Celeste N Rudisill

Treatment of Meningitis Caused by Vancomycin-Resistant Enterococcus faecium: High-Dose and Combination Daptomycin Therapy

Objective: To report 3 successful treatments of vancomycin-resistant Enterococcus faecium meningitis in adults using daptomycin and either linezolid or gentamicin. Case Summary: Three case reports involving males (aged 58-78 years) are presented; in each case (trigeminal nerve microvascular decompression and subdural hygroma; paraspinal abscess; and hydrocephalus with subsequent craniotomy and ventriculo-peritoneal shunt placement) CSF examination revealed vancomycin-resistant Enterococcus (VRE) susceptible to daptomycin, gentamicin, and/or linezolid. Three- to four-week treatment regimens with daptomycin 6-12 mg/kg and either gentamicin or linezolid led to clinical resolution and microbiological clearance of infection. Discussion: Daptomycin has previously been shown to be successful in treating methicillin-resistant Staphylococcus aureus–associated meningitis and other serious VRE and enterococcal infections. Higher than approved doses of daptomycin were used in 2 cases where in theory higher CSF concentrations would thus be obtained. Gentamicin and linezolid were added to daptomycin therapy based on in vitro data synergy results and because of documented successful treatment for VRE meningitis, respectively. Conclusions: The difficulty in treating VRE CSF infections involves both drug kinetics and microbial resistance factors, as well as external factors such as foreign bodies like shunts. This report highlighted 3 cases where daptomycin use in concert with either gentamicin or linezolid was successful in treating this infection. Additional controlled trials will be helpful in identifying the best strategies when using daptomycin to treat CSF infections.

Nighttime and Weekend Medication Error Rates in an Inpatient Pediatric Population

Background: Nighttime and weekend admission has been associated with increased morbidity and mortality and has been linked to a variety of factors. Medication errors in hospitalized patients occur frequently, but the association between error rates and time of day and day of week (weekday vs weekend) has not been extensively studied. Objective: To compare reported medication error rates over a 1-year period between daytime versus nighttime shifts and weekday versus weekend in a childrens hospital and to characterize the types of errors that occurred. Methods: One hundred forty errors reported between January and December 2008 were retrospectively reviewed and classified by error type and severity according to established standards. Two investigators independently classified errors, and a third investigator with pediatric pharmacy expertise resolved discrepancies. Data on doses dispensed were collected from pharmacy records. Results: Over the study period, the reported error rate during daytime nursing shifts was 1.17 errors per 1000 doses dispensed versus 2.12 errors per 1000 doses dispensed for nighttime nursing shifts (p = 0.005). The error rates during pharmacy shifts (1st, 2nd, and 3rd) were 1.01, 2.24, and 1.88 per 1000 doses dispensed, respectively (p = 0.0019). Reported errors for weekday versus weekend were 1.9 errors per 1000 weekday doses versus 2.55 errors per 1000 doses, respectively (p = 0.181), and error rate for weekend shifts relative to first shift on weekdays was greater (p = 0.0004). Errors in medication administration, followed by dispensing errors, occurred most frequently. Conclusions: There was an increase in medication error rate during evening and nighttime shifts relative to day shift and during weekends relative to weekdays at this institution. Additional studies to validate this finding are needed; however, error prevention efforts should be instituted now for evening, nighttime, and weekend medication dispensing and administration.

Intravenous ibuprofen: the first injectable product for the treatment of pain and fever

This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs) is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in a series of post-operative patient populations. Two recent studies have also noted the improvement in fever curves in critically ill and burn patients. These data, along with pharmacokinetic and pharmacologic properties, are explored in this review, which addresses the clinical utility of a parenteral NSAID in a hospitalized patient for post-operative pain management and fever reduction. Further data on intravenous ibuprofen are needed to define long-term utilization, management of acute pain, and use in special populations.

Cerebrospinal Fluid Penetration of High-Dose Daptomycin in Suspected Staphylococcus aureus Meningitis:

Objective: To report a case of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia with suspected MSSA meningitis treated with high-dose daptomycin assessed with concurrent serum and cerebrospinal fluid (CSF) concentrations. Case Summary: A 54-year-old male presented to the emergency department with generalized weakness and presumed health-care–associated pneumonia shown on chest radiograph. Treatment was empirically initiated with vancomycin, levofloxacin, and piperacillin/tazobactam. Blood cultures revealed S. aureus susceptible to oxacillin. Empiric antibiotic treatment was narrowed to nafcillin on day 4. On day 8, the patient developed acute renal failure (serum creatinine 1.9 mg/dL, increased from 1.2 mg/dL the previous day and 0.8 mg/dL on admission). The patients Glasgow Coma Score was 3, with normal findings shown on computed tomography scan of the head 72 hours following an episode of cardiac arrest on day 10. The patient experienced relapsing MSSA bacteremia on day 9, increasing the suspicion for a central nervous system (CNS) infection. Nafcillin was discontinued and daptomycin 9 mg/kg daily was initiated for suspected meningitis and was continued until the patients death on day 16. Daptomycin serum and CSF trough concentrations were 11.21 μg/mL and 0.52 μg/mL, respectively, prior to the third dose. Lumbar puncture results were inconclusive and no further blood cultures were positive for MSSA. Creatine kinase levels were normal prior to daptomycin therapy and were not reassessed. Discussion: Daptomycin was initiated in our patient secondary to possible nafcillin-induced acute interstitial nephritis and relapsing bacteremia. At a dose of 9 mg/kg, resultant penetration of 5% was higher than in previous reports, more consistent with inflamed meninges. Conclusions: High-dose daptomycin may be an alternative option for MSSA bacteremia with or without a CNS source in patients who have failed or cannot tolerate standard therapy. Further clinical evaluation in patients with confirmed meningitis is warranted.

Multiple toxic effects of low-dose methotrexate in a patient treated for psoriasis.

PURPOSE A case of toxicity encountered with low-dose methotrexate therapy is discussed. SUMMARY A 59-year-old African American woman receiving long-term therapy for psoriasis came to the hospital with painful ulcers, difficulty swallowing, cutaneous lesions, and acute renal failure. Her medical history included type 2 diabetes mellitus, hypertension, coronary artery disease, morbid obesity, and psoriasis. On admission, the patient looked ill and had a low-grade fever; maculopapular skin lesions; and bullae and vesicles in her mouth and on her hands, legs, groin, and buttocks. With the exception of carvedilol, all home medications, including methotrexate, were discontinued. A complete medication history revealed that the patient had been taking methotrexate 2.5 mg daily, instead of 2.5 mg three times weekly as prescribed. This error translated into an estimated cumulative dose of 360 mg, nearly twice the prescribed amount. There were no clinically significant drug-drug interactions noted among her prescribed medications; however, the patient did report increased ibuprofen use secondary to the painful ulcerations in the previous few months. Leucovorin 15 mg i.v. every six hours was initiated along with additional supportive care. Skin and mucosal lesions, as well as her pain, had dramatically improved on day 5 of hospitalization. The patient was discharged after a six-day hospitalization and was provided with leucovorin 15 mg orally ever day for seven additional days until rheumatology follow-up. The patient was instructed to avoid any future methotrexate therapy. CONCLUSION A patient who erroneously took oral methotrexate daily rather than thrice weekly for psoriasis developed multiple manifestations of methotrexate toxicity.

Primary Meningococcal Arthritis as Initial Presentation in a Previously Undiagnosed HIV-Infected Patient

A 38-year-old African-American male complaining of pain in multiple joints was initially diagnosed with gouty arthritis concurrent with gonococcal septic arthritis. The diagnosis was made based on arthrocentesis results showing Gram-variable cocci and monosodium urate crystals in the synovial fluid. Final blood and synovial fluid cultures confirmed a diagnosis of primary septic arthritis caused by Neisseria meningitidis, serogroup X. Further evaluation revealed a reactive HIV antibody test with enzyme- linked immunoassay (ELISA) confirmed by western blot. His CD4 count was 36 cells/mm3 and viral load was >500,000 copies/mL. We present a case of primary meningococcal arthritis caused by N meningitidis serogroup X as the initial presentation of a patient with previously undiagnosed HIV.

Differences in hospital glycemic control and insulin requirements in patients recovering from critical illness and those without prior critical illness

Introduction Hospital patients recovering from critical illness on general floors often receive insulin therapy based on protocols designed for patients admitted directly to general floors. The objective of this study is to compare glycemic control and insulin dosing in patients recovering from critical illness and those without prior critical illness. Methods Medical record review of blood glucose measurements and insulin dosing in 25 patients under general ward care while transitioning from the intensive care unit (transition group) and 25 patients admitted directly to the floor (direct floor group). Results Average blood glucose did not differ significantly between groups (transition group 9.49 mmol/L, direct floor group 9.6 mmol/L; P = 0.83). Significant differences in insulin requirements were observed between groups with average daily doses of 55.9 units in patients transitioning from the intensive care unit (ICU) versus 25.6 units in the direct floor group (P = 0.004). Conclusions Patients recovering from critical illness required significantly larger doses of insulin than those patients admitted directly to the floor. Managing insulin therapy in patients transitioning from the ICU may require greater insulin doses.

Review of Tigecycline: Focus on Clinical Utilization

This paper reviews the antimicrobial profile and available clinical data for the first member of the glycylcycline class, tigecycline. Emerging multi-drug resistance among gram-positive and gram-negative pathogens continues to limit the antibiotic armamentarium. Tigecycline, a derivative of minocycline, may provide a therapeutic option in select patients, given its broad spectrum of activity, including multi-drug resistant (MDR) strains. A search of Medline and EmBase of articles through April 2010 and references of select citations was conducted. Several randomized controlled studies have resulted in the approval of tigecycline in the treatment of skin and skin structure infections, complicated intra-abdominal infections, and community acquired pneumonia. Several other studies and single-center observations have demonstrated select efficacy in specific populations including ventilator-associated pneumonia, bacteremia, and other infections secondary to MDR pathogens. These data, along with pharmacokinetic and safety issues, are reviewed to offer insight into appropriate patient selection for tigecycline therapy.