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Pseudomonas aeruginosa causes serious infections whose outcome is highly dependent on antimicrobial therapy. The goal of this study was to predict the relative efficacies of three ciprofloxacin dosing regimens for P. aeruginosa infection using clinical outcome-based Monte Carlo simulations (MCS) with "real patient" demographics, pharmacokinetics, MICs, and pharmacodynamics (PDs). Each cohort consisted of 1,000 simulated study subjects. Three ciprofloxacin dosing regimens were studied, including (i) the recommended standard dose of 400 mg given intravenously (i.v.) every 12 h (q12h), (ii) the recommended high dose of 400 mg i.v. q8h, and (iii) a novel, PD-targeted regimen to attain a fAUC/MIC value of >86. Probability of target attainment (PTA) and probability of cure (POC) were determined for each regimen. POC with the standard dose was at least 0.90 if pathogen MICs were < or =0.25 microg/ml but only 0.59 or 0.27 if MICs were 0.5 or 1 microg/ml, respectively. Predicted cure rates in these MIC categories were significantly higher at 0.72 and 0.40 with the high dose and 0.91 and 0.72 with the PD-targeted regimen(P < 0.0001). Analyses based on the local susceptibility profile produced PTA and POC estimates of 0.44 and 0.74 with the standard ciprofloxacin dose, 0.58 and 0.81 with the high dose, and 0.84 and 0.93 with the PD-targeted regimen, respectively. In conclusion, as demonstrated by clinical outcome-based MCSs, the highest recommended ciprofloxacin dose of 400 mg i.v. q8h should be used in the treatment of P. aeruginosa infection to improve PD target attainment and clinical cure. However, even this appears ineffective if pathogen MICs are 1 mug/ml, warranting the consideration of a lower MIC breakpoint, < or =0.5 microg/ml. more...

Mycobacterium branderi, a potential human pathogen first characterized in 1995, has been isolated from respiratory tract specimens. We report here a case in which M. branderi was the only organism isolated upon culture from a hand infection. This isolate, along with a second isolate from a bronchial specimen, was subjected to conventional identification tests for mycobacterial species. Further analysis by high-performance liquid chromatography (HPLC) of mycolic acids and 16S rRNA gene sequencing was performed, and the antibiotic susceptibility profile was determined for both strains. Biochemical tests and the HPLC pattern were consistent with that of M. branderi and M. celatum, which are very similar. The 16S rRNA gene sequence of both strains corresponded to that of M. branderi and enabled us to confidently differentiate this organism from other closely related species such as M. celatum. This contributes to a further understanding of the status of this species as a potential human pathogen as well as illustrating the need for molecular diagnostics as a complementary method for the identification of rare mycobacterial species. more...

Clostridium difficile-associated diarrhea (CAD) is a very common nosocomial infection that contributes significantly to patient morbidity and mortality as well as to the cost of hospitalization. Previously, strains of toxin A-negative, toxin B-positive C. difficile were not thought to be associated with clinically significant disease. This study reports the characterization of a toxin A-negative, toxin B-positive strain of C. difficile that was responsible for a recently described nosocomial outbreak of CAD. Analysis of the seven patient isolates from the outbreak by pulsed-field gel electrophoresis indicated that this outbreak was due to transmission of a single strain of C. difficile. Our characterization of this strain (HSC98) has demonstrated that the toxin A gene lacks 1.8 kb from the carboxy repetitive oligopeptide (CROP) region but apparently has no other major deletions from other regions of the toxin A or toxin B gene. The remaining 1.3-kb fragment of the toxin A CROP region from strain HSC98 showed 98% sequence homology with strain 1470, previously reported by M. Weidmann in 1997 (GenBank accession number Y12616), suggesting that HSC98 is toxinotype VIII. The HSC98 strain infecting patients involved in this outbreak produced the full spectrum of clinical illness usually associated with C. difficile-associated disease. This pathogenic spectrum was manifest despite the inability of this strain to alter tight junctions as determined by using in vitro tissue culture testing, which suggested that no functional toxin A was produced by this strain. more...

Ampicillin, trimethoprim-sulfamethoxazole, mecillinam, nitrofurantoin, and ciprofloxacin mean resistance rates for 2,000 urinary tract isolates collected from outpatients across Canada in 1998 were 41.1, 19.2, 14.7, 5.0, and 1.8%, respectively. For Escherichia coli isolates alone (n = 1,681) comparable rates were 41. 0, 18.9, 7.4, 0.1, and 1.2%, respectively. The majority of E. coli isolates resistant to ampicillin, trimethoprim-sulfamethoxazole, or ciprofloxacin were susceptible (MIC, <16 microg/ml) to mecillinam. more...

A microculture plaque neutralization test is described for California-group arboviruses that is as precise and quantitative as the standard test conducted in 60-mm petri dishes. It was shown that there was no significant between-panel or between-day variation in determinations and that a single pipette could be used for all serum-dilution levels within a titration without inoculum carry-over effect. The experimental protocol and statistical methods used produce 50% neutralization end points that meet the assumptions of parametric statistics. This permits the power and versatility of the analysis of variance to be exploited in testing for treatment effects in serological and immunological studies with viruses. more...

Intravenous cefazolin and cefoxitin were compared in a prospective randomized trial in infections where the suspected pathogen was expected to be susceptible to both antibiotics. In the cefazolin group (12 patients) the diagnosis was pneumonia in 4, including 2 with pneumococcal bacteremia, soft tissue infection in 5, Staphylococcus aureus bacteremia in 1, acute pyelonephritis in 1, and disseminated gonococcal infection in 1. In the cefoxitin group (10 patients) the diagnosis was pneumonia in 4, including 2 with pneumococcal bacteremia, soft tissue infection in 4, acute pyelonephritis in 1, and disseminated gonococcal infection in 1. In the cefazolin group receiving an evaluable course of therapy, a good clinical response was seen in 10 of 11 patients, and a bacteriological response was seen in 5 of 7. Cefazolin failed to eradicate S. aureus bacteremia in 1 patient and S. aureus in a skin ulcer of another patient. All 10 cefoxitin patients had good clinical and bacteriological responses, but in 1 patient S. aureus colonization of a postoperative wound recurred after discontinuation of the drug. Side effects in both groups included skin rash, phlebitis, and elevation of the serum alkaline phosphatase. Both cefoxitin and cefazolin appeared effective in infections caused by susceptible aerobic pathogens with the possible exception of S. aureus, although all 11 strains of S. aureus isolated in this study were susceptible in vitro to both antibiotics. Cefoxitin appeared to be equivalent to cefazolin in efficacy and occurrence of side effects. more...

Introital colonization with Enterobacteriaceae is considered to be one of the principal predisposing factors to recurrent urinary tract infections (UTI) in adult females. One proposed mechanism allowing introital colonization in these patients is the absence of local cervicovaginal antibody. To test this hypothesis, we examined cervicovaginal washings from 22 patients with a history of recurrent UTI and 29 normal controls with no history of UTI for specific local antibody by using indirect immunofluorescence. No significant difference in antibody was found in these populations. Fourteen percent (3/22) of the patients had antibody to their introital Escherichia coli and 34% (10/29) of the controls had antibody to their fecal E. coli. Consequently, a sensitive radioimmunoassay technique was developed to detect cervicovaginal antibody. A solid phase was prepared by coupling to Sepharose 4B a pool of eight serogroups of E. coli which are frequently implicated in UTI. Serial dilutions of cervicovaginal washings were reacted with the solid phase, and the absorbed anti-E. coli antibodies were detected by the uptake of (125)I-labeled anti-human immunoglobulin G (IgG) or anti-human IgA. The antibody levels were quantitated by interpolation on a standard curve prepared by using immunospecifically purified human anti-E. coli antibodies. IgG and IgA levels were measured in washings from 10 colonized patients, 13 non-colonized patients, and 12 controls. There were no significant differences in IgG and IgA levels in cervicovaginal washings among the three groups. In these studies, introital colonization was not related to cervicovaginal antibody. more...