Rationale and development of a business case for antimicrobial stewardship programs in acute care hospital settings.

Background: Antimicrobial stewardship programs (ASPs) have been shown to reduce inappropriate antimicrobial use and its consequences. However, these programs lack legislative requirements in many places and it can be difficult to determine what human resources are required for these programs and how to create a business case to present to hospital administrators for program funding. The objectives of the current paper were to review legislative requirements and outline human resource requirements for ASPs, and to create a base business case for ASPs. Methods: A working group of antimicrobial stewardship experts from across Canada met to discuss the necessary components for creation of a business case for antimicrobial stewardship. A narrative review of the literature of the regulatory requirements and human resource recommendations for ASPs was conducted. Informed by the review and using a consensus decision-making process, the expert working group developed human resource recommendations based on a 1000 bed acute care health care facility in Canada. A spreadsheet based business case model for ASPs was also created. Results: Legislative and /or regulatory requirements for ASPs were found in 2 countries and one state jurisdiction. The literature review and consensus development process recommended the following minimum human resources complement: 1 physician, 3 pharmacists, 0.5 program administrative and coordination support, and 0.4 data analyst support as full time equivalents (FTEs) per 1000 acute care beds. Necessary components for the business case model, including the human resource requirements, were determined to create a spreadsheet based model. Conclusions: There is evidence to support the negative outcomes of inappropriate antimicrobial use as well as the benefits of ASPs. Legislative and /or regulatory requirements for ASPs are not common. The available evidence for human resource recommendations for ASPs using a narrative review process was examined and a base business case modelling scenario was created. As regulatory requirements for ASPs increase, it will be necessary to create accurate business cases for ASPs in order to obtain the necessary funding to render these programs successful.

Vancomycin-induced neutropenia resolves after substitution with teicoplanin.

Neutropenia is an uncommon adverse effect associated with prolonged vancomycin therapy. Neutrophil counts normally recover after discontinuation of vancomycin in this situation, but treatment options are needed for those patients who require ongoing antibiotic therapy. We describe a case of vancomycin-induced neutropenia in which the neutropenia resolved after vancomycin was replaced by the structurally related compound teicoplanin.

Impact of the dial access drug information service on patient outcome.

OBJECTIVE: To determine the impact of a drug information service on patient outcomes. DESIGN: Prospective evaluation of patient-specific drug information requests. SETTING: Healthcare professional and consumer drug information service located at a college of pharmacy. PARTICIPANTS: Consumers and healthcare professionals of the province. INTERVENTION: Patient-specific questions received by the drug information service were reviewed and evaluated for actual patient outcome, inquirers' opinion of impact of the service with respect to patient outcome, and for objectivity and timeliness of the response. An expert panel determined whether the responses and recommendations given by the service were appropriate, determined what impact the service had on the patient, and assessed the seriousness of the inquiry. MAIN OUTCOME MEASURE: Classification of patient outcome by objective and subjective data based on predetermined desired outcomes. RESULTS: Ninety-eight and 68 patient-specific requests were received from healthcare professionals and consumers, respectively. The panel concluded that 94.9% of the healthcare requests and 98.5% of the consumer requests were answered appropriately and that the majority of the requests involved potentially serious drug-related problems. The panel also determined that 46.8% of the recommendations to healthcare professionals and 41.0% of the recommendations to consumers resulted in positive patient outcomes. The majority of the positive outcomes involved the prevention of a disease or its symptoms (professional section) and the reduction or elimination of symptoms (consumer section). CONCLUSIONS: The drug information service not only met its objectives of providing drug information in an accurate, objective, and timely manner, but was also able to provide positive patient outcomes.

Recurrent Clostridium difficile diarrhea associated with mitoxantrone and etoposide: a case report and review.

Clostridium difficile colitis most commonly occurs in association with antibiotic administration and infrequently with antineoplastic agents. Our patient experienced recurrent C. difficile diarrhea associated with mitoxantrone and etoposide. He received antibiotics during the 6 months, but each episode of diarrhea was preceded by at least a 6-week antibiotic-free period. In addition, antineoplastic therapy preceded each episode by 8 or 9 days. Clinicians should be aware that antineoplastic drugs may precipitate overgrowth of C. difficile in the bowel.

Prospective, randomized, controlled evaluation of a gentamicin loading dose in neonates.

A prospective, randomized, controlled evaluation comparing a 4-mg/kg loading dose (LD) of gentamicin to the standard regimen of 2.5 mg/kg every 12, 18 or 24 h was conducted in critically ill neonates. The objective of the study was to compare the time required to achieve a therapeutic peak serum concentration (i.e. the number of dosing intervals) and to compare the number of serum concentrations outside the therapeutic range as an indicator of potential toxicity between the treatment groups. Eighteen of 26 patients, 5 of 13 in the control group and 13 of 13 in the LD group (p = 0.012) achieved an initial peak concentration of > or = 5 micrograms/ml following the first gentamicin infusion. There were no significant differences between the control and LD group in the number of potentially toxic serum concentrations. When patients were subdivided according to gestational age (GA), patients of < or = 34 weeks had significantly lower initial peak concentrations. A LD of 4 mg/kg in neonates, particularly those of < or = 34 weeks GA, produced a therapeutic peak concentration following the initial dose. There is a minimal risk of attaining serum concentrations commonly associated with toxicity providing the dosage interval is adjusted based on serum creatinine determinations. Based on this study, infants of > 34 weeks GA generally achieve therapeutic peak concentrations after the first dose with conventional dosing; however, in younger infants an appropriate LD is required to reach therapeutic concentrations early in therapy.

Contamination study of multiple-dose vials.

OBJECTIVE: To document the number of opened, dated, and expired multiple-dose vials (MDVs) in patient-care areas and to determine what proportion of MDVs were contaminated with bacteria or cellular debris. DESIGN: Every tenth opened MDV (69/656) identified on the wards was collected, ensuring representation from each nursing unit. Contents were examined for contamination. SETTING: Medical-school-affiliated, tertiary care center. MAIN OUTCOME MEASURES: (1) Visual inspection for debris, medication type, location, lot number, manufacturer's expiration date, and date of opening; (2) culture in solid and broth media for bacterial growth; and (3) staining and microscopic examination for cellular constituents. RESULTS: No vials had been dated after opening and 4.6 percent were expired according to the manufacturer's expiration date. No bacterial contamination was evident; however, one vial was contaminated with red blood cells. CONCLUSIONS: Transmission of infection via contaminated MDVs has been well documented and contamination with red blood cells raises concerns about potential for transmission of bloodborne pathogens. Recommendations include dating MDVs after opening, emphasizing the need for proper aseptic technique, and discarding MDVs on the manufacture's date of expiration.

Antibiotic-associated hypoprothrombinemia: a review of prospective studies, 1966-1988.

Many antimicrobial agents have been associated with hypoprothrombinemia. The precise mechanisms are unknown, but alteration in vitamin K status or utilization is involved. The two postulated mechanisms implicate either direct inhibition of biosynthesis of the vitamin K-dependent clotting factors by the N-methylthiotetrazole (NMTT) moiety found in certain antimicrobial agents or eradication of vitamin K-producing intestinal microflora in patients with reduced oral intake of vitamin K. An English-language review of all prospective studies reported between 1966 and 1988 in which serial prothrombin times were monitored in adult patients revealed that the incidence of hypoprothrombinemia varied from 3.7% to 64% with NMTT-containing regimens and from 0% to 24% with non-NMTT-containing regimens. Detailed evaluation of these and other studies suggests that certain risk factors, including malnutrition, hepatic and renal dysfunction, older age, and severity of illness, may be the major determinants of hypoprothrombinemia. The hypothesis that the NMTT side chain is primarily responsible for hypoprothrombinemia may not be justified. We conclude that patients at high risk for coagulopathy should be carefully monitored and that serious consideration should be given to the use of prophylactic vitamin K in such cases.

Quality assurance and certification program for an aminoglycoside monitoring service.

A Quality Assurance Program (QAP) should both evaluate and improve the quality of a service. In order to train newly employed pharmacists and ensure provision of a consistently high level of clinical service, a pharmacist training program for an Aminoglycoside Monitoring Service (AMS) and a QAP involving pharmacist certification was established. The certification program consists of a pretest, a reading/information package, an "on the job" training requirement and a posttest which pharmacists work through at their own speed. Certification requires completion of 45 hours of supervised AMS activity and a score of 90 percent on the posttest. Yearly recertification is required. As an integral part of the QAP, the clinical coordinator reviews the AMS monitoring forms monthly for specific performance standard indicators. Problems are identified and dealt with on an individual basis. The program is not mandatory, however, all pharmacists have elected to complete certification. Seven pharmacists and three pharmacy residents have participated in the certification program. All seven pharmacists and one resident received certification. A questionnaire completed by the pharmacists indicated that all felt certification was necessary and contributed to standardization and consistency of the AMS.

Aminoglycoside volume of distribution in pediatric patients.

Pharmacokinetic parameters of three aminoglycoside antibiotics were studied retrospectively in 218 pediatric patients to determine an apparent volume of distribution (Vd) for this age group and to determine if Vd is significantly different in pediatric patients compared with adults. Data on patients considered for inclusion in the study were obtained from the files of the aminoglycoside monitoring services at Saskatoon University Hospital and Regina General Hospital. Both services use a computer program that calculates pharmacokinetic parameters using the Sawchuk-Zaske method. Children between the ages of 1 and 16 years with normal renal function from whom serum concentration had been obtained were included in the study. Exclusion criteria included abnormal or unstable renal function, cystic fibrosis, and pregnancy. The mean age of the pediatric group was 8.65 +/- 5.37 years. Average values for Vd and half-life were 0.34 L/kg and 2.3 h, respectively. No strong correlation was found between the Vd (L/kg) and age. The patients were subdivided into three age groups: 1-4.9 years, 5-9.9 years, and 10-16 years. Group 1 (1-4.9 years) had a larger Vd than the other groups and the Vd of all three groups were significantly different from the estimated Vd of 0.20 L/kg for adult patients. A "normal" pediatric value for the Vd of aminoglycosides could not be determined; however, the Vd in children is significantly larger than the Vd in adults and dosage regimens should be adjusted accordingly.