John C. Williamson

Unique aspects of antimicrobial use in older adults.

Elderly persons consume a significant proportion of health care resources. Antimicrobials are just one class among many pharmaceuticals that are prescribed more frequently to elderly patients than to younger patients. There are unique aspects of antimicrobial use in elderly persons that make prescribing complicated and monitoring unpredictable. Physiologic changes associated with aging result in altered pharmacokinetics, and accurate estimates of renal function cannot be made with standard methods. Together, these qualities make antimicrobial dosing difficult. Because of a higher prevalence of other chronic diseases, there is a greater propensity for polypharmacy and a resulting risk of an adverse event or a significant drug interaction. Lastly, irrespective of altered pharmacokinetics, adverse effects of many antimicrobials are more common in elderly persons, which introduces an added dimension to ensuring safety with antimicrobial therapy.

Respiratory distress associated with zanamivir.

To the Editor: Zanamivir (Relenza, Glaxo Wellcome, Research Triangle Park, N.C.), a neuraminidase inhibitor, has been approved by the Food and Drug Administration for the treatment of uncomplicated...

Show Me the Money: Long-Term Financial Impact of an Antimicrobial Stewardship Program

The financial impact of an antimicrobial stewardship program in operation for more than 11 years was determined by calculating the reduction in antimicrobial expenditures minus program labor costs. Depending on the method of inflation adjustment used, the program was associated with average cost savings of

Successful treatment of ventriculostomy-related meningitis caused by vancomycin-resistant Enterococcus with intravenous and intraventricular quinupristin/dalfopristin.

920,070 to

The Addition of Intravenous Metronidazole to Oral Vancomycin is Associated With Improved Mortality in Critically Ill Patients With Clostridium difficile Infection

2,064,441 per year.

Modification of Diet in Renal Disease and Modified Cockcroft-Gault Formulas in Predicting Aminoglycoside Elimination:

We report a case of ventriculostomy-related meningitis caused by vancomycin-resistant Enterococcus faecium (VRE). The patient was successfully treated with administration of quinupristin/dalfopristin by both intravenous and intraventricular routes. A brief review of the literature is provided, which indicates that optimal management with quinupristin/dalfopristin should include daily intraventricular doses of at least 2 mg.

Neuraminidase Inhibitors in Patients with Underlying Airways Disease

BACKGROUND The optimal therapy for critically ill patients with Clostridium difficile infection (CDI) is not known. We aimed to evaluate mortality among critically ill patients with CDI who received oral vancomycin (monotherapy) vs oral vancomycin with intravenous (IV) metronidazole (combination therapy). METHODS A single-center, retrospective, observational, comparative study was performed. Patients with a positive C. difficile assay who received oral vancomycin while bedded in an intensive care unit (ICU) between June 2007 and September 2012 were evaluated. Patients meeting ≥3 of the following criteria were included: albumin <2.5 g/dL, heart rate >90 bpm, mean arterial pressure <60 mmHg, white blood cell count ≥15 000 cells/mL, age >60 years, serum creatinine ≥1.5 times baseline, or temperature ≥100.4°F. Patients in the combination therapy group received IV metronidazole within 48 hours after initiating vancomycin. Patients <18 years or with unrelated gastrointestinal disease were excluded. The primary outcome was in-hospital mortality. Patients were matched using Acute Physiology and Chronic Health Evaluation II scores. RESULTS Eighty-eight patients were included, 44 in each group. Patient characteristics were similar although more patients in the combination group had renal disease. Mortality was 36.4% and 15.9% in the monotherapy and combination therapy groups, respectively (P = .03). Secondary outcomes of clinical success, length of stay, and length of ICU stay did not differ between groups. CONCLUSIONS Our data are supportive of the use of combination therapy with oral vancomycin and IV metronidazole in critically ill patients with CDI. However, prospective, randomized studies are required to define optimal treatment regimens in this limited population of CDI patients.

Stability of Cefepime in Peritoneal Dialysis Solution

Background: The Modification of Diet in Renal Disease (MDRD) formula and a modified version of the Cockcroft-Gault (CGm) formula adjusting for body surface area have been found to moro accurately estimate glomerular filtration rate (GFR) compared with the original CG equation in specific patient populations. To date, the use of these formulas in determining drug dosage and estimating drug elimination has not been thoroughly investigated. Objective: To evaluate the ability of the MDRD and CGm formulas to predict aminoglycoside elimination rate and clearance. Methods: A 6-month prospective, noninterventional, pharmacokinetic study was conducted at a university teaching hospital. Patients receiving aminoglycoside antibiotics (amikacin, gentamicin, or tobramycin) were eligible for study inclusion. Predicted elimination rate and aminoglycoside clearance were calculated for each patient using the MDRD and CGm formulas. Actual (patient-specific) elimination rate and aminoglycoside clearance were calculated for each patient using measured aminoglycoside serum concentrations. Predictive ability of the formulas was compared through Spearman correlations and Students t-tests. Accuracy of formula estimates was also evaluated. Results: Seventy-one patients met study inclusion criteria; the majority (82%) were in an intensive care unit. The 6-variable MDRD formula was found to be a significantly better predictor of aminoglycoside clearance (p = 0.035) compared with CGm. There was no statistically significant difference between the 2 methods in predicting patient-specific elimination rates (p = 0.167). Among subgroups, the MDRD formula was a significantly better predictor of aminoglycoside clearance for patients with an estimated GFR less than 60 mL/min (p = 0.027). Conclusions: The 6-variable MDRD performs better than the CGm formula in predicting aminoglycoside clearance and may be considered as a tool in aminoglycoside dosing recommendations.

In Vitro Assessment of Urinary Isolates of Ampicillin-Resistant Enterococci

Influenza virus infection accounts for significant morbidity, mortality, and healthcare expenditures among persons worldwide. Approximately 20 000 to 40 000 people in the US die each year as a result of influenza. Individuals most susceptible to adverse outcomes include the elderly and those with asthma, chronic obstructive pulmonary disease (COPD), heart disease, renal failure, malignancy, or immunosuppression. Prior to the AIDS epidemic, underlying respiratory disease was the greatest risk factor for influenza-related hospitalization ranking third to heart disease and malignancy for risk of mortality. Although the influenza vaccine can help prevent pneumonia and hospitalization, it is limited by less than ideal immunization rates and the possibility of viral antigenic shifts that render the vaccine ineffective. Pharmacologic interventions play an important role in the management of influenza virus infection by shortening the duration of symptoms.The advent of the neuraminidase inhibitors (NAIs) zanamivir and oseltamivir has significantly affected the treatment of influenza. Unlike NAIs, the older therapeutic options amantadine and rimantadine may cause significant central nervous system adverse effects. In addition, amantadine and rimantadine are not active against influenza B viruses, whereas NAIs are active against both influenza A and B. Post-marketing surveillance of the NAIs has revealed that bronchospasm may occur in patients with underlying respiratory disease treated with the NAI zanamivir. Recent data suggest zanamivir is effective in patients with underlying respiratory disease, but the data are insufficient to elucidate the true risk of bronchospasm. Based on post-marketing reports, zanamivir should be used with caution in patients with asthma or COPD. Although oseltamivir has not been associated with any significant respiratory adverse effects, no data exist on the safety and efficacy of this NAI in patients with underlying respiratory disease.

BK Virus Encephalitis: Case Report, Review of the Literature, and Description of a Novel Treatment Modality

OBJECTIVE: To determine the stability of cefepime in peritoneal dialysis solution. DESIGN: Cefepime HCl was added to premade bags of Delflex peritoneal dialysis solution with 1.5% dextrose to produce a cefepime concentration of approximately 100 μg/mL. Peritoneal dialysis solution bags were stored at 4, 25, and 37 °C to simulate refrigeration, room temperature, and body temperature, respectively. Samples were drawn at scheduled times up to 336, 168, and 48 hours, respectively, after the addition of cefepime HCl. Cefepime concentrations were measured by HPLC. SETTING: This study was performed at a university-affiliated tertiary care hospital. OUTCOME MEASURE: If the mean concentration of the samples at a given time and condition was >90% of the initial concentration, cefepime was considered stable at that time and condition. RESULTS: The mean HPLC results for samples drawn at each time and condition were all >90%. CONCLUSIONS: Cefepime is stable in peritoneal dialysis solution with dextrose 1.5% for 14 days refrigerated, seven days at room temperature, and 48 hours at 37 °C.