ASP Scan (Weekly) for Jan 04, 2019

Stewardship cost-effectiveness
Klebsiella bacteremia in Taiwan
Novartis shares antibiotic data
New CARB-X funding
MCR-1 genes in food
Risk factors for resistant UTIs
MRSA pneumonia screening
Deadly superbug in Brazilian ICU
Staph decolonization in the NICU

Dutch study shows cost-effectiveness of stewardship intervention for RTIs

A study today in the Journal of Antimicrobial Chemotherapy shows that online training for general practitioners (GPs) and an online booklet for parents was associated with a decrease in antibiotic prescribing in children with respiratory tract infections (RTIs) and was cost-effective.

The study, conducted by Dutch researchers, was a cost-effectiveness analysis performed alongside the RAAK (RAtional Antibiotic use in Kids) randomized controlled trial, a study that assessed whether an intervention consisting of online training for GPs about RTIs in children and prudent antibiotic use combined with information booklets for parents could reduce antibiotic prescribing for kids with RTIs. The patient population consisted of children from 32 general practices in the Netherlands whose parents kept a 2-week cost diary. The researchers analyzed the difference in antibiotic prescribing and costs between the intervention group and the usual-care group.

Overall, 153 children from 15 practices in the intervention group and 107 children from 15 practices in the usual-care group were available for analysis. Antibiotic prescribing was 12 percentage points lower and the total costs per child were €10.27 ($11.71) higher in the intervention group, with much of the difference resulting from the productivity loss of parents. This resulted in an incremental cost-effectiveness ratio of €0.85 ($0.97) per percentage decrease in antibiotic prescribing. The probability that the intervention was effective, but more expensive, was 53%, while the probability that the intervention was more effective and less expensive compared with usual care was 41%.

"The online training for GPs and the information booklet for parents resulted in a decrease in antibiotic prescribing for children with RTI, at very low cost, and would therefore be suitable for implementation in quality assurance programmes in primary care," the authors of the study write, though they note that whether the intervention should be implemented depends on society's willingness to pay for a percentage decrease in antibiotic prescribing.
Jan 4 J Antimicrob Chemother study


Study describes different characteristics of Klebsiella bacteremia

A retrospective study of patients in Taiwan has found distinct differences in the clinical and microbiologic features of healthcare-associated (HCA), community-acquired (CA), and nosocomial Klebsiella pneumoniae bloodstream infections, researchers reported yesterday in Antimicrobial Resistance and Infection Control.

In the single-center study, researchers at Taipei Veterans General Hospital and National Yang-Ming University identified patients hospitalized with K pneumoniae bacteremia in 2015, collected clinical information on the demographic characteristics of the patients, and conducted antimicrobial susceptibility testing and capsular genotyping on all K pneumoniae isolates. They wanted to compare the clinical characteristics, antimicrobial resistance, and distribution of capsular types among HCA, CA, and nosocomial K pneumoniae bacteremia, which is a major cause of morbidity and mortality worldwide.

A total of 337 patients with K pneumoniae bacteremia were identified: 70 (20.8%), 102 (30.3%), and 165 (48.9%) had CA, HCA, and nosocomial infection, respectively. The 28-day mortality of HCA bacteremia was lower than that of nosocomial bacteremia (17.6% vs 30.9%, P = 0.016), but that of HCA and CA bacteremia was similar (17.6% vs 14.3%, P = 0.557). CA isolates had the highest prevalence of virulent capsular types (51.4%), followed by HCA (36.3%) and nosocomial isolates (19.4%). The proportion of multidrug-resistant isolates was highest in nosocomial infections (41.8%), followed by HCA (23.5%) and CA infections (5.7%).

The authors of the study conclude, "The characterization of the clinical characteristics of CA, HCA, and nosocomial bacteremia will help professionals to better manage patients. Further studies on the microbiological characteristics of HCA strains must be conducted to accurately identify the transmission of virulent or antimicrobial-resistant strains between community and hospital."
Jan 3 Antimicrob Resist Infect Control study


Novartis shares data from discontinued antibiotics program

Originally published by CIDRAP News Jan 3

The Pew Charitable Trusts announced today that Novartis has shared data from its discontinued antibiotics development program on Pew's open-access database, known as SPARK (Shared Platform for Antibiotic Research and Knowledge).

According to a Pew news release, Novartis shared data from its LpxA, LpxK, and LpxD antibacterial programs, which explore new ways to attack gram-negative bacteria. The company is no longer pursuing development of these molecules after announcing in July that it was ending its antibacterial and antiviral research programs.

SPARK is a cloud-based platform that's open to scientists from industry, academia, government, and nonprofit research groups who are working on antibiotic development. Launched by Pew in September, its aim is to help spur basic research into new antibiotics for gram-negative bacterial pathogens by providing scientists access to chemical and biological data from previously published and unpublished studies. SPARK's specific focus is on molecules that take new approaches to overcoming the defenses of gram-negative bacteria.

The move is significant because pharmaceutical company data on discontinued antibiotic development programs would normally remain with the companies. But in October, drug maker Achaogen became the first pharmaceutical company to release data from a discontinued antibiotic development program to SPARK.

Lynn Silver, an independent consultant in antibacterial discovery who's been working with Pew to update the SPARK database, said she hopes other pharmaceutical companies will follow suit. "The reality is that bacteria are developing resistance faster than we're finding new drugs to defeat them," Silver said in the news release. "In order to change that, we must salvage and make the most of every bit of data out there—published or unpublished." 
Jan 3 Pew news release
Oct 22, 2018, CIDRAP News story "Achaogen to share data from discontinued antibiotic program"


CARB-X to fund new antibiotic for multidrug-resistant lung infections

Originally published by CIDRAP News Jan 3

CARB-X announced today that it's awarding up to $5.7 million in funding to San Diego–based biotechnology company Forge Therapeutics to develop an antibiotic for lung infections caused by Pseudomonas aeruginosa and other multidrug-resistant gram-negative bacteria.

The money will enable the company to evaluate and further develop a class of novel, non-hydroxamate LpxC inhibitors, which target an enzyme that helps construct the tough outer membrane of gram-negative bacteria. Several companies have worked on drugs targeting LpxC, but to date no effective compounds have been developed. Forge's LpxC inhibitors have demonstrated safety and the ability to kill gram-negative superbugs in animals.

The award is the second that Forge has received from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), a public-private partnership that provides non-dilutive funding to companies in the pre-clinical stages of developing new antibiotics, diagnostics, and other therapeutics for the most critical antibiotic-resistant pathogens. Since 2016, CARB-X has awarded over $97.7 million to more than 30 projects.

"We are gratified to receive this opportunity to expand our collaboration with CARB-X," Forge CEO Zachary Zimmerman, PhD, said in a CARB-X news release. The company could receive an additional $5.4 million if it reaches certain project milestones.
Jan 3 CARB-X news release


Seven MCR-1 isolates identified in food samples in China

Originally published by CIDRAP News Jan 3

Scientists have identified seven colistin-resistance MCR-1–containing isolates from food samples collected from 2012 to 2016 in China, according to a letter yesterday in the Journal of Antimicrobial Chemotherapy.

The researchers analyzed 2,555 Salmonella isolates cultured from foods in the study period, varying from 174 to 1,100 samples in a given year. Using quantitative polymerase chain reaction, they identified seven MCR-1 genes, which convey resistance to colistin, a "last resort" antibiotic for multidrug-resistant organisms. The gene was first identified in 2015 in China and has since been detected in more than 30 countries.

Three MCR-1–positive isolates were from pork samples; 2 from dumplings, 1 of which contained pork; and 1 each from an egg and a whole chicken. The samples were from five provinces. Four isolates were Salmonella Typhimurium, with the others being Indiana, London, and Derby. The authors say this predilection for the Typhimurium strain is consistent with previously reported data.

The authors conclude, "There is a trend for Salmonella spp. becoming a reservoir for the mcr-1 gene. . . . Deep-level genomic characterization is required to understand fully the mechanism of the colistin resistance and its transmission."
Jan 2 J Antimicrob Chemother letter


Study identifies risk factors for community-acquired, ESBL UTIs

Originally published by CIDRAP News Jan 3

A case-control study today in Open Forum Infectious Diseases has found that patients in the community who have indwelling urinary catheters, a history of recurrent urinary tract infections (UTIs), or recent antimicrobial use are at heightened risk for UTIs caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.

In the study, researchers from the University of Utah and Intermountain Healthcare identified 251 patients admitted to Intermountain's 22-hospital system with an ESBL UTI from 2001 through 2016 and matched them 1:1 with patients who had UTIs caused by non-ESBL Enterobacteriaceae. They were looking to determine risk factors for community-acquired ESBL UTIs, which have been rising in recent years. ESBL infections can be difficult to treat and are associated with longer hospital stays and higher morbidity and mortality.

In a univariate analysis, the researchers found that a history of repeated UTIs, neurogenic bladder, urinary catheter presence at admission, and previous exposure to third-generation cephalosporins or fluoroquinolones within 3 months were associated with a higher risk of ESBL UTIs. After controlling for severity of illness and comorbid conditions during the multivariate analysis, history of repeated UTIs (adjusted odds ratio [aOR], 6.40; 95% confidence interval [CI], 3.42 to 12.66, P < 0.001), presence of urinary catheter at admission (aOR, 2.36; 95% CI, 1.15 to 4.98, P < 0.05), and prior antibiotic exposure (aOR, 7.98; 95% CI, 2.92 to 28.19, P < 0.001) remained associated with heightened risk.

The authors note that patients with ESBL and non-ESBL UTIs often have similar symptoms, which makes decisions about empiric antibiotic therapy more difficult. They say the findings could help clinicians initiate effective antibiotic therapy earlier and improve clinical outcomes.  
Jan 3 Open Forum Infect Dis abstract


Review supports MRSA nasal screening in pneumonia patients

Originally published by CIDRAP News Jan 2

A systematic review of 19 studies has found that methicillin-resistant Staphylococcus aureus (MRSA) nasal screening for patients with pneumonia has a high negative predictive value and could be a valuable tool for antibiotic stewardship programs (ASPs). The findings appear today in the Annals of Pharmacotherapy.

The 19 observational and retrospective studies, published from 1990 through 2018, included 21,790 patients, mostly in intensive care units. The review found that the negative predictive value for MRSA nasal screening ranged from 76% to 99.4% across all types of pneumonia, with most studies suggesting that few patients who are screened for MRSA soon after hospital admission and have a negative result will actually develop MRSA pneumonia.

Further evaluation found that using nasal MRSA screening for anti-MRSA antibiotic de-escalation could reduce the use of vancomycin in pneumonia patients and provide additional cost benefits. The reviewers determined that a cutoff of 7 days between nasal swab and culture or infection onset seems most appropriate for using the test to de-escalate anti-MRSA antibiotics.

"Consideration for the inclusion of the utility of MRSA nasal screening in MRSA pneumonia should be made for future pneumonia and ASP guidelines," the authors conclude. "Additional studies are warranted to fully evaluate specific pneumonia classifications, culture types, culture timing, and clinical outcomes associated with the use of this test in patients with pneumonia."
Jan 2 Ann Pharmacother study


Carbapenem-resistant Acinetobacter strains identified in Brazilian ICU

Originally published by CIDRAP News Dec 31, 2018

Brazilian researchers report in PLOS One that strains of carbapenemase-producing Acinetobacter baumannii in intensive care unit (ICU) patients at a tertiary teaching hospital were associated with high mortality and several healthcare-related risk factors.

To identify risk factors associated with the strains, the researchers conducted a case-control study among patients hospitalized in two ICUs at a hospital in Mato Grosso du Sul state from September 2013 through April 2015. For each patient admitted with an OXA-23–producing A baumannii strain isolated from clinical specimens during the study period, a respective control patient was selected from adult inpatients matched for age, clinical manifestation, and hospital ward. All medical, nursing, and microbiologic records of hospitalized patients were reviewed.

Of the 275 episodes of A baumannii infection or colonization observed during the study period, 41 OXA-23–producing strains were isolated from ICU patients with multiple comorbidities. No differences were observed between the 41 case and 41 control patients regarding baseline demographic data, but a multivariate analysis showed that acquisition of OXA-23–producing A baumannii strains was associated with the use of nasogastric tubes, hemodialysis, and therapy with cephalosporins. Analysis of patient outcomes revealed that patients with OXA-23–producing A baumannii had a mortality rate of 34.1%.

All 41 OXA-23–producing A baumannii isolates were multidrug-resistant and susceptible to only amikacin, gentamicin, tigecycline, and colistin. Polymerase chain reaction analysis identified the insertion sequence ISAba1—which is associated with increased gene expression leading to high carbapenem resistance—in all the isolates. Pulsed-field gel electrophoresis analysis revealed that 26 of the isolates belonged to the sequence type (ST) 79 lineage, a high-risk clone in ICUs that's been reported in several multidrug-resistant A baumannii hospital outbreaks in Brazil.

The authors of the study report that implementation of infection control measures, including hand hygiene promotion in the ICU, isolation of patients infected or colonized with carbapenem-resistant strains, and environmental cleaning and disinfection of reusable medical equipment helped reduce the incidence of carbapenem-resistant A baumannii after November 2014.
Dec 28 PLOS One study


Randomized trial supports use of mupirocin in NICU infants

Originally published by CIDRAP News Dec 28, 2018

The results of a phase 2 randomized clinical trial indicate that application of the topical antibiotic mupirocin to multiple body sites was safe and efficacious in eradicating Staphylococcus aureus from infants in the neonatal intensive care unit (NICU). The findings were published in Pediatrics.

In the multicenter study, infants under the age of 24 months in the NICU at eight US hospitals were screened for nasal S aureus colonization, and colonized infants who met eligibility criteria were randomly assigned 1:1 to receive either 5 days of mupirocin applied to the intranasal, periumbilical, or perianal areas or no mupirocin. Because S aureus is the second-leading cause of late-onset sepsis among infants in the NICU and colonization of the nasal mucosa or skin frequently precedes invasive infection, mupirocin application and other decolonization strategies have been explored as ways to prevent infection. However, data supporting these strategies has been limited.

From April 2014 to May 2016, 1,140 infants tested positive for S aureus, and 155 were randomly assigned. The investigators assessed safety and the effect of mupirocin treatment on primary decolonization (8 days) and persistent decolonization (22 days). Mupirocin was generally well-tolerated, though mild rashes were observed significantly more often in the infants who were treated. Primary decolonization occurred in 62 of 66 (93.9%) treated patients compared with 3 of 64 (4.7%) untreated infants, yielding on overall efficacy of 95%.  By day 22, 21 of 46 (45.7%) treated infants remained decolonized, compared with 1 of 48 (2.1%) of the untreated infants.

The authors of the study say the finding that more than 50% of the mupirocin-treated infants became recolonized after 22 days suggests supplemental strategies may be needed for infants undergoing lengthy hospitalization, including decolonization of family members and caregivers.
Dec 26 Pediatrics abstract

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