Donald R. Graham

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.

Telavancin Versus Vancomycin for the Treatment of Complicated Skin and Skin-Structure Infections Caused by Gram-Positive Organisms

BACKGROUND Telavancin is an investigational, rapidly bactericidal lipoglycopeptide with a multifunctional mechanism of action. METHODS We conducted 2 parallel, randomized, double-blind, active-control, phase 3 studies with a prespecified pooled analysis design. Patients aged > or = 18 years who had complicated skin and skin-structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin (10 mg/kg intravenously every 24 h) or vancomycin (1 g intravenously every 12 h). RESULTS A total of 1867 patients were randomized and received > or = 1 dose of study medication. In the clinically evaluable population, at 7-14 days after receipt of the last antibiotic dose, success was achieved in 88% and 87% of patients who received telavancin and vancomycin, respectively (95% confidence interval for the difference, -2.1 to 4.6). Methicillin-resistant Staphylococcus aureus was isolated at baseline from samples from 579 clinically evaluable patients. Among these patients with methicillin-resistant S. aureus infection, cure rates were 91% among patients who received telavancin and 86% among patients who received vancomycin (95% confidence interval for the difference, -1.1 to 9.3). Microbiologic eradication among patients infected with methicillin-resistant S. aureus was 90% in the telavancin treatment group and 85% in the vancomycin treatment group (95% confidence interval for the difference, -0.9 to 9.8). Therapy was discontinued because of adverse events in 8% and 6% of patients who received telavancin and vancomycin, respectively. Except for mild taste disturbance, nausea, vomiting, and serum creatinine concentration elevation in the telavancin treatment group and pruritus in the vancomycin treatment group, adverse events were similar between groups with regard to type and severity. CONCLUSIONS Telavancin given once daily is at least as effective as vancomycin for the treatment of patients with complicated skin and skin-structure infections, including those infected with methicillin-resistant S. aureus.

Outbreak of Leptospirosis among Triathlon Participants and Community Residents in Springfield, Illinois, 1998

We investigated an outbreak of leptospirosis among athletes and community residents after a triathlon was held in Springfield, Illinois. A telephone survey was conducted to collect clinical information and data on possible risk factors, community surveillance was established, and animal specimens and lake water samples were collected to determine the source of the leptospiral contamination. A total of 834 of 876 triathletes were contacted; 98 (12%) reported being ill. Serum samples obtained from 474 athletes were tested; 52 of these samples (11%) tested positive for leptospirosis. Fourteen (6%) of 248 symptomatic community residents tested positive for leptospirosis. Heavy rains that preceded the triathlon are likely to have increased leptospiral contamination of Lake Springfield. Among athletes, ingestion of 1 or more swallows of lake water was a predominant risk factor for illness. This is the largest outbreak of leptospirosis that has been reported in the United States. Health care providers and occupational and recreational users of bodies of freshwater in the United States should be aware of the risk of contracting leptospirosis, particularly after heavy rains.

Safety of Long-Term Oral Posaconazole Use in the Treatment of Refractory Invasive Fungal Infections

BACKGROUND Invasive fungal infections are found most frequently in immunosuppressed and critically ill hospitalized patients. Antifungal therapy is often required for long periods. Safety data from the clinical development program of the triazole antifungal agent, posaconazole, were analyzed. METHODS A total of 428 patients with refractory invasive fungal infections (n = 362) or febrile neutropenia (n = 66) received posaconazole in 2 phase II/III open-label clinical trials. Also, 109 of these patients received posaconazole therapy for > or = 6 months. Incidences of treatment-emergent, treatment-related, and serious adverse events and abnormal laboratory parameters were recorded during these studies. RESULTS Treatment-emergent, treatment-related adverse events were reported in 38% of the overall patient population. The most common treatment-related adverse events were nausea (8%) and vomiting (6%). Treatment-related serious adverse events occurred in 8% of patients. Low rates of treatment-related corrected QT interval and/or QT interval prolongation (1%) and elevation of hepatic enzymes (2%) were reported as adverse events. Treatment-emergent, treatment-related adverse events occurred at similar rates in patients who received posaconazole therapy for < 6 months and > or = 6 months. CONCLUSIONS Prolonged posaconazole treatment was associated with a generally favorable safety profile in seriously ill patients with refractory invasive fungal infections. Long-term therapy did not increase the risk of any individual adverse event, and no unique adverse event was observed with longer exposure to posaconazole.

Once-Daily, High-Dose Levofloxacin versus Ticarcillin-Clavulanate Alone or Followed by Amoxicillin-Clavulanate for Complicated Skin and Skin-Structure Infections: A Randomized, Open-Label Trial

This study tested whether levofloxacin, at a new high dose of 750 mg, was effective for the treatment of complicated skin and skin-structure infections (SSSIs). Patients with complicated SSSIs (n=399) were randomly assigned in a ratio of 1:1 to 2 treatment arms: levofloxacin (750 mg given once per day intravenously [iv], orally, or iv/orally) or ticarcillin-clavulanate (TC; 3.1 g given iv every 4-6 hours) followed, at the investigators discretion, by amoxicillin-clavulanate (AC; 875 mg given orally every 12 hours). In the clinically evaluable population, therapeutic equivalence was demonstrated between the levofloxacin and TC/AC regimens (success rates of 84.1% and 80.3%, respectively). In the microbiologically evaluable population, the overall rate of eradication was 83.7% in the levofloxacin treatment group and 71.4% in the TC/AC treatment group (95% confidence interval, -24.3 to -0.2). Both levofloxacin and TC/AC were well tolerated. These data demonstrate that levofloxacin (750 mg once per day) is safe and at least as effective as TC/AC for complicated SSSIs.

Epidemic neonatal gentamicin-methicillin-resistant Staphylococcus aureus infection associated with nonspecific topical use of genetamicin

One hundred sixteen infants in an intensive care nursery acquired Staphylococcus aureus resistant to gentamicin and methicillin; 54 patients acquired S. aureus sensitive to gentamicin and methicillin. Topical application of gentamicin ointment was significantly associated with acquisition of GMRS. Of 78 infants who acquired GMRS, 38 had received GmO before GMRS was first cultured, whereas only one of 49 infants with GMSS had previously received GmO (P = 8.6 X 10(-8)). Infants with GMRS were also more likely than patients with GMSS to have had a lower mean birth weight, Apgar score, and gestational age; systemic antibiotic therapy and incubator care were significantly prolonged for patients with GMRS, but these factors did not explain susceptibility to GMRS infection. Multivariate logistic regression analysis showed that use of GmO was the single most important risk factor.

Guidelines for the Care of Patients Hospitalized with Viral Hepatitis

For years patients hospitalized with viral hepatitis have been placed in two categories of isolation--enteric precautions and blood precautions. This strategy was based on the inability to differentiate between hepatitis A and B and on the assumption that feces and blood from patients with either type might be infective. It is now known that patients with hepatitis A do not pose a problem of disease transmission through direct contact with blood, and although blood of patients with hepatitis B may be infective, the virus is not transmitted via feces. The enteric route is the principal mode of transmission for hepatitis A, but maximal levels of hepatitis A virus excretion occur before the onset of jaundice. Non-A, non-B hepatitis is similar epidemiologically to hepatitis B. Thus, the major thrust for caring for patients hospitalized with viral hepatitis is toward blood precautions; the same precautions used when handling feces, urine, and excretions from all other hospitalized patients are appropriate for patients admitted with a diagnosis of hepatitis A.

Outbreak of pyrogenic reactions at a dialysis center: Association with infusion of heparinized saline solution

Twenty-three pyrogenic reactions occurred in 16 patients undergoing hemodialysis at a private dialysis center in the south central United States between November 23 and December 2, 1978. No deaths were attributed to reactions; however, 10 patients were hospitalized for observation after experiencing a reaction. Cultures of all blood specimens obtained from the patients gave negative results. Chills (75 percent), nausea and/or vomiting (30 percent), and fever (90 percent) were the most common signs and symptoms, with mean times of onset after starting dialysis of 1.1, 1.6, and 3.6 hours, respectively. An epidemiologic and laboratory investigation documented that reactions occurred only in patients who had anticoagulation with a dilute solution of heparin. Analyses of heparinized saline solution used during the outbreak revealed a bacterial count of 7.4 X 10(5)/ml and a bacterial endotoxin level of 1,300 ng/ml. Acinetobacter calcoaceticus var. Iwoffi was isolated from the solution. Diluted heparin solution was prepared at the dialysis center by adding commercially supplied sodium heparin to 0.9 percent sodium chloride infusion fluid. Bacteria and endotoxin were not detected in vials of stock heparin and bags of unopened 0.9 percent sodium chloride infusion fluid. We concluded that contamination of the solution occurred at the dialysis center. After changes in the preparation and use of heparin were instituted on December 4, 1978, no pyrogenic reactions occurred in more than 400 subsequent dialyses.

Hepatitis D virus infection in Illinois state facilities for the developmentally disabled. Epidemiology and clinical manifestations

OBJECTIVE To define the epidemiology and clinical manifestations of hepatitis D virus infection in an institutionalized population. DESIGN A case-control study of hepatitis B carriers with and without serologic evidence of hepatitis D virus infection. Demographic, institutional, and medical data were obtained through questionnaires and chart review. Clinical status was assessed by liver function assays. SETTING Thirteen Illinois state facilities for the developmentally disabled. PARTICIPANTS Clients (238) who were hepatitis B carriers. RESULTS Antibody to hepatitis D virus (anti-HDV) was detected in 71 of 238 (30%) hepatitis B carriers. Nine of thirteen facilities housed positive clients. Previous residence at one facility, designated B, was the strongest correlate of anti-HDV positivity; 85% of positive persons had lived there compared with 16% of negative controls (odds ratio 28.3 [95% CI, 13.2 to 60.7], P less than 0.001). Past hepatitis episodes were more common among anti-HDV-positive clients (37% compared with 7%) (odds ratio, 7.5 [95% CI, 3.0 to 19.1], P less than 0.001) and occurred mainly at facility B from 1950 to 1975. Liver function tests were infrequently abnormal among anti-HDV-positive clients. CONCLUSIONS Results show widespread hepatitis D virus infection in our institutionalized population and suggest that transmission occurred mainly in the past at the overcrowded facility B. The low prevalence of laboratory evidence of chronic liver disease in the anti-HDV-positive clients may be explained by increased mortality among those originally infected from 1950 to 1975.Abstract Objective:To define the epidemiology and clinical manifestations of hepatitis D virus infection in an institutionalized population. Design:A case-control study of hepatitis B carriers with...

An Outbreak of Pseudobacteremia Caused by Enterobacter cloacae from a Phlebotomist's Vial of Thrombin

In a 15-day period, seven patients in a small hospital each had one blood culture positive for Enterobacter cloacae. None of the seven patients was septic. All seven positive culture specimens had been obtained by phlebotomist A, who also had obtained 13 negative culture specimens in the same period. Seven other phlebotomists had drawn 69 blood samples for culture during the same period; none had yielded any microorganism (p = 0.00001). Vials of thrombin, routinely used to coagulate blood specimens for chemical analysis, had been carried on the phlebotomy trays. We observed that phlebotomist A occasionally spilled drops of the viscous thrombin on her finger during the procedures. Culture of the thrombin on her tray yielded E. cloacae. No further cases of E. cloacae bacteremia occurred after she stopped drawing blood for culture and the thrombin on her tray was removed from use.