Dalbavancin as suppressive antibiotic therapy in patients with prosthetic infections: efficacy and safety.

Suppressive antibiotic therapy (SAT) is a strategy to alleviate symptoms and/or to reduce the progression of an infection when other treatment options cannot be used. Dalbavancin, due to its prolonged half-life, enables (bi) weekly dosing. Here, we report our multicenter real-life clinical experience with dalbavancin used as SAT in patients with prosthetic joint or vascular infections. Medical records of all adult patients with documented vascular or orthopedic chronic prosthetic infections, who received dalbavancin as SAT between 2016 and 2018 from four Spanish hospitals were reviewed for inclusion. Descriptive analysis of demographic characteristics, Charlson Comorbidity index, Barthel index, isolated pathogens and indication, concomitant antibiotic use, adverse events, and clinical outcome of SAT were performed. Eight patients were eligible for inclusion, where six patients had prosthetic vascular infections (aortic valve) and two patients had knee prosthetic joint infections. The most common pathogens were methicillin-susceptible Staphylococcus aureus and Enterococcus faecium. All patients had a history of prior antibiotic treatment for the prosthetic infection [median duration of antibiotic days 125 days (IQR, 28-203 days)]. The median number of dalbavancin doses was 29 (IQR, 9-61) and concomitant antibiotic use (n = 5, 62.5%). Clinical success was reported in 75% (n = 6) of patients. Adverse events were reported in two patients (mild renal and hepatic impairment). The median estimated cost savings due to the avoided hospital days was €60185 (IQR, 19,916-94984) per patient. Despite the limitations of our study, this preliminary data provides valuable insight to support further evaluation of dalbavancin for SAT in patients with prosthetic infections in the outpatient setting when alternative treatments are not feasible.

Impact of ceftazidime/avibactam versus best available therapy on mortality from infections caused by carbapenemase-producing Enterobacterales (CAVICOR study).

BACKGROUND: Infections caused by carbapenemase-producing Enterobacterales (CPE) are not well represented in pivotal trials with ceftazidime/avibactam. The best strategy for the treatment of these infections is unknown. METHODS: We conducted a multicentre retrospective observational study of patients who received ≥48 h of ceftazidime/avibactam or best available therapy (BAT) for documented CPE infections. The primary outcome was 30 day crude mortality. Secondary outcomes were 21 day clinical response and microbiological response. A multivariate logistic regression model was used to identify factors predictive of 30 day crude mortality. A propensity score to receive treatment with ceftazidime/avibactam was used as a covariate in the analysis. RESULTS: The cohort included 339 patients with CPE infections. Ceftazidime/avibactam treatment was used in 189 (55.8%) patients and 150 (44.2%) received BAT at a median of 2 days after diagnosis of infection. In multivariate analysis, ceftazidime/avibactam treatment was associated with survival (OR 0.41, 95% CI 0.20-0.80; P = 0.01), whereas INCREMENT-CPE scores of >7 points (OR 2.57, 95% CI 1.18-1.5.58; P = 0.01) and SOFA score (OR 1.20, 95% CI 1.08-1.34; P = 0.001) were associated with higher mortality. In patients with INCREMENT-CPE scores of >7 points, ceftazidime/avibactam treatment was associated with lower mortality compared with BAT (16/73, 21.9% versus 23/49, 46.9%; P = 0.004). Ceftazidime/avibactam was also an independent factor of 21 day clinical response (OR 2.43, 95% CI 1.16-5.12; P = 0.02) and microbiological eradication (OR 0.40, 95% CI 0.18-0.85; P = 0.02). CONCLUSIONS: Ceftazidime/avibactam is an effective alternative for the treatment of CPE infections, especially in patients with INCREMENT-CPE scores of >7 points. A randomized controlled trial should confirm these findings.

Role of age and comorbidities in mortality of patients with infective endocarditis.

PURPOSE: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. METHODS: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. RESULTS: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32-3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39-1.88),and non-performed surgery (HR:1.64;95% CI:11.16-1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. CONCLUSION: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group.

Impact of ertapenem use on Pseudomonas aeruginosa and Acinetobacter baumannii imipenem susceptibility rates: collateral damage or positive effect on hospital ecology?

BACKGROUND: Conflicting evidence has been reported on the impact of ertapenem use on the susceptibility of Pseudomonas spp. to group 2 carbapenems. No extensive data for Acinetobacter baumannii are currently available. METHODS: A retrospective time-series segmented regression analysis was conducted in a tertiary centre from January 2001 to December 2011. Ertapenem was introduced in January 2005. Antimicrobial drug use was defined as the number of defined daily doses/100 patient-days (DDDs/100 PDs). Susceptibility (CLSI) was measured in terms of proportion and incidence density. RESULTS: Mean monthly use of imipenem was 2.9 ±â€Š0.9 DDDs/100 PDs, as compared with 1.2 ±â€Š0.7 DDDs/100 PDs for meropenem and 1.0 ±â€Š0.7 DDDs/100 PDs for ertapenem (after its introduction). After ertapenem adoption, a downward trend was seen in the use of imipenem (P = 0.016) and ciprofloxacin (P = 0.004). A total of 6272 Pseudomonas aeruginosa and 1093 A. baumannii isolates were evaluated. Susceptibility of P. aeruginosa to imipenem improved after ertapenem introduction, both according to the proportion of susceptible isolates (P = 0.002) and to the incidence density of resistance (P ≤ 0.001). No significant change was seen in A. baumannii susceptibility to imipenem (P = 0.772). By multiple linear regression analysis, the incidence density of imipenem-resistant P. aeruginosa increased with the use of imipenem (P = 0.003) and ciprofloxacin (P = 0.008). Occurrence of outbreaks (P ≤ 0.001) and use of gentamicin (P = 0.007) were associated with A. baumannii resistance to imipenem. CONCLUSIONS: Use of ertapenem was directly associated with a downward trend in the use of imipenem and ciprofloxacin, which may have contributed to improve the susceptibility of P. aeruginosa to imipenem. Ertapenem use had no impact on the susceptibility of A. baumannii to imipenem.