BACTERIAL MENINGITIS IN CHILDREN

Transcription

1 162 BACTERAL MENNGTS N CHLDREN LeutenantColonel K. VERNONJONES, B.Sc., M.B., M.R.C.P., D.C.H., R.A.M.C. Brtsh Mltary Hosptal, Munster SUMMARY: Features of dagnoss, treatment and complcatons n bacteral menngts ll chldren are revewed, based on 4 years experence n B.A.O.R. Ths remans a serous lfe threatenng, comparatvely common dsease. Early dagnoss and vgorous treatment produce a successful outcome n most cases beyond the frst month or so of lfe. ntroducton Bacteral menngts remans a serous, lfe threatenng dsease commonly encountered n paedatrc practce overseas. n ths survey, aspects of t related to dagnoss, treatment and complcatons have been consdered, based on a revew of 71 cases collected n B.A.O.R. over the 4 year perod Neonatal menngts, presentng as t does separate problems pecular to the age group, has been delberately excluded. The dsease s an nflammatory process nvolvng the coverngs of the central nervous system, caused by the drect nvason of one or other of a varety of bactera. Although n theory at least, almost any organsm may cause menngts, n actual fact few are nvolved. Over the age of 2 to 3 months, the only common pathogens are the Menngococcus, Pneumococcus, and Haemophlus nfluenza. Table shows the pattern Organsm Table Bacteral dagnoss n 71 cases of purulent menngts. B.A.O.R Number of Number treated Age range M : F rato cases before dagnoss Menngococcus weeks5 years 21 : 14 Pneumococcus weeks3 years 8 : 3 Haemophlus nfluenzae 8 3 8' months6 years 4 : 4 Streptococcus months + 8 months 2 males, Mcrococcus years 1 male Ē. Col days 1 female Proteus Mrabls 1 5 days 1 male, None solated weeks 7 years 7 : 5 Totals days7 years 44 : 27 of bactera solated from our cases n B.A.O.R. A specfc bacteral dagnoss was made n 59 out of 71 cases, 54 of them beng due to these three organsms. The Menngococcus wasby far the commonest, accountng for 35 out of 59. Ths ncdence s dfferent from that n most of the recently publshed reports from the Western Hemsphere, where the Haemophlus nfluenza has taken over frst place n endemc nfectons (Wehrle, Mathes and Leedom 1969). J R Army Med Corps: frst publshed as /jramc on 1 January Downloaded from on 30 Aprl 2018 by guest.

2 K. VernonJones 163 A successful outcome n ths dsease depends upon a number of factors, but of paramount mportance are early dagnoss, and the rapd establshment of" an effectve therapeutc regme. ~he latter mples the correct choce of antbotc, and ts admnstraton n bg enough dosage, by the optmum route, for a long enough perod, together wth adequate supportve measures. Dagnoss After the frst few months oflfe, the clncal pcture of bacteral menngts n chldren s usually a remarkably constant c:md unform one. The domnatng feature s an acute, rapdly advancng nfectous llness, producng prostraton and a deteroratng level of conscousness n a matter of hours rather than days. Table ndcates the tme Table 11 Tme nterval between onset of llness and hosptal dagnoss Days of llness Number of cases Number gven treatment Number wth pror to dagnoss before dagnoss dentfed organsm 30 2 (6.6 per cent) 25 (1) (18.2 per cent) 19 (2) (57.1 per cent) 6 (3) (66.6 per cent) 5 (4) (66.6 per cent) 1 (1) (1) 8 1 Totals (1) nterval between the onset of the llness and a. frm hosptal dagnoss beng made n B.A.O.R. The majorty of cases were dagnosed wthn the frst 48 hours of llnessmost of them wthn the frst 24 hours. t s of nterest that although a number of cases were treated wth antbotcs at home pror to admsson to hosptal, ths dd not seem to have affected the faclty to solate an organsm from the cerebrospnal flud. The fgures n brackets n the fnal column of Table show the number wth dentfed organsms who receved such treatment. Vomtng s almost nvarable. All our cases, except one, vomted, usually persstently. f a chld:s febrle and unwell but has not vomted after some hours, menngts s unlkely, but f protracted vomtng ensues n a febrle chld, hosptal admsson should be sought, and menngts excluded by lumbar puncture. Neck stffness s nearly always pr~sent after the frst few months of lfe, but ts elucdaton may requre experence n handlng a sck and fractous chld. A petechal rash can be regarded as one of the most mportant physcal sgns n paedatrcs. t s frequently a feature of menngococcal septcaema, and occasonally appears when other organsms are nvolved. t may be so extensve as to be almost confluent, when recognton s hardly dffcult. However, t may be lmted to one or two 59 J R Army Med Corps: frst publshed as /jramc on 1 January Downloaded from on 30 Aprl 2018 by guest.

3 164 Bacteral Menngts n Chldren solated pn head szed petechae, and these must be searched for n a good lght, wth the chld naked. A cranal brut may be present. Mace, Peters and Mathes (l968) drew attenton to the mportance of cranal auscultaton as a dagnostc ad n purulent menngts. Lstenng over the anteror fontanelle and posteror temple regons, sgnfcant bruts were heard n 34 per cent of ther patents wth menngts, n three quarters of whom t had dsappeared by the 4th hosptal day. They commented that the recurrence of a brut after 6 days of treatment may ndcate a subdural effuson, perhaps assocated wth rased ntracranal pressure. Examnaton of the cerebrospnal flud (c.s.f.) wll confrm or exclude the dagnoss. Organsms were dentfed by Gram stan n 24 of our cases, and grown on culture n 59. Other stes from whch an organsm may be grown nclude the blood, throat and necrotc petechae. The whte'blood cell count n the c.s.f. s usually over 1000/mm 3, mostly polymorphs. The range may be great. n two of our cases, ntal c.s.f. examnaton revealed no cells, only to show a rse to over 1000/mm 3 wthn 2448 hours. The hghest fgure we encountered was over 18000/mm 3 There s frequently a rse n the WBC count n the c.s.f. over the frst few days, and ths should not be regarded as a falure of treatment. Proten levels may be as hgh as 1000 mg/loo ml, although ntal values appeared to carry no value n prognoss. A rsng proten level, however, n a chld not dong well, may be of serous sgnfcance. n recent years, estmaton of the level of the enzyme lactc dehydrogenase n the c.s.f. has been used as a dagnostc ad n dsorders of the central nervous system (Neches and Platt 1968). t has been suggested that values over 60 unts may. dfferentate bacteral from nonbacteral nflammaton of the mennges. n the four cases n whch ths enzyme was estmated, we obtaned values of 350, 20, 115, and 51 and were not mpressed that t offered any advance over other c.s.f. bochemcal estmates. Treatment n consderng treatment, antmcrobal ther~py s of course of outstandng mportance. Hstorcally the ntroducton of sulphonamdes produced the frst major drop n the mortalty due to the menngococcus. Ths was so effectve that the subsequent appearance of penclln dd not apprecably lower mortalty further. Penclln dd, however, sgnfcantly reduce the mortalty due to the pneumococcus, followng ts use n hgh dosage gven at frequent ntervals. After chloramphencol was ntroduced, t was shown to be the most effectve agent then avalable n treatng menngts due to H. nfluenza. Thus, the regme of trple therapy was evolved, gvng all three antbotcs (Sulphadazne, Penclln and Chloramphencol) ntally, pror to bacterologcal dentfcaton. Ths therapy could then be modfed f need be, accordng to the type and senstvty pattern of the. organsm solated. Ths proved hghly effectve, and was n general use for many years. Then, n the md 1960s, n a seres of artcles from Los Angeles, Wehrle and hs colleagues descrbed ther enormous experence n the antmcrobal treatment of bacteral menngts (vler, Thrupp and Leedom 1963, Mathes, Leedom and Thrupp 1965, Wehrle, Mathes and Leedom)969). J R Army Med Corps: frst publshed as /jramc on 1 January Downloaded from on 30 Aprl 2018 by guest.

4 They showed that: K. VernonJones 165 (a) Ampclln exhbted bactercdal actvty aganst the Menngococcus and Pneumococcus equal to that of penclln. (b) Ampclln was at least as effectve aganst H. nfluenza as Chloramphencol, on the bass of both n vtro and n vvo data. (c) Controlled trals faled to demonstrate that the addton of other antbotcs had been benefcal, and moreover, sngle drug therapy wth Anpclln was shown to be more effectve overall, wth the three common types of organsm, than a combnaton of Ampclln and Chloramphencal. These factors, together wth ts lack of toxcty, make Ampclln the logcal choce for therapy. Up to September 1971, only 7 cases of drug falure wth Ampclln n the treatment of H. nfluenzae menngts had been reported n the lterature (Schulknd, Altemeer. and Ayoub 1971). n all these cases the organsm showed n vtro senstvty to Ampclln and the explanaton of the falure 'could be that adequate therapeutc levels of the antbotc n the c.s.f. were not acheved (Coleman et al 1969). t should be used n hgh dosage, between mg per Kg body weght per 24 hours, and, at least untl the nfecton s under control, admnstered n 4 hourly LV. bolus njectons. Penclln, n frequent bg doses, may stll be used effectvely aganst the Menngococcus and Pneumococcus, but Sulphonamdes should not now be used. The Menngococcus s showng an ncreasng ncdence of resstance to these compounds, 6 of our 35 cases of Menngococcal menngts showng n vtro nsenstvty to sulphonamde. Supportve measures are mportant. These chldren are frequently shocked, wth a low arteral or venous blood pressure, and poor perpheral crculaton. They may be dehydrated and have electrolyte mbalance. They usually vomt most of what s gven to them by mouth n the early stages. They show mpared conscousness to a greater or lesser degree. For these reasons, and to provde the optmum route for the admnstraton of antbotcs, t s mandatory that these patents be gven LV. fluds, at least for the frst few days of treatment. t was noted long ago that " fts are as dangerous to the nfant as the toxaema of the nfecton, and ther preventon s mperatve". Phenobarbtone should be admnstered prophylactcally n all cases, and we saw no convulsons n any chld to whom ths had been gven from the begnnng. The role of sterods remans controversal. de Lemos and Haggerty (1969) reported the results of a controlled clncal tral on 117 patents over month of age wth bacteral menngts; 54 were gven methylprednsolone 40 mg LV. 6 hourly, and 63 gven a placebo soluton. The groups were comparable for age, sex and aetology. Treatment was otherwse the same. There was no sgnfcant dfference between the groups n tme requred for sterlzaton of the cerebrospnal flud, return of the proten and sugar to normal or ncdence of subdunl effuson. Two patents ded n the treatment and 1 n the control group. The mean tme of dsappearance of fever was shorter n the treatment group, but a hgher ncdence of neurologcal sequelae was seen n these patents. n 1967 a group from the John Hopkns Hosptal studed adrenal functon n 48 cases of menngts, prncpally by measurng endogenous plasma cortsol levels (Mgeon et al 1967). They showed that: J R Army Med Corps: frst publshed as /jramc on 1 January Downloaded from on 30 Aprl 2018 by guest.

5 166 Bacteral Menngts n Chldren (a) Most cases due to the Menngococcus and H. nfluenzae showed elevated cortsol levels. Twelve severely ll chldren showed extremely hgh levels. (b) Only 4 cases demonstrated lower than normal levels. Three of these ded wth menngococcal septcaema and adrenal haemorrhage. (c) Eght cases of menngococcal nfecton ded altogether. Seven showed extensve adrenal haemorrhage, and of these 3 had low cortsol levels (see above), three had normal levels and 1 slghtly above normal levels. From ths study t would appear that chldren who are very ll and recover, usually show hgh plasma cortsol levels, and that most of those who de do so wth low or normal levels. Two chldren out of the 71 ded. Outcome One was a neonate, who developed Proteus menngts on the ffth day of lfe and ded sx months later wth a mnute, grossly damaged bran. The other was a 3 month old nfant who ded a few hours after the onset of a flord WaterhouseFrederchsen Syndrome, and at post mortem had extensve blateral adrenal haemorrhages. A further chld, 3 months old at the tme of a Pneumococcal menngts, subsequently showed a slow pattern of motor development and mpared hearng. The remanng 68, as far as could be assessed at Outpatent follow up, made a full recovery, and were developng normally when last seen. Ths s not to say that some of the patents dd not suffer complcatons along the path to recovery. Fortunately, such serous ones as acute bran swellng, whch has appeared as a potent cause of death n the past, and sgnfcant blockage to the c.s.f. crculaton, were not seen. Convulsons were uncommon, and dd not occur n any case n whch routne antconvulsant therapy was gven from the begnnng. Four of our patents developed clncally detectable subdural effusons (5.6 per cent). Ths s a lower ncdence than n many reported seres, where fgures have been as hgh as 10 per cent (Wehrle, Mathes and Leedom 1969) and 17 per cent (de Lemos and Haggerty 1969). Although t s sad that wth adequate treatment of bacteral menngts the temperature returns to normal n most by the 6th day, we found that prolonged or recurrent fever was farly common. A temperature of OO F or over, recorded on at least two consecutve occasons, occurred after the 6th day n 18 of our patents, an ncdence of 25 per cent. There can be a number of reasons for ths elevated temperature. Perhaps the commonest cause s therapy that s contnued for too long (Leadng artcle 1971) (Fg. 1). Other reports, from Amerca, ndcate that phlebts from prolonged use of an.v. catheter may also be a frequent factor (Balagtas et al 1970). A revew of our cases, a hgh proporton of whom had prolonged LV. therapy, dd not reveal a relatonshp between the occurrence of fever and the presence of phlebts. A recent paper from Florda (Schulkng, Altemeer and Ayoub 1971) n comparng the clncal course of patents treated for H. nfluenzae menngts wth ether Ampclln or Chloramphencol, commented that the only sgnfcant dfference noted between the two groups was a prolonged fever at tmes n the Ampclln treated group. The. cause of ths was unknown, but t dd not ndcate. a falure of treatment (Fg. 2). J R Army Med Corps: frst publshed as /jramc on 1 January Downloaded from on 30 Aprl 2018 by guest.

6 ~.. ~. K. VernonJones Fg. 1. Case J.D. Recurrence of temperature on 9th day, whch subsequently settled after stoppng Ampclln. ~Of_."". '0411. _.!!!.0' 1.. H. M.,., Ya'llS,., : f. S" 6 '9,'0, " 'n,.11 ".,,.!/r.')., "!w &.' u U 12. b!.:~ ~,~ ;! l:~ :'~ ;~ ~ :'~ l~!~,~!,,,, ~~ ~,~ ''!102 :~ 102 ~,~ ;' ~~ M' "' ' \ 1 L. "\.1!. 39, l6 v 5 ~ , \, " 37' V,.,,, 70 ~ la ~,, "'" ' " 1 l6' J' ;'41 t O.cJ ~.~! ~jo., '~ '2 s:!~,',.,h tu W: 130 ~ 1' j;;! t.':! ~ l" 120 ~, J:,. ~ ::. ~ " 10 'V,~!n., "1>{ '" 1 60, so A), El,.. 1,, 0. VV l/ VVV VVVVVVVVV/V///VV/ V/V/ Fg. 2. Case M.H. Persstent fever for 7 days on Ampclln. Despte ncreased dosage of Ampclln, and the.addjtjon of Chloramphencol, fever perssted untl antbotcs stopped on 21st day. : 167 J R Army Med Corps: frst publshed as /jramc on 1 January Downloaded from on 30 Aprl 2018 by guest.

7 168 Bacteral Menngts n Chldren _. ~! N. G. 1_1~~~s., 2. :t ~ S",., '.., ~ ~~ ~1'2l!!. l!l~ ~ 12! ~~.',~, :' M', M' ~,~ M' :~,'" ::~::,~ ;':~!:,~ ; :l:~ ;,~ ~ ~~ l!!!tt,,~! l!! l!" lo.2 "c'~. ~!!,!,, 'U ~.1!., 1', '"'.H : r 1., ~ a" f! \,, 1 a \. ' r _L ~" 1" ", } "'.: : 37" ~., Lk!' b.'.l ~ ", [ 37 36".+~=:~ 'c r_[~: _ ::.,~ r ;; ~. J, ' 150 wo dj: _C ~ ': 1:10 ~ 'H lh. :"":'. " '.L,r '" +Y 1;_. : v 120 ~ ~! ' V 100 ~ '~~', _,;. r,~_or ".~' ;= OD,!. j._! "'''''''Cd ~ 1" ~! 10 '1;' :~ 60 j ~:.j). 50,_. 1; ".",,;,., 1 ; :10 20 ' ' ',.,, l<,., 10. VVVvV V V V V VVV V/V V 1/'/ VVV!/VV ld 1: V 5! 110 ~ 100 <:) 00 10! Fg. 3. Case G.N. Clncal and c.s.f. relapse whlst on Ampclln. r~1' tj;j.1'0. /vv/v!/vl/vvvvvvvvvvvvvvvv /vv Fg. 4. Case R.S. Subdural effuson. J R Army Med Corps: frst publshed as /jramc on 1 January Downloaded from on 30 Aprl 2018 by guest.

8 K. VernonJones.169 n all these crcumstances the mportant features are that the c1ncalcourse of the patent, and the laboratory fndngs of the cerebrospnal flud contllue progressvely towards normalty, ndcatng a favourable outcome. ntercurrent nfectons of the skn, respratory and urnary tracts can of course cause an elevaton of temperature, and these should be looked for. On the other hand f the patent s unwell, or the cerebrospnal flud fndngs are not returnng to normal, then a more serous cause must be consdered, such as a relapse of nfecton (Fg. 3, th~ only case to relapse on treatment n our seres) localsaton wth block or abscess formaton, tssue necross, subdural effuson (Fg. 4) or thrombotc phenomena. Clncopathologcal study has demonstrated that wdespread ntravascular coagulaton may occur n the WaterhouseF;rederchsen Syndrome (Fox 1971). Whether or not ths s the drect cause of the adrenal haemorrhage characterstc of ths dsorder has not been exactly determ'ned, although t undoubtedly contrbutes to the severe shock and haemorrhages. Heparn has been suggested as the logcal treatment when ths syndrome arses, and successful case reports of ts use have appeared n the lterature (Wlloughby, McMorrs and Goel 1972). REFERENCES BALAGTAS, R. C., LEVN, S., NELSON, K. E. and GUTOFF, S. P. (1970). J. Pedat. 77, COLEMAN, S. J., AULD, E. B:, CONNOR, J. D.,.RoSENMAN, S. B. and WARREN, G. H. (1969). J. Pedat. 74, 781. delemos, R. A., and HAGGERTY, R. J. (1969). Pedatrcs 44, 30. Fox, B. (1971). Arch. Ds. Chld. 46, 680. VLER, D., THRUPP, L. D. and LEEDOM, J. M. (1963). Antmcrobal Agents and Chemotherapy. LEADNG ARTCLE (1971). Brt. med. J., 474. MACE, J. W., PETERS, E. R. and MATHES, A. W. (1968). New Engl. J. Med. 278, MATHES, J. W., LEEDOM, J. M. and THRUPP, L. D. (1965). Antmcrobal Agents and Chemotherapy. MGEON, C. J.; KENNY, F. M., HUNG, W., and VORHESS, M. L. (1967). Pedatrcs 40, 163. NEcHES, W. and PLATT, M. (1968). Pedatrcs 41, SCHULKND, M. L., ALTEMEER, W. A. and AYOUB, E. M. (1971). Pedatrcs 48,411. WEHRLE, P. F., MATHES, A. W., LEEDOM, J. M. and VLER, D. (1967). Ann. N. Y. Acad. Sc. 145,488. WEHRLE, P. F., MATHES, A. W. and LEEDOM, J. M. (1969). Pedatrcs 44, 991. WLLOUGHBY, M. L. N., McMoRRS, S. and GOEL, K. M. (1972). Arch. Ds. Chld. 47, 324. J R Army Med Corps: frst publshed as /jramc on 1 January Downloaded from on 30 Aprl 2018 by guest.