Retrospective review of intermittent and continuous infusion vancomycin for methicillin-resistant Staphylococcus aureus bacteremia.

PURPOSE: Vancomycin is commonly administered as an intermittent infusion (IIV), although vancomycin's stability at room temperature permits administration continuously over 24 h (CIV). At our institution, CIV has been the preferred infusion method for over 20 years due to ease of administration and simplicity of therapeutic drug monitoring. The purpose of this study was to examine the outcomes associated with IIV compared to CIV. METHODS: This was a retrospective study of patients who received vancomycin for MRSA bacteremia. The primary outcomes were the time to therapeutic goal and frequency of adverse drug reactions on IIV compared to CIV. Secondary outcomes evaluated all-cause readmission, relapse, and mortality 30 days after completion of therapy. RESULTS: Sixty-three patients were included. Significantly fewer patients were able to achieve a therapeutic goal on IIV compared to CIV (52.4% vs. 82.5%, p < 0.01). Patients on IIV took 3.6 days, on average, to reach the target goal, compared to 1.9 days when patients were switched to CIV (95% confidence interval, 0.48-3.04, p < 0.01). Six patients experienced adverse events on IIV, and 15 patients experienced adverse events on CIV (IIV 9.5%, CIV 23.8%, p = 0.035). One patient experienced relapse of infection, and six patients (9.5%) were readmitted 30 days after completion of therapy. There were no deaths in the cohort. CONCLUSION: For MRSA bacteremia, CIV enabled patients to achieve the AUC/MIC goal significantly faster than when patients received IIV. Furthermore, patients who were unable to achieve a therapeutic trough on IIV became therapeutic once switched to CIV.

Diagnostic testing and antibiotic utilization among inpatients evaluated for coronavirus disease 2019 (COVID-19) pneumonia.

We evaluated diagnostic test and antibiotic utilization among 252 patients from 11 US hospitals who were evaluated for coronavirus disease 2019 (COVID-19) pneumonia during the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) omicron variant pandemic wave. In our cohort, antibiotic use remained high (62%) among SARS-CoV-2-positive patients and even higher among those who underwent procalcitonin testing (68%).

Revisiting ß-Lactams for Treatment of Urinary Tract Infections: Assessing Clinical Outcomes of Twice-Daily Cephalexin for Empiric Treatment of Uncomplicated Urinary Tract Infections.

The 2011 Infectious Diseases Society of America guidelines for treatment of uncomplicated urinary tract infections (UTIs) recommend non-ß-lactam antibiotics for empiric therapy. However, increasing Escherichia coli and Klebsiella spp. resistance to first-line antibiotic therapies has necessitated the need for alternative agents. Based on local antibiogram data, cephalexin has become the preferred oral antibiotic for empiric treatment of UTIs at our institution. The purpose of this single-center retrospective review was to assess clinical outcomes of patients discharged from the emergency department (ED) who received cephalexin for the treatment of uncomplicated UTIs. The primary outcome of this study was to assess the proportion of patients with clinical success 30 days after discharge from the ED. Patients were excluded if they were <18 years of age, received ≥10 days of cephalexin, received antibiotics for any indication other than uncomplicated UTI, received antibiotics within 60 days of their ED visit, or had structural abnormalities. A total of 264 patients were included for evaluation, and 214 patients (81.1%) met the criteria for clinical success. Overall, 28 (10.6%) patients required a change in antibiotics based on cultures and sensitivities, 18 (6.8%) patients returned for nonresolving or worsening symptoms, and 4 (1.5%) patients required both a change in antibiotics and returned for nonresolving or worsening symptoms. Short courses of twice-daily cephalexin appear to be a safe and effective option for the empiric treatment of uncomplicated UTIs.

The impact of coronavirus disease 2019 (COVID-19) on the antimicrobial stewardship pharmacist workforce: A multicenter survey.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has required healthcare systems and hospitals to rapidly modify standard practice, including antimicrobial stewardship services. Our study examines the impact of COVID-19 on the antimicrobial stewardship pharmacist. Design: A survey was distributed nationally to all healthcare improvement company members. Participants: Pharmacist participants were mostly leaders of antimicrobial stewardship programs distributed evenly across the United States and representing urban, suburban, and rural health-system practice sites. Results: Participants reported relative increases in time spent completing tasks related to medication access and preauthorization (300%; P = .018) and administrative meeting time (34%; P = .067) during the COVID-19 pandemic compared to before the pandemic. Time spent rounding, making interventions, performing pharmacokinetic services, and medication reconciliation decreased. Conclusion: A shift away from clinical activities may negatively affect the utilization of antimicrobials.

A Retrospective Analysis of Intravenous vs Oral Antibiotic Step-Down Therapy for the Treatment of Uncomplicated Streptococcal Bloodstream Infections.

Evidence supporting intravenous-to-oral (IV-to-PO) antibiotic deescalation for uncomplicated streptococcal bloodstream infections (BSIs) are limited. The objective of this study was to compare clinical outcomes of patients treated with IV-only versus IV-to-PO antibiotic therapy for uncomplicated streptococcal BSIs. This was a single-center, retrospective study of patients aged ≥18 years who received treatment for uncomplicated streptococcal BSIs from January 2017 to December 2019. Patients were excluded if they had a polymicrobial BSI, endocarditis, osteomyelitis, septic arthritis, or received antibiotic therapy for >14 days. The primary outcome was clinical failure, defined as persistent bacteremia, recurrence of bacteremia, or mortality at 30 days. Secondary outcomes included length of hospital stay, all-cause readmissions, development of Clostridioides difficile infection, and adverse antibiotic reactions. There were 98 patients who met the inclusion criteria: 51 patients in the IV-to-PO therapy group and 47 patients who received IV-only antibiotics. Streptococcus pneumoniae and beta-hemolytic streptococci were the most common pathogens. Patients received an average of 4.4 days of IV antibiotics before being stepped down to an oral agent. Hospital length of stay (6.3 vs 12.6 days; P < .001) and total antibiotic duration of therapy (11.8 vs 13.9 days; P = .002) were significantly shorter in patients receiving IV-to-PO therapy. There were no clinical failures observed in patients who received IV-to-PO antibiotic therapy. IV-to-PO step-down therapy for uncomplicated streptococcal BSIs was not associated with worse clinical outcomes compared to patients receiving IV-only antibiotic therapy.

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.

Improving Emergency Access to Human Immunodeficiency Virus Prophylaxis for Patients Evaluated After Sexual Assault.

INTRODUCTION: Patients evaluated after sexual assault may benefit from nonoccupational postexposure prophylaxis (nPEP) to prevent infection with HIV, yet multiple barriers may prohibit nPEP delivery. The IN-STEP (Integrating nPEP after Sexual Trauma in Emergency Practice) project was designed to improve access to HIV screening and prevention for patients evaluated in the emergency department (ED) of our academic hospital after a sexual assault. METHODS: The IN-STEP team identified and addressed four key areas for improvement: (1) training of ED providers to perform nPEP assessments; (2) access to HIV testing in the ED; (3) provision of nPEP medications, using a patient-centered approach; and (4) continuity of care between the ED and follow-up sites in the community. Improvements were implemented using parallel plan-do-study-act cycles corresponding to these four key areas. RESULTS: IN-STEP resulted in significant systems improvements in HIV screening, prevention, and continuity of care. This program not only improved the care of patients affected by sexual assault but also those evaluated for HIV due to other indications. CONCLUSIONS: Involvement of a multidisciplinary leadership team, clear delineation of a patient-centered project focus, and coordination across four parallel areas for improvement were useful for completing this complex effort.

Emergence of Resistance in Klebsiella aerogenes to Piperacillin-Tazobactam and Ceftriaxone.

We examined the effects of piperacillin-tazobactam (TZP) concentration and bacterial inoculum on in vitro killing and the emergence of resistance in Klebsiella aerogenes The MICs for 15 clinical respiratory isolates were determined by broth microdilution for TZP and by Etest for ceftriaxone (CRO) and cefepime (FEP). The presence of resistance in TZP-susceptible isolates (n = 10) was determined by serial passes over increasing concentrations of TZP-containing and CRO-containing agar plates. Isolates with growth on TZP 16/4-µg/ml and CRO 8-µg/ml plates (n = 5) were tested in high-inoculum (HI; 7.0 log10 CFU/ml) and low-inoculum (LI; 5.0 log10 CFU/ml) time-kill studies. Antibiotic concentrations were selected to approximate TZP 3.375 g every 8 h (q8h) via a 4-h prolonged-infusion free peak concentration (40 µg/ml [TZP40]), peak epithelial lining fluid (ELF) concentrations, and average AUC0-24 values for TZP (20 µg/ml [TZP20] and 10 µg/ml [TZP10], respectively), the ELF FEP concentration (14 µg/ml), and the average AUC0-24 CRO concentration (6 µg/ml). For HI, FEP exposure significantly reduced 24-h inocula against all comparators (P ≤ 0.05) with a reduction of 4.93 ± 0.64 log10 CFU/ml. Exposure to TZP40, TZP20, and TZP10 reduced inocula by 0.81 ± 0.43, 0.21 ± 0.18, and 0.05 ± 0.16 log10 CFU/ml, respectively. CRO-exposed isolates demonstrated an increase of 0.42 ± 0.39 log10 CFU/ml compared to the starting inocula, with four of five CRO-exposed isolates demonstrating TZP-nonsusceptibility. At LI after 24 h of exposure to TZP20 and TZP10, the starting inoculum decreased by averages of 2.24 ± 1.98 and 2.91 ± 0.50 log10 CFU/ml, respectively. TZP demonstrated significant inoculum-dependent killing, warranting dose optimization studies.

A Single-Center Evaluation of Extended Infusion Piperacillin/Tazobactam for Empiric Treatment in the Intensive Care Unit.

Background: Piperacillin/tazobactam (PTZ) extended infusion (EI) is often used empirically in the intensive care unit (ICU). Gram-negative (GN) organisms with PTZ minimum inhibitory concentrations (MICs) >16/4 µg/mL are considered intermediate or resistant. Objective: The objective of this study was to evaluate MICs of GN isolates from the ICU to determine whether the hospital protocol for PTZ 3.375 g EI over 4 hours administered every 8 hours is an appropriate empiric regimen for ICU patients and to evaluate patient-specific risk factors associated with elevated MICs. Methods: All ICU patients admitted during 2017 with a confirmed GN organism from a non-urinary source were included for retrospective chart review. Patients with cystic fibrosis or cultures obtained >48 hours prior to ICU admission were excluded. Demographics, GN organism, culture source, risk factors for resistance, susceptibility profile, comorbidities, and creatinine clearance were collected. Appropriateness was defined as PTZ MIC ≤16/4 µg/mL in >80% of isolates. Results: Two hundred and thirty-one patients were included. The average patient was 56 years old. The majority of patients were white (64.1%) and male (69.7%). Pseudomonas aeruginosa (41%) was the most common organism isolated. Overall, 28% of GN isolates had MICs >16/4 µg/mL. Dialysis (P = .01), intravenous antibiotics within 90 days (P < .001), and presence of wounds/trauma (P = .01) were associated with elevated MICs. Conclusion: Current PTZ EI 3.375 g dosing regimens may not provide adequate empiric coverage for some GN organisms in ICU patients, especially for those who have previously received intravenous antibiotics, are on dialysis, or have wounds/trauma.

Predictors of Clostridium difficile infection and predictive impact of probiotic use in a diverse hospital-wide cohort.

BACKGROUND: Hospital-based predictive models for Clostridium difficile infection (CDI) may aid with surveillance efforts. METHODS: A retrospective cohort of adult hospitalized patients who were tested for CDI between May 1, 2011, and August 31, 2016, was formed. Proposed clinical and sociodemographic predictors of CDI were evaluated using multivariable predictive logistic regression modeling. RESULTS: In a cohort of 5,209 patients, including 1,092 CDI cases, emergency department location (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.51, 2.41; compared with an intensive care unit reference category, which had the lowest observed odds in the study) and prior exposure to a statin (aOR, 1.26, 95% CI, 1.06, 1.51), probiotic (aOR, 1.39; 95% CI, 1.08, 1.80), or high-risk antibiotic (aOR, 1.54; 95% CI, 1.29, 1.84), such as a cephalosporin, a quinolone, or clindamycin, were independent predictors of CDI. Probiotic use did not appear to attenuate the odds of CDI in patients exposed to high-risk antibiotics, but moderate-risk antibiotics appeared to significantly attenuate the odds of CDI in patients who received probiotics. CONCLUSIONS: Emergency department location, high-risk antibiotics, probiotics, and statins were independently predictive of CDI. Further exploration of the relationship between probiotics and CDI, especially in diverse patient populations, is warranted.

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.

ß-Lactams enhance vancomycin activity against methicillin-resistant Staphylococcus aureus bacteremia compared to vancomycin alone.

Vancomycin (VAN) is often used to treat methicillin-resistant Staphylococcus aureus (MRSA) bacteremia despite a high incidence of microbiological failure. Recent in vitro analyses of ß-lactams in combination with VAN demonstrated synergistic activity against MRSA. The goal of this study was to examine the impact of combination therapy with VAN and a ß-lactam (Combo) on the microbiological eradication of MRSA bacteremia compared to VAN alone. This was a retrospective cohort study of patients with MRSA bacteremia who received Combo therapy or VAN alone. Microbiological eradication of MRSA, defined as a negative blood culture obtained after initiation of therapy, was used to evaluate the efficacy of each regimen. A total of 80 patients were included: 50 patients in the Combo group and 30 patients in the VAN-alone group. Microbiological eradication was achieved in 48 patients (96%) in the Combo group compared to 24 patients (80%) in the VAN-alone group (P = 0.021). In a multivariable model, the Combo treatment had a higher likelihood of achieving microbiological eradication (adjusted odds ratio, 11.24; 95% confidence interval, 1.7 to 144.3; P = 0.01). In patients with infective endocarditis (n = 22), 11/11 (100%) who received Combo therapy achieved microbiological eradication compared to 9/11 (81.8%) treated with VAN alone, but the difference was not statistically significant (P = 0.20). Patients with MRSA bacteremia who received Combo therapy were more likely to experience microbiological eradication of MRSA than patients who received VAN alone.

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.