Middle ear fluid bacteriology of acute otitis media in neonates and very young infants

Znl~rnationalJournal of Pediatric Qtorhinolaryngologv, 14 (1987) 141-150 Ekevier

141

POR 00473

Pekka I-I. Karma .

1*4,Juhani S. Pukand Vesikari 214and

Departments of’ Otolaryngologv, ’ Pediatrics and 3 Microbiology, Tampere University Central Hospital Tampere (Finland); and ’ Department of Clinical Sciences, University of Tampere, Tampere (Finland) (Received 39 February 1987) (Revised version received 20 August 1987) (Accepted 29 September 1987)

Key wor&: Acute otitis media; Bacteriology; Very young infant

The middle ear fluid ( EF) bacteriology of 107 attacks of acute otitis media (AOM) in 101 infants less than was analyzed. A total of 108 bact were isolated from 85 attacks. pathogens, S. pneumoniae (19%), in_dluenzoe(9%) or B. cafarrhalis (7%) were cultured in approximately one-third of all the attacks. S. aure~ (17%) and coagulase-negative staphylococci (22%) without the above pathogens were commonly found, whereas gram-negative enteric bacteria were culturable from ~1~~ i=uj Jc attacks. c Only 8% of the MEFs were polymicrobial. More than half of all the bacterial strains produced beta-lactamase. The bacteriology of those younger than one month was not different fro,m that of the others. The same was true with attacks of out-patients and in-patients, except for a larger proportion of beta-lactamase producing strains in in-patients. Nasal-nasopharyngeal and MEF samples showed the same bacteriology in only 20% of cases. Two-thirds of AOM attacks were present in infants with perinatal or other concomitant morbidity, but their bacteriology was not different from those without other morbidity. In addition to the examination of ears in infants presenting with any illness before the age of 3 months, the study stresses the importance of bacteriological analysis of MEF in all cases of AOM at this age.

Correspondence: P. Karma, Department of Clinical Sciences, University of Tampere, SF-33520 Tampere, Finland.

0165~5876/87/$03.50

Q 1987 Elsevier Science Publishers B.V. (Biomedical Division)

142

Introduction

Acute otitis media (AO&I) is a major disease problem in young children [5,15,17]. However, AOM is considered rarer in infants less than 3 months old [5], and consequently the information about AOM and its bacteriology in the youngest infants is fragmentary and conflicting [1,2,4,14,16,19].The purpose of this paper is to contribute to the bacteriology of AOM in neonates and infants less than 3 months of age as well as to describe the associations of AOM and its bacteriology with different clinical situations of these infants. Materials and Methods

The study soup consisted of 101 consecutive infants with available Pdwiw. data. They were diagnosed as having AOM under the age of 3 months while being treated or observed as in-patients (because of AOM Llr other reasons) in the Department of Pediatrics or while visiting as out-patients the Departments of Otolaryngology or Pediatrics at the Tampere University Central Hospital between January 1,198O and December 31,1985. Detailed data about the patients and their AOM attacks are presented in Table I. Of the total of 107 attacks, 21 were diagnosed and analyzed during antimicrobial treatment, which was penicillin V in 16 cases, amoxicillin and cephalosporins each in two, and erythromycin in one. In one case erythromycin treatment had ended two days earlier. For the clinical diagnosis of AOM, in addition to fluid in the middle ear (MEF), at least one of the following acute symptoms or signs had to be present: fever, TABLE I St&y material Characteristic

Number

Infants

10155 46 70 107 69 38 14 93 55 52 97 9 1 155 31

Males Females With other morbidity Attacks of AOM Bilateral Unilateral At < 1 month age At l-2 months age In out-patients In in-patients First attack * Second attack Third attack MEFs bacterinlogicdly analyzed During or less !han one week after antimicrobial treatment * No earlier c;.tic-ia history.

143

TABLE II Other morbidity in 101 infants with AOM at less than 3 months

of age -

Perinatalproblems

n

Concurrent illnesses at the time of A OM

n

Pneumonia Bronchitis Gastroententis .. Congenital heart disease Gastroesophageal reflux Atopic disease Congenital hip luxation Laryngitis Cleft lip Cleft palate Pyloric stenosis Renal hypoplasy Peesequinovarus Multiple anomalies Urinary tract infection Conjunctivitis Septicemia Hypogammaglobuhnemia Mental retardation

12 11 10 6 6 5 3 2 1 1 1 1 1 1 1 I 1 1 1

Total infants

48

Total infants with perinatal problems and/or concurrent illnesses

70

FoetaI distress Prematurity * Twin (fraternal) Asphyxia Maternal hepatosis SmaII for date Severe jaundice Hypoglycemia Placental ablation Polyhydramnion Polycythemia Seizures Postmaturity HyaIine membrane disease Septicemia FAS ViiaI meningitis Maternal toxemia Intrauterine pneumonia Total infants

8 7 3 6 3 3 2 2 1 1 1 1 1 1 1 1 1 1 1 40

* -z 38 gestational weeks.

prolonged crying, irritability, restless sleep, loss of appetite, or other simultaneous respiratory tract infection or concurrent gastrointestinal symptoms. In addition to ear-related data, perinatal or concurrent other morbidity was also recorded (Table II). a myringotomy or a tympanoMEF-studies. In all the t sterilizing the ear canal. The centesis was performed and specimens were processed and bacteriologically analyzed using routine bacteriological methods as described earlier [ll]. The beta-lactamase production of If. inflzccnzae (Hi), B. cutarrhalis (Br) and staphylococci was tested using the chromogenic cephalosporin [13] or the clover leaf [I21 method. In each case aii the isolated bacterial species were recorded. Altogether 155 MEF samples were studied. Additionally, in 69 cases a nasal or nasopharyngeal sample was simultaneously obtained from the same patient and studied bacteriologically. Statistical analyses were done using the @hi-square test or Fisher’s exact test.

A total of 108 bacterial strains were isolated from 85 attacks, 128 strains from 155 MEFs. As seen in Tables III and IV, the distribution of different bacteria was

144 TABLE III Middle ear fluid bacterioiogy of AOM in 101 infants less than 3 months of age Organism

S.pneunwniae H. injluenzae B. c~tarrkalis Enteric bacteria S. aureus S. coag. negat. Other + Negative

Attacks without All ears (MEFs) antimicrobials (153) (85)

AN attacks (107) N’

W

NZ

%

N’

%

N’

%

NZ

%

20 10 5 5 18 24 3 22

19 9 5 5 17 22 3 21

20 10 7 5 22 38 6 22

19 9 7 5 21 36 6 21

16 10 3 3 14 22 3 14

19 12 4 4 16 26 4 16

22 12 6 6 22 40 5 42

14 8 4 4 14 26 3 27

22 12 8 6 24 49 7 42

14 8 5 4 15 32 5 27

N’, from each attack/ear only one bacterial species, following the preference order of the list, is included. N*, from each attack/ear all different bacterial species are included. %, percentage of attacks/ears. * Includes: Candida albicans (41, a-haemolytic streptococcus (2) and ‘mixed flora’ (1).

about the same, regardless of the way the results are presented. Of the major AOM pathogens (Il), S. pnezrmo&e (Pn) seemed to be the most common, isolated in almost 20% of the cases. Hi was found in about lO%, and none of them was of type b. Bt was cultured in only about 5% of the attacks. Altogether these 3 bacteria were found in 33% of all the attacks of AOM and in 41% of the attacks with culturable bacteria. Without the concomitant growth of the above-mentioned pathogens, S. aurtws (Sta) was found in 17% and coagulase-negative staphylococci (Stn) in 22% of the instances. If all the different bacterial species isolated from one or both ears in each case were included, the proportion of the attacks with Sta remained about the same but that with Stn increased up to 34%. In all, 91% of all Sta and 85% of all Stn strains were cultured from the MEF as pure growth. Ciroup A or group B streptococci were not isolated in any case. Gram-negative enteric bacteria were culturable in 6 MEFs of 5 attacks, pseudomonas in 3 attacks, bilateral E. coli in one, and Klebsiella pneumoniae in one attack. In 23 (26%) of the attacks and 13 (8%) of the MEFs two or three (in 3 attacks) bacterial species could be isolated (Table IV). If Stn were excluded the respective proportions were only IO and 4%. If Sta were also excluded, they were 6 and 3%. Fifteen (31%) of the 48 attacks with bilaterally cultured MEFs showed differing bacteriology in the two ears. This was mainly due to the finding of Stn (8) or Sta (4) in only one of the two ears. Thus, if staphylococci were excluded, there were only 3 (6%) cases with differing bacteria in the two ears. About 20% of all the attacks and 25R UI the MEFs gave negative results in culture (Table III). In infants who were undei antimicrobial treatment at the time of diagnosis of AOM the MEF cultures were negative in 36% of the cases as compared to 16% (P c 0.05) in those who were not yet receiving antimicrobials. The distribution of different MEF bacteria in these two groups did not show significant differences. -’

145

TABLE IV EateraJity of middle ear-fluid culture findings in 10X infants with ACM at less than 3 months of age Au different bacterial species isolated from each ear are included.

Right ear MEF present 93 86 MEF cultured SR S. pneumoniue 13 15 H. influenzae 8 9 B. catarrhnlis 5 6 Enteric bacteria 4 5 S. aurezu 11 13 S. coag. iieg~t. 26 311 Other 3 3 Negative 23 27 Total bacteria cultured 70 1 strain 57 2 strains 5 3 strains 1 Bilateral attacks Bilateral cultures Same bacteria Both negative One ear negative Differing bacteriology (S. coag. negar. excluded)

Total

Lef ear 83 69 9 4 3 2 13 23 4 19 58 43 6 1

% 13 6 4 3 19 33 6 28

176 155 22 12 8 6 24 49 7 42 128 100 11 2 69 48

%I :4 8 5 4 15 32 5 27

29 21 19 31 (10)

%, Percentage of ears/attacks cultured.

Evidence of chlamydial infection was looked for in 27 cases. Six infants, l-2 months old, showed a suggestive rise in serum antibody titers; in two of these, ChZamydia trachomatis was also found in conjunctival culture. Fourteen of the 107 attacks of ACM occurred in neonates less than one month old (Table V). Six of these (43%) showed negative MEF cultures; 5 of them, however, being under antimicrobial treatment. Otherwise, the bacteriological findings of these infants did not show any specific features significantly different from those of older infants. Gram-negative enteric MEF bacteria were not found in any of the neonates. If all the 107 attacks were divided into those of out-patients and those diagnosed while staying in hospital as in-patients, some intergroup differences in the occurrence of different bacteria, as shown in Table VI, did not reach statistical significance. However, Sta and Stn as counted together were significantly more common (P < 0.01) in in-patients. Eighteen infants had a history of being treated in the intensive care unit (KU). However, only one case of AOM was diagnosed at that time; in all others the time interval between discharge from the KU and presentation with AOM was at least two weeks. Of enteric bacteria only E. coli was once fou&, in these infants. Also otherwise the occurrence of different bacteria in these a;oackx +?id not significantly differ from that found in other attacks.

146 TABLE V Middle ear fluid bacteria cultured from 107 attacks of AOM according to age In each case aII different bacterial species isolated from one or both ears are included.

.

I- 2 months (93)

n

%

n

%

1

7 14

19 8

20

14

5

5

0

0

5

5

S. coag negat.

2 3

14 21

20 35

22 38

Other Negative

0 6*

0 43

6 15 *

6 16

Organism -~. j. pneumoniae H. influenzae B. catarrhalis

Enteric bacteria S. aurcus

c 1 month (14)

2 2

9

* PcO.05.

In this series, 70 (69%) of the infants had perinatal problems or had some other illness concomitant to AOM (Table II). The MEF bacteriology of these cases did not differ significantly from that of other infants. Fifty-eight percent of all bacterial strains (enteric bacteri;) excluded) isolated from the MEFs produced beta-lactamase, and these strains were found in 56% of all the attacks (Table VII). Beta-lactamase producing strains seemed to be more common in the attacks of in-patients than of out-patients (74% vs 38% P < 0.001). Nasal-nasopharyngeal specimens showed culturable bacteria in 93% of the 69 infants studied. Br was the most frequent finding, found in about 25% of the infants (Table VIIi). From the simultaneous MEF specimens Br was isolated in only 4 infants (P c 0.001). On the contrary, Stn and negative culture, were more common in the MEFs than in nasal-nasopharyngeal specimens (P < 0.001 and P -c 0.05,

TABLE VI Middle ear fiuid bacteria cultured from 107 attacks of AOM in out-patients and in-patients iess than 3 months of age

In each case all different bacterial species, isolated from one or both ears, are included. Organism

S. pneumoniae H. influenzae B. catarrhaiis

Enteric bacteria S. aureus S. coag. negat.

Other Negative culture

Out-patients (55)

-

In-patients (52)

n

%

n

w

10 5 4 3 8 15 3 14

18 9 7 5 15 27 5 25

10

19 10 6 4 27 44 6 13

5 3 2 14 23 3 7

--_

147 TABLE VII Beta-lactamase producing middle earfluid bacterial strains in 102 * attacks of AOM in 97 infants less than 3 months of age Beta + /all, attacks with beta-lactamase Organism

producing strains/all

Out-patients (52) Beta + /all

In-patients (50) Beta + /all

H. influenzae o/5 3/5 ,R.catarrhahs 213 3/4 S aui-cu 6/7 13/13 S. coag. negat. 12/14 18/20 All 20/52 37/w * 5 Attacks with enteric bacteria are excluded.

attacks. Ail (105) Beta +/all

%

3/10 5/7 19/28 30/34 57/102

30 71 95 88 56

TABLE VIII Nasal-nasopharyngeal (NP) and middle ear fluid (MEF) culture findings in A Oh4 of 69 infants less than 3 months of age In each case all bacterial species isolated from NP and from one or both ears are included. Organism

S. pneumoniae H. injluenrae B. catarrhalis Enteric bacteria S. aureus S. coag. negat. Other Negative

NP

-. P

MEF

n

%

n

z

15 10 18 2 13 5 I6 * 5

22 14 26 3 19 7 23 7

9 9 5 3 15 27 3** 14

13 13 7 4 22 39 4 20

N.S. N.S. -z 0.01 N.S. N.S.

-c 0.001 -z 0.01 -z 0.05

* 6 Cases with ‘normal flora’, 6 with a-hemolytic streptococci, two with diphtheroids, two with moraxella sp. * * One case with a-hemolytic streptococcus, one with ‘mixed flora’, and one with Candida afbicans.

{respectively). Bacteriological findings in nasal-nasopharyngeal and middle ear fluid specimens were identical in 20% of the cases and entirely different in 68%.

iscussion In Finland AOM of infants younger than 3 months is mainly treated in pediatric or otolaryngological departments. Because in this geographic area an unselected majority of such cases visited our hospital, our patient material fairly well reflected the characteristics of AOM in this age group in Finland in gener . ms matef+d

also made it possible for us to compare the bacteriological and some other aspects of AOM among those who had acquired their AOM outside hospital with those whose AOM had been diagnosed while staying in hospital. In some earlier studies on the bacteriology of AOM we have presented the MEF culture results by presenting only one bacterial species (from one or both ears) in each case as the main culture finding [lO,ll], following a certain preference order of assumed pathogenic&y of MEF bacteria (see Table III). Although this way of presenting the results shows the real causative bacteriology of AOM fairly well in older children [ll], it may underestimate the occurrence of unusual bacteria or bacteria not regarded as major pathogens in AOM. Because in very young infants the causative bacteriology of AOM is suggested to differ from that of older children [5], in this study we mainly analyzed our culture results by recording from each case (attack), or from each ear (MEF), all different bacterid species isolated. In general, the bacterial species found were usually &hesame as they are in the AOM of older children. While the proportion of the 3 ‘major pathogens’, I%, Hi and Br, was somewhat smaller than in AOM in general [IO], the incidence of Sta and Stn seemed to be greater in infants less than 3 months of age than in older children of our earlier series with similarly obtained and anaiyz.ed MEF specimens [f&10,11]. Also in this study, we did not sterilize the ear canal before obtaining the MEF specimen. Thus a contamination of the sample by the organisms resikdingin the ear canal might be possible. On the other hand, even a thorough disinfection of the canal does not guarantee its sterility. Although staphylococci isolated ia the MEF may be ear canal contaminants, Sta [5,8,18] and even Stn [3,7,8] are also suggested, at least partly, to play some active role in otitis media. In this study, the majsrity of attacks with staphylococci (especially Sta) showed only this bacterial species in MEF culture(s). Oh the other hand, in the relatively few attacks with more than one bacterial species in the MEF(s), Stn, but not Sta, was very frequently one of the isolated. Thus, it seems that in AOM of infants, usually caused by one bacterial species only, staphylococci may play some role, although a part of them, especially Stn, may also be contaminants. However, the definite role of staphylococci in AOM of infants remains still uncertain and awaits further study. Gram-negative enteric bacteria are reported [14,16 191, evei: very frequently [4], to be culturable from the MEFs of AOM of very yo;;ng infants mainly during the first 6 weeks of life [1,16,19], and as in-patients [1,2,14], ared especially if they have spent some time after birth in newborn nurseries or intensive care units [2,5]. In addition to being the characteristic of these infants themselves, these bacteria may also be of environmental origin [20]. In this St?-<-Qonly 5 attacks with enteric bacteria were found, 3 from the MEFs of 5-7 we&-old out-patient:. nnd two from 7-9 week-old in-patients. Group B st reptococci, suggested to be the cause of some AOM attacks of this age [5,16,19], were not fc,is& in .this series. Thus, the occurrence of these unusual AOM bacteria in MEFs of these infants was rare. So, it may be that the effect of ‘environmental’ factors varies, and at least partly depends on the sterility, hygienic standards, and ways infants are cared for [20] and treated in different settings.

Althougb the occurrence of major pathogens was s ar in out- and in-patients, the bacteriology from the MEFs of in-patients was somewhat more staph$)coccal and more resistant. This may also suggest that either the hospital-associated (environmental?) factors have affected the bacteriology of our hospitalized infants, or thai this hind of bacteriology is associated with the clinical picture necessitating the hospitalization of certain infants. Anyhow, the later otitis-related history of infants was rather similar in both groups and thus not affected by these differences. The proportion of culture-negative attacks in this series was, in accordance with previous experience, smaller than reported in older children [W]. It may suggest tbat the infant’s general and local defence systems, systems maturing with age, were not yet so effective in destroying bacteria as in older children. On the other hand, in this very young age group maternal s may still help in ove~colmiiag the infection and in killing A history of perinatal problems or the presence of other concurrent illnesses was very common in infants wh’o develop AOM before the age of 3 months. Thus, it may be that very young Infants with these probtems are especially prone to AO although they seem not to acquire middle ear bacteria different fro se usually other infants. Although we did not study the incidence of A in infants es, the finding stresses the importance of routine ear examination ts hospitalized or seen as out-patients for any illness. trains in the The proportion of beta-lactamase prod this study was clearly greater than in the A of older childre to reflect the greater incidence of %a and Stn at this age. So, more than half of the attacks of AOM were associated with bacteria resistant to beta-lactam antibiotics, If even the majority of these bacteria are such as penicillin and amoxi antibiotics camok routinely be used as primary considered as pathogens, beta-lx treatment alternatives in this age grn47, Also the finding of uzusual, resistant organisms in scme MEFs suppork~ this view. Therefore, and because nasal or nasopharyngeal bacterial analyses seemed unreliable in the prediction of the bacteri etiology, the antimicrobial treatment of AOM at this age should always be based on bacteriological analysis of the MEF itself. The MEF specimen is easily obtained by myringotomy, which for therapeutic purposes can also be regarded as being a mandatory procedure in the treatment of acute otitis media of very young infants

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