Candida Meningitis Research Articles

Candidal Meningitis in a Patient with Chronic Mucocutaneous Candidiasis

Candidal Meningitis in a Patient with Chronic Mucocutaneous Candidiasis

Meningitis Caused by Candida Species: An Emerging Problem in Neurosurgical Patients

Three cases of candida meningitis were encountered in a 3-year period in our hospital; all occurred in neurosurgical patients. We describe these three cases and review the 15 cases of neurosurgery-related candida meningitis previously reported in the English-language literature. Data regarding these 18 patients formed the basis for our review. Most patients with candida meningitis had recently received antibacterial agents, and it is notable that 50% of patients suffered from antecedent bacterial meningitis. The CSF analysis revealed neutrophilic pleocytosis that was indistinguishable from that of bacterial meningitis. The overall mortality was 11%. Administration of amphotericin B combined with flucytosine appeared to be the best therapeutic approach for candida meningitis.

“Unexplained” Delayed Death From Fungal Meningitis After Meningioma Resection

Progressive deterioration and ensuing death following a neurosurgical procedure often represents a diagnostic challenge to the team responsible for patient care. Many, but not all, causes are treatable if a diagnosis is made early. A 69-year-old woman who died 6 weeks post-operatively following a meningioma resection is reported. An initial routine post-operative course became complicated by progressive neurological deterioration 3-4 weeks later. Despite extensive investigation she died 6 weeks post-operatively without a diagnosis. Autopsy demonstrated extensive Candida meningitis. A review of the literature demonstrates this to be a reported complication in high risk patients, difficult to diagnose, but treatable when identified. Fungal meningitis should be high in the differential diagnosis in the post-operative patient with delayed, unexplained neurological deterioration, especially when associated with negative CSF cultures.

Chronic Candidal Meningitis: An Uncommon Manifestation of Candidiasis

Chronic meningitis is an uncommon manifestation of candidiasis. We present the case of an elderly woman who had symptoms such as headache, malaise, and fever for 8 months and was found to have Candida albicans meningitis, and we review 17 similar cases. An underlying illness or risk factor for candidiasis was present in only 13 (72%) of the 18 patients. Headache, fever, and nuchal rigidity were the predominant clinical findings. Analysis of CSF showed either mononuclear or neutrophilic pleocytosis, an elevated protein level, and a decreased level of glucose. Only 17% of CSF smears were positive, and only 44% of initial CSF cultures yielded Candida species. In four cases, Candida species grew only after special techniques were used; in three cases, CSF cultures remained negative. The overall mortality associated with candidal meningitis was 53%, but among 12 patients who were treated and followed, the rate was 33%. In addition to acute meningitis seen with disseminated infection, Candida species can cause chronic meningitis that mimics tuberculosis and the more common fungal meningitides, such as cryptococcosis.

Neonatal fungemia and amphotericin B.

Disseminated candidemia is a common nosocomial infection in the neonatal intensive care unit, though only a few studies have reported the outcome of amphotericin B therapy in neonatal candidiasis. Our treatment regimen consisted of an initial daily amphotericin B dose of 0.5 mg/kg. (For infants weighing > 1 kg, the second dose was increased to 1 mg/kg.) At 3 to 5 days, if the blood culture was negative, amphotericin B therapy was changed to every other day and continued for a total of 10 doses. Records of 36 patients given this regimen were reviewed for signs of toxicity or treatment failure. The mean birth weight was 988 +/- 510 g, and the gestational age was 28 +/- 3.9 weeks. The patients were ventilated for 13 +/- 15 days and had central lines for 6.7 +/- 9.3 days before development of candidemia. The mean age at onset of candidemia was 29.1 +/- 19.8 days. The interval from culture to treatment was 2.9 days. Six of 36 patients died, 2 of candidal meningitis and 4 of complications unrelated to candidal infection. Thirteen (36%) of the patients had candidal pustules during the course of their disease; 1 had osteomyelitis. There was no evidence of toxicity from this drug regimen and no apparent treatment failures. There were no changes in BUN and creatinine before or during therapy and no change in total urinary output. Blood cultures became sterile except in one patient who died on the first day of therapy. Most of the patients in this study had candidemia in the absence of a central indwelling catheter. Further prospective pharmacokinetic and therapeutic studies are warranted for this regimen of amphotericin B, which carries a low risk for toxicity.

Glioblastoma, transforming growth factor-β, and Candida meningitis: A potential link

The development of Candida meningitis in a patient following partial resection of a glioblastoma raised suspicion that transforming growth factor (TGF-β), an immunosuppressive cytokine known to be produced by this tumor, would be elevated in his cerebrospinal fluid (CSF). By using a highly specific bioassay, the concentration of TGF-β was found to be 609 pg/mL, which was 10-fold greater than the mean CSF TGF-β value in control subjects with no neurologic disease. Increased CSF TGF-β levels were also detected in patients with other central nervous system (CNS) diseases: malignancies and AIDS dementia complex. These findings suggest that TGF-β may play an immunopathogenetic role in the CNS.

Analysis of cases of central nervous system fungal infections reported in Japan between January 1979 and June 1989.

Data from 129 cases of central nervous systemic fungal infections reported in Japan between January 1979 and June 1989 were analyzed. Of 129 cases, 116 were cryptococcal meningitis, 6 candidal meningitis (including meningitis due to Trichosporon cutaneum) and 7 Aspergillus meningoencephalitis. Fifty-six of the patients with cryptococcal meningitis had an underlying systemic disease or condition. The overall survival rate was 72.4%, which was a markedly improved rate compared to earlier reports. Cryptococcal meningitis was treated most often with the combination of intravenous amphotericin B and 5-fluorocytosine and was associated with a survival rate of 81.8%. All 7 patients treated with fluconazole alone survived. Candidal meningitis occurred secondary to a shunt infection; some patients with candidemia did well when adequate therapy was instituted. Aspergillus meningoencephalitis is most often diagnosed at autopsy or in surgical specimens and the prognosis of Aspergillus meningoencephalitis is generally poor.

Progress in antifungal chemotherapy.

The field of antifungal chemotherapy is undergoing rapid change at present, with an accelerating pace of introduction of new agents. The problems at present include the need for more effective agents, particularly with novel modes of action. Fungal infection must be considered more frequently in differential diagnosis, and methods developed for early diagnosis. The literature must be improved, with more precise terms. Trials comparing agents are needed, as are studies directed at determining the appropriate length of therapy.In vitro susceptibility testing must be standardized, and clinical correlations examined. Particular problem areas in current therapy are deep candida infections, zygomycotic infections, fungal endocarditis and meningitis, cryptococcosis in AIDS patients, and ocular infections withFusarium species. Immunomodulating or “pro-host” drugs present an as yet unexplored avenue for clinical therapy. Regimes to prevent fungal infection need improvement. Until the needed advances occur, we must be resourceful in minimizing the toxicity of the agents presently available.

Clinical Approach to Infection in the Compromised Host

There is perhaps no greater challenge facing the clinician than the diagnosis and treatment of infection in the immunologically impaired patient. Diagnosis is particularly difficult because disease may appear in bizarre or unusual guise when a patient is granulocytopenic, and traditionally rarely encountered pathogens may be the most common in such settings. Treatment can be particularly perplexing, and response to therapy delayed. The second edition of Clinical Approach to Infection in the Compromised Host comes to the rescue! Here is an up-to-date volume targeted to the needs of the practitioner. How does one approach the patient with granulocytopenia and nodular pulmonary infiltrates? How is that approach different if the infiltrates are interstitial? Is candidal meningitis a concern in the patient with the acquired immunodeficiency syndrome? If a skin biopsy shows acid-fast bacilli, what possibilities come to mind? With admirable clarity the authors—all highly regarded experts in their respective fields—present the

Candida meningitis: Clinical and radiographic diagnosis

Two patients with Candida meningitis are presented to emphasize cranial polyneuropathy and ventricular isolation with septation. These clinical and radiographic criteria can be used for early diagnosis and treatment.

Problems in antifungal chemotherapy.

The field of antifungal chemotherapy is undergoing rapid change at present, with an accelerating pace of introduction of new agents. The problems at present include the need for more effective agents, particularly with novel modes of action. Fungal infection must be considered more frequently in differential diagnosis, and methods developed for early diagnosis. The literature must be improved, with more precise terms. Trials comparing agents are needed, as are studies directed at determining the appropriate length of therapy. In vitro susceptibility testing must be standardized, and clinical correlations examined. Particular problem areas in current therapy are deep candida infections, zygomycotic infections, fungal endocarditis and meningitis, cryptococcosis in AIDS patients, and ocular infections with Fusarium species. Immunomodulating or "pro-host" drugs present an as yet unexplored avenue for clinical therapy. Regimes to prevent fungal infection need improvement. Until the needed advances occur, we must be resourceful in minimizing the toxicity of the agents presently available.

Taking Candida Meningitis Seriously

Taking Candida Meningitis Seriously

Combined therapy with amphotericin B and 5-fluorocytosine for Candida meningitis.

The course and outcome of combined treatment with amphotericin B and 5-fluorocytosine were analyzed in 17 patients with candida meningitis. Eleven patients were twelve months of age or younger; seven of these were neonates. All but two patients had underlying conditions or therapy that could predispose them to systemic candidiasis. The median duration of concurrent dual therapy was 26 days; in ten cases, therapy with either drug alone was continued longer. Fifteen patients improved; 14 were cured of their infection. Cultures of cerebrospinal fluid became sterile a median of seven days after the start of therapy. Primary resistance to 5-fluorocytosine was found in four of the Candida isolates, and acquired resistance, in one. Serious adverse drug reactions were uncommon. The two patients who died had received intrathecal rather than systemic amphotericin B. One of eight infants who survived had psychomotor retardation; three of eleven infants developed hydrocephalus. Although experience with candida meningitis is limited, the combination of amphotericin B and 5-fluorocytosine is effective and offers potential advantages over amphotericin B alone.

Candida meningitis in two children with severe combinedimmunodeficiency

WE REPORT OUR EXPERIENCE with meningitis caused by Candida albicans in two infants with severe combined immunodeficiency. Although previously reported in neon a t e s a n d infants with recognized predisposing factors for systemic candidiasis such as prematurity, antibiotic therapy, and parenteral alimentation, a3 to our knowledge these are the first reported cases of Candida meningitis described in this patient population.

Mannose in body fluids as an indicator of invasive candidiasis.

Using gas-liquid chromatography, we measured five mannose in the serum of six nondiabetic patients with autopsy-proven invasive candidiasis. In all patients serum mannose concentrations were higher than mannose levels found in serum from normal adults and children or from patients with catheter-associated candidemia, mucosal candidiasis, and other mycoses. Spinal fluid from two patients with Candida meningitis showed increased free mannose as compared to seven non-inflammatory spinal fluid samples. However, free mannose in the serum of poorly controlled diabetics (blood glucose of greater than or equal to 300 mg/dl) did overlap concentrations in patients with invasive candidiasis. In vitro culture of Candida albicans demonstrated increasing concentrations of mannose associated with growth of the organism. We conclude that physical and chemical assay for mannose in body fluids may be a useful technique to assist in the diagnosis in invasive candidiasis.

Candida albicans Meningitis in a Premature Neonate Successfully Treated With 5-Fluorocytosine and Amphotericin B: A Case Report and Review of the Literature

Candida albicans meningitis was diagnosed in a 45-day-old premature infant whose birth weight was 1,616 gm. Symptoms consisted of poor weight gain and poor suckling. The combined use of amphotericin B and 5-fluorocytosine (5-FC) resulted in negative CSF cultures after 12 days of therapy. Amphotericin B was given for 45 days (total 83 mg) and 5-FC for 60 days (total 19 mg). Only one other premature infant has been reported in the literature who had similar treatment. A review of Candida meningitis diagnosed before death in 11 other infants less than 1 year of age is presented.

Successful treatment of Candida meningitis with amphotericin B and 5-fluorocytosine in combination

The combined use of amphotericin B and 5-fluorocytosine in the treatment of two children with Candida albicans meningitis is described. Therapy consisted of nine to 13 days of iv amphotericin B, combined with, or followed by six to nine weeks of oral 5-FC. Each organism was sensitive to 5-FC before starting therapy. Resistance did not develop during therapy. CSF administration was not necessary and toxic reactions were minimal and transient; neither patient has suffered a recurrence four years and 14 months, respectively, after discontinuance of therapy. The combination of short-term therapy with iv amphotericin B plus long-term oral 5-FC was successful in these two patients.

Recovery From Disseminated Candidiasis in a Premature Neonate

The management of candidemia in neonates is difficult since even transient episodes of fungal septicemia may lead to widespread tissue invasion and multiple secondary complications.1-8 The patient reported here was a premature neonate receiving parenteral hyperalimentation and broad spectrum antibiotic therapy when Candida septicemia developed. The septicemia was followed by Candida arthritis, osteomyelitis, meningitis, endophthalmitis and pyelonephritis. Initial treatment with 5-fluorocytosine rapidly resulted in the emergence of resistant organisms, but prolonged therapy with a combination of amphotericin B and 5-fluorocytosine brought about a satisfactory clinical response and reversed the destructive changes observed in the eyes, bones and joints. Four months after discontinuation of antifungal therapy, the patient had a recurrence of Candida ophthalmic infection which responded to another course of amphotericin B. CASE REPORT The patient was a 1,928-gm infant born to a 33-year-old primagravida at approximately 32 weeks' gestation. The infant, who was delivered by cesarean section because of placenta previa, required intubation and resuscitation in the delivery room. Because of persistent respiratory distress and periods of apnea, the patient was transferred to the University of Minnesota Neonatal Intensive Care Unit at approximately 12 hours of age. Severe hyaline membrane disease necessitated the use of respiratory therapy, and an umbilical artery catheter was inserted to monitor blood gases. On the fifth hospital day, apnea, acidosis, and questionable pneumatosis intestinalis observed on an abdominal x-ray prompted the institution and continuance of penicillin and kanamycin therapy, although blood, urine and cerebrospinal fluid cultures remained sterile. Hyperalimentation through the umbilical arterial catheter was started on the sixth hospital day.

Candidiasis of the larynx.

Candida albicans, the fungus which is responsible for moniliasis, is a common inhabitant of the throat and not ordinarily a pathogen in the adult. In the presence of lowered host resistance by disease, corticosteroid therapy, immunosuppressive drugs or in the presence of altered normal flora by prolonged use of broad spectrum antibiotics, a candida infection may occur. Usually there is little difficulty in assessing the significance of this fungus when it is associated with visible mucus membrane or cutaneous lesions in healthy individuals. However, multiple or persistent isolations of the fungus from body fluids even after the removal of provocative factors such as antibiotics and foreign bodies indicates an invasive disease which requires specific therapy. Mucocutaneous and superficial Candida infections usually respond to topical therapy such as nystatin spray or gargle. When this is ineffective and the patient is still symptomatic, low doses of intravenously administered amphotercin B should be considered as the next step in the management of the infection. In patients with Candida meningitis or endocarditis this regimen is not recommended.

SUCCESSFULLY TREATED CANDIDA ENDOPHTHALMITIS IN A CHILD

A 12-year-old boy with ulcerative colitis developed persistent fever following colectomy and protracted medical management including central hyperalimentation. Candida sepsis, meningitis, and endophthalmitis were diagnosed on the basis of the eye lesions and early cultures, and the child was treated with amphotericin B. The neurological signs cleared, and visual acuity improved dramatically.