Pediatric Annals

Overwhelming Infections in Infants and Children

David A Berman, DO

Abstract

Various signs and symptoms may be associated with infectious diseases - fever is a common presenting symptom. Although specific signs and symptoms may direct attention to a particular organ system, nonspecific findings are particularly common in young infants and children. The infant with meningitis, for example, may merely be febrile and irritable without definitive or even suggestive central nervous system signs. The clinical presentation depends on several factors: age, immunologic status of the patient, duration of the illness, and etiology of the infection.

A child is generally considered febrile when either the rectal temperature is 38.00C or greater or the oral temperature is greater than 3 7. 60C. Rectal temperatures provide the greatest precision; risks of rectal perforation and emotional trauma are minimal. Axillary temperatures do not adequately detect fever and should not be used in the ambulatory setting, if at all.1 The oral or sublingual site is only useful in cooperative older children who are not tachypneic.

The tympanic membrane has been employed because of the rapidity and ease of this technique, but the reliability of this method is questionable.

It is helpful to think about febrile children at increased risk for serious bacterial infections in terms of age and immune status. The pathogens responsible for serious infections are different in neonates and infants younger than 2 months of age than in children who are 2 months to 3 years old, and different again in immunocompromised children.

THE NEONATE AND INFANT UNDER TWO MONTHS OF AGE

Children under 2 months are "immunocompromised." Their immune system has not fully matured, yet passive protection from maternal antibody is beginning to wane.

Fever may not be the presenting symptom of sepsis. The history is rarely more specific than decreased feeding, irritability, or lethargy. The physical examination can be unreliable, even when performed by experienced clinicians.2 Several studies have shown that infants under 2 to 3 months of age presenting with a temperature of 38.O0C may have minimal signs and symptoms yet be bacteremic or "septic." Children under 3 months of age with a temperature over 38.50C are at a greater risk of having a serious bacterial infection than older children with a similar temperature. Investigators have found that both clinical judgment and laboratory studies together are sensitive enough to identify all bacteremic infants. 3'5 The most conservative approach to infants under 2 months of age with fever, irritability, or decreased feeding is to do a full "sepsis work up" and hospitalize the child. A complete evaluation generally includes culturing specimens of blood, spinal fluid, and a clean urine specimen for bacterial pathogens. Parenteral antibiotics are given empirically until cultures for bacterial pathogens have remained sterile for 48 hours. If the cultures are negative and the infant shows clinical improvement, antibiotics can be discontinued and the patient discharged.

Regimens during the first 4 weeks of life may include a combination of ampicillin and an aminoglycoside, such as gentamicin, to assure coverage of gram-negative organisms, as well as enterococci and Listeria monocytogenes. Some experts use a third generation cephalosporin in addition to ampicillin to provide coverage for these organisms as well as Hemophilus influenzae type B, Streptococcus pneumoniae, and Neisseria meningitis, which are seen with increasing frequency after 4 weeks of age.

TWO MONTHS TO THREE YEARS OF AGE

AfteT the neonatal period, the peak incidence of meningitis is between 3 and 8 months of age6; the child under 3 years of age remains at an increased risk for serious bacterial infections compared with the older child. From the age of 2 months to 3 years the bacterial pathogens of greatest concern are Hemophilus…

Various signs and symptoms may be associated with infectious diseases - fever is a common presenting symptom. Although specific signs and symptoms may direct attention to a particular organ system, nonspecific findings are particularly common in young infants and children. The infant with meningitis, for example, may merely be febrile and irritable without definitive or even suggestive central nervous system signs. The clinical presentation depends on several factors: age, immunologic status of the patient, duration of the illness, and etiology of the infection.

A child is generally considered febrile when either the rectal temperature is 38.00C or greater or the oral temperature is greater than 3 7. 60C. Rectal temperatures provide the greatest precision; risks of rectal perforation and emotional trauma are minimal. Axillary temperatures do not adequately detect fever and should not be used in the ambulatory setting, if at all.1 The oral or sublingual site is only useful in cooperative older children who are not tachypneic.

The tympanic membrane has been employed because of the rapidity and ease of this technique, but the reliability of this method is questionable.

It is helpful to think about febrile children at increased risk for serious bacterial infections in terms of age and immune status. The pathogens responsible for serious infections are different in neonates and infants younger than 2 months of age than in children who are 2 months to 3 years old, and different again in immunocompromised children.

THE NEONATE AND INFANT UNDER TWO MONTHS OF AGE

Children under 2 months are "immunocompromised." Their immune system has not fully matured, yet passive protection from maternal antibody is beginning to wane.

Fever may not be the presenting symptom of sepsis. The history is rarely more specific than decreased feeding, irritability, or lethargy. The physical examination can be unreliable, even when performed by experienced clinicians.2 Several studies have shown that infants under 2 to 3 months of age presenting with a temperature of 38.O0C may have minimal signs and symptoms yet be bacteremic or "septic." Children under 3 months of age with a temperature over 38.50C are at a greater risk of having a serious bacterial infection than older children with a similar temperature. Investigators have found that both clinical judgment and laboratory studies together are sensitive enough to identify all bacteremic infants. 3'5 The most conservative approach to infants under 2 months of age with fever, irritability, or decreased feeding is to do a full "sepsis work up" and hospitalize the child. A complete evaluation generally includes culturing specimens of blood, spinal fluid, and a clean urine specimen for bacterial pathogens. Parenteral antibiotics are given empirically until cultures for bacterial pathogens have remained sterile for 48 hours. If the cultures are negative and the infant shows clinical improvement, antibiotics can be discontinued and the patient discharged.

Regimens during the first 4 weeks of life may include a combination of ampicillin and an aminoglycoside, such as gentamicin, to assure coverage of gram-negative organisms, as well as enterococci and Listeria monocytogenes. Some experts use a third generation cephalosporin in addition to ampicillin to provide coverage for these organisms as well as Hemophilus influenzae type B, Streptococcus pneumoniae, and Neisseria meningitis, which are seen with increasing frequency after 4 weeks of age.

TWO MONTHS TO THREE YEARS OF AGE

AfteT the neonatal period, the peak incidence of meningitis is between 3 and 8 months of age6; the child under 3 years of age remains at an increased risk for serious bacterial infections compared with the older child. From the age of 2 months to 3 years the bacterial pathogens of greatest concern are Hemophilus influenzae type B, Neisseria meningitidis, and Streptococcus pneumoniae (Table 1).

The ability to evaluate patients in this age group is complicated by their inability or unwillingness to cooperate. One look at an unfamiliar face, even in the relatively well child, may result in the child crying inconsolably. Asking parents to aid in the exam may be fruitful.

Early antipyretic therapy may facilitate an optimal examination. Many children who are irritable and disinterested in their environment will improve markedly after receiving acetaminophen (15 mg/kg). The physical examination to assess responsiveness must be done systematically, focusing on careful observation of the child both at play and with parents. The overall assessment that has proved very useful includes: observation of the quality of cry, reaction to parent stimulation, state variation (awake, eyes close briefly then open, will not rouse), color, hydration, and response to social overtones.7

Table

TABLE 1Overwhelming Infections: Age, Condition, and type-Specific Bacteria

TABLE 1

Overwhelming Infections: Age, Condition, and type-Specific Bacteria

Evaluation should focus on finding the source of the fever. When specific findings are noted, further evaluation should be done, if indicated, and treatment begun. When a specific focus of infection cannot be identified, the possibility of bacteremia should be entertained. McGowen found that children presenting with a temperature of less than 38.9°C had an incidence of bacteremia of 1.25%, whereas those with temperatures between 39.4 and 39.9°C had a 12.4% incidence.8 Studies have also correlated elevated white blood cell counts, higher temperatures, and younger age with a higher incidence of occult bacteremia.8'10 McCarthy noted that children between the age of 6 and 24 months, who had a temperature of 40.00C or greater, white blood cell count of more than 15 000/mm3, or erythrocyte sedimentation rate of 30 mm/hr or greater were at increased risk for systemic bacterial illness. The figure depicts how these children should be evaluated and managed.

IMMUNOCOMPROMISED CHILDREN

Alteration of the normal immune defense system leads to an increased risk for infection. Impairment of natural mechanical barriers, neutrophil function, cell-mediated or humoral immunity, and splenic function increases the risk of bacterial infection. One example is asplenia associated with sickle cell disease or splenectomy following trauma. These children are susceptible to encapsulated bacteria such as S pneu' moniae and H influenzae type B. Children with sickle cell disease are also susceptible to infections with Salmonella species, which may be related to functional asplenia. Other immunocompromised children include those undergoing chemotherapy, receiving steroids, or experiencing underlying malignant disease, such as leukemia and Hodgkin's or nonHodgkin's lymphoma. The granulocytopenic child is at greatest risk for serious bacterial infection. ' '

Figure. Evaluation and management of febrile children under 2 years of age. *Ceftriaxone 50 mg/kg/dose IM/IV; ampicillin 50-75 mg/kg/dose IM/IV; or amoxicillin 70-75 mg/kg/24 hr g 8 hr PO. Adapted from Barkin RM. Rosen P. eds. Emergency Pediatrics: A Guide to Ambulatory Care. 3rd ed. St Louis. Mo: CV Mosby Co; 1990.

Figure. Evaluation and management of febrile children under 2 years of age. *Ceftriaxone 50 mg/kg/dose IM/IV; ampicillin 50-75 mg/kg/dose IM/IV; or amoxicillin 70-75 mg/kg/24 hr g 8 hr PO. Adapted from Barkin RM. Rosen P. eds. Emergency Pediatrics: A Guide to Ambulatory Care. 3rd ed. St Louis. Mo: CV Mosby Co; 1990.

The diminished inflammatory response that may occur in immunocompromised children may make it difficult to localize the site of infection. Classic signs and symptoms of overwhelming infection are blunted and may not be organ specific. Significant disease may, therefore, exist with minimal symptoms.

Table

TABLE 2Initial Empiric Therapy for Selected Infections

TABLE 2

Initial Empiric Therapy for Selected Infections

Bacteremia in the febrile neutropenic child is not infrequent and may be caused by enteric pathogens, such as Escherichia coli, Klebsiella, and Pseudomonas aeruginosa, as well as more common pathogens. Staphybcoccus aureus, S pneumoniae, H influenzae type B, and coagulase-negative staphylococci frequently cause bacteremia that is associated with tunneled central venous catheters.

Therapy for the febrile, neutropenic patient is started empirically once blood cultures are obtained. Optimal therapy consists of two or three antibiotics. A sound regimen employs an antipseudomonal penicillin (ticarcillin or mezlocillin), an antistaphylococcal agent (oxacillin or cephalosporin), and an aminoglycoside. A third generation cephalosporin like cefotaxime or ceftriaxone is usually given empirically to children who are asplenic or have splenic dysfunction.

The febrile, immunocompromised patient in a nontoxic condition represents a diagnostic dilemma. These children may experience a serious illness without appearing clinically ill. A conservative approach is to hospitalize these children. Laboratory analysis includes a complete blood count, blood cultures, and urine studies. Depending on clinical findings, additional studies may include a chest radiograph and spinal fluid analysis. Empiric antibiotics should be given pending culture results and improvement.

HYPERPYREXIA

Hyperpyrexia, defined as a fever over 41. 1°C, is an uncommon finding and not necessarily associated with an increased risk of a serious bacterial infection.

The management of children with very high temperatures is based on the age and appearance of the child. Children in a toxic condition need aggressive evaluation and management. Evaluation should include cultures of specimens of blood, urine, and spinal fluid for bacterial pathogens as well as ancillary data including chest radiographs, a complete blood count, and determination of serum electrolytes. Conservative management includes hospitalization and usually the administration of parenteral antibiotics.

SEPTIC SHOCK

The treatment of septic shock focuses on the prevention of cardiopulmonary failure or arrest and necessitates the recognition of early signs of shock and anticipatory or immediate interventions. Untreated shock results in a cascade that begins with hypoxemia and acidosis leading to end-organ dysfunction characterized by an altered state of consciousness, hypotonia, tachycardia, decreased capillary refill, and impaired urine output. Bradycardia, apnea, and hypotension are ominous late findings. Specific signs and symptoms may be absent and subtle findings are commonly recognized if sought. Toxicity, fever, and other changes are often noted.

Impending deterioration requires immediate intervention, focusing on the airway, breathing, and circulation, as is done in all patients with respiratory or circulatory failure, and will, it is hoped, prevent progression. Early antibiotic therapy should be initiated (Table 2).

SUMMARY

Infections in children may present with nonspecific findings, requiring early recognition and stabilization. Age, etiology, immunocompetency, and duration of illness should all be considered in the initial assessment. Antibiotics and aggressive support are mandatory to avoid deterioration and severe morbidity or death.

REFERENCES

1. Kresch Mj. Axillary temperature as a screening test fat fever in children. J Pedum. 1984;104:596-599.

2. Caspe W, Chamudes O, Louie B. The evaluation and treatment of the febrile infant. Pedia* Infect Dis]. 1983;2:131-135.

3. Pantell RH, Naber M, Lamar R, et al. Fever in the first six months of life: risk of underlying serious infection. CJm Pediatr. 1980;19:77-82.

4. Dagan R, Powell K. Hall C, et al. identification of infants unlikely to have serious bacterial infections hospitalized for sepsis. J Pediatr. 1985;107:855-860.

5. Krober M, Bass J, Powell, et al. Bacterial and viral pathogens causing fever in infants less than 3 months old. Am ) D» Chili 1983;137:889-892.

6. Klein J, reigin R, McCracken G. Report of task force on diagnosis and management of meningitis. Pediatrics. 1986;78:959-982.

7. McCarthy PL, Sharpe MR, Spiesel SZ, et al. Observation scales to identify serious illness in febrile children. Pediatrics. 1982:70:802-809.

8. McGowan JR, Bratton L, Klein J, et al. Bacteremia in febrile children seen in a walk-in pediatric clinic. N Engij Med. 1983:25:1309.

9. McCarthy P. Controversies in Pediatrics: what tests are indicated for the child under 2 with fever. Pediatrics in Review. 1979;1:51-56.

10. Croker P, Quick G1 McCombs W. Occult bacteremia in the emergency department: diagnostic criteria for the young febrile child. Ann Emerg MeA 1985;14:1172-1 177.

11. Allegretta G, Weisman S, Alonan A. Oncologic emergencies II. Pediatr CUn North Am. 1985;32(3):61 3-632.

Selected Readings

Nelson JD. 1989-)990 Pocketbook of Pediatric Antimicrobial Therapy. 8th ed. Baltimore, MD: Williams and Williams Publishing Company.

Sanford JP. Guide to Anrrrriicrobial Therapy. West Bethesda, MO. 1983.

Steele RW Clinical Manual of Pediatric Infectious Disease. England: Appleton Cenrury Croft; 1986.

American Academy of Pediatrics Committee on Infectious Disease. The Red Book. Elk Grove Village, E-: American Academy of Pediatrics; 1988

TABLE 1

Overwhelming Infections: Age, Condition, and type-Specific Bacteria

TABLE 2

Initial Empiric Therapy for Selected Infections

10.3928/0090-4481-19901001-10

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