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The minimal inhibitory concentrations (MICs) of antibiotics were determined by agar dilution method or by E-test®. The presence of vanA - vanG resistance and virulence genes (agg, esp, gelE and cylA, cylB, cylM) was investigated using PCR. The ability to form biofilm and the activity of gelatinase, hemolysins, lipase and DNase were tested.
Antimicrobial resistance should be emphasised during clinical therapy with antimicrobial agents, and trends in antimicrobial resistance of isolates should be followed.
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The effects of newly available broad-spectrum antibiotics, used for infection prophylaxis and therapy in cancer patients, on faecal aerobic and anaerobic bacteria were investigated. Quantitative and qualitative aerobic and anaerobic cultures were performed in 34 patients before therapy and between the sixth and eleventh day of therapy. Of the two prophylactic regimens norfloxacin plus amphotericin-B eliminated Enterobacteriaceae and enterococci without encouraging growth of yeasts or Clostridium difficile whereas trimethoprim-sulphamethoxazole did not eliminate enterococci and colonization with toxin producing C. difficile occurred in two of ten patients. The effect of the two infection prophylaxis regimens on counts of faecal anaerobes was comparable. Monotherapy with ceftazidime and combination therapy with ceftazidime plus tobramycin did not result in major changes (greater than or equal to 3 log increase or decrease) in faecal anaerobic bacteria. Enterobacteriaceae were eliminated except in one patient treated with ceftazidime. The effect of these therapeutic regimens on enterococci was variable. Colonization by yeasts or by toxin negative C. difficile (two of three patients) were found in the ceftazidime group only. During combination therapy with piperacillin plus amikacin for fever during granulocytopenia signs of a disturbed faecal flora were found in one of three patients. Changes in faecal anaerobic bacteria were most marked in the ceftazidime plus piperacillin group. Moreover the isolation of a toxin positive C. difficile occurred in this group, in a patient who was colonized with toxin negative C. difficile before treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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This study was carried out to provide information regarding resistance pattern of community acquired uropathogens in a tertiary care hospital. A retrospective analysis of culture proven urine isolates was carried out over a period of 1 year (Jan-Dec 2009). Antimicrobial susceptibility testing was done by Kirby Bauer disc diffusion method and results were interpreted in accordance with the recommendation of clinical and laboratory standard institute (CLSI). Out of the total 10698 mid-stream urine samples received from suspected cases of urinary tract infection (UTI), 2124 (19.9%) were culture proven UTI cases. Escherichia coli was the most common isolate (54.6%) followed by Staphylococcus aureus (14.7%). Among gram-negative organism (E. coli) showed high resistance to amoxiclavulanate (91.7%) & cefodroxyl (73.1%). Quinolones have shown resistance among majority of the pathogens (ranging from 30-90%). Staph aureus and enterococcus species were found to be resistant to ampicillin (84.4% and 64.5%) and norfloxacin (69% and 58.7%). Nitrofurantoin may be considered as a first line agent for empiric treatment of uncomplicated out patients. Drug resistance is a common problem and need is for judicious use of antimicrobial agents after laboratory monitoring.
Quinolones are gyrase inhibitors that are widely used as antibiotics in the clinic. When covalently attached to oligonucleotides as 5'-acylamido substituents, quinolones were found to stabilize duplexes of oligonucleotides against thermal denaturation. For short duplexes, such as qu-T*GCGCA, where qu is a quinolone residue and T is a 5'-amino-5'-deoxythymidine residue, an increase in the UV melting point of up to 27.8 degrees C was measured. The stabilizing effect was demonstrated for all quinolones tested, namely nalidixic acid, oxolinic acid, pipemidic acid, cinoxacin, norfloxacin, and ofloxacin. The three-dimensional structure of (oa-T*GCGCA)2, where oa is an oxolinic acid residue, was solved by two-dimensional NMR spectroscopy and restrained molecular dynamics. In this complex, the oxolinic acid residues disrupt the terminal T1:A6 base pairs and stack on the G2:C5 base pairs. The displaced adenosine residues bind in the minor groove of the core duplex, while the thymidine residues pack against the oxolinic acid residues. The "molecular cap" thus formed fits tightly on the G:C base pairs, resulting in increased base-pairing fidelity, as demonstrated in UV melting experiments with the sequence oa-T*GGTTGAC and target strands containing a mismatched nucleobase. The structure of the "molecular cap" with its disrupted terminal base pair may also be helpful for modeling how quinolones block re-ligation of DNA strands in the active site of gyrases.
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The photochemistry of some fluorinated 7-amino-4-quinolone-3-carboxylic acids used in therapy as antibacterials and known to be phototoxic has been investigated in water. All of them undergo heterolytic defluorination, and this appears to be a path for the generation of aryl cations in solution. 6-Fluoro derivatives such as norfloxacin (Phi(dec) = 0.06) and enoxacin (Phi(dec) = 0.13) give the corresponding phenols. Insertion of an electron-donating substituent makes defluorination inefficient; thus, ofloxacin, an 8-alkoxy derivative, is found to be rather photostable (Phi(dec) = 0.001) and reacts in part via a process different from defluorination (degradation of the N-alkyl side chain). With a 6,8-difluoro derivative, lomefloxacin, the reaction is more efficient (Phi = 0.55) and selective for position 8. Contrary to the previous cases, the aryl cation undergoes insertion in the neighboring N-ethyl group rather than solvent addition (a carbene-like chemistry). With all of the above fluoroquinolones an intensive triplet-triplet absorption is detected and is quenched by sulfite (k(q) = (1-5) x 10(8) M(-)(1) s(-)(1)). Under this condition, reductive defluorination via the radical anion takes place. The relation of the above chemistry to the phototoxicity of these drugs is commented upon briefly.
Five series of (Z)-5-(4-(2-oxo-2-phenylethoxy)benzylidene)-2-thioxothiazolidin-4-one derivatives (I-V) were synthesized, characterized, and evaluated for their anti-bacterial activity. Most of the synthesized compounds showed potent inhibition against several Gram-positive bacteria (including multidrug-resistant clinical isolates) with MIC values in the range of 1-32 μg/mL. Compounds IIIi, Vb and Vc presented the most potent activity, showing four-fold more potency than norfloxacin (MIC = 8 μg/mL and 4 μg/mL) and 64-fold more activity than oxacillin (MIC > 64 μg/mL) against MRSA CCARM 3167 and 3506 strains with MIC values of 1 μg/mL, and 64-fold more potency than norfloxacin (MIC > 64 μg/mL) and comparable activity to oxacillin (MIC = 1 μg/mL) against the QRSA CCARM 3505 and 3519 strains. None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64 μg/mL.
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Ofloxacin, a newer broad-spectrum fluoroquinolone, was evaluated against > 12,000 clinical isolates in a multicenter surveillance trial in the United States and Canada using the standardized disk diffusion method. A total of 53 geographically diverse clinical microbiology laboratories contributed zone diameter results for ofloxacin, ciprofloxacin, and norfloxacin for urinary tract infection (UTI) isolates; and ofloxacin and ciprofloxacin for respiratory tract infection (RTI) isolates, skin and soft tissue infection (SSTI) isolates, and genital tract pathogen isolates. In both the USA and Canada, ofloxacin was shown to have the wide spectrum of activity as follows: RTI isolates, ofloxacin (92.2%-93.8% susceptible) > ciprofloxacin (89.5%-90.4%); SSTI isolates, ofloxacin (87.1%-93.6%) > ciprofloxacin (78.8%-90.4%); UTI isolates, ofloxacin (91.6%-92.5%) > norfloxacin (87.3%-91.7%) > ciprofloxacin (86.4%-89.7%); and genital tract isolates, ofloxacin (94.0%) > ciprofloxacin (85.4%) (Canada only). US strains resistant to ofloxacin were confirmed by reference laboratory tests. Confirmed ofloxacin resistance, other than among staphylococci or nonenteric bacilli, was rare. The species most often found to be resistant to both ofloxacin and ciprofloxacin were methicillin-resistant staphylococci, Acinetobacter spp., and Enterococcus spp. From these contributing US and Canadian laboratory studies, ofloxacin appears to have a balanced spectrum of potential clinical use (91.8% susceptible aerobic isolates), particularly against Gram-positive pathogens and some species resistant to ciprofloxacin. The combined overall isolate (12,241 isolates) rates of susceptibility for ciprofloxacin (four infection sites) and norfloxacin (UTI only) were 87.3% and 88.8%, respectively. Monitoring for increasing fluoroquinolone resistance should be considered, however, as greater use of drugs in this class develops.
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Cell surface hydrophobicity and serum sensitivity of Klebsiella pneumoniae, after treatment with sub-minimum inhibitory concentrations (sub-MICs) of ciprofloxacin, norfloxacin and enoxacin, were studied. The quinolones tested at 1/4, 1/8 and 1/16 of the MICs decreased surface hydrophobicity. The most significant reduction of the bacterial cell surface hydrophobicity was found after treatment with antibiotics at 1/16 of the MICs (to 20.3% for both ciprofloxacin and norfloxacin, and to 23.6% for enoxacin, compared with control values). The most significant increase in the susceptibility of the bacteria to serum bactericidal activity was seen after 180 min incubation with ciprofloxacin and enoxacin at 1/16 of their MICs. Survival of treated bacteria was 55 +/- 8% 56 +/- 10% as compared with controls without antibiotics.
49 patients were given Trometamol Phosphomicine (TP) in a single oral dose; 36 took Pipemidic Acid (PA) and 21 Norfloxacine (NFX), both of these in a dose of 400 mg twice a day for 5 to 7 days.
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The outer membrane of mycobacteria presents an effective permeability barrier for many antibiotics. Transport pathways across this membrane are unknown for most drugs. Here, we examined which antibiotics utilize the porin pathway across the outer membrane of the model organism Mycobacterium smegmatis. Deletion of the porins MspA and MspC drastically increased the resistance of M. smegmatis ML10 to beta-lactam antibiotics, while its beta-lactamase activity remained unchanged. These results are consistent with the ninefold-reduced outer membrane permeability of the M. smegmatis porin mutants for cephaloridine and strongly indicate that beta-lactam antibiotics rely on the porin pathway. The porin mutant ML10 accumulated less chloramphenicol and norfloxacin and was less susceptible to these antibiotics than wild-type M. smegmatis. These results demonstrated that small and hydrophilic antibiotics use the Msp porins for entering the cell. In contrast to norfloxacin, the hydrophobic moxifloxacin was 32-fold more effective in inhibiting the growth of M. smegmatis, presumably because it was able to diffuse through the lipid membrane. Structural models indicated that erythromycin, kanamycin, and vancomycin are too large to move through the MspA channel. This study presents the first experimental evidence that hydrophilic fluoroquinolones and chloramphenicol diffuse through porins in mycobacteria. Thus, mutations resulting in less efficient porins or lower porin expression levels are likely to represent a mechanism for the opportunistic pathogens M. avium, M. chelonae, and M. fortuitum, which have Msp-like porins, to acquire resistance to fluoroquinolones.
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Loracarbef, a member of the carbacephem class of beta-lactam antibiotics, was tested in randomized, double-blind, parallel studies for the treatment of uncomplicated urinary tract infections (UTIs). In one study conducted in the United States, a 7-day course of once-daily doses of loracarbef (200 mg) was compared with a 7-day course of multiple daily doses of cefaclor (250 mg three times a day). Analysis of data from a small, homogeneous patient population of 108 college-aged women showed that loracarbef produced clinical and bacteriologic responses similar to those produced by cefaclor. At 5-9 days posttherapy, bacteriologic cure was observed in 96% of patients in the loracarbef group and 90% of patients in the cefaclor group (p = 0.614); at 4-6 weeks post-therapy, the same cure rate (81%) was observed in both groups. Analysis of the larger (333 patients) and more heterogeneous study population containing several male and elderly female patients showed that loracarbef again produced responses similar to those produced by cefaclor, with no statistically significant differences seen between the groups at 5-9 days or at 4-6 weeks posttherapy. The adverse events reported by the loracarbef and cefaclor groups were also comparable in both the small and large patient populations analyzed. Similarly favorable results were seen when a 7-day regimen of loracarbef (200 mg once a day) was compared with a 7-day regimen of norfloxacin (400 mg twice a day) in a large European study of approximately 300 patients with uncomplicated cystitis. These studies demonstrate that the safety and efficacy of once-daily loracarbef are comparable to the safety and efficacy of multiple-dose/day therapy with other antimicrobial agents commonly used in the treatment of uncomplicated UTIs.