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Indian Journal of Medical Microbiology
Medknow Publications on behalf of Indian Association of Medical Microbiology
ISSN: 0255-0857 EISSN: 1998-3646
Vol. 26, Num. 3, 2008, pp. 283-284

Indian Journal of Medical Microbiology, Vol. 26, No. 3, July-September, 2008, pp. 283-284

Correspondence

Abnormal morphology of bacteria in the cerebrospinal fluid of a patient on antibiotics

Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences(NIMHANS), Bangalore 560 029
Correspondence Address:Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences(NIMHANS), Bangalore 560 029
ritamani@rediffmail.com

Date of Submission: 21-Nov-2007
Date of Acceptance: 28-Nov-2008

Code Number: mb08091

Dear editor,

A five-month-old male child was referred to our hospital with a diagnosis of sacral meningocoele with meningitis and hydrocephalus from a private hospital. He had been treated with cefotaxime and amikacin for a week prior to admission to our hospital. The exact dosage of the drugs received by the patient was not known. A ventric tap performed at our hospital yielded a turbid cerebrospinal fluid (CSF) with a cell count of 700 cells/mm 3 , predominantly polymorphs, glucose of 10 mg/dL and protein of 165 mg/dL. Gram stain of the CSF showed the presence of gram negative bacilli ranging from 5 to 60 μm in length, surrounded by an unstained zone, suggestive of a capsule. Long, filamentous forms [Figure 1A], a few of them with central enlargement [Figure 1B] were also seen. Culture of the CSF on 5% sheep blood agar and MacConkey′s agar yielded a pure growth of Klebsiella oxytoca , sensitive to cefotaxime and amikacin by Kirby and Bauer′s disc diffusion method. The gram stain morphology of the organisms recovered on culture was not unusual.

Cephalosporins and other beta lactam antibiotics which inhibit cell wall synthesis are known to produce morphological changes in susceptible organisms, both in vivo and in vitro . Bacteria usually divide by forming a central septum across the middle of the cell. [1] Penicillin binding protein 3 (PBP-3) is a transpeptidase that plays a crucial role in cell septation of gram negative bacilli. Beta lactam antibiotics can inhibit PBP-3 and thereby prevent the formation of the dividing septum resulting in abnormal elongation and filamentation of rod shaped bacteria. [2],[3]

The patient was started on intravenous cefotaxime 400 mg, thrice a day (200 mg/kg/day) and amikacin 50 mg twice daily (15 mg/kg/day). Two subsequent ventric taps performed after 3 and 4 weeks of therapy respectively, yielded a clear CSF, which was bacteriologically sterile. Hence a ventriculo-peritoneal shunt was performed and the patient was discharged with an advice to follow-up.

Abnormal forms of bacteria have been observed in various clinical specimens including blood, sputum and cerebrospinal fluid of patients on antibiotic therapy. [3],[4],[5] The presence of such abnormal bacterial forms in the specimen of the patient, rather than in the culture of the specimen has clinical significance. Their presence may indicate a sub lethal antibiotic concentration at the site of infection resulting from a low dose of antibiotic or intermittent, possibly unsuspected antibiotic therapy. [4]

These bacteria are ′atypical′ in morphology but usually can be recovered on routine culture media unlike L-forms, protoplasts or spheroplasts which may require specialized media for growth. Such filamentous forms of bacteria in clinical specimens can be confused for anaerobes like Fusobacterium or Bacteroides species, filamentous actinomycetes or fungal hyphae. Hence it is important for microbiologists to be aware of antibiotic induced morphologic variations in bacteria which may pose a diagnostic dilemma.

References

1.Bramhill D. Bacterial Cell Division. Ann Rev Cell Develop Biol 1997;13:395-424.  Back to cited text no. 1    
2.Eberhardt C, Kuerschner L, Weiss DS. Probing the catalytic activity of a cell division-specific transpeptidase in vivo with beta lactams. J Bacteriol 2003;185:3726-34.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Chan-Tack KM, Johnson JK. Answer to photo quiz: An unusual gram stain finding. Clin Infect Dis 2005;40:1677-8.  Back to cited text no. 3    
4.Lorian V, Waluschka A, Kim Y. Abnormal morphology of bacteria in the Sputa of patients treated with antibiotics. J Clin Microbial 1982;16:382-6.  Back to cited text no. 4    
5.Middleton J, Chmel H. Aberrant form of Pseudomonas aeruginosa in sputum and cerebrospinal fluid causing infection in compromised patient. J Clin Pathol 1978;31:351-4.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]

Copyright 2008 - Indian Journal of Medical Microbiology

Indian Journal of Medical Microbiology, Vol. 26, No. 3, July-September, 2008, pp. 283-284

Correspondence

Abnormal morphology of bacteria in the cerebrospinal fluid of a patient on antibiotics

Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences(NIMHANS), Bangalore 560 029
Correspondence Address:Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences(NIMHANS), Bangalore 560 029
ritamani@rediffmail.com

Date of Submission: 21-Nov-2007
Date of Acceptance: 28-Nov-2008

Code Number: mb08091

Dear editor,

A five-month-old male child was referred to our hospital with a diagnosis of sacral meningocoele with meningitis and hydrocephalus from a private hospital. He had been treated with cefotaxime and amikacin for a week prior to admission to our hospital. The exact dosage of the drugs received by the patient was not known. A ventric tap performed at our hospital yielded a turbid cerebrospinal fluid (CSF) with a cell count of 700 cells/mm 3 , predominantly polymorphs, glucose of 10 mg/dL and protein of 165 mg/dL. Gram stain of the CSF showed the presence of gram negative bacilli ranging from 5 to 60 μm in length, surrounded by an unstained zone, suggestive of a capsule. Long, filamentous forms [Figure 1A], a few of them with central enlargement [Figure 1B] were also seen. Culture of the CSF on 5% sheep blood agar and MacConkey′s agar yielded a pure growth of Klebsiella oxytoca , sensitive to cefotaxime and amikacin by Kirby and Bauer′s disc diffusion method. The gram stain morphology of the organisms recovered on culture was not unusual.

Cephalosporins and other beta lactam antibiotics which inhibit cell wall synthesis are known to produce morphological changes in susceptible organisms, both in vivo and in vitro . Bacteria usually divide by forming a central septum across the middle of the cell. [1] Penicillin binding protein 3 (PBP-3) is a transpeptidase that plays a crucial role in cell septation of gram negative bacilli. Beta lactam antibiotics can inhibit PBP-3 and thereby prevent the formation of the dividing septum resulting in abnormal elongation and filamentation of rod shaped bacteria. [2],[3]

The patient was started on intravenous cefotaxime 400 mg, thrice a day (200 mg/kg/day) and amikacin 50 mg twice daily (15 mg/kg/day). Two subsequent ventric taps performed after 3 and 4 weeks of therapy respectively, yielded a clear CSF, which was bacteriologically sterile. Hence a ventriculo-peritoneal shunt was performed and the patient was discharged with an advice to follow-up.

Abnormal forms of bacteria have been observed in various clinical specimens including blood, sputum and cerebrospinal fluid of patients on antibiotic therapy. [3],[4],[5] The presence of such abnormal bacterial forms in the specimen of the patient, rather than in the culture of the specimen has clinical significance. Their presence may indicate a sub lethal antibiotic concentration at the site of infection resulting from a low dose of antibiotic or intermittent, possibly unsuspected antibiotic therapy. [4]

These bacteria are ′atypical′ in morphology but usually can be recovered on routine culture media unlike L-forms, protoplasts or spheroplasts which may require specialized media for growth. Such filamentous forms of bacteria in clinical specimens can be confused for anaerobes like Fusobacterium or Bacteroides species, filamentous actinomycetes or fungal hyphae. Hence it is important for microbiologists to be aware of antibiotic induced morphologic variations in bacteria which may pose a diagnostic dilemma.

References

1.Bramhill D. Bacterial Cell Division. Ann Rev Cell Develop Biol 1997;13:395-424.  Back to cited text no. 1    
2.Eberhardt C, Kuerschner L, Weiss DS. Probing the catalytic activity of a cell division-specific transpeptidase in vivo with beta lactams. J Bacteriol 2003;185:3726-34.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Chan-Tack KM, Johnson JK. Answer to photo quiz: An unusual gram stain finding. Clin Infect Dis 2005;40:1677-8.  Back to cited text no. 3    
4.Lorian V, Waluschka A, Kim Y. Abnormal morphology of bacteria in the Sputa of patients treated with antibiotics. J Clin Microbial 1982;16:382-6.  Back to cited text no. 4    
5.Middleton J, Chmel H. Aberrant form of Pseudomonas aeruginosa in sputum and cerebrospinal fluid causing infection in compromised patient. J Clin Pathol 1978;31:351-4.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]

Copyright 2008 - Indian Journal of Medical Microbiology


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