Neonatal infections Pathogenesis and Epidemiology - PowerPoint Presentation

1. Neonatal infections

2. Pathogenesis and EpidemiologyInfections are a frequent and important cause of neonatal and infant morbidity and mortality. As many as 2% of fetuses are infected in utero, and up to 10% of infants have infections in the 1st mo of life.Why infection in neonate is different?1.Different mode of transmission.2.Immunological defieciency3.Coexisting condition often complicate the diagnosis of neon. Infection.

3. 4.The clinical manifestations of newborn infections vary include subclinical infection, mild to severe manifestations of focal or systemic infection5. Maternal infection that is the source for transplacental inf. Often undiagnosed.6. A wide variety of etiologic agents 7.Immature, very low birthweight (VLBW) newborns have improved survival but remain in the hospital for a long time.

4. Etiology of Fetal and Neonatal InfectionA number of agents may infect newborns in utero, intrapartum, or postpartum .1.Intrauterine transplacental infections of significance to the fetus and/or newborn include syphilis, rubella, CMV, toxoplasmosis, parvovirus B19, and varicella

5. 2. during labor and delivery with passage through an infected birth canal (HIV, HSV, HBV), 3. postpartum, from contact with an infected mother or caretaker (TB) or with infected breast milk (HIV).

6. Sepsis and MeningitisThe incidence of sepsis is approximately 1:1500 in full-term infants and 1:250 in preterm infants. The sixfold-higher rate of sepsis among preterm infants compared with term infants relates to the more immature immunologic systems of preterm infants and to their prolonged periods of hospitalization, which increase risk of nosocomially acquired infectious diseases

7. Bacterial sepsis and meningitis often are linked closely in neonates. The incidence of meningitis is approximately 1 in 20 cases of sepsis. The causative organisms isolated most frequently are the same as for neonatal sepsis: group B streptococci, E. coli, and L. monocytogenes. Gram-negative organisms, such as Klebsiella and Serratia marcescens, are more common in less developed countries,

8. and coagulase-negative staphylococci need to be considered in VLBW infants. Male infants seem to be more susceptible to neonatal infection than female infants. Severely premature infants are at even greater risk secondary to less effective defense mechanisms and deficient transfer of antibodies from the mother to the fetus(which occurs mostly after 32 weeks).

9. Neonates in the neonatal ICU live in a hostile environment, with exposure to endotracheal tubes, central arterial and venous catheters, and blood draws all predisposing to bacteremia and meningitis. Genetic factors have been implicated in the ability of bacteria to cross the blood-brain barrier.

10. Neonatal sepsis presents during three periods. Early-onset sepsis (birth to 7 days) often begins in utero and usually is a result of infection caused by the bacteria in the mother's genitourinary tract (vertical mother-to-child transmission) so acquired before or during delivery.Organisms related to this sepsis include group B streptococci, E. coli, Klebsiella, L. monocytogenes, and nontypable H. influenzae.

11. Risk factors for early-onset sepsis include 1.vaginal colonization with group B streptococci, 2.prolonged rupture of the membranes (>18 hours). 3. amnionitis. 4.maternal fever or leukocytosis.

12. 5. fetal tachycardia. 6. preterm birth. 7. male sex is unexplained additional risk factors for neonatal sepsis.Clinical manifestations of sepsis as poor feeding, pallor, apnea, lethargy, hypothermia, or an abnormal cry-may be nonspecific. Profound neutropenia, hypoxia, and hypotension may be refractory to treatment with broad-spectrum antibiotics

13. mechanical ventilation, and vasopressors such as dopamine and dobutamine. In the initial stages of early-onset septicemia in a preterm infant, it is often difficult to differentiate sepsis from RDS. Because of this difficulty, premature infants with RDS receive broad-spectrum antibiotics.The clinical manifestations of sepsis are difficult to separate from the manifestations of meningitis in the neonate.

14. Infants with early-onset sepsis should be evaluated by blood and CSF cultures, CSF Gram stain, cell count, and protein and glucose levels.. Some infants with neonatal meningitis caused by group B streptococci do not have an elevated CSF leukocyte count but are seen to have microorganisms in the CSF on Gram stain.

15. In cases of neonatal meningitis, The PCR test primarily is used to identify viral infections. Serial complete blood counts should be performed to identify neutropenia, an increased number of immature neutrophils (bands), and thrombocytopenia.

16. C-reactive protein levels are often elevated in neonatal patients with bacterial sepsis.A chest radiograph also should be obtained to determine the presence of pneumonia. Arterial blood gases should be monitored to detect hypoxemia and metabolic acidosis (caused by hypoxia , shock or both).

17. The mainstay of treatment for sepsis and meningitis is antibiotic therapy. Antibiotics are used to suppress bacterial growth, allowing the infant's defense mechanisms time to respond. In addition, support measures, such as assisted ventilation and cardiovascular support, are equally important to the management of the infant.

18. A combination of ampicillin and an aminoglycoside (usually gentamicin) for 10 to 14 days. The combination of ampicillin and cefotaxime also is proposed as an alternative method of treatment. If meningitis is present, the treatment should be extended to 21 days or 14 days after a negative result from a CSF culture.

19. even with appropriate antibiotic treatment, and may be present for 2 to 3 days after antibiotic. High-dose penicillin (250,000 to 450,000 U/kg/24 hr) is appropriate for group B streptococcal meningitis.

20. Intrapartum antibiotics are used to reduce vertical transmission of GBS as well as to lessen neonatal morbidity after preterm rupture of membranes. Intrapartum chemoprophylaxis does not reduce the rates of late-onset GBS disease and has no effect on the rates of infection with non-GBS pathogens.

21. Late-onset sepsis (8 to 28 days) usually occurs in a healthy full-term infant who was discharged in good health from the normal newborn nursery. Clinical manifestations may include lethargy, poor feeding, hypotonia, apathy, seizures, bulging fontanel, fever, and direct-reacting hyperbilirubinemia.

22. The evaluation of infants with late-onset sepsis is similar to that for infants with early-onset sepsis, with special attention given to a careful physical examination of the bones (infants with osteomyelitis may exhibit pseudoparalysis) and to the laboratory examination and culture of urine obtained by sterile supra-pubic aspiration or urethral catheterization

23. Late-onset sepsis may be caused by the same pathogens as early-onset sepsis, but infants exhibiting sepsis late in the neonatal period also may have infections caused by the pathogens usually found in older infants (H. influenzae, S. pneumoniae, and Neisseria meningitidis). In addition, viral agents (HSV, CMV, or enteroviruses) may manifest with a late-onset, sepsis-like picture.

24. Because of the increased rate of resistance of H. influenzae and pneumococcus to ampicillin, some centers begin treatment with ampicillin and a third-generation cephalosporin (and vancomycin if meningitis is present) when sepsis occurs in the last week of the first month of life. The treatment of late-onset neonatal sepsis and meningitis is the same as that for early-onset sepsis

25. Nosocomial Infections:Nosocomial (hospital-acquired) infections are defined as infections occurring after 3 days of life that are not directly acquired from the mother's genital tract.

26. The majority of nosocomial infections occur in preterm or term infants who require intensive care(<1% in healthy term infant).Risk factors for nosocomial infection1. prematurity, LBW.2. invasive procedures, indwelling vascular catheters, parenteral nutrition with lipid emulsions, endotracheal tubes, ventricular shunts.3.alterations in the skin and/or mucous membrane barriers.

27. 4. frequent use of broad-spectrum antibiotics 5.prolonged hospital stay.Various bacterial and fungal agents colonize hospitalized infants, health care workers, and visitors. Pathogenic agents can be transmitted by direct contact or indirectly via contaminated equipment.

28. Coagulase-negative staphylococci are the most frequent neonatal nosocomial pathogens.other gram postive (staph.aureus, enterococci),gram negative(E.coli,klebsiella,),fungi(candida).Viral organisms may also cause nosocomial infection in the NICU; they include RSV, varicella, influenza, rotavirus, and enteroviruses.

29. The mean age at onset of the 1st episode of late-onset nosocomial sepsis is 2-3 wk. The initial clinical manifestations of nosocomial infection in a premature infant may be subtle and include apnea and bradycardia, temperature instability, abdominal distention, and poor feeding. In the later stages, signs of infection are shock, DIC, worsening respiratory status, and local reactions, such as omphalitis, eye discharge, diarrhea, and bullous impetigo.

30. Treatment Because S. aureus (occasionally methicillin-resistant), Staphylococcus epidermidis (methicillin-resistant), and gram-negative pathogens are common nosocomial bacterial agents in many nurseries, a combination of vancomycin or oxacillin/nafcillin (some use ampicillin) with an aminoglycoside (gentamicin or tobramycin) is appropriate.

31. Persistent signs of infection despite antibacterial treatment suggest candidal or viral sepsis.Complications and PrognosisComplications of bacterial or fungal infections may be divided into those related to the acute inflammatory process and those that underlie neonatal problems such as respiratory distress and fluid and electrolyte abnormalities.

32. Complications of bacteremic infections include endocarditis,septic joints with residual disability, and osteomyelitis and bone destruction. Recurrent bacteremia is rare (<5% of patients). Candidemia may lead to vasculitis, endocarditis, and endophthalmitis as well as abscesses in the kidneys, liver, lungs, and brain. Sequelae of sepsis may result from septic shock, DIC, or organ failure.

33. Reported mortality rates in neonatal sepsis are as low as 10%.The case fatality rate for neonatal bacterial meningitis is between 20% and 25%. Many of these patients have associated sepsis. Risk factors for death or for moderate or severe disability include seizure duration >72 hr, coma, need for inotropic agents, and leukopenia.

34. Ophthalmia Neonatorum This form of conjunctivitis, occurring in infants younger than 4 wk of age, is the most common eye disease of newborns. Silver nitrate instillation may result in a mild self-limited chemical conjunctivitis. Epidemiology Conjunctivitis during the neonatal period is usually acquired during vaginal delivery

35. and reflects the sexually transmitted infections prevalent in the community.the incidence of gonococcal ophthalmia neonatorum decreased in industrialized countries secondary to widespread use of silver nitrate prophylaxis and prenatal screening and treatment of maternal gonorrheaClinical ManifestationsThe clinical manifestations of the various forms of ophthalmia neonatorum are not specific enough to allow an accurate

36. diagnosis . Neonatal conjunctivitis is a potentially blinding condition. The infection may also have associated systemic manifestations that require treatment. Therefore, any newborn infant who develops signs of conjunctivitis needs a prompt and comprehensive systemic and ocular evaluation to determine the agent causing

37. the infection and the appropriate treatment. The onset of inflammation caused by silver nitrate drops usually occurs within 6-12 hr after birth, with clearing by 24-48 hr. The usual incubation period for conjunctivitis due to N. gonorrhoeae is 2-5 days, and for that due to C. trachomatis, it is 5-14 days. Gonococcal infection may be present at birth or be delayed beyond 5 days of life owing to partial suppression by ocular prophylaxis.

38. Gonococcal conjunctivitis begins with mild inflammation and a serosanguineous discharge. Within 24 hr, the discharge becomes thick and purulent, and tense edema of the eyelids with marked chemosis occurs.Complications include corneal ulceration and perforation, iridocyclitis, anterior synechiae, and rarely panophthalmitis.

39. Conjunctivitis caused by C. trachomatis (inclusion blennorrhea) may vary from mild inflammation to severe swelling of the eyelids with copious purulent discharge.Conjunctivitis due to Staphylococcus aureus or other organisms is similar to that produced by C. trachomatis. Conjunctivitis due to Pseudomonas aeruginosa is uncommon, acquired in the nursery, and a potentially serious process. It is characterized by the appearance on days 5-18 of edema, erythema of the lids,.

40. purulent discharge, pannus formation, endophthalmitis, sepsis, shock, and death.Diagnosis Conjunctivitis appearing after 48 hr should be evaluated for a possibly infectious cause. Gram stain of the purulent discharge should be performed and the material cultured. If a viral cause is suspected, a swab should be submitted in tissue culture media for virus isolation.

41. In chlamydial conjunctivitis, the diagnosis is made by examining Giemsa-stained epithelial cells scraped from the tarsal conjunctivae for the characteristic intracytoplasmic inclusions, by isolating the organisms from a conjunctival swab using special tissue culture techniques, by immunofluorescent staining of conjunctival scrapings for chlamydial inclusions, or by tests for chlamydial antigen or DNA..

42. The differential diagnosis of ophthalmia neonatorum includes dacryocystitis caused by congenital nasolacrimal duct obstruction with lacrimal sac distention (dacryocystocele).Treatment Treatment of infants in whom gonococcal infection should be initiated immediately with ceftriaxone, 50 mg/kg/24 hr for 1 dose, not to exceed

43. 125 mg.The eye should also be irrigated initially with saline every 10-30 min, gradually increasing to 2-hr intervals until the purulent discharge has cleared. An alternative regimen includes cefotaxime (100 mg/kg/24 hr given IV or IM every 12 hr for 7 days or 100 mg/kg as a single dose).Neonatal conjunctivitis secondary to Chlamydia is treated with oral erythromycin (50 mg/kg/24 hr in 4 divided doses) for 2 wk.

44. This cures conjunctivitis and may prevent subsequent chlamydial pneumonia. Pseudomonas neonatal conjunctivitis is treated with systemic antibiotics, including an aminoglycoside, plus local saline irrigation and gentamicin ophthalmic ointment. Staphylococcal conjunctivitis is treated with parenteral methicillin and local saline irrigation.

45. Prognosis and PreventionDrops of 0.5% erythromycin or 1% silver nitrate are instilled directly into the open eyes at birth using wax or plastic single-dose containers. Saline irrigation after silver nitrate application is unnecessary. Silver nitrate is ineffective against active infection and may have limited use against Chlamydia. Povidone-iodine (2% solution) may also be an effective prophylactic agent.

46. An infant born to a woman who has untreated gonococcal infection should receive a single dose of ceftriaxone, 50 mg/kg (maximum 125 mg) IV or IM, in addition to topical prophylaxis.Neither topical prophylaxis nor topical treatment prevents the afebrile pneumonia that occurs in 10-20% of infants exposed to C. trachomatis. It is important that infants with chlamydial disease receive systemic treatment.

47. Tetanus (Clostridium tetani)Etiology Tetanus is an acute, spastic paralytic illness historically called lockjaw that is caused by the neurotoxin produced by Clostridium tetani, a motile, gram-positive, spore-forming obligate anaerobe whose natural habitat worldwide is soil, dust, and the alimentary tracts of various animals. C. tetani forms spores terminally, producing a drumstick or tennis racket appearance microscopically.

48. EpidemiologyThe most common form, neonatal (or umbilical) tetanus, It occurs in infants whose mothers are not immunized. In addition, an estimated 15,000-30,000 unimmunized women worldwide die each year of maternal tetanus, which results from postpartum, postabortal, or postsurgical wound infection with C. tetani.

49. Pathogenesis Tetanus occurs after introduced spores germinate, multiply, and produce tetanus toxin in the low oxidation-reduction potential (Eh) of an infected injury site.Tetanus toxin binds at the neuromuscular junction and enters the motor nerve by endocytosis, after which it undergoes retrograde axonal transport to the cytoplasm of the α-motoneuron.

50. The toxin exits the motoneuron in the spinal cord and next enters adjacent spinal inhibitory interneurons, where it prevents release of the neurotransmitters glycine and γ-aminobutyric acid (GABA).The autonomic nervous system is also rendered unstable in tetanus.

51. Because C. tetani is not an invasive organism, its toxin-producing vegetative cells remain where introduced into the wound, which may display local inflammatory changes and a mixed bact.flora.

52. Clinical ManifestationsTetanus is most often generalized but may also be localized. The incubation period typically is 2-14 days but may be as long as months after the injury.Neonatal tetanus, the infantile form of generalized tetanus, typically manifests within 3-12 days of birth as progressive difficulty in feeding (sucking and swallowing), associated hunger, and crying. Paralysis or diminished movement, stiffness and rigidity to the touch, and

53. spasms, with or without opisthotonos, are characteristic. The umbilical stump may hold remnants of dirt, dung, clotted blood, or serum, or it may appear relatively benign.

54. Diagnosis The picture of tetanus is one of the most dramatic in medicine, and the diagnosis may be established clinically. The typical setting is an unimmunized patient (and/or mother) who was injured or born within the preceding 2 wk, who presents with trismus , other rigid muscles, and a clear sensorium.

55. A peripheral leukocytosis may result from a secondary bacterial infection of the wound or may be stress induced from the sustained tetanic spasms. The CSF fluid is normal, although the intense muscle contractions may raise intracranial pressure. Neither the EEG nor the EMG shows a characteristic pattern. C. tetani is not always visible on Gram stain of wound material and is isolated in only about 30% of cases

56. Treatment Management of tetanus requires eradication of C. tetani and the wound environment conducive to its anaerobic multiplication, neutralization of all accessible tetanus toxin, control of seizures and respiration, palliation, provision of meticulous supportive care, and, finally, prevention of recurrencesExcision of the umbilical stump in the neonate with tetanus is no longer recommended

57. Tetanus toxin cannot be neutralized by TIG after it has begun its axonal ascent to the spinal cord. TIG should be given as soon as possible in order to neutralize toxin that diffuses from the wound into the circulation before the toxin can bind at distant muscle groups.A single intramuscular injection of 500 U of TIG is sufficient to neutralize systemic tetanus toxin, but total doses as high as 3,000-6,000 U are also recommended

58. If TIG is unavailable, use of human intravenous immunoglobulin (IVIG) may be necessary.Another alternative is equine- or bovine-derived tetanus antitoxin (TAT). The usual dose of TAT is 50,000-100,000 U, with half given intramuscularly and half intravenously, but as little as 10,000 U may be sufficient.The human-derived immunoglobulins are much preferred because of their longer half-lives (30 days) and the virtual

59. absence of allergic and serum sickness adverse effects.Penicillin G (100,000 U/kg/day divided every 4-6 hr IV for 10-14 days) remains the antibiotic of choice because of its effective clostridiocidal action and its diffusibility, Metronidazole (500 mg every 8hr IV for adults) appears to be equally effective. Erythromycin and tetracycline (for persons >8 yr of age) are alternatives for penicillin-allergic patients.

60. All patients with generalized tetanus need muscle relaxants. Diazepam provides both relaxation and seizure control. The initial dose of 0.1-0.2 mg/kg every 3-6 hr given intravenously is subsequently titrated to control the tetanic spasms, after which the effective dose is sustained for 2-6 wk before a tapered withdrawal.Magnesium sulfate, other benzodiazepines (midazolam), chlorpromazine, dantrolene, and baclofen are also used.

61. The highest survival rates in generalized tetanus are achieved with neuromuscular blocking agents such as vecuronium and pancuronium.Autonomic instability is regulated with standard α- or β- (or both) blocking agents; morphine has also proved useful.Prognosis Recovery in tetanus occurs through regeneration of synapses within the spinal cord and thereby the restoration of muscle relaxation. However, because an episode.

62. of tetanus does not result in the production of toxin-neutralizing antibodies, active immunization with tetanus toxoid at discharge with provision for completion of the primary series is mandatory.The most important factor that influences outcome is the quality of supportive care.An unfavorable prognosis is associated with onset of trismus <7 days after injury and with onset of generalized tetanic spasms <3 days after onset of trismus. Sequelae of hypoxic brain injury, especially in

63. infants, include cerebral palsy, diminished mental abilities, and behavioral difficulties. Most fatalities occur within the 1st wk of illness.PreventionActive immunization should begin in early infancy with combined diphtheria toxoid–tetanus toxoid–acellular pertussis (DTaP) vaccine at 2, 4, and 6 mo of age, with a booster at 4-6 yr of age and at 10-yr intervals thereafter throughout adult life (tetanus and reduced diphtheria toxoid [

64. Td] or tetanus, and reduced diphtheria and pertussis toxoids [Tdap.Immunization of women with tetanus toxoid prevents neonatal tetanus, and the World Health Organization is currently engaged in a global campaign for elimination of neonatal tetanus through maternal immunization with at least 2 doses of tetanus toxoid..