Search Results (78)

Background/Objectives: Microhematuria is common in patients with infective endocarditis (IE). The present study aims to assess whether the addition of microhematuria in the 2023 Duke-International Society for Cardiovascular Infectious Diseases (ISCVID) minor immunological criteria could enhance its diagnostic performance. Methods: This retrospective study was conducted at the Lausanne University Hospital, Switzerland (2014–2024). All patients with suspected IE and urinalysis within 24 h from presentation were included. The Endocarditis Team classified episodes as IE or non-IE. Microhematuria was defined as >5 red blood cells per high power field (HPF). Results: Among 801 episodes with suspected IE, 263 (33%) were diagnosed with IE. Microhematuria (>5/HPF) was present in 462 (58%) episodes, with no difference between episodes with and without confirmed IE (61% versus 56%; p = 0.223). Based on the 2023 ISCVID-Duke, minor immunological criteria were present in 42 episodes (5%). By adding microhematuria, 473 (59%) episodes met the minor immunological criteria. Sensitivity of the clinical criteria of the 2023 ISCVID-Duke version without and with hematuria was calculated at 75% (69–80%) and 86% (81–90%), respectively. Specificity was at 52% (48–57%) and 40% (36–45%), respectively. Among episodes with suspected IE, microhematuria was associated with female sex, enterococcal bacteremia, sepsis or septic shock, acute kidney injury, non-cerebral embolic events, and bone and joint infection. Conclusions: Microhematuria was frequent among patients with suspected IE, but it was not associated with the diagnosis of IE. The addition of microhematuria in the 2023 ISCVID-Duke minor immunological criteria did not enhance the overall performance of the criteria. Full article

Background: Splenectomy remains necessary in selected oncologic and hematologic indications but is associated with significant postoperative morbidity and mortality. The data on outcomes in this high-risk population remain limited, particularly in mixed cohorts. Methods: We conducted a retrospective cohort study including all patients undergoing splenectomy for oncologic or hematologic causes between 2009 and 2022 at a cancer referral center. The primary outcomes were the occurrence of major complications at day 90 and the 1-year all-cause mortality. Multivariate logistic regression was used to identify independent predictors. Results: Among the 8503 ICU admissions from surgical wards, 204 splenectomies were performed; 179 patients were analyzed. The median age was 64 years, and 100 patients (55.9%) were female. Splenectomy was performed for hematologic malignancies in 76 cases (42.5%) and for oncologic causes in 103 cases (57.5%). Laparotomy was used in 154 cases (86.0%), and metastasectomy was performed in 54 patients (30.2%). At day 90, 86 patients (48.0%) developed a major complication: 12 deaths (6.7%), 44 surgical complications (24.6%), and 71 episodes of sepsis (39.7%). In a multivariate analysis, weight loss (OR 3.39, 95% CI [1.32–8.70], p = 0.011), laparotomy (OR 4.38 [1.09–17.60], p = 0.038), and a higher SAPS II score (OR 1.08 per point [1.03–1.13], p = 0.003) were associated with complications, while metastasectomy was protective (OR 0.23 [0.08–0.67], p = 0.007). At one year, the mortality reached 22.4%. Independent predictors of death were sepsis at one year (OR 5.04, 95% CI [1.30–25.96], p = 0.029), the Charlson Comorbidity Index (OR 1.30 per point, 95% CI [1.04–1.68], p = 0.030), invasive mechanical ventilation (OR 14.94, 95% CI [2.83–118.93], p = 0.003), and a performance status >1 (OR 7.84, 95% CI [2.38–27.75], p < 0.001). Encapsulated bacteria were not isolated; sepsis was mainly due to Gram-negative and enterococcal organisms. Conclusions: Splenectomy in onco-hematologic patients is associated with high rates of sepsis and mortality. In addition to surgical factors, frailty, immune status, and infection independently contribute to the patients’ outcomes. These results support risk-adapted perioperative strategies and long-term infectious surveillance in immunocompromised patients. Full article

Background: Ampicillin plus ceftriaxone (AC) is a first-line treatment for Enterococcus faecalis infective endocarditis (IE). Its administration in outpatient parenteral antibiotic treatment (OPAT) programs is challenging. The design of a ceftriaxone regimen suitable for OPAT requires deep knowledge of ceftriaxone pharmacokinetics (PK). Objective: We aim to explore ceftriaxone PK in elderly patients and propose dose regimens adapted to OPAT to maintain synergistic concentrations (Cs) with ampicillin against E. faecalis. Methods: We conducted a prospective observational pharmacokinetic study on patients (>55 years old) affected by E. faecalis IE. Ceftriaxone free concentration was measured at three time-points: before the administration (C_min) and two and four hours after ceftriaxone administration (C₂ and C₄). Both structural and covariate population pharmacokinetic models were built. Monte Carlo simulations of six ceftriaxone dosages were performed and the probability of target attainment (PTA) of an optimal Cs range was analyzed. The pharmacokinetic/pharmacodynamic index (PK/PD) to predict efficacy was defined as maintaining free ceftriaxone concentrations superior to the Cs at 50–100% of the dosing interval (fT ≥ Cs ≥ 50–100% of the dosing interval). Ceftriaxone dosing regimens were considered optimal if at least 90% of the simulated population was able to achieve the defined PK/PD targets. Results: Twenty-four episodes from 16 patients were included. Mean free ceftriaxone concentration pre-dose, +2 h, and +4 h were C_min = 7.8 ± 6.5 mg/L, C₂ = 34 ± 26.5 mg/L, and C₄ = 22.7 ± 19.7 mg/L, respectively. A two-compartment model with first-order absorption and elimination best described the data. Ceftriaxone one-hour infusions only achieved the minimum PK/PD target when the 2 g/12 h regimen was tested. On the other hand, ceftriaxone continuous infusion maintained a Cs above the PK/PD target for 100% of the dosing interval using ceftriaxone 4–6 g regimens. Conclusions: Our findings suggest that the optimal ceftriaxone exposure may be achieved using high-dose continuous infusions to ensure an ampicillin-killing effect when treating E. faecalis IE. Full article

Background/Objective: Vancomycin-resistant enterococci (VRE), particularly Enterococcus faecium (VREfm), are significant healthcare-associated infections, especially bloodstream infections (BSIs). Method: This study explored the genotypic and phenotypic characteristics of 29 VREfm isolates causing BSIs in Thailand. Bacterial species, sequence types (STs), virulence genes, and vancomycin antimicrobial-resistance genes were identified by multiplex PCR, multilocus sequence typing, and whole-genome sequencing (WGS). Antibiotic susceptibility was determined by disk diffusion, while an E-test or broth microdilution were used for daptomycin, teicoplanin, linezolid, and tigecycline. Biofilm formation was assessed using a microtiter plate assay. Results: All isolates harbored the vanA gene and exhibited resistance to ampicillin, erythromycin, norfloxacin, vancomycin, and rifampin. Resistance to ciprofloxacin, tigecycline, and nitrofurantoin was widespread as well. All isolates remained susceptible to chloramphenicol and linezolid. The majority of isolates belonged to clonal complex 17, with ST17 being predominant (21/29, 72.4%), followed by ST80 (6/29, 20.7%), ST761 (1/29, 3.4%), and ST117 (1/29, 3.4%). WGS analysis confirmed the presence of various antimicrobial resistance genes, including aac(6′)-Ii, ant-Ia, erm(B), and vanA. Additionally, virulence genes such as acm (collagen adhesin) and esp (enterococcal surface protein), which are involved in biofilm formation, were detected. Conclusion: This study provides insights into the genomic characteristics and clonal dissemination of invasive VREfm in Thailand, which is crucial for infection control and public health surveillance. Full article

Ventriculo-meningitis or nosocomial meningitis/ventriculitis is a severe nosocomial infection that is associated with devastating neurological sequelae. The cerebrospinal fluid isolates associated with the infection can be Gram-positive or -negative, while the Enterococcus spp. is rarely identified. We report a case of a 68-year-old woman with a past medical history of insulin-dependent diabetes mellitus, hypertension, and coronary artery disease. She was admitted to the intensive care unit following a scheduled sphenoid wing meningioma resection. Her course was complicated with left middle cerebral artery pseudoaneurysm and hemispheric hemorrhage, and an arterial stent and external ventricular drainage catheter were placed. Neurological evaluation showed a minimal conscious state. She presented high fever on the 35th intensive care unit day. Cerebrospinal fluid was sampled and the external ventricular catheter was removed. Enterococcus faecalis was isolated from the culture specimen. The patient received targeted treatment with an ampicillin plus ceftriaxone combination, and a follow-up culture confirmed the pathogen’s eradication. Although she was considered cured, she had a prolonged intensive care unit stay and finally died in the ward two months after the completion of treatment. This case highlights the first reported use of this combination in a severe, non-endocarditis, invasive enterococcal infection, while the review discusses treatment options for nosocomial ventriculitis/meningitis. Full article

The widespread resistance of enterococci to many commonly used antimicrobial agents is a growing concern. Given that the current treatment options for enterococcal infections are limited, the discovery of new therapies, including combination therapies, is necessary. We evaluated double-drug combinations of lefamulin with doxycycline, rifampin, and quinupristin/dalfopristin for in vitro synergy against strains of Enterococcus faecium (E. faecium) and Enterococcus faecalis (E. faecalis) by using checkerboard and time-kill assays. In the checkerboard assay, the synergistic effect of lefamulin with doxycycline and rifampin was observed in 29 (85.3%) and 33 (97.1%) of the 34 different E. faecium strains tested, respectively. These combinations also showed synergistic effects against 17 (94.4%) of the 18 different vancomycin-resistant E. faecium strains. Among the 33 different E. faecalis strains, the combination of lefamulin with doxycycline, quinupristin/dalfopristin, and rifampin displayed synergistic effects in 31 (93.9%), 26 (78.8%), and 20 (60.6%) strains, respectively. No antagonism was observed in any of the combinations. The time-kill assay confirmed the synergistic effects of all these combinations. These synergistic combinations exhibited bacteriostatic activity. Although lefamulin is not currently used to treat enterococcal infections, we suggest that these combinations may serve as alternative drug regimens. Full article

(1) Background: Alternative antibiotics are needed to treat infective endocarditis (IE) caused by non-faecalis/non-faecium enterococci; we aimed to assess the in vitro activity of ampicillin plus ceftriaxone (AMP + CTR) against these enterococci and to describe its clinical efficacy in IE cases. (2) Methods: Time–kill curves with standard (ISI) and high (IHI) inocula were performed to test VanC isolates [3 E. casseliflavus (ECAS) and 1 E. gallinarum (EGALL)] and non-VanC isolates [1 E. durans (EDUR), 1 E. hirae (EHIR) and 1 E. raffinosus (ERAF)]. The narrative literature review of IE cases treated with AMP + CTR was analyzed alongside three study cases. Clinical outcomes were relapse and death. (3) Results: Ampicillin plus gentamicin (AMP + GEN) showed synergistic and bactericidal activity against most isolates. AMP + CTR was synergistic at ISI for EGALL, EDUR, and EHIR and bactericidal against EHIR. At IHI, indifferent activity was observed for all isolates. In IE cases treated with AMP + CTR, it was only effective for EDUR and EHIR. Clinical information for EGALL IE is lacking. For IE caused by ECAS and ERAF, AMP + CTR seems suboptimal or ineffective, respectively. (4) AMP + CTR cannot be recommended for treating IE due to ECAS/ERAF. In contrast, this combination was effective in IE caused by EDUR/EHIR and could be recommended. Full article

Vancomycin (Van) is a glycopeptide antibiotic commonly used as a last resort for treating life-threatening infections caused by multidrug-resistant bacterial strains, such as Staphylococcus aureus and Enterococcus spp. However, its effectiveness is currently limited due to the rapidly increasing number of drug-resistant clinical strains and its inherent cytotoxicity and poor penetration into cells and specific regions of the body, such as the brain. One of the most promising strategies to enhance its efficacy appears to be the covalent attachment of cell-penetrating peptides (CPPs) to the Van structure. In this study, a series of vancomycin conjugates with CPPs—such as TP10, Tat (47–57), PTD4, and Arg₉—were designed and synthesized. These conjugates were tested for antimicrobial activity against four reference strains (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa) and two clinical drug-resistant strains: methicillin-resistant S. aureus and vancomycin-resistant E. faecium. In addition, cytotoxicity tests (using a human fibroblast cell line) and blood–brain barrier (BBB) permeability tests (using a parallel artificial membrane permeability assay—PAMPA-BBB assay) were conducted for selected compounds. Our research demonstrated that conjugation of Van with CPPs, particularly with Tat (47–57), Arg₉, or TP10, significantly enhances its antimicrobial activity against Gram-positive bacteria such as S. aureus and Enterococcus spp., reduces its cytotoxicity, and improves its access to brain tissues. We conclude that these findings provide a strong foundation for the design of novel antimicrobial agents effective in treating infections caused by drug-resistant staphylococcal and enterococcal strains, while also being capable of crossing the BBB. Full article

Dalbavancin, a semi-synthetic lipoglycopeptide with an extended half-life that allows for weekly dosing, is currently approved for the treatment of bacterial skin and soft tissue infections caused by susceptible gram-positive organisms. This case report discusses the successful treatment of septic arthritis with dalbavancin in a 38-year-old obese male. Septic arthritis, commonly caused by Staphylococcus aureus and Streptococcus species, was diagnosed in this patient following a mechanical fall that led to worsening shoulder pain. Given the patient’s morbid obesity and concerns about antibiotic penetration, dalbavancin 1500 mg IV biweekly was chosen for its extended half-life and ease of administration. This case underscores dalbavancin’s efficacy in managing septic arthritis in obese patients, offering a convenient alternative to traditional therapies that require a peripherally inserted central catheter (PICC line), frequent dosing, therapeutic monitoring, and prolonged hospital stays. Despite its higher cost, dalbavancin’s advantages include reduced need for PICC lines, additional staff and resources to monitor therapeutic drug levels, and fewer complications, which can offset some expenses. To our knowledge, this is the first documented case investigating the use of dalbavancin for enterococcal septic arthritis with a biweekly dosing regimen. Full article

Enterococcal bacteremia (EB) is on the rise both in Sweden and globally. While Enterococcus faecalis (E. faecalis) is susceptible to ampicillin and piperacillin/tazobactam (pip/taz), Enterococcus faecium (E. faecium) is not. Historically, most enterococcal infections have been caused by E. faecalis, but the epidemiology is changing with increasing recognition of enterococci as nosocomial pathogens and the emergence of resistance to commonly used antimicrobial agents. The use of pip/taz has increased dramatically in Sweden, but it is unknown if this has affected the relative incidence of E. faecalis/E. faecium bacteremia. Here, we investigate whether the number and proportion of E. faecium bacteremia (EfmB) cases have increased. Additionally, risk factors associated with EfmB with a focus on prior antibiotic exposure are analyzed. Medical journals of 360 patients with EB admitted to Sahlgrenska University Hospital are reviewed. The proportion of EfmB cases increased from 41% in 2015 to 51% in 2021. Hospital-acquired infection, previous exposure to pip/taz, and carbapenems are identified as independent risk factors for EfmB. There are considerable patient-related differences between the EfmB and EfsB groups, but there is no difference in mortality rates. In conclusion, the increasing proportion of EfmB cases is concerning and is seen parallel to the expanding use of pip/taz, one possible contributing factor. Our findings suggest that a cautious approach to antibiotic use is essential to prevent the spread of antibiotic-resistant bacteria. Full article

Enterococcus faecalis, responsible for a majority of human and nosocomial enterococcal infections, is intrinsically resistant to aminoglycoside antibiotics (such as gentamicin, GEN), which must be used in a combined therapy to be effective. Nitroxoline (NTX) is an old antibiotic, underused for decades, but rediscovered now in an era of growing antibiotic resistance. In this in vitro study, the types of interactions between NTX and GEN on 29 E. faecalis strains were analyzed with an aim to find synergistic antimicrobial and antiadhesion combinations. Transmission electron microscopy (TEM) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to analyze changes in cell morphology and bacterial proteome after monotreatments and combined treatments. The results showed the synergistic effect for six combinations on eight strains, including the ATCC29212, and an additive effect for most strains. Combinations causing a complete inhibition of adhesion were established. Cell membrane integrity was affected by NTX, while combined NTX/GEN treatment caused dramatic changes in cell morphology. Upregulation of the expression of many proteins was established, with some emerging only after combined treatment. The results strongly imply that NTX has the potential for use in combined therapy with GEN against enterococci and it could further provide a substantial contribution to an ongoing fight against antimicrobial resistance and nosocomial infections. Full article

Enterococci commonly cause nosocomial bloodstream infections (BSIs), and the global incidence of vancomycin-resistant enterococci (VRE) BSIs is rising. This study aimed to assess the risk factors for enterococcal BSIs and 30-day mortality, stratified by Enterococcus species, vancomycin resistance, and treatment appropriateness. We conducted a retrospective cohort study (2014–2021) including all hospitalized adult patients with at least one blood culture positive for Enterococcus faecalis or Enterococcus faecium. We included 584 patients with enterococcal BSI: 93 were attributed to vancomycin-resistant E. faecium. The overall 30-day mortality was 27.5%; higher in cases of BSI due to vancomycin-resistant E. faecium (36.6%) and vancomycin-sensitive E. faecium (31.8%) compared to E. faecalis BSIs (23.2%) (p = 0.016). This result was confirmed by multivariable Cox analysis. Independent predictors of increased mortality included the PITT score, complicated bacteremia, and age (HR = 1.269, p < 0.001; HR = 1.818, p < 0.001; HR = 1.022, p = 0.005, respectively). Conversely, male gender, consultation with infectious disease (ID) specialists, and appropriate treatment were associated with reduced mortality (HR = 0.666, p = 0.014; HR = 0.504, p < 0.001; HR = 0.682, p = 0.026, respectively). In conclusion, vancomycin-resistant E. faecium bacteremia is independently associated with a higher risk of 30-day mortality. Full article

The immunocompromised host is usually vulnerable to infectious diseases due to broad-spectrum treatments and immunological dysregulation. The Enterococcus genus consists of normal gut commensals, which acquire a leading role in infective processes among individuals with compromised immune systems. These microorganisms may express a potential virulence and resistance spectrum, enabling their function as severe pathogens. The Enterococcus spp. infections in immunocompromised hosts appear to be difficult to resolve due to the immunological response impairment and the possibility of facing antimicrobial-resistant strains. As regards the related risk factors, several data demonstrated that prior antibiotic exposure, medical device insertion, prolonged hospitalization and surgical interventions may lead to Enterococcus overgrowth, antibiotic resistance and spread among critical healthcare settings. Herein, we present a comprehensive review of Enterococcus spp. in the immunocompromised host, summarizing the available knowledge about virulence factors, antimicrobial-resistance mechanisms and host-pathogen interaction. The review ultimately yearns for more substantial support to further investigations about enterococcal infections and immunocompromised host response. Full article

Background: Despite advances in diagnosis and treatment, the incidence and mortality of infective endocarditis (IE) have increased in recent decades. Studies on the risk factors for mortality in endocarditis in Latin America are scarce. Methods: This retrospective cohort study included 240 patients diagnosed with IE according to the modified Duke criteria who were admitted to two university hospitals in Rio de Janeiro, Brazil from January 2009 to June 2021. Poisson regression analysis was performed for trend tests. The multivariate Cox proportional hazards model was used to estimate the hazard ratio (HR) of predictors of in-hospital mortality. Findings: The median age was 55 years (IQR: 39–66 years), 57% were male, and 41% had a Charlson comorbidity index (CCI) score > 3. Healthcare-associated infective endocarditis (54%), left-sided native valve IE (77.5%), and staphylococcal IE (26%) predominated. Overall, in-hospital mortality was 45.8%, and mortality was significantly higher in the following patients: aged ≥ 60 years (53%), CCI score ≥ 3 (60%), healthcare-associated infective endocarditis (HAIE) (53%), left-sided IE (51%), and enterococcal IE (67%). Poisson regression analysis showed no trend in in-hospital mortality per year. The adjusted multivariate model determined that age ≥ 60 years was an independent risk factor for in-hospital mortality (HR = 1.9; 95% CI 1.2–3.1; p = 0.008). Interpretation: In this 12-year retrospective cohort, there was no evidence of an improvement in survival in patients with IE. Since older age is a risk factor for mortality, consensus is needed for the management of IE in this group of patients. Full article

Ceragenins (CSAs) are a new class of antimicrobial agents designed to mimic the activities of endogenous antimicrobial peptides. In this study, the antibacterial activities of various ceragenins (CSA-13, CSA-44, CSA-90, CSA-131, CSA-138, CSA-142, and CSA-192), linezolid, and daptomycin were assessed against 50 non-repeated Enterococcus spp. (17 of them vancomycin-resistant Enterococcus-VRE) isolated from various clinical specimens. Among the ceragenins evaluated, the MIC₅₀ and MIC₉₀ values of CSA-44 and CSA-192 were the lowest (2 and 4 μg/mL, respectively), and further studies were continued with these two ceragenins. Potential interactions between CSA-44 or CSA-192 and linezolid were tested and synergistic interactions were seen with the CSA-192-linezolid combination against three Enterococcus spp., one of them VRE. The effects of CSA-44 and CSA-192 on the MIC values of vancomycin were also investigated, and the largest MIC change was seen in the vancomycin-CSA-192 combination. The in vivo effects of CSA-44 and CSA-192 were evaluated in a Caenorhabditis elegans model system. Compared to no treatment, increased survival was observed with C. elegans when treated with ceragenins. In conclusion, CSA-44 and CSA-192 appear to be good candidates (alone or in combination) for the treatment of enterococcal infections, including those from VRE. Full article