A call to action for outpatient antibiotic stewardship.

OBJECTIVES: To address the public health threat of antibiotic resistance, there has been an enhanced call for antibiotic stewardship programs throughout the health care continuum. SUMMARY: While antibiotic stewardship programs have been well described in the inpatient setting, data on effectiveness and guidance on implementing outpatient programs is scarce. Establishing stewardship practices in the outpatient setting is necessary because more than 60% of human antibiotic use occurs in this setting. CONCLUSION: In this article, we highlight the importance and need for stewardship in the outpatient setting, discuss strategies for the development of stewardship teams, and discuss potential metrics that can be used to assess effectiveness of antibiotic stewardship interventions.

Outpatient antibiotic stewardship: Interventions and opportunities.

Improving the use of antibiotics across the continuum of care is a national priority. Data outlining the misuse of antibiotics in the outpatient setting justify the expansion of antibiotic stewardship programs (ASPs) into this health care setting; however, best practices for outpatient antibiotic stewardship (AS) are not yet defined. In a companion article, we focused on recommendations to overcome challenges related to the implementation of an outpatient ASP (e.g., building the AS team and defining program metrics). In this document, we outline AS interventions that have demonstrated success and highlight opportunities to enhance AS in the outpatient arena. This article summarizes examples of point-of-care testing, policies and interventions, and education strategies to improve antibiotic use that can be used in the outpatient setting.

Recent Updates on the Role of Pharmacokinetics-pharmacodynamics in Antimicrobial Susceptibility Testing as Applied to Clinical Practice.

Given current challenges in antimicrobial resistance and drug development, infectious diseases clinicians must rely on their own ingenuity to effectively treat infections while preserving the current antimicrobial armamentarium. An understanding of pharmacokinetics (PK), pharmacodynamics (PD), antimicrobial susceptibility testing (AST), and how these concepts relate, is essential to this task. In this review, we discuss how and why PK-PD impacts AST and the way infectious diseases are being treated, with a particular focus on vancomycin for methicillin-resistant Staphylococcus aureus, penicillin for Streptococcus pneumoniae, and an update on cephalosporins for Enterobacteriaceae. Finally, we address how new ideas to exploit PK-PD can promote innovative study design and bring about more rapid regulatory review of new antimicrobials.

Comparative value of four measures of retention in expert care in predicting clinical outcomes and health care utilization in HIV patients.

This study compared the ability of four measures of patient retention in HIV expert care to predict clinical outcomes. This retrospective study examined Veterans Health Administration (VHA) beneficiaries with HIV (ICD-9-CM codes 042 or V08) receiving expert care (defined as HIV-1 RNA viral load and CD4 cell count tests occurring within one week of each other) at VHA facilities from October 1, 2006, to September 30, 2008. Patients were ≥18 years old and continuous VHA users for at least 24 months after entry into expert care. Retention measures included: Annual Appointments (≥2 appointments annually at least 60 days apart), Missed Appointments (missed ≥25% of appointments), Infrequent Appointments (>6 months without an appointment), and Missed or Infrequent Appointments (missed ≥25% of appointments or >6 months without an appointment). Multivariable nominal logistic regression models were used to determine associations between retention measures and outcomes. Overall, 8,845 patients met study criteria. At baseline, 64% of patients were virologically suppressed and 37% had a CD4 cell count >500 cells/mm3. At 24 months, 82% were virologically suppressed and 46% had a CD4 cell count >500 cells/mm3. During follow-up, 13% progressed to AIDS, 48% visited the emergency department (ED), 28% were hospitalized, and 0.3% died. All four retention measures were associated with virologic suppression and antiretroviral therapy initiation at 24 months follow-up. Annual Appointments correlated positively with CD4 cell count >500 cells/mm3. Missed Appointments was predictive of all primary and secondary outcomes, including CD4 cell count ≤500 cells/mm3, progression to AIDS, ED visit, and hospitalization. Missed Appointments was the only measure to predict all primary and secondary outcomes. This finding could be useful to health care providers and public health organizations as they seek ways to optimize the health of HIV patients.

Evaluation of the nanosphere Verigene BC-GN assay for direct identification of gram-negative bacilli and antibiotic resistance markers from positive blood cultures and potential impact for more-rapid antibiotic interventions.

The Verigene BC-GN assay correctly identified all 51 Gram-negative bacilli (GNB) from positive blood cultures and all 14 carbapenemase enzymes tested. The assay gave organism identification (ID) results an average of 24 h faster compared to conventional identifications. Medical management could have been modified for 31.8% of patients an average 33 h sooner. In conclusion, the BC-GN assay is a very accurate, rapid assay which would allow for more-immediate medical management decisions in patients with bacteremia from GNB.

Treatment failure and costs in patients with methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections: a South Texas Ambulatory Research Network (STARNet) study.

OBJECTIVE: To measure the incidence of treatment failure and associated costs in patients with methicillin-resistant Staphylococcus aureus skin and soft tissue infections (SSTIs). METHODS: This was a prospective, observational study in 13 primary care clinics. Primary care providers collected clinical data, wound swabs, and 90-day follow-up information. Patients were considered to have "moderate or complicated" SSTIs if they had a lesion ≥5 cm in diameter or diabetes mellitus. Treatment failure was evaluated within 90 days of the initial visit. Cost estimates were obtained from federal sources. RESULTS: Overall, treatment failure occurred in 21% of patients (21 of 98) at a mean additional cost of $1,933.71 per patient. In a subgroup analysis of patients who received incision and drainage, those with moderate or complicated SSTIs had higher rates of treatment failure than those with mild or uncomplicated SSTIs (36% vs. 10%; P=.04). CONCLUSIONS: One in 5 patients presenting to a primary care clinic for a methicillin-resistant S. aureus SSTI will likely require additional interventions at an associated cost of almost $2,000 per patient. Baseline risk stratification and new treatment approaches are needed to reduce treatment failures and costs in the primary care setting.

Declining susceptibilities of gram-negative bacteria to the fluoroquinolones: effects on pharmacokinetics, pharmacodynamics, and clinical outcomes.

PURPOSE: Published evidence of rising gram-negative bacterial resistance to fluoroquinolone therapy is reviewed, with a focus on the potential need for revising pharmacokinetic-pharmacodynamic (PK-PD) targets in order to maintain acceptable clinical outcomes. SUMMARY: With a more than threefold increase in fluoroquinolone use among U.S. adults since the introduction of second- and third-generation (i.e., "respiratory") fluoroquinolones 15 years ago, surveillance data indicate a decline in some gram-negative organisms' susceptibility to this antimicrobial class. These trends have raised concerns that the need to attain higher organism-specific minimum inhibitory concentrations (MICs) may lead to worse patient outcomes, even when MIC values are below current established "clinical breakpoints" for fluoroquinolone susceptibility. A growing body of evidence from PK-PD studies suggests that current fluoroquinolone dosing regimens are no longer adequate to achieve validated PK-PD targets. For example, a Monte Carlo simulation using PK data from U.S. hospitals showed decreasing rates of response to standard ciprofloxacin and levofloxacin i.v. dosing regimens among patients treated for infections with Escherichia coli and Klebsiella species. These findings suggest that currently accepted PK-PD targets may need to be revised for certain patient populations, including patients with bloodstream infections (BSIs). More research is needed to confirm the appropriateness of adjusting clinical breakpoints and other strategies to combat rising fluoroquinolone resistance. CONCLUSION: The use of the fluoroquinolones has markedly increased since the introduction of the respiratory fluoroquinolones. Surveillance data and PK-PD studies have raised concerns about suboptimal patient outcomes with the use of fluoroquinolones for some gram-negative infections, particularly BSIs. PK-PD goals and clinical breakpoints may need to be revised for these infections.

The environmental and social influences of HIV/AIDS in sub-Saharan Africa: a focus on rural communities.

The Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) pandemic has caused far-reaching effects in sub-Saharan Africa. The pandemic has effectively diminished the workforce, increased poverty rates, reduced agricultural productivity, and transformed the structure of many rural households. HIV/AIDS further strains the already fragile relationship between livelihood and the natural and social environments of these regions. Therefore, the objective of this review is to characterize the impact of HIV/AIDS on the environment and the social infrastructure of rural sub-Saharan Africa. There are many aspects of rural life that contribute to disease transmission of HIV/AIDS and that pose unique challenges to the population dynamics in sub-Saharan Africa. Widespread AIDS-related mortality has caused a decrease in population growth for many African countries. In turn, these alterations in population dynamics have resulted in a decrease in the percentage of prime-age working adults, as well as a gender disparity, whereby, females carry a growing burden of household responsibilities. There is a rising proportion of older adults, often females, who assume the role of provider and caretaker for other dependent family members. These changing dynamics have caused many to exploit their natural surroundings, adopting less sustainable land use practices and utilizing protected resources as a primary means of generating revenue.

Fluoroquinolones in community-acquired pneumonia: guide to selection and appropriate use.

Fluoroquinolone use has dramatically increased since the introduction of the first respiratory fluoroquinolone in the late 1990s. Over a relatively brief period of time, the respiratory fluoroquinolones have supplanted other first-line options as the predominant community-acquired pneumonia (CAP) therapy in hospitals. This article discusses the rise of the fluoroquinolone era, debates the comparative effectiveness of fluoroquinolones for CAP therapy, examines fluoroquinolone resistance and adverse drug reactions, and discusses new trends in pneumonia epidemiology and outcomes assessment. Overall, published data suggest that fluoroquinolone monotherapy is associated with improved patient survival compared with ß-lactam monotherapy and similar survival to ß-lactam plus macrolide combination therapy. Fluoroquinolone monotherapy may be associated with shorter hospital length of stay compared with ß-lactam plus macrolide combination therapy, particularly in severe pneumonia or with high-dose therapy. There is insufficient evidence to conclude that any individual fluoroquinolone therapy is better than another with regards to patient mortality. Fluoroquinolones are generally well tolerated and Streptococcus pneumoniae resistance remains low; however, rare but serious adverse effects have been reported. Some members of the fluoroquinolone class have been removed from the market amidst safety concerns. Pneumonia classifications have changed and antipseudomonal fluoroquinolones may have a role in healthcare-associated pneumonia when administered in combination with other antipseudomonal and anti-methicillin-resistant Staphylococcus aureus therapies.

Evaluation of dexmedetomidine versus propofol-based sedation therapy in mechanically ventilated cardiac surgery patients at a tertiary academic medical center.

Management of pain and sedation therapy is a vital component of optimizing patient outcomes; however, the ideal pharmacotherapy regimen has not been identified in the postoperative cardiac surgery population. We sought to evaluate efficacy and safety outcomes between postoperative mechanically ventilated cardiac surgery patients receiving dexmedetomidine versus propofol therapy upon arrival to the intensive care unit (ICU). We conducted a single center, descriptive study of clinical practice at a 20-bed cardiac surgery ICU in a tertiary academic medical center. Adult mechanically ventilated postcardiac surgery patients who received either dexmedetomidine or propofol for sedation therapy upon admission to the ICU between October 20, 2006 and December 15, 2006 were evaluated. A pharmacy database was used to identify patients receiving dexmedetomidine or propofol therapy for perioperative sedation during cardiac surgery. Patients were matched according to surgical procedure type. Fifty-six patients who received either dexmedetomidine (n = 28) or propofol (n = 28) were included in the analysis. No differences in the ICU length of stay (58.67 ± 32.61 vs. 61 ± 33.1 hours; P = 0.79) and duration of mechanical ventilation (16.21 ± 6.05 vs. 13.97 ± 4.62 hours; P = 0.13) were seen between the propofol and dexmedetomidine groups, respectively. Hypotension (17 [61%] vs. 9 [32%]; P = 0.04), morphine use (11 [39.3%] vs. 1 [3.6%]; P = 0.002), and nonsteroidal anti-inflammatory use (7 [25%] vs. 1 [3.6%]; P = 0.05) occurred more during dexmedetomidine therapy versus propofol. Dexmedetomidine therapy resulted in a higher incidence of hypotension and analgesic consumption compared with propofol-based sedation therapy. Further evaluation is needed to assess differences in clinical outcomes of propofol and dexmedetomidine-based therapy in mechanically ventilated cardiac surgery patients.