Haemophilus parainfluenzae infective endocarditis complicated by multiorgan septic emboli.

Infective endocarditis (IE) caused by Haemophilus parainfluenzae is a rare but serious condition if not diagnosed and treated promptly. In this article, we describe a patient with H. parainfluenzae IE who initially presented with non-specific symptoms but subsequently developed multiple sequelae of IE. The diagnosis of IE was made based on clinical, echocardiographic, radiological and microbiological findings. He was treated successfully with a mitral valve replacement along with 4 weeks of intravenous antibiotic therapy. Our case highlights the importance of obtaining a thorough history and a complete physical examination to ensure an early diagnosis of IE.

A case report of Vancomycin in the treatment of Q fever endocarditis.

The patient, a 43-year-old male, was admitted to the hospital with gradually aggravated exertional palpitations and chest tightness over a 2-day period. Upon hospital admission, a cardiac ultrasound revealed aortic valve redundancy, however multiple blood culture investigations came back negative. Blood mNGS was perfected, revealing Coxiella burnetii, and the diagnosis of Q fever (query fever) was established. The temperature and inflammatory indices of the patient were all normal with the treatment of vancomycin before cardiac surgery. But for the potential liver damage of and the Coxiella burnetii was still positive in the anti-phase II IgG titer, the doxycycline and hydroxychloroquine instead of vancomycin were applied for the patient. Despite receiving standardized anti-infective therapy of doxycycline combined with hydroxychloroquine, this patient had fever and increased leukocytes following surgery. After the addition of vancomycin as an anti-infective treatment, the temperature and leukocytes improved quickly. During the treatment of vancomycin, a discovery of liver injury may have resulted. These findings provide new therapy options for future professionals.

A Case of Infective Endocarditis Caused by Citrobacter koseri: Unraveling a Rare Pathogen and Dire Outcome.

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.

Association of persistent positive blood cultures and infective endocarditis: A cohort study among patients with suspected infective endocarditis.

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.

Infective Endocarditis by Capnocytophaga Species-A Narrative Review.

Bacteria belonging to the genus Capnocytophaga are thin, capnophilic, Gram-negative bacilli with tapered ends that include nine species that are isolated from the mouth of humans and animals and, from a phylogenetical perspective, they belong to the family Flavobacteriaceae. Two more species, namely C. endodontalis and C. stomatis have been recovered from a periapical abscess and human and animal infections, respectively. Capnocytophaga spp. can cause serious and potentially life-threatening infections in humans, such as bacteremia and meningitis, most commonly in the context of penetrating trauma as a result of contact with animals, especially after animal bites. Other invasive diseases such as osteomyelitis, septic arthritis, and infective endocarditis (IE) may also occur more rarely. The aim of this study was to review all previously described cases of IE by Capnocytophaga spp. and provide information about the epidemiology, microbiology, antimicrobial susceptibility, clinical characteristics, treatment, and outcomes of this infection. A narrative review based on a search in PubMed, the Cochrane Library, and Scopus was performed. Studies published until 11 September 2023 providing relevant data for IE caused by Capnocytophaga spp. in humans were included. A total of 31 studies containing data from 31 patients were included. A history of dog bites was present in 10 out of 26 patients (38.5%). A prosthetic valve was present in 3 patients (9.7%). The most commonly infected valve was the aortic valve, followed by the tricuspid valve. Fever, embolic phenomena, paravalvular abscess, and sepsis were the most common clinical presentations. Beta-lactams and aminoglycosides were the antimicrobials most commonly used. Surgery was performed in 20 patients (64.5%). Overall mortality reached 16.1%.

Comparative effectiveness of empirical antibiotic treatments in methicillin-susceptible Staphylococcus aureus infective endocarditis: A post hoc analysis of a prospective French cohort study.

OBJECTIVES: The empirical treatment of infective endocarditis is still debated. The aim of this study was to compare the impact of empirical treatment with antistaphylococcal penicillin (ASP) or cefazolin vs. other treatments in methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis. METHODS: A post hoc analysis of a prospective cohort study of patients hospitalized in a French reference centre with MSSA endocarditis was conducted between 2013 and 2022. The primary outcome was the duration of bacteraemia under treatment. RESULTS: Of the 208 patients included, 101 patients (48.6%) were classified in the reference group (ASP or cefazolin) and 107 (52.4%) in the non-reference group. Empirical treatment with ASP/cefazolin was associated with a shorter duration of bacteraemia compared to other treatments (3.6 d vs. 4.6 d, P = 0.01). This difference was not corrected by the addition of an aminoglycoside (3.6 d vs. 4.7 d, P < 0.01). In multivariate analysis, empirical treatment with ASP/cefazolin was associated with a duration of bacteraemia ≤72 h (P = 0.02), whereas endocarditis on native valves (P = 0.01), and intracardiac abscess were associated with longer duration of bacteraemia (P = 0.01). CONCLUSIONS: Empirical treatment of endocarditis with ASP or Cefazolin is more effective than other treatments in MSSA endocarditis, even when the other treatments are combined with aminoglycosides.

Suppressive antibiotic therapy for infectious endocarditis.

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.

Sensitizing methicillin-resistant Staphylococcus aureus (MRSA) to cefuroxime: the synergic effect of bicarbonate and the wall teichoic acid inhibitor ticlopidine.

Methicillin-resistant Staphylococcus aureus (MRSA) strains are a major challenge for clinicians due, in part, to their resistance to most ß-lactams, the first-line treatment for methicillin-susceptible S. aureus. A phenotype termed "NaHCO3-responsiveness" has been identified, wherein many clinical MRSA isolates are rendered susceptible to standard-of-care ß-lactams in the presence of physiologically relevant concentrations of NaHCO3, in vitro and ex vivo; moreover, such "NaHCO3-responsive" isolates can be effectively cleared by ß-lactams from target tissues in experimental infective endocarditis (IE). One mechanistic impact of NaHCO3 exposure on NaHCO3-responsive MRSA is to repress WTA synthesis. This NaHCO3 effect mimics the phenotype of tarO-deficient MRSA, including sensitization to the PBP2-targeting ß-lactam, cefuroxime (CFX). Herein, we further investigated the impacts of NaHCO3 exposure on CFX susceptibility in the presence and absence of a WTA synthesis inhibitor, ticlopidine (TCP), in a collection of clinical MRSA isolates from skin and soft tissue infections (SSTI) and bloodstream infections (BSI). NaHCO3 and/or TCP enhanced susceptibility to CFX in vitro, by both minimum inhibitor concentration (MIC) and time-kill assays, as well as in an ex vivo simulated endocarditis vegetations (SEV) model, in NaHCO3-responsive MRSA. Furthermore, in experimental IE (presumably in the presence of endogenous NaHCO3), pre-exposure to TCP prior to infection sensitized the NaHCO3-responsive MRSA strain (but not the non-responsive strain) to enhanced clearances by CFX in target tissues. These data support the notion that NaHCO3 is acting similarly to WTA synthesis inhibitors, and that such inhibitors have potential translational applications in the treatment of certain MRSA strains in conjunction with specific ß-lactam agents.

Getting to the heart of the matter-are two agents really better than one for the treatment of staphylococcal infective endocarditis?

The recently published European Society of Cardiology guidelines for infective endocarditis management recommends daptomycin combination therapy for the treatment of staphylococcal endocarditis in severe penicillin allergy, rather than daptomycin monotherapy. We discuss the evidence base behind this recommendation, highlighting concerns regarding the lack of robust clinical studies, increased cost and logistical considerations, and adverse effects of combination therapy. Although further studies are required to elucidate the role of combination vs monotherapy in these patients, we propose a pragmatic management approach to reduce the risk of adverse antimicrobial side effects and limit costs, while aiming to maintain treatment efficacy.

Differential in vitro susceptibility to ampicillin/ceftriaxone combination therapy among Enterococcus faecalis infective endocarditis clinical isolates.

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.

Staphylococcus succinus Infective Endocarditis, France.

Infective endocarditis is a rare condition in humans and is associated with high illness and death rates. We describe a case of infective endocarditis caused by Staphylococcus succinus bacteria in France. We used several techniques for susceptibility testing for this case to determine the oxacillin profile.

C-terminal deletion of RelA protein is suggested as a possible cause of infective endocarditis recurrence with Enterococcus faecium.

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.

Late Recurrence of Prosthetic Valve Endocarditis Due to Candida albicans.

BACKGROUND Candida prosthetic valve endocarditis is a rare disease that is increasing in incidence with the rising rates of fungemia and increased use of intracardiac devices. Chronic antifungal prophylaxis is used after primary treatment to prevent recurrence, but the optimal duration of prophylaxis is currently unknown. This case report is of a woman with a history of mitral valve replacement due to Candida endocarditis presenting 2 years later with prosthetic valve and native aortic valve Candida albicans endocarditis. CASE REPORT A 32-year-old woman with a history of intravenous drug abuse, Staphylococcus and Candida endocarditis, and 2 mitral valve replacements 2 years ago on long-term oral fluconazole presented with fevers, weight loss, and dyspnea. She had stopped taking her oral antifungals prior to presentation. She was found to have vegetations on her prosthetic mitral valve and on her native aortic valve. She was started on ceftriaxone, vancomycin, and micafungin, and blood cultures grew C. albicans. She also developed a C. albicans metatarsal abscess and a splenic infarct. She underwent redo mitral valve replacement and aortic valve debridement successfully and was continued on intravenous micafungin for 8 weeks. CONCLUSIONS This case highlights the association between prosthetic valve endocarditis, intravenous drug abuse, and opportunistic fungal infections. Lifelong oral fluconazole can be considered for all patients with C. albicans prosthetic valve endocarditis, especially in the setting of the presence of other risk factors, such as intravenous drug abuse, as demonstrated in our case. Further studies are needed to determine differences in outcomes.

A Case of Enterococcal Patent Ductus Arteriosus-associated Endarteritis in a Preterm Neonate.

INTRODUCTION: The persistent patency of the ductus arteriosus frequently occurs in premature neonates and can cause infective endocarditis (IE) or ductal endarteritis (DE) during sepsis. Even though neonatal IE and DE are believed to be a rare eventuality, their incidence has been increasing in the last decades due to the improved survival of even more preterm babies, favored by highly invasive procedures and therapies. In parallel, antimicrobial resistance is another rising problem in neonatal intensive care units, which frequently compels to treat infections with broad-spectrum or last generation antibiotics. CASE PRESENTATION: We report the case of a preterm neonate affected by patent ductus arteriosus-associated DE that followed an episode of sepsis caused by a high-level aminoglycoside-resistant enterococcus. The neonate was successfully treated with the synergistic combination of ampicillin and cefotaxime. DISCUSSION: IE and patent ductus arteriosus-associated DE are rising inside neonatal intensive care units and neonatologists should be aware of these conditions. Enterococcal IE and patent ductus arteriosus-associated DE sustained by high-level aminoglycoside-resistant strains can be successfully treated with the synergistic combination of ampicillin and cefotaxime even in preterm neonates.

Burkholderia cepacia: A Rare Source of Endocarditis.

A 37-year-old male with a past medical history of previous mitral valve replacement due to bacterial endocarditis and intravenous (IV) drug use was found to have Burkholderia cepacia bacteremia. Transesophageal echocardiogram revealed large mitral and tricuspid valve vegetations. Medical management was initially attempted but his bacteremia persisted, and he required urgent prosthetic mitral valve replacement and native tricuspid valve replacement. Prosthetic valve endocarditis has been associated with surgery in 48.9% of patients and a mortality of 22.8%. In patients with prosthetic valve endocarditis due to B. cepacia, valve replacement occurred in approximately 61.5% of patients and mortality is estimated to be 33.3%. To our knowledge, this is one of only a few prosthetic valve endocarditis cases caused solely by B. cepacia and our case is the first to affect multiple valves including prosthetic and native valves.