Evaluation of a Rapid Fungal Detection Panel for Identification of Candidemia at an Academic Medical Center.

This study was conducted to assess the utility of the T2Candida panel across an academic health center and identify potential areas for diagnostic optimization. A retrospective chart review was conducted on patients with a T2Candida panel and mycolytic/fungal (myco/f lytic) blood culture collected simultaneously during hospitalizations from February 2017 to March 2018. The primary outcome of this study was to determine the sensitivity, specificity, and positive and negative predictive values of the panel compared to myco/f lytic blood culture. Secondary outcomes included Candida species isolated from culture or detected on the panel, source of infection, days of therapy (DOT) of antifungals in patients with discordant results, and overall antifungal DOT/1,000 patient days. A total of 433 paired T2Candida panel and myco/f lytic blood cultures were identified. The pretest likelihood of candidemia was 4.4%. The sensitivity and specificity were 64.7% and 95.6%, respectively. The positive and negative predictive values were 40.7% and 98.5%, respectively. There were 16 patients with T2Candida panel positive and myco/f lytic blood culture negative results, while 6 patients had T2Candida panel negative and myco/f blood culture positive results. The overall antifungal DOT/1,000 patient days was improved after implementation of the T2Candida panel; however, the use of micafungin continued to decline after the panel was removed. We found that the T2Candida panel is a highly specific diagnostic tool; however, the sensitivity and positive predictive value may be lower than previously reported when employed in clinical practice. Clinicians should use this panel as an adjunct to blood cultures when making a definitive diagnosis of candidemia.

Antimicrobial and Biofilm-Preventing Activity of l-Borneol Possessing 2(5H)-Furanone Derivative F131 against S. aureus­C. albicans Mixed Cultures

Candida albicans and Staphylococcus aureus are human pathogens that are able to form mixed biofilms on the surface of mucous membranes, implants and catheters. In biofilms, these pathogens have increased resistance to antimicrobials, leading to extreme difficulties in the treatment of mixed infections. The growing frequency of mixed infections caused by S. aureus and C. albicans requires either the development of new antimicrobials or the proposal of alternative approaches to increase the efficiency of conventional ones. Here, we show the antimicrobial, biofilm-preventing and biofilm-eradicating activity of 2(5H)-furanone derivative F131, containing an l-borneol fragment against S. aureus-C. albicans mixed biofilms. Furanone F131 is also capable of inhibiting the formation of monospecies and mixed biofilms by S. aureus and C. albicans. The minimal biofilm-prevention concentration (MBPC) of this compound was 8-16 µg/mL for S. aureus and C. albicans mono- and two-species biofilms. While the compound demonstrates slightly lower activity compared to conventional antimicrobials (gentamicin, amikacin, fluconazole, terbinafine and benzalkonium chloride), F131 also increases the antimicrobial activity of fluconazole-gentamicin and benzalkonium chloride against mixed biofilms of S. aureus-C. albicans, thus reducing MBPC of fluconazole-gentamicin by 4-16 times and benzalkonium chloride twofold. F131 does not affect the transcription of the MDR1, CDR1 and CDR2 genes, thus suggesting a low risk of micromycete resistance to this compound. Altogether, combined use of antibiotics with a F131 could be a promising option to reduce the concentration of fluconazole used in antiseptic compositions and reduce the toxic effect of benzalkonium chloride and gentamicin. This makes them an attractive starting point for the development of alternative antimicrobials for the treatment of skin infections caused by S. aureus-C. albicans mixed biofilms.

Increasing the Efficacy of Treatment of Staphylococcus aureus-Candida albicans Mixed Infections with Myrtenol.

Infectious diseases caused by various nosocomial microorganisms affect worldwide both immunocompromised and relatively healthy persons. Bacteria and fungi have different tools to evade antimicrobials, such as hydrolysis damaging the drug, efflux systems, and the formation of biofilm that significantly complicates the treatment of the infection. Here, we show that myrtenol potentiates the antimicrobial and biofilm-preventing activity of conventional drugs against S. aureus and C. albicans mono- and dual-species cultures. In our study, the two optical isomers, (-)-myrtenol and (+)-myrtenol, have been tested as either antibacterials, antifungals, or enhancers of conventional drugs. (+)-Myrtenol demonstrated a synergistic effect with amikacin, fluconazole, and benzalkonium chloride on 64-81% of the clinical isolates of S. aureus and C. albicans, including MRSA and fluconazole-resistant fungi, while (-)-myrtenol increased the properties of amikacin and fluconazole to repress biofilm formation in half of the S. aureus and C. albicans isolates. Furthermore, myrtenol was able to potentiate benzalkonium chloride up to sixteen-fold against planktonic cells in an S. aureus-C. albicans mixed culture and repressed the adhesion of S. aureus. The mechanism of both (-)-myrtenol and (+)-myrtenol synergy with conventional drugs was apparently driven by membrane damage since the treatment with both terpenes led to a significant drop in membrane potential similar to the action of benzalkonium chloride. Thus, due to the low toxicity of myrtenol, it seems to be a promising agent to increase the efficiency of the treatment of infections caused by bacteria and be fungi of the genus Candida as well as mixed fungal-bacterial infections, including resistant strains.

Asymptomatic bacteriuria: Impact of an antimicrobial stewardship bundle to reduce unnecessary antibiotics in patients without urinary catheters.

PURPOSE: The purpose of this study was to evaluate the effect of an antimicrobial stewardship bundle on the management of asymptomatic bacteriuria (ASB). METHODS: In this quasi-experimental study, patients were selected by retrospective, consecutive sampling of patients with a positive urine culture report in 3 separate groups: preintervention, postdiagnostic intervention, and posteducation. Patients met the prespecified criteria for non-catheter-associated ASB. The diagnostic intervention involved a new urinalysis/urine culture ordering process in place of urinalysis with reflex to urine culture. Additionally, an educational intervention involved pharmacist-led sessions to educate providers with patient cases and guideline-based recommendations. The primary outcome of this study was the difference in the rate of inappropriate management of ASB, defined as the use of antimicrobial agents intended to treat ASB. Secondary outcomes included length of antimicrobial therapy, length of stay, and change in urine culture orders per 1,000 patient-days. RESULTS: A total of 120 patients were included. There was a significant reduction in the inappropriate management of ASB between the preintervention and postdiagnostic intervention groups (P = 0.0349). This was not seen when comparing the postdiagnostic intervention and posteducation groups (P = 0.93). Additionally, there was a significant difference in urinalysis/urine culture ordering between the preintervention and postdiagnostic intervention groups (370 vs 224 urinalysis orders per 1,000 days present, P < 0.0001; 131 vs 54 urine culture orders per 1,000 days present, P < 0.0001). CONCLUSION: An antimicrobial stewardship bundle involving a diagnostic stewardship intervention and pharmacist-led education reduced treatment of ASB in patients without urinary catheters.

COVID-19 paraclinical diagnostic tools: Updates and future trends.

MOTIVATION: COVID-19 is one of the most widely affecting pandemics. As for many respiratory viruses-caused diseases, diagnosis of COVID-19 relies on two main compartments: clinical and paraclinical diagnostic criteria. Rapid and accurate diagnosis is vital in such a pandemic. On one side, rapidity may enhance management effectiveness, while on the other, coupling efficiency and less costly procedures may permit more effective community-scale management. METHODOLOGY AND MAIN STRUCTURE: In this review, we shed light on the most used and the most validated diagnostic tools. Furthermore, we intend to include few under-development techniques that may be potentially useful in this context. The practical intent of our work is to provide clinicians with a realistic summarized review of the essential elements in the applied paraclinical diagnosis of COVID-19.

Dalbavancin and Oritavancin: An Innovative Approach to the Treatment of Gram-Positive Infections.

Health care-associated infections, especially those caused by multidrug-resistant gram-positive organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), are a growing public health threat. In 2014, the U.S. Food and Drug Administration approved two new lipoglycopeptides, oritavancin and dalbavancin, for the treatment of acute bacterial skin and skin structure infections. The rationale for the development of these antimicrobials was partly to aid in the battle against vancomycin resistance in both Staphylococcus and Enterococcus. Considered a subclass of the glycopeptide antibiotics, the new lipoglycopeptides have similar mechanisms of action of binding to the carboxyl terminal d-alanyl-d-alanine residue of the growing peptide chains but differ from their parent glycopeptides by the addition of lipophilic tails. This addition allows for these agents to have prolonged half-lives, giving them unique dosing profiles. In addition, by concentrating at the site of action, they have increased potency against MRSA compared with vancomycin, the current mainstay of therapy. In this review, we focus on comparing and contrasting these two new agents with regard to their pharmacology, mechanisms of action, spectrum of activity, safety profiles, dosage and administration, and drug and laboratory interactions, and we review the clinical trials evaluating their use.