Thomas R. Beam

Persistence of anti-HBs among health care personnel immunized with hepatitis B vaccine.

Health care personnel who received the hepatitis B vaccine (Heptavax-BR, MSD) were followed for persistence of hepatitis B surface antibody (anti-HBs). Response occurred in 135/146 (92.5 percent) vaccinees. Loss of anti-HBs (less than 72 RIA units; 10 S/N) occurred in 35.9 percent during the 36-month surveillance. Stepwise discriminant analysis found age and magnitude of initial antibody level, but not weight-height index, to be predictive of antibody loss over the 36 months. Twenty-four of 27 employees (88.9 percent) who lost anti-HBs responded to a fourth vaccine dose. In contrast, three of eight initial non-responders (37.5 percent) developed antibody after a fourth vaccine dose.

Comparative in vitro activities of teicoplanin, vancomycin, oxacillin, and other antimicrobial agents against bacteremic isolates of gram-positive cocci.

The in vitro activities of teicoplanin and vancomycin were compared with those of six other antimicrobial agents against 460 bacteremic isolates of gram-positive cocci. Teicoplanin was as active as vancomycin but less active than ciprofloxacin against staphylococci. Teicoplanin was the most potent of all agents tested against enterococci and had excellent activity against pneumococci.

Long-term Evaluation of the Hepatitis B vaccine (Heptavax-B) in Hemodialysis Patients

Hemodialysis patients were screened for hepatitis B surface antibody (anti-HBs) prior to immunization at two teaching hospitals. Thirty-one of 111 patients (28%) had baseline sera positive for anti-HBs, while anti-HBs was found in 30 of 420 (7.1%) health care employees (P less than 0.001). A total of 72 hemodialysis patients (mean age, 55.7), received the hepatitis B vaccine (Heptavax-B, Merck Sharp & Dohme, West Point, PA). The responder rates (34 of 72; 47%) and nonresponder (38 of 72; 53%) rates were similar to previous reports. Neither age (P greater than 0.05) nor injection site (P greater than 0.05) appeared to influence results. Nonresponders (16 of 17; 94%) who were given a fourth vaccine dose also failed to mount an antibody response. Of the 34 responders, 18 were followed by serial anti-HBs determinations. Seven transient responders (7 of 18; 39%) were identified, and anti-HBs fell below 10 S/N (sample/control counts per minute) within 12 to 15 months of the first vaccine dose. A fourth dose was administered to this group and it extended the presence of serum anti-HBs (S/N greater than or equal to 10) in four of six patients for another 2, 8, 10, and 15 months, respectively. Antibody persisted but declined over the study period in the remainder of responders followed serially (11 of 18; 61%). When compared with those responders who lost anti-HBs, those with persistent antibody had higher anti-HBs values at 7 (P less than 0.02) and 12 months (P less than 0.005) after the first injection, and were younger (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood, Brain, and Cerebrospinal Fluid Concentrations of Several Antibiotics in Rabbits with Intact and Inflamed Meninges

Because cerebrospinal fluid (CSF) antibiotic levels fail to predict either clinical success or relapse in the treatment of bacterial meningitis, we examined simultaneous antibiotic concentrations in the blood, brain, and CSF of control rabbits and of animals with experimental pneumococcal meningitis. Cefamandole pharmacokinetics were analyzed in detail and compared with those of cephalothin, ampicillin, penicillin G, and tobramycin. After 4 h of continuous intravenous infusion, cefamandole reached concentrations in both brain and CSF in excess of the minimal bactericidal concentration for the test organism and compared favorably with ampicillin and penicillin in achieving bacteriological cure. Cephalothin levels in the central nervous system remained undetectable in both control and infected animals during this time. Tobramycin concentrations were measurable in the CSF, but not in brain tissue in association with an inflammatory stimulus.

High-Performance Liquid Chromatographic Assay of Chloramphenicol in Serum

A new method for the analysis of serum chloramphenicol by reversed-phase, high-performance liquid chromatography (HPLC) is described. The method involves a preliminary extraction of 0.1 ml of serum with ethyl acetate containing an internal standard, chromatography with a reversed-phase C18 microparticulate column with an acetonitrile-acetate buffer mobile phase, and detection by measuring UV absorbance at 270 nm. Assay performance was compared with an existing microbiological assay. The HPLC method demonstrated both increased precision and increased sensitivity. The specificity of the HPLC method was also evaluated. The new method presents an alternative approach to the analysis of clinical specimens.

In vitro activities of ramoplanin, selected glycopeptides, fluoroquinolones, and other antibiotics against clinical bloodstream isolates of gram-positive cocci.

The susceptibilities of 316 gram-positive bacteremic isolates to ramoplanin, vancomycin, and teicoplanin and seven other antibiotics were tested. Ramoplanin demonstrated MICs of < or = 0.25 microgram/ml for at least 99% of Staphylococcus aureus isolates and 100% of coagulase-negative staphylococci tested. For both oxacillin-susceptible and oxacillin-resistant S. aureus and coagulase-negative staphylococci, the activity of ramoplanin surpassed those of both vancomycin and teicoplanin. Ramoplanin and teicoplanin had comparable activities against enterococci and Streptococcus pneumoniae and were superior to vancomycin.

The implications for europe of revised FDA guidelines for clinical trials with anti-infective agents

This article summarizes the current collaborative effort between the US Food und Drug Administration and the Infectious Diseases Society of America for the purpose of generating new General and Disease/Organism Specific Guidelines for the evaluation of anti-infective agents. Examples of proposed changes from draft documents are presented. The final documents may assist European colleagues in their efforts to establish a standardized new drug registration process by 1992. An area of mutual interest is the acceptability of safety and efficacy data from international clinical trials. In the interest of human and financial economies, both US and European Guidelines need to clarify the conditions, or criteria, for the conduct of valid ‘off-shore’ clinical trials.

Assessment of antibiotic efficacy in acute bacterial meningitis.

Currently, antibiotic efficacy in acute bacterial meningitis is evaluated in several stages. First, animals are used to assess antibiotic penetration into cerebrospinal fluid (CSF) in the absence and presence of an inflammatory stimulus. Second, concentrations of drug are correlated to in vitro killing studies. Third, clinical evaluations compare the new drugs to currently available antimicrobics—but drug failures nevertheless occur, e.g. the experiences with cephalosporins and aminoglycosides. We propose that brain tissue levels of antibiotics are an additional parameter to be monitored. Drugs that penetrate the brain substance should yield higher ventricular concentrations than drugs that penetrate the choroid plexus alone. A protective benefit may also be afforded to brain tissue per se. Experience with chloramphenicol, which penetrates the blood‐brain barrier, supports these concepts; so also, do the failures with cephalosporins and aminoglycosides which, despite high CSF concentrations of these agents, afford, evidence that currently monitored parameters are inadequate predictors of therapeutic‐efficacy.

Comparative in vitro susceptibilities of 504 bacteremic isolates to ticarcillin plus clavulanic acid and other antimicrobial agents

A total of 504 clinical bacteremic isolates were tested for susceptibility to ticarcillin-clavulanic acid and 12 other antibiotics. Ticarcillin-clavulanic acid showed superior antibacterial activity compared to penicillin, mezlocillin, piperacillin, ticarcillin, gentamicin, and amikacin against bacteremic isolates of methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis. However, ticarcillin-clavulanic acids activity was inferior to that of vancomycin against methicillin-resistant isolates of S. aureus and S. epidermidis. For Escherichia coli, Klebsiella oxytoca, Proteus mirabilis, Providencia stuartii, and lactose nonfermenting aerobic gram-negative bacilli, the activity of ticarcillin-clavulanic acid surpassed that of mezlocillin, piperacillin, and ticarcillin. Of the antimicrobial agents tested, ticarcillin, piperacillin, ceftazidime, and amikacin were the most active antibiotics against Pseudomonas aeruginosa.

A Comparison of the Safety, Efficacy, and Distribution of Ceforanide and Cephalothin in Coronary Artery Bypass Graft Surgery

Antibiotic prophylaxis in open-heart operations is a widely accepted practice. Introduction of new antibiotics with differences in tissue distribution, spectrum of activity and therapeutic index prompts their evaluation as possible effective prophylactic agents. We compared the distribution, clinical efficacy, and safety of ceforanide with cephalothin as a prophylactic agent in coronary artery bypass graft (CABG) procedures. The results indicated that the intravenous administration of ceforanide at the dose of 1 gm every 12 hours for 2.5 days was equivalent to cephalothin 1 gm every 6 hours for 2.5 days. Serum, muscle, and bone concentrations of ceforanide were significantly greater than those of cephalothin. These concentrations consistently exceeded the minimal inhibitory concentration for Staphylococcus aureus, the major pathogen implicated in wound infections. No toxicty was observed with either antibiotic. Ceforanide merits consideration as a prophylactic antibiotic in CABG operations.