Outcomes of the PIRASOA programme, an antimicrobial stewardship programme implemented in hospitals of the Public Health System of Andalusia, Spain: an ecologic study of time-trend analysis.

OBJECTIVES: Inappropriate antimicrobial use favours the spread of resistance, and multidrug-resistant microorganisms (MDR) are currently of major concern. Antimicrobial stewardship programmes (ASPs) are essential for improving antibiotic use in hospitals. However, their impact on entire healthcare systems has not been thoroughly assessed. Our objective was to provide the results of an institutionally supported ASP involving 31 public hospitals in Andalusia, Spain. METHODS: We designed an ecologic time-series study from 1 January 2014 to 31 December 2017. Quarterly, data on indicators were collected prospectively, and feedback reports were provided. PIRASOA is an ongoing clinically based quality-improvement programme whose key intervention is the educational interview, regular peer-to-peer interventions between advisors and prescribers to reinforce the appropriate use of antibiotics. Seventy-two indicators were monitored to measure prescribing quality (inappropriate treatments), antimicrobial consumption (defined daily doses per 1000 occupied bed-days), incidence density of MDR per 1000 occupied bed-days and crude mortality rate associated with bloodstream infections. We used Joinpoint regression software to analyse the trends. RESULTS: The quality of antimicrobial prescribing improved markedly, and the inappropriate treatment rate was significantly lower, with quarterly percentage change (QPC) = -3.0%, p < 0.001. Total antimicrobial consumption decreased (QPC = -0.9%, p < 0.001), specifically carbapenems, amoxicillin/clavulanic acid, quinolones and antifungal agents, whereas antipseudomonal cephalosporin use increased. While the incidence of MDR showed a sustained decreasing trend (QPC = -1.8%; p 0.002), the mortality of patients with bloodstream infections remained stable (QPC = -0.2%, p 0.605). CONCLUSIONS: To date, the PIRASOA programme has succeeded in optimizing the use of antimicrobial agents and has had a positive ecologic result on bacterial resistance at level of an entire healthcare system.

Population pharmacokinetics and pharmacodynamics of fosfomycin in non-critically ill patients with bacteremic urinary infection caused by multidrug-resistant Escherichia coli.

OBJECTIVES: To describe the population pharmacokinetics of fosfomycin for patients with bacteraemic urinary tract infection (BUTI). The analysis identified optimal regimens on the basis of pharmacodynamic targets and assessed the adequacy of Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) susceptibility breakpoints for Escherichia coli. METHODS: Data of 16 patients with BUTI caused by multidrug-resistant E. coli (FOREST clinical trial) received intravenous fosfomycin (4 g every 6 hours) were analysed. A population pharmacokinetic analysis was performed, and Monte Carlo simulations were undertaken using 4 g every 6 hours and 8 g every 8 hours. The probability of pharmacodynamic target attainment was assessed using pharmacodynamic targets for E. coli for static effect, 1-log drop in bacterial burden and resistance suppression. RESULTS: Sixty-four plasma samples were collected over a single dosing interval (day 2 or 3 after starting fosfomycin treatment). Fosfomycin concentrations were highly variable. Pharmacodynamic target attainment analysis showed mild improvement by increasing fosfomycin dosing (4 g every 6 hours vs. every 8 hours). These dosages showed success for decreasing 1-log bacterial burden in 89% to 96% (EUCAST breakpoints) and 33% to 54% (CLSI breakpoints) of patients, but they were unable to reach bacterial resistance suppression targets. CONCLUSIONS: Fosfomycin concentrations are highly variable-a fact partially explained by renal impairment. The present work supports the use of 4 g every 6 hours as an effective regimen for the treatment of non-critically ill patients with BUTI caused by multidrug-resistant E. coli, as higher dosages might increase toxicity but may not significantly increase efficacy. The current information may suggest that fosfomycin susceptibility breakpoints need to be reappraised.

Chronic Invasive Pulmonary Aspergillosis in Two Cats with Diabetes Mellitus.

Human patients with diabetes mellitus are at increased risk of fungal infections. Diabetes mellitus has also been implicated as a predisposing factor in the establishment of fungal lung infections in cats. Two diabetic cats of different origins presented with severe acute respiratory conditions that resulted in their death. At necropsy examination there was friable, black material in the main bronchi that obstructed the bronchial lumina. Microscopical examination of the lungs revealed the presence of pneumonia, calcium oxalate crystals and a large quantity of fungal hyphae and conidial heads. Fungal infection was confirmed with Grocott's methenamine silver stain. The results of the mycology analysis were compatible with Aspergillus section Nigri.

Eradication of an extensive outbreak in a neonatal unit caused by two sequential Klebsiella pneumoniae clones harbouring related plasmids encoding an extended-spectrum beta-lactamase.

Outbreaks caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae are difficult to control and closure of an affected unit is sometimes necessary. We describe an outbreak of ESBL-producing K. pneumoniae in a 28-bed neonatal unit that began in August 2005 and lasted for seven months. Weekly rectal swabs were taken from all babies admitted throughout the study period. Review of all procedures, contact precautions, thorough environmental cleaning and restriction of cephalosporin use were implemented. ESBL production was investigated according to CLSI recommendations, and characterised by isoelectric focusing and sequencing. Typing of isolates was assessed by pulsed-field gel electrophoresis. Plasmids were also studied. During the outbreak, 32% of 503 admitted babies became colonised and nine babies developed bacteraemia; all the babies recovered. The outbreak was finally terminated in February 2006. Two distinct clones were observed, the first circulating between August and October 2005, and the second between October 2005 and February 2006. Both of these clones carried the non-ESBL SHV-11 and TEM-4 ESBL. Plasmids harbouring TEM-4 from both clones were similar and molecular analysis suggested horizontal dissemination of a single plasmid between the two clones.