Bhatti, Atta-ul Aleem

Enam, Syed Ather

Jooma, Rashid

Khan, Aslam

English

eCommons@AKU

Pakistan Journal ofNeurological Sciences (PJNS)Volume 4 | Issue 1 Article 74-2009Intrathecal Use of Polyrnyxinb for MultiresistantAcineobacter MeningitisAtta-ul Aleem BhattiAga Khan UniversityAslam KhanAga Khan UniversitySyed Ather EnamAga Khan UniversityRashid JoomaAga Khan UniversityFollow this and additional works at: https://ecommons.aku.edu/pjnsPart of the Neurology CommonsRecommended CitationBhatti, Atta-ul Aleem; Khan, Aslam; Enam, Syed Ather; and Jooma, Rashid (2009) "Intrathecal Use of Polyrnyxinb for MultiresistantAcineobacter Meningitis," Pakistan Journal of Neurological Sciences (PJNS): Vol. 4 : Iss. 1 , Article 7.Available at: https://ecommons.aku.edu/pjns/vol4/iss1/7Meningitis is a serious complication that may occur afterany neurosurgical procedure. Management becomesespecially challenging when the organism responsible ismulti-drug resistant. Multi-resistant Acinetobacter hasbecome one of the more common nosocomial pathogensin hospitals.1Acinetobacter species are non-motile, oxidase-negative,gram-negative coccobacilli found commonly in soil andwater, but they can be part of normal flora. They areopportunistic pathogens that readily colonize patients whohave compromised host defenses. A variety of humaninfections caused by Acinetobacter species have beendocumented, including nosocomial pneumonia (mostoften related to endotracheal tubes or tracheostomies),endocarditis, meningitis, skin and wound infections,peritonitis (in patients receiving peritoneal dialysis), andurinary tract infections. Sporadic cases of conjunctivitis,osteomyelitis, and synovitis have also been reported.2Multi-drug resistant pathogens are becoming common inICU settings and are very difficult to treat with commonlyavailable antibiotics.1 In many situations involving post-neurosurgical meningitis, intrathecal use of antibiotics isnecessary to clear the infection. There is very limitedpublished experience with intrathecal use of Polymxin B inSouth Asia. In this report, we share our experience ofsuccessful intrathecal use of polymyxin B for thetreatment of multi-resistant Acinetobacter meningitis. CASE REPORTA 25-year-old gentleman sustained head injury after aroad traffic accident and presented to the emergencyroom with post-traumatic recurrent seizures. Onexamination, his Glasgow Coma Score (GCS) was 7/15(localizing pain but no eye/verbal response). Endotrachealintubation was performed due to poor neurological status. A CT scan showed bi-frontal contusions with compoundfrontal sinus and base of skull fractures. Craniotomy forfrontal reconstruction and debridement was performed.The patient was weaned off the ventilator in 3 days anddischarged on day 14 with no focal neurological deficit.One day after discharge he presented to the emergencyroom with fever, drowsiness and a generalized tonic-clonicseizure. Examination showed GCS 11/15 (E4, M5, V2)and a repeat CT scan showed a ring-enhancing lesion inr ight basal gangl ia, at the location of previousintracerebral hemorrhage. Radiologic appearance of thelesion was suggestive of an abscess with development ofhydrocephalus and acute cerebral edema.An urgent ventriculostomy drain was inserted and frankpus was drained. Gram stain revealed gram-negativediplococci and culture grew Acinetobacter lwoffi i,sensitive only to polymyxin B and resistant to imipenem,ceftaz id ime, cefepime, p iperaci l l in- tazobactam,V O L .  4 ( 1 )  J A N  -  M A R   2 0 0 9P A K I S T A N  J O U R N A L  O F  N E U R O L O G I C A L  S C I E N C E S  23C A S E  R E P O R TINTRATHECAL USE OF POLYMYXIN B FOR TREATMENTOF MULTI-RESISTANT MENINGITIS Atta-ul Aleem Bhatti,1 Aslam Khan,2 Syed Ather Enam,1 and Rashid Jooma1Departments of 1Neurosurgery and 2Medicine, Aga Khan University Hospital, Stadium Road, Karachi, PakistanCorrespondence to: Dr. Bhatti, Instructor, Section of Neurosurgery, Department of Surgery, Aga Khan University, Karachi 74800, Pakistan. Tel: +92-21-493-0051. Email:atta.bhatti@aku.eduABSTRACTMulti-resistant gram-negative nosocomial meningitis is a serious life-threatening infection presenting a therapeuticdilemma. We report a neurosurgical patient who developed a post-operative brain abscess due to multi-resistantAcinetobacter Iwoffii, sensitive only to polymyxin B. Successful management was accomplished by administration ofintravenous and intrathecal polymyxin B. Rapid CSF sterilization occurred with excellent clinical recovery and without anyserious side-effects related to polymyxin B. To our knowledge this is the first reported case of intrathecal use of polymyxin Bfrom Pakistan.Pak J Neurol Sci 2009; 4(1): 23-26ampicillin-sulbactam, quinolones, and amikacin. Thepat ient remained vent i lated and was started onintravenous polymyxin 750,000 units twice daily alongwith intrathecal polymyxin B 50,000 units (5 mg) oncedaily. Total treatment duration was two weeks ofintrathecal and 4 weeks of intravenous polymyxin B.Remarkable recovery was noted over the next two weeksand the patient was extubated on day 28 with GCS14/15 (E4, M5, V5). CSF culture became negative 48hours after starting intrathecal polymyxin B. A ventriculo-peritoneal shunt was inserted on day 41 and he wasdischarged home on day 50 of admission. Outpatientfollow-up three months post-discharge confirmed he wasdoing well.DISCUSSIONApproximately 60 - 70% cases of meningitis caused bygram-negative bacilli occur following neurosurgicalprocedures.3 Multiple antibiotic resistance threatenssuccessfu l  t reatment of  Acinetobacter infect ionworldwide. Overuse of ultra-broad spectrum antibioticssuch as imipenem has been associated with reports ofseveral outbreaks caused by carbapenem-resistantstrains, often leaving polymyxins and ampici l l in-sulbactam as the only antibiotics with in-vitro activityagainst these organisms, rendering therapy of thesecases as a serious challenge.4,5 Experience withnosocomial meningit is and ventr icul i t is fol lowingneurosurgical procedures indicates that the mostfavorable outcome results from removal of infectedshunts, creation of an external ventriculostomy opening,and daily administration of systemic and intraventricularbactericidal antibiotics capable of crossing the blood-brain barrier easily.3The case presented here posed a challenging problemsince the organism showed resistance to all antibioticsincluding ceftazidime, cefepime, imipenem, ampicillin-sulbactam and aminoglycosides, and was sensitive topolymyxin B alone. Multi-resistant pathogens arebecoming more common in ICU settings, especially inpatients who have been treated with multiple broadspectrum antibiotic agents, had invasive devicesimplanted or procedures performed in the hospital, andhad prolonged stay in an intensive care unit.1,6 Recentexperience with the use of intravenous polymxin B ismainly limited to these settings.Polymyxin B is one of the earliest agents employed in thetreatment of gram-negative baci l lary meningit is,particularly that due to Pseudomonas aeruginosa.7,8,9 Onlytwo polymyxins, B and E (colistin), have been producedcommercially; polymyxin B has been in clinical use morecommonly. Polymyxin B demonstrates potent bactericidalactivity against most strains of P. aeruginosa, Escherichiacoli, Enterobacter species, and Klebsiella species,damaging the plasma membrane in a manner similar tothat of cationic detergents. It penetrates poorly into CSF,and the presence of meningeal inflammation does notenhance absorption.10 Beneficial reduction in cerebraledema and endotoxin production has been demonstratedin experimental studies in rabbits when high-doseintravenous polymyxin is administered concurrently withanother antibiotic.11 Use of polymyxin alone has been successful in therapy formore than forty three patients with meningitis andventriculitis caused by a number of gram-negativebacteria.4 Although several authors advocate the separateuse of polymyxin B intramuscularly, intravenously, orintrathecally, cure rate seem to be more frequent amongpatients receiving combination systemic and local therapy(intrathecal or intraventricular) or local polymyxin B as anadjunct to other systemic therapy.7,12 Sterilization of CSFoccurs promptly (within 24-48 hours) when therapy isgiven in conjunction with surgical repair and/or foreign-body removal.13 The majority of reported patients received prolongedintrathecal or intraventricular therapy with polymyxin B (3-38 days; 13-205 mg). Most patients received 10-14 daysof therapy with a total dose of 30-50 mg (3-5 mg daily).Our patient received a 14-day course with a total of 70mg (5 mg intrathecally daily of pure polymyxin B base,which is equivalent to 50, 000 units of polymyxin B). V O L .  4 ( 1 )  J A N  -  M A R   2 0 0 9P A K I S T A N  J O U R N A L  O F  N E U R O L O G I C A L  S C I E N C E S  24Table1 Serial CSF AnalysisCSF Analysis Day 1 Day 7 Day 14 Day 24Glucose(mg/dl) 23 55 70 55Chloride(mEq/L) 120 115 118 110Protein(mg/dl) 114 715 398 96.1TLC(per cu mm) 2800 304 40 05Polymorphs(%) 90 60 70 *Lymphocytes(%) 10 40 30 *RBC(per u mm) 120 1346 40 *Pus cells Numerous Few Few RareGram stain +++ Nil Nil NilCulture¶ positive negative negative Negative*Cells insufficient for differential count¶CSF cultures negative 48 hours after starting intrathecal polymyxin BCSF levels range from 1.2-112 U / ml in children receiving10,000-40,000 U of polymyxin intrathecally.10 Bactericidalactivity in CSF was assayed in one patient who receivedintrathecal polymyxin B and was cured. The CSF trough wasbacteriostatic at a 1:8 dilution and bactericidal at a 1:4dilution.14 In vitro synergy of polymyxin B with imipenem andother antimicrobial agents against Acinetobacter, Klebsiella,and Pseudomonas species have been documented.15Polymyxin B is nephrotoxic and neurotoxic and has beenassociated with renal insufficiency, giddiness, neuromuscularblockade, and hyponatremia when used parenterally; andwith pain, numbness, paresthesia, confusion, coma andconvulsions when used intrathecally. The chemicalarachnoiditis seen with polymyxin is B is dose-dependent.9,13,16,17 The parenteral dose ranges from 2.5-3mg / kg per day in two divided doses. The intrathecal dosageis 5 mg once daily for adults, 2 mg daily for children <2years of age, and 3-4 mg daily for older children.Neurotoxicity is seen when the dosage exceeds 5 mg or50,000 U per day.10 Our patient did not develop any nephrotoxicity due topolymyxin. He had prolonged seizures, which started prior toadministration of polymyxin B and may have been related tothe development of brain abscess and late post-traumaticmeningitis. The seizures were probably not related to the useof polymyxin B as they subsided while the patient continuedto receive intrathecal polymyxin B.  CONCLUSIONThis report and our experience suggest the benefit ofreinstating polymyxin B as a potential life-savingantimicrobial therapy for multi-resistant, gram-negativemeningitis. Intrathecal polymyxin B appears to be safe andshould be combined with an effective systemic agent toimprove efficacy of therapy and minimize emergence ofresistance. REFERENCES1. Lortholary O, Fagon JY, Buu Hoi, A, Mahieu G, Gutmann L. Colonization by Acinetobacter baumanii in intensive-care-unit patients. Infection Control andHospital Epidemiology 1998 Mar; 19(3): 188-90 2. Glew RH, Moellering RC, Kunz LJ. Infections with Acinetobacter calcoaceticus (Herellea vaginicola): Clinical and laboratory studies. Medicine 1977 Mar;56(2):79-97 3. Rahal JJ. Diagnosis and management of meningitis due to gram-negative bacilli in adults. Curr Clin Top Infectious Dis 1980 1:68- 844. Segal-Maurer S, Mariano N, Qavi A, Urban C, Rahal JJ Jr. Successful treatment of ceftazidime-resistant Klebsiella pneumoniae ventriculitis with intravenous meropenem and intraventricular polymyxin B: case report and review. Clin Infect Dis 1999 May;28(5): 1134-385. Corbella X, Ariza J, Ardanuy C, Vuelta M, Tubau F, Sora M, Pujol M, Gudiol F. Efficacy of sulbactam alone and in combination with ampicillin in nosocomial infection caused by multiresistant Acinetobacter baumannii. J Antimicro Chem 1998 Dec;42(6):793-802.6. Jiménez-Mejías ME, Pachón J, Becerril B, Palomino-Nicás J, Rodríguez-Cobacho A, Revuelta M. Treatment of multidrug-resistant Acinetobacter baumannii meningitis with ampicillin/sulbactam. ClinInfect Dis 1997 May;24(5):932-5 7. Biehl JP, Hamburger M. Polymyxin B therapy of meningitis following procedures on central nervous system. Arch Intern Med 1954 Mar;93:367- 788. Geelhoed GW, Ketcham AS. Pseudomonas meningitis complicating radical resection for recurrent cancer of the paranasal sinuses: report of two patients successfully treated with intrathecal polymyxin. J Surg Oncol 5:365- 74, 19739. Heyes ER, Yow D. Meningitis due to Pseudomonas aeruginosa treated with polymyxin B. Am J Med Sci V O L .  4 ( 1 )  J A N  -  M A R   2 0 0 9P A K I S T A N  J O U R N A L  O F  N E U R O L O G I C A L  S C I E N C E S  25Table2 Clinical ResponseClinical Status Day 1 Day 7 Day 14 Day 24Seizures Generalized Generalized Generalized NoneFever High-grade High-grade Intermittent Persistent Persistent Spike NoneGCS 11/15 5/15 14/15 15/15Pupils BERL* Mid-dilated BERL BERLbut reactive to light*BERL   Bilaterally equal and reactive to light 1950 Dec;220(6):633-7.10. Everett ED, Strausbaugh LJ. Antimicrobial agents and the central nervous system. Neurosurgery 1980Jun;6(6):691-71411. Tauber MG, Shibl AM, Hackbarth C, Larrick JW, Sande MA. Antibiotic therapy, endotoxin concentration in CSF, and brain edema in experimental meningitis in rabbits. J Infect Dis 1987Sep;156(3):456-6212. Quintiliani R, Lentnek A. Polymyxin B in the treatment of Klebsiella pneumoniae meningoventriculitis. Intraventricular and intrathecal administration. Am J Dis Child 1971 Mar;121(3):239-4213. Wise BL, Mathis JL, Jawetz E. Infection of the central nervous system due to Pseudomonos aeruginosa. J Neurosurg 1969 Oct;31(4):432-414. Furey W, Ciric I, Parker RH. Monitoring of intrathecalpolymyxin B dosage during treatment of pseudomonas meningitis. IMJ Ill Med J 1971 May;139(5):506-1015. Chin NX, Scully B, Della- Latta P. In vitro synergy of polymyxin B with imipenem and other antimicrobial agents against Acinetobacter, Klebsiella, and Pseudomonas species [abstract no E- 56]. In: Program and abstracts of the 38th International Conference on Antimicrobial Agents and Chemotherapy (San Diego). Washington, DC: American Society for Microbiology, 1998:18416. McGill RJ, Mendel D. Polymyxin B: an intrathecal reaction. Lancet 1953 Dec 19;265(6799):1293-4.17. Teng P, Johnson BA. Experimental intracisternal injection of polymyxin B: its role in the treatment of septic meningitis. Neurology 1953 Nov;3(11):831-43V O L .  4 ( 1 )  J A N  -  M A R   2 0 0 9P A K I S T A N  J O U R N A L  O F  N E U R O L O G I C A L  S C I E N C E S  26

Intrathecal Use of Polyrnyxinb for Multiresistant Acineobacter Meningitis

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Intrathecal Use of Polyrnyxinb for Multiresistant Acineobacter Meningitis

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