L E T T E R S TO T H E E D I T O R Clinical notes

"Clinical notes" represent clinical and/or laboratory experiences which can be presented in 200 to 400 words, 3 or 4 references, and, if contributory, one illustration or short table. "Clinical notes" are subject to the same critical peer review and editing as papers published in other sections of THE JOURNAL.

Chloramphenicol-resistan t

Hemophilus influenzae To the Editor: We report the recovery of a strain of chloramphenicol-resistant

Hemophilus influenzae type b from an infant with meningitis. CASE REPORT A 9-month-old male infant who has resided solely in Philadelphia was in good health until he accidentally struck his head on November 2, 1976. He became lethargic and was examined six hours after the injury. He was drowsy and irritable. Temperature was 102~ There was no break in skin, Battle's sign, or

See related article p. 1031. hemotympanum. He was admitted to the hospital. A parietal skull fracture was confirmed roentgenographically. Lumbar puncture 12 hours after admission revealed turbid fluid with 2,240 white blood cells/mm ~(86% polymorphonuclear); glucose, 28 mg/dl; protein, 116 mg/dl, and gram-negative pleomorphic bacilli. He was given intravenous ampicillin (400 mg/kg day in 6 doses) and chloramphenicol (100 mg/kg day in 4 doses). H. influenzae type b susceptible to ampicillin was isolated from blood and spinal fluid. Ampicillin alone was continued. The patient's course was complicated by persistent fever, lethargy, hemiparesis, anemia, increasing peripheral white blood count from 9,600/mm :~ on admission to 58,200/mm :~ on day seven. Repeat lumbar puncture on day seven revealed sterile xanthochromic fluid with 163 white blood cells/mm' (68% mononuclear); glucose, 65 mg/dl; protein, 54 mg/dl. Computerized axial tomography on day eight revealed a subdural collection with a shift of midline structures. Chloramphenicol therapy was reinstituted at 100 mg/kg/day. Ampicillin was discontinued. Thirty milliliters of sterile xanthochromic nonpurulent fluid was removed from the subdural space. The infant improved, became afebrile by the fifteenth day, and received chloramphenicol until the twenty-third hospital day. He was discharged and has been followed for 60 days without relapse of meningitis and with recovery of previous neurologic abilities. The H. influenzae type b isolated from blood and spinal fluid on admission had a tube dilution minimum inhibitory concentration (MIC) for chloramphenicol of 32/~g/ml and for ampicillin of

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0.25/tg/ml (MICs were verified at the Bacteriology Division of the Center for Disease Control where the organism was also noted to have an MIC for tetracycline of 32 /tg/ml).' H. influenzae type b was not recovered from the nasopharynx of any of the patient's family of six adults and 12 children. Four isolates of nontypable H. influenzae and three isolates o f H. aphrophilus from family members were susceptible to ampicillin and chloramphenicol. DISCUSSION The patient inadvertently received only eight days of antibiotic therapy to which his causative organism was susceptible. Either he was bacteriologically cured by day eight, although fever continued for another seven days, chloramphenicol given intravenously reached the very high levels required to inhibit his organism, or resistance of his organism to chloramphenicol was not a stable characteristic. Chloramphenicol has been included in the recommended initial therapy of children with severe infections suspected to be due to H. influenzae type b inasmuch as the documentation of ampicillin-resistant strains extends over a wide geographic areaJ Because of reports of chloramphenicol resistance of two strains each of Streptococcus pneumoniae and Neisseria meningitidis ~and a single strain of H. influenzae type b ~ it is recommended that combination therapy with a penicillin (penicillin or ampicillin) is necessary initially. This is the first strain of H. influenzae (type b) in the United States confirmed by the Center for Disease Control to be resistant to chloramphenicol? Its recovery from a patient with meningitis strengthens the recommendation for inclusion of each of the antibiotics in the initial therapy of H. influenzae meningitis.

Sarah S. Long, M.D. Shirley E. Phillips, Ph.D. The Departments of Pediatrics and Microbiology Temple University Health Sciences Center St. Christopher's Hospital for Children Philadelphia, PA 19133 REFERENCES 1. American Academy of Pediatrics, Committee on Infectious Diseases: Current status of ampicillin resistant H. influenzae type b, Pediatrics 57:417, 1976.

Volume 90 Number 6

Letters to the Editor

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Mathies AW Jr: Penicillins in the treatment of bacterial meningitis, JR Coil Physicians Lond 6:139, 1972. 3. Barrett FF, Taber LH, Morris CR, Stephenson WB, Clark DJ, and Yow MD: A 12 year review of Hemophilus influenzae meningitis, J PEDIATR 81:370, 1972. 4. Center for Disease Control: Chloramphenicol-resistant Hemophilus influenzae-Pennsylvania, Morbidity and Mortality Weekly Report 25:385, 1976.

Meningitis due to Hemophilus influenzae type f To the Editor: Serious Hemophilus influenzae infections are usually caused by type b strains. A recent report of meningitis due to H. influenzae type e serves as a reminder that other capsular types may also be pathogenic. 1 Since many laboratories do not routinely type H. influenzae, the incidence and importance of types other than b is not dear. The present case is an example of type f meningitis with clinical and laboratory features similar to those typical of type b.

See related article, p. 1030. CASE REPORT The patient was a 10-month-old female infant with a 2-week history of cold, nasal discharge, and cough. Two days prior to admission she began to have fever (102 ~ to 104~ F) and was treated with aspirin and acetaminophen. The child became progressively worse and was taken to her doctor. Bilateral otitis media was diagnosed, and a lumbar puncture was performed. The cerebrospinal fluid (CSF) contained 6,800 white cells/mm 3 (86% polymorphonuclear) and 6,100 red cells/mm a. She was promptly referred to The Children's Hospital, where on arrival she appeared somewhat lethargic but irritable. Temperature was 99.6 ~ F, and mild nuchal rigidity was noted. Bilateral aspirations of the middle ear yielded purulent exudates. A repeat lumbar puncture showed 1,710 white cells/mm 3 (86% polymorphonuclear) and 131 red cells/mm 3, protein 74 mg/dl, glucose 61 mg/dl with serum glucose 80 mg/dl. The peripheral white count was 37,700/mm 3 with 10 bands, 53 polymorphonuclear cells, and 20 lymphocytes. Hemoglobin was 8.6 gm/dl. Electrolytes and blood urea nitrogen were normal. A Gram stain of CSF revealed gramnegative coccobacilli. Antibiotic therapy was initiated with intravenous ampicillin (400 mg/kg/24 hours) and chloramphenicol (50 mg/kg/24 hours); the latter was discontinued when susceptibility studies were reported. The hospital course was uneventful. The CSF 48 hours after the termination of a 10 day course of antibiotic was normal. Hemophilus influenzae type f was isolated from the CSF, from one of two blood cultures, and from the left, but not the right, middle-ear aspirate. Capsular typing was done by'slide agglutination and Quellung reaction using Hyland (Costa Mesa, CA) antisera. All isolates were susceptible to ampicillin and to chloramphenicol by the disc method.

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DISCUSSION At least four cases of H. influenzae type f have been reported, ~-~ and others have been noted informally. ~. 7 We know of no H. meningitis other than type b in our area in recent years; 54 CSF isolates during the 18-month period ending January, 1977, were all type b. Nasopharyngeal carriage of other types is, however, relatively common in our community, particularly types e, f, and occasionally d. We have not seen other disease associated with type f but have recovered H. influenzae type e from the middle ear on one occasion. Recognition of H. influenzae is facilitated by employing a transparent medium such as Levinthal's agar and examining colonies for characteristic iridescence in oblique light. 8 In the clinical laboratory, typing may be done by slide agglutination and Quellung reaction ~ with most commercially available antisera. When counterimmunoelectrophoresis is used as a rapid diagnostic test for H. influenzae in CSF, 9 only type b antiserum is commonly used; other types, though rare, may be missed by this technique alone.

Barry M. Gray, M.D. Department of Pediatrics University of Alabama in Birmingham School of Medicine Birmingham, AL 35294 REFERENCES 1. Buck LL, and Douglas GW: Meningitis due to Haemophilus influenzae type e, J Clin Microbiol 4:381, 1976. 2. Pittman M: The action of type-specific Hemophilus influenzae antiserum, J Exp Med 58:683, 1933. 3. Parke JG: Meningitis caused by type f Hemophilus influenzae, J PEDIATR 27:567, 1945. 4. Rosenblatt P, and Zweifler BM: Case reports-Type F Hemophilus influenzae meningitis, case report with a review of the literature, J PEDIATR 38:620, 1951. 5. Applebaum E, and Nelson J: Streptomycin in the treatment of influenzal meningitis, JAMA 143:715, 1950. 6. Birdsong M, Waddell WW Jr, and Whitehead BW: Influenzal meningitis, Am J Dis Child 67:194, 1944. 7. Sell S: Hemophilus influenzae, Nashville, 1973, Vanderbilt Press, p 34. 8. Turk DC, and May RL: Hemophilus influenzae: Its clinical importance, London, 1967, English Universities Press, p 114. 9. Coonrod JD, and Tytel MW: Determination of etiology of bacterial meningitis by counterimmunoelectrophoresis, Lancet hl154, 1972.

Methicillin-associated nephropathy or cystitis To the Editor: The frequency of methicillin-associated nephrotoxicity in infants and children has been reported to range from 0 to 16%.~-~

Chloramphenicol-resistant Hemophilus influenzae.

L E T T E R S TO T H E E D I T O R Clinical notes "Clinical notes" represent clinical and/or laboratory experiences which can be presented in 200 to...
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