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The misuse of antibiotics has been related to increased morbidity, mortality and bacterial resistance. The development of antimicrobial stewardship programmes (ASPs) has been encouraged by scientific societies as an essential measure. An educational, institutionally supported ASP was developed in our tertiary-care centre. Local guidelines on the management of infectious syndromes were created. Antimicrobial prescriptions were chosen arbitrarily weekly and counselling interviews by expert clinicians were carried out, using a paedagogic, non-restrictive methodology. Satisfaction with the interview was assessed using anonymous questionnaires. The appropriateness of antimicrobial prescriptions as well as consumption was assessed prospectively throughout the year. Feedback regarding the correct use of treatments was communicated to each participating department periodically. The improvement in antimicrobial prescription was included among the annual objectives linked to economic incentives in every department. A total of 1206 counselling interviews were carried out during the first year. Fifty-three per cent of antimicrobial prescriptions (176/332) were inappropriate when the programme started. The rate of inappropriate prescriptions continuously declined to 26.4% (107/405) in the fourth trimester (p <0.001; RR = 0.38; 95% CI, 0.23-0.43). Antimicrobial consumption decreased from 1150 defined daily doses (DDDs) per 1000 occupied bed-days in the first trimester to 852 DDDs in the fourth, reflecting a reduction in antimicrobial expenditures of 42%. A total of 352 satisfaction questionnaires were received and 98% described the advice as positive. In conclusion, the implementation of an education-based ASP achieved a significant improvement in all antimicrobial prescriptions in the centre and a reduction in antimicrobial consumption, even when no restrictive measures were implemented. The programme was highly accepted by all prescribers.

A multiinstitutional study of 307 heart transplant recipients was carried out to determine the clinical, radiographic, and prognostic characteristics, the incidence, and the etiology of pneumonias in the first year after transplantation. There were 21.1 cases of pneumonia per 100 heart transplantations. Seventy-five percent of the cases occurred in the first trimester. Eighty-two causal agents were identified, of which 60% were opportunistic, 25% were nosocomial, and 15% were community-acquired. The most frequent isolates were cytomegalovirus (20), Aspergillus species (13), and Pneumocystis carinii (11). Hemoptysis occurred more frequently in aspergillus pneumonias than in other pneumonias (54% vs. 6%, respectively; P < .05); aspergillus pneumonia was the only type of pneumonia during which cavitated nodules were noted on thoracic radiographs. The overall mortality rate was 30.8%; the independent factors of a poor prognosis were aspergillus infection (relative risk [RR], 7.4; 95% confidence interval [CI], 5.8-9.1) and bilateral pulmonary infiltrates (RR, 10; 95% CI, 8.5-11.4).

Objectives To investigate pharmacokinetics (PK) and safety (primary objectives) and efficacy (secondary objective) of the investigational monobactam/β-lactamase inhibitor combination aztreonam/avibactam in patients with complicated intra-abdominal infection (cIAI). Methods This Phase 2a open-label, multicentre study (NCT02655419; EudraCT 2015-002726-39) enrolled adults with cIAI into sequential cohorts for 5–14 days treatment. Cohort 1 patients received an aztreonam/avibactam loading dose of 500/137 mg (30 min infusion), followed by maintenance doses of 1500/410 mg (3 h infusions) q6h; Cohort 2 received 500/167 mg (30 min infusion), followed by 1500/500 mg (3 h infusions) q6h. Cohort 3 was an extension of exposure at the higher dose regimen. Doses were adjusted for creatinine clearance of 31–50 mL/min (Cohorts 2 + 3). All patients received IV metronidazole 500 mg q8h. PK, safety and efficacy were assessed. Results Thirty-four patients (Cohort 1, n = 16; Cohorts 2 + 3, n = 18) comprised the modified ITT (MITT) population. Mean exposures of aztreonam and avibactam in Cohorts 2 + 3 were consistent with those predicted to achieve joint PK/pharmacodynamic target attainment in &gt;90% patients. Adverse events (AEs) were similar between cohorts. The most common AEs were hepatic enzyme increases [n = 9 (26.5%)] and diarrhoea [n = 5 (14.7%)]. Clinical cure rates at the test-of-cure visit overall were 20/34 (58.8%) (MITT) and 14/23 (60.9%) (microbiological-MITT population). Conclusions Observed AEs were consistent with the known safety profile of aztreonam monotherapy, with no new safety concerns identified. These data support selection of the aztreonam/avibactam 500/167 mg (30 min infusion) loading dose and 1500/500 mg (3 h infusions) maintenance dose q6h regimen, in patients with creatinine clearance &gt;50 mL/min, for the Phase 3 development programme.

Background The global crisis of bacterial resistance urges the scientific community to implement intervention programs in healthcare facilities to promote an appropriate use of antibiotics. However, the clinical benefits or the impact on resistance of these interventions has not been definitively proved. Methods We designed a quasi-experimental intervention study with an interrupted time-series analysis. A multidisciplinary team conducted a multifaceted educational intervention in our tertiary-care hospital over a 5-year period. The main activity of the program consisted of peer-to-peer educational interviews between counselors and prescribers from all departments to reinforce the principles of the proper use of antibiotics. We assessed antibiotic consumption, incidence density of Candida and multidrug-resistant (MDR) bacteria bloodstream infections (BSIs) and their crude death rate per 1000 occupied bed days (OBDs). Results A quick and intense reduction in antibiotic consumption occurred 6 months after the implementation of the intervention (change in level, −216.8 defined daily doses per 1000 OBDs; 95% confidence interval, −347.5 to −86.1), and was sustained during subsequent years (average reduction, −19,9%). In addition, the increasing trend observed in the preintervention period for the incidence density of candidemia and MDR BSI (+0.018 cases per 1000 OBDs per quarter; 95% confidence interval, −.003 to .039) reverted toward a decreasing trend of −0.130 per quarter (change in slope, −0.029; −.051 to −.008), and so did the mortality rate (change in slope, −0.015; −.021 to −.008). Conclusions This education-based antimicrobial stewardship program was effective in decreasing the incidence and mortality rate of hospital-acquired candidemia and MDR BSI through sustained reduction in antibiotic use.

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Sulbactam and imipenem were compared in an experimental pneumonia model in immunocompetent mice, using a susceptible strain of Acinetobacter baumannii, and in an experimental endocarditis model in rabbits, using an intermediately susceptible strain. In the former, sulbactam was as efficacious as imipenem in terms of survival, sterility of lungs and in the bacterial clearance from lungs and blood, provided that the t > MIC for sulbactam (1.84 h) was similar to that for imipenem (2.01 h). In the endocarditis model, imipenem (t > MIC, 2.12 h) was more efficacious than sulbactam (t > MIC, 1.17 h) in bacterial clearance from vegetations. These results show the efficacy of sulbactam in infections caused by susceptible strains of A. baumannii, with an MIC up to 4 mg/L, provided that doses reach a t > MIC similar to that of imipenem. The activity of sulbactam was time dependent.