Norfloxacin in the treatment of uncomplicated gonococcal infections.

Norfloxacin, an oral fluoroquinolone antibacterial, is active in vitro against a variety of gram-positive and gram-negative pathogens, including both penicillinase-producing and non-penicillinase-producing strains of Neisseria gonorrhoeae. An earlier study demonstrated that a two-dose regimen of norfloxacin was as effective as standard therapy with spectinomycin for treating gonococcal urethritis, including infections caused by penicillinase-producing organisms. In this randomized study of treatment for uncomplicated gonococcal infection in men and women, three oral treatment regimens were compared: patients received either two doses of norfloxacin (600 mg twice daily), a single dose of norfloxacin (800 mg), or a single-dose ampicillin (3.5 g)/probenecid (1.0 g) regimen (as recommended by the Centers for Disease Control). All three treatment regimens achieved similar cure rates. Although the number of patients treated was too small to yield statistically significant conclusions, it appears that norfloxacin may be slightly better treatment for rectal and pharyngeal gonococcal infections than ampicillin and probenecid. Additionally, norfloxacin was well tolerated in this study. Thus, based on a review of these data, norfloxacin appears to be an alternative, single-dose, oral treatment regimen for uncomplicated gonococcal infection.

Multiple-dose pharmacokinetics of piperacillin and azlocillin in 12 healthy volunteers.

The pharmacokinetic profile of piperacillin and azlocillin after multiple-dose administration to healthy volunteers was studied. Twelve healthy volunteers received either piperacillin 4 g (as the sodium salt) or azlocillin 4 g (as the sodium salt) as a 20-minute infusion every six hours for five doses. After a one-week washout period, subjects received identical treatment with the alternate drug. Serum and urine concentrations of piperacillin and azlocillin were measured using a reversed-phase high-performance liquid chromatographic assay, and the pharmacokinetic analysis of serum concentration-versus-time data was performed using a computerized program. A standard open-model equation for i.v. infusions was used. Mean serum concentrations of piperacillin and azlocillin after dose 5 were 344 +/- 66 micrograms/mL and 414 +/- 86 micrograms/mL, respectively. The terminal elimination half-life of azlocillin (1.1 +/- 0.2 hr) was significantly longer than that of piperacillin (0.75 +/- 0.13 hr) (p less than 0.05). Total body clearance of azlocillin (125 +/- 25 mL/min) was significantly less than that of piperacillin (226 +/- 43 mL/min) after dose 5. Azlocillin showed accumulation between the first and fifth doses. Twelve hours after administration of dose 5, 75% of azlocillin and 57% of piperacillin were excreted unchanged into the urine. In healthy volunteers, azlocillin produced higher and more prolonged serum concentrations than piperacillin after administration of equivalent i.v. doses. Further studies are needed to determine the clinical importance of these observations.

Comparative pharmacokinetics of two multiple-dose mezlocillin regimens in normal volunteers.

Mezlocillin was previously reported to exhibit dose-dependent pharmacokinetics. These reports suggest that it may be possible to administer a relatively large dose at a longer interval than is usual and still achieve therapeutic concentrations in serum. In a randomized, crossover study, we compared concentrations of mezlocillin in serum after a single dose and at steady state in 12 healthy volunteers who received 4 g every 6 h and 5 g every 8 h. A slight, but statistically significant, dose-dependent effect was observed upon the area under the concentration-time curve and total body clearance. No accumulation was observed with either schedule. Although concentrations in serum were higher after the 5-g dose, the more frequent administration of the 4-g dose schedule produced serum concentrations above the MIC for susceptible bacteria for a greater portion of the day. In the absence of clear guidelines from human studies which relate serum concentrations to clinical response, the available data indicate that the more frequent dosage schedule is appropriate for severe infections.

Psychological factors in recurrent genital herpes infection: stress, coping style, social support, emotional dysfunction, and symptom recurrence.

The relationship among stress, coping style, emotional dysfunction, social support, and severity of symptoms (frequency of recurrence, and pain, duration, and bother of recurrences) was investigated in 35 females and 32 males suffering from severe cases of genital herpes infection. Level of emotional dysfunction as measured by the SCL-90 approached two standard deviations above the mean as compared with non-patient normals, and frequency, pain, and bother of recurrences were associated with level of emotional dysfunction. Negative life stress (as measured by the Life Experiences Survey) was unrelated to psychopathology, and was associated only with duration among the symptom measures. Regression analyses indicated that higher frequencies of recurrence and greater discomfort associated with symptoms were associated with an external locus of control orientation and with a tendency to use emotion-focused wishful thinking and to avoid using cognitive strategies to cope with the stress associated with herpes. It was suggested that stress management procedures involving teaching of problem-focused coping strategies and provision of social support would be most effective for this population.

Plasmid-pattern analysis for the differentiation of infecting from noninfecting Staphylococcus epidermidis.

Isolation of Staphylococcus epidermidis from cultures of blood was differentiated from culture contamination by the detection of identical isolates in two or more consecutive cultures from an infected patient. We used plasmid-pattern analysis as a tool for establishing the identity of individual isolates. In a control study of 15 patients with two or more cultures of blood contaminated with S. epidermidis, analysis revealed that none of the isolates had identical plasmid patterns. This reflected the variety of plasmid patterns among colonizing coagulase-negative staphylococci cultured from skin sites of uninfected patients. In contrast, plasmid-pattern identity was seen among sequential or paired S. epidermidis isolates from a given patient in 32 of 36 patients with documented S. epidermidis infection. The plasmid pattern of each set of isolates from patients was unique. Infections included prosthetic-valve endocarditis in 26 patients, cerebrospinal fluid-shunt or ventriculostomy infections in six patients, intravenous-catheter sepsis in two patients, urinary tract infection in one patient, and osteomyelitis in one patient. Plasmid-pattern analysis may therefore be useful in the diagnosis of S. epidermidis infections.

Aspergillus fumigatus endocarditis on a normal heart valve.

We have described an elderly man with no known underlying predisposing systemic or valvular disease who had mitral valve infection and endophthalmitis due to Aspergillus fumigatus. Two-dimensional echocardiography was valuable in detecting fungal vegetations.

Plasmid pattern analysis of Staphylococcal epidermidis isolates from patients with prosthetic valve endocarditis.

The electrophoretic pattern formed by individual bacterial plasmid DNA molecules of differing molecular size was evaluated as an epidemiological marker among isolates of Staphylococcus epidermidis from patients with prosthetic valve endocarditis (PVE). Purified covalently closed circular plasmid DNA was obtained from selected isolates, and 79% of the plasmids were found to be less than 10 megadaltons in size; only these small plasmids were sought in subsequent screening gels. Crude cell lysates obtained by a rapid lysis technique and screened by agarose gel electrophoresis revealed the presence of one or more small plasmids in 54 of 58 (93%) PVE isolates; 79% contained two or more. Among 45 plasmid-containing isolates from cases of sporadic PVE at three institutions there were no identical plasmid patterns, although several isolates differed by a single plasmid. In contrast, among nine isolates from a cluster of cases of PVE in Canada, two groups of three isolates each had identical plasmid patterns. Additional clinical data suggested that these isolates were epidemiologically related. Phage typing distinguished one of the groups with plasmid pattern identity, but not the other, from the three isolates with dissimilar patterns. Plasmid pattern analysis shows promise as an epidemiological marker for clinically important isolates of S. epidermidis.