Antimicrobial consumption, costs and resistance patterns: a two year prospective study in a Romanian intensive care unit.

BACKGROUND: Due to the vulnerable nature of its patients, the wide use of invasive devices and broad-spectrum antimicrobials used, the intensive care unit (ICU) is often called the epicentre of infections. In the present study, we quantified the burden of hospital acquired pathology in a Romanian university hospital ICU, represented by antimicrobial agents consumption, costs and local resistance patterns, in order to identify multimodal interventional strategies. METHODS: Between 1st January 2012 and 31st December 2013, a prospective study was conducted in the largest ICU of Western Romania. The study group was divided into four sub-samples: patients who only received prophylactic antibiotherapy, those with community-acquired infections, patients who developed hospital acquired infections and patients with community acquired infections complicated by hospital-acquired infections. The statistical analysis was performed using the EpiInfo version 3.5.4 and SPSS version 20. RESULTS: A total of 1596 subjects were enrolled in the study and the recorded consumption of antimicrobial agents was 1172.40 DDD/ 1000 patient-days. The presence of hospital acquired infections doubled the length of stay (6.70 days for patients with community-acquired infections versus 16.06/14.08 days for those with hospital-acquired infections), the number of antimicrobial treatment days (5.47 in sub-sample II versus 11.18/12.13 in sub-samples III/IV) and they increased by 4 times compared to uninfected patients. The perioperative prophylactic antibiotic treatment had an average length duration of 2.78 while the empirical antimicrobial therapy was 3.96 days in sample II and 4.75/4.85 days for the patients with hospital-acquired infections. The incidence density of resistant strains was 8.27/1000 patient-days for methicilin resistant Staphylococcus aureus, 7.88 for extended spectrum ß-lactamase producing Klebsiella pneumoniae and 4.68/1000 patient-days for multidrug resistant Acinetobacter baumannii. CONCLUSIONS: Some of the most important circumstances collectively contributing to increasing the consumption of antimicrobials and high incidence densities of multidrug-resistant bacteria in the studied ICU, are represented by prolonged chemoprophylaxis and empirical treatment and also by not applying the definitive antimicrobial therapy, especially in patients with favourable evolution under empirical antibiotic treatment. The present data should represent convincing evidence for policy changes in the antibiotic therapy.

Budget impact assessment of Aprokam® compared with unlicensed cefuroxime for prophylaxis of post-cataract surgery endophthalmitis.

BACKGROUND: Intracameral cefuroxime is recommended as prophylaxis against postoperative endophthalmitis (POE) following cataract surgery. Aprokam is the only licensed product for prophylaxis of POE, although unlicensed intracameral cefuroxime may be administered using pre-filled syringes (PFS), either prepared in hospital by reconstituting cefuroxime via serial dilution (prepared PFS), or commercially purchased (purchased PFS). This study aimed to estimate the potential budget impact of using Aprokam over unlicensed cefuroxime for intracameral administration. METHODS: A budget impact model (BIM) was developed from UK NHS hospital perspective to estimate the economic impact of adopting Aprokam compared with purchased PFS or prepared PFS for the prophylaxis of POE following cataract surgery over a 5-year time horizon. The BIM incorporated direct costs only, associated with the acquisition, delivery, storage, preparation, and administration of cefuroxime. Resource utilisation costs were also incorporated; resource utilisation was sourced from a panel survey of hospital pharmacists, surgeons, and theatre nurses who are involved in the delivery, storage, preparation, quality assurance, or administration of cefuroxime formulations. Unit costs were sourced from NHS sources; drug acquisition costs were sourced from BNF. The model base case used a hypothetical cohort comprising of 1000 surgeries in the first year and followed a 5.2 % annual increase each year. RESULTS: The model predicts Aprokam is cost saving compared with purchased PFS, with a modest increase compared prepared PFS over 5 years. There are total savings of £ 3490 with Aprokam compared with purchased PFS, driven by savings in staff costs that offset greater drug acquisition costs. Compared with prepared PFS, there are greater drug acquisition costs which drive an increased total cost over 5 years of £ 13,177 with Aprokam, although there are substantial savings in staff costs as well as consumables and equipment costs. CONCLUSIONS: The lower direct costs of using Aprokam compared with purchased PFS presents a strong argument for the adoption of Aprokam where purchased PFS is administered. The additional benefits of Aprokam include increased liability coverage and possible reduction in dilution errors and contaminations; as such, in hospitals where unlicensed prepared PFS is used, modest additional resources should be allocated to adoption of Aprokam.

Prophylactic use of levofloxacin during medicinal leech therapy.

BACKGROUND: Medicinal leech therapy is effective in establishing venous outflow in congested flaps and replants. However, its use is also associated with infections, especially from Aeromonas species. To prevent this nosocomial infection, levofloxacin has been established as prophylaxis during leech therapy in our hospital. OBJECTIVES: To study the implementation rate of a guideline, to study the effect of levofloxacin on possible Aeromonas infections, and to evaluate the financial impact of this preventive measure. SETTING: A retrospective analysis on all patients treated with Hirudo medicinalis between July 2007 and March 2011 was performed at the Ghent University Hospital, Belgium. METHOD: A list of patients treated with leeches was retrieved from the pharmacy database. Patient characteristics, date of start and stop of leech therapy were collected. Data on routine diagnostic cultures during leech therapy, date and type of clinical sample, while cultivated micro-organism with antibiotic susceptibility were obtained from the laboratory database. MAIN OUTCOME MEASURE: percentage implementation rate of a guideline, presence of Aeromonas infections, financial impact of levofloxacin prophylaxis. RESULTS: Fifty-one patients were treated with leeches. Forty-six (90.2 %) patients were treated according the guideline. Fourteen out of 51 patients (27.5 %) were suspected for postoperative wound infections. From them, 60 clinical samples were sent for microbiological analysis. These included exudates (26.7 %), peroperative samples (5.0 %), puncture fluid (1.7 %), blood cultures (3.3 %) or smears from burns (63.3 %). No Aeromonas species were cultivated. Comparison between period before and after implementation of levofloxacin prophylaxis revealed that levofloxacin prevents colonization or infection with Aeromonas species in relation to leech therapy. The direct cost for levofloxacin prophylaxis in the current study was 2,570 euro. Based on data obtained in a previous study, we presume that a minimum cost-saving of 20,500 euro was realised during the current study period by implementation of antimicrobial prophylaxis. CONCLUSIONS: This study demonstrates successful implementation of a guideline for levofloxacin prophylaxis during leech therapy. Following its introduction, no Aeromonas species related to the use of leeches were isolated as compared to 8.5 % in the baseline period.

Cost-effectiveness of the introduction of specialized oral care with laser therapy in hematopoietic stem cell transplantation.

Oral mucositis (OM) is one of the side effects of hematopoietic stem cell transplantation (HSCT), resulting in major morbidity. The aim of this study was to determine the cost-effectiveness of the introduction of a specialized oral care program including laser therapy in the care of patients receiving HSCT with regard to morbidity associated with OM. Clinical information was gathered on 167 patients undergoing HSCT and divided according to the presence (n = 91) or absence (n = 76) of laser therapy and oral care. Cost analysis included daily hospital fees, parenteral nutrition (PN) and prescription of opioids. It was observed that the group without laser therapy (group II) showed a higher frequency of severe degrees of OM (relative risk = 16.8, 95% confidence interval -5.8 to 48.9, p < 0.001), with a significant association between this severity and the use of PN (p = 0.001), prescription of opioids (p < 0.001), pain in the oral cavity (p = 0.003) and fever > 37.8°C (p = 0.005). Hospitalization costs in this group were up to 30% higher. The introduction of oral care by a multidisciplinary staff including laser therapy helps reduce morbidity resulting from OM and, consequently, helps minimize hospitalization costs associated with HSCT, even considering therapy costs.

Evaluation of a novel web-based prior approval application for palivizumab prophylaxis of respiratory syncytial virus in a state Medicaid program.

BACKGROUND: Recent disproportionate increases in use of specialty medications, such as palivizumab (Synagis), compared with steady utilization of traditional medication use, have prompted complex utilization management strategies that require frequent evaluation to facilitate cost-effectiveness while preserving patient access. Clinical criteria utilized by North Carolina (NC) Medicaid for use of palivizumab for respiratory syncytial virus (RSV) prophylaxis are consistent with the most recent guidelines published in the Red Book: Report of the Committee on Infectious Diseases. Prior to the 2011-2012 RSV season, prior approval (PA) requests were submitted by facsimile using the NC Medicaid Synagis PA form. A web-based PA application, which includes automatic approval capability, monthly dose prompts to providers, and a standardized dose projection formula, was developed for the 2011-2012 RSV season. OBJECTIVES: To evaluate the timeliness of palivizumab coverage determination, compliance with palivizumab prophylaxis regimen, and the accuracy of the dose projection formula achieved with this novel web-based PA application for palivizumab prophylaxis in NC Medicaid recipients. METHODS: A historically controlled retrospective cohort study was conducted in which all palivizumab PA submissions and supporting documentation from the 2010-2011 and 2011-2012 RSV seasons were retrospectively reviewed for date and time of original submission and final coverage determination. Submissions from the 2011-2012 season were also retrospectively reviewed for number of doses approved, number of doses administered, date of administration of each dose, and actual dosage administered. These data were used to evaluate compliance and the projected versus actual beneficiary weight and dose to assess the accuracy of the dose projection formula. Submissions lacking required information were excluded. Time from PA submission to coverage determination was compared between seasons using a 2-sample t-test. The proportion of compliant recipients was calculated based on number of doses received and dosing interval of no more than 35 days. Accuracy of the dose projection formula was evaluated using a paired Student's t-test. RESULTS: Time to coverage determination decreased overall, on average, by 3.7 days (mean [SD] 8.5 [15.4] vs. 4.8 [9.3]; P<0.001) for the 2011-2012 season using the electronic web-based PA application compared with the traditional facsimile-based system used in the 2010-2011 season. Decreased time to coverage determination was observed in both PA requests that required medical review and those that did not. Of all palivizumab recipients who were eligible to receive at least 2 doses (n=1,233), 61.1% were fully compliant with all doses, and 86.9% received all but one documentable dose. Of those who received at least 2 documented doses (n=1,091), 62.8% received all doses within 35 days of the previous dose. When both definitions of compliance were applied concurrently, 39.3% of all palivizumab recipients were considered compliant; the mean difference between projected and actual doses was 7.1 mg (95% CI: 6.8-7.5; P=0.001) or 8.6% (95% CI: 8.0-10.0). Projected and actual doses did not vary significantly in the sensitivity analysis when excluding entries with ≥50% difference. CONCLUSIONS: The 2011-2012 web-based PA application improved the timeliness of palivizumab coverage determination compared with the 2010-2011 facsimile-based system. Observed compliance rates for NC Medicaid recipients were slightly lower than those reported in the literature when defined by number of doses received but were higher when defined by interval between doses. The dose projection formula used for the web-based application appears to be accurate for infants 0-2 years of age.

Variation in practice patterns and resource utilization surrounding management of intussusception at freestanding Children's Hospitals.

PURPOSE: To characterize variation in practice patterns and resource utilization associated with the management of intussusception at Children's Hospitals. METHODS: A retrospective cohort study (1/1/09-6/30/11) of 27 Children's Hospitals participating in the Pediatric Health Information System database was performed. Hospitals were compared with regard to their rates of operative management following attempted enema reduction, prophylactic antibiotic utilization, same-day discharge for those successfully managed non-operatively, 48-h readmission rates, and case-related cost and charges. RESULTS: 2544 patients were identified (median: 93 cases/center) with a median age of 17 months. The rate of operation following attempted enema reduction varied significantly across hospitals (overall rate: 21.1%: range: 11%-62.8%; p<0.0001). For patients managed non-operatively, significant variability was found for prophylactic antibiotic utilization (overall rate: 23.3%; range: 1.4%-93.2%; p<0.0001), same-day discharge (overall rate: 15.2%; range: 0%-83.8%; p<0.0001), readmission rates (overall rate: 17.5%; range: 5.3%-32.1%; p<0.0001), treatment-related costs (overall median: $2490; range: $829-$5905; p<0.0001), and charges (overall median: $6350; range: $2497-$10,306; p<0.0001). Variability in costs and charges was even greater when analyzing all patients (operative and non-operative) with intussusception (overall cost median: $2865; range: $1574-$6763; p<0.0001; overall charge median: $7110; range: $3544-$22,097; p<0.0001). CONCLUSION: Significant variation in practice patterns and resource utilization exists between Children's Hospitals in the management of intussusception. Prospective analysis of practice variation and appropriately risk-adjusted outcomes through a collaborative quality-improvement platform could accelerate the dissemination of best-practice guidelines for optimizing cost-effective care.

Prevention and management of catheter-related infection in hemodialysis patients.

Central venous catheter-related infections have been associated with high morbidity, mortality, and costs. Catheter use in chronic hemodialysis patients has been recognized as distinct from other patient populations who require central venous access, leading to recent adaptations in guidelines-recommended diagnosis for catheter-related bacteremia (CRB). This review will discuss the epidemiology and pathogenesis of hemodialysis CRB, in addition to a focus on interventions that have favorably affected CRB outcomes. These include: (1) the use of prophylactic topical antimicrobial ointments at the catheter exit site, (2) the use of prophylactic catheter locking solutions for the prevention of CRB, (3) strategies for management of the catheter in CRB, and (4) the use of vascular access managers and quality initiative programs.

Cost effectiveness of posaconazole in the prophylaxis of invasive fungal infections in acute leukaemia patients for the French healthcare system.

BACKGROUND: Acute myeloblastic leukaemia (AML) patients are at high risk of suffering from invasive fungal infections (IFI). Posaconazole demonstrated higher efficacy than standard azole agents (SAA) in the prophylaxis of IFI in this population. The authors estimated the cost effectiveness of posaconazole versus SAA in France. METHODS: A decision-tree model was developed to compare posaconazole with SAA with the results of a published clinical trial. Clinical events were modelled with chance nodes reflecting probabilities of IFI, IFI-related death, and death from other causes. Medical resource consumption and costs were obtained from results of the clinical trial and from a dedicated survey on the costs of treating IFI using a retrospective chart review design. RESULTS: IFI treatment costs were estimated using medical files from 50 AML patients from six French centres, with a proven and probable IFI, who had been followed-up for 298 days on average. Direct costs directly related to IFI were estimated at €51,033, including extra costs of index hospitalisation, costs of antifungal therapy and additional hospitalisations related to IFI treatment. The model indicated that the healthcare costs for the posaconazole strategy were €5,223 (€2,697 for prophylaxis and €2,526 for IFI management), which was €859 less than the €6,083 in costs with SAA (€469 for prophylaxis and €5614 for IFI management). A sensitivity analysis indicated that there was an 80% probability that prophylaxis using the posaconazole strategy would be superior. CONCLUSION: The findings from this analysis suggest that posaconazole use is a clinically and economically dominant strategy in the prophylaxis of IFI in AML patients, given the usual limits of economic models and the uncertainty of costs estimates.

Assessing cost effectiveness of empirical and prophylactic therapy for managing leptospirosis outbreaks.

This study evaluates the utility and cost effectiveness of empirical and prophylactic antibiotic treatment of leptospirosis compared with conventional management. We developed decision trees comparing empirical antibiotic treatment (within 4-7 days of symptom onset) or prophylaxis to conventional antibiotic treatment (initiated 7 days post-onset). Costs were calculated using both US and Barbados pricing. Empirical treatment provided slightly lower probability of survival, while prophylactic treatment resulted in slightly higher survival rates. Antibiotic treatment initiated after 4-7 symptomatic days was ineffective in preventing serious health outcomes, but cost less with the exception of azithromycin (US pricing). Empirical treatment in Barbados cost less than conventional treatment. Prophylaxis reduced rare serious health outcomes and resulted in significant cost savings for the United States and Barbados. Prophylactic therapy for high-risk individuals or prompt diagnosis and early treatment (before 4 days of symptoms) appear to be cost-effective approaches to prevent severe complications of leptospirosis.

Clinical and economic outcomes for term infants associated with increasing administration of antibiotics to their mothers.

Implementation of national guidelines for the prevention of group B streptococcal (GBS) infections has led to an increase in intrapartum antibiotic use and reduction in early-onset GBS infections in newborns. Other outcomes, including the clinical diagnosis of sepsis in term infants, treatment with antibiotics, length of stay, and cost have not been described. To examine these outcomes, we performed an analysis of maternal and newborn data collected between 1998 and 2002 of 130 447 in-hospital births of newborns >or=37 weeks gestation and their mothers from a large vertically integrated healthcare organisation in Utah. The main outcome measures included: (i) the number of women delivering at term who received intravenous antibiotics; (ii) the number of newborns treated for 'clinical sepsis', which was defined as receiving antibiotics for >72 h and the number of newborns who received antibiotics for

Is antibiotic prophylaxis for bacterial endocarditis cost-effective?

BACKGROUND: Antibiotic prophylaxis for bacterial endocarditis is recommended by the American Heart Association (AHA) before undergoing certain dental procedures. Whether such antibiotic prophylaxis is cost-effective is not clear. The authors' objective is to estimate the cost-effectiveness of predental antibiotic prophylaxis in patients with underlying heart disease. METHODS: The authors conducted a cost-effectiveness analysis using a Markov model to compare cost-effectiveness of 7 antibiotic regimens per AHA guidelines and a no prophylaxis strategy. The study population consisted of a hypothetical cohort of 10 million patients with either a high or moderate risk for developing endocarditis. RESULTS: Prophylaxis for patients with moderate or high risk for endocarditis cost $88,007/quality-adjusted life years saved if clarithromycin was used. Prophylaxis with amoxicillin and ampicillin resulted in a net loss of lives. All other regimens were less cost-effective than clarithromycin. For 10 million persons, clarithromycin prophylaxis prevented 119 endocarditis cases and saved 19 lives. CONCLUSION: Predental antibiotic prophylaxis is cost-effective only for persons with moderate or high risk of developing endocarditis. Contrary to current recommendations, our data demonstrate that amoxicillin and ampicillin are not cost-effective and should not be considered the agents of choice. Clarithromycin should be considered the drug of choice and cephalexin as an alternative drug of choice. The current published guidelines and recommendations should be revised.

[Comparison of the effects of prophylactic antibiotic therapy and cost-effectiveness between cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway].

The present study was designed to investigate the effects of prophylactic antibiotic therapy and the cost-effectiveness of Cefazolin (CEZ) and Sulbactam/Ampicillin (SBT/ABPC) in gastric cancer surgery employing clinical pathway. 157 patients (62 in the CEZ group and 95 in the SBT/ABPC group), who underwent surgery for gastric cancer at the First Department of Surgery of our hospital, were investigated. There was no significant difference between the groups with regard to sex, age, incidence of complication, stage of cancer, surgical method, operative time and blood loss, length of hospitalization, the appearance of systemic inflammatory response syndrome (SIRS), changes body temperature, white blood cell count (WBC), C-reactive protein (CRP), or clinical outcome of postoperative care by a nurse during post-operation for 7 days. The prophylactic effect of infection was also no different between the CEZ (69.4%) and SBT/ABPC (69.5%) groups. In contrast, decision analysis strongly indicated that the anticipate cost of antibiotics was higher in the latter group (yen 20402) than in the CEZ group (yen 15556), suggesting that the prophylactic effect of CEZ may be more cost-effective. Thus, evaluations of pharmacotherapy from the aspect of cost may be one of the important responsibility of hospital pharmacists in the future.

[Health Economical Evaluation of antibiotic prophylaxis against postoperative endophthalmitis]. / Gesundheitsökonomische Bewertung einer antibiotischen Prophylaxe gegenüber postoperativen Endophthalmitiden.

BACKGROUND: Two independent epidemiological studies recently suggested the prophylactic relevance of an intraocular antibiosis against endophthalmitis after cataract surgery. The resulting intervention programme, however, has not only ethical drawbacks, but also has a health economical dimension, which will be focussed in this paper. MATERIAL AND METHODS: A cost analysis is performed to compare the direct costs saved by prevention of endophthalmitis cases and the costs generated by the prophylaxis itself. Furthermore, the clinics' indirect costs due to treatment of unprevented endophthalmitis cases are estimated. RESULTS: The overall gain in direct costs turns out to be about 368 000 Euro p. a., the indirect costs from the clinics' view can be reduced by about 260 000 Euro p. a. due to prevention of endophthalmitis cases by the antibiotic intervention. CONCLUSIONS: From an economical point of view, antibiotic prophylaxis can be suggested; the risk of longitudinally reduced antibiotic effectiveness of the antibiotic agents, however, strongly calls for an overall health political decision rather than for an immediate implementation of the corresponding intervention programme.

Pharmacokinetics of antibiotic prophylaxis in major orthopedic surgery and blood-saving techniques.

The pharmacokinetics of cefuroxime, cefotiam, cefamandole, and ampicillin/sulbactam were randomly measured in 40 patients undergoing major orthopedic surgery associated with high blood and volume turnover and intraoperative blood salvage. Serum and bone concentrations and the pharmacokinetics occurring in the context of these procedures were measured. No changes in elimination half-life relative to a normal population occurred with cefuroxime, cefotiam, and ampicillin. Serum and tissue concentrations were slightly lower with cefamandole and sulbactam, but reapplication of the initial dose was required with all antibiotics 4 hours after the first application.

Actuación del servicio de farmacia en la puesta en marcha del protocolo de Profilaxis antimicrobiana quirúrgica (revisión del primer año) / Management of a pharmacy service in the establishment of a surgical antimicrobiology prophylaxis protocol (review of the first year)

Se analiza el número y el tipo de las intervenciones farmacéuticas realizadas al incorporar al farmacéutico clínico en el circuito de validación de la prescripción de las profilaxis antimicrobiana quirúrgica, protocolizada como dosis única a administrar en la inducción anestésica.En el primer año se realizaron 148 intervenciones farmacéuticas previas al envío de la medicación que fueron bien aceptadas por los clínicos, como colaboración al incremento de la calidad de la profilaxis administrada (AU)

Efficacy of one dose fluoroquinolone before prostate biopsy.

OBJECTIVES: To demonstrate the efficacy of a simple preparation for prostate biopsy (PBX) and to determine its potential cost savings. METHODS: One hundred fifty consecutive PBXs were performed using a Fleet enema and a single oral dose (300 mg) of ofloxacin as the pre-PBX preparation. RESULTS: Of the 150 PBXs we performed, only 1 (0.67%) patient developed a urinary tract infection. CONCLUSIONS: A simple and inexpensive pre-PBX preparation proved to be successful in preventing infectious complications and is presented as a potential model for inclusion in clinical pathways for diagnosing adenocarcinoma of the prostate.