Heading off infection in asplenic children:
Antibiotics, and more

By Crawford J. Strunk, MD, and Jeffrey Taylor, MD

Prophylactic antibiotics have long provided asplenic children with a measure of protection against bacteremia and sepsis. Recent progress in vaccines promises to strengthen the defense.

Antibiotics have been used since the early 1950s to prevent bacteremia and sepsis in the asplenic patient. The advent of vaccines against Haemophilus influenzae type b and pneumococcal disease has reduced the incidence of bacteremia and sepsis in these susceptible patients by approximately 80%. How best to manage patients with asplenia is the subject of an ongoing dialogue among hematologists, infectious disease experts, and immunologists, with discussion revolving around management of acute infections, choice of antibiotics, emerging antibiotic resistance, patient adherence, and new vaccines that may alter overall management strategies.

In 1952, King and Schumacker published the first report of sepsis in asplenic patients, a case series of infants who developed sepsis following splenectomy for hereditary spherocytosis.¹ Since then, it has been recognized that infection in postsplenectomy patients and those with functional asplenia can best be prevented with antibiotics. Systematic research into prophylactic use of antibiotics in asplenia did not begin until the 1970s, however, and prophylaxis was not demonstrated to be effective in human beings until the 1980s. The addition of a 23-valent pneumococcal polysaccharide vaccine (23PS, Pneumovax) and Haemophilus conjugate vaccine (HibTITER) to the armamentarium in the 1980s further diminished the risk of overwhelming sepsis. Nevertheless, pneumococcal infection in young children remains a significant risk because of their poor immunologic response to polysaccharide vaccines. The recent introduction of a conjugate pneumococcal vaccine may lessen that risk.

How the spleen prevents infection

Any discussion of prophylactic antibiotics requires a review of basic splenic function, especially the immunologic and host defense roles the spleen plays (for an excellent review, see the chapter on splenic function in Nathan and Oski's Hematology of Infancy and Childhood²). The spleen serves as a site for hematopoiesis until approximately the seventh month of gestation, at which time the bone marrow assumes the primary role in hematopoiesis. The spleen maintains its hematopoietic ability later in life, however, as demonstrated in patients suffering from myelofibrotic or myelodysplastic syndromes. The mechanism by which the spleen controls hematopoiesis is poorly understood.

The spleen is also the site of phagocytosis of bacteria, platelets, leukocytes, and senescent red cells, and serves as a reservoir of platelets—containing as many as a third of all circulating platelets—and coagulation Factor VIII. The spleen eliminates abnormally shaped red cells, such as schistocytes or tear drop cells, from the bloodstream and removes intraerythrocytic inclusions such as Heinz bodies and Howell-Jolly bodies, which are denatured hemoglobin and DNA remnants, respectively. Last, the spleen plays a vital role in immunologic and host defense mechanisms.

The spleen, along with the liver, bone marrow, and the rest of the reticuloendothelial system, serves as a biologic filter. It contains strategically situated macrophages and other phagocytic cells that clear bacteria and other particulate matter from the bloodstream. The spleen clears particles the size of individual bacteria and erythrocytes, whereas the liver filters larger complexes. The role of each organ in clearing immune complexes is determined largely by a patient's immune status.

In the immune child, complement-fixing antibodies cover the bacteria, complement is activated, and the bacteria-antibody-complement complexes are cleared by the liver. The spleen assumes a much larger role in the immunocompromised patient because it is 10 to 60 times more efficient than the liver at clearing uncoated bacteria—perhaps because of the large number of macrophages that are available in the spleen as the blood is filtered. The spleen is therefore the first line of defense in clearing bacteremia in infants and young children, whose immune response is not yet fully developed. They are the patients most susceptible to overwhelming infection; hence the age-related, bacteremia-based workup for fevers.

Native immune dysfunction also has been reported in asplenic patients. These patients have been found to have a decreased level of immunoglobulin, in particular IgM, compared to peers with normal splenic function³ and may have delayed conversion of IgM to IgG. They also have a well-defined inability to activate complement through the properdin pathway. They have normal activation of complement by way of the classical pathway, however, and a normal response to vaccination.

Based on early studies that noted the poor response of asplenic and hyposplenic patients to intravenously administered particulate and polysaccharide antigens, it is believed that the spleen plays a critical role in first capturing and processing intravenous antigens, particularly those of encapsulated bacteria such as pneumococcus. The spleen contains a large number of lymphocytes capable of producing antibody to the bacterial capsular polysaccharide. Regrettably, the polysaccharide coat does not induce memory B cells, which is part of the reason why younger children and infants are more often bacteremic than older children. Asplenic patients do respond normally to intramuscular or subcutaneous injections of antigen because the local lymph nodes are the primary site of the immune response to these injections.

The conjugate vaccines were developed to help prevent bacteremia and sepsis in young children and infants, whose immune systems cannot mount a sustained and permanent response to encapsulated bacteria. Conjugate vaccines, which are made by covalently bonding a polysaccharide of a particular organism serotype to a known immunogenic protein, increase the immune response of all young children and infants, including those who are asplenic, by inducing memory B cell formation even in infants as young as 2 months. 23PS and the meningococcal vaccines currently on the market cannot induce a memory B cell response because they are purely polysaccharide vaccines, to which children under 2 years of age do not respond. Conjugated polysaccharide vaccines allow the production of antibodies that activate complement much better than polysaccharide-only antibody, thus improving coating, opsonization, and clearing of bacteria.

Types of asplenia

Asplenia is defined as either an anatomic or physiologic absence of the spleen or its functions. Asplenia may be congenital, surgical, or functional; functional asplenia is the most common form.

Two readily available laboratory tests are used to evaluate splenic function. The first is the peripheral smear. The presence on the smear of Howell-Jolly bodies, which are old remnants of DNA within the erythrocyte, suggest diminished splenic function. More than 1% to 2% Howell-Jolly bodies indicates poor or absent splenic function. The second test is a pitted RBC count. A pit is a little indentation in the erythrocyte membrane thought to be caused by the cell's traversing the microvasculature. The spleen remodels this pitted RBC. A pit count greater than 3.5% indicates splenic dysfunction or absence. Splenic function also can be evaluated using ⁹⁹technetium-labelled colloid or red blood cells, which are taken up by a spleen with adequate function.

Congenital asplenia or polysplenia may occur as either bilateral rightsidedness (asplenia) or bilateral leftsidedness (polysplenia). The result of both conditions is usually the same: little true native splenic function. Congenital asplenia may occur as an isolated malformation or in association with other congenital defects such as heterotaxy or congenital heart disease. It also may be a manifestation of an underlying syndrome. A patient may exhibit physical findings related to his (or her) syndrome at birth, or the syndrome may come to light in early childhood when he develops overwhelming infection. Because relatively few children have congenital asplenia, little research on prophylactic antibiotics has been done in this group.

Splenectomy may be performed for either medical or surgical reasons. Medical reasons include chronic idiopathic thrombocytopenic purpura, hereditary spherocytosis, and cytopenias in which hypersplenism is a contributing factor. Surgical reasons include cysts and, in the past, staging for Hodgkins disease.

Today, splenectomy is most often secondary to trauma. Because of the risk of postsplenectomy sepsis, careful observation of patients with splenic trauma, as an alternative to surgery, has become more common. If surgery is needed, partial splenectomy may be performed in an attempt to preserve splenic function. Other options include splenorrhaphy, splenic artery ligation, and splenectomy with autotransplantation, in which some splenic tissue remains in the body and provides a measure of protection against infection. This process is known as surgical splenosis.

Sickle cell disease is the prototypical cause of functional asplenia. Other conditions that cause acquired splenic hypofunction include celiac disease, inflammatory bowel disease and other autoimmune disorders, glomerulonephritis and the nephrotic syndrome, amyloidosis, and young or old age. Asplenia is more likely in patients with Hgb SS disease or Sb⁰ thalassemia. Patients with Hgb SC disease and Sb+ thalassemia also may develop asplenia, but not as severe a form or as early in life as patients in the other two groups. Because patients with sickle cell disease make up a large percentage of asplenic patients, they are the group most studied with regard to prophylactic antibiotics.

The risk of infection and the infecting organisms are similar regardless of whether asplenia is congenital, surgical, or functional. Patients with asplenia have an increased risk of invasive infection, including bacteremia and sepsis, meningitis, osteomyelitis, and pneumonia. The causative organisms are most often encapsulated bacteria, specifically Streptococcus pneumoniae, H influenzae, Neisseria meningitidis, Escherichia coli, and Salmonella species.

Before prophylactic antibiotics became standard, sepsis was the most common cause of morbidity and mortality in patients with functional asplenia and sickle cell disease. Based on the Cooperative Study of Sickle Cell Disease, the incidence of septicemia among children under 3 years of age is 11.5/100 patient years, with a 24% fatality rate; 4.5% of patients have at least one episode of pneumococcal bacteremia.^4,5 By contrast, in children with normal splenic function, the overall incidence of invasive pneumococcal disease is 0.0232/100 patient years, and the overall death rate is 0.9%. The incidence is 0.1669/100 patient years in children under 2 years of age, 0.0352/100 patient years in children 2 to 4 years old, and 0.0039/100 patient years in children over 5 years.⁶

Evaluating the efficacy of antibiotics

Although, as previously noted, prophylactic antibiotics were long recommended to reduce morbidity and mortality in children with asplenia, the first randomized, controlled trial to document the benefit of using prophylactic antibiotics was not published until 1984 by John and colleagues.⁷ In that five-year study, 242 Jamaican children with Hgb SS disease were randomized to receive IM injections (to prevent noncompliance) of penicillin or no antibiotic prophylaxis and were vaccinated with either 23PS or Hib vaccine. Antibiotic prophylaxis was stopped at 3 years of age because it was thought that the older children would not comply with painful injections.

None of the children on penicillin developed S pneumoniae infection, but six isolates were found among 99 patients in the placebo group. After prophylaxis was stopped, seven isolates were found among 143 patients in the penicillin group. There were no reports of antibiotic resistance or patient deaths.

In 1986, the Prophylaxis with Oral Penicillin in Children with Sickle Cell Disease study (PROPS I) was published.⁸ This was the first and only multicenter, randomized, controlled trial in the United States to evaluate the use of prophylactic antibiotics compared with no therapy. PROPS I studied 215 children 3 to 36 months of age with Hgb SS disease who were randomized to twice daily penicillin or placebo and received 23PS at 1 and 2 years of age. Patients on long-term antibiotics to prevent urinary tract infection or for other reasons and patients receiving chronic transfusion therapy were eliminated because those on long-term antibiotics would already be at decreased risk of infection and those on chronic transfusion therapy had a decrease in Hgb SS and also would be less susceptible to infection.

The trial was terminated eight months early because 15 cases of pneumococcal sepsis occurred—13 in the placebo group and two in the penicillin group (a reduction of 84%). Three patients in the placebo group died of fulminant H influenzae infection.

PROPS I has been criticized because of the low number of children enrolled and termination of the study a full eight months prematurely because of the extreme results. Considering these limitations, the reported benefits of prophylaxis may have been overestimated. Despite criticism of its methodology, however, PROPS I became the benchmark with which all subsequent data have been compared. A number of studies have looked at the incidence of pneumococcal bacteremia and sepsis, but all were done in single institutions and none was randomized or placebo controlled. PROPS I demonstrated such striking clinical efficacy for antibiotic prophylaxis that its use has become the standard of care not only for sickle cell patients but for all patients with asplenia.

Because the John study found seven cases of S pneumoniae infection among 143 patients after penicillin prophylaxis was stopped at 3 years of age, the PROPS II study, completed in 1993 and published in 1995, investigated whether it was safe to discontinue antibiotics at 5 years of age.⁹ This age was selected based on the decreased risk of bacteremia and sepsis after that time in healthy children.

The PROPS II study continued PROPS I with the same groups (twice daily penicillin and placebo). Two episodes of sepsis occurred in the penicillin group and four in the placebo group. A systematic review of the PROPS studies showed that the risk of pneumococcal bacteremia in children under 5 years of age was 1.5/100 patient years in the penicillin group and 9.8/100 patient years in the placebo group.¹⁰ In children older than 5 years, the risk of pneumococcal bacteremia was 0.33/100 patient years in the penicillin group and 0.67/100 patient years in the placebo group. These data are similar to those reported recently by Hord and colleagues, who found an incidence of 2.5/100 patient years and a mortality rate of 11% in children under 5 years of age.¹¹ Mortality rates in the PROPS studies were not calculated specifically, but PROPS I recorded three deaths caused by streptococcal pneumonia, and PROPS II recorded no deaths.

The PROPS studies are the basis of recommendations for preventing pneumococcal sepsis in patients with sickle cell disease. The recommendations include early diagnosis of sickle cell disease by universal screening in every state and starting prophylaxis as soon as the diagnosis is made. In addition to regular immunizations, the patient should receive 23PS at 2 years of age. Patients may discontinue prophylaxis at 5 years if they are receiving regular care and have had no episodes of documented pneumococcal bacteremia. Last, patients with any degree of fever need prompt evaluation and therapy.

These recommendations have been established for patients with sickle cell disease. They may or may not be fully applicable to patients with other types of asplenia. Hard data on antibiotic prophylaxis in congenital asplenia are lacking. Moreover, such patients may have other immune problems. For these reasons, the point at which to discontinue antibiotics has not been well established. Some clinicians stop penicillin at 5 years of age; others continue treatment until at least 18 years. Other recommendations, including needed immunizations, remain the same for patients with sickle cell disease and those with congenital asplenia.¹²

The greatest differences of opinion regarding the use of prophylactic antibiotics generally center on patients who have undergone splenectomy. The prevailing belief is that children should be started on prophylactic antibiotics postoperatively and that antibiotics should be continued until at least one year after surgery.^12,13 When a child's spleen is removed electively, meningococcal vaccine and 23PS should be given two to four weeks before the operation; Hib vaccine should be given if the child has not been immunized previously. In cases of emergency splenectomy, immunizations should be given two to four weeks postoperatively.¹²

Current opinion holds that adults who undergo splenectomy do not need prophylactic antibiotics because of their lifelong exposure, and hence immunity, to encapsulated organisms. Adults should, however, receive 23PS and Hib vaccine if they have not been immunized previously. Meningococcal vaccine should be given to adult patients at risk.

The foregoing recommendations are not universal—British guidelines, for example, recommend lifelong prophylactic antibiotics for all patients regardless of age.^14,15 Clinical judgment also must come into play. Psychosocial environment, parental reliability, and distance from a clinic all influence the decision whether or not to continue antibiotics.

What about antibiotic resistance?

Antibiotic resistance is an issue with which all physicians must come to terms. Several studies have investigated penicillin resistance in sickle cell patients. The best known study is associated with PROPS II and is known as the Ancillary Nasopharyngeal Culture Study (ANCS).¹⁶ ANCS concluded that children receiving penicillin prophylaxis were at no greater risk of being carriers of resistant pneumococcus than those given placebo.

Twenty-seven percent of children in the study had at least one nasopharyngeal culture that was positive for pneumococcus, and about 9% had at least one isolate that was intermediately susceptible or resistant to penicillin. The nasopharyngeal carriage rates were similar in both groups, however. The study also found a notable (but statistically insignificant) trend toward increased multidrug-resistant pneumococcus in children older than 5 years.

In 1996, Wang and colleagues reported increased resistance to cephalosporins, erythromycin, trimethoprim-sulfamethoxasole, and clindamycin in nasopharyngeal cultures.¹⁷ They also noted more resistance in their study group than in the ANCS group. A similar trial at Wayne State University actually showed less colonization by S pneumoniae in sickle cell disease patients than in the general population. The number of resistant organisms was higher in sickle cell disease patients, however.¹⁸

The problem of compliance

A potential barrier to effective antibiotic prophylaxis is patient adherence. It is difficult for adults, let alone children, to take medicine appropriately. Berkovitch achieved a best compliance rate of 82% among sickle cell disease patients using education and other interventions, such as weekly reminders by phone.¹⁹ Another study evaluated the beliefs of parents of children with sickle cell disease regarding the severity of the child's illness by asking parents to refill the antibiotic prescriptions every two weeks for several months. Approximately 42% of parents said they did so, but when researchers contacted the pharmacy for confirmation, they found that only about 12% of parents had actually called for a prescription refill.²⁰ Parents of children younger than 5 years were more likely to call for a refill on time than parents of children older than 5 years.

Teach and colleagues investigated compliance by examining Micrococcus inhibition in urine samples of patients on penicillin prophylaxis.²¹ Patient-reported compliance was 66%, but test-confirmed compliance was only about 43%. Compliance was better for children younger than 5 years (61%) than for older children (37%). These studies show that the concept of prophylaxis needs to be enforced at every visit.

Another protective option—PCV7

Because of the continued risk of pneumococcal sepsis in asplenic patients and increasing reports of antimicrobial resistance and poor patient compliance, other measures to protect asplenic patients from infection are clearly necessary. The most likely option is the conjugate pneumococcal vaccine.

As noted earlier, the 23-valent pneumococcal polysaccharide vaccine is relatively ineffective in children younger than 2 years—the population at highest risk of infection. In February 2000, a seven-valent conjugate pneumococcal vaccine—PCV7 (Prevnar)—was licensed in this country for use in infants. The vaccine includes serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Immunizing against these serotypes may prevent about 86% of bacteremia and 83% of meningitis in children younger than 6 years.²² Like the Hib vaccine, PCV7 is thought to produce long-lasting immunity.

One study so far has investigated the immunogenicity and safety of PCV7 in sickle cell disease patients.²³ This open label study looked at preimmunization and postimmunization titers to pneumococcal antigens in sickle cell disease patients compared to titers in healthy patients. Children enrolled before 2 months of age were immunized with PCV7 at 2, 4, and 6 months (schedule A); those enrolled between 2 and 12 months of age were given a single dose of the vaccine at 12 to 15 months (schedule B). All patients with sickle cell disease were given a dose of 23PS at 24 months. Titers were checked before each vaccination and one month after the last PCV7 and 23PS doses.

The results revealed that PCV7 was just as immunogenic in the sickle cell patients as in the healthy patients. The PCV7 dose was highly immunogenic for all serotypes in schedule A. Each serotype produced a titer level of 0.15 µg/mL in at least 89% (89% to 100%) of the infants and 1.0 µg/mL in at least half (56% to 100%) of the infants. For schedule B, each serotype produced titers of 0.15 µg/mL in at least half (53% to 92%) of the patients and 1.0 µg/mL in at least a third (31% to 71%) of the patients. Giving a dose of 23PS greatly increased the titers. It is reasonable to conclude that patients with sickle cell disease should be given PCV7 with the expectation that they will demonstrate an appropriate immune response.

AAP recommendations

In 2000, The Committee on Infectious Diseases of the American Academy of Pediatrics published a policy statement regarding the use PCV7, 23PS, and prophylactic antibiotics to prevent pneumococcal infections in children.^24,25 The statement includes specific recommendations for asplenic children (see "Preventing pneumococcal infection in asplenic children: AAP's recommendations"). The AAP recommends giving PCV7 to all children at 2, 4, and 6 months of age with a booster between 12 and 15 months. Patients with any form of asplenia should receive a dose of 23PS at least six to eight weeks after their last PCV7 dose or at 2 years of age, whichever is later. An additional dose of 23PS should be given three to five years after the initial dose.

Prophylaxis with oral penicillin V potassium (125 mg bid until 3 years of age and 250 mg bid from 3 years to 5 years) is recommended regardless of vaccination status in all children with functional, congenital, or surgical asplenia. Antibiotics should be started at 2 months of age or whenever the diagnosis of sickle cell disease or asplenia is made or suspected. (Diagnosis is facilitated by the fact that 44 states, the District of Columbia, Puerto Rico, and the Virgin Islands provide universal screening; the other six states test by request.²⁶) The drugs can be discontinued at 5 years of age if the child has had no invasive pneumococcal infections and has been appropriately vaccinated. Children who are allergic to penicillin can be given oral erythromycin at a dose of 20 mg/kg divided bid.²⁶

Patients with asplenia and fever should be evaluated if the temperature is higher than 38.0° C. Based on an algorithm by Embury and Vichinsky, all febrile asplenic patients require an appropriate history and physical exam to look for any source of infection.²⁷ The initial laboratory evaluation should include a complete blood count with differential, blood and urine cultures, and a chest radiograph when appropriate. The CBC may show an elevated white blood cell count (usually above 20,000 to 25,000/µL) with an increase in segmented neutrophils and bands. (A WBC count of 15,000 to 20,000/µL may not be unusual for most children with Hgb SS disease, however, because overall bone marrow turnover increases in response to chronic hemolysis.) Platelets are usually normal or increased (as an acute phase reactant) as part of a bacteremic picture. A lumbar puncture should be performed if meningitis is suspected. Patients may then be divided into a high-risk or low-risk category.

Patients in the high-risk category include those with Hgb SS disease, Sb⁰ thalassemia, or asplenia who have a temperature higher than 40° C, appear toxic, or are not compliant with or not receiving prophylactic antibiotics. They should be admitted for IV antibiotics and followed in the hospital until cultures are negative for 48 hours.

Patients considered at low risk include those with Hgb SS disease or Sb⁰ thalassemia and a temperature below 40° C but above 38.0° C who are compliant with prophylaxis; those with Hgb SC disease or Sb⁺ thalassemia and a temperature higher than 38.5° C, and those with congenital asplenia and a temperature between 38° C and 40° C who are receiving antibiotic prophylaxis. They should be evaluated, including blood cultures, and may be given a long-acting antibiotic such as ceftriaxone with follow-up in 24 hours. Patients with Hgb SC disease or Sb+ thalassemia and a temperature under 38.5° C should be treated symptomatically.

A promising future

The future for asplenic patients looks promising. Since the first routine use of prophylactic antibiotics 30 years ago, great strides have been made in preventing invasive bacterial infections. Further research is needed to investigate the use of conjugate pneumococcal vaccines and better document compliance and resistance issues. The truly great benefit to asplenic patients will be the addition of PCV7 and other second-generation conjugate pneumococcal vaccines in clinical trials. Clinicians today only rarely see invasive H influenzae type B disease in either healthy or asplenic patients. It is hoped that conjugate vaccines will have a similar impact on pneumococcus. For this to occur, additional invasive serotypes of S pneumoniae must be added to the conjugate vaccine and the vaccine must be made readily available—especially for the populations of larger cities, where the prevalence of sickle cell syndromes is highest.

REFERENCES

1. King H, Shumacker HB: Splenic Studies I. Susceptibility to infection after splenectomy performed in infancy. Ann Surg 1952;136:259

2. Pearson HA: The spleen and disturbances of splenic function, in Nathan DG, Orkin SH (eds): Nathan and Oski's Hematology of Infancy and Childhood, Volume 2, ed 5. Philadelphia: WB Saunders Company, 1998, pp 1051–1068

3. Overturf GD: Infections and immunizations in children with sickle cell disease. Adv Pediatr Infect Dis 1999; 14:191

4. Zarkowsky HS, Gallagher D, Gill FM, et al: Bacteremia in sickle hemoglobinopathies. J Pediatr 1986;109(4):579

5. Leikin SL, Gallagher D, Kinney TR, et al: Mortality in children and adolescents with sickle cell disease. Pediatrics 1989;84(3): 500

6. Robinson KA, Baughman W, Rothrock G, et al: Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995–1998. JAMA 2001; 285(13):1729

7. John AB, Ramlal A, Jackson H, et al: Prevention of pneumococcal infection in children with homozygous sickle cell disease. BMJ 1984;288(6430):1567

8. Gaston MH, Verter JI, Woods G, et al: Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med 1986;314(25):1593

9. Falletta JM, Woods GM, Verter JI, et al: Discontinuing penicillin prophylaxis in children with sickle cell anemia. Prophylactic Penicillin Study II. J Pediatr 1995;127(5):685

10. Riddington C, Owusu-Ofori S: Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease (Cochrane Review). The Cochrane Library, issue 3, 2002, Oxford, Update Software

11. Hord J, Byrd R, Stowe L, et al: Streptococcus pneumoniae sepsis and meningitis during the penicillin prophylaxis era in children with sickle cell disease. J Pediatr Hematol Oncol 2002;24(6):470

12. American Academy of Pediatrics: Immunization in special clinical circumstances: Asplenic children, in Pickering LK (ed): 2000 Red Book: Report of the Committee of Infectious Diseases, ed 25. Elk Grove Village, IL, American Academy of Pediatrics, 2000, pp 66–67

13. Jugenburg M, Haddock G, Freedman MH, et al: The morbidity and mortality of pediatric splenectomy: Does prophylaxis make a difference? J Pediatr Surg 1999; 34(7):1064

14. Lortan JE: Management of asplenic patients. Br J Haematol 1993;84(4):566

15. Working Party of the British Committee for Standards in Hematology Clinical Hematology task force; Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. BMJ 1996; 312(7028):430

16. Woods GM, Jorgensen JH, Waclawiw MA, et al: Influence of penicillin prophylaxis on antimicrobial resistance in nasopharyngeal S pneumoniae on children with sickle cell anemia. The Ancillary Nasopharyngeal Culture Study of Prophylactic Penicillin Study II. J Pediatr Hematol Oncol 1997;19(4):327

17. Wang WC, Wong WY, Rogers ZR, et al: Antibiotic resistant pneumococcal infection in children with sickle cell disease in the US. J Pediatr Hematol Oncol 1996; 18(2):140

18. Sakhalkar VS, Sarnaik SA, Asmar BI, et al: Prevalence of penicillin-nonsusceptible Streptococcus pneumoniae in nasopharyngeal cultures from patients with sickle cell disease. South Med J 2001;94(4):401

19. Berkovitch M, Papadouris D, Shaw D, et al: Trying to improve compliance with prophylactic penicillin therapy in children with sickle cell disease. Br J Clin Pharmacol 1998;45(6):605

20. Elliott V, Morgan S, Day S, et al: Parental health beliefs and compliance with prophylactic penicillin administration in children with sickle cell disease. J Pediatr Hematol Oncol 2001;23(2):112

21. Teach SJ, Lillis KA, Grossi M: Compliance with penicillin prophylaxis in patients with sickle cell disease. Arch Pediatr Adolesc Med 1998;152(3):274

22. Peters TR, Edwards KM: Pneumococcal vaccines: Present and future. Pediatr Ann 2002;31(4):261

23. O'Brien KL, Swift AJ, Winkelstein JA, et al: Safety and immunogenicity of heptavalent pneumococcal vaccine conjugated to CRM(197) among infants with sickle cell disease. Pneumococcal Conjugate Vaccine Study Group. Pediatrics 2000;106(5):965

24. American Academy of Pediatrics Committee on Infectious Diseases: Policy statement: Recommendations for the prevention of pneumococcal infections, including the use of pneumococcal conjugate vaccine (Prevnar), pneumococcal polysaccharide vaccine and antibiotic prophylaxis. Pediatrics 2000;106(2 Pt 1):362

25. American Academy of Pediatrics Committee on Infectious Diseases: Technical report: Prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis. Pediatrics 2000;106(2 Pt1):367

26. National Heart, Lung, and Blood Institute Division of Blood Diseases and Resources: Child health care maintenance, in Management of Sickle Cell Disease. Bethesda, Md., National Institutes of Health, NIH publication 02-2117, revised June 2002, p 30

27. Embury SH, Vichinsky EP: Overview of the management of sickle cell disease. UpToDate 2002;10(3)

DR. STRUNK is a fellow in the division of pediatric hematology/oncology, Rainbow Babies and Children's Hospital, Cleveland.

DR. TAYLOR is an attending physician in the division of pediatric hematology/oncology, Geisinger Medical Center, Danville, Pa.

The authors have nothing to disclose in regard to affiliations with, or financial interests in, any organization that may have an interest in any part of this article.

A febrile 8-month-old with complex heart disease

The patient and the problem. An 8-month-old white girl with complex cyanotic heart disease and heterotaxy with asplenia is seen in clinic with a fever of 38.5° C, which she has had for about a day. She is compliant with prophylactic antibiotics. The infectious disease attending physician recommends that the child be brought to the emergency department (ED) for evaluation. On examination, her temperature is 38.7° C; she is active and alert without focal signs of infection. A complete blood count with differential is unremarkable. Urinalysis is normal. A chest radiograph is also normal. No lumbar puncture is performed because of the child's clinical status.

The solution. Although this baby is receiving antibiotic prophylaxis, she has several risk factors for sepsis and bacteremia. Her age, in particular, puts her at high risk of occult bacteremia, despite a normal physical exam and unremarkable laboratory values. She should be given a dose of ceftriaxone in the ED and subsequent doses at 24-hour intervals until cultures are negative for 48 hours. She should continue her usual antibiotic prophylaxis once the febrile episode subsides. If cultures are positive, she will need to be treated with a full, 10-day course of antibiotic.

A 3-year-old with high fever and sickle cell disease

The patient and the problem.A 3-year-old African-American boy with Hgb SS disease is seen because of a fever of 40° C that has persisted for two days. He is not adherent to prophylactic antibiotics and has not been seen in clinic for about eight months. He has been vaccinated with 23 PS (Pneumovax) but not with PCV7 (Prevnar). Physical examination reveals a lethargic child with a temperature of 40.3° C and no other focal signs of infection. The white blood cell count is elevated at 20,000/µL with 65% segmented neutrophils and 18% bands. Blood is drawn for culture. Urinalysis and a chest radiograph are normal. Lumbar puncture is traumatic but otherwise unremarkable.

The solution. This child is at significant risk of sepsis and bacteremia because he is younger than 5 years, is noncompliant with his antibiotics, and has the most severe form of sickle cell disease. High fever, elevated WBC count, and left shift make the risk of sepsis particularly high. Meningitis must be excluded in this patient. Because of his tenuous clinical status, he must be admitted to the hospital for at least 48 hours to rule out sepsis while culture results are obtained.

A 7-year-old with a low-grade fever

The patient and the problem.A 7-year-old African-American boy with Hgb SC disease is brought to the clinic after running a fever of 38.3° C for one day. He has no other sign of infection. His sister has a common cold. Apart from the fever, the physical examination is normal—as are the CBC with differential and chest radiographs. Urinalysis is likewise unremarkable.

The solution. Because this child has a mild form of hemoglobinopathy and a low-grade fever, his risk for sepsis is fairly low and he can be treated symptomatically. His parents should be cautioned to bring him back to the clinic for reevaluation if his fever rises or his clinical status deteriorates.

Preventing pneumococcal infection in asplenic children:
AAP's recommendations

The American Academy of Pediatrics recommends the following regimen of immunizations and antibiotic prophylaxis for children with sickle cell disease, congenital or acquired asplenia, or splenic dysfunction.

Immunization

Children should receive heptavalent pneumococcal conjugate vaccine (PCV7) and 23-valent pneumococcal polysaccharide (23PS) vaccine as follows:

Under 24 months of age (all children):

• PCV7 at 2, 4, and 6 months of age

• PCV7 booster between 12 and 15 months of age

Children 24 to 59 months of age who have received one to three previous doses of PCV7:

• One dose of PCV7

• One dose of 23PS vaccine six to eight weeks after the last dose of PCV7

• One dose of 23PS vaccine three to five years after the first dose of 23PS vaccine

Children 24 to 59 months of age who have received one previous dose of 23PS vaccine:

• Two doses of PCV7 six to eight weeks apart at least six to eight weeks after the last dose of 23PS vaccine

• One dose of 23PS vaccine three to five years after the first dose of 23PS vaccine

Children 24 to 59 months of age who have received no previous doses of PCV7 or 23PS:

• Two doses of PCV7 six to eight weeks apart

• One dose of 23PS vaccine six to eight weeks after the last dose of PCV7

• One dose of 23PS vaccine three to five years after the first dose of 23PS vaccine

Prophylaxis

Antibiotic prophylaxis is recommended for all children with sickle cell disease and functional or anatomic asplenia whether or not they have received pneumococcal immunizations.

Begin prophylaxis before 2 months of age or as soon as sickle cell disease or asplenia is identified.

Give penicillin V potassium orally as follows:

• 125 mg twice a day until 3 years of age

• 250 mg twice a day after 3 years of age

Prophylaxis may be discontinued after 5 years of age if the child has not had an invasive pneumococcal infection and has received recommended pneumococcal immunizations.

Source: American Academy of Pediatrics Committee on Infectious Diseases²⁴

 

Crawford Strunk, Jeffrey Taylor. Heading off infection in asplenic children: Antibiotics, and more. Contemporary Pediatrics November 2003;20:61.