Findings increasingly suggest the mortality risk may be reduced by initiating daptomycin within 3 days of infection.

Daptomycin as Frontline Therapy for MRSA Bacteremia: Has the Time Come?

A review of selected investigational long-active treatment options for HIV.

Examining the HIV Treatment Pipeline

Kevin J. Downes, MD, and Contagion® Section Editor Conan MacDougall, PharmD, MAS, BCPS, BCIDP, discuss these important topics as another season approaches.

Children, COVID-19, and Another Crazy Respiratory Viral Season

"Humans dislike change, especially when it is rapid, unexpected, or negative. Delta is all 3."

Delta Means Change

As the number of etiologies increases, we must ground our application of new diagnostic modalities with appropriate assessments.

Fever of Unknown Origin: What Do We Know and Where Do We Go?

The evolution of the major variants, including the delta mutation.

The Variety of Variants in COVID-19

Kevin Kunzmann is the managing editor for 

. Prior to joining parent company MJH Life Sciences in 2017, he worked as a health care and government reporter for The Pocono Record, and as a freelance writer for NJ Advance Media, The Express-Times, The Daily Journal, and more. He graduated from Rowan University with a degree in journalism in 2015. In his spare time, he enjoys reading, cooking, running his dog, and complaining about the Mets. Follow him on Twitter 

The US Food and Drug Administration (FDA) is anticipated to advise that Americans may receive a different 

 as a booster dose than the one they were initially administered.

comes just days after the FDA’s Vaccines and Related Biologic Products Advisory Committee (VRBPAC) deliberated on the provided data of the 

 booster doses—a pair of day-long discussions which both concluded with supporting panel votes but notes of criticism on the strategic distribution of COVID-19 vaccine booster doses.

But more importantly, the report comes after data from a “

” clinical trial showed that patients initially administered a single-dose Janssen COVID-19 adenovirus-based vaccine reported significantly greater antibody titers from a booster dose of Moderna’s mRNA-1273 than a homologous booster dose.

Now, the FDA is anticipated to significantly expand the subpopulation eligible for booster doses—which currently includes persons aged ≥65 years old, those who may be immunocompromised, and those who work in areas of high-risk for SARS-CoV-2 infection—as early as this week. According to the 

, they are also anticipated to grant emergency use authorization (EUA) for the Moderna and Janssen booster doses by Wednesday evening.

 Pfizer-BioNTech’s mRNA vaccine BNT162b2

 is the lone COVID-19 vaccine granted EUA as a booster dose by the FDA.

Articles

The decision comes after supporting data from a "mix and match" trial last week, and may align with emergency authorizations for the Moderna and Janssen booster doses.

FDA Expected to Authorize Heterologous COVID-19 Vaccine Boosters

. Prior to joining MJH Life Sciences in 2020, he has covered a variety of fields and markets including diabetes, oncology, ophthalmology, IT, travel, and local news. You can email him at 

Currently, there are 2 Food and Drug Administration (FDA) approved 

 therapies, which are both daily oral pills. There are studies underway looking at various dosing schedules and different forms of PrEP including pills, injectables, and implants. For the latter, Merck is studying its islatravir (MK-8591) for a potential PrEP indication and recently announced their phase 1 results.

The phase 1 study looked at the pharmacokinetics (PK) of the implant for 3 months, but the goal is eventually to have an implant work for a full year according to Randy Matthews, PhD, MD, senior principal scientist, Merck said.

Islatravir a highly potent nucleoside reverse transcriptase translocation inhibitor (NRTTI) with a long intracellular half-life, is currently in development to treat and prevent HIV. The therapy works by rapidly converting to its active triphosphate (TP) form, islatravir-TP, within targeted cells. Islatravir-TP inhibits reverse transcriptase to suppress HIV replication. In addition to its long intracellular half-life, islatravir has high antiviral potency against HIV and its drug-resistant variants.

, investigators conducted a randomized, double-blind, placebo-controlled trial in adults without HIV. There were 16 participants in 2 cohorts. In what they called Panel A, 6 participants received the implant with 54 mg dose of islatravir, and 2 received a placebo. All the participants were white males with an average age 35.9 years. In Panel B, 6 received the 62mg dose of islatravir and 2 received a placebo. This cohort had 6 males, and 2 females with an average age of 36.8 years. All the participants were white in this cohort.

They had the implants in for 12 weeks and they were followed up to 4 weeks afterwards.

"In the high dose implants we did see the concentrations that we wanted in everybody, and the mean concentrations for both the low dose and the high dose implant were above the PK threshold,” Matthews said.

 spoke to Matthews on the therapy’s mechanism of action, the study’s results, implant placement, and potential benefits including it possibly being a yearly administration.

Videos

Merck recently announced results looking at their islatravir implant studied for HIV prevention for 3 months. The long-term goal is to have the implant last 12 months following administration.   

Islatravir: Investigating Long-Term Treatment Options for PrEP

Nina Cosdon is the assistant editor for Contagion. Before joining MJH Life Sciences, she graduated magna cum laude from Denison University in 2021 with a degree in Communication. You can find her reading, hiking, or antiquing, or by emailing her at ncosdon@mjhlifesciences.com.

 that the US Food and Drug Administration (FDA) has approved their low-dose tablet Biktarvy (bictegravir 30 mg/emtricitabine 120 mg/tenofovir alafenamide 15 mg tablets) for pediatric HIV patients.

Biktarvy’s supplemental New Drug Application (sNDA) was approved for young children weighing 30.9-55.1 lbs. (14-25 kgs.) who are virologically suppressed or new to antiretroviral therapy (ART).

Recent developments in treatments for pregnant women living with HIV have lowered mother-to-child incidence, but 850 children still become 

Gilead Sciences voiced their hope that Biktarvy will help close the gap in HIV treatment options between children and adults. “To address this unmet need, innovations in pediatric formulations must strive towards expanding treatment options for children. The sNDA approval is an important step in fulfilling Gilead’s commitment to a goal of bringing pediatric formulations of Biktarvy to children living with HIV around the world,” said Merdad Parsey, MD, PhD, and Chief Medical Officer of Gilead Sciences.

The FDA approved Biktarvy based upon its phase 2-3 open-label, single-arms study (

), finding the low-dose tablets effective and fairly well-tolerated through 24 weeks. Cohort 3 of the phase 1-2 trials included 22 participants 14-25 kgs, 20 of whom (91%) remained virally suppressed at week 24. The average change in CD4 count was 0.2%.

Biktarvy is a single-tablet ART indicated as a complete HIV-1 treatment regimen for adults and now children living with HIV. Biktarvy is safe for virologically suppressed patients (HIV-1 RNA less than 50 copies per mL) with no ART history or as a replacement for current ART.

Biktarvy combines 3 medicines, bictegravir 30 mg, emtricitabine 120 mg, and tenofovir alafenamide 15 mg, and is the smallest single-tablet regimen (STR) with an integrase strand transfer inhibitor (INSTI). Biktarvy has limited drug interaction potential and a high barrier to resistance, and is taken once a day with or without food. Biktarvy comes with a warning for post treatment acute exacerbation of hepatitis B.

“Finding an efficacious treatment option is paramount, but tolerability and safety are keys to ensuring treatment success,” said Carina Rodriguez, MD, Professor of Pediatrics and Division Chief of Pediatric Infectious Diseases at the University of South Florida Morsani College of Medicine. “With this expanded approval, clinicians can add Biktarvy to their arsenal of options to help ensure these children maintain virologic suppression with a treatment option that makes sense for them.”

Children living with HIV have a new once-daily treatment option to maintain virologic suppression.

FDA Approves Expanded Indication for Biktarvy for HIV Treatment in Young Children

Saskia v. Popescu, PhD, MPH, MA, CIC, is a hospital epidemiologist and infection preventionist. During her work as an infection preventionist, she performed surveillance for infectious diseases, preparedness, and Ebola-response practices. She holds a doctorate in Biodefense from George Mason University where her research focuses on the role of infection prevention in facilitating global health security efforts. She is certified in Infection Control and has worked in both pediatric and adult acute care facilities.

Centers for Disease Control and Prevention

 (CDC) 44 million cases of COVID-19 have occurred within the United States—of these individuals, over 714,243 have died. Access to care, widening social and racial inequities, and the realities of living in a pandemic have impacted health globally. This impact will likely be farther than we could imagine and take years to understand. 

Beyond morbidity and mortality associated with COVID-19 or as a result of hurdles to care, there are health implications of living in a pandemic. One of the infrequently discussed health outcomes that can be impacted by a pandemic is fertility. While there are many aspects of fertility, access to infertility care is a significant piece to those hoping to conceive. A new study published in 

 sought to address the impact and trends in infertility care 

 those in the United States who are commercially insured.

It was recommended by the American Society for Reproductive Medicine (ASRM) in March 2020 that infertility care be suspended due to the pandemic. The following month, ASRM recommended cautious continuation of care, which sheds light into one of the potential factors that led to the decreased birth rate in the United States during the pandemic.

Utilizing a cross-sectional study, the research team harnessed the power of an interrupted time series design and de-identified claims data for those insured within the United States and aged between 18-50 years between February 2018 to December 2020. Pulling socio-economic data for a majority of the enrollees and utilizing a linear spline regression to evaluate the COVID-19 pandemic impact on fertility outcomes. From the 8.7 million women eligible for the study, the research team found that there were “incremental increases in infertility and ART service utilization rates before the pandemic (1.2 vs 0.72 per 10 000/y), sharp decreases during care suspension (−50.4 vs −21.6 per 10 000/y), and sharp recoveries after care continuation (96.0 vs 42.6 per 10 000/y) that were sustained through the end of the study. Patterns in infertility and ART services use were similar in all analyses. Before the pandemic, women aged 35 to 37 years had the highest ART utilization rate (29.8 per 10 000), followed by women aged 38 to 40 (24.0 per 10 000), 41 to 42 (16.8 per 10 000), 18 to 34 (6.4 per 10 000), and 43 to 50 (5.0 per 10 000). The decline and recovery in utilization rates varied by age.” Moreover, the authors noted prior to the COVID-19 pandemic, “the ART utilization rate was highest among Asian women (19.1 per 10 000), followed by White, Black, and Hispanic women (9.2, 5.3, and 4.5 per 10 000, respectively; 

Overwhelmingly, there is a desperate need to understand and address the impact the pandemic has had on fertility. The findings point to a concern and swift increase in infertility care after April 2020 that frankly exceeded previous levels—meaning that prioritizing access to infertility care and ART in times of crisis is critical.

One of the infrequently discussed health outcomes that can be impacted by a pandemic is fertility. Using a cross-sectional study, a research team reported incremental increases in infertility during this period.

Infertility Care and the COVID-19 Pandemic  

Richard J. Hankins, MD, is an assistant professor in the Division of Infectious Diseases, Department of Internal Medicine, at the University of Nebraska Medical Center in Omaha.

Laura Selby, DO, completed her internal medicine residency training at Samaritan Health Services in Corvallis, Oregon, and is an infectious diseases fellow in the Division of Infectious Diseases, Department of Internal Medicine, at the University of Nebraska Medical Center in Omaha.

Peripheral venous catheters (PVCs) are one of the most frequently used medical devices.

 Approximately 350 million PVCs are sold in the United States each year.

 Patients receive PVCs in many clinical settings, including outpatient infusions, emergency medical care, and inpatient care, with 30% to 80% of hospitalized patients requiring PVC insertion during their stay.

 In fact, an estimated 80% to 90% of all vascular catheters are PVCs, far exceeding central venous catheters (CVCs).

 Despite the large number of PVCs utilized yearly, data for infectious complication rates are less robust than with the less-prevalent central venous catheters. This can be at least partially attributed to the requirement of acute care hospitals to track and report central-line associated bloodstream infections (CLABSIs) but not peripheral venous catheter–bloodstream infections (PVC-BSI).

Central Venous Catheter vs Peripheral Venous Catheter Bloodstream Infections

BSIs from PVCs are reported at lower rates than for CVCs.

 However, the rate of PVC-BSI varies widely around the world. Results of studies of PVCs performed in the United Kingdom, US, and Australia have shown rates of 0.2 to 0.7 per 1000 catheter days.

 A prospective study in resource-limited areas of Southeast Asia found 2.65 PVC-BSI events per 1000 catheter days for patients in intensive care units.

 Although in resource-rich countries the overall risk of PVC-BSI is low, considering that up to 350 million PVCs could be placed per year in the United States, the potential for morbidity and mortality from PCV-BSI could easily rival that of CLABSI. If only half of purchased PVCs in the US are placed successfully, a conservative estimate, with an average dwell time of 3 days and a rate of 0.4 PVC-BSI events per 1000 catheters days, then 210,000 PVC-BSI potentially could occur each year in the United States alone.

 Compare this with the estimated 30,100 used in the US in 2018.

 Please note, this is an estimate based on limited data to illustrate the possible magnitude of PVC-BSI; the true number of PVC-BSI is unknown.

Data on the causative organism of PVC-BSI are more limited than for CLABSI.

 In adult patients, gram-positive cocci are the primary cause of PVC-BSI (

). However, gram-negative rod bacteremia occurred at nearly twice the rate, 33.0% vs 18.8% compared with CLABSI . Results of a 2021 pediatric study identified gram-negative bacteria as more prevalent than gram-positive bacteremia, with 59.3% of PVC-BSI being caused by gram-negative bacteria.

 This study included a large number of children with chronic illnesses and recent health care exposures, which may have contributed to the higher-than-expected gram-negative bacteremia. Regardless, results of studies in both children and adults demonstrate gram-negative bacteremia as a substantial cause of PVC-BSI. Patients with PVC-BSI caused by 

 are more likely to have metastatic seeding of the infection and higher mortality than PVC-BSI caused by other pathogens.

Placement and Management of Peripheral Vascular Catheters

As with all vascular catheters, one should consider the type of access required prior to the placement of the catheter. PVCs are appropriate for patients who have an anticipated vascular access need of less than 6 days and do not require medications that should be infused via central access. Midline catheters should be considered if access is known to be needed for more than 6 days, but central venous access is not required.

Reductions in CLABSI rates have been achieved through implementing care bundles designed to standardize practices and ensure infection prevention strategies are utilized during placement and maintenance of a CVC. Placement and maintenance bundles for PVCs are less well-studied, and lack of consistency across components and end points has made systematic review problematic.

 More research is needed to determine if bundles are effective at PVC-BSI prevention, and if so what elements of a bundle are needed to reduce complications.

 A study published in July 2021 demonstrated that alcohol-based chlorhexidine for skin preparation prior to PVC placement decreased both BSI and catheter colonization compared with iodine-based skin antiseptic preparation.

 Guidelines recommend hand hygiene, alcohol-based chlorhexidine skin prep, disinfection of needleless connectors, and implantation of a PVC insertion bundle; however, the guidelines acknowledge the lack of evidence for specific bundle components.

Patients who have difficult venous access sometimes have a central venous catheter or peripherally inserted central venous catheter placed due to inability to place a PVC.

 For patients with difficult venous access, multiple attempts to place a PVC can cause physical and emotional distress; for some patients this distress is enough to delay hospitalized care.

 Placement of PVCs under ultrasound guidance decreases need for CVCs in patients with difficult venous access.

The dwell time has a complicated association with PVCs and PVC-BSIs. Results of studies have shown that longer indwell times are associated with both an increase in catheter colonization and increased rates of PVC-BSIs.

 However, current evidence suggests that removal of PVCs does not result in the same benefits seen in removal of CVCs. Routine removal and replacement of PVCs every 72 to 96 hours to prevent complications has similar rates of PVC-BSI when compared with clinically indicated removal.

 Clinically indicated removal means that a PVC would be removed if signs of infection, inflammation, blockage, or infiltration are present.

 PVCs should be inspected each shift to assess for complications and removed if complications are noted.

 Clinically indicated removal does not increase risk of PVC-BSI, but the overall exposure to PVC is a risk factor for PVC-BSI.

 When no longer clinically needed, PVCs should be removed, as unused catheters remain a risk for infection even when not in use.

PVC-BSIs are studied less than CVC-associated infections, yet the number of PVCs placed yearly far exceeds those of CVCs. Based on available data, bloodstream infections due to PVCs outnumber those from CVCs. The medical community needs to be aware of the serious risks and complications from PVCs, and as such PVCs should be treated with similar respect afforded to CVCs. PVCs should be removed when no longer clinically necessary because the total number of catheter days increases the risk of PVC-BSI. Similarly, they should not be inserted unless there is a clinical necessity. Based on recent literature, it would be reasonable to consider chlorhexidine and alcohol for skin preparation prior to PVC insertion, although further research will need to be done to evaluate if this is lowering only localized insertion site infections or PVC-BSI as well. PVCs should be assessed daily and removed when they are no longer clinically indicated as routine replacement does not decrease rates of PVC-BSI. Further research is desperately needed to identify if bundles are effective strategies to decrease PVC-BSI and, if so, which components are needed to reduce infection rates.

Zhang L, Cao S, Marsh N, et al. Infection risks associated with peripheral vascular catheters. 

. 2016;17(5):207-213. doi:10.1177/1757177416655472

Steere L, Ficara C, Davis M, Moureau N. Reaching one peripheral intravenous catheter (PIVC) per patient visit with LEAN multimodal strategy: the PIV5rights bundle. 

 2019;24(3):31-43. doi:10.2309/j.java.2019.003.004

Mermel LA. Short-term peripheral venous catheter-related bloodstream infections: a systematic review. 

. 2017;65(10):1757-1762. doi:10.1093/cid/cix562

Gorski L, Hadaway L, Hagle ME, et al. Infusion Therapy Standards of Practice, 8th Edition. 

. 2021;44(suppl 1S):S1-S224. doi:10.1097/NAN.0000000000000396

Rosenthal VD, Bat-Erdene I, Gupta D, et al. Six-year multicenter study on short-term peripheral venous catheters-related bloodstream infection rates in 727 intensive care units of 268 hospitals in 141 cities of 42 countries of Africa, the Americas, eastern Mediterranean, Europe, south east Asia, and western Pacific regions: International Nosocomial Infection Control Consortium (INICC) findings. 

. 2020;41(5):553-563. doi:10.1017/ice.2020.20

Hopkinson S, Green AK, Hewitt BE, Grace SA. Short peripheral catheter dwell time and associated complications: a systematic review. 

. 2020;43(4):200-207. doi:10.1097/NAN.0000000000000374

Current HAI progress report. CDC. Updated December 2, 2020. Accessed 22 August 2021. https://www.cdc.gov/hai/data/portal/progress-report.html

Tsuboi M, Hayakawa K, Mezaki K, et al. Comparison of the epidemiology and microbiology of peripheral line- and central line-associated bloodstream infections. 

. 2019;47(2):208-210. doi:10.1016/j.ajic.2018.08.016

Berger I, Cohen T, Rahmani E, et al. Peripheral venous catheter-related bloodstream infections in hospitalized children: the role of gram-negative bacteria. 

. Published online July 6, 2021. doi:10.1097/INF.0000000000003255

Sato A, Nakamura I, Fujita H, et al. Peripheral venous catheter-related bloodstream infection is associated with severe complications and potential death: a retrospective observational study. 

. 2017;17(1):434. doi:10.1186/s12879-017-2536-0

Cawcutt KA, Hankins RJ, Micheels TA, Rupp ME. Optimizing vascular-access device decision-making in the era of midline catheters. 

. 2019;40(6):674-680. doi:10.1017/ice.2019.49

Ray-Barruel G, Xu H, Marsh N, Cooke M, Rickard CM. Effectiveness of insertion and maintenance bundles in preventing peripheral intravenous catheter-related complications and bloodstream infection in hospital patients: a systematic review. 

. 2019;24(3):152-168. doi:10.1016/j.idh.2019.03.001

Guenezan J, Marjanovic N, Drugeon B, et al. Chlorhexidine plus alcohol versus povidone iodine plus alcohol, combined or not with innovative devices, for prevention of short-term peripheral venous catheter infection and failure (CLEAN 3 study): an investigator-initiated, open-label, single centre, randomised-controlled, two-by-two factorial trial. 

. 2021;21(7):1038-1048. doi:10.1016/S1473-3099(20)30738-6

Galen BT, Southern WN. Ultrasound-guided peripheral intravenous catheters to reduce central venous catheter use on the inpatient medical ward. 

. 2018;27(1):30-32. doi:10.1097/QMH.0000000000000156

Plohal A. A qualitative study of adult hospitalized patients with difficult venous access experiencing short peripheral catheter insertion in a hospital setting. 

. 2021;44(1):26-33. doi:10.1097/NAN.0000000000000408

Safdar N, McKinley LM, Davidson B, Broome C, Schenk J. Recommendations to replace peripheral venous catheters every 72-96 hours: is a single reference enough? 

 2011;79(2):172-173. doi:10.1016/j.jhin.2011.06.005

Maki DG, Ringer M. Evaluation of dressing regimens for prevention of infection with peripheral intravenous catheters. Gauze, a transparent polyurethane dressing, and an iodophor-transparent dressing. 

Webster J, Osborne S, Rickard CM, Marsh N. Clinically‐indicated replacement versus routine replacement of peripheral venous catheters. 

 2019;1(1):CD007798. doi:10.1002/14651858.CD007798.pub5

Lack of data may mean bloodstream infections caused by PVCs are an overlooked cause of morbidity in hospitalized patients.

Reducing Peripheral Venous Catheter Infections

, coronavirus and other infectious diseases.

Comparing 2020 to 2019, investigators saw a reduction in the number of HIV tests, the number of in-person consultations, and new enrollments in care, due to the disruption in HIV care throughout the COVID-19 pandemic.

HIV Care Disrupted by COVID-19 Pandemic

Ken reports on medical innovations and advances in practice and edits presentations for news and professional education publications. He previously taught and mentored pharmacy and medical students, and provided and managed pharmacy care and drug information services. He regularly contributes to Contagion Live, HCP Live, Neurology Live, and Pain Medicine News.

New survey finds little more than half of US adults are planning to obtain vaccination against influenza despite urging by health officials.

National Survey Finds Low Interest in Influenza Vaccination

The VRBPAC committee unanimously voted in favor of the Janssen (Johnson & Johnson) COVID-19 vaccine for use under EUA as a booster dose in individuals 18 years and older at least 2 months after a single dose primary vaccination.

VRBPAC Unanimously Supports EUA for Janssen COVID-19 Booster Shot

Torey Roesch is a second-year infectious diseases fellow at Temple University Hospital in Philadelphia, Pennsylvania. His current interests include infections affecting solid organ transplant recipients and antibiotic stewardship.

Outside of vaccines, these underutilized therapies are the best defense against severe disease.

A Review of the Currently Available Monoclonal Antibodies for COVID-19

Brian P. Dunleavy has been covering health and medical research for more than 25 years, for United Press International and EverydayHealth.com, among other outlets. He is also the former editor of Infectious Disease Special Edition. In addition, he has written on other subjects for Biography.com, History.com, the 

, among others. He holds a master’s degree from the University of Missouri School of Journalism.

Lower rates of COVID-19 vaccination may be due to access, not hesitancy.

Public Health Watch: CDC Analysis Highlights Vaccine Challenges for People with Disabilities

The VRBPAC meeting precedes deliberation from the FDA on amending the company's emergency authorization to include booster doses for adult patients.

FDA Panel Votes Unanimously to Support Moderna COVID-19 Vaccine Booster Dose

In a recent study, taniborbactam restored in vitro activity of cefepime against Enterobacterales.

Combination Cefepime-Taniborbactam (FTB) May Be a New Treatment Option for Resistant Infections

While receiving a booster of one’s original COVID-19 shot leads to an immune boost, this was heightened among individuals who received a different booster than their primary vaccine.

Mixing COVID-19 Vaccine Boosters Increases Immune Response

There are MSM who are indicated for PrEP use that don’t use it, and vice versa, the study authors found.

Top Medical News

FDA Expected to Authorize Heterologous COVID-19 Vaccine Boosters

Islatravir: Investigating Long-Term Treatment Options for PrEP

FDA Approves Expanded Indication for Biktarvy for HIV Treatment in Young Children

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Reducing Peripheral Venous Catheter Infections

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