Susan J. Rehm

Practice Guidelines for Outpatient Parenteral Antimicrobial Therapy

These guidelines were formulated to assist physicians and other health care professionals with various aspects of the administration of outpatient parenteral antimicrobial therapy (OPAT). Although there are many reassuring retrospective studies on the efficacy and safety of OPAT, few prospective studies have been conducted to compare the risks and outcomes for patients who receive treatment as outpatients rather than as inpatients. Because truly evidence-based studies are lacking, the present guidelines are formulated from the collective experience of the committee members and advisors from related organizations.

Venous Thrombosis Associated with Peripherally Inserted Central Catheters: A Retrospective Analysis of the Cleveland Clinic Experience

Peripherally inserted central catheters (PICCs) have become popular for long courses of intravenously administration of antibiotics. Although these devices are generally regarded as safe, thrombotic complications have been associated with their use. In a retrospective review, 51 (2.47%) of 2063 patients who had a PICC placed during 1994-1996 were found to have developed a total of 52 PICC-associated venous thromboses (VTs). Two patients received the diagnosis of pulmonary embolism that was a complication of VT. Risk factors for VT identified by multiple logistic regression analysis were younger age, history of VT, discharge to a skilled-nursing facility, and therapy with amphotericin B. VT is a significant complication of PICC placement. It may occur more frequently than previously recognized and may be complicated by pulmonary embolism. Clinicians should maintain a high index of suspicion, especially for high-risk patients.

Practice Guidelines for Community-Based Parenteral Anti-Infective Therapy

This is the fourth in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of this guideline is to provide assistance to clinicians when making decisions on when and how to best administer parenteral antimicrobial therapy. The targeted providers are internists, pediatricians, family practitioners, and other providers of outpatient antiinfective therapy. Criteria for selecting the appropriate patients and settings to deliver therapy in the community are described. Panel members represented experts in adult and pediatric infectious diseases. The guidelines are evidence-based. A standard ranking system is used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary and tables highlight the major recommendations.

Daptomycin versus vancomycin plus gentamicin for treatment of bacteraemia and endocarditis due to Staphylococcus aureus: subset analysis of patients infected with methicillin-resistant isolates

Objectives In a prospective, randomized trial, daptomycin was non-inferior to standard therapy for Staphylococcus aureus bacteraemia and right-sided endocarditis. Since rates of infection due to methicillin-resistant S. aureus (MRSA) infection are increasing and treatment outcomes for bacteraemia caused by MRSA are generally worse than those observed with methicillin-susceptible S. aureus bacteraemia, clinical characteristics and treatment results in the trial’s pre-specified subset of patients with MRSA were analysed. Methods Clinical characteristics and outcomes of patients receiving daptomycin were compared with those receiving vancomycin plus low-dose gentamicin. Success was defined as clinical improvement with clearance of bacteraemia among patients who completed adequate therapy, received no potentially effective non-study antibiotics and had negative blood cultures 6 weeks after end of therapy. Results Twenty of the 45 (44.4%) daptomycin patients and 14 of the 43 (32.6%) vancomycin/gentamicin patients were successfully treated (difference 11.9%; confidence interval −8.3 to 32.1). Success rates for daptomycin versus vancomycin/gentamicin were 45% versus 27% in complicated bacteraemia, 60% versus 45% in uncomplicated bacteraemia and 50% versus 50% in right-sided MRSA endocarditis. Cure rates in patients with septic emboli and in patients who received pre-enrolment vancomycin were similar between treatment groups. However, in both treatment groups, success rates were lower in the elderly (≥75 years). Persisting or relapsing bacteraemia occurred in 27% of daptomycin and 21% of vancomycin/gentamicin patients; among these patients, MICs of ≥2 mg/L occurred in five daptomycin and four vancomycin/gentamicin patients. The clinical course of several patients may have been influenced by lack of surgical intervention. Conclusions Daptomycin was an effective alternative to vancomycin/gentamicin for MRSA bacteraemia or right-sided endocarditis.

Treatment of Vancomycin-Resistant Enterococcus faecium Infections with Quinupristin/Dalfopristin

Clinicians caring for patients with vancomycin-resistant Enterococcus faecium (VREF) infections face severe constraints in the selection of treatment. Quinupristin/dalfopristin (Synercid) is active in vitro against VREF, with a MIC(90) of 1.0 microg/mL. We investigated the clinical efficacy and safety of this agent in a multicenter, prospective, noncomparative, emergency-use study of 396 patients. Patients were included if they had signs and symptoms of active infection, including bacteremia of unknown origin, intra-abdominal infection, and skin and skin-structure infection, with no alternative antibiotic therapy available. The mean duration of treatment was 20 days (range, 4-40 days). The clinical response rate was 68.8% in the evaluable subset, and the overall response rate was 65.6%. The most common adverse events related to quinupristin/dalfopristin were arthralgias and myalgias. Related laboratory abnormalities were rare. In this severely ill patient population, quinupristin/dalfopristin was efficacious and demonstrated an acceptable safety profile in the treatment of VREF infection.

Staphylococcus aureus: Methicillin-Susceptible S. aureus to Methicillin-Resistant S. aureus and Vancomycin-Resistant S. aureus

The evolution of methicillin-resistant and vancomycin-resistant Staphylococcus aureus has demanded serious review of antimicrobial use and development of new agents and revised approaches to prevent and overcome drug resistance. Depending on local conditions and patient risk factors, empirical therapy of suspected S. aureus infection may require coverage of drug-resistant organisms with newer agents and novel antibiotic combinations. The question of treatment with inappropriate antibiotics raises grave concerns with regard to methicillin-resistant S. aureus selection, overgrowth, and increased virulence. Several strategies to reduce the nosocomial burden of resistance are suggested, including shortened hospital stays and outpatient parenteral antimicrobial therapy of the most serious infections.

Community-based outpatient parenteral antimicrobial therapy (CoPAT) for Staphylococcus aureus bacteraemia with or without infective endocarditis: analysis of the randomized trial comparing daptomycin with standard therapy

Objectives Administering outpatient parenteral antimicrobial therapy in the community setting (CoPAT) is becoming more common with the increasing emphasis on controlling costs. However, few controlled trials have evaluated this treatment modality. Methods Using data from a recent randomized trial comparing daptomycin with standard therapy (semi-synthetic penicillin or vancomycin, each with initial low-dose gentamicin) for Staphylococcus aureus bacteraemia and infective endocarditis (SAB/IE), patient characteristics and outcomes were evaluated. Patients receiving their full course of therapy in the hospital setting were compared with those who received some portion outside of the hospital (CoPAT). Results Among the 200 patients, 51.5% received CoPAT. These patients were generally younger (median age 50 versus 54 years, P = 0.028). In the CoPAT group, there tended to be fewer patients with endocardial involvement (8.7% versus 18.6%, P = 0.061) and pre-existing valvular heart disease (7.8% versus 15.5%, P = 0.120). CoPAT patients received longer therapy courses (mean 25.4 versus 13.5 days, P < 0.001) and had higher rates of therapy completion (90.3% versus 45.4%, P < 0.001) and clinical success (86.4% versus 55.7%, P < 0.001). Persisting or relapsing S. aureus was less frequent in the CoPAT group (3.9% versus 15.5%, P = 0.007) and there were fewer deaths (3.9% versus 18.6%, P = 0.001) 6 weeks after the end of therapy. Hospital readmission occurred for 18 of the 103 (17.5%) CoPAT patients. Clinical success rates were similar for CoPAT patients receiving daptomycin (90.0%) or standard therapy (83.0%). Conclusions With proper monitoring, stable patients can complete treatment for SAB/IE as outpatients in the community setting. Daptomycin is an appropriate option for this setting.

Inflammatory progressive multifocal leukoencephalopathy in human immunodeficiency virus-negative patients.

Inflammatory progressive multifocal leukoencephalopathy (iPML) with enhancing magnetic resonance imaging (MRI) lesions and leukocyte infiltration occurs in human immunodeficiency virus (HIV)–infected individuals after highly active antiretroviral therapy (HAART) treatment. MRI diagnostic criteria for PML suggest that iPML does not occur in HIV‐negative individuals.

Contribution of infectious disease consultation toward the care of inpatients being considered for community-based parenteral anti-infective therapy.

BACKGROUND In the acute care setting in a multidisciplinary healthcare environment, the contribution of infectious disease (ID) specialists to overall patient care is difficult to measure. This study attempts to quantify the contribution of ID specialists when consulted for an activity specific to ID practice, community-based parenteral anti-infective therapy (CoPAT). METHODS In February 2010, an electronic form for requesting ID consultations was introduced in the computerized provider order entry (CPOE) system at the Cleveland Clinic. This allowed for easy identification of ID consultations for CoPAT. Hospital records for all patients with CoPAT consultation requests between February 11, 2010 and May 15, 2010 were reviewed for specific defined contributions in the domains of optimization of antimicrobial therapy, significant change in patient assessment, and additional medical care contribution. RESULTS Over a 3-month period, there were 263 CoPAT consultation requests via CPOE, of which 172 were initial consultations and 91 reconsultations. Antimicrobial treatment was optimized in 84%, a significant change in patient assessment made in 52%, and additional medical care contribution provided in 71% of consultations. In 33% of consultations, there was contribution in all 3 domains. CoPAT was deemed not to be necessary in 27%. For patients requiring CoPAT, effective care transition from the inpatient to outpatient setting was assured at least 86% of the time. CONCLUSION Infectious disease consultation before discharge on parenteral antibiotics adds value by contributing substantially to inpatient care, and providing antimicrobial stewardship and continuity of care at a critical patient care transition point.

Antimicrobial stewardship at transition of care from hospital to community

Mandatory infectious disease consultation for parenteral antimicrobials at hospital discharge resulted in avoiding postdischarge parenteral antimicrobials in 28% of patients. No emergency department visit or rehospitalization within 30 days for these patients was a consequence of parenteral antimicrobial avoidance. Antimicrobial stewardship at transition of care is effective in reducing unnecessary antimicrobial use.