Sequential Time to Positivity as a Prognostic Indicator in Staphylococcus aureus Bacteremia.

Background: We aimed to determine the factors associated with sequential blood culture time to positivity (STTP) and validate the previously defined time to positivity (TTP) ratio threshold of 1.5 in predicting adverse disease outcomes and mortality of Staphylococcus aureus bacteremia (SAB). Methods: We conducted an observational study of adult patients with SAB. The TTP ratio was calculated by dividing the TTP of the second blood culture by that of the first. Results: Of 186 patients, 69 (37%) were female, with a mean age of 63.6 years. Median TTP was 12 hours (interquartile range [IQR], 10-15 hours) from the initial and 21 hours (17-29) from sequential blood cultures. Methicillin-resistant S aureus (MRSA)-infected patients had significantly shorter STTPs (P < .001) and lower TTP ratios (P < .001) compared to patients with methicillin-susceptible S aureus (MSSA). A significant correlation between initial and STTP was observed in patients with MRSA (r = 0.42, P = .002) but not in those with MSSA. A higher rate of native valve endocarditis (NVE) significantly correlated with a TTP ratio of ≤1.5 (odds ratio, 2.65 [95% confidence interval, 1.3-5.6]; P = .01). The subgroup having an initial TTP <12 hours combined with a TTP ratio ≤1.5 showed the highest prevalence of NVE. Conclusions: The STTP varies based on methicillin susceptibility of S aureus isolate. This study suggests a potential clinical utility of the STTP to identify patients at a higher risk of NVE. However, prospective studies are required to validate these findings.

Characteristics and management of periprosthetic joint infections caused by rapidly growing mycobacteria: a retrospective study and a review of the literature.

Background: Periprosthetic joint infection (PJI) following total joint arthroplasty is a serious complication associated with significant morbidity. While Gram-positive cocci are the predominant causative organisms, PJIs caused by rapidly growing mycobacteria (RGM) have been reported, albeit at a lower frequency. This study aimed to investigate the characteristics and management of PJI caused by RGM. Methods: A retrospective review was conducted using an institutional PJI database to identify patients diagnosed with PJI due to RGM from January 2010 to December 2021. Clinical data, including demographics, symptoms, comorbidity information, laboratory parameters, surgical procedures, medical treatment and outcomes, were collected and analyzed. Results: A total of eight patients were identified with PJI caused by RGM during the study period. The median age was 66 years old, and most cases occurred in patients with total knee arthroplasty (n=6). The isolated RGM species included Mycobacterium abscessus (three cases), M. fortuitum (three cases), and one case each of M. immunogenum and M. mageritense. Surgical debridement was performed in all cases, with six patients undergoing two-stage revision and two patients requiring amputation. Combination antimicrobial therapy was administered based on antimicrobial susceptibility testing, and the median duration of treatment was 7.5 months. Adverse events related to therapy occurred in 75 % of cases. No relapses were observed during the median follow-up period of 39.6 months. Conclusions: PJI caused by RGM is a rare complication of total joint arthroplasty. Surgical debridement and combination antimicrobial therapy are the mainstays of treatment. Although clinical cure rates are high, amputation may be required in severe cases.

Effect of Preoperative Antibiotic Therapy on Operative Culture Yield for Diagnosis of Native Joint Septic Arthritis.

BACKGROUND: Native joint septic arthritis (NJSA) is definitively diagnosed by a positive Gram stain or culture, along with supportive clinical findings. Preoperative antibiotics are known to alter synovial fluid cell count, Gram stain and culture results and are typically postponed until after arthrocentesis to optimize diagnostic accuracy. However, data on the impact of preoperative antibiotics on operative culture yield for NJSA diagnosis are limited. METHODS: We retrospectively reviewed adult cases of NJSA who underwent surgery at Mayo Clinic facilities from 2012-2021 to analyze the effect of preoperative antibiotics on operative culture yield through a paired analysis of preoperative culture (POC) and operative culture (OC) results using logistic regression and generalized estimating equations. RESULTS: Two hundred ninety-nine patients with NJSA affecting 321 joints were included. Among those receiving preoperative antibiotics, yield significantly decreased from 68.0% at POC to 57.1% at OC (p < .001). In contrast, for patients without preoperative antibiotics there was a non-significant increase in yield from 60.9% at POC to 67.4% at OC (p = 0.244). In a logistic regression model for paired data, preoperative antibiotic exposure was more likely to decrease OC yield compared to non-exposure (OR = 2.12; 95% CI = 1.24-3.64; p = .006). Within the preoperative antibiotic group, additional antibiotic doses and earlier antibiotic initiation were associated with lower OC yield. CONCLUSION: In patients with NJSA, preoperative antibiotic exposure resulted in a significant decrease in microbiologic yield of operative cultures as compared to patients in whom antibiotic therapy was held prior to obtaining operative cultures.

Perimyocarditis Associated with Immune Checkpoint Inhibitors: A Case Report and Review of the Literature.

Patient prognoses have been significantly enhanced by immune checkpoint inhibitors (ICIs), altering the standard of care in cancer treatment. These novel antibodies have become a mainstay of care for metastatic non-small-cell lung cancer (mNSCLC) patients. Several types of adverse events related to ICIs have been identified and documented as a result of the launch of these innovative medicines. We present here a 74-year-old female patient with a stage IV lung adenocarcinoma, treated with nivolumab plus ipilimumab, who developed perimyocarditis two weeks after receiving the third cycle of immune checkpoint inhibitor therapy. The patient was diagnosed using troponin levels, computed tomography (CT) angiography, and echocardiography. After hospitalization, her cardiac condition was successfully resolved with corticosteroids, colchicine, and symptomatic treatment. To the best of our knowledge, this is one of the rarest cases to be reported of perimyocarditis as a toxicity of immunotherapy in a patient treated for adenocarcinoma of the lung.

Impact of hypoalbuminemia on clinical outcomes among patients with obesity treated with ceftriaxone.

The use of ceftriaxone, a highly protein-bound drug, in the setting of hypoalbuminemia may result in suboptimal drug exposure. Patients with obesity also exhibit higher absolute drug clearance. We aimed to evaluate the impact of hypoalbuminemia on clinical success among hospitalized adults with obesity who were treated with ceftriaxone. This retrospective review included adult inpatients with weight >100 kg or body mass index >40 kg/m2 who received ceftriaxone 2 g intravenously every 12 hours for at least 72 hours. The primary outcome was clinical success, a composite of clinical cure and microbiologic cure. Secondary outcomes included clinical cure, microbiologic cure, length of stay, ICU length of stay, mortality, 30-day readmission, and adverse events. In all, 137 patients were included, 34 of whom had a serum albumin of ≤2.5 g/dL. In a propensity-score-weighted analysis, clinical success was significantly more common among those without hypoalbuminemia (91.2%) as compared to those with hypoalbuminemia (77.8%) (P = 0.038). Death within 30 days (13.7% vs 0%, P < 0.001) and 30-day readmission (31.6% vs 12.0%, P = 0.008) were more common in the hypoalbuminemia group. In a univariate analysis, serum albumin and indication for ceftriaxone use were found to be predictors of clinical success. Hypoalbuminemia was associated with a lower rate of clinical success among patients with obesity who were treated with ceftriaxone 2 g every 12 hours.

Temporal trends in antifungal susceptibility of Cryptococcus neoformans isolates from a reference laboratory in the United States, 2011-2021.

BACKGROUND: There are no established clinical breakpoints for antifungal agents against Cryptococcus species; however, epidemiological cut-off values can help distinguish wild-type (WT) isolates without any acquired resistance from non-WT strains, which may harbour resistance mechanisms. PATIENTS/METHODS: We describe the trends of antifungal MICs and percentages of WT C. neoformans species complex (CNSC) isolates processed in our reference laboratory from November 2011 to June 2021. There were only nine isolates in 2011, thus, we included them in the year 2012 for data analysis. Clinical data is also described when available. RESULTS: We identified 632 CNSC, the majority collected from blood (n = 301), cerebrospinal fluid (n = 230), and respiratory (n = 71) sources. The overall percentage of WT isolates for amphotericin B (AMB), 5-flucytosine, and fluconazole was 77%, 98%, and 91%, respectively. We noticed a statistically significant change in the percentage of AMB WT isolates over the years, with 98% of isolates being WT in 2012 compared to 79% in 2021 (p < .01). A similar change was not observed for other antifungal agents. Clinical data was available for 36 patients, primarily non-HIV immunocompromised patients with disseminated cryptococcosis. There were no statistically significant differences in the clinical characteristics and outcomes between patients with WT (58.3%) versus non-WT (41.7%) isolates, but we noticed higher mortality in patients infected with an AMB non-WT CNSC isolate. CONCLUSIONS: We observed an increase in the percentage of AMB non-WT CNSC isolates in the past decade. The clinical implications of this finding warrant further evaluation in larger studies.

Powassan Virus Encephalitis: A Tertiary Center Experience.

BACKGROUND: Powassan virus (POWV) is an emerging arthropod-borne flavivirus, transmitted by Ixodes spp. ticks, which has been associated with neuroinvasive disease and poor outcomes. METHODS: A retrospective study was conducted at Mayo Clinic from 2013 to 2022. We included clinical and epidemiologic data of probable and confirmed neuroinvasive POWV cases. RESULTS: Sixteen patients with neuroinvasive POWV were identified; their median age was 63.2 years, and 62.5% were male. Six patients presented with rhombencephalitis, 4 with isolated meningitis, 3 with meningoencephalitis, 2 with meningoencephalomyelitis, and 1 with opsoclonus myoclonus syndrome. A median time of 18 days was observed between symptom onset and diagnosis. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein and normal glucose in the majority of patients. Death occurred within 90 days in 3 patients (18.8%), and residual neurologic deficits were seen in 8 survivors (72.7%). CONCLUSIONS: To our knowledge, this is the largest case series of patients with neuroinvasive POWV infection. We highlight the importance of a high clinical suspicion among patients who live in or travel to high-risk areas during the spring to fall months. Our data show high morbidity and mortality rates among patients with neuroinvasive disease.

Cemiplimab as First Line Therapy in Advanced Penile Squamous Cell Carcinoma: A Real-World Experience.

In the treatment of cancer, immune checkpoint inhibitors (ICIs) have demonstrated significantly greater effectiveness compared to conventional cytotoxic or platinum-based chemotherapies. To assess the efficacy of ICI's in penile squamous cell carcinoma (pSCC) we performed a retrospective observational study. We reviewed electronic medical records of patients with penile squamous cell carcinoma (SCC), diagnosed between January 2020 and February 2023. Nine patients were screened, of whom three were ineligible for chemotherapy and received immunotherapy, cemiplimab, in a first-line setting. Each of the three immunotherapy-treated patients achieved almost a complete response (CR) after only a few cycles of therapy. The first patient had cerebral arteritis during treatment and received a high-dose steroid treatment with resolution of the symptoms of arteritis. After tapering down the steroids dose, the patient continued cemiplimab without further toxicity. The other two patients did not have any toxic side effects of the treatment. To the best of our knowledge, this is the first real world report of near CR with cemiplimab as a first-line treatment in penile SCC.

Unexpected and Rare Sites of Metastasis in Oncologic Patients.

Case studies of rare oncologic metastases are an important source of clinical data for health care professionals and researchers. While infrequent, the knowledge base and clinical recommendations derived from such cases aid in advancements in the field. As such, we aim to add five cases to the growing body of literature. The first two male patients, aged 69 and 73, were diagnosed with colon adenocarcinoma, suspected to be a second primary prostate carcinoma, following positron emission tomography-computer tomography (PET-CT). This suspicion was ruled out by prostatectomy and histopathological investigations, which instead found adenocarcinoma of colonic origin. The next two male patients, ages 63 and 68, were diagnosed, respectively, with metastatic pancreatic adenocarcinoma with cardiac metastases and metastatic melanoma with distant metastases to the pancreas. The final patient was a 73-year-old male diagnosed with metastatic breast cancer after a radiological investigation of suspected renal cell carcinoma.

Majocchi's granuloma-A multicenter retrospective cohort study.

Background: Majocchi's granuloma (MG) is an uncommon deep fungal folliculitis predominantly caused by dermatophytes. Given the rarity of this condition, available data regarding predisposing comorbidities/risk factors, clinical characteristics, offending microbiologic pathogens, diagnostics, pathologic findings, and treatment approaches has been inferred from historical cases. Objectives: To review our institutional experience with MG. Methods: We retrospectively analyzed a multicenter cohort of adult patients diagnosed with MG between 1992 and 2022. Results: We analyzed 147 patients with MG, 105 of which were male with a median age of 55.6 years. Immunosuppressant and topical corticosteroid use were common prior to development of MG. Dermatologic lesions and their sites of involvement did not differ based on the immune status of patients. Trichophyton rubrum was the most common causative pathogen of MG, in addition to other dermatophytes. Treatment duration for all prescribed agents was median 31.5 days with oral terbinafine being the most frequently utilized agent. Clinical resolution was achieved in 96.6% of cases. Limitations: Retrospective, nonrandomized study. Conclusions: Although rare and clinically variable in presentation, diagnosis of MG often requires histopathologic confirmation to subsequently direct prolonged treatment with systemic antifungal therapy for mycological cure.

Bullous Pemphigoid Occurring after Stopping Imatinib Therapy of CML: Is a Continuation of Post-Treatment Follow-Up Needed?

Advancements and the use of tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of Chronic Myeloid Leukemia (CML), achieving unprecedented success rates and expanding their applications to various neoplasms. However, the use of TKIs is not without its drawbacks. Skin, gastrointestinal, and central nervous systems are particularly susceptible to adverse effects, including a higher incidence of autoimmune responses in treated individuals. In this report, we present a unique case of bullous pemphigoid, a rare autoimmune disease, which has not been previously associated with TKI therapy as an adverse effect, particularly appearing after discontinuing Imatinib® treatment.

Carpal Tunnel Syndrome Associated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic approach to diverse malignancies, leading to substantial enhancements in patient prognosis. However, along with their benefits, ICIs also increase the incidence of immune-related adverse events (irAEs). In the present paper, we highlight four cases of carpal tunnel syndrome (CTS) as an uncommon manifestation of toxicity induced by ICIs. Although diagnosed with different malignancies, the patients were undergoing ICI therapy when they developed CTS-consistent side effects accompanied by severe neuropathy. Prompt treatment with corticosteroids, intravenous immunoglobulins, or methotrexate resulted in complete symptomatic relief for all patients. This article therefore emphasizes the importance of recognizing and managing rare adverse events associated with ICI use to ensure optimal patient care.

'How to' Guide for Pharmacist-led Implementation of Beta-Lactam Therapeutic Drug Monitoring in the Critically Ill.

Beta-lactam therapeutic drug monitoring (TDM) can improve precision dosing and clinical outcomes in critically ill patients, but has not been implemented widely in the United States. Mayo Clinic recently implemented a beta-lactam TDM program. This single-center experience forms the basis of the manuscript which outlines practical considerations involved with implementation, including the pharmacist's role as a leader. Our implementation effort focused on three primary domains. First, we aimed to ensure a supportive organizational infrastructure. Early leadership engagement by the pharmacist-led core team facilitated advocacy for the clinical need, allocation of resources, and assay development. Second, core clinical workflows were developed that addressed the preferred patient population for use, desirable pharmacokinetic and pharmacodynamic targets, and the preferred sampling strategy. Clinical tools to guide pharmacists in interpreting the results (e.g., pharmacokinetics calculator) and documenting decisions were developed. Third, stakeholders were offered repeated exposure to evidence and expertise to facilitate understanding and application of the new practice. This act of 'individual internalization' seems to be uniquely important to beta-lactam TDM implementation compared with implementation of other antimicrobial TDM programs. Educational strategies and supportive materials that were developed were focused on providing substantive and varied information tailored to the stakeholders' role in the process. For pharmacists, this included both clinical and operational considerations. A continuous improvement plan to support management of the process was instituted to address necessary updates and changes that inevitably emerged. In summary, the described approach to implementation of a pharmacist led beta-lactam TDM program could be used as a roadmap to aid other institutions that aim to develop such a program.

PD-1 Inhibitors in Elderly and Immunocompromised Patients with Advanced or Metastatic Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common form of skin cancer, with aging and prolonged exposure to ultraviolet rays being the main causes of the disease. Cemiplimab and pembrolizumab recently gained regulatory approval for the treatment of locally advanced and metastatic cSCC-conditions that are not treatable by surgical resection and/or radiotherapy. Although the results from the clinical trials have been promising, these studies have not included immunosuppressed, elderly patients. In this study, we included all immunocompromised and immunocompetent patients over the age of 75 years diagnosed with locally advanced or metastatic cSCC and treated with cemiplimab or pembrolizumab. The median duration of follow-up from cSCC diagnosis was 35.6 months, 82.9% of patients were male, and the median age was 83 years old. The median progression-free survival was 8.94 months. The incidence of treatment-related adverse events was 85.6%, the majority of which were grades 1 or 2. The disease control rate was 91.4%, the complete response rate was 17.1%, the partial response rate was 51.4%, the stable disease rate was 23%, and the progressive disease rate was 8.7%. Based on this study, cemiplimab and pembrolizumab for the treatment of locally advanced or metastatic cSCC in elderly, immunocompromised patients are efficacious, with acceptable safety profiles.

Antifungal Susceptibility Pattern of Candida glabrata from a Referral Center and Reference Laboratory: 2012-2022.

The prevalence of invasive candidiasis caused by non-Candida albicans has rapidly increased. Candida glabrata (Nakaseomyces glabrata) is an important pathogen associated with substantial mortality. Our study examined the antifungal temporal susceptibility of C. glabrata and cross-resistance/non-wild-type patterns with other azoles and echinocandins. Laboratory data of all adult patients with C. glabrata isolated from clinical specimens at the Mayo Clinic, Rochester, from 2012 to 2022 were collected. Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were used. We obtained 1046 C. glabrata isolates from 877 patients. Using CLSI and EUCAST breakpoints, 187 (17.9%) isolates and 256 (24.5%) isolates were fluconazole-resistant, respectively. Focusing on C. glabrata bloodstream infections, fluconazole-resistance ranged from 16 to 22%. Among those 187 fluconazole-resistant isolates, 187 (100%) and 184 (98.4%) isolates were also voriconazole and posaconazole non-wild-type, respectively, with 97 (51.9%) isolates deemed non-wild type for itraconazole. The fluconazole susceptibility pattern has not changed over the past decade. The proportion of fluconazole-resistant C. glabrata is relatively high, which could be due to the complexity of patients and fluconazole exposure. Itraconazole appears to be a compelling step-down therapy for fluconazole-resistant C. glabrata, given the high proportion of wild-type isolates. Further research to examine clinical outcomes is warranted.

"Let the Cat Out of the Heart": Clinical Characteristics of Patients Presenting With Blood Culture-Negative Endocarditis Due to Bartonella Species.

Patients with blood culture-negative endocarditis due to Bartonella infection frequently presented with fever, cytopenias, kidney failure, and positive PR3-ANCA. Bartonella IgG titers were variable. Patients commonly underwent surgery with overall low mortality.

Clinical characteristics of central nervous system phaeohyphomycosis: A brief report of 20 years' experience.

Central nervous system (CNS) phaeohyphomycosis is a rare and often fatal fungal infection. Our study reported a case series of eight CNS phaeohyphomycosis cases at our institution over the past 20 years. We did not observe the common pattern of risk factors, abscess location, or number of abscesses among them. Most patients were immunocompetent without classic risk factors for fungal infection. Early diagnosis and aggressive management with surgical intervention and prolonged antifungal therapy can lead to a favorable outcome. The study highlights the need for further research to better understand the pathogenesis and optimal management of this challenging rare infection.

Prototheca Infection: A Descriptive Study.

Prototheca is a microalgae known to cause infections in humans, with protothecosis most commonly presenting as olecranon bursitis or localized soft tissue infection. Disseminated disease can be seen in immunocompromised patients. In this retrospective single-institution case series, we describe our experience with 7 patients with Prototheca infections.