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 

Kenneth Bender, PharmD, MA

CDC Recommends HCV Testing of Perinatally Exposed Infants Children

 The Centers for Disease Control and Prevention (CDC) has issued new 

 for hepatitis C virus (HCV) testing of all perinatally exposed infants and children and for referral of those testing positive to appropriate care and the curative treatments that are approved for children as young as 3 years.

"Proper identification of perinatally infected children, referral to care, and curative treatments are critical to achieving the goal of hepatitis C elimination," declared Lakshmi Panagiotakopoulos, MD, Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, sexually transmitted diseases (STD), and tuberculosis (TB) Prevention, CDC, Atlanta, GA, and colleagues.

Four new recommendations were issued to address a greater than three-fold increase in HCV incidence among persons of reproductive age during the period of 2010-2021 and the 6 to 7 percent of perinatally exposed infants and children who acquire HCV infection.

The recommendations supplement those of 2020 for universal hepatitis C screening among adults, which includes universal screening of pregnant persons during each pregnancy, and they update guidance from 1998 on the type and timing of indicated testing as that technology has evolved.

HCV testing of all perinatally exposed infants with a nucleic acid test (NAT) for detection of HCV RNA aged 2 to 6 months

Consultation with a health care provider with expertise in pediatric hepatitis C management for all infants and children with detectable HCV RNA

Perinatally exposed infants and children with an undetectable HCV RNA result at or after age 2 months do not require further follow-up unless clinically warranted.

A NAT (nucleic acid test) for HCV RNA is recommended for perinatally exposed children aged 18 months or older who previously have not been tested.

Perinatal exposure occurs in infants born to pregnant persons with detectable HCV RNA, in testing which Panagiotakopoulos and colleagues acknowledge is not consistently obtained during pregnancy.

"Because recommendations have recently shifted from risk-based to universal screening, uptake of HCV screening during pregnancy is evolving," they commented.

The CDC emphasizes the importance of testing all perinatally exposed infants for the hepatitis C virus (HCV) using a nucleic acid test (NAT) to detect HCV RNA between the ages of 2 and 6 months.

Infants and children with undetectable HCV RNA at or after age 2 months do not require further follow-up unless clinically warranted, streamlining interventions for those who do not test positive.

The recommendations highlight factors affecting HCV transmission, such as the association with poorly controlled HIV coinfection, the impact of antiretroviral therapy for HIV during pregnancy, and various aspects of delivery.

Panogiotakopoulos and colleagues note that transmission occurs more frequently with poorly controlled HIV coinfection, which might be more common in pregnant persons injecting drugs. They also indicate that the use of antiretroviral therapy for HIV during pregnancy to lower HIV viral load is associated with lower rates of perinatal HCV transmission.

Several aspects of transmission are considered, including that HCV transmission risk is increased with membrane rupture lasting more than 6 hours before delivery and with the use of internal fetal monitoring. Panogiotakopoulos and colleagues also note that amniocentesis is usually recommended over chorionic villus sampling when invasive testing is indicated.

There is no evidence, they point out, that caesarean delivery is less likely than vaginal delivery to prevent perinatal HCV transmission. Breastfeeding after delivery is also not associated with an increased risk of HCV transmission unless nipples are cracked or bleeding.

Recognizing that costs are a barrier to treatment, the recommendations include cost-effectiveness calculations: costs and health outcomes of various testing strategies incorporated rates of spontaneous clearance of infection. Outcomes had diagnosed infections, treated or cured infections, hepatocellular carcinoma, liver transplants, and liver-related deaths. Among several modeling studies, testing known perinatally exposed infants with a NAT (nucleic acid test) for HCV RNA at age 2 to 6 months was determined to achieve both cost-savings and improve health outcomes.

"Better understanding is needed regarding how to improve linkage to care for these infants. Specifically, barriers to testing and reasons why testing is not done and identified children are not referred to appropriate providers for follow-up," Panogiotakopoulos and colleagues urge.

1. Panagiotakopoulos L, Sandul AI, Conners EE, et al. CDC Recommendations for hepatitis C testing among perinatally exposed infants and children—United States, 2023. 

Articles

The CDC recommends HCV testing for perinatally exposed infants and children to address the increasing incidence of hepatitis C among reproductive-age individuals, focusing on early detection and appropriate care.

CDC's Recommendation for Hepatitis C Testing in Infants Exposed During Perinatal Period

Antidepressants appeared to induce antimicrobial resistance (AMR) and “persistence” in ostensibly susceptible bacteria in a multifaceted 

 of bacterial cultures challenged by antibiotics after exposure to clinically relevant concentrations of antidepressants.

“Although antibiotic resistance has become a major threat to human health worldwide, the phenomenon caused by antidepressants has been largely overlooked,” observed Jianhua Guo, DEng, Australian Centre for Water and Environmental Biotechnology, The University of Queensland, Brisbane, QLD, Australia, and colleagues.

“Our findings illustrate how antidepressants induce bacterial resistance and persistence to a range of antibiotics,” they indicate. "The antibiotic persistence (

) helps to maintain bacterial resistance, and the persisters could evolve to resistant bacteria during the long-term evolutionary process,” Guo and colleagues explain.

In his profile at the University of Queensland, Guo and his team are credited for the “ground-breaking findings” that non-antibiotic pharmaceuticals/chemicals contribute to the spread of antimicrobial resistance, “which has substantially augmented our understanding of the causes of AMR.”

The investigators’ interest in the possibility arose from the evidence that antidepressants modify the 

; their current investigation follows from having found AMR after exposing bacteria to 

 fluoxetine. They conducted the current research to ascertain whether that finding reflects a drug-specific action or is common to other antidepressants and to identify possible mechanisms.

 plate culturing under both aerobic and anaerobic conditions, fluorescence-based flow cytometry detection, and genome-wide analyses to discern changes in antibiotic susceptibility after antidepressant exposure. They tested the commonly prescribed antidepressants representing different classes, sertraline, escitalopram, bupropion, and duloxetine, as well as agomelatine, from an additional class of antidepressant not approved in the US.

Exposure to the antidepressants was found to increase the production of intracellular reactive oxygen species (ROS) and induce efflux pump expression; both of which the investigators correlate to the emergence of antibiotic-resistant and persistent phenotypes. In addition, they determined that conjugative gene transfer was promoted.

“Together, our findings describe a mechanism by which exposure to antidepressants can lead to enhanced resistance to antibiotics,” the investigators indicated.

After only 1 day of exposure to sertraline and duloxetine at a concentration typical in the colon, the ratio of resistant cells to total cell number was more than 10,000-fold compared to the non-antidepressant control. Guo and colleagues point out that this was a greater magnitude of emergence than others have found with several sub-inhibitory antibiotics, including nalidixic acid, ampicillin, rifampicin, and carbenicillin.

The resistant traits were determined to be heritable, but the rate and magnitude of effect were not constant across all antidepressants. In contrast to sertraline and duloxetine, bupropion, escitalopram, and agomelatine were found to exert “limited” effects on resistance. These were associated with up to eightfold growth of resistant cells relative to the non-antidepressant control, which was at higher concentrations of the antidepressants (100 mg/L).

In phenotypic and genotypic analyses, the investigators determined that induced resistance with sertraline and duloxetine was associated with enhanced ROS generation and that this did not occur in anaerobic conditions. Sertraline and duloxetine were also found to enhance efflux pump expression, which, the investigators point out, is one of the principal mechanisms of the cell expelling antibiotics and reducing susceptibility.

The investigators indicate that their findings implicate antidepressants as a contributing driver of the increasing AMR. They suggest that additional studies should be conducted to validate the effects, employing more bacterial strains and possibly conducted in-vivo in the gut microbiota.

“The findings might be also useful for pharmaceutical factories and public health organizations to comprehensively evaluate antimicrobial sides of antidepressants,” Guo and colleagues indicate.

A new study shows antibiotics are not the only widely used pharmaceuticals that can induce the emergence of treatment-resistant bacteria.


Kenneth Bender, PharmD, MA

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