Linda M. Spooner

Survey of physician knowledge regarding antiretroviral medications in hospitalized HIV-infected patients

BackgroundAntiretroviral prescribing errors are common among hospitalized patients. Inadequate medical knowledge is likely one of the factors leading to these errors. Our objective was to determine the proportion of hospital physicians with knowledge gaps about prescribing antiretroviral medications for hospitalized HIV-infected patients and to correlate knowledge with length and type of medical training and experience.MethodsWe conducted an electronic survey comprising of ten clinical scenarios based on antiretroviral-prescribing errors seen at two community teaching hospitals. It also contained demographic questions regarding length and type of medical training and antiretroviral prescribing experience. Three hundred and forty three physicians at both hospitals were asked to anonymously complete the survey between February 2007 and April 2007.ResultsOne hundred and fifty-seven physicians (46%) completed at least one question. The mean percentage of correct responses was 33% for resident physicians, 37% for attending physicians, and 93% for Infectious Diseases or HIV (ID/HIV) specialist physicians. Higher scores were independently associated with ID/HIV specialty, number of outpatients seen per month and physician reported comfort level in managing HIV patients (P <.001).ConclusionNon-ID/HIV physicians had uniformly poor knowledge of common antiretroviral medication regimens. Involvement of ID/HIV specialists in the prescribing of antiretrovirals in hospitalized patients might mitigate prescribing errors stemming from knowledge deficits.

Tigecycline for the Treatment of Severe Clostridium difficile Infection

Objective: To evaluate the evidence for the use of tigecycline in the treatment of Clostridium difficile infection (CDI). Data Sources: Searches were performed (2004 to June 2011), using the EMBASE and MEDLINE databases, with the terms tigecycline, Tygacil, Clostridium difficile, C. difficile, Clostridium difficile infection, and CDI. Study Selection: Six case reports that described the use of tigecycline for treatment of CDI were included for review. No clinical trials were identified. Data Synthesis: In all case reports except 1, tigecycline (alone or in combination with other CDI therapies) was used for the treatment of CDI that was refractory to metronidazole and/or vancomycin. In 6 of the cases, treatment success was reported following initiation of tigecycline therapy; 1 patient died following a complicated hospitalization. The treatment duration with tigecycline was 2-4 weeks. In the cases with successful outcomes, symptoms began to improve within 1 week. None of these patients experienced recurrence during follow-up of various lengths. In vitro studies demonstrated a 90% minimum inhibitory concentration range for tigecycline of 0.016-0.25 mg/L for all C. difficile isolates. Tgecycline exhibited good fecal penetration because of primary biliary excretion of unchanged drug. Up to 59% of the dose is recovered in feces following administration over 4 days in healthy volunteers. Conclusions: Case reports have suggested that tigecycline may be successful for treatment of severe or severe complicated CDI, when prior therapy has failed. Data demonstrating tigecycline use as initial therapy for CDI are limited; therefore, this option should be reserved for patients in whom other therapeutic options, including metronidazole and vancomycin, have failed. A randomized controlled trial is needed to assess the safety and efficacy of tigecycline in this patient population and better define the drugs role in the treatment of CDI.

Fidaxomicin: A Macrocyclic Antibiotic for the Management of Clostridium difficile Infection

Objective: To evaluate the efficacy and safety of fidaxomicin for the treatment of Clostridium difficile infection. Data Sources: Literature retrieval was accessed through MEDLINE (1966–January 2010) and International Pharmaceutical Abstracts (1970–January 2010) using the terms OPT-80, difimicin, PAR-101, fidaxomicin, tiacumicin, lipiarmycin, and Clostridium difficile. In addition, reference citations from publications identified were reviewed. Study Selection and Data Extraction: All articles published in English that were identified from the data sources were evaluated and pertinent information was included. Data Synthesis: Fidaxomicin is an 18-membered macrocyclic antibiotic with activity against gram-positive aerobes and anaerobes, including C. difficile. Microbiologic studies comparing in vitro activity of fidaxomicin with that of metronidazole and vancomycin have shown good activity against all strains of C. difficile tested; however, minimum inhibitory concentrations were consistently lower for fidaxomicin. Studies showed that fidaxomicin lacks activity against gram-negative pathogens, thereby preserving normal gastrointestinal flora. Small pharmacokinetic trials have shown that fidaxomicin administration leads to low concentrations in plasma, high concentrations in stool, and a postantibiotic effect of greater than 24 hours, all of which are potentially advantageous characteristics for treating C. difficile infection. Data from 2 Phase 2A trials and 1 Phase 3 (multicenter, randomized, double-blind) trial suggest that fidaxomicin is effective for the treatment of mild-to-moderate C. difficile infection at a dose of 200 mg orally every 12 hours. Limited early results from the Phase 3 trial showed favorable outcomes for fidaxomicin when compared to oral vancomycin. Overall, fidaxomicin has been well tolerated to date. Conclusions: The activity of fidaxomicin and limited clinical data suggest that it may have a future role in the treatment of mild-to-moderate C. difficile infection. The complete pharmacokinetic/pharmacodynamic profile, safety, and place in therapy have yet to be determined as trials comparing this agent to vancomycin are forthcoming.

Boceprevir: A Protease Inhibitor for the Treatment of Chronic Hepatitis C

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of boceprevir, a novel oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor for the treatment of chronic HCV infection, specifically, genotype 1. Data Sources: A literature search was conducted through MEDLINE and EMBASE (1966-May 2011) using the terms boceprevir and SCH 503034. Data from the package insert, abstracts obtained from conferences, and unpublished Phase 2-3 clinical trials, obtained through clinicaltrials.gov, were also reviewed. Study Selection And Data Extraction: All English-language articles identified from the data sources were evaluated. References from selected articles were used to identify other pertinent citations. Article selection focused on pharmacology, clinical trials, safety analyses, and resistance. Preference was given to human data. Data Synthesis: Boceprevir is an oral protease inhibitor that binds to the NS3 protein of HCV, ultimately inhibiting viral intracellular replication. Boceprevir displays linear pharmacokinetics and is rapidly absorbed upon oral administration. In clinical studies of treatment-naïve and treatment-experienced patients, boceprevir, in combination with standard of care (pegylated interferon [Peg-IFN]-α-2b with or without ribavirin) achieved greater sustained viral response (SVR) rates compared to standard of care. Safety analyses showed an increased incidence of adverse effects when boceprevir was used with Peg-IFN-α-2b and ribavirin. The most common adverse events reported include fatigue, headache, nausea, dysguesia, and anemia; the incidence of the latter 2 adverse effects may be increased it boceprevir is added to standard therapy. Additional Phase 2 and 3 studies are currently enrolling participants. Conclusions: Boceprevir should be used in combination with Peg-IFN-α-2b and ribavirin in the treatment of chronic HCV genotype 1 infection. The improved response rates achieved with that combination will make boceprevir a viable option compared with other developing and approved NS3 protease inhibitors for treatment-naïve and treatment-experienced nonresponders/relapsers. Additional data are needed to clarify the potential for resistance and drug interactions.

Adverse-drug-reaction reporting by pharmacy students in a teaching hospital.

PURPOSE Adverse-drug-reaction (ADR) reporting by pharmacy students in a teaching hospital is described. SUMMARY Faculty and pharmacy staff collaborated to modify the existing data collection form for suspected ADRs. During the orientation session for each new rotation, pharmacy students received an overview of ADRs, ADR trigger medications, and the hospitals ADR reporting program. Pharmacy students collected ADR data by prospectively and retrospectively reviewing inpatient charts for suspected ADRs that were identified through various means. The students were responsible for completely and accurately documenting all aspects of the suspected ADRs. At least once a week, patient charts were requested to aid students in their investigation of suspected ADRs. Data from patient cases involving allergy-related ADRs were confirmed and updated in the hospitals computer system. All documented ADRs were entered into a spreadsheet for the purpose of generating quarterly reports. Report data were analyzed by faculty and students to identify hospitalwide trends in an effort to develop new ADR prevention strategies. Pharmacy student involvement with the ADR process began in January 2006. A total of 310 ADRs were documented for 2006, compared with 42 for 2005, when pharmacy students were not involved in data collection. ADR reports also led to allergy updates for 42 patients. With students collecting and analyzing ADR data, the hospital was able to recognize those medications that commonly caused ADRs and track hospitalwide trends in an effort to target new initiatives to prevent their occurrence. CONCLUSION Pharmacy student participation in the ADR reporting program led to a significant increase in the number of ADRs documented.

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet for HIV-1 Infection Treatment

Objective: To review the clinical trials, pharmacologic characteristics, safety, and efficacy of the elvitegravir/cobicistat/emtricitabine/tenofovir single tablet formulation (Stribild). Data Sources: Literature searches were performed in MEDLINE (1948-September 2012) and PubMed (1966-September 2012) using the search terms GS-9137, elvitegravir, GS 9350, cobicistat, quad pill, Stribild, and integrase inhibitors. Abstracts from HIV/AIDS conferences were reviewed. Study Selection and Data Extraction: Phase 3 studies evaluating the safety and efficacy of Stribild were preferentially evaluated, as well as relevant references from the published studies. Data Synthesis: Stribild contains complete antiretroviral therapy for HIV-1 infection in a single tablet. It is the first once-daily therapy option available with an integrase inhibitor and a novel pharmacokinetic boosting agent. Stribild has shown non-inferiority in viral load suppression at 48 weeks when compared with dual nucleoside/nucleotide reverse transcriptase inhibitor and either a ritonavir-boosted protease inhibitor or nonnucleoside reverse transcriptase inhibitor regimen. Stribild was well tolerated, but some patients experienced increases in serum creatinine early in treatment that stabilized over time. Conclusions: Stribild is the first single-tablet regimen for HIV-1 infection treatment containing an integrase inhibitor. It is expected to have a prominent place in the formularies of health plans providing care for individuals with HIV-1 infection.

Vigabatrin for Infantile Spasms

Infantile spasms describe a pediatric epilepsy syndrome characterized by frequent clusters of brief symmetric muscle contractions; the condition is often associated with developmental delay. When infantile spasms are accompanied by hypsarrhythmia on electroencephalogram, the condition is labeled West syndrome. The mainstay of treatment for infantile spasms is adrenocorticotropic hormone; however, vigabatrin, a vinyl derivative of 7‐aminobutyric acid, has been used for the treatment of infantile spasms in Europe since 1989. In 2009, vigabatrin was approved by the United States Food and Drug Adminstration (FDA) for use as monotherapy in the treatment of infantile spasms in patients aged 1 month‐2 years when the benefits of treatment outweigh the risks. Results from numerous trials examining the role of vigabatrin in infantile spasms have been published; many of these trials were small, open‐label, or noncontrolled. Although clinical trials have provided some insight into the utility of vigabatrin for the treatment of infantile spasms, these studies have notable limitations. In addition, vigabatrin is associated with a black‐box warning that describes the potential for permanent bilateral concentric visual field defects. Currently, vigabatrin is available through a manufacturer‐sponsored program in accordance with its FDA‐approved Risk Evaluation and Mitigation Strategy. Although several guidelines recommend vigabatrin as a first‐line therapy for infantile spasms, specifically infantile spasms related to tuberous sclerosis, it is still unclear whether vigabatrin should supersede hormone therapy as first‐line therapy. Further research comparing the two therapies is needed.

Excretion of Antimicrobials Used to Treat Methicillin‐Resistant Staphylococcus aureus Infections During Lactation: Safety in Breastfeeding Infants

Community‐acquired strains of methicillin‐resistant Staphylococcus aureus(MRSA) have become a common cause of skin and soft tissue infections in the United States. These infections sometimes require treatment with antibiotics, and with the increasing resistance of pathogens to these agents, choosing the appropriate drug can be difficult. In lactating women who develop these infections, selecting an antibiotic is even more challenging, as clinicians need to be aware of risks to the infant from the drug excreted during lactation. To our knowledge, no review has addressed the safety of antibiotics in breastfeeding infants when the drugs are used to treat maternal skin and soft tissue infections from MRSA. Thus, we performed a literature search of the PubMed‐MEDLlNE and EMBASE databases (1974‐March 2009), reviewed reference citations from identified publications, researched antibiotic prescribing information, and corresponded with drug manufacturers. Case reports, case series, and both in vivo and in vitro clinical trials were evaluated for the following antibiotics: clindamycin, daptomycin, linezolid, quinupristin‐dalfopristin, rifampin, tetracycline, doxycycline, minocycline, tigecycline, trimethoprim‐sulfamethoxazole, and vancomycin. lnformation for the newer antibiotics (linezolid, quinupristin‐dalfopristin, tigecycline, and daptomycin) was limited. Despite heterogeneity in the data for the older antibiotics (clindamycin, rifampin, tetracyclines, trimethoprim‐sulfamethoxazole, and vancomycin), all appear to be relatively safe in the minimal quantities nursing infants ingest through breast milk. Although the risk to infants seems to be relatively low for most of the agents we explored, the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection.

Paradoxical Bronchoconstriction with Albuterol Administered by Metered-Dose Inhaler and Nebulizer Solution

OBJECTIVE To report a case of a patient who experienced bronchoconstriction following both a single dose of albuterol via metered-dose inhaler and a subsequent rechallenge with nebulized albuterol and review previously published case reports of albuterol-induced paradoxical bronchoconstriction. CASE SUMMARY A 92-year-old white man with a history of chronic obstructive pulmonary disease was prescribed an albuterol inhaler for treatment of cold symptoms. Within 30 minutes of his first inhalation, he became short of breath and had difficulty speaking. During emergency department examination for the initial event, the bronchospasm improved with administration of oxygen 15 L/min via a non-rebreather mask. Two hours later, the patient received albuterol via nebulizer and experienced stridor, shortness of breath, and severe bronchospasm. He was admitted, treated with methylprednisolone, and discharged the following day. DISCUSSION Paradoxical bronchoconstriction is a rare complication of bronchodilator therapy. Although theories have been proposed about components of albuterol solutions and preservatives as causative agents, the true mechanism of the phenomenon remains unknown. Several previous case reports described bronchospasm with albuterol given via tablet, inhaler, and nebulizer. In 2 of these cases, symptoms recurred upon rechallenge; however, none of these cases demonstrates rechallenge using albuterol as both the index and challenge agent. In our patient, paradoxical bronchoconstriction was considered to be probable according to the Naranjo probability scale. CONCLUSIONS β2-Agonists are generally well-tolerated medications. However, clinicians should remain vigilant in their monitoring of adverse effects so they will be able to provide immediate care and minimize the chance of an unfavorable outcome.

Daptomycin-Induced Acute Renal and Hepatic Toxicity Without Rhabdomyolysis

Objective: To report a case of a patient who experienced acute renal and hepatic toxicity following administration of daptomycin and review previously published case reports of renal and hepatic dysfunction with daptomycin. Case Summary: A 35-year-old man receiving daptomycin 4 mg/kg (275 mg) intravenously once daily (started 5 wk prior to presentation for presumed osteomyelitis) presented to the emergency department with elevations in serum creatinine and hepatic transaminase levels. He did not experience creatine kinase (CK) elevation or rhabdomyolysis. Following discontinuation of daptomycin, his renal and hepatic function improved. Discussion: To our knowledge, this is the first case of daptomycin-induced hepatotoxicity with acute renal failure in the absence of rhabdomyolysis and CK abnormalities. Previously published case reports described patients with a variety of elevations in liver function tests, serum creatinine, and CK with daptomycin. In our patient, the acute renal and hepatic toxicity was probable according to the Naranjo probability scale. Conclusions: Although daptomycin is a well-tolerated antibacterial agent, clinicians should consider periodic monitoring of liver function and renal function tests to identify potential adverse effects.