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2.
Sci Rep ; 14(1): 10466, 2024 05 07.
Article in English | MEDLINE | ID: mdl-38714772

ABSTRACT

Right-sided infective endocarditis (RSIE) is less common than left-sided infective endocarditis (LSIE) and exhibits distinct epidemiological, clinical, and microbiological characteristics. Previous studies have focused primarily on RSIE in patients with intravenous drug use. We investigated the characteristics and risk factors for RSIE in an area where intravenous drug use is uncommon. A retrospective cohort study was conducted at a tertiary hospital in South Korea. Patients diagnosed with infective endocarditis between November 2005 and August 2017 were categorized into LSIE and RSIE groups. Of the 406 patients, 365 (89.9%) had LSIE and 41 (10.1%) had RSIE. The mortality rates were 31.7% in the RSIE group and 31.5% in the LSIE group (P = 0.860). Patients with RSIE had a higher prevalence of infection with Staphylococcus aureus (29.3% vs. 13.7%, P = 0.016), coagulase-negative staphylococci (17.1% vs. 6.0%, P = 0.022), and gram-negative bacilli other than HACEK (12.2% vs. 2.2%, P = 0.003). Younger age (adjusted odds ratio [aOR] 0.97, 95% confidence interval [CI] 0.95-0.99, P = 0.006), implanted cardiac devices (aOR 37.75, 95% CI 11.63-141.64, P ≤ 0.001), and central venous catheterization  (aOR 4.25, 95%  CI 1.14-15.55, P = 0.029) were independent risk factors for RSIE. Treatment strategies that consider the epidemiologic and microbiologic characteristics of RSIE are warranted.


Subject(s)
Endocarditis , Humans , Male , Republic of Korea/epidemiology , Female , Risk Factors , Retrospective Studies , Middle Aged , Aged , Endocarditis/epidemiology , Endocarditis/mortality , Endocarditis/microbiology , Adult , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Endocarditis, Bacterial/epidemiology , Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/mortality , Staphylococcus aureus/isolation & purification , Staphylococcus aureus/pathogenicity , Prevalence , Tertiary Care Centers
5.
J Cardiothorac Surg ; 19(1): 300, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807242

ABSTRACT

BACKGROUND: A fistulous tract in the mitro-aortic intervalvular fibrosa (MAIVF) is a rare entity, which presents as a complication of endocarditis or surgical trauma. Generally, it is associated to a pseudoaneurysm of the MAIVF (p-MAIVF) or aortic abscesses. MAIVF fistulas could potentially lead to devastating complications and a high mortality rate. This condition is managed surgically, either by a percutaneous closure or an open surgical approach. Herein we report the complex case of a patient with a MAIVF fistula secondary to bacterial endocarditis. Further clinical deterioration was caused by severe aortic valve insufficiency and hemodynamic compromise, requiring surgical intervention. CASE PRESENTATION: A 74-year-old male patient was admitted to a primary care center with complaints of malaise, asthenia, adynamia, hyporexia, and lower limb edema over the past eight days. His past medical history is positive for arterial hypertension and being monorenal. A transesophageal echocardiogram (TEE) was performed, exhibiting a 56% left ventricle ejection fraction (LVEF) and complicated aortic valve endocarditis. Surgical management through an open approach included vegetation resection, valve replacement, and closure of the MAIVF fistula. After completing antibiotic therapy, the patient was discharged without complications. During postoperative follow-up, the patient remained asymptomatic, and the control echocardiogram showed no signs of MAIVF fistula.4. CONCLUSIONS: The clinical case of a patient with a MAIVF fistula secondary to endocarditis by Streptococcus Anginous was presented. The fistulous tract was not associated to p-MAIVF or aortic abscess, findings which further deteriorate the patient's condition and increase the likelihood of fatality. This case reinforces the importance of a prompt diagnosis through cardiac imaging and timely surgical closure of the defect.


Subject(s)
Aortic Valve , Endocarditis, Bacterial , Mitral Valve , Humans , Male , Aged , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/surgery , Endocarditis, Bacterial/microbiology , Aortic Valve/surgery , Mitral Valve/surgery , Echocardiography, Transesophageal , Fistula/surgery
7.
Int J Infect Dis ; 143: 107022, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38561042

ABSTRACT

OBJECTIVES: To ascertain whether infective endocarditis (IE) was associated with persistent bacteraemia/candidaemia among patients with suspected IE. METHODS: This study included bacteraemic/candidaemic adult patients with echocardiography and follow-up blood cultures. Persistent bacteraemia/candidaemia was defined as continued positive blood cultures with the same microorganism for 48 h or more after antibiotic treatment initiation. Each case was classified for IE by the Endocarditis Team. RESULTS: Among 1962 episodes of suspected IE, IE (605; 31%) was the most prevalent infection type. Persistent bacteraemia/candidaemia was observed in 426 (22%) episodes. Persistent bacteraemia was more common among episodes with Staphylococcus aureus bacteraemia compared to episodes with positive blood cultures for other pathogens (32%, 298/933 vs 12%, 128/1029; P < 0.001). Multivariable analysis demonstrated that cardiac predisposing factors (aOR 1.84, 95% CI 1.31-2.60), community or non-nosocomial healthcare-associated (2.85, 2.10-3.88), bacteraemia by high-risk bacteria, such as S. aureus, streptococci, enterococci or HACEK (1.84, 1.31-2.60), two or more positive sets of index blood cultures (6.99, 4.60-10.63), persistent bacteraemia/candidaemia for 48 h from antimicrobial treatment initiation (1.43, 1.05-1.93), embolic events within 48h from antimicrobial treatment initiation (12.81, 9.43-17.41), and immunological phenomena (3.87, 1.09-1.78) were associated with infective endocarditis. CONCLUSIONS: IE was associated with persistent bacteraemia/candidaemia, along with other commonly associated factors.


Subject(s)
Bacteremia , Blood Culture , Endocarditis , Humans , Male , Female , Middle Aged , Bacteremia/microbiology , Bacteremia/diagnosis , Bacteremia/drug therapy , Bacteremia/epidemiology , Aged , Endocarditis/microbiology , Endocarditis/diagnosis , Endocarditis/drug therapy , Candidemia/drug therapy , Candidemia/diagnosis , Candidemia/microbiology , Candidemia/epidemiology , Cohort Studies , Adult , Risk Factors , Anti-Bacterial Agents/therapeutic use , Echocardiography , Staphylococcus aureus/isolation & purification , Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/epidemiology , Retrospective Studies , Staphylococcal Infections/microbiology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/diagnosis
8.
JAMA Dermatol ; 160(5): 564, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38568680

ABSTRACT

This case report describes Osler nodes and Janeway lesions on a man in his 70s.


Subject(s)
Endocarditis, Bacterial , Humans , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/microbiology , Male , Female
9.
J Investig Med High Impact Case Rep ; 12: 23247096241239544, 2024.
Article in English | MEDLINE | ID: mdl-38577758

ABSTRACT

Citrobacter koseri (formerly classified as Citrobacter diversus) is a gram-negative bacillus (GNB) that occurs as an opportunistic pathogen in neonates and immunocompromised patients. Citrobacter species have been implicated in nosocomial settings leading to infections involving the urinary tract, respiratory tract, liver, biliary tract, meninges, and even in rarer conditions-blood stream infection and infective endocarditis (IE). Gram-negative bacilli are responsible for 3% to 4% of all IE cases and have been traditionally associated with intravenous drug users. Patients with non-HACEK (species other than Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kinglella species) GNB IE have poor clinical outcomes with higher rates of in-hospital mortality and complications. The American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) both recommend the use of combination antibiotic therapy with a beta-lactam (penicillins, cephalosporins, or carbapenems) and either an aminoglycoside or fluoroquinolones for 6 weeks (about 1 and a half months) to treat IE due to non-HACEK GNB. Citrobacter koseri is becoming more recognized due to its inherent resistance to ampicillin and emerging drug resistance to beta lactams and aminoglycosides requiring carbapenem therapy. Our case is of a 75-year-old male with no previously reported history of primary or secondary immunodeficiency disorders who developed C koseri blood stream infection. His infectious work-up revealed mitral valve IE and septic cerebral emboli resulting in ischemic infarcts. This case illustrates the importance of recognizing GNB organisms as rising human pathogens in IE cases even without active injection drug use or nosocomial exposure.


Subject(s)
Citrobacter koseri , Cross Infection , Endocarditis, Bacterial , Heart Valve Diseases , United States , Male , Infant, Newborn , Humans , Aged , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/microbiology , Gram-Negative Bacteria , Anti-Bacterial Agents/therapeutic use , Cross Infection/drug therapy , Cross Infection/microbiology
12.
Clin Infect Dis ; 78(4): 956-963, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38330240

ABSTRACT

BACKGROUND: Revised diagnostic criteria for infective endocarditis (IE), the 2023 Duke-ISCVID criteria, were recently presented and need validation. Here, we compare the 2000 modified Duke criteria for IE with Duke-ISCVID among patients with bacteremia and relate the diagnostic classification to IE treatment. METHODS: We reanalyzed patient cohorts with Staphylococcus aureus, Staphylococcus lugdunensis, non-ß-hemolytic streptococci, Streptococcus-like bacteria, Streptococcus dysgalactiae, Enterococcus faecalis, and HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) bacteremia. Episodes were classified as definite, possible, or rejected IE with the modified Duke and Duke-ISCVID criteria. Reclassification included the microbiology criteria, positron emission tomography-computed tomography, and cardiac implanted electronic devices. To calculate sensitivity, patients treated for IE were considered as having IE. RESULTS: In 4050 episodes of bacteremia, the modified Duke criteria assigned 307 episodes (7.6%) as definite IE, 1190 (29%) as possible IE, and 2553 (63%) as rejected IE. Using the Duke-ISCVID criteria, 13 episodes (0.3%) were reclassified from possible to definite IE, and 475 episodes (12%) were reclassified from rejected to possible IE. With the modified Duke criteria, 79 episodes that were treated as IE were classified as possible IE, and 11 of these episodes were reclassified to definite IE with Duke-ISCVID. Applying the decision to treat for IE as a reference standard, the sensitivity of the Duke-ISCVID criteria was 80%. None of the 475 episodes reclassified to possible IE were treated as IE. CONCLUSIONS: The Duke-ISCVID criteria reclassified a small proportion of episodes to definite IE at the expense of more episodes of possible IE. Future criteria should minimize the possible IE group while keeping or improving sensitivity.


Subject(s)
Bacteremia , Communicable Diseases , Endocarditis, Bacterial , Endocarditis , Humans , Retrospective Studies , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/microbiology , Endocarditis/diagnosis , Endocarditis/microbiology , Bacteremia/diagnosis , Bacteremia/microbiology
13.
Infect Dis Now ; 54(3): 104867, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38369059

ABSTRACT

OBJECTIVES: Suppressive antibiotic therapy (SAT) is a long-term antibiotic strategy at times applied when an indicated surgical management of infective endocarditis (IE) is not possible. Our aim was to describe the characteristics and outcomes of patients having received SAT for IE. METHODS: We conducted a retrospective, observational study at Strasbourg University Hospital, France between January 2020 and May 2023. We reviewed all medical files taken into consideration at weekly meetings of the local Multidisciplinary Endocarditis Team (MET) during the study period. We included patients having received SAT following the MET evaluation. The primary endpoint was all-cause mortality at most recent follow-up. Secondary endpoints included all-cause mortality at 3 and 6 months, infection relapse, and tolerance issues attributed to SAT. RESULTS: The MET considered 251 patients during the study time, among whom 22 (9 %) had received SAT. Mean age was 77.2 ± 12.3 years. Patients were highly comorbid with a mean Charlson index score of 6.6 ± 2.5. Main indication for SAT was surgery indicated but not performed or an infected device not removed (20/22). Fourteen patients had prosthetic valve IE, including 9 TAVIs. Six patients had IE affecting cardiac implantable electronic devices. Staphylococcus aureus and enterococci were the main bacteria involved (6/22 each). Median follow-up time was 249 days (IQR 95-457 days). Mortality at most recent follow-up was 23 % (5/22). Three patients (14 %) presented tolerance issues attributed to SAT, and two patients suffered late infectious relapse. CONCLUSION: Mortality at most recent follow-up was low and tolerance issues were rare for patients under SAT, which might be a palliative approach to consider when optimal surgery or device removal is not possible.


Subject(s)
Endocarditis, Bacterial , Endocarditis , Humans , Middle Aged , Aged , Aged, 80 and over , Retrospective Studies , Treatment Outcome , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/surgery , Endocarditis, Bacterial/microbiology , Anti-Bacterial Agents/therapeutic use , Endocarditis/drug therapy , Endocarditis/surgery , Recurrence , Observational Studies as Topic
14.
Radiographics ; 44(3): e230031, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38329903

ABSTRACT

Infective endocarditis (IE) is a complex multisystemic disease resulting from infection of the endocardium, the prosthetic valves, or an implantable cardiac electronic device. The clinical presentation of patients with IE varies, ranging from acute and rapidly progressive symptoms to a more chronic disease onset. Because of its severe morbidity and mortality rates, it is necessary for radiologists to maintain a high degree of suspicion in evaluation of patients for IE. Modified Duke criteria are used to classify cases as "definite IE," "possible IE," or "rejected IE." However, these criteria are limited in characterizing definite IE in clinical practice. The use of advanced imaging techniques such as cardiac CT and nuclear imaging has increased the accuracy of these criteria and has allowed possible IE to be reclassified as definite IE in up to 90% of cases. Cardiac CT may be the best choice when there is high clinical suspicion for IE that has not been confirmed with other imaging techniques, in cases of IE and perivalvular involvement, and for preoperative treatment planning or excluding concomitant coronary artery disease. Nuclear imaging may have a complementary role in prosthetic IE. The main imaging findings in IE are classified according to the site of involvement as valvular (eg, abnormal growths [ie, "vegetations"], leaflet perforations, or pseudoaneurysms), perivalvular (eg, pseudoaneurysms, abscesses, fistulas, or prosthetic dehiscence), or extracardiac embolic phenomena. The differential diagnosis of IE includes evaluation for thrombus, pannus, nonbacterial thrombotic endocarditis, Lambl excrescences, papillary fibroelastoma, and caseous necrosis of the mitral valve. The location of the lesion relative to the surface of the valve, the presence of a stalk, and calcification or enhancement at contrast-enhanced imaging may offer useful clues for their differentiation. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.


Subject(s)
Aneurysm, False , Endocarditis, Bacterial , Endocarditis , Humans , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/pathology , Endocarditis/diagnostic imaging , Tomography, X-Ray Computed/methods , Multimodal Imaging
15.
J Cardiovasc Med (Hagerstown) ; 25(4): 334-341, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38407841

ABSTRACT

AIMS: The clinical benefits of mitral valve repair over replacement in the setting of mitral infective endocarditis are not clearly established. METHODS: Data of patients who underwent cardiac surgery for infective endocarditis over a 20-year period (2001-2021) at two cardiac centres were reviewed. Among them, 282 patients underwent native mitral valve surgery and were included in the study. Nearest-neighbour propensity-score matching was performed to account for differences in patients' profile between the repair and replacement subgroups. RESULTS: Mitral valve replacement was performed in 186 patients, while in 96 cases patients underwent mitral valve repair. Propensity match analysis provided 89 well matched pairs. Mean age was 60 ±â€Š15 years; 75% of the patients were male. Mitral valve replacement was more commonly performed in patients with involvement of both mitral leaflets, commissure(s) and mitral annulus. Patients with lesion(s) limited to P2 segment formed the majority of the cases undergoing mitral valve repair. There was no difference in terms of microbiological findings. In-hospital mortality was 7% with no difference between the repair and the replacement cohorts. Survival probabilities at 1, 5 and 10 years were 88%, 72% and 68%, respectively after mitral repair, and 88%, 78% and 63%, respectively after mitral replacement (log-rank P  = 0.94). CONCLUSIONS: Mitral valve repair was more commonly performed in patients with isolated single leaflet involvement and provided good early and 10-year outcomes. Patients with annular disruption, lesion(s) on both leaflets and commissure(s) were successfully served on early and mid-term course by mitral valve replacement.


Subject(s)
Endocarditis, Bacterial , Endocarditis , Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Humans , Male , Middle Aged , Aged , Female , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Heart Valve Prosthesis Implantation/adverse effects , Treatment Outcome , Endocarditis, Bacterial/microbiology , Endocarditis/diagnostic imaging , Endocarditis/surgery , Mitral Valve Insufficiency/surgery
16.
J Gen Intern Med ; 39(7): 1252-1256, 2024 May.
Article in English | MEDLINE | ID: mdl-38332441

ABSTRACT

A 63-year-old man was admitted to the hospital for nausea, vomiting, and right flank pain. He was found to have septic emboli in multiple organs secondary to aortic valve endocarditis. He was started on broad-spectrum antibiotics and underwent valve replacement. Blood cultures from admission were negative, but a blood polymerase chain reaction (PCR) test for fastidious difficult-to-culture pathogens showed a positive result for Tropheryma whipplei. Valve histopathological evaluation confirmed Tropheryma whipplei endocarditis. He was treated with intravenous penicillin followed by oral trimethoprim-sulfamethoxazole. A high index of suspicion for causes of culture-negative endocarditis needs to be maintained when blood cultures are negative despite clear evidence of endocarditis especially with large vegetation sizes and other complications such as septic emboli. Multiple imaging modalities are available to assist with diagnosis including transthoracic and transesophageal echocardiogram as well as cardiac computed tomography. A blood PCR test can identify the implicated pathogen in a more expeditious manner compared to valve histopathological evaluation. Treatment is complex and usually requires surgical intervention and prolonged antimicrobial therapy.


Subject(s)
Embolism , Endocarditis, Bacterial , Tropheryma , Whipple Disease , Humans , Male , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/complications , Middle Aged , Whipple Disease/diagnosis , Whipple Disease/complications , Whipple Disease/drug therapy , Tropheryma/isolation & purification , Embolism/diagnosis , Embolism/microbiology , Embolism/etiology , Embolism/complications , Heart Valve Diseases/microbiology , Heart Valve Diseases/diagnosis , Heart Valve Diseases/complications , Aortic Valve/microbiology , Aortic Valve/diagnostic imaging , Aortic Valve/pathology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage
18.
Eur J Clin Microbiol Infect Dis ; 43(5): 999-1002, 2024 May.
Article in English | MEDLINE | ID: mdl-38376633

ABSTRACT

This case report details the management of a 79-year-old male with recurrent methicillin-resistant Staphylococcus capitis bacteremia and endocarditis. The patient's clinical journey encompassed multiple hospital admissions, with challenges in managing endocarditis, pacemaker replacements, and potential cutaneous sources of infection. The treatment regimen included intravenous antibiotic therapy during hospitalization and suppressive antibiotic treatment upon discharge, alongside a decolonization strategy for his scalp lesions.


Subject(s)
Anti-Bacterial Agents , Bacteremia , Endocarditis, Bacterial , Staphylococcus capitis , Humans , Male , Aged , Bacteremia/drug therapy , Bacteremia/microbiology , Anti-Bacterial Agents/therapeutic use , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/diagnosis , Staphylococcus capitis/drug effects , Staphylococcus capitis/isolation & purification , Staphylococcus capitis/genetics , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcal Infections/diagnosis , Recurrence
19.
Antimicrob Agents Chemother ; 68(3): e0108323, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38349158

ABSTRACT

Infective endocarditis (IE) caused by Enterococcus spp. represents the third most common cause of IE, with high rates of relapse compared with other bacteria. Interestingly, late relapses (>6 months) have only been described in Enterococcus faecalis, but here we describe the first reported IE relapse with Enterococcus faecium more than a year (17 months) after the initial endocarditis episode. Firstly, by multi locus sequence typing (MLST), we demonstrated that both isolates (EF646 and EF641) belong to the same sequence type (ST117). Considering that EF641 was able to overcome starvation and antibiotic treatment conditions surviving for a long period of time, we performed bioinformatic analysis in identifying potential genes involved in virulence and stringent response. Our results showed a 13-nucleotide duplication (positions 1638-1650) in the gene relA, resulting in a premature stop codon, with a loss of 167 amino acids from the C-terminal domains of the RelA enzyme. RelA mediates the stringent response in bacteria, modulating levels of the alarmone guanosine tetraphosphate (ppGpp). The relA mutant (EF641) was associated with lower growth capacity, the presence of small colony variants, and higher capacity to produce biofilms (compared with the strain EF646), but without differences in antimicrobial susceptibility patterns according to standard procedures during planktonic growth. Instead, EF641 demonstrated tolerance to high doses of teicoplanin when growing in a biofilm. We conclude that all these events would be closely related to the long-term survival of the E. faecium and the late relapse of the IE. These data represent the first clinical evidence of mutations in the stringent response (relA gene) related with E. faecium IE relapse.


Subject(s)
Endocarditis, Bacterial , Endocarditis , Enterococcus faecium , Gram-Positive Bacterial Infections , Humans , Enterococcus faecium/genetics , Enterococcus faecium/metabolism , Multilocus Sequence Typing , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/microbiology , Endocarditis/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/metabolism , Guanosine Tetraphosphate/metabolism , Enterococcus faecalis/metabolism , Recurrence , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/microbiology
20.
J Antimicrob Chemother ; 79(4): 801-809, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38334390

ABSTRACT

OBJECTIVES: To investigate the genomic diversity and ß-lactam susceptibilities of Enterococcus faecalis collected from patients with infective endocarditis (IE). METHODS: We collected 60 contemporary E. faecalis isolates from definite or probable IE cases identified between 2018 and 2021 at the University of Pittsburgh Medical Center. We used whole-genome sequencing to study bacterial genomic diversity and employed antibiotic checkerboard assays and a one-compartment pharmacokinetic-pharmacodynamic (PK/PD) model to investigate bacterial susceptibility to ampicillin and ceftriaxone both alone and in combination. RESULTS: Genetically diverse E. faecalis were collected, however, isolates belonging to two STs, ST6 and ST179, were collected from 21/60 (35%) IE patients. All ST6 isolates encoded a previously described mutation upstream of penicillin-binding protein 4 (pbp4) that is associated with pbp4 overexpression. ST6 isolates had higher ceftriaxone MICs and higher fractional inhibitory concentration index values for ampicillin and ceftriaxone (AC) compared to other isolates, suggesting diminished in vitro AC synergy against this lineage. Introduction of the pbp4 upstream mutation found among ST6 isolates caused increased ceftriaxone resistance in a laboratory E. faecalis isolate. PK/PD testing showed that a representative ST6 isolate exhibited attenuated efficacy of AC combination therapy at humanized antibiotic exposures. CONCLUSIONS: We find evidence for diminished in vitro AC activity among a subset of E. faecalis IE isolates with increased pbp4 expression. These findings suggest that alternate antibiotic combinations against diverse contemporary E. faecalis IE isolates should be evaluated.


Subject(s)
Endocarditis, Bacterial , Endocarditis , Gram-Positive Bacterial Infections , Humans , Ceftriaxone/pharmacology , Ceftriaxone/therapeutic use , Enterococcus faecalis , Ampicillin/pharmacology , Ampicillin/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/microbiology , Endocarditis/drug therapy , Microbial Sensitivity Tests , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/microbiology , Drug Therapy, Combination
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