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Biomedical subjects

M H Nguyen

Publications and source records attributed to M H Nguyen.

At least 37 records · Page 2Linked to original sources
PubMed1998

Invasive sinus aspergillosis in apparently immunocompetent hosts.

OBJECTIVES: to describe the clinical, microbiological and pathological features of invasive sinus aspergillosis affecting immunocompetent hosts, and to identify the risk factors for mortality. METHODS: we report three apparently immunocompetent patients with invasive sinus aspergillosis, and review all cases reported in the English literature since 1987, the year in which the triazole antifungal agents were introduced. RESULTS: twenty-nine patients (including three of our own) were identified. The presenting symptoms were non-specific and indistinguishable from viral, bacterial or allergic causes of sinusitis. The findings on computed tomography scan were also non-specific, and histopathology and culture of sinus tissue biopsy had low yield. These factors, along with the mistaken impression that Aspergillus can only affect immunocompromised hosts, frequently delayed the diagnosis. Fifty-nine percent of patients either failed therapy or died. The following factors were associated with a poor prognosis: delayed diagnosis, intracranial extension of infection, and histopathology demonstrating hyphal invasion of blood vessel or tissue. Complete surgical extirpation was the key element of successful therapy; antifungal agents played an adjunctive role. CONCLUSIONS: invasive sinus aspergillosis carries high morbidity and mortality, even in immunocompetent hosts. To improve outcome, the diagnosis must be recognized early, before the organism can invade the central nervous system or vascular structures. Aggressive surgical resection of the infected areas is of utmost importance in the management of this infection.

Adult↗
PubMed1998

Effectiveness of infection control program in controlling nosocomial Clostridium difficile.

OBJECTIVE: To report the effectiveness of use of comprehensive infection control measures to reduce the incidence of Clostridium difficile (CD) in an acute-care teaching hospital. METHODS: All CD infections were reviewed by the infection control coordinator from 1987 to 1996. The Centers for Disease Control and Prevention's nosocomial infection definition was used. CD-inclusion criteria remained unchanged during the study period. Interventions were started in 1990. INTERVENTIONS: The interventions used were: (1) Isolation policy-revision and enforcement, which included universal precautions policy, (2) educational program-monthly to all health care workers, (3) phenolic disinfectant for environmental cleaning, (4) triclosan (0.03%) soap for handwashing, (5) centralization of sterilization department, (6) cart-washer installation, and (7) aggressive surveillance activity. RESULTS: From 1987 to 1989, before the interventions, a total of 466 CD infections (mean 155 per year) occurred. From 1990 to 1996, after the interventions, 475 infections (mean 67 per year) occurred. Incidence of CD decreased by 60% from 1990 to 1996. CONCLUSION: The sustained decrease of nosocomial CD during the 7-year period demonstrated the effectiveness of aggressive infection control measures that involve multiple disciplines.

Clostridioides difficile↗
PubMed1998

Do in vitro susceptibility data predict the microbiologic response to amphotericin B? Results of a prospective study of patients with Candida fungemia.

Outcome for 105 patients with candidemia treated with amphotericin B was correlated with amphotericin B in vitro susceptibility results. Thirty-three patients had microbiologic failure, which was defined as persistence of Candida in the bloodstream despite > or = 3 days of amphotericin B. Amphotericin B minimum inhibitory concentrations (MICs) were determined by the National Committee for Clinical Laboratory Standards methodology. After determination of MICs, the minimal lethal concentrations (MLCs) were determined. The isolates tested yielded a narrow range of amphotericin B MICs (0.06-2 microg/mL); only 5% (5/105) exhibited MICs > or = 1 microg/mL. The MLC range, on the other hand, was significantly broader (0.125 to > 16 microg/mL); 24% (25/105) exhibited MLCs > or = 1 microg/mL. The strongest predictor for microbiologic failure was 48-h MLC (P < .001), followed by 24-h MLC (P = .03) and 48-h MIC (P = .11). A resistant break point for amphotericin B of > 1 microg/mL for MLC and > or = 1 microg/mL for MIC could be inferred from this study.

Amphotericin B↗
PubMed1998

The combination of amphotericin B and azithromycin as a potential new therapeutic approach to fusariosis.

We investigated the interaction between amphotericin B and azithromycin in vitro against 26 clinical isolates of Fusarium. Synergy was demonstrated in all isolates. Amphotericin B MICs were reduced from a mean of 1 mg/L when tested alone to a mean of 0.37 mg/L when tested in combination with azithromycin. Azithromycin demonstrated no activity against Fusarium when tested alone (MIC > 128 mg/L). When combined with amphotericin B the mean MIC was reduced to 5.5 mg/L, a level readily achieved in tissue. Given the resistance of Fusarium to conventional therapy, the in-vitro synergy between amphotericin B and azithromycin might prove to be important in therapy for fusariosis.

Amphotericin B↗
PubMed1998

Voriconazole against fluconazole-susceptible and resistant candida isolates: in-vitro efficacy compared with that of itraconazole and ketoconazole.

We compared the in-vitro activity of fluconazole, itraconazole, ketoconazole and voriconazole against 67 blood isolates of Candida spp. exhibiting a wide range of fluconazole MICs (0.125 to >64 mg/L). Voriconazole was the most potent in vitro, followed by itraconazole, ketoconazole and fluconazole. Itraconazole and voriconazole had in-vitro activity against fluconazole-susceptible and -resistant candida isolates. Higher itraconazole and voriconazole MICs were observed in isolates exhibiting higher fluconazole MICs, suggesting cross-resistance. Itraconazole and voriconazole MICs of > or =16 mg/L were observed only in Candida albicans and Candida tropicalis. Candida krusei and Candida glabrata exhibited itraconazole MICs of 0.5-1 mg/L and voriconazole MICs of 0.25-0.5 mg/L.

Antifungal Agents↗
PubMed1998

In vitro comparative efficacy of voriconazole and itraconazole against fluconazole-susceptible and -resistant Cryptococcus neoformans isolates.

In vitro susceptibility testing for 50 clinical isolates of fluconazole-susceptible or -resistant Cryptococcus neoformans was performed with itraconazole and voriconazole. Voriconazole was more potent than itraconazole for fluconazole-susceptible isolates and as potent as itraconazole for fluconazole-susceptible dose-dependent isolates and for fluconazole-resistant isolates. For fluconazole-resistant isolates, the voriconazole and itraconazole MICs ranged from 1 to 2 microg/ml.

Antifungal Agents↗
PubMed1998

Inhibition of RNA synthesis as a therapeutic strategy against Aspergillus and Fusarium: demonstration of in vitro synergy between rifabutin and amphotericin B.

We investigated the in vitro antifungal activity of amphotericin B, alone and in combination with rifabutin, an inhibitor of bacterial RNA polymerase, against 26 clinical isolates of Aspergillus and 25 clinical isolates of Fusarium. Synergy or additivism between these drugs was demonstrated against all isolates tested. Amphotericin B MICs were reduced upon combination with rifabutin from a mean of 0.65 microg/ml to a mean of 0.16 microg/ml against Aspergillus, and from a mean of 0.97 microg/ml to a mean of 0.39 microLg/ml against Fusarium (P < 0.000001 for both). Similarly, the MICs of rifabutin were reduced upon combination with amphotericin B from a mean of >32 microg/ml to a mean of 1.1 microg/ml against both fungi (P < 0.000001 for both). These positive interactions were corroborated by a colony count study with two Fusarium isolates, for which treatment with the combination of subinhibitory concentrations of amphotericin B (at concentrations 2- and 4-fold less than the MIC) and rifabutin (at concentrations ranging from 4- to 64-fold less than the MIC) resulted in 3.2-log reductions in colony counts compared to those after treatment with either drug alone. Inhibition of RNA synthesis was shown to be the mechanism of antifungal activity. These results suggest that inhibition of fungal RNA synthesis might be a potential target for antifungal therapy.

Amphotericin B↗
PubMed1998

Acute community-acquired pneumonia due to Aspergillus in presumably immunocompetent hosts: clues for recognition of a rare but fatal disease.

This article reports a case of acute community-acquired pneumonia due to Aspergillus fumigatus in a healthy patient and reviews 11 previously reported cases occurring in presumably immunocompetent hosts. The diagnosis was delayed for all patients; mortality was 100%. Clues that might suggest Aspergillus as a pathogen in community-acquired pneumonia include a chest radiograph revealing diffuse infiltrates or new cavitation; lack of bacterial or viral cause; a preceding influenza A infection; and respiratory secretion cultures positive for Aspergillus. When these clues are present, the physician should consider an early biopsy of lung tissue. Increased recognition and more timely diagnosis in future cases will improve the outcome of this rare but fatal infection.

Acute Disease↗
PubMed1997

Potentiation of antifungal activity of amphotericin B by azithromycin against Aspergillus species.

The potential role of azithromycin in combination with amphotericin B against 25 clinical isolates of Aspergillus was assessed. The MIC of amphotericin B was 1 microg/ml for 44% of the isolates, 0.5 microg/ml for 48%, and 0.25 microg/ml for 8%. All isolates were resistant to azithromycin. Synergism, defined as a > or = twofold reduction in the MIC of both drugs upon combination, was demonstrated between amphotericin B and azithromycin for all 25 isolates. To prove that azithromycin exerts its antifungal effect by inhibiting protein synthesis, we studied [35S]-methionine incorporation into protein in one Aspergillus isolate. Neither amphotericin B at 0.125 microg/ml (fourfold below its MIC) nor azithromycin at 16 microg/ml (> or = 16-fold below its MIC) had any effect on protein synthesis when tested alone. Upon combination, however, a 68% inhibition in protein synthesis was evident by the inhibition of [35S]-methionine incorporation.

Amphotericin B↗
PubMed1997

Candidal mediastinitis: an emerging clinical entity.

Candidal mediastinitis is rare. We report nine cases encountered at our institutions since 1985; seven cases were diagnosed since 1993. All cases followed thoracic surgery, with a median time from surgery to disease onset of 11 days (range, 6-100 days). All patients received prior antibiotic therapy. Common clinical manifestations were chest wall erythema in 4 cases (44%), drainage in 5 (56%), fever in 4 (44%), and sternal instability in 4 (44%). Failure to obtain appropriate intraoperative specimens for cultures and the dismissal of cultures positive for Candida as contaminants delayed diagnosis in three cases (33%). Mediastinitis was complicated by contiguous or hematogenous spread in seven cases (78%); five patients (56%) had two or more complications. The mortality rate was 56%. Optimal therapy remains undefined, but on the basis of our experience, aggressive surgical debridement combined with antifungal therapy for at least 6 weeks is recommended. Prompt recognition and institution of therapy appear to be the keys to improving prognosis.

Aged↗
PubMed1997

Combination therapy with fluconazole and flucytosine in the murine model of cryptococcal meningitis.

This study elucidates the role of combined fluconazole and flucytosine as therapy for cryptococcosis in the murine model of meningitis. Three strains of Cryptococcus neoformans for which the range of fluconazole MICs was wide--2 microg/ml (susceptible strain), 8 microg/ml (moderately susceptible strain), and 32 microg/ml (resistant strain)--were used for infection. One day postinfection, the mice were randomized into eight treatment groups: placebo; flucytosine (40 mg/kg of body weight/day); fluconazole at 3 mg/kg/day (low dosage), 10 mg/kg/day (moderate dosage), or 20 mg/kg/day (high dosage); and combined flucytosine and fluconazole at low, moderate, or high doses of fluconazole. Three major findings were demonstrated: (i) correlation between the MICs for the isolates and the in vivo effectiveness of fluconazole as assessed by the reduction in cryptococcal brain burden, (ii) a dose-response curve (a higher dose of fluconazole was significantly more efficacious than a lower dose [P < 0.001]), and (iii) synergism between fluconazole and flucytosine (therapy with a combination of fluconazole and flucytosine was superior to therapy with either agent alone [P < 0.01]).

Animals↗
PubMed1997

Comparison of a photometric method with standardized methods of antifungal susceptibility testing of yeasts.

We determined the fluconazole MICs for 101 clinical isolates of Candida and Cryptococcus neoformans using the macro- and microdilution methods recommended by the National Committee for Clinical Laboratory Standards. We compared the MICs obtained by these methods with those obtained by a photometric assay that quantified the reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) by viable fungi. The MIC determined by this method was defined as the highest fluconazole concentration associated with the first precipitous drop in optical density. For Candida, both the MTT and the microdilution methods demonstrated excellent agreement with the standard macrodilution method. The MTT method, however, generated MICs at 24 h that were comparable to those generated by the standard macrodilution method, whereas the microdilution method required 48 h. For C. neoformans, the levels of agreement between the MICs determined by the MTT and microdilution methods after 48 h and those determined by the standard 72-h macrodilution method were 94% (29 of 31) and 94% (29 of 31), respectively. The MTT method therefore provided results comparable to those of currently recommended methods and had the advantages of a more rapid turnaround time and potential adaptability to use as an automated system. Furthermore, the MICs determined by the MTT method were determined photometrically, thereby eliminating reader bias.

AIDS-Related Opportunistic Infections↗
PubMed1996

Determinants of nontraditional therapy use in patients with HIV infection. A prospective study.

BACKGROUND: The popularity and use of nontraditional therapies among patients with human immunodeficiency virus (HIV) infection has grown enormously. DESIGN: A prospective, longitudinal cohort study of 56 patients aged 23 through 68 years with HIV infection followed up at the HIV clinic at a university-affiliated Veterans Affairs Medical Center. OBJECTIVE: To assess the demographic and psychologic characteristics of patients who seek nontraditional remedies, and their impact on disease progression and mortality from HIV. METHODS: A standardized, self-administered questionnaire to assess the incidence and type of nontraditional therapies used by patients with HIV. Data on demographics, medical status, physical functioning (Karnofsky performance score), CD4 lymphocyte counts, depression (Beck Depression Inventory), coping (inventory of coping with illness scale), psychological and/or emotional stress (Profile of Mood States scores), and compliance with prescribed therapy were prospectively assessed on all patients at baseline and every 6 months. RESULTS: Thirty percent of patients reported using nontraditional therapies. Nontraditional therapy users were significantly older than patients who did not use such therapies (44 vs 38 years, P = .03); with 94% of patients who used nontraditional therapy being older than 35 years compared with 56% of conventional therapy users (P = .005). Alternative therapy use did not correlate with race, education, HIV-risk group affiliation, duration of HIV seropositivity, stage of HIV disease, CD4 cell count, or Karnofsky performance scores. Nontraditional therapy users reported greater community-based acquired immunodeficiency syndrome group support (P = .06), greater perceived social support (P = .08), and significantly higher recreational or "street drugs" use (P = .02). Depression, adaptive coping, and emotional stress were not different between nontraditional and conventional therapy users; however, nontraditional therapy users were significantly more assertive (P = .04). On follow-up, CD4 cell count, HIV disease progression, physical functioning, or mortality were similar between the two groups. CONCLUSIONS: Recourse to nontraditional therapy is common among patients with HIV. Because of the possibility of untoward effects and potential adverse drug interactions associated with nontraditional therapy, HIV care givers should be aware of its use in their patients and take a history of nontraditional therapy first. Patients who choose nontraditional remedies do so not because they are depressed or emotionally disturbed, but rather because they seek greater control of the outcome of their disease. However, no beneficial effect on disease progression, CD4 cell count, or mortality was observed in these patients when compared with patients receiving only conventional medical therapy.

Adaptation, Psychological↗
PubMed1996

The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance.

OBJECTIVES: To assess the changing epidemiology of candidemia in the 1990s, to evaluate the clinical implications for the presence of non-Candida albicans in blood, and to evaluate the presence of antifungal resistance in relation to prior antifungal administration. DESIGN: Multicenter prospective observational study of patients with positive blood cultures for Candida species or Torulopsis glabrata. SETTING: Four tertiary care medical centers. RESULTS: Four hundred twenty-seven consecutive patients were enrolled. The frequency of candidemia due to non-C. albicans species significantly increased in each hospital throughout the 3.5-year study period (P = 0.01). Thirteen percent of candidemias occurred in patients who were already receiving systemic antifungal agents. Candidemias developing while receiving antifungal therapy were more likely caused by non-C. albicans species than by C. albicans species (P = 0.0005). C. parapsilosis and C. krusei were more commonly seen with prior fluconazole therapy, whereas T. glabrata was more commonly seen with prior amphotericin B therapy. Candida species isolated during episodes of breakthrough candidemia exhibited a significantly higher MIC to the antifungal agent being administered (P < 0.001). CONCLUSION: In this large scale study, the non-C. albicans species, especially T. glabrata, emerged as important and frequent pathogens causing fungemia. This finding has major clinical implications given the higher complication and mortality rate associated with the non-C. albicans species. The change in the pattern of candidemia might be partly attributed to the increase in number of immunocompromised hosts and the widespread use of prophylactic or empiric antifungal therapy. This is an ominous sign given the in vitro resistance of the non-C. albicans species to currently available antifungal agents.

Amphotericin B↗