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1、Int J Clin Exp Med 2015;8(11):21833- ReportPost-neurosurgical meningitis caused by acinetobacter baumannii:case series and review of the literatureShunlan Ni1,Shanshan Li1,Naibin Yang1,Sainan Zhang1,Danping Hu2,Qian Li3,Mingqin Lu11Department of Infectious Diseases,The First Affiliated Hospital of W

2、enzhou Medical University,Wenzhou Key Laboratory of Hepatology,Hepatologic Institute of Wenzhou Medical University,Wenzhou,Zhejiang,P.R.China;2Department of Infectious Diseases,Ruian City Peoples Hospital,The Third Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,P.R.China;3Departm

3、ent of Neurology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,P.R.ChinaReceived August 23,2015;Accepted October 25,2015;Epub November 15,2015;Published November 30,2015Abstract:Background:Acinetobacter baumannii(A.baumannii),a gram-negative bacterium,has now become an

4、 important hospital pathogen,which causes various serious nosocomial infections worldwide.Bacterial meningitis is a common complication after neurosurgical operation,and the percentage of A.baumannii meningitis is grow-ing,especially the one resisting multiple drugs.Method:We retrospectively reviewe

5、d the cases with postoperative A.baumannii meningitis(PABM)in the First Affiliated Hospital of Wenzhou Medical University from January 2013 to October 2014.And we retrieved the PubMed for cases with PABM and reviewed them.Result:Five cases were included in our retrospective study.Two cases with sens

6、itive A.baumannii and one with multidrug-resistant acineto-bacter baumannii(MRAB)were cured,and other two with MRAB died.Conclusion:Intraventricular or intrathecal colistin could be a treatment to the MRAB.Keywords:Acinetobacter baumannii,postoperative meningitis,colistinIntroductionAcinetobacter ba

7、umannii(A.baumannii)is a gram-negative bacillus of the acinetobacter.Infection caused by A.baumannii becomes more and more common in hospital worldwide,due to it possessing multiple mechanisms of drug resistance 1.It is an opportunistic patho-gen that can be detected on human skin and in human tract

8、s connected with the outside world.Thus A.baumannii easily causes serious infec-tion of critical patients,such as the one with pneumonia,septicemia,meningitis,etc.2,3.The patients after craniocerebral operations in neurosurgery have a high risk to suffer from bacterial meningitis caused by A.baumann

9、ii and get potentially fatal consequences.The meningitis caused by A.baumannii is well rec-ognized and has been described by many doc-tors worldwide.Most of case reports about the meningitis were associated with external ven-tricular drainage(EVD),cerebrospinal fluid(CSF)leaking,or head trauma 4-6.H

10、ere we reported five cases of PABM in the same neuro-surgical intensive care Unit.Materials and methodsWe performed a retrospective clinical study of PABM in neurosurgery during the period between 1 January 2013 and 31 October 2014.During this period,A.baumannii was isolated from the CSF of five pat

11、ients treated at the First Affiliated Hospital of Wenzhou Medical Univer-sity.When the patients symptoms or signs disap-peared,clinical cure was considered 5.Bacteriologic cure was considered when A.bau-mannii was not found in CSF during therapy for two successive cultures 7.A patient was con-sidere

12、d to be cured for both clinical cure and bacteriologic cure.At the same time,death was considered to be related to meningitis when the patient died during treatment for meningitis with no other obvious explanation for death.Postoperative meningitis with acinetobacter baumannii21834 Int J Clin Exp Me

13、d 2015;8(11):21833-21838ResultsThere were five cases of nosocomial A.bau-mannii meningitis over the study period(four males and one female).All patients received broad-spectrum antibiotics prior to their infec-tions.Three patients were cured and two patients died of the serious meningitis.Case 1:A 3

14、5-year-old man without any medical history was admitted to the hospital because of the thalamus and brainstem hemorrhage breaking into the ventricles.Cerebral arteriog-raphy was performed that demonstrated a Moyamoya disease,and two EVDs were implanted into both sides.The right EVD was removed on da

15、y 16 and the left one on day 31.On day 30 of hospitalization,his condition worsened,fever appearing(peak 39.7C)with narcosis.CSF analysis was performed and revealed a WBC count of 1240106/L with 98%polymorphonuclear leukocytes and 1%lympho-cytes,a glucose concentration of 1.1 mmol/L,a protein level

16、of 2470 mg/L and chloride of 112 mmol/L.CSF culture yielded A.baumannii just resisting Aztreonam and Ceftriaxone and sensitizing to other antibiotics.Recurrent hydrocephalus was detected,brain CT images showed ventriculomegaly,so another EVD was re-implanted into the right ventricle and an OMMAYA re

17、servoir sac was implanted to left ventricle.12 days later,the EVD was removed.Linezolid 0.6 g,meropenem 1 g,Ciprofloxacin 100 ml and Fosfomycin 8 g 12 hourly were administrated successively for 12 days.On day 46 and 48 of hospitalization,CSF culture yield-ed sterile,but functional recovery was poor

18、despite rehabilitation.The patient was dis-charged on day 53 to a rehabilitation centre and he fully recovered after 2 months in there.Case 2:A 57-year-old man with a medical his-tory of hypertension was admitted to the neuro-surgical intensive care unit(NSICU)because of the thalamus hemorrhage brea

19、king into the ventricles.The patient had another medical his-tory of diabetes.On day 2,an OMMAYA reser-voir sac was implanted and tracheotomy was performed.Linezolid and Augmentin were directly applied as prior antibiotics.On day 7 of hospitalization,because of fever(peak 38.4C),a CSF tap was perfor

20、med and revealed a WBC count of 360106/L with 98%polymorphonu-clear leukocytes and 2%lymphocytes,a glu-cose concentration of 1.1 mmol/L,a protein level of 2173 mg/L and chloride of 113 mmol/L.Ceftriaxone and Betamipron were added into therapeutic regimen.On day 16,sputum and CSF culture yielded MRAB

21、,which were only sensitive to Tobramycin.So Tobramycin,ceftri-axone,linezolid and minocycline were adminis-trated.On the 15th day of treatment,CSF cul-ture yielded sterile.On day 34 of hospitaliza-tion,the patient was discharged.Case 3:A 5-year-old boy with medulloblastoma required craniotomy in hos

22、pital.On day 4 of hospitalization,intracranial tumor resection was performed without an EVD.Because of intracranial pressure increasing,the operation of lumbar continuous drainage of fluid was per-formed on day 13 and the drainage tube was removed 7 days later.On day 16,because of the hyperpyrexia(p

23、eak 39.2C),CSF analyses revealed a WBC count of 560106/L with 96%polymorphonuclear leukocytes and 4%lympho-cytes,a glucose concentration of 2.2 mmol/L,a protein level of 2413 mg/L and chloride of 118 mmol/L.At the same time,CSF and blood culture yielded sensitive A.baumannii.Sub-sequently,after 3 da

24、ys of meropenem and line-zolid administrated,repeated cerebrospinal fluid cultures were negative.On day 28 of hos-pitalization,the patient was discharged with improved clinical symptoms.Case 4:A 41-year-old man was admitted to the NSICU because of subarachnoid hemorrhage(SAH).Cerebral arteriography

25、was performed to demonstrate right vertebral dissecting aneu-rysm and anterior communicating aneurysms.Endovascular aneurysm and parent artery embolization was performed when he was admitted to hospital immediately.On day 3,the patient underwent a tracheotomy.On day 18,sputum culture yielded A.bauma

26、nnii.On day 30,ventriculo-peritonal shunt operation was performed.Because of ardent fever(peak 39.5C),intravenous Tazocin 4.5 g 8 hourly and Meropenem 0.5 g 6 hourly were commenced.On day 40,MRAB was isolated from CSF and EVD,which was only sensitive to Sulfame-thoxazole.CSF analysis revealed a WBC

27、count of 41600106/L with 97%polymorphonuclear leukocytes,a glucose concentration of 1.1 mmol/L,a protein level of 3000 mg/L and chlo-ride of 103 mmol/L.Intravenous Sulperazone and Sulfamethoxazole were commenced for 17 days,and intravenous Norvancomycin for 14 days.On day 58 of hospitalization,the p

28、atient died from the serious intracranial infection.Postoperative meningitis with acinetobacter baumannii21835 Int J Clin Exp Med 2015;8(11):21833-21838Table 1.Published cases of A.baumannii meningitis treated with colistin.ReferenceAge/sex DosageRoute OutcomeBenifla et al.,2004 1649/F3.2 mg q24 h f

29、or 17 daysIVTCuredBukhary et al.,2005 1723/F10 mg q12 h for 21 daysIVTCuredKasiakou et al.,2005 1828/MEpisode 1:1.6 mg for 3 weeks;Episode 2:3.2 mg q24 h for 42 days IVTCuredBerlana et al.,2005(2 cases)19UPatient 1:10 mg q12 h for 8 days;Patient 2:20 mg q24 h for 10 daysIVTOne cured,one diedNg et al

30、.,2006(5 cases)2074/F5 mg 1st day and10 mg q24 h for 18 daysIVTCured56/F5 mg 1st day and10 mg q24 h for 3 daysIVTCured38/F5 mg 1st day and10 mg q24 h for 12 daysIVTCured26/M5 mg 1st day and 10 mg q24 h for 6 daysITCured4/M1 mg q24 h 1st day,2 mg q24 h 2nd and 3rd day,then 4 mg q24 h for 13 daysITCur

31、edAl Shirawi et al.,2006 2128/M3.2 mg q24 h for 28 daysITCuredMotaouakkil et al.,2006 2236/M5 mg q24 h 1st day,10 mg q24 h for 21 daysITCuredHo et al.,2007(2 episodes)2368/FEpisode 1:1.6 mg q24 h 1st day,3.2 mg q24 h 2nd,4.8 mg q24 h 3rd day,2.4 mgq 24 h 4th day,then 4.4 mg q48 h for 13 days.Episode

32、 2:6.4 mg q24 h for 12 daysITCuredHachimi et al.,2008 2473/M5 mg q24 h 1st day,10 mg q24 h for 21 daysIVTCuredPascale et al.,2009 2542/M75 000 IU every 24 hours for 3 days,150 000 IU every 24 hours for 22 daysITCuredAntonio Cascio et al.,2010 436/M10 mg q24 h for 10 daysITCuredKaraiskos et al.,2013(

33、6 cases)660/MIVT,40 mg q24 h 1st day,20 mg q24 h 2nd and 3rd days and 10 mg q48 h for 12 days.IT,20 mg q48 h for 4 daysIVT,ITCured26/M40 mg q24 h for 6 days,20 mg q48 h for 15 daysIVTCured53/MIVT,40 mg q24 h 1st day,20 mg q24 h 2nd and 3rd days,20 mg q48 h for 8 days.IT,20 mg q48 h for 10 daysIVT,IT

34、Cured44/FIVT,40 mg 1st day,10 mg q24 h for 8 days.IT,10 mg q48 h for 6 daysIVT,ITCured60/M40 mg 1st day,10 mg q24 h for 14 daysIVTCured62/F40 mg 1st day,30 mg 2nd day,10 mg q24 h for 3 days,10 mg q48 h for 7 daysIVTCuredM,male;F,female;U,unknown;IVT,intraventricular;IT,intrathecal;IU,international u

35、nits.Postoperative meningitis with acinetobacter baumannii21836 Int J Clin Exp Med 2015;8(11):21833-21838Case 5:A 65-year-old woman with a medical history of hypertension was admitted to the NSICU because of right basal ganglia hemor-rhage.The patient had a medical history of dia-betes.On the day of

36、 admission,an OMMAYA reservoir sac was implanted to left frontal and an EVD removed 8 days later to right ventricle.On day 4,the patient underwent a tracheotomy.After intracranial operation,sulperazone was commenced to prevent infection for 20 days.On day 23,the OMMAYA was removed.On day 24 of hospi

37、talization,the patient presented with fever(peak 39.0C)accompanied with altered mental status.CSF analyses revealed a WBC count of 1880106/L with 95%polymor-phonuclear leukocytes and 2%lymphocytes,a glucose concentration of 1.1 mmol/L,a protein level of 2158 mg/L and chloride of 109 mmol/L.CSF cultu

38、re yielded MRAB resisting to-lactam,quinolones and sulfonamides antibiotics.And we administrated tobramycin,imipenem and tazocin for 5 days.Then CSF culture yielded not only MRAB,also klebsiella pneumonia and pseudomonas aeruginosa.Thus,vancomycin,tobramycin,fosfomycin,cefoperazone and meropenem wer

39、e successive and combined to treat the meningitis for 23 days.However,repeated CSF cultures were all positive during this period with symptoms getting worse and signs becoming more obvious.The patient died from serious intracranial infection on day 53 of hospitalization.Literature review and discuss

40、ionIntracranial infections including ventriculitis and meningitis caused by A.baumannii in the neurosurgery setting have been challenging situations 8,9.The percentage of intracranial infection caused by A.baumannii in postopera-tive infection continuously increased in recent years.Meningitis develo

41、ping within 3 months after neurosurgery is defined as“post-neurosurgical meningitis”10.Post-neurosurgical A.bau-mannii meningitis was diagnosed after meeting following criteria:(1)A.baumannii was cultured from the cerebrospinal fluid(CSF)of a patient;(2)CSF changed in white cells increasing,pro-tein

42、 elevating,glucose decreasing,etc.;(3)the patient had at least one symptom or sign with-out other apparent causes:fever(38C),headache,vomiting,confusion,irritability or meningeal irritation;(4)the patient underwent an operation procedure of neurosurgery within 3 months 7.A patient was considered to

43、be cured when both symptoms and signs disap-peared and the CSF was sterile.In this report,we reported 5 cases with infec-tion of A.baumannii after craniocerebral opera-tion,and 3 of them were infected by MRAB.Two patients with MRAB died during treatment.Thus,the mortality of postoperative meningitis

44、 with MRAB was high.Reducing the death rates and improving cure rates was very important and urgent clinically.There were various antibiotics clinically used to treat the infection.Carbapenems used to be the empirical drugs for choice 11.However,more than 30%of A.baumannii strains were resistant to

45、at least three kinds of antibiotics in many general hospitals.And MRAB generally resisting to fluoroquinolones and carbapenems gradually increased in recent years 12.At present,more and more reports about postop-erative infections with A.baumannii in neuro-surgery cured by intraventricular(IVT)or in

46、tra-thecal(IT)colistin were published in various journals around the world.Colistin was introduced in clinical use from 1950s,and abrogated in 1980s due to serious renal toxicity and neurovirulence.However,colistin was found to be effective for the multi-drug resistance(MDR)and extensive drug resist

47、ance(XDR)Gram-negative bacteria,including the Acinetobacter 9,13.Maartens et pared colistin with car-bapenems and tobramycin,and found that colistin was still effective for A.baumannii in resistance of other antibiotics,and no differ-ence in renal toxicity was revealed among these antibiotics 14.Rol

48、ain et al.indicated that colistin worked through modifying the negative charges of outer membranes in Gram-negative bacteria 15.We retrieved the cases of PABM treated with colistin in PubMed,and reviewed them as Table 1.And we found that IVT or IT colistin was one optional way to treat the postopera

49、tive menin-gitis with sensitive or resistant A.baumannii.Disclosure of conflict of interestNone.Address correspondence to:Dr.Mingqin Lu,Depart-ment of Infectious Diseases,The First Affiliated Hos-Postoperative meningitis with acinetobacter baumannii21837 Int J Clin Exp Med 2015;8(11):21833-2183811 M

50、etan G,Alp E,Aygen B and Sumerkan B.Car-bapenem-resistant Acinetobacter baumannii:an emerging threat for patients with post-neu-rosurgical meningitis.Int J Antimicrob Agents 2007;29:112-113.12 Metan G,Alp E,Aygen B and Sumerkan B.Aci-netobacter baumannii meningitis in post-neu-rosurgical patients:cl