Saleh, Omar M. Abu

ABSTRACT Achromobacter species are Gram-negative bacilli that predominantly affect individuals with cystic fibrosis or those with immunocompromising conditions. Clinical and microbiologic data on Achromobacter species are limited due to the rarity of these organisms and challenges with species-level identification. We conducted a 10-year retrospective analysis (1 January 2013 to 14 March 2023) of all bloodstream and non-bloodstream Achromobacter isolates identified at three tertiary-care Mayo Clinic locations (Minnesota, Arizona, and Florida). Additionally, we examined clinical characteristics of adult patients with Achromobacter bloodstream isolates. A total of 1,598 Achromobacter isolates, encompassing 1,545 non-bloodstream isolates and 53 bloodstream isolates, were identified. The most frequently identified species was Achromobacter xylosoxidans , though species-level identification was not possible for many isolates. Among adult patients with Achromobacter bloodstream infection, the mean age was 58.3 years (standard deviation ± 16.7), 73.1% had a central venous catheter, and 59.6% were immunocompromised. All-cause mortality was 10.2% at 30 days and 18.4% at 90 days. Bloodstream isolates exhibited greater than 90% susceptibility to meropenem, piperacillin-tazobactam, and trimethoprim-sulfamethoxazole. The respiratory tract was the most common source of non-bloodstream isolates (57.5%). Non-bloodstream isolates showed high susceptibility to imipenem (94.6%), piperacillin-tazobactam (92.8%), trimethoprim-sulfamethoxazole (92.1%), and meropenem (87.5%) while demonstrating significant resistance to fluoroquinolones and aminoglycosides. Our findings support the use of piperacillin-tazobactam, carbapenems, or trimethoprim-sulfamethoxazole as initial therapy for Achromobacter infections. Further research is needed to better define the clinical and microbiologic characteristics of Achromobacter infections. IMPORTANCE Achromobacter is a rare but important genus of bacteria that tends to cause infection in those with cystic fibrosis, recurrent healthcare exposures, and/or an immunocompromising condition. There is limited data on the clinical profile of Achromobacter infections as well as optimal antibiotic selection for affected patients. We conducted a retrospective study to improve understanding of the microbiologic and clinical characteristics of Achromobacter . Our study consists of a 10-year survey of all Achromobacter isolates processed by three Mayo Clinic tertiary-care centers in Minnesota, Florida, and Arizona from 2013 to 2023. We report multiple findings, including the clinical characteristics of patients with Achromobacter bloodstream infection, the number of different Achromobacter species identified, and the sources of isolates not obtained from blood cultures. We additionally present antimicrobial susceptibility results for Achromobacter isolates. Our study provides guidance to clinicians treating Achromobacter infections and, it is hoped, will facilitate ongoing study of Achromobacter .

Infective endocarditis (IE) remains a diagnostic challenge, particularly in cases where microbiological diagnosis is not established. Advances in molecular diagnostics have expanded the ability to identify causative pathogens beyond traditional culture-based methods. This review explores the role of molecular assays, including pathogen-specific PCR, multiplex PCR, broad-range PCR, and shotgun metagenomic sequencing, in diagnosing IE. These molecular techniques enhance pathogen detection, especially in patients with prior antibiotic exposure, and improve diagnostic accuracy in culture-negative IE. Broad-range PCR assays and metagenomic sequencing offer the untargeted detection of a wide spectrum of organisms. Despite their advantages, limitations such as availability, interpretation challenges, and a lack of antimicrobial susceptibility testing remain. A multimodal approach integrating molecular diagnostics with conventional methods is essential to optimize patient management. Further research is needed to refine diagnostic algorithms and improve cost-effectiveness in clinical practice.

Background: Isavuconazole (ISA) has a favorable side effect profile that makes it attractive for treatment of invasive fungal infections (IFI). It carries FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data for other organisms and non-pulmonary infections. We conducted this review to investigate how ISA performed at treating IFI, with an especial interest in these non-approved indications. Methods: We retrospectively identified and reviewed 131 patients who received ISA as treatment for IFI at our institution, some of whom received ISA as their first anti-fungal therapy and others who received ISA as either step-down therapy or salvage therapy. We identified the microbiologic cause of infection as well as the anatomic site involved for each patient. We then classified patients according to their response to ISA: namely cured, partially responded, or stabilized. Results: The majority of patients were immunocompromised (n = 76, 58%). ISA was used primarily as a secondary therapy (n = 116, 89%); either as a step-down/switching from other agents, or as salvage therapy. The most common reasons for switching to ISA were toxicities with prior agents followed by QT prolongation. Although pulmonary aspergillosis and mucormycosis were represented in more than half of the cohort, ISA was also used off-label for treatment of other organisms such as endemic fungi (n = 19, 15%) as well as central nervous system (CNS) infections (n = 15, 11%). We have described the detailed clinical characteristics of these CNS infections cases. The overall clinical response rate varied by type of infection and site involved (57–73% response rate). Conclusions: We demonstrated encouraging clinical responses, particularly outside the FDA-approved indications, as well as good tolerability. This report highlights the critical need for expanded scope of prospective studies to delineate the efficacy of this better-tolerated agent, especially in central nervous system infections.