Severe murine typhus complicated by multiple organ dysfunctions: A case report.

Background: Rickettsioses are infectious diseases which are caused by intracellular bacteria which belong to the family Rickettsiaceae. This zoonosis endemically prefers tropical and subtropical regions of which the Mediterranean is included. Murine typhus is a type of rickettsial disease that commonly presents with undulating fever, headache rash, chills, malaise, and myalgias. It can lead to complications such as multi-organ failure and has a lethality rate of <5% in such cases. Case Presentation: A 70-year-old male was hospitalized at the Unit of Infectious Diseases, Mother Teresa Hospital, Tirana, Albania in a comatose condition. He had a seven-day history of fever up to 39-40°C, headache, fatigue, anorexia, vomiting, cough, and myalgia. He was a farmer and had contact with animals. Upon admission, he had scleral hemorrhages, hepatosplenomegaly, jaundice, maculopapular rash over the trunk, abdomen, and palms of his hands as well as severe acidosis, depressed bicarbonate levels, alteration in liver, kidney, and pancreas function tests. He was urgently transferred to the Intensive care unit of the Infectious Diseases Department. He was hemodynamically unstable and was put immediately on vasoactive agents and mechanical ventilation. ELISA Rickettsia typhi IgM resulted positive. Supportive treatment along with antibiotics Levofloxacin and Ceftriaxone was initiated. However, the patient died on the 4th day of hospitalization and the 11th of the disease onset. Conclusion: Murine typhus should be included in the investigation of possible causes when dealing with patients presenting with fever and maculopapular rash complicated by multi-organ failure and coming from a typhus-endemic area, especially in the summer season.

Pharmacokinetic parameters of CAZ-AVI in the normal lung and in models of pneumonia: lessons for treatment optimization in critical care.

The spread of multidrug-resistant Gram-negative bacterial infections is a significant issue for worldwide public health. Gram-negative organisms regularly develop resistance to antibiotics, especially to ß-lactam antimicrobials, which can drastically restrict the number of therapies. A third-generation cephalosporin and the non-ß-lactam ß-lactamase inhibitor avibactam, which exhibits broad-spectrum ß-lactamase inhibition in vitro, are combined to form ceftazidime-avibactam (CAZ-AVI). In this narrative review, we summarize data on pharmacokinetic (PK) parameters for CAZ-AVI in both animal and human models of pneumonia, as well as in healthy individuals. We assessed current literature performing an extensive search of the literature, using as search words 'CAZ-AVI', 'pharmacokinetics', 'pneumonia', 'lung', and 'epithelial lining fluid'. Overall, lung exposure studies of CAZ-AVI revealed that the epithelial lining fluid penetration ranges between 30% and 35% of plasma concentration. Despite the fair lung penetration of CAZ-AVI, this antimicrobial agent has a pivotal role in managing patients with multi-drug resistant Gram-negative pneumonia, however further studies are needed to better assess its PK profile.

Cefiderocol and Sulbactam-Durlobactam against Carbapenem-Resistant Acinetobacter baumannii.

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) remain a clinical challenge due to limited treatment options. Recently, cefiderocol, a novel siderophore cephalosporin, and sulbactam-durlobactam, a bactericidal ß-lactam-ß-lactamase inhibitor combination, have been approved by the Food and Drug Administration for the treatment of A. baumannii infections. In this review, we discuss the mechanisms of action of and resistance to cefiderocol and sulbactam-durlobactam, the antimicrobial susceptibility of A. baumannii isolates to these drugs, as well as the clinical effectiveness of cefiderocol and sulbactam/durlobactam-based regimens against CRAB. Overall, cefiderocol and sulbactam-durlobactam show an excellent antimicrobial activity against CRAB. The review of clinical studies evaluating the efficacy of cefiderocol therapy against CRAB indicates it is non-inferior to colistin/other treatments for CRAB infections, with a better safety profile. Combination treatment is not associated with improved outcomes compared to monotherapy. Higher mortality rates are often associated with prior patient comorbidities and the severity of the underlying infection. Regarding sulbactam-durlobactam, current data from the pivotal clinical trial and case reports suggest this antibiotic combination could be a valuable option in critically ill patients affected by CRAB infections, in particular where no other antibiotic appears to be effective.

Clinical results with the use of ceftaroline and ceftobiprole: real-life experience in a tertiary care hospital.

INTRODUCTION: Ceftaroline and ceftobiprole show activity against resistant Gram-positive cocci as well as good tolerability and are increasingly used in diverse infections. No comparative data on the efficacy and safety of ceftaroline and ceftobiprole in real-life are available. METHODS: In this single-centre, observational, retrospective clinical study, the outcomes of patients treated with ceftaroline or ceftobiprole in our hospital were compared, assessing clinical data, use and drug exposure of study antibiotics, and outcomes. RESULTS: A total of 138 patients were included in this study, including 75 treated with ceftaroline and 63 treated with ceftobiprole. Patients treated with ceftobiprole had more comorbidities [median Charlson comorbidity index 5 (4-7) vs. 4 (2-6) for ceftaroline; P = 0.003], a higher prevalence of multiple site infections (P < 0.001) and were more often treated empirically (P = 0.004), whilst ceftaroline was more frequently used in patients with healthcare-related infections. No differences were observed in terms of hospital mortality, length of stay, and rates of clinical cure, improvement or failure. The only independent predictor of outcome was Staphylococcus aureus infection. Both treatments were generally well tolerated. CONCLUSION: In our real-life experience, ceftaroline and ceftobiprole, applied in different clinical scenarios, were comparable in terms of clinical efficacy and tolerability in a range of severe infections with variable aetiology and different levels of clinical severity. We believe our data may support the clinician in choosing the best option for each therapeutic setting.

CEFTO-CURE study: CEFTObiprole Clinical Use in Real-lifE - a multi-centre experience in Italy.

BACKGROUND: Ceftobiprole is approved in Europe for treatment of community-acquired pneumonia and non-ventilator-associated hospital-acquired pneumonia (HAP) in adults. Real-world data are limited. METHODS: This multi-centre, observational, ambispective investigator-initiated study was undertaken in Italy from January 2018 to December 2019 in order to evaluate the use of ceftobiprole in a real-world setting. RESULTS: Overall, 195 patients from 10 centres were evaluated (68% retrospectively). Male sex was prevalent (n=121, 62%). Median age was 67 [interquartile range (IQR) 53-75] years. Median Charlson Comorbidity Index score was 5 (IQR 3-7). The most common indication was pneumonia (151/195, 77%), especially HAP. Other uses were skin and soft tissue infections (5%), endocarditis (4%) and bone infections (4%). Ceftobiprole was usually an empiric choice (65%), in combination with other drugs (66%) and as second-line therapy (58%). A causative agent was found in 39% of cases. A diagnosis of sepsis was made in 59 cases (30%). Success in the clinically evaluable population (excluding 12 cases due to isolation of pathogens outside ceftobiprole's spectrum of activity) was obtained in 79% of cases, with all-cause mortality of 20%. On multi-level analysis, three predictors were positively associated with clinical success: male gender, pneumonia and detection of causal agent. Sepsis was a negative predictor. Nine factors were independently associated, favourably or unfavourably, with fatal outcome. CONCLUSIONS: Ceftobiprole is a safe and effective therapeutic choice, even in a real-world setting. More data are needed to establish its efficacy in patients with sepsis.

Evidence-Based Treatment of Pseudomonas aeruginosa Infections: A Critical Reappraisal.

Multidrug-resistant (MDR)/extensively drug-resistant (XDR) Pseudomonas aeruginosa is emerging as a major threat related to adverse patient outcomes. The goal of this review is to describe evidence-based empiric and targeted treatment regimens that can be exploited when dealing with suspected or confirmed infections due to MDR/XDR P. aeruginosa. P. aeruginosa has inherent resistance to many drug classes, the capacity to form biofilms, and most importantly, the ability to quickly acquire resistance to ongoing treatments. Based on the presence of risk factors for MDR/XDR infections and local epidemiology, where large proportions of strains are resistant to classic beta-lactams, the recommended empirical treatment for suspected P. aeruginosa infections is based on ceftolozane-tazobactam or ceftazidime-avibactam. Where local epidemiology indicates low rates of MDR/XDR and there are no risk factors, a third or fourth generation cephalosporin can be used in the context of a "carbapenem-sparing" strategy. Whenever feasible, antibiotic de-escalation is recommended after antimicrobial susceptibility tests suggest that it is appropriate, and de-escalation is based on different resistance mechanisms. Cefiderocol and imipenem-cilastatin-relebactam withstand most resistance mechanisms and may remain active in cases with resistance to other new antibiotics. Confronting the growing threat of MDR/XDR P. aeruginosa, treatment choices should be wise, sparing newer antibiotics when dealing with a suspected/confirmed susceptible P. aeruginosa strain and choosing the right option for MDR/XDR P. aeruginosa based on specific types and resistance mechanisms.

Clinical efficacy and safety of cefiderocol for resistant Gram-negative infections: a real-life, single-centre experience.

OBJECTIVES: Cefiderocol is a 'siderophore' cephalosporin active against Gram-negative bacteria, including carbapenem-resistant strains. Data on the use of cefiderocol in real life are limited. We evaluated the efficacy and safety of cefiderocol in the context of our hospital clinical practice. METHODS: This was a single-centre, observational, retrospective clinical study. We collected data for all patients who received cefiderocol therapy in our hospital, with a focus on clinical outcomes and adverse events. RESULTS: The study cohort included 28 patients, with a median age of 73 years (25-83 years) and a high burden of co-morbidities. Up to 45 Gram-negative isolates were cultured from the study patients, the most common pathogen being Acinetobacter baumannii (31.1%). Cefiderocol was mostly prescribed for pneumonia (37.8% of cases), bloodstream infection (24.4%), urinary tract infection (22.2%) and intra-abdominal infection (20%), and largely as salvage therapy (92.8%). Of the 18 patients for whom follow-up cultures were available, 14 (77.8%) achieved eradication of the causative micro-organism. Therapeutic success (improvement/resolution of infection) occurred in 64.3% of cases at 7 days and 50% at 14 days from treatment start. Treatment failed in 9 cases (32.1%). No effects on kidney, liver or bone marrow function were observed. CONCLUSIONS: Cefiderocol showed fair efficacy and excellent tolerability in highly co-morbid patients with a range of multiresistant infections. It may be an option for infections due to colistin-resistant pathogens, when other regimens fail or in cases at risk of kidney dysfunction.

Risk factors for Gram-negative bacterial infection of cardiovascular implantable electronic devices: multicentre observational study (CarDINe Study).

BACKGROUND: Infections of cardiovascular implantable electronic devices (CIED) are mainly due to Gram-positive bacteria (GPB). Data about Gram-negative bacteria CIED (GNB-CIED) infections are limited. This study aimed to investigate risk factors, clinical and diagnostic characteristics, and outcome of patients with GNB-CIED. METHODS: A multicentre, international, retrospective, case-control-control study was performed on patients undergoing CIED implantation from 2015 to 2019 in 17 centres across Europe. For each patient diagnosed with GNB-CIED, one matching control with GPB-CIED infection and two matching controls without infection were selected. RESULTS: A total of 236 patients were enrolled: 59 with GNB-CIED infection, 59 with GPB-CIED infection and 118 without infection. No between-group differences were found regarding clinical presentation, diagnostic and therapeutic management. A trend toward a higher rate of fluorodeoxyglucose positron emission computed tomography (FDG PET/CT) positivity was observed among patients with GNB than in those with GPB-CIED infection (85.7% vs. 66.7%; P = 0.208). Risk factors for GNB-CIED infection were Charlson Comorbidity Index Score (relative risk reduction, RRR = 1.211; P = 0.011), obesity (RRR = 5.122; P = 0.008), ventricular-pacing ventricular-sensing inhibited-response pacemaker implantation (RRR = 3.027; P = 0.006) and right subclavian vein site of implantation (RRR = 5.014; P = 0.004). At 180-day survival analysis, GNB-CIED infection was associated with increased mortality risk (HR = 1.842; P = 0.067). CONCLUSIONS: Obesity, high number of comorbidities and right subclavian vein implantation site were associated with increased risk of GNB-CIED infection. A prompt therapeutic intervention that may be guided using FDG PET/CT is suggested in patients with GNB-CIED infection, considering the poorer outcome observed in this group.

Clinical Characteristics and Outcome of MDR/XDR Bacterial Infections in a Neuromuscular Semi-Intensive/Sub-Intensive Care Unit.

(1) Background: The aim of this study was to assess the clinical and microbiological characteristics of multidrug-resistant infections in a neuromuscular semi-intensive/sub-intensive care unit; (2) Methods: Retrospective analysis on data from 18 patients with NMD with proven MDRO/XDRO colonisation/infection from August 2021 to March 2022 was carried out; (3) Results: Ten patients were males (55.6%), with a median age of 54 years, and there were fourteen patients (77.8%) with amyotrophic lateral sclerosis. All patients had at least one invasive device. Ten (55.6%) patients developed MDRO/XDRO infection (with a median time of 24 days) while six (33.3%) were colonised. The Charlson comorbidity index was >2 in both groups but higher in the infected compared with the colonised (4.5 vs. 3). Infected patients were mostly females (seven patients) with a median age of 62 years. The most common pathogens were Acinetobacter baumannii and Pseudomonas aeruginosa, infecting four (28.6%) patients each. Of eighteen infectious episodes, nine were pneumonia (hospital-acquired in seven cases). Colistin was the most commonly active antibiotic while carbapenems were largely inactive. Eradication of infection occurred in seven infectious episodes (38.9%). None of those with infection died; (4) Conclusions: MDRO/XDRO infections are common in patients with neuromuscular diseases, with carbapenem-resistant non-fermenting Gram-negative bacilli prevailing. These infections were numerically associated with the female sex, greater age, and comorbidities. Both eradication and infection-related mortality appeared low. We highlight the importance of infection prevention in this vulnerable population.

Dissecting the correlates of N-terminal prohormone brain natriuretic peptide in acute infective endocarditis.

PURPOSE: To explore the prognostic value and the correlates of NT-proBNP in patients with acute infective endocarditis, a life-threatening disease, with an often unpredictable outcome given by the lack of reliable prognostic parameters. METHODS: We retrospectively studied 337 patients admitted to our centre between January 1, 2006 and September 30, 2020 with available NT-proBNP level at admission. Our analyses were performed considering NT-proBNP as both a categorical variable, using the median value as the cut-off level, and numerical variable. Study end points were in-hospital mortality, cardiac surgery and 1 year survival. RESULTS: NT-proBNP was an independent predictor of in-hospital mortality (OR 14.9 [95%C.I. 2.46-90.9]; P = .003). Levels below 2926 pg/mL were highly predictive of a favorable in-hospital outcome (negative predictive value 96.6%). Patients with higher NT-proBNP levels showed a significantly lower survival rate at 1 year follow-up (log-rank P = .005). NT-proBNP was strongly associated with chronic kidney disease (P < .001) and significantly higher in patients with prior chronic heart failure (P = .001). NT-proBNP was tightly related to staphylococcal IE (P = .001) as well as with higher CRP and hs-troponin I (P = 0.023, P < .001, respectively). CONCLUSION: Our results confirm the remarkable prognostic role of NT-proBNP in patients with IE and provide novel evidences of its multifaceted correlates in this unique clinical setting. Our data strongly support the incorporation of NT-proBNP into the current diagnostic work-up of IE.

Visceral Leishmaniasis and Herpes Zoster as a Component of Syndrome of Immune Reconstitution Inflammatory Syndrome in an HIV-Positive Patient.

Immune reconstitution syndrome (IRIS) is a state of unusual hyperinflammatory response against latent infections which occurs after CD4 cell count improvement and as a consequence of immune response once highly active antiretroviral therapy for HIV is introduced. Leishmania parasites and varicella zoster virus (VZV) may be a manifestation of IRIS, but few data exist in literature in particular regarding Leishmania parasites. Case Presentation. A 47-year-old man was admitted to our hospital with fever. He was diagnosed with HIV infection and was a late presenter according to CD4+ count of 98 cells/mm3/9.5% and baseline illness (chronic diarrhea, weight loss, and oral candidiasis). The patient started highly active antiretroviral therapy (abacavir plus lamivudine plus efavirenz). Clinical symptoms improved and CD4+ increased to 22%, 374 cells/mm3. After 88 days, he presented with a 17-day history of high fever, sweat, fatigue, further weight loss, and lethargy. According to clinical image findings and hematochemical parameters, the patient was diagnosed with visceral leishmaniasis. He improved under treatment with liposomal amphotericin B. He presented again, 105 days after with disseminated herpes zoster infection. CD4+ count was 28.5%, 455 cell/mm3. The patient started treatment with acyclovir for 10 days. Four weeks later, he had no skin elements. At present, the patient continues HAART and is under regular monitoring. Conclusions. Early diagnosis of IRIS-associated diseases and treatment were fundamental in the patient's prognosis. Our patient presented with two different components of IRIS in two different time frames, confirming IRIS to be a broad-spectrum disease, heterogeneous and unique for each patient. A close monitoring during ART initiation, in particular in late presenters, is important in preventing IRIS. In case of IRIS development, a detailed investigation of rare associated diseases not only common ones is of great importance for the management and the prognosis of these patients.

Prognostic Value of Decreased High-Density Lipoprotein Cholesterol Levels in Infective Endocarditis.

(1) Background: Simple parameters to be used as early predictors of prognosis in infective endocarditis (IE) are lacking. The aim of this study was to evaluate the prognostic role of high-density-lipoprotein cholesterol (HDL-C) and also of total-cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and triglycerides, in relation to clinical features and mortality, in IE. (2) Methods: Retrospective analysis of observational data from 127 consecutive patients with a definite diagnosis of IE between 2016 and 2019. Clinical, laboratory and echocardiography data, mortality, and co-morbidities were analyzed in relation to HDL-C and lipid profile. (3) Results: Lower HDL-C levels (p = 0.035) were independently associated with in-hospital mortality. HDL-C levels were also significantly lower in IE patients with embolic events (p = 0.036). Based on ROC curve analysis, a cut-off value was identified for HDL-C equal to 24.5 mg/dL for in-hospital mortality. HDL-C values below this cut-off were associated with higher triglyceride counts (p = 0.008), higher prevalence of S. aureus etiology (p = 0.046) and a higher in-hospital mortality rate (p = 0.004). Kaplan-Meier survival analysis showed higher 90-day mortality in patients with HDL-C ≤ 24.5 mg/dL (p = 0.001). (4) Conclusions: Low HDL-C levels could be used as an easy and low-cost marker of severity in IE, particularly to predict complications, in-hospital and 90-day mortality.

Clinical Significance and Prognostic Value of Hemostasis Parameters in 337 Patients with Acute Infective Endocarditis.

(1) Background: The aim of this study was to assess the clinical significance and prognostic role of the main hemostasis parameters in infective endocarditis (IE): prothrombin time as international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimers, platelet count, homocysteine. (2) Methods: We studied 337 patients with IE. Clinical, hemato-chemical and echocardiography parameters were analyzed. Coagulation parameters were measured on admission. (3) Results: D-dimers levels (p = 0.012) and a prolonged PT-INR (p = 0.013) were associated with higher in-hospital mortality, while prolonged aPTT (p = 0.021) was associated with increased 1-year mortality. Staphylococcus aureus (S. aureus) infection (p = 0.003), prosthetic valve endocarditis (PVE) (p = 0.001), surgical indication (p = 0.002) and higher D-dimer levels (p = 0.005) were independent predictors of in-hospital mortality. PVE (p = 0.001), a higher Charlson Comorbidity Index (p = 0.049), surgical indication (p = 0.001) and prolonged aPTT (p = 0.012) were independent predictors of 1-year mortality. Higher levels of D-dimers (p < 0.001) and a shorter aPTT (p < 0.001) were associated with embolic complications of IE. S. aureus etiology was bound to higher D-dimers levels (p < 0.001) and a shorter aPTT (p = 0.006). (4) Conclusions: Elevated D-dimers are associated with a higher risk for in-hospital mortality in IE patients. High D-dimers and a short aPTT are associated with a higher risk for embolic events in IE. A longer aPTT is associated with 1-year mortality.

Risk Factors and Outcome of Multidrug-Resistant Infections after Heart Transplant: A Contemporary Single Center Experience.

(1) Background: The aim of this study was to assess risk factors for multidrug-resistant/extensively drug-resistant (MDR/XDR) bacterial infections in heart transplant (HT) patients within three months after surgery and its impact on patient outcome. (2) Methods: Retrospective analysis of clinical, hemato-chemical, imaging, treatment and outcome data from 47 heart transplant recipients from January 2016 to December 2018. MDR/XDR infections were compared to non-MDR/XDR and noninfected patients. (3) Results: Most participants were males, median age 51 years: 35 (74.5%) developed an infection after HT; 14 (29.8%) were MDR/XDR infections. Prolonged hospital stay before HT correlated to MDR/XDR infection (p < 0.001). Sequential organ failure assessment (SOFA) score at sampling day was higher in MDR/XDR (p = 0.027). MDR/XDR were mostly blood-stream (BSI) (p = 0.043) and skin-soft tissue (SSTI) (p = 0.047) infections. Gram-negative infections were the most frequent, specifically carbapenem-resistant Klebsiella pneumoniae. Antibiotic therapy duration for MDR/XDR infections was longer (p = 0.057), eradication rate lower (p = 0.083) and hospital stay longer (p = 0.005) but not associated with a worse outcome. (4) Conclusions: MDR/XDR infections affect compromised HT recipients with a history of prolonged hospitalization, causing a lower rate of eradication and increased hospital stay. These frequently present as BSI and SSTI. We emphasize the need to prevent contamination of central venous catheters and the surgical site.

Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience.

Background: The aim of this study was to assess the drivers of multidrug-resistant (MDR) bacterial infection development in coronavirus disease 2019 (COVID-19) and its impact on patient outcome. Methods: Retrospective analysis on data from 32 consecutive patients with COVID-19, admitted to our intensive care unit (ICU) from March to May 2020. Outcomes considered were MDR infection and ICU mortality. Results: Fifty percent of patients developed an MDR infection during ICU stay after a median time of 8 [4-11] days. Most common MDR pathogens were carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, causing bloodstream infections and pneumonia. MDR infections were linked to a higher length of ICU stay (p = 0.002), steroid therapy (p = 0.011), and associated with a lower ICU mortality (odds ratio: 0.439, 95% confidence interval: 0.251-0.763; p < 0.001). Low-dose aspirin intake was associated with both MDR infection (p = 0.043) and survival (p = 0.015). Among MDR patients, mortality was related with piperacillin-tazobactam use (p = 0.035) and an earlier onset of MDR infection (p = 0.042). Conclusions: MDR infections were a common complication in critically ill COVID-19 patients at our center. MDR risk was higher among those dwelling longer in the ICU and receiving steroids. However, MDR infections were not associated with a worse outcome.

Effect of immunosuppression maintenance in solid organ transplant recipients with COVID-19: Systematic review and meta-analysis.

BACKGROUND: The aim of this study was to assess the effect of continuing immune suppressive therapy in solid organ transplant recipients (SOTR) with coronavirus disease 2019 (COVID-19). METHODS: Systematic review and meta-analysis of data on 202 SOTR with COVID-19, published as case reports or case series. We extracted clinical, hemato-chemical, imaging, treatment, and outcome data. RESULTS: Most patients were kidney recipients (61.9%), males (68.8%), with median age of 57 years. The majority was on tacrolimus (73.5%) and mycophenolate (65.8%). Mortality was 18.8%, but an equal proportion was still hospitalized at last follow up. Immune suppressive therapy was withheld in 77.2% of patients, either partially or completely. Tacrolimus was continued in 50%. One third of survivors that continued immunosuppressants were on dual therapy plus steroids. None of those who continued immunosuppressants developed critical COVID-19 disease. Age (OR 1.07, 95% CI 1-1.11, P = .001) and lopinavir/ritonavir use (OR 3.3, 95%CI 1.2-8.5, P = .013) were independent predictors of mortality while immunosuppression maintenance (OR 0.067, 95% CI 0.008-0.558, P = .012) and tacrolimus continuation (OR 0.3, 95% CI 0.1-0.7, P = .013) were independent predictors of survival. CONCLUSIONS: Our data suggest that maintaining immune suppression might be safe in SOTR with moderate and severe COVID-19. Specifically, receiving tacrolimus could be beneficial for COVID-19 SOTR. Because of the quality of the available evidence, no definitive guidance on how to manage SOTR with COVID-19 can be derived from our data.

Dalbavancin for infective endocarditis: a single centre experience.

Infective endocarditis (IE) is a life-threatening disease, mostly caused by gram-positive cocci, needing a 4-6 weeks antibiotic course. Dalbavancin is a lipoglycopeptide active on gram-positive microorganisms, with a unique pharmacokinetic profile. We describe our experience with dalbavancin to complete the intravenous antibiotic regimen for difficult-to-treat IE cases due to gram-positive bacteria. We treated 10 severely ill patients, each presenting several comorbidities. Seven patients were microbiologically cured from IE, but two patients experienced IE relapse due to the same microrganism. Short-term mortality after dalbavancin was nil, but late mortality (within 1 year of hospital discharge) was 60%. No death was related to dalbavancin therapy. Treatment was generally well tolerated. Dalbavancin may be an option to complete IE treatment in selected cases, once blood culture clearance and improvement of clinical conditions under standard therapy is reached, allowing shortening of hospitalization.

Enterococcal infective endocarditis is a marker of current occult or future incident colorectal neoplasia.

BACKGROUND: Few studies suggest an association between Enterococcal infective endocarditis (EIE) and colorectal disease, including colorectal neoplasia (CRN) and colorectal cancer (CRC). In this study, we analyze differences in prevalence, risk factors and outcome of CRN and CRC between EIE and Streptococcus gallolyticus infective endocarditis (SGIE). METHODS: Single center, observational study of 166 patients with definite EIE or SGIE. Clinical data were collected prospectively in a standardized IE protocol. Colonoscopy data were collected retrospectively on 90 patients. RESULTS: 85 patients had EIE, 81 SGIE. EIE patients had a higher rate of prior cancer (20% vs 6%) and health-care associated infection (12% vs 1%), but similar mortality than SGIE. Colonoscopy performed in 90 patients showed intestinal diseases in 30 of 42 (71%) EIE patients vs. 40 of 48 (83%) SGIE patients (p = 0.174), with a predominance of CRN. Among 78 patients who underwent colonoscopy after IE diagnosis, no difference between EIE and SGIE was observed in the rate of non-neoplastic lesions (48% vs 47%), benign (32% vs 40%) or malignant (13% vs 15%) neoplastic lesions. Adverse events during colonoscopy were uncommon, although a careful handling of anticoagulation was required. CONCLUSIONS: EIE seems to be associated with colorectal disease, including colorectal neoplasia and colorectal cancer, to the same extent as SGIE. EIE should be considered a marker of colorectal neoplasia, even in patients with a clear health-care related acquisition. Colonoscopy is generally safe in EIE patients, and should be considered to early diagnose and treat colorectal disease.

Real-life experience with ceftobiprole in a tertiary-care hospital.

OBJECTIVES: Ceftobiprole is a new therapeutic option for bacterial pneumonia, with activity against most antimicrobial-resistant Gram-positive cocci, including methicillin-resistant Staphylococcus aureus. Data on the use of ceftobiprole in real life are limited. We evaluated the efficacy and safety of ceftobiprole in a context of a hospital practice. METHODS: In a single-centre, observational, retrospective clinical study, we collected data of 29 patients undergoing ceftobiprole therapy, with a focus on clinical outcomes and adverse events. RESULTS: There was a high burden of comorbidities in the study cohort, including kidney dysfunction (38%) and cancer (24%), and a high proportion of patients with sepsis/septic shock (72%), a central line (41%) or on mechanical ventilation (21%). Most infections were nosocomial (24, 82.8%). Ceftobiprole was mostly prescribed for pneumonia (17 patients, 58.6%), and bloodstream infections (10 patients, 34.5%), both empirically (9 cases, 31%) and as targeted therapy (20, 69%, with staphylococci as the dominant pathogens). It was the first-line drug in 15 cases (51.7%). Overall, a favourable clinical outcome was observed in the majority of cases (68.9%), with clinical cure in 3 (10.3%) and clinical improvement in 17 (58.6%). Failure of treatment occurred in seven cases (24.1%). Three patients experienced a definite ceftobiprole-related adverse event, with two cases of myoclonus. No major adverse effect on bone marrow, kidney or liver function was observed. CONCLUSIONS: Ceftobiprole, even outside current indications, may be a safe and effective treatment for resistant Gram-positive cocci infections where other drugs are inactive or poorly tolerated, and for salvage therapy.