Applications for Bacteriophage Therapy during Pregnancy and the Perinatal Period

Abstract

Pregnant women and their unborn children are a population that is particularly vulnerable to bacterial infection. Physiological changes that occur during pregnancy affect the way women respond to such infections and the options that clinicians have for treatment. Antibiotics are still considered the best option for active infections and a suitable prophylaxis for prevention of potential infections, such as vaginal/rectal Streptococcus agalactiae colonization prior to birth. The effect of such antibiotic use on the developing fetus, however, is still largely unknown. Recent research has suggested that the fetal gut microbiota plays a critical role in fetal immunologic programming. Hence, even minor alterations in this microbiota may have potentially significant downstream effects. An ideal antibacterial therapeutic for administration during pregnancy would be one that is highly specific for its target, leaving the surrounding microbiota intact. This review first provides a basic overview of the challenges a clinician faces when administering therapeutics to a pregnant patient and then goes on to explore common bacterial infections in pregnancy, use of antibiotics for treatment/prevention of such infections and the consequences of such treatment for the mother and infant. With this background established, the review then explores the potential for use of bacteriophage (phage) therapy as an alternative to antibiotics during the antenatal period. Many previous reviews have highlighted the revitalization of and potential for phage therapy for treatment of a range of bacterial infections, particularly in the context of the increasing threat of widespread antibiotic resistance. However, information on the potential for the use of phage therapeutics in pregnancy is lacking. This review aims to provide a thorough overview of studies of this nature and discuss the feasibility of bacteriophage use during pregnancy to treat and/or prevent bacterial infections.

Perinatal Streptococcus agalactiae Epidemiology and Surveillance Targets

“…They concluded that Ն70% vaccine efficacy in addition to IAP for unvaccinated women would prevent more disease than current strategies, with a similar economic burden (145). Epidemiological data about GBS are invaluable not only for vaccine development and success but also for other future targeted therapeutic agents, such as bacteriophage therapy (146).…”

Infection‐mediated preterm birth: Bacterial origins and avenues for intervention

“…If lytic phages specific for these bacteria were to be identified, these bacteria could be eliminated from the genital tract without affecting the surrounding vaginal microbiota. However, phage therapy has yet to be explored in pregnancy …”

Bacteriophages: Protagonists of a Post-Antibiotic Era

“…The lytic cycle implies bacterial death, which generates virion output. For this, they take advantage of the replication system of the host cell, and when their proteins and viral components are formed, they induce cell lysis [ 18 , 19 ]. In contrast, lysogenic cycles are based in the integration of the genetic material of the phage into the genome of the host cell.…”

“…In contrast, lysogenic cycles are based in the integration of the genetic material of the phage into the genome of the host cell. At the end of the replication cycle, no new virions are obtained, but bacterial cells with phage genetic material are created, as temperate phages [ 18 ]. Due to the variability between phages, it is important to determine which are the most appropriate bacteriophages for each potential application [ 20 ].…”