Fluconazole Administration Leading to Anaphylactic Shock in a Preterm Newborn Esad Koklu, MD Salih Kalay, MD Selmin Koklu, MD Erdal Avni Ariguloglu, MD
Continuing Nursing Education (CNE) Credit A total of 1.6 contact hours may be earned as CNE credit for reading the articles in this issue identified as CNE and for completing an online posttest and evaluation. To be successful the learner must obtain a grade of at least 80% on the test. Test expires three (3) years from publication date. Disclosure: The authors/planning committee has no relevant financial interest or affiliations with any commercial interes ts related to the subjects discussed within this article. No commercial support or sponsorship was provided for this educational activity. ANN/ANCC does not endorse any commercial products discussed/displayed in conjunction with this educational activity. The Academy of Neonatal Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center ’s Commission on Accreditation. Provider, Academy of Neonatal Nursing, approved by the California B oard of R egis tered Nursing, Provider #CEP 6261; and Florida Board of Nursing, Provider #FBN 3218, content code 2505. The purpose of this article is to describe an unusual case of anaphylaxis in a preterm infant receiving fluconazole.
International Content The medical treatment or care p resented in this international article may not represent standards of practice in the United States.
Abstract Preterm infants, born with immature innate immunity, are less likely to develop anaphylaxis. Fluconazole prophylaxis during the first six weeks of life decreases invasive candidiasis in very low birth weight infants. Adverse effects of fluconazole are very rare. In this study, we report a newborn (a male, 26 weeks gestation and 900 g birth weight) who developed anaphylaxis after fluconazole administration. Hypotension and erythematous rash were present. We believe this to be the first anaphylaxis case in newborns caused by fluconazole in literature. Clinicians should be aware of the possibility of this potentially fatal adverse effect occurring with intravenous fluconazole. Keywords: fluconazole; preterm; anaphylaxis
F
luconazole is a triazole a ntifungal
agent that is widely used in the nursery. It is available in both intravenous and oral formulations and is active against most of the fungal pathogens that neonatal intensive care (NICU) infants encounter.1 Fluconazole prophylaxis during the first six weeks of life for preterm neonates with birth weights of ,1,000 g and/or those who were 27 weeks gestation or less has the potential of reducing and potentially eliminating invasive fungal infections and Candida-related mortality. 2– 4 Empiric antifungal therapy was associated with increased survival without neurodevelopmental impairment.1 However, its safety has not been established for this indication, and, as yet, the product has not been shown to reduce mortality in neonates.5 Targeted f luconazole prophylaxis may be beneficial in very low birth weight (VLBW) neonates who receive care in NICUs with lower rates of invasive fungal infections.6 It is known to be safe without significant toxicity in preterm newborns. Surveillance studies
show a low incidence of adverse drug reactions to fluconazole.7 The most common side effects of fluconazole mentioned in the literature are mild and include nausea, vomiting, headache, and elevation of hepatic transaminases.8 To date, anaphylaxis or any other life-threatening adverse effect in either the neonatal period or in childhood have, to our knowledge, not been reported. In this case, we report a preterm newborn developing anaphylaxis after fluconazole administration.
CASE REPORT
A 900 g, preterm male infant with premature rupture of the membranes and acute fetal distress was born by spontaneous vaginal delivery at 26 weeks gestation. The mother was 16 years of age with no allergic specification present in the family history. No drugs were mentioned to have been used in the prenatal period. At birth, the infant was tachypneic and with retractions and an Apgar score of 5 at one minute and 9 at five minutes, and surfactant
Accepted for publication November 2013.
N E O N A T A L N E T W O R K VOL. 33, NO. 2, MARCH/APRIL 2014 © 2014 Springer Publishing Company http://dx.doi.org/10.1891/0730-0832.33.2.83
83
was given at 5 minutes of age. He was started on ampicillin (25 mg/kg/day), gentamicin (5 mg/kg/2 days), and intravenous fluconazole (lumen, 100 mL, 2 mg/mL [Mustafa Nevzat, Istanbul, Turkey]) prophylaxis therapy (3 mg/kg/dose) every third day for two weeks. In our NICU, prophylactic intravenous fluconazole (3 mg/kg/dose every third day for two weeks) is routinely adminstered. The infant was extubated on the second day of life (DOL). From extubation on DOL 2 until DOL 4, the infant was stable. On DOL 4, an erythematous rash developed two minutes after fluconazole administration. The rash began at the scalp and face and extended to cover the entire body. An anaphylactic reaction was suspected. The infant demonstrated sudden poor sensorium, flaccidity, apnea, bradycardia, and cyanosis. He was intubated and placed on a ventilator. Intramuscular adrenaline was administered and cardiopulmonary resuscitation performed. Investigation showed a normal full blood count, urea and electrolytes, glucose, calcium, magnesium, liver function tests, and C-reactive protein. The chest x-ray was also normal, and the blood culture was negative. Moderate metabolic acidosis was detected at the time of the reaction (pH, 7.17; PCO2, 78 mmHg; PO2, 27 mmHg; HCO3, 13 mmol/liter; and base excess, 212 mmol/liter). Intravenous dexamethasone (0.3 mg/kg) and diphenhydramine (2 mg/kg) were administered immediately after the blood pressure was detected as hypotensive (19/11 mmHg mean blood pressure: 14 mmHg; prior to the administration of fluconazole, the infant’s blood pressure was 35/25 mmHg, mean 30 mmHg). The rash began to fade 13 minutes after it first appeared. Blood pressure and blood gases normalized after 45 minutes. The generalized rash faded away entirely at the end of the second hour. The infant improved and was extubated on DOL 5. He was discharged on DOL 45. There were no adverse sequelae from this reaction. He remains well at four months of age without any further allergic reactions.
DISCUSSION
An anaphylactic reaction occurs only in previously exposed and sensitized patients. An anaphylactoid reaction can occur following a single, first-time exposure, even in nonsensitized patients. The term anaphylaxis is often used to refer to both the conditions.9 Anaphylaxis and anaphylactoid reactions are medical emergencies that usually require resuscitative measures such as airway management, supplemental oxygen, volume replacement, and close monitoring. Anaphylaxis is an acute, severe, Type I hypersensitivity reaction developing over minutes to hours with multisystem involvement caused by the systemic effects of histamine release. Anaphylactic reactions can result in laryngotracheal edema and spasm as well as circulatory collapse. Administration of adrenaline is the treatment of choice, with antihistamines and steroids often used as adjuncts.9 The newborn in this case study presented with sudden poor sensorium, flaccidity, apnea, and cyanosis which is in sharp contrast to the classical symptoms of anaphylaxis. The most common organs affected in anaphylaxis
include the following: skin (80–90 percent), respiratory (70 percent), gastrointestinal (30–45 percent), heart and vasculature (10–45 percent), and central nervous system (10–15 percent).9 Clinicians should have a high index of suspicion and be aware of all possible presentations of anaphylaxis. Newborns, and particularly those born preterm, are less likely to develop anaphylaxis via either immunoglobulin E (IgE)-mediated immunity or nonimmune mechanisms because their immune system is less developed than older infants and children.10 Reports of patient and animal studies with anaphylaxis are available in limited number in the literature.11 Rare cases of newborns with anaphylaxis or anaphylactoid shock due to administration of cefotaxime, thiopentone, and atracurium have also been reported.12,13 A 2010 study reported a preterm newborn with anaphylactic shock resulting from administration of hepatitis B immunoglobulin.14 Similar life-threatening anaphylactic reactions have been reported with ceftriaxone.15–17 In two cases, anaphylaxis occurred with the first dose and in the other after receiving multiple doses. Hypersensitivity could not be demonstrated by skin testing by ceftriaxone-specific IgE. However, in one infant, a controlled, intravenous challenge was clearly positive. We did not attempt an intravenous challenge test because of ethical concerns. It was not likely that the anaphylaxis was caused by administration of ampicillin in our patient because the reaction occurred eight hours after exposure. Causes of adverse reactions to f luconazole are not yet thoroughly understood. The potential immunologic mechanisms in anaphylaxis include involvement of immune aggregates, immunoglobulin G (IgG), immunoglobulin M (IgM), platelets, and T cells; shift in eicosanoid metabolism toward leukotriene formation; and activation of the complement or coagulation systems.10 The fluconazole (lumen) preparation includes only 0.009 percent NaCl and distilled water. Anaphylaxis due to these agents has not been reported, leaving indirect activation of the complement system by fluconazole as the most likely cause of anaphylaxis in our patient.
Recommendation
Clinicians need to be aware of the possibility of a potentially fatal adverse effect occurring with administration of intravenous fluconazole. To our knowledge, this is the first case of neonatal anaphylaxis developing because of fluconazole administration.
REFERENCES
1. Castagnola E, Jacqz-Aigrain E, Kaguelidou F, et al. Fluconazole use and safety in the nursery. Early Hum Dev. 2012;88(suppl 2):S11-S15. http://dx.doi.org/10.1016/S0378-3782(12)70005-1 2. Tripathi N, Watt K, Benjamin DK Jr. Treatment and prophylaxis of invasive candidiasis. Semin Perinatol. 2012;36:416-423. 3. Healy CM, Campbell JR, Zaccaria E, Baker CJ. Fluconazole prophylaxis in extremely low birth weight neonates reduces invasive candidiasis mortality rates without emergence of fluconazole-resistant Candida species. Pediatrics. 2008;121:703-710.
N E O N A T A L N E T W O R K 84
MARCH/APRIL 2014, VOL. 33, NO. 2
4. Blyth CC, Barzi F, Hale K, Isaacs D. Chemoprophylaxis of neonatal fungal infections in very low birthweight infants: efficacy and safety of fluconazole and nystatin. J Paediatr Child Health. 2012;48:846-851. 5. Tripathi N, Watt K, Benjamin DK Jr. Treatment and prophylaxis of invasive candidiasis. Semin Perinatol. 2012;36(6):416-423. http:// dx.doi.org/10.1053/j.semperi.2012.06.003 6. Shane AL, Stoll BJ. Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis [published online ahead of print January 7, 2013]. Am J Perinatol. 2013;30(2):131-141. http://dx.doi.org/10.1055/s-0032-1333413 7. Bradbury BD, Jick SS. Itraconazole and fluconazole and certain rare, serious adverse events. Pharmacotherapy. 2002;22:697-700. 8. Egunsola O, Adefurin A, Fakis A, Jacqz-Aigrain E, Choonara I, Sammons H. Safety of fluconazole in paediatrics: a systematic review. Eur J Clin Pharmacol. 2013;69:1211-1221. 9. Simons FE. Anaphylaxis: recent advances in assessment and treatment. J Allergy Clin Immunol. 2009;124:625-636. 10. Simons FE. Anaphylaxis. J Allergy Clin Immunol. 2008;121:402-407. 11. Rupa P, Hamilton K, Cirinna M, Wilkie BN. A neonatal swine model of allergy induced by the major food allergen chicken ovomucoid (Gal d 1). Int Arch Allergy Immunol. 2008;146:11-18. 12. Pollock EM, MacLeod AD, McNicol LR. Anaphylactoid reaction complicating neonatal anaesthesia. Anaesthesia. 1986;41:178-180. 13. Babu TA, Sharmila V. Cefotaxime-induced near-fatal anaphylaxis in a neonate: a case report and review of literature. Indian J Pharmacol. 2011;43:611-612. 14. Bulbul A, Karadag A, Koklu E, Pamuk U, Sarici SU. Anaphylactic shock due to hepatitis B immunoglobulin in a newborn. J Matern Fetal Neonatal Med. 2010;23:1257-1259.
15. Belliard CR, Sibille G. Anaphylactoid shock or precipitation of calciumceftriaxone in a premature newborn. A case report [in French]. Arch Pediatr. 2007;14:199-200. 16. Ernst MR, van Dijken PJ, Kabel PJ, Draaisma JM. Anaphylaxis after first exposure to ceftriaxone. Acta Paediatr. 2002;91:355-356. 17. Baumgartner-Bonnevay C, Choquet-Kastylevsky G, Putet G, Bleyzac N, Vial T, Descotes J. Anaphylactic shock associated with ceftriaxone therapy in a newborn [in French]. Arch Pediatr. 2002;9:1050-1052.
About the Authors
Esad Koklu, MD, is a specialist in Neonatology, Megapark Hospital, Department of Pediatrics, Division of Neonatology, Kahramanmaras, Turkey. Salih Kalay, MD, is on the Faculty of Medicine, Department of Neonatology, Akdeniz University School of Medicine, Antalya, Turkey. Selmin Koklu, MD, is a specialist in Pediatrics, Turkey Ministry of Health Necip Fazıl Hospital. Erdal Avni Ariguloglu, MD, is a specialist in Obstetrics and Gynecology, Megapark Hospital, Department of Obstetrics and Gynecology, Kahramanmaras, Turkey. For further information, please contact: Esad Koklu, MD Megapark Hospital Department of Pediatrics Division of Neonatology Kahramanmarass, Turkey E-mail: [email protected]
N E O N A T A L N E T W O R K VOL. 33, NO. 2, MARCH/APRIL 2014
85
Continuing Nursing Education (CNE) Credit A total of 1.6 contact hours may be earned as CNE credit for reading the articles in this issue identified as CNE and for completing an online posttest and evaluation. To be successful the learner must obtain a grade of at least 80% on the test. Test expires three (3) years from publication date. Disclosure: The authors/planning committee has no relevant financial interest or affiliations with any commercial interes ts related to the subjects discussed within this article. No commercial support or sponsorship was provided for this educational activity. ANN/ANCC does not endorse any commercial products discussed/displayed in conjunction with this educational activity. The Academy of Neonatal Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center ’s Commission on Accreditation. Provider, Academy of Neonatal Nursing, approved by the California B oard of R egis tered Nursing, Provider #CEP 6261; and Florida Board of Nursing, Provider #FBN 3218, content code 2505. The purpose of this article is to describe an unusual case of anaphylaxis in a preterm infant receiving fluconazole.
International Content The medical treatment or care p resented in this international article may not represent standards of practice in the United States.
Abstract Preterm infants, born with immature innate immunity, are less likely to develop anaphylaxis. Fluconazole prophylaxis during the first six weeks of life decreases invasive candidiasis in very low birth weight infants. Adverse effects of fluconazole are very rare. In this study, we report a newborn (a male, 26 weeks gestation and 900 g birth weight) who developed anaphylaxis after fluconazole administration. Hypotension and erythematous rash were present. We believe this to be the first anaphylaxis case in newborns caused by fluconazole in literature. Clinicians should be aware of the possibility of this potentially fatal adverse effect occurring with intravenous fluconazole. Keywords: fluconazole; preterm; anaphylaxis
F
luconazole is a triazole a ntifungal
agent that is widely used in the nursery. It is available in both intravenous and oral formulations and is active against most of the fungal pathogens that neonatal intensive care (NICU) infants encounter.1 Fluconazole prophylaxis during the first six weeks of life for preterm neonates with birth weights of ,1,000 g and/or those who were 27 weeks gestation or less has the potential of reducing and potentially eliminating invasive fungal infections and Candida-related mortality. 2– 4 Empiric antifungal therapy was associated with increased survival without neurodevelopmental impairment.1 However, its safety has not been established for this indication, and, as yet, the product has not been shown to reduce mortality in neonates.5 Targeted f luconazole prophylaxis may be beneficial in very low birth weight (VLBW) neonates who receive care in NICUs with lower rates of invasive fungal infections.6 It is known to be safe without significant toxicity in preterm newborns. Surveillance studies
show a low incidence of adverse drug reactions to fluconazole.7 The most common side effects of fluconazole mentioned in the literature are mild and include nausea, vomiting, headache, and elevation of hepatic transaminases.8 To date, anaphylaxis or any other life-threatening adverse effect in either the neonatal period or in childhood have, to our knowledge, not been reported. In this case, we report a preterm newborn developing anaphylaxis after fluconazole administration.
CASE REPORT
A 900 g, preterm male infant with premature rupture of the membranes and acute fetal distress was born by spontaneous vaginal delivery at 26 weeks gestation. The mother was 16 years of age with no allergic specification present in the family history. No drugs were mentioned to have been used in the prenatal period. At birth, the infant was tachypneic and with retractions and an Apgar score of 5 at one minute and 9 at five minutes, and surfactant
Accepted for publication November 2013.
N E O N A T A L N E T W O R K VOL. 33, NO. 2, MARCH/APRIL 2014 © 2014 Springer Publishing Company http://dx.doi.org/10.1891/0730-0832.33.2.83
83
was given at 5 minutes of age. He was started on ampicillin (25 mg/kg/day), gentamicin (5 mg/kg/2 days), and intravenous fluconazole (lumen, 100 mL, 2 mg/mL [Mustafa Nevzat, Istanbul, Turkey]) prophylaxis therapy (3 mg/kg/dose) every third day for two weeks. In our NICU, prophylactic intravenous fluconazole (3 mg/kg/dose every third day for two weeks) is routinely adminstered. The infant was extubated on the second day of life (DOL). From extubation on DOL 2 until DOL 4, the infant was stable. On DOL 4, an erythematous rash developed two minutes after fluconazole administration. The rash began at the scalp and face and extended to cover the entire body. An anaphylactic reaction was suspected. The infant demonstrated sudden poor sensorium, flaccidity, apnea, bradycardia, and cyanosis. He was intubated and placed on a ventilator. Intramuscular adrenaline was administered and cardiopulmonary resuscitation performed. Investigation showed a normal full blood count, urea and electrolytes, glucose, calcium, magnesium, liver function tests, and C-reactive protein. The chest x-ray was also normal, and the blood culture was negative. Moderate metabolic acidosis was detected at the time of the reaction (pH, 7.17; PCO2, 78 mmHg; PO2, 27 mmHg; HCO3, 13 mmol/liter; and base excess, 212 mmol/liter). Intravenous dexamethasone (0.3 mg/kg) and diphenhydramine (2 mg/kg) were administered immediately after the blood pressure was detected as hypotensive (19/11 mmHg mean blood pressure: 14 mmHg; prior to the administration of fluconazole, the infant’s blood pressure was 35/25 mmHg, mean 30 mmHg). The rash began to fade 13 minutes after it first appeared. Blood pressure and blood gases normalized after 45 minutes. The generalized rash faded away entirely at the end of the second hour. The infant improved and was extubated on DOL 5. He was discharged on DOL 45. There were no adverse sequelae from this reaction. He remains well at four months of age without any further allergic reactions.
DISCUSSION
An anaphylactic reaction occurs only in previously exposed and sensitized patients. An anaphylactoid reaction can occur following a single, first-time exposure, even in nonsensitized patients. The term anaphylaxis is often used to refer to both the conditions.9 Anaphylaxis and anaphylactoid reactions are medical emergencies that usually require resuscitative measures such as airway management, supplemental oxygen, volume replacement, and close monitoring. Anaphylaxis is an acute, severe, Type I hypersensitivity reaction developing over minutes to hours with multisystem involvement caused by the systemic effects of histamine release. Anaphylactic reactions can result in laryngotracheal edema and spasm as well as circulatory collapse. Administration of adrenaline is the treatment of choice, with antihistamines and steroids often used as adjuncts.9 The newborn in this case study presented with sudden poor sensorium, flaccidity, apnea, and cyanosis which is in sharp contrast to the classical symptoms of anaphylaxis. The most common organs affected in anaphylaxis
include the following: skin (80–90 percent), respiratory (70 percent), gastrointestinal (30–45 percent), heart and vasculature (10–45 percent), and central nervous system (10–15 percent).9 Clinicians should have a high index of suspicion and be aware of all possible presentations of anaphylaxis. Newborns, and particularly those born preterm, are less likely to develop anaphylaxis via either immunoglobulin E (IgE)-mediated immunity or nonimmune mechanisms because their immune system is less developed than older infants and children.10 Reports of patient and animal studies with anaphylaxis are available in limited number in the literature.11 Rare cases of newborns with anaphylaxis or anaphylactoid shock due to administration of cefotaxime, thiopentone, and atracurium have also been reported.12,13 A 2010 study reported a preterm newborn with anaphylactic shock resulting from administration of hepatitis B immunoglobulin.14 Similar life-threatening anaphylactic reactions have been reported with ceftriaxone.15–17 In two cases, anaphylaxis occurred with the first dose and in the other after receiving multiple doses. Hypersensitivity could not be demonstrated by skin testing by ceftriaxone-specific IgE. However, in one infant, a controlled, intravenous challenge was clearly positive. We did not attempt an intravenous challenge test because of ethical concerns. It was not likely that the anaphylaxis was caused by administration of ampicillin in our patient because the reaction occurred eight hours after exposure. Causes of adverse reactions to f luconazole are not yet thoroughly understood. The potential immunologic mechanisms in anaphylaxis include involvement of immune aggregates, immunoglobulin G (IgG), immunoglobulin M (IgM), platelets, and T cells; shift in eicosanoid metabolism toward leukotriene formation; and activation of the complement or coagulation systems.10 The fluconazole (lumen) preparation includes only 0.009 percent NaCl and distilled water. Anaphylaxis due to these agents has not been reported, leaving indirect activation of the complement system by fluconazole as the most likely cause of anaphylaxis in our patient.
Recommendation
Clinicians need to be aware of the possibility of a potentially fatal adverse effect occurring with administration of intravenous fluconazole. To our knowledge, this is the first case of neonatal anaphylaxis developing because of fluconazole administration.
REFERENCES
1. Castagnola E, Jacqz-Aigrain E, Kaguelidou F, et al. Fluconazole use and safety in the nursery. Early Hum Dev. 2012;88(suppl 2):S11-S15. http://dx.doi.org/10.1016/S0378-3782(12)70005-1 2. Tripathi N, Watt K, Benjamin DK Jr. Treatment and prophylaxis of invasive candidiasis. Semin Perinatol. 2012;36:416-423. 3. Healy CM, Campbell JR, Zaccaria E, Baker CJ. Fluconazole prophylaxis in extremely low birth weight neonates reduces invasive candidiasis mortality rates without emergence of fluconazole-resistant Candida species. Pediatrics. 2008;121:703-710.
N E O N A T A L N E T W O R K 84
MARCH/APRIL 2014, VOL. 33, NO. 2
4. Blyth CC, Barzi F, Hale K, Isaacs D. Chemoprophylaxis of neonatal fungal infections in very low birthweight infants: efficacy and safety of fluconazole and nystatin. J Paediatr Child Health. 2012;48:846-851. 5. Tripathi N, Watt K, Benjamin DK Jr. Treatment and prophylaxis of invasive candidiasis. Semin Perinatol. 2012;36(6):416-423. http:// dx.doi.org/10.1053/j.semperi.2012.06.003 6. Shane AL, Stoll BJ. Recent developments and current issues in the epidemiology, diagnosis, and management of bacterial and fungal neonatal sepsis [published online ahead of print January 7, 2013]. Am J Perinatol. 2013;30(2):131-141. http://dx.doi.org/10.1055/s-0032-1333413 7. Bradbury BD, Jick SS. Itraconazole and fluconazole and certain rare, serious adverse events. Pharmacotherapy. 2002;22:697-700. 8. Egunsola O, Adefurin A, Fakis A, Jacqz-Aigrain E, Choonara I, Sammons H. Safety of fluconazole in paediatrics: a systematic review. Eur J Clin Pharmacol. 2013;69:1211-1221. 9. Simons FE. Anaphylaxis: recent advances in assessment and treatment. J Allergy Clin Immunol. 2009;124:625-636. 10. Simons FE. Anaphylaxis. J Allergy Clin Immunol. 2008;121:402-407. 11. Rupa P, Hamilton K, Cirinna M, Wilkie BN. A neonatal swine model of allergy induced by the major food allergen chicken ovomucoid (Gal d 1). Int Arch Allergy Immunol. 2008;146:11-18. 12. Pollock EM, MacLeod AD, McNicol LR. Anaphylactoid reaction complicating neonatal anaesthesia. Anaesthesia. 1986;41:178-180. 13. Babu TA, Sharmila V. Cefotaxime-induced near-fatal anaphylaxis in a neonate: a case report and review of literature. Indian J Pharmacol. 2011;43:611-612. 14. Bulbul A, Karadag A, Koklu E, Pamuk U, Sarici SU. Anaphylactic shock due to hepatitis B immunoglobulin in a newborn. J Matern Fetal Neonatal Med. 2010;23:1257-1259.
15. Belliard CR, Sibille G. Anaphylactoid shock or precipitation of calciumceftriaxone in a premature newborn. A case report [in French]. Arch Pediatr. 2007;14:199-200. 16. Ernst MR, van Dijken PJ, Kabel PJ, Draaisma JM. Anaphylaxis after first exposure to ceftriaxone. Acta Paediatr. 2002;91:355-356. 17. Baumgartner-Bonnevay C, Choquet-Kastylevsky G, Putet G, Bleyzac N, Vial T, Descotes J. Anaphylactic shock associated with ceftriaxone therapy in a newborn [in French]. Arch Pediatr. 2002;9:1050-1052.
About the Authors
Esad Koklu, MD, is a specialist in Neonatology, Megapark Hospital, Department of Pediatrics, Division of Neonatology, Kahramanmaras, Turkey. Salih Kalay, MD, is on the Faculty of Medicine, Department of Neonatology, Akdeniz University School of Medicine, Antalya, Turkey. Selmin Koklu, MD, is a specialist in Pediatrics, Turkey Ministry of Health Necip Fazıl Hospital. Erdal Avni Ariguloglu, MD, is a specialist in Obstetrics and Gynecology, Megapark Hospital, Department of Obstetrics and Gynecology, Kahramanmaras, Turkey. For further information, please contact: Esad Koklu, MD Megapark Hospital Department of Pediatrics Division of Neonatology Kahramanmarass, Turkey E-mail: [email protected]
N E O N A T A L N E T W O R K VOL. 33, NO. 2, MARCH/APRIL 2014
85
