BACTERIAL SEPSIS AND MENINGITIS - Nizet Laboratory at UCSD

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250 SECTION II Bacterial Infections as the lower limit of the definition of fever. Although some clinical studies indicate that axillary [455], skinmattress [456], and infrared tympanic membrane thermometry [457] are accurate and less dangerous than rectal measurements for obtaining core temperature, the reliability of these methods, particularly in febrile infants, has been questioned [458–460]. A study established that statistically significant differences are present between the rectal and axillary temperatures obtained in newborns during the first 4 days of life even with the same electronic temperature device [461]. The current method of choice for determining the presence of fever in neonates is a rectal temperature taken at a depth of 2 to 3 cm past the anal margin. In infants with suspected sepsis without fever, it has been shown that a difference between core (rectal) and skin (sole of the foot) temperature of more than 3.5 C can be a more useful indicator of infection than measurement of core temperature alone [453]. There is no study of temperatures in neonates that is prospective, assesses all infants (febrile and afebrile), includes rectal and axillary temperatures, includes preterm and term infants, and requires positive cultures of blood or other body fluids to define invasive bacterial infection. Voora and colleagues [462] observed 100 term infants in Chicago with an axillary or rectal temperature of equal to or greater than 37.8 C( 100.1 F) during the first 4 days of life, and Osborn and Bolus [463] conducted a retrospective review of 2656 term infants in Los Angeles. Both groups of investigators reported that temperature elevation in healthy term infants was uncommon. Approximately 1% of neonates born at term had at least one episode of fever, measured as equal to or greater than 37.8 C( 100.1 F) per axilla [462]. Temperature elevation infrequently was associated with systemic infection when a single evaluation occurred. None of 64 infants in these two studies who had a single episode of fever developed clinical evidence of systemic infection (cultures of blood or other body fluids were not obtained). By contrast, temperature elevation that was sustained for more than 1 hour frequently was associated with infection. Of seven infants with sustained fever in the study by Osborn and Bolus [463], five had proven bacterial or viral infections. Of 65 infants reported by Voora and colleagues [462], 10 had documented systemic bacterial disease. Temperature elevation without other signs of infection was infrequent. Only one infant (with cytomegalovirus infection) of the five Los Angeles infants had fever without other signs. Only 2 infants (with bacteremia caused by E. coli or GBS) of the 10 Chicago infants with fever and proven bacterial disease had no other signs of infection. In addition to infection, fever may be caused by an elevation in ambient temperature, dehydration, retained blood or extensive hematoma, and damage to the temperature-regulating mechanisms of the CNS. Less common noninfectious causes of fever are hyperthyroidism, cystic fibrosis, familial dysautonomia, and ectodermal dysplasia. When thermoregulatory devices that monitor and modify infant temperature are introduced, the use of fever or hypothermia as a diagnostic sign of sepsis sometimes is impeded. RESPIRATORY DISTRESS Signs of respiratory distress, including tachypnea, grunting, flaring of the alae nasi, intercostal retractions, rales, and decreased breath sounds, are common and important findings in the infant suspected to have sepsis. Respiratory distress syndrome and aspiration pneumonia must be considered in the differential diagnosis. Apnea is one of the most specific signs of sepsis, but usually occurs in the setting of a fulminant onset or after other nonspecific signs have been present for hours or days. Clinical signs of cardiovascular dysfunction, including tachycardia, arrhythmia, and poor peripheral perfusion, that occur in the absence of congenital heart disease are sensitive and specific signs of sepsis. JAUNDICE Jaundice is present in approximately one third of infants with sepsis and is a common finding in infants with urinary tract infection [353,464–468]. It can develop suddenly or subacutely and occasionally is the only sign of sepsis. Jaundice usually decreases after institution of appropriate antimicrobial therapy. It occurs in septic infants regardless of the type of bacterial pathogen. ORGANOMEGALY The liver edge is palpable in premature infants and can extend to 2 cm below the costal margin in healthy term infants. Ashkenazi and colleagues [469] evaluated liver size in healthy term infants examined within 24 hours of birth and again at 72 to 96 hours. Measurements ranged from 1.6 to 4 cm below the costal margin, and there was no significant difference between early and late examinations. Reiff and Osborn [470] suggested that determination of liver span by palpation and percussion is a more reliable technique than identifying the liver projection below the costal margin. Hepatomegaly is a common sign of in utero infections and of some noninfectious conditions, such as cardiac failure and metabolic diseases, including galactosemia and glycogen storage disease. Tender hepatomegaly can be a sign of bacterial liver abscess in neonates, a potential complication of misplaced central umbilical catheters [125]. Splenomegaly is less common than hepatomegaly and infrequently is mentioned in reports of bacterial sepsis of the newborn [471]. Lymph nodes infrequently are palpable in newborns unless they are infected with viruses, spirochetes, or protozoa. Bamji and coworkers [472] examined 214 healthy neonates in New York and identified palpable nodes at one or more sites in one third of the infants. Embree and Muriithi [473] examined 66 healthy term Kenyan neonates during the first 24 hours of life and found palpable axillary nodes (27.7%), but no palpable inguinal nodes. Adenopathy is a sign of congenital infection caused by rubella virus, T. gondii, T. pallidum, and enteroviruses. Adenitis can occur in drainage areas involved with bacterial soft tissue infection. Although adenopathy is not an important sign of systemic bacterial infection in neonates, cellulitis-adenitis syndrome, a rare clinical manifestation of late-onset group B streptococcal infection in infants,
is a condition in which local inflammation can be the only initial sign of sepsis that can include concurrent meningitis [474–476]. GASTROINTESTINAL SIGNS Gastrointestinal disturbances, including poor feeding, regurgitation or vomiting, large gastric residuals in infants fed by tube, diarrhea, and abdominal distention, are common and significant early signs of sepsis. The first indications of illness can be a change in feeding pattern or lethargy during feedings. SKIN LESIONS Various skin lesions can accompany bacteremia, including cellulitis, abscess, petechiae, purpuric lesions, sclerema, erythema multiforme, and ecthyma. These lesions are described in Chapter 10. NEUROLOGIC SIGNS The onset of meningitis in the neonate is accompanied by identical signs of illness as observed in infants with sepsis. Meningitis can be heralded by increasing irritability, alteration in consciousness, poor tone, tremors, lip smacking, or twitching of facial muscles or an extremity. Seizures were present in 31% of the infants reviewed in Table 6–14, but Volpe [350] identified seizures, in many cases subtle, in 75% of infants with bacterial meningitis. Approximately half of the seizures were focal, and at their onset, they usually were subtle. Focal signs, including hemiparesis; horizontal deviation of the eyes; and cranial nerve deficits involving the seventh, third, and sixth cranial nerves, in that order of frequency, can be identified [350]. Because cranial sutures in the neonate are open and allow for expansion of the intracranial contents and for increasing head size, a full or bulging fontanelle can be absent [448,477]. The presence of a bulging fontanelle is not related to gestational age. Among 72 newborns with gram-negative enteric bacillary meningitis, a bulging fontanelle was seen in 18% of term infants and 17% of preterm infants [23]. Nuchal rigidity, an important sign in older children and adults, is uncommon in neonates [23]. In addition to the physical findings observed in infants with meningitis, several investigators have reported the occurrence of fluid and electrolyte abnormalities associated with inappropriate antidiuretic hormone secretion, including hyponatremia, decreased urine output, and increased weight gain [432,438]. Occasionally, the onset of meningitis has been followed by a transient or persistent diabetes insipidus [477]. Early clinical signs of brain abscess in the newborn are subtle and frequently unnoticed by the physician or parent. Presenting signs include signs of increased intracranial pressure (e.g., emesis, bulging fontanelle, enlarging head size, separated sutures), focal cerebral signs (e.g., hemiparesis, focal seizures), and acute signs of meningitis. Of six infants with brain abscesses described by Hoffman and colleagues [429], two were febrile, two had seizures, and five had increased head size. Other focal infections in the nervous system include pneumococcal endophthalmitis in a neonate with meningitis [478], pseudomonal endophthalmitis in a CHAPTER 6 Bacterial Sepsis and Meningitis 251 premature neonate with late-onset sepsis [479], and epidural abscess caused by S. aureus in 3-week-old [480], 4-week-old [481], and 7-week-old infants [482]. DIAGNOSIS The diagnosis of systemic infection in the newborn is difficult to establish on the basis of clinical findings alone. A history of one or more risk factors for neonatal sepsis associated with the pregnancy and delivery often is associated with early-onset infection, but there can be no clues before the onset of subtle signs in a term infant who develops late-onset sepsis. The extensive list of conditions that must be considered in the differential diagnosis for the various signs that are associated with sepsis or meningitis and noninfectious conditions is presented in Table 6–15. Laboratory tests to assist in the diagnosis of sepsis are discussed in Chapter 36. MATERNAL HISTORY Many infants, particularly infants born prematurely, who develop systemic infection just before or shortly after delivery are born to women who have one or more risk features for early-onset sepsis in their infants. These features include preterm labor, premature rupture of the membranes at any time during gestation, prolonged rupture of membranes, chorioamnionitis, prolonged labor, intrauterine scalp electrodes, and traumatic delivery. The following features are identified by the American College of Obstetrics and Gynecology (ACOG) as the basis for identification of women who should receive intrapartum antibiotic prophylaxis to prevent early-onset group B streptococcal disease:[483,484] 1. Antenatal colonization with GBS 2. Unknown group B streptococcal colonization status and a. Preterm labor (
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Page 35 and 36: ampicillin. Many of these organisms
Page 37 and 38: infant’s body fluids. If the infa
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