Multidrug-resistant strains of Shigella dysenteriae type 1 were implicated in three outbreaks and sporadic cases of dysentery in eastern India in 2002 and 2003. After a hiatus of 14 years, this pathogen reemerged with an altered antibiotic resistance pattern. In addition to ampicillin, co-trimoxazole, tetracycline, chloramphenicol, and nalidixic acid, all the recent strains were resistant to norfloxacin, lomefloxacin, pefloxacin, and ofloxacin and showed reduced susceptibility to ciprofloxacin. Pulsed-field gel electrophoresis identified a new clone of S. dysenteriae type 1 that was associated with the recent outbreaks and sporadic cases. Based on the spatial and temporal spread of multidrug-resistant S. dysenteriae type 1, we predict that this clonal type may spread further in this region.
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A 86-year-old woman became psychotic one day after starting treatment with 800 mg norfloxacin daily. Discontinuation and short-term treatment with haloperidol were followed by rapid disappearance of symptoms within two days. Since 1984, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 19 similar reports of which 12 were attributed to norfloxacin, 3 to ofloxacin and 4 to pipemidic acid. The risk appears to be relatively high in the elderly, especially if they have fever, renal dysfunction and a psychiatric history. Lowering the doses may solve this problem provided the bacterial susceptibility is taken into account.
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This study was designed to investigate the prevalence of metallo-β-lactamase (MBL) in Pseudomonas aeruginosa isolates collected from Suez Canal University Hospital in Ismailia, Egypt. Antibiotic susceptibility testing and phenotypic and genotypic screening for MBLs were performed on 147 isolates of P. aeruginosa. MICs were determined by agar dilution method for carbapenem that was ≥2 μg/mL for meropenem. MBL genes were detected by multiplex and monoplex PCR for P. aeruginosa-harbored plasmids. Mutation profile of sequenced MBL genes was screened using online software Clustal Omega. Out of 147 P. aeruginosa, 39 (26.5%) were carbapenem-resistant isolates and 25 (64%) were confirmed to be positive for MBLs. The susceptibility rate of P. aeruginosa toward polymyxin B and norfloxacin was 99% and 88%, respectively. Identification of collected isolates by API analysis and constructed phylogenetic tree of 16S rRNA showed that the isolates were related to P. aeruginosa species. The frequency of blaGIM-1, blaSIM-1, and blaSPM-1 was 52%, 48%, and 24%, respectively. BlaVIM and blaIMP-like genes were 20% and 4% and the sequences confirm the isolate to be blaVIM-1, blaVIM-2, blaVIM-4, and blaIMP-1. Three mutations were identified in blaVIM-4 gene. Our study emphasizes the high occurrence of multidrug-resistant P. aeruginosa-producing MBL enzymes.
The in vitro activities of nine quinolones (seven fluoroquinolones, nalidixic acid, and acrosoxacin) against methicillin-resistant Staphylococcus aureus (MRSA) were compared with those of the glycopeptides teicoplanin and vancomycin. MICs against 160 strains of ciprofloxacin-susceptible (MIC, less than 2.0 micrograms/ml) MRSA and 40 strains of ciprofloxacin-resistant (MIC, greater than or equal to 2.0 micrograms/ml) MRSA were determined. The following MICs for 50% of the strains tested (in micrograms per milliliter) were obtained for ciprofloxacin-susceptible and -resistant strains, respectively: tosufloxacin, 0.06 and 2.0; ofloxacin, 0.25 and 16; ciprofloxacin, 0.5 and 16; pefloxacin, 0.5 and 32; acrosoxacin, 1.0 and greater than 256; enoxacin, 1.0 and 64; fleroxacin, 1.0 and 32; norfloxacin, 2.0 and 64; nalidixic acid, 64 and 512; teicoplanin, 1.0 and 1.0; vancomycin, 2.0 and 2.0. In mutation rate studies using a range of antibiotic concentrations to reflect those achievable in vivo, resistant mutants grew only on plates containing nalidixic acid (rate of mutation to resistance, 10(-7) to 10(-8) and on plates containing low concentrations of ciprofloxacin, enoxacin, and norfloxacin (rate of mutation to resistance, 10(-8) to 10(-9). In time-kill studies, 99.9% killing was found within 8 h for all of the quinolones tested (norfloxacin and nalidixic acid were not tested). Teicoplanin and vancomycin were less rapidly bactericidal. For the clinical isolates of ciprofloxacin-resistant MRSA, different levels and patterns of quinolone resistance were found. Generally, cross-resistance among the fluoroquinolones was complete; however, incomplete cross-resistance did occur with the nonfluorinated quinolone acrosoxacin.
We studied 75 patients (36 males and 39 females), suffering from typhoid fever. 64 patients were treated with ofloxacin and 11 with amikacin, dosage regimens of the two drugs were 300 mg and 300-400 mg twice daily. Clinical effective rate was 100% with ofloxacin and 36.4% with amikacin. A total of 72 strains of salmonella typhi was isolated from all the patients of both groups. Bacteriological elimination rate was 100% with ofloxacin after treatment. Sensitive rates for S. Typhi isolated was 100% with ofloxacin, norfloxacin and ceftriaxone, 98.6% with amikacin and 20-21.4% with chloramphenicol, ampicillin and sulfamethoxazole Co. There were fewer adverse reactions and better acceptance, one had skin rash and one had gastrointestinal disturbance. In amikacin group, abnormality of urine routine and serum creatinine was observed. Ofloxacin was well absorbed orally. Its high bioavailability, satisfactory therapeutic efficacy excellent tolerability and convenience for use make it a very useful medication in the therapy of typhoid fever resulted from multiresistant strains.
Pefloxacin is a new quinolone carboxylic acid with a broad spectrum of antibacterial activity. A comparison was made of the in-vitro activity of pefloxacin and that of nine other antibiotics (ampicillin, ticarcillin, piperacillin, cefazolin, cefotaxime, ceftazidime, gentamicin, amikacin and norfloxacin). The MIC90 of pefloxacin against 500 strains of Enterobacteriaceae ranged from 0.25 mg/l (Escherichia coli, indole + Proteus spp., Enterobacter cloacae, Salmonella spp. and Shigella spp.) to 1 mg/l (Klebsiella pneumoniae). Pefloxacin inhibited 90% of 52 strains of Pseudomonas aeruginosa at 2.5 mg/l (range 0.25 mg/l-4 mg/l). The MIC90 of pefloxacin against 100 Staphylococcus aureus strains (78 oxacillin resistant strains) was 0.4 mg/l (range 0.12-0.5 mg/l). It was markedly less active against Streptococcus faecalis and Str. pneumoniae (37 strains of each species) the MIC90 being 4 mg/l against both species. Overall, pefloxacin was at least as active as the third-generation cephalosporins against Enterobacteriaceae and was more active than any other antibiotic tested against P. aeruginosa, S. epidermidis, and S. aureus. Against E. coli, pefloxacin had a more rapid anti-bacterial activity than piperacillin. A paradoxical effect was observed with pefloxacin. An optimal killing rate was observed at concentrations of pefloxacin compatible with those one can expect in blood of patients treated with this drug.
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Because ciprofloxacin and pefloxacin are fluoroquinolones active against many mycobacterial species, both drugs were tested against Mycobacterium leprae in the mouse foot-pad system. Preliminary pharmacokinetic studies in the mouse showed that after a single oral dose of 150 mg/kg ciprofloxacin the peak serum concentration was 3.6 micrograms/ml, and after 50 mg/kg or 150 mg/kg pefloxacin peak serum concentrations were, respectively, 9.2 micrograms/ml and 16.9 micrograms/ml, the half-lives for serum elimination being about 2 hr for both drugs. The activity of daily 50 mg/kg and 150 mg/kg ciprofloxacin and pefloxacin against M. leprae was then tested in mice infected with 5 X 10(3) M. leprae. The growth of M. leprae was not prevented in mice treated continuously with either 50 mg/kg or 150 mg/kg ciprofloxacin, indicating that this drug had no or a limited bacteriostatic effect at the dosages used. In mice treated continuously with 50 mg/kg pefloxacin, growth of M. leprae was not prevented, but at monthly harvests the number of bacilli in the foot pads remained less than those of control mice (p less than 0.05). No growth of M. leprae occurred in mice treated continuously with 150 mg/kg pefloxacin. In mice treated for only 3 months with daily 150 mg/kg pefloxacin, the growth-delay that followed the stopping of the drug was 126 days, suggesting that approximately 99% of the M. leprae were killed. The pharmacokinetics of pefloxacin being more favorable in man than in the mouse, pefloxacin appears a possible drug for the chemotherapy of leprosy.
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The genus Weissella contains 14 bacterial species that usually occur in nutrient-rich environments and in fermented foods and beverages. Outbreaks of hemorrhagic septicemia were reported in three commercial rainbow trout (Oncorhynchus mykiss) farms in Brazil in 2008 and 2009. Seventy-seven Gram-positive isolates were obtained from 41 diseased fish from these farms. The bacterial strains were identified as Weissella at the genus level using biochemical tests, Weissella genus-specific PCR, and 16S rRNA sequencing. To evaluate potential routes of infection, rainbow trout juveniles were experimentally infected with the pathogen. In addition, the resistance of the pathogen to five antibiotics was tested, and provisional epidemiological cut-off values were calculated using the normalized resistance interpretation (NRI). All isolates presented similar phenotypic profiles and positive reactions for Weissella genus-specific PCR. The 16S rRNA sequences of the Brazilian strains showed 100% similarity with sequences of Chinese isolates that previously were identified as the first case of Weissella sp. infection in fish. The disease was successfully reproduced in the laboratory by intraperitoneal injection, immersion, and cohabitation between diseased and healthy fish. All isolates were resistant to sulfonamide, and based on NRI analysis, one, two, and three isolates were classified as non-wild-type (NWT) for erythromycin, oxytetracycline, and norfloxacin, respectively. This is the first description of multiple cases of Weissella sp. infection in rainbow trout farms outside of China, of infectious routes for the disease, and of provisional epidemiological cut-off values for resistance of these bacteria to four antibiotics.