novobiocin and Pseudomonas-Infections

Retrospective analysis of 189 nonredundant strains of Pseudomonas aeruginosa sequentially recovered from the sputum samples of 46 cystic fibrosis (CF) patients over a 10-year period (1998 to 2007) revealed that 53 out of 189 (28%) samples were hypersusceptible to the beta-lactam antibiotic ticarcillin (MIC < or = 4 microg/ml) (phenotype dubbed Tic(hs)). As evidenced by trans-complementation and gene inactivation experiments, the mutational upregulation of the efflux system MexXY was responsible for various degrees of resistance to aminoglycosides in a selection of 11 genotypically distinct strains (gentamicin MICs from 2 to 64 microg/ml). By demonstrating for the first time that the MexXY pump may evolve in CF strains, we found that a mutation leading to an F1018L change in the resistance-nodulation-cell division (RND) transporter MexY was able to increase pump-promoted resistance to aminoglycosides, cefepime, and fluoroquinolones twofold. The inactivation of the mexB gene (which codes for the RND transporter MexB) in the 11 selected strains showed that the Tic(hs) phenotype was due to a mutational or functional loss of function of MexAB-OprM, the multidrug efflux system known to contribute to the natural resistance of P. aeruginosa to beta-lactams (e.g., ticarcillin and aztreonam), fluoroquinolones, tetracycline, and novobiocin. Two of the selected strains synthesized abnormally low amounts of the MexB protein, and 3 of 11 strains expressed truncated MexB (n = 2) or MexA (n = 1) polypeptide as a result of mutations in the corresponding genes, while 7 of 11 strains produced wild-type though nonfunctional MexAB-OprM pumps at levels similar to or even higher than that of reference strain PAO1. Overall, our data indicate that while MexXY is necessary for P. aeruginosa to adapt to the hostile environment of the CF lung, the MexAB-OprM pump is dispensable and tends to be lost or inactivated in subpopulations of P. aeruginosa.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Bacterial Proteins; beta-Lactams; Cystic Fibrosis; Gene Expression Regulation, Bacterial; Humans; Membrane Transport Proteins; Microbial Sensitivity Tests; Mutation; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum

The in vitro activities of 10 families of antimicrobial agents alone and in combination with a synthetic polycationic polymer, polyethylenimine (PEI), against a resistant clinical isolate of Pseudomonas aeruginosa were investigated by MIC assays, checkerboard testing, and killing curve studies. At a concentration of 250 nM, PEI (10 kDa) was not directly bactericidal or bacteriostatic; but when it was used in combination with novobiocin, ceftazidime, ampicillin, ticarcillin, carbenicillin, piperacillin, cefotaxime, chloramphenicol, rifampin, or norfloxacin, it significantly reduced the MICs of these antibiotics by 1.5- to 56-fold. However, the MICs of aminoglycosides, polymyxins, and vancomycins were increased by 1.2- to 5-fold when these drugs were combined with PEI; and the MICs of tetracycline, erythromycin, ciprofloxacin, and ofloxacin were not affected when these drugs were combined with PEI. In the killing curve studies, combinations of PEI with novobiocin, ceftazidime, chloramphenicol, or rifampin resulted in 5- to 8-log(10) CFU/ml reductions in bacterial counts when 25% of the MIC of each antibiotic was used. These results indicate that infections due to resistant Pseudomonas strains could be treated by the use of a synergistic combination of PEI and antimicrobial drugs.

Topics: Aminoglycosides; Anti-Bacterial Agents; Carbenicillin; Ceftazidime; Ciprofloxacin; Drug Resistance, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Novobiocin; Ofloxacin; Piperacillin; Polyethyleneimine; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Ticarcillin; Tobramycin

Macrolide antibiotics modulate the quorum-sensing system of Pseudomonas aeruginosa. We tested the effect of macrolide antibiotics on the cell density-dependent expression of the MexAB-OprM efflux pump and found that 1.0 mug/ml (MIC/6.25) of azithromycin suppressed the expression of MexAB-OprM by about 70%, with the result that the cells became two- to fourfold more susceptible to antibiotics such as aztreonam, tetracycline, carbenicillin, chloramphenicol, and novobiocin.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Outer Membrane Proteins; Down-Regulation; Humans; Macrolides; Membrane Transport Proteins; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Quorum Sensing

Pseudomonas cepacia, considered a phytopathogenic organism for many years, has been shown recently to be widely distributed geographically. The hospital environment has become an important source of this organism but the resistance of Ps. cepacia to most antibiotics has made the treatment of infections a problem. One hundred per cent of the strains tested have proved to be sensitive to the sulphonamides and to novobiocin, 93.0% to the combination of trimethoprim and sulfamethoxazole (co-trimoxazole); 85.2% to minocycline; 77.8% to chloramphenicol and dibekacin and 44.4% to nalidixic acid. One hundred per cent of the strains exhibit resistance to ampicillin, cephalothin, cefamandole, cefoxitin, colistin, cefuroxime, tetracycline and cefazolin; 88.9% to amikacin, tobramycin and sisomycin; 85.2% to carbenicillin. The new beta-lactams, apalcillin, ceftazidime, N-formimidoyl-thienamycin, piperacillin, cefotaxime and azlocillin proved to be the most potent of the molecules tested, inhibiting 90% of the strains, at concentrations of 4, 8, 8, 8, 32 and 16 mg/l and 100% of the strains at 8, 16, 16, 32, 32 and 64 mg/l, respectively. In contrast to the usual sensitivity patterns of Pseudomonas spp, Ps. cepacia has been shown to be resistant to colistin, cefsulodin and the aminoglycosides. However, unlike Ps. aeruginosa, Ps. cepacia has been shown, by the dilution method, to be sensitive to co-trimoxazole, 92.3% of the strains being inhibited by 16 mg/l.

Topics: Anti-Bacterial Agents; Ceftazidime; Cross Infection; Drug Combinations; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Minocycline; Novobiocin; Pseudomonas; Pseudomonas Infections; Species Specificity; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Cephalothin; Colistin; Enterococcus faecalis; Escherichia coli Infections; Gentamicins; Humans; Kanamycin; Kidney Failure, Chronic; Kidney Function Tests; Male; Novobiocin; Postoperative Complications; Prostatectomy; Pseudomonas aeruginosa; Pseudomonas Infections; Streptococcal Infections; Urinary Tract Infections; Urologic Diseases

Topics: Abscess; Adult; Amputation Stumps; Amputation, Surgical; Chloramphenicol; Humans; Male; Melioidosis; Military Medicine; Novobiocin; Osteomyelitis; Pseudomonas; Pseudomonas Infections; Sepsis; Sulfisoxazole; Surgical Wound Infection; Tetracycline; Wound Infection

Topics: Adolescent; Bronchopneumonia; Child; Child, Preschool; Chloramphenicol; Cloxacillin; Cystic Fibrosis; Female; Fusidic Acid; Humans; Infant; Lincomycin; Male; Neomycin; Novobiocin; Penicillin Resistance; Penicillin V; Pseudomonas Infections; Staphylococcal Infections; Tetracycline

Topics: Adult; Aged; Ampicillin; Bacteriuria; Cephaloridine; Chloramphenicol; Female; Furans; Humans; Kidney Diseases; Leucomycins; Male; Middle Aged; Novobiocin; Proteus Infections; Pseudomonas Infections; Streptomycin; Tetracycline; Urinary Tract Infections

Topics: Animals; Anti-Infective Agents, Local; Colistin; Dihydrostreptomycin Sulfate; Female; Genital Diseases, Female; Gentamicins; Horse Diseases; Horses; Hydrocortisone; Infertility, Female; Nitrofurantoin; Novobiocin; Oxytetracycline; Penicillin G; Penicillin G Procaine; Penicillins; Polymyxins; Povidone; Pregnancy; Pregnancy, Animal; Pseudomonas Infections

Topics: Adult; Chloramphenicol; Diabetes Complications; Escherichia coli Infections; Gangrene; Humans; Leg; Liver Cirrhosis; Male; Novobiocin; Pseudomonas Infections; Skin Transplantation; Sulfacetamide; Tetracycline; Transplantation, Autologous

Topics: Anemia; Chloramphenicol; Chlorpromazine; Eye; Glutethimide; Herpes Zoster; Herpes Zoster Ophthalmicus; Hodgkin Disease; Lung Abscess; Mechlorethamine; Meprobamate; Nitrofurantoin; Novobiocin; Ophthalmology; Oxytetracycline; Pentobarbital; Polymyxins; Pseudomonas Infections; Quinine; Retina; Sepsis; Streptomycin; Toxicology

Topics: Adolescent; Anti-Bacterial Agents; Antibiotic Prophylaxis; Burns; Child; Chloramphenicol; Colistin; Erythromycin; Escherichia coli Infections; gamma-Globulins; Humans; Immune Sera; Infant; Infant, Newborn; Kanamycin; Novobiocin; Polymyxins; Proteus Infections; Pseudomonas Infections; Salmonella Infections; Sepsis; Serum Albumin; Shigella; Sodium Chloride; Solutions; Staphylococcal Infections; Streptococcal Infections; Tetracycline; Vancomycin

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anti-Bacterial Agents; Cataract Extraction; Chloramphenicol; Endophthalmitis; Methicillin; Novobiocin; Oxacillin; Postoperative Complications; Proteus Infections; Pseudomonas Infections; Staphylococcal Infections; Streptomycin; Tetracycline; Toxicology; Vancomycin