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Neonatal Sepsis Clinical Presentation

  • Author: Ann L Anderson-Berry, MD, PhD; Chief Editor: Ted Rosenkrantz, MD  more...
 
Updated: Dec 31, 2015
 

History

An awareness of the many risk factors associated with neonatal sepsis prepares the clinician for early identification and effective treatment, thereby reducing mortality and morbidity. Among these risk factors are the following:

  • Maternal group B Streptococcus (GBS) status
  • Premature rupture of membranes (PROM)
  • Prematurity
  • Chorioamnionitis

Maternal GBS status

The most common cause of neonatal bacterial sepsis is GBS. There are 9 serotypes, each of which is related to the polysaccharide capsule of the organism. Types I, II, and III are commonly associated with neonatal GBS infection. The type III strain has been shown to be most highly associated with central nervous system (CNS) involvement in early-onset infection, whereas types I and V have been associated with early-onset disease without CNS involvement.

The GBS organism colonizes the maternal gastrointestinal (GI) tract and birth canal. Approximately 25% of women have asymptomatic GBS colonization during pregnancy. GBS is responsible for approximately 50,000 maternal infections per year in women, but only 0.36-2 neonates per 1000 live births are infected.

Women with heavy GBS colonization and chronically positive GBS culture results have the highest risk of perinatal transmission. Also, heavy colonization at 23-26 weeks’ gestation is associated with prematurity and low birth weight. Colonization at delivery is associated with neonatal infection.

Intrapartum chemoprophylaxis for women with positive culture results for GBS has been shown to decrease the transmission of the organism to the neonate during delivery. Mothers may have a negative prenatal culture for GBS but a positive one at the time of labor.[3]

Premature rupture of membranes

PROM may occur in response to an untreated urinary tract infection (UTI) or birth canal infection. Other risk factors are previous preterm delivery, uterine bleeding in pregnancy, and heavy cigarette smoking during pregnancy. Rupture of membranes without other complications for more than 24 hours before delivery is associated with a 1% increase in the incidence of neonatal sepsis; however, when chorioamnionitis accompanies the rupture of membranes, the incidence of neonatal infection is quadrupled.

A multicenter study demonstrated that clinical chorioamnionitis and maternal colonization with GBS are the most important predictors of subsequent neonatal infection after PROM.[16] Seaward et al found that more than 6 vaginal digital examinations, which may be carried out as part of the evaluation for PROM, were associated with neonatal infection even when considered separately from the presence of chorioamnionitis.[16]

When membranes have ruptured prematurely before 37 weeks’ gestation, a longer latent period precedes vaginal delivery, increasing the likelihood that the infant will be infected. The duration of membrane rupture before delivery and the likelihood of neonatal infection are inversely related to gestational age. Thus, the more premature an infant is, the longer the delay between rupture of membranes and delivery and the higher the likelihood of neonatal sepsis.

Prematurity

In addition to the relation between preterm PROM and neonatal sepsis, there are other associations between prematurity and neonatal sepsis that increase the risk for premature infants.

Preterm infants are more likely to require invasive procedures, such as umbilical catheterization and intubation. Prematurity is associated with infection from cytomegalovirus (CMV), herpes simplex virus (HSV), hepatitis B virus (HBV), Toxoplasma,Mycobacterium tuberculosis, Campylobacter fetus, and Listeria species. Intrauterine growth retardation and low birth weight are also observed in CMV infection and toxoplasmosis.

Premature infants have less immunologic ability to resist and combat infection. Consequently, they are more susceptible to infection caused by common organisms such as coagulase-negative Staphylococcus— an organism usually not associated with severe sepsis.

Chorioamnionitis

The relationship between chorioamnionitis and other risk variables is strong. Suspect chorioamnionitis in the presence of fetal tachycardia, uterine tenderness, purulent amniotic fluid, an elevated maternal white blood cell (WBC) count, and an unexplained maternal temperature higher than 100.4°F (38°C).

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Physical Examination

The clinical signs of neonatal sepsis are nonspecific and are associated with the characteristics of the causative organism and the body’s response to the invasion. These nonspecific clinical signs of early sepsis are also associated with other neonatal diseases, such as respiratory distress syndrome (RDS), metabolic disorders, intracranial hemorrhage, and a traumatic delivery. In view of the nonspecificity of these signs, it is prudent to provide treatment for suspected neonatal sepsis while excluding other disease processes.

To obtain the most information from the examination, systematic physical assessment of the infant is best performed in a series that should include observation, auscultation, and palpation, in that order. Changes in findings from one examination to the next provide important information about the presence and evolution of sepsis.[17]

Congenital pneumonia and intrauterine infection

Inflammatory lesions are observed post mortem in the lungs of infants with congenital and intrauterine pneumonia. They may result not from the action of the microorganisms themselves but, rather, from aspiration of amniotic fluid containing maternal leukocytes and cellular debris. Tachypnea, irregular respirations, moderate retraction, apnea, cyanosis, and grunting may be observed.

Neonates with intrauterine pneumonia may also be critically ill at birth and require high levels of ventilatory support. The chest radiograph may depict bilateral consolidation or pleural effusions.

Congenital pneumonia and intrapartum infection

Neonates who are infected during the birth process may acquire pneumonia through aspiration of microorganisms during delivery. Klebsiella species and S aureus are especially likely to generate severe lung damage, producing microabscesses and empyema. Early-onset GBS pneumonia has a particularly fulminant course, with significant mortality in the first 48 hours of life.

Intrapartum aspiration may lead to infection with pulmonary changes, infiltration, and destruction of bronchopulmonary tissue. This damage is partly due to the granulocytes’ release of prostaglandins and leukotrienes. Fibrinous exudation into the alveoli leads to inhibition of pulmonary surfactant function and respiratory failure, with a presentation similar to that of RDS. Vascular congestion, hemorrhage, and necrosis may occur. Infectious pneumonia is also characterized by pneumatoceles within the pulmonary tissue.

Coughing, grunting, costal and sternal retractions, nasal flaring, tachypnea or irregular respiration, rales, decreased breath sounds, and cyanosis may be observed. Radiographic evaluation may demonstrate segmental or lobar atelectasis or a diffuse reticulogranular pattern, much like what is observed in RDS. Pleural effusions may be observed in advanced disease.

Postnatal infection

Postnatally acquired pneumonia may occur at any age. Because these infectious agents exist in the environment, the likely cause depends heavily on the infant’s recent environment. If the infant has remained hospitalized in a neonatal intensive care unit (NICU), especially with endotracheal intubation and mechanical ventilation, the organisms may include Staphylococcus or Pseudomonas species.

Additionally, these hospital-acquired organisms frequently demonstrate multiple antibiotic resistances. Therefore, the choice of antibiotic agents in such cases requires knowledge of the likely causative organisms and the local antibiotic-resistance patterns.

Cardiac signs

In overwhelming sepsis, an initial early phase characterized by pulmonary hypertension, decreased cardiac output, and hypoxemia may occur. This phase is followed by further progressive decreases in cardiac output with bradycardia and systemic hypotension. The infant manifests overt shock with pallor, poor capillary perfusion, and edema. These late signs of shock are indicative of severe compromise and are strongly associated with mortality.

Metabolic signs

Hypoglycemia, hyperglycemia, metabolic acidosis, and jaundice are all metabolic signs that commonly accompany neonatal sepsis. The infant has an increased glucose requirement as a result of the septic state. The infant may also be malnourished as a consequence of diminished energy intake. Hypoglycemia accompanied by hypotension may be secondary to an inadequate response from the adrenal gland and may be associated with a low cortisol level.

Metabolic acidosis is due to a conversion to anaerobic metabolism with the production of lactic acid. When infants are hypothermic or are not kept in a neutral thermal environment, efforts to regulate body temperature can cause metabolic acidosis. Jaundice occurs in response to decreased hepatic glucuronidation caused by both hepatic dysfunction and increased erythrocyte destruction.

Neurologic signs

Meningitis is the common manifestation of CNS infection. Acute and chronic histologic features are associated with specific organisms.

Meningitis due to early-onset neonatal sepsis usually occurs within 24-48 hours and is dominated by nonneurologic signs. Neurologic signs may include stupor and irritability. Overt signs of meningitis occur in only 30% of cases. Even culture-proven meningitis may not demonstrate white blood cell (WBC) changes in the cerebrospinal fluid (CSF).

Meningitis due to late-onset disease is more likely to demonstrate neurologic signs (80-90%); however, many of these physical examination findings are subtle or inapparent. Neurologic signs include the following:

  • Impairment of consciousness (ie, stupor with or without irritability)
  • Coma
  • Seizures
  • Bulging anterior fontanelle
  • Extensor rigidity
  • Focal cerebral signs
  • Cranial nerve signs
  • Nuchal rigidity

Temperature instability is observed with neonatal sepsis and meningitis, either in response to pyrogens secreted by the bacterial organisms or from sympathetic nervous system instability. The neonate is most likely to be hypothermic. The infant may also have decreased tone, lethargy, and poor feeding. Signs of neurologic hyperactivity are more likely when late-onset meningitis occurs.

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Contributor Information and Disclosures
Author

Ann L Anderson-Berry, MD, PhD Associate Professor of Pediatrics, Section of Newborn Medicine, University of Nebraska Medical Center, Creighton University School of Medicine; Medical Director, NICU, Nebraska Medical Center

Ann L Anderson-Berry, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, Nebraska Medical Association, Society for Pediatric Research

Disclosure: Nothing to disclose.

Coauthor(s)

Linda L Bellig, MA, RN NNP, (Retired) Track Coordinator, Instructor, Neonatal Nurse Practitioner Program, Medical University of South Carolina College of Nursing

Disclosure: Nothing to disclose.

Bryan L Ohning, MD, PhD Medical Director of NICU, Medical Director of Neonatal Transport, Division of Neonatology, Children's Hospital, Greenville Hospital System, University Medical Center; GHS Professor of Clinical Pediatrics, University of South Carolina School of Medicine; Clinical Associate Professor of Pediatrics, Medical University of South Carolina

Bryan L Ohning, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, South Carolina Medical Association

Disclosure: Received salary from Pediatrix Medical Group of SC for employment.

Chief Editor

Ted Rosenkrantz, MD Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Eastern Society for Pediatric Research, American Medical Association, Connecticut State Medical Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

David A Clark, MD Chairman, Professor, Department of Pediatrics, Albany Medical College

David A Clark, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Pediatric Society, Christian Medical & Dental Society, Medical Society of the State of New York, New York Academy of Sciences, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Scott S MacGilvray, MD Clinical Professor, Department of Pediatrics, Division of Neonatology, The Brody School of Medicine at East Carolina University

Scott S MacGilvray, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
  1. Klinger G, Levy I, Sirota L, et al. Epidemiology and risk factors for early onset sepsis among very-low-birthweight infants. Am J Obstet Gynecol. 2009 Jul. 201(1):38.e1-6. [Medline].

  2. van den Hoogen A, Gerards LJ, Verboon-Maciolek MA, Fleer A, Krediet TG. Long-term trends in the epidemiology of neonatal sepsis and antibiotic susceptibility of causative agents. Neonatology. 2010. 97(1):22-8. [Medline].

  3. Lin FY, Weisman LE, Azimi P, et al. Assessment of Intrapartum Antibiotic Prophylaxis for the Prevention of Early-onset Group B Streptococcal Disease. Pediatr Infect Dis J. 2011 Sep. 30(9):759-763. [Medline]. [Full Text].

  4. Morales WJ, Dickey SS, Bornick P, Lim DV. Change in antibiotic resistance of group B streptococcus: impact on intrapartum management. Am J Obstet Gynecol. 1999 Aug. 181(2):310-4. [Medline].

  5. Srinivasan L, Kirpalani H, Cotten CM. Elucidating the role of genomics in neonatal sepsis. Semin Perinatol. 2015 Dec. 39 (8):611-6. [Medline].

  6. Groer MW, Gregory KE, Louis-Jacques A, Thibeau S, Walker WA. The very low birth weight infant microbiome and childhood health. Birth Defects Res C Embryo Today. 2015 Dec 10. [Medline].

  7. Arnon S, Litmanovitz I. Diagnostic tests in neonatal sepsis. Curr Opin Infect Dis. 2008 Jun. 21(3):223-7. [Medline].

  8. Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev. 2014 Jan. 27(1):21-47. [Medline].

  9. Graham PL, Begg MD, Larson E. Risk factors for late onset gram-negative sepsis in low birth weight infants hospitalized in the neonatal intensive care unit. Pediatr Infect Dis J. 2006 Feb. 25(2):113-7. [Medline].

  10. [Guideline] American Academy of Pediatrics. Red Book 2003. 26th ed. 2003. 117-123, 237-43, 561-73,584-91.

  11. [Guideline] Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Recomm Rep. 2002 Aug 16. 51(RR-11):1-22. [Medline].

  12. Kermorvant-Duchemin E, Laborie S, Rabilloud M, Lapillonne A, Claris O. Outcome and prognostic factors in neonates with septic shock. Pediatr Crit Care Med. 2008 Mar. 9(2):186-91. [Medline].

  13. Adams-Chapman I, Stoll BJ. Neonatal infection and long-term neurodevelopmental outcome in the preterm infant. Curr Opin Infect Dis. 2006 Jun. 19(3):290-7. [Medline].

  14. Volpe JJ. Postnatal sepsis, necrotizing entercolitis, and the critical role of systemic inflammation in white matter injury in premature infants. J Pediatr. 2008 Aug. 153(2):160-3. [Medline]. [Full Text].

  15. Stoll BJ, Hansen NI, Adams-Chapman I, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA. 2004 Nov 17. 292(19):2357-65. [Medline].

  16. Seaward PG, Hannah ME, Myhr TL, et al. International multicenter term PROM study: evaluation of predictors of neonatal infection in infants born to patients with premature rupture of membranes at term. Premature Rupture of the Membranes. Am J Obstet Gynecol. 1998 Sep. 179(3 Pt 1):635-9. [Medline].

  17. Short MA. Guide to a systematic physical assessment in the infant with suspected infection and/or sepsis. Adv Neonatal Care. 2004 Jun. 4(3):141-53; quiz 154-7. [Medline].

  18. Delanghe JR, Speeckaert MM. Translational research and biomarkers in neonatal sepsis. Clin Chim Acta. 2015 Dec 7. 451 (Pt A):46-64. [Medline].

  19. Chan KY, Lam HS, Cheung HM, et al. Rapid identification and differentiation of Gram-negative and Gram-positive bacterial bloodstream infections by quantitative polymerase chain reaction in preterm infants. Crit Care Med. 2009 Aug. 37(8):2441-7. [Medline].

  20. Enomoto M, Morioka I, Morisawa T, Yokoyama N, Matsuo M. A novel diagnostic tool for detecting neonatal infections using multiplex polymerase chain reaction. Neonatology. 2009. 96(2):102-8. [Medline].

  21. Sarkar S, Bhagat I, DeCristofaro JD. A study of the role of multiple site blood cultures in the evaluation of neonatal sepsis. J Perinatol. 2006 Jan 1. 26(1):18-22. [Medline].

  22. Khashu M, Osiovich H, Henry D. Persistent bacteremia and severe thrombocytopenia caused by coagulase-negative Staphylococcus in a neonatal intensive care unit. Pediatrics. 2006 Feb. 117(2):340-8. [Medline].

  23. Hawk M. C-reactive protein in neonatal sepsis. Neonatal Netw. 2008 Mar-Apr. 27(2):117-20. [Medline].

  24. Ng PC, Lam HS. Diagnostic markers for neonatal sepsis. Curr Opin Pediatr. 2006 Apr. 18(2):125-31. [Medline].

  25. Meem M, Modak JK, Mortuza R, Morshed M, Islam MS, Saha SK. Biomarkers for diagnosis of neonatal infections: A systematic analysis of their potential as a point-of-care diagnostics. J Glob Health. 2011 Dec. 1(2):201-9. [Medline].

  26. Altunhan H, Annagür A, Örs R, Mehmetoglu I. Procalcitonin measurement at 24 hours of age may be helpful in the prompt diagnosis of early-onset neonatal sepsis. Int J Infect Dis. 2011 Dec. 15(12):e854-8. [Medline].

  27. Ng PC, Li K, Leung TF. Early prediction of sepsis-induced disseminated intravascular coagulation with interleukin-10, interleukin-6, and RANTES in preterm infants. Clin Chem. 2006 Jun. 52(6):1181-9. [Medline].

  28. Garges HP, Moody MA, Cotten CM. Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters?. Pediatrics. 2006 Apr. 117(4):1094-100. [Medline].

  29. Davis KL, Shah SS, Frank G, Eppes SC. Why are young infants tested for herpes simplex virus?. Pediatr Emerg Care. 2008 Oct. 24(10):673-8. [Medline].

  30. Tzialla C, Borghesi A, Pozzi M, Stronati M. Neonatal infections due to multi-resistant strains: Epidemiology, current treatment, emerging therapeutic approaches and prevention. Clin Chim Acta. 2015 Dec 7. 451 (Pt A):71-7. [Medline].

  31. Shipp KD, Chiang T, Karasick S, Quick K, Nguyen ST, Cantey JB. Antibiotic stewardship challenges in a referral neonatal intensive care unit. Am J Perinatol. 2015 Dec 18. [Medline].

  32. Zaidi AK, Tikmani SS, Warraich HJ, Darmstadt GL, Bhutta ZA, Sultana S, et al. Community-based Treatment of Serious Bacterial Infections in Newborns and Young Infants: A Randomized Controlled Trial Assessing Three Antibiotic Regimens. Pediatr Infect Dis J. 2012 Jul. 31(7):667-72. [Medline].

  33. The INIS Collaborative Group. Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med. 2011 Sep 29. 365(13):1201-11. [Medline].

  34. Manzoni P, Decembrino L, Stolfi I, et al. Lactoferrin and prevention of late-onset sepsis in the preterm neonate in the NICU. Early Hum Dev. 2010 Feb 5. [Medline].

 
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