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By Carol A. Kemper, MD, FIDSA
Medical Director, Infection Prevention, El Camino Hospital, Palo Alto Medical Foundation
Transcatheter Aortic Valve Endocarditis
SOURCE: Mangner N, Panagides V, del Val D, et al. Incidence, clinical characteristic, and impact of absent echocardiographic signs in patients with infective endocarditis after transcatheter aortic valve implantation. Clin Infect Dis 2023;76:1003-1012.
The occurrence of positive blood cultures in patients with transcatheter aortic valve implantation (TAVI) should prompt immediate investigation for infective endocarditis (IE) and initiation of antibacterial therapy for possible device infection. Even then, these patients are at high risk for complications, and outcomes are generally poor. Further, the sensitivity of echocardiography is reduced in prosthetic valve endocarditis, and especially in TAVI-IE. While the combined sensitivity of trans-thoracic and transesophageal echocardiography in prosthetic valve endocarditis is estimated at 89%, it is only ~68% in TAVI-IE. This can lead to delays in treatment or the use of inadequate regimens. The reasons for false-negative echocardiographic imaging are due to small or nonexistent vegetation size, or other conditions that obscure the prosthesis; the type of TAVI device also may play a role.
These authors examined the clinical characteristics and outcomes for 578 patients with reported TAVI-associated endocarditis (as defined by Duke criteria), depending on whether they had echocardiographic evidence of infection (85%) (TAVI-IE-positive) or not (15%) (TAVI-IE-negative). Cases were retrieved from the TAVI International Registry. The average age was 79 years for each group, and the proportion of men in each group was similar and slightly more than half. A greater proportion of TAVI-IE-negative cases compared with TAVI-IE-positive cases had transfemoral placement of self-expanding devices (62% vs. 45%; P = 0.003); the remainder in each group had balloon-expandable devices, suggesting that perhaps the self-expanding devices are more likely to present with occult infection without echocardiographic findings.
A greater proportion of TAVI-IE-negative cases compared with TAVI-IE-positive cases had Staphylococcus aureus bacteremia (34% vs. 23%) or Enterococcus spp. infection (37 % vs. 24%) but lower rates of coagulase-negative staphylococcal infection (5% vs. 20%). Persistent bacteremia occurred in 23% of TAVI-IE-negative cases vs. 32% of TAVI-IE-positive cases. Antibiotics alone were used in 97% of TAVI-IE-negative cases vs. 79% of TAVI-IE-positive cases; thus, combined antibiotic treatment plus surgical intervention was done for only 3% of the TAVI-IE-negative cases vs. 21% of TAVI-IE-positive cases. The median time to surgery was 15 days vs. 17 days for TAVI-IE-negative vs. TAVI-IE-positive cases. Isolated pacemaker extraction was done for none of the TAVI-IE-negative cases and for 3.7% of the TAVI-IE-positive cases.
Outcomes for these patients were remarkably poor. In-hospital mortality was 40% vs. 32% for TAVI-IE-negative vs. TAVI-IE-positive cases, respectively (P = NS). One-year mortality was 54% vs. 48% for TAVI-IE-negative vs. TAVI-IE-positive cases, respectively (P = NS), regardless of whether patients were treated with antibiotics alone or antibiotics plus surgical intervention.
Positron emission tomography-computed tomography (PET-CT) or white blood cell single-photon emission CT (WBC-SPECT CT) may provide additional information about suspected TAVI-associated infection, although concerns have been raised about falsely positive results from post-procedural sterile inflammation. In this retrospective analysis, F-fluorodeoxyglucose (F-FDG) PET-CT (or less commonly WBC-SPECT/CT) was used in only 25% of the TAVI-IE-negative patients and 15% of the TAVI-IE-positive patients. Abnormal radiolabeled tracer uptake was observed in 50% of the IE-negative cases and 82% the IE-positive cases.
Limitations to this study include the observational and retrospective nature of the data; the use of Duke criteria, which could theoretically result in some of the TAVI-IE-negative cases being mis-classified as endocarditis; and there was no external validation of these cases as IE as reported to the TAVI Registry. However, the poor outcome of the TAVI-IE-negative cases suggests these cases were not just isolated bacteremias but true IE cases. The somewhat higher rates of mortality for the TAVI-IE-negative group suggest that delays in recognition of infection and initiation of treatment occurred, although conceivably the greater proportion of coagulase-negative staphylococcal infections in the TAVI-IE-positive group may have led to better outcomes. Surgical intervention did not appear to improve outcomes in the smaller number of patients treated with both antibiotics plus surgery.
Daptomycin-Associated Eosinophilic Pneumonia: The Lyon Algorithm
SOURCE: Pham T-T, Garreua R, Craighero F, et al. Seventeen cases of daptomycin-induced eosinophilic pneumonia in a cohort of patients treated for bone and joint infections: Proposal for a new algorithm. Open Forum Infect Dis 2022;9:ofac577.
These investigators tracked referrals to the French Referral Center for Complex Bone and Joint Infection in Lyon, France, from January 2012 to March 2021, focusing on cases of suspected daptomycin-associated eosinophilic pneumonia. During this time period, 4,664 patients were referred for care (more than 500 patients per year), 1,021 of whom received treatment with daptomycin. Twenty-two patients (2.2%) initially were believed to have developed daptomycin-eosinophilic pneumonia, although five cases were excluded later based on alternate diagnosis (pulmonary embolism, cryptogenic organizing pneumonia, acute respiratory distress syndrome [ARDS], aspiration pneumonia, and drug reaction with eosinophilia and systemic symptoms [DRESS], not related to daptomycin).
Of the 17 remaining cases (1.7%), only one met the formal criteria for daptomycin-induced eosinophilic pneumonia, as defined by the United States Food and Drug Administration criteria (which requires the presence of > 25% eosinophilia on a bronchoalveolar lavage [BAL] specimen). Patients received a median initial dose of daptomycin of 700 mg (median dose 8.2 mg/kg of actual body weight) (range, 5.6 mg/kg to 10 mg/kg). The median age was 76 years, 29% had diabetes, 18% had chronic obstructive pulmonary disease (COPD), and 24% had chronic kidney disease. The remainder had normal renal function.
Patients presented with diffuse crackles (100%), peripheral eosinophilia (88%), hypoxia (87%), dyspnea (76%), and fever (59%). One patient required mechanical ventilation. Fifteen of the patients (88%) developed symptoms within one month of starting daptomycin; the other two developed worsening symptoms at 39 and 78 days of treatment — both had radiographic evidence of acute and chronic eosinophilic pneumonia. Ten patients underwent BAL: eight of them had a neutrophilic profile, one had a mixed neutrophilic-eosinophilic profile, and only one had an eosinophilic profile with > 25% eosinophils in the lavage, despite the presence of significant peripheral eosinophilia in nine of them. Chest tomographic scanning was performed in 14 patients: Bilateral infiltrates were observed in 100%, and ground glass infiltrates were observed in 93%; two-thirds of this was peripheral and one-third was combined peripheral and central infiltrates.
All cases resolved with discontinuation of daptomycin. Only two patients received corticosteroids. One case was rechallenged three months later and developed peripheral eosinophilia within 12 days, and the drug was stopped. Interestingly, one patient had received daptomycin six months earlier for 14 days without any reaction.
These authors believe the current criteria to diagnose daptomycin-induced eosinophilic pneumonia is too restrictive and requires performing a bronchoscopy, which is an invasive procedure not without some risk. Rechallenging with daptomycin also has been suggested as a diagnostic criterion, which is too risky and generally should be avoided. The authors proposed an alternate algorithm using the presence of computed tomography (CT) evidence of bilateral infiltrates compatible with a diagnosis of eosinophilic pneumonia PLUS the presence of peripheral eosinophilia, the combination of which should prompt the discontinuation of drug. Should symptoms fail to resolve with discontinuation of daptomycin, then alternative diagnoses should be contemplated and bronchoscopy performed.
Transcatheter Aortic Valve Endocarditis; Daptomycin-Associated Eosinophilic Pneumonia: The Lyon Algorithm
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