Effect of ß-Lactam Plus Macrolide Versus Fluoroquinolone on 30-Day Readmissions for Community-Acquired Pneumonia.

BACKGROUND: Antibiotic therapy with a macrolide and ß-lactam or a fluoroquinolone for the empirical treatment of community-acquired pneumonia (CAP) in an inpatient non-intensive care setting is recommended per guidelines. Studies show that these treatments have similar outcomes, including death, adverse effects, and bacterial eradication. However, a comparison of 30-day readmission rates between these treatments is limited. STUDY QUESTION: To determine whether 30-day readmissions for patients treated for CAP in a regional hospital differed between a fluoroquinolone monotherapy and a ß-lactam plus macrolide combination therapy. STUDY DESIGN: Retrospective cohort study of patients aged ≥18 years with a CAP diagnosis who were admitted to the same regional hospital from December 1, 2011, through December 1, 2016. MEASURES AND OUTCOMES: Patients receiving a third-generation cephalosporin plus macrolide were compared with those receiving a respiratory fluoroquinolone. Exclusion criteria were concurrent or recent use of the study antibiotics; death, transfer, or transition to hospice; and diagnosis of hospital-acquired pneumonia or health care-associated pneumonia. The collected data were 30-day readmission rates, antibiotic regimens, demographic characteristics, and pneumonia severity index and comorbidity scores. Association between treatment group and readmissions was assessed with logistic regression. Association between readmissions and individual data points between the 2 treatment groups was calculated with multivariate regression and odds ratio (95% confidence interval). RESULTS: Of 432 patients, 171 met inclusion criteria (fluoroquinolone group, n = 101; ß-lactam plus macrolide group, n = 70). Thirty-day readmissions were not significantly different between the fluoroquinolone group and ß-lactam plus macrolide group (P = 0.58). Increased 30-day readmissions were independently associated with male sex and hospital length of stay (P < 0.05). Length of stay was approximately 3 days and did not differ between treatment groups. CONCLUSIONS: No difference was seen in 30-day readmissions between CAP patients who received fluoroquinolone monotherapy and those who received ß-lactam plus macrolide combination therapy.

Reevaluation of commercial reagents for detection of Histoplasma capsulatum antigen in urine.

Detection of the Histoplasma capsulatum urinary antigen (UAg) is among the most sensitive and rapid means to diagnose histoplasmosis. Previously, we evaluated analyte-specific reagents (ASR) manufactured by IMMY (Norman, OK) for detection of Histoplasma galactomannan (GM) in urine using an enzyme immunoassay (EIA), and we showed low positive agreement (64.5%) with the MiraVista (MVista) Histoplasma antigen (Ag) quantitative EIA (MiraVista Diagnostics, Indianapolis, IN). Here we reevaluated the IMMY GM ASR following modification of our original assay protocol and introduction of an indeterminate range. A total of 150 prospectively collected urine samples were tested with both the IMMY and MVista EIAs, and clinical histories were recorded for all study subjects. The IMMY GM ASR showed positive and negative agreements of 82.3% (14/17 samples) and 100% (121/121 samples), respectively (with exclusion of 12 indeterminate results), and overall agreement of 90% (135/150 samples) with respect to the MVista EIA. Of the three patients with negative IMMY GM ASR results and positive MVista EIA results, testing was performed for initial diagnostic purposes for one patient (<0.4 ng/ml by the MVista EIA) and UAg levels were being monitored for the remaining two patients (both<0.7 ng/ml by the MVista EIA). The MVista EIA results were positive for 6/12 samples that tested indeterminate by the IMMY GM ASR. We also show that the IMMY GM ASR can be used to serially monitor Histoplasma UAg levels. In conclusion, we demonstrate that, with modification, the IMMY GM ASR is a reliable rapid assay for detection of Histoplasma UAg.

Effect of Pharmacist Audit on Antibiotic Duration for Pneumonia and Urinary Tract Infection.

OBJECTIVE: To assess the effect of clinical pharmacists in daily audits, under the direction of an antimicrobial stewardship program, of antibiotic treatment durations for the common inpatient disease states of community-acquired pneumonia (CAP) and urinary tract infection (UTI). PATIENTS AND METHODS: This was a retrospective single-center cohort study that evaluated the difference in the duration of antibiotic therapy for CAP or non-catheter-associated UTI of hospitalized patients who received a daily audit by clinical pharmacists compared with patients who did not receive a daily audit. Retrospective chart review included randomly selected hospitalized patients diagnosed with CAP or UTI during preaudit and postaudit periods. RESULTS: The preaudit group had 64 patients; and the postaudit group, 51 patients. The therapy duration was 7 days in the preaudit group and 6 days in the postaudit group (P=.55). Fluoroquinolone use was reduced in the postaudit group and was significantly less than in the preaudit group (24 [37.5%] vs 7 [13.7%]; P=.007). CONCLUSION: The daily audits of clinical pharmacists may be an effective method to reduce the duration of antibiotic therapy and are effective in the reduction of fluoroquinolone use. Additional studies must be done to further investigate the effects of clinical pharmacist antimicrobial stewardship efforts.

A Framework for Outpatient Infusion of Antispike Monoclonal Antibodies to High-Risk Patients with Mild-to-Moderate Coronavirus Disease-19: The Mayo Clinic Model.

The administration of spike monoclonal antibody treatment to patients with mild to moderate COVID-19 is very challenging. This article summarizes essential components and processes in establishing an effective spike monoclonal antibody infusion program. Rapid identification of a dedicated physical infrastructure was essential to circumvent the logistical challenges of caring for infectious patients while maintaining compliance with regulations and ensuring the safety of our personnel and other patients. Our partnerships and collaborations among multiple different specialties and disciplines enabled contributions from personnel with specific expertise in medicine, nursing, pharmacy, infection prevention and control, electronic health record (EHR) informatics, compliance, legal, medical ethics, engineering, administration, and other critical areas. Clear communication and a culture in which all roles are welcomed at the planning and operational tables are critical to the rapid development and refinement needed to adapt and thrive in providing this time-sensitive beneficial therapy. Our partnerships with leaders and providers outside our institutions, including those who care for underserved populations, have promoted equity in the access of monoclonal antibodies in our regions. Strong support from institutional leadership facilitated expedited action when needed, from a physical, personnel, and system infrastructure standpoint. Our ongoing real-time assessment and monitoring of our clinical program allowed us to improve and optimize our processes to ensure that the needs of our patients with COVID-19 in the outpatient setting are met.

Outcomes of COVID-19 With the Mayo Clinic Model of Care and Research.

OBJECTIVE: To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes. METHODS: We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models. RESULTS: A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19-directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care. CONCLUSION: Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.

Pharmacist-Driven MRSA Nasal PCR Screening and the Duration of Empirical Vancomycin Therapy for Suspected MRSA Respiratory Tract Infections.

OBJECTIVE: To assess the effect of a pharmacist-driven, polymerase chain reaction (PCR)-based nasal screening protocol for methicillin-resistant Staphylococcus aureus (MRSA) on vancomycin therapy duration and on rates of adverse drug events and 30-day hospital readmission. PATIENTS AND METHODS: From July 8, 2017, through January 31, 2019, we performed a retrospective, multicenter, preimplementation-postimplementation study. Patients with a vancomycin order to treat lower respiratory tract infection (LRTI) underwent MRSA PCR screening; tests were ordered by health care providers, including physicians, physician assistants, and advanced practice registered nurses. During the preimplementation period (July 8, 2017, through September 30, 2018), pharmacists could order MRSA PCR screening only after receiving a verbal order from a health care provider. During the postimplementation period (October 1, 2018, through January 31, 2019), a collaborative practice agreement allowed pharmacists to order MRSA PCR screening tests. RESULTS: The preimplementation group included 241 patients, and the postimplementation group included 74 patients. Of these patients, 124 in the preimplementation group and 62 in the postimplementation group received MRSA PCR screening. Twenty patients (16.1%) in the preimplementation group and 9 (14.5%) in the postimplementation group had a positive MRSA PCR screening test result (between-group difference, 1.6%; P=.80). Duration of therapy was significantly shorter in the postimplementation group (median [interquartile range], 14.3 [5.0-28.6] hours vs 24.0 [12.4-47.0] hours; P<.001). CONCLUSION: Vancomycin therapy carries a risk of adverse events and may increase health care costs. A pharmacist-driven protocol for MRSA nasal swab PCR screening effectively reduces the duration of vancomycin therapy for patients with lower respiratory tract infection.

GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Cohort Study.

OBJECTIVE: To assess the efficacy and safety of lenzilumab in patients with severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Hospitalized patients with COVID-19 pneumonia and risk factors for poor outcomes were treated with lenzilumab 600 mg intravenously for three doses through an emergency single-use investigational new drug application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. We also identified a cohort of patients matched to the lenzilumab patients for age, sex, and disease severity. Study dates were March 13, 2020, to June 18, 2020. All patients were followed through hospital discharge or death. RESULTS: Twelve patients were treated with lenzilumab; 27 patients comprised the matched control cohort (untreated). Clinical improvement, defined as improvement of at least 2 points on the 8-point ordinal clinical endpoints scale, was observed in 11 of 12 (91.7%) patients treated with lenzilumab and 22 of 27 (81.5%) untreated patients. The time to clinical improvement was significantly shorter for the lenzilumab-treated group compared with the untreated cohort with a median of 5 days versus 11 days (P=.006). Similarly, the proportion of patients with acute respiratory distress syndrome (oxygen saturation/fraction of inspired oxygen<315 mm Hg) was significantly reduced over time when treated with lenzilumab compared with untreated (P<.001). Significant improvement in inflammatory markers (C-reactive protein and interleukin 6) and markers of disease severity (absolute lymphocyte count) were observed in patients who received lenzilumab, but not in untreated patients. Cytokine analysis showed a reduction in inflammatory myeloid cells 2 days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab. CONCLUSION: In high-risk COVID-19 patients with severe pneumonia, granulocyte-macrophage colony-stimulating factor neutralization with lenzilumab was safe and associated with faster improvement in clinical outcomes, including oxygenation, and greater reductions in inflammatory markers compared with a matched control cohort of patients hospitalized with severe COVID-19 pneumonia. A randomized, placebo-controlled clinical trial to validate these findings is ongoing (NCT04351152).

First Clinical Use of Lenzilumab to Neutralize GM-CSF in Patients with Severe COVID-19 Pneumonia.

BACKGROUND: In COVID-19, high levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and inflammatory myeloid cells correlate with disease severity, cytokine storm, and respiratory failure. With this rationale, we used lenzilumab, an anti-human GM-CSF monoclonal antibody, to treat patients with severe COVID-19 pneumonia. METHODS: Hospitalized patients with COVID-19 pneumonia and risk factors for poor outcomes were treated with lenzilumab 600 mg intravenously for three doses through an emergency single-use IND application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. All patients receiving lenzilumab through May 1, 2020 were included in this report. RESULTS: Twelve patients were treated with lenzilumab. Clinical improvement was observed in 11 out of 12 (92%), with a median time to discharge of 5 days. There was a significant improvement in oxygenation: The proportion of patients with SpO2/FiO2 < 315 at the end of observation was 8% vs. compared to 67% at baseline (p=0.00015). A significant improvement in mean CRP and IL-6 values on day 3 following lenzilumab administration was also observed (137.3 mg/L vs 51.2 mg/L, p = 0.040; 26.8 pg/mL vs 16.1 pg/mL, p = 0.035; respectively). Cytokine analysis showed a reduction in inflammatory myeloid cells two days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab, and no mortality in this cohort of patients with severe COVID-19 pneumonia. CONCLUSIONS: In high-risk COVID-19 patients with severe pneumonia, GM-CSF neutralization with lenzilumab was safe and associated with improved clinical outcomes, oxygen requirement, and cytokine storm.

Diagnosis and Treatment of Isolated Cerebral Mucormycosis: Patient-Level Data Meta-Analysis and Mayo Clinic Experience.

BACKGROUND: Isolated cerebral mucormycosis is a rare and serious infection associated with intravenous drug abuse. METHODS: We performed a comprehensive meta-analysis of cases reported in studies and have included an unreported case from our institution. We searched PubMed/Medline, EMBASE, Scopus, Cochrane Databases, and our institution's electronic medical health records from inception through March 31, 2018. The cases were considered isolated (only affecting the cerebrum, cerebellum, or brainstem) if the absence of other primary sources of infection had been documented. Continuous variables were summarized using the median and interquartile range and categorical variables using frequencies and proportions. The relationships between variables were tested using the Wilcoxon rank sum and Pearson χ2 tests. RESULTS: A total of 130 studies (141 patients) met the eligibility requirements and were screened; 68 patients were included. The median age was 28 years (interquartile range, 24-38); 57% were men. Most patients had a history of intravenous drug abuse (82%), and 20% had positive human immunodeficiency virus findings. The lesion location was mostly supratentorial (91%), especially in the basal ganglia (71.2%). The cultures were positive in 38%, with Rhizopus the most common organism (59%). The mortality rate was 65%. The survivors were significantly more likely to have received amphotericin B (92% vs. 43%; P < 0.001) or to have undergone stereotactic aspiration (58% vs. 25%; P < 0.01). CONCLUSIONS: Isolated cerebral mucormycosis has a pooled mortality rate of 65%. The presence of lesions in the basal ganglia, rapidly progressive symptoms, and a history of intravenous drug abuse should raise suspicion for the early initiation of amphotericin B and stereotactic aspiration.

Actinomyces meyeri Popliteal Cyst Infection and Review of the Literature.

A 66-year-old, Caucasian male presented with pain and swelling involving the left knee of one-week duration. Arthrocentesis was negative for evidence of septic arthritis. Magnetic resonance imaging (MRI) study of the left knee showed degenerative arthritis, partial tear of medial meniscus, and a complex fluid collection along the posteromedial aspect of the left knee suggestive of popliteal cyst. He underwent arthroscopy with partial medial meniscectomy. Intraoperative joint fluid was noted to be cloudy but cultures were negative. Arthroscopic procedure provided him with temporary relief but the pain and swelling in the posterior aspect of the left knee recurred in 6 weeks. Repeat MRI showed complex fluid collection in the posterolateral aspect of left knee. Ultrasound guided aspiration of the fluid collection revealed purulent material and cultures grew Actinomyces meyeri. He was treated with 6 weeks of intravenous penicillin regimen followed by 18 months of oral penicillin.

Lactobacillus gasseri Causing Bilateral Empyema.

Lactobacilli are common commensal bacteria found in the gastrointestinal and genitourinary tract. Although they are usually thought to be nonpathogenic, there have been several cases that demonstrate severe infections caused by these microorganisms. This is a case of a 49-year-old male with previously undiagnosed type two diabetes mellitus who presented with a 3-month history of cough and was found to have right sided Lactobacillus gasseri empyema for which he underwent video-assisted thoracoscopic surgery (VATS) with chest tube placement. He subsequently developed a left sided pleural empyema for which the aspiration also grew out L. gasseri. The patient made a complete recovery and was seen for four months in follow-up after his initial presentation.

Acute infection of Viabahn stent graft in the popliteal artery.

Peripheral stents are increasingly used for treatment of peripheral arterial disease, yet all implanted devices are potentially at risk for infection. We describe a 51-year-old man who underwent stenting in the femoropopliteal artery and presented 3 days later with leg pain, fever, and evidence of peripheral stigmata of embolization. Blood cultures grew methicillin-resistant Staphylococcus aureus and remained persistently positive despite antibiotic therapy. At surgical exploration, the popliteal artery had essentially been disintegrated by the infection, with only visible stent graft maintaining arterial continuity. Acute stent graft infections are rare and must be managed promptly to reduce morbidity.

Streptococcus gordonii prosthetic joint infection in the setting of vigorous dental flossing.

A 65-year-old woman with osteoarthritis, who underwent knee replacement 5 years prior, developed sudden onset knee pain and swelling. She had voluntarily starting a vigorous dental flossing regimen prior to the onset of symptoms. The patient underwent right knee arthrotomy, irrigation and debridement of right total knee arthroplasty and exchange of polyethylene with retention of the prosthesis. Intraoperative cultures grew Streptococcus gordonii. She was treated with 6 weeks of ceftriaxone and was later placed on oral antibiotic suppression.

Clostridium hathewayi bacteraemia and surgical site infection after uterine myomectomy.

A 42-year-old woman with uterine fibroids underwent myomectomy. She developed postoperative sepsis and bloodstream infection with Clostridium hathewayi secondary to an infected haematoma. The patient was readmitted after failure of oral antibiotic therapy and underwent intrauterine drainage followed by prolonged parenteral antibiotic therapy. The patient was followed for 1 year and did not have any relapse of infection.

Cardiovascular implantable electronic device infection: a stepwise approach to diagnosis and management.

Infection related to cardiovascular implantable electronic devices is a serious complication, necessitating removal of the device and prolonged parenteral antibiotic therapy. Accurate diagnosis and optimal management of these infections are challenging. This review highlights the critical management decisions.

Mycobacterium wolinskyi: a case series and review of the literature.

Mycobacterium wolinskyi is an uncommonly encountered rapidly growing mycobacterium. To date, only 12 clinical cases have been reported in the literature. In this report, we describe 5 additional cases of M. wolinskyi infection seen at the Mayo Clinic in Rochester, MN, since 2009. The clinical manifestations were sternal wound infections (n = 2), a surgical site wound infection, a cardiac-device pocket site infection, and a vascular graft infection with bacteremia. The infections occurred in both immunocompetent and immunosuppressed patients, including a lung transplant recipient. Treatment of M. wolinskyi infections required a prolonged course of combination antimicrobial treatment and surgical debridement.