Cost analysis of disease including treatment with dalbavancin in a Spanish hospital: ECODAL ANALYSIS.

INTRODUCTION AND AIM: Dalbavancin is an antibiotic with activity against gram-positive bacteria that allows early discharge of patients requiring intravenous therapy. Outpatient treatment helps offset hospitalisation costs associated with standard intravenous treatment. Our objective was to assess the cost of disease management, including treatment with dalbavancin, in a Spanish hospital for 1 year, and the hypothetical costs associated with treatment with other therapeutic alternatives to dalbavancin. METHODS: A single-centre, observational, retrospective post-hoc analysis was conducted based on electronic medical records analysing all patients who received dalbavancin treatment throughout 1 year; cost analysis was performed for the whole process. In addition, three scenarios designed on the basis of real clinical practice by clinical experts were hypothesised: (i) individual therapeutic alternative to dalbavancin, (ii) all patients treated with daptomycin, and (iii) all days of dalbavancin as outpatient treatment transformed into hospital stay. Costs were obtained from the hospital. RESULTS: Thirty-four patients were treated with dalbavancin; their mean age was 57.9 years, and 70.6% were men. The main reasons for dalbavancin use were outpatient management (61.7%, n = 21) and ensuring treatment adherence (26.5%, n = 9). The main indications were: osteoarticular infection (32.4%) and infective endocarditis (29.4%). One-half (50%) of the infections were due to Staphylococcus aureus (23.5% were methicillin resistant). All patients achieved clinical resolution, and no costs associated with dalbavancin-associated adverse events or re-admissions were reported. The mean total cost of treatment was 22,738€ per patient, with the greatest expenditures in interventions (8,413€) and hospital stay (6,885€). The mean cost of dalbavancin treatment was 3,936€; without dalbavancin, this cost could have been increased to 3,324-11,038€ depending on the scenario, mainly due to hospital stays. MAIN LIMITATION: Limited sample size obtained from a single centre. CONCLUSION: The economic impact of the management of these infections is high. The cost of dalbavancin is offset by the decreased length of stay.

The burden of perioperative hypertension/hypotension: A systematic review.

STUDY OBJECTIVE: Our goal is to review the outcomes of acute hypertensive/hypotensive episodes from articles published in the past 10 years that assessed the short- and long-term impact of acute hypertensive/hypotensive episodes in the perioperative setting. METHODS: We conducted a systematic peer review based upon PROSPERO and Cochrane Handbook protocols. The following study characteristics were collected: study type, author, year, population, sample size, their definition of acute hypertension, hypotension or other measures, and outcomes (probabilities, odds ratio, hazard ratio, and relative risk) and the p-values; and they were classified according to the type of surgery (cardiac and non-cardiac). RESULTS: A total of 3,680 articles were identified, and 66 articles fulfilled the criteria for data extraction. For the perioperative setting, the number of articles varies by outcome: 20 mortality, 16 renal outcomes, 6 stroke, 7 delirium and 34 other outcomes. Hypotension was reported to be associated with mortality (OR 1.02-20.826) as well as changes from the patient's baseline blood pressure (BP) (OR 1.02-1.36); hypotension also had a role in the development of acute kidney injury (AKI) (OR 1.03-14.11). Postsurgical delirium was found in relation with BP lability (OR 1.018-1.038) and intra- and postsurgical hypotension (OR 1.05-1.22), and hypertension (OR 1.44-2.34). Increased OR (37.67) of intracranial hemorrhage was associated to postsurgical systolic BP >130 mmHg. There was a wide range of additional diverse outcomes related to hypo-, hypertension and BP lability. CONCLUSIONS: The perioperative management of BP influences short- and long-term effects of surgical procedures in cardiac and non-cardiac interventions; these findings support the burden of BP fluctuations in this setting.

Applying reflective multicriteria decision analysis to understand the value of therapeutic alternatives in the management of gestational and peripartum anaemia in Spain.

BACKGROUND: The objective of the FeminFER project was to assess the value of ferric carboxymaltose following a multicriteria decision analysis in obstetrics and gynaecology in Spain. METHODS: Ferric carboxymaltose (FCM) and ferrous sulphate were evaluated using the EVIDEM framework. Ten stakeholders participated to collect different perspectives. The framework was adapted considering evidence retrieved with a PICO-S search strategy and grey literature. Criteria/subcriteria were weighted by level of relevance and an evidence-based decision-making exercise was developed in each criterion; weights and scores were combined to obtain the value of intervention relative to each criterion/subcriterion, that were further combined into the Modulated Relative Benefit-Risk Balance (MRBRB). RESULTS: The most important criterion favouring FCM was Compared Efficacy/Effectiveness (0.183 ± 0.07), followed by Patient Preferences (0.059 ± 0.10). Only Direct medical costs criterion favoured FS (-0.003 ± 0.03). MRBRB favoured FCM; 0.45 ± 0.19; in a scale from -1 to + 1. CONCLUSIONS: In conclusion, considering the several criteria involved in the decision-making process, participants agreed with the use of FCM according to its MRBRB.

Novel multiplex PCRs for detection of the most prevalent carbapenemase genes in Gram-negative bacteria within Germany.

Introduction. Gram-negative bacteria are a common source of infection both in hospitals and in the community, and antimicrobial resistance is frequent among them, making antibiotic therapy difficult, especially when these isolates carry carbapenem resistance determinants.Hypothesis/Gap Statement. A simple method to detect all the commonly found carbapenemases in Germany was not available.Aim. The aim of this study was to develop a multiplex PCR for the rapid and reliable identification of the most prevalent carbapenemase-encoding genes in Gram-negative bacteria in Germany.Methodology. Data from the German Gram-negative reference laboratory revealed the most prevalent carbapenemase groups in Germany were (in order of prevalence): bla VIM, bla OXA-48, bla OXA-23, bla KPC, bla NDM, bla OXA-40, bla OXA-58, bla IMP, bla GIM, bla GES, ISAba1-bla OXA-51, bla IMI, bla FIM and bla DIM. We developed and tested two multiplex PCRs against 83 carbapenem-resistant Gram-negative clinical isolates. Primers were designed for each carbapenemase group within conserved regions of the encoding genes obtained from publicly available databases. Multiplex-1 included the carbapenemase groups bla VIM, bla OXA-48, bla OXA-23, bla KPC, bla NDM and bla OXA-40, while multiplex-2 included bla OXA-58, bla IMP, bla GIM, bla GES, ISAba1-bla OXA-51 and bla IMI.Results. In the initial evaluation, all but one of the carbapenemases encoded by 75 carbapenemase-positive isolates were detected using the two multiplex PCRs, while no false-positive results were obtained from the remaining eight isolates. After evaluation, we tested 546 carbapenem-resistant isolates using the multiplex PCRs, and all carbapenemases were detected.Conclusion. A rapid and reliable method was developed for detection and differentiation of 12 of the most prevalent carbapenemase groups found in Germany. This method allows for the rapid testing of clinical isolates prior to species identification and does not require prior phenotypical characterization, constituting a rapid and valuable tool in the management of infections in hospitals.

Mobile Genetic Elements Harboring Antibiotic Resistance Determinants in Acinetobacter baumannii Isolates From Bolivia.

Using a combination of short- and long-read DNA sequencing, we have investigated the location of antibiotic resistance genes and characterized mobile genetic elements (MGEs) in three clinical multi-drug resistant Acinetobacter baumannii. The isolates, collected in Bolivia, clustered separately with three different international clonal lineages. We found a diverse array of transposons, plasmids and resistance islands related to different insertion sequence (IS) elements, which were located in both the chromosome and in plasmids, which conferred resistance to multiple antimicrobials, including carbapenems. Carbapenem resistance might be caused by a Tn2008 carrying the bla OXA-23 gene. Some plasmids were shared between the isolates. Larger plasmids were less conserved than smaller ones and they shared some homologous regions, while others were more diverse, suggesting that these big plasmids are more plastic than the smaller ones. The genetic basis of antimicrobial resistance in Bolivia has not been deeply studied until now, and the mobilome of these A. baumannii isolates, combined with their multi-drug resistant phenotype, mirror the transfer and prevalence of MGEs contributing to the spread of antibiotic resistance worldwide and require special attention. These findings could be useful to understand the antimicrobial resistance genetics of A. baumannii in Bolivia and the difficulty in tackling these infections.

Acinetobacter baumannii analysis by core genome multi-locus sequence typing in two hospitals in Bolivia: endemicity of international clone 7 isolates (CC25).

In total, 95 Acinetobacter baumannii isolates recovered from patients from two hospitals in Cochabamba, Bolivia were studied. The presence of class D and B ß-lactamases was investigated using polymerase chain reaction, and antimicrobial susceptibility testing was performed by agar dilution and broth microdilution. The resistance rate to carbapenems was 53.7%. All carbapenem-resistant A. baumannii (CRAb, n=51) and four carbapenem-susceptible isolates were further analysed by whole-genome sequencing. The resulting genome assemblies were used to identify the acquired resistome, and core genome multi-locus sequence typing (cgMLST) was used to determine their molecular epidemiology. All but one of the CRAb isolates (n=50) belonged to international clone (IC) 7 and they clustered into five sequence types; on cgMLST, they were found to be separated by ≥40 alleles. All CRAb isolates carried blaOXA-23 on transposon Tn2008. Metallo-ß-lactamases were not detected. These data show that dissemination of several IC7 A. baumannii clones harbouring the carbapenem resistance determinant blaOXA-23 is occurring in these two hospitals in Cochambamba.

Identification of Acinetobacter seifertii isolated from Bolivian hospitals.

Acinetobacter seifertii is a recently described species that belongs to the Acinetobacter calcoaceticus-Acinetobacter baumannii complex. It has been recovered from clinical samples and is sometimes associated with antimicrobial resistance determinants. We present here the case of three A. seifertii clinical isolates which were initially identified as Acinetobacter sp. by phenotypic methods but no identification at the species level was achieved using semi-automated identification methods. The isolates were further analysed by whole genome sequencing and identified as A. seifertii. Due to the fact that A. seifertii has been isolated from serious infections such as respiratory tract and bloodstream infections, we emphasize the importance of correctly identifying isolates of the genus Acinetobacter at the species level to gain a deeper knowledge of their prevalence and clinical impact.

High Prevalence of Extensively Drug-resistant Acinetobacter baumannii at a Children Hospital in Bolivia.

Acinetobacter baumannii causes serious hospital-acquired infections and has been positioned as a priority organism by the World Health Organization. This study includes 36 A. baumannii isolates from a children hospital recovered between March 2014 and May 2015 in Cochabamba. The majority of the isolates were recovered from blood cultures (n = 10, 31.3%) and respiratory samples (n = 11, 34.4%); 53% of the patients were younger than 1 month old. Most of these isolates (n = 30, 80.6%) were extremely drug resistant and 8.3% were multidrug resistant. The circulation of 2 predominant clones including 25 isolates was determined by pulsed-field gel electrophoresis; 9 of the isolates were considered sporadic strains. The isolates grouped in the predominant clones and 5 of the unrelated sporadic strains were single-locus variant or double locus variant of clonal complex (CC110), belonging to international clone 7; the rest of the isolates were single-locus variant or double locus variant of another clonal complex. All the carbapenem-resistant isolates (88.9%) carried the blaOXA-23-like in a similar structure to Tn2008 located on the chromosome, and the aac(3)-IIa gene was present in all the aminoglycoside-resistant isolates (86.1%). Strong biofilm producers were found among these isolates, being the strongest ones those recovered from the hospital environment, catheter, blood and cerebrospinal fluid (CSF) all of them belonged to the unrelated sporadic strains. The present study demonstrated the predominance and spread of closely related extremely drug-resistant A. baumannii isolates, what confers increasing risk to children and is of major concern because of the kind of infections and the lack of therapeutic alternatives to treat them.