Evaluation of impact of statin use on development of CPK elevation during daptomycin therapy.

BACKGROUND: Because both daptomycin and statins may increase creatine phosphokinase (CPK) levels, the manufacturer of daptomycin suggests considering holding statins during daptomycin therapy. Published evidence suggests potential detrimental effects of withdrawing statin therapy. OBJECTIVES: The objectives of this study were to determine the impact of concurrent statin therapy on peak CPK values, incidence of CPK elevation in patients receiving daptomycin therapy, and clinical factors associated with increased risk of developing CPK elevation. METHODS: This was a single-center, retrospective cohort study of patients ≥18 years of age who received daptomycin for ≥72 hours and had ≥1 follow-up CPK during a 5-year period. A Kaplan-Meier curve was used to evaluate time to CPK elevation. Cox regression analyses were used to compare the risk of developing elevated CPK between 3 study groups: those receiving daptomycin alone, daptomycin with concurrent statin therapy, and statin therapy held while on daptomycin. RESULTS: 498 patients were included in the study-384 received daptomycin alone, 63 received daptomycin concurrent with statin, and 51 with statin held during daptomycin therapy. Cumulative incidence of CPK elevation was 5.1% and 12% at 7 and 14 days. Those on daptomycin and statin concurrent therapy demonstrated an approximately 2-fold risk of CPK elevation compared with those having their statin therapy held, but the overall group effect was not statistically significant (P = .17). CONCLUSIONS: Our findings suggest that holding statin during daptomycin therapy may not be necessary, but may indicate need for increased frequency of CPK monitoring when these medications are used concurrently.

Efficacy of inactivated vaccines in patients treated with immunosuppressive drug therapy.

Inactivated vaccines are generally considered safe in immunocompromised patients but the ability of immunocompromised patients to generate an effective immune response to vaccines is uncertain. Although recent reviews have focused on the effects of vaccines in patients who are immunocompromised due to various disease states (primary immunodeficiency), the effects of immunosuppressive drug therapy (secondary immunodeficiency) has received relatively less attention. This review evaluates evidence regarding the efficacy of inactivated vaccines against influenza, COVID-19, and other diseases in patients treated with immunosuppressive oncologic agents, immunosuppressants used for transplant recipients, and immunosuppressants used for autoimmune disorders. Although evidence is mixed for many immunosuppressive agents and vaccines, most studies have found an attenuated immune response to inactivated vaccines, with the majority of data indicate anti-B-cell antibodies have a more severe and prolonged negative effect on vaccine efficacy.

Efficacy of ertapenem for consolidation therapy of extended-spectrum beta-lactamase-producing gram-negative infections: a case series report.

BACKGROUND: Infections caused by extended-spectrum beta-lactamase (ESBL)-producing gram-negative organisms are becoming increasingly common and present significant challenges in terms of treatment. Carbapenems is the antibiotic class of choice for treatment of these types of infections. Ertapenem is the newest carbapenem, capable of being dosed once daily, and has some in vitro but little in vivo evidence supporting its use for the treatment of these resistant infections. OBJECTIVE: To examine the clinical and microbiologic outcomes associated with ertapenem therapy of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis infections. METHODS: This was a retrospective case series that examined the clinical and microbiologic outcomes of 22 patients who received ertapenem for treatment of an ESBL infection at Rush University Medical Center in Chicago, IL, during 2003-2005. RESULTS: The majority (16/22) of patients received ertapenem for consolidation rather than initial therapy. Different antibiotics most commonly used were other carbapenems, piperacillin/tazobactam, and aminoglycosides. The most common infections treated were lower urinary tract infections and osteomyelitis. Clinical efficacy was determined in all 22 patients, with 20 (91%) patients having a positive outcome, defined as either clinical improvement or clinical cure. The best clinical cure rate was seen with wound infections, where all 3 patients examined were found to be clinically cured. Microbiologic efficacy was determined in 7 patients, with 6 (85.7%) defined as microbiologic cure. One patient was found to be both a clinical and microbiologic failure and was also found to have developed an ertapenem-resistant strain of E. coli. CONCLUSIONS: These results demonstrate potential microbiologic and clinical efficacy of ertapenem for treatment of ESBL-producing infections and the need for a prospective, randomized study examining its efficacy versus that of other carbapenems.

Is Abnormal Urine Protein/Osmolality Ratio Associated with Abnormal Renal Function in Patients Receiving Tenofovir Disoproxil Fumarate?

BACKGROUND: Risk factors for and optimal surveillance of renal dysfunction in patients on tenofovir disoproxil fumarate (TDF) remain unclear. We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF. METHODS: This retrospective, single-center study investigated the relationship between parameters of renal function (estimated glomerular filtration rate (eGFR) and P/O-ratio) and risk factors for development of kidney dysfunction. Subjects were HIV-infected adults receiving TDF with at least one urinalysis and serum creatinine performed between 2010 and 2013. Regression analyses were used to analyze risk factors associated with abnormal P/O-ratio and abnormal eGFR during TDF therapy. RESULTS: Patients were predominately male (81%); (65%) were Caucasian. Mean age was 45.1(±11.8) years; median [IQR] TDF duration was 3.3 years. [1.5-7.6]. Median CD4+ T cell count and HIV viral load were 451 cells/µL [267.5-721.5] and 62 copies/mL [0-40,150], respectively. Abnormal P/O-ratio was not associated with low eGFR. 68% of subjects had an abnormal P/O-ratio and 9% had low eGFR. Duration of TDF use, age, diabetes and hypertension were associated with renal dysfunction in this study. After adjustment for age, subjects on TDF > 5 years had almost a four-fold increased likelihood of having an abnormal P/O-ratio than subjects on TDF for < 1yr (OR 3.9; 95% CI 1.2-14.0; p = 0.024). CONCLUSION: Abnormal P/O-ratio is common in HIV-infected patients on TDF but was not significantly associated with low eGFR, suggesting that abnormal P/O-ratio may be a very early biomarker of decreased renal function in HIV infected patients.

Iatrogenic cushing syndrome secondary to ritonavir-epidural triamcinolone interaction: an illustrative case and review.

HIV positive patients on ritonavir-containing antiretroviral therapy (ART) can develop iatrogenic Cushing syndrome (IACS) and adrenal insufficiency as a result of drug-drug interactions with inhaled or intranasal glucocorticoid therapy. Reports related to epidural triamcinolone injections are relatively uncommon but increasingly reported. We describe a 48-year-old woman with immunologically and virologically well-controlled HIV on ritonavir-based ART, who developed headache, dizziness, and candida and herpes simplex virus (HSV) ulcerative esophagitis 7 days after receiving an epidural triamcinolone injection for cervical radicular pain. Iatrogenic Cushing syndrome and relative adrenal insufficiency were suspected and proven. The patient's ART was changed to a non-HIV protease inhibitor- (PI-) containing program, her symptoms improved, and she did not require hydrocortisone replacement. In this paper, we review the literature on IACS and relative secondary adrenal insufficiency from epidural triamcinolone injections in HIV patients on ritonavir-containing ART regimens. A high index of clinical suspicion is needed for diagnosis. Prevention of drug-drug interactions by taking a thorough medication history for patients on ritonavir-containing ART regimens before prescribing any form of corticosteroid is crucial and effective and sustained interdisciplinary communication in the care of such patients.

Assessment of the presence and quality of osteoporosis prevention education among at-risk internal medicine patients.

OBJECTIVE: Appropriate calcium and vitamin D intake for the prevention of osteoporosis represents an important component of osteoporosis prevention education (OPE). We sought to assess the presence and quality of OPE among osteoporotic and at-risk inpatients. DESIGN: Prospective chart review plus cross-sectional interview. SETTING: One academic tertiary referral medical center in Rochester, Minnesota. PARTICIPANTS: Adults admitted to an inpatient medicine service who were determined to be at risk for osteoporosis based on an investigator-developed screening tool or previously diagnosed with osteoporosis. Four hundred sixtyfour patients were screened, 192 patients were approached for participation, and 150 patients consented to be interviewed for the study. MAIN OUTCOME MEASURES: Source of OPE, rates of appropriate calcium intake and supplementation. RESULTS: OPE from a health care provider was reported by 31.3% of patients, with only one patient reporting education from a pharmacist. Self OPE and no OPE were received by 29.3% and 39.3% of patients, respectively. Appropriate overall calcium intake was found in 30.7% of patients, and only 21.3% of patients were taking an appropriate calcium salt. CONCLUSION: Patients with osteoporosis and risk factors for osteoporosis lack adequate education from health care providers regarding appropriate intake of dietary and supplemental calcium and vitamin D. A particular deficit was noted in pharmacist-provided education. Specific education targeting elemental calcium amounts, salt selection, and vitamin D intake should be provided to increase the presence of appropriate overall calcium consumption.

Development and evaluation of a pharmacogenomics educational program for pharmacists.

Objectives. To evaluate hospital and outpatient pharmacists' pharmacogenomics knowledge before and 2 months after participating in a targeted, case-based pharmacogenomics continuing education program.Design. As part of a continuing education program accredited by the Accreditation Council for Pharmacy Education (ACPE), pharmacists were provided with a fundamental pharmacogenomics education program.Evaluation. An 11-question, multiple-choice, electronic survey instrument was distributed to 272 eligible pharmacists at a single campus of a large, academic healthcare system. Pharmacists improved their pharmacogenomics test scores by 0.7 questions (pretest average 46%; posttest average 53%, p=0.0003).Conclusions. Although pharmacists demonstrated improvement, overall retention of educational goals and objectives was marginal. These results suggest that the complex topic of pharmacogenomics requires a large educational effort in order to increase pharmacists' knowledge and comfort level with this emerging therapeutic opportunity.