Necrotizing Otitis Externa During Induction Therapy for Acute Lymphoblastic Leukemia

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Necrotizing

Otitis

Externa

During

Induction

Therapy

for Acute

Lymphoblastic

Leukemia

Lawrence

J. Wolff,

MD

From the Department of Pediatrics, Doernbecher Memorial Hospital for Children, The Oregon Health Sciences University, Portland

ABSTRACT. In three children who were receiving acute

lymphoblastic leukemia induction therapy and were

se-verely neutropenic, necrotizing otitis externa developed. Two patients had a probing maneuver to their ear canal.

Pseudomonas aeruginosa was isolated in heavy growth

from the external canal ofthree patients and other tissues of one patient. Staphylococcus aureus was cultured from

the ear canal and tissues of one patient and Streptococcus fuecalis from the ear canal of another patient. Necrotizing otitis externa resolved in two patients after 2 weeks of intravenous antibiotics, debridement, and resolution of neutropenia. One patient required prolonged intravenous antibiotics and several surgical procedures. The occur-rence of necrotizing otitis externa in children with acute

lymphoblastic leukemia and severe neutropenia, the

as-sociation of Gram-positive cocci with necrotizing otitis externa, and the importance of protecting anatomic bar-riers like the external ear canal in immunocompromised patients are emphasized. Pediatrics 1989;84:882-885; nec-rotizing otitis externa, acute lymphoblastic leukemia, neu-tropenia.

During induction therapy, children who have acute lymphoblastic leukemia are vulnerable to in-fections; they are neutropenic and have qualitative and quantitative abnormalities of cellular and hu-moral function.’ When an anatomic barrier such as the skin or the mucous membrane is broken in a child receiving acute lymphoblastic leukemia therapy, a defense mechanism has been disrupted,

making the patient more vulnerable to an

infec-tion.5

Necrotizing otitis externa, also called invasive otitis externa or malignant otitis externa, is a severe infection of the ear canal with deep invasion of

Received for publication Feb 17, 1988; accepted Dec 15, 1988. Reprint requests to (L.J.W.) Doernbecher Memorial Hospital for Children, Dept of Pediatrics, The Oregon Health Sciences University, Portland, OR 97201.

periauricular tissue.6’7 Pseudornonas species is the most frequent microorganism associated with nec-rotizing otitis externa.8’9 Adults with diabetes mel-litus constitute the largest group of patients with necrotizing otitis externa; they have a high mci-dence of cranial nerve involvement and significant mortality.7’8 Since the initial report of necrotizing otitis externa, children have represented about 5% of the reported cases. It has been reported in chil-dren with diabetes mellitus, malnutrition, Stevens Johnson syndrome with associated neutropenia, neuroblastoma while receiving anticancer chemo-therapy, and acute monocytic leukemiaY’2

In this paper, we report the occurrence of necro-tizing otitis externa in neutropenic children receiv-ing acute lymphoblastic leukemia induction ther-apy; we describe the association of Gram-positive cocci and emphasize the potential problem that can occur when a protective barrier such as the external ear canal is injured. The clinical features of the three children are listed in the Table.

DISCUSSION

Most patients with necrotizing otitis externa have been adults with diabetes mellitus and

vascu-lar

disease7; however, in children, diabetes mellitus has been the associated illness in 3 of 14 patients.’2 Other conditions in children in which necrotizing otitis externa has been reported suggest that neu-trophil quantity and function and other host de-fense mechanisms are a factor in the development of this condition.9”’3 The 3 patients reported in this paper had several factors compromising their host defenses: they were severely neutropenic, they were receiving induction chemotherapy for acute lymphoblastic leukemia, and two patients had trauma to their ear canals.

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TABLE. Clinical and Laboratory Features of Patients With Necrotizing Otitis Extema

ARTICLES 883

Patient 1 Patient 2 Patient 3

Age (y) 4 2#{189} 6#{189}

Diagnosis Acute lymphoblastic leukemia

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia Chemotherapy L-Asparginase,

predni-sone, vincristine L-Asparginase, prednisone, yin-cristine L-Asparginase, predni-sone, vincristine

History of trauma to Yes Yes No

canal

Pain Yes Yes Yes

Fever (‘C) 39.0 39.4 38.0

Discharge from canal Purulent Purulent,

sangui-neous

Purulent

Abnormal external Yes Yes Yes

canal

Tympanic membrane Abnormal Normal Abnormal

Facial nerve function Normal Normal Normal

Granulocyte count (per 28 64 0

L)

Blood culture No growth No growth No growth

External canal culture Pseudomonas aerugi-nose, Staphylococcus aureus Pseudomonas aeru-ginosa Pseudomonas aerugi-nose, Streptococcus faecaiis

Serum immunoglobulins A-55, G-900, M-50 A-28, G-600, M-42 A-SO, G-760, M-110

(mg/dL)

Radiograph temporal “Temporal bone poorly “Excess liquid air “Excess liquid in air

bone aerated” cells” cells”

Surgery Surgical debridement

canal, myringotomy, antrotomy

Wash and suction canal

Wash and suction canal

Antibiotic therapy Ampicillin, tobramycin, ticarcillin, cefaman-dole Cefamandole, tobra-mycin, ticarcillin Cefamandole, ticardilin, tobramycin, ampici-lin

Outcome Recovered Recovered Recovered

Complications None None None

Pseudomoruzs aeruginosa was isolated in heavy

growth from the external canals of all three patients and the myringotomy fluid, ear tissue, and mastoid fluid from one patient. The microorganisms that reside in the external auditory canal are the same found on normal skin elsewhere. Warmth, mois-ture, and antibiotic therapy decrease the proportion of Gram-positive bacteria and increase the mci-dence of Pseudomonas, Gram-negative enteric

bac-teria, and fungi in the ear canal.’’6 Although Ps

aeruginosa is the preponderant microorganism as-sociated with necrotizing otitis externa, two of the patients had moderate numbers of Gram-positive cocci swabbed from the ear canal and stained with Gram stain. S aureus was cultured from the ear canal, middle ear, and soft tissue of one patient. A culture specimen from the ear canal of the other patient was positive for Streptococcus faecalis. Pre-vious experience in children with acute lympho-blastic leukemia and severe infections shows a high incidence of Gram-positive cocci as infectious agents and would give strength to the finding of S

aureus and S faecalis in patients 1 and 3#{149}2.17

S

aureus has been reported twice as the only

microorganism associated with necrotizing otitis externa.’8”9 Another series reports Gram-positive cocci in 11 of 21 patients with necrotizing otitis externa and Ps aeruginosa cultured from the exter-nal auditory canal or material removed at surgery.7 Gram-positive organisms identified were

Staphylo-coccus epidermis, S aureus, nonhemolytic strepto-cocci, enterococci, and unknown staphylococci. Be-cause quantification of the Gram-positive cocci by Gram stain or culture was not mentioned, the role of Gram-positive cocci in necrotizing otitis externa in this series is unclear.7

The distinction between severe otitis externa and early necrotizing otitis externa is not obvious and often difficult because they have the common early clinical findings of pain, drainage, and an abnormal auditory canal.8’#{176}23 All 3 patients had pain, exten-sive soft tissue involvement, profound discharge, significant granulation tissue, and a heavy growth of Ps aeruginosa from the ear canal. Radiographs of the patients’ temporal bones showed abnormali-ties. With the exception of positive temporal bone scans, which were not done, the patients met the diagnostic criteria for necrotizing otitis externa as

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described by both Babiatzki et al#{176}and Cohen and Friedman.22 Although bone scan, computed tomog-raphy, and magnetic resonance imaging are helpful in defining necrotizing otitis externa, they do not distinguish in all cases.#{176}If an otitis externa does not respond promptly to suctioning the ear canal, eliminating moisture, and antimicrobial ear drops in patients with congenital or acquired host defects, necrotizing otitis externa should be suspected and broad-spectrum intravenous antibiotics begun. Pain was an initial complaint of the 3 patients and is a symptom of most patients.7”6 The use of acet-aminophen and codeine orally was sufficient to control the pain of 2 patients. Patient 1 needed morphine intravenously to manage her pain. Facial nerve palsy was not noted in the 3 patients. Of the

14 children with necrotizing otitis externa previ-ously reported, 6 have had permanent facial nerve palsy’2; no child with necrotizing otitis externa and facial nerve palsy has died secondary to necrotizing otitis externa. In contrast, Doroghazi et al7 in their review stated that only 47% of adults with necro-tizing otitis externa and facial nerve palsy survived.

Because Gram-negative rods were seen in signif-icant numbers on smears of the ear drainage of all three patients, tobramycin initially and later tobra-mycin and ticarcillin were begun intravenously un-til culture and sensitivity results confirmed Ps aeru-ginosa and its antimicrobial sensitivity. Other investigators7’24’ have reported good results using other 9-lactam penicillins and aminoglycosides. In adults with necrotizing otitis externa, intravenous cefsulodin compared favorably with the combina-tion of an intravenous $-lactam penicillin and an intravenous aminoglycoside. Imipenem with cilas-tin has been shown to be effective in adults with life-threatening Pseudornonas infection and may be suitable monotherapy for necrotizing otitis ex-terna.26 Initially, all three patients received intra-venous cefamandole. The Gram stain of patient 2 showed scant Gram-positive cocci, but the culture showed no organisms with Gram-positive charac-teristics. S aureus was isolated from the ear canal and other tissues of patient 1, and she continued to receive cefamandole. Ear canal cultures from pa-tient 3 was positive for S faecalis and cefamandole treatment was replaced with intravenous ampicil-lin.

The three patients reported received intravenous antibiotics for a minimum of 2 weeks. Because they received tobramycin and had extensive infection, their hearing was monitored closely. In contrast to adults with necrotizing otitis externa, there was rapid healing of the ear canal when the absolute neutrophil counts of patients 2 and 3 exceeded 1OOO/L. The correction of the neutropenia may

explain the relative short course of intravenous antibiotics two patients received compared with other patients.25 When patient 1 reached and main-tamed an absolute neutrophil counts of 2OOO/L, she still required several surgical procedures and intravenous antibiotics for 6 weeks. During this period, prophylactic cranial irradiation was started and may have affected the healing process.

An ear curette was used without visualization to remove cerumen or other debris from the canals of two patients. It is not certain whether the external ear canals were injured by use of the ear probe. However, use of a curette should be considered cautiously in a severely neutropenic patient, and the benefits should clearly outweigh the risks before a protective barrier is challenged.

SUMMARY

Three children with acute lymphoblastic leuke-mia who were neutropenic during induction therapy were described. All three patients had severe in-volvement of their external ear canal. Two patients had a history of an antecedent probing maneuver to their ear canal. All patients had prolific growth

ofPseudomonas from their external canals, and two

patients had Gram-positive cocci also cultured from

their external canals. All patients required at least

2 weeks of intravenous antibiotics and regular suc-tioning and washing of the canal to remove debris and necrotic tissue. Several factors are important in the management of children with necrotizing otitis externa: a high degree of suspicion in children with congenital or acquired host defense abnormal-ities and a smoldering otitis externa, use of the microbiology laboratory for early and definitive mi-croorganism identity, early involvement of an oto-laryngologist, and expeditious use of intravenous antibiotics.

REFERENCES

1. Hughes WT, Smith DR. Infection during induction of re-mission in acute lymphocytic leukemia. Cancer. 1973;31:

1008-1014

2. Saarinen UM. Severe infections in childhood leukemia: a

follow-up study of 100 consecutive acute lymphoblastic leu-kemia patients. Acta Paediatr Scand. 1984;73:515-522 3. Bodey GR, Bolivar R, Fainstein V. Infectious complications

in leukemic patients. Semin HematoL 1982;19:193-226 4. Pizzo PA. Infectious complications in the child with cancer,

I: pathophysiology of the compromised host and the initial evaluation and management of the febrile cancer patient. J Pediatr. 1981;98:341-354

5. Pilworth JA, MandellGL. Infections in patients with cancer. Semin OncoL 1975;2:349-359

6. Marcy SM. Infections ofthe external ear. Pediatr Infect Dis. 1985;4:192-201

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ARTICLES 885 Am J Med. 1981;71:603-614

8. Chandler JR. Malignant external otitis: further considera-tions. Ann OtoL 1977;86:417-428

9. Sherman P, Black 5, Grossman M. Malignant external otitis due to Pseudomono.s aeruginosa in childhood. Pediatrics. 1980;66:782-783

10. Merritt WT, Bass JW, Bruhn FW. Malignant external otitis in an adolescent with diabetes. J Pediatr. 1980;96:872-873 11. Rubinstein E, Ostfeld E, Ben-Zaray 5, et al. Necrotizing

external otitis. Pediatrics. 1980;66:618-619

12. Sobie 5, Brodsky L Stanievich JF. Necrotizing external otitis in children: report of 2 cases and review of the litera-ture. Laryngoscope. 1987;97:598-601

13. Ichimura K, Hoshino T, Yano J, et al. Neutrophil disorder in a child with necrotizing external otitis. J OtolaryngoL 1983;12:129-133

14. Isenberg H. Indigenous and pathogenic microorganism in man. In: Blair JE, Lennette EH, Truant JP, eds. Manual of Clinical Microbiology. Bethesda, MD: American Society of Microbiology; 1970:35

15. Marcy SM. External otitis due to infection. Pediatr Infect Dis. 1985;4:S27-S30

16. Ostfeld E, Rubenstein E, Gazil E, et a!. Effect of systemic antibiotics on the microbial flora of the external ear canal in hospitalized children. Pediatrics. 1977;60:364-366

17. Chilcote RR, Baehner RL. Septicemia in association with acute lymphoblastic leukemia. J Pediatr. 1979;94:715-718 18. Bayardelle P, Jolivet-Granger M, Larochelle D.

Staphylo-coccal malignant external otitis. CMA J. 1982;126:155-156 19. Giguere P, ROUiIIard G. Otite exterme maligne bilaterale

chez une flilette de 10 ans. J OtolaryngoL 1976;5:159-166 20. Babiatzki A, Sade J. Malignant external otitis. J Laryngol

OtoL 1987;101:205-210

21. Cohen D, Friedman P, Elion A. Malignant external otitis versus acute external otitis. J Laryngol OtOL 1987;101:211-215

22. Cohen D, Friedman P. The diagnostic criteria of malignant external otitis. J Laryngol OtoL 1987;101:216-222

23. O’Sullivan TJ, Dickson RI, Blokmanis A. The pathogenesis, differential diagnosis and treatment of malignant otitis ex-terna. J OtolaryngoL 1978;7:297-303

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OPINION

FROM

GREAT

BRITIAN

CONCERNING

WITHDRAWAL

OF

TREATMENT

FROM

NEWBORN

INFANTS

Discussion and debate about decision making should form an important part of the continuing education of medical and nursing staff in neonatal units. Often it may be helpful to discuss cases which the staff have not been involved with the care of the baby and here film material can be valuable. Discussions with parents whose children died in the neonatal period or who survived with or without damage may be valuable, as are role play techniques. The aim of such continuing education is to improve decision-making practice in a situation where it is probably impossible to evolve specific guidelines to cover all even-tualities. If a decision has been taken to cease active treatment, it is then the responsibility of the staff to ensure that a baby dies quickly and as painlessly as possible.

Submitted by Student

From Richards MPM. Reflection on the withdrawal oftreatment from newborn infants. Early Hum Dev. 1989;18:263-272.

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1989;84;882

Pediatrics

Lawrence J. Wolff

Leukemia