Is Ceftizoxime an Appropriate Surrogate for Amikacin in Neonatal Sepsis Treatment? A Randomized Clinical Trial
Neonatal sepsis, a life-threatening condition, presents with non-specific clinical manifestations and needs immediate empirical antimicrobial therapy. Choosing an appropriate antibiotic regimen covering the most probable pathogens is an important issue. In this study we compared the effectiveness of ceftizoxime and amikacin in the treatment of neonatal sepsis both in combination with ampicillin. In a randomized clinical trial, all term neonates with suspected sepsis referred to Bahrami hospital during March 2008 to March 2010 were evaluated. Patients were randomly recruited into two groups; one group receiving ampicillin and amikacin and the other ampicillin and ceftizoxime. Blood, urine and cerebrospinal fluid cultures, leukocyte count and C-reactive protein level were measured in all neonates. A total of 135 neonates were evaluated, 65 in amikacin group and 70 in ceftizoxime group. 60 neonates (85.7%) in ceftizoxime group and 54 neonates (83.1%) in amikacin group responded to the treatment (P= 0.673 and χ2 = 0.178). Only 24 (18%) blood samples had a report of positive blood culture. The most frequent pathogen was coagulase negative staphylococcus with the frequency of 58.32% of all positive blood samples. Ceftizoxime in combination with ampicillin is an appropriate antimicrobial regimen for surrogating the combination of ampicillin and amikacin to prevent bacterial resistance against them.
Luck S, Torny M, d'Agapeyeff K, Pitt A, Heath P, Breathnach A, Russell AB. Estimated early-onset group B streptococcal neonatal disease. Lancet 2003; 361(9373):1953-4.
Modi N, Doré CJ, Saraswatula A, Richards M, Bamford KB, Coello R, Holmes A. A case definition for national and international neonatal bloodstream infection surveillance. Arch Dis Child Fetal Neonatal Ed 2009;94(1):F8-12.
Ahmed AS, Chowdhury MA, Hoque M, Darmstadt GL. Clinical and bacteriological profile of neonatal septicemia in a tertiary level pediatric hospital in Bangladesh. Indian Pediatr 2002;39(11):1034-9.
Jain NK, Jain VM, Maheshwari S. Clinical profile of neonatal sepsis. Kathmandu Univ Med J (KUMJ) 2003;1(2):117-20.
Gheibi Sh, Fakoor Z, Karamyyar M, Khashabi J, Ilkhanizadeh B, Asghari-Sana F, Mahmoodzadeh H, Majlesi AH. Coagulase negative staphylococcus; the most common cause of neonatal septicemia in Urmia, Iran. Iran J Pediatr 2008;18(3):237-43.
Alistair GS, Philip MB, Hewitt JR. Early diagnosis of neonatal sepsis. Pediatrics 1980;65(5):1036-41.
Siegel JD, McCracken GH Jr. Sepsis neonatorum. N Engl J Med 1981;304(11):642-7.
Muller-Pebody B, Johnson AP, Heath PT, Gilbert RE,Henderson KL, Sharland M; iCAP Group (Improving Antibiotic Prescribing in Primary Care). Empirical treatment of neonatal sepsis: are the current guidelines adequate? Arch Dis Child Fetal Neonatal Ed 2011;96(1):F4-8.
Mtitimila EI, Cooke RW. Antibiotic regimens for suspected early neonatal sepsis. Cochrane Database Syst Rev 2004;(4):CD004495.
Freedman RM, Ingram DL, Gross I, Ehrenkranz RA, Warshaw JB, Baltimore RS. A half century of neonatal sepsis at Yale: 1928 to 1978. Am J Dis Child 1981;135(2):140-4.
Clark RH, Bloom BT, Spitzer AR, Gerstmann DR. Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death. Pediatrics 2006;117(1):67-74.
Désinor OY, Silva JL, Ménos MJ. Neonatal sepsis and meningitis in Haiti. J Trop Pediatr 2004;50(1):48-50.
Aurangzeb B, Hameed A. Neonatal sepsis in hospitalborn babies: bacterial isolates and antibiotic susceptibility patterns. J Coll Physicians Surg Pak 2003;13(11):629-32.
Hufnagel M, Burger A, Bartelt S, Henneke P, Berner R. Secular trends in pediatric bloodstream infections over a 20-year period at a tertiary care hospital in Germany. Eur J Pediatr 2008;167(10):1149-59.
Reyna J, Ortiz F. Therapeutic failure of the ampicillin plus aminoglycoside scheme in the treatment of early neonatal sepsis. Arch Med Res 2008;39(5):546-7.
Guadalupe Vásquez-Mendoza M, Vargas-Origel A, Del Carmen Ramos-Jiménez A, Aguilar-Orozco G, Romero- Gutiérrez G. Efficacy and renal toxicity of one daily dose of amikacin versus conventional dosage regime. Am J Perinatol 2007;24(2):141-6.
Hammerberg O, Bialkowska-Hobrzanska H, Gregson D, Potters H, Gopaul D, Reid D. Comparison of blood cultures with corresponding venipuncture site cultures of specimens from hospitalized premature neonates. J Pediatr 1992;120(1):120-4.
Allen TR, da Silva OP. Choice of antibiotics in late neonatal sepsis in the extremely low birth weight infant. Can J Infect Dis 2003;14(1):28-31.
Yamauchi T, Hill DE, Steele RW. The use of ceftizoxime in neonates. J Antimicrob Chemother 1982;10 Suppl C:297-301.
Motohiro T, Sakata Y, Tominaga K, Oda K, Aramaki M, Tanaka K, Kawakami A, Shimada Y, Koga T, Tomita S, et al. Pharmacokinetic, bacteriological and clinical studies of ceftizoxime in neonates and low birth weight infants. Jpn J Antibiot 1988;41(8):1116-28.
Mosayebi Z, Movahedian AH, Moniri R. Profile of bacterial sepsis in neonates from Kashan in Iran. J Infect Dis Antimicrob Agents 2003;20(2):97-102.
Waseem R, Khan M, Izhar T, Qureshi AW. Neonatal sepsis. Professional Med J 2005;12(4):451-56.
Chacko B, Sohi I. Early onset neonatal sepsis. Indian J Pediatr 2005;72(1):23-6.
Agnihotri N, Kaistha N, Gupta V. Antimicrobial susceptibility of isolates from neonatal septicemia. Jpn J Infect Dis 2004;57(6):273-5.
Hashemieh M, Fatahi Bayat GA. Evaluation of neonatal sepsis in neonatal wards of Amir Kabir and Taleghanihospitals of Arak city in 1999. Arak Med Uni J (Rahavard Danesh) 2001;14(4):37‐42. [Persian]
Ghadamli P. Neonatal sepsis in Shaheed Beheshti teaching hospital. J Qazvin Uni Med Sci 1998;7(6):53‐7. [Persian]
Kaplan SL, Deville JG, Yogev R, Morfin MR, Wu E, Adler S, Edge-Padbury B, Naberhuis-Stehouwer S, Bruss JB; Linezolid Pediatric Study Group. Linezolid versus vancomycin for treatment of resistant Gram-positive infections in children. Pediatr Infect Dis J 2003;22(8):677-86.
Stoll BJ, Hansen NI, Higgins RD, Fanaroff AA, Duara S, Goldberg R, Laptook A, Walsh M, Oh W, Hale E; National Institute of Child Health and Human Development. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gramnegative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003. Pediatr Infect Dis J 2005;24(7):635-9.
Hyde TB, Hilger TM, Reingold A, Farley MM, O'Brien KL, Schuchat A; Active Bacterial Core surveillance (ABCs) of the Emerging Infections Program Network. Trends in incidence and antimicrobial resistance of earlyonset sepsis: population-based surveillance in San Francisco and Atlanta. Pediatrics 2002;110(4):690-5.
Isaacs D; Australasian Study Group For Neonatal Infections. A ten year, multicentre study of coagulase negative staphylococcal infections in Australasian neonatal units. Arch Dis Child Fetal Neonatal Ed 2003;88(2):F89-93.
Huang SY, Tang RB, Chen SJ, Chung RL. Coagulasenegative staphylococcal bacteremia in critically ill children: risk factors and antimicrobial susceptibility. J Microbiol Immunol Infect 2003;36(1):51-5.