The microbiology of chronic sinus disease in children with respiratory allergy

M. J. Goldenhersh, MD,* Gary S. Rachelefsky, MD,*

James Dudley, MD, *** Judith Brill, MD,* Roger M. Katz, MD,*

Albert S. Rohr, MD,** Sheldon L. Spector, MD,** Sheldon C. Siegel, MD,*

Paula Summanen,**** Ellen Jo Baron, PhD,*** **** and Sydney Finegold, MD,*** **** Los Angeles, Calif.

Chronic maxillary sinusitis is common in children with respiratory allergy and is associated with increased morbidity. The bacteriology of chronic sinus disease in these children has not been adequately evaluated. Between May 1987 and January 1988, 12 children (aged 3 to 9 years), all with documented respiratory allergy and chronic respiratory symptoms consistent with chronic sinusitis (>30 days), were fully evaluated. History, physical examination, complete blood count, nasal smear, and Waters x-ray were done. All patients had opactfication of one or both maxillary sinuses, failed to respond to multiple courses of antibiotics, and subsequently underwent maxillary sinus aspiration and irrigation. Specimens were cultured for aerobic and anaerobic organisms with standard technique, and sensitivities were obtained. Culture results revealed a single organism (Moraxella [Brauhamella] catarrhahs) in five patients, one patient yielded M. catarrhalis plus Streptococcus species, three were negative, and three patients grew multiple organisms (two with multiple aerobic streptococcal species and one patient with aerobic streptococci and Peptostreptococcus). All children received appropriate culture-directed antimicrobial therapy. Sequential biweekly follow-up revealed progressive radiographic clearing and significant symptomatic improvement. M. catarrhahs is a common pathogen, whereas anaerobic organisms are unusual as a cause of chronic maxillary sinusitis in allergic children. Some children, despite negative cultures, may benejt from maxillary sinus irrigation. (J ALLERGY CLIN IMUUNOL 1990;85:1030-9.)

Studies have revealed a 53% prevalence of abnor- mal sinus radiographs in allergic children with chronic respiratory symptoms. ’ Despite the surprisingly high incidence of sinus disease in such children, the bac- teriology of chronic sinus disease in children with respiratory allergy has not been adequately evaluated.

Cultures of normal sinuses probably do not yield bacteria.’ Previous bacteriologic studies of acute sinus disease in children have demonstrated Streptococcus pneumoniae, Haemophilus injluenzae, and Moraxella

From the Departments of *Pediatrics, **Medicine, and ***Head and Neck Surgery, University of California-Los Angeles, and the ****Veterans Administration Wadsworth Medical Center, Los Angeles, Celif.

Supported by grants from the Allergy Research Foundation, Inc., Los Angeles, Calif., and Eli Lilly & Co. Research Laboratories, Indianapolii, Ind.

Received for publication July 24, 1989. Revised Jan. 23, 1990. Accepted for publication Feb. 7, 1990. Reprint requests: Gary S. Rachelefsky, MD, 11645 Wilshire Blvd.,

Suite 600, Los Angeles, CA 90025. 111/2o08!J

1030

Abbreviations used IV: Intravenous

TSBV: Trypticase-soy-bacitracin-vancomyciu

(Branhamella) catarrhalis as the predominant organ- isms, usually with a high percentage (40%) of negative cultures.3-6 Sinus cultures from adults with acute dis- ease most commonly yielded H. influenzae, S. pneu- moniae, viridans streptococci ad Staphylococcus au- reus.’ Although cultures of sinus material from adults with chronic sinus disease frequently have yielded anaerobes,’ including Bacteroides species, Veillonella species, as well as a-hemolytic streptococci and Co- rynebacterium species, and Brook9 consistently found anaerobes in cultures from children with chronic si- nusitis, little is known about the bacteriology of chronic childhood sinusitis in the allergic popu- lation.

Studies have demonstrated that antimicrobials

VOLUME 85 NUMBER 6

Microbiology of sinusitis 1031

appear to be effective in evoking a clinical and radiographic response in allergic as well as nonaller- gic children with both chronic and acute sinus dis- ease. lo, ” Amoxicillin is often recommended as the initial antimicrobial therapy for these infections. The emergence of increasing bacterial resistance, includ- ing the increase in P-lactamase-producing organisms, has made antimicrobial therapy more difficult. This study was performed in an attempt to identify both (1) the prevalent offending pathogens in sinus cavities of children with respiratory allergy and chronic si- nusitis and (2) effective first-line therapy for this syndrome.

MATERIAL AND fUlETHODS

Between May 1987 and January 1988, 12 children with known respiratory allergy (documented by history, physical examination, nasal eosinophilia, and positive IgE-mediated skin tests consistent with history) between the ages of 3 and 9 years were selected for study entry on the basis of history and (provided inclusion criteria were met) on the basis of an abnormal Waters radiograph. All children had a history of chronic respiratory symptoms, which included nasal dis- charge (any quality) and cough (daytime or nighttime). Other symptoms could include one or more of the following: headache, facial pain, change in taste or smell, and frequent throat clearing and/or wheezing. The following inclusion criteria were used: (1) symptoms for more than 30 days, (2) absence of documented temperature elevation within 1 week before the study, (3) no antimicrobial therapy for 1 week before the study, and (4) a Waters radiograph that demonstrated >SO% mucoperiosteal thickening, complete opacification, or an air-fluid level in one or both maxillary sinuses.

Each patient underwent an evaluation (Fig. I), in- cluding a comprehensive history, physical examination, and a variety of diagnostic tests (complete blood count with differential, quantitative immunoglobulins, IgG sub- classes, and nasal smear), and subsequent maxillary sinus aspiration/irrigation with appropriate bacteriologic culture and susceptibility testing. Each patient (and/or parent) completed a symptom questionnaire every 2 weeks during the study period based on daily symptoms during the time between study visits. Sign scores were assigned to each patient by the examining physician at each study visit (Ad- dendum 1). Each patient whose culture revealed an organism believed to be significant received treatment with an appro- priate antimicrobial regimen.

Bilateral maxillary sinus aspiration/irrigation was per- formed on each child in the treatment room of the outpatient ear, nose, and throat clinic at University of Califomia- Los Angeles. Appropriate cardiac monitoring was per- formed, and resuscitative equipment was available. The fol- lowing sedation protocol was performed by a pediatric anes- thesiologist (J. B.): (1) Children younger than 6 years of age received, either IV or intramuscularly, ketamine, with a small dose of midazolam. Recovery occurred within 10

to 15 minutes after an IV dose of ketamine, while recovery after intramuscularly administered ketamine required 20 to 25 minutes. The midazolam was used in addition to the ketamine to minimize any psychic sequeiae from the kc- tamine. There was complete amnesia, anesthesia, and an- algesia without respiratory depression, cardiovascular in- stability, or emergence reactions. (2) Children tjlder than 6 years of age were treated with IV drugs, including mida- zolam, a narcotic, and droperidol. Some patients were ad- ministered naloxone after the procedure to hasten emergence by reversing the effect of the narcotic. All patients were allowed to emerge from the analgesia in a quiet, nonstim- ulating environment to minimize adverse psychic seyuelae. Such sequelae were not observed in any patients treated with the above regimen. The children were discharged when they were fully awake and able to ambulate safe!-\. generally 20 to 30 minutes after the procedure.

After sedation, all patients received intranasal4% cocame instillation by cottonoid pledgets administered by a pediatric otolaryngologist (J. D.). A sterile antral puncture needle (16-gauge) was then used for entrance to each sinus (a separate needle for each side). The needle was directed to enter the maxillary sinus below the inferior turbmates in the inferior meatus. Sinus contents were aspirated intff a sterile syringe. The drained sinus cavity was subsequently irrigated with 3 to 5 ml of sterile physiologic saline. All aspiration and irrigation samples were labeled and immediately trans- ferred into anaerobic transport vials (Port-A-011 vial: BBL, Microbiology Systems, Tustin, Calif.) for maintenance of anaerobiosis during transportation. For comparative pur- poses, before disinfection of the nasal cavity. a swab culture was taken from both the right and left nasal cavities of several of the patients; swabs were transferred into tubes of prereduced, anaerobically sterilized agar with resazurin in- dicator (Port-A-Cl11 tubes; BBL). Aspirates were transported in Port-A-Cul tubes and cultured directly from fluid.

Bacteriologic evaluation

The samples were transported to the Veterans Ad- ministration Wadsworth Clinical Anaerobic Bacteri- ology Research Laboratory, usually within 2 hours of specimen collection, and the cultures were processed in an anaerobic chamber immediately on arrival at the laboratory. There is minimal loss of viability of or- ganisms up to 12 hours of delay between collection and specimen processing. 12, I3

Aliquots of 100 ~1 from the aspiration and irrigation samples were inoculated onto nonselective and selec- tive media, and an original Gram stain was performed. Aerobic media used were Brucella agar with 5% defibrinated sheep blood and without cysteine (BBL), pyridoxal-supplemented chocolate agar (BBL), phe- nylethyl alcohol agar (BBL), and trypticase-soy- bacitracin (75 U/ml)-vancomycin (5 *g/ml) agar.” TSBV was used to enhance isolation of Actinobacillus actinomycetemcomitans. All anaerobic media were supplemented with vitamin K, (10 &g/ml\ and hemin

1032 Goldenhersh et al. J. ALLERGY CLIN. IMMUNOL. JUNE 1990

Hx ch chronic sinusitis (a) Sx > 30 days (b) No ha. tehp. abx or steroid one dv

I + A/F level I I

\L + culture Abx treatment . . . bv sgls~uyltv

I 1 ik 14dayspostsinuspmcedwV 1

I I

4 week &it, PE. Waters x-ray

CBC = com#te blood count

sx = symptoms N/s =nadsmear Abx = antibiotics Hx = history

MIT = mucqeriateal thickening A/F=~flUikl F/u = follow up

FIG. 1. Chronic sinusitis evaluated.

(5 kg/ ml). Anaerobic media included nonselective Bacferoides sp, phenylethyl alcohol agar (BBL) and supplemented Brucella blood agar (BBL) for total bac- TSBV supplemented with vitamin K, and hemin for krial counts, Fusobucterium egg yolk agaP for iso- isolating and enumerating A. acetinomycetemcomi- lation of Fusobacterium sp, kanamycin (75 p,g/ml)- tuns and for most of the corroding organisms, such vancomycin (7.5 ~g/ml)-laked blood agaP for se- as the Bacteroides ureolyficus group. For nonselective lective isolation of pigmenting and nonpigmenting enrichment, > 100 ~1 of each aspiration and irrigation

VOLUME 65 NUMBER 6

Microbiology of sinur;itw ‘11033

TABLE 1. Study patient population

Patient Age Sex Aethma Prior antibiotics ~.---

Affected sinus

B. A.

C. M. D. B. IL’. F. D. T. E. M. E. T. J. K. J. I J. L. M. S. s. F.

9 5 9 5 3 5 8 4 5 3

5

M M M M M M M M F F M F

+

+

+ -

+ + + + -

+ -

+

C Boeh

K, Pz Both

A, C, Pz Bdi

Au. C. TS Rorf1

‘4, Au, C, TS Both

.4, c Both Au, E Both

A, E, TS Both

Au, A, C. K Both

A. K. Pz Both

Au, C, K, TS Ri@lt

A, Au, C, Pz Right

A. Amoxicillin; Au, amoxicillin clavulanate; C, cefaclor; E, erythromycin; K, cephalexin; Pz, erythromycin + sulfamethoxazole; 73, trimethoprim/ sulfamethoxazole.

sample was inoculated into 10 ml of supplemented thioglycollate broth.” For optimal recovery of bac- teria, nasal swabs were transferred into tubes con- taining 1 ml of sterile broth and thereafter vigorously agitated on a vortex mixer for 20 seconds.16 Aliquots of 100 ~1 of this fluid were inoculated directly onto a Brucellu blood agar and a chocolate agar plate for isolation of aerobic mucosal flora. Aerobic media were incubated at 37” C in air plus 5% CO1 for 2 days before primary examination, and reincubated for 7 days before discarding. Anaerobic media were incu- bated at 37” C in an anaerobic chamber (Coy Labo- ratory Products, Inc., AM Arbor, Mich.) for 5 days before examination, and reincubated and examined thereafter for up to 2 weeks. If no growth was recov- ered on primary plates after 7 days, the thioglycollate broth was examined and subcultured for presence of bacterial growth.

Identification. All colonies of different morphology were quantified and identified by standard morpho- logic and biochemical tests, including gas chromato- graphic analysis of metabolic end products, with methods outlined in the Wadsworth Anaerobic Bac- teriology Manual,15 the VP1 Manual,” and Bailey and Scott’s Diagnostic Microbiology. ‘*

Susceptibility testing. All isolates were tested for the presence of B-la&rmase with nitrocefin disks (Ce- finase; BBL) according to manufacturer’s instructions. Aerobic organisms were tested against amoxicillin plus clavulanic acid, erythromycin, cefazolin, and trimethoprim/sulfamethoxazole by the agar disk- diffusion method standardized by the National Com- mittee for Clinical Laboratory Standards. 19* z”

Radiography. A Waters view radiograph was used for the examination of the maxillary sinuses. Each sinus was evaluated separately by a radiologist blinded

to the randomization. The radiographs were classified as abnormal if there was at least 50% mucoperiosteal thickening, opacification, or an air-fluid level in one or both maxillary sinuses. Radiographs were done at initial study entry, 2 weeks after aspiration/irrigation procedure, and, if radiographs were still abnormal, at 4 weeks after sinus aspiration/irrigation. Seven chil- dren had three Waters radiographs, and five children had two Waters radiographs during the course of l’/z months.

This study was approved by the Human Subject Protection Committee at University of California- Los Angeles. Written informed consent was obtained from parents (and children).

RESULTS

The study population (Table I) consisted of 12 chil- dren aged 3 years to 9 years of age. There were nine boys and three girls. Nine of the children had asthma (documented by history and pulmonary function test- ing), and all children had allergic rhinitis. Eleven of the 12 subjects had received at least two antibiotics for 5 or more weeks. Ten of the 12 patients had bi- lateral radiographic sinus disease; two patients had isolated right-sided radiogmpbic sinus disease.

Bacterial culture and susceptibility results are sum- marized in Table II. The quantitative determination of bacterial recovery was performed from nonselective media; if an organism was isolated from t~~Iy~~late subculture only, the yield was considered to be < 10 colony-forming units per milliliter. Cram stains of the sinus aspirates were generally negative for bacteria. A total of five of 12 patients revealed a pure growth of M. catarrhalis, four of which were &&&art~ase positive. Four patients grew mixed species (one mixed M. catarrhdis and Streptococcus species ES, F.] and

1034 Goldenhersh et al. J. ALLERGY CLIN. IMMUNOL. JUNE 1990

TABLE II. Summary of cultures and sensitivities

Right Left Susceptibilities

Irrigation Irrigation Pt Aspirate fluid Aspirate fluid Cef Cefox E Aug TS A

B. A.

C. M.

D. B.

D. F.

D. T. E. M.

E. T.

J. K.

J. I.

J. L.

M. S. NSG NSG

S. F.

NW* NSG M. catarr M. catarr 20 cfdm 150 cfdml M. catarr M. catarr 90 cfulml 90 cfu/ml M. catarr M. catarr 280 cfu/ml 320 cfulml NSG NSG NSG NSG

vir strep----> 11,000 cfu/ml

M. catarr NSG 200 cfdrnl NSG NSG ND ND

M. catarr NSG 9ooo cfdml

(1000 S. mitis

NSG M. catarr 10 cfu/ml NSG

M. catarr 200 cfdml NSG NSG

NSG

M. catarr 3000 &l/ml NSG NSG

Peptostrep magnus

400 cflllml vir strep 300 cfLl/ml ND

NSG M. catarr 500 cfu/ml NSG

M. catarr 200 cfu / ml NSG

(3000 S. morb cfulml (1000 S. sanguis

(1000 group C Strep NSG

NSG M. catarr 100 cfdml scant specimen NSG

S

S

S

S S R

R I

R

S

S

(S to PenG)

S

ND

S

S

S

S R

R

S

S

S

S

S

S

S

S I

R

I

S

S

S

S

S

S

s s

I s S R R

S

S

R

s s

cfdml (1000 S. salivarius (3000 CN Staph

Pt. Patient; NSG, no significant growth; M. catarr, M. catarrhalis; Peptostrep, Peptostreptococcus; Strep, Streptococcus; cfu, colony- forming units; cef, cefazolin; cefox, cefoxitin; E, erythromycin; Aug, amoxicillin/clavulanate (Augmentin; Be&ham Products, Pittsburgh, Pa.); TS, trimethroprim/sulfamethoxazole; A, amoxicillin; vir, viridans; CN Staph, coagulase-negative StaphyZococcus; S. morb, Strep- tococcus morbillorum; S, susceptible; R, resistant; I, intermediate; Pen G, penicillin G.

*No significant growth (<50 cots/unless same organism was obtained in large numbers from another specimen from same source or P. acnes or coaguiase-negative Staphylococcus).

three mixed streptococcal species [E. M., E. T., and M. S.]). One of these patients (M. S.), who appeared to have an abscess, yielded Pepfosfrepfococcus mixed with viridans streptococcus. Three patients’ sinus cul- tures yielded no growth. All hf. catarrhalis strains were susceptible to cefoxitin, erythromycin, amoxi- cillin/clavulanate, and trimethoprim/ sulfamethoxa- zole. All patients with hf. catarrhalis had been treated with one or more of these antimicrobials. The sus- ceptibilities of the streptococci varied.

Occasional (four sinus specimens of 24) cultures also yielded low numbers of organisms that were con-

sidered to be possible contaminants. These included Propionibacterium acnes, coagulase-negative staph- ylococci, Actirwmyces odontolyticus, Stomatococcus, and < 10 colony-forming units per milliliter of Strep- tococcus morbillorum, S. sanguis, or S. salivarius.

Because of coordination problems, nasal swabs were obtained from only three patients. Cultures were procured in the procedure room immediately before antral puncture and lavage. Nasal swabs from two patients whose sinuses yielded mixed streptococci (mixed viridans streptococci or Peptostreptococcus and viridans streptococci) revealed viridans strepto-

VOLUME 85 NUMBER 6

Microbiology of sinusitis WEi

pLadamase Nasal swab culture

rasults

-t

-

+

ND ND

ND ND Right: negative Left: negative ND ND

Right: vir strep V Left: CN Staph ND

ND ND

Right: vir strep Left: vir strep

cocci. One patient whose sinus culture yielded pure M. ca$urrkLis had bilateral negative nasal cultures; however, psence of very low counts could have been overlooked because of possible loss of organisms on the swab or in the transport medium.16

The distribution of radiographic findings is sum- marized in Table III. In all patients, a gradual radio- logic clearing of opacification and a decrease in mu- coperioateal thickening occurred in the 4 weeks after sinus irrigation and (if this were indicated) antibiotic therapy.

Nasal smear findings confirmed what has been pub- lished in the past.‘, *’ The progression of macroscopic purulence and nasal polymorphonuclear leukocytosis pretmatment to predominant eosinophilia on posttreat- ment follow-up nasal cytology are presented in Table

IV. The presence of nasal bacteria visualized on smears also disappears after treatment, although it may take up to 4 weeks after irrigationitrerttment f’or a complete response.

“Symptom scores” (assessed every 2 weeks by pa- tient and parent), as well as “sign scores” (assessed every 2 weeks by a physician), revealed unanimous patient improvement after irrigation and treatment (Table V). The clinical response was marked and oc- curred rapidly (within 2 to 7 days) after sinus irrigation and treatment. There was a significant decrease in postnasal drip, cough, throat clearing, and wheezing. Sequential physical examinations revealed a decrease in purulent nasal discharge, nasal mucosal erythema, posterior pharyngeal cobblestoning, and wheezing; all these findings correlated with laboratory (radiograph and nasal smear and pulmonary function testing) im- provement

Quantitative immunoglobulins were normal in all patients studied with the exception of one patient who was found to have selective IgA deficiency. IgG sub- classes determined by immunoradiometric assay (Spe- cialty Laboratories, Inc., Santa Monica. Calif. j were also within normal limits for each study patient (data not presented).

All but three study patients received culture- directed treatment after irrigation. Seven patients re- ceived amoxicillin/clavulanate for 4 full weeks. One patient was treated with amoxicillin, and another pa- tient was treated with trimethoprimi sulfamethoxazole (amoxicillin/clavulanate not used because of penicil- lin allergy). All patients except two were asymptom- atic (symptoms defined as sinus related) by 2 weeks after the procedure. The remaining two patients were asymptomatic by 4 weeks after irrigation.

DISCUSSION

Our study was designed, first, to identify prevalent bacterial pathogens in chronic childhood sinusitis in patients with respiratory allergy and, second, to define effective therapy for such children.

There is a high incidence of chronic sinus disease in children with respiratory allergy.’ Studies of the bacteriology of acute childhood sinusitis have revealed approximately 60% culture positivity. S. pneumoniue, H. injuenzae, and M. catarrhalis have been found most frequently in cultures of pediatric acute sinus infection. Adult sinus disease (both acute and chronic) has also been extensively investigated. S. pneumo- niae, H. in.uenzae, viridans streptococci, and S. au- reus most commonly are implicated in acute adult sinusitis.” Anaerobes play a large role in chronic sinus disease in adults. Unusual sinus pathogens, such as

1036 Goldenhersh et al. J. ALLERGY CLIN. IMMUNOL. JUNE 1990

TABLE 111. Radiographic findings

Initial 2 Week 4 Week

PT R L R L R L

B. A. 6mm* OPT N$ N N N C. M. OP OP 6mm OP N N D. B. OP OP N N N N D. F. OP OP ND ND N N D. T. op 5mm OP N N N E. M. OP op ND ND 2mm N

E. T. 7mm 5mm ND ND 2mm N J. K. 6mm OP ND ND N N J. I. 6mm OP OP OP 3mm N J. L. OP OP 6mm 6mm 4mm 4mm M. S. OP smm ND ND 2mm N S. F. OP 4mm OP N 5mm N

Pt, Patient; R, right; L, left, ND, not done; OP, opacified completely; N, normal. *Millimeters, mucoperiosteal thickening.

TABLE IV. Nasal smear results

No. of

No. of subjacts Pos both EOS studied Pos PMNs only Pos EOS only and PMNs Pos bacteria

Initial 12 7 0 5 12 2 Weeks 9 3 3 3 3 4 Weeks* 9 1 6 0 0

Pos, Positive 1 10% of each of five high-powered fields; PMN, polymorphonuclear leukocyte; EOS, eosinophil. *Two patients had negative smears (no EOS, PMNs, or bacteria).

fungi or viruses, have been isolated infrequently. Very little has been known about the microbial etiology of chronic sinus disease in the allergic pediatric popu- lation. In fact, chronic sinusitis in childhood was largely assumed to be due to the same organisms that cause chronic sinus disease in adults, and Brook’s9 study supported this. According to our study results, however, and results reported by Tinkelman and Silk, this assumption may have been incorrect. In addition, Wald et alz3 studied 40 children who had chronic sinusitis without underlying allergic disease; the chil- dren ranged in age from 2 to 12 years, and the symp- toms had lasted more than 30 but less than 120 days. Sinus aspirations were positive in 30 (58%) of 52 sinuses obtained from 26 (65%) children. The bac- terial species recovered were S. pneumoniae, H. in- jhenzae, and M. catarrhulis. Some 25% of the iso- lates were p-lactamase producing, and no anaerobes were isolated.

Although our patient population was small and rep- resented a group of children with relatively resistant disease (five patients received two consecutive anti-

biotic courses [ ~2 weeks] and seven patients received at least three courses [of 2 to 3 weeks each] of different consecutive antibiotics before study entry), we be- lieved that they were representative of a large popu- lation of children observed in both the pediatrician’s and the allergist’s office who pose both a diagnostic and treatment dilemma. In reviewing our study patient population, it becomes obvious that most of the chil- dren received appropriate antibiotics before sinus ir- rigation but failed to improve. It also appears that despite radiographic opacification consistent with pa- tient symptomatology and physical examination, sinus aspiration may be negative. All patients (regardless of previous antibiotic therapy or sinus culture results) responded rapidly (both clinically and radiographi- tally) to sinus aspiration and mechanical irrigation with subsequent culturedirected antimicrobial treat- ment. Whether antimicrobial therapy is necessary af- ter sinus irrigation cannot be stated, since we did not include the appropriate control. It is possible that clin- ical response was due, in large part, to the mechanical irrigation and was independent of the subsequent an-

VOLUME 85 NUMBER 6

Microbiology of sinusilk 1037

TABLE V. Clinical symptom/sign score .-_-.I -___ _._.. - - ---

Initial 2 Week 4 Week .-_ .-----

Pt Symptom* Signt Symptom Sign Symptom Sign

B. A. 27 20 13 12 Y 7 C. M. 27 19 14 12 12 7 D. B. 22 26 14 12 1X 0 I). F. 21 24 12 9 14 $ D. T. 25 26 21 13 11 12

E. M. 24 23 13 10 14 I? E. T. 28 19 18 13 11 x J. K. 26 26 16 18 1.5 1 h J. I. 23 16 14 12 12 (4 J. L. 21 24 1.5 17 15 13 M. S. 27 18 15 16 11 i3 S. F. 24 22 16 9 14 t 3

-_lll- Pt, Patient. For scale, please refer to Addendum. *Symptoms include any or all of the following: cough. thick and/or colored nasal discharge, headache, wheezing, and facial sweHmg. Wgns include any or all of the following: nasal turbinate edema, postnasal drainage, orbital/facial tenderness/edema. nasal polyps.

wheezing, and otitis.

tibiotic treatment. Patient symptoms, physical ex- aminations (signs), and laboratory evaluation were useful gauges of response to surgical and antimicrobial therapy. As noted in previous studies,” asthma control was much more easily obtained after resolution of sinus symptoms.

Our study identified M. catarrhalis as the predom- inant bacterial pathogen in chronic sinusitis in children from 3 to 9 years in age with respiratory allergy. Interestingly, this is the same organism often impli- cated in both acute otitis and acute sinus disease and has been reportedly recovered in a variety of respi- ratory tract infections, including conjunctivitis, pneu- monia, tracheobronchitis, chronic otitis media, and recurrent tonsillitis.ze28 These data suggest that the antibiotic tmatment that our study population received before study entry did not alter the microbiology of their chronic sinus disease. Unlike adult chronic sinus disease and in contrast to Brook’s’ study cited earlier, anaerobic organisms were found to be unusual as a cause of chronic maxillary sinusitis in our study of allergic pe&atric population. This may reflect a dif- ference in the allergic pediatric patient, the effect of prior antimicrobial therapy, or problems relating to technique. it is not likely that Brook’s positive cultures represent “contamination” with normal nasal mucosal flora. The transport set ups and the culture media and procedures used regularly result in the recovery of fastidious anaerobes in the Wadsworth Laboratory. It is possible that the specimens were aerated during collection or placement into the transport set ups, but this appears unlikely because care was taken to avoid

this. It may be that residual cocaine exhibited an an- tibacterial effect. Furthermore, the mean age of our patients (5.7 years) was less than that in Brook’s study (11 years), and this difference, as also noted by Tin- kelman and Sib? earlier, may account for the differ- ences in bacteriologic fhrdings. The children that Tin- kelman and Silk6 studied were even ymger, and S. pnemoniae and H. infuenzae were the most com- monly isolated pathogens, especialiy in the age group 0 to 2 years. Because our patients had faiIed initially to respond to antibiotic therapy that was ultimately determined to be qpropriate by culture and sensitiv- ity, it may be that children with such “resistant” chronic maxillary sinusitis may, in some instances, benefit from manual irrigation preceding subsequent antimicrobial therapy.

The role of ethmoid disease and endoacopic surgery of the osteomeatal complex has recently received con- siderable attention, especially in adults. I=Iowever, our experience in children has been that chronic ethmoid disease is usually not present without chronic max- illary disease and that antral lavage of the maxillary sinus does provide benefit. The role of endoscopic surgery in children with chronic sinusitis awaits fur- ther clinical trials.

Our recommendation for treating allergic children with chronic sinus disease would be a 3-week trial of an antimicrobial agent (~xic~~~cl~v~l~ic acid, an oral cephalosporin [cefuroxime, or if the child can- not swallow a tablet, cefaclor], or erythrornycin and a sulfonamide administered together or as full separate daily doses). If the child fails to respond completely,

1038 Goldenhersh et al. J. ALLERGY CLIN. IMMUNOL. JUNE 1990

then a second 3-week trial of another antibiotic should be instituted. If clinical and laboratory responses are inadequate, we would then strongly urge considera- tion of mechanical sinus aspiration and lavage with appropriate cultures and antimicrobial therapy appro- priate for the organisms recovered.

Addendum

Symptomlsign questionnaire Symptoms

1. a. b. C.

d. e. f. lx, h. 1.

lf :

Headache Postnasal drip Jaw ache Toothache Facial pain Eye pain Ear pain, congestion, stuffiness Nasal obstruction Taste change Smell change Ear complaint(specify) No, 1; clear, 2; severe, 3

2. Rhinorrhea

3.

a. No, 1; clear, 2; thick, 3 b. Color: yellow, 1; green, 2; gray/white, 3 Cough a. No, 1; daytime, 2; nighttime, 3; day and

night, 4 b. Type: hacking, wet, productive, croupy, non-

4. productive, chesty

Fever

5.

6.

7.

a. No, 1; <lOl”, 2; >lOl”, 3 Sore, itchy or irritated throat a. No, 1; yes, 2 Epistaxis a. No, 1; yes, 2 Throat clearing

8. a. No, 1; yes, 2 Itchy palate

9.

10.

11.

12.

a. No, 1; yes, 2 Itchy nose a. No, 1; yes, 2 Wheezing a. No, 1; yes, 2 History of nasal polyps a. No, 1; yes, 2 Aspirin, yellow dye, or sodium benzoate sensitivity a. No, 1; yes, 2

Edema of the nasal turbinates a. Unilateral: 25%, 1; 50%. 2; 75%, 3; occluded, 4 b. Bilateral: 25%, 5; 5096, 6; 758, 7; occluded, 8 Postnasal drip a. No, 1; thin, 2; thick, 3 b. Color: yellow, 1; green, 2; gray/white, 3 Orbital or facial edema a. No, 1; maxillary, 2; frontal, 3; suborbital, 4; su-

praorbital, 5; glabella, 6; eyelid, 7

4. Tenderness a. No, 1; yes, 2

5. Nasal polyps

a. No, 1; yes, 2

6. Wheezing a. No, 1; yes, 2; with forced expiration, 3; inspi-

ration and expiration, 3 7. Otitis media

a. Serous or acute: No, 1; yes, 2 b. Unilateral, 1; bilateral, 2

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Rachelefsky GS, Katz RM, Siegel SC. Diseases of paranasal sinuses in children. In: Gluck L, ed. Current problems in pe- diatrics, vol 12, no. 5. Chicago: Year Book, 1982. Bjorkwall T. Bacterial flora of nose and maxillary sinus in normal and inflammatory conditions. Acta Oto-Lar 1950; 83:35-58. Wald ER, Milmor GJ, Bowen AI, et al. Acute maxillary si- nusitis in children. N Engl J Med 1981;304:749-54. Nylen 0, Jeppsson PH, Bransfor-Helander P. Acute sinusitis. Stand J Infect Dis 1972;4:43-9. Axelsson A, Brotaon JE. The correlation between bacterio- logical findings in the nose and maxillary sinus in acute max- illary sinusitis. Laryngoscope 1973;88:2003-11. Tinkelman DG, Silk HJ. Clinical and bacteriologic features of chronic sinusitis in children. Am J Dis Child 1989;143:938- 41. Evans FD, Sydnor JB, Moore WEC, et al. Sinusitis of the maxillary antrum. N Engl J Med 1975;293:735-9. Frederick J, Braude AI. Anaerobic infection of the paranasal sinuses. N Engl J Med 1974;290:135-7. Brook I. Bacteriologic features of chronic sinusitis in children. JAMA 1981;246:967-9. Rachelefsky GS, Katz RM, Siegel SC. Chronic sinus disease with associated reactive airway disease in children. Pediatrics 1984;73:526-9. Wald ER, Cliponis D, Ledesma-Medena J. Comparative ef- fectiveness of amoxicillin and amoxicillin-clavulanate potas- sium in acute paranasal sinus infections in children: a double- blind, placebo-controlled trial. Pediatrics. 1986;77:795-800. Brook I. Comparison of two transport systems for recovery of aerobic and anaerobic bacteria from abscesses. J Clin Microbial 1987;25:2020-2. Mena E, Thompson FS, Armtield AY, Dowel1 VR Jr, Reinhardt DJ. Evaluation of Port-A-Cul transport system for protection of anaerobic bacteria. J Clin Microbial 1978;8:28-35. Slots J. Selective medium for isolation of ActinobucilZus ac- tinomycetemcomitans. J Clin Microbial 1982;15:606-9. Sutter VL, Citron DM, Edelstein, Finegold SM. Wadsworth anaerobic bacteriology manual. 4th ed. Belmont, Calif.: Star Publishing, 1985. Hoffmann S, Jensen AM, Justesen T. The recovery of anaer- obic bacteria from swabs in three transport systems. Acta Pa- thol Mictobiol Immunol Stand [B] 1983;91:23-6. Holdeman LV, Cato EP, Moore WBC. Anaerobe laboratory manual. 4th ed. Blacksburg, Va.: VP1 Anaembc Laboratory, Virginia Polytechnic institute. and State University, 1977. Finegold SM, Baron El. Bailey and Scott’s diagnostic micro- biology. 7th ed. St. Louis: CV Mosby, 1986. National Committee for Clinical Laboratory Standards. Per- formance standards for antimicrobial disk susoeptibility tests, M2-A3, ~014, No. 16.3rd ed. Villanova, Pa.: NCCLS, 1984.

VOLUME 85 NUMBER 6

Microbiology of sinusitis

20. National Committee for Clinical Laboratory Standards. Per- formance standards for antimicrobial susceptibility testing, MlOOS2, vol 7, No. 10. Villanova, Pa.: NCCLS, 1987.

21. Jousimies-Somer HR, Savolainen S, Ylikoski J. Macroscopic pmulence, leukocyte counts, and bacterial morphotypes in re- lation to culture findings for sinus secretions in acute maxillary sinusitis. J Clin Microbial 1988;26: 1926-33.

22. Jousimies-Somer HR, Savolainen S, Ylikoski J. Bacteriolog- ical findings of acute maxillary sinusitis in young adults. J Clin Microbial 1988;26: 1919-25.

23. Wald ER, Byers C, Guerra N, Casselbrant M, Beste D. Sub- acute sinusitis in children. J Pediatr 1989;115:28-32.

24. Brook I, Pettit TH, Martin WJ, Finegold SM. Aerobic and

anaerobic bacteriology of acute conjunctivitis. .Ann t~phthalmol

1978;11:13-6. 25. Brook I. Prevalence of beta-lactamase-producing bacteria in

chronic suppurative otitis media. Am J Dis Child 1985;139: 280-3.

26. Brook I, Yocum P. Bacteriology of chronic tonsillitis in young adults. Arch Otolaryngol 1984;110:803-5.

27. Brook I, Yocum P, Friedman EM. Aerobic and anaerobic flora recovered from tonsils of children with recurrent tonsillitis. Ann Otol Rhino1 Laryngol 1981;90:261-3.

28. Brook I. Pathogenicity of Branhamellu cururr~li,s in respi- ratory tract infections. Immunol Allergy Pratt 19X8:2$-31

ison betaween RAsr em: A new autom

Jean Bwsqmet, MD, Pascal Chanez, MD, Isa Chad, MD, ad Franqois-B. Wtkhel, MD Montpellier, France

RAST represents the standard technique to titrate serum-spectjic IgE and was found to have u higher efjiciency in the diagnosis of &E-mediated allergy than other in vitro tests. Pharmacia CAP system (CAP) is a new solid-phase immunoassay, fUray automated, used for the titration oj specific IgE antibodies. Results are listed in kilounits per liter, equilibrated against the World Health Organization standard for IgE. RAST and CAP were compared in IO6 unselected patients (6 to 59 years) characterized by a detailed clinical history and skin prick tests with standardized allergen extracts. IgE to cat, Dermalophagoides pteronyssinus, Aiternaria, orchard grass, olive, and Parietaria pollen were tested; 470 tests were run. The specificity, sensitivity, and eflciency of both in vitro tests ranged from 85.5% to 100% except for olive pollen, in which the sensitivity of both in vitro tests was low (68.2% for the new test and 63.6% for RAST). Except for orchard-grass pollen, the sensitivity and specifiity of CAP were better than that of RAST. There was a highly significant correlation between both tests (r range, between 0.864 to 0.987). CAP competes favorably with RAST and has the advantage of being automated

and eliciting results in kilounits per liter. (J ALLERGY CLIN IMMJNOL 1990;85:1039-43. j

Specific serum IgE is widely used in the diagnosis of IgE-mediated allergic diseases. Although several techniques have been proposed within the past 10 years, RAST represents the standard technique. In-

From the Clinique des Maladies Respiratoires, Hopital I’Aigue- longue, Montpellier, France.

Received for publication April 17, 1989. Revised Jan. 23, 1990. Accepted for publication Jan. 31, 1990. Reprint requests: Jean Bousquet, MD, Clinique des Maladies Res-

pirataiis. Hop&al l’Aiguelongue, Avenue du Major Flandre, 34059, Montpellier Cedex, France.

111/20890

Abbreviations used CAP: Pharmacia CAP system

PRIST: Paper radioimmunosorbent test PRU: Pharmacia RAST unit

BU: Biological unit RIA: Radioimmunoassay

I

traduced in 1967 for the semiquantitative titration of allergen-specific IgE in serum,‘.2 RAST was improved during the years,3, 4 and its accuracy to diagnme spe- cific IgE was widely documented.‘. 6 However, in

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