PCR-Based Microarray Enhances Diagnosis of Culture-Negative Biopsied Tissue in Patients with Invasive Mold Infections: Real-World Experience in a Tertiary Medical Center.

A fungal polymerase chain reaction (PCR) amplifies conserved genes across diverse species, combined with the subsequent hybridization of amplicons using a specific oligonucleotide microarray, allowing for the rapid detection of pathogens at the species level. However, the performance of microarrays in diagnosing invasive mold infections (IMI) from infected tissue samples is rarely reported. During the 4-year study period, all biopsied tissue samples from patients with a suspected IMI sent for microarray assays were analyzed. A partial segment of the internal transcribed spacer (ITS) region was amplified by nested PCR after DNA extraction. Amplicons were hybridized with specific probes for a variety of mold species using an in-house oligonucleotide microarray. A total of 80 clinical samples from 74 patients were tested. A diagnosis of an IMI was made in 10 patients (4 proven, 1 probable, 3 possible, 2 clinical suspicion). The PCR/microarray test was positive for three out of four proven IMIs, one probable IMI, and one out of three possible IMIs. Two patients with positive PCR/microarray findings were considered to have clinical suspicion of an IMI, and their responsible physicians initiated antifungal therapy despite the absence of supporting microbiological and histological evidence. Clinical diagnoses were categorized into non-IMI and IMI groups (including proven, probable, possible, and clinical suspicion). The sensitivity and specificity of the microarray in diagnosing the IMIs were 70% and 95.7%, respectively, while the sensitivity and specificity of the culture and histological findings were 10%/96.3% and 40.0%/100%, respectively. PCR-based methods provide supportive microbiological evidence when culture results are inconclusive. The combination of a microarray with fungal culture and histology promotes the precise diagnosis of IMIs in difficult-to-diagnose patients.

Efficacy of short- versus prolonged-courses of antimicrobial therapy for carbapenem-resistant Klebsiella pneumoniae bloodstream infections: A propensity score-matched cohort study.

BACKGROUND: As limited antibiotic options are available for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSIs), the optimal treatment duration for CRKP BSIs is unclear. Our objective was to investigate whether short courses (6-10 days) are as effective as prolonged courses (≥11 days) of active antibiotic therapy for CRKP BSIs. METHODS: A retrospective cohort study comprising adults with monomicrobial CRKP BSI receiving a short or prolonged course of in vitro active therapy at a medical center was conducted between 2010 and 2021. Comparisons of two therapeutic strategies were assessed by the logistic regression model and propensity score analysis. The primary endpoint was 30-day crude mortality. Secondary outcomes included recurrent BSIs, the emergence of multidrug-resistant organisms and candidemia during hospitalization after completing antibiotic therapy for CRKP BSIs. RESULTS: Of 263 eligible adults, 160 (60.8%) were male, and the median (interquartile range) age was 69.0 (53.0-76.0) years. Common comorbidities included diabetes (143 patients, 54.4%), malignancy (75, 28.5%), cerebrovascular accident (58, 22.1%), and hemodialysis (49, 18.6%). The 30-day mortality rate was 8.4% (22 patients). Of 84 propensity score well-balanced matched pairs, the 30-day mortality was similar in the short-course and prolonged-course group (6.0% and 7.1%, respectively; P = 1.00). However, there were less episodes candidemia in the short-course group (1.2% versus 13.1%; odds ratio, 0.08; 95% confidence interval, 0.01-0.63; P = 0.005). CONCLUSION: Short courses of active therapy for CRKP BSIs demonstrate comparable clinical outcomes to prolonged courses and are associated with a lower risk of subsequent candidemia.

Clinical impact of the combination of rapid species identification and antifungal stewardship intervention in adults with candidemia.

BACKGROUND: Candidemia is associated with a high mortality rate. This study aimed to evaluate the clinical impact of a diagnostic intervention and antifungal stewardship in adults with candidemia, including effectiveness in facilitating appropriate antifungals and improving patient outcomes. METHODS: A pre-post quasi-experimental study was conducted to analyze the impact of the integrated workflow of rapid species identification and antifungal stewardship intervention provided by infectious disease specialists for adults with candidemia at a medical center in southern Taiwan from March 1st, 2014 to February 29th, 2016. The primary endpoint was 30-day crude mortality, and secondary outcomes included the time to species identification, time to initial antifungal modification, and length of hospital stay. RESULTS: Total 303 patients with candidemia were included, including 152 adults in the pre-intervention period (Mar. 1st, 2014-Feb. 28th, 2015; control group) and 151 in the intervention period (Mar. 1st, 2015-Feb. 29th, 2016; case group). Demographic and clinical characteristics of patients in two groups were similar. The case group had a shorter time to species identification (72 vs. 96 h, P < 0.001) and earlier receipt of antifungals (47 vs. 59 h, P < 0.001) than the control group. Of note, the 30-day mortality rate (27.2% vs. 39.5%, P = 0.028) was lower and the hospital stay (43.5 vs. 46.0 days, P = 0.006) was shorter in the case group. CONCLUSION: Rapid diagnostic workflow and antifungal stewardship provided by infectious disease specialists can promote early initiation of antifungal therapy and improve outcome for adults with candidemia.

The first case of Francisella novicida infection in Taiwan: bacteraemic pneumonia in a haemodialysis adult.

Tularaemia is a zoonotic disease caused by Francisella tularensis (F. tularensis). Human infection is rare and can be life-threatening. F. tularensis subsp. novicida used to be a subspecies of F. tularensis, is now considered a different species, F. novicida. Though less virulent, F. novicida can cause morbidity and mortality among debilitated or immunocompromised patients. We reported that an adult with end-stage renal disease undergoing haemodialysis and a history of melioidotic aortic aneurysm developed F. novicida bacteraemic pneumonia, which was uneventfully treated by antimicrobial therapy. The microbiological confirmation of F. novicida infection relies on 16S rRNA sequencing. It is the first case of F. novicida infection in Taiwan.