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Treatment of Haemophilus influenzae type b meningitis in children with cerebrospinal fluid shunts
424
The Journal of Pediatrics September 1980
Brief cfinical and laboratory observations
opments in antimicrobial agent susceptibility testing, Cumitech 6(American Society for Microbiology) 1, 1978. 9. Delage G, DeClerck Y, Lescop J, Dery P, and Shareck F: Hemophilus influenzae type b infections: Recurrent disease due to ampicillin-resistant strains. J PEDIATR90:319, 1977. 10. Albritton WL, Hammond G, Hoban S, and Ronald AR: Ampicillin-resistant H. influenzae subdural empyema following successful treatment of apparently ampicillin-sensitive H. Influenzae meningitis, J PEDIATR90:320, 1977. 11. Azimi PH, and Cole KE: Ampicillin-resistant Haemophilus
influenzae meningitis following an ampicillin-sensitive bacteremia in an infant, Am J Dis Child 131:812, 1977. 12. Van Klingeren B, van Embden JDA, and Dessens-Kroon M: Plasmid-mediated chloramphenicol resistance in Haemophilus influenzae, Antimicrob Agents Chemother 11;383, 1977. 13. Bryan LE: Transferable chloramphenicol and ampicillin resistance in a strain of Haemophilus influenzae, Antimicrob Agents Chemother 14:154, 1978.
Treatment of Haemophilus influenzae type b meningitis in children with cerebrospinal fluid shunts Margaret B. Rennels, M.D.,* and Ellen R. Wald, M.D., Baltimore, Md.
BACTERIAL INFECTIONS of the central nervous system in children with cerebrospinal fluid shunts are a serious and c o m m o n problem. Staphylococci are the most frequent etiologic agents in shunt-associated infections. 1-~ There is general agreement that parenteral antibiotic therapy alone is unsatisfactory in eradicating these infections 1, 2, 5-8; removal of the entire shunt is usually recommended?, ~, ~-7 This paper reports the treatment of Haemophilus influenzae type b meningitis, without shunt removal, in four children with CSF shunts.
METHODS Patients. Beginning in 1971, every admission to the pediatric wards of the University of Maryland Hospital has been documented in a "ward book." All admissions from July, 1971, through July, 1978, were reviewed to determine: (1) the n u m b e r of children admitted with CSF shunts or for shunting procedure, and (2) the number of children with CSF shunts who developed H. influenzae meningitis. This information was supplemented by referral to the medical charts of the infected patients. The investigators personally examined these patients. Bacteriology. Primary isolation, speciation, and serotyping of all organisms were performed by standard methods as described in the Manual o f Clinical Microbiology, second edition, American Society for Microbiology,
From the Departments of Pediatrics and Internal Medicine, University of Maryland School of Medicine. Supported in part by a Bristol Fellowship in Infectious Diseases (M.B.R.). *Reprint address: Department of Pediatrics, Room 5-12~1C, University of Maryland Hospital, 22 South Greene St., , Baltimore, MD 21201.
1974. All of the organisms were identified as H. influenzae type b. RESULTS Fifty-seven children were admitted with C S F shunts or for a shunting procedure over the seven years studied; 33 of these children were less than 6 years of age. Between August, 1974, and April, i977, four of these 33 younger children were hospitalized with H. influenzae meningitis. Abbreviations used CNS: central nervous system CSF: cerebrospinal fluid WBC: white blood cells P: polymorphonuclear cells B: band cells L: lymphocytes M: mononuclear cells RBC: red blood cells LP: lumbar puncture CASE R E P O R T S
Patient 1 developed communicating hydrocephalus secondary to histiocytosis X at age 4 years. A lumbar-peritoneal shunt was placed. Nine months later she presented with nasal discharge, cough, headache, abdominal pain, and fever (39.4~ At that time she was receiving 10 mg of methotrexate twice weekly. Physical examination revealed an irritable but alert child. Meningeal signs were absent. Peripheral white blood cell count was 3,000/ram ~ (14% polymorphonuclear leukocytes, 36% band forms, 31% lymphocytes, 19% mononuclear cells); platelet estimate was normal and hemoglobin was 13.4 gm/dl. Lumbar CSF contained 450 red blood cells/mm 3, 4,450 WBC/mm ~(88% P, 1% L, 11% M), glucose concentration 66 mg/dl (peripheral glucose
0022-3476/80/090424+03500.30/0 9 1980 The C. V. Mosby Co.
Volume 97 Number 3 127 mg/dl), and a 2 + Pandy test. Gram stain revealed small, pleomorphic, gram-negative rods. She was treated with chloramphenicol (100 mg/kg/day) and aqueous penicillin G (200,000 U/kg/day) intravenously. H. influenzae was recovered from CSF and blood cultures. Penicillin therapy was discontinued. Clinical improvement was prompt. Repeat lumbar puncture after three days of therapy was sterile. Chloramphenicol (100 mg/kg/day orally) was prescribed to complete a 10-day course. Through two years of follow-up her shunt has continued to function and there has been no recurrence of infection. Psychological testing has not been performed; however, based on informal assessments, she appears to be developing normally. Patient 2 received bilateral ventriculoperitoneal shunts at one month of age because of an enlarging porencephalic cyst and hydrocephalus. He had a seizure disorder. At 30 months of age he was admitted in severe status epilepticus following three days of nasal discharge, cough, and high fever. On physical examination he was stuporous and hypotonic; temperature was 41.5~ Lumbar CSF contained eight WBC, all mononuclear. The Gram stain and cultures were negative for organisms. Chest radiograph revealed a right upper lobe infiltrate. He was treated for pneumonia with ampicillin (100 mg/kg/day iv the first day and 300 mg/kg the second day). Two days after admission his initial blood culture grew H. influenzae, sensitive to ampicillin and chloramphenicol. Because he had not regained full consciousness, a second LP was performed. There were 1,550 WBC/mm ~ (87% P, 13% M); protein concentration was 275 mg/dl, and glucose 83 mg/dl (peripheral glucose 141 mg/dl). A Gram stain and culture again were negative for organisms. Ampicillin therapy was discontinued and chloramphenicol (100 mg/kg/day iv) was given for 16 days. Forty-eight hours after termination of therapy, the lumbar CSF contained 35 WBC (2 P, 31 L, 2 M), protein concentration was 70 mg/dl, and glucose 70 mg/dl (peripheral glucose 130 mg/dl); CSF obtained from the shunt revealed two WBC/mm ~ (2 M), glucose concentration 71 mg/dl, and protein 27 mg/dl. Cultures were negative. His shunt continued to function throughout this hospitalization. At follow-up he is severely spastic and unable to perform any voluntary action, Patient 3 was the 1.4 kg product of a 34-week gestation; she developed Escheriehia eoli meningitis while in the nursery. At 45 days of age she was diagnosed as having communicating hydrocephalus and a ventriculoperitoneal shunt was placed. Two weeks later she developed a coagulase-negative staphylococcal shunt infection which necessitated complete shunt removal and delayed replacement, in addition to parenteral antibiotic therapy, for eradication of the infection. At 12 months of age she was brought to the emergency room because of fever, irritability, and vomiting. She was lethargic and hypotonic and had a tense fontanel, bilateral otitis media, and a purulent nasal discharge. Nuchal rigidity and the Brudzinski sign were present. Her shunt was functioning; it was tapped, yielding CSF which contained 90,000 RBC/mm 3, 3,200 WBC/mm ~ (79% P, 21% L), and a 3 + Pandy test. Gram stain revealed Gram negative, pleomorphic rods. Intravenous aqueous penicillin G
Brief clinical and laboratory observations
4 25
(300,000 U/kg/day), chloramphenicol (100 mg/kg/day), phenobarbital, and methylprednisolone were begun. H. influenzae was cultured from the CSF. Penicillin was discontinued and chloramphenicol was given for two weeks. A repeat shunt tap 36 hours after antibiotic treatment was stopped had 1 WBC/mm~; the culture was negative. She has been followed for three years without recurrence of infection; her shunt continues to function. Her development appears to be normal as judged by repeated Denver Developmental Screening Tests and neurological examinations. Patient 4 was a premature infant who developedhydrocephalus and received a ventriculoatrial shunt at 3 months of age. Five weeks later she was brought to the Pediatric Clinic in shock. Lumbar CSF contained WBC 12,500/mm 3 (97% P, 3% L), no detectable glucose (blood glucose concentration was 75 mg/dl), and protein 67 mg/dl. In spite of immediate, high intravenous doses of ampicillin, chloramphenicol, and dexamethasone she had a cardiopulmonary arrest and died within a few hours of admission. Hi influenzae was cultured from the nasopharynx, blood, and CSF. DISCUSSION Eradication o f shunt-associated infection is usually difficult. Failure is c o m m o n with p a r e n t e r a l antibiotic therapy alone or with incomplete s h u n t removal. 1, 2, ~ 8 M c L a u r i n 9 has reported a 58% cure r a t e in patients treated with systemic plus i n t r a v e n t r i c u l a r a d m i n i s t r a t i o n of antibiotics; h e advocates this a p p r o a c h for initial treatment. O t h e r investigators r e c o m m e n d complete s h u n t removal in addition to antibiotics as initial therapy, followed b y either i m m e d i a t e or delayed r e p l a c e m e n t of the shunt?. 2.... These r e c o m m e n d a t i o n s are based judiciously o n the general experience with shunt-associated infections, but infections with H. influenzae m a y be exceptions. In addition to our four patients, there are reports of five children with C S F shunts who have developed H. (nfluenzae CNS infection. Sells et al 6 reported two patients with H. influenzae shunt-associated infection. One was successfully treated with systemic antibiotics alone a n d the other recovered following incomplete s h u n t r e m o v a l a n d parenteral antibiotic therapy. In their series o f 20 patients with shunt-associated infections, this was the only organism which could be eradicated without complete s h u n t removal. The three other r e p o r t e d cases of H. influenzae infections were successfully treated with parenteral therapy alone2 . . . . . . In three of o u r four patients the infection was eradicated p r o m p t l y with i n t r a v e n o u s use o f antibiotics. T h e fourth child was in septic shock on admission a n d died within a few hours. If that child is excluded, seven of eight children infected with H. influenzae h a v e b e e n successfully treated with s y s t e m i c antibiotic therapy alone. This
426
Brief cfinical and laboratory observations
result is in direct contrast to the usual failure o f this form of therapy for shunt-associated CNS infections. To our knowledge the only statement in the literature suggesting that shunt removal may not be necessary when H. influenzae is the infecting organism is that of Sells et al, 6 "The preferred treatment for gram-negative shuntassociated infections, with the possible exception of H. influenzae, appears to be systemic and intraventricular antibiotics and complete shunt removal or replacement of the shunt in a new site." Our experience supports their comment. We recommend that patients with H. influenzae CNS infection be managed initially with parenteral antibiotics alone. Shunt removal appears to be unnecessary. The authors express their appreciation to Mrs. Linda M. Gilbert for her cheerful and patient assistance in preparation of this manuscript and Merrill J. Snyder, Ph.D., and Stephen C. Schimpff, M.D., for their critical reviews of the manuscript. REFERENCES
I.
Luthardt T: Bacterial infections in ventriculo-auricular shunt systems, Dev Med Child Neurol 12(Suppl 22):105, 1970. 2. Morrice JJ, and Young DG: Bacterial colonization of Holter
The Journal of Pediatrics September 1980
3.
4.~
5.
6.
7.
8.
9.
10.
11.
valves: A ten-year survey, Dev Med Child Neurol 16(Suppl 32):85, 1974. Bayst0n R, and Lari J: A study of the sources of infection in colonized shunts, Dev Med Child Neurol 16(Suppl 32): 16, 1974. Myers MG, and Schoenbaum SC: Shunt fluid aspiration: An adjunct in the diagnosis of cerebrospinal fluid shunt infection, Am J Dis Child 129:220, 1975. Schoenbaum SC, Gardner P, and Shillito J: Infections of cerebrospinal fluid shunts: Epidemiology, clinical manifestations and therapy, J Infect Dis 131:543, 1975. Sells CJ, Shurtleff DB, and Loeser JD: Gram negative cerebrospinal fluid shunt-associated infections, Pediatrics 59:614, 1977. Nicholas JL, Kamal IM, and Eckstein HB: Immediate'shunt replacement in the treatment of bacterial colonization of Holter valves, Dev Med Child Neurol 12(Suppl 22):110, 1970. Shurtleff DB, Foltz EL, Weeks RD, and Loeser J: Therapy of Staphylococcus epidermidis: Infections associated with cerebrospinal fluid shunts, Pediatrics 53:55, 1974. McLaurin RL: Treatment of infected ventricular shunts, Child's Brain 1:306, 1975. Shurtleff DB, Christie D, and Foltz EL: Ventriculoauriculostomy-associated infection: A 12 year study, J Neurosurg 35:686, 1971. Schoenbaum SC: Personal communication.
Blocking coagulation inhibitors in children taking penicillin Donald J. Orris, M.D., Jessica H. Lewis, M.D., Joel A. Spero, M.D., and
Ute Hasiba, M.D., Pittsburgh, Pa.
A C Q U I R E D INHIBIT'ORS 1 of blood coagulation fall into two major categories: blocking inhibitors and specific factor depressants. The former are usually proteins, ~ but not necessarily antibodies, which interfere with an entire coagulation reaction and are rarely, if ever, associated with clinical bleeding. These are found in some patients with systemic lupus erythematosus (lupus inhibitors), other collagen vascular diseases or malignancies, or following exposure to certain drugs. The clotting pathway which appears to be the most frequently interfered with is the intrinsic clotting system which is monitored via the activated partial thromboplastin time. In the presence of this type of inhibitor, all clotting factors may assay normally. Specific factor depressants, on the other hand, neutral-
From the Central Blood Bank of Pittsburgh and thet Department of Medicine, University of Pittsburgh. Reprint address: Coagulation Labo~.utory,CentralBlood Bank of Pittsburgh, 812 Fifth Ave., PittsbuFgh,PA 15219.
ize or inactivate a single clotting factor. Inhibitors specifically directed against Factors V, VIII, IX, XI, and XIII have been described?, ~ Factor VIII inhibitors are the most common. These specific factor depressants appear to be antibodies, frequently cause severe bleeding, and may Abbreviation used APTT: activated partial thromboplastin time occur in various a u t o i m m u n e disorders, especially rheumatoid arthritis, certain skin disorders such as pemphigus and psoriasis, in patients with drug hypersensitivity to penicillin, in postpartum women, and also in apparently previously healthy individuals. Such inhibitors arise in about 10% of patients with hemophilia as an immune reaction to factor therapy. This study presents coagulation data on 13 children evaluated in this laboratory for abnormal APTTs. Each was receiving either penicillin or a derivative, and in each case a blocking-type inhibitor was demonstrated.
0022-3476/80/090426+04500.40/0 9 1980 The C. V. Mosby Co.
The Journal of Pediatrics September 1980
Brief cfinical and laboratory observations
opments in antimicrobial agent susceptibility testing, Cumitech 6(American Society for Microbiology) 1, 1978. 9. Delage G, DeClerck Y, Lescop J, Dery P, and Shareck F: Hemophilus influenzae type b infections: Recurrent disease due to ampicillin-resistant strains. J PEDIATR90:319, 1977. 10. Albritton WL, Hammond G, Hoban S, and Ronald AR: Ampicillin-resistant H. influenzae subdural empyema following successful treatment of apparently ampicillin-sensitive H. Influenzae meningitis, J PEDIATR90:320, 1977. 11. Azimi PH, and Cole KE: Ampicillin-resistant Haemophilus
influenzae meningitis following an ampicillin-sensitive bacteremia in an infant, Am J Dis Child 131:812, 1977. 12. Van Klingeren B, van Embden JDA, and Dessens-Kroon M: Plasmid-mediated chloramphenicol resistance in Haemophilus influenzae, Antimicrob Agents Chemother 11;383, 1977. 13. Bryan LE: Transferable chloramphenicol and ampicillin resistance in a strain of Haemophilus influenzae, Antimicrob Agents Chemother 14:154, 1978.
Treatment of Haemophilus influenzae type b meningitis in children with cerebrospinal fluid shunts Margaret B. Rennels, M.D.,* and Ellen R. Wald, M.D., Baltimore, Md.
BACTERIAL INFECTIONS of the central nervous system in children with cerebrospinal fluid shunts are a serious and c o m m o n problem. Staphylococci are the most frequent etiologic agents in shunt-associated infections. 1-~ There is general agreement that parenteral antibiotic therapy alone is unsatisfactory in eradicating these infections 1, 2, 5-8; removal of the entire shunt is usually recommended?, ~, ~-7 This paper reports the treatment of Haemophilus influenzae type b meningitis, without shunt removal, in four children with CSF shunts.
METHODS Patients. Beginning in 1971, every admission to the pediatric wards of the University of Maryland Hospital has been documented in a "ward book." All admissions from July, 1971, through July, 1978, were reviewed to determine: (1) the n u m b e r of children admitted with CSF shunts or for shunting procedure, and (2) the number of children with CSF shunts who developed H. influenzae meningitis. This information was supplemented by referral to the medical charts of the infected patients. The investigators personally examined these patients. Bacteriology. Primary isolation, speciation, and serotyping of all organisms were performed by standard methods as described in the Manual o f Clinical Microbiology, second edition, American Society for Microbiology,
From the Departments of Pediatrics and Internal Medicine, University of Maryland School of Medicine. Supported in part by a Bristol Fellowship in Infectious Diseases (M.B.R.). *Reprint address: Department of Pediatrics, Room 5-12~1C, University of Maryland Hospital, 22 South Greene St., , Baltimore, MD 21201.
1974. All of the organisms were identified as H. influenzae type b. RESULTS Fifty-seven children were admitted with C S F shunts or for a shunting procedure over the seven years studied; 33 of these children were less than 6 years of age. Between August, 1974, and April, i977, four of these 33 younger children were hospitalized with H. influenzae meningitis. Abbreviations used CNS: central nervous system CSF: cerebrospinal fluid WBC: white blood cells P: polymorphonuclear cells B: band cells L: lymphocytes M: mononuclear cells RBC: red blood cells LP: lumbar puncture CASE R E P O R T S
Patient 1 developed communicating hydrocephalus secondary to histiocytosis X at age 4 years. A lumbar-peritoneal shunt was placed. Nine months later she presented with nasal discharge, cough, headache, abdominal pain, and fever (39.4~ At that time she was receiving 10 mg of methotrexate twice weekly. Physical examination revealed an irritable but alert child. Meningeal signs were absent. Peripheral white blood cell count was 3,000/ram ~ (14% polymorphonuclear leukocytes, 36% band forms, 31% lymphocytes, 19% mononuclear cells); platelet estimate was normal and hemoglobin was 13.4 gm/dl. Lumbar CSF contained 450 red blood cells/mm 3, 4,450 WBC/mm ~(88% P, 1% L, 11% M), glucose concentration 66 mg/dl (peripheral glucose
0022-3476/80/090424+03500.30/0 9 1980 The C. V. Mosby Co.
Volume 97 Number 3 127 mg/dl), and a 2 + Pandy test. Gram stain revealed small, pleomorphic, gram-negative rods. She was treated with chloramphenicol (100 mg/kg/day) and aqueous penicillin G (200,000 U/kg/day) intravenously. H. influenzae was recovered from CSF and blood cultures. Penicillin therapy was discontinued. Clinical improvement was prompt. Repeat lumbar puncture after three days of therapy was sterile. Chloramphenicol (100 mg/kg/day orally) was prescribed to complete a 10-day course. Through two years of follow-up her shunt has continued to function and there has been no recurrence of infection. Psychological testing has not been performed; however, based on informal assessments, she appears to be developing normally. Patient 2 received bilateral ventriculoperitoneal shunts at one month of age because of an enlarging porencephalic cyst and hydrocephalus. He had a seizure disorder. At 30 months of age he was admitted in severe status epilepticus following three days of nasal discharge, cough, and high fever. On physical examination he was stuporous and hypotonic; temperature was 41.5~ Lumbar CSF contained eight WBC, all mononuclear. The Gram stain and cultures were negative for organisms. Chest radiograph revealed a right upper lobe infiltrate. He was treated for pneumonia with ampicillin (100 mg/kg/day iv the first day and 300 mg/kg the second day). Two days after admission his initial blood culture grew H. influenzae, sensitive to ampicillin and chloramphenicol. Because he had not regained full consciousness, a second LP was performed. There were 1,550 WBC/mm ~ (87% P, 13% M); protein concentration was 275 mg/dl, and glucose 83 mg/dl (peripheral glucose 141 mg/dl). A Gram stain and culture again were negative for organisms. Ampicillin therapy was discontinued and chloramphenicol (100 mg/kg/day iv) was given for 16 days. Forty-eight hours after termination of therapy, the lumbar CSF contained 35 WBC (2 P, 31 L, 2 M), protein concentration was 70 mg/dl, and glucose 70 mg/dl (peripheral glucose 130 mg/dl); CSF obtained from the shunt revealed two WBC/mm ~ (2 M), glucose concentration 71 mg/dl, and protein 27 mg/dl. Cultures were negative. His shunt continued to function throughout this hospitalization. At follow-up he is severely spastic and unable to perform any voluntary action, Patient 3 was the 1.4 kg product of a 34-week gestation; she developed Escheriehia eoli meningitis while in the nursery. At 45 days of age she was diagnosed as having communicating hydrocephalus and a ventriculoperitoneal shunt was placed. Two weeks later she developed a coagulase-negative staphylococcal shunt infection which necessitated complete shunt removal and delayed replacement, in addition to parenteral antibiotic therapy, for eradication of the infection. At 12 months of age she was brought to the emergency room because of fever, irritability, and vomiting. She was lethargic and hypotonic and had a tense fontanel, bilateral otitis media, and a purulent nasal discharge. Nuchal rigidity and the Brudzinski sign were present. Her shunt was functioning; it was tapped, yielding CSF which contained 90,000 RBC/mm 3, 3,200 WBC/mm ~ (79% P, 21% L), and a 3 + Pandy test. Gram stain revealed Gram negative, pleomorphic rods. Intravenous aqueous penicillin G
Brief clinical and laboratory observations
4 25
(300,000 U/kg/day), chloramphenicol (100 mg/kg/day), phenobarbital, and methylprednisolone were begun. H. influenzae was cultured from the CSF. Penicillin was discontinued and chloramphenicol was given for two weeks. A repeat shunt tap 36 hours after antibiotic treatment was stopped had 1 WBC/mm~; the culture was negative. She has been followed for three years without recurrence of infection; her shunt continues to function. Her development appears to be normal as judged by repeated Denver Developmental Screening Tests and neurological examinations. Patient 4 was a premature infant who developedhydrocephalus and received a ventriculoatrial shunt at 3 months of age. Five weeks later she was brought to the Pediatric Clinic in shock. Lumbar CSF contained WBC 12,500/mm 3 (97% P, 3% L), no detectable glucose (blood glucose concentration was 75 mg/dl), and protein 67 mg/dl. In spite of immediate, high intravenous doses of ampicillin, chloramphenicol, and dexamethasone she had a cardiopulmonary arrest and died within a few hours of admission. Hi influenzae was cultured from the nasopharynx, blood, and CSF. DISCUSSION Eradication o f shunt-associated infection is usually difficult. Failure is c o m m o n with p a r e n t e r a l antibiotic therapy alone or with incomplete s h u n t removal. 1, 2, ~ 8 M c L a u r i n 9 has reported a 58% cure r a t e in patients treated with systemic plus i n t r a v e n t r i c u l a r a d m i n i s t r a t i o n of antibiotics; h e advocates this a p p r o a c h for initial treatment. O t h e r investigators r e c o m m e n d complete s h u n t removal in addition to antibiotics as initial therapy, followed b y either i m m e d i a t e or delayed r e p l a c e m e n t of the shunt?. 2.... These r e c o m m e n d a t i o n s are based judiciously o n the general experience with shunt-associated infections, but infections with H. influenzae m a y be exceptions. In addition to our four patients, there are reports of five children with C S F shunts who have developed H. (nfluenzae CNS infection. Sells et al 6 reported two patients with H. influenzae shunt-associated infection. One was successfully treated with systemic antibiotics alone a n d the other recovered following incomplete s h u n t r e m o v a l a n d parenteral antibiotic therapy. In their series o f 20 patients with shunt-associated infections, this was the only organism which could be eradicated without complete s h u n t removal. The three other r e p o r t e d cases of H. influenzae infections were successfully treated with parenteral therapy alone2 . . . . . . In three of o u r four patients the infection was eradicated p r o m p t l y with i n t r a v e n o u s use o f antibiotics. T h e fourth child was in septic shock on admission a n d died within a few hours. If that child is excluded, seven of eight children infected with H. influenzae h a v e b e e n successfully treated with s y s t e m i c antibiotic therapy alone. This
426
Brief cfinical and laboratory observations
result is in direct contrast to the usual failure o f this form of therapy for shunt-associated CNS infections. To our knowledge the only statement in the literature suggesting that shunt removal may not be necessary when H. influenzae is the infecting organism is that of Sells et al, 6 "The preferred treatment for gram-negative shuntassociated infections, with the possible exception of H. influenzae, appears to be systemic and intraventricular antibiotics and complete shunt removal or replacement of the shunt in a new site." Our experience supports their comment. We recommend that patients with H. influenzae CNS infection be managed initially with parenteral antibiotics alone. Shunt removal appears to be unnecessary. The authors express their appreciation to Mrs. Linda M. Gilbert for her cheerful and patient assistance in preparation of this manuscript and Merrill J. Snyder, Ph.D., and Stephen C. Schimpff, M.D., for their critical reviews of the manuscript. REFERENCES
I.
Luthardt T: Bacterial infections in ventriculo-auricular shunt systems, Dev Med Child Neurol 12(Suppl 22):105, 1970. 2. Morrice JJ, and Young DG: Bacterial colonization of Holter
The Journal of Pediatrics September 1980
3.
4.~
5.
6.
7.
8.
9.
10.
11.
valves: A ten-year survey, Dev Med Child Neurol 16(Suppl 32):85, 1974. Bayst0n R, and Lari J: A study of the sources of infection in colonized shunts, Dev Med Child Neurol 16(Suppl 32): 16, 1974. Myers MG, and Schoenbaum SC: Shunt fluid aspiration: An adjunct in the diagnosis of cerebrospinal fluid shunt infection, Am J Dis Child 129:220, 1975. Schoenbaum SC, Gardner P, and Shillito J: Infections of cerebrospinal fluid shunts: Epidemiology, clinical manifestations and therapy, J Infect Dis 131:543, 1975. Sells CJ, Shurtleff DB, and Loeser JD: Gram negative cerebrospinal fluid shunt-associated infections, Pediatrics 59:614, 1977. Nicholas JL, Kamal IM, and Eckstein HB: Immediate'shunt replacement in the treatment of bacterial colonization of Holter valves, Dev Med Child Neurol 12(Suppl 22):110, 1970. Shurtleff DB, Foltz EL, Weeks RD, and Loeser J: Therapy of Staphylococcus epidermidis: Infections associated with cerebrospinal fluid shunts, Pediatrics 53:55, 1974. McLaurin RL: Treatment of infected ventricular shunts, Child's Brain 1:306, 1975. Shurtleff DB, Christie D, and Foltz EL: Ventriculoauriculostomy-associated infection: A 12 year study, J Neurosurg 35:686, 1971. Schoenbaum SC: Personal communication.
Blocking coagulation inhibitors in children taking penicillin Donald J. Orris, M.D., Jessica H. Lewis, M.D., Joel A. Spero, M.D., and
Ute Hasiba, M.D., Pittsburgh, Pa.
A C Q U I R E D INHIBIT'ORS 1 of blood coagulation fall into two major categories: blocking inhibitors and specific factor depressants. The former are usually proteins, ~ but not necessarily antibodies, which interfere with an entire coagulation reaction and are rarely, if ever, associated with clinical bleeding. These are found in some patients with systemic lupus erythematosus (lupus inhibitors), other collagen vascular diseases or malignancies, or following exposure to certain drugs. The clotting pathway which appears to be the most frequently interfered with is the intrinsic clotting system which is monitored via the activated partial thromboplastin time. In the presence of this type of inhibitor, all clotting factors may assay normally. Specific factor depressants, on the other hand, neutral-
From the Central Blood Bank of Pittsburgh and thet Department of Medicine, University of Pittsburgh. Reprint address: Coagulation Labo~.utory,CentralBlood Bank of Pittsburgh, 812 Fifth Ave., PittsbuFgh,PA 15219.
ize or inactivate a single clotting factor. Inhibitors specifically directed against Factors V, VIII, IX, XI, and XIII have been described?, ~ Factor VIII inhibitors are the most common. These specific factor depressants appear to be antibodies, frequently cause severe bleeding, and may Abbreviation used APTT: activated partial thromboplastin time occur in various a u t o i m m u n e disorders, especially rheumatoid arthritis, certain skin disorders such as pemphigus and psoriasis, in patients with drug hypersensitivity to penicillin, in postpartum women, and also in apparently previously healthy individuals. Such inhibitors arise in about 10% of patients with hemophilia as an immune reaction to factor therapy. This study presents coagulation data on 13 children evaluated in this laboratory for abnormal APTTs. Each was receiving either penicillin or a derivative, and in each case a blocking-type inhibitor was demonstrated.
0022-3476/80/090426+04500.40/0 9 1980 The C. V. Mosby Co.