Kristi Rosa

Baloxavir marboxil has been shown to significantly cut the time to improvement of flu symptoms compared with placebo in patients deemed to be at high risk of serious complications from influenza. The treatment was also found to be well-tolerated with no new safety signals observed.

Results from the phase 3 CAPSTONE-2 study were presented by Michael G. Ison, MD, MS, FIDSA, a professor at Northwestern University Feinberg School of Medicine, in a 

Discovered by Shionogi & Co., Ltd., and further developed and commercialized by Roche Group, baloxavir marboxil is a first-in-class, investigational medicine to be taken by mouth via a single dose, with a novel mechanism of action.

“I think the most important feature of baloxavir is that it’s a new class of antiviral medications for influenza,” Dr. Ison told 

 in an exclusive interview. “The currently approved medications that are available to us are the m2 inhibitors that inhibit the m2 ion channel and the neuraminidase inhibitors that inhibit the neuraminidase. Baloxavir affects the flow rates in the PA segment, and therefore, is active against viruses that may be resistant to either the neuraminidase or the m2 ion channel.”

For the phase 3, multicenter, randomized, double-blind trial, investigators set out to evaluate how safe and effective baloxavir marboxil would be in comparison with oseltamivir or placebo in individuals 12 years of age or older with high risk of complications from the flu. These individuals included those 65 years of age or older or those with conditions such as asthma, chronic lung disease, morbid obesity, or heart disease.

The investigators enrolled 2184 participants in the trial and randomized (1:1:1) them to receive either a single, oral dose of 40 mg or 80 mg of baloxavir marboxil (in accordance with body weight), placebo, or oseltamivir 75 mg, twice daily for the duration of 5 days.

Of the 2184 participants, 1163 were confirmed to be infected with influenza via the use of reverse transcription polymerase chain reaction (RT-PCR) testing. Of those with confirmed influenza infections, 47.9% had subtype A/H3N2, 6.9% had A/H1N1, and 41.6% had subtype B.

Dr. Ison added that the most common risk factors observed in participants were asthma or chronic lung disease (39.2%), being 65 years of age or older (27.4%), endocrine disorders (32.8%), metabolic disorders (13.5%), heart disease (12.7%), and morbid obesity (10.6%).

The investigators found that baloxavir marboxil significantly reduced the time to improvement of flu symptoms in patients with high risk of serious complications compared with placebo (median time of 73.2 hours vs 102.3 hours, p<.0001). Specifically, when it came to patients with influenza type A/H3N2, the investigative treatment demonstrated efficacy of reducing time to improvement of flu symptoms compared with placebo (median time of 75.4 hours vs 100.4 hours, p<.05); it was also effective in those with influenza B compared to placebo (median time of 74.6 hours vs 100.6 hours; p<.05).

In the overall patient population, those who received baloxavir marboxil demonstrated a shorter time to improvement of flu symptoms compared with oseltamivir, with a median time to improvement of 73.2 hours versus 81.0 hours, respectively, p=.8347).

The investigators highlight that when looking specifically at a subset of patients with influenza B—a subgroup for which some antiviral treatments only show limited efficacy&mdash;baloxavir marboxil was found to be “significantly efficacious” compared with oseltamivir in cutting time to improvement of flu symptoms (median time of 74.6 hours vs 101.6 hours, p<.05).

The virologic clearance was faster in the patients who received baloxavir marboxil compared with oseltamivir and placebo (viral shedding; median time of 48.0 hours, 96.0, 96.0, p<.0001, respectively). The investigative treatment was also found to cut the use of antibiotics and incidence of flu complications (3.4% and 2.8%, respectively) in comparison with placebo (7.5% and 10.4%; p=.01, p<.05).

“The patients tolerated the medicine very well,” Dr. Ison said, adding that there was a lower overall incidence of adverse events in those who received baloxavir marboxil (25.1%), compared with placebo or oseltamivir (29.7% and 28%, respectively).

In our interview, Dr. Ison discussed the important takeaways from the study (

“Most importantly, it will bring a therapy that only requires a single dose, so, patients will be able to take a pill and will be done taking the medication for the treatment for influenza,” he concluded. “And after taking it, they will be at reduced risk for complications, including those requiring antibiotics or other complications of influenza.”

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The phase 3 CAPSTONE-2 trial shows treatment with baloxavir marboxil significantly reduced the time to improvement of flu symptoms compared with placebo.

Baloxavir Marboxil Significantly Reduces Time to Improvement of Flu Complications

The US Centers for Disease Control and Prevention (CDC) has expressed concern over an increase in the number of cases reported across the United States of a rare, polio-like illness.

Acute flaccid myelitis, an extremely rare condition that affects the nervous system—specifically the spinal cord&mdash;and causes weakness in the arms or legs.

From August 2014 to September 2018, a total of 386 cases of acute flaccid myelitis have been confirmed throughout the country, with 62 cases reported in 22 states for 2018 alone, Nancy Messonnier, MD, the director at the CDC’s National Center for Immunization and Respiratory Diseases, said in a telebriefing held earlier this week.

Although the CDC has not been able to pinpoint the cause for the majority of these cases, they have launched an active investigation to find more answers.

Many of the patients are presenting with symptoms similar to those of poliovirus, non-polio enteroviruses, adenoviruses, and West Nile virus. The sudden onset of weakness leads patients to seek medical care, and patients are then assessed by neurologists, infectious disease doctors, and pediatricians.

Milder cases of the disease might not be reported; however, Dr. Messonnier explained that the CDC is likely receiving information pertaining to the majority of cases. Their efforts to promote awareness of the issue is working to encourage those who might be infected with the illness to seek medical care. The CDC does not believe that the growing awareness of the rare disease is contributing to the increase in cases.

, officials tested all suspected cases for poliovirus—all came back negative. Furthermore, although enteroviruses are capable of causing neurological illnesses such as meningitis, and acute flaccid myelitis, the investigators state that instances of this happening are few and far between.

Specimens collected from those affected were tested for a wide array of pathogens that can potentially cause acute flaccid myelitis. To date, none of the pathogens have been consistently detected in any of the patients’ spinal fluid, which would provide a strong indication of the cause of the condition because acute flaccid myelitis affects the spinal cord. 

An influx of acute flaccid myelitis cases reported in 2014 coincided with a large national outbreak of enterovirus D68 associated with severe respiratory illness, according to the CDC. However, officials did not identify EV-D68 in every patient confirmed to have acute flaccid myelitis.

Officials will continue to explore other viruses, environmental toxins, and other avenues, in order to identify the cause of these cases, Dr. Messonnier said.

The CDC is also working on verifying clinical information reported to them by health departments and testing specimens collected from suspected cases. Other efforts are dedicated to gaining a better understanding of the disease and its potential causes, providing new information to providers, health departments, policymakers, and the public, and further exploring the potential association of the rare condition with possible causes as well as risk factors.

To do this, officials will be working with experts to review MRI scans taken from people over the last 10 years to identify how many cases of acute flaccid myelitis occurred previous to 2014. The CDC also aims to update treatment and management guidance for the disease and to work with academic centers across the country to conduct active surveillance for the condition as well as respiratory viruses.

 will provide updates on the investigation as more information becomes available.

From August 2014 to September 2018, the CDC received information on a total of 386 confirmed US cases of a polio-like illness occurring mostly among children.

CDC Investigating Increase in Polio-like Illness Reported Throughout the United States

In most healthy individuals, the immune system is able to prevent cytomegalovirus (CMV) from causing illness but those who are immunocompromised are not so lucky; these individuals are prone to suffer from more serious symptoms that often affect the eyes, liver, esophagus, stomach, and intestines. Furthermore, congenital CMV infection can result in severe, and sometimes permanent, neurological injury in newborns.

To date, there are no approved vaccines available to protect against the virus, but progress toward this goal has been made in recent clinical trials.

Just last week, promising findings from a first-in-human phase 1 trial evaluating VBI Vaccine’s vaccine candidate, VBI-1501A, were presented at 

, by Soren Gantt, MD, PhD, MPH, associate professor with the division of Infectious Disease in the department of pediatrics at the University British Columbia Faculty of Medicine, BC Children’s Hospital.

“Neutralizing antibodies (nAb) to the CMV envelope glycoprotein B (gB) in natural infection are thought to confer protection, and there was a recombinant gB/MF59 vaccine that was shown to be partially protective against infection and disease,” Dr. Gantt said, “but higher, longer-lived gB nAb titers are needed for a more effective vaccine.”

Enter VBI Vaccine’s candidate, VBI-1501A, an enveloped virus-like particle vaccine (VLP), designed via VBI’s 

. eVLPS, according to VBI, are a new, innovative class of synthetic vaccines that are developed to closely mimic the structure of viruses.

The idea is that because the vaccines are designed to be structurally similar to viruses found in nature, vaccination with a target protein expressed in an eVLP should have the potential to impart greater immunity than vaccination with the same recombinant target protein by itself.

According to Dr. Gantt, his team was pleased to see that an antigenic domain (AD) of gB—AD-2&mdash;was recognized on VBI-1501; this domain is increasingly recognized to have a functional importance when it comes to CMV.

In the first-in-humans dose-ranging, controlled, observer-blinded phase 1 trial, the investigators set out to study the safety and immunogenicity of an eVLP expressing the ectodomain of gB fused to transmembrane and cytoplasmic domains of the vesicular stomatitis virus G protein (gB-G), according to the 

A total of 125 healthy CMV-negative participants between 18 and 40 years of age were enrolled in the trial, which was conducted at 3 Canadian Immunization Research Network (CIRN) sites in Canada—Vancouver, Montreal, and Halifax.

Participants were randomized to 1 of 5 treatment groups. The first group received .5 μg VBI-1501A + alum; the second received 1.0 μg VBI-1501A; the third were given 2.0 μg VBI-1501A; the fourth received 1.0 μg VBI-1501 (unadjuvanted); and the fifth group received placebo. Each participant received 3 intramuscular doses of the CMV eVLP vaccine or placebo on days 0, 56, and 168, according to Dr. Gantt.

Outcome measures for the trial were solicited and unsolicited adverse events (AEs) and serious AEs. Specifically, local and systemic AEs 7 days following each injection, any AEs 28 days following each injection and SAEs through day 336 of the trial or early withdrawal, and any laboratory abnormality at the following days: 28, 56, 84, 168, 196, 280, or 336.

Secondary outcome measures pertained to immunogenicity; specifically, gB binding antibody titers and avidity assessment, as well as nAB to CMV infection of fibroblast and epithelial cells, study authors write.

Dr. Gantt reported that the most common AEs reported were headache, infections, and fatigue. However, the vaccine was not found to be associated with any clinically significant AEs compared with the placebo group. Further, there were no significant differences observed in abnormal laboratory results compared with those who received placebo.

He added that the events reported ranged from mild to moderate in severity and none of the events resulted in withdrawal from the trial. SAEs, according to Dr. Gantt, were “relatively infrequent” and did not seem to be associated with dose.

After doses 2 and 3, a dose-dependent boosting of nAB titers was noted, with the highest titers in the third treatment group, who received the highest dose of the vaccine. Dr. Gantt said that fibroblast cell nAb were observed in 100% of subjects who received the 2.0 μg dose of the vaccine, while epithelial cell nAb was noted in 31%.

“Epithelial cell nAb was correlated with higher geometric mean gB binding titers,” the authors write, “and there was a correlation between fibroblast and epithelial cell nAb titers.”

Overall, Dr. Gantt and his team concluded that VBI-1501A was safe and well-tolerated at all the doses tested in the phase 1 trial, and that the vaccine is immunogenic.

“We saw gB binding titers induced at all dose levels, with clear evidence of dose-dependent boosting,” he said. “There was good neutralizing activity in fibroblasts in 100% of subjects at highest dose with titers comparable to CMV-positive controls. And there was modest epithelial cell neutralizing activity that correlated with higher gB binding titers.”

The next steps for the vaccine are currently under discussion. 

 will provide the public with updates as more information becomes available.

S. Gantt, VBI Vaccines: Investigator, No direct financial benefit—company provided institutional support for clinical trial; C. Quach, VBI Vaccines: Investigator, No direct financial benefit&mdash;company provided institutional support for clinical trial; D. E. Anderson, VBI Vaccines: Employee and Shareholder, Salary; F. Diaz-Mitoma, VBI Vaccines: Consultant and Shareholder, Salary; J. Langley, VBI Vaccines: Investigator, No direct financial benefit&mdash;company provided institutional support for clinical trial.

An eVLP cytomegalovirus (CMV) vaccine was found to be safe and immunogenic at very low doses in healthy seronegative adults.

Cytomegalovirus Vaccine Candidate Found to Be Safe & Immunogenic in First-in-Humans Trial

Patients with HIV-1 who switched over to a once-daily, single-tablet regimen of darunavir 200 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (D/C/F/TAF), marketed as SYMTUZA, had maintained high virologic suppression rates with no resistance development at 96 weeks.

New 96-week data from the pivotal phase 3 EMERALD trial were presented by Joseph Eron, Jr. MD, professor of medicine from the University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, at 

, held this year in San Francisco, California.

 demonstrate that SYMTUZA can offer clinically appropriate people living with HIV a single-tablet option that may help them maintain high rates of virologic suppression over time,” Dr. Eron said in a recent statement.

In the randomized, active-controlled, open-label, noninferiority phase 3 trial, virologically suppressed (VL <50c/mL for ≥2 months), HIV-infected adults were randomized (2:1) to continue on boosted-protease inhibitors (bPI) plus emtricitabine/tenofovir disoproxil fumarate (F/TDF) or to switch over to D/C/F/TAF over 48 weeks. Patients could either continue on the D/C/F/TAF regimen or switch from the bPI F/TDF regimen over to D/C/F/TAF at week 52 (late switch, 44 weeks D/C/F/TAF exposure) in a single-arm extension phase of the trial, up until week 96.

The primary and secondary endpoints of the trial were the percentage of patients with virologic rebound (confirmed VL ≥50 c/mL) cumulative through week 48 and week 96, respectively, according to Dr. Eron and colleagues.

The investigators report that 1080 patients out of the total 1141 patients who were randomized and treated continued on to the extension phase of the trial; of the 1080 patients, 728 continued to receive the D/C/F/TAF regimen, while 352 switched over from bPI F/TDF to D/C/F/TAF.

Dr. Eron reported that few patients in the D/C/F/TAF treatment arm experienced virologic rebound cumulative through week 96 (3.1%, 24/763); virologic rebound occurred in 2.3% (8/352) of patients in the late switch arm. However, many of the patients who rebounded resuppressed at week 96 (14/24, D/C/F/TAF and 2/8, late switch).

A high percentage, 90.7% (602/763), of those in the D/C/F/TAF arm were suppressed at week 96. After 44 weeks of treatment, 93.8% (330/352) of patients in the late switch arm maintained virologic suppression. Virologic failure (≥50 c/mL) rates for D/C/F/TAF were 1% (9/763) at week 96 and 2% (6/352) after 44 weeks of D/C/F/TAF exposure in the late switch arm at week 96.

No darunavir, primary protease inhibitor, tenofovir, or emtricitabine resistance-associated mutations were seen post-baseline.

Overall, D/C/F/TAF was found to be well tolerated with few serious adverse events (9%, 66/763) and treatment-associated discontinuations (2%, [17/763]) observed over 96 weeks. Over 44 weeks, 6% (21/352) and 2% (7/352) in the late switch group experienced serious adverse events and treatment-associated discontinuations.

The most common adverse events in the extension period were as follows: upper respiratory tract infection (16%, 122/763), viral upper respiratory tract (13%, 98/763), diarrhea (11%, 80/763), headache (10%, 79/763), and back pain (10%, 79/763).

Investigators observed improvements in renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late switch arm (week 52 to 96), with a small change in TC/HDL-C ratio, which investigators deemed to be consistent with the known effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide based regimens.

“Switching to D/C/F/TAF maintained high virologic suppression rates (>90%) at week 96 with no resistance development, and was well-tolerated over 96 weeks with bone, renal, and lipid safety consistent with known TAF and cobicistat profiles,” the authors write.

The 96-week extension study reinforced the long-term safety, efficacy, and resistance profile of D/C/F/TAF previously demonstrated at 24 and 48 weeks in virologically suppressed adult patients with HIV-1.

“D/C/F/TAF combines the efficacy and high genetic barrier to resistance of darunavir with the safety benefits of TAF, even in patients with a history of non-DRV VF,” Dr. Eron and colleagues conclude.

J. Eron Jr., Gilead: Consultant and Grant Investigator, Consulting fee and Research grant. Janssen: Consultant, Consulting fee and Research grant; C. Orkin, AbbVie, Abbott, Boehringer Ingelheim, BMS, Gilead, GSK, Janssen, ViiV: Grant Investigator and Research Contractor, Research grant and Research support; D. Cunningham, Janssen: Investigator, Research grant. Gilead: Investigator, Research grant; F. Pulido, Janssen: Consultant, Investigator and Scientific Advisor, Consulting fee, Research support, and Speaker honorarium;  F. Post, Gilead: Consultant and Grant Investigator, Consulting fee and Grant recipient. Viiv: Grant Investigator, Grant recipient. Janssen: Consultant, Consulting fee. MSD: Consultant, Consulting fee; S. De Wit, Janssen: Investigator, Research grant;  E. Lathouwers, Janssen: Employee and Shareholder, Salary; V. Hufkens, Janssen: Employee and Shareholder, Salary;  R. Petrovic, Janssen R&D: Independent Contractor, Consulting fee; E. Van Landuyt, Janssen: Employee and Shareholder, Salary.

Long-term safety and efficacy data from the pivotal phase 3 EMERALD trial were presented at ID Week 2018.

Switch to D/C/F/TAF Results in Maintained High Virologic Suppression in Adults with HIV

Results of a phase 3 clinical trial indicate that the combination of daptomycin plus fosfomycin was more effective than daptomycin alone for the treatment of patients with methicillin-resistant 

The combination treatment has demonstrated synergistic and bactericidal effect in animal models of MRSAB, but up until now, there has been a lack of data in humans. Results of the phase 3 trial were presented at 

 by Miquel Pujol, MD, PhD, Infectious Diseases Department, Hospital de Bellvitge, L’Hospitalet Ilobregat, Spain.

“The aim of the study was to test the hypothesis that high-dose of daptomycin combined with fosfomycin can achieve a better response than therapy with high-dose of daptomycin alone,” Dr. Pujol said, “measured in terms of clinical success and microbiological eradication, among patients with MRSA bacteremia.”

The randomized (1:1), open-label clinical trial enrolled adult patients with MRSAB and was conducted at 18 medical centers throughout Spain.

Patients were included in the trial if they had at least 1 blood culture that was positive for MRSAB in the 72 hours up to randomization and were 18 years of age or older.

Participants were randomized into 1 of 2 arms: those who would receive intravenous (IV) daptomycin 10 mg/kg daily plus IV fosfomycin, 2 g/6h and those who would receive just IV daptomycin 10 mg/kg/24h. The duration of treatment was 10 to 14 days for uncomplicated bacteremia and 28 to 42 days for complicated bacteremia.

The 2 primary efficacy endpoints for the trial were treatment success at Test-of-Cure (ToC) visit (6 weeks after end of therapy), and treatment success at 7 days, defined as alive at day 7 and clearance of bacteremia without relapse from 8 to 90 days post-randomization.

A total of 674 patients with MRSAB were evaluated in the trial, which was conducted from December 2013 to November 2017; a total of 155 patients were randomized, according to Dr. Pujol. Seventy-four patients were given the combination treatment, while 81 were given the monotherapy.

Dr. Pujol and his team found that at ToC visit, a successful outcome was achieved in 54.1% (40/74) of patients who were given the combination therapy compared with 42% (34/81) of patients who received the monotherapy (absolute difference, 12.1%; 95 confidence interval (CI), 0%-27.0%). At 7 days after the treatment was started, a successful outcome was achieved in 93.2% (69/74) of patients who received the combination therapy compared with 76.5% (62/81) who were given the monotherapy (absolute difference, 16.7%; 95% CI, 5.4%-27.7%).

At ToC visit, the combination therapy was found to be associated with lower rates of microbiologic failure compared with the monotherapy (0 vs 9 patients, 

When assessing for survival, the team noted that the cumulative mortality incidence at day 7 for the combination treatment group was 4% (CI 95% 0.8 to 11.4), while it was 7.4% (CI 95% 2.8 to 15.4) in the monotherapy group. The cumulative mortality incidence at ToC was 24.3% (CI 95% 15.1 to 35.7) in the combination therapy group, compared with 27.2% (CI 95% 17.9 to 38.2) in the monotherapy group.

A total of 48.6% of those in the combination treatment group experienced adverse events (AEs) compared with 46.9% of those in the monotherapy group; 40.5% reported serious AEs in the combination group compared with 42% in the monotherapy group; and 6.8% of those in the combination therapy group reported AEs leading to treatment discontinuation compared with 0% in the monotherapy group, Dr. Pujol reported.

Five patients withdrew from the trial due to serious adverse events such as heart failure with hypernatremia/metabolic alkalosis/hypokalemia (2), respiratory insufficiency (2), and digestive tract bleeding (1).

Dr. Pujol and his team concluded that the combination therapy was more effective than the monotherapy for the treatment of MRSAB.

“The combination therapy was highly effective to negativize blood cultures and avoid relapses and complicated bacteremia,” he said. “Mortality in both groups was similar in the TOC visit; however, a lower mortality was observed with the combination therapy at day 7.”

Overall, the combination therapy was deemed safe, although some patients needed to discontinue treatment due to serious AEs.

Adding fosfomycin to daptomycin—at least during the first 7 days of therapy&mdash;could potentially improve outcomes of patients with MRSAB, they conclude.

The combination of daptomycin plus fosfomycin was more effective than daptomycin alone for treating patients with MRSA bacteremia.

Adding Fosfomycin to Daptomycin Could Improve Outcomes of MRSA Bacteremia

Surgical site infections are among the most common causes of health care-associated infections, and the human and financial costs of treating them continue to increase.

In fact, the US Centers for Disease Control and Prevention (CDC) 

 that there are 157,500 surgical site infections reported in the United States each year, and they account for $3.2 billion in attributable cost per year in acute care hospitals.

To prevent these infections, health care providers have turned to the use of antimicrobial prophylaxis. New 

 emphasized that the benefits of surgical antimicrobial prophylaxis are limited to the first 24 hours post-operation, and prolonging prophylaxis is associated with increased likelihood of acute kidney injuries and 

In an oral abstract presentation, Judith M. Strymish, MD, assistant professor of medicine, VA Boston Healthcare System and Harvard Medical School, stressed that when it comes to surgical prophylaxis “every day matters.”

Multi-society prophylaxis guidelines recommend that antimicrobials be initiated within 1 hour prior to surgery and discontinued within 24 hours for most procedures. These recommendations were also based on data indicating that increasing duration of prophylaxis will not lead to additional surgical site infection risk reduction; however, not much is known about the harms are in doing so.

As such, Dr. Strymish and her team set out to characterize the relationship between duration of prophylaxis and postoperative outcomes, including surgical site infection, acute kidney injury, and 

 infections. To do this, they evaluated surgical patients who were entered into the VA pre- and post-operative quality databases which include information pertaining to the type and duration of prophylaxis as well as patient outcomes.

From October 1, 2008, to September 30, 2013, the investigators analyzed data on all patients who underwent cardiac, orthopedic total joint, vascular, and colorectal procedures and who had received planned manual review for type and duration of prophylaxis.

The team’s exposure variables of interest were the type and duration of prophylaxis, which were divided into several mutually-exclusive groups of antibiotics, with a single 

-lactam as the referent group. Other groups included vancomycin and aminoglycoside, aminoglycoside alone or in combination, vancomycin alone or in combination, and an “other” category which consisted mostly of clindamycin or fluoroquinolone.

The duration of prophylaxis was divided into groups of “less than 24 hours,” “24 to 48 hours,” “48 to 72 hours,” and “greater than 72 hours;” “less than 24 hours” served as the referent group. The investigators then used logistic regression analysis to assess the impact of type and duration of prophylaxis on outcomes. The surgical site infection outcome was a 30-day endpoint, according to Dr. Strymish, while acute kidney injury was a 7-day endpoint and 

 infection was a 90-day endpoint. Risk factors for each syndrome were selected a priori.

Out of 79,092 total patients, all patients had surgical site infection and 

 outcomes available; 67,729 had acute kidney injury outcomes available. After stratifying via type of surgery and then adjusting for age, sex, race, diabetes, smoking, pre-operative methicillin-resistant 

 colonization status, mupirocin receipt, and type of prophylaxis, the investigators did not find a significant link between surgical site infection and duration of prophylaxis (ie, longer treatment durations did not lead to additional surgical site infection reduction.

In terms of the risk of acute kidney injury in their adjusted models, Dr. Strymish stressed that there were 2 key take-home points. “The first is about the impact of antimicrobial choice on acute kidney injury and the second is about duration,” she said.

Risk of acute kidney injury increased significantly in patients who received vancomycin as their agent, she said. There was an odds increase of about 22% in both cardiac and non-cardiac surgeries, with the risk being very similar in both groups. In the non-cardiac surgery—which consisted of the majority of the study cohort (~50,000 patients)&mdash;there was an increased risk which appeared to be synergistic if patients received vancomycin and an aminoglycoside.

“In terms of antimicrobial duration, there was an increased risk of acute kidney injury with every additional day of prophylaxis in the cardiac surgery group,” shared Dr. Strymish. “And so, the odds increased from about 14% for 24 to 48 hours, to approximately 30% in 48 to 72 hours, then doubled in patients who received greater than 72 hours of prophylaxis.”

Similar results were seen when it came to 

infections. “There was a 7% increase in odds for 24 to less than 48 hours. The odds then went up to 140% for 48 to 72 hours, and then 265% for greater than 72 hours,” she said. “There was also impact of antimicrobial choice on the rates of post-operative 

infections and this was predominately driven by clindamycin and fluoroquinolones.”

Dr. Strymish and her team concluded that increasing the duration of postoperative prophylaxis was associated with higher likelihood of acute kidney injury and 

 infection in a dose-dependent manner, and additional days of treatment are not linked with reduced odds of SSI. Risk of acute kidney injury increases with type and duration of prophylaxis, with regimens that contain vancomycin at particularly high risk.

“It is our hope that these findings can be used to ‘choose wisely’ and reduce unnecessary exposures,” Dr. Strymish concluded, “and to counsel both providers and surgeons about the best use of antimicrobials. In summary, every day really does matter.”

Instead, increasing duration of postoperative antimicrobial prophylaxis is associated with higher odds of acute kidney injury and C diff infection in a dose-dependent manner. 

Kristi Rosa

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