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 to 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 = .244). In a logistic regression model for paired data, preoperative antibiotic exposure was more likely to decrease OC yield compared to non-exposure (odds ratio [OR] = 2.12; 95% confidence interval [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. CONCLUSIONS: 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.

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.

Use of the DMAIC Lean Six Sigma quality improvement framework to improve beta-lactam antibiotic adequacy in the critically ill.

Beta-lactam antibiotics are widely used in the intensive care unit due to their favorable effectiveness and safety profiles. Beta-lactams given to patients with sepsis must be delivered as soon as possible after infection recognition (early), treat the suspected organism (appropriate), and be administered at a dose that eradicates the infection (adequate). Early and appropriate antibiotic delivery occurs in >90% of patients, but less than half of patients with sepsis achieve adequate antibiotic exposure. This project aimed to address this quality gap and improve beta-lactam adequacy using the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework. A multidisciplinary steering committee was formed, which completed a stakeholder analysis to define the gap in practice. An Ishikawa cause and effect (Fishbone) diagram was used to identify the root causes and an impact/effort grid facilitated prioritization of interventions. An intervention that included bundled education with the use of therapeutic drug monitoring (TDM; i.e. drug-level testing) was projected to have the highest impact relative to the amount of effort and selected to address beta-lactam inadequacy in the critically ill. The education and TDM intervention were deployed through a Plan, Do, Study, Act cycle. In the 3 months after "go-live," 54 episodes of beta-lactam TDM occurred in 41 unique intensive care unit patients. The primary quality metric of beta-lactam adequacy was achieved in 94% of individuals after the intervention. Ninety-four percent of clinicians gauged the education provided as sufficient. The primary counterbalance of antimicrobial days of therapy, a core antimicrobial stewardship metric, was unchanged over time (favorable result; P = .73). Application of the Define, Measure, Analyze, Improve, and Control Lean Six Sigma quality improvement framework effectively improved beta-lactam adequacy in critically ill patients. The approach taken in this quality improvement project is widely generalizable to other drugs, drug classes, or settings to increase the adequacy of drug exposure.

Post-treatment outcomes of ceftriaxone versus antistaphylococcal penicillins or cefazolin for definitive therapy of methicillin-susceptible Staphylococcus aureus bacteremia.

Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with poor outcomes. Ceftriaxone offers logistical advantages over other standard therapies, though in vitro studies have questioned its efficacy and clinical studies of ceftriaxone in MSSA bacteremia are conflicting.We performed a multicenter, retrospective cohort study of adult patients who received ceftriaxone, cefazolin, or antistaphylococcal penicillins as definitive therapy for MSSA bacteremia from 2018 to 2019. Definitive therapy was defined as the antibiotic used in the outpatient setting. Patients were excluded if they received less than 7 days of outpatient therapy. Follow-up started on the date of definitive therapy completion. The primary outcome was 90-day treatment failure, defined as a composite of mortality and microbiologic recurrence. This was analyzed with multivariable Cox regression. A total of 223 patients were included, 37 (16.6%) of whom received ceftriaxone. The most common ceftriaxone dose was 2 g daily (83.8%). The most common primary site of infection was skin/soft tissue (37.2%), unknown (21.1%), and catheter-related (15.2%). Twenty-six (11.7%) developed infective endocarditis. Median total duration of treatment was 31.0 days, and median outpatient duration was 24.0 days. Twenty-six (11.7%) developed 90-day treatment failure. After adjusting for Charlson comorbidity index, duration of therapy, and use of transesophageal echocardiography, definitive treatment with ceftriaxone was associated with treatment failure (hazard ratio 2.66, 95% confidence interval 1.15-6.12; p=0.022). Among patients with MSSA bacteremia, definitive treatment with ceftriaxone was associated with a higher risk of treatment failure within 90 days as compared to cefazolin or antistaphylococcal penicillins.

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.

Does metabolite matter? Defining target itraconazole and hydroxy-itraconazole serum concentrations for blastomycosis.

BACKGROUND: Itraconazole is the recommended first-line treatment for mild-to-moderate blastomycosis and consolidation treatment of moderate-to-severe disease. Itraconazole is metabolised into three metabolites, including an active metabolite hydroxy-itraconazole. Literature provides little evidence indicating whether therapeutic drug monitoring targets should be based on itraconazole parent compound alone or a sum of itraconazole and hydroxy-itraconazole serum concentrations. OBJECTIVES: This study aims to compare clinical outcomes and adverse drug events (ADEs) of combined itraconazole and hydroxy-itraconazole concentrations versus itraconazole parent compound alone in patients with blastomycosis. PATIENTS/METHODS: This study was a retrospective cohort review of patients ≥18 years with probable or proven Blastomyces infection who received itraconazole with at least one documented serum itraconazole concentration. The primary outcome was rate of partial or complete treatment response across three patient groups: (1) Itraconazole parent compound >1.0 mcg/ml (parent), (2) parent compound <1.0 mcg/ml, but a combined itraconazole and hydroxy-itraconazole >1.0 mcg/ml (combined) and (3) failure to achieve a combined or parent concentration >1.0 mcg/ml (subtherapeutic) for >75% of the duration of itraconazole therapy. RESULTS: A total of 80 patients were included (parent = 32, combined = 36, subtherapeutic = 12). No statistically significant difference was observed for rate of partial or complete treatment response (97% parent vs 94% combined, p = .99). Significantly higher mortality due to blastomycosis was observed in patients in the subtherapeutic group (0% parent vs 3% combined vs 25% subtherapeutic, p = .01). CONCLUSIONS: This study supports an itraconazole therapeutic target combining itraconazole and hydroxy-itraconazole >1.0 mcg/ml for blastomycosis treatment.

Retrospective Analysis of Antimicrobial Susceptibility Profiles of Nocardia Species from a Tertiary Hospital and Reference Laboratory, 2011 to 2017.

Nocardia species are found worldwide and are opportunistic pathogens of both immunocompromised and immunocompetent hosts. Recent updates to the taxonomy of this genus have indicated that there are more than 90 recognized species of Nocardia with 54 species reported to be clinically relevant. In this paper, we report the species distribution, specimen source distribution, and antimicrobial susceptibility profiles of 2,091 clinical isolates recovered for the years 2011 to 2017 using the updated taxonomy. The most commonly isolated species included Nocardia nova complex, Nocardia cyriacigeorgica, and Nocardia farcinica complex, with an additional 25 species or species complexes recovered from clinical specimens. The antimicrobial susceptibility profile was highly variable between the species, but in general, amikacin, linezolid, and trimethoprim-sulfamethoxazole demonstrated good in vitro activity against most species.

Mycobacterium septicum: a 6-Year Clinical Experience from a Tertiary Hospital and Reference Laboratory.

Mycobacterium septicum is a rarely identified nontuberculous mycobacterium capable of causing infections in both healthy and immunocompromised individuals. Only a few cases of M. septicum infections have been reported, which makes recognizing corresponding clinical disease more challenging for clinicians. Antimicrobial susceptibility profiles for this organism are not well described, and corresponding optimal therapeutic regimens have not been established. We report a tertiary care center's experience with M. septicum from 2014 to 2020. Twelve adult patients with positive cultures for M. septicum were identified. Most cases were identified from sputum samples of individuals with underlying lung disease. Most cases involving M. septicum isolation in culture were not felt to be clinically significant. Two cases were considered possible infections, while only one case was considered a definite infection that required antimicrobial treatment. All M. septicum isolates were susceptible in vitro to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole. Isolates were universally resistant to clarithromycin and doxycycline. The isolation of M. septicum in culture is uncommon and requires clinical correlation to determine its clinical relevance and need for treatment. Susceptibility testing should be performed to guide therapy.

Clostridium paraputrificum septic arthritis and osteomyelitis of shoulder: A case report and review of literature.

Septic arthritis due to Clostridium species is rare. We report the first case of Clostridium paraputrificum native shoulder septic arthritis and osteomyelitis. An 86-year-old woman with osteoarthritis presented with acute-onset right shoulder pain. Injection of the glenohumeral joint with methylprednisolone resulted in worsening of pain. Synovial fluid analysis was consistent with septic arthritis and culture of the synovial fluid grew C. paraputrificum. Arthroscopic irrigation and debridement of shoulder joint with 6 weeks of ertapenem was unsuccessful, with persistence of C. paraputrificum from synovial fluid and tissue culture. She underwent right shoulder resection followed by a second course of ertapenem for 6 weeks. She was pain free at 12 months follow-up visit.

Diagnostic evaluation and management of culture-negative cardiovascular implantable electronic device infections.

BACKGROUND: Culture-negative (CN) cardiovascular implantable electronic device (CIED) infections represent a significant management challenge for clinicians with no specific guidelines addressing this subgroup of patients. The aim of the current investigation is to report our institutional experience of CN CIED infections and propose a systematic approach to diagnostic evaluation and management of these complicated cases based on our observations. METHODS: We retrospectively screened all CIED infection cases at Mayo Clinic from 2005 through 2017. Using standardized criteria to define significant microbial growth, all patients with positive blood or pocket/device cultures were excluded. RESULTS: A total of 835 cases of CIED infection were screened, and of these, 47 (6%) met CN-CIED infection criteria. Majority of patients (77%) in this cohort had received antimicrobial therapy prior to device cultures with a median duration of 8 days. The most common presentation was device pocket infection (81%). All patients underwent device removal. Route of antibiotics was switched from oral to parenteral and spectrum of activity expanded from initial therapy in 23% of patients despite negative cultures. Majority of patients (80%) were dismissed on parenteral therapy. Adverse events attributed to intravenous antibiotic therapy were documented in 63% of the cases. No recurrence was reported and 6-month survival was 94.8%. CONCLUSIONS: Pocket and device cultures in suspected CIED infections may be negative due to preextraction oral antibiotics. However, frequently these patients are managed with broad-spectrum parenteral therapy postextraction.

Efficacy of Antitoxin Therapy in Treating Patients With Foodborne Botulism: A Systematic Review and Meta-analysis of Cases, 1923-2016.

Background: Botulism is a rare, potentially severe illness, often fatal if not appropriately treated. Data on treatment are sparse. We systematically evaluated the literature on botulinum antitoxin and other treatments. Methods: We conducted a systematic literature review of published articles in PubMed via Medline, Web of Science, Embase, Ovid, and Cumulative Index to Nursing and Allied Health Literature, and included all studies that reported on the clinical course and treatment for foodborne botulism. Articles were reviewed by 2 independent reviewers and independently abstracted for treatment type and toxin exposure. We conducted a meta-analysis on the effect of timing of antitoxin administration, antitoxin type, and toxin exposure type. Results: We identified 235 articles that met the inclusion criteria, published between 1923 and 2016. Study quality was variable. Few (27%) case series reported sufficient data for inclusion in meta-analysis. Reduced mortality was associated with any antitoxin treatment (odds ratio [OR], 0.16; 95% confidence interval [CI], .09-.30) and antitoxin treatment within 48 hours of illness onset (OR, 0.12; 95% CI, .03-.41). Data did not allow assessment of critical care impact, including ventilator support, on survival. Therapeutic agents other than antitoxin offered no clear benefit. Patient characteristics did not predict poor outcomes. We did not identify an interval beyond which antitoxin was not beneficial. Conclusions: Published studies on botulism treatment are relatively sparse and of low quality. Timely administration of antitoxin reduces mortality; despite appropriate treatment with antitoxin, some patients suffer respiratory failure. Prompt antitoxin administration and meticulous intensive care are essential for optimal outcome.

Coadministration of Liposomal Amphotericin B and Contrast Medium Does Not Increase Risk of Kidney Injury.

Intravenous radiographic contrast medium and amphotericin B are commonly required in the care of patients with fungal infections. Both interventions have proposed nephrotoxicity through similar mechanisms. We systematically examined patients who received coadministration of liposomal amphotericin B (AmBisome; GE Healthcare) and intravenous contrast medium within a 24-h period and compared the results for those patients with the results for patients who underwent non-contrast medium studies. We found 114 cases and 85 controls during our study period. Overall, no increased risk of renal injury was seen with coadministration of these 2 agents. Adjustment for age, baseline kidney function, and other clinical factors through propensity score adjustment did not change this result. Our observations suggest that, when clinically indicated, coadministration of contrast medium and liposomal amphotericin B does not present excess risk compared with that from the administration of liposomal amphotericin B alone.

Periprosthetic Joint Infection: What's New?

Total joint arthroplasty (TJA) ranks among the most commonly performed orthopedic surgeries, with its annual incidence on the rise globally. Periprosthetic joint infection (PJI) remains a leading cause of arthroplasty failure. This review aims to summarize recent literature updates on the epidemiology, diagnosis, and management of PJI.

Outcomes of Invasive Fungal Infections Treated with Isavuconazole: A Retrospective Review.

BACKGROUND: Isavuconazole (ISA) has a favorable side effect profile that makes it attractive for treatment of invasive fungal infections (IFI). It carries FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data for other organisms and non-pulmonary infections. We conducted this review to investigate how ISA performed at treating IFI, with an especial interest in these non-approved indications. METHODS: We retrospectively identified and reviewed 131 patients who received ISA as treatment for IFI at our institution, some of whom received ISA as their first anti-fungal therapy and others who received ISA as either step-down therapy or salvage therapy. We identified the microbiologic cause of infection as well as the anatomic site involved for each patient. We then classified patients according to their response to ISA: namely cured, partially responded, or stabilized. RESULTS: The majority of patients were immunocompromised (n = 76, 58%). ISA was used primarily as a secondary therapy (n = 116, 89%); either as a step-down/switching from other agents, or as salvage therapy. The most common reasons for switching to ISA were toxicities with prior agents followed by QT prolongation. Although pulmonary aspergillosis and mucormycosis were represented in more than half of the cohort, ISA was also used off-label for treatment of other organisms such as endemic fungi (n = 19, 15%) as well as central nervous system (CNS) infections (n = 15, 11%). We have described the detailed clinical characteristics of these CNS infections cases. The overall clinical response rate varied by type of infection and site involved (57-73% response rate). CONCLUSIONS: We demonstrated encouraging clinical responses, particularly outside the FDA-approved indications, as well as good tolerability. This report highlights the critical need for expanded scope of prospective studies to delineate the efficacy of this better-tolerated agent, especially in central nervous system infections.

Acute Coxiella burnetii Infection: A 10-Year Clinical Experience at a Tertiary Care Center in the United States.

Background: Identifying and treating patients with acute Q fever who are at an increased risk of progressing to persistent disease is crucial for preventing future complications. In this study, we share our decade-long clinical experience with acute Q fever, highlighting the challenges that clinicians encounter from making an initial diagnosis and performing risk stratification to determining the appropriate prophylaxis regimen and duration. Methods: We retrieved records of adult Mayo Clinic patients (≥18 years) with positive Coxiella burnetii serology results between 1 January 2012 and 31 March 2022. Patients with Q fever anti-phase II immunoglobulin G ≥1:256 by indirect immunofluorescence were further analyzed. Results: Thirty-one patients were included. Their median age was 58 years (IQR, 50-64), and the majority were men (84%). Acute hepatitis (29%), flu-like illness (25.8%), and pneumonia (16%) were the most common presentations. Thirteen patients (42%) received antibiotic prophylaxis to prevent disease progression, with significant variation in the indications and duration across physicians. The combination of doxycycline and hydroxychloroquine was the preferred regimen. Prophylaxis was administered for a median 333 days (IQR, 168-414). Four patients (13%) progressed to Q fever native valve infective endocarditis, with elevated anticardiolipin immunoglobulin G levels being the sole risk factor in 2 cases. The small sample size precluded drawing conclusions on the impact of prophylaxis in preventing disease progression. Conclusions: Management of acute Q fever is complicated by the lack of comprehensive clinical guidelines leading to varied clinical practices. There is a critical need for randomized trials to establish robust evidence-based protocols for management.

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 Antibiotic Therapy Before Arthrocentesis on Synovial Fluid Cell Count and Differential for Diagnosis of Native Joint Septic Arthritis.

We examined the effect of preoperative antibiotic exposure and duration on synovial fluid samples from patients with native joint septic arthritis of the hip/knee. While exposure before diagnostic arthrocentesis did not affect fluid parameters, increased duration was associated with a decreased total nucleated cell count, underscoring the complex antibiotic effects on synovial fluid parameters.

Karius With a Q: Role for Microbial Cell-Free DNA Next-Generation Sequencing in Diagnosis of Acute Q Fever.

The diagnosis of Q fever can be challenging and a high index of suspicion is necessary. Within this case series, we highlight the utility of the microbial cell-free DNA next-generation sequencing or Karius Test in the timely diagnosis and management of acute Q fever.