Meropenem monotherapy for the treatment of hospital-acquired pneumonia: results of a multicenter trial.

The efficacy and tolerability of meropenem as empirical treatment in patients with hospital-acquired pneumonia was determined in a prospective, open-label, non-randomized trial. Patients from 28 centers in the USA received meropenem 1 g every 8 h intravenously. Of 255 patients enrolled, 111 were evaluable for efficacy, including 60 patients with ventilator-associated pneumonia. At end of treatment 74% of patients had a satisfactory clinical response and 64% had this response at follow-up, which could last up to 28 days after treatment. In patients with ventilator-associated pneumonia, a satisfactory clinical response was observed in 68% at the end of treatment and 63% at follow-up. The overall satisfactory response rate for individual pretreatment pathogens ranged from 65% to 100%. This study demonstrates that meropenem monotherapy is effective and well tolerated for patients with hospital-acquired pneumonia, including a subgroup of patients with ventilator-associated pneumonia.

Infections in patients with end-stage renal disease. An overview.

One of the best kept secrets in medicine is the problem of infections in patients with end-stage renal disease. The prescription of chronic hemodialysis has not reduced the problem of infection; it has only changed the paradigm. Dialysis superimposes myriad new problems onto patients with relentless deterioration from underlying multisystem disease and poor wound healing. All end-stage renal disease and transplant programs require the input from an individual with the specialized knowledge of laboratory diagnosis, pharmacokinetics of antibiotics, antibiotic choice, antimicrobial resistance, infection control, and infection prevention. This article gives an overview of some of the complexities of infectious problems experienced by this unique biological model.

Out-patient parenteral antibiotic therapy (OPAT): clinical outcomes and adverse events.

A chart review was conducted of patients in a program featuring self directed, home infusion of antibiotics for serious infections utilizing an out-patient medical office for teaching, mixing of drugs, and monitoring of patients. 302 courses of out-patient parenteral antibiotic therapy (OPAT) were administered to 221 patients. Therapy was successful in 94% of the episodes. Objective adverse events were noted in 25% of patients. To maximize the chance for a successful outcome, treatment plans should be individualized and structured to include systematic monitoring for adverse effects.

Extended degree and continuing education preferences of California public health professionals.

The authors conducted a randomized mail survey of members of six public health organizations in California. The purpose of the survey was to assess public health practitioner interest and resources available to participate in public health extended degree programs and public health continuing education (CE). The response rate was 52 percent (N = 262). Three CE topics of greatest interest to public health professionals were health policy, computer applications, and community-based interventions. Respondents were interested in both distance-based and on-site learning formats.

Empiric treatment of hospital-acquired lower respiratory tract infections with meropenem or ceftazidime with tobramycin: a randomized study. Meropenem Lower Respiratory Infection Group.

OBJECTIVE: To evaluate the efficacy and tolerability of intravenous empiric treatment with meropenem compared with ceftazidime-tobramycin in patients with hospital-acquired lower respiratory tract infections. DESIGN: Prospective, nonblind, randomized trial. SETTING: Multicenter trial conducted at 22 centers. PATIENTS: Two hundred eleven patients were enrolled and 121 were evaluable for the analysis of both clinical and bacteriologic efficacy. INTERVENTIONS: One hundred four patients were randomized to receive intravenous meropenem (1000 mg) every 8 hrs and 107 patients were randomized to receive intravenous ceftazidime (2000 mg) plus tobramycin (1 mg/kg) every 8 hrs. Sixty-three meropenem-treated patients and 58 ceftazidime-tobramycin-treated patients were eligible for the analysis of clinical and bacteriologic efficacy. In the ceftazidime-tobramycin group, 32 (55%) evaluable patients received more than six doses of tobramycin, 24 (41%) received six doses or fewer, and two (3%) did not receive any tobramycin. MEASUREMENTS AND MAIN RESULTS: The analysis of efficacy was based on the clinical and bacteriologic responses at the end of treatment. Satisfactory clinical responses occurred in 56 (89%) of 63 of the meropenem-treated patients and in 42 (72%) of 58 of the ceftazidime-tobramycin-treated patients (p = .04). Corresponding bacteriologic response rates were 89% and 67%, respectively (p = .006). The frequency and profile of drug-related adverse events was similar across treatment groups. Seizures were reported in three meropenem-treated patients, but these seizures were considered by the investigator to be unrelated to treatment. CONCLUSIONS: Meropenem is well tolerated and more efficacious than the combination of ceftazidime and tobramycin for the initial empiric treatment of hospital-acquired bacterial pneumonia.

A continuing education preference survey of public health graduates.

Continuing education (CE) is a vital component in strengthening the public health work force, and its importance has been emphasized by the Institute of Medicine and the Council for Education in Public Health. A CE preference survey was undertaken of alumni of the University of California, Berkeley, School of Public Health (UCB-SPH). Questionnaires were mailed to a one-third random sample of 1,500 graduates from 1981-1992 who currently reside in U.S. Department of Health and Human Services (HHS) Region IX. A response rate of 57% was achieved. Results of the survey show that CE activities are highly desired among respondents. Overall, 58% of respondents prefer a half-day to one-day seminar format during regular business hours, as opposed to night classes. They prefer a traditional didactic classroom presentation that is within one hour's automobile travel. The optimal setting for CE courses would be at the University of California, Berkeley, or in-house at their institution. Subject areas of interest noted by respondents are health policy development, communication in public health, community involvement, and research. Schools of public health may respond to the CE needs of their alumni through a variety of channels, including the mainstreaming of CE as part of a school's teaching responsibility, special seminars or institutes, extension courses through the larger university system, distance-based learning, and through a separately funded for-profit CE activity.

Multiple-dose study of imipenem/cilastatin in patients with end-stage renal disease undergoing long-term hemodialysis.

Multiple doses of imipenem/cilastatin were administered to patients with end-stage renal disease undergoing long-term hemodialysis. Schedules of 250 mg every six hours, 500 mg every six hours, and 500 mg every 12 hours were studied. Five hundred mg every 12 hours was the most efficient schedule that maintained effective trough antibiotic activity. Twelve volunteers including two patients with clinical infections using the dose schedule of 500 mg every 12 hours received imipenem/cilastatin for two to 14 days without any notable clinical side effects. Imipenem peak and trough concentrations averaged 29 +/- 5 micrograms/ml and 10 +/- 3 micrograms/ml, respectively. No accumulation of imipenem occurred during the trial. Cilastatin peak and trough concentrations were 89 +/- 38 micrograms/ml and 70 +/- 27 micrograms/ml, respectively. The plasma concentration of cilastatin increased with each dose until the next hemodialysis session.

Ceftriaxone pharmacokinetics in patients with various degrees of renal impairment.

The effects of renal impairment on the pharmacokinetics of ceftriaxone in humans were examined after intravenous infusion of a 1-g dose over 15 min to 30 renally impaired patients. The study included 12 dialysis patients and 18 patients with severe, moderate, or mild renal impairment. Plasma and, where appropriate, urine and dialysate samples were collected at predetermined times and analyzed for ceftriaxone by high-pressure liquid chromatography. The elimination half-life (group mean ranged from 11.7 to 17.3 h) and plasma clearance (group mean ranged from 529 to 705 ml/h) did not correlate linearly with creatinine clearance. The renal clearance and fraction of dose excreted unchanged in urine were related linearly, however weakly, with creatinine clearance. Ceftriaxone was not removed from plasma to a significant extent during hemodialysis. The half-life was prolonged twofold, the plasma clearance was lowered less than 50%, and the volume of distribution was relatively unchanged in renally impaired patients compared with young or elderly healthy subjects with normal renal function at an equivalent dose. Since these changes are moderate, adjustment in the dosage regimen of ceftriaxone for patients with impaired renal function should not be necessary when ceftriaxone dosage is 2 g or less per day (2 g every 24 h or 1 g every 12 h). It was reported that the elimination half-life of ceftriaxone is substantially prolonged in a small percentage of patients with end-stage renal disease maintained on hemodialysis. Therefore, plasma concentrations of ceftriaxone should be monitored in dialysis patients to determine whether dosage adjustments are necessary.

Pharmacokinetics of ceforanide in patients with end stage renal disease on hemodialysis.

The pharmacokinetics of ceforanide were evaluated in 11 patients with end stage renal disease (creatinine clearance less than 5 ml/min). A single intravenous dose of 750 mg/m2 produced peak plasma concentrations of 123 +/- 29 microgram/ml. The plasma half-life (T 1/2) of the drug was 19.1 +/- 2.5 h. A 5.5 h hemodialysis session removed 53% of the drug and reduced the T 1/2 to 5 +/- 0.7 h. Plasma concentrations greater than 10 microgram/m2 were maintained without adverse effects with a 1.5-g/m2 dose administered three times a week for 2 weeks.

Laboratory evaluation of amikacin susceptibility testing by the AutoBac I system.

A total of 319 clinical isolates were compared for amikacin susceptibility by AutoBac I and Bauer-Kirby disk diffusion methods. There was an overall agreement of 98.5% between AutoBac I and Bauer-Kirby. An additional 23 strains resistant to amikacin, obtained from Bristol Laboratories, registered a 65% overall agreement. The sensitivity readings differed between the two methods for 13 organisms: 11 were minor discrepancies, intermediate by one of the two methods, and 2 were very major discrepancies, resistant by disk diffusion and susceptible by AutoBac I.

Pharmacokinetics of cefaclor in patients with end stage renal disease and during hemodialysis.

A single 1.0-g dose of cefaclor administered to patients with stable end stage renal disease whose creatinine clearances were <5 ml/min produced a mean peak serum concentration of 48.3 +/- 19.8 mug/ml. The half-life was 2.3 +/- 0.3 h. Hemodialysis shortened the half-life of a similar dose to 1.6 +/- 0.3 h. Approximately one-third (340 mg) of the administered drug was recovered in the dialysate. Multiple doses of 500 mg every 6 h between hemodialysis sessions produced effective serum concentrations and no bioassay evidence of drug accumulation.

Hemodialysis-associated infections: treatment with cephapirin.

Large doses of cephapirin (50 mg/kg) administered during the first and last half hours of routine hemodialysis produced effective antimicrobial serum concentrations for 48 h. Repetitive administration during five successive hemodialysis sessions did not result in accumulation or accelerated metabolism of cephapirin. Ten infectious episodes in nine patients were treated in this manner with good clinical results and no toxicity.

Hyperendemic subperiodic Bancroftian filariasis: a search for clinical and immunological correlates of microfilaraemia.

A study was carried out in the Kingdom of Tonga, an area of hyperendemic Bancroftian filariasis, to determine whether correlations could be made between microfilaraemia, as diagnosed by membrane filter concentration, and immunological (skin test, immunoglobulin levels) or clinical findings. There was no relationship between the presence or degree of microfilaraemia and any clinical manifestation or skin test reaction. The skin test positivity rate for microfilaraemic and amicrofilaraemic individuals was approximately the same for all age groups. Among those aged 0 to 4 years, 48% of microfilaria positives were negative in the skin test. The highest average IgG and IgE levels were found in the groups with the highest microfilarial densities, i.e., in children with a history of fever and in adults with a history of lymphangitis/lymphadenitis. Over a period of a year, the microfilarial density changed significantly in 18 (34%) of 53 adults.