ASP Scan (Weekly) for Aug 18, 2017

Antifungal susceptibility testing
Bacteriophage therapy
Expanded AMR monitoring
MDR- and XDR-TB in China
Patient empowerment tool for hand hygiene
Recurrent C diff treatment
Multidrug-resistant BSIs in India

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

Data show gaps in antifungal susceptibility testing at US hospitals

A new study by researchers with the US Centers for Disease Control and Prevention indicates that availability of antifungal susceptibility testing (AFST) at US hospitals has improved in recent years, but substantial gaps remain.

The study, published Aug 16 in Open Forum Infectious Diseases, analyzed data for 2011 and 2015 from the Patient Safety Component Annual Hospital Survey, completion of which is required for all hospitals participating in the National Healthcare Safety Network. Hospital characteristics were examined in a multivariate analysis that included medical school affiliation, bed size, availability of AFST in the hospital's own laboratory or an affiliated medical center, and rates of Candida central-line associated bloodstream infections (CLABSIs).

Of the 4,690 acute care hospitals that participated in the survey in 2015, 95.5% offered AFST of any type, but only 28.4% offered AFST at their own laboratory or at an affiliated medical center, and 32.5% offered reflexive AFST. Pediatric (55.3%) and oncology (64.7%) hospitals more commonly offered AFST at their own laboratory or an affiliated medical center compared with general hospitals (28.0%), and more commonly offered reflexive testing (pediatric, 57.6%; oncology, 70.6%; and general hospitals, 33.0%). Of the general hospitals with a non-zero Candida CLABSI rate, 37.5% offered AFST at their own lab or an affiliated medical center, and 42.2% offered reflexive AFST.

Comparison of the 3,947 hospitals that completed surveys in 2011 and 2015 showed that the proportion of hospitals offering any AFST increased from 91.9% to 95.3%, while the proportion of hospitals offering AFST at their own laboratory or an affiliated medical center increased from 26.2% to 28.4%, and the proportion of hospitals offering reflexive AFST rose from 25.5% to 33.1%.

Factors associated with offering AFST at the hospital's own laboratory or an affiliated medical center included having a medical school affiliation (adjusted odds ratio [aOR], 1.46), having a non-zero Candida CLABSI rate (aOR, 1.41), and having a higher number of hospital beds (up to aOR of 3.23 for hospitals with 500 beds or more compared with hospitals with fewer than 100 beds). Factors associated with offering reflexive AFST included having AFST available at a hospital's own laboratory or an affiliated medical center (aOR, 9.61), medical school affiliation (aOR, 1.24), a non-zero CLABSI rate (aOR, 1.24), and higher number of hospital beds (aOR, 1.73).

The authors say that with the rise in drug-resistant Candida species, including multidrug-resistant Candida auris and echinocandin-resistant C glabrata, it's important that clinicians have access to AFST to make optimal treatment decisions.
Aug 16 Open Forum Infect Dis abstract


Case study: Phage therapy successfully treats multidrug-resistant infection

A case study in Antimicrobial Agents and Chemotherapy describes the successful use of a personalized bacteriophage-based therapeutic treatment in a patient with a life-threatening multidrug-resistant (MDR) infection.

The patient, a 68-year-old diabetic man, developed necrotizing pancreatitis that was complicated by an MDR Acinetobacter baumannii infection. Despite treatment with courses of vancomycin, meropenem, colisitin, tigecycline, and rifampin, the patient's condition continued to deteriorate for 4 months, and he became unresponsive. Because of the availability of any additional effective antimicrobial agents to treat the infection, an application was submitted to the Food and Drug Administration to request authorization to treat the infection with a combination of phages.

Using a cocktail of nine different phages that showed lytic activity against A baumannii, physicians initiated phage therapy intravenously and percutaneously into abscess cavities on day 109 of the infection, and a clear turning point was observed within 48 hours. Over the ensuing 11 weeks, the patient continued to receive bacteriophage therapy along with an antibiotic regimen of meropenem, fluconazole, and minocycline, during which time he showed steady clinical improvement. On day 245, the patient was discharged, and he subsequently returned to work.

"This case supports further study of the use of phage therapy in treating patients suffering from MDR bacterial infections with limited therapeutic options," the authors write. They add that future clinical trials focusing on delineating the extent to which bacteriophage-based therapeutics can be used as a last resort, either on their own or as an adjunct to traditional antibiotics, are warranted.
Aug 14 Antimicrob Agents Chemother study


Global health experts call for expanded AMR monitoring

A collection of infectious disease and global health experts says expanded national and subnational monitoring of countries' efforts to limit antimicrobial resistance (AMR) is needed to help governments maintain their commitments to tackle the problem.

In a commentary yesterday in PLoS Medicine, the group writes that while knowledge about the causes, consequences, and magnitude of AMR has improved in recent years, large information gaps about how nations are attempting to limit AMR remain. Surveillance data for low- and middle-income countries is lacking, variety in methodology and data collection hampers comparability across regions, the understanding of the clinical and public health burden of AMR is limited, and few data exist on how countries are responding to the problem. 

For successful implementation of the World Health Organization's (WHO's) Global Action Plan on AMR to occur, the group argues, these gaps need to be addressed. Expanded monitoring and harmonized data collection will enable countries to benchmark their national and subnational performance against other countries and use the best scientific evidence to shape policy, and it could result in greater involvement of health professionals and the public. In addition, the experts suggest regular data collection across countries could serve as a basis for a longitudinal assessment of AMR control that guides implementation of national and subnational policies.

"Ultimately, the goal of expanded monitoring is to trigger a virtuous circle in which the collection of data constantly improves our understanding and capacity to tackle AMR, which in turn calls for new evidence," the authors write.

The authors argue that the goal of expanded monitoring should be to "measure the problem and progress across its multiple dimensions while at the same time making it more tractable to policy makers and the public." Although there are many challenges to expanding monitoring programs, they suggest the focus should be on choosing an appropriate scientific approach to conceptualizing AMR and related control efforts; defining what to measure; selecting appropriate measurements from human, animal, and planetary health; developing surveillance capabilities; and creating an online platform that employs data visualization methods to communicate findings. 

The authors say the WHO should lead the process but also call for a broad coalition of global health actors to assist in the effort.
Aug 17 PLoS Med commentary


Study finds poor treatment outcomes for MDR- and XDR-TB patients in China

Originally published by CIDRAP News Aug 16

A study today in BMC Infectious Diseases reports that patients with multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB) in China's Hunan province had low rates of treatment success.

The aim of the retrospective study, which used data from patients in Hunan province who were treated for TB from 2011 through 2014, was to assess treatment outcomes for patients with MDR-TB (TB resistant to at least isoniazid and rifampicin) and XDR-TB (MDR-TB plus resistance to any fluoroquinolone and at least one second-line injectable drug) and identify factors associated with poor treatment outcomes. Information about patients with drug-resistant TB in China, one of the top 30 MDR-TB and TB burden countries in the world, is limited.

Of the 481 bacteriologically-confirmed patients, 10 (2%) had XDR-TB and 471 (98%) had MDR-TB. Evaluation of treatment outcomes showed that 262 patients (54%) were cured, 14 (3%) completed treatment, 13 (3%) died, 63 (13%) had treatment failure, and 130 (27%) were lost to follow-up. For the entire cohort, the treatment success rate was 57% (n=275), with a success rate of 58% for MDR-TB (n=272) and 30% for XDR-TB (n=3 patients). Resistance to oxifloxacin was an independent predictor of poor treatment outcomes (associated hazard ratio [AHR] = 3.1) and unfavorable treatment outcomes (AHR = 1.7), and those patients who started treatment during 2011-2012 had nearly three times the risk of treatment failure (AHR = 2.8) as those who started treatment in 2014.

The authors note that while the overall treatment success rate of 57% for MDR- and XDR-TB patients in Hunan province is consistent with reported global (52%) and national (56%) MDR-TB treatment success rates, it is still far short of the World Health Organization target of 75% treatment success.

"This low rate of treatment success among MDR-TB patients poses a serious threat for national TB control efforts as patients may develop additional resistance and may also transmit drug resistant forms of TB to others," they write.
Aug 16 BMC Infect Dis study


Surveys examine patients' role in promoting hand hygiene

Originally published by CIDRAP News Aug 16

A study yesterday in the American Journal of Infection Control suggests most parents and adult patients feel it's their role to remind healthcare providers to perform hand hygiene, while providers are less open to the idea.

In the study, researchers at a tertiary care teaching hospital in Morgantown, W. Va., performed a cross-sectional survey of parents of hospitalized children, adult patients, and primary care physicians to examine their attitudes toward a new patient empowerment tool (PET) that can be used by patients to remind doctors and nurses to wash their hands. The PET, introduced in 2015, consists of a picture with a reminder phrase (eg "Did you wash your hands?") attached to a tongue depressor. From 2015 to 2016, hand hygiene rates at the hospital increased from 48% to 75%.

A total of 222 parents and adult patients responded to the survey (114 parents and 108 adult patients). Parents were more likely than adult patients to feel that it's their role to speak up if a physician (95.6% vs. 77.6%) or a nurse (99.1% vs. 86.0%) did not perform hand hygiene. A smaller number of parents (77% for physicians and 81.4% for nurses) and adult patients (64.8% for physicians and 71.2% for nurses) felt comfortable using the PET to remind healthcare workers to perform hand hygiene.

Of the 89 physicians who responded to the survey (29 residents 60 attending physicians), only 54.9% (65.5% of resident physicians and 49.0% of attending physicians) agreed that patients should be involved in reminding providers to perform hand hygiene. Of the physicians who did not support patient involvement, 37% felt it was not the patient's responsibility to remind them to perform hand hygiene, 16.2% said it was embarrassing to the doctor, and 13.5% said it would negatively affect the doctor patient relationship. Physicians said they would be more likely to sanitize their hands if a patient made a verbal request rather than using the PET.

"Health care providers should not see patient participation as a threat, but instead as another tool to improve patient care," the authors write. "We should work to make patients and families more comfortable in participating in their care, but even more importantly, we need to change the culture of medicine."

Hand hygiene is considered the single most effective measure to reduce health-associated infections, which occur in 5% to 10% of patients admitted to acute care hospitals in the United States. 
Aug 15 Am J Infect Control study


Study: Bezlotoxumab reduces hospital readmission in C difficile patients

Originally published by CIDRAP News Aug 15

A new study in Clinical Infectious Diseases reports that treatment with bezlotoxumab reduced 30-day hospital readmissions in patients with high risk of recurrent Clostridium difficile infection(CDI).

Bezlotoxumab is a human clonal antibody that acts against toxin B, the primary virulence factor in causing CDI symptoms. The drug is used in combination with antibiotic treatment to reduce the risk of recurrent CDI, which occurs in approximately 25% of patients after completing initial antibiotic therapy. In two large phase 3 randomized clinical trials, MODIFY I and MODIFY II, bezlotoxumab significantly reduced recurrent CDI and had a favorable safety profile. The drug was approved for use in C difficile patients by the Food and Drug Administration in October 2016.

In the current study, researchers used pooled data from MODIFY I and MODIFY II to estimate 30-day CDI-associated hospital readmission rates and all-cause readmission rates among a subgroup of patients who were hospitalized at the time of randomization and for participants who had high-risk prognostic factors for recurrent CDI. One group of patients received bezlotoxumab, and the other group received a placebo.

In the 30 days after hospital discharge, the 530 patients treated with bezlotoxumab had fewer CDI-associated hospital readmissions compared to the 520 patients in the placebo group (absolute difference -6.1%, relative difference -53.4%), and fewer all cause readmissions (absolute difference -3.7%, relative difference -12.1%), although that difference did not reach statistical significance. Bezlotoxumab also reduced CDI-associated hospital readmissions in patients at high risk of recurrent CDI, including those aged 65 years and older (absolute difference -8.3%, relative difference -60%) and those with severe CDI (absolute difference -7.7%, relative difference -69%).

The authors say the results of the analysis, combined with previously reported findings, provide support for using bezlotoxumab as a treatment option in CDI patients.
Aug 11 Clin Infect Dis study


Study finds high mortality for colistin- and carbapenem-resistant BSIs

Originally published by CIDRAP News Aug 14

An in-hospital mortality rate of nearly 70% was observed in Indian patients with dual colistin- and carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CCRKP BSI), researchers report in a new study in the American Journal of Infection Control.

In a small trial conducted at a single tertiary care hospital in India from January 2011 through December 2015, the researchers found that out of 75 patients identified as having CCRKP BSI, 52 (69.3%) died in hospital. Among the patients who died, 27 died within 48 hours of developing bacteremia.

In univariate analysis, risk factors significantly associated with increased mortality included intensive care unit stay at the time of BSI (66% of patients who survived vs 88% of patients who died), length of stay prior to BSI onset (10.1 vs 19.3 days), Pitt bacteremia score of 4 or greater (21.7% vs 84.6%), and pneumonia as the source of BSI (4.3% vs 26.9%). In multivariate analysis, only Pitt bacteremia score of 4 or greater was significantly associated with increased mortality (odds ratio 19.8). Carbapenem-based combination therapy was administered to 55 patients (17 of 23 patients who survived, 38 of 52 patients who died), but no survival benefit was observed.

The authors note that the findings are consistent with those of a previous study from Greece that reported a 75% in-hospital mortality among patient with CCRKP BSI. The emergence of CCRKP strains in India is believed to be the result of increasing use of polymixin-based therapies to treat carbapenem-resistant K pneumoniae infections.

"In conclusion, CCRKP BSIs are associated with high mortality," the authors write. "There is an urgent need for new antibiotics to treat these infections."
Aug 11 Am J Infect Control abstract

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