ASP Scan (Weekly) for Mar 08, 2019

Home therapy for kids' cellulitis
Antibiotics and UTI relapse
Outpatient surgery overprescribing
Resistance prevalence and sepsis
Resistant gonorrhea strain
Empiric antibiotics and UTI
Surgery-linked resistant Pseudomonas
Preventing healthcare-related infection
Resistance and sustainable development
New CARB-X funding
ESBL prediction models

Australian study shows promise for home IV antibiotics for peds cellulitis

A non-inferiority trial in Australia has determined that intravenous (IV) ceftriaxone at home may be an alternative to IV flucloxacillin in the hospital for children who have cellulitis, according to a study yesterday in The Lancet Infectious Diseases.

An area of increased focus in antimicrobial stewardship has been outpatient parenteral antimicrobial therapy (OPAT), which involves IV antibiotic administration in the home rather than at the hospital. OPAT can reduce costs, but the authors of the new study also wanted to ensure it provided good outcomes. They write that their study is the first randomized controlled trial of any acute infection requiring IV antibiotic therapy in children comparing efficacy and safety of home or ambulatory treatment with standard hospital management.

One hundred ninety children 6 months to 18 years old were randomly assigned to receive either 50 milligrams per kilogram (mg/kg) of ceftriaxone once daily at home or 50 mg/kg of flucloxacillin every 6 hours in the hospital.

Overall, treatment failure occurred in 2 (2%) children in the home group and in 7 (7%) children in the hospital group, and, in the per-protocol analysis, it occurred in 1 (1%) of 89 children in the home group and in 7 (8%) of 91 children in the hospital group. In addition, only 2 children in the home group compared with 10 in the hospital group had an adverse event. And there was no difference between the groups in the rates of nasal acquisition of methicillin-resistant Staphylococcus aureus (MRSA) or gastrointestinal acquisition of extended-spectrum beta-lactamase-producing bacteria or Clostridioides difficile after 3 months.

The authors conclude, "Findings from our study provide robust evidence that children with moderate to severe cellulitis can be effectively treated at home without the need for hospital admission. Additionally, we have shown that this management pathway is highly acceptable to families and has cost-saving benefits for the hospital."

An accompanying commentary noted, "Although OPAT has several benefits compared with hospitalisation, the burden of OPAT is still substantial for both patients and caregivers, especially compared with oral therapy. A growing body of evidence suggests that intravenous antibiotics are overused in place of equally effective oral therapy across a variety of serious infections in children that might require hospitalisation."
Mar 7 Lancet Infect Dis abstract
Mar 7 Lancet Infect Dis commentary


Study finds link between antibiotic therapy, urinary infection relapse

The results of a study today in Epidemiology and Infection on urinary tract infections (UTIs) among college-aged women suggest that initial treatment with trimethoprim-sulfamethoxazole may increase the risk of UTI relapse.

In the study, researchers from the University of Florida sought to understand the relationship between empiric antibiotic treatment for uncomplicated UTI and the likelihood of recurrent infections, theorizing that women who received treatment with antibiotics associated with higher rates of antibiotic resistance (trimethoprim-sulfamethoxazole and fluoroquinolones) would be more likely to have a recurrent UTI.

They also looked at the associations between empiric therapy and UTI recurrence within 2 weeks, which was defined as a potential infection relapse rather than a recurrent infection. In addition, baseline patient characteristics, including age, race, and region of origin, were analyzed for association with recurrence and relapse.

The retrospective study analyzed electronic medical record data on 6,620 women who were diagnosed with a UTI at the University of Florida Student Health Care Center from 2006 through 2014. Of those women, 1,051 (15.9%) developed a recurrent UTI and 215 (3.2%) experienced relapse. In the multivariate analysis, Asian women were found to have greater odds of experiencing a recurrent UTI than Caucasian women, while African-American women had lower odds. But there was no association between initial antibiotic treatment and recurrent UTI.

However, multivariate analysis of women who suffered a relapse found that women treated with trimethoprim-sulfamethoxazole had more than twice the increased risk of UTI relapse compared with women treated with combination therapy (adjusted odds ratio [aOR], 2.14; 95% confidence interval [CI], 1.23 to 4.09). Women born outside the United States also had increased odds of UTI relapse compared with those born in the United States (aOR, 2.12; 95% CI, 1.30 to 3.31).

The authors of the study say that the link between UTI relapse and trimethoprim-sulfamethoxazole may be related to increasing rates of resistance to the drug, and that further study of this link is warranted. They also call for more research on how race and region of origin contribute to recurrence and relapse. 
Mar 8 Epidemiol Infect abstract


VA study finds 5% rate of prolonged antibiotics after outpatient surgery

Originally published by CIDRAP News Mar 7

A 2-year multicenter Veterans Administration (VA) retrospective cohort study published yesterday discovered that 5% of patients having outpatient surgeries received antimicrobial prophylaxis longer than 24 hours after surgery, with rates varying by procedure, facility type, and surgical specialty.

Writing in Antimicrobial Resistance & Infection Control, VA researchers said they analyzed data from Oct 1, 2015, through Sep 30, 2017, on any veteran undergoing an outpatient surgical procedure in any of five specialties: general surgery; urology; ophthalmology; ears, nose, and throat (ENT); or orthopedics. Guidelines recommend postoperative preventive antimicrobials for no longer than 24 hours after incision closure.

Among 153,097 outpatient surgeries, 7,712 patients (5.0%) received antimicrobial prophylaxis lasting longer than 24 hours. Rates ranged from 0.4% for eye surgeries to 13.7% for genitourinary procedures. Cystoscopies (16%) and cystoureteroscopy with lithotripsy (20%) had the highest rates, while hernia repair, cataract surgeries, and laparoscopic cholecystectomies had the lowest rates, at 0.2% to 0.3.

The investigators also found that lower-complexity ambulatory surgical centers and hospital outpatient departments had about a 30% higher incidence of prolonged antimicrobial prophylaxis compared with complex hospitals.

The authors conclude, "Increasing pharmacy, antimicrobial stewardship and/or infection prevention resources to promote more evidence-based care may support surgical providers in lower complexity ambulatory surgery centers and hospital outpatient departments in their efforts to improve this facet of patient safety." They add that genitourinary and ENT specialists may especially benefit from stewardship interventions.
Mar 6 Antimicrob Resist Infect Control study


Study links antibiotic resistance prevalence to sepsis-related outcomes

Originally published by CIDRAP News Mar 7

A paper published yesterday in the International Journal of Antimicrobial Agents suggests an association between the prevalence of antibiotic resistance and rates of hospitalization and mortality for sepsis in the United States, with a particularly strong association observed for fluoroquinolone-resistant Escherichia coli.

While antibiotic resistance is known to contribute to rates of septicemia and associated mortality, which have risen significantly over the past 2 decades, less is known about the relationship between the prevalence of resistance to various antibiotics and rates of sepsis-related outcomes.

Using data from the Centers for Disease Control and Prevention's (CDC's) Antibiotic Resistance Patient Safety Atlas, researchers from Harvard, the US Department of Health and Human Services, and the National Institutes of Health (NIH) explored the issue by looking at the relationship between state-specific percentage of resistant bacteria samples in patients with catheter-associated urinary tract infections and rates of hospitalization and mortality for sepsis. They evaluated the associations for different age-roups and different combinations of antibiotics and bacteria.

Many positive correlations between prevalence of antibiotic resistance and rates of septicemia hospitalization and mortality were found in the study, particularly for older adults. But among the different combinations of antibiotics and bacteria, resistance to fluoroquinolones in E coli had the strongest association with septicemia hospitalization rates for patients over 50, and with sepsis mortality rates for patients between 18 and 84 years old. The authors note that E coli is a major source of gram-negative septicemia in the United States, and that the prevalence of fluoroquinolone-resistant E coli isolates in urinary tract and bloodstream infections is high.

The authors say the results support the need to enhance antibiotic stewardship, step up efforts to prevent infection with antibiotic-resistant bacteria, and examine whether replacing certain antibiotics with other agents in the treatment of different syndromes could reduce the rate of severe outcomes associated with bacterial infections.
Mar 6 Int J Antimicrob Agents abstract


Resistant gonorrhea clone identified in two UK women

Originally published by CIDRAP News Mar 7

A team of British scientists reported today that a Neisseria gonorrhoeae clone with ceftriaxone resistance and intermediate resistance to azithromycin has been detected in the United Kingdom.

Writing in Eurosurveillance, the investigators describe a cluster of cases involving the N gonorrhoeae FC428 clone, which was first reported in Japan in 2015 and has since been detected in Australia, Canada, Denmark, Ireland, and France. The clone was detected in two women (Case 1 and Case 2) from the United Kingdom who tested positive for gonorrhea in October and November 2018 after having unprotected sex with men from the UK while in Ibiza, Spain.

The two sexual contacts of Case 1 could not be contacted for testing but are suspected of also being infected. The contact of Case 2, who was also linked to the sexual network of Case 1, was asymptomatic when tested in November 2018, but the investigators believe he may have been the source of Case 2's infection.

Case 1 was treated empirically with ceftriaxone and azithromycin and was cured; Case 2 failed the first two treatments but cleared the infection after treatment with intravenous ertapenem.

Whole-genome sequencing revealed that the genomes of the isolates from the two cases were indistinguishable, and comparison with previously sequenced ceftriaxone-resistant isolates demonstrated that the isolates belonged to the FC428 clone. Except for one other case, all previous FC428 cases had been linked to sexual contact in Southeast Asia, which is believed to be the reservoir for the clone.

"There is growing evidence that the FC428 clone has the potential to spread globally, which is of concern given it is resistant and intermediate resistant to the only two remaining empirical treatment options for N. gonorrhoeae, ceftriaxone and azithromycin," the authors of the report write. "As the transmission between our cases is likely to have occurred between UK residents visiting Ibiza, a well-known European party destination, there is a risk that further undetected transmission has occurred."
Mar 7 Eurosurveill rapid communication


Study finds improper empiric therapy not tied to worse UTI outcomes

Originally published by CIDRAP News Mar 5

A University of Toronto study has discovered no connection between adequate empiric antibiotic therapy and cure time for patients with UTIs caused by bacteria, suggesting a potential for sparing antibiotics, according to a study yesterday in Clinical Microbiology and Infection.

For the retrospective cohort study, the investigators enrolled all patients 16 years and older admitted to Sunnybrook Health Sciences Centre from Apr 1, 2000, to Jul 15, 2015 who had a first episode of bacteremic UTI. They then classified them as to whether they had adequate or inadequate antibiotic therapy within 24 hours of culture collection. They defined adequate therapy as receipt of at least one dose of an empiric antibiotic active in vitro against the infecting pathogen, based on lab-reported susceptibility tests.

The researchers noted that 368 (78.5%) of the 469 patients received adequate empiric antibiotic therapy. But they found no statistical difference between those patients and the patients who were prescribed inadequate empiric antibiotics in mortality, time-to-cure, or time-to-normalization.

The authors conclude, "Our findings add to a body of literature challenging the notion that early empiric therapy is necessary for good outcomes in patients with UTI." They add, "It may be appropriate to accept a higher risk threshold when choosing empiric antibiotic regimens, even in centres with high rates of resistant uropathogens."
Mar 4 Clin Microbiol Infect study


Surgery-linked resistant Pseudomonas from Mexico sickens 20 in 9 states

Originally published by CIDRAP News Mar 5

The World Health Organization (WHO) today said 20 adults in nine states have contracted antibiotic-resistant Pseudomonas aeruginosa after invasive procedures performed in Tijuana, Mexico.

Sixteen of the cases have been confirmed, the WHO said, and the rest are suspected. A confirmed case is defined as Verona integron-encoded metallo-beta-lactamase–producing carbapenem-resistant P aeruginosa (VIM-CRPA) isolated from a patient.

On Jan 9, the CDC issued a travel advisory over the cluster of infections but did not cite the number of cases or give many specifics. On Feb 13 the Public Health Agency of Canada followed suit in posting a travel advisory.

The WHO said in today's update that 2 of the 20 case were retrospectively identified and occurred in 2015 and 2017, but the other 18 infections occurred from Sep 5, 2018, to Jan 24, 2019. Fifteen patients reported having surgery, primarily for weight loss, at Grand View Hospital in Tijuana.

"Half of the total cases reported the use of the same medical tourism travel agency based in the United States to coordinate their surgical procedure in Mexico," the WHO said. The travel agency has referred patients to Grand View from the United States, Canada, and elsewhere.

Thirteen patients were hospitalized in the United States for complications associated with VIM-CRPA infections, and most had surgical-site infections. One patient who had a bloodstream infection and several underlying conditions died. Of the 17 patients with available information, 14 (82%) were female, and they ranged in age from 29 to 62 years.

The WHO says it will continue to monitor the situation.
Mar 5 WHO news release
Jan 10 CIDRAP News scan on CDC alert


Interventions fail to lower hospital-acquired infections except in subset

Originally published by CIDRAP News Mar 5

Two infection control practices for bacterial infections—including those caused by MRSA—failed to reduce hospital-acquired infections, except in patients being treated with medical devices, according to a very large study today in The Lancet.

The ABATE (Active Bathing to Eliminate) Infection trial, sponsored by the National Institutes of Health (NIH), evaluated whether daily bathing with the antiseptic soap chlorhexidine—and, in patients with MRSA, adding the nasal antibiotic mupirocin—more effectively reduced hospital-acquired bacterial infections than bathing with ordinary soap and water. Researchers enrolled 333,000 patients in 48 hospitals in the HCA Healthcare system for the 21-month study, which amounted to 1.3 million days of care.

Among all patients, the scientists found no statistically significant difference between the study arms. Patients with medical devices, however, such as central venous catheters or lumbar drains, benefitted from the chlorhexidine-mupirocin intervention. Among those patients, investigators recorded a 30% decrease in bloodstream infections and a nearly 40% drop in antibiotic-resistant bacteria, including MRSA and vancomycin-resistant enterococcus.

"The results of the ABATE Infection trial are already being incorporated into infection prevention efforts," Jonathan Perlin, MD, PhD, chief medical officer of HCA Healthcare and a study co-author, said in an NIH news release. "The HCA system is using this decolonization strategy as a best practice for patients with medical devices across our 179 affiliated hospitals."
Mar 5 Lancet study
Mar 5 NIH news release


Report: Antibiotic resistance, sustainable development are intertwined

Originally published by CIDRAP News Mar 4

A new report from ReAct and the Dag Hammerskjold Foundation calls for antibiotic resistance to be integrated into the sustainable development agenda.

The report, titled "When the Drugs Don't Work: Antibiotic Resistance as a Global Development Problem," argues that if antibiotics continues to lose their effectiveness, efforts to achieve the United Nation's 2030 Agenda for Sustainable Development could be in jeopardy. Using data from the WHO, World Bank, and other sources, the report focuses on how antibiotic resistance could hinder efforts to eradicate poverty, promote economic growth, reduce inequality, fight hunger, improve public health, and protect the environment.

The report also illustrates how antibiotic resistance is intertwined with many of these issues. For example, the authors note, poor people in low- and middle-income countries are more vulnerable to infection, and lack of access to affordable and effective medical care to treat drug-resistant infections may push them deeper into poverty because they have to pay out of pocket for more expensive second-line drugs or for hospitalization. It could also lead people to self-medicate and use antibiotics inappropriately, thereby promoting more resistance. Conversely, efforts to eradicate poverty could help reduce vulnerability to resistant infections.

The report concludes that antibiotic resistance should be included in national or regional target-setting to reach the Sustainable Development Goals, and that stakeholders in sectors beyond health and agriculture need to get involved in efforts to combat resistance.

"The Sustainable Development Goals are deeply interconnected and many goals and targets rely on one another to achieve the envisioned state of wellbeing and sustainability," the authors write.  "Antibiotic resistance knows no sectorial limits, country borders or other divisions and therefore requires a level of cooperation that other challenges have not demanded before."
Feb 28 ReAct/Dag Hammerskjold Foundation report
Feb 28 ReAct news release


CARB-X provides funding for Contrafect's amurin platform

Originally published by CIDRAP News Mar 4

CARB-X announced today that it will award up to $1.75 million in funding to Contrafect Corporation, of Yonkers, New York, to develop a new approach to treating serious infections caused by gram-negative ESKAPE pathogens (E coli, Klebsiella pneumoniae, Acinetobacter baumannii, P aeruginosa, and Enterobacter species).

The funding will support Contrafect's work on amurins, a class of phage-encoded lytic agents that have demonstrated broad-spectrum activity in vitro against all ESKAPE pathogens and Salmonella Typhimurium, and have also show the ability to clear biofilms and act synergistically with a range of antibiotics. The company could receive an additional $5.9 million if certain project milestones are met.

"Amurins are highly differentiated from conventional antibiotics through their novel mechanism of action and potent spectrum of activity against the most threatening Gram-negative pathogens," Contrafect chief medical officer Cara Cassino, MD, said in a CARB-X press release. "We look forward to advancing development of this promising new class of antimicrobial agents with the support of CARB-X."

CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) is supporting the development of amurins to treat acute exacerbations of cystic fibrosis caused by multidrug-resistant gram-negative pathogens and potentially hospital-acquired bacterial pneumonia.

This is the second award that Contrafect has received from CARB-X, which to date has awarded more than $110 million for pre-clinical development of new antibiotics, diagnostics, and alternative therapies for drug-resistant infections.
Mar 4 CARB-X press release


Study compares prediction methods for multidrug-resistant infections

Originally published by CIDRAP News Mar 4

A study today in Infection Control and Hospital Epidemiology found that two methods for predicting multidrug-resistant infections performed similarly in a head-to-head comparison.

The single-center study by investigators from Johns Hopkins Bloomberg School of Public Health and the University of Maryland School of Medicine compared two statistical models for identifying multidrug-resistant gram-negative infections: logistic regression–derived risk scores and machine learning–derived decision trees. They compared the performance of the two models using a dataset of 1,288 patients hospitalized at Johns Hopkins Hospital with E coli or Klebsiella bloodstream infections to determine which one was better at identifying patients with an extended-spectrum beta-lactamase (ESBL) producer. They also reviewed the practical and methodologic attributes of the two approaches.

A total of 194 patients (15%) in the cohort were ESBL-positive, based on previous microbiologic test results. The results of the comparison showed that in practice the 14-variable risk score and the 5-variable decision tree performed similarly in identifying these patients, with positive predictive values of 94.6% and 90.8% and negative predictive values of 91.8% and 91.9%, respectively. While the C-statistic of the risk score was higher (0.87 vs. 0.77), suggesting better predictive value, the investigators also determined that the decision tree was more intuitive and user friendly.

"Statistical models for predicting drug resistance can provide important information in settings when laboratory diagnostics are challenging to implement," the authors of the study conclude. "These methodologies offer different strengths and limitations, and we hope that their continued utilization in infectious disease research will assist with improving patient outcomes."
Mar 4 Infect Control Hosp Epidemiol abstract

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