Michael Cimino

Relationship of serum antibiotic concentrations to nephrotoxicity in cancer patients receiving concurrent aminoglycoside and vancomycin therapy

Methicillin-resistant coagulase-negative staphylococci have become increasingly responsible for febrile episodes in cancer patients, often necessitating the addition of vancomycin to an aminoglycoside-containing broad-spectrum antibiotic regimen. A total of 229 courses of antibiotic therapy in 229 patients were evaluated for nephrotoxicity associated with the administration of an aminoglycoside and/or vancomycin. The incidence of nephrotoxicity observed in patients administered an aminoglycoside (Group A) was 18 percent; vancomycin (Group B) 15 percent; and an aminoglycoside concurrently with vancomycin (Group C) 15 percent. The following pharmacokinetic/dosing factors were significantly associated with increased nephrotoxicity in the groups: baseline serum creatinine level, mean daily dose during the first three days of therapy (Group B), and elevated serum trough aminoglycoside or vancomycin concentrations (2 micrograms/ml or more or 10 micrograms/ml or more, respectively). No cumulative nephrotoxicity was demonstrated with the concurrent administration of vancomycin and an aminoglycoside. A higher incidence of nephrotoxicity was seen in Group C (42 percent) and Group B (27 percent) patients, in whom trough serum vancomycin concentrations were 10 micrograms/ml or more.

Assessing medication prescribing errors in pediatric intensive care units.

Objective To evaluate a matrix for determining the predominant type, cause category, and rate of medication prescribing errors, and to explore the effectiveness of hospital-based improvement initiatives among pediatric intensive care units (PICUs). Design This study involved the prospective identification of medication errors for categorization and evaluation by using a matrix methodology. A pretest-posttest design without a control group was used to explore the impact of initiatives employed to reduce medication error rates and severity. Setting PICUs in nine freestanding, collaborating tertiary care children’s hospitals that participated in both baseline and postintervention analyses. Methods We evaluated 12,026 PICU medication orders at baseline and 9,187 orders postintervention for prescribing errors, excluding resuscitation orders. A standardized tool and process captured error type, cause category, and severity for 2 wks before and after intervention. Three levels of error detection were used and included pharmacy order entry, PICU nurse order transcription, and team-based overview. Site-specific interventions were implemented, which included predominantly provider education as well as informational (47%) and dosing “assists” via preprinted orders, forcing functions, or prompts (39%). Results Of baseline orders, 11.1% had at least one prescribing error. The interception of prescribing errors improved 30.9% (1.6% of all orders at baseline, 2.0% post intervention). Preventable adverse drug events were uncommon (0.6% of all medication errors) and of low severity at baseline; most were wrong dose errors. The implementation of improvement initiatives, specific for each facility, resulted in a 31.6% reduction in prescribing errors from 11.1% to 7.6%. However, site results varied considerably. Conclusions A benchmark for medication prescribing errors in the PICU was identified among nine children’s hospitals. The methodology was successful in accounting for site-specific differences with regard to identifying and documenting errors as well as reporting results of improvement initiatives. Furthermore, the methodology employed was generalizable in the identification of predominant prescribing error types, which helped to track individual hospital improvement initiative development and implementation. Overall improvement in prescribing error rates was noted; however, considerable variation in the success of improvement initiatives was noted and bears further attention.

Methadone dosage for prevention of opioid withdrawal in children

Background Opioids are frequently used for sedation in the Paediatric Intensive Care Unit (PICU). With time the dosing often increases because of tolerance. On cessation of the sedation there is a risk of the opioid withdrawal syndrome. The aim of our study was to evaluate methadone dosing as a risk factor for opioid withdrawal and to determine optimal dose and efficacy of methadone to prevent withdrawal.

Risk Reduction for Adverse Drug Events Through Sequential Implementation of Patient Safety Initiatives in a Children's Hospital

BACKGROUND. Medication management is a complex, multifaceted system. Prescribing errors occur upstream in the process, and as such, their effects can be perpetuated, and sometimes even exacerbated, in subsequent steps. These errors place patients at risk of adverse drug events. Children, especially young infants, are at particular risk because of their size, unique physiology, and immature ability to metabolize drugs. OBJECTIVE. The purpose of this study was to reduce the risk of harm to children resulting from prescribing errors. METHODS. We sequentially implemented patient safety initiatives over a 1-year time frame at a pediatric tertiary care academic facility. The initiatives included an educational Web site with competency examination, distribution of a personal digital assistant-based standardized dosing reference, a zero-tolerance policy for incomplete or incorrect medication orders, prescriber performance feedback, and presentation of outcome data at citywide grand rounds. A total of 8718 orders were collected and analyzed to assess the impact of these initiatives. RESULTS. The absolute risk reduction from prescribing errors was 38 per 100 orders, with a relative risk reduction of 49%. Web-based education with point-of-care drug references and a zero-tolerance policy for incomplete or incorrect orders were most effective in decreasing potential adverse drug events. Documentation of appropriate weight-based dosing and indication for therapy increased by 24% and 42%, respectively. CONCLUSIONS. Process-improvement initiatives focusing on prescriber education and behavior modification can reduce the risk of harm to pediatric patients from prescribing errors.

Assessment of Cost-Effective Antibiotic Therapy in the Management of Infections in Cancer Patients

OBJECTIVE: To describe the economic benefits of a quality improvement effort directed at optimizing clinical outcome. DESIGN: A before—after observational design was used to evaluate the cost-effectiveness of a consensus approach to antimicrobial therapy. SETTING: The evaluation was conducted at a cancer research hospital. PATIENTS: Oncology patients requiring parenteral antibiotic therapy were consecutively observed. MAIN OUTCOME MEASURES: Outcome (clinical and microbiologic response), safety, and cost of therapy were assessed during a baseline period and compared to a period during which the consensus approach was used. INTERVENTIONS: The influence of a designated individual, in this case a clinical pharmacist, responsible for promotion of the consensus approach was explored. RESULTS: The consensus approach in combination with the promotional efforts of the clinical pharmacist was associated with a 13 percent increase in overall clinical response and a reduction of pathogen persistence from 22 to 11 percent. No difference in the average number of adverse effects per patient was observed over the two observation periods. These findings were associated with an estimated

Cefoperazone plus piperacillin versus mezlocillin plus tobramycin as empiric therapy for febrile episodes in neutropenic patients

22000/month cost savings. The consensus approach alone, without benefit of the clinical pharmacist, was not associated with improved therapeutic outcome or cost savings over the same observation periods. CONCLUSIONS: These data suggest that a consensus approach to antibiotic therapy can be cost-effective. An individual, such as a clinical pharmacist, may add significantly to quality improvement and cost-effective efforts in a hospital setting.

Patterns and changes in prescriber attitudes toward PDA prescription-assistive technology

The double beta-lactam combination of cefoperazone plus piperacillin was compared with an aminoglycoside-containing regimen of mezlocillin plus tobramycin in a prospective, randomized trial of empiric therapy for febrile neutropenic patients (neutrophils no more than 1,000/mm3). Thirty febrile episodes were treated with cefoperazone plus piperacillin and mezlocillin plus tobramycin, respectively. There was no significant difference between the two groups with respect to age, sex, pretherapy neutrophil count, and mean duration of therapy. The majority of patients had neutrophil counts of no more than 200/mm3 at the initiation of therapy. Only microbiologically and clinically documented infections were evaluated for efficacy. The cefoperazone plus piperacillin regimen appeared to have a comparable response rate with the mezlocillin plus tobramycin regimen (20 of 24 patients [83 percent] versus 16 of 23 patients [70 percent]). Gram-positive micro-organisms were seen predominantly in this study, with the cefoperazone plus piperacillin regimen achieving a bacteriologic response in 84 percent, as opposed to 60 percent for those organisms treated with the mezlocillin plus tobramycin regimen. Neither regimen was totally effective against coagulase-negative staphylococci. Eight superinfections occurred in the cefoperazone plus piperacillin arm, whereas 11 superinfections occurred in the mezlocillin plus tobramycin arm. Although fungal superinfections were most common, the number of gram-positive superinfections in the mezlocillin plus tobramycin arm exceeded those seen in the cefoperazone plus piperacillin arm. The incidence of antibiotic-related side effects was similar in the two groups. Hypokalemia was most frequently seen. Both skin rashes and nephrotoxicity were more common with mezlocillin plus tobramycin. Cefoperazone plus piperacillin was found to be effective empiric therapy in febrile neutropenic patients. This double beta-lactam combination may be particularly useful for patients who have or are at high risk for the development of renal insufficiency.

Experience of a Clinical Outcome-Based Pediatric Nutrition Support Service

CONTEXT Medication error prevention is a priority for the U.S. healthcare system in the 21st century. Use of technology is considered by some as critical to achieve this goal. Knowledge of the attitudinal barriers to such adoption, however, is limited. OBJECTIVE To determine the attitudes of frontline prescriber clinicians towards technology in general, and PDAs specifically, before and after introduction of a PDA in the clinical setting of medication prescribing. DESIGN A pre- and post-intervention web-based survey, 12-14 months apart. SETTING Academic tertiary care childrens hospital. PARTICIPANTS Total of 244 prescriber clinicians. INTERVENTION Distribution of a PDA with pediatric-specific medication prescribing information after completion of an on-line medication safety certification and other safety focused educational sessions. MAIN OUTCOME MEASURES Ratings (5-point Likert scale) reflecting perceptions and attitudes towards technology in general and technology in medical settings along with self-reported usage of the PDA for Rx. RESULTS Early Adopters and Late Adopters were identified statistically, and the group membership reflected their prior exposure to and ownership of other technologies. Early Adopters tended to be younger and less experienced clinically (e.g., residents) and more frequent owners and users of technology. Early Adopters expressed significantly more favorable attitudes toward technology and PDAs on both pre- to post-intervention survey occasions. They also utilized the PDA for Rx more often than LAs. Interestingly, PDA use for Early Adopters was based on its ease of use, while PDA use among later adopters was based on its clinical usefulness. CONCLUSIONS Provision of point of care information using PDAs and a user-friendly, pediatric-specific medication information software package did not positively affect the attitudes of prescriber clinicians among those already favorable toward technology. However, a significant change was found among those with initially less favorable attitudes. Organizations need to understand the nature of both Early and Late Adopters and plan appropriately for managing the respective needs and expectations when potentially beneficial technologies are introduced. In order to ensure the success of an implementation, the training and supportive interventions need to be carefully designed and specifically catered to the personality-based outcome expectations of the prescriber.

An Integrated Approach to Antimicrobial Stewardship in the Hospital Setting

In an era of reduced health care resources, ongoing documentation of nutrition interventions and resultant clinical outcomes are essential in supporting nutrition support services. Nutrition interventions and clinical outcomes obtained from an ongoing quality-improvement program for a nutrition support service in a tertiary care pediatric hospital is presented. Consecutive cases of inpatients with intermediate- to high-level nutrition risk who were hospitalized from June 1996 through May 1997 were reviewed for standard interventions offered by nutrition support staff members, including recommendations for diet alteration, supplements, TPN, enteral feedings, and nutrition instruction. Of 5369 admissions, 1422 (26.5%) were classified as intermediate- to high-level nutritional risk, requiring 2896 initial and follow-up interventions for which outcome was documented in 1184 cases (83.3%). Improvement was noted more often for cases receiving interventions within 72 hours of admission (91% vs. 82%, p = .031) an...

Single-dose antibiotic prophylaxis during cesarean section.

The use of antimicrobials for the therapy and prevention of infection is pervasive in the North American health care system. Antimicrobials are now the second most commonly used class of drugs in the United States and Canada (1,2). In addition, antimicrobial agents contribute significantly to hospital expenditures and account for 5% to 20% of a hospital’s global budget (3), while comprising 20% to 50% of an institution’s drug acquisition budget (4,5). Moreover, between 25% and 33% of hospitalized patients are treated with antimicrobial agents (6,7). With such widespread use, it is understandable that surveys have suggested that antimicrobials are inappropriately or incorrectly used in 22% to 65% of patients (6-8). In an era of cost containment, controlling antimicrobial use will reduce hospital expenditures; however, the motivation for controlling antimicrobial use is not restricted to monetary issues. Emerging antimicrobial-resistant organisms have developed from selective pressure applied by the misuse and overuse of antimicrobial agents in the hospital setting (9,10). In addition, adverse drug events due to the use of antimicrobial agents affect patient length of stay, costs and attributable mortality (11,12). Appropriate prescribing of anti-infective agents in the hospital setting improves the quality of clinical care provided to patients (13). An integrated antimicrobial stewardship program is a multidisciplinary activity that attempts to achieve the aforementioned principles (14,15). The specific goals of antimicrobial stewardship are: to prevent the emergence of antimicrobialresistant organisms, to control costs, to enhance the quality of medical care by improving physician performance, to reduce adverse drug events and to provide continuing medical education to physicians and other health care personnel. The strategies employed to promote an antimicrobial stewardship program in the hospital setting have included both persuasive and restrictive approaches (Table 1). Persuasive techniques attempt to alter physician prescribing behaviour through educational activities for physicians through either direct interaction with prescribers (eg, conferences or lectures) or indirect advice by means of simple chart entry (16); through peer review with delayed feedback on antimicrobial use (17); through academic detailing (18,19); through drug detailing by pharmaceutical representatives (20); through distribution of an antimicrobial handbook (21,22), through development of clinically-based therapeutic guidelines (23) and through computer-assisted decision support (13). In contrast, restrictive strategies have a direct impact on antimicrobial use patterns by limiting prescribing behaviour. Techniques employed to alter physician prescribing behaviour have included a controlled formulary system (24-26), automatic stop orders (25), automatic therapeutic interchange (24,27,28), antimicrobial order forms (25,29-31), restricted antimicrobial agents (24) and infectious diseases consultations for specific agents. Consultations vary from verbal authorization to employ a particular antimicrobial agent (32), to actual authorization granted