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Penicillin-resistant pneumococcal meningitis in an immunocompromised infant
506
Letters to the Editor
The Journal of Pediatrics September 1977
Table I. Operations in sickle h e m o g l o b i n o p a t t i i e s Cholecystectomy (two with common duct exploration) Hernias Splenectomy Tonsillectomy and adenidectomy _+ myringotomy Multiple dental extractions _+ infection Bronchoscopy-laryngoscopy Skin graft-chronic leg ulcer Ventricular peritoneal shunt and subsequent revision [6 Osteoid osteoma Reduction and intussusception and incidental appendectomy Spinal debridements and fusion Laparotomy to drain a b c e s s e s . , I patient Total operations
6 6 3 3 5
2 3 34
hyperthermia was critical. Children in his series were transfused to hemoglobin levels of 12 gm/dl prior to surgeryY Flye and Silver6 concurred and also stated that long periods of anesthesia could be well tolerated as long as the above factors were carefully controlled. Our experience demonstrates that children with sickle hemoglobinopathy can be operated on safely and that indicated elective surgical p)'ocedures should not be denied these children. Joseph S. Janik, M.D. Ruth Andrea Seeler, M.D. Division of Pediatric Hematology-Oncology Cook County Hospital 1825 W. Harrison St. Chicago, I L 60612 REFERENCES
temperature related to the procedure could increase erythrostasis, producing a vasoocclusive crisis and its consequent ischemic infarction? -~As recently as 1976, serial transfusions beginning 10 to 15 days before surgery or a two-volume exchange transfusion for urgent and emergent situations has been recommended for such children/Our ten-year experience showed that such conversion to hemoglobin A is not necessary for excellent results. Since July 1, 1967, 27 children (15 boys, 12 girls; three months to 18 years) with sickle hemoglobinopathy underwent 34 surgical procedures. Twenty-five had hemoglobin SS; one, S-thalassemia; one, hemoglobin SC. The children were transfused with 15 to 20 ml/kg hemoglobin A packed erythrocytes, rounding off to the nearest unit. Pretransfusion hematocrit values ranged from 10 to 30%; posttransfusion hematocrit values, 36 to 45%. Our goal was a hematocrit of 36%, including 15 hematocrit points of hemoglobin A. All transfusions were well tolerated. Two children were receiving chronic transfusion therapy (one with a leg ulcer and one with chronic staphylococcal vertebral osteomyelitis). Two children were admitted as emergencies and were taken to the operating room immediately upon completion of the transfusion. The operations are summarized in Table I. In the patients who received chronic transfusion therapy, hemoglobin S was 20.9% in the child with the leg ulcer, and under 25% in a child who had five operations for osteomyelitis. The posttransfusion hemoglobin S values in the other patients ranged from 23.1 to 60%. Preanesthetic medication included atropine, scopolamine, hypnotic drugs, tranquilizing agents, and/or narcotics. All children were managed interoperatively with nasal oxygen, assisted or controlled ventilation, and a variety of anesthetic agents; one had spinal anesthesia. Intravenous fluids were infused at one and one half times normal maintenance for the child's size. There was no unusual morbidity or mortality related to the sickle hemoglobinopathy, operation, or anesthesia. No child had a generalized postoperative "pain crisis." Wound healing and the time of discharge from the hospital were similar to normal children with the same operations. Holzmann and associates -~reviewed anesthetics in adults and children with sickle syndromes and concluded that the choice of anesthetic agent was not of particular importance, but the avoidance of hypoxia, acidosis, ,hypotension, hypovolemia, and
1. Spigelman A, and Warden M J: Surgery in patients with sickle cell disease, Arch Surg 104:761, 1972. 2. Holzmann L, Finn H, Lichtman HC, et al: Anesthesia in patients with sickle cell disease. A review of 112 cases, Anesth Analg 48:566, 1969. 3. Nadel JA, and Spivack AP: Surgical management of sickle cell anemia. The use of packed red blood cell transfusions, Ann Intern Med 48:399, 1958. 4. Burrington JD, and Smith MD: Elective and emergency surgery in children with sickle cell disease, Surg Clin North Am 56"55, 1976. 5. Ariyan S, Shessel FS, and Pickett LK: Cholecystitis and cholelithiasis masking as abdominal crisis in sickle cell disease, Pediatrics 58:252, 1976. 6. Flye MW, and Silver D: Biliary tract disorders and sickle cell disease, Surgery 72:361, 1972. 71 McPhillips FL, and Bickers JN: Operations in patients with sickle cell anemia at Charity Hospital in New Orleans, Surg Gynecol Obstet 135:870, 1972.
Penicillin-resistant pneumococcal meningitis in an immunocompromised infant Despite the fact that Streptococcus pneumoniae has been assumed to be universally susceptible to penicillin, Naraqi and associates 1 have described a patient with sickle cell anemia who developed penicillin-resistant pneumococcal meningitis. Our group ~ presented, in part, an immunocompromised infant who also had penicillin-resistant pneumococcal meningitis. Most recently Paredes and associates:' have described an immunologically normal child with penicillin-resistant pneumococcal meningitis, who was infected with a type 14 pneumococcus relatively resistant to penicillin G. This report describes an infant with pneumococcal meningitis Dr. at. J. Quilligan is career investigatorNIAID 5 K06 A1 20517-15.
Volume 91 Number 3
who failed to respond to massive intravenous administration of penicillin G and whose pneumococcus was subsequently shown to be insensitive to penicillin. Our patient had a splenectomy at ten months of age and he has since had a triad of hypergammaglobulinemia, leukocytosis, and an increased number of null cells. CASE REPORT Patient J. K., a 33-month-old Caucasian female, presented at 20 months of age after sudden onset of lethargy, vomiting, and fever to 105~ which progressed to vascular collapse over a onehour period. Because of culture-documented pneumococcemia three months previously, she had been maintained with monthly injections of 600,000 units of benzathine penicillin G; she received her last injection four days prior to the onset of this illness. She was begun on methicillin, 200 mg/kg/day, intravenously in four divided doses, after obtaining blood, nasopharyngeal, and spinal fluid (CSF) cultures. The initial white blood cell (WBC) count was 117,000 mm 3, with 50% neutrophils, 26% bands, and 20% lymphocytes. Platelets were 45,000/ram ~, and hemoglobin was 13.6 gm/dl. The cell count of the CSF was normal (two monocytes), as were the sugar and protein contents. There was no growth of organisms from the CSF culture. She appeared to improve, but on the second day her temperature was 103~ At this time, blood cultures were reported to be growing Streptococcuspneumoniae. The antibiotic was changed to intravenous aqueous sodium penicillin G, 500,000 units/kg/day, in four divided doses. The second CSF and blood culture specimens obtained 24 hours after initial treatment grew S. pneumoniae, the CSF sugar was 32 mg/dl; protein, 277 mg/dl. Slow clinical improvement continued until the sixth day of admission, when she again developed nuchal rigidity. Another lumbar puncture and blood culture were obtained. The CSF contained 28,000 neutrophils mm', 900 monocytes/mm :~, and numerous bacteria, which on Gram stain resembled S. pneumoniae. Spinal fluid sugar was 6 mg/dl; the protein, 100 mg/dt; S. pneumoniae was cultured from the spinal fluid and the blood. The dose of intravenous aqueous sodium penicillin G was increased to 1,000,000 units/kg/day in six divided doses, and chloramphenicol, 100 m g / k g / d a y in six divided doses, was added. Within 48 hours after beginning this combined therapy, repeat CSF and blood cultures showed no growth. She had gradual resolution of symptoms over the next ten days. Anderson's ~ tube dilution sensitivities of the pneumococcus (type 6A) grown from blood and CSF, obtained on the sixth hospital day, a time when there was clinical evidence of a relapse despite penicillin therapy, revealed a minimal inhibitory concentration and minimal bactericidal concentration of sodium penicillin G of 0.39 #/ml. This represents about a 15-fold increase in resistance as reported in the literature? Penicillin resistance was reconfirmed by two independent laboratories. Resistance was also recorded to methicillin. The reason for this patient's persistent hypergammaglobulinemia, leukocytosis, and increased susceptibility to infection is under investigation and will be the subject of another report. CONCLUSION It is recommended that sensitivity studies of a pneumococcus be instituted in any patient (particularly one with an impaired immune apparatus) who is not responding to adequate doses of penicillin. Re-examination of the status of resistant vs relatively
Letters to the Editor
507
resistant bacteria seems to be in order. In addition it would seem appropriate to continue to periodically re-examine sensitivities of pneumococci to penicillin in various areas throughout the country, as has been previously suggested by a number of authors. We thank Dr. Robert Austrian of the University of Pennsylvania, the National Center for Disease Control, and the State of California Laboratories, for typing and measuring resistance to the organism in this study. John V~ Mace, M.D. Professor of Pediatrics D. Scott Janik, M.D. Ronald L. Sauer, M.S., S.M. J. J. Quilligan, Jr., M.D. Research Professor of Pediatrics Department of Pediatrics Loma Linda University Medical Center Loma Linda, CA 92354 REFERENCES 1. Naraqi S, Kirkpatrick GP, and Kabins S: Relapsing pneumococcal meningitis: Isolation of an organism with decreased susceptibility to penicillin G, J PEDIATR 85:671, 1974. 2. Janik DS, Mace JW, Sauer RL, and Quilligan JJ Jr: Penicillin resistant pneumococcal meningitis in an immunocompromised infant, Clin Res 24-184A, 1976 (abstr). 3. Paredes A, Taber LH, Yow MD, Clark D, and Nathan W: Prolonged pneumococcal meningitis due to an organism with increased resistance to penicillin, Pediatrics 58"378, 1976. 4. Anderson TB: Testing of susceptibility to antimicrobial agents and assay of antimicrobial agents in body fluids, Blair JE, et al, editors: in Manual of clinical microbiology. Bethesda, Md., 1970, American Society for Microbiologists. 5. Kislak JW, Razavi LMB, Daly AK, and Finland M: Susceptibility of 9 pneumococci to antibiotics, Am J Med Sci 250:261, 1965.
Preleukemic phase in childhood acute lymphoblastic leukemia A diagnosis of acute lymphoblastic leukemia (ALL) is easily established when in addition to the characteristic signs and symptoms, the marrow aspirate reveals almost complete replacement of the normal hematopoietic elements by lymphoblasts. This report describes a child with preleukemia who presented with recurrent anemia and neutropenia for a seven-month period prior to the development of ALL. CASE REPORT A 16-month-old white boy was admitted to Keesler Air Force Base Medical Center on 12/1/74 for treatment of an abscess. Physical findings were limited to a temperature of 39~ and a swollen erythematous right index finger. Although he was anemic and neutropenic (Table I), bone marrow findings (Table II) were not diagnostic. Culture of the abscess grew Staphylococcus
Letters to the Editor
The Journal of Pediatrics September 1977
Table I. Operations in sickle h e m o g l o b i n o p a t t i i e s Cholecystectomy (two with common duct exploration) Hernias Splenectomy Tonsillectomy and adenidectomy _+ myringotomy Multiple dental extractions _+ infection Bronchoscopy-laryngoscopy Skin graft-chronic leg ulcer Ventricular peritoneal shunt and subsequent revision [6 Osteoid osteoma Reduction and intussusception and incidental appendectomy Spinal debridements and fusion Laparotomy to drain a b c e s s e s . , I patient Total operations
6 6 3 3 5
2 3 34
hyperthermia was critical. Children in his series were transfused to hemoglobin levels of 12 gm/dl prior to surgeryY Flye and Silver6 concurred and also stated that long periods of anesthesia could be well tolerated as long as the above factors were carefully controlled. Our experience demonstrates that children with sickle hemoglobinopathy can be operated on safely and that indicated elective surgical p)'ocedures should not be denied these children. Joseph S. Janik, M.D. Ruth Andrea Seeler, M.D. Division of Pediatric Hematology-Oncology Cook County Hospital 1825 W. Harrison St. Chicago, I L 60612 REFERENCES
temperature related to the procedure could increase erythrostasis, producing a vasoocclusive crisis and its consequent ischemic infarction? -~As recently as 1976, serial transfusions beginning 10 to 15 days before surgery or a two-volume exchange transfusion for urgent and emergent situations has been recommended for such children/Our ten-year experience showed that such conversion to hemoglobin A is not necessary for excellent results. Since July 1, 1967, 27 children (15 boys, 12 girls; three months to 18 years) with sickle hemoglobinopathy underwent 34 surgical procedures. Twenty-five had hemoglobin SS; one, S-thalassemia; one, hemoglobin SC. The children were transfused with 15 to 20 ml/kg hemoglobin A packed erythrocytes, rounding off to the nearest unit. Pretransfusion hematocrit values ranged from 10 to 30%; posttransfusion hematocrit values, 36 to 45%. Our goal was a hematocrit of 36%, including 15 hematocrit points of hemoglobin A. All transfusions were well tolerated. Two children were receiving chronic transfusion therapy (one with a leg ulcer and one with chronic staphylococcal vertebral osteomyelitis). Two children were admitted as emergencies and were taken to the operating room immediately upon completion of the transfusion. The operations are summarized in Table I. In the patients who received chronic transfusion therapy, hemoglobin S was 20.9% in the child with the leg ulcer, and under 25% in a child who had five operations for osteomyelitis. The posttransfusion hemoglobin S values in the other patients ranged from 23.1 to 60%. Preanesthetic medication included atropine, scopolamine, hypnotic drugs, tranquilizing agents, and/or narcotics. All children were managed interoperatively with nasal oxygen, assisted or controlled ventilation, and a variety of anesthetic agents; one had spinal anesthesia. Intravenous fluids were infused at one and one half times normal maintenance for the child's size. There was no unusual morbidity or mortality related to the sickle hemoglobinopathy, operation, or anesthesia. No child had a generalized postoperative "pain crisis." Wound healing and the time of discharge from the hospital were similar to normal children with the same operations. Holzmann and associates -~reviewed anesthetics in adults and children with sickle syndromes and concluded that the choice of anesthetic agent was not of particular importance, but the avoidance of hypoxia, acidosis, ,hypotension, hypovolemia, and
1. Spigelman A, and Warden M J: Surgery in patients with sickle cell disease, Arch Surg 104:761, 1972. 2. Holzmann L, Finn H, Lichtman HC, et al: Anesthesia in patients with sickle cell disease. A review of 112 cases, Anesth Analg 48:566, 1969. 3. Nadel JA, and Spivack AP: Surgical management of sickle cell anemia. The use of packed red blood cell transfusions, Ann Intern Med 48:399, 1958. 4. Burrington JD, and Smith MD: Elective and emergency surgery in children with sickle cell disease, Surg Clin North Am 56"55, 1976. 5. Ariyan S, Shessel FS, and Pickett LK: Cholecystitis and cholelithiasis masking as abdominal crisis in sickle cell disease, Pediatrics 58:252, 1976. 6. Flye MW, and Silver D: Biliary tract disorders and sickle cell disease, Surgery 72:361, 1972. 71 McPhillips FL, and Bickers JN: Operations in patients with sickle cell anemia at Charity Hospital in New Orleans, Surg Gynecol Obstet 135:870, 1972.
Penicillin-resistant pneumococcal meningitis in an immunocompromised infant Despite the fact that Streptococcus pneumoniae has been assumed to be universally susceptible to penicillin, Naraqi and associates 1 have described a patient with sickle cell anemia who developed penicillin-resistant pneumococcal meningitis. Our group ~ presented, in part, an immunocompromised infant who also had penicillin-resistant pneumococcal meningitis. Most recently Paredes and associates:' have described an immunologically normal child with penicillin-resistant pneumococcal meningitis, who was infected with a type 14 pneumococcus relatively resistant to penicillin G. This report describes an infant with pneumococcal meningitis Dr. at. J. Quilligan is career investigatorNIAID 5 K06 A1 20517-15.
Volume 91 Number 3
who failed to respond to massive intravenous administration of penicillin G and whose pneumococcus was subsequently shown to be insensitive to penicillin. Our patient had a splenectomy at ten months of age and he has since had a triad of hypergammaglobulinemia, leukocytosis, and an increased number of null cells. CASE REPORT Patient J. K., a 33-month-old Caucasian female, presented at 20 months of age after sudden onset of lethargy, vomiting, and fever to 105~ which progressed to vascular collapse over a onehour period. Because of culture-documented pneumococcemia three months previously, she had been maintained with monthly injections of 600,000 units of benzathine penicillin G; she received her last injection four days prior to the onset of this illness. She was begun on methicillin, 200 mg/kg/day, intravenously in four divided doses, after obtaining blood, nasopharyngeal, and spinal fluid (CSF) cultures. The initial white blood cell (WBC) count was 117,000 mm 3, with 50% neutrophils, 26% bands, and 20% lymphocytes. Platelets were 45,000/ram ~, and hemoglobin was 13.6 gm/dl. The cell count of the CSF was normal (two monocytes), as were the sugar and protein contents. There was no growth of organisms from the CSF culture. She appeared to improve, but on the second day her temperature was 103~ At this time, blood cultures were reported to be growing Streptococcuspneumoniae. The antibiotic was changed to intravenous aqueous sodium penicillin G, 500,000 units/kg/day, in four divided doses. The second CSF and blood culture specimens obtained 24 hours after initial treatment grew S. pneumoniae, the CSF sugar was 32 mg/dl; protein, 277 mg/dl. Slow clinical improvement continued until the sixth day of admission, when she again developed nuchal rigidity. Another lumbar puncture and blood culture were obtained. The CSF contained 28,000 neutrophils mm', 900 monocytes/mm :~, and numerous bacteria, which on Gram stain resembled S. pneumoniae. Spinal fluid sugar was 6 mg/dl; the protein, 100 mg/dt; S. pneumoniae was cultured from the spinal fluid and the blood. The dose of intravenous aqueous sodium penicillin G was increased to 1,000,000 units/kg/day in six divided doses, and chloramphenicol, 100 m g / k g / d a y in six divided doses, was added. Within 48 hours after beginning this combined therapy, repeat CSF and blood cultures showed no growth. She had gradual resolution of symptoms over the next ten days. Anderson's ~ tube dilution sensitivities of the pneumococcus (type 6A) grown from blood and CSF, obtained on the sixth hospital day, a time when there was clinical evidence of a relapse despite penicillin therapy, revealed a minimal inhibitory concentration and minimal bactericidal concentration of sodium penicillin G of 0.39 #/ml. This represents about a 15-fold increase in resistance as reported in the literature? Penicillin resistance was reconfirmed by two independent laboratories. Resistance was also recorded to methicillin. The reason for this patient's persistent hypergammaglobulinemia, leukocytosis, and increased susceptibility to infection is under investigation and will be the subject of another report. CONCLUSION It is recommended that sensitivity studies of a pneumococcus be instituted in any patient (particularly one with an impaired immune apparatus) who is not responding to adequate doses of penicillin. Re-examination of the status of resistant vs relatively
Letters to the Editor
507
resistant bacteria seems to be in order. In addition it would seem appropriate to continue to periodically re-examine sensitivities of pneumococci to penicillin in various areas throughout the country, as has been previously suggested by a number of authors. We thank Dr. Robert Austrian of the University of Pennsylvania, the National Center for Disease Control, and the State of California Laboratories, for typing and measuring resistance to the organism in this study. John V~ Mace, M.D. Professor of Pediatrics D. Scott Janik, M.D. Ronald L. Sauer, M.S., S.M. J. J. Quilligan, Jr., M.D. Research Professor of Pediatrics Department of Pediatrics Loma Linda University Medical Center Loma Linda, CA 92354 REFERENCES 1. Naraqi S, Kirkpatrick GP, and Kabins S: Relapsing pneumococcal meningitis: Isolation of an organism with decreased susceptibility to penicillin G, J PEDIATR 85:671, 1974. 2. Janik DS, Mace JW, Sauer RL, and Quilligan JJ Jr: Penicillin resistant pneumococcal meningitis in an immunocompromised infant, Clin Res 24-184A, 1976 (abstr). 3. Paredes A, Taber LH, Yow MD, Clark D, and Nathan W: Prolonged pneumococcal meningitis due to an organism with increased resistance to penicillin, Pediatrics 58"378, 1976. 4. Anderson TB: Testing of susceptibility to antimicrobial agents and assay of antimicrobial agents in body fluids, Blair JE, et al, editors: in Manual of clinical microbiology. Bethesda, Md., 1970, American Society for Microbiologists. 5. Kislak JW, Razavi LMB, Daly AK, and Finland M: Susceptibility of 9 pneumococci to antibiotics, Am J Med Sci 250:261, 1965.
Preleukemic phase in childhood acute lymphoblastic leukemia A diagnosis of acute lymphoblastic leukemia (ALL) is easily established when in addition to the characteristic signs and symptoms, the marrow aspirate reveals almost complete replacement of the normal hematopoietic elements by lymphoblasts. This report describes a child with preleukemia who presented with recurrent anemia and neutropenia for a seven-month period prior to the development of ALL. CASE REPORT A 16-month-old white boy was admitted to Keesler Air Force Base Medical Center on 12/1/74 for treatment of an abscess. Physical findings were limited to a temperature of 39~ and a swollen erythematous right index finger. Although he was anemic and neutropenic (Table I), bone marrow findings (Table II) were not diagnostic. Culture of the abscess grew Staphylococcus