S. Scott Sutton

Azithromycin and Levofloxacin Use and Increased Risk of Cardiac Arrhythmia and Death

PURPOSE Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. We conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin. METHODS We studied a cohort of US veterans (mean age, 56.8 years) who received an exclusive outpatient dispensation of either amoxicillin (n = 979,380), azithromycin (n = 594,792), or levofloxacin (n = 201,798) at the Department of Veterans Affairs between September 1999 and April 2012. Azithromycin was dispensed mostly for 5 days, whereas amoxicillin and levofloxacin were dispensed mostly for at least 10 days. RESULTS During treatment days 1 to 5, patients receiving azithromycin had significantly increased risk of death (hazard ratio [HR] = 1.48; 95% CI, 1.05–2.09) and serious arrhythmia (HR = 1.77; 95% CI, 1.20–2.62) compared with patients receiving amoxicillin. On treatment days 6 to 10, risks were not statistically different. Compared with patients receiving amoxicillin, patients receiving levofloxacin for days 1 to 5 had a greater risk of death (HR = 2.49, 95% CI, 1.7–3.64) and serious cardiac arrhythmia (HR = 2.43, 95% CI, 1.56–3.79); this risk remained significantly different for days 6 to 10 for both death (HR = 1.95, 95% CI, 1.32–2.88) and arrhythmia (HR = 1.75; 95% CI, 1.09–2.82). CONCLUSIONS Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.

Use of alternative or adjuvant pharmacologic treatment strategies in the prevention and treatment of Clostridium difficile infection

Infection with Clostridium difficile is currently the leading cause of infectious diarrhea in hospitalized patients, and recent surveillance data indicate that C. difficile has surpassed methicillin-resistant Staphylococcus aureus as the number one cause of hospital-acquired infections in some areas of the USA. In addition, concern over C. difficile has increased over the past decade due to the appearance of new hypervirulent strains. Metronidazole and vancomycin have remained the treatments of choice for initial therapy of primary infection with C. difficile for the past 25 years, but the persistence of spores leads to a recurrence of infection in an estimated 20-25% of patients. Patients who have one recurrent episode have up to a 65% chance of having additional recurrence. While the judicious use of antimicrobials in accordance with antibiotic stewardship guidelines remains the most effective method for the control of C. difficile, the high recurrence rate, increasing incidence, and changing epidemiology of C. difficile has led to an increased interest in the study of alternative strategies for the prevention and treatment of C. difficile disease. These alternative strategies attempt to eliminate C. difficile spores, replenish the normal gut flora, reduce the C. difficile toxin load in the bowel, or bolster the patients own immune response to the C. difficile toxins. To evaluate the available evidence on these alternative strategies, we conducted a literature search of MEDLINE (1966-March 2011) and International Pharmaceutical Abstracts (1970-March 2011). Available citations from these articles were also utilized. The aim of this review is to summarize the available evidence for alternative treatment strategies for C. difficile disease and to make recommendations for their place in therapy.

Impact of Pill Burden on Adherence, Risk of Hospitalization, and Viral Suppression in Patients with HIV Infection and AIDS Receiving Antiretroviral Therapy.

To evaluate the impact of pill burden on outcomes in patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) receiving antiretroviral therapy (ART) as a single‐tablet regimen (STR) or multiple‐tablet regimen (MTR).

Cardiac risks associated with antibiotics: azithromycin and levofloxacin

Introduction: Azithromycin and levofloxacin have been shown to be efficacious in treating infections. The adverse drug events associated with azithromycin and levofloxacin were considered rare. However, the US FDA released warnings regarding the possible risk of QT prolongation with azithromycin and levofloxacin. Areas covered: Case reports/case series, observational studies and clinical trials assessing cardiovascular risks associated with azithromycin and levofloxacin were critically reviewed, including 15 case reports/series, 5 observational studies and 5 clinical trials that investigated the cardiac risks associated azithromycin and levofloxacin. Expert opinion: Results are discordant. Two retrospective studies utilizing large databases demonstrated an increased risk of cardiovascular death with azithromycin, when azithromycin was compared with amoxicillin. Two other retrospective studies found no difference in cardiovascular death associated with azithromycin and other antibiotics. For levofloxacin, the increased risk of cardiovascular death was only found in one retrospective study. Therefore, the risks and benefits of antibacterial therapies should be considered when making prescription decisions. This study should not preclude clinicians from avoiding azithromycin and levofloxacin. If a patient has an indication to receive an antibiotic and if azithromycin or levofloxacin is needed, it may be used, but the potential risks must be understood.

Odds of Viral Suppression by Single-Tablet Regimens, Multiple-Tablet Regimens, and Adherence Level in HIV/AIDS Patients Receiving Antiretroviral Therapy

To evaluate the odds of achieving viral suppression in human immunodeficiency virus (HIV) patients using antiretroviral therapy as a single‐tablet regimen (STR) or multiple‐tablet regimen (MTR).

Role of Raltegravir in HIV-1 Management:

Objective: To review the literature concerning the role of raltegravir in the treatment of HIV-1 in antiretroviral (ARV)-experienced and ARV-naïve patients. Data Sources: A PubMed search was conducted for published data through March 2012 using the search terms raltegravir, MK-0518, and integrase strand transfer inhibitor. An additional search of International Pharmaceutical Abstracts for unpublished data, including data from the Infectious Diseases Society of America, the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society, and the Interscience Conference on Antimicrobial Agents and Chemotherapy, was conducted using similar search terms. Study Selection and Data Extraction: In vitro and in vivo Phase 2, Phase 3, and postmarketing studies available in English, evaluating antiretroviral regimens that contain raltegravir for the treatment of HIV-1 infection in both ARV-naïve and ARV-experienced patients, were evaluated. Studies assessing raltegravir pharmacokinetics and pharmacodynamics were included for review. Data Synthesis: The nucteoside-based regimen of raltegravir with tenofovir/emtricitabine provides an effective first-line treatment option. However, nucleoside-sparing regimens appear unfavorable in ARV-naïve subjects and should be reserved for patients with limited treatment options. Raltegravir used with optimized background therapy provides an alternative regimen for ARV-experienced patients. This review describes the available in vitro and in vivo data on raltegravir potency, defined as the ability to achieve undetectable viral load, and safety profile, as well as comparison to standard HIV-1 therapies. Conclusions: Raltegravir has demonstrated potent antiretroviral activity against HIV-1 in both ARV-naïve and ARV-experienced subjects, with the benefits of a favorable adverse effect profile and minimal drug interactions. Raltegravir must be dosed twice daily, as once daily raltegravir displays decreased virologic efficacy compared to twice daily dosing. However, the ongoing development of new integrase strand transfer inhibitors may provide potent once daily regimens.

Tackling community-acquired methicillin-resistant Staphylococcus aureus in collegiate football players following implementation of an anti-MRSA programme

Competitive football players’ safety has become an important concern at the high school, collegiate and professional level and warrants attention.1–4 From 2003 to 2008, five players at our institution developed clinically significant community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections requiring hospitalisation and intravenous antibiotics. In 2008, the University of South Carolina team instituted anti-MRSA precautions based on recommendations made by the Centers for Disease Prevention and Control (CDC) (box 1). In an attempt to understand if guidelines recommended by the CDC resulted in low MRSA colonisation rates, we randomly selected players on a Division I collegiate football programme to evaluate colonisation for MRSA obtained from nares, helmets and shoulder pads. Inclusion criteria were age 18 or older and current team member. Exclusion criteria were presence of skin infection, receiving antibiotics or hospitalisation in the prior month. The study received IRB approval and informed consent was obtained from study participants. A research assistant or team physician obtained specimens from the nares, helmet and shoulder pads with a cotton-tipped swab from …

Biostatistics Training Through the Eyes of Residency Program Directors

Directors TO THE EDITOR: As part of an American Society of Health-System Pharmacists (ASHP)–accredited postgraduate year 1 (PGY1) residency program, pharmacy residents are required to demonstrate, evaluate, and apply evidence-based medicine (EBM) principles.1 Application of such principles requires a baseline understanding of biostatistics. When EBM principles have been assessed objectively, pharmacists and pharmacy residents have been found to demonstrate a poor aptitude for biostatistical concepts that are often encountered in peer-reviewed literature.2-5 Confidence of residents in their abilities correlated with their knowledge; however, assessment scores are generally poor.3 A study by Ellis et al. demonstrated no change in a resident’s knowledge related to research concepts, including biostatical and analytical skills, following completion of a residency year.4 Deficiency in biostatistics knowledge among pharmacists has the potential to compromise patient care. In the case of pharmacy residents, if residency mentors or directors have a falsely inflated perception of a resident’s biostatistics skill set, trainee development in this area may be deferred. The purpose of this study was to determine residency program director (RPD) confidence in residents’ ability to interpret biostatistical concepts and to assess their attitudes toward training of these concepts within their program. We conducted an anonymous cross-sectional survey from May to June 2009 of RPDs from accredited PGY1 pharmacy residency programs in the US. We requested participation via email in an online survey (Survey Monkey) to assess RPD satisfaction and confidence in resident knowledge and understanding of biostatistics, as well as the level of training of biostatistics within their program. Email reminders for nonresponders were sent 2 weeks after the initial mailing, providing a 4-week window to complete the survey. The survey consisted of 6 Likert scale questions (1 = strongly agree; 5 = strongly disagree) and an open-ended comment field. This study was considered exempt by the institutional review board at the University of South Carolina. Table 1 shows the answers of 157 RPDs who completed the online survey. Distribution of respondents was similar to residency program distribution in 2009.6 Approximately 65% were affiliated with a health sciences college. Overall, 80.1% of RPDs were confident in resident abilities to interpret biostatistical concepts and form their own conclusions (median score, 2). However, only 51% of RPDs agreed or strongly agreed that they were confident in residents’ abilities to explain biostatistical concepts to a colleague (median score, 2). RPDs were satisfied 59% of the time with the training residents received regarding biostatistics and application of EBM principles during their residency year; however, 84% of RPDs indicated that they would like to improve upon this train-

Longitudinal trends in base antiretroviral therapy utilization for human immunodeficiency virus from 2000 to 2016

The aim of this retrospective, observational study was to describe utilization trends in the base antiretroviral therapy (ART) for management of human immunodeficiency virus in United States Veterans for the time period of 1998 to 2016.

Clostridium tertium Peritonitis and Concurrent Bacteremia in a Patient With a History of Alcoholic Cirrhosis

Spontaneous bacterial peritonitis (SBP) is a recognized cause of morbidity and mortality in cirrhotic patients. Enterobacteriaceae have been isolated from the majority of peritonitis cases and the gram negative aerobe Escherichia coli is the most commonly isolated organism. Anaerobic organisms are rarely isolated because of the high oxygen tension in ascetic fluid. We report a patient with a history of alcoholic cirrhosis who developed SBP and concurrent bacteremia with the anaerobe Clostridium tertium. The patient was successfully treated with intravenous antibiotics and was discharged home on oral ciprofloxacin. This case report is unique in that it is the fourth documented Clostridium tertium SBP case, utilized MALDI-TOF mass spectrometry for organism identification, and susceptibility testing for select antibiotics was performed.