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Department of Infectious Diseases Chair of Gastroenterology, Hepatology and Infectious Diseases Jagiellonian University Collegium Medicum in Cracov Department of Gastroenterology, Hepatology and Infectious Diseases University Hospital in Cracov
ABSTRACT
%DFWHULDOPHQLQJLWLVLVDVVRFLDWHGZLWKVLJQLILFDQWPRUELGLW\DQGPRUWDOLW\GHVSLWHWKHDYDLODELOLW\RIHIIHFWLYH DQWLPLFURELDOWKHUDS\7KHPDQDJHPHQWDSSURDFKWRSDWLHQWVZLWKVXVSHFWHGRUSURYHQEDFWHULDOPHQLQJLWLVLQ - FOXGHVHPHUJHQWFHUHEURVSLQDOIOXLGDQDO\VLVDQGLQLWLDWLRQRIDSSURSULDWHDQWLPLFURELDODQGDGMXQFWLYHWKHUDSLHV 7KHFKRLFHRIHPSLULFDODQWLPLFURELDOWKHUDS\LVEDVHGRQWKHSDWLHQW¶VDJHDQGXQGHUO\LQJGLVHDVHVWDWXV RQFH WKHLQIHFWLQJSDWKRJHQLVLVRODWHGDQWLPLFURELDOWKHUDS\FDQEHPRGLILHGIRURSWLPDOWUHDWPHQW 6XFFHVVIXOWUHDWPHQWRIEDFWHULDOPHQLQJLWLVUHTXLUHVWKHNQRZOHGJHRQHSLGHPLRORJ\LQFOXGLQJSUHYDOHQFHRI DQWLPLFURELDOUHVLVWDQWSDWKRJHQVSDWKRJHQHVLVRIPHQLQJLWLVSKDUPDFRNLQHWLFVDQGSKDUPDFRG\QDPLFVRI DQWLPLFURELDODJHQWV7KHHPHUJHQFHRIDQWLELRWLFUHVLVWDQWEDFWHULDOVWUDLQVLQUHFHQW\HDUVKDVQHFHVVLWDWHGWKH GHYHORSPHQWRIQHZVWUDWHJLHVIRUHPSLULFDQWLPLFURELDOWKHUDS\IRUEDFWHULDOPHQLQJLWLV
.H\ZRUGV : bacterial meningitis, antimicrobial therapy, antibiotic-resistant
INTRODUCTION RIGLVHDVHEXWDOVRRQVXVSLFLRQRULGHQWLILFDWLRQRI HWLRORJLFDODJHQWDQGSRVVLEO\WKHTXLFNHVWDSSOLFDWLRQRI Bacterial meningitis and encephalitis are the acute DQWLELRWLFDQGVXSSOHPHQWDU\WUHDWPHQW 7DNLQJLQWR LQIHFWLRXVGLVHDVHVDFFRPSDQLHGE\LQIODPPDWLRQRI account the serious course of the disease, high mortal- PHQLQJHVSURWHFWLQJWKHEUDLQVSLQDOFRUGVXEDUDFKQRLG LW\DQGSRVVLELOLW\RIHDUO\FRPSOLFDWLRQVRFFXUUHQFH FDYLW\DQGEUDLQSDUHQFK\PD7KHFKDUDFWHULVWLFHOHPHQW WKHWUHDWPHQWVKRXOGEHSURYLGHGLQWKHILUVWSKDVHRI RIFHUHEURVSLQDOIOXLG &6) DQDO\VLVLVSOHRF\WRVLVZLWK the disease and on the intensive care unit of infectious significant predominance of neutrophiles, increase of diseases (5, 6). protein concentration and decrease of glucose level (1). 7KHLQFLGHQFHRIEDFWHULDOPHQLQJLWLVZRUOGZLGHLVDS - SUR[LPDWHO\FDVHVSHURQDQDQQXDOEDVLVLQ ANTIBIOTIC TREATMENT OF MENINGITIS the West Europe and the United States. However, in the GHYHORSHGFRXQWULHVWKHPRUELGLW\DQGPRUWDOLW\PD\EH 7KHDQWLELRWLFWUHDWPHQWLVRIVLJQLILFDQFHLQWKH WLPHVKLJKHU ,Q3RODQGDWRWDORIFDVHVRI WKHUDS\RIEDFWHULDOPHQLQJLWLV'XHWRWKHIDFWWKDWWKH EDFWHULDOPHQLQJLWLVZHUHQRWLILHGLQ LQFLGHQFH disease is life-threatening, the decision of applying an- SHU *LYHQWKHWKUHHPDMRUHWLRORJLFDO WLELRWLFVDIWHUGLDJQRVLQJRUVXVSHFWLQJWKHPHQLQJLWLV DJHQWVWKHLQFLGHQFHSHUSRSXODWLRQLQ VKRXOGEHDVTXLFNDVSRVVLEOH7KHHPSLULFDQWLELRWLF amounted to 0.5, 0.45 and 0.03 for N. menigitidis, S. WKHUDS\VKRXOGEHLQWURGXFHGDIWHUFROOHFWLQJWKHVDPSOH pneumoniae and H. influenzae, respectively (3). The RIFHUHEURVSLQDOIOXLGDQGRUEORRGIRUODERUDWRU\WHVW prognosis is also serious and is dependent on etiological ,QWKHFDVHZKHUHWKHLPDJLQJH[DPLQDWLRQRI agent, patient’s age, coexisting diseases and the quick- &16LVUHTXLUHGEHIRUHOXPEDUSXQFWXUHWKHILUVWGRVH ness of introducing appropriate treatment (4). The treat- RIDQWLELRWLFVKRXOGEHDGPLQLVWHUHGSULRUWRUDGLRORJL - ment effectiveness depends not only on early diagnosis cal examination. However, prior to administration of
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DQWLELRWLFWKHFROOHFWLRQRIEORRGVDPSOHIRUFXOWXUH cocci resistant to penicillin and III cephalosporin, is recommended, especially if invasive meningococcal increase of prevalence of N. meningitidis resistant RUSQHXPRFRFFDOGLVHDVHLVVXVSHFWHG $FFRUGLQJ to penicillin and multiresistance of Gram-negative WRWKHUHFRPPHQGDWLRQVWKHDQWLELRWLFWKHUDS\VKRXOG FRFFREDFLOOL EHVWDUWHGZLWKLQPLQXWHVDIWHUSDWLHQW¶VDGPLVVLRQ x neurosurgical procedures, the presence of ventricular WRKRVSLWDODQGLWVKRXOGQRWH[FHHG PLQXWHV GUDLQEUDLQLQMXULHVDUHWKHUHDVRQRI Staphylococcus (DFKGHOD\LQDQWLELRWLFWUHDWPHQWFRPPHQFHPHQW increase, including methicillin-resistant deteriorates the prognosis. According to the Danish 7KHDQDO\VLVRIWKHDIRUHVDLGGDWDHQDEOHVWRGHWHU - UHVHDUFKHUVWKHGHOD\LQDQWLELRWLFWUHDWPHQWRIRQH mine the suspected etiological agent and the selection of KRXULQFUHDVHVWKHULVNRIFRPSOLFDWLRQVRI RSWLPDOWUHDWPHQWVFKHPH,QWKHWUHDWPHQWRIEDFWHULDO 7KHDSSURSULDWHVHOHFWLRQRIDQWLELRWLFGHWHUPLQHVWKH PHQLQJLWLVWKHSRVVLEO\ORZHVWQXPEHURIDQWLELRWLFV VXFFHVVRIWKHUDS\7KHEDVLFUXOHRIDQWLELRWLFWUHDWPHQW VKRXOGEHHPSOR\HG7KHLGHDOVROXWLRQZRXOGEHWR LHVHOHFWLRQRIDQWLELRWLFRQDEDVLVRIDQWLELRJUDP administer one drug covering with its spectrum all sus- RILVRODWHGSDWKRJHQLVQRWDOZD\VSUDFWLFDEOHLQWKH SHFWHGHWLRORJLFDODJHQWV0XOWLGUXJVFKHPHVFRQWULEXWH FDVHRIEDFWHULDOPHQLQJLWLV7KHPDMRUUHDVRQZKLFK WRWKHVHOHFWLRQRIUHVLVWDQWVWUDLQVRIEDFWHULDDQGUDLVH SUHFOXGHVIURPLQWURGXFLQJWKHWDUJHWHGDQWLELRWLF the risk of drug side-effects occurrence (11). treatment is negative test result of CSF culture (9). ,,'LUHFWEDFWHULRVFRS\RI&6)LVLQGLVSHQVDEOHDQG 7KHFHUHEURVSLQDOIOXLGLVDYHU\VSHFLILFPDWHULDOIRU YDOXDEOHHOHPHQWLQWKHGLDJQRVWLFVRIEDFWHULDO PLFURELRORJLFDOGLDJQRVWLFVEHFDXVHWKHPLVWDNHVPDGH PHQLQJLWLV7KHVWDLQLQJRIVSHFLPHQRI&6)E\XV - during its collecting have negative effects on test result. LQJ*UDKP¶VPHWRGHQDEOHVWRGHWHUPLQHWKHW\SHRI 7KXVWKHTXLFNWUDQVSRUWRIPDWHULDOWRWKHODERUDWRU\ EDFWHULD*UDPSRVLWLYHRU*UDPQHJDWLYHDQGWKHLU storage of collected CSF samples in the temperature of PRUSKRORJ\ FRFFLFRFFREDFLOOL7KLVGDWDHQDEOHV FLUFD 0C and collecting the material to proper, heated WRSRWHQWLDOPRGLILFDWLRQRIHPSLULFWKHUDS\ JURZWKPHGLXPDWSDWLHQW¶VEHGDUHRIVLJQLILFDQFHLQ III. Serologic and molecular examination of CSF en- the CSF diagnostics. The successive factor delaying DEOHWRLGHQWLI\WKHW\SH VHURW\SH RIHWLRORJLFDO the implementation of targeted therapy is the wait- DJHQWZKLFKVHUYHVDVWKHEDVLVRIDQWLELRWLFWKHUDS\ ing time for test result which includes isolation time, GLUHFWHGWRDJLYHQSDWKRJHQ 7KHH[DPSOHV identification of etiological agent and determination of RIHPSLULFWKHUDS\VFKHPHVDUHSUHVHQWHGLQ7DEOH, GUXJVHQVLWLYLW\7KHDYHUDJHWLPHRIEDFWHULRORJLFDO GLDJQRVWLFVUDQJHVIURPWRKRXUV7KLVORQJSHULRG of time results in the fact that the physician is forced to ANTIMICROBIAL DRUGS IN CNS LQWURGXFHHPSLULFDQWLELRWLFWKHUDS\LQWKHWUHDWPHQWRI INFECTIONS EDFWHULDOPHQLQJLWLV 7KHPRVWLPSRUWDQWDVSHFWLQWKHWUHDWPHQWRIEDFWH- ULDOPHQLQJLWLVLVTXLFNLQWURGXFLQJRIHPSLULFDQWLELRWLF EMPIRIC ANTIBIOTIC THERAPY therapy, immediately after collecting the material to PLFURELRORJLFDOH[DPLQDWLRQV7KHYDOLGHOHPHQWLQ 7KHHPSLULFDQWLELRWLFWKHUDS\FRQVLVWVLQHVWLPDWLQJ WKHVHOHFWLRQRIDQWLELRWLFFKHPLRWHUDSHXWLFDJHQWLV WKHSUREDEOHHWLRORJLFDOIDFWRUVGHSHQGLQJRQSDUWLFXODU the knowledge on drug properties regarding the trans- FOLQLFDOVLWXDWLRQDQGVHOHFWLRQRIDQWLELRWLFFKHPLRWHUD - PLVVLRQYLDWKHEORRGFHUHEURVSLQDOIOXLGEDUULHU7KH SHXWLFDJHQWRISRVVLEO\WKHEHVWDQWLPLFURELDOVSHFWUXP DQWLPLFURELDOHIIHFWLYHQHVVRIDGUXJGHSHQGVODUJHO\ ,QWKHHPSLULFWKHUDS\RIEDFWHULDOPHQLQJLWLVWKUHH RQDFKLHYHGFRQFHQWUDWLRQRIDQWLELRWLFLQ&6) VLJQLILFDQWHOHPHQWVPD\EHGLVWLQJXLVKHG,IWKHVHHOH - The factors which have an effect on transmission of a PHQWVDUHPHWWKHWUHDWPHQWVKRXOGEHHIIHFWLYH GUXJYLDEORRG&6)EDUULHUDQGPD[LPXPDQWLPLFURELDO , 'XULQJWKHVHOHFWLRQRIDQWLELRWLFWKHUDS\DIWHUGL - effectiveness are as follows: DJQRVLVHVWDEOLVKLQJWKHIROORZLQJVKRXOGEHWDNLQJ x IDUPDFRNLQHWLFVSURSHUWLHVRIDQWLELRWLFFKHPLRWHUD - into account: : peutic agent – more effective transmission ensure: x patient’s age ORZPROHFXODUPDVVSHSWLGHERQGJRRGVROXELOLW\ x environmental epidemiological data in lipids, low ionization in physiological pH x coexisting diseases - alcoholism, cancers, immuno- x inflammation intensification – the higher inflam- GHILFLHQF\GLDEHWHVHWF PDWRU\SURFHVVWKHEHWWHUWUDQVPLVVLRQWRWKHVXE - x community and health-care acquired infection – arachnoid cavity WKHLQFUHDVHRIPXOWLUHVLVWDQWVWUDLQVRIEDFWHULDLV x FKDUDFWHULVWLFVRIEDFWHULDOPHQLQJLWLV±WKHQHJD - REVHUYHGERWKKRVSLWDODQGFRPPXQLW\VWUDLQV7KH tive effects have: high protein concentration, high H[DPSOHFRXOGEHWKHLQIHFWLRQFDXVHGE\SQHXPR - EDFWHULDGHQVLW\ No 3 Bacterial meningitis
7DEOH, (PSLULFDQWLELRWLFUHJLPHQVSXUXOHQWPHQLQJLWLVGHSHQGLQJRQWKHHVWLPDWHGULVNIDFWRUVDQGRWKHUYDULDEOHVWKDW affect the choice of treatment. 5LVNIDFWRU (WLRORJLFDODJHQW (PSLULFWKHUDS\VFKHPH Patient’s age ampicilin + cefotaxime S.agalactiae; E.coli; L.monocytogenes to 1 month old or *UDPQHJDWLYHLQWHVWLQDOFRFFREDFLOOL ampicilin + aminoglicosyde N.meningitidis; S.pneumoniae; 1 month - 5 y.o. ceftriaxone + vankomycin +LQÀXHQ]DH Children from 5 y.o. and N.meningitidis; S.pneumoniae ceftriaxone + vankomycin adults to 50 y.o. S.pneumoniae; N.meningitidis; !UĪ ampicilin + ceftriaxone + vankomycin L. monocytogenes L.monocytogenes; ,PPXQRGH¿FLHQF\FDQFHUDONRKROLVP ampicilin + ceftriaxone + vankomycin *UDPQHJDWLYHLQWHVWLQDOFRFFREDFLOOL S.pneumoniae; S.aureus SDáHF]NL cefepime + vankomycin 1HXURVXUJLFDOSURFHGXUH EUDLQLQMXU\ *UDPQHJDWLYHLQWHVWLQDOFRFFREDFLOOL or P.aeruginosa meropenem + vankomycin S.aureus cefepime + vankomycin Infection of ventriculo-peritoneal valve Staphylococcus FRDJXODVHQHJDWLYH or *UDPQHJDWLYHLQWHVWLQDOFRFFREDFLOOL meropenem + vankomycin 0XOWLUHVLVWDQW*UDPQHJDWLYHFRFFREDFLOOL Nosocomial infection meropenem + vankomycin methicillin resistant staphylococci Allergy to penicilin S.pneumoniae; N.meningitidis; meropenem + vankomycin +LQÀXHQ]DH or PR[LÀR[DFLQ L.monocytogenes co-trimoxazole or meropenem Results of Gram staining Cocci (diplococcii) N.meningitidis ceftriaxone or cefotaxime Gram-negative Cocci (diplococcii) S.pneumoniae ceftriaxone + vankomycin Gram-positive &RFFREDFLOOL L.monocytogenes ampicilin + aminoglicosyde Gram-positive +LQÀXHQ]DH *UDPQHJDWLYHLQWHVWLQDO &RFFREDFLOOL FRFFREDFLOOL *UDPQHJDWLYHQRQ cefepime + aminoglicosyde Gram-negative IHUPHQWLQJFRFFREDFLOOL x WKHDQWLELRWLFVDELOLW\WRDFKLHYHFRQFHQWUDWLRQLQ GUXJVXVHGLQEDFWHULDOPHQLQJLWLVZDVSUHVHQWHGLQ &6)VLJQLILFDQWO\H[FHHGLQJPLQLPDOLQKLELWRU\ 7DEOH,,$PRQJWKHJURXSVRIDQWLELRWLFVFKHPLRWHUD - FRQFHQWUDWLRQ 0,& EHWDODFWDPV peutic agents which are well-known since many years x DGPLQLVWUDWLRQRIDQWLELRWLFVRIEDFWHULFLGDOSURSHU - DQGQHZDQWLPLFURELDOGUXJVZKLFKKDYHEHHQLQWUR - ties GXFHGUHFHQWO\DGPLQLVWHUHGLQWKHFRXUVHRIEDFWHULDO x DGPLQLVWUDWLRQRIGUXJLQPD[LPXPSHUPLVVLEOH PHQLQJLWLVDUHXVHGEHWDODFWDPVLQFOXGLQJSHQLFLOOLQ doses and continuing of such dosage scheme in the FHSKDORVSRULQVPRQREDFWDPVFDUEDSHQHPVDQGLQ - course of treatment KLELWRUVRIEHWDODFWDPV'HVSLWHWKHIDFWWKDWWKH\GR x intravenous route of administration (15) QRWDUHIXOO\WUDQVPLWWHGYLDEORRG&6)EDUULHUWKH\ In special clinical situations, the intraspinal and achieve significantly higher concentration compared intraventicular routes of drug administration may to MIC for the majority of pathogens causing menin- EHDSSOLHGHJDIWHUQHXURVXUJLFDOSURFHGXUHVRULQ JLWLV7KHDELOLW\WRSHQHWUDWHLQFUHDVHVVLJQLILFDQWO\LQ SDWLHQWVZLWKWUDQVXUHWKUDODEODWLRQRIYDOYHVLQLQIHF - WKHLQIODPPDWLRQSURFHVV7KXVWKHDQWLELRWLFVRIWKLV WLRQVFDXVHGE\PXOWLUHVLVWDQWVWUDLQVRI Staphylococcus JURXSDUHWKHEDVLFGUXJVDSSOLHGLQWKHWUHDWPHQWRI aureus RU*UDPQHJDWLYHQRQIHUPHQWLQJFRFFREDFLOOL VXFKLQIHFWLRQV In the intraspinal or intraventicular treatment, the most 1DWXUDOSHQLFLOLQV±EHQ]\OSHQLFLOOLQ SHQLFLOLQ* ± frequently used are vancomycin, aminoglycosides or the therapeutic concentration in CSF is achieved with colistin. The daily dose for the adult in intraventicular WKHGDLO\GRVHRIPLOOLRQXQLWVDQGKLJKHUDQGWKH WUHDWPHQWLVPJPJPJDQGPJIRU dosage of 4 - 6 times a day. Nowadays, penicillin is amikacin, gentamicin, vancomycin and colistin (11, QRWUHFRPPHQGHGDVWKHDQWLELRWLFRIWKHILUVWOLQH 7KHUHFRPPHQGHGGRVDJHRIDQWLPLFURELDO empiric therapy, which results from the increasing 0LURVáDZ-DZLHĔ$OHNVDQGHU0*DUOLFNL No 3
7DEOH,, 7KHUHFRPPHQGHGGRVDJHRIDQWLELRWLFV FKHPRWKHUDS\ LQWKHWUHDWPHQWRISXUXOHQWPHQLQJLWLV 5RXWHRI 'RVDJH 'RVDJH 'UXJ DGPLQLVWUDWLRQ LQDGXOWV K LQFKLOGUHQ K Penicilin G intravenous 4 x 6 mln units [WKRVXDQGXQLWVNJ Ampicilin intravenous [J 6 x 50 mg/kg Ceftriaxone intravenous [J 1 x 100 mg/kg Cefotaksime intravenous 4 x 3 g 4 x 50 mg/kg Ceftazidime intravenous [J 3 x 50 mg/kg Cefepime intravenous [J 3 x 50 mg/kg Meropenem intravenous [J 3 x 40 mg/kg Aztreonam intravenous [J 3 x 50 mg/kg Amikacin intravenous 3 x 5 mg/kg 3 x 5 mg/kg Amikacin intraspinal [J Gentamicin intravenous [PJNJ [PJNJ Vankomycin intravenous [J 4 x 15 mg/kg Vankomycin intraspinal [±J &LSURÀRNVDFLQ intravenous [J - 0R[LÀR[DFLQ intravenous 1 x 0,4 g - Linezolid intravenous [J [PJNJ Metronidazole intravenous 3 x 0,5 g 3 x 10 mg/kg Rifampicin intravenous 1 x 0,6 g [PJNJ Colistin intraspinal [PLOOLRQXQLWV - 4 x 5 mg/kg 4 x 5mg/kg Co-trimoxazole intravenous (calculation for trimethoprim) (calculation for trimethoprim)
resistance to this drug, especially in pneumococci &HIWULD[RQHLVWKHPRVWDFWLYHDQWLELRWLFDPRQJ (16). The indications too use penicilin G are as follows cephalosporins of 3rd generation in relation to the LQIHFWLRQVFDXVHGE\PHQLQJRFRFFLSQHXPRFRFFL IROORZLQJEDFWHULD Haemophilus influenzae and group B streptococci and Listeria monocytogenes, of Neisseria meningitidis . In the case of confirmed confirmed sensitiveness to this drug. meningitis of Pseudomonas aeruginosa etiology , Ampicilin – in CSF achieves approximately 15% WKHDQWLELRWLFRIFKRLFHLVFHIWD]LGLPH FRQFHQWUDWLRQLQVHUXP WKHPDMRULQGLFDWLRQVDUHWKH Cephalosporins of 4th generation – cefepime is infections of Listeria monocytogenes HWLRORJ\ WKH FKDUDFWHUL]HGE\WKHVLPLODUVSHFWUXPRIDFWLY - JUHDWHUEDFWHULFLGDOHIIHFWLVREWDLQHGZKLOHXVLQJ ity as the cephalosporins of 3rd generation and FRPELQHGWKHUDS\ZLWKDPLQRJO\FRVLGHV PD\EHHPSOR\HGLQWKHWUHDWPHQWRIEDFWHULDO Cephalosporins of 3rd generation – due to the PHQLQJLWLWLV extended spectrum of activity in relation to Gram- 0RQREDFWDPV±D]WUHRQDPLVPDLQO\XVHGLQWKH SRVLWLYHDQG*UDPQHJDWLYHEDFWHULDFDXVLQJWKH targeted therapy of meningitis of H.influenzae or EDFWHULDOPHQLQJLWLVWKH\DUHWKHILUVWOLQHDQWLEL - P.aerugionosa etiology. Is is transmitted well via otics in the empiric therapy. Among the numerous EORRG&6)EDUULHUDQGDFKLHYHVLQ&6)IURP cephalosporins of 3 rd generation, the usage of WRRIFRQFHQWUDWLRQLQEORRG ceftriaxone or cefotaxime is recommended (19). &DUEDSHQHPV±LQWKLVJURXSRIDQWLELRWLFVRQO\ &HIRWD[LPHLVHVSHFLDOO\UHFRPPHQGHGLQEDFWH - meropenem is recommended as the usage of imi- rial meningitis in children as it is characterized SHQHPUDLVHVWKHULVNRIWUHPRURFFXUUHQFH E\ORZHUOHYHORISURWHLQERQGDQGORZHUULVNRI 0HURSHQHPLVZHOOWUDQVPLWWHGYLDEORQG&6) KLSHUELOLUXELQHPLDWKDQLQWKHFDVHRIFHIWULD[RQH EDUULHUDQGKDVZLGHVSHFWUXPRIDFWLYLW\±JHQHU - (15). The lack of improvement after introducing ally it has an effect on the majority of pathogens of ceftriaxone or cefotaxime may indicate the FDXVHGEDFWHULDOPHQLQJLWLV LQIHFWLRQVFDXVHGE\*UDPQHJDWLYHFRFFRED - x *O\FRSHSWLGHV±IURPWKHDYDLODEOHDQWLELRWLFVRIWKLV FLOOLZKLFKGHPRQVWUDWHWKH(6ȕ/UHVLVWDQFH group, the only used medicine in the treatment of ȕODFWDPVRIZLGHQHGVSHFWUXPRIDFWLYLW\ EDFWHULDOPHQLQJLWLVLVYDQFRP\FLQ7HLFRSODQLQGRHV $03& ȕODFWDPVRI$PS&W\SH 0%/ PHWDOR QRWSHQHWUDWHWKHEORRG&6)EDUULHU 9DQFRP\ - ȕODFWDPV RU.3& FDUEDSHQHPRI.3&W\SH FLQVKRXOGEHXVHGLQWDUJHWHGWKHUDS\+RZHYHUWKH LQIHFWLRQFDXVHGE\EDFWHULDQDWXUDOO\UHVLVWDQWWR XVDJHRIYDQFRP\FLQLQHPSLULFWKHUDS\VKRXOGEH WKHVHDQWLELRWLFV L.monocytogenes , Staphyloc- justified with the strong epidemiological rationale, cocus spp . or Enterococcus spp. and pneumo- i.e. known risk factors indicating the infection of FRFFLUHVLVWDQWWRSHQLFLOOLQDQGFHIWULD[RQH Staphylococcus REVHUYHGKLJKSHUFHQWDJHRI056$ No 3 Bacterial meningitis
strains or pneumococci resistant to penicillin and x 5LIDPSLFLQ±EHFDXVHRIWKHJRRGOLSRSKLOLFLW\LW cephalosporins. Due to the fact that vancomycin PD\EHXVHGDVWKHVHFRQGOLQHDQWLELRWLFLQFRP - SRRUO\SHQHWUDWHVWR&6)VKRXOGEHDGPLQLVWHUHG ELQHGWKHUDS\ZLWKYDQFRP\FLQLQWKHWUHDWPHQWRI WRJHWKHUZLWKEHWDODFWDPV EDFWHULDOPHQLQJLWLVFDXVHGE\056$VWUDLQV,QWKH x )OXRURTXLQRORQHV±JLYHQWKHREVHUYHGSKHQRPHQRQ case of S. pneumoniae LQIHFWLRQULIDPSLFLQPD\EH RILQFUHDVLQJUHVLVWDQFHWRTXLQRORQHVRIQGJHQHUD - added to vancomycin as the synergistic activity is tion, they are not recommended in empiric therapy REVHUYHG DVZHOODVLQPRQRWKHUDS\0R[LIOR[DFLQVKRXOGEH x Sulfonamides – co-trimoxazole achieves in CSF the drug of choice. It penetrates well to the CSF and approximately 40-50% concentration in serum and achieves approximately 50% of concentration in is used as a second-line drug in the targeted therapy EORRG,WLVDOVRRIKLJKDFWLYLW\LQUHODWLRQWR*UDP RILQIHFWLRQVFDXVHGE\056$VWUDLQV positive cocci, including S. pneumoniae resistant to x Derivatives of nitroimidazole – metronidazole in SHQLFLOLQ ,Q3RODQGPR[LIOR[DFLQLVQRWUHJ - CSF achieves the concentration similar to the one LVWHUHGLQWKHIRUPWREHDGPLQLVWHUHGLQWUDYHQRXVO\ REVHUYHGLQVHUXP7KLVFKHPLRWHUDSHXWLFDJHQWLV x $PLQRJO\FRVLGHV±DQWLELRWLFVSHQHWUDWLQJWR&6) XVHGLQWKHPHQLQJLWLVRUFHUHEUDODEVFHVVFDXVHGE\ RQO\LQWKHLQIODPPDWRU\SURFHVV WKXVWKH\DUHXVHG DQDHURELFEDFWHULD FRQGLWLRQDOO\LQWKHWUHDWPHQWRIEDFWHULDOPHQLQJLWLV x 2[D]ROLGLQRQHV±DQWLELRWLFVRIWKLVJURXSGHPRQ - It results from the fact that they poorly penetrate strate activity in relation to multiresistant strains of YLDOLSLGEDUULHUVGHPRQVWUDWHSRRUDFWLYLW\LQWKH S. pneumoniae , enterococci resistant to vancomycin HQYLURQPHQWRIIOXLGORZS+DQGEHFDXVHRIWKH and Staphylococcus resistant to methicillin and van- UHODWLYHO\DQDHURELFFRQGLWLRQV7RDFKLHYHWKHDS - comycin. Linezolid in CSF achieves approximately propriate concentration in CSF, it is necessary to ap- FRQFHQWUDWLRQLQEORRG,WLVUHFRPPHQGHGLQ ply large doses, which raises the risk of side-effects WKHWUHDWPHQWRIPHQLQJLWLVFDXVHGE\ Staphylococ- RFFXUUHQFH$QWLELRWLFVRIWKLVJURXSVKRXOGEHRQO\ cus strains of decreased sensitiveness or resistant to employed in the targeted therapy and together with vancomycin (VISA / VRSA) or enterococci resistant WKHEHWDODFWDPVRUJO\FRSHSWLGHV WRYDQFRP\FLQ 95(
7DEOH,,,3URSRVHGWUHDWPHQWUHJLPHQVSXUXOHQWPHQLQJLWLVGHSHQGLQJRQWKHUHVLVWDQFHSDWWHUQLVRODWHGHWLRORJLFDOIDFWRUV (WLRORJLFDODJHQW 3URSRVHGWUHDWPHQW $OWHUQDWLYHWKHUDS\ S. pneumoniae resistant to penicylin penicilin G FHIWULD[RQH FHIRWDNVLPH decreased sensitivity to penicilin ceftriaxone or cefotaksime PHURSHQHP FHIHSLPH ceftriaxone or cefotaksime + resistant to penicilin (PRSP) PR[LÀR[DFLQ PR[LÀR[DFLQULIDPSLFLQ vancomicin N. meningitidis sensitive to penicilin penicylina G ceftriaxone or cefotaksime decreased sensitivity to penicilin ceftriaxone or cefotaksime PHURSHQHP PR[LÀR[DFLQ +LQÀXHQ]DH FHIWULD[RQH FHIRWDNVLPHFHIHSLPH ȕODFWDPHVQHJDWLYH ampicilin aztreonam ȕODFWDPHVSRVLWLYH ceftriaxone or cefotaksime FHIHSLPH D]WUHRQDP ÀXRURTXLQRORQHV S. aureus staphylococii koagulaso-negative OLQH]ROLG FRWULPR[D]ROHRUULIDPSLFLQLQ methicillin resistant (MRSA / MRCNS) vancomicin FRPELQHGWKHUDS\ REQLĪRQDZUDĪOLZRĞüRUUHVLVWDQWWR FRWULPR[D]ROHRUULIDPSLFLQLQFRPELQHG linezolid vancomicin (VISA / VRSA) therapy Enterococcus spp linezolid resistant to vancomicin (VRE) FLSURÀR[DFLQ PR[LÀR[DFLQ *UDPQHJDWLYHFRFFREDFLOOL(6ȕ/ meropenem aminoglicosydes FHIHSLPH DPLQRJOLFRV\GHV *UDPQHJDWLYHFRFFREDFLOOL$03& meropenem ÀXRURTXLQRORQHV DPLQRJOLFRV\GHV D]WUHRQDPH ÀXRURTXLQRORQHV *UDPQHJDWLYHFRFFREDFLOOL0%/ colistin aminoglicosydes *UDPQHJDWLYHFRFFREDFLOOL.3& colistin 0LURVáDZ-DZLHĔ$OHNVDQGHU0*DUOLFNL No 3
7KHDQWLELRWLFVZKLFKDUHQRWXVHGLQWKHWUHDWPHQW temperature, hyperventilation (in the case of respira- RIEDFWHULDOPHQLQJLWLVGXHWRWKHLUXQIDYRXUDEOHSKDU - tory equipment usage). The anticonvulsants treatment macokinetic and pharmadynamic properties are: macro- LVQHFHVVDU\WRSUHYHQWIURPGDPDJHVFDXVHGE\WKH lides, lincosamides, tetracyclines, tigecycline, ketolides ischemia of CNS, especially the sensitive temporal area, DQGFROLVWLQ &ROLVWLQPD\EHXVHGFRQGLWLRQDOO\ FHUHEHOOXPDQGWKHKLOO7KHDQWLFRDJXODQWSURSK\OD[LV in the intraventicular therapy in the case of infections LVDOVRLQGLVSHQVDEOHXVDJHRISURWRQSXPSLQKLELWRUV FDXVHGE\PXOWLUHVLVWDQWVWUDLQVRIQRQIHUPHQWLQJFRF - and in the case of respiratory failure the oxygen therapy, FREDFLOOL 7KHHPSLULFDQWLELRWLFWKHUDS\VKRXOGEH UHSODFHPHQWRUVXSSOHPHQWDU\EUHDWKLQJLVQHFHVVDU\ always verified after identification of etiological agent The treatment of water-electrolytes accompanied IURP&6)RUEORRGDQGVHOHFWHGRQWKHEDVLVRIDQWLELR - E\K\SRQDWUHPLDDQGQRUPRYROHPLDLVDQLPSRUWDQW gram results. The phenomenon of increasing resistance element of therapy as the duration of hyponatremia cor- WRDQWLELRWLFZKLFKLVREVHUYHGUHFHQWO\FRPSHOVWR relates with neurological complications. It is indispens- IUHTXHQWPRGLILFDWLRQRIVWDQGDUGVFKHPHVRIEDFWHULDO DEOHWRVXVWDLQWKHEORRGSUHVVXUHZLWKLQQRUPDOOLPLWVWR meningitis treatment. The therapeutic options for pos- SUHYHQWIURPWKHFRQVHTXHQFHVRIEUDLQK\SRSHUIXVLRQ VLEOHPHFKDQLVPRIUHVLVWDQFHIRUSDWKRJHQVFDXVLQJWKH 7KHSDWLHQWVKRXOGVWD\DWEHGLQWKHDFXWH EDFWHULDOPHQLQJLWLVZHUHSUHVHQWHGLQ7DEOH,,, SKDVHRIWKHGLVHDVHDQGVKRXOGEHDOVRSURYLGHGZLWK physical therapy and proper nourishment. THE PERIOD OF ANTIBIOTIC THERAPY APPLICATION REFERENCES
7KHDSSURSULDWHWLPHRIDQWLELRWLFWUHDWPHQWDSSOLFD - 1. Nudelman Y, Tunkel AR. Bacterial meningitis. Epide- tion constitutes a very important element affecting the miology, pathogenesis and management update, Drugs EDFWHULDOPHQLQJLWLVWKHUDS\HIIHFWLYHQHVV7KHGXUDWLRQ 6FKXW(6GH*DQV-YDQGH%HHN'&RPPXQLW\±DF - RIDQWLPLFURELDOWUHDWPHQWGHSHQGVRQFOLQLFDOFRXUVHRI TXLUHGEDFWHULDOPHQLQJLWLVLQDGXOWV3UDFW1HXURO WKHGLVHDVHDQGHWLRORJLFDODJHQW7KHDQWLELRWLFWKHUDS\ VKRXOGODVWPLQLPDOO\IURPWRGD\V$IWHUWKHWHP - 0HOGXQNLHSLGHPLRORJLF]QH&KRURE\]DNDĨQHL]DWUXFLD SHUDWXUHGLVDSSHDUVWKHWKHUDS\VKRXOGEHFRQWLQXHG Z3ROVFHZURNX1,=3±3=+ for the next 5 days. Taking into account the isolated 4. Proulx N, Fréchette D, Toye B, et al. Delays in the ad- SDWKRJHQWKHPLQLPDOWKHUDS\GXUDWLRQDPRXQWVWR PLQLVWUDWLRQRIDQWLELRWLFVDUHDVVRFLDWHGZLWKPRUWDOLW\ days for Neisseria meningitidis and Heamophilus influ- IURPDGXOWDFXWHEDFWHULDOPHQLQJLWLV4-0 enzae infection, 14 days for Streptococcus pneumoniae, Streptococcus agalactiae and Staphylococcus aureus 5. Bashir WE, Laundy M, Booy R. Diagnosis and treatment UHPRYDORILQIHFWHGYDOYH LQIHFWLRQDQGGD\VIRU RIEDFWHULDOPHQLQJLWLV$UFK'LV&KLOG - Listeria monocytogenes , Pseudomonas aeruginosa in- *DUOLFNL$%RFLąJD-DVLN0,QZD]\MQDFKRUREDPH QLQJRNRNRZD±VWDáH]DJURĪHQLH=DNDĪHQLD IHFWLRQDVZHOODVWKHLQIHFWLRQFDXVHGE\*UDPQHJDWLYH ± LQWHVWLQDOFRFFL +DVEXQ5$EUDKDPV--HNHO-HWDO&RPSXWHGWRPRJ - 7KHWUHDWPHQWRIEDFWHULDOPHQLQJLWLVLVPXOWLGL - UDSK\RIWKHKDHGEHIRUHOXPEDUSXQFWXUHLQDGXOWVZLWK PHQVLRQDODQGGHVSLWHDGPLQLVWUDWLRQRIDQWLELRWLFV VXVSHFWHGPHQLQJLWLV1(QJO-0HG includes also the anti-inflammatory drugs, drugs for .¡VWHU5DVPXVVHQ5.RUVKLQ$0H\HU&1$QWLELRWLF UHGXFLQJWKHZDWHUHOHFWURO\WHVLPEDODQFHLQWUDFUDQLDO WUHDWPHQWGHOD\DQGRXWFRPHLQDFXWHEDFWHULDOPHQLQ - pressure and supportive care depending on the emerg- JLWLV-,QIHFW ing complications. *UD\/')HGRUNR'3/DERUDWRU\GLDJQRVLVRIEDFWHULDO In the supportive treatment, which is to reduce the PHQLQJLWLV&OLQ0LFURELRO5HY inflammatory process, the administration of first dose 5yĪDOVND0'LDJQRVW\ND]DNDĪHĔRĞURGNRZHJRXNáDGX QHUZRZHJR>Z @'LDJQRVW\NDEDNWHULRORJLF]QD5HG RIGH[DPHWKDVRQHLQDSSUR[LPDWHO\PLQXWHV 6]HZF]\N(0:DUV]DZD 3:1 SULRUWRRUWRJHWKHUZLWKWKHILUVWGRVHRIDQWLELRWLFLV 11. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice UHFRPPHQGHG,WVKRXOGEHFRQWLQXHGIRUGD\V JXLGHOLQHVIRUWKHPDQDJHPHQWRIEDFWHULDOPHQLQJLWLV (10 mg per every 6 hours). The aim of dexamethasone &OLQ,QIHFW'LV administration is the reduction of inflammation, asso- YDQGH%HHN'GH*DQV-6SDQMDDUG/HWDO&OLQLFDO FLDWHGZLWKWKHEDFWHULFLGDODQWLELRWLFVDSSOLFDWLRQDQG IHDWXUHVDQGSURJQRVWLFIDFWRUVLQDGXOWVZLWKEDFWHULDO UHOHDVHRISURLQIODPPDWRU\HOHPHQWVRIEDFWHULD&H - PHQLQJLWLV1(QJO-0HG UHEUDOHGHPDDQGLQFUHDVHRILQWUDFUDQLDOSUHVVXUHPD\ 13. Karre T, Vetter EA, Mandrekar JN, et al. Comparison EHLPPHGLDWHO\UHGXFHGE\KHDGHOHYDWLRQDW 0, RIEDFWHULDODQWLJHQWHVWDQGJUDPVWDLQIRUGHWHFWLQJ XVDJHRIPDQQLWRODQGIXURVHPLGHORZHULQJRIERG\ No 3 Bacterial meningitis
FODVVLFPHQLQJLWLVEDFWHULDLQFHUHEURVSLQDOIOXLG-&OLQ 5LFDUG-':ROII0/DFKHUDGH-&HWDO/HYHOVRIYDQ - 0LFURELRO FRP\FLQLQFHUHEURVSLQDOIOXLGRIDGXOWSDWLHQWVUHFHLYLQJ 14. Welinder-Olsson C, Dotevall L, Hogevik H, et al. Com- adjunctive corticosteroids to treat pneumococcal menin- SDULVRQRIEURDGUDQJHEDFWHULDO3&5DQGFXOWXUHRI JLWLV DSURVSHFWLYHPXOWLFHQWHUREVHUYDWLRQDOVWXG\&OLQ FHUHEURVSLQDOIOXLGIRUGLDJQRVLVRIFRPPXQLW\DFTXLUHG ,QIHFW'LV EDFWHULDOPHQLQJLWLV&OLQ0LFURELRO,QIHFW 5RGULJXH]&HUUDWR90F&RLJ&&0LFKHORZ,&HWDO 3KDUPDFRG\QDPLFVDQGEDFWHULFLGDODFWLYLW\RIPR[L - 15. Andes DR, Craig WA. Pharmacokinetics and pharma- floxacin in experimental Escherichia coli meningitis, FRG\QDPLFVRIDQWLELRWLFVLQPHQLQJLWLV,QIHFW'LV&OLQ $QWLPLFURE$JHQWV&KHPRWKHU 1RUWK$P $JXLODU-8UGD\&RUQHMR9'RQDEHGLDQ6HWDO6WDSK\ - /D[PL67XQNHO$5+HDOWKFDUHDVVRFLDWHGEDFWHULDO lococcus aureus meningitis: case series and literature PHQLQJLWLV&XUU,QIHFW'LV5HS UHYLHZ0HGLFLQH %ULQN0+DJEHUJ/2XWFRPHRIKRXUGRVLQJLQWHU - 6KDLNK=+3HORTXLQ&$(ULFVVRQ&'6XFFHVVIXOWUHDW - YDOVZLWKEHWDODFWDPDQWLELRWLFVLQDGXOWDFXWHEDFWHULDO ment of vancomycin-resistant Enterococcus faecium PHQLQJLWLV6FDQG-,QIHFW'LV meningitis with linezolid: case report and literature 6LSDKL257XUKDQ73XOOXNFX+HWDO0R[LIOR[DFLQ UHYLHZ6FDQG-,QIHFW'LV versus ampicillin + gentamicin in the therapy of experi- .KDZFKDURHQSRUQ7$SLVDUQWKDQDUDN$0XQG\/0 PHQWDO/LVWHULDPRQRF\WRJHQHVPHQLQJLWLV-$QWLPLFURE ,QWUDWKHFDOFROLVWLQIRUGUXJUHVLVWDQW$FLQHWREDFWHU &KHPRWKHU EDXPDQQLLFHQWUDOQHUYRXVV\VWHPLQIHFWLRQ DFDVHVHULHV 19. Prasad K, Kumar A, Gupta PK, et al. Third generation DQGV\VWHPDWLFUHYLHZ&OLQ0LFURELRO,QIHFW FHSKDORVSRULQVYHUVXVFRQYHQWLRQDODQWLELRWLFVIRUWUHDW - LQJDFXWHEDFWHULDOPHQLQJLWLV&RFKUDQH'DWDEDVH6\VW YDQGH%HHN'&RUWLFRVWHURLGHVIRUDFXWHDGXOWEDFWHULDO 5HY &' PHQLQJLWLV0HGLFLQHHWPDODGLHVLQIHFWLHXVHV &KDQJ&-