- Email: [email protected]
Ampicillin-resistant H. influenzae subdural empyema following successful treatment of apparently ampicillin-sensitive H. influenzae meningitis
3 20
Letters to the Editor
rent disease, even if the initial strain was reported as sensitive to ampicillin.
Gilles Delage, M.D., F.R.C.P. (C) Yves DeClerck, M.D. Jo~lle Lescop, M.D., F.R.C.P.(C) Pierre Dery. M.D., F.R.C.P.(C) Fram;ois Shareek, B.Sc. Departments of Pediatrics and Microbiology and Immunology Sainte Justine's Hospital for Children Montreal, Canada Centre Hospitalier Universitaire de Laval Qukbec, Canada REFERENCES
I.
2.
3. 4. 5.
Thomas WJ, McReynolds JW, Mock CR, and Bailey DW: Ampicillin-resistant Haemophilus influenzae meningitis, Lancet 1:313, 1974. Schiffer MS, Schneerson R, MacLowry J, Robbins JB, McReynolds JW, Thomas W J, Bailey DW, Clarke E J, Mueller EJ, and Escamilla J: Clinical, bacteriological and immunological characterisation of ampicillin resistant Hemophilus influenzae type b, Lancet 1:257, 1974. Turk, DC: Ampicillin resistant Hemophilus influenzae meningitis, Lancet 1:453, 1974. Williams JD, and Cavanagh P: Ampicillin resistant Hemophilus influenzae meningitis, Lancet 1:864, 1974. Tomeh MO, Starr SE, MeGowan JE, Terry PM, and Nahmias A J: Ampicillin resistant Hemophilus influenzae type b infection, JAMA 229:295, 1974.
Ampicillin-resistant H. influenzae subdural empyema following successful treatment of apparently ampicillin-sensitive H. influenzae meningitis To the Editor: In accordance with recent recommendations' regarding antimicrobial therapy for bacterial meningitis, we initiate treatment o f suspected Hemophilus influenzae meningitis with intravenous ampicillin at 400 m g / k g / d a y and chloramphenicol at 100 mg/ kg/day. Chloramphenicol is discontinued, if H. influenzae is isolated and if the isolate is ampicillin sensitive as measured by tube dilution minimal inhibitory concentration (MIC) and does not produce fl-lactamase. The following case report describes the apparent emergence of an ampicillin-resistant strain of H. influenzae type b in a subdural empyema following successful treatment of meningitis due to an apparently ampicillin-sensitive strain of the same organism. CASE REPORT
A 9-month-old boy was admitted to a rural hospital on March 14 with pyrexia (41~ and a diagnosis of pneumonia of the left
The Journal ofPediatrics February 1977
lower lobe. Therapy was begun with oral Amoxicillin, 125 mg three times a day, but after failing to improve over the next several days, he was transferred to the Children's Centre in Winnipeg on March 19 for further evaluation and treatment. On admission to the Children's Centre examination of the cerebrospinal fluid (CSF) (WBC 5,900, 97% PMN: protein 814 mg/dl: glucose 94 mg/dl) was compatible with bacterial meningitis, and intravenous therapy with chloramphenicol and ampicillin was initiated. H. influenzae type b was isolated from the CSF. The isolate was ampicillin sensitive (MIC 0.125 ~tg/ml) as determined by tube dilution in Eugon broth supplemented with 1% Fildes reagent with an inoculum of 10:' organisms/ml (modified from 2) and was negative for fl-lactamase activity. ~ A prompt clinical response to therapy was noted, chloramphenicol was discontinued on March 22 and a repeat examination of CSF (4 PMN: 15 lymphocytes; protein 17 mg/dl: glucose 47 mg/dlI on March 25 was compatible with resolution of the bacterial meningitis. He became afebrile within 96 hours after admission and remained so until discharged on April 3: intravenous ampicillin had been discontinued on March 31. He was readmitted to the rural hospital on April 8 with irritability, vomiting, and pyrexia o f 24 hours duration. Examination of the CSF at that time revealed only 5 WBC/mm'. The fluid, unfortunately, was lost in transit to Winnipeg and was not cultured. The possibility of a subdural empyema was considered and he was again transferred to the Children's Centre on April 9. A repeat examination of the CSF was not performed, but subdural taps revealed purulent fluid bilaterally that grew H. influenzae type b. The isolate was resistant to ampicillin (MIC 16 /*g/ml) and was positive for B-lactamase activity. The same resistant strain was isolated from a blood culture on readmission. Attempts to recover ampicillin-resistant organisms from the stock culture (obtained from an area of dense growth on chocolate agar) from the first admission by looking for resistant colonies within the zone of inhibition on ampicillin disc sensitivity testing and by subculture in broth and on chocolate agar containing 1 ttg/ml ampicillin using heavy inocula ( > 10~ organisms/rely were unsuccessful. Both strains retained their sensitivity' or resistance to ampicillin through multiple subcultures. Therapy was again begun with intravenous chloramphenicol and ampiciUin with the ampicillin being discontinued when sensitivity data were available. Intravenous chloramphenicol was continued until April 28. Repeated subdural taps were sterile and there was gradual resolution of the subdural fluid over the subsequent three weeks and he was discharged apparently well on May 5. DISCUSSION Echeverria and associates 4 have previously reported a case o f apparent emergence of resistance during therapy for Escherichia colt meningitis and the report by Khan and colleagues ~ included a case of H. influenzae meningitis responsive to ampicillin in which both sensitive and resistant strains were simultaneously cultured from the CSF. Presumably such cases arise from a mixed population of organisms either by loss of resistance factors by a portion of the population or by the presence of both sensitive and resistant organisms in the initial inoculum. We were unable to recover resistant colonies from the initial CSF stock culture, and, although one of the above mechanisms is suspected, the acquisition of a new resistant strain in a previously sterile subdural effusion cannot be excluded, The implication of such apparent emergence of resistance is
Volume 90 Number 2
Letters to the Editor
32 !
obvious and again raises the question: "Should ampicillin be abandoned for treatment of Haemophilus influenzae disease? .... W. L. Albritton, M.D., Ph.D. G. Hammond, M.D. S. Hoban, A.R.T. A. R. Ronald, M.D, Departments of Pediatrics and Medical Microbiology 700 William Ave. Winnipeg, Manitoba, Canada R3E OZ3 REFERENCES 1. American Academy of Pediatrics, Committee on Infectious Disease: Ampicillin-resistant strains of Hemophilus influenzae type B. Pediatrics 55:145, 1975. 2. Thornsberry C, and Kirven LA: Antimicrobial susceptibility of Haemophilus influenzae, Antimicrob Agents Chemother 6:620, 1974. 3. Thornsberry C, and Kirven LA: Ampicillin resistance in Haemophilus influenzae as determined by a rapid test for/~lactamase production, Antimicrob Agents Chemother 6:653, 1974. 4. Echeverria P, et al: Apparent emergence of aminoglycosideresistant Escherichia coli during neonatal meningitis, N Engl J Med 293:913, 1975. 5. Khan W, et al: Haemophilus influenzae type b resistant to ampicillin: A report of two cases. JAMA 229:298, 1974. 6. Nelson JD: Should ampicillin be abandoned for treatment of Haemophilus influenzae disease? J A M A 229:322, 1974.
Suppurative thyroiditis with gas formation due to mixed anaerobic infection To the Editor: Suppurative thyroiditis is rare, and anaerobic infections in otherwise healthy children are uncommon. A 12-year-old boy is presented who was initially treated as having nonsuppurative thyroiditis, but who deteriorated clinically. At operation, he was found to have suppurative thyroiditis, ultimately proved to be due to a mixed aerobic-anaerobic infection. This case demonstrates the value of radiographic studies of the neck and the need for aerobic and ahaerobic cultures at the time of drainage. It also suggests that thyroiditis, with organisms that normally reside in the pharynx, may be due to persistent thyroglossal duct remnants. CASE REPORT A 12-year-old boy was admitted to St. Louis Children's Hospital because of a 4-day history of sore throat, cough, neck swelling, and fever. The left lobe of the thyroid was mildly tender and enlarged to 5 cm and the temperature was 40.4 ~ C. Physical examination was otherwise unremarkable, and he appeared euthyroid and nontoxic. Serum concentrations of T4, PBI, and TSH were normal. White blood cell count was 22,500/mm :~with
Fig. 1. Lateral projection of neck showing collections of gas in region of thyroid gland.
73% polymorphonuclear leukocytes, 15% lymphocytes, and 11% monocytes. Blood cultures were sterile and throat cultures grew normal flora. After three days of aspirin and two days of prednisone therapy his condition changed dramatically. The anterior neck became swollen, erythematous, and tender with extension of the swelling laterally and down to the sternum. Lateral neck roentgenograms (Fig. 1) revealed gas dissection in the soft tissues of the neck. Intravenous gentamycin and clindamycin therapy was initiated. At operation, a large thyroidal and prethyroidal abscess was drained of foul-smelling purulent material. Bacteroides fragilis, peptococcus magnus, and beta hemolytic streptococci (not groups A or B) were grown in culture. Postoperatively the patient was treated with clindamycin and made a rapid recovery. Serum concentrations of T4 and TSH were normal. DISCUSSION The most common organisms associated with a thyroid abscess have been the streptococci, staphylococci, and pneumococci, although recent reports have indicated a variety of unusual organisms including Baeteroides melaninogenicus, Aspergillus
Letters to the Editor
rent disease, even if the initial strain was reported as sensitive to ampicillin.
Gilles Delage, M.D., F.R.C.P. (C) Yves DeClerck, M.D. Jo~lle Lescop, M.D., F.R.C.P.(C) Pierre Dery. M.D., F.R.C.P.(C) Fram;ois Shareek, B.Sc. Departments of Pediatrics and Microbiology and Immunology Sainte Justine's Hospital for Children Montreal, Canada Centre Hospitalier Universitaire de Laval Qukbec, Canada REFERENCES
I.
2.
3. 4. 5.
Thomas WJ, McReynolds JW, Mock CR, and Bailey DW: Ampicillin-resistant Haemophilus influenzae meningitis, Lancet 1:313, 1974. Schiffer MS, Schneerson R, MacLowry J, Robbins JB, McReynolds JW, Thomas W J, Bailey DW, Clarke E J, Mueller EJ, and Escamilla J: Clinical, bacteriological and immunological characterisation of ampicillin resistant Hemophilus influenzae type b, Lancet 1:257, 1974. Turk, DC: Ampicillin resistant Hemophilus influenzae meningitis, Lancet 1:453, 1974. Williams JD, and Cavanagh P: Ampicillin resistant Hemophilus influenzae meningitis, Lancet 1:864, 1974. Tomeh MO, Starr SE, MeGowan JE, Terry PM, and Nahmias A J: Ampicillin resistant Hemophilus influenzae type b infection, JAMA 229:295, 1974.
Ampicillin-resistant H. influenzae subdural empyema following successful treatment of apparently ampicillin-sensitive H. influenzae meningitis To the Editor: In accordance with recent recommendations' regarding antimicrobial therapy for bacterial meningitis, we initiate treatment o f suspected Hemophilus influenzae meningitis with intravenous ampicillin at 400 m g / k g / d a y and chloramphenicol at 100 mg/ kg/day. Chloramphenicol is discontinued, if H. influenzae is isolated and if the isolate is ampicillin sensitive as measured by tube dilution minimal inhibitory concentration (MIC) and does not produce fl-lactamase. The following case report describes the apparent emergence of an ampicillin-resistant strain of H. influenzae type b in a subdural empyema following successful treatment of meningitis due to an apparently ampicillin-sensitive strain of the same organism. CASE REPORT
A 9-month-old boy was admitted to a rural hospital on March 14 with pyrexia (41~ and a diagnosis of pneumonia of the left
The Journal ofPediatrics February 1977
lower lobe. Therapy was begun with oral Amoxicillin, 125 mg three times a day, but after failing to improve over the next several days, he was transferred to the Children's Centre in Winnipeg on March 19 for further evaluation and treatment. On admission to the Children's Centre examination of the cerebrospinal fluid (CSF) (WBC 5,900, 97% PMN: protein 814 mg/dl: glucose 94 mg/dl) was compatible with bacterial meningitis, and intravenous therapy with chloramphenicol and ampicillin was initiated. H. influenzae type b was isolated from the CSF. The isolate was ampicillin sensitive (MIC 0.125 ~tg/ml) as determined by tube dilution in Eugon broth supplemented with 1% Fildes reagent with an inoculum of 10:' organisms/ml (modified from 2) and was negative for fl-lactamase activity. ~ A prompt clinical response to therapy was noted, chloramphenicol was discontinued on March 22 and a repeat examination of CSF (4 PMN: 15 lymphocytes; protein 17 mg/dl: glucose 47 mg/dlI on March 25 was compatible with resolution of the bacterial meningitis. He became afebrile within 96 hours after admission and remained so until discharged on April 3: intravenous ampicillin had been discontinued on March 31. He was readmitted to the rural hospital on April 8 with irritability, vomiting, and pyrexia o f 24 hours duration. Examination of the CSF at that time revealed only 5 WBC/mm'. The fluid, unfortunately, was lost in transit to Winnipeg and was not cultured. The possibility of a subdural empyema was considered and he was again transferred to the Children's Centre on April 9. A repeat examination of the CSF was not performed, but subdural taps revealed purulent fluid bilaterally that grew H. influenzae type b. The isolate was resistant to ampicillin (MIC 16 /*g/ml) and was positive for B-lactamase activity. The same resistant strain was isolated from a blood culture on readmission. Attempts to recover ampicillin-resistant organisms from the stock culture (obtained from an area of dense growth on chocolate agar) from the first admission by looking for resistant colonies within the zone of inhibition on ampicillin disc sensitivity testing and by subculture in broth and on chocolate agar containing 1 ttg/ml ampicillin using heavy inocula ( > 10~ organisms/rely were unsuccessful. Both strains retained their sensitivity' or resistance to ampicillin through multiple subcultures. Therapy was again begun with intravenous chloramphenicol and ampiciUin with the ampicillin being discontinued when sensitivity data were available. Intravenous chloramphenicol was continued until April 28. Repeated subdural taps were sterile and there was gradual resolution of the subdural fluid over the subsequent three weeks and he was discharged apparently well on May 5. DISCUSSION Echeverria and associates 4 have previously reported a case o f apparent emergence of resistance during therapy for Escherichia colt meningitis and the report by Khan and colleagues ~ included a case of H. influenzae meningitis responsive to ampicillin in which both sensitive and resistant strains were simultaneously cultured from the CSF. Presumably such cases arise from a mixed population of organisms either by loss of resistance factors by a portion of the population or by the presence of both sensitive and resistant organisms in the initial inoculum. We were unable to recover resistant colonies from the initial CSF stock culture, and, although one of the above mechanisms is suspected, the acquisition of a new resistant strain in a previously sterile subdural effusion cannot be excluded, The implication of such apparent emergence of resistance is
Volume 90 Number 2
Letters to the Editor
32 !
obvious and again raises the question: "Should ampicillin be abandoned for treatment of Haemophilus influenzae disease? .... W. L. Albritton, M.D., Ph.D. G. Hammond, M.D. S. Hoban, A.R.T. A. R. Ronald, M.D, Departments of Pediatrics and Medical Microbiology 700 William Ave. Winnipeg, Manitoba, Canada R3E OZ3 REFERENCES 1. American Academy of Pediatrics, Committee on Infectious Disease: Ampicillin-resistant strains of Hemophilus influenzae type B. Pediatrics 55:145, 1975. 2. Thornsberry C, and Kirven LA: Antimicrobial susceptibility of Haemophilus influenzae, Antimicrob Agents Chemother 6:620, 1974. 3. Thornsberry C, and Kirven LA: Ampicillin resistance in Haemophilus influenzae as determined by a rapid test for/~lactamase production, Antimicrob Agents Chemother 6:653, 1974. 4. Echeverria P, et al: Apparent emergence of aminoglycosideresistant Escherichia coli during neonatal meningitis, N Engl J Med 293:913, 1975. 5. Khan W, et al: Haemophilus influenzae type b resistant to ampicillin: A report of two cases. JAMA 229:298, 1974. 6. Nelson JD: Should ampicillin be abandoned for treatment of Haemophilus influenzae disease? J A M A 229:322, 1974.
Suppurative thyroiditis with gas formation due to mixed anaerobic infection To the Editor: Suppurative thyroiditis is rare, and anaerobic infections in otherwise healthy children are uncommon. A 12-year-old boy is presented who was initially treated as having nonsuppurative thyroiditis, but who deteriorated clinically. At operation, he was found to have suppurative thyroiditis, ultimately proved to be due to a mixed aerobic-anaerobic infection. This case demonstrates the value of radiographic studies of the neck and the need for aerobic and ahaerobic cultures at the time of drainage. It also suggests that thyroiditis, with organisms that normally reside in the pharynx, may be due to persistent thyroglossal duct remnants. CASE REPORT A 12-year-old boy was admitted to St. Louis Children's Hospital because of a 4-day history of sore throat, cough, neck swelling, and fever. The left lobe of the thyroid was mildly tender and enlarged to 5 cm and the temperature was 40.4 ~ C. Physical examination was otherwise unremarkable, and he appeared euthyroid and nontoxic. Serum concentrations of T4, PBI, and TSH were normal. White blood cell count was 22,500/mm :~with
Fig. 1. Lateral projection of neck showing collections of gas in region of thyroid gland.
73% polymorphonuclear leukocytes, 15% lymphocytes, and 11% monocytes. Blood cultures were sterile and throat cultures grew normal flora. After three days of aspirin and two days of prednisone therapy his condition changed dramatically. The anterior neck became swollen, erythematous, and tender with extension of the swelling laterally and down to the sternum. Lateral neck roentgenograms (Fig. 1) revealed gas dissection in the soft tissues of the neck. Intravenous gentamycin and clindamycin therapy was initiated. At operation, a large thyroidal and prethyroidal abscess was drained of foul-smelling purulent material. Bacteroides fragilis, peptococcus magnus, and beta hemolytic streptococci (not groups A or B) were grown in culture. Postoperatively the patient was treated with clindamycin and made a rapid recovery. Serum concentrations of T4 and TSH were normal. DISCUSSION The most common organisms associated with a thyroid abscess have been the streptococci, staphylococci, and pneumococci, although recent reports have indicated a variety of unusual organisms including Baeteroides melaninogenicus, Aspergillus