A study found no statistically significant differences in surgical site infections between the two groups, suggesting that both antiseptics are effective when used consistently.

Povidone iodine was found non-inferior to chlorhexidine gluconate in the largest randomized trial to compare the alcohol-based solutions for skin antisepsis in surgery.The findings support the CDC recommendation that either can be used, and should serve as impetus for the WHO to reconsider recommending only chlorhexidine gluconate.¹

In an editorial accompanying the study, JAMA associate editors Anthony Charles, MD, MPH, Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC, and Preeti Malani, MD, MS, Infectious Diseases and Geriatric Medicine, University of Michigan, Ann Arbor, MI, consider the implications for global surgery.²

“In addition to other evidence-based perioperative measures, the results of the study by Widmer et al provide more options for skin antisepsis, particularly in resource-limited settings given the large cost differential between povidone iodine and chlorhexidine gluconate in alcohol and the limited commercial availability of chlorhexidine gluconate-based antiseptics in some settings,” Charles and Malani indicate.

Andreas Widmer, MD, MS, University Hospital Basel and University of Basel, Basel, Switzerland, and colleagues evaluated outcomes in over 3000 patients after cardiac or abdominal surgery with skin antisepsis from the different alcohol-based solutions, in a cluster-randomized, crossover non-inferiority trial at 3 tertiary care hospitals.

“Currently the preferred preparation remains controversial because choice of drug, exposure time, and number of applications likely influence the results of skin preparation,” Widmer and colleagues observe.

“There has been a lack of standardization of these factors in previous trials, which did not compare compounds with similar alcohol-based formulations but also had relatively small sample sizes were single center, and/or were limited to specific surgical procedures,” they pointed out.

To address these gaps in evaluating the antiseptics, the investigators randomly assigned each of the 3 sites to one month periods of use of either povidone iodine or chlorhexidine, over 18 consecutive months between September 2018 and March 2020. The sites utilized consistent formulations of the antiseptics, and maintainedstandardized processes of disinfectant application consistent with published protocols.

“Importantly, postdischarge patient follow-up was exceptionally good and ensured adequate identification of outcomes,” the investigators noted. “The risk of confounding through contaminated operations, where proper skin preparation might be less relevant, was reduced by only including elective operations.”

The primary outcome was surgical site infection within 30 days after abdominal surgery and within 1 year after cardiac surgery; with noninferiority margin of 2.5%. Secondary outcomes included surgical site infections, stratified by depth of infection and type of surgery. A total of 1598 patients received povidone iodine and 1762 chlorhexidine gluconate.

Widmer and colleagues report surgical site infections occurred in 80 (5.1%) of those in the povidone iodine group and in 97 (5.5%) of those receiving chlorhexidine gluconate; a difference of 0.4% (95% CI, -1.1%-2.0%).When corrected for clustering, the difference was well within the margin for noninferiority. The calculated unadjusted relative risk for povidone iodine vs chlorhexidine gluconate was 0.92 (0.69-1.23).There were no statistically significant differences between groups by type of surgical procedure.

Noting that the most recent WHO guidelines recommending only chlorhexidene-alcohol are based on low to moderate quality of evidence, Charles and Malani declare, “the current study by Widmer and colleagues provides evidence to the contrary and should prompt a change in the WHO guidance.”

References

1.Widmer AF, Atkinson A, Kuster SP, et al. Povidone iodine vs chlorhexidine gluconate in alcohol for preoperative skin antisepsis. JAMA 2024;332(7):541-549.

2.Charles A, Malani PN. Skin antisepsis to prevent surgical site infections. Implications for global surgery. JAMA 2024;332(7):550.

Erika Lee, MD, MSc, Division of Clinical Immunology and Allergy, Department of Medicine, University of Toronto, Toronto, Ontario, Canada

Six classes of oral antibiotics were found to present increased risk of serious cutaneous adverse drug reactions (cADR) relative to macrolides, in a population-based study1 of over 21,000 patients requiring emergency department (ED) treatment or hospitalization for cADR from over 3 million receiving outpatient antibiotic prescriptions.

“Although speculation exists that some antibiotics are more likely than others to cause cADRS, no population-based studies have explored this claim,” observed Erika Lee, MD, MSc, Division of Clinical Immunology and Allergy, Department of Medicine, University of Toronto, Toronto, Ontario, Canada, and colleagues.

In their earlier review and meta-analysis2 of worldwide prevalence of the rare, but life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), antibiotics were implicated for more than one-quarter of the cases worldwide.Among the antibiotic classes, however, they found macrolides associated with lowest risk. The investigators conducted this nested case-control population-based study to ascertain risk of other antibiotic classes relative to the macrolides.

“The present study looked at the class as a whole, but not individual antibiotics in that class,” Lee told Contagion.”The general approach is that once a patient has a severe allergic reaction to one antibiotic, the whole class is generally avoided due to the risk of cross-reactivity.”

The cohort comprised older adults, median age 75 years. This age group is at increased risk for cADRS, Lee and colleagues explain, with several possible contributing factors, including: disproportionately more antibiotic prescriptions than younger people, more exposure to polypharmacy, and more likely to have such comorbidities as kidney insufficiency, liver disease, and malignancies.

Lee and colleagues accessed administrative health databases in Ontario, Canada from April 1, 2002 to March 31, 2022, to identify a cohort of outpatients receiving at least 1 oral antibiotic over that period, and defining the case patients who required ED care or were hospitalized for cADR and who received an antibiotic prescription in the preceding 60 days.Each was matched with up to 4 controls from the same cohort on age, sex, and an antibiotic prescription in the preceding 60 days, but without subsequent cADR.

Patients were excluded if they had received antibiotics from more than 1 class in the 60 days preceding the index date; as well as for prescriptions for other medications associated with serious cADRS in the preceding 90 days, including anticonvulsants, nonsteroidal anti-inflammatory drugs, and allopurinol.

Among a total of 34,114,254 courses of antibiotics, 72,449 were associated with serious cADR requiring ED treatment or hospitalization; a crude rate of 2.12 antibiotic-associated cADRs per 1,000 prescriptions (95% CI, 2.11-2.14).

All antibiotic classes were associated with higher risk for serious cADR than macrolides, with the sulfonamides presenting the highest relative risk (adjusted OR. 2.9; 95% CI, 2.7-3.1). The risk relative to macrolides, in decreasing order are: cephalosporins (aOR, 2.6; 2.5-2.8); “other” antibiotics (aOR, 2.3; 2.2-2.5); nitrofurantoin (aOR, 2.2; 2.1-2.4), penicillins (aOR, 1.4; 1.3-1.5); and fluoroquinolones (aOR, 1.3; 1.2-1.4).

“The finding of nitrofurantoin-associated severe drug allergy is surprising,” Lee commented.” The only indication for this antibiotic is urinary tract infection (UTI), so it is not as commonly used in the general population compared to other antibiotics that are prescribed for various indications.

In our study that concentrated in older adults, and UTI is one of the most common infections in this age group, we were able to identify this association.It would be interesting to see if this association is reproducible in the general population,” Lee suggested.

The investigators advise that “prescribers should preferentially use lower-risk antibiotics when clinically appropriate,” Lee elaborated, in discussing the study and findings.

“When prescribing an antibiotic, there are many factors that go through a physician’s head to balance the safety and efficacy of the treatment,” Lee said. “When there are equally effective options available, our study adds to the knowledge of safety, to consider when selecting an optimal option for the patient.”

References

1. Lee EY, Gomes T, Drucker AM, et al. Oral antibiotics and risk of serious cutaneous adverse drug reactions JAMA Online August 8, 2024. doi:10.1001/jama.2024.11437. Accessed August 20, 2024.

2. Lee EY, Knox C, Phillips EJ. Worldwide prevalence of antibiotic-associated Stevens-Johnson and toxic epidermal necrolysis: A systematic review and meta-analysis. JAMA Dermatol 2023. 159(4):384-392.

This week, Pfizer launched its digital platform, PfizerForAll, designed to initiate better access to managing health and wellness.

According to the company, the platform is designed for patients with migraine, COVID-19 or influenza, and adults seeking vaccines for COVID-19, influenza, RSV, and pneumococcal pneumonia.¹

The platform enables users to find telemedicine or in-person options to find care. Pfizer is working within the existing US healthcare system and partnering with a growing network of healthcare organizations to launch and develop PfizerForAll. Patients will be able to use existing insurance and pharmacy programs and will also benefit from new direct services from partners including UpScriptHealth, Alto Pharmacy, and Instacart.

The platform offers the following features:

• Access to same-day appointments with independent healthcare professionals, either in-person or via telehealth. People living with migraine or suffering from common respiratory symptoms can connect to qualified healthcare professionals within minutes, no matter where they are in the US, or find a provider in their local area with availability.
• Home delivery of prescription medicines, over-the-counter treatments and diagnostic tests. Patients can have prescription medicines delivered either directly to their home or for pick up at a preferred local pharmacy. People can also order over-the-counter treatments and diagnostic tests for COVID-19 and flu.
• Appointment scheduling for adult COVID-19, flu, RSV and pneumococcal pneumonia vaccinations. All adults over the age of 18 can check their eligibility for COVID-19, flu, RSV and pneumococcal vaccines, find vaccine availability in their local area and book an appointment at a preferred retail pharmacy.
• Help paying for Pfizer medicines and access to patient support services. PfizerForAll puts Pfizer’s savings and support solutions in one place, making it easier for patients with commercial insurance to find co-pay cards and for eligible patients to access Pfizer’s affordability programs and patient support services. Among other resources, patients can access information to assist with efficiently navigating the insurance process for those prescribed migraine and COVID-19 treatments, including a live customer support option.

Pfizer referenced a recent survey by the American Academy of Physician Associates, which found that 65% of respondents say coordinating and managing healthcare is overwhelming and time-consuming, and 73% of respondents feel that the healthcare system is failing to meet their needs. Additionally, a survey from Experian Health reported a majority of patients want more digital options for managing their care.

“People often experience information overload and encounter roadblocks when making decisions for themselves or their family in our complex and often overwhelming US healthcare system. This can be extremely time-consuming and lead to indecision or inaction—and as a result, poor health outcomes,” Pfizer Executive Vice President and Chief US Commercial Officer, Aamir Malik, said in statement. “We are pleased to offer PfizerForAll to help relieve this burden on people, especially as we enter the fall season in the US, and streamline the path for those seeking better health.”

Interested parties can go here to access the platform.

Reference

1. Pfizer Launches PfizerForAll™, a Digital Platform that Helps Simplify Access to Healthcare Pfizer Launches PfizerForAll™, a Digital Platform that Helps Simplify Access to Healthcare. Pfizer news release. August 27, 2024. Accessed August 30, 2024.

Rapid Diagnostic Tests for Gastrointestinal Infectious Diseases

MP Biomedicals has introduced a new series of in vitro diagnostic tests utilizing immunochromatographic technology to detect gastrointestinal pathogens, specifically Helicobacter pylori, Salmonella typhi, and Vibrio cholerae serogroups O1 and O139. These rapid diagnostic tools are designed to deliver accurate results quickly, thereby improving the capability of healthcare professionals to identify and manage gastrointestinal infections efficiently.

Monoclonal Antibody Reduces Symptomatic COVID-19 Risk by 84% in Immunocompromised

Invivyd’s investigational monoclonal antibody, pemivibart (Pemgarda), which received FDA emergency use authorization earlier this year, has demonstrated continued efficacy in preventing disease onset over a 6-month exploratory period in the patient population. Recent topline data from the ongoing CANOPY phase 3 clinical trial reveals that pemivibart significantly outperformed placebo in preventing symptomatic COVID-19. Participants treated with pemivibart had a 1.9% rate of confirmed symptomatic COVID-19, compared to 11.9% in the placebo group, reflecting an 84% relative risk reduction.

Concerns Over Mosquito-Borne Illness Causes Massachusetts Town to Create Curfew for Parks, Spraying in Counties

The town of Plymouth has decided to close its parks from dusk to dawn due to concerns over eastern equine encephalitis (EEE) following a case reported in the state. Updated August 28: In addition to a reported case in Massachusetts, the New Hampshire Department of Health and Human Services (DHHS) has confirmed the death of an individual from EEE, who was hospitalized with severe central nervous system disease. This is the first human EEE case in New Hampshire since 2014, when three infections, including two fatalities, were reported. The DHHS also noted a confirmed case in Vermont this summer.

Nestlé Health Science Aquires Global Rights to Vowst

Nestlé aims to enhance the global availability of Vowst, an FDA-approved therapy for healthcare-associated infections, while exploring new international opportunities for the product. Earlier this month, Nestlé Health Science announced an agreement to acquire global rights to Vowst from Seres Therapeutics, Inc., pending Seres’ shareholder approval. This acquisition will give Nestlé full control over Vowst’s development, commercialization, and manufacturing worldwide. Since its launch in June 2023, Nestlé has been marketing Vowst (fecal microbiota spores, live-brpk) in the U.S. This orally administered, microbiota-based therapy is designed to prevent the recurrence of Clostridioides difficile infection (CDI) in adults after antibacterial treatment for recurrent CDI, a serious gastrointestinal infection that incurs significant healthcare costs, averaging $43,000 per patient annually.

Pfizer-06425090 C Diff Vaccine Falls Short on Primary Endpoint

The Phase 3 CLOVER trial evaluated the PF-06425090 vaccine for Clostridioides difficile infection (CDI). While the vaccine did not meet the primary goal of preventing CDI, it was safe and well-tolerated. It showed promise in reducing the duration of CDI symptoms, medical attention needs, and antibiotic use. Specifically, the vaccine reduced the median duration of CDI from 4 days to 1 day compared to placebo. The vaccine’s efficacy was 31% for those receiving three doses and 28.6% for those receiving two doses, although these figures had wide confidence intervals.

CDC’s Hospital Sepsis Program Core Elements include seven core elements.
Image credits: CDC

In 2023, the National Healthcare Safety Network (NHSN) Annual Survey revealed significant improvements in sepsis program implementation across US hospitals. 78% percent of hospitals now have sepsis committees, up from 73% in 2022. Additionally, 59% have dedicated time for sepsis program leaders, an increase from 55% the previous year. The inclusion of Antibiotic Stewardship Programs in sepsis committees has also risen to 66%, representing an increase of 629 hospitals.¹

In an interview with Contagion, Raymund Dantes, MD, MPH, Medical Advisor – NHSN, CDC provided insight into these developments. Dantes explained, “From January to March 2024, we asked over 5,000 US hospitals about their sepsis program practices for all of 2023, so this data represents practices both before and after the launch of our Sepsis Core Elements in late August of 2023.”

Sepsis is a severe reaction to an infection that can lead to widespread inflammation, tissue damage, organ failure, and even death. The CDC estimates that sepsis affects at least 1.7 million Americans annually, with at least 350,000 adults who develop sepsis in the hospital either dying or transitioning to hospice care.¹

Dantes also highlighted some challenges hospitals face with the Sepsis Core Elements. “The most recent survey included new questions that reflect the complete scope of the Core Elements. In our summary report, we concluded that many programs could benefit from executive sponsorship, improved assessment of the usability of local hospital sepsis tools, processes to support recovery from sepsis, education to certified nursing assistants and patient care technicians, processes to support prompt antimicrobial administration, and access to key sepsis data.”

The Sepsis Core Elements, inspired by the CDC’s Core Elements of Antibiotic Stewardship, are designed to help hospitals structure their sepsis programs effectively. These elements assist hospitals in organizing staff, identifying resources, and improving the rapid identification and treatment of sepsis to enhance patient outcomes.

Regarding the impact of this data on future sepsis management initiatives, Dantes stated, “Future NHSN annual surveys will continue to monitor uptake of these Sepsis Core Elements. These surveys will highlight the strengths and weaknesses of hospital sepsis programs, and future initiatives may be needed to address areas of need.”

Specific details from the CDC’s survey published in MMWR out of 5,221 hospitals surveyed, 73% reported having a sepsis committee. Although, the presence of these committees varied significantly by hospital size, with 53% of hospitals with 0–25 beds and 95% of those with over 500 beds having committees. Additionally, only 55% of hospitals provided dedicated time for sepsis program leaders, and the same percentage of committees were involved in antibiotic stewardship programs.

These findings highlight the need for improved sepsis care, especially in smaller hospitals. Key areas for enhancement include allocating dedicated time for sepsis program leaders, engaging medical specialists, and integrating antimicrobial stewardship.

Dantes concluded by emphasizing the CDC’s ongoing efforts, “CDC works to prevent and reduce infections that lead to sepsis, optimize healthcare quality, and improve patient safety by raising awareness and knowledge both among the public and healthcare professionals. CDC’s Get Ahead of Sepsis educational effort works year-round with additional effort in September for Sepsis Awareness Month, in order to both promote these messages.”

The CDC’s Hospital Sepsis Program Core Elements provide a framework for developing effective sepsis programs, and future NHSN surveys will monitor their implementation.

References

1. Hospital Sepsis Program Core Elements. CDC. August 13, 2024. Accessed August 30, 2024. https://www.cdc.gov/sepsis/hcp/core-elements/index.html

2. Sepsis Program Activities in Acute Care Hospitals — National Healthcare Safety Network, United States, 2022. MMWR. August 25, 2024. Accessed August 30, 2024. https://www.cdc.gov/mmwr/volumes/72/wr/mm7234a2.htm