Erythromycin and Vitamin K Prophylaxis in the Newborn Lynette Barnhart, RNC, SNNP Magidah Kobty, RNC, SNNP University of Texas Medical Branch at Galveston School of Nursing Neonatal AHA GNRS 5303

Objectives Explain the origin of Erythromycin and Vitamin K Review Texas requirements for administration Briefly review erythromycin usage Briefly review vitamin K usage Review evidence based practice Discuss long term outcomes and management of positive findings Upon review of this presentation, the learner will understand the following objectives.

Origin Erythromycin Vitamin K (Phytonadione) 1881 Carl Crede Prophylaxis of ophthalmia neonatorum (ON) Gonococcal or Chlamydial infection treatment (Rai, et al, 2012) (CDC, 2010) Vitamin K (Phytonadione) 1894 Townsend 1943 Dam and Doisy Prophylaxis of Vitamin K Deficiency Bleeding (VKDB) (“Hemorrhagic disease, 2012”). Administration of Erythromycin and Vitamin K at birth was initiated to provide prophylaxis of opthalmia neonatorum (ON) and Vitamin K Deficiency Bleeding (VKDB). ON is a type of eye infection that can result in blindness of the infant if not treated appropriately. It is caused by viruses, blocked tear ducts, and sexually transmitted infections of gonorrhea and chlamydia. Gonococcal infections are caused by the bacteria Neisseria gonorrhea while Chlamydial infections are caused by the bacteria Chlamydia trachomatis (CDC, 2010). In 1881, a physician by the name of Carl Crede realized that infants born vaginally to mothers infected with gonorrhea were infected with ON. His correlation of this sexually transmitted infection to ON led to his treatment of silver nitrate in the newborn’s eyes shortly after delivery (Rai, et al, 2012). Over the years, the use of silver nitrate has been discontinued and replaced with erythromycin ophthalmic ointment for the prevention of both gonorrhea and chlamydia. Vitamin K deficiency bleeding (VKDB) was formerly known as Hemorrhagic Disease of the Newborn and is a life threatening neonatal bleeding disorder. In 1894 Townsend described a bleeding disorder that was self limiting and not like Hemophilia (“Hemorrhagic disease, 2012”). In 1943 Hendrik Dam and Edward Doisy won a Nobel Prize for the discovery of the association between vitamin K and coagulation factors VII, IX, and X (“Hemorrhagic disease, 2012”).

Mandatory Erythromycin prophylaxis Texas Health and Safety Code 81.091 Physician, nurse, or midwife Administer within 2 hours after birth Failure to treat Class B misdemeanor Free of charge If family is unable to pay for prophylaxis Parental refusal May result in a CPS referral Texas Health and Safety Code 81.091 was made effective in March 16, 1994 and several amendments have been made in 2003, 2008, and 2010. This code states that a Physician, nurse, or midwife in the state of Texas must administer 0.5% opthalmic erythromycin solution to each eye within tow hours of birth. Failure to treat according to this code is considered a Class B misdemeanor. In the event a family is unable to pay for prophylaxis it is administered free of charge. A family’s refusal of this prophylactic treatment in the state of Texas may potentially result in a CPS referral. (Texas Administrative Code, 2013) (Texas Administrative Code, 2013)

Erythromycin usage in patient care Erythromycin Ophthalmic Ointment USP, 0.5% Topical administration to eyes bilaterally at birth Premature Infants Eyes fused Mechanism of action (“Truven Health”, 2013). A ribbon of ophthalmic Erythromycin 0.5% ointment is administered to both eyes within two hours of birth (“Truven Health” 2013). Premature infants will receive the same dose as term infants. In the even the infant is born with the eyes fused one dose of Erythromycin is to be administered at delivery and a second dose when the eyes open for the first time (“Truven Health”, 2013). Erythromycin is the only CDC recommended antibiotic ointment for infants in the prevention of opthalmia neonatourm (2010). The solution flows over the conjunctiva and inhibits the protein synthesis of infectious organisms such as Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenza, Neisseria gonorrhea, and Chlamydia trachomatis (“Truven Health, 2013).

Adverse Effects of Erythromycin May cause irritation and blurred vision Allergic reaction Rash, swelling, breathing difficulties (“Truven Health”, 2013). Ophthalmic administration of Erythromycin may cause irritation, blurred vision, and/or allergic reactions. Allergic reactions present with rash, swelling, and breathing difficulties (“Truven Health”, 2013).

Vitamin K prophylaxis Currently not mandated in TX Recommended by AAP Administration at delivery Now rare condition in the United States (“Hemorrhagic disease”, 2013) Although not mandated in the state of Texas, the American Academy of Pediatrics (AAP) recommends every baby receives an injection of Vitamin K immediately after birth (“Hemorrhagic disease”, 2013). With the implementation of Vitamin K administration after delivery this potentially fatal condition is rare in the United States (“Hemorrhagic disease”, 2013).

Vitamin K Fat soluble vitamin At birth After birth Essential for function of blood coagulation At birth Reduced vitamin K stores Minimal placental transfer After birth Vitamin K is limited in breast milk (Van Winckel et al, 2008) Vitamin K is a fat soluble vitamin that act as a co factor for y-glutaml carboxylase and the modification to y-carboxyglutamate (Van Winckel, et al, 2008). The Y-carboxylated proteins function in blood coagulation (Van Winckel et al, 2008). Newborn infants are at risk for Vitamin K Deficiency Bleeding (VKDB) because Vitamin K has minimal placental transfer and infants are born with reduced Vitamin K stores (Van Winckel et al, 2008). Vitamin K availability in human milk is limited and considered a poor source (Van Winckel et al, 2008). Vitamin K administration at birth is used as prophylaxis against Vitamin K Deficiency Bleeding in newborns.

VKDB Three classifications Early onset Classic onset Late onset Within 24 hours Maternal drugs that inhibit vitamin K Classic onset 24 hours-7 days Delayed/insufficient feedings Late onset 2-12 weeks Exclusive breastfeeding Malabsorption syndroms Cholestasis (Lippi & Fanchini, 2011) There are three classifications of VKDB as a result of no administration of Vitamin K at birth. Early onset occurs within the first 24 hours of life and is most often associated with maternal drugs that inhibit vitamin K, such as anticonvulsants, antituberculosis drugs, cephalosporins, and warfarin (Lippi & Fanchini, 2011). Infants with early VKDB present with a severe cephalic haematoma, intracranial and intra-abdominal hemorrhages (Lippi & Fanchini, 2011). Classic onset occurs between 24 hours and 7 days and is associated with delayed or insufficient feeding (Lippi & Fanchini, 2011). Infants with classic VKDB present with bruising, GI blood loss , bleeding from umbilicus, and puncture sites (Lippi & Fanchini, 2011). Late onset which occurs between 2 weeks and 12 weeks is associated with exclusive breastfeeding, malabsoprtion syndromes and cholestasis (Lippi & Fanchini, 2011). Late VKDB symptoms are severe and present with intracranial hemorrhage 50% of the time (Lippi & Fanchini, 2011). Late VKDB has a 20% mortality rate (Lippi & Fanchini, 2011).

Vitamin K Dosage Term infants Preterm infants (<32 weeks) 0.5mg-1mg IM at birth Preterm infants (<32 weeks) >1000gms 0.5mg IM at birth <1000gms 0.3mg/kg IM at birth (“Truven Health”, 2013). Neofax recommended dosage is 0.5mg-1mg Vitamin K (Phytonadione) IM at birth (“Truven Health”, 2013). Preterm infants who are less than 32 weeks with a birth weight greater then 1000gms are to receive 0.5mg IM, and those less than 1000gms are to receive 0.3mg /kg IM (“Truven Health”, 2013).

Adverse effects of Vitamin K administration Injection site irritation Black box warning Shock Cardiac arrest Respiratory arrest (“Truven Health”, 2013). Vitamin K has a black box warning for fatalities immediately after IV and IM administration presenting with shock, cardiac and/or respiratory arrest (“Truven Health”, 2013).

Evidence Based Practice Erythromycin Meta analysis Reduction of chlamydial and gonorrheal ON (Darling, 2010) Vitamin K Randomized trials Single dose reduces a life threatening bleeding occurrence in newborns (Puckett & Offringa, 2009) A meta analysis studied the effects of prophylactic treatment of ON with several different eye ointments and Erythromycin was found to effectively reduce the risk of chlamydial and gonorrheal ON (Darling, 2010). In this study the efficacy of erythromycin was shown to decrease the infection risk of ON to the newborn (Darling, 2010). The CDC currently recommends the usage of erythromycin as the antibiotic solution of ON in the newborn period (CDC, 2010). According to (Puckett & Offringa, 2009), two randomized trials concluded that a single dose of Vitamin K administered at birth effectively reduced clinical bleeding and improves biochemical coagulation status at 1-7 days of life when compared to a placebo or no treatment at all.

Long Term Outcome Erythromycin Vitamin K With treatment ON cases are very rare Resistance to N. gonorrhea (CDC, 2010) Vitamin K With prophylaxis fatal condition is now rare (“Hemorrhagic disease”, 2013) Although treatment of opthalmia neotorum is a one time dose due at the time of an infant’s delivery, long term usage of erythromycin may result in antibiotic resistance to Neisseria gonorrhea (CDC, 2010) The use of cephalosporins has been shown to be effective in cases where there is resistance to erythromycin treated gonorrhea (CDC, 2010). The failure to administer erythromycin to an infant at delivery may lead to blindness if the infant suffers from persistent conjuctivitis from a gonorrheal or chlamydial infection (CDC, 2010). With the AAP recommendation and implementation of Vitamin K administration after delivery this potentially fatal condition is now rare in the United States (“Hemorrhagic disease”, 2013). With the implementation of Vitamin K administration at birth in the United States the incidence of Vitamin K deficiency bleeding is 0.25-1.7% during the first week of life (“Hemorrhagic disease”, 2013). Both Asia and Europe report a decrease in late vitamin K deficiency bleeding from 4.4-7.2 cases per 100,000 births to 1.4-6.4 cases per 100,000 births after Vitamin K prophylaxis was initiated (“Hemorrhagic disease”, 2013).

References Center for Disease Control and Prevention (2010). Retrieved on October 10, 2014 from http://www.cdc.gov/std/treatment/2010/gonococcal-infections.htm Darling, Elizabeth (2010). A Meta-analysis of the Efficacy of Ocular Prophylactic Agents used for the Prevention of Gonococcal and Chlamydial Ophthalmia Neonatorum. Journal of Midwifery & Women’s Health, 55(4), 319-327. Dekker, Rebecca (2012). Is Erythromycin Eye Ointment Always Necessary for Newborns? Retrieved October 9, 2013 from http://evidencebasedbirth.com/is-erythromycin-eye-ointment-always-necessary-for-newborns/ Hemorrhagic disease of the newborn (2012) Retrieved October 13, 2013, from http://emedicine.medscape.com/article/974489-overview Hemorrhagic disease of the newborn (2013) Retrieved October 6, 2013, from http://www.nlm.nih.gov/medlineplus/ency/article/007320.htm Lippi, G., and Franchini, M. (2011). Vitamin K in neonates: facts and myths Blood Transfusion 9(1) 4-9. doi: 10.2450/2010.0034-10

References Puckett, R. M., & Offringa, M. (2009, Jan 21, 2009). Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. The Cochrane Library. http://dx.doi.org/10.1002/14651858.CD002776 Rai, M.K., Deshmukh, S.D., Ingle, A.P., & Gade, A.K. (2012) Silver nanoparticles: the powerful nanoweapon against multidrug-resistant bacteria. Journal of Applied Microbiology, 112(5), 841-852. Doi:10.1111/j.1365-2672.2012.05253.x Texas Administrative Code. (2013) Retrieved on October 3, 2013 from http://info.sos.state.tx.us/pls/pub/readtac$ext.TacPage?sl=R&app=9&p_dir=&p_rloc=&p_tloc=&p_ploc=&pg=1&p_tac=&ti=25&pt=1&ch=97&rl=136 Truven Health Analytics Inc (2013). Micromedex Neofax. (Version1.12.0b1425) (Mobile application software). Retrieved from http.//itunes.apple.com. Van Winckel, M., De Bruyne, R., Van Develde, S., and Van Biervliet, S. (2008). Vitamin K, and update for the Pediatrician. European Journal of Pediatrics. 168(2). P 127-134.