Antibiotic Prescribing in Adults Presenting with Pharyngitis Pre- and Post-Implementation of a Rapid Group A Streptococcus Test.

Background: Group A Streptococcus (GAS) pharyngitis is the most common bacterial cause of acute pharyngitis and is often over treated with unnecessary antibiotics. The purpose was to evaluate if implementation of a rapid antigen detection test (RADT) for GAS would reduce the number of inappropriately prescribed antibiotics for adult patients presenting with symptoms of pharyngitis. Methods: This was a retrospective cohort study of adult urgent care clinic patients pre- and post-implementation of a GAS RADT. We included patients who had a diagnosis of GAS identified via ICD-10 codes and either a throat culture, GAS RADT, or antibiotic prescribed for GAS. Antibiotic prescribing was assessed as appropriate or inappropriate based on testing and IDSA guideline recommendations. Thirty-day follow-up visits related to pharyngitis or the prescribed antibiotics was also evaluated. Results: A total of 1734 patients were included; 912 and 822 in the pre- and post-implementation groups, respectively. Following implementation of the GAS RADT, there was an increase in the number of antibiotics prescribed for GAS (43.4% vs 59.1%, P < .001) as well as an increase in appropriate prescribing (67.6% vs 77.5%, P < .001). More 30-day pharyngitis-related follow-up visits were seen in the pre-intervention group (12.5% vs 9.3%, P = .03). Conclusion: Implementation of a RADT for GAS pharyngitis was associated with an increase in both the overall number of antibiotic prescriptions for GAS and the proportion of appropriately prescribed antibiotics. There was also a reduction in follow up visits related to GAS pharyngitis, however educational efforts to further increase appropriate prescribing is needed.

Candida auris: Disinfectants and Implications for Infection Control.

Candida auris is a rapidly emerging pathogen and is able to cause severe infections with high mortality rates. It is frequently misidentified in most clinical laboratories, thus requiring more specialized identification techniques. Furthermore, several clinical isolates have been found to be multidrug resistant and there is evidence of nosocomial transmission in outbreak fashion. Appropriate infection control measures will play a major role in controlling the management and spread of this pathogen. Unfortunately, there are very few data available on the effectiveness of disinfectants against C. auris. Chlorine-based products appear to be the most effective for environmental surface disinfection. Other disinfectants, although less effective than chlorine-based products, may have a role as adjunctive disinfectants. A cleaning protocol will also need to be established as the use of disinfectants alone may not be sufficient for maximal decontamination of patient care areas. Furthermore, there are fewer data on the effectiveness of antiseptics against C. auris for patient decolonization and hand hygiene for healthcare personnel. Chlorhexidine gluconate has shown some efficacy in in vitro studies but there are reports of patients with persistent colonization despite twice daily body washes with this disinfectant. Hand hygiene using soap and water, with or without chlorhexidine gluconate, may require the subsequent use of alcohol-based hand sanitizer for maximal disinfection. Further studies will be needed to validate the currently studied disinfectants for use in real-world settings.

Candidiasis and the impact of flow cytometry on antifungal drug discovery.

INTRODUCTION: Invasive candidiasis continues to be associated with significant morbidity and mortality as well as substantial health care costs nationally and globally. One of the contributing factors is the development of resistance to antifungal agents that are already in clinical use. Moreover, there are known treatment limitations with all of the available antifungal agents. Since traditional techniques in novel drug discovery are time consuming, high-throughput screening using flow cytometry presents as a potential tool to identify new antifungal agents that would be useful in the management of these patients. Areas covered: In this review, the authors discuss the use of automated high-throughput screening assays based upon flow cytometry to identify potential antifungals from a library comprised of a large number of bioactive compounds. They also review studies that employed the use of this research methodology that has identified compounds with antifungal activity. Expert opinion: High-throughput screening using flow cytometry has substantially decreased the processing time necessary for screening thousands of compounds, and has helped enhance our understanding of fungal pathogenesis. Indeed, the authors see this technology as a powerful tool to help scientists identify new antifungal agents that can be added to the clinician's arsenal in their fight against invasive candidiasis.

An Optimized Lock Solution Containing Micafungin, Ethanol and Doxycycline Inhibits Candida albicans and Mixed C. albicans - Staphyloccoccus aureus Biofilms.

Candida albicans is a major cause of catheter-related bloodstream infections and is associated with high morbidity and mortality. Due to the propensity of C. albicans to form drug-resistant biofilms, the current standard of care includes catheter removal; however, reinsertion may be technically challenging or risky. Prolonged exposure of an antifungal lock solution within the catheter in conjunction with systemic therapy has been experimentally attempted for catheter salvage. Previously, we demonstrated excellent in vitro activity of micafungin, ethanol, and high-dose doxycycline as single agents for prevention and treatment of C. albicans biofilms. Thus, we sought to investigate optimal combinations of micafungin, ethanol, and/or doxycycline as a lock solution. We performed two- and three-drug checkerboard assays to determine the in vitro activity of pairwise or three agents in combination for prevention or treatment of C. albicans biofilms. Optimal lock solutions were tested for activity against C. albicans clinical isolates, reference strains and polymicrobial C. albicans-S. aureus biofilms. A solution containing 20% (v/v) ethanol, 0.01565 µg/mL micafungin, and 800 µg/mL doxycycline demonstrated a reduction of 98% metabolic activity and no fungal regrowth when used to prevent fungal biofilm formation; however there was no advantage over 20% ethanol alone. This solution was also successful in inhibiting the regrowth of C. albicans from mature polymicrobial biofilms, although it was not fully bactericidal. Solutions containing 5% ethanol with low concentrations of micafungin and doxycycline demonstrated synergistic activity when used to prevent monomicrobial C. albicans biofilm formation. A combined solution of micafungin, ethanol and doxycycline is highly effective for the prevention of C. albicans biofilm formation but did not demonstrate an advantage over 20% ethanol alone in these studies.

Antimicrobial Stewardship Intervention and Feedback to Infectious Disease Specialists: A Case Study in High-Dose Daptomycin.

Infectious Diseases specialists have used high-dose daptomycin (≥6 mg/kg/day) in select patients with difficult to treat methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) infections to optimize outcomes. Antimicrobial stewardship programs enforce antimicrobial formulary restrictions; however, interventions specifically aimed at Infectious Disease specialists can be particularly challenging. The purpose of this study was to create a high-dose daptomycin algorithm for Infectious Disease specialists that are consistent with best-practices. Daptomycin prescribing habits pre- and post-daptomycin algorithm implementation were evaluated using a quasi-experimental study design. Patients were included if ≥18 years of age and received daptomycin for ≥48 h. Patients were excluded if daptomycin was initiated on an outpatient setting. During the 12-month pre-intervention phase, 112 patients were included, with 73 patients in the 12-month post-intervention phase. A statistically significant decrease in the mean daptomycin dose from 9.01 mg/kg to 7.51 mg/kg (p < 0.005) was observed, resulting in an annual drug cost-savings of over $75,000 without adversely affecting readmission rates due to infection. Creation of a daptomycin algorithm with consideration of pathogen, disease state, and prior treatment, is an effective means of influencing prescribing habits of Infectious Disease specialists.

In vitro analysis of finasteride activity against Candida albicans urinary biofilm formation and filamentation.

Candida albicans is the 3rd most common cause of catheter-associated urinary tract infections, with a strong propensity to form drug-resistant catheter-related biofilms. Due to the limited efficacy of available antifungals against biofilms, drug repurposing has been investigated in order to identify novel agents with activities against fungal biofilms. Finasteride is a 5-α-reductase inhibitor commonly used for the treatment of benign prostatic hyperplasia, with activity against human type II and III isoenzymes. We analyzed the Candida Genome Database and identified a C. albicans homolog of type III 5-α-reductase, Dfg10p, which shares 27% sequence identity and 41% similarity to the human type III 5-α-reductase. Thus, we investigated finasteride for activity against C. albicans urinary biofilms, alone and in combination with amphotericin B or fluconazole. Finasteride alone was highly effective in the prevention of C. albicans biofilm formation at doses of ≥16 mg/liter and the treatment of preformed biofilms at doses of ≥128 mg/liter. In biofilm checkerboard analyses, finasteride exhibited synergistic activity in the prevention of biofilm formation in a combination of 4 mg/liter finasteride with 2 mg/liter fluconazole. Finasteride inhibited filamentation, thus suggesting a potential mechanism of action. These results indicate that finasteride alone is highly active in the prevention of C. albicans urinary biofilms in vitro and has synergistic activity in combination with fluconazole. Further investigation of the clinical utility of finasteride in the prevention of urinary candidiasis is warranted.

Paradoxical antifungal activity and structural observations in biofilms formed by echinocandin-resistant Candida albicans clinical isolates.

Echinocandin-resistant clinical isolates of Candida albicans have been reported, and key-hot spot mutations in the FKS1 gene, which encodes a major glucan synthase subunit, have been identified in these (caspofungin-resistant [CAS-R]) strains. Although these mutations result in phenotypic resistance to echinocandins in planktonic cells, there is little data on antifungal susceptibilities of CAS-R C. albicans strains within biofilms. Thus, we analyzed biofilms formed by 12 C. albicans CAS-R clinical strains in which we previously identified FKS1 hot-spot mutations and compared the sessile antifungal and paradoxical activity of anidulafungin (ANID), caspofungin (CAS), and micafungin (MICA). Biofilms were formed in a 96-well static microplate model and assayed using both tetrazolium-salt reduction and crystal violet assays, as well as examination by scanning electron microscopy. We first sought to assess biofilm formation and structure in these fks1 mutants and found that the biofilm mass and metabolic activities were reduced in most of the fks1 mutants as compared with reference strain SC5314. Structural analyses revealed that the fks1 mutant biofilms were generally less dense and had a clear predominance of yeast and pseudohyphae, with unusual "pit"-like cell surface structures. We also noted that sessile minimum inhibitory concentrations (MICs) to ANID, CAS, and MICA were higher than planktonic MICs of all but one strain. The majority of strains demonstrated a paradoxical effect (PE) to particular echinocandins, in either planktonic or sessile forms. Overall, biofilms formed by echinocandin-resistant clinical isolates demonstrated varied PEs to echinocandins and were structurally characterized by a preponderance of yeast, pseudohyphae, and pit-like structures.

Antifungal lock therapy.

The widespread use of intravascular devices, such as central venous and hemodialysis catheters, in the past 2 decades has paralleled the increasing incidence of catheter-related bloodstream infections (CR-BSIs). Candida albicans is the fourth leading cause of hospital-associated BSIs. The propensity of C. albicans to form biofilms on these catheters has made these infections difficult to treat due to multiple factors, including increased resistance to antifungal agents. Thus, curing CR-BSIs caused by Candida species usually requires catheter removal in addition to systemic antifungal therapy. Alternatively, antimicrobial lock therapy has received significant interest and shown promise as a strategy to treat CR-BSIs due to Candida species. The existing in vitro, animal, and patient data for treatment of Candida-related CR-BSIs are reviewed. The most promising antifungal lock therapy (AfLT) strategies include use of amphotericin, ethanol, or echinocandins. Clinical trials are needed to further define the safety and efficacy of AfLT.

In vitro analyses of ethanol activity against Candida albicans biofilms.

Candida albicans is a common cause of catheter-related bloodstream infections (CR-BSI). Ethanol (EtOH) lock therapy has been attempted despite limited data on optimal dose and duration. Concentrations of 35% EtOH or higher for a minimum of 4 h demonstrated a >99% reduction in mature C. albicans biofilm metabolic activity and prevented regrowth. Concentrations of 10% EtOH or higher reduced C. albicans biofilm formation by >99%. Further investigation of EtOH lock therapy for treatment and prevention of C. albicans CR-BSI is warranted.

Diagnostic and therapeutic evaluation of community-acquired methicillin-resistant Staphylococcus Aureus (MRSA) skin and soft tissue infections in the emergency department.

BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections commonly present as skin and soft-tissue infections (SSTIs). Treatment often includes incision and drainage with or without adjunctive antibiotics. Emergency department (ED) pharmacists wished to provide specific data to emergency physicians to better inform antibiotic choices for patients with SSTIs. STUDY OBJECTIVES: The objectives of this study were to describe local susceptibility trends of CA-MRSA isolates obtained from patients with SSTIs and describe diagnostic and empiric therapeutic management of CA-MRSA SSTIs among ED health care providers at University of Utah Hospitals and Clinics. METHODS: Susceptibility of all unique CA-MRSA SSTI isolates for 2008 were identified and compiled into an antibiogram. ED providers evaluated their diagnostic and treatment habits using a self-assessment questionnaire, which was verified against charted information documented in the electronic medical records for patients presenting to the ED with a CA-MRSA SSTI. RESULTS: The ED antibiogram indicated that 57/58 (98%) CA-MRSA SSTI isolates were susceptible to sulfamethoxazole/trimethoprim (SMX/TMP); 50/58 (86%) isolates were susceptible to tetracycline, and 47/58 (81%) isolates were susceptible to clindamycin. Incision and drainage were performed in 23/25 (92%) patient cases, which was consistent with providers' perceived habits (100%). SMX/TMP monotherapy was preferred among 23/35 (66%) providers, however, SMX/TMP combined with cephalexin was the antibiotic regimen prescribed in 9/22 (41%) patient cases. CONCLUSIONS: Cephalexin was often added to cover for potential cellulitis due to Streptococcus spp., however, the surrounding erythema may simply be an extension of the CA-MRSA infection. Department-specific antibiograms are useful in guiding empiric antibiotic selection and may help providers judiciously prescribe antibiotics only when necessary.

Fatal disseminated Cryptococcus gattii infection in New Mexico.

We report a case of fatal disseminated infection with Cryptococcus gattii in a patient from New Mexico. The patient had no history of recent travel to known C. gattii-endemic areas. Multilocus sequence typing revealed that the isolate belonged to the major molecular type VGIII. Virulence studies in a mouse pulmonary model of infection demonstrated that the strain was less virulent than other C. gattii strains. This represents the first documented case of C. gattii likely acquired in New Mexico.

Site of infection rather than vancomycin MIC predicts vancomycin treatment failure in methicillin-resistant Staphylococcus aureus bacteraemia.

BACKGROUND: Therapeutic use of vancomycin is characterized by decreased susceptibilities and increasing reports of clinical failures. Few studies have examined the clinical outcomes of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia treated with vancomycin. The primary objective was to compare clinical outcomes of patients with MRSA bacteraemia treated according to standard of care practices. METHODS: Patients were included if: (i) admitted to University of New Mexico Hospital between 2002 and 2009; (ii) ≥18 years of age; (iii) had one blood culture positive for MRSA; and (iv) received vancomycin. Clinical outcomes were defined as cure, failure (relapse of infection 30 days after completion of therapy, death or change in therapy) or unevaluable. Patient demographics, source of bacteraemia, treatment regimen, and microbiological characteristics were determined. RESULTS: Two hundred patients with MRSA bacteraemia were included. Sixty-one patients were unevaluable, leaving 139 patients for the final analysis. Seventy-two (51.8%) patients were cured and 67 (48.2%) experienced vancomycin failure. Vancomycin MIC(90) was 2 mg/L for both groups by Etest. Patients with endocarditis (P = 0.02) or pneumonia (P = 0.02) were more likely to fail therapy. Panton-Valentine leucocidin, loss of agr functionality and strain type were not predictors of outcomes in this study. CONCLUSIONS: High failure rates were observed in patients with MRSA bacteraemia treated with vancomycin, despite high vancomycin troughs and low rates of nephrotoxicity. Predictors of vancomycin failure included endocarditis and pneumonia. In these situations, vancomycin provides suboptimal therapy.