Influence of Antibiotic Exposure Intensity on the Risk of Clostridioides difficile Infection.

BACKGROUND: Antibiotics are a strong risk factor for Clostridioides difficile infection (CDI), and CDI incidence is often measured as an important outcome metric for antimicrobial stewardship interventions aiming to reduce antibiotic use. However, risk of CDI from antibiotics varies by agent and dependent on the intensity (i.e., spectrum and duration) of antibiotic therapy. Thus, the impact of stewardship interventions on CDI incidence is variable, and understanding this risk requires a more granular measure of intensity of therapy than traditionally used measures like days of therapy (DOT). METHODS: We performed a retrospective cohort study to measure the independent association between intensity of antibiotic therapy, as measured by the antibiotic spectrum index (ASI), and hospital-associated CDI (HA-CDI) at a large academic medical center between January 2018 and March 2020. We constructed a marginal Poisson regression model to generate adjusted relative risks for a unit increase in ASI per antibiotic day. RESULTS: We included 35,457 inpatient encounters in our cohort. Sixty-eight percent of patients received at least one antibiotic. We identified 128 HA-CDI cases, which corresponds to an incidence rate of 4.1 cases per 10,000 patient-days. After adjusting for known confounders, each additional unit increase in ASI per antibiotic day is associated with 1.09 times the risk of HA-CDI (Relative Risk = 1.09, 95% Confidence Interval: 1.06 to 1.13). CONCLUSIONS: ASI was strongly associated with HA-CDI and could be a useful tool in evaluating the impact of antibiotic stewardship on HA-CDI rates, providing more granular information than the more commonly used days of therapy.

Shared Decision-Making for Partial Oral Antibiotic Treatment of Infective Endocarditis: A Case Series.

Although literature has demonstrated the noninferiority of oral antibiotics in the treatment of infectious endocarditis, widespread adoption of this practice has yet to occur in the United States. We report on 32 patients with infectious endocarditis treated by a multidisciplinary endocarditis team and a standardized approach to partial oral antibiotic therapy with a high rate of clinical success.

Dalba Got Back? Use of Dalbavancin for the Treatment of Vertebral Osteomyelitis.

Data evaluating dalbavancin use for vertebral osteomyelitis remain limited. In our retrospective cohort, 29 of 34 (85.3%) patients completed their dalbavancin course. Adverse reactions occurred for 6 (17.6%) and infection recurrence in 3 (8.8%) within 90 days. Dalbavancin appears to be safe and well-tolerated for vertebral osteomyelitis.

Use of electronic health record data to identify hospital-associated Clostridioides difficile infections: a validation study.

Background: Clinical research focused on the burden and impact of Clostridioides difficile infection (CDI) often relies upon accurate identification of cases using existing health record data. Use of diagnosis codes alone can lead to misclassification of cases. Our goal was to develop and validate a multi-component algorithm to identify hospital-associated CDI (HA-CDI) cases using electronic health record (EHR) data. Methods: We performed a validation study using a random sample of adult inpatients at a large academic hospital setting in Portland, Oregon from January 2018 to March 2020. We excluded patients with CDI on admission and those with short lengths of stay (< 4 days). We tested a multi-component algorithm to identify HA-CDI; case patients were required to have received an inpatient course of metronidazole, oral vancomycin, or fidaxomicin and have at least one of the following: a positive C. difficile laboratory test or the International Classification of Diseases, Tenth Revision (ICD-10) code for non-recurrent CDI. For a random sample of 80 algorithm-identified HA-CDI cases and 80 non-cases, we performed manual EHR review to identify gold standard of HA-CDI diagnosis. We then calculated overall percent accuracy, sensitivity, specificity, and positive and negative predictive value for the algorithm overall and for the individual components. Results: Our case definition algorithm identified HA-CDI cases with 94% accuracy (95% Confidence Interval (CI): 88% to 97%). We achieved 100% sensitivity (94% to 100%), 89% specificity (81% to 95%), 88% positive predictive value (78% to 94%), and 100% negative predictive value (95% to 100%). Requiring a positive C. difficile test as our gold standard further improved diagnostic performance (97% accuracy [93% to 99%], 93% PPV [85% to 98%]). Conclusions: Our algorithm accurately detected true HA-CDI cases from EHR data in our patient population. A multi-component algorithm performs better than any isolated component. Requiring a positive laboratory test for C. difficile strengthens diagnostic performance even further. Accurate detection could have important implications for CDI tracking and research.

The hidden cost of dalbavancin: OPAT RN time required in coordination for persons who use drugs.

Background: Serious infections in persons who use drugs (PWUD) are rising. Dalbavancin, due to its extended half-life, offers an alternative treatment for patients in whom standard of care antibiotics are not feasible or practical, allowing for reduced hospital days and the avoidance of central line placement or the use of complex oral regimens. Objectives: We aim to describe the time and effort required for coordination of dalbavancin courses by outpatient registered nurses (RNs) and other outpatient parenteral antimicrobial therapy (OPAT) staff. Design and methods: We conducted a retrospective review of adult patients with documented substance use who received at least one dose of dalbavancin and quantified the number of interventions required by our OPAT RNs and other OPAT staff for coordination of dalbavancin courses. Additionally, detailed data on time spent per intervention were prospectively collected for a 1-month period. Results: A total of 52 patients with 53 dalbavancin courses were included. Most substance use was intravenous. Infectious diagnoses included bone and joint infections (61%) and endocarditis (7%), in addition to skin and soft tissue infections (19%). Infections were most commonly caused by Staphylococcus aureus (62%). RN intervention was required in the coordination of 60% of all courses and in 77% of courses in which at least one outpatient dose was needed. Adverse reactions occurred in one patient (2%) and 90-day readmissions due to infectious complications occurred in two patients (4%). Detailed time analysis was performed for seven consecutive patients, with a total of 179 min spent by OPAT RNs on coordination. Conclusions: The ease of dalbavancin administration does not eliminate the need for extensive RN coordination for successful administration of doses in the outpatient setting for PWUD. This need should be accounted for in program staffing to help increase successful dalbavancin course completion.

Open-Label Trial of Amikacin Liposome Inhalation Suspension in Mycobacterium abscessus Lung Disease.

BACKGROUND: Mycobacterium abscessus is the second most common nontuberculous mycobacterium respiratory pathogen and shows in vitro resistance to nearly all oral antimicrobials. M abscessus treatment success is low in the presence of macrolide resistance. RESEARCH QUESTION: Does treatment with amikacin liposome inhalation suspension (ALIS) improve culture conversion in patients with M abscessus pulmonary disease who are treatment naive or who have treatment-refractory disease? STUDY DESIGN AND METHODS: In an open-label protocol, patients were given ALIS (590 mg) added to background multidrug therapy for 12 months. The primary outcome was sputum culture conversion defined as three consecutive monthly sputum cultures showing negative results. The secondary end point included development of amikacin resistance. RESULTS: Of 33 patients (36 isolates) who started ALIS with a mean age of 64 years (range, 14-81 years), 24 patients (73%) were female, 10 patients (30%) had cystic fibrosis, and nine patients (27%) had cavitary disease. Three patients (9%) could not be evaluated for the microbiologic end point because of early withdrawal. All pretreatment isolates were amikacin susceptible and only six isolates (17%) were macrolide susceptible. Eleven patients (33%) were given parenteral antibiotics. Twelve patients (40%) received clofazimine with or without azithromycin as companion therapy. Fifteen patients (50%) with evaluable longitudinal microbiologic data demonstrated culture conversion, and 10 patients (67%) sustained conversion through month 12. Six of the 33 patients (18%) demonstrated mutational amikacin resistance. All were patients using clofazimine or clofazimine plus azithromycin as companion medication(s). Few serious adverse events occurred for ALIS users; however, reduction of dosing to three times weekly was common (52%). INTERPRETATION: In a cohort of patients primarily with macrolide-resistant M abscessus, one-half of the patients using ALIS showed sputum culture conversion to negative findings. The emergence of mutational amikacin resistance was not uncommon and occurred with the use of clofazimine monotherapy. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03038178; URL: www. CLINICALTRIALS: gov.

Expanding the Team: Optimizing the Multidisciplinary Management of Drug Use-Associated Infective Endocarditis.

Amidst a substance use epidemic, hospitalizations and valve surgeries related to drug use-associated infective endocarditis (DU-IE) rose substantially in the last decade. Rates of reoperation and mortality remain high, yet in many hospitals patients are not offered valve surgery or evidence-based addiction treatment. A multidisciplinary team approach can improve outcomes in patients with infective endocarditis; however, the breadth of expertise that should be incorporated into this team is inadequately conceptualized. It is our opinion that incorporating addiction medicine services into the team may improve outcomes in DU-IE. Here, we describe our experience incorporating addiction medicine services into the multidisciplinary management of DU-IE and share implications for other hospitals and health systems looking to improve care for people with DU-IE.

"OPTIONS-DC", a feasible discharge planning conference to expand infection treatment options for people with substance use disorder.

BACKGROUND: Serious bacterial infections associated with substance use often result in long hospitalizations, premature discharges, and high costs. Out-of-hospital treatment options in people with substance use disorder (SUD) are often limited. METHODS: We describe a novel multidisciplinary and interprofessional care conference, "OPTIONS-DC," to identify treatment options agreeable to both patients and providers using the frameworks of harm reduction and patient-centered care. We retrospectively reviewed charts of patients who had an OPTIONS-DC between February 2018 and July 2019 and used content analysis to understand the conferences' effects on antibiotic treatment options. RESULTS: Fifty patients had an OPTIONS-DC during the study window. Forty-two (84%) had some intravenous (IV) substance use and 44 (88%) had an active substance use disorder. Participants' primary substances included opioids (65%) or methamphetamines (28%). On average, conferences lasted 28 min. OPTIONS-DC providers recommended out-of-hospital antibiotic treatment options for 34 (68%) of patients. OPTIONS-DC recommended first line therapy of IV antibiotics for 35 (70%) patients, long-acting injectable antibiotics for 14 (28%), and oral therapy for 1 (2%). 35 (70%) patients that had an OPTIONS-DC completed an antibiotic course and 6 (12%) left the hospital prematurely. OPTIONS-DC expanded treatment options by exposing and contextualizing SUD, psychosocial risk and protective factors; incorporating patient preferences; and allowing providers to tailor antibiotic and SUD recommendations. CONCLUSIONS: OPTIONS-DC is a feasible intervention that allows providers to integrate principles of harm reduction and offer patient-centered choices among patients needing prolonged antibiotic treatment.

Reductions in vancomycin and meropenem following the implementation of a febrile neutropenia management algorithm in hospitalized adults: An interrupted time series analysis.

OBJECTIVE: To evaluate broad-spectrum intravenous antibiotic use before and after the implementation of a revised febrile neutropenia management algorithm in a population of adults with hematologic malignancies. DESIGN: Quasi-experimental study. SETTING AND POPULATION: Patients admitted between 2014 and 2018 to the Adult Malignant Hematology service of an acute-care hospital in the United States. METHODS: Aggregate data for adult malignant hematology service were obtained for population-level antibiotic use: days of therapy (DOT), C. difficile infections, bacterial bloodstream infections, intensive care unit (ICU) length of stay, and in-hospital mortality. All rates are reported per 1,000 patient days before the implementation of an febrile neutropenia management algorithm (July 2014-May 2016) and after the intervention (June 2016-December 2018). These data were compared using interrupted time series analysis. RESULTS: In total, 2,014 patients comprised 6,788 encounters and 89,612 patient days during the study period. Broad-spectrum intravenous (IV) antibiotic use decreased by 5.7% with immediate reductions in meropenem and vancomycin use by 22 (P = .02) and 15 (P = .001) DOT per 1,000 patient days, respectively. Bacterial bloodstream infection rates significantly increased following algorithm implementation. No differences were observed in the use of other antibiotics or safety outcomes including C. difficile infection, ICU length of stay, and in-hospital mortality. CONCLUSIONS: Reductions in vancomycin and meropenem were observed following the implementation of a more stringent febrile neutropenia management algorithm, without evidence of adverse outcomes. Successful implementation occurred through a collaborative effort and continues to be a core reinforcement strategy at our institution. Future studies evaluating patient-level data may identify further stewardship opportunities in this population.

Population-based trends in hospitalizations due to injection drug use-related serious bacterial infections, Oregon, 2008 to 2018.

BACKGROUND: Injection drug use has far-reaching social, economic, and health consequences. Serious bacterial infections, including skin/soft tissue infections, osteomyelitis, bacteremia, and endocarditis, are particularly morbid and mortal consequences of injection drug use. METHODS: We conducted a population-based retrospective cohort analysis of hospitalizations among patients with a diagnosis code for substance use and a serious bacterial infection during the same hospital admission using Oregon Hospital Discharge Data. We examined trends in hospitalizations and costs of hospitalizations attributable to injection drug use-related serious bacterial infections from January 1, 2008 through December 31, 2018. RESULTS: From 2008 to 2018, Oregon hospital discharge data included 4,084,743 hospitalizations among 2,090,359 patients. During the study period, hospitalizations for injection drug use-related serious bacterial infection increased from 980 to 6,265 per year, or from 0.26% to 1.68% of all hospitalizations (P<0.001). The number of unique patients with an injection drug use-related serious bacterial infection increased from 839 to 5,055, or from 2.52% to 8.46% of all patients (P<0.001). While hospitalizations for all injection drug use-related serious bacterial infections increased over the study period, bacteremia/sepsis hospitalizations rose most rapidly with an 18-fold increase. Opioid use diagnoses accounted for the largest percentage of hospitalizations for injection drug use-related serious bacterial infections, but hospitalizations for amphetamine-type stimulant-related serious bacterial infections rose most rapidly with a 15-fold increase. People living with HIV and HCV experienced increases in hospitalizations for injection drug use-related serious bacterial infection during the study period. Overall, the total cost of hospitalizations for injection drug use-related serious bacterial infections increased from $16,305,129 in 2008 to $150,879,237 in 2018 (P<0.001). CONCLUSIONS: In Oregon, hospitalizations for injection drug use-related serious bacterial infections increased dramatically and exacted a substantial cost on the health care system from 2008 to 2018. This increase in hospitalizations represents an opportunity to initiate substance use disorder treatment and harm reduction services to improve outcomes for people who inject drugs.

Top Questions in the Diagnosis and Treatment of Pulmonary M. abscessus Disease.

Mycobacterium abscessus disease is particularly challenging to treat, given the intrinsic drug resistance of this species and the limited data on which recommendations are based, resulting in a greater reliance on expert opinion. We address several commonly encountered questions and management considerations regarding pulmonary Mycobacterium abscessus disease, including the role of subspecies identification, diagnostic criteria for determining disease, interpretation of drug susceptibility test results, approach to therapy including the need for parenteral antibiotics and the role for new and repurposed drugs, and the use of adjunctive strategies such as airway clearance and surgical resection.

Gordonia bronchialis-Associated Endophthalmitis, Oregon, USA.

Gordonia bronchialis is an aerobic actinomycetes that rarely causes infections in humans. Few reports describe Gordonia spp. causing eye-related infections. We report a case of chronic infectious endophthalmitis in Oregon, USA, associated with infection by G. bronchialis.

Diagnostic accuracy of TB-LAMP for pulmonary tuberculosis: a systematic review and meta-analysis.

BACKGROUND: The need for a rapid, molecular test to diagnose tuberculosis (TB) has prompted exploration of TB-LAMP (Eiken; Tokyo, Japan) for use in resource-limited settings. We conducted a systematic review to assess the accuracy of TB-LAMP as a diagnostic test for pulmonary TB. METHODS: We analyzed individual-level data for eligible patients from all studies of TB-LAMP conducted between Jan 2012 and October 2015 to compare the diagnostic accuracy of TB-LAMP with that of smear microscopy and Xpert MTB/RIF® using 3 reference standards of varying stringency. Pooled sensitivity and specificity and pooled differences in sensitivity and specificity were estimated using random effects meta-analysis. Study quality was evaluated using QUADAS-2. RESULTS: Four thousand seven hundred sixty individuals across 13 studies met eligibility criteria. Methodological quality was judged to be low for all studies. TB-LAMP had higher sensitivity than sputum smear microscopy (pooled sensitivity difference + 13·2, 95% CI 4·5-21·9%) and similar sensitivity to Xpert MTB/RIF (pooled sensitivity difference - 2·5, 95% CI -8·0 to + 2·9) using the most stringent reference standard available. Specificity of TB-LAMP was similar to that of sputum smear microscopy (pooled specificity difference - 1·8, 95% CI -3·8 to + 0·2) and Xpert MTB/RIF (pooled specificity difference 0·5, 95% CI -0·9 to + 1·8). CONCLUSIONS: From the perspective of diagnostic accuracy, TB-LAMP may be considered as an alternative test for sputum smear microscopy. Additional factors such as cost, feasibility, and acceptability in settings that continue to rely on sputum smear microscopy should be considered when deciding to adopt this technology. Xpert MTB/RIF should continue to be preferred in settings where resource and infrastructure requirements are adequate and where HIV co-infection or drug-resistance is of concern.

Clinical Practice Variation Among Adult Infectious Disease Physicians in the Management of Staphylococcus aureus Bacteremia.

Infectious disease management of Staphylococcus aureus bacteremia (SAB) was surveyed through the Emerging Infections Network. Although there were areas of consensus, we found substantial practice variation in diagnostic evaluation and management of adult patients with SAB. These findings highlight opportunities for further research and guidance to define best practices.

Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV.

BACKGROUND: Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy. METHODS: Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and July 2013 with a cough ≥ 2 weeks were enrolled. Patients underwent extensive evaluation for pulmonary TB. Concentrations of 43 cytokines/chemokines were measured at the same time point as C-reactive protein (CRP) in banked plasma samples using commercially-available multiplex kits. Advanced classification algorithms were used to rank cytokines/chemokines for their ability to identify TB, and to model the specificity of the top-ranked cytokines/chemokines individually and in combination with sensitivity constrained to ≥ 90% as recommended for TB screening. RESULTS: The median plasma level of 5 biomarkers (IL-6, INF-γ, MIG, CRP, IL-18) was significantly different between patients with and without TB. With sensitivity constrained to 90%, all had low specificity with IL-6 showing the highest specificity (44%; 95% CI 37.4-49.5). Biomarker panels were found to be more valuable than any biomarker alone. A panel combining IFN-γ and IL-6 had the highest specificity (50%; 95% CI 46.7-53.3). Sensitivity remained high (>85%) for all panels among sputum smear-negative TB patients. CONCLUSIONS: Direct measurement of unstimulated plasma cytokines/chemokines in peripheral blood is a promising approach to TB screening. Cytokine/chemokine panels retained high sensitivity for smear-negative TB and achieved improved specificity compared to individual cytokines/chemokines. These markers should be further evaluated in outpatient settings where most TB screening occurs and where other illnesses associated with systematic inflammation are less common.

Treatment of Mycobacterium abscessus Complex.

Of the nontuberculous mycobacteria (NTMs) causing lung disease, members of the Mycobacterium abscessus complex (MABc) present a formidable obstacle to successful management. This challenge starts from a poorly understood pathogenesis, continues with complicated subspecies variation in treatment response, and extends to the multidrug-resistant nature of these organisms. The disease often necessitates the use of intravenous therapy, toxic drug combinations, and, in some cases, lung resection. Like many NTMs, MABc treatment requires prolonged therapy with multiple medications, and pulmonary disease in some subspecies can be impossible to eradicate or cure. This disease also represents a frequent and unique problem in certain populations, including cystic fibrosis and lung transplant recipients, and providers who manage such patients should be familiar with how MABc disease influences management. Because of the rising prevalence of the MABc, especially in patients with complicated underlying pulmonary disease, it is increasingly necessary for infectious diseases and pulmonary medicine clinicians to understand the unique aspects of MABc management and understand when to obtain expert consultation in the care of these patients.