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Citrobacter diversus ventriculitis and brain abscesses in an adult
journal of Infection (I993) z6, 2o7-209
CASE REPORT
Citrobacter diversus ventriculitis
and brain abscesses
in an
adult L. V. Booth,*~ J. D. P a l m e r , t J. P a t e m a n ~ a n d A. C. T u c k *
*Public Health Laboratory and ~fWessex Neurological Centre, Southampton General Hospital, Tremona Road, Southampton S 0 9 4 X Y and ~Department of Medicine, St Richards Hospital, Chichester, Sussex, U.K. Accepted for publication 20 August I992 Summary A case of Citrobacter diversus brain abscesses following urinary infection in an adult is described. The patient was treated with surgical drainage, netilmicin and cefotaxime. Citrobacter species CNS infection is discussed.
Introduction
Citrobacter diversus can cause neonatal meningitis with a high incidence of associated brain a b s c e s s e s / b u t it has not previously been reported in adults. We report an adult case of CNS infection which occurred following a urinary infection. Case report A 66-year-old woman with T y p e II diabetes mellitus was admitted with confusion, headache and mild photophobia. She had no fever, neck stiffness or focal neurology. One month earlier she had been treated for a C. diversus urinary infection associated with a staghorn calculus. Nine years before admission she had suffered a spontaneous intracranial haemorrhage following which an anterior communicating artery aneurysm was clipped. Cerebrospinal fluid examined initially and after 5 days contained 460 x io6/1 W B C / ( 8 o % polymorphs) and I63OX IO6/1 WBC (predominantly atypical lymphocytes) respectively. T h e r e was no bacterial growth. In spite of intravenous benzyl penicillin and acyclovir she developed pyrexia and neck stiffness and she was then transferred to the Neurosurgical Department where she was found to be localising to pain only and to have a fixed lateral gaze. A CAT scan showed moderate hydrocephalus with distortion of the right lateral ventricle by an occipital lesion and a second ring enhancing lesion in the periphery of the right parietal lobe. Intravenous benzyl penicillin (24 million units daily), chloramphenicol (I g, 6 hourly) and metronidazole (500 mg, 8 hourly) were commenced. A ventricular drain revealed pus which later grew C. diversus (API no. I I44513) sensitive to gentamicin, netilmicin, Address correspondence to: Dr L . V . Booth, Public Health Laboratory, Southampton General Hospital, Tremona Road, Southampton SO9 4XY, U.K.
o•63=4453/93/o2o2o7+o3 $08.00/o
© I993 The British Society for the Study of Infection
208
L. V. B O O T H E T A L .
cotrimoxazole, cefotaxime and ciprofloxacin, and resistant to ampicillin. T r e a t m e n t was changed to netilmicin Ioo mg, 8 hourly and cefotaxime 2 g 4 hourly. T h e M I C s to netilmicin and cefotaxime were I mg/1 and o'I25 mg/1 respectively. C S F and b l o o d cefotaxime values 2 h after injection were 38 mg/1 and Ioo mg/1 respectively on day 4 of treatment. T w o days later, serum values before and I h after injection were 0"3 mg/1 and 5"9 mg/1 (netilmicin) and 40 mg/1 and I32 mg/1 (cefotaxime). C S F values were 0"3 rag/1 and I mg/1 (netilmicin), and I6 mg/1 and 40 mg/1 (cefotaxime). S e r u m bactericidal titres before and I h after injection were 4 and 64. Similar titres for C S F were 4 and 8. T h e ventricles were drained for 8 days. S u b s e q u e n t C S F specimens were sterile. Netilmicin and cefotaxime were continued for I6 days only. Clinical recovery was incomplete; 6 months later the patient was able to sit, follow objects with her eyes and say occasional words. T h e r e was p r o n o u n c e d weakness and some spasticity. L o n g term continuing care will be required. Discussion
Citrobacter species account for about 6 % all laboratory isolates of Enterobacteriaceae and 5 ~o significant urine isolates. ~ T w o studies of Citrobacter species bacteraemia gave incidences of 1.2 per IOOOO discharges ~ and 4 per I Oooo admissions 4 with C. diversus and C. freundii respectively predominating. T h e genitourinary tract was the c o m m o n e s t source of infection and most bacteraemias were hospital acquired. O u r patient's C. diversus urinary infection was c o m m u n i t y acquired, the staghorn calculus possibly contributing to infection with an unusual organism. C. diversus is a k n o w n cause of neonatal meningitis with a high incidence of associated brain abscesses (77%). 1 Nosocomial 5 and vertical 6 transmission have been d o c u m e n t e d for neonatal infections. In neonatal C. diversus infections cerebral lesions m a y represent areas of infarction with necrosis, liquefaction and cavitation rather than true abscesses. 7 Consequently, surgical treatment may be ill advised and lead to further damage. 7 In neonates, it has been suggested that i m m u n o c o m p e t e n c y and the astroglial response may not be sufficient to confine infection to a limited area. 7 O u r patient was not i m m u n o c o m p r o m i s e d except b y age and m a t u r e onset diabetes. Fatal C. diversus bacteraemia with meningitis has been reported in an adolescent patient with neoplasia, b u t there was no mention of concomitant brain abscesses. 4 C. freundii can cause neonatal brain abscesses 1 and one adult case has been documented. 8 W e believe our case of C. diversus causing brain abscesses in an adult is the first to be reported. T h e C S F cefotaxime values in our patient exceeded several-fold the M I C of the isolate and the in-vitro C S F bacterial titres showed a 'killing' effect. Despite surgical drainage the clinical o u t c o m e was poor. Kline r e c o m m e n d s that neonatal Citrobacter species meningitis and brain abscesses should be treated with cefotaxime and an aminoglycoside for 3 and 6 weeks respectively after sterilisation of the C S F . 9 H e states that surgical drainage is p r o b a b l y
C. d i v e r s u s ventriculitis a n d abscesses
209
d e s i r a b l e b u t n o t m a n d a t o r y . C. diversus b r a i n a b s c e s s e s h a v e b e e n c u r e d b y a n t i b i o t i c s a l o n e ) ° C o t r i m o x a z o l e ~ a n d m o x a l a c t a m ~° h a v e also b e e n u s e d w i t h success. A l t h o u g h this case a p p e a r s to b e t h e first C. diversus b r a i n a b s c e s s to b e e n c o u n t e r e d in a n a d u l t , it is o f c o n c e r n t h a t t h e s o u r c e was p r o b a b l y a u r i n a r y i n f e c t i o n . As Citrobacter species p r e d o m i n a n t l y c a u s e n o s o c o m i a l i n f e c t i o n s in e l d e r l y , d e b i l i t a t e d p a t i e n t s a n d p a r t i c u l a r l y u r i n a r y i n f e c t i o n s , 2 it will b e i n t e r e s t i n g to see if f u r t h e r a d u l t cases o f l i f e - t h r e a t e n i n g C N S i n v o l v e m e n t o c c u r s e c o n d a r y to u r i n a r y i n f e c t i o n .
I. 2. 3. 4. 5. 6. 7. 8. 9. io. I I.
References Graham DR, Band JD. Citrobacter diversus brain abscess and meningitis in neonates. J Am Med Assoc I98I; 245: I923-I925. Lipsky BA, Hook E W I I I , Smith AA, Horde JJ. Citrobacter infections in humans: experience at the Seattle Veterans Administration Medical Center and a review of the literature. Rev Infect Dis I98o; 2: 746-760. Drelichman V, Band JD. Bacteraemias due to Citrobacter diversus and Citrobacter freundii. Arch Intern Med I985; I45: i8o8-i8io. Samonis G~ Anaissie E~ Eking L, Bodey GP. Review of Citrobacter bacteremia in cancer patients over a sixteen year period. Euro J Clin Microbiol Infect Dis I99I ; xo: 479-485. Williams WW, Mariano J, Spurrier M e t al. Nosocomial meningitis due to Citrobacter diversus in neonates: new aspects of the epidemiology. J Infect Dis I984; xSO: 229-235. Kline MW, Mason EO Jr, Kaplan SL. Characterization of Citrobacter diversus strains causing neonatal meningitis. J Infect Dis I988; x57: IoI-IO5. Foreman SD, Smith EE, Ryan NS, Hogan GR. Neonatal Citrobacter meningitis: pathogenesis of cerebral abscess formation. Ann Neurol I984; I6: 655-659. Scheld WM, Tyson GW. Citrobacter freundii meningitis in an adult. South Med J I979; 72: I598-I599. Kline MW. Citrobacter meningitis and brain abscess in infancy: epidemiology, pathogenesis and treatment. J~Pediatr I988; II3: 430-434. Levy RL, Saunders RL. Citrobacter meningitis and cerebral abscess in early infancy: cure by maxalactam. Neurology I98I ; 3I : I575-I577. Greene GR, Heitlinger L, Madden JD. Citrobacter ventriculitis in a neonate responsive to trimethoprim-sulfamethoxazole. Clin Pediatr I983 ; 22 : 515-517.
CASE REPORT
Citrobacter diversus ventriculitis
and brain abscesses
in an
adult L. V. Booth,*~ J. D. P a l m e r , t J. P a t e m a n ~ a n d A. C. T u c k *
*Public Health Laboratory and ~fWessex Neurological Centre, Southampton General Hospital, Tremona Road, Southampton S 0 9 4 X Y and ~Department of Medicine, St Richards Hospital, Chichester, Sussex, U.K. Accepted for publication 20 August I992 Summary A case of Citrobacter diversus brain abscesses following urinary infection in an adult is described. The patient was treated with surgical drainage, netilmicin and cefotaxime. Citrobacter species CNS infection is discussed.
Introduction
Citrobacter diversus can cause neonatal meningitis with a high incidence of associated brain a b s c e s s e s / b u t it has not previously been reported in adults. We report an adult case of CNS infection which occurred following a urinary infection. Case report A 66-year-old woman with T y p e II diabetes mellitus was admitted with confusion, headache and mild photophobia. She had no fever, neck stiffness or focal neurology. One month earlier she had been treated for a C. diversus urinary infection associated with a staghorn calculus. Nine years before admission she had suffered a spontaneous intracranial haemorrhage following which an anterior communicating artery aneurysm was clipped. Cerebrospinal fluid examined initially and after 5 days contained 460 x io6/1 W B C / ( 8 o % polymorphs) and I63OX IO6/1 WBC (predominantly atypical lymphocytes) respectively. T h e r e was no bacterial growth. In spite of intravenous benzyl penicillin and acyclovir she developed pyrexia and neck stiffness and she was then transferred to the Neurosurgical Department where she was found to be localising to pain only and to have a fixed lateral gaze. A CAT scan showed moderate hydrocephalus with distortion of the right lateral ventricle by an occipital lesion and a second ring enhancing lesion in the periphery of the right parietal lobe. Intravenous benzyl penicillin (24 million units daily), chloramphenicol (I g, 6 hourly) and metronidazole (500 mg, 8 hourly) were commenced. A ventricular drain revealed pus which later grew C. diversus (API no. I I44513) sensitive to gentamicin, netilmicin, Address correspondence to: Dr L . V . Booth, Public Health Laboratory, Southampton General Hospital, Tremona Road, Southampton SO9 4XY, U.K.
o•63=4453/93/o2o2o7+o3 $08.00/o
© I993 The British Society for the Study of Infection
208
L. V. B O O T H E T A L .
cotrimoxazole, cefotaxime and ciprofloxacin, and resistant to ampicillin. T r e a t m e n t was changed to netilmicin Ioo mg, 8 hourly and cefotaxime 2 g 4 hourly. T h e M I C s to netilmicin and cefotaxime were I mg/1 and o'I25 mg/1 respectively. C S F and b l o o d cefotaxime values 2 h after injection were 38 mg/1 and Ioo mg/1 respectively on day 4 of treatment. T w o days later, serum values before and I h after injection were 0"3 mg/1 and 5"9 mg/1 (netilmicin) and 40 mg/1 and I32 mg/1 (cefotaxime). C S F values were 0"3 rag/1 and I mg/1 (netilmicin), and I6 mg/1 and 40 mg/1 (cefotaxime). S e r u m bactericidal titres before and I h after injection were 4 and 64. Similar titres for C S F were 4 and 8. T h e ventricles were drained for 8 days. S u b s e q u e n t C S F specimens were sterile. Netilmicin and cefotaxime were continued for I6 days only. Clinical recovery was incomplete; 6 months later the patient was able to sit, follow objects with her eyes and say occasional words. T h e r e was p r o n o u n c e d weakness and some spasticity. L o n g term continuing care will be required. Discussion
Citrobacter species account for about 6 % all laboratory isolates of Enterobacteriaceae and 5 ~o significant urine isolates. ~ T w o studies of Citrobacter species bacteraemia gave incidences of 1.2 per IOOOO discharges ~ and 4 per I Oooo admissions 4 with C. diversus and C. freundii respectively predominating. T h e genitourinary tract was the c o m m o n e s t source of infection and most bacteraemias were hospital acquired. O u r patient's C. diversus urinary infection was c o m m u n i t y acquired, the staghorn calculus possibly contributing to infection with an unusual organism. C. diversus is a k n o w n cause of neonatal meningitis with a high incidence of associated brain abscesses (77%). 1 Nosocomial 5 and vertical 6 transmission have been d o c u m e n t e d for neonatal infections. In neonatal C. diversus infections cerebral lesions m a y represent areas of infarction with necrosis, liquefaction and cavitation rather than true abscesses. 7 Consequently, surgical treatment may be ill advised and lead to further damage. 7 In neonates, it has been suggested that i m m u n o c o m p e t e n c y and the astroglial response may not be sufficient to confine infection to a limited area. 7 O u r patient was not i m m u n o c o m p r o m i s e d except b y age and m a t u r e onset diabetes. Fatal C. diversus bacteraemia with meningitis has been reported in an adolescent patient with neoplasia, b u t there was no mention of concomitant brain abscesses. 4 C. freundii can cause neonatal brain abscesses 1 and one adult case has been documented. 8 W e believe our case of C. diversus causing brain abscesses in an adult is the first to be reported. T h e C S F cefotaxime values in our patient exceeded several-fold the M I C of the isolate and the in-vitro C S F bacterial titres showed a 'killing' effect. Despite surgical drainage the clinical o u t c o m e was poor. Kline r e c o m m e n d s that neonatal Citrobacter species meningitis and brain abscesses should be treated with cefotaxime and an aminoglycoside for 3 and 6 weeks respectively after sterilisation of the C S F . 9 H e states that surgical drainage is p r o b a b l y
C. d i v e r s u s ventriculitis a n d abscesses
209
d e s i r a b l e b u t n o t m a n d a t o r y . C. diversus b r a i n a b s c e s s e s h a v e b e e n c u r e d b y a n t i b i o t i c s a l o n e ) ° C o t r i m o x a z o l e ~ a n d m o x a l a c t a m ~° h a v e also b e e n u s e d w i t h success. A l t h o u g h this case a p p e a r s to b e t h e first C. diversus b r a i n a b s c e s s to b e e n c o u n t e r e d in a n a d u l t , it is o f c o n c e r n t h a t t h e s o u r c e was p r o b a b l y a u r i n a r y i n f e c t i o n . As Citrobacter species p r e d o m i n a n t l y c a u s e n o s o c o m i a l i n f e c t i o n s in e l d e r l y , d e b i l i t a t e d p a t i e n t s a n d p a r t i c u l a r l y u r i n a r y i n f e c t i o n s , 2 it will b e i n t e r e s t i n g to see if f u r t h e r a d u l t cases o f l i f e - t h r e a t e n i n g C N S i n v o l v e m e n t o c c u r s e c o n d a r y to u r i n a r y i n f e c t i o n .
I. 2. 3. 4. 5. 6. 7. 8. 9. io. I I.
References Graham DR, Band JD. Citrobacter diversus brain abscess and meningitis in neonates. J Am Med Assoc I98I; 245: I923-I925. Lipsky BA, Hook E W I I I , Smith AA, Horde JJ. Citrobacter infections in humans: experience at the Seattle Veterans Administration Medical Center and a review of the literature. Rev Infect Dis I98o; 2: 746-760. Drelichman V, Band JD. Bacteraemias due to Citrobacter diversus and Citrobacter freundii. Arch Intern Med I985; I45: i8o8-i8io. Samonis G~ Anaissie E~ Eking L, Bodey GP. Review of Citrobacter bacteremia in cancer patients over a sixteen year period. Euro J Clin Microbiol Infect Dis I99I ; xo: 479-485. Williams WW, Mariano J, Spurrier M e t al. Nosocomial meningitis due to Citrobacter diversus in neonates: new aspects of the epidemiology. J Infect Dis I984; xSO: 229-235. Kline MW, Mason EO Jr, Kaplan SL. Characterization of Citrobacter diversus strains causing neonatal meningitis. J Infect Dis I988; x57: IoI-IO5. Foreman SD, Smith EE, Ryan NS, Hogan GR. Neonatal Citrobacter meningitis: pathogenesis of cerebral abscess formation. Ann Neurol I984; I6: 655-659. Scheld WM, Tyson GW. Citrobacter freundii meningitis in an adult. South Med J I979; 72: I598-I599. Kline MW. Citrobacter meningitis and brain abscess in infancy: epidemiology, pathogenesis and treatment. J~Pediatr I988; II3: 430-434. Levy RL, Saunders RL. Citrobacter meningitis and cerebral abscess in early infancy: cure by maxalactam. Neurology I98I ; 3I : I575-I577. Greene GR, Heitlinger L, Madden JD. Citrobacter ventriculitis in a neonate responsive to trimethoprim-sulfamethoxazole. Clin Pediatr I983 ; 22 : 515-517.