Relapsing bacterial meningitis in adults

Transcription

1 QJ Med 1994; 87: Relapsing bacterial meningitis in adults L.M. TANG S.T. CHEN From the Department of Neurology, Chang Gung Memorial Hospital Medical College, Taipei, Taiwan Received 4 May 1994; Accepted 23 May 1994 Summary Relapsing bacterial meningitis is a rare condition, diagnosed in eight patients between at our institution. These accounted for 3.4% of 234 adult patients with blood /or cerebrospinal fluid cultureproven bacterial meningitis. A review of the Englishlanguage literature from 1966 to the present revealed only five further adult cases of relapsing bacterial meningitis with indepth case histories. Of these 13 total patients, nine were female four male, aged 1761 years. Ten were neurosurgical Introduction Reports about reappearance of symptoms signs of bacterial meningitis have focused mainly on recurrence, which is defined as a new episode of bacterial meningitis after convalescence, 1 caused by reinfection with the same or different bacteria. Only a few studies have reported the occurrence of relapse, the reappearance of clinical laboratory signs of bacterial meningitis from a prior episode of infection caused by the same microorganism. Relapse results from persistence of the initial infection rather than reinfection, usually occurs within 4 weeks of the completion of antibiotic therapy for the initial episode. In 1981, there was a collected series of relapsed bacterial meningitis in children. 2 However, in adults, only a few sporadic cases of relapsing bacterial meningitis have been reported. 3 " 7 In a recent study of acute bacterial meningitis in 445 adults, neither clinical nor pathological features were described for the six patients with relapse of infection. 8 This study describes the adult cases of relapsing bacterial meningitis diagnosed at our institution, examines the incidence of this rare condition, patients. Gramnegative bacilli, especially Klebsiella species, were the commonest microorganisms identified for both the initial episode the relapse of infection. Three patients died in the course of relapse. Four or more weeks of antibiotic therapy may be needed to treat postsurgical patients with Gramnegative bacillary meningitis. Even a normal cerebrospinal fluid study at the end of treatment of bacterial meningitis is not a guarantee of freedom from relapse. also reviews adult cases reported in the Englishlanguage literature, to delineate the clinical laboratory features of relapsing bacterial meningitis in adults. Methods Patients We reviewed both microbiological records of cerebrospinal fluid (CSF) blood cultures medical records of patients aged 16 years or older in whom bacterial meningitis was diagnosed at Chang Gung Memorial Hospital from January 1981 to December The criteria for inclusion were: (i) reappearance of clinical laboratory features of bacterial meningitis within 4 weeks of discontinuation of antibiotic therapy for the initial episode of infection; (ii) isolation of the microorganism from the CSF culture in the relapse /or in the initial episode. Cases with different aetiological agents in the relapse in the initial episode were not included. We recorded clinical manifestations, associated Address correspondence to Or LokMing Tang, Department of Neurology, Chang Gung Memorial Hospital, 199 Tung Hwa North Road, Taipei, Taiwan Oxford University Press 1994

2 512 L.M. Tang S.T. Chen Table 1 Clinical features of 13 patients with relapsing bacterial meningitis Reference Sex/age (years) Associated conditions Duration of the initial course of antibiotic therapy Time from completion of initial therapy to relapse Duration of antibiotics used in relapse Outcome Bradsher 3 Eng et a/. 4 Hickstein Dillon s Hollifield ef a/. 6 Madhavan ef a/. 7 [PR] Patient 1 [PR] Patient 2 F/27 F/61 F/24 F/29 M/21 F/28 F/51 Serous cystadenocarcinoma of the ovary; colostomy for bowel obstruction caused by recurrent tumor; lumboperitoneal shunt Positive HIV antibody drug abuse Cranial neurosurgery for a pituitary tumor Cranial neurosurgery for a pituitary tumor Nelson's syndrome; cranial neurosurgery for a pituitary tumor; lumbar drainage for CSF leak Subarachnoid hemorrhage; craniotomy for aneurysm clipping; pregnancy Craniotomy for meningioma 10 days of 21 days of cefotaxime 30 days of ceftazidime tobramycin 10 days of 8 days of ; then 21 days of tobramycin 18 days of cefotaxime 7 days of ceftriaxone; then 42 days of moxalactam 5 days 7 days 9 days 6 days 1st relapse: 9 days 2nd relapse: 4 days 7 days 14 days None 5 days of imipenem; then 28 days of ceftazidime tobramycin 11 days of ; then 16 days of trimethoprimsulfamethoxazole 49 days of About 15 days of less than 21 days of 5 days of cefotaxime; then 33 days of moxalactam Death Vegetative state Relapse

3 Relapsing bacterial meningitis 513 Table 1 {continued) Reference Sex/age (years) Associated conditions Duration of the initial course of antibiotic therapy Time from completion of initial therapy to relapse Duration of antibiotics used in relapse Outcome [PR] Patient 3 [PR] Patient 4 [PR] Patient 5 [PR] Patient 6 [PR] Patient 7 [PR) Patient 8 M/42 F/56 F/49 M/48 M/53 F/17 Subarachnoid hemorrhage; ventriculoperitoneal shunt for hydrocephalus Ventriculoperitoneal shunt for hydrocephalus due to tuberculous meningitis External ventricular drainage then ventriculoperitoneal shunt for thalamic hemorrhage complicated with hydrocephalus Diabetes mellitus alcoholism Evan's syndrome ventriculoperitoneal shunt for hydrocephalus 15 days of penicillin 30 days of moxalactam 22 days of cefotaxime 10 days of oxacillin, 7 days of penicillin ceftriaxone cefotaxime; then 10 days of piperacillin ceftriaxone 1 day 5 days 11 days 27 days 26 days 1 st relapse: 7 days 2nd relapse: 7 days 21 days of penicillin 5 days of moxalactam, 50 days of ceftriaxone amikacin 17 days of cefotaxime 15 days of vancomycin 11 days of ceftriaxone & penicillin 42 days of ceftriaxone 42 days of cetriaxone Death Death Relapse PR, present report. conditions, laboratory findings, durations of use of antibiotics in both initial therapy relapse, time from completion of the initial course of antibiotic therapy to relapse, outcome. Meningitis was defined as either nosocomial or communityacquired. 9 Only the CSF findings at the first lumbar puncture in the initial episode of infection, at the end of the initial course of antibiotic therapy in the relapse were analysed. Antibiotic therapy was considered appropriate if the antibiotics administered on the day of diagnosis were demonstrated to be effective against the causative microorganism by sensitivity test, the antibiotics used were capable of reaching the central nervous system (CNS) in adequate amounts. Literature review The MEDLINE service was used to review cases of relapsing bacterial meningitis reported in the Englishlanguage literature from 1966 to the present day. Key words in the search were relapsing bacterial meningitis. Only adults with indepth case histories were included.

4 514 L.M. Tang S.T. Chen Results Eight patients were diagnosed at our institution. The main clinical features are summarized in Table 1. Three cases are presented in detail to exemplify certain salient features. Case reports Patient 1 A 28yearold pregnant woman was well until four weeks before admission, when she experienced a sudden onset of headache disturbance of consciousness for 24 h. She was evaluated at another hospital, an emergency CT scan of the brain showed blood filling the basal cisterns the cortical sulci. The patient was delivered of a premature baby, was then transferred to our hospital for further evaluation of the subarachnoid haemorrhage. On admission, the patient was alert with a supple neck. Cerebral angiography revealed a left anterior communicating artery aneurysm, craniotomy for aneurysm clipping was performed. The immediate postoperative course was uneventful; however, 36 h after surgery, the patient became confused. Her body temperature was 39.2 C. Her neck was rigid, there was moderate weakness of the right upper lower limbs. The leucocyte count was 11 x 10 9 cells/i, with 88% polymorphonuclear neutrophils, 6% bs, 4% lymphocytes 2% monocytes. Lumbar puncture yielded a fluid containing 1565 x10 6 leucocytes/i with 95% polymorphonuclear cells, glucose 0.11 mmol/l, protein 2.44 g/l, lactate 13.7 mmol/l. Gram stain showed Gramnegative bacilli. Both CSF blood cultures grew Escherichia co//that was sensitive to aminoglycosides thirdgeneration cephalosporins, but resistant to. The patient was treated with cefotaxime 8 g/day dexamethasone 20 mg/day i.v. She was alert, the strength of her right limbs started to improve on day 3 of treatment. The patient became afebrile on day 10. On day 15, a CSF study showed only 17 x 10 6 leucocytes/i with normal glucose protein; Gram stain bacterial culture were negative. Dexamethasone was stopped on day 15 cefotaxime on day 18. Seven days after stopping cefotaxime, fever recurred her body temperature rose to 39.6 C. The leucocyte count was 9.3 xio 9 cells/i with a normal differential cell count. Both CSF blood cultures again grew E. coli. A second course of antibiotic therapy with cefotaxime 8 g/day was initiated, but on day 6 was changed to moxalactam 3 g/day 240 mg/day for the persistence of fever. The fever subsided on day 15. Moxalactam were discontinued on day 38 of antibiotic treatment. Culture of CSF taken on day 35 of antibiotic therapy was sterile. The patient was discharged after nearly 3 months in hospital remained well at followup examination 4 years later. Patient 3 A 42yearold man was admitted with a 12h history of headache, vomiting disturbance of consciousness. Past history was unremarkable. On admission, he was confused with a temperature of 38 C. Physical examination revealed no abnormality except that the neck was rigid. The leucocyte count was 17.8 x 10 9 cells/l, with 71% polymorphonuclear neutrophils, 15% bs, 8% lymphocytes 6% monocytes. Lumbar CSF examination revealed 2700 x10 6 leucocytes/i, with 89% polymorphonuclear cells, glucose 0.28 mmol/l (blood glucose 11.4 mmol/l), protein 6.6 g/l, lactate 23 mmol/l. Gram stain showed Grampositive cocci. Both CSF blood cultures grew Streptococcus pneumoniae that was sensitive to penicillin. The patient became afebrile alert within 3 days of antibiotic treatment with penicillin 24 x 10 6 ILJ/day. After 15 days penicillin treatment, a repeat CSF study showed 3x10 6 leucocytes/i. Gram stain bacterial culture were negative. The patient was then discharged. One week after discharge, the patient was readmitted because of the occurrence of intermittent fever for 6 days. His neck was slightly rigid. The leucocyte count was 9.9 x10 9 cells/l, with 59% polymorphonuclear neutrophils, 28% lymphocytes, 12% monocytes 1% bs. CSF examination revealed 2160 x 10 6 leucocytes/i, with 88% polymorphonuclear cells, glucose 2.8 mmol/l (blood glucose 6.4 mmol/l), protein 3.3 g/l, lactate 5.8 mmol/l. Gram stain bacterial culture were negative. The patient received a 3week course of antibiotic therapy (penicillin 24x10 6 ILJ/day 4 g/day). He made an uneventful recovery from the illness, returned to his normal activities, remained well at followup examination 3 years later. Patient 7 A 53yearold man was sent to our emergency room after an episode of generalized convulsion. Past history revealed that the patient was diabetic alcoholic. On admission, he was confused with a temperature of 40 C, a stiff neck. The leucocyte count was 8.2 x 10 9 cells/l, with 91% polymorphonuclear neutrophils. ESR was 98 mm/h. Lumbar CSF examination revealed 172x10 6 leucocytes/i, with 99% polymorphonuclear cells, glucose 4.6 mmol/l (blood glucose 24.8 mmol/l), protein 3.24 g/l, lactate 18.2 mmol/l. was

5 Relapsing bacterial meningitis 515 grown from the cultures of CSF, urine blood, was sensitive to all thirdgeneration cephalosporins tested. Six days after treatment with penicillin 24 x 10 6 lu/day ceftriaxone 4 g/day, the patient became alert. The leucocyte count was 15.4x10 9 cells/i, with 66% polymorphonuclear neutrophils 17% bs. Penicillin was discontinued 7 days later ceftriaxone 14 days later. The patient was discharged in good physical condition. Four weeks later, he was readmitted because of fever drowsiness for 2 days. He was confused his neck was stiff. The leucocyte count was 10.3 x10 9 cells/i, with 88% polymorphonuclear neutrophils 6% bs. Lumbar CSF revealed 296 x 10 6 leucocytes/i, with 99% polymorphonuclear cells, glucose 0.94 mmol/l (blood glucose 15.9 mmol/l), protein 2.36 g/l lactate 19 mmol/l. CSF, urine blood cultures all yielded K. pneumoniae, which was still sensitive to thirdgeneration cephalosporins. Penicillin ceftriaxone were again administered. However, the patient's level of consciousness continued to deteriorate. Three days after admission, a ventriculoperitoneal shunt was performed, as a CT scan of the head showed marked hydrocephalus. Since then, the patient has had frequent attacks of gr mal seizures despite vigorous therapy with anticonvulsants. Eleven days after admission, the patient was taken home against our advice, died 5 days later. Summary of cases in the present report The clinical features of the eight patients with relapsing bacterial meningitis are summarized in Table 1. There were five females three males, aged 1756 years. These patients were diagnosed between , comprising 3.4% of 234 cases with CSF /or bloodcultureproven bacterial meningitis in patients over 16 years of age. The infection was communityacquired in two patients, nosocomial in six. One or more underlying conditions were present in all but one patient (Patient 3). Six patients had had cranial neurosurgery, one patient had a previous history of diabetes mellitus alcoholism. Appropriate antibiotics were administered for all patients in the initial infection. The duration of the initial course of antibiotic therapy ranged from 10 to 49 days, with a mean of 22.7 days. It was 25.5 days for the six patients with cranial neurosurgery, 14 days for the patient with diabetes, 15 days for the patient without associated conditions. Only 2/8 patients had a course of antibiotic therapy for more than 4 weeks. Four patients had the meningitis relapse in the first week after discontinuation of antibiotic therapy for the initial episode of infection. One patient had two relapses. In five patients, different antibiotics were used for the relapse of meningitis. The duration of antibiotics used for the relapse of meningitis ranged from 11 to 55 days, with a mean of 26.5 days. The CSF cultures were positive in the initial episode of meningitis in all patients in the relapse in all but one patient (Patient 3) (Table 2). In six patients, the causative organism isolated in the initial infection was identical to that in the relapse. One patient (Patient 5) had a mixed bacterial meningitis with Klebsiella oxytoca Proteus mirabilis isolated from the CSF culture in the initial infection, but only K. oxytoca in the relapse. Five patients had CSF studies at the end of the initial course of antibiotic therapy: two with a leucocyte count greater than 10 x 10 6 /l, three with a slightly reduced glucose concentration one with a protein level higher than 1 g/l. In general, the CSF findings in the relapse were not qualitatively different from those in the initial episode (Table 3). Two patients died in the relapse of meningitis; the other six had a followup neurological examination. The median followup period was 2.3 years (2 months to 5 years). All survivors resumed a normal life, although one had minor neurological deficits. Literature review Only five adult patients with relapsing bacterial meningitis had indepth case histories (Table 1): four women one man, aged 2161 years. 3 " 7 One had a past history of surgery, irradiation chemotherapy for an ovarian tumour. Another had a history of drug abuse, was HIVantibody positive. The remaining three patients had meningitis following cranial neurosurgery. K. pneumoniae was grown from cultures of the CSF in four patients Pseudomonas aeruginosa from another. Only one patient received a course of antibiotic therapy for more than 4 weeks in the initial episode of infection. One patient had two relapses of infection. The levels of protein glucose, the leucocyte count in the CSF of all patients are summarized in Table 3. Discussion The incidence of relapsing bacterial meningitis is low in both paediatric adult patients. In one study, 8/1300 (0.6%) infants children with bacterial meningitis had relapse of the infection. 2 In a review of adult meningitis, 6/445 (1.3%) adult patients with culturepositive or culturenegative bacterial meningitis exhibited relapse. 8 In our study, relapsing bacterial meningitis occurred in 8/234

6 516 L.M. Tang S.T. Chen Table 2 Reference Bacteria isolated from cerebrospinal fluid cultures in the initial episode in the relapse Causative organisms isolated Bradsher 3 Eng ef a/. 4 Hickstein Dillon 5 Hollifield ef a/. 6 Madhavan ef a/. 7 [PR] Patient 1 [PR] Patient 2 [PR] Patient 3 [PR] Patient 4 [PR] Patient 5 [PR] Patient 6 [PR] Patient 7 [PR] Patient 8 PR, present report. Initial episode Pseudomonas aeruginosa Escherichia coli Escherichia coli Streptococcus pneumoniae Enterobacter cloacae Klebsiella oxytoca Proteus mirabilis Staphylococcus epidermidis Salmonella serogroup B Relapse Pseudomonas aeruginosa Escherichia coli Escherichia coli? Enterobacter cloacae Klebsiella oxytoca Staphylococcus epidermidis Salmonella serogroup B (3.4%) patients with cultureproven bacterial meningitis. The mortality rate of our eight patients with relapsing bacterial meningitis was 25%, the same as the overall case fatality rate (25%) in a study of acute bacterial meningitis in adults. 8 In our study, relapsing bacterial meningitis occurred more frequently in nosocomial meningitis than in communityacquired meningitis. Also, it was more common in women. Of the five previously reported patients our eight patients, nine were female, four male. Most patients were in their third decade of life or middle age. Only one patient was over 60 years of age. Thus old age, although an adverse prognostic factor for bacterial meningitis, is not a predisposing factor for relapsing bacterial meningitis. Subdural empyema, subdural effusions, ventriculitis, brain abscess mastoiditis were the common causes of relapse of the infection following adequately treated bacterial meningitis in paediatric patients. 2 They were all absent in the 13 adult patients, of whom 10 were neurosurgical cases. It therefore seems that neurosurgical procedures are a predisposing factor for the relapse of infection in adults. Of the 10 patients, six had a shunt system at the time of relapse. The shunt apparatus may well serve as a parameningeal focus of persistent infection. The reason for relapse might be inappropriate antibiotic therapy in two previously reported patients; inadequate duration (10 days) of treatment in one patient 5 inadequate amount of tobramycin to reach the CNS by systemic intralumbar administrations in another. 6 Persistent dural defect was responsible for the relapse of infection in one patient. 7 However, the reason for relapse was undefined in the two neurosurgical patients (Patients 1 2) who had adequate antibiotic treatment. The cause of relapse might be related to an immunological defect, as one (Patient 7) had diabetes mellitus alcoholism the other 4 was HIVantibody positive. It was unknown in the healthy individual (Patient 3). Gramnegative bacilli are important in bacterial meningitis; accounting for 16% of adult patients with a single episode of acute bacterial meningitis in one review. 8 In a study of Gramnegative bacillary meningitis, 10 these bacilli caused 69% of the proved cases of meningitis in the postsurgical period. In this review of relapsing bacterial meningitis, Gramnegative bacilli were identified in 11/13 patients. K. pneumoniae is an important cause of nosocomial communityacquired meningitis. In a recent study, K. pneumoniae accounted for 13% of the 317 patients with cultureproven bacterial meningitis. 11 For relapsing bacterial meningitis, K. pneumoniae was the causative microorganism in 4/5 previously reported patients (Table 2). However, it was identified in only one of our eight patients. 5. pneumoniae has been known to be a common pathogen for adults with communityacquired meningitis, causing 60% of all episodes of recurrent bacterial meningitis. 1 In this study, it was found in only one (Patient 3) of the 13 patients with relapsing bacterial meningitis. Patient 3 in this report is unusual, being a healthy individual, with no evidence of underlying conditions or inappropriate antibiotic therapy, who had relapsing 5. pneumoniae meningitis. There is no stard rule on the duration of treatment for bacterial meningitis. 12 Usually, a course of 23 weeks of antibiotic therapy is needed for adult meningitis. 13 The course may even be longer in patients with an underlying condition. 14 In this

7 Protein (g/d Glucose Lactate t d' r> 2 3 d' Table 3 Cerebrospinal fluid findings in 13 patients with relapsing bacterial meningitis Reference Initial episode of infection Leucocytes (x10 6 /l) Protein (g/d Glucose Lactate End of initial course of therapy Leucocytes (x10 6 /l) Protein (g/d Glucose Lactate Relapse of infection Leucocytes (x10 6 /l) Bradsher 3 Eng et a/. 4 Hickstein Dillon 5 Hollifield ef a/. 6 Madhavan et al. 7 [PR] Patient 1 [PR] Patient 2 [PR] Patient 3 [PR] Patient 4 [PR] Patient 5 [PR Patient 6 [PR] Patient 7 [PR] Patient st relapse: nd relapse: st relapse: nd relapse: 6 PR, present report.

8 518 L.M. Tang S.T. Chen study, all four previously reported neurosurgical patients 4/6 neurosurgical patients had less than 4 weeks of antibiotic therapy. It seems, therefore, that 4 or more weeks of therapy should be used to treat postsurgical patients with Gramnegative bacillary meningitis to ensure a cure. The CSF study at the end of treatment for bacterial meningitis is not reliable evidence of cure, because the ranges of cell counts, glucose protein are wide after treatment. Abnormal CSF findings immediately after treatment of bacterial meningitis are the rule rather than the exception, are often found in cured patients. 15 Of the five patients reported in the literature our eight, a CSF examination was done in eight at the end of the treatment of the first episode of infection. The results were normal in two, 16 nearly normal in five. These results emphasize that a posttreatment CSF study is not a reliable test of cure; even a normal CSF result does not guarantee freedom from relapse. References 1. Kline MW. Review of recurrent bacterial meningitis. Pediatr Infect D/sy 1989; 8: Schaad UB, Nelson JD, McCracken CH Jr. Recrudescence relapse in bacterial meningitis of childhood. Pediatr 1981; 67: Bradsher RW. Relapse of Gramnegative bacillary meningitis after cefotaxime therapy. JAMA 1982; 248: Eng RHK, Lynch AM, Smith SM, Ambros RA, FanHavard P, Mangia A, TecsonTumang F, Cherubin C. Imipenem resistance in a case of AIDS with relapsing Pseudomonas meningitis. South Medj 1990; 83: Hickstein DD, Dillon JT. meningitis: intravenous trimethoprimsulfamethoxazole treatment. 7/U/f/U982; 248: Hollifield JW, Kaiser AB, McCee ZA. Cramnegative bacillary meningitis therapy: polyradiculitis following intralumbar aminoglycoside administration. JAMA 1976; 236: Madhavan T, Kiani D, Saravolatz L, Burch K, Mellinger RC. Recurrent Klebsiella meningitis following transsphenoidal hypophysectomy for Nelson's syndrome: resistance during relapse. Henry Ford Hosp Medj 1980; 28: Dur ML, Calderwood SB, Weber DJ, Miller SI, Southwick FS, Caviness VS, Jr, Swartz MN. Acute bacterial meningitis in adults: a review of 493 episodes. N Engl J Med 1993; 328: Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, Am J Infect Control 1988; 16:12840 (Erratum, Am J Infect Control 1988; 16:177). 10. Mangi RJ, Quintiliani R, Andriole VT. Gramnegative bacillary meningitis. Am J Med 1975; 59: Tang LM, Chen ST. meningitis: prognostic factors. ScJ Infect Dis 1994; 26: Radetsky M. Duration of treatment in bacterial meningitis: a historical inquiry. Pediatr Infect Dis J 1990; 9: Beam TR Jr. Bacterial meningitis in adults. In: Kass EH, Platt R, eds. Current therapy in infectious disease 3. Philadelphia, BC Decker, 1990: Braun M, Cherubin CE. Gramnegative bacillary meningitis. In: Lambert HP, ed. Infections of the central nervous system. Philadelphia, BC Decker, 1991: Durack DT, Spanos A. Endoftreatment spinal tap in bacterial meningitis: is it worthwhile. JAMA 1982; 248: Jordan CD, Flood JG, Laposata M, Lewrowski KB. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Normal reference laboratory values. N Engl J Med 1992; 327:71824.