Lai-Chu See

Clinical correlates of antifungal macrodilution susceptibility test results for non-AIDS patients with severe Candida infections treated with fluconazole.

ABSTRACT Although the clinical correlates of the reference antifungal susceptibility test results in hematogenous and deep-seatedCandida infection are still controversial, we evaluated the clinical correlates of this test in deep-seatedCandida infections in non-AIDS patients. Thirty-two non-AIDS patients with hematogenous or deep-seated Candidainfections were treated with intravenous fluconazole (400 mg a day), and the clinical outcomes were evaluated. Coexisting bacterial infections were treated with appropriate antibiotics, superinfection or reinfection was excluded, inadequate fluconazole therapy was avoided, and essential surgical intervention was performed. The MICs of fluconazole for these 32 Candida isolates were determined according to the M27-A procedure approved by the National Committee on Clinical Laboratory Standards. MICs were interpreted as susceptible (≤8 μg/ml), dose-dependent susceptible (16 to 32 μg/ml), and resistant (≥64 μg/ml) according to the criteria of the M27-A standard. The success rates were 79% (19 of 24; 95% confidence interval [CI], 59 to 93%) in the susceptible category, 66% (4 of 6; 95% CI, 19 to 95%) in the dose-dependent susceptible category, and 0% (0 of 2; 95% CI, 0 to 84%) in the resistant category. We conclude that the clinical correlation of the reference antifungal susceptibility test results is high in hematogenous and deep-seatedCandida infections.

Candida peritonitis due to peptic ulcer perforation: incidence rate, risk factors, prognosis and susceptibility to fluconazole and amphotericin B

Sixty-two cases of peritonitis due to peptic ulcer perforation were diagnosed between January 2000 and December 2000. Of these 62 cases, 23 isolates of Candida in 23 cases (CP) were cultured from peritoneal fluid. Cultures of peritoneal fluid of 10 (BP) of the remaining 39 cases was positive for bacteria only. Cultures of peritoneal fluid of the remaining 29 cases was negative. Comparison of CP, BP and culture-negative cases did not reveal any significant risk factor. Of the 23 Candida isolates, the Candida species and 48-h MICs of fluconazole and amphotericin B (mean, range ug/ml) were C. albicans 18 (0.688, 0.125-1.0; 0.297, 0.031-0.5), C. glabrata 3 (0.542, 0.125-1.0; 0.25, 0.125-0.5), C. tropicalis 1 (0.25; 0.5), C. intermedia 1 (1.0; 0.125) respectively. Mortality rates of CP, BP and culture-negative peritonitis due to infection were 5/23(21.7%), 0/10 and 1/29(3.4%) respectively. Without effective antifungal therapy, the mortality rate of CP was not low.

Fluconazole Disk Diffusion Test with Methylene Blue- and Glucose-Enriched Mueller-Hinton Agar for Determining Susceptibility of Candida Species

ABSTRACT A 25-μg fluconazole disk diffusion test using a Mueller-Hinton agar plate containing 2% glucose and 5 μg of methylene blue/ml (GM-MH) was compared to the macrodilution reference method for 210Candida species. The GM-MH agar plate was read at 24 h. The predictive values of disks with susceptible, intermediate, and resistant results on the GM-MH agar plate at 24 h were 97.1, 56.3, and 76.5%, respectively.

Nosocomial Infections With Ceftazidime-Resistant Pseudomonas aeruginosa : Risk Factors and Outcome

Prospective studies were conducted for nosocomial Pseudomonas aeruginosa infections from February 1, 1994, to October 30, 1995. Of 97 P. aeruginosa isolates from 97 patients, 35 were resistant to ceftazidime. Logistic regression revealed previous cephalosporin or piperacillin use as independent risk factors for nosocomial ceftazidime-resistant P. aeruginosa infection. Pulsed-field gel electrophoresis revealed that four nosocomial ceftazidime-resistant P. aeruginosa infections were caused by cross-infection, probably through medical personnel.

Risk factors of mortality for nosocomial pneumonia: importance of initial anti-microbial therapy.

Nosocomial pneumonia is a common nosocomial infection and has high mortality rate. Risk factors of mortality of nosocomial pneumonia were studied in 132 hospitalised patients who developed nosocomial pneumonia. The overall mortality rate was 64/132, 48.5%. Of the 11 risk factors univariately associated with mortality due to nosocomial pneumonia, only the inappropriate initial anti‐microbial therapy, high simplified acute physiology score and multiple organ failures remained significant after stepwise logistic regression. Gram‐negative bacilli were still the most pre‐dominant causative microbiologic agents of nosocomial pneumonia with Pseudomonas aeruginosa (20.3%), Acinetobacter baumannii (18.6%) and Escherichia coli (5.9%) being the three most predominant pathogens. A. baumannii were significantly more predominant among non‐survivors than survivors (13.56 vs. 5.08%, p = 0.0418). The incidence rate of methicillin‐resistant Staphylococcus aureus was 19.5% higher than previous reports. We conclude that inappropriate initial anti‐microbial therapy for nosocomial pneumonia is associated with the mortality rate of nosocomial pneumonia, and appropriate anti‐microbial therapy improves outcome of nosocomial pneumonia.

Comparison of Refined and Crude Indigo Naturalis Ointment in Treating Psoriasis: Randomized, Observer-Blind, Controlled, Intrapatient Trial

individual cycles in secondary analyses. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% CIs. Analyses were updated because the main exposure, outcome, and covariates were all time varying. We had multivariate models with or without smoking. Analyses were conducted using SAS software, version 9.2 (SAS Institute Inc). The study was approved by the institutional review board of Brigham and Women’s Hospital. Our receipt of each completed questionnaire implied participant’s informed consent of the present study.

Treatment of psoriatic nails with indigo naturalis oil extract: a non-controlled pilot study.

Background: In the treatment of nail psoriasis, standardized therapeutic regimens are currently lacking. Objective: To evaluate the therapeutic efficacy of indigo naturalis oil extract in patients with nail psoriasis. Methods: Patients with nail psoriasis applied indigo naturalis oil extract on affected nails twice daily for 24 weeks. Efficacy was evaluated using the Nail Psoriasis Severity Index (NAPSI) and modified target NAPSI for the single most severely affected nail. Results: Twenty-eight out of 32 patients completed the study. The mean NAPSI was 36.1 ± 14.7 at baseline and decreased to 14.9 ± 11.1 at week 24 while the mean modified target NAPSI was 11.7 ± 3.9 at baseline and decreased to 3.6 ± 3.2 at week 24. Conclusions: Indigo naturalis oil extract appeared to improve nail psoriasis. Although preliminary, these results indicate that it could provide a novel therapeutic option for nail psoriasis, a disease notoriously difficult to treat.

Clinical features and risk factors of mortality for bacteremia due to community-onset healthcare-associated methicillin-resistant S. aureus

Studies comparing adult community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-onset healthcare-associated MRSA (COHCA MRSA bacteremia have not been available. From 1 January 2010 through 30 October 2010, a prospective observational program was conducted among all patients aged >16 years with positive Staphylococcus aureus blood cultures within 48 h after their arrival at the emergency department of our hospital. Clinical course of infection and infection foci of bacteremia were evaluated. Resistance to oxacillin was confirmed with the presence of mecA gene examined by polymerase chain reaction. Presence of TSST-1, PVL gene, SCCmec elements (I-V), mecA gene, and multilocus sequence typing were identified through methods described elsewhere. Univariate and multivariate analysis revealed that chronic renal failure was significantly more common in COHCA-MRSA than in CA-MRSA. In addition, APACHE III score was significantly higher in COHCA-MRSA than in CA-MRSA. Both the 7-day and 30-day mortality rates in COHCA-MRSA, 14.6% (7/48) and 29.2% (14/48), respectively, were higher than those in CA-MRSA without a significant difference. SCCmec II was more common in COHCA-MRSA, but SCCmecVT was more common in CA-MRSA. The majority of MRSA isolates belonged to ST59, ST239, and ST5. ST59 was significantly more common in CA-MRSA, while ST239 was nearly equally common in both CA-MRSA and COHCA-MRSA. SCCmec III and II isolates were the first and second most resistant to the antibiotics commonly used for S. aureus, whereas SCCmecVT isolates were the most susceptible to these antibiotics. We conclude that, although both CA-MRSA and COHCA-MRSA bacteremia had community onset, these 2 MRSA infections were different in underlying diseases, risk of mortality, SCCmec types, sequence types, and antimicrobial susceptibility. It is more appropriate to understand the MRSA pathogen and clinical features based on etiology and ST types than based on the location of disease onset. CA-MRSA and HCA-MRSA should be differentiated also based on etiology and ST types, in addition to location of acquisition.

Risk factors of mortality and comparative in-vitro efficacy of anidulafungin, caspofungin, and micafungin for candidemia

BACKGROUND Although echinocandins have high in vitro antifungal efficacy according to prior reports, comparative studies on the clinical cure rates of anidulafungin, caspofungin, and micafungin in systemic candida infections have not yet been reported. METHODS Interpretation of clinical and microbiological responses to anidulafungin, caspofungin, and micafungin in 109 cases of candidemia was done according to the published criteria. The clinical cure rates between patients treated with echinocandins and patients treated with fluconazole were also compared. The minimal inhibitory concentrations (MICs) of anidulafungin, caspofungin, micafungin, and fluconazole for these 109 blood isolates of candida were determined with the Clinical and Laboratory Standards Institute M27-A reference microdilution method. Logistic regression with forward selection was used to determine the important factors of prognosis with variables such as age, underlying diseases, acute physiology and chronic health evaluation (APACHE) III score, persistent candidemia, and antimicrobial therapy. RESULTS Among the 109 cases of candidemia, 70 were treated with echinocandins, azoles, or amphotericin B for ≥7 days. The clinical cure rate of cases treated with antifungal agents adequately (≥7 days) and inadequately (<7 days) were 44/70 (62.9%) and 4/39 (10.2%), respectively, with significant difference (p < 0.0001). Clinical cure rates of anidulafungin, caspofungin, micafungin, and fluconazole were 18/30 (60.0%), 8/9 (88.9%), 5/7 (71.4%), and 9/18 (50%), respectively. The difference in APACHE III score between treatment success and failure cases was significant. The MIC50/MIC90 of anidulafungin, caspofungin, and micafungin for all Candida spp. were 0.03/1 μg/mL, 0.06/0.5 μg/mL, and 0.008/1 μg/mL, respectively. CONCLUSION Adequate antifungal therapy and APACHE III score are both independent factors affecting the clinical outcome. The clinical cure rate of the echinocandins group was higher than that of the fluconazole group without significant difference. Although caspofungin had the best clinical cure rate in this study, there was no significant difference between the clinical cure rates among these three echinocandins. All Candida spp. were susceptible in vitro to these three echinocandins.