and facility exposures in the previous year. Centrality metrics were calculated from 2016 Medicare data and then compared with CRE-transfer derived centrality metrics.

During 2016, 283 CRE incident cases with concurrent or prior-year facility stays were identified, and positive cultures were most often collected at ACHs (141, 50%) and SNFs (113, 40%) and less frequently at LTACHs (29, 10%). The patient-sharing network as identified by Medicare transfer data included 93 facilities, with CRE cases originating in 17 of 20 ACHs (85%), 7 of 8 LTACHs (88%), but only 35 of 65 SNFs (54%).

The analysis of connectedness showed that the movement of patients with CRE between healthcare facilities (both direct and indirect transfers) mirrored the flow of Medicare patients between facilities, but the association was strong and significant only for ACHs and LTACHs. In six of the SNFs, the movement of CRE patients was not correlated with the movement of Medicare patients.

The authors of the study conclude, "In summary, we found patients with CRE move throughout the Georgia Health District 3 region, where initial CRE culture positive specimens as indicators of infection originated at almost all of the ACHs and over half of SNFs. Furthermore, we identified a subset of nursing homes involved in the flow of CRE patients that could not easily be explained by Medicare defined centrality measures, suggesting other factors may better explain CRE patient movement in nursing homes."
Feb 27 Clin Infect Dis abstract

 

Penicillin skin testing linked to antimicrobial de-escalation, reduced costs

Originally published by CIDRAP News Feb 28

The results of a quasi-experimental study published today in Open Forum Infectious Diseases show that penicillin skin esting (PST) in a community health system led to antimicrobial de-escalation in 71% of patients who tested negative and reduced costs.

In the study, which was conducted at SouthCoast Health Savannah in Savannah, Georgia, an intervention group of 100 adult patients who completed PST for a self-reported penicillin allergy was compared to a matched control group of patients who had a listed penicillin allergy as well as infectious diseases consultation. The patients in the control group were matched to infection diagnosis codes of members of the intervention group and then randomly selected and matched 1:1. Antimicrobial therapy and duration was documented for each patient, along with changes in therapy in the PST group.

The primary outcome was non-carbapenem beta-lactam DOT, and the secondary outcome was the average cost of antimicrobial therapy for the intervention group before and after PST.

Of the 100 patients in the intervention group, 98 tested negative for a penicillin skin allergy, and 70 (71%) of those 98 patients had changes directly made to their antimicrobial regimens. The most common change after a negative test (34 of 70 patients) was from carbapenems to penicillins. For the primary outcome, beta-lactam DOT for the PST group were 666 out of 1,094 (60.88%, with 34.82% being a penicillin specifically). Beta-lactam DOT for the control group were 386 out of 984 (39.64%, with 6.4% being a penicillin specifically). Changes to the antimicrobial regimen after PST saved the average patient $353.03.

The authors say further study is required to evaluate the overall clinical and economic benefit of PST in community health systems with limited resources.
Feb 27 Open Forum Infect Dis abstract

 

Review finds short antibiotic course not tied to worse bacteremia outcome

Originally published by CIDRAP News Feb 26

A meta-analysis of five studies published today in Antimicrobial Agents and Chemotherapy determined that, in patients with bacteremia caused by Enterobacteriaceae, short- and long-course antibiotic treatment did not differ significantly in terms of clinical outcomes.

Experts from Brown University in Providence, Rhode Island, included four retrospective cohort studies and one randomized controlled trial comprising 2,865 patients overall in their analysis. They found that short and long courses (greater than 10 days) of antibiotics did not differ in terms of 30-day all-cause mortality (relative risk [RR], 0.99), 90-day all-cause mortality (RR, 1.16), clinical cure (RR, 1.02), or relapse at 90 days (RR, 1.0).

The authors noted, however, "Further well-designed studies are needed before treatment for 10 days or less is adopted in clinical practice."
Feb 26 Antimicrob Agent Chemother study

 

CARB-X adds 6 new organizations to its Global Accelerator Network

Originally published by CIDRAP News Feb 26

The public-private partnership CARB-X today announced it has added six new life sciences organizations from around the world, expanding its Global Accelerator Network to 10 groups, according to a CARB-X news release.

"We are expanding our accelerator network to increase support for the development of new antibiotics, rapid diagnostics, vaccines and other life-saving products that the world so urgently needs to fight the rise of drug-resistant bacteria," said Kevin Outterson, JD, CARB-X executive director.

"Antibacterial product development is challenging, and CARB-X's portfolio is growing rapidly. This new network will provide a broader range of scientific, technical, and business support our innovative projects need to progress and succeed." The six new groups add expertise in the development of drugs and rapid diagnostics, business and regulatory strategy, and other highly specialized areas, CARB-X said.

Hailing from six nations, the six organizations are: BaselArea.swiss, the BioInnovation Institute, the Centre for Cellular and Molecular Platforms (C-CAMP), the Foundation for Innovative New Diagnostics (FIND), the German Center for Infection Research (DZIF), and the Institute for Life Sciences Entrepreneurship (ILSE). They join CLSI, MassBio, and RTI International in the United States and the Wellcome Trust in the United Kingdom as CARB-X accelerators.

Since it was established in 2016, CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) has awarded more than $107.4 million, plus additional funds if project milestones are met, to accelerate the development of antibiotics, rapid diagnostics and other life-saving antibacterial products. Its aim is to invest up to $500 million by 2021.
Feb 26 CARB-X news release

Stewardship / Resistance Scan for Mar 01, 2019

News brief

CDC study links reduced antibiotic use with decrease in C difficile rates

Researchers with the US Centers for Disease Control and Prevention (CDC) reported today in Clinical Infectious Diseases that reductions in antibiotic use, particularly fluoroquinolones and third- and fourth-generation cephalosporins, was associated with a decrease in Clostridioides difficile rates in US acute care hospitals.

To examine cross-sectional and temporal associations between levels of antibiotic use and incidence of hospital-onset C difficile infection (HO-CDI), the researchers conducted an ecological analysis using data from 549 US hospitals from 2006 to 2012. Cross-sectional associations between annual rates of antibiotic use and HO-CDI were examined using multivariable generalized estimating equation models, and temporal trends in HO-CDI and antibiotic use rates were assessed through analysis of monthly rates of HO-CDI, total antibiotic use, and use of antibiotic classes for which significant cross-sectional associations with HO-CDI were observed.

During 2006-2012, the unadjusted annual rates of HO-CDI and total antibiotic use were 7.3 per 10,000 patient-days (PD) and 811 days of therapy (DOT)/1,000 PD, respectively. In the cross-sectional analysis, for every 50 DOT/1,000 PD increase in total antibiotic use, there was a 4.4% increase in HO-CDI. In particular, higher use of third- and fourth-generation cephalosporins and carbapenems was associated with increases in HO-CDI.

In the time-series analysis, hospitals that reduced total antibiotic use by 10% or lower experienced a 3% decrease in annual HO-CDI rates, and the 6 acute care hospitals with a decrease in total antibiotic use of 30% or more had a 33% decrease in HO-CDI. In addition, acute care hospitals with a decrease in fluoroquinolone or third- and fourth-generation cephalosporin use of 20% or more had a corresponding decrease in HO-CDI of 8% and 13%, respectively.

"These findings support the evidence that effective antibiotic stewardship programs can have major impact on HO-CDI in the U.S.," the authors of the study write.
Mar 1 Clin Infect Dis abstract

 

Carbapenem-producing Enterobacteriaceae activity increasing in Europe

Only 14 of 37 European countries have national action plans to address carbapenem-producing Enterobacteriaceae (CPE), while 11 nations report a worsening CPE situation, researchers from the Public Health Agency of Sweden and the European Centre for Disease Prevention and Control reported yesterday in Eurosurveillance.

The investigators conducted a survey on the epidemiological situation, surveillance, and containment activities for CPE in European countries in 2018. All 37 participating nations reported cases, but since 2015, CPE activity has increased in 11 countries. The authors also found that 33 countries have reference laboratory capability, 27 have dedicated surveillance efforts, but only 14 have a specific national containment plan.

The researchers ranked CPE epidemiologic activity from stage 0 (no cases reported) to stage 5 (endemic situation), with Greece, Italy, Malta, and Turkey reaching stage 5. In 2010, Greece was the only country with endemic CPE. Eleven countries were at stage 4—inter-regional spread, compared with only two in 2010.

"These results do not provide information on the factors driving the apparent increasing dissemination of CPE in Europe, which would require further investigations," the authors concluded.
Feb 28 Eurosurveill report

News Scan for Mar 01, 2019

News brief

MERS sickens 1 more in Saudi Arabia

Saudi Arabia's health ministry today reported new MERS-CoV case, which involves a 78-year-old man from Afif in the in the central part of the country, according to an update to its epidemiological week 9 report.

An investigation revealed the man had contact with camels before his MERS-CoV (Middle East respiratory syndrome coronavirus) symptoms began. He is currently hospitalized for his infection.

Today's new case raises Saudi Arabia's total number of MERS-CoV illnesses this year to 83, of which 51 were from Wadi ad-Dawasir where a large hospital-related outbreak is under way and illnesses linked to camel exposure have also occurred.
Mar 1 Saudi health ministry update

 

UNICEF sounds alarm over measles surge

UNICEF today warned that measles cases this year are surging to alarmingly high levels, with 10 countries accounting for more than 74% of the total increase.

The United Nations agency notes that, for 2018, 98 countries reported more measles than the previous year, a sign of eroding progress against the highly preventable but potentially fatal and highly communicable disease. Countries with the 10 highest increases last year, in order of number of cases, are Ukraine, Philippines, Brazil, Yemen, Venezuela, Serbia, Madagascar, Sudan, Thailand, and France.

For 2018, the Ukraine reported 35,120 cases, and already this year the country has reported 24,042 measles cases. Similarly, the Philippines last year reported 15,559 cases in all of 2018 but has already recorded 12,736, including 203 deaths, in the first 2 months of 2019.

UNICEF highlighted several countries that had no reported measles cases in 2017, but reported cases in 2018. They are Brazil, Moldova, Montenegro, Colombia, Timor-Leste, Peru, Chile, and Uzbekistan.

Gaps in health infrastructure, civil unrest, low community awareness, complacency, and vaccine hesitancy have led to outbreaks in both developing and developed countries. The United States, for example, experienced a sixfold increase between 2017 and 2018.

In a statement, Henrietta Fore, UNICEF's executive director, said, "This is a wake up call. We have a safe, effective, and inexpensive vaccine against a highly contagious diseases—a vaccine that has saved almost a million lives each year over the last two decades." She also warned that a lack of action today will have disastrous consequences tomorrow.

UNICEF and its partners have stepped up efforts in several parts of the world, including the Ukraine, the Philippines, Brazil, Yemen, and Madagascar.
Mar 1 UNICEF press release

In other measles developments, the World Health Organization (WHO) said yesterday that it is collaborating with Nigeria's government to curb further spread of measles and rubella in the country. A measles outbreak is occurring across five states, with one—Ogun—also experiencing a rubella outbreak.

Though the vaccine is part of the routine immunization schedule and measles vaccination campaigns were held in 2017 and 2018, population immunity remains low because of poor belief in immunization and vaccine refusal during the campaigns, especially in border areas.
Feb 28 WHO Nigeria office statement

 

More positive contacts found in Mozambique and Nigeria polio outbreaks

Mozambique and Nigeria reported more positive vaccine-derived polio samples, all in community contacts of earlier cases, according to a weekly update today from the Global Polio Eradication Initiative (GPEI).

Mozambique is currently experiencing a circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreak, and the latest positive sample was collected Dec 17 from a community contact in Zambezia province.

Nigeria reported eight positive cVDPV2 samples collected Jan 13 and 14 from health contacts of a patient with acute flaccid paralysis in Kwara state. The country is experiencing two vaccine-derived polio outbreaks, the other involving cVDPV1.
Feb 28 GPEI weekly report

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