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

Study links resistance rates with national income status

A study of antibiotic resistance surveillance systems and gross national income (GNI) in 67 countries suggests that low-income status is linked to higher rates of invasive infections caused by antibiotic-resistant pathogens, German and Italian researchers reported today in The Journal of Antimicrobial Chemotherapy.

Of the 67 countries with available surveillance data from 2012 onward, 38 (57%) were high income, 16 (24%) were upper-middle income, 11 (16%) were lower-middle income, and 2 (3%) were low income, based on GNI per capita. For the purposes of the study, the researchers focused on the top-ranked antibiotic-resistant bacteria from the World Health Organization's 2017 priority pathogens list: carbapenem-resistant (CR) Acinetobacter spp, CR Klebsiella spp, CR Pseudomonas aeruginosa, third-generation cephalosporin–resistant (3GCR) Escherichia coli, 3GCR Klebsiella spp, vancomycin-resistant Enterococcus faecium, and methicillin-resistant Staphylococcus aureus(MRSA). The association between antibiotic resistance prevalence data and GNI per capita was investigated individually for each bacterium through linear regression analysis.

The analysis showed a significant inverse association (P < 0.0001) between the prevalence of infections caused by the selected pathogens and GNI per capita. The highest rate of increase per unit decrease in log GNI per capita was observed in 3GCR Klebsiella  (22.5%; 95% confidence interval [CI], 18.2% to 26.7%; P < 0.0001), followed by CR Acinetobacter  (19.2%; 95% CI, 11.3% to 27.1%; P < 0.0001) and 3GCR E coli (15.3%; 95% CI, 11.6% to 19.1%; P < 0.0001). The rate of increase per unit decrease in log GNI per capita was slightly lower in gram-positive bacteria (MRSA 9.5%, 95% CI 5.2% to 13.7%, P < 0.0001; VR E faecium 1%; 95% CI, −6.3% to 8.3%, P = 0.78).

The authors of the study suggest that several factors could explain the relationship between increased antibiotic resistance and lower income status, including suboptimal hygiene conditions, inadequate sanitation, lack of access to clean water, climate, and unregulated access to antibiotics.

They conclude, "Public health interventions designed to limit the burden of antimicrobial resistance should also consider determinants of poverty and inequality, especially in lower middle-income and low income countries."
Sep 6 J Antimicrob Chemother study

Impact of national stewardship interventions hard to assess, analysis finds

In another study today in the Journal of Antimicrobial Chemotherapy, researchers conducting a systematic review of national initiatives to reduce the overuse and misuse of antibiotics report that more evidence is needed to assess their long-term impact.

The researchers identified 34 articles detailing interventions in 21 high- and upper-middle-income countries. The differences in study designs, populations, analytical strategies, and effect measures made it impossible to conduct a meta-analysis. But the researchers said the overall evidence suggested that interventions addressing inappropriate antibiotic access, including antibiotic committees, clinical guidelines, and prescribing restrictions, were effective at reducing antibiotic use and prescribing. The evidence for other interventions, such as education campaigns aimed at healthcare professional and the general public, was mixed, with several studies showing no impact on overall antibiotic consumption.

The researchers also found that only five of the studies established a direct link between antibiotic consumptions and resistance rates, and that these studies reported mixed results. "Establishing an association between antibiotic consumption and resistance rates could help to determine the extent to which reducing antibiotic consumption is an effective intervention, as well as to assess how this compares with other types of interventions, such as improving vaccination coverage and reducing animal antibiotic use," they write.

The researchers conclude, "Based on the available evidence from primarily high-income countries, our systematic review highlights that strategies to reduce inappropriate demand and access to antibiotics appear to have a quantifiable impact primarily on antibiotic consumption, but more evidence is needed on the long-term impacts of these interventions, such as increases in the consumption of antibiotic subtypes, impacts on prevalence of antibiotic-resistant organisms, as well as the health and economic burden of these infections."
Sep 6 J Antimicrob Chemother study

Trump administration sued over expanded use of antibiotics on citrus trees

Originally published by CIDRAP News Sep 5

The Center for Biological Diversity today sued the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA) for refusing to provide documents related to the EPA's decision to allow expanded use of medically important antibiotics on citrus trees.

The organization filed a Freedom of Information Act (FOIA) request for the documents in March. The lawsuit says the delay in providing those records is a violation of FOIA, and is asking the court to order the agencies to provide the documents.

In December 2018, the EPA approved expanded use of the antibiotic oxytetracycline in Florida and other citrus-growing states to combat citrus greening disease, a bacterial infection that has devastated the citrus industry. It's currently reviewing a request for expanded use of streptomycin.

Under expanded use, citrus growers could use 388,000 pounds of oxytetracycline and 650,000 pounds of streptomycin—amounts far greater than those used to treat human bacterial infections. The Center for Biological Diversity and other concerned groups, including the Centers for Disease Control and Prevention (CDC), have warned that spraying massive amounts of antibiotics on citrus trees could spur antibiotic resistance in soil bacteria, and resistant pathogens in the soil could ultimately impact human health.

Earlier in the year, the center obtained a 2017 CDC report to the EPA that concluded that using antibiotics as pesticides has the potential to select for antibiotic-resistant bacteria in the environment, including bacteria that pose a risk to human health. The organization is currently seeking all communications among the EPA, FDA, and CDC regarding the use of oxytetracycline and streptomycin as pesticides.

"The Trump administration is recklessly endangering public health by allowing these human medicines to be sprayed on crops," Center for Biological Diversity senior scientist Nathan Donley, PhD, said in a press release from the organization. "The EPA is trying to conceal conversations revealing the risks these careless actions pose to public health and wildlife."
Sep 5 Center for Biological Diversity press release
Aug 29 CIDRAP News story "Lawmakers urge EPA to rethink use of antibiotics on citrus trees"

Telehealth-based stewardship program shows promise in 2 small hospitals

Originally published by CIDRAP News Sep 5

Implementation of a telehealth-based antimicrobial stewardship program (ASP) at two Pennsylvania community hospitals was associated with a nearly 25% reduction in broad-spectrum antibiotic use, researchers reported today in Clinical Infectious Diseases.

The telehealth-based ASP implemented in two community hospitals in the Heritage Valley Health System involves hospital pharmacists without previous stewardship training who were trained to provide audit and feedback to providers. During weekly hour-long telehealth meetings, the pharmacists and infectious disease (ID) physicians from another health system (Allegheny Health Network) review patients on broad-spectrum antibiotics and those admitted with lower respiratory tract infections and skin and soft-tissue infections. The ID physicians then make ASP intervention recommendations that are relayed to provider teams by the pharmacists.

To study the impact of the program, researchers from both health systems tracked antibiotic use and local ID consults  at the two hospitals over a12-month baseline period and the 6-month intervention period, and estimated the antibiotic cost savings. Their analysis found that during the intervention period (March 2018 through August 2018), 1,419 recommendations were made, of which 1,262 (88.9%) were accepted. Broad-spectrum antibiotic use decreased by 24.4% from the baseline period (342.1 vs 258.7 days of therapy per 1,000 patient-days). ID consults increased by 40.2% (15.4 vs 21.5 consults per 1,000 patient-days), and the estimated annualized cost savings on antibiotic expenditures was $142,629.

"In conclusion, we describe a practical model by which an intense ASP may be implemented in a community hospital setting via telehealth," the authors of the study write. "It represents a unique and viable strategy by which community hospitals not affiliated with a large system may gain access to robust stewardship support, and a mechanism by which larger institutions with such infrastructure may assist unaffiliated hospitals with expansion of ASP efforts."
Sep 5 Clin Infect Dis abstract

Pharmacist-led review of outpatient antibiotics linked to better outcomes

Originally published by CIDRAP News Sep 4

A pharmacist-led review of outpatient cultures and antibiotic treatment at a Veterans Administration (VA) hospital was associated with decreased rates of treatment failure and hospital admission, researchers reported yesterday in the American Journal of Infection Control.

In the prospective study, a team of ID pharmacists from the VA Western New York Healthcare System were alerted when oral antibiotics were prescribed for outpatient use, paying special attention to prescriptions with patient cultures. The cultures were reviewed daily to ensure the appropriate antibiotic choice, dose, and duration, and to evaluate for drug allergies and interactions. Interventions were communicated directly to providers and included changes to antibiotic regimens, diagnostic recommendations, and patient counseling. The primary objective was to compare outcomes in patients with accepted interventions versus those with rejected interventions.

From January 2018 to January 2019, the ID pharmacists reviewed a total of 7,360 antibiotic orders and intervened on 20.1% (n = 194) of encounters with related cultures. Interventions were most frequent in the emergency department (42%), followed by primary care (38.7%). Ciprofloxacin required the most interventions (26%), followed by third-generation cephalosporins (22%). The intervention acceptance rate was 76%, with 73.8% of interventions involving a change to the prescribed antibiotic regimen. Intervention was associated with decreased rates of 30-day treatment failure (5% vs 28%, P < .001) and 30-day admission (0.7% vs 11%, P = .001) when interventions were accepted rather than rejected. There was no difference in 30-day mortality.

The authors of the study conclude, "Culture review services can improve patient care by closing a gap in follow up between various levels of care in the outpatient setting. Implementing a culture review service can decrease rates of re-presentation to the health care system, thereby decreasing health care utilization and saving health care dollars."
Sep 3 Am J Infect Control study

Oral vancomycin for C diff doesn’t raise risk for VRE infection, study finds

Originally published by CIDRAP News Sep 4

A nationwide study of VA patients who had Clostridioides difficile infection (CDI) indicates that a shift to oral vancomycin does not increase the risk of developing vancomycin-resistant enterococci (VRE) infection, researchers from the University of Utah School of Medicine reported yesterday in Clinical Infectious Diseases.

The researchers conducted a retrospective, propensity-matched cohort study of patients within the VA system who were diagnosed as having CDI from January 2006 through December 2016. The goal was to assess how oral vancomycin and metronidazole impact the risk of developing a clinically relevant VRE infection.

While metronidazole has long been the first-line treatment for CDI, the newest clinical practice guidelines from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America recommend treating all initial CDI episodes with vancomycin. The patients treated with oral vancomycin were compared with those treated with metronidazole, and the primary outcomes of interest were positive VRE clinical cultures within 3 and 6 months after treatment initiation.

Overall, 5,267 patients treated with vancomycin alone were matched to one or more metronidazole-treated patients, for an average total of 10,513 patients included in the analysis. The results from multivariable models within the propensity-matched cohorts showed that patients treated with oral vancomycin were no more likely to develop VRE within 3 months than metronidazole-treated patients (adjusted relative risk [RR], 0.96; 95% CI, 0.77 to 1.20), equating to an absolute risk difference of -0.11% (95% CI, -0.68% to 0.47%). RR estimates were similar for clinical cultures at 6 months.

The authors of the study conclude that in settings of stable CDI incidence, replacement of metronidazole with oral vancomycin is unlikely to be a significant driver of increased VRE risk, and that continued antimicrobial stewardship and infection control efforts will likely have a greater impact on VRE acquisition and transmission.

"Future research efforts should focus on identifying patients with self-limiting CDI who may not need antibiotic therapy and on balancing the tradeoffs of vancomycin and metronidazole with a broader range of important risks and benefits," they write.
Sep 3 Clin Infect Dis abstract

Young doctor survey shows influence of culture, specialty on antibiotic use

Originally published by CIDRAP News Sep 4

A survey of young European physicians in training has found that country of specialization and type of specialty are the most important determinants of attitudes toward antibiotic use and resistance. The findings were detailed yesterday in the Journal of Antimicrobial Chemotherapy.

The cross-sectional survey, designed by an international team of experts for the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), was focused on young doctors after graduation from medical school and the start of specialty training. The idea was to see which factors influence the culture and habits of antibiotic prescribing, and whether socio-cultural environmental influences play a role. Principle component analysis (PCA) and bivariate and multivariate analyses were used to investigate the differences among young doctors according to their country of specialization, specialty, year of training, and gender.

The survey was completed by 2,842 participants from 29 countries and 61 specialties, and further analysis was performed on 2,366 participants from six countries (Spain, France, Italy, Portugal, Greece, and Slovenia) with more than 100 respondents. Young doctors from Italy reported the most frequent prescribing and those from Slovenia the least, and trainees in infectious diseases and related specialties were more frequent prescribers than colleagues from surgery or internal medicine. Very few differences were associated with the year of training or gender. More than half of those surveyed (54.2%) prescribed antibiotics as instructed by their mentor.

PCA revealed five dimensions of antibiotic prescribing culture: self-assessment of knowledge, consideration of side effects, perception of prescription patterns, consideration of patient sickness, and perception of antibiotic resistance. Multivariate analyses indicated that the country of specialization had the strongest influence on all five dimensions, followed by specialty training, with the strongest effect observed on self-assessed knowledge and perception of antibiotic resistance.

The authors say the survey results indicate a need for education in responsible antibiotic prescribing at an international level and in all specialty curricula.
Sep 3 J Antimicrob Chemother study

CARB-X to fund Group A Strep vaccine candidate

Originally published by CIDRAP News Sep 3

CARB-X today announced an award of more than $1.6 million to biopharmaceutical company SutroVax of Foster City, Calif., to develop a vaccine to prevent infections caused by Group A Streptococcus.

The Group A Streptococcus (GAS) bacterium can cause a variety of infections that range from minor illnesses such as pharyngitis (strep throat)—a major source of antibiotic prescriptions worldwide—to more severe and deadly infections like necrotizing fasciitis. It can also cause post-infectious immune-mediated rheumatic heart disease, which is a leading cause of mortality in the developing world. There is currently no vaccine for GAS. 

According to a press release from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), SutroVax's vaccine candidate consists of a GAS carbohydrate antigen combined with an immunogenic protein carrier, and has been modified to avoid triggering an immune response that can adversely affect human cardiac or brain tissue.

"The SutroVax project is in the early stages of development but if successful and approved for use in patients, it could save lives, improve public health and strengthen health security worldwide," said CARB-X executive director Kevin Outterson, JD.

SutroVax could receive an addition $13.4 million in funding if certain project milestones are met.
Sep 3 CARB-X press release

Study highlights drawbacks of pre-operative urine testing

Originally published by CIDRAP News Sep 3

A study by Boston-area researchers indicates pre-operative urine screening and identification of pyuria increases antibiotic exposure but does not improve post-operative outcomes.

In the study, which was published in Clinical Infectious Diseases, researchers from the VA Boston Healthcare System, Boston University School of Medicine, and Harvard Medical School analyzed a cohort of pre-operative patients within the national VA system who had a urinalysis performed during the 30-day pre-operative period. The primary exposure of interest was the presence of pyuria, which is frequently treated with antibiotics, even when patients are asymptomatic. The primary outcome was antibiotic initiation. Secondary outcomes included post-operative surgical site infections (SSIs), urinary tract infections (UTIs), and C difficile infections.

Of the 70,277 patients who underwent surgical procedures at the VA during the study period (October 2008 through September 2013), 41,373 patients had a urinalysis performed in the 30-day window prior to surgery, and 3,617 had varying degrees of pyuria detected (43.8% low, 21.9% moderate, and 34% high). In patients with any degree of pyuria, 887 (24.5%) received antimicrobials, and the odds of receiving antimicrobials increased as the degree of pyuria increased (low pyuria, 14.7%, moderate pyuria, 24.0%, high pyuria, 37.4%).

Pre-operative pyuria was associated with post-operative C difficile infections (adjusted odds ratio [aOR], 1.7; 95% CI, 1.2 to 2.4), but the risk was higher in patients who received antimicrobials (aOR 2.4; 95% CI, 1.7 to 3.4). Pyuria was not associated with SSI but was associated with increases in UTI after orthopedic (aOR, 1.5; 95%, 1.1 to 2.1) and vascular procedures (aOR, 2.5; 95% CI, 1.4 to 4.5). However, antimicrobial therapy did not significantly change this association.

The researchers say the study highlights the importance of diagnostic stewardship and avoiding low-value tests.

"These findings underscore the need to avoid testing in asymptomatic patients to reduce unnecessary and excessive antimicrobial treatment in patients who will not benefit from the intervention," the authors of the study write. "Once something is seen in clinical medicine, it cannot be unseen; thus, the best strategy is to not perform tests that do not have a clinical indication."
Aug 30 Clin Infect Dis abstract

More ASP training for medical residents linked to better prescribing

Originally published by CIDRAP News Sep 3

A study conducted at a small community teaching hospital in Michigan has found that adding antibiotic stewardship-focused educational training sessions for medical residents was associated with better adherence to antibiotic prescribing guidelines, researchers reported yesterday in Infection Control and Hospital Epidemiology.

The retrospective cohort study looked at antibiotic prescribing practices for three common infections (pneumonia, cellulitis, and UTI) among three physician services at the hospital—the family medicine (FM) resident service, the internal medicine (IM) resident service, and the hospitalist service. While all three services receive daily audit and feedback on antibiotic prescribing and baseline ASP training, the FM residents also receive bi-weekly stewardship-focused rounding and education sessions with an ASP physician and a clinical pharmacist. The aim of the study was to compare guideline-concordant therapy among the three groups, based on the hospital's ASP guidelines.

Of 1,572 patients discharged from the hospital from July 2016 through June 2017 with diagnoses of pneumonia, cellulitis, or UTI, 295 were eligible for inclusion; 96 were treated by the FM group, 69 by the IM group, and 130 by the hospitalist group. The percentage of patients receiving guideline-concordant antibiotic selection empirically was similar between groups for all diagnoses (FM, 87.5%; IM, 87%; hospitalist, 83.8%; P = .702), and no differences were observed in appropriate definitive antibiotic selection among groups (FM, 92.4%; IM, 89.1%; hospitalist, 89.9%; P = .746). But the FM resident service was more likely to prescribe a guideline-concordant duration of therapy across all diagnoses (FM, 74%; IM, 56.5%; hospitalist, 44.6%; P < .001). 

"The FM team overall prescribed more appropriate durations of therapy than the IM and hospitalist services when all disease states were considered, which may reflect the added benefit of consistent biweekly presence of the ASP team during patient care rounds on top of routine audit and feedback," the authors of the study write. "These results suggest that more frequent and multifaceted interactions with the ASP team may positively impact guideline-concordant prescribing habits."
Sep 2 Infect Control Hosp Epidemiol abstract