Pharmacoeconomic considerations in the ambulatory use of parenteral cephalosporins.

It has been clearly documented that outpatient parenteral antibiotic therapy (OPAT) saves money compared with hospital care for patients who need intravenous antimicrobial therapy. The reduced expenses come primarily from savings in facility and hospital staffing costs. In addition to shortening hospital stay, OPAT programmes can be developed so that hospital care is avoided altogether. However, even with the clear potential for savings, to have a successful programme it is necessary to align the interests of the payers, the physicians, the administrators and the patients. The cost of OPAT programmes can also be reduced through patient evaluation and careful selection of the appropriate delivery model, antibiotic, dosage intervals and infusion technology. The fact that antibiotics such as ceftriaxone, the aminoglycosides and vancomycin can be given once daily in the elderly offers particular advantages in terms of convenience as well as cost. In order to achieve cost savings, managed care will increasingly rely on home and outpatient therapy. This pressure will need to be counterbalanced by quality assurance programmes and outcomes measurements.

International outpatient parenteral antimicrobial therapy.

On an international basis, outpatient parenteral antimicrobial therapy (OPAT) varies greatly. There are cultural as well as economic issues which make it different in every country. In general, the duration of hospital stay varies with the outpatient resources available and the economic base for them. In some countries, there may not be money available for any intravenous antibiotics, even in the hospital. In addition, there are great differences in outpatient intravenous therapy, with infusion clinics proliferating in China, yet these are scarce in the UK. There is also considerable variation in the use of intramuscular compared with intravenous therapies. In Italy, intramuscular ceftriaxone is used more often than intravenous therapy. While ceftriaxone use is high in the US, its use is surpassed on a per capita basis by Italy, and it is most interesting that the rate of antimicrobial resistance is lower in Italy than in most other European countries. Whether this relates to outpatient use, parenteral use or other unknown factors is unclear. Obviously, further studies are necessary.

Outpatient parenteral antimicrobial therapy for central nervous system infections.

Patients with central nervous system (CNS) infections are increasingly treated with intravenous antimicrobials outside the hospital, but the safety and problems associated with this therapy have not been well defined. To examine this issue, we reviewed 68 cases in which outpatient intravenous antimicrobial therapy (OPAT) was received through our physician office-based infusion clinic. All infections were cured, and no deaths occurred during therapy. Seizures occurred in 2 patients but without significant injury and apparently were unrelated to antimicrobial therapy. Eleven patients (16%) were hospitalized after starting OPAT, 5 for procedures and 6 for medical reasons. The antimicrobial used was changed in 13 cases (19%) because of an adverse effect or clinical failure. OPAT can be safe and effective for patients with CNS infections, but patients must be carefully selected and monitored closely.

Comparison of sparfloxacin and ciprofloxacin in the treatment of community-acquired acute uncomplicated urinary tract infection in women. Sparfloxacin Multicenter Uncomplicated Urinary Tract Infection Study Group.

Urinary tract infection (UTI) is a common illness, with > or =30% of all women experiencing a UTI during their lifetime. Less than a decade ago, the standard therapy for acute uncomplicated UTIs involved treatment with > or =7 days of an antibacterial agent, but recent studies using a variety of newly introduced antibiotics, including the fluoroquinolones, have demonstrated that a 1- to 5-day treatment regimen can be equally effective. This randomized, double-masked, multicenter study was conducted to compare the efficacy and tolerability of a single dose of sparfloxacin with those of a 3-day regimen of sparfloxacin and a 7-day regimen of ciprofloxacin in the treatment of women with community-acquired acute uncomplicated urinary tract infection. A total of 1175 women were enrolled; 395 received sparfloxacin as a single 400-mg dose on day 1, 394 received sparfloxacin as a 400-mg loading dose on day 1 followed by 200 mg once daily for 2 additional days, and 386 received ciprofloxacin 250 mg twice daily for 7 days. Patients were comparable with respect to demographic characteristics and underlying conditions. A total of 954 patients were clinically assessable; 490 of these were also bacteriologically assessable. All patients treated were included in the tolerability analysis. Escherichia coli (75.4%), Klebsiella pneumoniae (4.9%), Enterococcus faecalis (4.6%), and Staphylococcus saprophyticus (4.1%) were the most commonly isolated organisms. In the all-treated population, clinical success was achieved 5 to 9 days after therapy in 91.8%, 92.2%, and 91.6% of patients in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; bacteriologic success was observed in 91.7%, 92.6%, and 96.6% of those in the 3 groups. Sustained clinical success rates 4 to 6 weeks after therapy were 76.6%, 80.2%, and 79.5% in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; sustained bacteriologic success rates were 80.7%, 90.1%, and 92.6%. The most common adverse events were nausea, headache, vaginal thrush, dizziness, and diarrhea; >92% of adverse events were mild or moderate in severity. The 2 drugs had comparable frequencies of adverse events, except for photosensitivity, which occurred in 3.3% of the 3-day sparfloxacin group, 1.3% of the single-dose sparfloxacin group, and 0.3% of the ciprofloxacin group (P = 0.005). The 3-day sparfloxacin regimen was effective and well tolerated. The initial response to single-dose sparfloxacin treatment was comparable to the response to the other 2 regimens, but the single-dose regimen proved less effective over time, with higher rates of clinical recurrence and bacteriologic relapse. Sparfloxacin provides an alternative to ciprofloxacin for patients with acute uncomplicated urinary tract infection who are not at risk for photosensitivity reactions or adverse events associated with a prolonged corrected QT interval.

Demographic, clinical, and treatment parameters influencing the outcome of acute cystitis.

A meta-analysis of six double-blinded clinical trials was undertaken to identify risk factors associated with bacteriologic outcome in 3,108 women with acute cystitis. Eleven antibiotic regimens were used, including ciprofloxacin, ofloxacin, norfloxacin, trimethoprim-sulfamethoxazole, and nitrofurantoin. Entry criteria for all studies were identical. Among 2,409 patients who were defined to be valid for efficacy analysis, pathogens included Escherichia coli (78.6%), Staphylococcus saprophyticus (4.4%), Klebsiella pneumoniae (4.3%), Proteus mirabilis (3.7%), and "other" (9%). Causative bacteria were eradicated at the end of treatment in 93% of patients. The following parameters were associated with successful bacteriologic outcome: not using a diaphragm (P = .0041), treatment for > or = 3 days (P = .0043), pathogen not "other" (P = .0043), symptom duration of < 2 days (P = .0096), and African American race (P = .0147). K. pneumoniae (P = .0496) and "other" pathogens (P = .0018) were associated with increased probability of bacteriologic treatment failure. The presence of pyuria (> or = 10 WBCs per high-power field) did not correlate with outcome and was inversely correlated with the finding of > or = 10(5) bacterial colony-forming units per mL of urine (P < .001). This large database identifies new parameters associated with treatment outcomes of acute cystitis and calls into question current clinical trial guidelines.

Short-course therapy of acute cystitis: a brief review of therapeutic strategies.

Acute cystitis is one of the commonest medical problems encountered by primary care physicians. It affects more women than men (8:1), but the incidence among men is increasing. Uncomplicated cystitis by definition occurs in healthy patients with a normal urinary tract, whereas complicated cystitis implies a predisposing or underlying condition. A narrow range of aetiological agents is responsible for most uncomplicated cystitis in women (Escherichia coli in 80% of cases). Recently, however, pathogens usually associated with sexually transmitted disease have been implicated. In women with typical symptoms of acute uncomplicated cystitis, an abbreviated laboratory work-up followed by empirical therapy is recommended. Single-dose and 3 day regimens of co-trimoxazole and the quinolones are as effective as longer regimens and have a higher eradication rate than other commonly used antimicrobials. Relapse rates are slightly higher with single-dose therapy. With this success rate plus the reduced cost and improved patient compliance, these regimens have replaced traditional 5 to 14 day courses of treatment. With increasing resistance of the common urinary pathogens to amoxycillin and, now, co-trimoxazole, the quinolones are a logical choice for empirical therapy of uncomplicated urinary tract infections.

Medicare coverage of outpatient ambulatory intravenous antibiotic therapy: a program that pays for itself.

A number of studies have documented the safety, efficacy, and cost-effectiveness of outpatient intravenous (i.v.) antibiotic therapy for patients with infectious diseases. Nevertheless, Medicare policy prohibiting coverage of outpatient, self-administered drugs has severely limited access of Medicare patients to ambulatory i.v. therapy, thus forcing them to rely on more costly, impatient hospital care. To test the hypothesis that a new Medicare benefit providing coverage for ambulatory i.v. antibiotic therapy could significantly reduce the program's expenditures for the treatment of infectious diseases (including pneumonia, osteomyelitis, cellulitis, and endocarditis), a cost model was constructed with use of patient care information from the clinical literature as well as clinical experts, Medicare data, and other medical claims databases. The model shows cumulative 5-year savings of nearly $1.5 billion associated with the new Medicare benefit. Policy makers should consider implementing such a benefit.

Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group.

This randomized, multicenter, open-label study compared the efficacy and safety of monotherapy with 2 g of intravenous ceftriaxone once daily for 4 weeks with those of combination therapy with 2 g of intravenous ceftriaxone and 3 mg of intravenous gentamicin/kg once daily for 2 weeks as therapy for endocarditis due to penicillin-susceptible streptococci. Sixty-one patients were enrolled in the study. Clinical cure was observed for 51 evaluable patients both at termination of therapy and at the 3-month follow-up: 25 (96.2%) of 26 monotherapy recipients and 24 (96%) of 25 combination therapy recipients. Of the 23 patients in each treatment group who were microbiologically evaluable, 22 (95.7%) in each group were considered cured. No patient had evidence of relapse. Fourteen patients (27.5%) required cardiac surgery after initiation of treatment, including five monotherapy recipients and nine combination therapy recipients. Adverse effects were minimal in both treatment groups. We conclude that 2 g of ceftriaxone once daily for 4 weeks and 2 g of ceftriaxone in combination with 3 mg of gentamicin/kg once daily for 2 weeks are both effective and safe for the treatment of streptococcal endocarditis.

Outpatient parenteral antimicrobial therapy for osteomyelitis.

OPAT for osteomyelitis is effective, safe, and well-established. There are particular considerations with osteomyelitis, however, that relate to patient selection and the plans of therapy. Orthopedic infections may impose physical considerations that need to be considered. Concomitant medical problems, such as diabetes, must be considered and may be good reasons for hospital care aside from the infection. Further investigations of treatment of osteomyelitis are clearly needed, with OPAT patients being good subjects to study.

Outpatient parenteral antibiotic therapy for fever and neutropenia.

The treatment of fever and neutropenia following chemotherapy lends itself well to outpatient parenteral antimicrobial therapy (OPAT). Patients prefer to be at home rather than hospitalized again. There is a clear cost advantage of outpatient therapy. With a quality program and careful patient selection, OPAT can be provided effectively and safely. The chances of an infection due to resistant bacteria also appear to be reduced. There are an increasing number of studies that support the use of empiric antibiotic therapy for the first fever in neutropenic patients. The choice of antimicrobial, dose, as well as vascular access and infusion devices must be tailored to the individual patient needs and circumstances.

Practice guidelines for community-based parenteral anti-infective therapy. ISDA Practice Guidelines Committee.

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.

Managed care and the infectious diseases specialist.

There is growing demand to contain health care costs and to reassess the value of medical services. The traditional hospital, academic, and research roles of the infectious disease (ID) specialist are threatened, yet there is an increasing need for expertise because of growing antimicrobial resistance and emerging pathogens. Opportunities exist to develop and expand services for the care of patients infected with human immunodeficiency virus and in infection control, epidemiology, outcomes research, outpatient intravenous therapy, and resource management. It is important for ID physicians to appreciate the principles involved in managed care and the areas in which ID services can be valuable. To be effective, physicians need to know about tools such as practice guidelines, physician profiling, outcomes monitoring, computerized information management, risk sharing, networking, and marketing, as well as related legal issues. With a positive attitude toward learning, application, and leadership, ID physicians can redefine their role and expand their services through managed care.

Alternate site infusion: the physician-directed, office-based model.

The physician-directed, clinic-based system for alternate site infusion therapy offers the advantages of easy communication and integrated decision making through the close teamwork and particular expertise of the nurse, physician, and pharmacist. With this system, any type of delivery model for home or outpatient IV antibiotic can be administered safely and efficiently. Through the involvement of the physician, it is easy to do clinical outcomes studies and develop bundling of services for risk-sharing contracts under managed care.

Selecting infusion devices for use in ambulatory care.

Intravenous infusion devices commonly used in home care and ambulatory care settings are reviewed and factors to consider in selecting a device are suggested. The type of therapy to be administered, the patient or caregiver's ability to understand and carry out instructions, staff time required for patient teaching and drug and device preparation, drug stability, frequency of doses, reservoir volume, control of flow rate, type of venous access, cost and availability of devices and supplies, and reimbursement should be considered. Cost-effectiveness of a device can be evaluated only by analyzing all of the costs associated with administering a medication. Decisions must be based on an individual agency's needs, but usually one type of single-dose infuser and one brand of electronic ambulatory-care infusion pump can meet the needs of most of an agency's patients. For patients self-administering up to four doses per day, appropriate methods may include slow intravenous injection (i.v. push), infusion from minibags and tubing, and the use of elastomeric infusers, electronic or mechanical syringe pumps, or a new device based on infusion across a bioelectric membrane. Some of these types of infusers can also be used for continuous infusion. Syringe pumps are reliable and affordable and control infusion rates well, but infusion volume is limited and these devices must be recovered, cleaned, and tested between patients. Although elastomeric pumps may have higher price tags than other devices, they are simple for patients to use and dispose of. While elastomeric devices have tubing permanently attached, the disposable tubing of some other devices is detachable and can be reused if institutional policy permits. Electronic ambulatory-care infusion pumps can meet a wide range of infusion requirements. They vary in size, weight, ability to detect occlusions, features, and reliability. All use proprietary infusion sets, but the costs of sets and disposable supplies vary. Some pumps can be used for a single infusion mode, such as patient-controlled analgesia (PCA); others offer two or more modes (for example, continuous, intermittent, and PCA). "Multichannel" pumps can be used for simultaneous infusion of up to four medications; the rate of each infusion is programmed separately, and some multichannel devices offer multiple infusion modes. Some can be programmed remotely by telephone. Before an agency decides on a pump, it can investigate current users' and rental firms' experiences with the device. Also, all relevant personnel should try programming the device. Determining which devices to use requires a comparison of features that are pertinent to the particular agency or institution and a cost analysis that considers acquisition, reimbursement, patient training time, and the cost of disposable supplies.

Experience with a physician-directed, clinic-based program for outpatient parenteral antibiotic therapy in the USA.

The experience with 538 patients who received outpatient parenteral antibiotic therapy (OPAT) in 1993 in a private institute in Tacoma, Washington, USA, is reviewed here. Clinical outcomes suggested a successful resolution of infection in 99% of cases. Bacteriological outcomes showed that eradication of the organism had occurred in 92% of patients by the end of therapy. The success of the program indicates that 91% of properly selected patients can be treated without adverse events. Antibiotics were changed in 45 (8%) instances, but only half of these changes were made because of an adverse event. The development of rash was the most frequent adverse event and resulted in hospitalization in only 1 instance. Hospitalization was necessary before the OPAT program was completed in 42 cases--20 of those were for surgery and 13 for medical reasons unrelated to the infection or antibiotic therapy. In 8 cases, patients were hospitalized because of failure of home care or inability to administer the antibiotics effectively. Three patients were taken off the program because of failure to comply. Patient satisfaction surveys suggested that 99% of patients were satisfied with the program. With careful patient selection and a well-developed program, OPAT can be safe, effective and beneficial to patients and can save costs in healthcare services.

Short-course ciprofloxacin treatment of acute uncomplicated urinary tract infection in women. The minimum effective dose. The Urinary Tract Infection Study Group [corrected].

BACKGROUND: Three studies were undertaken to determine the minimum effective dosing regimen of ciprofloxacin for the treatment of acute, symptomatic, uncomplicated lower urinary tract infection. METHODS: All studies were multicenter, prospective, randomized, double-blind trials. A total of 970 evaluable patients with a diagnosis of urinary tract infection received oral ciprofloxacin (200 mg to 500 mg daily in one or two divided doses for 1, 3, 5, or 7 days) or norfloxacin (400 mg twice daily [BID] for 7 days). The primary measure of efficacy was bacteriologic eradication at the end of therapy. RESULTS: In study 1, bacteriologic eradication was reported in 95 (89%) and 101 (98%) of patients in the groups who received ciprofloxacin, 500-mg single dose and 250 mg BID for 7 days, respectively. Clinical success occurred in 101 patients (94%) who received a 500-mg single dose and in 103 patients (100%) who were administered 250 mg BID for 7 days. In study 2, eradication rates in the groups who received ciprofloxacin, 100 mg BID for 3 days, 250 mg BID for 3 days, and 250 mg BID for 7 days, were 98 (93%), 95 (90%), and 98 (93%), respectively. Clinical success was reported in 102 (97%), 105 (100%), and 104 (98%) of the patients, respectively. In study 3, the eradication rates in the groups who received ciprofloxacin in dosages of 500 mg once daily for 3 days and 500 mg once daily for 5 days and norfloxacin in a dosage of 400 mg BID for 7 days were 137 (92%), 134 (90%), and 133 (94%) of the women, respectively. Clinical success was the same (97%) in all three groups. Overall, short-course (either 3- or 5-day) therapy with ciprofloxacin was statistically equivalent to conventional (7-day) therapy with either ciprofloxacin or norfloxacin. Single-dose ciprofloxacin therapy was statistically less effective than conventional treatment. CONCLUSIONS: Ciprofloxacin at a dosage of 100 mg BID for 3 days was the minimum effective dose for the treatment of uncomplicated urinary tract infection in women.

The importance of teamwork for outpatient parenteral antibiotic therapy.

A variety of treatment models can be constructed to provide intravenous antibiotic therapy outside the hospital. The type and details of each model must be adapted to local needs and resources, but those that coordinate the resources of all the primary members of the team necessary to care for patients, offer the greatest potential for a safe and efficient programme. We believe that the teamwork of the physician, nurse, and pharmacist in our clinic-based, physician-directed model can provide a safe and effective service, which is appreciated by the patients we care for.

Outpatient parenteral antibiotic therapy. Management of serious infections. Part II: Amenable infections and models for delivery. Osteomyelitis.

Osteomyelitis is one of the most common and well-established indications for outpatient parenteral antibiotic therapy. Because patients are usually otherwise healthy and therapy is prolonged (four to six weeks), this infection is especially suited to outpatient management. While most gram-negative infections in adults can be treated with an oral quinolone, others usually require IV therapy.

Outpatient parenteral antibiotic therapy. Management of serious infections. Part I: Medical, socioeconomic, and legal issues. The team concept.

The delivery of outpatient parenteral antibiotic therapy is a team effort that, at minimum, requires a physician, a nurse, and a pharmacist. Other specialists may be added as needed. The team may be structured in several different ways, but two basic models emerge: physician-directed and nonphysician-directed. Whatever the structure, the physician should maintain a leadership role in the care of the patient.