ACUTE BACTERIAL MENINGITIS (LEPTOMENINGITIS) The Biology of Bacterial Meningiti The i!!e"iate effect of #acteria or other !icroorgani !

in the $#arachnoi" %ace i to ca$ e an infla!!atory reaction in the %ia an" arachnoi" a &ell a in the cere#ro %inal fl$i" (CS')( Since the $#arachnoi" %ace i contin$o$ aro$n" the #rain) %inal cor") an" o%tic ner*e ) an infecti*e agent gaining entry to any one %art of the %ace !ay %rea" ra%i"ly to all of it) e*en it !o t re!ote rece e + in other &or" ) !eningiti i al&ay cere#ro %inal( Infection al o reache the *entricle of the #rain) either "irectly fro! the choroi" %le,$ e or #y refl$, thro$gh the fora!ina of Magen"ie an" L$ ch-a( The fir t reaction to #acteria or their to,in i hy%ere!ia of the !eningeal *en$le an" ca%illarie an" an increa e" %er!ea#ility of the e *e el ) follo&e" hortly #y e,$"ation of %rotein an" the !igration of ne$tro%hil into the %ia an" $#arachnoi" %ace( The $#arachnoi" e,$"ate increa e ra%i"ly) %artic$larly o*er the #a e of the #rain+ it e,ten" into the heath of cranial an" %inal ner*e an") for a *ery hort "i tance) into the %eri*a c$lar %ace of the corte,( .$ring the fir t fe& "ay ) !at$re an" i!!at$re ne$tro%hil ) !any of the! containing %hagocyti/e" #acteria) are the %re"o!inant cell ( 0ithin a fe& "ay ) ly!%hocyte an" hi tiocyte increa e gra"$ally in relati*e an" a# ol$te n$!#er ( .$ring thi ti!e there i e,$"ation of fi#rinogen) &hich i con*erte" to fi#rin after a fe& "ay ( In the latter %art of the econ" &ee-) %la !a cell a%%ear an" $# e1$ently increa e in n$!#er( At a#o$t the a!e ti!e the cell$lar e,$"ate #eco!e organi/e" into t&o layer 2an o$ter one) 3$ t #eneath the arachnoi" !e!#rane) !a"e $% of ne$tro%hil an" fi#rin) an" an inner one) ne,t to the %ia) co!%o e" largely of ly!%hocyte ) %la !a cell ) an" !onon$clear cell or !acro%hage ( Altho$gh fi#ro#la t #egin to %roliferate early) they are not con %ic$o$ $ntil later) &hen they ta-e %art in the organi/ation of the e,$"ate) re $lting in fi#ro i of the arachnoi" an" loc$lation of %oc-et of e,$"ate( .$ring the %roce of re ol$tion) the infla!!atory cell "i a%%ear in al!o t the a!e or"er a they ha" a%%eare"( Ne$tro%hil #egin to "i integrate #y the fo$rth to fifth "ay) an" oon thereafter) &ith treat!ent) no ne& one a%%ear( Ly!%hocyte ) %la !a cell ) an" !acro%hage "i a%%ear !ore lo&ly) an" a fe& ly!%hocyte an" !onon$clear cell !ay re!ain in !all n$!#er for e*eral !onth ( The co!%letene of re ol$tion "e%en" to a large e,tent on the tage at &hich the infection i arre te"( If it i controlle" in the *ery early tage ) there !ay not #e any re i"$al change in the arachnoi"+ follo&ing an infection of e*eral &ee- 4 "$ration) there i a %er!anent fi#ro$ o*ergro&th of the !eninge ) re $lting in a thic-ene") clo$"y) or o%a1$e arachnoi" an" often in a"he ion #et&een the %ia an" arachnoi" an" e*en #et&een the arachnoi" an" "$ra( 'ro! the earlie t tage of !eningiti ) change are al o fo$n" in the !all5 an" !e"i$!5 i/e" $#arachnoi" arterie ( The en"othelial cell &ell) !$lti%ly) an"

cro&" into the l$!en( Thi reaction a%%ear &ithin 67 to 89 h an" increa e in the "ay that follo&( The a"*entitial connecti*e ti $e heath #eco!e infiltrate" #y ne$tro%hil ( 'oci of necro i of the arterial &all o!eti!e occ$r( Ne$tro%hil an" ly!%hocyte !igrate fro! the a"*entitia to the $#inti!al region) often for!ing a con %ic$o$ layer( Later there i $#inti!al fi#ro i ( Thi i a tri-ing feat$re of nearly all ty%e of $#ac$te an" chronic infection of the !eninge #$t !o t nota#ly of t$#erc$lo$ an" y%hilitic !eningiti (:e$#ner4 arteriti )( In the *ein ) &elling of the en"othelial cell an" infiltration of the a"*entitia al o occ$r( S$#inti!al layering) a occ$r in arteriole ) i not o# er*e") #$t there !ay #e a "iff$ e infiltration of the entire &all of the *e el( It i in *ein o affecte" that focal necro i of the *e el &all an" !$ral thro!#i are !o t often fo$n"( Cortical thro!#o%hle#iti of the larger *ein "oe not $ $ally "e*elo% #efore the en" of the econ" &ee- of the infection( The $n$ $al %ro!inence of the *a c$lar change !ay #e relate" to their anato!ic %ec$liaritie ( The a"*entitia of the $#arachnoi" *e el ) #oth of arteriole an" *en$le ) i act$ally for!e" #y an in*e t!ent of the arachnoi" !e!#rane) &hich i in*aria#ly in*ol*e" #y the infectio$ %roce ( Th$ ) in a en e) the o$ter *e el &all i affecte" fro! the #eginning #y the infla!!atory %roce 2an infectio$ *a c$liti ( The !$ch !ore fre1$ent occ$rrence of thro!#o i in *ein than in arterie i %ro#a#ly acco$nte" for #y the thinner &all an" the lo&er c$rrent (%o i#ly tagnation) of #loo" in the for!er( Altho$gh the %inal an" cranial ner*e are $rro$n"e" #y %$r$lent e,$"ate fro! the #eginning of the infection) the %erine$rial heath #eco!e infiltrate" #y infla!!atory cell only after e*eral "ay ( E,ce%tionally) in o!e ner*e ) there i infiltration of the en"one$ri$! an" "egeneration of !yelinate" fi#er ) lea"ing to the for!ation of fatty !acro%hage an" %roliferation of Sch&ann cell an" fi#ro#la t ( More often) there i little or no "a!age to ner*e fi#er ( Occa ionally cell$lar infiltration !ay #e fo$n" in the o%tic ner*e or olfactory #$l# ( The arachnoi" !e!#rane ten" to er*e a an effecti*e #arrier to the %rea" of infection) #$t o!e reaction in the $#"$ral %ace !ay occ$r ne*erthele ( $#"$ral eff$ ion )( Thi ha%%en far !ore often in infant than in a"$lt + accor"ing to Sne"e-er an" co&or-er ) a%%ro,i!ately 6; %ercent of infant &ith !eningiti &ho are le than <7 !onth of age "e*elo% $#"$ral eff$ ion ( A a r$le) there i no $#"$ral %$ ) only a yello&i h e,$"ate( In an e*en higher %ercentage of ca e ) !all a!o$nt of fi#rino$ e,$"ate are fo$n" in !icro co%ic ection that incl$"e the cranial an" %artic$larly the %inal "$ra( 0hen fi#rino%$r$lent e,$"ate acc$!$late in large 1$antitie aro$n" the %inal cor") it #loc- off the %inal $#arachnoi" %ace( :y"roce%hal$ i %ro"$ce" #y e,$"ate in the fora!ina of Magen"ie an" L$ ch-a or in the $#arachnoi" %ace aro$n" the %on an" !i"#rain) interfering &ith the flo& of CS' fro! the lateral rece e of the fo$rth *entricle an" ci terna !agna to the #a al ci tern an"

cere#ral con*e,itie ( In the later tage ) fi#ro$ $#arachnoi" a"he ion are an a""itional an" o!eti!e the !o t i!%ortant factor interfering &ith the circ$lation of CS'( An infre1$ent late e1$ela of #acterial !eningiti i chronic a"he i*e arachnoi"iti or chronic !eningo!yeliti ( In the early tage of !eningiti ) *ery little change in the $# tance of the #rain can #e "etecte"( Ne$tro%hil a%%ear in the =ircho&5Ro#in %eri*a c$lar %ace #$t enter the #rain only if there i necro i ( After e*eral "ay ) !icroglia an" a trocyte increa e in n$!#er) at fir t in the o$ter /one an" later in all layer of the corte,( The a ociate" ner*e cell change !ay #e *ery light( O#*io$ ly o!e "i or"er of the cortical ne$ron !$ t ta-e %lace fro! the #eginning of the infection to acco$nt for the t$%or) co!a) an" con*$l ion that are o often o# er*e") #$t e*eral "ay !$ t ela% e #efore any change can #e "e!on trate" !icro co%ically( It i $ncertain &hether the e cortical change are "$e to the "iff$ ion of to,in fro! the !eninge ) to a circ$latory "i t$r#ance) or to o!e other factor) $ch a increa e" intracranial %re $re( The afore!entione" change are not "$e to in*a ion of #rain $# tance #y #acteria an" ho$l" therefore #e regar"e" a a noninfectio$ ence%halo%athy( 0hen !acro%hage an" a trocyte are e,%o e" to en"oto,in in *itro) the cell ynthe i/e an" relea e cyto-ine ) the !o t i!%ortant of &hich are interle$-in < an" t$!or necro i factor( The e cyto-ine are #elie*e" to ti!$late an" !o"$late the local i!!$ne re %on e( In the early tage of !eningiti ) there !ay #e little change in the e%en"y!a an" the $#e%en"y!al ti $e + #$t in the later tage ) con %ic$o$ change are in*aria#ly fo$n"( The !o t %ro!inent fin"ing i infiltration of the $#e%en"y!al %eri*a c$lar %ace an" often of the #rain ti $e &ith ne$tro%hilic le$-ocyte an" later &ith ly!%hocyte an" %la !a cell ( There !ay #e "e 1$a!ation of e%en"y!al cell ( Microglia an" a trocyte %roliferate) the latter o!eti!e o*ergro&ing an" #$rying re!nant of the e%en"y!al lining( 0e #elie*e that the #acteria %a thro$gh the e%en"y!al lining an" et $% thi infla!!atory reaction( Thi e1$ence of e*ent i fa*ore" #y a "e*elo%ing hy"roce%hal$ ) &hich tretche an" #rea- the e%en"y!al lining( The glial change are econ"ary to "a!age of $#e%en"y!al ti $e ( Collection of $#e%en"y!al a trocyte %rotr$"e into the *entricle) gi*ing ri e to a gran$lar e%en"y!iti ) &hich) if %ro!inent) !ay narro& an" o# tr$ct the a1$e"$ct of Syl*i$ ( The choroi" %le,$ i at fir t conge te") #$t &ithin a fe& "ay it #eco!e infiltrate" &ith ne$tro%hil an" ly!%hocyte an" e*ent$ally !ay #e co*ere" &ith e,$"ate( A in the ca e of the !eningeal e,$"ate) ly!%hocyte ) %la !a cell ) an" !acro%hage later %re"o!inate( E*ent$ally there i organi/ation of the e,$"ate co*ering the %le,$ ( A any !eningiti #eco!e !ore chronic) the %ia5arachnoi" e,$"ate ten" to acc$!$late aro$n" the #a e of the #rain (#a ilar !eningiti )) o# tr$cting the flo& of CS' an" gi*ing ri e to hy"roce%hal$ ( The e,$"ate !ay al o encircle cranial ner*e an" lea" to focal ne$ro%athie (

The rea"er !ay 1$e tion thi long "igre ion into !atter that are !ore %athologic than clinical) #$t only a -no&le"ge of the !or%hologic feat$re of !eningiti ena#le one to $n"er tan" the clinical tate an" it e1$elae( The !eningeal an" e%en"y!al reaction to #acterial infection an" the clinical correlate of the e reaction are $!!ari/e" in Ta#le >95<) &hich ho$l" #e con $lte" together &ith thi ection(

Ta#le >95< Pathologic5clinical correlation in ac$te) $#ac$te) an" chronic !eningeal reaction

Ty%e of Bacterial Meningiti Al!o t any #acteri$! gaining entrance to the #o"y !ay %ro"$ce !eningiti ) #$t) a alrea"y note") #y far the !o t co!!on are :( infl$en/ae) N( !eningiti"i ) an" Stre%( %ne$!oniae) &hich acco$nt for a#o$t 8? %ercent of %ora"ic ca e ( Infection &ith L( !onocytogene i no& the fo$rth !o t co!!on ty%e of nontra$!atic or non $rgical #acterial !eningiti in a"$lt ( The follo&ing are le fre1$ent ca$ e @ Sta%h( a$re$ an" gro$% A an" gro$% . tre%tococci) $ $ally in a ociation &ith #rain a# ce ) e%i"$ral a# ce ) hea" tra$!a) ne$ro $rgical %roce"$re ) or cranial thro!#o%hle#iti + E( coli an" gro$% B tre%tococci in ne&#orn + an" the other Entero#acteriaceae $ch a Ale# iella) Prote$ ) an" P e$"o!ona ) &hich are $ $ally a con e1$ence of l$!#ar %$nct$re) %inal ane the ia) or h$nting %roce"$re to relie*e hy"roce%hal$ ( Rarer !eningeal %athogen incl$"e Sal!onella) Shigella) Clo tri"i$!) Nei eria gonorrhoeae) an" Acineto#acter calcoacetic$ ) &hich !ay #e "iffic$lt to "i ting$i h fro! :ae!o%hil$ an" Nei eria( In en"e!ic area ) !yco#acterial infection (to #e con i"ere" f$rther on) are a fre1$ent a tho e "$e to other #acterial organi ! ( They ha*e al o a $!e" greater i!%ortance in "e*elo%e" co$ntrie a the n$!#er of i!!$no $%%re e" %er on increa e ( E%i"e!iology Pne$!ococcal) infl$en/al (:( infl$en/ae)) an" !eningococcal for! of !eningiti ha*e a &orl"&i"e "i tri#$tion) occ$rring !ainly "$ring the fall) &inter) an" %ring an" %re"o!inating in !ale ( Each ha a relati*ely con tant yearly inci"ence)

altho$gh e%i"e!ic of !eningococcal !eningiti ee! to occ$r ro$ghly in <;5year cycle ( .r$g5re i tant train a%%ear &ith *arying fre1$ency) an" $ch infor!ation) gleane" fro! national $r*eillance re%ort i $e" #y the Center for .i ea e Control an" Pre*ention an" fro! re%ort of local health agencie ) are of great %ractical i!%ortance( :( infl$en/ae !eningiti ) for!erly enco$ntere" !ainly in infant an" yo$ng chil"ren) ha #een nearly eli!inate" in thi age gro$% a a re $lt of *accination %rogra! in "e*elo%e" co$ntrie ) It contin$e to #e co!!on in le "e*elo%e" nation an" i no& occ$rring &ith increa ing fre1$ency in a"$lt (in the Unite" State there are #et&een <9);;; an" <?);;; ca e each year)( Meningococcal !eningiti occ$r !o t often in chil"ren an" a"ole cent #$t i al o enco$ntere" thro$gho$t !$ch of a"$lt life) &ith a har% "ecline in inci"ence after the age of ?;( Pne$!ococcal !eningiti %re"o!inate in the *ery yo$ng an" in ol"er a"$lt ( Perha% the greate t change in the e%i"e!iology of #acterial !eningiti ) a i"e fro! the one relate" to :( infl$en/ae *accination) ha #een the increa ing inci"ence of no oco!ial infection ) acco$nting for 6; %ercent of ca e in large $r#an ho %ital (.$ran" an" colleag$e )+ gra!5negati*e #acilli an" ta%hylococc$ acco$nt for a large %ro%ortion of the e( Note&orthy i the re%ort of Sch$chat et al) &ho fo$n" that in <BB?) o!e ? year after the intro"$ction of the con3$gate :( infl$en/ae *accine) the o*erall inci"ence of #acterial !eningiti in the Unite" State ha" #een hal*e"( The yearly inci"ence rate (%er <;;);;;) of the re %on i#le %athogen no& are a follo& @ Stre%( %ne$!oniae) <(<+ Nei eria !eningiti"i ) ;(C+ gro$% B tre%tococc$ ) ;(>+ Li teria !onocytogene ) ;(9+ an" :( infl$en/ae) ;(9( Pathogene i The three !o t co!!on !eningeal %athogen are all inha#itant of the na o%haryn, in a ignificant %art of the %o%$lation an" "e%en" $%on anti%hagocytic ca% $lar or $rface antigen for $r*i*al in the ti $e of the infecte" ho t( To a large e,tent they e,%re their %athogenicity #y e,tracell$lar %roliferation( It i e*i"ent fro! the fre1$ency &ith &hich the carrier tate i "etecte" that na al coloni/ation i not a $fficient e,%lanation of infection of the !eninge ( 'actor that %re"i %o e the coloni/e" %atient to in*a ion of the #loo" trea!) &hich i the $ $al ro$te #y &hich #acteria reach the !eninge ) are o# c$re #$t incl$"e antece"ent *iral infection of the $%%er re %iratory %a age or) in the ca e of Stre%( %ne$!oniae) infection of the l$ng( Once #loo"5#orne) it i e*i"ent that %ne$!ococci) :( infl$en/ae) an" !eningococci %o e a $ni1$e %re"ilection for the !eninge ) altho$gh the %reci e factor that "eter!ine thi !eningeal locali/ation are not -no&n( 0hether the organi ! enter the CS' *ia the choroi" %le,$ or !eningeal *e el i al o $n-no&n( It ha #een *ario$ ly %o t$late" that the entry of #acteria into the $#arachnoi" %ace i facilitate" #y "i r$%tion of the #loo"5CS' #arrier #y tra$!a) circ$lating en"oto,in ) or an initial *iral infection of the !eninge (

A*en$e other than the #loo" trea! #y &hich #acteria can gain acce to the !eninge incl$"e congenital ne$roecto"er!al "efect ) cranioto!y ite ) "i ea e of the !i""le ear an" %arana al in$ e ) -$ll fract$re ) an") in ca e of rec$rrent infection) "$ral tear fro! re!ote !inor or !a3or tra$!a( Occa ionally a #rain a# ce !ay r$%t$re into the $#arachnoi" %ace or *entricle ) th$ infecting the !eninge ( The i olation of anaero#ic tre%tococci) Bacteroi"e ) Actino!yce ) or a !i,t$re of !icroorgani ! fro! the CS' ho$l" $gge t the %o i#ility of a #rain a# ce &ith an a ociate" !eningiti ( Clinical 'eat$re A"$lt an" Chil"ren The early clinical effect of ac$te #acterial !eningiti are fe*er) e*ere hea"ache) an" tiffne of the nec- (re i tance to %a i*e !o*e!ent on for&ar" #en"ing)) o!eti!e &ith generali/e" con*$l ion an" a "i or"er of con cio$ ne (i(e() "ro& ine ) conf$ ion) t$%or) an" co!a)( 'le,ion at the hi% an" -nee in re %on e to for&ar" fle,ion of the nec- (Br$"/in -i ign) an" ina#ility to co!%letely e,ten" the leg (Aernig ign) ha*e the a!e ignificance a tiff nec#$t are le con i tently elicita#le( Ba ically) all of the e ign are %art of a fle,or %rotecti*e refle,( Stiffne of the nec- that i %art of %aratonic or e,tra%yra!i"al rigi"ity ho$l" not #e !i ta-en for that of !eningeal irritation( The for!er i !ore or le e1$al in all "irection of !o*e!ent) in "i tinction to that of !eningiti ) &hich i %re ent only or %re"o!inantly on for&ar" fle,ion( .iagno i of !eningiti !ay #e "iffic$lt &hen the initial !anife tation con i t only of fe*er an" hea"ache) &hen tiffne of the nec- ha not yet "e*elo%e") an" &hen there i only %ain in the necor a#"o!en or a fe#rile conf$ ional tate or "eliri$!( Al o) tiffne of the nec- !ay not #e a%%arent in the "ee%ly t$%oro$ or co!ato e %atient or in the infant) a in"icate" f$rther on( The y!%to! co!%ri e" #y the !eningitic yn"ro!e are co!!on to the three !ain ty%e of #acterial !eningiti ) #$t certain clinical feat$re an" the etting in &hich each of the! occ$r correlate !ore clo ely &ith one ty%e than another( Meningococcal !eningiti ho$l" al&ay #e $ %ecte" &hen the e*ol$tion i e,tre!ely ra%i" ("eliri$! an" t$%or !ay $%er*ene in a !atter of ho$r )) &hen the on et i atten"e" #y a %etechial or %$r%$ric ra h or #y large ecchy!o e an" li*i"ity of the -in of the lo&er %art of the #o"y) &hen there i circ$latory hoc-) an" e %ecially "$ring local o$t#rea- of !eningiti ( Since a %etechial ra h acco!%anie a%%ro,i!ately ?; %ercent of !eningococcal infection ) it %re ence "ictate i!!e"iate in tit$tion of anti#iotic thera%y) e*en tho$gh a i!ilar ra h !ay #e o# er*e" &ith certain *iral (EC:O5B an" o!e other entero*ir$ e an" rarely &ith other #acterial !eningiti"e ) a &ell a Sta%h( a$re$ infection ( Pne$!ococcal !eningiti i often %rece"e" #y an infection in the l$ng ) ear ) in$ e ) or the heart *al*e ( In a""ition) a %ne$!ococcal etiology ho$l" #e $ %ecte" in alcoholic ) in %lenecto!i/e" %atient ) in the *ery el"erly) an" in tho e &ith rec$rrent #acterial !eningiti ) "er!al in$ tract ) ic-le cell ane!ia

(Da$to %lenecto!i/e"E)) an" #a ilar -$ll fract$re( :( infl$en/ae !eningiti $ $ally follo& $%%er re %iratory an" ear infection in the chil"( Other %ecific #acterial etiologie are $gge te" #y %artic$lar clinical etting ( Meningiti in the %re ence of f$r$nc$lo i or follo&ing a ne$ro $rgical %roce"$re ho$l" rai e the %o i#ility of a coag$la e5%o iti*e ta%hylococcal infection( =entric$lo*eno$ h$nt ) in erte" for the control of hy"roce%hal$ ) are %artic$larly %rone to infection &ith coag$la e5negati*e ta%hylococci( :I= infection) !yelo%roliferati*e or ly!%ho%roliferati*e "i or"er ) "efect in cranial #one (t$!or) o teo!yeliti )) collagen "i ea e ) !eta tatic cancer) an" thera%y &ith i!!$no $%%re i*e agent are clinical con"ition that fa*or in*a ion #y $ch %athogen a Entero#acteriaceae) Li teria) A( calcoacetic$ ) P e$"o!ona ) an" occa ionally #y %ara ite ( 'ocal cere#ral ign in the early tage of the "i ea e) altho$gh el"o! %ro!inent) are !o t fre1$ent in %ne$!ococcal an" :( infl$en/ae !eningiti"e ( So!e of the tran itory focal cere#ral ign !ay re%re ent %o tictal %heno!ena (To""4 %araly i )+ other !ay #e relate" to an $n$ $ally inten e focal !eningiti 2for e,a!%le) %$r$lent !aterial collecte" in one yl*ian fi $re( Sei/$re are enco$ntere" !o t often &ith :( infl$en/ae !eningiti ( Altho$gh ei/$re are !o t fre1$ent in infant an" chil"ren) it i "iffic$lt to 3$"ge their ignificance) ince yo$ng chil"ren !ay con*$l e &ith fe*er of any ca$ e( Per i tent focal cere#ral le ion or intracta#le ei/$re ) &hich "e*elo% !o t often in the econ" &ee- of the !eningeal infection) are ca$ e" #y an infectio$ *a c$liti ) a "e cri#e" a#o*e2$ $ally &ith occl$ ion of $rface cere#ral *ein 2an" infarction of cere#ral ti $e( Cranial ner*e a#nor!alitie are %artic$larly fre1$ent &ith %ne$!ococcal !eningiti ) the re $lt of in*a ion of the ner*e #y %$r$lent e,$"ate an" %o i#ly i che!ic "a!age a the ner*e tra*er e the $#arachnoi" %ace( Infant an" Ne&#orn Ac$te #acterial !eningiti "$ring the fir t !onth of life i ai" to #e !ore fre1$ent than in any $# e1$ent >;5"ay %erio" of life( It %o e a n$!#er of %ecial %ro#le! ( Infant ) of co$r e) cannot co!%lain of hea"ache) tiff nec- !ay #e a# ent) an" one ha only the non %ecific ign of a y te!ic illne 2fe*er) irrita#ility) "ro& ine ) *o!iting) con*$l ion 2 an" a #$lging fontanel to $gge t the %re ence of !eningeal infection( Sign of !eningeal irritation "o occ$r) #$t only late in the co$r e of the illne ( A high in"e, of $ %icion an" li#eral $ e of the l$!#ar %$nct$re nee"le are the -ey to early "iagno i ( L$!#ar %$nct$re i cr$cial) an" it !$ t #e %erfor!e" #efore any anti#iotic are a"!ini tere" for other neonatal infection ( An anti#iotic regi!en $fficient to control a e%tice!ia !ay allo& a !eningeal infection to !ol"er an" to flare $% after anti#iotic thera%y for the y te!ic infection ha #een "i contin$e"( A n$!#er of other fact a#o$t the nat$ral hi tory of neonatal !eningiti are note&orthy( It i !ore co!!on in !ale than in fe!ale ) in a ratio of a#o$t >@<( O# tetric a#nor!alitie in the thir" tri!e ter (%re!at$re #irth) %rolonge" la#or)

%re!at$re r$%t$re of fetal !e!#rane ) occ$r fre1$ently in !other of infant &ho "e*elo% !eningiti in the fir t &ee- of life( The !o t ignificant factor in the %athogene i of the !eningiti i !aternal infection ($ $ally a $rinary tract infection or %$er%eral fe*er of $n-no&n ca$ e)( The infection in #oth !other an" infant i !o t often "$e to gra!5negati*e entero#acteria) %artic$larly E( coli) an" gro$% B tre%tococci an" le often to P e$"o!ona ) Li teria) Sta%h( a$re$ or e%i"er!i"i (for!erly al#$ )) an" gro$% A tre%tococci( Analy i of %o t!orte! !aterial in"icate that in !o t ca e infection occ$r at or near the ti!e of #irth) altho$gh clinical ign of infection !ay not #eco!e e*i"ent $ntil e*eral "ay or a &ee- later( In infant &ith !eningiti ) one ho$l" #e %re%are" to fin" a $nilateral or #ilateral $#"$ral eff$ ion regar"le of #acterial ty%e( Fo$ng age) ra%i" e*ol$tion of the illne ) lo& %oly!or%hon$clear cell co$nt) an" !ar-e"ly ele*ate" %rotein in the CS' correlate &ith the for!ation of eff$ ion ) accor"ing to Sne"e-er an" co&or-er ( Al o) the e attri#$te greatly increa e the li-elihoo" of the !eningiti #eing a ociate" &ith ne$rologic ign ( Tran ill$!ination of the -$ll i the i!%le t !etho" of "e!on trating the %re ence of an eff$ ion) #$t CT canning an" MRI are the "efiniti*e "iagno tic te t ( 0hen a %irate") !o t of the eff$ ion %ro*e to #e terile if the %atient i re %on"ing &ell to anti#iotic thera%y( If reco*ery i "elaye" an" ne$rologic ign %er i t) a $cce ion of a %iration i re1$ire"( In o$r e,%erience an" that of other ) %atient in &ho! !eningiti i co!%licate" #y $#"$ral eff$ ion are no !ore li-ely to ha*e re i"$al ne$rologic ign than tho e &itho$t eff$ ion ( S%inal 'l$i" E,a!ination A alrea"y in"icate") the l$!#ar %$nct$re i an in"i %en a#le %art of the e,a!ination of %atient &ith the y!%to! an" ign of !eningiti or of any %atient in &ho! thi "iagno i i $ %ecte"( Bactere!ia i not a contrain"ication to l$!#ar %$nct$re( If there i clinical e*i"ence of a focal le ion &ith increa e" intracranial %re $re) then CT canning of the hea" or MRI) loo-ing for a !a le ion) i a %r$"ent fir t te%) #$t in !o t ca e thi i not nece ary an" ho$l" not "elay the a"!ini tration of anti#iotic ( The "ile!!a concerning the ri - of %ro!oting tran tentorial or cere#ellar herniation #y l$!#ar %$nct$re) e*en &itho$t a cere#ral !a ) a in"icate" in Cha%( 9 an" Cha%( <8) ha #een ettle" in fa*or of %erfor!ing the ta% if there i a rea ona#le $ %icion of !eningiti ( The highe t e ti!ate of ri - co!e fro! t$"ie $ch a tho e of Rennic-) &ho re%orte" a 6 %ercent inci"ence of &or ening a!ong 66? chil"ren $n"ergoing l$!#ar %$nct$re for the "iagno i of ac$te !eningiti ( It !$ t #e %ointe" o$t that a cere#ellar %re $re cone !ay occ$r in f$l!inant !eningiti in"e%en"ent of l$!#ar %$nct$re+ therefore the ri - of the %roce"$re i %ro#a#ly e*en le than $ $ally tate"(

The %inal fl$i" %re $re i o con i tently ele*ate" (a#o*e <7; !!:9O) that a nor!al %re $re on the initial l$!#ar %$nct$re in a %atient &ith $ %ecte" #acterial !eningiti rai e the %o i#ility that the nee"le i %artially occl$"e" or the %inal $#arachnoi" %ace i #loc-e"( Pre $re o*er 6;; !!:9O $gge t the %re ence of #rain &elling an" the %otential for cere#ellar herniation( Many ne$rologi t fa*or the a"!ini tration of intra*eno$ !annitol if the %re $re i thi high) #$t thi %ractice "oe not %ro*i"e a $rance that herniation &ill #e a*oi"e"( A %leocyto i i "iagno tic( The n$!#er of le$-ocyte in the CS' range fro! 9?; to <;;);;; %er c$#ic !illi!eter) #$t the $ $al n$!#er i fro! <;;; to <;);;;( Occa ionally) in %ne$!ococcal an" infl$en/al !eningiti ) the CS' !ay contain a large n$!#er of #acteria #$t fe& if any ne$tro%hil for the fir t fe& ho$r ( Cell co$nt of !ore than ?;);;; %er c$#ic !illi!eter rai e the %o i#ility of a #rain a# ce ha*ing r$%t$re" into a *entricle( Ne$tro%hil %re"o!inate (7? to B? %ercent of the total)) #$t an increa ing %ro%ortion of !onon$clear cell i fo$n" a the infection contin$e ) e %ecially in %artially treate" !eningiti ( In the early tage ) caref$l cytologic e,a!ination !ay "i clo e that o!e of the !onon$clear cell are !yelocyte or yo$ng ne$tro%hil ( Later) a treat!ent ta-e effect) the %ro%ortion of ly!%hocyte ) %la !a cell ) an" hi tiocyte tea"ily increa e( The %rotein content i higher than 6? !gG"L in !ore than B; %ercent of the ca e + in !o t it fall in the range of <;; to ?;; !gG"L( The gl$co e content i "i!ini he") $ $ally to a concentration #elo& 6; !gG"L) or le than 6; %ercent of the #loo" gl$co e concentration (!ea $re" conco!itantly) %ro*i"e" that the latter i le than 9?; !gG"L( :o&e*er) in aty%ical or c$lt$re5negati*e ca e ) other con"ition a ociate" &ith a re"$ce" CS' gl$co e ho$l" #e con i"ere"( The e incl$"e hy%oglyce!ia fro! any ca$ e+ arcoi"o i of the CNS+ f$ngal or t$#erc$lo$ !eningiti + an" o!e ca e of $#arachnoi" he!orrhage) !eningeal carcino!ato i ) che!ically in"$ce" infla!!ation fro! cranio%haryngio!a or terato!a) or !eningeal glio!ato i ( Gra! tain of the %inal fl$i" e"i!ent %er!it i"entification of the ca$ ati*e agent in !o t ca e of #acterial !eningiti + %ne$!ococci an" :( infl$en/ae are i"entifie" !ore rea"ily than !eningococci( S!all n$!#er of gra!5negati*e "i%lococci in le$-ocyte !ay #e in"i ting$i ha#le fro! frag!ente" n$clear !aterial) &hich !ay al o #e gra!5negati*e an" of the a!e ha%e a #acteria( In $ch ca e ) a thin fil! of $ncentrif$ge" CS' !ay len" it elf !ore rea"ily to !or%hologic inter%retation than a !ear of the e"i!ent( The co!!one t error in rea"ing Gra!5 taine" !ear of CS' i the !i inter%retation of %reci%itate" "ye or "e#ri a gra!5%o iti*e cocci or the conf$ ion of %ne$!ococci &ith :( infl$en/ae( The latter organi ! !ay tain hea*ily at the %ole ) o that they re e!#le gra!5%o iti*e "i%lococci) an" ol"er %ne$!ococci often lo e their ca%acity to ta-e a gra!5%o iti*e tain( C$lt$re of the %inal fl$i") &hich %ro*e to #e %o iti*e in 8; to B; %ercent of ca e of #acterial !eningiti ) are #e t o#taine" #y collecting the fl$i" in a terile t$#e an"

i!!e"iately inoc$lating %late of #loo") chocolate) an" MacCon-ey agar+ t$#e of thioglycolate (for anaero#e )+ an" at lea t one other #roth( The a"*antage of $ ing #roth !e"ia i that large a!o$nt of CS' can #e c$lt$re"( The i!%ortance of o#taining #loo" c$lt$re i !entione" #elo&( The %ro#le! of i"entifying ca$ ati*e organi ! that cannot #e c$lt$re") %artic$larly in %atient &ho ha*e recei*e" anti#iotic ) !ay #e o*erco!e #y the a%%lication of e*eral %ecial la#oratory techni1$e ( One of the e i co$nteri!!$noelectro%hore i (CIE)) a en iti*e techni1$e that %er!it the "etection of #acterial antigen in the CS' in a !atter of >; to C; !in( It i %artic$larly $ ef$l in %atient &ith %artially treate" !eningiti ) in &ho! the CS' till contain #acterial antigen #$t no organi ! "etecte" on a !ear or gro&n in c$lt$re( Se*eral !ore recently "e*elo%e" erologic !etho" ) ra"ioi!!$noa ay (RIA) an" late, %article aggl$tination (LPA)) a &ell a an en/y!e5lin-e" i!!$no or#ent a ay (ELISA)) !ay #e e*en !ore en iti*e than CIE( An arg$!ent ha #een !a"e that the e %roce"$re are not co t5effecti*e) ince2in *irt$ally all in tance in &hich the #acterial antigen can #e "etecte"2the Gra! tain al o ho& the organi !( O$r en e i that the !ore e,%en i*e te t are till of o!e a i tance) %artic$larly if the Gra! tain i "iffic$lt to inter%ret an" one or !ore "o e of anti#iotic ren"er the c$lt$re negati*e( Gene a!%lification #y the %oly!era e chain reaction (PCR) i the !o t recently "e*elo%e" an" !o t en iti*e techni1$e( A it #eco!e !ore &i"ely a*aila#le in clinical la#oratorie ) ra%i" "iagno i !ay #e facilitate" (.e forge + Na#er)) #$t the $ e of caref$l Gra!5 tain %re%aration till nee" to #e enco$rage"( Mea $re!ent of chlori"e concentration in the CS' are not *ery $ ef$l) #$t they are $ $ally fo$n" to #e lo& (le than 8;; !gG"L)) reflecting "ehy"ration an" lo& er$! chlori"e le*el ( In contra t) CS' lactate "ehy"rogena e (L.:)) altho$gh !ea $re" infre1$ently) can #e of "iagno tic an" %rogno tic *al$e( A ri e in total L.: acti*ity i con i tently o# er*e" in %atient &ith #acterial !eningiti + !o t of thi i "$e to fraction 6 an" ?) &hich are "eri*e" fro! gran$locyte ( 'raction < an" 9 of L.:) &hich are %re $!a#ly "eri*e" fro! #rain ti $e) are only lightly ele*ate" in #acterial !eningiti #$t ri e har%ly in %atient &ho "e*elo% ne$rologic e1$elae or later "ie( Ly o/y!al en/y!e in the CS'2"eri*e" fro! le$-ocyte ) !eningeal cell ) or %la !a2!ay al o #e increa e" in !eningiti ) #$t the clinical ignificance of thi o# er*ation i $n-no&n( Le*el of lactic aci" in the CS' ("eter!ine" #y either ga chro!atogra%hy or en/y!atic analy i ) are al o ele*ate" in #oth #acterial an" f$ngal !eningiti"e (a#o*e >? !gG"L) an" !ay #e hel%f$l in "i ting$i hing the e "i or"er fro! *iral !eningiti"e ) in &hich lactic aci" le*el re!ain nor!al( Other La#oratory 'in"ing In a""ition to CS' c$lt$re ) #loo" c$lt$re ho$l" al&ay #e o#taine" #eca$ e they are %o iti*e in 6; to C; %ercent of %atient &ith :( infl$en/ae) !eningococcal) an" %ne$!ococcal !eningiti ) an" they !ay %ro*i"e the only "efinite cl$e a to the ca$ ati*e agent( Ro$tine c$lt$re of the oro%haryn,

are a often !i lea"ing a they are hel%f$l) #eca$ e %ne$!ococci) :( infl$en/ae) an" !eningococci are co!!on inha#itant of the throat of healthy %er on ( In contra t) c$lt$re of the na o%haryn, !ay #e hel%f$l in "iagno i ) tho$gh often not in a ti!ely &ay+ the fin"ing of enca% $late" :( infl$en/ae or gro$%a#le !eningococci !ay %ro*i"e the cl$e to the etiology of the !eningeal infection( Con*er ely) the a# ence of $ch a fin"ing %rior to anti#iotic treat!ent !a-e an :( infl$en/ae an" !eningococcal etiology $nli-ely( The le$-ocyte co$nt in the #loo" i generally ele*ate") an" i!!at$re for! are $ $ally %re ent( Meningiti !ay #e co!%licate" after e*eral "ay #y e*ere hy%onatre!ia) the re $lt of ina%%ro%riate ecretion of anti"i$retic hor!one (A.:)( Ra"iologic St$"ie In %atient &ith #acterial !eningiti che t fil! are e ential #eca$ e they !ay "i clo e an area of %ne$!oniti or a# ce ( Sin$ an" -$ll fil! !ay %ro*i"e cl$e to the %re ence of cranial o teo!yeliti ) %arana al in$ iti ) !a toi"iti ) or cranial o teo!yeliti ) #$t the e tr$ct$re are #etter *i $ali/e" on CT can ) &hich ha*e $%%lante" con*entional fil! in !o t ca e ( The CT can i %artic$larly $ ef$l in "etecting le ion that ero"e the -$ll or %ine an" %ro*i"e a ro$te for #acterial in*a ion) $ch a t$!or or in$ &all "efect ) a &ell a in "e!on trating a #rain a# ce or $#"$ral e!%ye!a( MRI &ith ga"olini$! enhance!ent !ay "i %lay the !eningeal e,$"ate an" cortical reaction) an" #oth ty%e of i!aging) &ith a%%ro%riate techni1$e ) &ill "e!on trate *eno$ occl$ ion an" a"3acent infarction ( Rec$rrent Bacterial Meningiti Thi i o# er*e" !o t fre1$ently in %atient &ho ha*e ha" o!e ty%e of *entric$lo*eno$ h$nting %roce"$re for the treat!ent of hy"roce%hal$ or &ho ha*e an inco!%letely clo e" "$ral o%ening after $rgery( 0hen the rec$rrence i of ina%%arent origin) one ho$l" al&ay $ %ect a congenital ne$roecto"er!al in$ or a fi t$lo$ connection #et&een the na al in$ e an" the $#arachnoi" %ace( The fi t$la in the e latter ca e i !ore often tra$!atic than congenital in origin (a %re*io$ #a ilar -$ll fract$re)) altho$gh the inter*al #et&een in3$ry an" the initial #o$t of !eningiti !ay #e e*eral year ( The ite of tra$!a i in the frontal or eth!oi" in$ e or the cri#rifor! %late) an" Stre%( %ne$!oniae i the $ $al %athogen( Often it reflect the %re"o!inance of $ch train in na al carrier ( The e ca e $ $ally ha*e a goo" %rogno i + !ortality i !$ch lo&er than in or"inary ca e of %ne$!ococcal !eningiti ( CS' rhinorrhea i %re ent in !o t ca e of %o ttra$!atic !eningiti ) #$t it !ay #e tran ient an" "iffic$lt to fin"( S$ %icion of it %re ence i rai e" #y the recent on et of ano !ia or #y the occ$rrence of a &atery na al "i charge that i alty to the ta te an" increa e in *ol$!e &hen the hea" i "e%en"ent( One &ay of confir!ing the %re ence of a CS' lea- i to !ea $re the gl$co e concentration of na al ecretion + or"inarily they contain little gl$co e) #$t in CS' rhinorrhea the a!o$nt of gl$co e a%%ro,i!ate that o#taine" #y l$!#ar %$nct$re (t&o5thir" of the er$!

*al$e)( The ite of a CS' lea- can o!eti!e #e "e!on trate" #y in3ecting a "ye) ra"ioacti*e al#$!in) or &ater5 ol$#le contra t !aterial into the %inal $#arachnoi" %ace an" "etecting it a%%earance in na al ecretion or it ite of e,it #y CT canning( Thi te ting i #e t %erfor!e" after the ac$te infection ha $# i"e"( Per i tence of CS' rhinorrhea re1$ire $rgical re%air( .ifferential .iagno i The "iagno i of #acterial !eningiti i not "iffic$lt %ro*i"e" that one !aintain a high in"e, of $ %icion( All fe#rile %atient 2e*en tho e &ith lo&5gra"e fe*er an" tho e &ith only lethargy) hea"ache) or conf$ ion of $""en on et2 ho$l" #e $#3ecte" to l$!#ar %$nct$re) ince a "efiniti*e "iagno i of #acterial !eningiti can #e !a"e only #y e,a!ination of the CS'( It i %artic$larly i!%ortant to thin- of !eningiti in "ro& y) fe#rile) an" e%tic %atient in an inten i*e care $nit( O*er&hel!ing e% i it elf) or the !$ltiorgan fail$re that it engen"er ) !ay ca$ e an ence%halo%athy) #$t if there i a !eningiti ) it i i!%erati*e) in "eci"ing on the choice of anti#iotic ) to i"entify it early( The a!e can #e ai" for the conf$ e" alcoholic %atient( Too often the y!%to! are a cri#e" to alcohol into,ication or &ith"ra&al) or to he%atic ence%halo%athy) $ntil e,a!ination of the CS' re*eal a !eningiti ( Altho$gh thi a%%roach !ay re $lt in !any negati*e %inal fl$i" e,a!ination ) it i %refera#le to the con e1$ence of o*erloo-ing a #acterial !eningiti ( =iral !eningiti (&hich i far !ore co!!on than #acterial !eningiti )) $#arachnoi" he!orrhage) che!ical !eningiti (follo&ing l$!#ar %$nct$re) %inal ane the ia) or !yelogra%hy)) an" t$#erc$lo$ ) le%to %iral) arcoi") an" f$ngal !eningoence%haliti enter into the "ifferential "iagno i a &ell( Al o) a n$!#er of non#acterial !eningiti"e !$ t #e con i"ere" in the "ifferential "iagno i &hen the !eningiti rec$r re%eate"ly an" all c$lt$re are negati*e( Incl$"e" in thi gro$% are E% tein5Barr *ir$ (EB=) infection + BehHet "i ea e) &hich i characteri/e" #y rec$rrent oro%haryngeal !$co al $lceration) $*eiti ) orchiti ) an" !eningiti + o5calle" Mollaret !eningiti ) &hich con i t of rec$rrent e%i o"e of fe*er an" hea"ache in a""ition to ign of !eningeal irritation ("$e in !any ca e to her%e i!%le,) a "i c$ e" in Cha%( >>)+ an" the =ogt5Aoyanagi5:ara"a yn"ro!e) in &hich rec$rrent !eningiti i a ociate" &ith iri"ocycliti an" "e%ig!entation of the hair an" -in( The CS' in the e rec$rrent ty%e !ay contain large n$!#er of ly!%hocyte or %oly!or%hon$clear le$-ocyte #$t no #acteria) an" the gl$co e content i not re"$ce" ( ee "i c$ ion of chronic an" rec$rrent !eningiti on %age 877)( Carcino!ato$ an" ly!%ho!ato$ !eningiti rarely %re ent in the f$l!inant !anner of #acterial !eningiti ) #$t o!eti!e they "o) an" the CS' for!$la can #e i!ilar( Rarely) a f$l!inant ca e of cere#ral angiiti or intra*a c$lar ly!%ho!a &ill %re ent &ith hea"ache) fe*er) an" conf$ ion in con3$nction &ith a !eningeal infla!!atory reaction( The other intracranial $%%$rati*e "i ea e an" their "ifferentiation fro! #acterial !eningiti are con i"ere" f$rther on in thi cha%ter(

Treat!ent Bacterial !eningiti i a !e"ical e!ergency( The fir t thera%e$tic !ea $re are "irecte" to $ taining #loo" %re $re an" treating e%tic hoc- (*ol$!e re%lace!ent) %re or thera%y) an" choo ing an anti#iotic that i -no&n to #e #acterici"al for the e ta#li he" or $ %ecte" organi ! an" i a#le to enter the CS' in effecti*e a!o$nt ( Treat!ent ho$l" #egin &hile a&aiting the re $lt of "iagno tic te t an" ho$l" #e change" later in accor"ance &ith the fin"ing ( 0herea %enicillin for!erly $ffice" to treat al!o t all !eningiti"e ac1$ire" o$t i"e the ho %ital) the initial choice of anti#iotic ha #eco!e increa ingly co!%licate" a re i tant train of !eningitic #acteria ha*e e!erge"( The election of "r$g to treat no oco!ial infection %re ent %ecial "iffic$ltie ( In recent year ) !any re%ort ha*e "oc$!ente" an increa ing inci"ence of %ne$!ococcal i olate that al o ha*e a relati*ely high re i tance to %enicillin) reaching ?; %ercent in o!e E$ro%ean co$ntrie ( C$rrent e ti!ate are that in o!e area of the Unite" State ) <? %ercent of the e i olate are %enicillin re i tant to o!e "egree (!o t ha*e a relati*ely lo& le*el of re i tance)( In the <B8; ) the no& le fre1$ent :( infl$en/ae ty%e B train %ro"$cing #eta5lacta!a e) an" th$ re i tant to a!%icillin an" %enicillin) &ere recogni/e"( C$rrently >; %ercent of :( infl$en/ae i olate %ro"$ce the #eta5lacta!a e en/y!e) #$t al!o t all re!ain en iti*e to thir"5generation ce%halo %orin (cefo,ati!e) cefo%era/one) cefti/o,i!e) etc()( I olation fro! the #loo" or CS' of a highly re i tant organi ! re1$ire the $ e of ceftria,one) &ith the a""ition of *anco!ycin an" rifa!%in( N( !eningiti"e ) at lea t in the Unite" State ) re!ain highly $ ce%ti#le to %enicillin an" a!%icillin( The e regional *ariation an" ongoing anti#iotic5in"$ce" change in the infecting !icroorgani ! $n"er core the nee" for con tant a&arene of "r$g re i tance in the %hy ician4 local area) e %ecially in the ca e of %ne$!ococcal infection ( Thro$gho$t the co$r e of treat!ent) it i nece ary to ha*e acce to a "e%en"a#le la#oratory that can carry o$t ra%i" an" "etaile" "r$g5re i tance te ting( Reco!!en"ation for the in tit$tion of e!%iric treat!ent of !eningiti ha*e #een re*ie&e" #y I$agliarello an" Schel" an" are $!!ari/e" in !o"i5fie" for! in Ta#le >959( In chil"ren an" a"$lt ) thir"5 generation ce%halo %orin are %ro#a#ly the #e t initial thera%y for the three !a3or ty%e of co!!$nity5ac1$ire" !eningiti"e ( In area &ith $# tantial or increa ing n$!#er of high5le*el %enicillin5re i tant %ne$!ococci) con i"eration ho$l" #e gi*en to a""ing *anco!ycin an" rifa!%in $ntil the $ ce%ti#ility of the i olate i e ta#li he"( A!%icillin ho$l" #e a""e" to the regi!en in ca e of $ %ecte" Li teria !eningiti ( 0hen erio$ allergy to %enicillin an" ce%halo %orin %recl$"e their $ e) chlora!%henicol i a $ita#le alternati*e(

Ta#le >959 E!%iric thera%y of #acterial !eningiti

In ca e of !eningiti "$e to Sta%h( a$re$ ) incl$"ing tho e that occ$r after ne$ro $rgery or !a3or hea" in3$ry) a"!ini tration of *anco!ycin an" cefta/i"i!e i a rea ona#le fir t a%%roach( U%on "eter!ining the en iti*ity of the organi !) thera%y !ay ha*e to #e altere" or !ay #e i!%lifie" #y $ ing *anco!ycin or nafcillin alone( The reco!!en"e" "o age of the !a3or anti#iotic are gi*en in Ta#le >95>) an" the choice of anti#iotic for the o%ti!al treat!ent of %ecific #acterial i olate i gi*en in Ta#le >956(

Ta#le >95> Reco!!en"e" "o age of anti!icro#ial agent for #acterial !eningiti in a"$lt &ith nor!al renal an" he%atic f$nctiona

Ta#le >956 S%ecific anti!icro#ial thera%y for ac$te !eningiti

.$ration of Thera%y Mo t ca e of #acterial !eningiti ho$l" #e treate" for a %erio" of <; to <6 "ay e,ce%t &hen there i a %er i tent %ara!eningeal foc$ of infection( Anti#iotic ho$l" #e a"!ini tere" in f$ll "o e %arenterally (%refera#ly

intra*eno$ ly) thro$gho$t the %erio" of treat!ent( Treat!ent fail$re &ith certain "r$g ) nota#ly a!%icillin) !ay #e attri#$ta#le to oral or intra!$ c$lar a"!ini tration) re $lting in ina"e1$ate concentration in the CS'( Re%eate" l$!#ar %$nct$re are not nece ary to a e the effect of thera%y a long a there i %rogre i*e clinical i!%ro*e!ent( The CS' gl$co e !ay re!ain lo& for !any "ay after other ign of infection ha*e $# i"e" an" ho$l" occa ion concern only if #acteria are %re ent in the fl$i" an" the %atient re!ain fe#rile an" ill( Prolongation of fe*er or the late a%%earance of "ro& ine or he!i%are i ho$l" rai e the $ %icion of $#"$ral eff$ ion) !a toi"iti ) in$ thro!#o i ) cortical *ein or 3$g$lar %hle#iti ) or #rain a# ce + all re1$ire that thera%y #e contin$e" for a longer %erio"( Bacteriologic rela% e after treat!ent i "i contin$e" re1$ire i!!e"iate rein tit$tion of thera%y( Cortico teroi" Early controlle" t$"ie "e!on trate" no #eneficial effect of cortico teroi" in the treat!ent of %yogenic !eningiti ( More recent t$"ie ha*e re5e*al$ate" the thera%e$tic *al$e of "e,a!etha one in chil"ren &ith !eningiti ( Altho$gh !ortality &a not affecte") fe*er $# i"e" !ore ra%i"ly an" the inci"ence of en orine$ral "eafne an" other ne$rologic e1$elae &a re"$ce") %artic$larly in tho e &ith :( infl$en/ae !eningiti ( On the e gro$n" ) it i reco!!en"e" that the treat!ent of chil"hoo" !eningiti incl$"e "e,a!etha one in high "o e (;(<? !gG-g fo$r ti!e "aily for 6 "ay )) in tit$te" a oon a %o i#le( Analogo$ "ata in neonate an" a"$lt are lac-ing( Ne*erthele ) &e fa*or the $ e of cortico teroi" in ca e &ith o*er&hel!ing infection at any age (*ery high CS' %re $re or ign of herniation) high CS' #acterial co$nt &ith !ini!al %leocyto i ) an" ign of ac$te a"renal in $fficiency) i(e() the 0aterho$ e5'ri"erich en yn"ro!e)( Other 'or! of Thera%y There i no e*i"ence that re%eate" "rainage of CS' i thera%e$tically effecti*e( In fact) increa e" CS' %re $re in the ac$te %ha e of #acterial !eningiti i largely a con e1$ence of cere#ral e"e!a) in &hich ca e the l$!#ar %$nct$re !ay %re"i %o e to cere#ellar herniation( Mannitol an" $rea ha*e #een e!%loye" &ith a%%arent $cce in o!e ca e of e*ere #rain &elling &ith $n$ $ally high initial CS' %re $re (J6;; !!:9O)( Acting a o !otic "i$retic ) the e agent enter cere#ral ti $e lo&ly) an" their net effect i to "ecrea e #rain &ater( :o&e*er) neither !annitol nor $rea ha #een t$"ie" in controlle" fa hion in the !anage!ent of !eningiti ( An a"e1$ate #$t not e,ce i*e a!o$nt of intra*eno$ nor!al aline (a*oi"ing fl$i" &ith free &ater) ho$l" #e gi*en) an" anticon*$l ant ho$l" #e %re cri#e" &hen ei/$re are %re ent( In chil"ren) %artic$lar care ho$l" #e ta-en to a*oi" hy%onatre!ia an" &ater into,ication2 %otential ca$ e of #rain &elling( Anticon*$l ant nee" not #e a"!ini tere" ro$tinely #$t ho$l" #e gi*en if a ei/$re ha occ$rre" or there i e*i"ence of cortical *ein occl$ ion(

Pro%hyla,i All ho$ ehol" contact of %atient &ith !eningococcal !eningiti ho$l" #e %rotecte"( The ri - of econ"ary ca e i !all for a"ole cent an" a"$lt #$t range fro! 9 to 6 %ercent for tho e le than ? year of age( A "aily oral "o e of rifa!%in2C;; !g e*ery <9 h in a"$lt an" <; !gG-g e*ery <9 h in chil"ren2for 9 "ay $ffice ( If 9 &ee- or !ore ha*e ela% e" ince the in"e, ca e &a fo$n") no %ro%hyla,i i nee"e"( I!!$ni/ation again t :( infl$en/ae i tea"ily re"$cing the inci"ence of !eningiti fro! thi organi !( Al o) !any in tit$tion ho$ ing yo$ng a"$lt ) $ch a college an" the !ilitary) ha*e in tit$te" %rogra! of i!!$ni/ation again t N( !eningiti"i ( Progno i Untreate") #acterial !eningiti i $ $ally fatal( The o*erall !ortality rate of $nco!%licate" :( infl$en/ae an" !eningococcal !eningiti ha re!aine" at a#o$t ? %ercent for !any year + in %ne$!ococcal !eningiti ) the rate i con i"era#ly higher (<? to >; %ercent)( '$l!inant !eningococce!ia) &ith or &itho$t !eningiti ) al o ha a high !ortality rate #eca$ e of the a ociate" *a o!otor colla% e an" infecti*e hoc-) a ociate" &ith a"renocortical he!orrhage (0aterho$ e5 'ri"erich en yn"ro!e)( A "i %ro%ortionate n$!#er of "eath fro! !eningiti occ$r in infant an" in the age"( The !ortality rate i highe t in neonate ) fro! 6; to 8? %ercent in re%orte" erie ) an" at lea t half of tho e &ho reco*er ho& erio$ ne$rologic e1$elae( The %re ence of #actere!ia) co!a) ei/$re ) an" a *ariety of conco!itant "i ea e 2incl$"ing alcoholi !) "ia#ete !ellit$ ) !$lti%le !yelo!a) an" hea" tra$!a2all &or en the %rogno i ( The tria" of %ne$!ococcal !eningiti ) %ne$!onia) an" en"ocar"iti ha a %artic$larly high fatality rate( It i often i!%o i#le to e,%lain the "eath of the %atient or at lea t to trace it to a ingle %ecific !echani !( The effect of o*er&hel!ing infection) &ith #actere!ia an" hy%oten ion or #rain &elling an" cere#ellar herniation) are clearly i!%licate" in the "eath of o!e %atient "$ring the initial 67 h( The e e*ent !ay occ$r in #acterial !eningiti of any etiology+ ho&e*er) they are !ore fre1$ent in !eningococcal infection (0aterho$ e5'ri"erich en yn"ro!e)( So!e of the "eath occ$rring later in the co$r e of the illne are attri#$ta#le to re %iratory fail$re) often con e1$ent to a %iration %ne$!onia( Relati*ely fe& %atient &ho reco*er fro! !eningococcal !eningiti ho& re i"$al ne$rologic "efect ) &herea $ch "efect are enco$ntere" in at lea t 9? %ercent of chil"ren &ith :( infl$en/ae !eningiti an" $% to >; %ercent of chil" an" a"$lt %atient &ith %ne$!ococcal !eningiti ( 'erry an" co&or-er ) in a %ro %ecti*e t$"y of ?; infant &ho $r*i*e" :( infl$en/ae !eningiti ) fo$n" that a#o$t ?; %ercent &ere nor!al) &herea B %ercent ha" #eha*ioral %ro#le! an" a#o$t >; %ercent ha" ne$rologic "eficit ( ei/$re an"Gor i!%air!ent of hearing) lang$age) !entation) an" !otor f$nction)( In a re%ort of a %er onal erie of <7? chil"ren reco*ering fro! #acterial !eningiti ) Po!eroy an" a ociate fo$n" that CB &ere till not nor!al

ne$rologically at the en" of a !onth+ ho&e*er) at the en" of a year) only 9C "e!on trate" ne$rologic a#nor!alitie + <7 &ere left &ith a hearing "eficit) <> &ith late afe#rile ei/$re ) an" 7 &ith !$lti%le "eficit ( The %re ence of %er i tent ne$rologic "eficit &a the only in"e%en"ent %re"ictor of late ei/$re ( .o"ge an" colleag$e fo$n" that >< %ercent of chil"ren &ith %ne$!ococcal !eningiti &ere left &ith %er i tent en orine$ral hearing lo + for !eningococcal an" :( infl$en/ae !eningiti ) the fig$re &ere <;(? an" C %ercent) re %ecti*ely( Cranial ner*e %al ie other than "eafne ten" to "i a%%ear after a fe& &ee- or !onth ( .eafne in the e infection i "$e to $%%$rati*e cochlear "e tr$ction or to the ototo,ic effect of a!inoglyco i"e anti#iotic ( Bacteria reach the cochlea !ainly *ia the cochlear a1$e"$ct) &hich connect the $#arachnoi" %ace to the cala ty!%ani( Thi occ$r 1$ite early in the co$r e of infection) hearing lo #eing e*i"ent &ithin a "ay of on et of the !eningiti + in a#o$t half $ch ca e ) the "eafne re ol*e ( :y"roce%hal$ ) a rare co!%lication) !ay #eco!e !anife t !onth after treat!ent an" !ay re1$ire h$nting if gait or !entation i affecte"( It !ay #e "iffic$lt to "eter!ine on clinical gro$n" &hether a re i"$al tate of i!#alance i the re $lt of hy"roce%hal$ or of eighth ner*e "a!age( 0e ha*e een e*eral in tance of $%%er cer*ical cor" infarction) &ith 1$a"ri%are i an" re %iratory fail$re) a a re $lt of co!%re ion fro! "e cent of the cere#ellar ton il (Ro%%er an" Aani )( The role of l$!#ar %$nct$re in thi co!%lication ha not #een clarifie"( The ac$te co!%lication of #acterial !eningiti ) the inter!e"iate an" late ne$rologic e1$elae) an" the %athologic #a i of the e effect are $!!ari/e" in Ta#le >95<( Other a %ect of c$rrent treat!ent ha*e #een $!!ari/e" #y La!#ert(