BACKGROUND: Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. RESEARCH QUESTION: There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. STUDY DESIGN AND METHODS: This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. RESULTS: The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. INTERPRETATION: This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia.

No abstract

ImportanceThe effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown.ObjectiveTo evaluate the efficacy of ivermectin, 400 μg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19.Design, Setting, and ParticipantsACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US.InterventionsParticipants were randomized to receive ivermectin, 400 μg/kg (n = 817), daily for 3 days or placebo (n = 774).Main Outcomes and MeasuresTime to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28.ResultsAmong 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]).Conclusions and RelevanceAmong outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19.Trial RegistrationClinicalTrials.gov Identifier: NCT04885530

The decision to hospitalize a patient with CAP due to 2009 H1N1 influenza should not be based on current CAP severity scores, as they underestimate mortality rates in a significant number of patients. Patients with obesity or wheezing should be considered at an increased risk for mortality.

ImportanceThe effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear.ObjectiveTo evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US.Design, Setting, and ParticipantsThe ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial was designed to test repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 participants aged 30 years or older with test-confirmed SARS-CoV-2 infection and experiencing 2 or more symptoms of acute COVID-19 for 7 days or less were enrolled between August 6, 2021, and May 27, 2022, at 91 sites in the US.InterventionsParticipants were randomized to receive 50 mg of fluvoxamine twice daily for 10 days or placebo.Main Outcomes and MeasuresThe primary outcome was time to sustained recovery (defined as the third day of 3 consecutive days without symptoms). There were 7 secondary outcomes, including a composite outcome of hospitalization, urgent care visit, emergency department visit, or death through day 28.ResultsAmong 1331 participants who were randomized (median age, 47 years [IQR, 38-57 years]; 57% were women; and 67% reported receiving ≥2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (674 in the fluvoxamine group and 614 in the placebo group). The median time to sustained recovery was 12 days (IQR, 11-14 days) in the fluvoxamine group and 13 days (IQR, 12-13 days) in the placebo group (hazard ratio [HR], 0.96 [95% credible interval, 0.86-1.06], posterior P = .21 for the probability of benefit [determined by an HR >1]). For the composite outcome, 26 participants (3.9%) in the fluvoxamine group were hospitalized, had an urgent care visit, had an emergency department visit, or died compared with 23 participants (3.8%) in the placebo group (HR, 1.1 [95% credible interval, 0.5-1.8], posterior P = .35 for the probability of benefit [determined by an HR <1]). One participant in the fluvoxamine group and 2 participants in the placebo group were hospitalized; no deaths occurred in either group. Adverse events were uncommon in both groups.Conclusions and RelevanceAmong outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.Trial RegistrationClinicalTrials.gov Identifier: NCT04885530

The coronavirus disease 2019 (COVID-19) pandemic is provoking a global public health crisis. Even though the academic world is intensively pursuing new therapies, there is still no ''game changer'' in the management of COVID 19. The Mammalian Target of Rapamycin (mTOR) is an ancient signaling system that has been proposed as a molecular tool used by coronaviruses and other RNA and DNA viruses in order to replicate and persist in the host cell. In recent years, Intermittent Fasting (IF), a practice consisting on a strict calorie restriction during a prolonged period of time during the day, has gained popularity due to its potential benefits in multiple health systems and in regulating inflammation. IF inhibits the mTOR pathway which is similar to the effects of Rapamycin in some animal models. mTOR inhibition and promotion of autophagy could potentially be the link between the possible direct benefits of IF in COVID-19 due to the interruption of the viral cycle (protein synthesis). Besides, IF has shown to be a strong anti-inflammatory in multiple prior studies, and may play a role in attenuating COVID -19 severity. This review hypothesizes the possible intersection between viral, immunological, and metabolic pathways related to mTOR and the potential mechanisms through which IF may improve clinical outcomes. Future prospective randomized controlled clinical trials to evaluate intermittent fasting (IF) regimens in order to prevent and treat moderate to severe forms of COVID-19 in humans are needed.

Varicella Zoster when described has the typical presentation of a dermatomal distribution of a rash and can further lead to CNS complications. This can be treated accordingly with the proper protocol, but if the presentation is atypical and the protocol is challenged or changed per specific patient outcomes, new developments can occur. Here we present a case of a 29-year-old Caucasian female that presented to the emergency department with headache, photophobia, and chills for 5 days. She was previously healthy and immunocompetent; CSF PCR analysis revealed a VZV infection causing acute aseptic meningitis with no shingles rash eruption on physical examination. The patient was not willing to stay hospitalized for the duration of the treatment. This gave us an opportunity to treat her with an oral, rather than IV, antiviral. The patient was successfully treated with oral valacyclovir 2 g Q6H after only receiving two days of IV acyclovir. To the best of our knowledge, this is the first reported case of a patient with VZV-associated meningitis successfully treated with oral valacyclovir.

In-hospital mortality, but not 30-day mortality, was significantly better in the macrolide group. Our data support the use of a macrolide in hospitalized patients with CAP and bacteraemia.