Impact of Extended- Versus Intermittent-Infusion Cefepime on Clinical Outcomes in Hospitalized Patients.

Background: Pharmacodynamic models support potential improved antimicrobial pharmacokinetic and pharmacodynamic goal attainment in patients treated with extended-infusion (EI) versus intermittent-infusion (II) cefepime. Small clinical studies demonstrate inconsistent findings in patient outcomes, necessitating a deeper review of this administration method. Methods: This was a retrospective cohort study comparing patients receiving EI versus II cefepime between September 1, 2017, and March 31, 2018. The primary outcome was in-hospital all-cause mortality. Secondary objectives included length of hospital and ICU stay, time to defervescence, duration of therapy, duration of mechanical ventilation, and readmission rate. Subgroup analyses for the primary objective were conducted based on comorbid burden and isolate susceptibilities. Results: No statistically significant differences were noted in the 645 included patients for the primary outcome between the EI and II groups (7.8% vs 10.4%, P = .32). Median length of stay was 9 days (IQR 12) versus 11 days (IQR 14) (P = .30), respectively. In addition, statistical significance was not seen in any of the subgroups for the primary outcome including patients with APACHE II score ≥ 20 (17.4% vs 30.6%, P = .26) and for infections caused by Pseudomonas aeruginosa (5.9% vs 20.0%, P = .23) or Enterobacteriaceae (11.1% vs 20.0%, P = .13) with minimum inhibitory concentration (MIC) ≥ 4. Conclusion: No statistically significant differences were noted between EI and II groups, although benefits in specific subpopulations may exist when these results are correlated with findings from studies examining alternative antipseudomonal beta lactams.

Use of Pamidronate for Hypercalcemia of Malignancy in Renal Dysfunction.

BACKGROUND: Few studies have been conducted investigating the use of bisphosphonates in hypercalcemia of malignancy (HCM) in the setting of renal dysfunction. OBJECTIVE: The primary objective was to compare the incidence of acute kidney injury (AKI) within 7 days of receiving pamidronate for the treatment of HCM with pre-existing renal dysfunction versus normal renal function at the time of pamidronate administration. The secondary objectives explored the effects of pamidronate doses and infusion rates on the safety and efficacy in those with pre-existing renal dysfunction for the treatment of HCM. METHODS: A retrospective chart review was conducted on patients who received pamidronate for the treatment of HCM at a community teaching hospital in Indianapolis, Indiana, from January 1, 2013, to May 31, 2017. RESULTS: A total of 141 pamidronate administrations were included (116 patients had normal baseline renal function, and 25 patients had pre-existing renal dysfunction before pamidronate administration for the treatment of HCM). Two (8%) patients developed AKI in the pre-existing renal dysfunction group, compared with 4 (3.4%) patients in those without pre-existing renal dysfunction (P = .288). For those with pre-existing renal dysfunction, the incidence of AKI did not differ based on the dosage of pamidronate given (P = .762) or infusion rates (P = .373). CONCLUSION: Pamidronate appears to have limited impact on renal function at doses up to 90 mg in the setting of pre-existing renal dysfunction for the treatment of HCM.

Benzodiazepine Initiation and Dose Escalation.

BACKGROUND: Benzodiazepines (BZDs) place patients at a significant risk of falling. The current literature does not address if this risk is increased during initiation or dose escalations of BZDs. OBJECTIVE: To determine if initiation or dose escalations of BZD regimens are associated with an increased risk of falls in hospitalized patients compared with patients maintained on their home dose or who had their dose decreased from baseline. METHODS: This retrospective case-control study evaluated hospitalized patients aged 45 years or older who received a BZD. Patients who did not fall were collected in a 3:1 ratio to patients who fell. Comparisons were made between BZD regimens prior to admission and those 48 hours prior to the index date. The date of fall served as the index date for patients who fell, and the median time-to-fall served as the index date for all other patients. RESULTS: A total of 132 patients were included in the study (33 falls and 99 without a fall). No significant differences were noted in demographics, baseline mobility, or past medical history. Patients who fell had a significantly longer median length of stay (15 vs 10 days; P = 0.025). Additionally, patients who fell were more likely to have had their BZD regimen initiated or dose escalated compared with patients who did not fall (63.6% vs 41.4%; P = 0.043). CONCLUSIONS: The risk of falling while on a BZD is increased on initiation and dose escalations. Hospitals should ensure judicious use of BZDs in inpatients to reduce the risk of falls.

I.V. ascorbic acid for treatment of apparent rasburicase-induced methemoglobinemia in a patient with acute kidney injury and assumed glucose-6-phosphate dehydrogenase deficiency.

PURPOSE: A case of apparent rasburicase-induced methemoglobinemia and acute kidney injury treated with i.v. ascorbic acid because of suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency is reported. SUMMARY: A 46-year-old African-American man with a recent diagnosis of multiple myeloma and renal insufficiency was admitted to the hospital with a cough, hemoptysis, and fatigue. His medical history included hypertrophic cardiomyopathy, ventricular tachycardia, attention deficit/hyperactivity disorder, and pleural effusion. No treatments for multiple myeloma were started before hospital admission. Levofloxacin 750 mg orally daily for possible pneumonia, lenalidomide 10 mg orally daily, and dexamethasone 20 mg orally weekly were administered. Plasmapheresis was also initiated. Laboratory test results revealed sustained hyperuricemia, which was believed to be due in part to tumor lysis, and a single dose of rasburicase 6 mg i.v. was administered. Subsequently, the patient experienced a decrease in oxygen saturation. Methemoglobinemia was suspected, and the patient's methemoglobin fraction was found to be 14.5%. The patient developed worsening shortness of breath and a drop in hemoglobin concentration, consistent with methemoglobinemia and hemolysis. Ascorbic acid 5 g i.v. every 6 hours was initiated for a total of six doses. Because the patient was assumed to have G6PD deficiency, which was later confirmed, methylene blue was avoided. Within 24 hours, the patient's oxygen saturation values and symptoms improved. CONCLUSION: A patient with apparent rasburicase-induced methemoglobinemia and acute kidney injury was treated with i.v. ascorbic acid (5 g every six hours for six doses) because of the possibility, later proved, that he had G6PD deficiency. The methemoglobinemia resolved without worsening of renal function.

Ceftriaxone Potentiates Warfarin Activity Greater Than Other Antibiotics in the Treatment of Urinary Tract Infections.

BACKGROUND: The cephalosporin class has been associated with an increased risk of bleeding among elderly patients receiving warfarin. Urinary tract infections (UTI) are the most prevalent infection in elderly patients. OBJECTIVE: To determine the extent of interaction between antibiotics used in the treatment of UTI, particularly specific cephalosporins and warfarin. METHODS: A retrospective chart review was conducted on chronic warfarin patients with a diagnosis of UTI treated with ceftriaxone, a first-generation cephalosporin, penicillin, or ciprofloxacin. The primary outcome was the comparison of the extent of international normalized ratio (INR) change from baseline between each antibiotic group. RESULTS: The ceftriaxone group was found to have a statistically significant higher peak INR value compared to all other studied antibiotics (ceftriaxone: 3.56, first-generation cephalosporins: 2.66, penicillins: 2.98, ciprofloxacin: 2.3; P = .004), a statistically significant greater extent of change in INR value (+1.19, +0.66, +0.8, +0.275; P = .006), and a statistically significant greater percentage change in INR value when compared to ciprofloxacin (54.4% vs 12.7%; P = .037). CONCLUSION: Ceftriaxone interacts with warfarin to increase a patient's INR value more than other commonly administered antibiotics for UTI treatment. Other antibiotics should be preferred for UTI treatment in patients on warfarin.