Fast food arthritis--a clinico-pathologic study of post-Salmonella reactive arthritis.

OBJECTIVE: To study the clinical presentation, immunogenetics, and serum immune response to lipopolysaccharide (LPS) in a cohort of patients with post-Salmonella reactive arthritis (ReA). METHODS: A validate ReA screening questionnaire (Quest 2) was mailed to 919 individuals reporting symptoms of gastroenteritis to the health department after eating at a single restaurant. Three hundred twenty-one persons returned questionnaires; 170 reported symptoms outside the gastrointestinal tract; 23 of those 170 reporting persistent joint symptoms were seen 4 to 16 weeks after the outbreak and 5 of the 23 were seen in followup 12 to 20 weeks later. Clinical features, HLA Class I typing, serum soluble CD8 levels, and serum antibodies to gram negative LPS by ELISA were determined. RESULTS: Joint complaints were reported more frequently by individuals with a longer duration of diarrhea. Upper extremity joints were frequently involved, and 66% reported one or more extraarticular symptoms of Reiter's syndrome. Three of 5 typed individuals were HLA-B27 positive, including 3 of the 4 most severely involved. Serum soluble CD8 levels correlated poorly with disease activity measured either clinically or by C-reactive protein. Antibodies to Klebsiella and Shigella LPS rose over time, while antibodies to Salmonella LPS fell. CONCLUSION: The clinical picture of post-Salmonella ReA is less stereotyped than often assumed, although severity correlated with HLA-B27 status. The association of joint symptoms with duration of diarrhea and the kinetics of the anti-LPS antibody response support the hypothesis that abnormal gut permeability plays a role in the pathogenesis of post-Salmonella ReA.

Erythromycin.

Erythromycin is the only macrolide antibiotic to have gained widespread use in the United States. Introduced in 1952, it rapidly gained a popularity that it enjoys to this day. Numerous other antimicrobial agents have been marketed since that time: Whole new classes of antibiotics, both natural and synthetic, have been discovered, studied, and released for general use. Many of these newer agents boast a broader spectrum of antimicrobial activity, yet erythromycin's place in the clinician's arsenal is unthreatened because erythromycin remains the drug of first choice for a number of pathogens against which the new drugs are inactive. It is one of the safest antibiotics available for use today and when used against susceptible organisms and in indicated clinical situations, its effectiveness is unquestioned.

In vitro activity of Ro 23-6240, a new fluorinated 4-quinolone.

The in vitro activity of Ro 23-6240 (AM833), 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-7(4-methyl-1-piper azinyl) quinolone-3-carboxylic acid, was compared with those of norfloxacin, enoxacin, ofloxacin, and ciprofloxacin. Ro 23-6240 inhibited the majority of Enterobacteriaceae isolates at a concentration of less than or equal to 0.5 microgram/ml. It was especially active against Shigella sp., Salmonella sp., Escherichia coli, and Yersinia enterocolitica, with an MIC for 90% of the strains of less than or equal to 0.12 microgram/ml. The MIC for 90% of the strains was 1 microgram/ml for Serratia marcescens and 8 micrograms/ml for Pseudomonas aeruginosa. Staphylococcus aureus isolates, including methicillin-resistant strains, were inhibited by less than or equal to 1 microgram/ml. Streptococcal and anaerobic species were inhibited by 8 to 16 micrograms/ml. Ro 23-6240 inhibited beta-lactamase-producing bacteria resistant to broad-spectrum cephalosporins. The overall activity of Ro 23-6240 was similar to those of enoxacin, norfloxacin, and ofloxacin, but less than that of ciprofloxacin. The frequency of spontaneous resistance was low, although resistant bacteria could be isolated by repeated subculture. The activity of Ro 23-6240 was decreased in the presence of magnesium at concentrations similar to those present in urine.

Ticarcillin plus clavulanic acid in the treatment of pneumonia and other serious infections.

Clavulanic acid is a potent inhibitor of bacterial beta-lactamases, and ticarcillin is a potent antipseudomonal penicillin. The combination of ticarcillin disodium and clavulanate potassium provides an excellent spectrum of activity against the majority of bacterial pathogens responsible for serious infections in both normal and abnormal hosts. Eighteen courses of therapy were administered to 16 patients; 35 percent of the patients were in poor or critical condition, and all but one had severe underlying disease. Thirteen separate episodes of pneumonia were treated, of which nine were in patients with cystic fibrosis, and 11 involved Pseudomonas aeruginosa. Of the 13 cases of pneumonia, 11 showed clinical cure or improvement, whereas only three showed bacteriologic cure. Of the four nonpulmonary cases, three showed clinical improvement or cure, and one showed a bacteriologic cure. In two patients, phlebitis developed at the site of intravenous infusion. The combination of ticarcillin and clavulanic acid is safe and effective therapy for pneumonia in anatomically compromised hosts.

The pharmacokinetic and bactericidal characteristics of oral cefixime.

The pharmacokinetics of cefixime (FK 027), a broad-spectrum cephalosporin, were assessed in 12 normal subjects after single oral doses of 50, 100, 200, and 400 mg. Mean peak serum concentrations were 1.02, 1.46, 2.63, and 3.85 micrograms/ml after the four respective doses. Respective mean serum levels at 12 hours were 0.16, 0.33, 0.72, and 1.13 micrograms/ml. Volumes of distribution averaged 0.1 L/kg body weight, and the elimination t1/2 was 3 hours for all doses. The AUC was 7.01, 11.4, 22.5, and 36.4 micrograms X hr/ml for the four doses, respectively. Serum clearance averaged 0.4 mg/min/kg and mean 24-hour urinary recovery was 21%, 19%, 20%, and 16% for the four respective doses. Serum bactericidal titers at 4 hours exceeded 1:16 for Streptococcus pneumoniae, S. pyogenes, Hemophilus influenzae, and Branhamella catarrhalis. Urine bactericidal titers exceeded 1:8 for Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae resistant to the available oral cephalosporins.

The pharmacokinetics and serum and urine bactericidal activity of ciprofloxacin.

Ciprofloxacin is an investigational quinolone agent possessing an impressive antibacterial spectrum. Its pharmacokinetics were studied in six volunteers after 250-mg and 500-mg single oral doses, and its bactericidal activity compared to that of trimethoprim-sulfamethoxazole given to the same volunteers. Mean peak serum levels were 1.45 micrograms/mL and 2.46 micrograms/mL for 250-mg and 500-mg doses, and time to peak was 1 and 1.3 hours. The 12-hour levels were 0.12 micrograms and 0.22 microgram. Half-life (T1/2)alpha were 0.32 and 0.43 with T1/2 beta were 3.97 and 4.15 and volume of distribution (area) were 80L and 90L, respectively. Area under the concentration curve (AUC) was 5.65 h X micrograms/mL and 10.37h X micrograms/mL. Serum clearance was 23L for both doses. Approximately 49% of the 250-mg dose and 43% of the 500-mg dose was recovered in the urine. Bactericidal levels were determined against clinical isolates. Sera at 1.5 hours after the 500-mg dose averaged bactericidal levels of 1:20 or better for an Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and beta-lactamase producing Haemophilus influenzae and Branhamella catarrhalis. Urinary bactericidal levels at eight to 12 hours were greater than or equal to 1:157 for E coli, K pneumoniae, gentamicin-piperacillin resistant P aeruginosa, Staphylococcus aureus, and 1:20 for Streptococcus faecalis. Serum bactericidal levels were superior, and urine bactericidal levels were superior or equal to the bactericidal levels obtained with trimethoprim-sulfamethoxazole.(ABSTRACT TRUNCATED AT 250 WORDS)

The pharmacology of orally administered ciprofloxacin.

Ciprofloxacin pharmacokinetics were studied in 6 volunteers after 250 and 500 mg single oral doses. Mean peak serum levels were 1.45 micrograms/ml and 2.5 micrograms/ml for 250 and 500 mg doses. The 12-h levels were 0.12 micrograms and 0.22 micrograms. T1/2 alpha values were 0.32 and 0.43 h; T1/2 beta was 4 h and Vd (area) values were 80L and 90L for the two doses respectively. AUC was 5.65 h. micrograms/ml and 10.37 h. micrograms/ml. Serum clearance was 23L for both doses. Approximately 49% of the 250 mg dose and 43% of the 500 mg dose was recovered in the urine. Ciprofloxacin's in vitro activity and human pharmacology should permit a twice or once-daily dosing schedule for systemic infections due to most Enterobacteriaceae, Haemophilus, Branhamella and Pseudomonas and S. aureus, and once-daily doses for urinary and gastrointestinal infections.