Piperacillin as a single agent was compared in a prospective randomized trial with carboxypenicillin-aminoglycoside combinations in empirical therapy of serious bacterial infections. The difference in the clinical response rates with piperacillin (77% of 26 infection episodes) and combination therapy (75% of 24 infection episodes) were not statistically significant. Fewer adverse effects occurred in the piperacillin-treated group (42%) than in the combination-treated group (71%) (P = 0.0399 by Fisher's exact test), although neither nephrotoxicity nor hypokalemia alone was significantly less frequent in patients receiving piperacillin. However, the emergence of resistant organisms during therapy was more frequent among patients receiving piperacillin alone (42% of patients) than among patients receiving combination therapy (17% of patients) (P = 0.0465 by Fisher's exact test). Moreover, emergence of resistance accounted for 5 of 9 patients with treatment failure, superinfection, or both when piperacillin was used as a single agent, compared with 2 of 10 similar patients in the combination group (P = 0.1299 by Fisher's exact test). The use of piperacillin as a single agent in the treatment of serious bacterial infections is not advocated, and the addition of an aminoglycoside to prevent emergence of resistance during empirical therapy of such infections is strongly recommended.

New fluoroquinolones have generally been well tolerated. In a double-blind evaluation of oral fleroxacin, using 400, 600, or 800 mg once daily for 7 days in an ambulatory setting for treatment of uncomplicated genital infections, we encountered unexpectedly high rates of adverse reactions. The objective of this analysis was to determine whether any factors in addition to dose could be found to account for our observations. Adverse Fluoroquinolones have generally been considered to be relatively safe antimicrobial agents (7, 9). The most frequently reported adverse reactions were gastrointestinal (2.9 to 5.6%), central nervous system (0.9 to 1.7%), and skin (0.4 to 2.2%) reactions, with overall rates of adverse reactions of 4 to 8% (7). Reactions were reversible, not dose dependent, and similar among different fluoroquinolones (7).Our own experience with norfloxacin in a sexually transmitted disease clinic setting was very favorable (3). However, not all quinolones have been well tolerated, and adverse reactions have prevented marketing of some (8,12). In a double-blind clinical trial of fleroxacin, using 400, 600, and 800 mg once daily for 7 days, adverse reactions were dose related, frequent at higher doses, and often reported by the patient as being severe. Especially frequent or troublesome were insomnia, bad dreams or nightmares, and photosensitivity reactions resulting in desquamation. Consequently, in this study we attempted to ascertain what factors might have accounted for our observations. MATERIALS AND METHODSStudy population and protocol. Men and women 18 years of age and older who presented to the Vancouver and Calgary Sexually Transmitted Disease Clinics were eligible for the study. Entrance criteria and study design are described in our companion paper (4). At the initial visit, individuals completed a detailed questionnaire about symptoms, sexual history, prior use of antimicrobial agents, use of other medications (prescribed, over the counter, and recreational), and exclusion criteria. After the initial evaluation, all were then given medication to be taken with or immediately after meals at a similar time each day. All took * Corresponding author.four identical tablets daily, of which two, three, or four contained active medication. Thus, they received 400, 600, or 800 mg daily for 7 days. The patients and the investigators were blind as to the regimen received.Subjects were specifically warned not to use antacids.They were also warned that caffeine might interact unfavorably with fleroxacin. In the last two-thirds of the study, they were urged to avoid sun exposure or else to take more precautions than usual, including use of sunscreens, long sleeves, and hats.

The antimicrobial susceptibility of a low-laboratory-passage, slow-growing, genital Chlamydia trachomatis strain was studied by five different procedures with the use of McCoy cells pretreated with 5-iodo-2-deoxyuridine. The effects of antimicrobial agents when added to cultures on day 0 or day 2 after inoculation with C. trachomatis and the effects of washing and reincubating treated cultures in antimicrobial-free media were investigated. Tetracycline and erythromycin inhibited C. trachomatis growth at concentrations attainable in human serum, although their actions were reversible and significantly higher concentrations were needed to "cure" 48-h infected cultures. On a weight basis, spectinomycin was relatively ineffective in inhibiting C. trachomatis growth. The minimal inhibitory concentration of penicillin measured by our assay procedures was higher than that reported by other investigators. The five assay procedures used in this study were reproducible, and our results indicate that we can obtain more pertinent information about the efficacy of an antimicrobial agent in controlling C. trachomatis growth by using a combination of these assays than by simple minimal inhibitory concentration determinations, as had been previously described by other investigators. In addition, we failed to demonstrate changes in tetracycline susceptibility,of C. trachomatis isolates from two patients who had received tetracycline therapy.In vitro studies on the antimicrobial susceptibility of Chiamydia trachomatis in cell culture systems have been described (1-3, 8, 11). These studies often utilized fast-growing laboratoryadapted C. trachomatis strains, usually assayed inhibitory effects of drugs by the concurrent addition of drugs and C. trachomatis, and did not assay for the noninfectious reticulate body formn of C. trachomatis.In this study we examined the effects of tetracycline, erythromycin, spectinomycin, and penicillin on C. trachomatis in a 5-iodo-2-deoxyuridine (IUdR)-treated McCoy cell system. The bacteriostatic and bactericidal effects of these antimicrobial agents were measured by five different assay procedures. We attempted to parallel the in vivo situation by (i) using a nonlymphogranuloma venereum C. trachomatis strain that is slow growing, in low laboratory passage, and of a serotype common to United States isolates, (ii) treating already-infected cultures since, in vivo, antimicrobial agents must act on preestablished infections, and (iii) removing antimicrobial agents and reincubating cultures after treatment because antimicrobial agents are metabolically cleared in vivo and it is possible that organisms could survive in the reticulate body form and develop to the infective stage after removal of the antimicrobial agents. In addition to the one test strain used in all experiments, we also tested the tetracycline susceptibility of post-tetracycline-treatment isolates from two individuals. MATERIALS AND METHODS Celis. McCoy cells (mouse heteroploid cells) (4)were carried in antibiotic-free medium for at leas...

Previous treatment with any antibiotic, and not only a FQ, is associated with a delay in TB diagnosis.

The stimulus for the migration of polymorphonuclear leukocytes (PMNs) in acute chlamydial infection was studied in vitro by examining the chemotaxigenic effect of L2 and DE Chlamydia trachomatis elementary bodies (EB) upon the plasma of three healthy donors. In each individual experiment, chemotactic response was assessed with PMNs and plasma from the same respective donor, and no specific antibodies against C. trachomatis were detected in the plasma of any donor. Chemotaxis was observed in an agarose plate assay and was quantitated as the chemotactic differential, or CD (directed migration of PMNs minus random movement of PMNs). For each donor, the mean CD was significantly greater (P less than 0.005) when plasma preincubated for 2 h with L2 EB was used as the chemoattractant than when (i) plasma alone, (ii) plasma preheated to 56 degrees C for 30 min before incubation with L2 EB, or (iii) L2 EB in phosphate-buffered saline (PBS) was used as the potential chemoattractant. Similarly, in the one donor in whom DE EB were studied, the mean CD was also significantly greater (P less than 0.005) for plasma preincubated with DE EB as compared with (i) plasma alone or (ii) DE EB in PBS. Complement activation by C. trachomatis EB was assessed by radioimmunoassay for C5a des-arginine in all chemoattractant preparations used in the chemotaxis assay. Mean C5a des-arginine levels were high in plasma samples preincubated with L2 EB (171.00 +/- 10.64, 107.00 +/- 4.76, and 89.70 +/- 1.74 ng per ml) or DE EB (37.40 +/- 15.76 ng per ml) but were undetectable (less than 4.0 ng per ml) in (i) plasma alone, (ii) preheated plasma incubated with L2 EB, and (iii) PBS containing L2 EB. Thus, L2 EB and DE EB of C. trachomatis exert a chemotaxigenic effect upon normal antibody-negative plasma, and this effect is at least in part a result of complement activation and generation of the potent chemotaxin C5a.