By Stan Deresinski, MD, FACP, FIDSA
Synopsis: A selection of reports published in the last two months cover microbiologic diagnosis and management issues.
Dealing with infective endocarditis (IE) due to Staphylococcus aureus remains a difficult challenge. A national study from Switzerland found that the most frequent etiologic agent causing IE from 2012-2021 was, unsurprisingly, Staphylococcus aureus.1 Furthermore, this organism accounted for 30.0% of cases in 2021, a remarkable increase from 19.8% in 2012. Among all the etiologic agents, it was associated with the highest in-hospital and six-month mortality at 19.9% and 30.3%, respectively. The following is a selection of studies dealing with S. aureus endocarditis published in just the last two months.
Microbiological Diagnosis
The standard recommended procedure for obtaining blood for culture for diagnosis of IE is to obtain three samples, each from a separate venipuncture. With the knowledge that the most important factor in the detection of bacteremia is the total volume of blood cultured rather than the timing of sampling, Goehringer and colleagues prospectively enrolled 256 patients, 101 of whom proved to have IE.2 Blood for three aerobic and anaerobic cultures (samples 1, 2, and 3) was obtained simultaneously with a single venipuncture, while two additional samplings (samples 4 and 5) were obtained with a separate single venipuncture at least one hour later. The results from samples 1, 2, and 3 constituted the single sample strategy (SSS), and this was compared to the multiple sample strategy (MSS) consisting of samples 1, 4, and 5.
The diagnostic sensitivity of SSS in patients with IE was 50.5% (95% confidence interval [CI], 40.7-60.2), while that of MSS was 45.5% (95% CI, 35.8-55.3); P = 0.063). There also was no statistically significant difference in specificity between the two groups, which were 94.8% and 95.5%, respectively. As a consequence of these results, the investigators concluded that “SSS may be regarded as standard practice for IE diagnosis.” Of note, however, is that the study included only 12 patients with S. aureus endocarditis and three patients with bacteremia in the absence of endocarditis.
Strömdahl and colleagues examined the predictive value of the time required to detect blood culture positivity — time to positivity (TTP) — in the diagnosis of S. aureus endocarditis.3 TTP was defined as the time from the start of incubation to detection of positive signal of bacterial growth using BacT/ALERT 3D (bioMérieux). The diagnosis of IE was based on Swedish national guidelines, which are based on the Duke criteria. A TTP < 13 hours was independently associated with endocarditis (odds ratio [OR], 3.59; [95% CI, 2.35-5.3]; P < 0.001). The negative predictive value of a TTP > 13 hours was 96% (95% CI, 95% to 97%). Concurrent antibiotic exposure at the time of blood sampling was not provided.
The diagnosis and management of infections involving implanted cardiac electronic devices is difficult. Karchmer and colleagues used quantitative microbial cell-free deoxyribonucleic acid (mcfDNA) sequencing of plasma samples in determining the presence of infection involving cardiac implantable electronic devices (CIED; CIED-IE) in patients with S. aureus bacteremia.4 Detection of mcfDNA was persistent for a median of 11 days (interquartile range [IQR], 7.5 days) in 10 of 11 patients with definite IE, while it was undetectable after six days (IQR, 2 days) of antibiotic therapy in five patients with possible IE. Furthermore, lead extraction in definite IE was associated with a significant increase in mcfDNA followed by a rapid decrease. In contrast, mcfDNA remained undetectable after lead extraction in patients without definite IE. The difference between detection patterns was significant (P = 0.001). If confirmed, these findings could affect management of patients with CIED and S. aureus bacteremia.
Management Issues
A perplexing problem arises when fever persists despite the initiation of antibiotic therapy. Stavropoulou identified this problem, defined as a temperature > 38°C for ≥ 96 hours in 82/536 (15%) patients with IE, including 55/173 (31.8%) cases caused by S. aureus.5 This frequency was significantly greater than observed with other causes of IE. Independent predictors of persistent fever in the entire cohort of IE cases were persistent microbemia for ≥ 96 hours (P < 0.001) and native infection of bone and joint (P = 0.020).
Surgical intervention often is a key component of the management of IE involving prosthetic cardiac valves, but in some cases surgery is not performed even when it appears to be indicated, and chronic suppressive antibiotic therapy (SAT) is administered instead. Tillement and colleagues prospectively examined the outcomes in 88 patients in whom cardiac surgery was deemed to be indicated but in whom it was not performed.6 The most common indications for surgery were prevention of further embolic events in 44%, resistant or virulent pathogens in 48%, and local cardiac complications (e.g., abscess) in 33%. The reason for not performing surgery was high surgical risk in 89% of cases. Of the 88 patients, 42 received SAT and 46 received conventional antimicrobial therapy (CAT) after receiving a usual acute course of therapy. Twenty-five (28.4%) infections were caused by S. aureus, only two of which were methicillin-resistant Staphylococcus aureus (MRSA), and nine of the 25 received SAT, while 16 received CAT.
At one year, SAT was associated with a lower incidence (hazard ratio [HR], 0.23; 95% CI, 0.08-0.67; P = 0.007) of occurrence of the primary outcome, a composite endpoint including one-year all-cause mortality or unplanned prosthetic valve endocarditis-related readmission. Antibiotic-related adverse events occurred in 6/42 (14.3%) SAT patients, with only one leading to discontinuation. Thus, antibiotic suppression is effective and well tolerated in some patients with prosthetic valve endocarditis in the absence of surgical intervention.
Stan Deresinski, MD, FACP, FIDSA, is Clinical Professor of Medicine, Stanford University.
References
1. Buergler H, Gregoriano C, Laager R, et al. Microbiological trends, in-hospital outcomes, and mortality in infective endocarditis: A Swiss nationwide cohort study. Clin Infect Dis. 2025;80(4):784-794.
2. Goehringer F, Soudant M, Alauzet C, et al; UniEndo-AEPEI Study group. Single- versus multiple-sampling strategy for blood cultures in the diagnosis of infective endocarditis: The prospective multicenter UniEndo study. Clin Infect Dis. 2025; Apr 3:ciaf163. doi: 10.1093/cid/ciaf163. [Online ahead of print].
3. Strömdahl M, Hagman K, Hedman K, et al. Time to Staphylococcus aureus blood culture positivity as a risk marker of infective endocarditis: A retrospective cohort study. Clin Infect Dis. 2025;80(4):727-734.
4. Karchmer AW, Kaufman NJ, Park SY, et al. Quantitative microbial cell-free DNA sequencing from plasma: A potential biomarker for the diagnosis of staphylococcal infection of cardiac implantable electronic devices. Clin Infect Dis. 2025;Mar 11:ciaf113. doi: 10.1093/cid/ciaf113. [Online ahead of print].
5. Stavropoulou E, Monney P, Tzimas G, et al. Predictors of persistent fever among patients with suspected infective endocarditis: Think outside the box. Clin Infect Dis. 2025;80(4):795-803.
6. Tillement J, Issa N, Ternacle J, et al. Antimicrobial suppressive therapy in prosthetic valve endocarditis rejected from surgery despite indication. Int J Antimicrob Agents. 2025; Apr 29:107526. doi: 10.1016/j.ijantimicag.2025.107526. [Online ahead of print].
A selection of reports published in the last two months cover microbiologic diagnosis and management issues.
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