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Community-acquired Serratia marcescens meningitis
Case Repots
Community-acquired S e r r a t i a
303
marcescens
Meningitis
A. Peeters 2, B. V a n d e r c a m 1, C. J. M. Sindic 2, P. Hantson 3 and P. M a h i e u 3 Departments of ~Internal Medicine, 2Neurology and 3Intensive Care, St-Luc University Hospital, B - 1 2 0 0 Brussels, Belgium Serratia marcescens is an unusual cause of community-acquired meningitis in adults. We report a case of S. marcescens meningitis occurring 29 years after a head injury and preceded by 3 years of intermittent nasal discharge of cerebrospinal fluid (CSF). One month before admission, the patient had received treatment with cefadroxil. This case illustrates the risk of Gram-negative bacillary meningitis in patients with a CSF leak when they are treated with antibiotics. When patients have a chronic clear nasal discharge, one should look for a past medical history of head injury before prescribing antibiotics. In the presence of a fistula, any antibiotherapy may lead to the selection of resistant organisms which may be difficult to treat. Due to the high risk of meningitis and the fact that spontaneous closure in delayed CSF rhinorrhoea is unlikely, surgical repair of any associated fistulae is mandatory.
Case Report In September 1993 a 46-year-old man was admitted to hospital with a lO-day history of nausea, fever and headaches. Two days prior to admission he had been treated at home with oral amoxycifiin/clavulanate (0.5 g q 6 h) for a presumed urinary tract infection. The diagnosis was subsequently refuted by negative urine cultures. One month earlier he had received 2 weeks' treatment with cefadroxil for an elbow bursitis. In 1964 he had suffered a severe craniocerebral trauma. Physical examination revealed obvious signs of meningitis. CSF analysis showed 6700 leucocytes/mm3 with 99% neutrophils, 6 mg/dl glucose and 580mg/dl protein. Treatment with cefotaxime (8 g/day), penicillin (24M units/day) and gentamicin (240 mg/ day) was started. Due to lack of local experience with intrathecal gentamicin, and in the absence of clear guidelines as to the appropriate doses, the gentamicin was given intravenously. Cerebrospinal fluid (CSF) and nasal swab cultures grew Serratia marcescens resistant to amoxycillin/clavulanate, cefadroxil, cefazolin and cefuroxime, but sensitive to cefotaxime, gentamicin and aztreonam. A cerebral computerized tomography (CT) scan revealed a left frontal hypodense area (the result of the cerebral trauma) and hydrocephalus. The patient's condition rapidly deteriorated; he was intubated and a ventriculoexternal catheter was ~nserted to measure intracranial pressure and to drain hydrocephalus. After 7 days of therapy, CSF cultures were still positive. Aztreonam (6 g/day), an antibiotic with excellent CSF penetration and proven efficacy in case of Gram-negative bacterial meningitis, was used subsequently in place of gentamicin. The following day, cultures were negative. A magnetic resonance imaging (MRI) scan confirmed the CT findings, and showed signs of ventriculitis and a mesencephalic lesion. The patient died of cerebral oedema 1 month after admission. The autopsy showed two fistulae in the frontal lobe, one of 1.5 by 1 cm and the other of 0.3 by 0.4 cm, about 5 cm away from the sella turcica. Evidence of a left frontobasal concussion in communication with the left ventricule, chronic bacterial
* Address for correspondence: Dr B. Vandercam, Division of General Internal Medicine, Infectious Diseases, St-Luc University Hospital, Avenue Hippocrate 10, 1200 Brussels, Belgium. Accepted for publication 4 January 1997.
meningitis with ventriculitis, and liquefaction necrosis in the periaqueductal region were also observed. Unfortunately, no post-mortem cultures of the CSF or brain were performed. The patient's wife later declared that her husband had suffered from left-sided rhinorrhoea for 3 years prior to this hospital admission.
Discussion Gram-negative bacilli (e.g. Klebsiella spp., Escherichia coli, S. marcescens, Pseudomonas aeruginosa, Salmonella spp.) are a common cause of meningitis in neonates. L2 In adults, Gram-negative bacillary meningitis is rare and is usually only observed in patients with a history of head trauma or neurosurgical procedures. A few cases have also been reported in the elderly, the immunosuppressed, the chronically debilitated or those suffering from Gram-negative septicaemia. Finally, a few cases also occur by direct extension of an infective focus such as mastoiditis or chronic sinusitis.~-7 Our patient had a history of head trauma and CSF rhinorrhoea. What makes this case unusual is the length of time (26 years) between the injury and the onset of rhinorrhoea. Indeed, CSF rhinorrhoea usually occurs within 3 months of injury; delays beyond 20 years have been reported in only four cases. 8-1. One of these cases developed Haemophilus influenzae type B meningitis after suffering from intermittent rhinorrhoea for 18 monthsJ ~ In our patient the duration of the rhinorrhoea was 36 months, which may represent the longest recorded interval before the occurrence of meningitis. In patients with CSF fistulae, the CSF is exposed to the flora of the nasopharynx, the sinuses, or of the auditory canal. Streptococcus pneumoniae, It. influenzae and group A beta haemolytic streptococcus are the main causes of meningitis occurring in 3-50% of cases. 12 Prophylactic antibiotic use has been suggested in these patients. However, there have been no prospective controlled trials to prove the efficacy of prophylaxis. Overall, the use of prophylactic antibiotics does not appear to influence the incidence of posttraumatic bacterial meningitis, and it may be responsible for the selection of resistant organismsJ 2 In our patient, the use of antibiotics led to the selection of a resistant strain of S. marcescens which was found in the nasopharynx and in the CSF, clearly demonstrating the risk of antibioprophylaxis in this type of patient.
Case Reports
304
In conclusion, CSF r h i n o r r h o e a c a n occur more t h a n 2 0 years after h e a d t r a u m a , a n d t h u s the p a t i e n t r e m a i n s at risk of developing meningitis for the rest of his life. Surgical repair of the fistula is mandatory, as s p o n t a n e o u s closure is u n likely. ~2-~7 It is w o r t h m e n t i o n i n g t h a t meningitis c a n occur w h a t e v e r the d u r a t i o n of CSF r h i n o r r h o e a (3 years in this case). It is also i m p o r t a n t to r e m e m b e r t h a t antibiotics prescribed before the repair is completed c a n select for antibiotic-resistant organisms, w h i c h m a y prove difficult to t r e a t should they gain access to t h e CSF. The possibility of a CSF leak should be considered in a n y p a t i e n t w i t h a chronic clear n a s a l discharge. The p a t i e n t should be questioned in detail a b o u t a n y previous h e a d t r a u m a , n o m a t t e r w h e n it occurred. The n a s a l fluid should be analysed w i t h sensitive i m m u n o c h e m i c a l methods for the presence of CSF-speciflc proteins, especially the beta-2transferrin, is Finally, in patients w i t h Gram-negative bacillary meningitis, in the absence of classical risk factors, t h e possibility of a CSF leak should be considered, as well as a n y associated prior antibiotic treatment.
References 1 Campbell JR, Diacovo 3", Baker C]. Serratia marcescensmeningitis in neonates. Pediatr Infect Dis J 1992; 11: 881-886. 2 Unhanand M, Mustafa MM, McCracken GH, Nelson ]D. Gramnegative enteric bacillary meningitis: a twenty-one-year experience. J Pediatr 1993; 122: 15-21. 3 Gower DJ, Barrows AA, Kelly DL, Pegram S. Gram-negative bacillary meningitis in the adult: review of 39 cases. South Med ] 1986; 79: 1499-1502. 4 Mangi R], Quintiliani R, Andriole VT. Gram-negative bacillary meningitis. Am l Med 1975; 59: 829-836.
5 Cherubin CE, Marr IS, Sierra MF, Becket S. Listeria and Gramnegative bacillary meningitis in New York City, 1972-1979. Frequent causes of meningitis in adults. Am ] Med 1981; 71:199-209. 6 Berk SL, McCabe WR. Meningitis caused by Gram-negative bacilli. Ann Intern Med 1980; 93: 253-260. 7 Durand ML, Calderwood SB, Weber D]et al. Acute bacterial meningitis in adults. A review of 493 episodes. N Engl ] Med 1993; 328: 21-28. 8 Calhoun KH, Weiner RL, Theilen FW, Quinn FB, Stiernberg CM. Cerebrospinal fluid rhinorrhoea 41 years after injury. Otolaryngol Head Neck Surg 1988; 98: 90-91. 9 Hingorani RK. Cerebrospinai fluid rhinorrhoea. ] Laryngol Otol 1971; 85: 99-1006. 10 Okada J, Tsuda T, Takasugi S, Nishida K, Toth Z, Matsumoto K. Unusually late onset of cerebrospinal fluid rhinorrhoea after head trauma. Surg Neurol 1991; 35: 213-217. 11 Crawford C, Kennedy N, Weir WRC. Cerebrospinal fluid rhinorrhoea and Haemophilusinfluenzae meningitis 37 years after a head injury. J Infect 1994; 28: 93-97. 12 Kaufman BA, Tunkel AR, Pryor ]C, Dacey RG. Meningitis in the neurosurgical patient. Infect Dis Clin North Am 1990; 4: 677-701. 13 Eljamel MS, Foy PM. Acute traumatic CSF fistulae, the risk of intracranial infection. Br ] Neurosurg 1990; 4: 381-385. 14 Eljamel MS. Fractures of the middle third of the face and cerebrospinal fluid rhinorrhoea. Br ] Neurosurg 1994; 8: 289-93. 15 Eljamel MSM, Foy PM. Post-traumatic CSF fistulae, the case for surgical repair. Br ] Neurosurg 1990; 4: 479-83. 16 Griffith HB. CSF fistula and the surgeon. Br ] Neurosurg 1990; 4: 369-371. 17 ]amieson KG, Yelland IDN. Surgical repair of the anterior fossa because of rhinorrhoea, aerocele or meningitis. ] Neurosurg 1973; 39: 328-331. 18 Fransen P, Sindic C]M, Thauvoy C, Laterre C, Stroobandt G. Highly sensitive detection of beta-2-transferrin in rhinorrhoea and otorrhea as a marker of cerebrospinal fluid (CSF) leakage. Acta Neurochir (Wien) 1991; 109: 98-101.
Haemophilus aphrophilus Bacteraemia Complicated with Vertebral Osteomyelitis and Spinal Epidural Abscess in a Patient with Liver Cirrhosis C. C. Hung 1, P. R. Hsueh 2, Y. C. Chen 1, C. T. Fang 1, S. C. Chang .1, K. T. Luh z and W. C. Hsieh ~ 1Section of Infectious Diseases, Department of Internal Medicine and 2Department of Laboratory Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan Haemophilus aphrophflus is rarely implicated as a n aetiology of spinal epidural abscess. A 73-year-old w o m a n w i t h liver cirrhosis w h o developed H. aphrophilus b a c t e r a e m i a complicated w i t h vertebral osteomyelitis a n d spinal epidural abscess is presented. W i t h o u t surgical decompression, she w a s successfully treated w i t h cefotaxime for 3 weeks, followed by m a i n t e n a n c e w i t h ciprofloxacin for another IO weeks. The clinical features of eight previously reported cases of vertebral osteomyelitis without epidural abscess due to H. aphrophilus are reviewed.
Introduction While Haemophilus aphroph~lus is a n o r m a l c o m p o n e n t of oral flora a n d c a n be recovered from gingival scrapings a n d inter-
* Address correspondence to: Dr S, C. Chang. Accepted for publication 10 January 1997.
dental material with a selective medium, 1 it h a s been a n infrequent aetiology of h u m a n infections. 2 Reported infections due to H. aphrophilus include endocarditis, bacteraemia, b r a i n abscess, meningitis, p n e u m o n i a , osteomyelitis, meningitis, dental abscess, sinusitis, a n d soft tissue infections, a4 Vertebral osteomyelitis due to H. aphrophilus is u n c o m m o n , a n d to o u r knowledge, only eight cases h a v e b e e n described previously in
Community-acquired S e r r a t i a
303
marcescens
Meningitis
A. Peeters 2, B. V a n d e r c a m 1, C. J. M. Sindic 2, P. Hantson 3 and P. M a h i e u 3 Departments of ~Internal Medicine, 2Neurology and 3Intensive Care, St-Luc University Hospital, B - 1 2 0 0 Brussels, Belgium Serratia marcescens is an unusual cause of community-acquired meningitis in adults. We report a case of S. marcescens meningitis occurring 29 years after a head injury and preceded by 3 years of intermittent nasal discharge of cerebrospinal fluid (CSF). One month before admission, the patient had received treatment with cefadroxil. This case illustrates the risk of Gram-negative bacillary meningitis in patients with a CSF leak when they are treated with antibiotics. When patients have a chronic clear nasal discharge, one should look for a past medical history of head injury before prescribing antibiotics. In the presence of a fistula, any antibiotherapy may lead to the selection of resistant organisms which may be difficult to treat. Due to the high risk of meningitis and the fact that spontaneous closure in delayed CSF rhinorrhoea is unlikely, surgical repair of any associated fistulae is mandatory.
Case Report In September 1993 a 46-year-old man was admitted to hospital with a lO-day history of nausea, fever and headaches. Two days prior to admission he had been treated at home with oral amoxycifiin/clavulanate (0.5 g q 6 h) for a presumed urinary tract infection. The diagnosis was subsequently refuted by negative urine cultures. One month earlier he had received 2 weeks' treatment with cefadroxil for an elbow bursitis. In 1964 he had suffered a severe craniocerebral trauma. Physical examination revealed obvious signs of meningitis. CSF analysis showed 6700 leucocytes/mm3 with 99% neutrophils, 6 mg/dl glucose and 580mg/dl protein. Treatment with cefotaxime (8 g/day), penicillin (24M units/day) and gentamicin (240 mg/ day) was started. Due to lack of local experience with intrathecal gentamicin, and in the absence of clear guidelines as to the appropriate doses, the gentamicin was given intravenously. Cerebrospinal fluid (CSF) and nasal swab cultures grew Serratia marcescens resistant to amoxycillin/clavulanate, cefadroxil, cefazolin and cefuroxime, but sensitive to cefotaxime, gentamicin and aztreonam. A cerebral computerized tomography (CT) scan revealed a left frontal hypodense area (the result of the cerebral trauma) and hydrocephalus. The patient's condition rapidly deteriorated; he was intubated and a ventriculoexternal catheter was ~nserted to measure intracranial pressure and to drain hydrocephalus. After 7 days of therapy, CSF cultures were still positive. Aztreonam (6 g/day), an antibiotic with excellent CSF penetration and proven efficacy in case of Gram-negative bacterial meningitis, was used subsequently in place of gentamicin. The following day, cultures were negative. A magnetic resonance imaging (MRI) scan confirmed the CT findings, and showed signs of ventriculitis and a mesencephalic lesion. The patient died of cerebral oedema 1 month after admission. The autopsy showed two fistulae in the frontal lobe, one of 1.5 by 1 cm and the other of 0.3 by 0.4 cm, about 5 cm away from the sella turcica. Evidence of a left frontobasal concussion in communication with the left ventricule, chronic bacterial
* Address for correspondence: Dr B. Vandercam, Division of General Internal Medicine, Infectious Diseases, St-Luc University Hospital, Avenue Hippocrate 10, 1200 Brussels, Belgium. Accepted for publication 4 January 1997.
meningitis with ventriculitis, and liquefaction necrosis in the periaqueductal region were also observed. Unfortunately, no post-mortem cultures of the CSF or brain were performed. The patient's wife later declared that her husband had suffered from left-sided rhinorrhoea for 3 years prior to this hospital admission.
Discussion Gram-negative bacilli (e.g. Klebsiella spp., Escherichia coli, S. marcescens, Pseudomonas aeruginosa, Salmonella spp.) are a common cause of meningitis in neonates. L2 In adults, Gram-negative bacillary meningitis is rare and is usually only observed in patients with a history of head trauma or neurosurgical procedures. A few cases have also been reported in the elderly, the immunosuppressed, the chronically debilitated or those suffering from Gram-negative septicaemia. Finally, a few cases also occur by direct extension of an infective focus such as mastoiditis or chronic sinusitis.~-7 Our patient had a history of head trauma and CSF rhinorrhoea. What makes this case unusual is the length of time (26 years) between the injury and the onset of rhinorrhoea. Indeed, CSF rhinorrhoea usually occurs within 3 months of injury; delays beyond 20 years have been reported in only four cases. 8-1. One of these cases developed Haemophilus influenzae type B meningitis after suffering from intermittent rhinorrhoea for 18 monthsJ ~ In our patient the duration of the rhinorrhoea was 36 months, which may represent the longest recorded interval before the occurrence of meningitis. In patients with CSF fistulae, the CSF is exposed to the flora of the nasopharynx, the sinuses, or of the auditory canal. Streptococcus pneumoniae, It. influenzae and group A beta haemolytic streptococcus are the main causes of meningitis occurring in 3-50% of cases. 12 Prophylactic antibiotic use has been suggested in these patients. However, there have been no prospective controlled trials to prove the efficacy of prophylaxis. Overall, the use of prophylactic antibiotics does not appear to influence the incidence of posttraumatic bacterial meningitis, and it may be responsible for the selection of resistant organismsJ 2 In our patient, the use of antibiotics led to the selection of a resistant strain of S. marcescens which was found in the nasopharynx and in the CSF, clearly demonstrating the risk of antibioprophylaxis in this type of patient.
Case Reports
304
In conclusion, CSF r h i n o r r h o e a c a n occur more t h a n 2 0 years after h e a d t r a u m a , a n d t h u s the p a t i e n t r e m a i n s at risk of developing meningitis for the rest of his life. Surgical repair of the fistula is mandatory, as s p o n t a n e o u s closure is u n likely. ~2-~7 It is w o r t h m e n t i o n i n g t h a t meningitis c a n occur w h a t e v e r the d u r a t i o n of CSF r h i n o r r h o e a (3 years in this case). It is also i m p o r t a n t to r e m e m b e r t h a t antibiotics prescribed before the repair is completed c a n select for antibiotic-resistant organisms, w h i c h m a y prove difficult to t r e a t should they gain access to t h e CSF. The possibility of a CSF leak should be considered in a n y p a t i e n t w i t h a chronic clear n a s a l discharge. The p a t i e n t should be questioned in detail a b o u t a n y previous h e a d t r a u m a , n o m a t t e r w h e n it occurred. The n a s a l fluid should be analysed w i t h sensitive i m m u n o c h e m i c a l methods for the presence of CSF-speciflc proteins, especially the beta-2transferrin, is Finally, in patients w i t h Gram-negative bacillary meningitis, in the absence of classical risk factors, t h e possibility of a CSF leak should be considered, as well as a n y associated prior antibiotic treatment.
References 1 Campbell JR, Diacovo 3", Baker C]. Serratia marcescensmeningitis in neonates. Pediatr Infect Dis J 1992; 11: 881-886. 2 Unhanand M, Mustafa MM, McCracken GH, Nelson ]D. Gramnegative enteric bacillary meningitis: a twenty-one-year experience. J Pediatr 1993; 122: 15-21. 3 Gower DJ, Barrows AA, Kelly DL, Pegram S. Gram-negative bacillary meningitis in the adult: review of 39 cases. South Med ] 1986; 79: 1499-1502. 4 Mangi R], Quintiliani R, Andriole VT. Gram-negative bacillary meningitis. Am l Med 1975; 59: 829-836.
5 Cherubin CE, Marr IS, Sierra MF, Becket S. Listeria and Gramnegative bacillary meningitis in New York City, 1972-1979. Frequent causes of meningitis in adults. Am ] Med 1981; 71:199-209. 6 Berk SL, McCabe WR. Meningitis caused by Gram-negative bacilli. Ann Intern Med 1980; 93: 253-260. 7 Durand ML, Calderwood SB, Weber D]et al. Acute bacterial meningitis in adults. A review of 493 episodes. N Engl ] Med 1993; 328: 21-28. 8 Calhoun KH, Weiner RL, Theilen FW, Quinn FB, Stiernberg CM. Cerebrospinal fluid rhinorrhoea 41 years after injury. Otolaryngol Head Neck Surg 1988; 98: 90-91. 9 Hingorani RK. Cerebrospinai fluid rhinorrhoea. ] Laryngol Otol 1971; 85: 99-1006. 10 Okada J, Tsuda T, Takasugi S, Nishida K, Toth Z, Matsumoto K. Unusually late onset of cerebrospinal fluid rhinorrhoea after head trauma. Surg Neurol 1991; 35: 213-217. 11 Crawford C, Kennedy N, Weir WRC. Cerebrospinal fluid rhinorrhoea and Haemophilusinfluenzae meningitis 37 years after a head injury. J Infect 1994; 28: 93-97. 12 Kaufman BA, Tunkel AR, Pryor ]C, Dacey RG. Meningitis in the neurosurgical patient. Infect Dis Clin North Am 1990; 4: 677-701. 13 Eljamel MS, Foy PM. Acute traumatic CSF fistulae, the risk of intracranial infection. Br ] Neurosurg 1990; 4: 381-385. 14 Eljamel MS. Fractures of the middle third of the face and cerebrospinal fluid rhinorrhoea. Br ] Neurosurg 1994; 8: 289-93. 15 Eljamel MSM, Foy PM. Post-traumatic CSF fistulae, the case for surgical repair. Br ] Neurosurg 1990; 4: 479-83. 16 Griffith HB. CSF fistula and the surgeon. Br ] Neurosurg 1990; 4: 369-371. 17 ]amieson KG, Yelland IDN. Surgical repair of the anterior fossa because of rhinorrhoea, aerocele or meningitis. ] Neurosurg 1973; 39: 328-331. 18 Fransen P, Sindic C]M, Thauvoy C, Laterre C, Stroobandt G. Highly sensitive detection of beta-2-transferrin in rhinorrhoea and otorrhea as a marker of cerebrospinal fluid (CSF) leakage. Acta Neurochir (Wien) 1991; 109: 98-101.
Haemophilus aphrophilus Bacteraemia Complicated with Vertebral Osteomyelitis and Spinal Epidural Abscess in a Patient with Liver Cirrhosis C. C. Hung 1, P. R. Hsueh 2, Y. C. Chen 1, C. T. Fang 1, S. C. Chang .1, K. T. Luh z and W. C. Hsieh ~ 1Section of Infectious Diseases, Department of Internal Medicine and 2Department of Laboratory Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan Haemophilus aphrophflus is rarely implicated as a n aetiology of spinal epidural abscess. A 73-year-old w o m a n w i t h liver cirrhosis w h o developed H. aphrophilus b a c t e r a e m i a complicated w i t h vertebral osteomyelitis a n d spinal epidural abscess is presented. W i t h o u t surgical decompression, she w a s successfully treated w i t h cefotaxime for 3 weeks, followed by m a i n t e n a n c e w i t h ciprofloxacin for another IO weeks. The clinical features of eight previously reported cases of vertebral osteomyelitis without epidural abscess due to H. aphrophilus are reviewed.
Introduction While Haemophilus aphroph~lus is a n o r m a l c o m p o n e n t of oral flora a n d c a n be recovered from gingival scrapings a n d inter-
* Address correspondence to: Dr S, C. Chang. Accepted for publication 10 January 1997.
dental material with a selective medium, 1 it h a s been a n infrequent aetiology of h u m a n infections. 2 Reported infections due to H. aphrophilus include endocarditis, bacteraemia, b r a i n abscess, meningitis, p n e u m o n i a , osteomyelitis, meningitis, dental abscess, sinusitis, a n d soft tissue infections, a4 Vertebral osteomyelitis due to H. aphrophilus is u n c o m m o n , a n d to o u r knowledge, only eight cases h a v e b e e n described previously in