OBJECTIVE: To report a case of Eikenella corrodens and Actinomyces odontolyticus foot abscess secondary to a toothpick puncture in a penicillin-allergic patient that was successfully treated with a long-term course of doxycycline.
CASE SUMMARY: A 39-year-old woman with diabetes mellitus type 2 and hyperlipidemia presented with difficulty ambulating as well as pain and swelling of her right foot. Prior to presentation, she sustained a toothpick puncture to her right foot; she removed the toothpick intact and did not know whether it had been used. Due to a penicillin allergy, she began treatment with levofloxacin, which was changed to clindamycin one day later. The patient was diagnosed with right Achilles tendonitis/cellulitis and was discharged on a one-week course of clindamycin. Twenty-five days later she was readmitted, complaining of pain and swelling in the same area, which this time presented as an abscess. Upon this admission, vancomycin and levofloxacin were initiated and incision and drainage (I & D) was performed. Cultures and sensitivities from I & D were significant for E. corrodens and A. odontolyticus, and treatment was changed to intravenous doxycycline 100 mg every 12 hours for 10 weeks. Oral doxycycline 100 mg every 12 hours was then used for 3 months, and treatment was successful.
DISCUSSION: E. corrodens and A. odontolyticus are 2 slow-growing organisms that are part of the normal oropharyngeal flora. Extraoral infections due to either of these organisms may be difficult to treat and might need lengthier treatments than are necessary for most infections. First-line treatment for such infections is penicillins and cephalosporins; however, in a patient with penicillin allergy, treatment options become limited, as there is potential cross-reactivity with other agents.
CONCLUSIONS: Patients with infections secondary to E. corrodens and/or A. odontolyticus in whom penicillin allergy is a concern can be treated effectively with doxycycline.
]]>OBJECTIVE: To describe emerging therapies, such as levofloxacin, moxifloxacin, rifabutin, rifaximin, tinidazole, doxycycline, minocycline, lactoferrin, and plaunotol for the eradication of Helicobacter pylori infection.
DATA SOURCES: Relevant information was identified through a search of MEDLINE (1966-July 2008), PubMed (1955-July 2008), American Search Premier (1975-July 2008), International Pharmaceutical Abstracts (1960-2008), Science Citation Index Expanded (1996-2008), Cochrane Databases (publications archived until July 2008), and various tertiary sources using the terms Helicobacter pylori, fluoroquinolones, levofloxacin, moxifloxacin, rifabutin, rifaximin, lactoferrin, plaunotol, tinidazole, doxycycline, minocycline, faropenem, new treatments, refractory, and salvage alone or in combination.
STUDY SELECTION AND DATA EXTRACTION: Relevant information was identified and selected based on clinical relevance and value of information. In vitro and in vivo data were included if available.
DATA SYNTHESIS: Data exist supporting the use of levofloxacin or rifabutin as salvage therapies for H. pylori infection. Levofloxacin triple therapy has been recommended in the current treatment guideline, but more data are needed, especially from studies conducted in the US. A rifabutin-based regimen is better tolerated than conventional quadruple therapy, but its use is limited due to cost, hematologic adverse effects, drug interactions, and predicted development of resistance. Tinidazole appears to be an option, particularly as sequential therapy when combined with other agents; however, its use is limited by the high prevalence of nitroimidazole-resistant H. pylori strains in the US. Moxifloxacin data are limited. Data supporting the use of rifaximin, doxycycline, and minocycline are lacking or do not show benefit of these drugs over standard treatments.
CONCLUSIONS: H. pylori infection remains one of the most significant infections worldwide, and treatment failure rate with the current standard therapy continues to rise. Other treatment options should be explored to meet the emerging challenge.
]]>BACKGROUND: The AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) trial demonstrated that rate control and rhythm control strategies result in similar survival and quality of life for patients with atrial fibrillation (AF). Because of superior safety and lower cost, rate control is now the recommended strategy for the management of most elderly, high-risk AF patients.
OBJECTIVE: To determine the extent to which the AFFIRM trial results have been adopted into actual practice.
METHODS: We conducted a time-series analysis of 3 population-based cohorts of patients with AF who were 66 years of age or older in Pennsylvania and Ontario. We stratified patients in Ontario by socioeconomic status (SES) and examined changes in quarterly prescription rates for rate control and rhythm controlling medications as well as cardioversion procedures before and after publication of the AFFIRM trial.
RESULTS: The publication of the AFFIRM trial resulted in statistically significant reductions in the use of rhythm controlling medications in all 3 cohorts (p < 0.01). The magnitude of these changes in the non-low SES Canadian cohort was approximately 1% per quarter and was greater than the magnitude observed in the other cohorts (p < 0.001). The use of cardioversion procedures also decreased in all study regions (p < 0.01). In contrast, AFFIRM publication was also associated with a small increase in the use of rate controlling medications in Canada (p < 0.01) but not in the US (p = 0.23).
CONCLUSIONS: Publication of the AFFIRM trial resulted in small but statistically significant changes in the care of patients with AF.
]]>BACKGROUND: Attainment of blood pressure (BP) goals in patients with diabetes is critical both to reduce the risk of cardiovascular events and to delay the progression of renal disease. While therapeutic guidelines advise initial therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, monotherapy with these agents may not be sufficient to attain target BP.
OBJECTIVE: The ADHT (Amlodipine Diabetic Hypertension Efficacy Response Evaluation Trial) evaluated the efficacy and safety of adding amlodipine to the treatment regimen of patients with hypertension and diabetes who were already receiving either quinapril or losartan as monotherapy
METHODS: ADHT was a double-blind, double-dummy, 22-week trial conducted in the US. After a washout period of 7-13 days, patients (aged 30-75 y) with hypertension and diabetes were randomized to receive quinapril 20 mg/day plus placebo or losartan 50 mg/day plus placebo for 4 weeks, titrated to 40 mg or 100 mg (if required), respectively, for an additional 4 weeks to achieve their BP goals (<130/80 mm Hg). At week 8, either amlodipine 5 mg/day or placebo was added for an additional 12 weeks, with titration to 10 mg at week 14 if the BP goal was not achieved.
RESULTS: Efficacy of add-on therapy was evaluated in 411 patients (amlodipine 211, placebo 200). BP goal was reached by 27.5% of patients when amlodipine was added to quinapril or losartan monotherapy, compared with 12.5% when placebo was added (OR 2.73; 95% CI 1.61 to 4.64; p < 0.001). When added to quinapril or losartan monotherapy, amlodipine reduced BP by 8.1/5.4 mmHg, compared with a 1.6/0.7 mm Hg decrease with add-on placebo (p < 0.001). Amlodipine, quinapril, and losartan were well tolerated.
CONCLUSIONS: Amlodipine is safe and effective when added to quinapril or losartan monotherapy to help lower BP toward therapeutic targets in patients with hypertension and diabetes.
]]>OBJECTIVE: To describe the management of a pharmacokinetic interaction between azole antifungals (fluconazole and voriconazole) and everolimus in a patient who underwent an orthotopic liver transplant.
CASE SUMMARY: A 65-year-old male who received an orthotopic liver transplant experienced an iatrogenic retroperitoneal duodenal perforation on postoperative day 55. His condition was subsequently complicated by severe sepsis and acute renal failure. Intravenous fluconazole 400 mg, followed by 100 mg every 24 hours according to impaired renal function, was immediately started; to avoid further nephrotoxicity, immunosuppressant therapy was switched from cyclosporine plus mycophenolate mofetil to oral everolimus 0.75 mg every 12 hours. Satisfactory steady-state minimum concentration (Cmin) of everolimus was achieved (~5 ng/mL). On day 72 posttransplant, because of invasive aspergillosis, antifungal therapy was switched to intravenous voriconazole 400 mg every 12 hours on the first day, followed by 200 mg every 12 hours; to prevent drug toxicity, the everolimus dosage was promptly lowered to 0.25 mg every 24 hours. At that time, the everolimus Cmin averaged approximately 3 ng/mL. The concentration/dose ratio of everolimus (ie, Cmin reached at steady-state for each milligram per kilogram of drug administered) was markedly lower during fluconazole versus voriconazole cotreatment (mean ± SD, 3.49 ± 0.29 vs 11.05 ± 0.81 ng/mL per mg/kg/daily; p < 0.001). Despite intensive care, the patient's condition continued to deteriorate and he died on day 84 posttransplant.
DISCUSSION: Both azole antifungals were considered probable causative agents of an interaction with everolimus according to the Drug Interaction Probability Scale. The interaction is due to the inhibition of CYP3A4-mediated everolimus clearance. Of note, prompt reduction of the everolimus dosage since the first azole coadministration, coupled with intensive therapeutic drug monitoring, represented a useful strategy to prevent drug overexposure.
CONCLUSIONS: Our data suggest that during everolimusazole cotreatment, a dose reduction of everolimus is needed to avoid overexposure. According to the different inhibitory potency of CYP3A4 activity, the reduction should be lower during fluconazole than during voriconazole cotreatment.
]]>OBJECTIVE: To describe a case of severe sepsis, cavitary pneumonia, and pyomyositis caused by Arcanobacterium haemolyticum.
CASE SUMMARY: An 18-year-old male with a medical history significant for mild asthma presented to the emergency department complaining of a 7-day history of fever, diffuse myalgias, nausea, vomiting, diarrhea, and pain in his right upper quadrant, right shoulder, and left thigh. Cultures of blood, bronchoalveolar fluid, and surface and surgical swabs from the patient's left lower extremity grew A. haemolyticum. The patient was successfully treated with intravenous penicillin G 4 million units every 4 hours and azithromycin 500 mg once daily for 14 days. Within 36 hours after initiation of focused therapy, he became afebrile, pain decreased, and pulmonary symptoms abated. Oral azithromycin 500 mg/day for an additional 3 weeks was prescribed on discharge, and the patient showed no relapse at 2-month follow-up.
DISCUSSION: A. haemolyticum is a weakly acid-fast, branching gram-positive bacillus most commonly implicated in pharyngitis in healthy adolescents and skin and soft-tissue infections in older, immunocompromised patients. Systemic infections are rarely reported in the literature. This organism remains susceptible to most classes of antimicrobials, including penicillins, cephalosporins, carbapenems, macrolides, tetracyclines, clindamycin, and vancomycin. Routine resistance has been reported only with trimethoprim/sulfamethoxazole.
CONCLUSIONS: To our knowledge, there are no published case reports of severe sepsis caused by A. haemolyticum. While treatment options are numerous, we recommend the use of intravenous penicillin or a cephalosporin as first-line pharmacologic management of deep-seated infections caused by this rare organism.
]]>BACKGROUND: Drugs used in clinical trials supported by the pharmaceutical industry are supplied free of charge by the companies. However, maintenance of treatment with those drugs when the trials have finished can generate extra cost for patients who participated in the trials.
OBJECTIVE: To assess whether HIV-infected patients' participation in clinical trials results in drug cost savings or increases.
METHODS: An analysis of all antiretrovirals dispensed to HIV-infected outpatients prior to, during, and after their participation in clinical trials in a university hospital during a 2-year period was conducted. Only patients who completed the trial during the study period were included. The following outcomes were measured: (1) cost saved (difference between cost per day during the trial and cost per day before study entry), (2) cost generated (difference between cost per day at the end of the trial and cost per day before study entry), (3) balance between cost saved and cost generated, and (4) number of days that a patient received a drug once the trial was finished to generate cost, considering costs saved. All data were extracted from the hospital pharmacy database. A stratified analysis by type of clinical trial (ordinary or expanded use) was undertaken.
RESULTS: Data from 61 patients were analyzed. The cost of drug therapy during patient participation in a clinical trial was lower than the cost prior to inclusion. Therefore, mean drug savings of $10.38 (US) per patient day resulted (95% CI -5.9 to 14.84). The mean cost generated was $8.74 per patient day (95% CI 3.95 to 13.52).
CONCLUSIONS: A patient's participation in a clinical trial or expanded-access clinical trial generated extra cost once the trial had finished because the cost of drug therapy was higher at the end of the study. In our study, the daily drug costs saved during the trial were similar to the daily drug costs generated.
]]>OBJECTIVE: To report a case of alcohol withdrawal and delirium tremens successfully treated with adjunctive dexmedetomidine.
CASE SUMMARY: A 30-year-old man with a history of alcohol abuse was admitted to the general medical unit because of altered mental status and agitation. He was initially treated for alcohol withdrawal with benzodiazepines; his condition then deteriorated and he was transferred to the intensive care unit. Because of the patient's poor response to benzodiazepines (oxazepam and lorazepam, with midazolam the last one used), intravenous dexmedetomidine was started at an initial dose of 0.2 µg/kg/h and titrated to 0.7 µg/kg/h to the patient's comfort. Midazolam was subsequently tapered to discontinuation due to excessive sedation. In the intensive care unit, the patient's symptoms remained controlled with use of dexmedetomidine alone. He remained in the intensive care unit for 40 hours; dexmedetomidine was then tapered to discontinuation and the patient was transferred back to the general medical unit on oral oxazepam and thiamine, which had been started in the emergency department. He was discharged after 5 days.
DISCUSSION: A review of the PubMed database (1989-2007) failed to identify any other instances of dexmedetomidine having been used as the principal agent to treat alcohol withdrawal. The use of sedative to treat delirium tremens is well documented, with benzodiazepines being the agents of choice. The clinical utility of benzodiazepines is limited by their stimulation of the -aminobutyric acid receptors, an effect not shared by dexmedetomidine, a central 2-receptor agonist that induces a state of cooperative sedation and does not suppress respiratory drive.
CONCLUSIONS: In patients with delirium tremens, dexmedetomidine should be considered as an option for primary treatment. This case illustrates the need for further studies to investigate other potential uses for dexmedetomidine.
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