Transition to Oral Antibiotic Therapy for Hospitalized Adults With Gram-Negative Bloodstream Infections.

Importance: Management of gram-negative bloodstream infections (GN-BSIs) with oral antibiotics is highly variable. Objective: To examine the transition from intravenous (IV) to oral antibiotics, including selection, timing, and associated clinical and microbial characteristics, among hospitalized patients with GN-BSIs. Design, Setting, and Participants: A retrospective cohort study was conducted of 4581 hospitalized adults with GN-BSIs at 24 US hospitals between January 1 and December 31, 2019. Patients were excluded if they died within 72 hours. Patients were excluded from the oral therapy group if transition occurred after day 7. Statistical analysis was conducted from July 2022 to October 2023. Exposures: Administration of antibiotics for GN-BSIs. Main Outcomes and Measures: Baseline characteristics and clinical parameters reflecting severity of illness were evaluated in groups receiving oral and IV therapy. The prevalence of transition from IV to oral antibiotics by day 7, median day of transition, sources of infection, and oral antibiotic selection were assessed. Results: Of a total of 4581 episodes with GN-BSIs (median age, 67 years [IQR, 55-77 years]; 2389 men [52.2%]), 1969 patients (43.0%) receiving IV antibiotics were transitioned to oral antibiotics by day 7. Patients maintained on IV therapy were more likely than those transitioned to oral therapy to be immunosuppressed (833 of 2612 [31.9%] vs 485 of 1969 [24.6%]; P < .001), require intensive care unit admission (1033 of 2612 [39.5%] vs 334 of 1969 [17.0%]; P < .001), have fever or hypotension as of day 5 (423 of 2612 [16.2%] vs 49 of 1969 [2.5%]; P < .001), require kidney replacement therapy (280 of 2612 [10.7%] vs 63 of 1969 [3.2%]; P < .001), and less likely to have source control within 7 days (1852 of 2612 [70.9%] vs 1577 of 1969 [80.1%]; P < .001). Transitioning patients from IV to oral therapy by day 7 was highly variable across hospitals, ranging from 25.8% (66 of 256) to 65.9% (27 of 41). A total of 4109 patients (89.7%) achieved clinical stability within 5 days. For the 3429 episodes (74.9%) with successful source control by day 7, the median day of source control was day 2 (IQR, 1-3 days) for the oral group and day 2 (IQR, 1-4 days) for the IV group (P < .001). Common infection sources among patients administered oral therapy were the urinary tract (1277 of 1969 [64.9%]), hepatobiliary (239 of 1969 [12.1%]), and intra-abdominal (194 of 1969 [9.9%]). The median day of oral transition was 5 (IQR, 4-6 days). Total duration of antibiotic treatment was significantly shorter among the oral group than the IV group (median, 11 days [IQR, 9-14 days] vs median, 13 days [IQR, 8-16 days]; P < .001]. Fluoroquinolones (62.2% [1224 of 1969]), followed by ß-lactams (28.3% [558 of 1969]) and trimethoprim-sulfamethoxazole (11.5% [227 of 1969]), were the most commonly prescribed oral antibiotics. Conclusions and Relevance: In this cohort study of 4581 episodes of GN-BSIs, transition to oral antibiotic therapy by day 7 occurred in fewer than half of episodes, principally with fluoroquinolones, although this practice varied significantly between hospitals. There may have been additional opportunities for earlier and more frequent oral antibiotic transitions because most patients demonstrated clinical stability by day 5.

Nirmatrelvir/ritonavir Use With Tacrolimus in Lung Transplant Recipients: A Single-center Case Series.

BACKGROUND: Limited data and guidelines exist for using nirmatrelvir/ritonavir in solid organ transplant recipients stabilized on tacrolimus for the treatment of mild-to-moderate coronavirus disease. Concern exists regarding the impact of utilizing a 5-d course of nirmatrelvir/ritonavir with calcineurin inhibitors because of significant drug-drug interactions between ritonavir, a potent cytochrome P450 3A inhibitor, and other cytochrome P450 3A substrates, such as tacrolimus. METHODS: We report the successful use of nirmatrelvir/ritonavir in 12 outpatient lung transplant recipients with confirmed severe acute respiratory syndrome coronavirus 2 infection stabilized on tacrolimus immunosuppression. All patients stopped tacrolimus and started nirmatrelvir/ritonavir 10 to 14 h after the last dose of tacrolimus. Tacrolimus was withheld and then reinitiated at a modified dose 48 h following the completion of nirmatrelvir/ritonavir therapy. Tacrolimus trough levels were checked during nirmatrelvir/ritonavir therapy and tacrolimus reinitiation. RESULTS: Ten (10/12) patients were able to resume their original tacrolimus dose within 4 d of completing nirmatrelvir/ritonavir therapy and maintain therapeutic levels of tacrolimus. No patients experienced tacrolimus toxicity or acute rejection during the 30-d postcompletion of nirmatrelvir/ritonavir therapy. CONCLUSIONS: In this cohort of lung transplant recipients on tacrolimus, we demonstrated that nirmatrelvir/ritonavir can be safely used with close monitoring of tacrolimus levels and appropriate dose adjustments of tacrolimus. Further confirmatory studies are needed to determine the appropriate use of therapeutic drug monitoring and tacrolimus dose following completion of nirmatrelvir/ritonavir in the solid organ transplant population.

The epidemiology, demographics, and comorbidities of pulmonary and extra-pulmonary non-tuberculous mycobacterial infections at a large central Florida Academic Hospital.

RATIONALE: In the United States, non-tuberculous mycobacterium (NTM) infections are considered an important cause of morbidity and mortality, especially in people with progressive lung disease. The state of Florida has an extremely high incidence and prevalence of NTM disease which is likely a rapidly emerging infection in the state due to environmental and demographic factors. OBJECTIVES: Adjemian et al. [1] To determine the burden of NTM disease of patients admitted to a large Central Florida academic center, Falkinham [2] to identify the most common risk factors associated with developing NTM disease in this area, and Sfeir et al. [4] to categorize antimicrobial susceptibilities and genetic resistance markers. METHODS: We conducted a retrospective case review from January 1, 2011 to December 31, 2017 in a large university-associated metropolitan hospital in west-central Florida. NTM infections were identified using TheraDoc® during the study period with the inclusion criteria of any inpatient admission, culture confirmed NTM at any site, and age ≥ 12 years. Demographic variables (including residential zip code) and comorbidity data (including solid organ transplant status, HIV status and subsequent testing results, intrinsic pulmonary disease, and cancer diagnosis of any site) were collected for each patient. Microbiologic data collected included NTM species/subspecies, anatomic location of specimen collection, antimicrobial susceptibility including minimum inhibitory concentration (MIC). All collected data were analyzed within Stata/IC14.2. Geospatial relationships between zip codes, diagnosis type, and co-morbidities were computed using Arc GIS Pro. RESULTS: Our results demonstrated that a substantial number of our inpatient cases with NTM were of the M. abscessus group, and with M. avium complex and M. fortuitum also representing the pathogen in numerous cases. Novel findings included compilation of the first hospital wide comprehensive NTM resistance plot to our knowledge. Our results did show a concordance with previous data with expected predominance of NTM inpatient cases in Caucasian males with pre-existing pulmonary disease, though additional work could be done with isolates within the transplant and immunosuppressed populations. CONCLUSIONS: Our data set demonstrates the most common species/subspecies of NTM infections and their associated conditions seen at our central Florida hospital, and includes an antimicrobial sensitivity analysis in toto. This could be insight into the possible prevalence of NTM in the area, and provides the foundation for future studies on both the acquisition and prevention for NTM infections in central Florida.

Disseminated blastomycosis in a patient with polycythemia vera on ruxolitinib.

Ruxolitinib (RUX) is a kinase inhibitor used in the treatment of various medical conditions and its mechanism of action involves suppression of the immune system. While beneficial in treatment of polycythemia vera, myelofibrosis and other indications, it can also increase a patient's susceptibility to various infections, including bacterial, viral and fungal. We present a case of a patient being treated with RUX who presented with a disseminated fungal infection. This case emphasises the need for vigilance of endemic fungal infections in individuals who are on RUX therapy.

Multi-organ involvement secondary to varicella zoster virus, herpes simplex virus and cytomegalovirus in an immunocompromised patient.

The use of immunosuppressing agents can act as a catalyst for viral reactivation, promoting systemic infection with organ involvement. Current literature remains sparse on this topic but does provide individual case reports involving single viruses. We present the case of an immunocompromised patient with skin lesions, pancreatitis, colitis and hepatitis. Work-up revealed varicella zoster virus, which likely put the patient at risk for multi-organ involvement, as well as clinical suspicion of other implicated viruses, specifically herpes simplex virus and cytomegalovirus. A high clinical index of suspicion along with biopsy guidance for viral involvement in immunocompromised patients is crucial for early diagnosis and treatment of these conditions.

Successful use of subcutaneous ivermectin for the treatment of Strongyloides stercoralis hyperinfection in the setting of small bowel obstruction and paralytic ileus in the immunocompromised population.

Severe Strongyloides stercoralis, such as hyperinfection syndrome, carries a high mortality risk. Even with appropriate treatment, patients may experience infectious complications and failure of therapy. Currently, there are no Food and Drug Administration-approved parenteral therapies available for treatment in patients who develop gastrointestinal complications from hyperinfection, including small bowel obstruction. A veterinary form of ivermectin is available as a subcutaneous injection, although current literature in humans is limited. We report on the successful treatment of two surviving immunocompromised patients with S. stercoralis hyperinfection syndrome after prompt recognition and initiation of veterinary subcutaneous ivermectin therapy.

Fecal microbiota transplantation outcomes in immunocompetent and immunocompromised patients: A single-center experience.

BACKGROUND: Clostridium difficile infection (CDI) is a major infectious disease focus for which fecal microbiota transplantation (FMT) has been used with success in various patient populations. METHODS: We conducted a retrospective study of FMT in immunocompetent and immunocompromised patients to review outcomes at our center, with a focus on identifying risk factors for FMT failure in solid organ transplant (SOT) patients. FMT was conducted using universal banked frozen stool via naso-duodenal tube in patients with recurrent CDI of 3 or more episodes per our institutional protocol. RESULTS: Thirteen patients were included in the analysis, 6 who were immunocompetent and 7 who were immunocompromised. Of these, 6 patients had a history of SOT and were primarily abdominal organ recipients. All immunocompetent patients experienced success with FMT, while 3 immunocompromised SOT patients experienced failure. Two patients who failed FMT had a second FMT, which was successful in one patient and failed in the second patient. No adverse events were noted with FMT administration. A predictor of FMT failure was antimicrobial exposure pre-FMT. CONCLUSIONS: This study highlights the safe use of FMT for recurrent CDI with variable efficacy in immunocompromised patients. Antimicrobial exposure prior to FMT was an identified risk factor for FMT failure. The use of sequential FMT in SOT patients may be considered but ultimately requires further investigation.