Outpatient Treatment of Confirmed COVID-19: Living, Rapid Practice Points From the American College of Physicians (Version 1).

DESCRIPTION: Strategies to manage COVID-19 in the outpatient setting continue to evolve as new data emerge on SARS-CoV-2 variants and the availability of newer treatments. The Scientific Medical Policy Committee (SMPC) of the American College of Physicians (ACP) developed these living, rapid practice points to summarize the best available evidence on the treatment of adults with confirmed COVID-19 in an outpatient setting. These practice points do not evaluate COVID-19 treatments in the inpatient setting or adjunctive COVID-19 treatments in the outpatient setting. METHODS: The SMPC developed these living, rapid practice points on the basis of a living, rapid review done by the ACP Center for Evidence Reviews at Cochrane Austria at the University for Continuing Education Krems (Danube University Krems). The SMPC will maintain these practice points as living by monitoring and assessing the impact of new evidence. PRACTICE POINT 1: Consider molnupiravir to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 to 7 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 2: Consider nirmatrelvir-ritonavir combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 3: Consider remdesivir to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 7 days of the onset of symptoms and at high risk for progressing to severe disease. PRACTICE POINT 4: Do not use azithromycin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 5: Do not use chloroquine or hydroxychloroquine to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 6: Do not use ivermectin to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 7: Do not use nitazoxanide to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 8: Do not use lopinavir-ritonavir combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 9: Do not use casirivimab-imdevimab combination therapy to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 10: Do not use regdanvimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 11: Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting unless it is considered effective against a SARS-CoV-2 variant or subvariant locally in circulation. PRACTICE POINT 12: Do not use convalescent plasma to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 13: Do not use ciclesonide to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. PRACTICE POINT 14: Do not use fluvoxamine to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting.

Appropriate Use of Short-Course Antibiotics in Common Infections: Best Practice Advice From the American College of Physicians.

DESCRIPTION: Antimicrobial overuse is a major health care issue that contributes to antibiotic resistance. Such overuse includes unnecessarily long durations of antibiotic therapy in patients with common bacterial infections, such as acute bronchitis with chronic obstructive pulmonary disease (COPD) exacerbation, community-acquired pneumonia (CAP), urinary tract infections (UTIs), and cellulitis. This article describes best practices for prescribing appropriate and short-duration antibiotic therapy for patients presenting with these infections. METHODS: The authors conducted a narrative literature review of published clinical guidelines, systematic reviews, and individual studies that addressed bronchitis with COPD exacerbations, CAP, UTIs, and cellulitis. This article is based on the best available evidence but was not a formal systematic review. Guidance was prioritized to the highest available level of synthesized evidence. BEST PRACTICE ADVICE 1: Clinicians should limit antibiotic treatment duration to 5 days when managing patients with COPD exacerbations and acute uncomplicated bronchitis who have clinical signs of a bacterial infection (presence of increased sputum purulence in addition to increased dyspnea, and/or increased sputum volume). BEST PRACTICE ADVICE 2: Clinicians should prescribe antibiotics for community-acquired pneumonia for a minimum of 5 days. Extension of therapy after 5 days of antibiotics should be guided by validated measures of clinical stability, which include resolution of vital sign abnormalities, ability to eat, and normal mentation. BEST PRACTICE ADVICE 3: In women with uncomplicated bacterial cystitis, clinicians should prescribe short-course antibiotics with either nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole (TMP-SMZ) for 3 days, or fosfomycin as a single dose. In men and women with uncomplicated pyelonephritis, clinicians should prescribe short-course therapy either with fluoroquinolones (5 to 7 days) or TMP-SMZ (14 days) based on antibiotic susceptibility. BEST PRACTICE ADVICE 4: In patients with nonpurulent cellulitis, clinicians should use a 5- to 6-day course of antibiotics active against streptococci, particularly for patients able to self-monitor and who have close follow-up with primary care.

Decreasing High-risk Exposures for Healthcare Workers Through Universal Masking and Universal Severe Acute Respiratory Syndrome Coronavirus 2 Testing on Entry to a Tertiary Care Facility.

We describe the impact of universal masking and universal testing at admission on high-risk exposures to severe acute respiratory syndrome coronavirus 2 for healthcare workers. Universal masking decreased the rate of high-risk exposures per patient-day by 68%, and universal testing further decreased those exposures by 77%.

An Integrated Hospital Protocol for Persons With Injection-Related Infections May Increase Medications for Opioid Use Disorder Use but Challenges Remain.

BACKGROUND: Hospital-based strategies that link persons with infectious complications of opioid use disorder (OUD) to medications for OUD (MOUD) are of great interest. The objective of this study is to determine whether a hospital-based protocol would increase the use of MOUD and to identify barriers to MOUD during admission and at the time of discharge. METHODS: This study included participants with a documented or suspected history of injection drug usage receiving care for an infection at the University of Alabama at Birmingham Hospital from 2015 to 2018. The protocol, the intravenous antibiotic and addiction team (IVAT), included Addiction Medicine and Infectious Diseases consultation and a 9-item risk assessment. We quantified MOUD use before and after IVAT and used logistic regression to determine factors associated with MOUD. We explored barriers to MOUD uptake using chart review. RESULTS: A total of 37 and 98 patients met criteria in the pre- and post-IVAT periods, respectively. With IVAT, the percentage with OUD receiving MOUD significantly increased (29% pre-IVAT and 37% post-IVAT; P = .026) and MOUD use was higher in "high risk" participants (62%). Clinical and sociodemographic factors were not associated with MOUD receipt. CONCLUSIONS: A hospital-based protocol may increase the use of MOUD; however, the uptake of MOUD remains suboptimal (<50%).

Impact of Infectious Disease Consultation on Clinical Management and Mortality in Patients With Candidemia.

Candidemia has a high attributable mortality. The objective of this study was to determine the impact of infectious disease consultation on mortality and clinical outcomes in candidemia. Infectious disease consultation was associated with better adherence to guidelines and improved survival, even in patients with high Acute Physiology and Chronic Health Evaluation II scores.

A 9-Point Risk Assessment for Patients Who Inject Drugs and Require Intravenous Antibiotics: Focusing Inpatient Resources on Patients at Greatest Risk of Ongoing Drug Use.

A 9-point risk assessment identified persons with a history of injection drug use who were safe for discharge. "Low-risk" patients were discharged with outpatient antibiotics; others continued inpatient treatment. Use of the assessment reduced the mean length of stay by 20 days and total direct cost by 33%, creating capacity for an additional 333 patients.

Socio-demographic and comorbid risk factors for poor prognosis in patients hospitalized with community-acquired bacterial pneumonia in southeastern US.

BACKGROUND: How socio-demographic characteristics and comorbidities affect bacterial community-acquired pneumonia (CAP) prognosis during/after hospitalization is important in disease management. OBJECTIVES: To identify predictors of medical intensive care unit (MICU) admission, length of hospital stay (LOS), in-hospital mortality, and bacterial CAP readmission in patients hospitalized with bacterial CAP. METHODS: ICD-9/10 codes were used to query electronic medical records to identify a cohort of patients hospitalized for bacterial CAP at a tertiary hospital in Southeastern US between 01/01/2013-12/31/2019. Adjusted accelerated failure time and modified Poisson regression models were used to examine predictors of MICU admission, LOS, in-hospital mortality, and 1-year readmission. RESULTS: There were 1956 adults hospitalized with bacterial CAP. Median (interquartile range) LOS was 11 days (6-23), and there were 26 % (513) MICU admission, 14 % (266) in-hospital mortality, and 6 % (117) 1-year readmission with recurrent CAP. MICU admission was associated with heart failure (RR 1.38; 95 % CI 1.17-1.62) and obesity (RR 1.26; 95 % CI 1.04-1.52). Longer LOS was associated with heart failure (adjusted time ratio[TR] 1.27;95 %CI 1.12-1.43), stroke (TR 1.90;95 %CI 1.54,2.35), type 2 diabetes (TR 1.20;95 %CI 1.07-1.36), obesity (TR 1.50;95 %CI 1.31-1.72), Black race (TR 1.17;95 %CI 1.04-1.31), and males (TR 1.24;95 %CI 1.10-1.39). In-hospital mortality was associated with stroke (RR 1.45;95 %CI 1.03-2.04) and age ≥65 years (RR 1.34;95 %CI 1.06-1.68). 1-year readmission was associated with COPD (RR 1.55;95 %CI 1.05-2.27) and underweight BMI (RR 1.74;95 %CI 1.04-2.90). CONCLUSIONS: Comorbidities and socio-demographic characteristics have varying impacts on bacterial CAP in-hospital prognosis and readmission. More studies are warranted to confirm these findings to develop comprehensive care plans and inform public health interventions.

Short-course antibiotics for common infections: what do we know and where do we go from here?

BACKGROUND: Over the past 25 years, researchers have performed >120 randomized controlled trials (RCTs) illustrating short courses to be non-inferior to long courses of antibiotics for common bacterial infections. OBJECTIVE: We sought to determine whether clinical data from RCTs affirm the mantra of 'shorter is better' for antibiotic durations in 7 common infections: pneumonia, urinary tract infection, intra-abdominal infection, bacteraemia, skin and soft tissue infection, bone and joint infections, pharyngitis and sinusitis. SOURCES: Published RCTs comparing short- versus long-course antibiotic durations were identified through searches of PubMed and clinical guideline documents. CONTENT: Short-course antibiotic durations consistently result in similar treatment success rates as longer antibiotic courses among patients with community-acquired pneumonia, complicated urinary tract infections in women, gram-negative bacteraemia, and skin and soft tissue infections when the diagnosis is confirmed, appropriate antimicrobials are used, and patients show clinical signs of improvement. For patients with osteomyelitis, 6 weeks of antibiotics is adequate for the treatment of osteomyelitis in the absence of implanted foreign bodies and surgical debridement. Whether durations can be further shortened with debridement is unclear, although small studies are promising. IMPLICATIONS: With few exceptions, short courses were non-inferior to long courses; future research should focus on appropriately defining the patient population, ensuring the correct choice and dose of antimicrobials and developing meaningful outcomes relevant for frontline clinicians.

Understanding risk factors and microbial trends implicated in the development of Whipple-related surgical-site infections.

Objective: The purpose of this study is to understand the role of risk factors and postoperative complications seen in patients undergoing Whipple procedures in the development of surgical site infections. Our secondary goal was to evaluate whether microbial patterns differed between preoperative antibiotic classes, offering insight into the effectiveness of current practices while promoting antibiotic stewardship. Design: We performed a retrospective cohort study comparing patients with and without SSIs. Setting: This study was conducted at a tertiary-care center in the southeastern United States. Participants: Patients who underwent a Whipple procedure between 2012 and 2021 were acquired from the National Surgical Quality Improvement Program (NSQIP) database. Results: Patients with a bleeding disorder reported higher SSI rates (P = .04), whereas patients with a biliary stent reported lower surgical site infection (SSI) rates (P = .02) Those with postoperative complications had higher SSI rates, including delayed gastric emptying (P < .001) and pancreatic fistula (P < .001). Patients with longer operative times were 1.002 times more likely to develop SSIs (adjusted odds ratio [aOR], 1.002; 95% confidence interval [CI], 1.001-1.004; P = .006) whereas surgical indications for malignancy correlated with decreased SSIs risk (aOR, 0.578; 95% CI, 0.386-866) when adjusting for body mass index, surgical indication, and duration of surgical procedure. Conclusions: Optimizing preoperative management of modifiable risk factors for patients undergoing pancreatoduodenectomies and decreasing operative times may reduce SSI rates and patient and hospital burden. Further research is needed to understand whether stent placement reduces SSI risk in pancreatoduodenectomy.

Infectious Disease Hospital Preparedness: Lessons Learned From the 2019 Measles Outbreak.

OBJECTIVE: This paper: (1) explores the real and perceived threats to Emergency Departments (EDs) in addressing infectious disease cases in the US, like measles, and (2) identifies priorities for protecting employees, patients, and others stakeholders through hospital preparedness while streamlining processes and managing costs. METHODS: A case study approach was used to describe the events that triggered an infectious disease emergency response in 1 ED in the southeast. Development of the case study was informed by emergency preparedness literature on Homeland Security Exercise and Evaluation Program processes. RESULTS: Hospital staff and administrators identified a number of factors that either positively contributed to disease containment or exacerbated conditions for disease transmission. Successes included early recognition of the potential threat, development of a multidisciplinary taskforce, and implementation of a pre-incident response plan. Challenges comprised of patient flow in crisis response, lab turnaround time, and employee records. CONCLUSIONS: The threat of exposure challenged daily operations and raised situational awareness among administrators and providers to issues that might arise during an infectious disease exposure. Recording emergency preparedness successes, remediating challenges, and sharing information with others may help minimize the threat of communicable diseases within hospital settings in the future.

Clinical risk factors for admission with Pseudomonas and multidrug-resistant Pseudomonas community-acquired pneumonia.

BACKGROUND: Microbial etiology for community-acquired pneumonia (CAP) is evolving with pathogens known for high CAP mortality e.g., Pseudomonas species. Chronic obstructive pulmonary disease (COPD) patients are at risk for hospitalization for CAP. Understanding regional patterns and risk factors for multidrug-resistant (MDR) Pseudomonas acquisition has implications for antimicrobial stewardship. OBJECTIVES: To evaluate the regional epidemiology of MDR Pseudomonas CAP and its association with COPD. METHODS: We queried the electronic medical records of the University of Alabama at Birmingham Healthcare System to identify patients hospitalized for CAP with Pseudomonas positive respiratory samples between 01/01/2013-12/31/2019. Log binomial regression models were used to examine associations between COPD diagnosis and risk of Pseudomonas/MDR Pseudomonas CAP. RESULTS: Cohort consisted of 913 culture positive CAP cases aged 59-year (IQR:48-68), 61% (560) male, 60% (547) white, 65% (580) current/past smokers, and 42% (384) COPD. Prevalence of Pseudomonas CAP in culture positive CAP was 18% (167), MDR Pseudomonas CAP in Pseudomonas CAP was 22% (36), and yearly incidence of MDR Pseudomonas CAP was stable (p = 0.169). COPD was associated with Pseudomonas CAP (RR 1.39; 95% CI 1.01, 1.91; p = 0.041) but not with MDR Pseudomonas CAP (0.71; 95% CI 0.35, 1.45; p = 0.349). Stroke (RR 2.64; 95% CI 1.51, 4.61; p = 0.0006) and use of supplemental oxygen (RR 2.31; 95% CI 1.30, 4.12; p = 0.005) were associated with MDR Pseudomonas CAP. CONCLUSION: Incidence of MDR Pseudomonas CAP was stable over time. COPD was associated with Pseudomonas CAP but not with MDR Pseudomonas CAP. Larger cohort studies are needed to confirm findings.

Oral Is the New IV. Challenging Decades of Blood and Bone Infection Dogma: A Systematic Review.

BACKGROUND: We sought to determine if controlled, prospective clinical data validate the long-standing belief that intravenous (IV) antibiotic therapy is required for the full duration of treatment for 3 invasive bacterial infections: osteomyelitis, bacteremia, and infective endocarditis. METHODS: We performed a systematic review of published, prospective, controlled trials that compared IV-only to oral stepdown regimens in the treatment of these diseases. Using the PubMed database, we identified 7 relevant randomized controlled trials (RCTs) of osteomyelitis, 9 of bacteremia, 1 including both osteomyelitis and bacteremia, and 3 of endocarditis, as well as one quasi-experimental endocarditis study. Study results were synthesized via forest plots and funnel charts (for risk of study bias), using RevMan 5.4.1 and Meta-Essentials freeware, respectively. RESULTS: The 21 studies demonstrated either no difference in clinical efficacy, or superiority of oral versus IV-only antimicrobial therapy, including for mortality; in no study was IV-only treatment superior in efficacy. The frequency of catheter-related adverse events and duration of inpatient hospitalization were both greater in IV-only groups. DISCUSSION: Numerous prospective, controlled investigations demonstrate that oral antibiotics are at least as effective, safer, and lead to shorter hospitalizations than IV-only therapy; no contrary data were identified. Treatment guidelines should be modified to indicate that oral therapy is appropriate for reasonably selected patients with osteomyelitis, bacteremia, and endocarditis.

How fluoroquinolone preauthorization affects third- and fourth-generation cephalosporin use and resistance in a large academic hospital.

OBJECTIVE: We observed an overall increase in the use of third- and fourth-generation cephalosporins after fluoroquinolone preauthorization was implemented. We examined the change in specific third- and fourth-generation cephalosporin use, and we sought to determine whether there was a consequent change in non-susceptibility of select Gram-negative bacterial isolates to these antibiotics. DESIGN: Retrospective quasi-experimental study. SETTING: Academic hospital. INTERVENTION: Fluoroquinolone preauthorization was implemented in the hospital in October 2005. We used interrupted time series (ITS) Poisson regression models to examine trends in monthly rates of ceftriaxone, ceftazidime, and cefepime use and trends in yearly rates of nonsusceptible isolates (NSIs) of select Gram-negative bacteria before (1998-2004) and after (2006-2016) fluoroquinolone preauthorization was implemented. RESULTS: Rates of use of ceftriaxone and cefepime increased after fluoroquinolone preauthorization was implemented (ceftriaxone RR, 1.002; 95% CI, 1.002-1.003; P < .0001; cefepime RR, 1.003; 95% CI, 1.001-1.004; P = .0006), but ceftazidime use continued to decline (RR, 0.991, 95% CI, 0.990-0.992; P < .0001). Rates of ceftazidime and cefepime NSIs of Pseudomonas aeruginosa (ceftazidime RR, 0.937; 95% CI, 0.910-0.965, P < .0001; cefepime RR, 0.937; 95% CI, 0.912-0.963; P < .0001) declined after fluoroquinolone preauthorization was implemented. Rates of ceftazidime and cefepime NSIs of Enterobacter cloacae (ceftazidime RR, 1.116; 95% CI, 1.078-1.154; P < .0001; cefepime RR, 1.198; 95% CI, 1.112-1.291; P < .0001) and cefepime NSI of Acinetobacter baumannii (RR, 1.169; 95% CI, 1.081-1.263; P < .0001) were increasing before fluoroquinolone preauthorization was implemented but became stable thereafter: E. cloacae (ceftazidime RR, 0.987; 95% CI, 0.948-1.028; P = .531; cefepime RR, 0.990; 95% CI, 0.962-1.018; P = .461) and A. baumannii (cefepime RR, 0.972; 95% CI, 0.939-1.006; P = .100). CONCLUSIONS: Fluoroquinolone preauthorization may increase use of unrestricted third- and fourth-generation cephalosporins; however, we did not observe increased antimicrobial resistance to these agents, especially among clinically important Gram-negative bacteria known for hospital-acquired infections.

Daptomycin-Resistant Enterococcus Bacteremia Is Associated With Prior Daptomycin Use and Increased Mortality After Liver Transplantation.

BACKGROUND: Risk factors for acquisition of vancomycin-resistant Enterococcus (VRE) include immunosuppression, antibiotic exposure, indwelling catheters, and manipulation of the gastrointestinal tract, all of which occur in liver transplant recipients. VRE infections are documented in liver transplantation (LT); however, only one single center study has assessed the impact of daptomycin-resistant Enterococcus (DRE) in this patient population. METHODS: We conducted a retrospective multicenter cohort study comparing liver transplant recipients with either VRE or DRE bacteremia. The primary outcome was death within 1 year of transplantation. Multivariable logistic regression analyses were performed to calculate adjusted odds ratios for outcomes of interest. RESULTS: We identified 139 cases of Enterococcus bacteremia following LT, of which 78% were VRE and 22% were DRE. When adjusted for total intensive care unit days in the first transplant year, liver-kidney transplantation, and calcineurin inhibitor use, patients with DRE bacteremia were 2.65 times more likely to die within 1 year of transplantation (adjusted odds ratio [aOR], 2.648; 95% CI, 1.025-6.840; P = .044). Prior daptomycin exposure was found to be an independent predictor of DRE bacteremia (aOR, 30.62; 95% CI, 10.087-92.955; P < .001). CONCLUSIONS: In this multicenter study of LT recipients with Enterococcus bacteremia, DRE bacteremia was associated with higher 1-year mortality rates when compared with VRE bacteremia. Our data provide strong support for dedicated infection prevention and antimicrobial stewardship efforts for transplant patients. Further research is needed to support the development of better antibiotics for DRE and practical guidance focusing on identification and prevention of colonization and subsequent infection in liver transplant recipients at high risk for DRE bacteremia.

Infectious Diseases Consultation Is Associated With Decreased Mortality in Enterococcal Bloodstream Infections.

BACKGROUND: Enterococcus species frequently cause health care-associated bacteremia, with high attributable mortality. The benefit of consultation with infectious disease (ID) specialists has been previously illustrated with Staphylococcus aureus bacteremia. Whether ID consultation (IDC) improves mortality in enterococcal bacteremia is unknown. METHODS: This is a retrospective cohort single-center study from January 1, 2015, to June 30, 2016, that included all patients >18 years of age admitted with a first episode of Enterococcus bacteremia. Patients were excluded if death or transfer to palliative care occurred within 2 days of positive blood culture. RESULTS: Two hundred five patients were included in the study, of whom 64% received IDC. Participants who received IDC were more likely to undergo repeat cultures to ensure clearance (99% vs 74%; P < .001), echocardiography (79% vs 45%; P < .001), surgical intervention (20% vs 7%; P = 0.01), and have appropriate antibiotic duration (90% vs 46%; P < .001). Thirty-day mortality was significantly higher in the no-IDC group (27 % vs 12 %; P < .007). In multivariate analysis, 30-day in-hospital mortality was associated with both E. faecium bacteremia (adjusted odds ratio [aOR], 2.39; 95% confidence interval [CI], 1.09-5.23) and IDC (aOR, 0.35; 95% CI, 0.16-0.76). CONCLUSIONS: Patients who received IDC for Enterococcus bacteremia had significantly lower 30-day mortality. Further prospective studies are necessary to determine if these outcomes can be validated in other institutions for patients who receive IDC with Enterococcus bacteremia.