The interplay of infectious diseases consultation and antimicrobial stewardship in candidemia outcomes: A retrospective cohort study from 2016 to 2019.

OBJECTIVE: To evaluate the need for mandatory infectious diseases consultation (IDC) for candidemia in the setting of antimicrobial stewardship guidance. DESIGN: Retrospective cohort study from January 2016 to December 2019. SETTING: Academic quaternary-care referral center. PATIENTS: All episodes of candidemia in adults (n = 92), excluding concurrent bacterial infection or death or hospice care within 48 hours. METHODS: Primary outcome was all-cause 30-day mortality. Secondary outcomes included guideline-adherence and treatment choice. Guideline-adherence was assessed with the EQUAL Candida score. RESULTS: Of 186 episodes of candidemia, 92 episodes in 88 patients were included. Central venous catheters (CVCs) were present in 66 episodes (71.7%) and were the most common infection source (N = 38, 41.3%). The most frequently isolated species was Candida glabrata (40 of 94, 42.6%). IDC was performed in 84 (91.3%) of 92 candidemia episodes. Mortality rates were 20.8% (16 of 77) in the IDC group versus 25% (2 of 8) in the no-IDC group (P = .67). Other comparisons were numerically different but not significant: repeat blood culture (98.8% vs 87.5%; P = .17), echocardiography (70.2% vs 50%; P = .26), CVC removal (91.7% vs 83.3%; P = .45), and initial echinocandin treatment (67.9% vs 50%; P = .44). IDC resulted in more ophthalmology examinations (67.9% vs 12.5%; P = .0035). All patients received antifungal therapy. Antimicrobial stewardship recommendations were performed in 19 episodes (20.7%). The median EQUAL Candida score with CVC was higher with IDC (16 vs 11; P = .001) but not in episodes without CVC (12 vs 11.5; P = .81). CONCLUSIONS: In the setting of an active antimicrobial stewardship program and high consultation rates, mandatory IDC may not be warranted for candidemia.

Efficacy of Low Dose Chemoprophylaxis for Coccidioidomycosis Infection in Liver Transplant Recipients.

BACKGROUND: Coccidioidomycosis (CM) infections among transplant recipients result in significant morbidity and mortality. The goal of our study was to establish the efficacy of low dose (LD) versus standard dose (LD, 50 mg daily) fluconazole in preventing CM infection. METHODS: This was a retrospective study utilizing electronic medical records of liver transplant recipients at the University of Arizona. The primary end point was post-transplant CM status, such as infection, complications and survival. RESULTS: We detected a statistically significant correlation between positive pre-transplant status and positive post-transplant status (hazards ratio: 8.25 (95% confidence interval: 1.028 - 66.192)). There was a trend towards improved survival in patients who had a positive post-transplant CM status in the SD group versus LD group (90.9% versus 81.3%), although not statistically significant. CONCLUSION: The risk of CM infection among transplant recipients in the absence of prophylaxis is associated with high morbidity and mortality. We currently use SD fluconazole as universal prophylaxis in all transplant recipients despite not establishing statistical significance between LD and SD. We believe that the survival trend detected may have not reached statistical significance due to low power impact. Since the standardization of SD prophylaxis at our institution, we have not diagnosed further new post-transplant CM infections.

Epidemiology, Diagnosis, Treatment, and Prevention of Influenza Infection in Oncology Patients.

Influenza infection causes increased morbidity and higher mortality in patients receiving treatment of underlying cancer, particularly in those with hematological malignancy or patients who have undergone hematopoietic stem-cell transplantation. The illness is characterized by seasonality and nonspecific clinical manifestations of upper respiratory infection at a time when other respiratory illnesses are common in the community, making the diagnosis challenging. However, accurate and timely diagnosis by new molecular techniques is crucial in the management of immunocompromised patients, because delays in initiating appropriate therapy can have devastating consequences. Emergence of viral resistance to currently used antiviral agents is of concern, particularly in immunocompromised hosts, and warrants continued monitoring and surveillance. Early and effective treatment improves outcomes, but optimal therapeutic strategies in patients with cancer are not well defined. Health care and research efforts should focus on defining treatment guidelines in patients with cancer and attempt to improve on current vaccination strategies.

Hybridization assay performed at ambient temperature for typing high-risk human papillomaviruses.

BACKGROUND: Human papillomavirus (HPV) infection with oncogenic types is a prerequisite for cervical cancer development. HPV typing is required in the management of pre-cancerous lesions, epidemiological studies, and vaccination trials. None of the available HPV assays are satisfactory for routine diagnosis. OBJECTIVES: In order to develop an assay for clinically relevant HPV types, we generated HPV probes using in vitro selection scheme of iterative hybridization. STUDY DESIGN: Starting from a mixture of random oligonucleotides, through several rounds of hybridization with 39 type-specific GP5+/6+ L1 sequences, we aimed to obtain specific probes to discriminate between these HPV types. RESULTS: In vitro selection led to pools of specific probes, from which individual probes were cloned and tested for their diagnostic performance at ambient temperature. Typically, 10-fold stronger hybridization signals were obtained between each of the selected probes and their specific targets compared to signals with the remaining 38 HPV types. High sensitivity and specificity of selected probes was demonstrated a series of clinical samples in the hybridization assay. CONCLUSIONS: A new panel of probes for detecting HPV types is described. Probes can be adapted for use in a simple clinical setting, or incorporated into different detection systems.

An in vitro selection scheme for oligonucleotide probes to discriminate between closely related DNA sequences.

Using an in vitro selection, we have obtained oligonucleotide probes with high discriminatory power against multiple, similar nucleic acid sequences, which is often required in diagnostic applications for simultaneous testing of such sequences. We have tested this approach, referred to as iterative hybridizations, by selecting probes against six 22-nt-long sequence variants representing human papillomavirus, (HPV). We have obtained probes that efficiently discriminate between HPV types that differ by 3-7 nt. The probes were found effective to recognize HPV sequences of the type 6, 11, 16, 18 and a pair of type 31 and 33, either when immobilized on a solid support or in a reverse configuration, as well to discriminate HPV types from the clinical samples. This methodology can be extended to generate diagnostic kits that rely on nucleic acid hybridization between closely related sequences. In this approach, instead of adjusting hybridization conditions to the intended set of probe-target pairs, we 'adjust', through in vitro selection, the probes to the conditions we have chosen. Importantly, these conditions have to be 'relaxed', allowing the formation of a variety of not fully complementary complexes from which those that efficiently recognize and discriminate intended from non-intended targets can be readily selected.