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1.  Single-dose cephalexin therapy for acute bacterial urinary tract infections and acute urethral syndrome with bladder bacteriuria. 
The efficacy of single-dose therapy with 3 g of cephalexin was evaluated in 129 women with symptoms of acute uncomplicated lower urinary tract infections. Of 91 patients with significant bacteriuria, 61 (67%) were cured of their original infection; this was similar to the 54 to 79% cure rates reported in unselected populations of women of a wide age range treated for acute uncomplicated urinary tract infections with a single dose of amoxicillin or trimethoprim-sulfamethoxazole (J. Rosenstock, L. P. Smith, M. Gurney, K. Lee, W. G. Weinberg, J. N. Longfield, W. B. Tauber, and W. W. Karney, Antimicrob. Agents Chemother. 27:652-654, 1985; N. E. Tolkoff-Rubin, M. E. Wilson, P. Zuromskis, I. Jacoby, A. R. Martin, and R. H. Rubin, Antimicrob. Agents Chemother. 25:626-629, 1984). The cure rates of (87%) for our younger patients, those less than 25 years of age, was better than that (46%) for our patients over 40 years of age (P less than 0.001). Patients with infections that were negative in an antibody-coated bacteria test were cured at a significantly higher rate than those with infections that were positive in an antibody-coated bacteria test (71 versus 19%; P = 0.003). Those patients with infections caused by cephalexin-susceptible organisms were cured at a rate similar to that for patients with infections caused by cephalexin-resistant organisms (68 versus 50%; P = 0.62). The cure rate for suburban patients was 90%, versus 45% for inner-city patients (P = 0.008). Of the 28 women with acute urethral syndrome due to low-level bacteriuria, 27 were cured.
PMCID: PMC180398  PMID: 3717940
2.  Enzymology and pathogenicity in mice of a herpes simplex virus type 1 mutant resistant to 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodocytosine. 
The deoxypyrimidine nucleoside analog 2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodocytosine (FIAC) is a potent and selective inhibitor of herpes simplex virus type 1 in vitro (C. Lopez, K. A. Watanabe, and J. J. Fox, Antimicrob. Agents Chemother. 17:803-806, 1980). Isopycnographic analysis demonstrated that 1 microM FIAC inhibited herpes simplex virus DNA replication by more than 95% but inhibited cellular DNA replication by only 32%. Mutant herpes simplex virus type 1 selected resistant to FIAC displayed linked resistance to other nucleoside analogs, including arabinosylthymine and acyclovir. Lysates derived from Vero cells infected with FIAC-resistant virus showed markedly lower levels of thymidine kinase activity and were unable to phosphorylate selectively arabinosylthymine or FIAC, in contrast to lysates from cells infected with wild-type herpes simplex virus type 1. Finally, drug-resistant virus displayed a 6,000-fold decrease in pathogenicity when inoculated intraperitoneally into genetically susceptible A/J mice. These results indicate that resistance to deoxypyrimidine nucleoside analogs is due, at least in part, to alterations in viral thymidine kinase and is accompanied by decreased pathogenicity in vivo.
PMCID: PMC284171  PMID: 3015008
3.  Streptomycin accumulation by Bacillus subtilis requires both a membrane potential and cytochrome aa3. 
Cytochrome aa3 concentrations in the cytoplasmic membrane of Bacillus subtilis were altered by growth conditions, and the effects on the membrane potential (delta psi) in whole cells were measured. When cytochrome aa3 was absent, the magnitude of delta psi was not diminished by comparison with the delta psi measured in cells containing normal cytochrome aa3 concentrations. In addition, the energy-dependent uptake of proline and glutamate was comparable at both cytochrome aa3 concentrations. However, in the cytochrome aa3-deficient cell preparation, accumulation of the aminoglycoside antibiotic streptomycin was much lower than that of the cytochrome aa3-sufficient cells. When cells were cultured under conditions that stimulated higher than normal concentrations of cytochrome aa3, delta psi was also increased, and enhanced streptomycin accumulation was observed. Phenazine methosulfate-ascorbate was used both in delta psi measurements and in uptake studies to provide high rates of electron transport and maximal delta psi values. These results, taken together with those previously published (A. S. McEnroe and H. W. Taber, Antimicrob. Agents Chemother. 26:507-512, 1984) suggest that the uptake of streptomycin by B. subtilis requires adequate levels both of delta psi and cytochrome aa3.
PMCID: PMC180379  PMID: 2425730
4.  Penicillin-binding proteins of penicillin-susceptible and -resistant pneumococci: immunological relatedness of altered proteins and changes in peptides carrying the beta-lactam binding site. 
There are several major differences between the penicillin-binding proteins (PBPs) of highly penicillin-resistant and -susceptible strains of pneumococci. The highest-molecular-size PBP 1a (98 kilodaltons [kDa]) of susceptible pneumococci is not detectable in resistant bacteria. Instead, resistant strains contain a PBP of smaller size: 92 and 94 kDa in South African strains 8249 and A95210, respectively, and 96 kDa in New Guinea strain 2955 (S. Zighelboim and A. Tomasz, Antimicrob. Agents Chemother. 17:434-442, 1980). Using antibodies prepared against PBP 1a of penicillin-susceptible pneumococci, we demonstrated that these anomalous-sized proteins in the resistant strains are immunologically related to PBP 1a of penicillin-susceptible bacteria. A second difference between the PBP patterns of strain 8249 and the susceptible pneumococci is that the 78-kDa PBP 2b is not detectable by the radioactive penicillin binding assay in the resistant strain. Using antibodies prepared against PBP 2b of susceptible cells, we demonstrated the presence of PBP 2b in membrane preparations from strain 8249 cells. Thus, the poor detection of this PBP appears to be related to its greatly decreased affinity for the antibiotic molecule. We also compared the patterns of penicillin-labeled peptides derived from PBPs of resistant and susceptible cells during partial proteolysis by V8 protease. Several changes were observable in small peptides carrying the beta-lactam binding site generated from the high Mr (PBP 1a-related) binding proteins. In contrast, no differences in the pattern of penicillin-labeled peptides were seen when the pattern of PBP 2a of susceptible pneumococci was compared with the peptide pattern of PBP 2a from resistant strains. One of the resistant isolates (strain 2955) also had a PBP 3 with a higher-than-normal molecular weight. This protein gave strong positive reaction with antibodies against PBP 3 of susceptible cells. Examination of the pattern of penicilloyl peptides generated from the susceptible and resistant PBP 3s during partial proteolysis revealed only differences which seem to reside distant from the beta-lactam binding site.
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PMCID: PMC176479  PMID: 3539010
5.  Alterations in kinetic properties of penicillin-binding proteins of penicillin-resistant Streptococcus pneumoniae. 
Earlier studies have shown that the highly penicillin-resistant South African Strains of pneumococci contain altered penicillin-binding proteins (PBPs) (S. Zighelboim and A. Tomasz, Antimicrob. Agents Chemother. 17:434-442, 1980). We now describe a detailed quantitative characterization of the reaction of radioactively labeled penicillin with the PBPs of the penicillin-susceptible and penicillin-resistant pneumococci and several intermediate-resistance-level genetic transformants as well. The altered binding of the antibiotic by the PBPs of resistant cells appears to be due to a combination of two factors: lower drug affinity and change in the cellular amounts of PBPs. No alteration in the rates of deacylation of the penicilloyl-PBPs of the resistant cells was detected.
PMCID: PMC176435  PMID: 3638932
6.  Cefuroxime axetil for treatment of uncomplicated gonorrhea. 
Oral cefuroxime axetil (1 g) plus probenecid cured 29 of 30 urethral and 6 of 6 rectal gonococcal infections in men; alone the drug cured 22 of 23 urethral and 4 of 6 rectal infections. No toxicity was observed. Cefuroxime axetil alone is effective for urethral gonorrhea in males; rectal gonorrhea probably requires additional probenecid.
PMCID: PMC180547  PMID: 3767347
7.  Comparative in vitro activity of seven quinolones against 100 clinical isolates of Clostridium difficile. 
The in vitro activity of seven quinolone derivatives against 100 clinical isolates of Clostridium difficile was determined. CI934 was the most active, inhibiting 90% of the strains at 4 micrograms/ml and 100% at 8 micrograms/ml. Ofloxacin and ciprofloxacin had moderate activity (16 and 32 micrograms/ml) whereas enoxacin, pefloxacin, norfloxacin, and nalidixic acid had poor activity (128 micrograms/ml).
PMCID: PMC176416  PMID: 2940968
8.  Susceptibility of Campylobacter pyloridis to three macrolide antibiotics (erythromycin, roxithromycin [RU 28965], and CP 62,993) and rifampin. 
The presence of Campylobacter pyloridis in the gastric mucosa was recently linked to peptic ulcer disease. This study compared the inhibitory activity of three macrolide compounds (erythromycin, roxithromycin [RU 28965], and CP 62,993) and rifampin against 10 clinical isolates of C. pyloridis. The macrolides were equally effective against the test strains, with MICs ranging from 0.06 to 0.5 microgram/ml; rifampin was less active, with MICs ranging from 0.25 to greater than 1 microgram/ml. Erythromycin and the two new macrolide derivatives are potentially useful agents in the treatment of infections caused by C. pyloridis.
PMCID: PMC180545  PMID: 3767346
9.  Ciprofloxacin in the treatment of pneumonia. 
The use of ciprofloxacin as the sole agent in the treatment of 25 patients with pneumonias caused by susceptible organisms resulted in rapid cure. No side effects, superinfections, or recurrences were observed.
PMCID: PMC180504  PMID: 2942104
10.  LY164846 in vitro antimicrobial activity testing, including disk diffusion susceptibility tests using 30-microgram disks. 
A new oral cephalosporin, LY164846 (Eli Lilly & Co., Indianapolis, Ind.), was found to have a unique antimicrobial spectrum confined to methicillin-susceptible Staphylococcus spp., streptococci (except Enterococcus spp.), Haemophilus influenzae, Branhamella catarrhalis, and some anaerobes. Cephalothin in vitro tests (30-microgram disks or dilution) can represent LY164846 for laboratory testing if comparable interpretive breakpoints are applied to strains within the spectrum of LY164846. Organisms not inhibited by LY164846 (MICs greater than or equal to 32 micrograms/ml) were members of the family Enterobacteriaceae, Pseudomonas spp., Acinetobacter spp., enterococci, and some strains of Staphylococcus haemolyticus and of the Bacteroides fragilis group.
PMCID: PMC180430  PMID: 3755018
11.  In vitro activity of A-56619 and A56620, two new aryl-fluoroquinolone antimicrobial agents. 
The in vitro antimicrobial activity of two new aryl-fluoroquinolone antibiotics, A-56619 and A-56620, was compared with those of norfloxacin and several other antibiotics against 448 bacterial isolates. A-56620 was the most active agent tested. The usual 90% MIC of A-56620 was less than or equal to 2 micrograms/ml, except for enterococci, gentamicin-resistant Serratia marcescens, and gentamicin-resistant Pseudomonas aeruginosa, for which the 90% MIC was 4 micrograms/ml. A-56619 and norfloxacin were generally severalfold less active than A-56620. Cross resistance was observed between the quinolone antibiotics and other unrelated antibiotic classes.
PMCID: PMC176411  PMID: 3717937
12.  Antistaphylococcal activity of a cyclic peptide, LY146032, and vancomycin. 
The inhibitory and bactericidal activities of a novel cyclic peptide antibiotic, LY146032, and vancomycin against oxacillin-susceptible and oxacillin-resistant staphylococci were compared. The MICs for 90% of strains were two- to fourfold higher for vancomycin than for LY146032. MBC/MIC ratios for all strains were less than or equal to 2. In killing rate studies with four strains of staphylococci, there was no detectable growth in the presence of 4X the MIC of either LY146032 or vancomycin after 24 h of incubation.
PMCID: PMC180623  PMID: 3028254
13.  Novel mechanism for plasmid-mediated erythromycin resistance by pNE24 from Staphylococcus epidermidis. 
We describe an unusual type of erythromycin resistance (Emr) mediated by a plasmid designated pNE24 from Staphylococcus epidermidis. This 26.5-kilobase plasmid encodes resistance strictly to 14-membered macrolide antibiotics, erythromycin, and oleandomycin. Resistance to other macrolide-lincosamide-streptogramin B (MLS) antibiotics was not observed even after a prior induction stimulus with various MLS antibiotics. Plasmid pNE24 was found to express resistance constitutively and manifested a low to intermediate MIC (62.5 micrograms/ml) for erythromycin. The resistance gene, designated erpA, appears to mediate resistance by altering the permeability of the host cell for erythromycin, because the measured uptake of 14C-labeled erythromycin by strain 958-2 (containing pNE24) was lower than for the erythromycin-susceptible, isogenic strain 958-1. No inactivation of erythromycin in overnight broth culture supernatants could be detected. In addition, no significant loss in binding affinity between [14C]erythromycin and ribosome could be detected for ribosomes isolated from strain 958-2 relative to 958-1, indicating that pNE24 probably does not produce a modification of the bacterial ribosome. No other selectable marker was found associated with pNE24; however, a 60,000-dalton protein was present only in the membrane fractions of cells (958-2) containing pNE24 and may play a role in mediating resistance to erythromycin.
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PMCID: PMC176508  PMID: 3800341
14.  Ciprofloxacin therapy for Mediterranean spotted fever. 
We report the treatment of five patients with Mediterranean spotted fever with the antimicrobial agent ciprofloxacin. The treatment was administered intravenously for 2 days and then perorally for 8 days. All five patients were cured. These preliminary data seem to correlate with the in vitro activity of ciprofloxacin against Rickettsia conorii.
PMCID: PMC176489  PMID: 3789693
16.  In vitro and in vivo antibacterial activity of AM-833, a new quinolone derivative. 
AM-833 showed potent activity against members of the family Enterobacteriaceae, Neisseria spp., and Haemophilus influenzae and good activity against staphylococci, Pseudomonas aeruginosa, and Branhamella catarrhalis. Against these bacteria, its activity was roughly comparable to that of norfloxacin and ofloxacin but was slightly less potent than that of ciprofloxacin. This compound also showed good activity against drug-resistant strains such as methicillin-resistant Staphylococcus aureus and gentamicin-resistant Pseudomonas aeruginosa. The protective effects of a single oral dose of AM-833 on systemic bacterial infections in mice were greater than those of norfloxacin. AM-833 was as effective as ofloxacin and ciprofloxacin against systemic infections with Escherichia coli and Pseudomonas aeruginosa, and it showed somewhat higher activity against staphylococcal infections than did the other quinolones. AM-833 exhibited good prophylactic activity against E. coli infections. AM-833 also proved effective against localized infections such acute pneumonia and ascending urinary tract infections in mice. The excellent therapeutic efficacy of AM-833 against these systemic and local infections may be a result of its good oral absorption and high levels in tissues.
PMCID: PMC180500  PMID: 2942103
17.  Antibacterial activity of niridazole against Salmonellae. 
Fifty-six strains, representing eight species of salmonellae of diverse geographic origin and possessing a variety of antimicrobial resistance profiles, were tested for susceptibility to niridazole by the agar dilution method. Calculated MICs for 50 and 90% of strains were 4.8 and 16.0 mg/liter, respectively, with a susceptibility range of 0.25 to 32 mg/liter. No obvious species differences were noted. Niridazole was found to be rapidly and powerfully bactericidal. No significant difference was detected between MICs and MBCs. Except for a strain-dependent effect with a subset of multiply resistant salmonella isolates, no inoculum effect was demonstrated.
PMCID: PMC284181  PMID: 3729350
18.  In vitro activity of clofazimine against rapidly growing nonchromogenic mycobacteria. 
The in vitro activity of clofazimine against 80 isolates of rapidly growing nonchromogenic mycobacteria was studied by an agar dilution method. The drug inhibited 96% of strains tested at concentrations less than or equal to 1 microgram/ml, and it appears to be an agent of potential efficacy against Mycobacterium fortuitum and M. chelonae.
PMCID: PMC284191  PMID: 3729356
19.  Properties of a novel carbenicillin-hydrolyzing beta-lactamase (CARB-4) specified by an IncP-2 plasmid from Pseudomonas aeruginosa. 
CARB-4, a novel carbenicillin-hydrolyzing beta-lactamase with an isoelectric point of 4.3, was discovered in a strain of Pseudomonas aeruginosa from France. It was determined by a multiresistant transmissible plasmid belonging to the P-2 incompatibility group.
PMCID: PMC180426  PMID: 3087285
20.  In vitro susceptibility of Brucella melitensis to new cephalosporins crossing the blood-brain barrier. 
The in vitro susceptibilities of 83 clinical isolates of Brucella melitensis to seven cephalosporins and a monobactam were determined. Ceftizoxime, ceftriaxone, and cefotaxime were the most effective agents tested, with MICs ranging from 0.25 to 2 micrograms/ml. Moxalactam, cefoperazone, cefuroxime, and ceftazidime showed MICs between 4 and 64 micrograms/ml, with moxalactam being the most active agent in this group. Aztreonam showed poor activity, with MICs higher than 64 micrograms/ml.
PMCID: PMC180392  PMID: 3729331
21.  Characterization of beta-lactamases in situ on polyacrylamide gels. 
An inhibitor-based characterization system which allowed the identification of beta-lactamases after isoelectric focusing on polyacrylamide gels was developed. This system, using potassium clavulanate and oxacillin, distinguished type I chromosomally mediated enzymes from other beta-lactamases of gram-negative bacteria.
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PMCID: PMC180628  PMID: 3492960
22.  Antibacterial activity of cefmetazole alone and in combination with fosfomycin against methicillin- and cephem-resistant Staphylococcus aureus. 
In vitro and in vivo antibacterial activities of cefmetazole alone and in combination with fosfomycin against methicillin- and cephem-resistant (MR) strains of Staphylococcus aureus were investigated, and the mechanism of synergistic effect between cefmetazole and fosfomycin was also studied. Cefmetazole inhibited the growth of 71 strains of MR S. aureus at concentrations ranging from 1.56 to 50 micrograms/ml; the antibacterial activity of cefmetazole against these strains was enhanced approximately 4 times with the addition of fosfomycin at a concentration of 1.56 micrograms/ml. The binding affinity of cefmetazole for the penicillin-binding protein 2' fraction specific for MR S. aureus was higher than that of methicillin, cloxacillin, cefazolin, and cefotaxime. A synergy experiment in vitro was performed by checkerboard titration with Mueller-Hinton agar plates containing various concentrations and ratios of cefmetazole and fosfomycin. The fractional inhibitory concentration index ranged from 0.09 to 0.75. Exposure of cefmetazole plus fosfomycin to exponentially growing cultures at a concentration at which both antibiotics had no bactericidal effect when given alone exerted bactericidal action. Combined administration of cefmetazole with fosfomycin at a ratio of 1:1 against systemic MR S. aureus infections with mice showed an excellent therapeutic efficacy as compared with administration of either antibiotic alone. Penicillin-binding protein 2', 2, and 4 fractions were scarcely detectable in MR S. aureus strains grown in the presence of fosfomycin at concentrations of 0.25 MIC and 0.5 MIC, respectively.
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PMCID: PMC180619  PMID: 3468883
23.  Comparison of two beta-lactamase-producing strains of Streptococcus faecalis. 
A second strain of enterococcus (PA) producing beta-lactamase (Bla+ phenotype) was compared with the previously reported Bla+ enterococcus, strain HH22. As with the original strain, there was a marked inoculum effect when PA was tested with penicillin, ampicillin, and piperacillin; no difference was noted with methicillin, cephalothin, imipenem, or vancomycin; the difference with ticarcillin was intermediate. High-level gentamicin resistance (Gmr) transferred from PA to an enterococcal recipient strain at a frequency approximately 100-fold lower than for HH22; all Gmr transconjugants from both strains were Bla+, but only PA showed linkage of Gmr and Bla+ with transfer of resistance to streptomycin, tetracycline, and chloramphenicol. EcoRI digestion of plasmid DNA from Gmr Bla+ transconjugants showed no similarities between the two strains. A 5.1-kilobase EcoRI Bla+-encoding fragment derived from HH22 was cloned into an Escherichia coli cloning vector and shown to hybridize to a 10.2-kilobase EcoRI fragment derived from PA; both fragments hybridized to an 840-base-pair staphylococcal Bla+ gene probe. These data indicate that the penicillinases are similar but encoded on different or differently arranged plasmids. The fact that both are transferable emphasizes the potential for this new streptococcal resistance determinant to disseminate.
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PMCID: PMC180608  PMID: 3028251
24.  Antimicrobial activity of U-70138F (paldimycin), roxithromycin (RU 965), and ofloxacin (ORF 18489) against Chlamydia trachomatis in cell culture. 
The MICs of three new antimicrobial agents of different classes, U-70138F, roxithromycin (RU 965), and ofloxacin (ORF 18489), versus Chlamydia trachomatis in McCoy cell cultures were 0.25, 0.8, and 1.0 microgram/ml, respectively. For each test drug, the MIC and MBC were identical or were within 1 dilution of one another. These drugs possessed sufficient activity in cell culture to suggest possible clinical effectiveness.
PMCID: PMC176541  PMID: 3467650
25.  In vitro activity of LY146032 against staphylococci, streptococci, and enterococci. 
The in vitro activities of LY146032 and seven comparative antimicrobial agents against 14 species of staphylococci, streptococci, and enterococci were studied. MICs of LY146032 were less than or equal to 0.5 microgram/ml for all staphylococci, including oxacillin-resistant strains; less than or equal to 0.25 microgram/ml for all streptococci (except viridans group streptococci); and less than or equal to 4 micrograms/ml for all viridans group streptococci and enterococci. MICs were minimally affected by variations in inoculum size, and LY146032 was bactericidal against all species tested.
PMCID: PMC176533  PMID: 3026240

Results 1-25 (471)