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Growth inhibition of pathogenic yeast isolates by alpha-difluoromethylornithine: an inhibition of ornithine decarboxylase.

A large body of evidence exists suggesting that polyamines can play essential roles in cellular growth and differentiation. We examined the ability of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, the major rate-limiting enzyme in polyamine biosynthesis, to inhibit the growth of Candida albicans, C. tropicalis, and C. parapsilosis. Substantial growth-inhibition was observed for all three species at DFMO concentrations ranging from 1 to 100 mM. C. tropicalis was significantly more susceptible to DFMO than C. albicans or C. parapsilosis. Depletion of cellular polyamine pools was seen in all 3 species following exposure to DFMO and polyamine depletion enhanced the susceptibility of the organisms to DFMO. The action of DFMO was specifically antagonized by exogenous polyamines. These data suggest that polyamines are important in the growth of Candida spp. and that inhibitors of polyamine biosynthesis may be useful as antifungal agents.

Candida↗

A seven-year survey of susceptibility to marbofloxacin of pathogenic strains isolated from pets.

This study, Vetoquinol S.A. epidemiosurveillance, was conducted from 1994 to 2001 in order to determine the susceptibility (by MIC determination) to marbofloxacin (a third generation fluoroquinolone used only in individual administration for animals). Strains from infected pets originated from six European countries. Isolates were collected from urinary infections (Escherichia coli), respiratory infections (Pasteurella multocida), dermatological infections (Staphylococcus intermedius, Pseudomonas aeruginosa) and otitis (S. intermedius, P. aeruginosa). The MIC distribution for each species was the same both before and after the launch of marbofloxacin in 1995. In E. coli, a resistant population was present before the use of marbofloxacin; this resistance was induced by co- or cross-resistance to other antibiotics used previously. Over this period, there was no significant evolution of MIC(90) for any bacterial species studied and no development of resistance was observed. Marbofloxacin was the most active antibiotic against P. multocida isolates and had the lowest MIC. No difference in MIC distribution was seen between the S. intermedius (unimodal distribution) isolated from dermatological infections and those from otitis. This was also true for P. aeruginosa. The use of marbofloxacin was not found to have induced a significant increase or spread of resistant bacteria.

Animals↗

A randomized trial of short-course ciprofloxacin, ofloxacin, or trimethoprim/sulfamethoxazole for the treatment of acute urinary tract infection in women. Ciprofloxacin Urinary Tract Infection Group.

PURPOSE: Bladder infections are very common in otherwise healthy women, and short-course antimicrobial treatment appears effective for many episodes of cystitis. This study reports the results of short-course ciprofloxacin, ofloxacin, and trimethoprim/sulfamethoxazole therapy. PATIENTS AND METHODS: We performed a randomized, double-blind study of the efficacy and safety of a 3-day course of oral ciprofloxacin 100 mg twice daily, ofloxacin 200 mg twice daily, or trimethoprim/sulfamethoxazole 160/800 mg twice daily in women with acute, uncomplicated, symptomatic lower urinary tract infection. RESULTS: A total of 866 patients were enrolled, of whom 688 (79%) were evaluated for the efficacy of treatment (229 treated with ciprofloxacin, 228 treated with trimethoprim/sulfamethoxazole, and 231 treated with ofloxacin). The most frequent reason for exclusion was the failure to identify a pretreatment pathogen. The most commonly isolated pathogen was Escherichia coli (81%). Eradication of the pretreatment pathogen at the end of therapy occurred in 94% of ciprofloxacin, 93% of trimethoprim/sulfamethoxazole, and 97% of ofloxacin-treated patients. At follow-up evaluation at 4 to 6 weeks, recurrence rates (relapse or reinfection) were 11% in the ciprofloxacin, 16% in the trimethoprim/sulfamethoxazole, and 13% in the ofloxacin treatment group. Clinical success at the end of therapy was 93% in the ciprofloxacin, 95% in the trimethoprim/sulfamethoxazole, and 96% in the ofloxacin treatment groups. The frequency of all adverse events was 31% for ciprofloxacin, 41% for trimethoprim/sulfamethoxazole, and 39% for ofloxacin-treated patients (P = 0.03). Premature discontinuation of study drug due to an adverse event was more common in trimethoprim/sulfamethoxazole-treated patients (n = 9) compared with those given ciprofloxacin (n = 2) or ofloxacin (n = 1; P = 0.02). CONCLUSION: Ciprofloxacin, ofloxacin, and trimethoprim/sulfamethoxazole had similar efficacy when given for 3 days to treat acute, symptomatic, uncomplicated lower urinary tract infection in women.

Acute Disease↗

Contemporary in vitro spectrum of activity summary for antimicrobial agents tested against 18569 strains non-fermentative Gram-negative bacilli isolated in the SENTRY Antimicrobial Surveillance Program (1997-2001).

The frequency of occurrence and antimicrobial susceptibility patterns of 18569 non-fermentative Gram-negative bacilli consecutively collected as part of the SENTRY Antimicrobial Surveillance Program were summarized. The isolates were tested by the broth microdilution method in three coordinator laboratories using common reagents and reference methodologies. The most frequently isolated pathogen was Pseudomonas aeruginosa (11968 isolates; 64.5%) followed by Acinetobacter spp. (3468 isolates; 18.7%) and Stenotrophomonas maltophilia (1488 isolates; 8.0%). The lowest resistance rates for P. aeruginosa documented were for amikacin (8%), meropenem (10%) and cefepime (10%), and all fluoroquinolones tested showed similar resistance rates (22-24%). The most active compounds against Acinetobacter spp. were the carbapenems, imipenem (11% resistance) and meropenem (12% resistance) followed by cefepime (31% resistance) and gatifloxacin (32% resistance). Very few compounds showed reasonable in vitro activity against S. maltophilia, with the most active antimicrobial agents being trimethoprim/sulphamethoxazole, gatifloxacin and levofloxacin (5-6% resistance). Resistance surveillance among these organisms remains necessary to guide empirical antimicrobial therapy, especially for these less frequently isolated and difficult to test pathogens.

Bacterial Infections↗

The use of piperacillin/tazobactam (in association with amikacin) in neonatal sepsis: efficacy and safety data.

Piperacillin/tazobactam (P/T) has been used in NICU since 1999 as part of the empirical treatment for presumed sepsis. We studied the microbiological and clinical efficacy and safety of P/T use in newborns with sepsis, using a retrospective analysis of medical records of all newborns treated with P/T (in association with amikacin) during 1999-2003. P/T plus amikacin was used for 353 episodes of presumed sepsis occurring in 252 newborns: 105 episodes occurred in 100 newborns treated for 5-14 d while in 248 (70%) episodes the treatment was discontinued after 2-3 d. 123 pathogens were isolated from the blood cultures (40 in the 5-14 d group and 83 in those treated for 2-3 d only). There were 56 Gram-negative, 55 Gram-positive and 12 Candida spp. isolates. Klebsiella spp. (40%) and E. coli (30%) were the most commonly isolated Gram-negative pathogens; coagulase-negative Staphylococcus (CONS) represented 95% of the Gram-positive pathogens isolated. Pathogen eradication was achieved within 48-72 h of therapy in 93% Gram-negative organisms. There were no clinical, laboratory or cranial ultrasound adverse effects associated with P/T use. We conclude that P/T in association with amikacin is microbiologically and clinically efficacious and safe in the treatment of sepsis in newborns.

Amikacin↗

Loperamide in the treatment of acute gastroenteritis in early childhood. Report of a two centre, double-blind, controlled clinical trial.

Loperamide at a dose of 0 . 2 mg/kg/day was compared with placebo in the treatment of acute infantile gastro-enteritis in hospital-based double-blind clinical trials carried out in parallel in Liverpool, England and Benghazi, Libya. Fifty patients aged one month to four years entered the study in each centre. Rotavirus was the predominant pathogen isolated in both centres. Pathogenic Escherichia coli was cultured from five children in the Liverpool study only. No statistically significant differences were observed in the duration of diarrhoea, length of stay in hospital or weight gain during the first 48 h after admission, between loperamide and placebo groups in either centre. Loperamide, in the dosage used in this study, appears to have no significant effect on the course of acute gastro-enteritis in early childhood. The possibility that these results may reflect specifically on rotavirus infection is discussed. No toxic effects of loperamide were observed.

Body Weight↗