Martha G. Blackford

Emergence of Linezolid-Resistant Staphylococcus aureus after Prolonged Treatment of Cystic Fibrosis Patients in Cleveland, Ohio

ABSTRACT Linezolid (LZD)-resistant Staphylococcus aureus (LRSA) isolates were monitored from 2000 to 2009 in Cleveland, OH. LRSA first emerged in 2004 only in cystic fibrosis (CF) patients, with 11 LRSA-infected CF patients being identified by 2009. LRSA was isolated from 8 of 77 CF patients with S. aureus respiratory tract infection treated with LZD from 2000 to 2006. Analysis of clinical data showed that the 8 CF patients with LRSA received more LZD courses (18.8 versus 5.9; P = 0.001) for a longer duration (546.5 versus 211.9 days; P < 0.001) and had extended periods of exposure to LZD (83.1 versus 30.1 days/year; P < 0.001) than the 69 with LZD-susceptible isolates. Five LRSA isolates included in the clinical analysis (2000 to 2006) and three collected in 2009 were available for molecular studies. Genotyping by repetitive extrapalindromic PCR and pulsed-field gel electrophoresis revealed that seven of these eight LRSA strains from unique patients were genetically similar. By multilocus sequence typing, all LRSA isolates were included in clonal complex 5 (seven of sequence type 5 [ST5] and one of ST1788, a new single-locus variant of ST5). However, seven different variants were identified by spa typing. According to the Escherichia coli numbering system, seven LRSA isolates contained a G2576T mutation (G2603T, S. aureus numbering) in one to four of the five copies of domain V of the 23S rRNA genes. One strain also contained a mutation (C2461T, E. coli numbering) not previously reported. Two strains, including one without domain V mutations, possessed single amino acid substitutions (Gly152Asp or Gly139Arg) in the ribosomal protein L3 of the peptidyltransferase center, substitutions not previously reported in clinical isolates. Emergence of LRSA is a serious concern for CF patients who undergo prolonged courses of LZD therapy.

Assessment of the Clinical Use of Intravenous and Oral N-Acetylcysteine in the Treatment of Acute Acetaminophen Poisoning in Children: A Retrospective Review

BACKGROUND N-acetylcysteine (NAC) is the most effective therapy for acetaminophen (APAP) toxicity and is currently available for oral and intravenous (IV) administration. Although both routes are effective, use of the IV formulation has been increasing since becoming available in the United States in 2004, raising questions about cost/benefit comparisons between the 2 formulations. Decreased length of treatment and hospital stay have been used to justify the use of IV NAC; however, some patients may receive extended therapy of either NAC regimen. OBJECTIVE This retrospective review assessed the clinical use of oral and IV NAC in pediatric patients with APAP intoxication from June 1, 2004 through May 31, 2008. METHODS Electronic medical charts for patients aged ≤21 years were identified with International Classification of Diseases, Ninth Revision (ICD-9) codes for APAP overdose. Descriptive statistics were used to describe the overall patient population and route of NAC administration. The primary outcome variable was the length of treatment with IV and oral NAC therapy. RESULTS A total of 62 charts for patients with APAP toxicity were reviewed; 37 patients (60%) received IV NAC and 25 patients (40%) received oral NAC. The average lengths of treatment and stay for IV dosing were 23.5 hours (range, 17.6-54.9 hours) and 1.6 days (range, 1-3 days), respectively; those for oral dosing were 69.5 hours (range, 33-133 hours) and 1.95 days (range, 1-5 days), respectively. Of 16 patients who received oral NAC and were admitted for <3 days, 14 were transferred to an inpatient psychiatric unit and completed the 72-hour therapy. A total of 3 patients received extended NAC dosing-2 with IV dosing and 1 with oral dosing. CONCLUSIONS Based on our review, the majority of patients received recommended dosing of NAC therapy; however, 3 patients received extended NAC therapy. Patient-specific factors should be considered when assessing whether NAC therapy should be extended and if one route of administration may be preferred. ClinicalTrials.gov identifier: NCT00725179.

Fomepizole : A Critical Assessment of Current Dosing Recommendations

Fomepizole, 4‐methylpyrazole (4‐MP), is a competitive antagonist of alcohol dehydrogenase with a binding affinity >8000 times that of ethanol. The drug is currently labeled by the United States Food and Drug Administration for the treatment of adult patients with known or suspected ethylene glycol or methanol poisoning. Fomepizoles wide therapeutic dose range and safety profile confer several advantages over standard ethanol therapy for the treatment of toxic alcohol exposures, including the lack of ethanol‐associated side effects. Published data and data obtained from the drugs manufacturer implies that the dose escalation after 48 hours is to compensate for fomepizole‐induced increased body clearance resulting from autoinduction of the cytochrome P450 (CYP) drug metabolizing enzyme CYP2E1. However, we were unable to identify any evidence of fomepizoles metabolism occurring via CYP2E1 in humans while the data most frequently cited as evidence for induction do not appear to support this claim. Based on this data along with the apparent zero‐order kinetics, the current dose increase recommendations may be unnecessary and considering the safety margin described for fomepizole, an extremely conservative constant higher dose administered every 12 hours would appear to assure efficacy and tolerability. Despite the evidence, dose changes should only be implemented after careful clinical trials.

Longitudinal assessment of bone growth and development in a facility-based population of young adults with cerebral palsy

Osteoporosis is a significant clinical problem in persons with moderate to severe cerebral palsy (CP), causing fractures with minimal trauma. Over the past decade, most studies examining osteoporosis and CP have been cross‐sectional in nature, focused exclusively on children and adolescents and only involving one evaluation of bone mineral density (BMD). The purpose of this study was to assess BMD in a group including adults with CP, and changes in each individuals BMD over a 5‐ to 6‐year period.

Valproic Acid and topiramate induced hyperammonemic encephalopathy in a patient with normal serum carnitine.

A 17-year-old female developed hyperammonemic encephalopathy 2 weeks after valproic acid (VPA), 500 mg twice a day, was added to her regimen of topiramate (TPM), 200 mg twice a day. She presented to the emergency department (ED) with altered mental status, hypotension, bradycardia, and lethargy. Laboratory analysis showed mild non-anion gap hyperchloremic acidosis, serum VPA concentration of 86 mg/L, and urine drug screen result that was positive for marijuana. She was admitted to the pediatric intensive care unit for persistent symptoms, prolonged QTc, and medical history. Blood ammonia concentrations were obtained because of her persistent altered mental status, initially 94 μmol/L and a peak of 252 μmol/L. A serum carnitine profile was obtained at the time of hyperammonemia and was found to be normal (results were available postdischarge). VPA and TPM were discontinued on day 1 and day 2, respectively, as the patients blood ammonia concentration remained elevated. On day 3, her mental status had returned to baseline, and blood ammonia concentrations trended downward; by day 4 her blood ammonia concentration was 23 μmol/L. VPA has been associated with numerous side effects including hyperammonemia and encephalopathy. Recently, drug interactions with TPM and VPA have been reported; however, serum carnitine concentrations have not been available. We discuss the possible mechanisms that VPA and TPM may affect serum ammonia and carnitine concentrations and the use of levocarnitine for patients or treating toxicity.

Nausea, Vomiting, and Weight Loss in a Young Adult Patient With a History of a Gunshot Wound.

Abstract Assessing victims of gunshot wounds with retained bullets/bullet fragments for lead toxicity is not always considered until the patient develops signs and symptoms of toxicity. We discuss the case of a 19-year-old young man who received a diagnosis of chronic lead toxicity (serum lead concentration 51 &mgr;g/dL) 5 weeks after a hunting accident. Extensive wound debridement occurred following the accident; however, lead toxicity was not diagnosed until after his fourth emergency department visit. Oral chelation therapy was required for the management of his lead toxicity.

The Case of the Previously Shaky, Unimmunized, Itchy Infant With Rash and Pancytopenia:

A 10-month-old, unimmunized male with history of complex febrile seizure presented to the pediatric emergency department for fever and progressing rash. His mother described an erythematous, urticarial rash starting on his chest 4 days prior to presentation and spreading to involve his back, face, and extremities. At onset of rash, he developed persistent fevers to a maximum of 40.5°C, cough, and increasing fussiness. Parents denied recent travel, known sick contacts, daycare attendance, neck stiffness, eye redness, vomiting, diarrhea, rhinorrhea, or obvious oral lesions. Fifteen days prior to presentation, he was evaluated for complex febrile seizure. He presented to the emergency department with a generalized tonic-clonic seizure of 30-minute duration associated with a fever of 39.1°C. He received rectal lorazepam at presentation and a loading dose of intravenous phenobarbital with resolution of activity. Computed tomography scan of the head was normal. Lumbar puncture was declined by parents, but urine and blood cultures were negative. He was continued on maintenance dosing of phenobarbital during his hospitalization. He was discharged home with the presumptive diagnosis of complex febrile seizure secondary to viral illness and with instructions to continue phenobarbital at home.

Assessment of serum creatine kinase among adolescent patients following jimsonweed (Datura stramonium) and moonflower (Datura inoxia) ingestions: a review of 11 cases.

Introduction. Datura stramonium (DS) (jimsonweed) is well known for its abuse potential for hallucinogenic effects and Datura inoxia (DI) (moonflower) has been abused for similar effects. To our knowledge, only one case report describes rhabdomyolysis in association with DS or DI ingestion. Case identification and details. Patient hospital charts were retrospectively screened from January 1, 2002 to December 31, 2007 to identify patients with qualifying ICD-9 codes for toxic plant ingestions. We report on 11 patient cases of DS/DI ingestions in which serum creatine kinase (CK) concentrations were monitored. These admissions occurred at our hospital over a 6-year period. Serum CK concentrations ranged from 72 to 70,230 U/L. Only three patients had serum CK concentrations greater than 1,000 U/L. One patient with a peak concentration of 70,230 U/L and a positive myoglobinuria was diagnosed with rhabdomyolysis. Discussion. Based on our review of the literature and these cases, it is possible that serum CK concentrations may be elevated more frequently than previously realized. The clinical significance of this abnormal laboratory value is uncertain with the majority of patients remaining asymptomatic without any clinical evidence of rhabdomyolysis.