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Voriconazole treatment of Candida tropicalis meningitis: persistence of (1,3)-β-D-glucan in the cerebrospinal fluid is a marker of clinical and microbiological failure: A case report.

Ceccarelli G, Ghezzi MC, Raponi G, Brunetti G, Marsiglia C, Fallani S, Novelli A, Venditti M - Medicine (Baltimore) (2016)

Bottom Line: Even though fungal etiologies are considered to be rare, they are associated with significant morbidity and mortality.Despite appropriate treatment with VOR, in terms of adequate achieved CSF drug concentrations and initial effective therapeutic response, loss of VOR susceptibility of the C tropicalis and treatment failure were observed.Rising titers of this marker were associated with relapse of fungal infection.

View Article: PubMed Central - PubMed

Affiliation: aDepartment of Public Health and Infectious Diseases. University of Rome "Sapienza", Azienda Policlinico Umberto I, Rome bDepartment of Health Sciences (DSS), Section of Clinical Pharmacology and Oncology, Università degli Studi, Florence, Italy.

ABSTRACT

Introduction: Infections are still the most common complications of cerebral shunt procedures. Even though fungal etiologies are considered to be rare, they are associated with significant morbidity and mortality. Due to their uncommonness, diagnostic procedures and optimal therapy are poorly defined. We report a case of Candida tropicalis infection of ventriculo-peritoneal cerebrospinal fluid (CSF) shunt in a 49-year-old immune competent male treated with voriconazole (VOR).

Methods: Microbiological and CSF markers (1,3-b-D-glucan-BDG) of fungal infection, biofilm production capacity, sensitivity of serial isolates of the pathogen, and the concentration of the antifungal drug have been monitored and related to the clinical course of this infection.

Results: Despite appropriate treatment with VOR, in terms of adequate achieved CSF drug concentrations and initial effective therapeutic response, loss of VOR susceptibility of the C tropicalis and treatment failure were observed.

Conclusion: Biofilm production of the C. tropicalis isolate might have had a significant role in treatment failure. Of interest, clinical and microbiological unfavorable outcome was anticipated by persistence of BDG in CSF. Rising titers of this marker were associated with relapse of fungal infection.

No MeSH data available.


Related in: MedlinePlus

Clinical course, microbiological and laboratory monitoring of meningitis caused by C tropicalis. CSF BDG = cerebrospinal fluid (1,3)-β-d-Glucan, CSF WBC = cerebrospinal fluid white blood cells, CSF = cerebrospinal fluid, EDV = external ventricular drainage, MICs = minimal inhibitory concentrations, VOR BDG (conc) = voriconazole concentrations in cerebrospinal fluid).
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Figure 1: Clinical course, microbiological and laboratory monitoring of meningitis caused by C tropicalis. CSF BDG = cerebrospinal fluid (1,3)-β-d-Glucan, CSF WBC = cerebrospinal fluid white blood cells, CSF = cerebrospinal fluid, EDV = external ventricular drainage, MICs = minimal inhibitory concentrations, VOR BDG (conc) = voriconazole concentrations in cerebrospinal fluid).

Mentions: A 49-year-old immune-competent male was admitted to the Neurosurgical Intensive Care for fever (up to 38°C) associated with ideomotor slowdown, severe confusional state, and meningism. Two months prior hospitalization, the patient underwent surgical removal of a pontocerebellar acoustic neuroma with placement of a ventriculo-peritoneal (VP) shunt and received an successful 10-day Fluconazole (FLU) treatment course for a catheter-related C tropicalis urinary tract infection. CSF analysis, performed at the admission, revealed glucose concentration of 34.2 mg/dL, protein level of 332 mg/dL, and leukocytes cell count of 471 cells/μL (75% polymorphonucleocytes). No signs of persistent Candida urinary tract infection were found in serial urine analysis and cultures performed during this second hospitalization. Fungal meningitis was diagnosed on the basis of C tropicalis isolation from the CSF culture. The same pathogen was also cultured from the removed VP shunt, while blood cultures were negative. Intravenous voriconazole (VOR) was started (loading dose 6 mg/Kg/q12 for 2 doses, then 4 mg/Kg/q12) and an external ventricular drainage (EVD) was inserted. The clinical course and the main laboratory findings, expressed in function of time, are shown in Fig. 1.


Voriconazole treatment of Candida tropicalis meningitis: persistence of (1,3)-β-D-glucan in the cerebrospinal fluid is a marker of clinical and microbiological failure: A case report.

Ceccarelli G, Ghezzi MC, Raponi G, Brunetti G, Marsiglia C, Fallani S, Novelli A, Venditti M - Medicine (Baltimore) (2016)

Clinical course, microbiological and laboratory monitoring of meningitis caused by C tropicalis. CSF BDG = cerebrospinal fluid (1,3)-β-d-Glucan, CSF WBC = cerebrospinal fluid white blood cells, CSF = cerebrospinal fluid, EDV = external ventricular drainage, MICs = minimal inhibitory concentrations, VOR BDG (conc) = voriconazole concentrations in cerebrospinal fluid).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979841&req=5

Figure 1: Clinical course, microbiological and laboratory monitoring of meningitis caused by C tropicalis. CSF BDG = cerebrospinal fluid (1,3)-β-d-Glucan, CSF WBC = cerebrospinal fluid white blood cells, CSF = cerebrospinal fluid, EDV = external ventricular drainage, MICs = minimal inhibitory concentrations, VOR BDG (conc) = voriconazole concentrations in cerebrospinal fluid).
Mentions: A 49-year-old immune-competent male was admitted to the Neurosurgical Intensive Care for fever (up to 38°C) associated with ideomotor slowdown, severe confusional state, and meningism. Two months prior hospitalization, the patient underwent surgical removal of a pontocerebellar acoustic neuroma with placement of a ventriculo-peritoneal (VP) shunt and received an successful 10-day Fluconazole (FLU) treatment course for a catheter-related C tropicalis urinary tract infection. CSF analysis, performed at the admission, revealed glucose concentration of 34.2 mg/dL, protein level of 332 mg/dL, and leukocytes cell count of 471 cells/μL (75% polymorphonucleocytes). No signs of persistent Candida urinary tract infection were found in serial urine analysis and cultures performed during this second hospitalization. Fungal meningitis was diagnosed on the basis of C tropicalis isolation from the CSF culture. The same pathogen was also cultured from the removed VP shunt, while blood cultures were negative. Intravenous voriconazole (VOR) was started (loading dose 6 mg/Kg/q12 for 2 doses, then 4 mg/Kg/q12) and an external ventricular drainage (EVD) was inserted. The clinical course and the main laboratory findings, expressed in function of time, are shown in Fig. 1.

Bottom Line: Even though fungal etiologies are considered to be rare, they are associated with significant morbidity and mortality.Despite appropriate treatment with VOR, in terms of adequate achieved CSF drug concentrations and initial effective therapeutic response, loss of VOR susceptibility of the C tropicalis and treatment failure were observed.Rising titers of this marker were associated with relapse of fungal infection.

View Article: PubMed Central - PubMed

Affiliation: aDepartment of Public Health and Infectious Diseases. University of Rome "Sapienza", Azienda Policlinico Umberto I, Rome bDepartment of Health Sciences (DSS), Section of Clinical Pharmacology and Oncology, Università degli Studi, Florence, Italy.

ABSTRACT

Introduction: Infections are still the most common complications of cerebral shunt procedures. Even though fungal etiologies are considered to be rare, they are associated with significant morbidity and mortality. Due to their uncommonness, diagnostic procedures and optimal therapy are poorly defined. We report a case of Candida tropicalis infection of ventriculo-peritoneal cerebrospinal fluid (CSF) shunt in a 49-year-old immune competent male treated with voriconazole (VOR).

Methods: Microbiological and CSF markers (1,3-b-D-glucan-BDG) of fungal infection, biofilm production capacity, sensitivity of serial isolates of the pathogen, and the concentration of the antifungal drug have been monitored and related to the clinical course of this infection.

Results: Despite appropriate treatment with VOR, in terms of adequate achieved CSF drug concentrations and initial effective therapeutic response, loss of VOR susceptibility of the C tropicalis and treatment failure were observed.

Conclusion: Biofilm production of the C. tropicalis isolate might have had a significant role in treatment failure. Of interest, clinical and microbiological unfavorable outcome was anticipated by persistence of BDG in CSF. Rising titers of this marker were associated with relapse of fungal infection.

No MeSH data available.


Related in: MedlinePlus