Missed Opportunities for Antifungal Stewardship during the COVID-19 Era.

Significant increases in antibacterial use were observed during the COVID-19 pandemic. However, subsequent analyses found this increase in antibiotic use to be excessive in comparison with the relatively low rates of bacterial coinfection. Although patients who are critically ill with COVID-19 may be at an increased risk for pulmonary aspergillosis, antifungal use in these populations remained underreported, particularly in later phases of the pandemic. This single-center, population-level cohort analysis compares the monthly use rates of mold-active antifungal drugs in the medical intensive care unit during April 2019-March 2020 (baseline) with those during April 2020-November 2022. The antifungal drugs included in the analysis were liposomal amphotericin B, anidulafungin, isavuconazonium, posaconazole, and voriconazole. We found that during 2020-2022, the usage of antifungal drugs was not significantly different from baseline for all included agents except isavuconazonium, which was used significantly more (p = 0.009). There were no changes in diagnostic modalities between the two time periods. The reported prevalence of and mortality from COVID-19-associated pulmonary aspergillosis (CAPA) may have resulted in higher rates of prescribing antifungal drugs for critically ill patients with COVID-19. Antimicrobial stewardship programs should develop and apply tools to facilitate more effective and appropriate antifungal use.

Incidence and Predictors of Gram-Negative Bacilli in Hospitalized People Who Inject Drugs with Injection Drug Use-Attributable Infections.

The objective of this study was to quantify incidence and determine predictors of Gram-negative bacilli (GNB) in people who inject drugs (PWID) with injection-drug use (IDU)-related infections. The investigation was a retrospective cohort of hospitalized PWID from January 2017 to December 2019. Inclusion criteria were age of ≥18 years, active IDU, treated IDU-attributable infection, and organism growth from microbiology cultures. Infection types included infective endocarditis (IE), acute bacterial skin/skin structure infection (ABSSSI), osteoarticular infection (OAI), and other bloodstream infections (BSI). Primary outcome was GNB identification from microbiologic culture; descriptive statistics were used to describe the cohort. Multivariable regression was used to identify variables associated with GNB infection. A total of 230 PWID were included, 65 (28%) with GNB infections and 165 (72%) with Gram-positive infections. The median (interquartile range [IQR]) population age was 38 (31 to 45) years. Most patients were women (56%); 37% had no insurance. Infection types were as follows: IE, 41%; ABSSSI, 37%; OAI, 20%; and other BSI, 2%. A total of 278 organisms were isolated from 230 patients. The most common organisms were methicillin-resistant Staphylococcus aureus (43%), Streptococcus spp. (19%), methicillin-susceptible S. aureus (17%), and Serratia marcescens (8%); 10% of infections were mixed GNB and Gram-positive infections. A total of 80% of patients received empirical Pseudomonas aeruginosa coverage; only 7% had P. aeruginosa infections. In multivariable regression, age of >50 years (adjusted odds ratio [adjOR], 2.9; 95% confidence interval [CI], 1.2 to 7.2), prior hospitalization within 90 days (adjOR, 2.2; 95% CI, 1.2 to 4.3), and OAI (adjOR, 3.2; 95% CI, 1.5 to 6.6) were associated with GNB infection. GNB in PWID with IDU-attributable infections were more frequently observed in recently hospitalized, older patients with OAI. The majority of patients received empirical antipseudomonal antibiotic coverage, but P. aeruginosa was infrequent. PWID are a potential population to target improved empirical antibiotic use.

Comparison of linezolid step-down therapy to standard parenteral therapy in methicillin-resistant Staphylococcus aureus bloodstream infections.

Data supporting oral step-down therapy in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) are sparse; linezolid offers potential in this setting. This study aimed to determine the effectiveness and safety of oral step-down linezolid compared with standard parenteral therapy (SPT) in MRSA-BSI. This was a retrospective cohort performed in adults receiving step-down/outpatient linezolid or SPT (vancomycin, daptomycin) for MRSA-BSI from 2011-2019. Primary outcome was 90-day infection-related re-admission (IRR) from clinical worsening/relapse or infection recurrence. 215 patients included (54 linezolid, 161 SPT). Infection sources were skin (34%), bone/joint (15%), endocarditis (13%), other (32%), multiple (6%). Patients receiving SPT more commonly had complicated bacteraemia (72% vs. 41%; P < 0.0001) and metastatic foci (45% vs. 20%; P = 0.001). 90-day IRR occurred in 17% and 26% of linezolid and SPT groups, respectively (P = 0.159). When accounting for disease severity, linezolid use was not independently associated with 90-day IRR (adjOR, 1.0, 95% CI 0.24-4.3; P = 0.986). There were no differences in all-cause 90-day mortality (4% vs. 6%, P = 0.487) or overall incidence of drug-related adverse events (AEs) (17% vs. 16%; P = 0.843) between the groups. More patients in the SPT group developed an AE requiring re-hospitalisation (12% vs. 2%; P = 0.024), most commonly line-related complications. Oral step-down linezolid demonstrated similar clinical and safety outcomes compared with SPT for MRSA-BSI, except linezolid was associated with fewer AEs requiring re-hospitalisation. Additional research is needed exploring step-down linezolid in MRSA-BSI, particularly in patients requiring shorter durations of outpatient therapy.

Central nervous system blastomycosis clinical characteristics and outcomes.

Blastomycosis is a local or systemic infection, caused by Blastomyces dermatitidis (B. dermatitidis) or B. gilchristii. Blastomycosis has been described as "the great pretender," alluding to the fact that it manifests in a wide range of symptoms and disease severity. Central nervous system (CNS) involvement, although rare, carries significant mortality. Due to the limited published reports of CNS blastomycosis, we present an updated cohort with eight cases of proven or probable CNS blastomycosis describing presentation, diagnosis, treatment and outcomes. Headache was the most common presenting symptom. Magnetic resonance imaging (MRI) proved to be the superior imaging study. All patients in our cohort were diagnosed by histopathological staining or cultures of tissue or fluid obtained from CNS or extra-CNS lesions. All patients that received treatment with Liposomal amphrotericin B for at least 10 days followed by a prolonged azole therapy did not have relapse. Two patients with late diagnoses died during hospitalization. Our findings confirm the importance of timely diagnosis and treatment of CNS blastomycosis to improve outcomes especially with an azole that have a high CNS penetration and a good intrinsic activity for B. dermatitidis such as voriconazole.

Candida spp. infective endocarditis: Characteristics and outcomes of twenty patients with a focus on injection drug use as a predisposing risk factor.

BACKGROUND: Candida spp. infective endocarditis (CIE) although rare is associated with high morbidity and mortality. Risk factors include prosthetic heart valves and injection drug use (IDU). We reviewed all cases of CIE at our institution to describe the microbiology, treatment and outcomes of patients focusing on IDU as a predisposing factor. METHODS: Retrospective cohort of patients with definite CIE between 2013 and 2019 at a university hospital was analysed. Demographic data collected included IDU, microbiologic, treatment and mortality. The primary outcome of interest was 12-month, all-cause mortality. RESULTS: Twenty patients were included (one had two separate episodes of CIE); CIE accounted for 4% of total infective endocarditis (IE) cases during the study period. The median (IQR) age was 38 (30-58) years, 10 (50%) had a previous history of IE, and 4 (20%) patients had prosthetic heart valves or an implanted cardiac device. Thirteen (65%) patients were IDU. The tricuspid valve was the primary valve involved (8/18, 44%), and C albicans was the most frequently isolated organism (8, 36%). Echinocandin was the most common treatment strategy (8, 40%). Only three (15%) patients underwent valve replacement during hospitalisation. There were no in-hospital fatalities, and 5 (25%) patients died at one year; all were IDU (39% to 0%, p = .11). CONCLUSION: CIE is a rare infectious disease seen more commonly in the IDU population. Cardiac surgery was rarely performed, and long-term mortality was 25%. Additional data are needed to identify ideal management strategies in this population.

Percutaneous Mechanical Aspiration vs Valve Surgery for Tricuspid Valve Endocarditis in People Who Inject Drugs.

BACKGROUND: Valve surgery in tricuspid valve infective endocarditis (TVIE) is controversial in people who inject drugs (PWID) due to perceived risks of reinfection because of recidivism. The study objective was to compare outcomes of percutaneous mechanical aspiration (PMA) using the Penumbra Indigo system to valve surgery in PWID with TVIE. METHODS: Retrospective cohort of adult PWID hospitalized with definite TVIE and received PMA or valve surgery from January 2014 to April 2019. Primary endpoint was all-cause 12-month mortality; secondary endpoints included in-hospital mortality and all-cause 12-month readmission. RESULTS: In total, 85 patients were included: 42 undergoing PMA and 43 undergoing valve surgery. Baseline patient demographics were similar between groups; 62 (73%) patients were women, and the median age was 31 (interquartile range, 27-41) years. Seventy-four (86%) patients had a previous history of infective endocarditis and received long-term antibiotic therapy before surgical intervention; 33 (38%) patients presented with septic shock on admission. The most commonly organism was methicillin-resistant Staphylococcus aureus (n = 32 of 84, 38%). Five (12%) PMA patients died in hospital compared with 1 (2%) patient who received valve surgery (P = .11). All-cause 12-month mortality was 24% and 19% for the PMA and surgery groups, respectively (P = .57). When considering confounders, there was no difference in all-cause 12-month mortality between the PMA and valve surgery groups (adjusted odds ratio, 1.5; 95% confidence interval, 0.48-4.8); no significant differences in secondary outcomes were identified. CONCLUSIONS: PMA was associated with similar outcomes to valve surgery for management of TVIE in PWID. PMA may be an alternative to valve surgery as a treatment or bridging strategy to surgery while PWID undergo addiction treatment.

Comparison of dalbavancin to standard-of-care for outpatient treatment of invasive Gram-positive infections.

OBJECTIVE: To assess the efficacy and safety of dalbavancin compared to standard-of-care (SOC) or vancomycin and daptomycin in invasive infections due to suspected or confirmed Gram-positive organisms. METHODS: Retrospective cohort of adults who received dalbavancin or SOC on discharge or as an outpatient from 12/2016 to 11/2019. Indications were osteoarticular infection (OAI), infective endocarditis (IE), or other bloodstream infection (BSI). Primary endpoint was 90-day infection-related readmission (IRR); secondary endpoints included time-to-IRR, frequency of adverse drug events (ADEs), and all-cause readmission and mortality. RESULTS: 215 patients were included: 70 (33%) receiving dalbavancin, and 145 (67%) receiving SOC. Indications were OAI (47%), IE (27%), and other BSI (26%). OAI was more common in patients on dalbavancin compared with those receiving SOC (70% vs. 37%, P<0.001). Dalbavancin patients had shorter median (interquartile range [IQR]) length of stay (LOS) prior to drug initiation compared with those receiving SOC (10 [7-17] vs. 13 [9-19], P=0.021). IRR incidence was 17% for dalbavancin patients and 28% for SOC patients. Dalbavancin use was independently associated with lower IRR (adjusted odds ratio [adjOR], 0.10; 95% confidence interval [CI], 0.04-0.31). There was longer median (IQR) time-to-IRR in the dalbavancin group (43 [30-87] vs. 23 [11-63] days, P=0.039), but no differences in all-cause readmission or mortality. Treatment-related ADE incidence was 3% and 14% for the dalbavancin and SOC groups, respectively (P=0.013). Infusion reactions (1/2) and catheter-related complications (1/2) were the most common dalbavancin ADEs; catheter-related complications (14/21), nephrotoxicity (3/21), rhabdomyolysis (2/21), and rash (2/21) were the most common SOC ADEs. CONCLUSIONS: Dalbavancin use was associated with lower 90-day IRR, a shorter hospital LOS prior to therapy, and longer time-to-IRR compared with SOC.

Impact of a Plan of Care Protocol on Patient Outcomes in People Who Inject Drugs With Infective Endocarditis.

BACKGROUND: People who inject drugs (PWID) are at increased risk of deleterious sequelae due to infective endocarditis (IE). A standardized, hospital-wide drug use-associated infection protocol targeting medication safety, pain management, and limiting external risk factors was implemented at an academic medical center to improve outcomes in PWID with IE. METHODS: A quasi-experimental study included patients with active injection drug use and definite IE from January 2013 to July 2017 (preintervention group) and from September 2017 to January 2019 (intervention group). The primary outcome of interest was the 90-day all-cause readmission rate. Secondary outcomes included infection-related readmission rates, in-hospital and all-cause mortality rates, and the frequency of patients leaving against medical advice. RESULTS: A total of 168 patients were included, in the 100 preintervention and 68 in the intervention group. Patients in the intervention group had reduced odds of 90-day all-cause readmission (adjusted odds ratio, 0.2; 95% confidence interval, 0.08-0.6) after adjustment for confounding variables. The 12-month all-cause mortality rate was also significantly reduced in the intervention group (adjusted odds ratio, 0.25; 95% confidence interval, .07-.89). The intervention group had a higher proportion of patients leaving against medical advice (6% for the preintervention group vs 35% for the intervention group, P < .001). CONCLUSIONS: A drug use-associated infection protocol demonstrated reduced 90-day all-cause readmission and 12-month all-cause mortality rates in PWID with IE. This study highlights the importance of standardized care processes for improving care in this specialized patient population.

Maternal Bacteremia Caused by Staphylococcus Aureus With a Focus on Infective Endocarditis.

BACKGROUND: Sepsis is an important cause of morbidity and mortality in the pregnant patient. Injection drug use in pregnant populations has led to increased cases of bacteremia and infective endocarditis (IE) due to Staphylococcus aureus. We describe all cases of S. aureus bacteremia and IE among admitted pregnant patients at our hospital over a 6-year period. METHODS: This was a retrospective review of pregnant patients hospitalized with S. aureus bacteremia between April 2013 and November 2019. Maternal in-hospital mortality and fetal in-hospital mortality were the primary outcomes measured; the secondary outcome was the rate of 6-month maternal readmission. RESULTS: Twenty-seven patients were included; 15 (56%) had IE. The median (interquartile range [IQR]) age was 29 (25-33) years; 22 (82%) patients had methicillin-resistant S. aureus. Infection onset occurred at a median (IQR) of 29 (23-34) weeks' gestation. Twenty-three (85%) mothers reported active injection drug use, and 21 (78%) were hepatitis C seropositive. Fifteen (56%) mothers required intensive care unit (ICU) care. Twenty-two (81%) patients delivered 23 babies; of the remaining 5 mothers, 3 (11%) were lost to follow-up and 2 (7%) terminated pregnancy. Sixteen (73%) babies required neonatal ICU care, and 4/25 (16%) infants/fetuses died during hospitalization. One (4%) mother died during hospitalization, and 7/26 (27%) mothers were readmitted to the hospital within 6 months for infectious complications. CONCLUSIONS: Injection drug use is a modifiable risk factor for S. aureus bacteremia in pregnancy. Fetal outcomes were poor, and mothers were frequently readmitted secondary to infection. Future targeted interventions are needed to curtail injection drug use in this population.

Epidemiology and outcomes of non-HACEK infective endocarditis in the southeast United States.

OBJECTIVES: Infective endocarditis (IE) with non-HACEK Gram-negative (GN) organisms is rare, but associated with poor outcomes. The purpose of this study was to quantify the microbiology, treatment strategies, and frequency of poor outcomes in patients with non-HACEK GN IE. MATERIALS: Retrospective cohort of adults with definite non-HACEK GN IE from 1/11-1/19. The primary endpoint was poor patient outcome, defined as a composite of all-cause death or infection-related readmission within 90-days of index infection. RESULTS: 43 patients were included: 51% patients were men, and the median (IQR) age was 40 (31-50) years. Forty patients reported injection drug use. The most common organisms were Pseudomonas aeruginosa (68%) and Serratia marcescens (9%). Seventy-six percent of patients received definitive combination therapy; the most common antibiotics used in combination with a ß-lactam were aminoglycosides (50%) and fluoroquinolones (34%). Three patients discontinued combination therapy due to toxicity. Twelve-month, all-cause mortality and readmission was 30% and 54%, respectively. In multivariable logistic regression, variables independently associated with composite poor outcome were receipt of fluoroquinolone-based IE combination therapy and septic shock. CONCLUSIONS: Long-term mortality and readmission rates were high. Patients who received fluoroquinolone-based IE combination therapy more frequently developed poor outcomes than those who did not.

Elevated troponin level as a predictor of inpatient mortality in patients with infective endocarditis in the Southeast United States.

BACKGROUND: Despite recent improvement in management, infective endocarditis (IE) continues to be associated with considerable risk of morbidity and mortality. Early identification of predictors of inpatient mortality is key in improving patient outcomes in IE. The aim of our study was to evaluate the role of serum troponin levels measurements as a marker of increased mortality. METHODS: A case-control study included adult patients with IE admitted to a tertiary care hospital in east Tennessee between December 2012 and July 2017. Cases were defined as patients with definitive IE who died in-hospital; controls were patients who did not die in hospital. First patient admission was included only. Data collected included the patients' demographic and baseline clinical information, microbiological data, injection drug use status, elevated serum troponins levels. RESULTS: Two hundred eighty three patients with definitive IE were included; median (IQR) age was 41 (30-57) years, and 153 (54%) patients were men. One-hundred sixty-four (58%) were injection drug users. The most frequent IE type was: 167 (59%) right-sided, 86 (30%) left-sided, 24 (9%) both left and right-sided, and 10 (4%) device related. The most commonly isolated organism was Staphylococcus aureus (n = 141), and 64% were methicillin-resistant. Two-hundred twelve (75%) patients had a troponin level obtained, and 57 (27%) had an elevated troponin value. Thirty-six (13%) patients died in-hospital; in-hospital mortality was associated elevated troponin values (adjusted odds ratio [adjOR], 7.3; 95%CI, 3.3-15.9), and methicillin-resistant S. aureus IE (adjOR 2.6; 95%CI, 1.2-5.8). Forty-four (16%) patients received IE valve surgery, and none of these patients died in the hospital. CONCLUSION: Inpatient mortality was higher in patients with IE and elevated cardiac troponin levels compared to patients with normal levels.

Long-term vancomycin use had low risk of ototoxicity.

BACKGROUND: Vancomycin is a commonly used antibiotic with potent activity against Gram-positive organisms, but prolonged use and high doses can lead to toxicity. While vancomycin-associated nephrotoxicity is widely reported, few cases of ototoxicity have been described. The objective of this study was to determine the prevalence of negative changes in audiograms in patients receiving long-term intravenous (IV) vancomycin and to identify high-risk patients who need audiogram monitoring. METHODS: This was an IRB approved, cross-sectional study performed at an academic medical center from 1/2012-3/2019. Patients who were prescribed IV vancomycin for ≥ 14 days and had baseline and follow-up weekly audiometry were included. All data was extracted from the electronic medical record. The primary endpoint was worsening audiogram while on vancomycin. Descriptive and bivariate statistics were used to describe the patient population. RESULTS: 424 patients were screened for inclusion; 92 received at least two audiograms while on vancomycin. Fifty-three percent of patients were men, the median (IQR) patient age was 44 (34-58) years, and 8% of patients had an estimated Cockcroft-Gault creatinine clearance ≤ 30 mL/min or received hemodialysis. The median (IQR) vancomycin exposure up until the last recorded audiogram was 30 (17-42) days. Vancomycin indications were: 53 (58%) bone and joint infections, 17 (18%) infective endocarditis, 10 (11%) bacteremia, 12 (13%) other infections. Seven (8%) patients experienced a worsening change in hearing from baseline, two (2%) of them suffered mild loss, two (2%) had mild to moderate loss, and three (3%) developed moderate-to-severe hearing loss. In bivariate analyses, no variables were found to be associated with a worsening change in audiogram, including baseline abnormal audiogram, age ≥ 40 years, elevated serum vancomycin levels, or vancomycin doses ≥ 4 grams/day. CONCLUSIONS: The prevalence of negative changes in audiograms among patients receiving long-term intravenous vancomycin was low. The utility of routine audiogram testing in this population remains questionable except in high-risk patients; however, larger prospective studies with controls may be warranted to further explore the risk of ototoxicity.

Microbial Epidemiology of Infectious Endocarditis in the Intravenous Drug Abuse Population: A Retrospective Study.

INTRODUCTION: The microbial epidemiology differs between infective endocarditis (IE) patients with and without a history of injection drug use. We set out to determine the prevalence and microbial epidemiology of infective endocarditis in our region, the Southeastern USA, to determine if any changes need to be made in empiric antimicrobial treatment. METHODS: The electronic medical record was reviewed for patients with IE between January 2013 and July 2017, which revealed 299 cases. The cases were then sorted between patients with and without a history of injection drug use. The growth of their initial set of blood cultures and side of cardiac involvement were then recorded. Statistical analyses were run on the data sets. RESULTS: There were statistically significant effects associated with both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas species infections occurring more often in individuals with active injection drug use, while streptococcus and enterococcus infections were more likely to occur in the population of individuals who do not inject drugs. CONCLUSION: In IE patients who use or are suspected of injection drug use, first-line broad-spectrum antibiotics with excellent MRSA and Pseudomonas coverage are essential.

First description of plasmid mediated quinolone resistance genes in salmonella isolates from Saudi hospitals.

OBJECTIVES: To detect resistance genes to fluoroquinolones and ß-lactams in Salmonella strains from a Saudi hospital. METHODS: From October 2015 to December 2016, a total of 149 Salmonella strains were collected from stool specimens from patients admitted to King Fahad Hospital of the University, AlKhobar, Saudi Arabia using CHROMagar Salmonella. The organism identification and antimicrobial susceptibility testing were performed using Vitek 2 system. Strain serogrouping was performed using Wellcolex color Salmonella kit. Fluoroquinolone resistance genes, extended-spectrum ß-lactamases (ESBLs), and AmpC ß-lactamase were determined using polymerase chain reaction (PCR). Enterobacterial repetitive intergenic consensus sequence-based PCR (ERIC-PCR) was used to determine clonal relatedness. RESULTS: The resistance rates to cefotaxime were 1.3% and ciprofloxacin 19.5%. Plasmid mediated quinolone resistance (PMQR) genes, qnrB and qnrS, were detected in 8 strains, qnrB (n=5) and qnrS (n=3), respectively. No ESBLs, AmpC, or mutations in the topoisomerases were detected. Salmonella isolates formed 7 clusters with similarity. CONCLUSIONS: This study reveals the emergence of fluoroquinolone resistant Salmonella in the region imposing public health concerns.

Strongyloides stercoralis infection in kidney transplant recipients.

Strongyloides stercoralis is an uncommon infection in Saudi Arabia. It can establish latency and cause an autoinfection in humans that lasts for years. The infection can get reactivated during immunosuppression and can result in a life-threatening Strongyloides hyperinfection syndrome. We present three cases of renal transplant recipients who developed Strongyloides infection following transplantation. A bronchoalveolar lavage specimen, a duodenal biopsy and/or a stool specimen from these patients revealed evidence of S. stercoralis larvae. The first two patients received kidneys from the same deceased donor, a native of Bangladesh, an area that is highly endemic for S. stercoralis. The data suggest that the first two cases might be donor derived. High-risk donors and recipients should be screened for Strongyloides infection to initiate treatment before transplantation thus reducing morbidity and mortality.