Prophylactic Penicillin Therapy Research Articles

P1471: CURRENT INDICATIONS AND RISKS OF SPLENECTOMY IN A LARGE MODERN COHORT OF CHILDREN WITH SCA

Background: In children with sickle cell anemia (SCA), the spleen is altered early in life and may be the site of serious complications such as acute splenic sequestration (ASS) or hypersplenism. Surgical splenectomy may be necessary in those who experience such complications, but both the consequent infectious and thrombo-embolic risks, and the age at which splenectomy may be safely performed, remain unclear. Aims: The objective of our study was to determine the post-splenectomy incidence of invasive bacterial infections and thrombo-embolic complications in a large cohort of children with SCA. The secondary objective was to analyze the effect of age at splenectomy on these risks. Methods: Retrospective review of children with SCA (SS or SB0-thalassemia) splenectomized during the 2000-2018 period at Robert Debré University Hospital (Paris, France) was undertaken. The study received ethical approval. The main clinical characteristics of patients, indications for splenectomy and outcomes were analyzed. Results: A total of 188 children were included, with 164 (87.2%) SS children. Median (Q1-Q3) age at splenectomy was 4.1 yrs (2.5-7.3). Median duration of post splenectomy follow-up (FU) was 5.9 yrs (2.7-9.2) yielding 1192.6 patients-years (PY) of observation. One death (0.5%) occurred during FU, unrelated to splenectomy. Indications for splenectomy were ASS in 101 (53.7%) cases, hypersplenism in 75 (39.9%) and diverse reasons in the remaining children (splenomegaly n=5; delayed hemolytic post transfusion reaction n=5, other n=2). Pneumococcal immunization coverage was good with 166 (95.9%) eligible children immunized with polysaccharidic pneumococcal vaccination at the time of splenectomy and 7 (4.0%) after the procedure. Regarding the conjugated pneumococcal vaccination, 158 (91.9%) of eligible patients had received at least one injection at the time of splenectomy. All patients received penicillin prophylaxis. Overall incidence of invasive bacterial infection was 0.005 /PY (n=6 in 5 patients, no pneumococcal infections). Overall incidence of thrombo-embolic events was 0.003 /PY (n= 4 in 4 patients). In this cohort, 123 (65.4%) and 65 (34.6%) children were splenectomized > or < 3 years of age, respectively. Overall incidence of invasive bacterial infection and thrombo-embolic events was not different according to the age at splenectomy (0.005/ PY in both groups) and 0.004/ PY versus 0.003/ PY (p= 0.7), respectively. Likewise, there was no difference between these groups in the incidence of acute chest syndrome or vaso-occlusive events. Conversely, a significant increase in the overall incidence of cerebral vasculopathy (including abnormal TCD, stroke and cerebral stenosis) was found in children splenectomized before 3 (0.037/PY) versus after 3 (0.011/ PY), p<0.01). Patients who presented with ASS (n=101) were splenectomized at a median age of 3.3 yrs (2.4-5.4), following a median number of 3 (2-4) episodes of ASS and therefore contributed to a large proportion of patients splenectomized under 3 (n=44/65, 67.7 %). Summary/Conclusion: To date this is the largest pediatric cohort study of splenectomized patients with SCA. We show that surgical splenectomy does not result in a significant increased risk of complications, notably invasive bacterial infections or thrombo-embolic complication. Splenectomy should not be delayed in patients once there is an indication for surgical removal, and the children have received recommended vaccines and prophylactic penicillin therapy. The relationship between ASS, splenectomy and cerebral vasculopathy needs to be further assessed.

A61: Prevalence of Streptococcal Antibodies in Pediatric Non‐Rheumatic Fever Syndromes in Areas of Low Rheumatic Fever Incidence

Background/Purpose:Streptococcus pyogens infect an estimated 5 million children in United States/year. Various syndromes are attributed to elevated Streptococcal antibody titer (SAT) &amp; are treated with prophylactic penicillin therapy (PPT). We hypothesize the elevated SAT has no diagnostic &amp; PPT has no therapeutic significance in pediatric non‐Rheumatic Fever Syndromes in areas of Low Rheumatic Fever Incidence.Methods:A cross‐sectional retrospective electronic chart review was conducted. Patients who met the criteria had tics, chronic pain syndrome (CPS) or joint symptoms as presenting complaints, had streptococcal antibody titers (SAT) performed &amp; were seen by pediatricians in past 5 years at Women's and Children's Hospital. Patients were classified into 3 subgroups. Group 1: 184 presented with joint pain with or without (w/o) swelling, Group 2: 105 presented with tics &amp; Group 3: 324 presented with CPS. Reference lab values were: Antistreptolysin O (ASO);0–1 yr:0–200 IU/mL, 2–12 yrs: 0–240 IU/mL, 13 yrs &amp; older: 0–330 IU/mL &amp; DNAse‐B Ab; 0–6 yrs: Less than 250 U/mL, 7–17yrs:Less than 310 U/mL, 18 yrs &amp; older: Less than 260 U/mL. Elevation of titers by ≥1.5 times for age was considered abnormal for research purposes.Results:Six hundred and thirteen charts were reviewed. Chi‐square test was used to identify proportion of abnormal ASO &amp; DNAse‐B Ab among the 3 diagnostic groups ranged from 26% (JS) to 35% (TICS), and 25.5% to 26.7% respectively; the difference in the abnormal ASO &amp; DNAse‐B Ab in the 3 groups was not significant (ASO p = 0.25, DNAse‐B Ab p = 0.97). An exact Pearson chi‐square test compared the proportion of abnormal ASO &amp; DNAse‐B Ab on patients w/o PPT. The proportion of abnormal results w/o PPT were 5.88% (8/136) &amp; 10.87% (5/46) for ASO &amp; 5.88% (8/136) &amp; 4.35% (2/46) for DNAse‐B Ab, which was not statistically significant (p = 0.74 for ASO, p = 0.32 for DNAse‐B Ab). McNemar's test revealed that the proportion of abnormal ASO results (178/613 = 29.04%) was significantly higher (P‐value = 0.0002) than of DNAse‐B Ab (158/613 = 25.77%). For both ASO &amp; DNAse‐B Ab, odds of abnormal results in males were about 1.73 times higher than in females (CI = 95%, OD = 1.19, 2.51); the highest probability of abnormal results occurred around 129 months. Mean Ab test costs for CPS was $426, JS was $377 &amp; Tics was $556. While 137 patients received PPT, 47 received no therapy; there was no difference in abnormal SAT in both groups at 6 months.Conclusion:In low Rheumatic Fever Incidence areas, abnormal SAT in Pediatric non‐rheumatic fever syndromes have poor diagnostic &amp; therapeutic value; repeat testing adds cost without treatment value.

Correlates of Adherence to Prophylactic Penicillin Therapy in Children With Sickle Cell Disease

Research has found that prophylactic penicillin therapy greatly reduces the incidence of bacterial infections in children with sickle cell disease (SCD). This study describes the prevalence and assesses correlates of adherence to this medication. Thirty caregivers of children with SCD participated in this study. Adherence was obtained through caregiver reports, provider estimates, and pharmacy records. Results indicated problematic adherence, with only one third of children receiving appropriate medication according to pharmacy records. Adherence to prophylactic penicillin continues to be inadequate, with the caregivers' beliefs, reported barriers, and personal experience with SCD related to their adherence to the medication regimen.

Discontinuing penicillin prophylaxis in children with sickle cell anemia

Objective: To evaluate the consequences of discontinuing penicillin prophylaxis at 5 years of age in children with sickle cell anemia who had received prophylactic penicillin for much of their lives. Design: Randomized, double-blind, placebo-controlled trial. Setting: Eighteen teaching hospitals throughout the United States. Patients: Children with sickle cell anemia (hemoglobin SS or hemoglobin S β 0-thalassemia) who had received prophylactic penicillin therapy for at least 2 years immediately before their fifth birthday and had received the 23-valent pneumococcal vaccine between 2 and 3 years of age and again at the time of randomization. Of 599 potential candidates, 400 were randomly selected and followed for an average of 3.2 years. Interventions: After randomization, patients received the study medication twice daily-either penicillin V potassium, 250 mg, or an identical placebo tablet. Patients were either seen in the clinic or contacted every 3 months thereafter for an interval history and dispensing of the study drug. A physical examination was scheduled every 6 months. Main outcome measures: The primary end point was a comparison of the incidence of bacteremia or meningitis caused by Streptococcus pneumoniae in children continuing penicillin prophylaxis versus those receiving the placebo. Results: Six children had a systemic infection caused by S. pneumoniae, four in the placebo group (2.0%; 95% confidence interval 0.5%, 5.0%) and two in the continued penicillin prophylaxis group (1.0%; 95% confidence interval 0.1%, 3.6%), with a relative risk of 0.5 (95% confidence interval 0.1, 2.7). All invasive isolates were either serotype 6(A or B) or serotype 23F. Four of the isolates were penicillin susceptible, and two (one from each treatment group) were penicillin and multiply antibiotic resistant. Adverse effects of the study drug were reported for three patients (nausea, vomiting, or both), one of whom was in the placebo group. Conclusion: Children with sickle cell anemia who have not had a prior severe pneumococcal infection or a splenectomy and are receiving comprehensive care may safely stop prophylactic penicillin therapy at 5 years of age. Parents must be aggressively counseled to seek medical attention for all febrile events in children with sickle cell anemia. (J P EDIATR 1995;127:685-90)

Bacteremia in children with sickle hemoglobin C disease and sickle beta +-thalassemia: Is prophylactic penicillin necessary?

Objective: To characterize the incidence of bacteremia and its potential for progression to septicemia in children with sickle hemoglobin C disease and sickle β +-thalassemia to assess the need for penicillin prophylaxis. Study design: Retrospective chart review of the frequency and natural history of bloodstream infection in such patients not receiving prophylactic penicillin therapy and followed up in a single institution. Results: During more than 842 patient-years of observation in 242 patients with sickle hemoglobin C disease, 15 episodes of bacteremia occurred in nine patients. Septicemia was fatal in one patient. The overall incidence of bacteremia, 1.8 events per 100 patient-years (95% confidence limits: 0.8, 2.8) in patients with sickle hemoglobin C disease, was similar to that in hematologically normal children. One episode of bacteremia occurred in a patient with sickle β +-thalassemia. Conclusions: The incidence of bacteremia is not increased in young patients with sickle hemoglobin C disease and sickle β +-thalassemia. Further, unlike its course in children with sickle cell anemia, it rarely evolves into life-threatening septicemia. This probably results from the maintenance of relatively intact splenic function during infancy and early childhood in patients with sickle hemoglobin C disease and sickle β +-thalassemia. Prophylactic penicillin therapy may not be required in these patients. (J P EDIATR 1995;127:348-54)

Fatal pneumococcal septicemia in hemoglobin SC disease

We retrospectively examined the medical and autopsy records of seven previously unpublished cases of fatal pneumococcal septicemia in children with hemoglobin SC disease. The earliest death occurred in a 1-year-old child who had congenital heart disease with cyanosis; the other children were aged 3 1/2 to 15 years. Only one child had received pneumococcal vaccine or prophylactic penicillin therapy. All seven children had an acute febrile illness and rapid clinical deterioration despite parenterally administered antibiotic therapy and intensive medical support. Erythrocyte pit counts in two patients were 40.3% and 41.7%, respectively (normal, < or = 3.6%). Autopsy data from five cases showed marked splenic congestion without infarction in five, splenomegaly in four, and bilateral adrenal hemorrhage in three. These cases illustrate that functional asplenia predisposes some children with hemoglobin SC disease to the development of fatal septicemia after the age of 3 years. We conclude that pneumococcal vaccine should be administered to all children with hemoglobin SC disease and that acute febrile illnesses should be investigated promptly for the possibility of septicemia. The routine use of prophylactic penicillin therapy in infants and children with hemoglobin SC disease remains controversial.

Newborn Screening for Sickle Cell Disease

Success of programs to screen newborns for sickle cell disease depends on timely follow-up. Education regarding fever and splenic palpation, and initiation of prophylactic penicillin therapy, will reduce morbidity and mortality and should occur prior to 4 months of age. However, contacting parents to permit implementation of care may be difficult, particularly in large urban populations; only nine (36%) of 25 infants recently identified as having sickle cell disease arrived at our institution for initial appointments. Medical providers must be aware of medical and legal obligations related to follow-up of newborns with sickle cell disease to prevent untoward events in "missed cases."

Outpatient management of febrile illness in infants and young chlidren with sickle cell anemia

Young children with sickle cell anemia remain at high risk of overwhelming bacterial infection despite the use of prophylactic penicillin therapy and pnuemococcal vaccine. Recognition of the potential for a fulminant course has led to the general recommendation that febrile illness in these children be promptly treated with parenterally administered antibiotics. 1-6 This approach has generally required hospitalization, because frequent intravenously administered doses are needed to maintain adequate blood levels of antibiotics for consistent effectiveness against the most common pathogens, Streptococcus pneumoniae and Haemophilus influenzae type b. We thought that a safe alternative to routine hospitalization may exist for selected patients: cephalosporins, which have a long half-life (allowing onceor twice-daily dosing), provide excellent coverage of the two common organisms. 7-9 For the past 5 years we have used a standardized protocol to guide the initial management of febrile children with sickle cell disease. This protocol mandates prompt evaluation by a physician, complete blood cell count and blood culture, and empiric intravenous administration of a long-acting antibiotic (usually ceftriaxone) before any test results are available or the patient's disposition has been determined. The purpose of this review was to assess the safety, efficacy, and cost-effectiveness of outpatient management according to this protocol.

Rarity of Failure of Penicillin Prophylaxis to Prevent Postsplenectomy Sepsis

All splenectomized individuals are at risk of developing pneumococcal sepsis, but most reports fail to mention how many patients are given prophylactic penicillin therapy. Fourteen reported cases of postsplenectomy bacterial sepsis in patients receiving prophylactic penicillin therapy are reviewed. In only five cases, the patients had penicillin-sensitive pneumococcal infection. Hence, the exact frequency of the failure of penicillin prophylaxis cannot be calculated, but it appears to be very rare. Continuous antibiotic prophylaxis used indefinitely and pneumococcal vaccine are both strongly recommended for all children and adults undergoing splenectomy.

Recurrent Bacterial Meningitis: Coronal Thin-Section Cranial Computed Tomography to Delineate Anatomic Defects

Three patients with histories of recurrent bacterial meningitis were previously examined with skull and sinus radiographs, routine cranial computed tomography, intrathecal radioisotope tracer studies, and immunologic evaluation. None of these studies were diagnostic. Pneumococcal vaccine and prophylactic penicillin therapy were ineffective in preventing recurrent episodes in two cases. Thin-section (2-mm) direct coronal computed cranial tomography demonstrated anatomic defects in all three patients. The use of metrizamide cisternography was not necessary to diagnose the defects. All patients had basiethmoidal encephaloceles which were repaired surgically. Direct coronal computed tomography offers a relatively easy noninvasive method for delineating anatomic abnormalities in patients with recurrent meningitis.

1167 RECURRENT BACTERIAL MENINGITIS

Seventeen patients with 2 or more episodes of meningitis and no clinically apparent anatomic defect have been referred during the previous 3 years. Predisposing abnormalities were demonstrated in 10 of these cases, 4 anatomic defects and 6 immune deficiencies. One had a fracture of the petrous bone, apparent on routine CT scan. Three other patients had previously been examined with skull and sinus radiographs, routine cranial computed tomography, intrathecal radioisotope tracer studies, and immunologic evaluation. δ11 of these studies were non-diagnostic. Pneumococcal vaccine and prophylactic penicillin therapy were ineffective in preventing recurrent episodes in two cases. We therefore employed a unique method for examining intracranial anatomy, i.e. thin section (2mm) coronal cranial computed tomography which demonstrated anatomic defects in all three patients. The use of metrizamide cisternography was not necessary to diagnose the defects., All had fronto-ethmoidal encephaloceles which were repaired surgically. Direct coronal computed tomography therefore offered a relatively easy noninvasive method for delineating anatomic abnormalities in these patients with recurrent meningitis. Six others had immunologic abnormalities, two with absent C2, one lacked C6, two had common variable hypogammaglobulinemia and one, transient hypogammaglobulinemia of infancy. The evaluation of recurrent meningitis should include Ig, CH100, and a CT scan, using coronal plane thin sections.

Postsplenectomy Infection

Partial splenectomy or repair should be considered as an alternative to total splenectomy whenever possible. All splenectomized patients should be vaccinated with pneumococcal vaccine. Use of the meningococcal vaccine should be considered. When a suitable Hemophilus influenzae B vaccine is available, it should be used. Certain patients should receive prophylactic penicillin therapy. Any flu-like illness after splenectomy should prompt the taking of cultures and treatment with an anti-pneumococcal anti-H. influenzae antibiotic.

Dangers of Splenectomy

To the Editor.— Juan F. Jaramillo, MD, and Leroy C. Barry, MD (243:1656, 1980), advocated repair for the traumatic spleen in agnogenic myeloid metaplasia because of the operative and some postoperative complications. However, they did not mention the real risk of grave and often fatal course of certain blood born infections, especially pneumococcemia, in patients who have undergone splenectomies. This risk apparently persists for the entire lifetime of the patients. 1 The preventive and prophylactic measures, such as immunization, autotransplantation, and long-term penicillin therapy, are under investigation, although these measures also have some inherent difficulties, such as patient compliance. It has been recently reported 2 that a patient who has undergone splenectomy and who discontinued prophylactic penicillin therapy for only two weeks died of pneumococcemia. Burrington 3 has reported successful repair of ruptured spleens in eight cases. In my opinion every spleen that has sustained traumatic injury deserves a serious

Candida Albicans Endocarditis

TO OUR knowledge only 37 cases ofCandida albicansendocarditis have so far been reported,1with only four survivals among them. The first diagnosis ofCandidaendocarditis before death was made in 1940.2 In the patient to be described in the present report,C albicanswas cultured from the blood during life, and she was still well eight months after treatment had been concluded. Report of a Case An 8-year-old Bantu girl was admitted to the Pretoria General Hospital on Oct 12, 1964, with a history of epistaxis for three days, and dyspnea on effort for a few months. About ten months earlier, she had been treated in the same hospital for Sydenham's chorea, and mitral stenosis and insufficiency had then been noted. After a ten-week period of hospitalization she was discharged, but failed to attend the outpatient department thereafter for observation and continuation of prophylactic penicillin therapy.