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Objectives To assess and compare subsequent hospital admissions within 30 days for patients after receiving a prescription for either oral nirmatrelvir/ritonavir or oral molnupiravir. Methods We conducted a retrospective review of 3207 high-risk, non-hospitalized adult COVID-19 patients who received a prescription for molnupiravir (n = 209) or nirmatrelvir/ritonavir (n = 2998) at an academic medical centre in New York City from April to December 2022. Variables including age, vaccination status, high-risk conditions and demographic factors were pulled from the electronic medical record. We used multivariable logistic regression to adjust for potential confounding variables. Results All-cause 30 day hospitalization was not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (1.4% versus 1.9%, P value = 0.55). The association between COVID-related hospitalization and medication was also not significant (0.7%versus 0.5%, P value = 0.99). Patients who received molnupiravir were more likely to have more underlying high-risk conditions. After adjusting for potential confounders, the odds of all-cause hospitalizations were not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (OR = 1.16, 95% CI: 0.4–3.3, P value = 0.79). Conclusions These data provide additional evidence to support molnupiravir as a suitable alternative when other COVID-19 antivirals cannot be given.

Background Despite multiple studies indicating a low prevalence of bacterial coinfection in coronavirus disease 2019 (COVID-19) patients, the majority of hospitalized COVID-19 patients receive one or more antibiotics. Patients with coinfection usually have multiple risk factors and poor clinical outcomes. Methods A retrospective case control study was conducted comparing clinical characteristics and antimicrobial use in hospitalized adult COVID-19 patients with bacterial co-infections vs. randomly selected patients without co-infections (matched on month of admission). The study was conducted at three hospitals within the Montefiore Medical Center, Bronx, NY between March 1, 2020 and October 31, 2020. A multivariable logistic regression model was developed to assess the relationship of each predictor variable with coinfection status. Secondary outcomes included hospital mortality, antibiotic days of therapy (DOT), and C. difficile infection. Results A total of 150 patients with coinfection and 150 patients without co-infection were included in the analysis. Table 1 summarized baseline characteristics and risk factors. The multivariable logistic regression model indicated that presence of a central line (OR=5.4, 95% CI: 2.7-11.1), prior antibiotic exposure within 30 days (OR=5.3, 95% CI: 2.8-10.0), prior ICU admission (OR=3.6, 95% CI: 1.7-7.6), steroid use (OR=2.7, 95% CI: 1.4-4.9), and any comorbid condition (OR=2.7, 95% CI: 1.4-5.2) were significantly associated with the development of coinfection (table 2). Mortality was higher in patients with coinfection (56% vs. 11%, p < 0.0001) (table 3). Average antibiotic DOT was 10.5 in coinfected patients compared to 4 in non-coinfected patients, (p < 0.0001). Forty-one percent of coinfected patients had a multidrug resistant organism isolated. C. difficile rate was higher in coinfected patients (4% vs. 0%, p=0.03). Conclusion As the healthcare community contends with a 3rd year of COVID-19 pandemic, understanding risk factors most predictive of bacterial coinfection can guide empiric antimicrobial therapy and targeted stewardship interventions. Ideally, co-infection risk scores are developed which may be useful for future inpatient surges. Disclosures Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support Kelsie Cowman, MPH, Merck: Grant/Research Support.

Background The 2022 IDSA Guidance on the Treatment of Antimicrobial-Resistant Gram-negative Infections recommends the use of a novel beta-lactam/beta-lactamase inhibitor, such as ceftolozane-tazobactam (C/T) or ceftazidime-avibactam (C/A), as first-line for treatment of resistant Pseudomonas aeruginosa infections. C/T is often preferred for these infections due to a narrower spectrum and lower cost. However, from December 2020 to January 2022, a global shortage of C/T resulted in widespread adoption of C/A as an alternative. While in vitro susceptibilities support the use of C/A for P. aeruginosa, real-world experience comparing clinical outcomes to C/T is limited. Methods This multicenter, retrospective analysis was conducted at an urban, academic healthcare system in the Bronx, NY. Between January 2018 and December 2020, admitted adult patients who received C/A or C/T to treat P. aeruginosa infections were included. Patients were excluded if in vitro resistance to either drug was demonstrated or if susceptibility was missing. The primary outcome was clinical success, defined as resolution of signs and symptoms of infection, by end of treatment. Secondary outcomes included 30-day mortality, resistance to study drug after therapy, modification of therapy, 14-day microbiological failure, 90-day infection recurrence, and length of stay. Results A total of 46 patients received C/A and 56 patients received C/T to treat P. aeruginosa infections. Most baseline characteristics were similar between the two arms, though more patients were critically ill in the C/A arm (Table 1). Clinical success was similar between C/A and C/T patients (72% vs. 63%, p=0.33). No significant differences between arms were identified for secondary outcomes (Table 2). Development of drug resistance within 90 days of treatment occurred more frequently in the C/A arm, approaching significance. On multivariate regression analysis, vasopressor use at the time of study drug initiation was the only variable associated with reduced clinical success. Conclusion C/A may be an effective alternative treatment for multidrug-resistant P. aeruginosa infections with close monitoring for development of resistance. Larger comparative studies are needed to confirm these findings. Disclosures Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support.

Background Montefiore Medical Center (MMC), Bronx, NY, established an ambulatory program to offer COVID-19 treatments (monoclonal antibodies [mAB] and oral antivirals) to patients with mild-moderate illness according to emergency use authorization criteria. Given multiple pandemic waves in the area, several patients have been reinfected and were treated twice. The objective of this analysis is to identify clinical characteristics and outcomes in patients with repeated COVID-19 infections and treatments. Methods Electronic health records were reviewed to identify patients between December 1, 2020 and April 28, 2022 who received COVID-19 treatment on more than one occasion at MMC. Data collected included demographics, risk factors for progression to severe illness, name and date of COVID-19 treatments received, vaccination status, and clinical outcomes of 30-day emergency department (ED) presentation or hospital admission following each treatment. Results Out of 3,042 total treated patients, 13 (0.4%) received multiple treatments with either mAB or oral antivirals for COVID-19 reinfection during the study period. Median age of reinfected patients requiring treatment was 50 years. Median days between first and second treatments was 298 days (range 91-468 days). The most common risk factor for progression to severe disease were cardiovascular disease (54%) and immunocompromised status (62%) (Table 1). Ten patients had received at least two doses of vaccine (77%) with Pfizer (54%) or Moderna (23%) vaccines prior to reinfection. No patients reported any adverse reactions to either treatment. Four patients presented to the ED or were hospitalized following treatment of reinfection, three of which were for COVID-related symptoms. Of these, two had two risk factors for progression and the third had been hospitalized previously for initial COVID-19 infection. Conclusion Though COVID-19 reinfection has been described, especially during Omicron surges, there were relatively few reinfected patients requiring treatment in our cohort. Patients with risk factors for disease progression may also be at increased risk for reinfection, especially the immunocompromised. Disclosures Kelsie Cowman, MPH, Merck: Grant/Research Support Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support.

Introduction Intensive care unit (ICU) delirium is a major contributing factor to increased mortality, length of stay, and cost of care. Psychotropic medications may often require extensive tapering to prevent withdrawal symptoms; during ICU admission, home psychotropics are frequently held which may precipitate acute drug withdrawal and subsequent delirium. Methods This is a single-center, observational, retrospective chart review. The primary endpoint was the total number of new-start antipsychotics used to treat ICU delirium. Secondary endpoints included use of restraints, ICU length of stay, and hospital length of stay. Results A total of 2334 charts were reviewed for inclusion; 55 patients were categorized into each group. There was no statistically significant difference in the requirement for new-start antipsychotics (P = 1.0), restraint use (P = .057), or ICU length of stay (P = .71). There was a statistically significant decrease in hospital length of stay (P = .048). Discussion Early reinitiation was associated with a decrease in hospital length of stay but was not associated with a decrease in the number of new-start antipsychotics, use of restraints, or ICU length of stay.

Boceprevir is a protease inhibitor indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in combination with peginterferon and ribavirin for treatment-naive patients and those who previously failed to improve with interferon and ribavirin treatment.This article provides an overview of the mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of boceprevir.Relevant information was identified through a search of PubMed (1990-July 2012), EMBASE (1990-July 2012), International Pharmaceutical Abstracts (1970-July 2012), and Google Scholar using the key words boceprevir, SCH 503034, non-structural protein 3 (NS3) serine protease inhibitor, and direct-acting antiviral agent (DAA). Additional information was obtained from the US Food and Drug Administration's Web site, review of the reference lists of identified articles, and posters and abstracts from scientific meetings.Clinical efficacy of boceprevir was assessed in 2 Phase III trials, Serine Protease Inhibitor Therapy-2 (SPRINT-2) for treatment-naive patients and Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) for treatment-experienced patients. In SPRINT-2, patients were randomized to receive peginterferon + ribavirin (PR) or peginterferon + ribavirin + boceprevir (PRB); duration of boceprevir therapy varied from 24, 32, to 44 weeks on the basis of HCV RNA results. The primary endpoint was achievement of sustained virologic response (SVR; lower limit of detection, 9.3 IU/mL). The addition of boceprevir was shown to be superior, with overall SVR rates ranging from 63% to 66% compared with 38% with PR (P0.001). Results of SVR in SPRINT-2 were also reorganized to monitor SVRs in black and non-black patients. Treatment-experienced patients were assessed in RESPOND-2; however, null responders were excluded. Patients were again randomized to PR or PRB; duration of boceprevir therapy varied from 32 to 44 weeks on the basis of HCV RNA results. SVR was significantly higher in patients receiving boceprevir (59%-66% vs 21% with PR; P0.001). This benefit was seen in both previous nonresponders (SVR, 40%-52% vs 7% with PR), as well as previous relapsers (SVR, 69%-75% vs 29% with PR). Importantly, SVR could be attained with a shortened course of therapy in almost one half of all treated patients in SPRINT-2 (44%) and RESPOND-2 (46%).Boceprevir was well tolerated in clinical trials and a welcomed addition to our HCV armamentarium.

Background: Skin and soft tissue infections (SSTIs) have become the second most common type of infection among persons residing in long-term care facilities. Objective: The purpose of this article was to review the latest information on SSTIs among the elderly, including age-related changes, challenges, and treatment strategies in the era of emerging bacterial resistance. Methods: Relevant information was identified through a search of MEDLINE (1970—April 2010), International Pharmaceutical Abstracts (1970—April 2010), and Google Scholar using the terms skin and soft tissue infection, skin and skin structure infection, cellulitis, treatment guidelines , and elderly . Additional publications were found by searching the reference lists of the identified articles. Trials published since 1970 were selected for this review if they prospectively evaluated mostly adults (≥18 years of age), included >50 patients, and reported diagnostic criteria as well as clinical outcomes in patients treated for simple or complicated SSTIs. Results: Fifty-eight of 664 identified studies were selected and included in this review. A search of the literature did not identify any prospective clinical trials that were conducted exclusively in the elderly. Information on the treatment of SSTIs in the elderly was based solely on clinical studies that were conducted in adults in general. As recommended by the Infectious Diseases Society of America (IDSA) 2008 update, SSTIs should be suspected in elderly patients who have skin lesions and present with a decline in functional status, with or without fever. Patients who present with symptoms of systemic toxicity should be hospitalized for further evaluation. Current challenges in the management of SSTIs include the rapid emergence of community-acquired, methicillin-resistant Staphylococcus aureus (CA—MRSA), the emergence of macrolide-resistant streptococci within the past decade, and the lack of a reliable algorithm to differentiate potentially life-threatening SSTIs that require aggressive interventions and prompt hospitalization from those that can be managed in an outpatient setting. S aureus was the most common cause of SSTIs, being isolated in 42.8% (5015/11,723) of wounds, followed by streptococci. Common SSTIs in the elderly such as shingles, diabetic foot infections, infected pressure ulcers, and scabies, and their treatment were also discussed. Based on reviews of published trials, treatment of simple SSTIs generally consisted of administration of agents with activity against S aureus and Streptococcus species such as a penicillinase-resistant β-lactam, a first-generation cephalosporin, or clindamycin. Broadening of the antimicrobial spectrum to include gram-negative and anaerobic organisms should be implemented for complicated SSTIs such as diabetic foot infections and infected pressure ulcers. Local rates of MRSA, CA—MRSA, and macrolide-resistant streptococci should be considered when selecting empiric therapy. Conclusions: A search of the literature did not identify any prospective clinical trials on the treatment of SSTIs in the elderly; therefore, it is recommended to follow treatment based on the current IDSA guidelines. More research and publications are needed to establish proper selection of antimicrobial agents, treatment strategies, and duration of therapy of SSTIs in the elderly population.

Data are sparse on long-term renal toxicity of tenofovir as measured by estimated glomerular filtration rate (eGFR) and progression to advanced stages of chronic kidney disease (CKD). The objective of the study is to determine the incidence of renal impairment associated with the use of tenofovir in HIV-infected patients, using abacavir as a control. In a single tertiary care center, all HIV-infected patients with baseline CKD stage 0 or 1 (CKD-1), who were started on either tenofovir or abacavir from 1998 to 2008 and had at least 1 follow-up eGFR measure on therapy, were included in this retrospective analysis. Progression to CKD stages 2 to 5 was compared using Kaplan-Meier analysis. Progression to CKD-2 and CKD-3 occurred more frequently in patients who received tenofovir than those receiving abacavir (CKD-2, 2-year actuarial frequency, 48.8% vs 23.7%; P < .001, log rank; CKD-3, 5.8% vs 0.0%; P = .028). Only 1 patient in the tenofovir group progressed to CKD-4 and none to CKD-5. Treatment with tenofovir was the only independent factor associated with progression to CKD-2 (hazard ratio [HR], 2.12; 95% confidence interval [CI]: 1.41-3.18; P < .001) and to CKD-3 (HR, 4.91; 95% CI, 1.02-23.7; P = .048). In HIV-infected patients, long-term therapy with tenofovir is associated with mild-to-moderate nephrotoxicity which is significantly higher than in abacavir-treated patients.

Background Ceftaroline is a cephalosporin with expanded gram-positive activity recently approved for clinical uses by the US Food and Drug Administration. Objective This article provides an overview of the in vitro and in vivo activities, mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of ceftaroline. Methods Relevant information was identified through a search of PubMed (1990–April 2011), EMBASE (1990–April 2011), International Pharmaceutical Abstracts (1970–April 2011), and Google Scholar using the key words ceftaroline, PPI-0903, PPI-0903M, T-91825, and TAK-599 . A review of the reference lists of identified articles, a search of the US Food and Drug Administration Web site, and posters and abstracts from scientific meetings yielded additional publications. Results In vitro, ceftaroline exhibits activity against most aerobic gram-positive isolates, common aerobic gram-negative respiratory pathogens, and some gram-positive anaerobes. The MIC range for most Staphylococcus aureus isolates, including vancomycin-resistant strains was between ≤0.008 and 4 μg/mL. In Phase III studies (CANVAS 1 and CANVAS 2), ceftaroline was found to be noninferior to vancomycin + aztreonam for the treatment of complicated skin and skin-structure infections, with a clinical cure rate of 91.6% among clinically evaluable patients (ceftaroline versus vancomycin + aztreonam: difference, −1.1; 95% CI, −4.2 to 2.0; P = NS). Ceftaroline's efficacy has also been assessed for the treatment of community-acquired pneumonia in 2 Phase III studies (FOCUS 1 and FOCUS 2) and was equivalent to ceftriaxone, with cure rates of 84.3% and 77.7%, respectively, among clinically evaluable patients in the combined analysis (ceftaroline versus ceftriaxone: difference, 6.7; 95% CI, 1.6 to 11.8). The recommended dosage for patients 18 years and older is 600 mg IV every 12 hours. Dosage adjustment is necessary in patients with renal impairment (creatinine clearance ≤50 mL/min). The pharmacokinetic properties of ceftaroline in patients with hepatic impairments are currently unavailable. Ceftaroline appeared to be well tolerated generally. The most frequently (>3%) reported adverse events were nausea, headaches, diarrhea, pruritus, rash, and insomnia; all were usually mild to moderate, self-limiting, and of little clinical significance. Conclusions Ceftaroline is a cephalosporin with broad gram-positive activity, including Methicillin-resistant S aureus and vancomycin-resistant S aureus . Its gram-negative activity includes common respiratory pathogens and members of the Enterobacteriaceae. Clinical trials have reported that ceftaroline was noninferior to ceftriaxone, and vancomycin + aztreonam for the treatment of community-acquired pneumonia and complicated skin and skin-structure infections, respectively.

Background: Besifloxacin is a topical ophthalmic fluoroquinolone that was approved by the US Food and Drug Administration (FDA) in May 2009 for the treatment of bacterial conjunctivitis caused by susceptible bacterial strains. Objective: This article provides an overview of the pharmacology, clinical efficacy, and tolerability of ophthalmic besifloxacin when used for the treatment of bacterial conjunctivitis. Methods: Relevant reports pertaining to the pharmacology, efficacy, and tolerability of besifloxacin were identified through a search of MEDLINE (1985–December 2009) and International Pharmaceutical Abstracts (1985–December 2009) using the terms besifloxacin, BOL-303224-A, ophthalmic fluoroquinolones, and bacterial conjunctivitis. Additional publications were identified by reviewing the reference lists of identified articles and searching the FDA Web site. Results: Besifloxacin has potent in vitro inhibitory activity against most common ocular bacterial pathogens (MIC90 values generally ≤4 μg/mL), including Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. In an ocular pharmacokinetic study in 64 healthy volunteers, the Cmax in tears (mean [SD], 610 [540] μg/mL) was reached 10 minutes after a single ocular instillation of besifloxacin; concentrations ≥1.6 μg/g of tear were sustained for at least 24 hours; and the elimination t1/2 was ~3.4 hours. In a study in 24 patients with a clinical diagnosis of bilateral bacterial conjunctivitis, systemic exposure (Cmax) after administration of besifloxacin ophthalmic suspension 3 times daily for 5 days was