bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective inhibition of functional lymphocyte subpopulations by ribavirin
Authors: Powers C N , Peavy D L , Knight V
Published: June 2012

The present studies were designed to examine the effects of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), a broad-spectrum antiviral agent, on the generation of murine antibody responses in vitro. Whereas primary and secondary sheep erythrocyte-specific, plaque-forming cell responses by normal murine spleen cells were enhanced by low concentrations of ribavirin (1 microgram per culture), they were strongly inhibited by higher concentrations of ribavirin (5 to 10 micrograms per culture). Both phenomena occurred with the greatest magnitude when spleen cells were exposed to ribavirin 48 to 72 h after culture initiation. Enhancement appeared to result from selective interference with suppressor T cells, since ribavirin failed to augment lipopolysaccharide-specific plaque-forming cell responses in T cell-depleted spleen cell cultures but inhibited concanavalin A-induced lymphocyte proliferation and suppressor T cell generation in cultures of normal spleen cells. The immunosuppressive properties of ribavirin were mediated by a direct antiproliferative effect and, at higher concentrations, a cytotoxic effect for B lymphocytes, since the drug inhibited plaque-forming cell responses in T cell-depleted spleen cell cultures, suppressed lipopolysaccharide-induced lymphocyte proliferation and reduced viable spleen cell recoveries.
Aminoglycoside-resistant gram-negative bacilli in a community hospital: comparative in vitro activity of cefotaxime, moxalactam, cefoperazone, and piperacillin
Authors: Magnussen C R , Sammartino M T , Ernest K D
Published: June 2012

All aminoglycoside-resistant gram-negative bacilli isolated during 1 year at a community hospital were tested for in vitro sensitivity to cefotaxime, moxalactam, cefoperazone, and piperacillin. The majority of Enterobacteriaceae were susceptible to all four antibiotics. Cefoperazone and piperacillin were the most active for pseudomonas aeruginosa, and activity for other nonfermentative gram-negative bacilli was variable.
In vitro activity of the two principal oxidative metabolites of metronidazole against Bacteroides fragilis and related species
Authors: Haller I
Published: June 2012

Metronidazole and its two principal oxidative metabolites were tested in vitro against 20 clinical isolates of the Bacteroides fragilis group. Both metabolites were bactericidal, and the exhibited 65 and 5%, respectively, of the inhibitory effect of metronidazole. Additive or weak synergistic effects resulted in combination with the parent compound.
Penicillin-binding proteins in a Staphylococcus aureus strain resistant to specific beta-lactam antibiotics
Authors: Georgopapadakou N H , Smith S A , Bonner D P
Published: June 2012

The penicillin-binding proteins (PBPs) of a clinical isolate of Staphylococcus aureus specifically resistant to oral cephalosporins were compared with those of a susceptible strain. In the resistant strain, PBP3 (75,000 molecular weight) was missing or had substantially (greater than 100-fold) reduced affinity for penicillin; PBP2 (80,000 molecular weight) was increased in amount and contained a satellite band, PBP2'; PBPs 1 and 4 were unchanged. Oral cephalosporins bound poorly to PBP2 in both susceptible and resistant strains, but only in the latter did binding correlate with antibiotic activity. The results are consistent with the suggestion that PBP2 is essential in S. aureus. PBP2 might in addition compensate for PBP3 when the latter is missing. In the susceptible strain the lack of correlation between binding to PBP2 and beta-lactam antibiotic activity is due to the very high affinity of the also essential PBP3 for beta-lactam antibiotics.
Decreased susceptibility to 4'-deoxy-6'-N-methylamikacin (BB-K311) conferred by a mutant plasmid in Escherichia coli
Authors: Perlin M H , Lerner S A
Published: June 2012

Escherichia coli MP6 contains a plasmid that encodes aminoglycoside 3'-phosphotransferase II, which phosphorylates kanamycin and confers high-level kanamycin resistance, Amikacin is a minor substrate of this enzyme, but MP6 is susceptible to amikacin. Strain MP10 has a spontaneous mutation in the plasmid of MP6 that increases the aminoglycoside 3'-phosphotransferase II activity not only against kanamycin but also against amikacin. This mutation is also responsible for the appearance of resistance to amikacin in MP10. Resistance to 4'-deoxy-6'-N-methylamikacin (BB-K311) by enzymatic modification has not been reported previously. As with amikacin, MP6 was susceptible to BB-K311 and its aminoglycoside 3'-phosphotransferase II did not phosphorylate this amikacin derivative appreciably. We found that the plasmid-borne mutation in MP10, however, localized by being cloned with a 3.7-megadalton HindIII fragment containing the aminoglycoside 3'-phosphotransferase II gene, resulted in increased phosphorylation of BB-K311 and resistance to it. Thus, the mutation distinguishing MP6 and MP10 has increased the activity of an existing aminoglycoside-modifying enzyme and produced new bacterial resistance to two previously minor substrates of the enzyme.
In vitro activity of temocillin, a new beta-lactamase-stable penicillin active against enterobacteria
Authors: Greenwood D , Cowlishaw A , Eley A
Published: June 2012

The activity of temocillin was investigated in vitro against 523 clinical isolates of enterobacteria and Pseudomonas aeruginosa. The minimum inhibitory concentration of the new compound for all ampicillin-susceptible enterobacteria and for 90% of ampicillin-resistant enterobacteria was 16 micrograms/ml or less, a concentration readily achieved in plasma. P. aeruginosa strains were uniformly resistant to temocillin. All but 3 of a separate group of 48 enterobacteria exhibiting resistance to the combination of clavulanic acid and amoxicillin were found to be inhibited by 16 micrograms or less of temocillin per ml. The new compound also displayed good activity against a group of laboratory stock cultures selected on the basis of differential resistance to presently available beta-lactam agents. Two of these strains were cefotaxime resistant.
Pharmacokinetics of the cephalosporin SM-1652 in mice, rats, rabbits, dogs, and rhesus monkeys
Authors: Matsui H , Yano K , Okuda T
Published: June 2012

The pharmacokinetics of SM-1652 were studied in mice, rats, rabbits, dogs, and rhesus monkeys. The plasma half-lives of SM-1652, administered intravenously at a dose of 20 mg/kg, were 11.0 min in mice, 26.0 min in rats, 65.8 min in rabbits, 72.6 min in dogs, and 150.9 min in monkeys. The 24-h urinary excretion of SM-1652 was 30 to 35% of the dose in mice and rats, 70 to 75% in rabbits and dogs, and 45% in monkeys. Biliary excretion of the antibiotic over a 24-h period was 60 and 19% in rats and rabbits, respectively; it was 19% in dogs over a 9-h period after SM-1652 administration. Approximately 95% of the intravenous dose of SM-1652 was recovered as the unchanged form in the urine and bile of rats and rabbits. The binding of SM-1652 to serum protein was 44.0% in mice, 46.0% in rats, 90.4% in rabbits, 93.2% in monkeys, 30.0% in dogs, and 96.3% in humans.
Impact of cefoperazone therapy on fecal flora
Authors: Mulligan M E , Citron D M , McNamara B T , Finegold S M
Published: June 2012

To evaluate the effects of parenteral cefoperazone therapy upon human fecal flora, fecal specimens obtained from four patients before and during therapy (as well as after therapy for one patient) were cultured quantitatively for facultative, aerobic, and anaerobic bacteria and for fungi. Cefoperazone therapy was associated with major changes in fecal flora. There was suppression to undetectable levels or an appreciable reduction in all anaerobic bacteria as well as suppression of all initially detected Enterobacteriaceae. During therapy, there was acquisition or an increase in counts of Candida spp., so that these became the most numerous fecal microorganisms in all patients. In addition, Pseudomonas spp. and coagulase-negative Staphylococcus sp. were acquired by three patients. These marked alterations in flora have potentially important consequences.
Resistance of Pseudomonas aeruginosa PAO to nalidixic acid and low levels of beta-lactam antibiotics: mapping of chromosomal genes
Authors: Rella M , Haas D
Published: June 2012

Resistance to high concentrations of nalidixic acid in Pseudomonas aeruginosa PAO was due to mutations in one locus designated nalA, which was mapped by transduction between hex-9001 and leu-10. The nalA mutants were cross-resistant to pipemidic acid, a nalidixic acid analog, at relatively low concentrations. Replicative DNA synthesis was resistant to both drugs in permeabilized cells of nalA mutants. A locus coding for low-level resistance to nalidixic acid, nalB, was cotransducible with pyrB, proC, and met-28. The nalB mutants were also resistant to low levels of pipemidic acid, novobiocin, and beta-lactam antibiotics (e.g., carbenicillin, azlocillin, and cefsulodin), but not to other drugs, such as gentamicin, rifampin, kanamycin, or tetracycline. In nalB mutants, DNA replication showed wild-type sensitivity to nalidixic acid, whereas carbenicillin-induced filamentation required higher drug levels than in the wild-type strain. Thus, nalB mutations appear to decrease cell permeability to some antibiotics. The sensitivity of replicative DNA synthesis to nalidixic acid and novobiocin was very similar in P. aeruginosa and Escherichia coli; by contrast, the concentrations of these drugs needed to inhibit growth of P. aeruginosa were higher than those reported for E. coli by one or two orders of magnitude.
Effects of azlocillin in combination with clavulanic acid, sulbactam, and N-formimidoyl thienamycin against beta-lactamase-producing, carbenicillin-resistant Pseudomonas aeruginosa
Authors: Calderwood S B , Gardella A , Philippon A M , Jacoby G A , Moellering R C
Published: June 2012

We investigated the effects of the combination of azlocillin with the beta-lactamase inhibitors clavulanic acid and sulbactam and with N-formimidoyl thienamycin against strains of Pseudomonas aeruginosa with R-factor-mediated carbenicillin resistance. The 10 strains tested (1 R-, 9 R+) were isogenic, except for the presence of individual plasmids determining each of nine plasmid-mediated beta-lactamases found in P. aeruginosa. We utilized a checkerboard technique for testing antibiotic combinations. Low concentrations of clavulanic acid produced synergy with azlocillin against the strains producing the TEM-1, TEM-2, PSE-1, PSE-3, and PSE-4 beta-lactamases; for the strains producing the OXA-1, OXA-2, OXA-3, and PSE-2 beta-lactamases, such synergy was not found. With sulbactam, synergy was demonstrated in all strains except that producing PSE-2 beta-lactamase; for several strains, however, the concentration of sulbactam required to produce synergy was substantially higher than that for clavulanic acid. N-Formimidoyl thienamycin was highly active as a single agent against all of the strains, regardless of beta-lactamase production. The combination of N-formimidoyl thienamycin and azlocillin produced synergy against only two of the strains tested.
Resistance to beta-lactam antibiotics in Streptococcus faecium
Authors: Eliopoulos G M , Wennersten C , Moellering R C
Published: June 2012

Clinical isolates of Streptococcus faecium are characteristically resistant to beta-lactam antibiotics. Two strains, selected for hypersusceptibility to penicillin, were derived from normally resistant isolates treated with novobiocin. These strains were also found to be hypersusceptible to other beta-lactams. Differences in beta-lactam susceptibility between the original isolates and the hypersusceptible strains could not be attributed to alterations in penicillin-binding protein affinities, and no evidence of a relative permeability barrier was found in the resistant strains. Isolated cell membranes prepared from resistant strains were found to possess two protein bands which were absent or greatly diminished in the membranes of susceptible strains. Hypersusceptibility to beta-lactam antibiotics in these strains may be due to the absence or alteration of one or more cell membrane proteins distinct from the penicillin-binding proteins of these organisms.
Transposon-mediated multiple antibiotic resistance in Acinetobacter strains
Authors: Devaud M , Kayser F H , Bächi B
Published: June 2012

Acinetobacter calcoaceticus subsp. anitratus, which is unusually resistant to multiple antibiotics, was the cause of an epidemic of respiratory tract infections in patients in an intensive care unit. A representative isolate of the epidemic strain was found to contain the aminoglycoside-modifying enzymes 3-N-acetyltransferase, 3'-phosphotransferase, and 3"-adenylyltransferase, which confer resistance to gentamicin, kanamycin, and streptomycin, respectively. In addition, the strain produced a cephalosporinase and was resistant to penicillins due to the production of a TEM-2 beta-lactamase. The bacterial isolate also exhibited resistance to chloramphenicol, tetracycline, and sulfonamides. The resistant phenotype of this strain was similar to resistance patterns frequently observed in endemic hospital flora, suggesting that the transfer of an R plasmid into Acinetobacter sp. may have occurred. However, antibiotic resistance could not be transferred to any recipient by various mating procedures. After plasmid RP4 was transferred into an ampicillin- and kanamycin-susceptible derivative of the epidemic strain, mobilization of resistance to chloramphenicol, gentamicin, streptomycin, sulfonamides, and possibly tetracycline could be achieved. This mobilization was due to the transposition of a 16-megadalton DNA sequence from the Acinetobacter chromosome into plasmid RP4. Insertion of the transposable sequence occurred near the PstI and SmaI sites around position 22.5 on the physical map of plasmid RP4. We suggest that a plasmid resistant to multiple antibiotics was transferred from the hospital flora into Acinetobacter sp. but could not be maintained stably in this host. Instead, a multiply resistant DNA sequence was transposed and stably integrated into the Acinetobacter chromosome. The occurrence of such multiply resistant transposons on conjugative plasmids contributes greatly to the genetic variability of bacteria and may sometimes have serious epidemiological and therapeutic consequences.
Comparison of cefuroxime and penicillin in the treatment of uncomplicated gonorrhea
Authors: Lossick J G , Thompson S E , Smeltzer M P
Published: June 2012

In a randomized double-blind trial, 216 men and 142 women infected with uncomplicated gonorrhea were treated with either 1.5 g of cefuroxime or 4.8 x 10(6) U of aqueous procaine penicillin G intramuscularly and 1.0 g of probenecid. The cure rates in the treatment groups were 96 and 95%, respectively. Intramuscularly administered cefuroxime was better tolerated than was procaine penicillin. Comparative antibiotic susceptibility studies revealed that cefuroxime and penicillin were about equally active and that both were more active than cefamandole or cefoxitin. Because cefuroxime is not degraded by the action of beta-lactamase enzymes, it has promise as an alternative to spectinomycin in the treatment of penicillinase-producing Neisseria gonorrhoeae infections.
Treatment of experimental herpes simplex virus encephalitis with (E)-5-(2-bromovinyl)-2'-deoxyuridine in mice
Authors: de Clercq E , Zhang Z X , Sim I S
Published: June 2012

(E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU) was examined for its ability to increase the survival rate of mice infected intracerebrally with herpes simplex virus type 1 (strain KOS). BVDU was administered orally (through the drinking water), intraperitoneally, or subcutaneously at doses ranging from 40 to 400 mg/kg per day, starting 0, 2, 4, or 6 days postinfection. Regardless of the route of administration, BVDU effected a significant reduction in the mortality rate of mice infected with herpes simplex virus type 1 if treatment was initiated shortly after virus infection, i.e., day 0 or 2 (or day 4, if BVDU was administered subcutaneously) postinfection, at a dosage of 80 mg/kg per day or higher. Similar beneficial effects were noted with orally administered BVDU in mice inoculated intraperitoneally or intranasally with herpes simplex virus type 1. These findings establish the therapeutic efficacy of BVDU in the systemic treatment of herpes simplex virus type 1 encephalitis in mice.
Disposition of arildone, an antiviral agent, after various routes of administration
Authors: Benziger D P , Edelson J
Published: June 2012

[14C]arildone was administered both topically and intravaginally to mice 5 times a day for 7 days to simulate conditions of clinical usage. Urinary and fecal excretion of radioactivity indicated that arildone was extensively absorbed by both routes of administration. The levels of radioactivity in the vagina and skin declined from about 12 micrograms equivalents per g to 3 micrograms equivalents per g between 1 and 2 days after the last application. Only small amounts of unchanged arildone were found in urine from the vaginally treated animals; the major urinary metabolites were chloromethoxyphenol, its sulfate ester, and chlorohydroquinone sulfate. After about 1 month of daily oral administration of arildone to rats and monkeys or vaginal administration three times a day for 20 days to dogs, only low levels of intact drug were found in the systemic circulation. The disposition or beta-phase half-life of arildone in monkeys after intravenous administration was about 0.5 h. The disposition of [14C]arildone in mice, rats, dogs, and monkeys after various routes of administration was also investigated.
Reduction of experimental gentamicin nephrotoxicity in rats by dietary calcium loading
Authors: Bennett W M , Elliott W C , Houghton D C , Gilbert D N , DeFehr J , McCarron D A
Published: June 2012

Since gentamicin accumulates in the renal cortex before renal failure and calcium reduces gentamicin binding to cell membranes, we examined the effect of dietary calcium loading on gentamicin toxicity in male F344 rats. Rats were fed either a normal (0.5%)- or a high (4%)-calcium-content chow. Calcium loading did not alter inulin clearance, urinary excretion of sodium or total osmoles, or serum ionized calcium. However, calcium loading caused elevation of urinary calcium excretion and lowered urinary cyclic AMP levels. The data suggest that calcium loading may have slowed the accumulation of gentamicin (40 mg/kg per day) by the renal cortex. Histological and functional evidence of nephrotoxicity was delayed in onset and attenuated in magnitude. The results indicate that dietary calcium loading reduces experimental gentamicin nephrotoxicity. Protection may be associated with slower renal cortical accumulation of gentamicin. Calcium-dependent membrane or intracellular events may mediate this effect.
Effect of rifampin on ampicillin killing of group B streptococci
Authors: Smith S M , Eng R H , Landesman S
Published: June 2012

The activity of rifampin against group B streptococci as a single agent and in combination with ampicillin was examined. The minimum concentration of rifampin required to inhibit 90% of the isolates of group B streptococci (18 of 20 isolates) was 0.6 microgram/ml. The checkerboard double-dilution studies of these two antibiotics and the time-killing studies both indicate that rifampin inhibits the bactericidal activity of ampicillin for group B streptococci.
In vitro activity of temocillin (BRL 17421), a novel beta-lactam antibiotic
Authors: Van Landuyt H W , Pyckavet M , Lambert A , Boelaert J
Published: June 2012

The minimal inhibitory concentration of temocillin (BRL 17421) against 476 clinical isolates was determined by an agar dilution method. Temocillin was active against most of the Enterobacteriaceae, Haemophilus, and Neisseria strains tested. The compound showed low activity or was inactive against Bacteroides, Campylobacter, Acinetobacter, Pseudomonas, and Staphylococcus aureus strains. Within each species, individual strains showed a high degree of uniformity in their susceptibility to temocillin; the drug concentrations that inhibited the growth of 90% of organisms were the same or close to those which inhibited the growth of 50% of organisms. In contrast, the same strains showed a very wide range of susceptibility to the other antibiotics tested, including third-generation cephalosporins. Against strains of Enterobacteriaceae highly susceptible to third-generation cephalosporins, temocillin was considerably less active than cefotaxime, ceftazidime, and moxalactam, although it was more active than cefazolin and piperacillin. Against certain strains of Enterobacter and Citrobacter resistant to third-generation cephalosporins, temocillin was more active than cefotaxime and ceftazidime. An increase in the inoculum size did not alter the activity of temocillin, indicating that the compound has high stability to beta-lactamases. The minimal lethal concentration was also very similar to the minimal inhibitory concentration when an inoculum of 10(5) colony-forming units was used.
Synergy of fosmidomycin (FR-31564) and other antimicrobial agents
Authors: Neu H C , Kamimura T
Published: June 2012

Fosmidomycin (FR-31564), a phosphonic acid derivative, was combined with cefazolin, cephalexin, ampicillin, carbenicillin, ticarcillin, gentamicin, and trimethoprim. Synergy between fosmidomycin and penicillins or cephalosporins was found for 37 to 52% of the Enterobacteriaceae tested. Synergy with trimethoprim was found against 55% of bacteria isolated, but only 17% of the strains showed synergy between formidomycin and gentamicin. Synergy between fosmidomycin and ticarcillin was shown for 35% of the Pseudomonas isolates. Cefazolin-, ampicillin-, and gentamicin-resistant isolates of various species were synergistically inhibited by fosmidomycin, as were ticarcillin- and gentamicin-resistant isolates. Antagonism was not encountered. This study illustrates another example of synergistic activity of compounds which attack different mechanisms in bacterial cells.
Purification and properties of inducible penicillin beta-lactamase isolated from Pseudomonas maltophilia
Authors: Saino Y , Kobayashi F , Inoue M , Mitsuhashi S
Published: June 2012

Two types of beta-lactamase were found in the cell-free extract from Pseudomonas maltophilia GN12873. One was an inducible penicillin beta-lactamase, and the other was an inducible cephalosporin beta-lactamase. The purified penicillin beta-lactamase gave a single protein band on polyacrylamide gel electrophoresis. The isoelectric point was 6.9, and the approximate molecular weight was 118,000 by gel filtration and 26,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that this enzyme consisted of four subunits. For the hydrolysis of penicillin G, the optimal pH was 8.0 and the optimal temperature was 35 degrees C. The enzyme activity was inhibited by cephamycin derivatives, carpetimycins A and B, iodine, and HgCl2, but not by clavulanic acid. Furthermore, beta-lactamase activity was almost completely inhibited by EDTA but was recovered by the addition of zinc ion. The enzyme showed a unique substrate profile, hydrolyzing N-formimidoyl thienamycin at a significant rate.
Pharmacokinetics and cerebrospinal fluid bactericidal activity of ceftriaxone in the treatment of pediatric patients with bacterial meningitis
Authors: Del Rio M , McCracken G H , Nelson J D , Chrane D , Shelton S
Published: June 2012

Single-dose pharmacokinetics of ceftriaxone were determined in 19 patients with proven bacterial meningitis. The dosage was 50 mg of ceftriaxone per kg. The plasma concentration time curve declined in a biexponential manner. The mean peak plasma concentration was 207 micrograms/ml, and the elimination half-life was 4 h. In 12 patients, multiple-dose pharmacokinetics were determined after a loading dose of 75 mg of ceftriaxone per kg, followed by 50-mg/kg doses every 8 h in 5 patients or every 12 h in 7 patients. The mean peak plasma concentration was 230 micrograms/ml after the first dose and 263 micrograms/ml after the last dose. Of 12 patients, 5 had trough values that were larger after multiple doses than after a single dose. Mean penetration of ceftriaxone into cerebrospinal fluid was 3.1%. The median cerebrospinal fluid bactericidal titer against the patients pathogens was greater than 1:1,024 and less than 1:2,048. The drug was well tolerated without adverse effects.
Comparison of ceforanide and cephalothin prophylaxis for vaginal hysterectomies
Authors: Jacobson J A , Hebertson R , Kasworm E
Published: June 2012

We compared the safety and efficacy of a six-dose regimen of cephalothin with a two-dose regimen of ceforanide for the prevention of infection after elective vaginal hysterectomy. A total of 150 patients were randomly assigned to either regimen. The overall incidence of documented pelvic infection was 5.3% and did not differ significantly between the prophylaxis groups when stratified by type of surgery. No serious adverse reactions were encountered in either group, but phlebitis was significantly more common in patients receiving cephalothin. We conclude that a two-dose regimen of ceforanide given intramuscularly is as effective as, and possibly better tolerated than, a six-dose regimen of cephalothin.
Treatment of urinary tract infections with a combination of amoxicillin and clavulanic acid
Authors: Iravani A , Richard G A
Published: June 2012

A 10-day course of amoxicillin (250 mg)-potassium clavulanate (125 mg) was administered three times daily to 116 female college students with urinary tract infections. All of the bacterial isolates from these patients were susceptible to amoxicillin-potassium clavulanate in vitro; only 81.0% were susceptible to amoxicillin alone. Evaluations at 1 week after completion of this course showed that clinical and bacteriological cures had been achieved in 96.9% of those who completed therapy. Cures were sustained in 85.6% of the patients examined at 4 weeks after the end of therapy. Therapeutic responses were comparable, irrespective of the results of antibody-coated bacteria tests. All strains of Enterobacteriaceae isolated from the rectal and urogenital sites at 1 week after therapy were susceptible to amoxicillin-potassium clavulanate. The proportion of fecal Escherichia coli resistant to amoxicillin alone increased from 13.3% before therapy to 35.6% at 1 week after therapy. Adverse drug reactions consisted of gastrointestinal symptoms (9.8%) and rashes (4.1%). Sixteen patients (14.2%) developed symptomatic candida vaginitis by 1 week after therapy.
Antimicrobial susceptibility of 103 strains of Haemophilus ducreyi isolated in Johannesburg
Authors: Bilgeri Y R , Ballard R C , Duncan M O , Mauff A C , Koornhof H J
Published: June 2012

Of 103 strains of Haemophilus ducreyi isolated in Johannesburg, 96 produced beta-lactamase and were resistant to penicillin and ampicillin. Most strains showed resistance to tetracycline, sulfisoxazole, and sulfamethoxazole. All isolates were susceptible to rifampin, erythromycin, and cefoxitin, moderately susceptible to trimethoprim-sulfamethoxazole (1:19) and minocycline, and somewhat less susceptible to doxycycline.
Comparative Stability of Newly Introduced β-Lactam Antibiotics to Renal Dipeptidase
Authors: Mikami Hidetada , Ogashiwa Mieko , Saino Yushi , Inoue Matsuhisa , Mitsuhashi Susumu
Published: June 2012

Renal dipeptidase purified from swine kidney hydrolyzed
N
-formimidoyl thienamycin, carpetimycins A and B, and Sch29482, but not azthreonam, penicillin G, or cephaloridine.
Immunological responsiveness of guinea pigs to antibiotics diffusing from bone cement
Authors: Petersen B H , Steimel L A , Black H R
Published: June 2012

The sustained release of antibiotics from bone cement provides an opportunity for the induction of hypersensitivity. We evaluated the cellular and humoral immune responsiveness of guinea pigs to antibiotics diffusing from bone cement. We were unable to detect the presence of antibodies or skin hypersensitivity to any of the antibiotics tested.
In vitro activity of new beta-lactam antibiotics and other antimicrobial drugs against anaerobic isolates from obstetric and gynecological infections
Authors: Ohm-Smith M J , Hadley W K , Sweet R L
Published: June 2012

The in vitro activities of N-formimidoyl thienamycin, clindamycin, chloramphenicol, metronidazole, cefoperazone, cefotaxime, cefoxitin, moxalactam, penicillin G, and piperacillin were determined against 158 anaerobic bacteria isolated from endometrial wash cultures of women with pelvic infections. In general, N-formimidoyl thienamycin was the most active, with all organisms inhibited by less than or equal to 0.5 microgram/ml. Chloramphenicol, clindamycin, and metronidazole inhibited all organisms by less than or equal to 8 microgram/ml. The penicillins and cephalosporins exhibited variable activity of lesser degrees.
Selection for mercurial resistance in hospital settings
Authors: Porter F D , Silver S , Ong C , Nakahara H
Published: June 2012

The frequency of resistance to Hg2+ in 1980 to 1981 collections from Barnes Hospital, St. Louis, Mo., was only 2% for Staphylococcus aureus and 9% for Escherichia coli. The frequency of Hg2+ resistance in E. coli isolates from Jikei University Hospital, Tokyo, Japan, was 57% during 1972 to 1977 and decreased to 29% in 1979 to 1982; for S. aureus the frequency of Hg2+ resistance dropped from 36% in 1972 to 1977 to 10% in 1979 to 1982. Frequencies of resistances to cadmium (S. aureus) and arsenic (S. aureus and E. coli) remained approximately constant during this time. The decrease in frequency of mercurial resistance is attributed to the termination of the use of organomercurials (largely phenylmercury and thimerosal) in hospital liquid detergents and disinfectants. It is proposed that selection for mercurial resistance occurred within the hospital setting when there was widespread use of mercurials. The resistance patterns and phage types for each of four new mercurial-resistant S. aureus isolates from St. Louis were distinct, indicating that no single type of "hospital staph" predominates. Furthermore, resistance to thimerosal, merbromin, and methylmercury and the ability to volatilize 14C from [14C]methylmercury were found with the new isolates and never with previously known mercurial resistance plasmids in S. aureus.
In vitro susceptibility of methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains to N-formimidoyl thienamycin
Authors: Witte J L , Sapico F L , Canawati H N
Published: June 2012

A total of 82 clinical isolates of methicillin-resistant Staphylococcus aureus and 21 isolates of methicillin-susceptible S. aureus were studied for in vitro susceptibility to N-forminidoyl thienamycin at incubation temperatures of 30 and 35 degrees C. The disk diffusion test results were correlated with the macrobroth dilution test by means of the error rate-bounded method of analysis. Both methicillin-susceptible and (to a lesser degree) methicillin-resistant strains were generally susceptible to the antibiotic as judged from their minimum inhibitory concentrations. The discrepancy between in vitro results obtained at 30 and at 35 degrees C was not very remarkable. However, tolerance of N-formimidoyl thienamycin was observed in 37% of methicillin-resistant strains and 24% of methicillin-susceptible strains at an incubation temperature of 30 degrees C; at 35 degrees C, the values were 54% (methicillin-resistant strains) and 14% (methicillin-susceptible strains).
Susceptibility of Neisseria meningitidis and Neisseria gonorrhoeae isolates to N-formimidoyl thienamycin
Authors: Dudek E J , Stephenson J D , Bohnhoff M , Lerner S A
Published: June 2012

A diverse collection of 123 meningococcal and 126 gonococcal isolates was tested for susceptibility to N-formimidoyl thienamycin (N-F-thienamycin; MK0787) and to penicillin G (PEN). All of the meningococci were susceptible to both of these, as well as to rifampin. Among gonococci, beta-lactamase-producing strains, which were resistant to PEN, were susceptible to N-F-thienamycin. Among non-beta-lactamase-producing strains, the minimal inhibitory concentrations of N-F-thienamycin and PEN were less than or equal to 1.28 micrograms/ml. Of these, the strains with PEN minimal inhibitory concentrations toward the higher end of the range were likely to be more susceptible to N-F-thienamycin, whereas the strains that were highly susceptible to PEN were likely to have higher minimal inhibitory concentrations of N-F-thienamycin.
Activity of nine antimicrobial agents against Lancefield group C and group G streptococci
Authors: Rolston K V , LeFrock J L , Schell R F
Published: June 2012

The activity of nine antimicrobial agents against 44 strains of group C and group G streptococci was studied using a microtiter broth dilution technique. Several antimicrobial agents, including third-generation cephalosporins, the newer semisynthetic penicillins, and erythromycin, exhibited good activity against the organisms. Occasional tolerance to various agents was observed. No cross-tolerance was observed in this study.
Tromantadine: inhibitor of early and late events in herpes simplex virus replication
Authors: Rosenthal K S , Sokol M S , Ingram R L , Subramanian R , Fort R C
Published: June 2012

Unlike amantadine (1-adamantanamine), tromantadine (N-1-adamantyl-N-[2-(dimethyl amino)ethoxy]acetamide hydrochloride) inhibits herpes simplex virus type 1 (KOS strain)-induced cytopathic effect and virus replication with limited toxicity to the cells. Vero and HEp-2 cells tolerated up to 2 mg of tromantadine per 2 X 10(6) cells for 24-, 48-, or 96-h incubation periods with little change in cell morphology. Treatment of the cells with 10 to 50 micrograms of tromantadine reduced herpes simplex virus-induced cytopathic effect. Treatment with 100 to 500 micrograms of tromantadine inhibited herpes simplex virus-induced cytopathic effect and reduced virus production. Complete inhibition of virus production was observed with treatments of 500 micrograms to 1 mg. The antiherpetic activity of tromantadine was dependent upon the viral inoculum size and the time of addition of the compound with respect to infection. Virion synthesis and viral polypeptide synthesis were inhibited by addition of tromantadine at the time of infection or 4 h postinfection. The results are consistent with tromantadine inhibition of an early event in herpes simplex virus infection, before macromolecular synthesis, and a late event, such as assembly or release of virus.
Effect of Protein Synthesis Inhibition on the Induction of Cell Lysis in
Escherichia coli
by Mecillinam plus Nocardicin A
Authors: Berenguer José , de Pedro Miguel A. , Vázquez David
Published: June 2012

Cell lysis can be induced in
Escherichia coli
by the combined use of the β-lactam antibiotics nocardicin A and mecillinam. Apparently, the induction of cell lysis occurs by a sequential mechanism in which mecillinam acts first, and nocardicin A has a triggering action insensitive to the inhibition of protein synthesis.
Determination of cefoperazone concentration in serum and muscle tissue with a versatile high-pressure liquid chromatographic method
Authors: Muder R R , Diven W F , Yu V L , Johnson J
Published: June 2012

A rapid, specific, and reproducible high-pressure liquid chromatographic method was developed for the determination of cefoperazone concentration in serum and tissue. The assay uses a simple methanol extraction, with cefoxitin as the internal standard. The limits of detection are 1 to 150 micrograms/ml; the maximum coefficient of variation is 7.4%. Using the same chromatography column, muBondapak phenyl, and mobile-phase 0.005 M tetrabutylammonium buffer-acetonitrile (80:20), the method can be easily adapted for the analysis of cefoxitin and moxalactam.
Radioimmunoassay for metabolites of 9,3"-diacetylmidecamycin, a macrolide antibiotic
Authors: Shimada N , Ueda T , Yokoshima T , Umemura K , Shomura T
Published: June 2012

A radioimmunoassay system has been developed for the measurement of two major metabolites of 9,3"-diacetylmidecamycin, Mb-6 and Mb-12. A radioimmunoassay for Mb-6 was performed by using anti-Mb-6 serum and a [125I]tyramined Mb-6 derivative as a radiolabeled antigen. The labeled antigen was prepared by the chloramine T method. The antiserum was obtained from a rabbit immunized with Mb-6 conjugated to bovine serum albumin. The obtained antiserum was cross-reactive with two other metabolites of 9,3"-diacetylmidecamycin, Mb-2 and Mb-12, in addition to Mb-6. This Mb-6 radioimmunoassay system could detect Mb-6 concentrations as low as 100 pg/ml of serum. The coefficients of variation were 4.5% (intra-assay) and 5.1% (inter-assay). A radioimmunoassay for Mb-12, using anti-midecamycin serum and a [125I]tyramined-Mb-12 derivative, has also been developed. The antiserum was cross-reactive only with Mb-12 among the 9,3"-diacetylmidecamycin metabolites. This Mb-12 radioimmunoassay system could detect Mb-12 concentrations as low as 2 ng/ml. The intra- and inter-assay variances were 5.9 and 5.8%, respectively.
Antibacterial activity of norfloxacin
Authors: Norrby S R , Jonsson M
Published: June 2012

Norfloxacin, a new quinoline derivative, was studied in vitro, and determinations of agar dilution minimal inhibitory concentrations (MICs) and broth dilution MICs and MBCs were made. Nalidixic acid and cinoxacin were used as comparative agents. Norfloxacin was found to be extremely active against all strains tested of Escherichia coli, Klebsiella spp., Proteus mirabilis, indole-positive Proteus spp. Serratia spp., Citrobacter spp., and Enterobacter spp., with MICs normally below 1 microgram/ml. It also was found to be highly active against Pseudomonas aeruginosa, Staphylococcus saprophyticus, and enterococci, which are all resistant to nalidixic acid and cinoxacin. The MICs for norfloxacin obtained by broth dilution were slightly higher than those obtained by agar dilution, whereas the reverse was true for nalidixic acid and cinoxacin. The MBCs of norfloxacin were only slightly higher than the MICs, even at high inocula. The in vitro activity of norfloxacin was not dependent on the inoculum size, whereas both the MICs and the MBCs of nalidixic acid increased markedly for many of the strains tested when the inoculum was increased in broth dilution from 10(3) to 10(6) colony-forming units per ml. Norfloxacin seems to be a promising antibacterial agent for the treatment of urinary tract infections, especially those caused by Pseudomonas spp. and other species today requiring the use of injectable antibiotics.
Bactericidal and synergistic activity of moxalactam alone and in combination with gentamicin against Pseudomonas aeruginosa
Authors: Yu P K , Edson R S , Washington J A , Hermans P E
Published: June 2012

The bactericidal activity of moxalactam, alone and in combination with gentamicin, was studied with macrobroth two-dimensional checkerboard and killing curve techniques against gentamicin-resistant and -susceptible strains of Pseudomonas aeruginosa. Moxalactam was bactericidal at concentrations equal to or at least two to four times its inhibitory concentrations. Synergy at clinically applicable concentrations of moxalactam and gentamicin occurred with 6 of 14 gentamicin-resistant strains and 4 of 4 gentamicin-susceptible strains by the checkerboard technique and with 7 of 14 gentamicin-resistant strains by the killing curve technique. Synergy between moxalactam and gentamicin against gentamicin-resistant strains of P. aeruginosa is unpredictable and strain- and method-dependent.
Rapid selection of organisms with increasing resistance on subinhibitory concentrations of norfloxacin in agar
Authors: Tenney J H , Maack R W , Chippendale G R
Published: June 2012

Serial passage of Pseudomonas aeruginosa ATCC 27853 or Escherichia coli ATCC 25922 on agar with subinhibitory concentrations of norfloxacin rapidly produced isolates with minimal inhibitory concentrations (MICs) of norfloxacin up to 512-fold higher than that for the original strain. Although MICs of seven unrelated antibiotics were unchanged, increasing MICs occurred in parallel with norfloxacin, cinoxacin, and nalidixic acid regardless of which of these three organic acids was used to select for increased resistance. P. aeruginosa with a norfloxacin MIC of greater than 256 micrograms/ml could be selected; however, E. coli with MICs greater than the clinically achievable level of 16 micrograms/ml could not be produced.
Application of the fluorescamine reaction with 6-aminopenicillanic acid to estimation and detection of penicillin acylase activity
Authors: Baker W L
Published: June 2012

6-Aminopenicillanic acid may be quantitatively estimated by its reaction with fluorescamine in the concentration range of 1 to 10 micrograms/ml. The difference in reactivity between 6-aminopenicillanic acid and benzylpenicillin, which does not react with fluorescamine, can be used to determine penicillin acylase activity and obtain data on enzyme parameters and inhibitors. Unlike amino acids and peptides, 6-aminopenicillanic acid reacts strongly with fluorescamine at pH 4, an observation which can be used to determine the presence of penicillin acylase in whole bacterial cell preparations.
Penicillin Therapy of Experimental Endocarditis Induced by Tolerant
Streptococcus sanguis
and Nontolerant
Streptococcus mitis
Authors: Lowy Franklin D. , Neuhaus Ellen G. , Chang Daniel S. , Steigbigel Neal H.
Published: June 2012

The response of tolerant
Streptococcus sanguis
and nontolerant
Streptococcus mitis
infections to penicillin therapy was compared in the rabbit model of endocarditis. The minimal inhibitory and bactericidal concentrations of penicillin were 0.1 and 0.1 μg/ml, respectively, for
S. mitis
and 0.05 and 6.2 μg/ml, respectively, for
S. sanguis
. Time-kill studies done in vitro with penicillin concentrations of 2 and 20 μg/ml demonstrated minimal killing of the tolerant strain, with a 3 log difference in survival between the two strains after 24 and 48 h. Both strains produced endocarditis with comparable bacterial densities on the valvular vegetations. Rabbits were treated with procaine penicillin G in two dosage regimens, 80,000 or 5,000 U/kg given every 8 h. There was no difference between bacterial densities in valvular vegetations removed from rabbits infected with either strain after 2, 4, or 6 days of treatment with the high-dose regimen (serum penicillin concentration at 0.5 h, 9.4 μg/ml), despite the fact that serum bactericidal activity against the tolerant strain at 0.5 h was minimal. With the low-dose penicillin regimen (serum concentration at 0.5 h, 2.5 μg/ml), therapy was significantly less effective in the tolerant group only after 6 days of treatment. Similar results were obtained when penicillin was administered in low and high doses to prevent infection. In this animal model of infection, penicillin tolerance was associated with a diminished response to penicillin therapy only when the dose was severely restricted. In the high-dose regimen, there was no difference in the response to penicillin therapy between animals infected with either strain, despite the presence of only minimal serum bactericidal activity in the rabbits infected with the tolerant strain.
In vitro antibacterial activity of norfloxacin (MK-0366, AM-715) and other agents against gastrointestinal tract pathogens
Authors: Shungu D L , Weinberg E , Gadebusch H H
Published: June 2012

A comparison was made of the in vitro activities of norfloxacin and of nine other orally administered antibacterial agents against 180 clinical isolates representing the bacterial species most frequently implicated in infections of the gastrointestinal tract in humans. The 90% minimal inhibitory concentrations showed norfloxacin to be 4, 15, 4, 17, 17, 17, and 33 times more active than the next best compound tested against Campylobacter fetus subsp. jejuni, Escherichia coli, Salmonella spp., Shigella spp., Vibrio cholerae, Vibrio parahaemolyticus, and Yersinia enterocolitica, respectively, with an overall 90% minimal inhibitory concentration of less than or equal to 0.5 micrograms/ml. Norfloxacin was least active against Clostridium difficile (90% minimal inhibitory concentration, 128 micrograms/ml). These results should encourage further evaluation of norfloxacin as a potential chemotherapeutic agent in the treatment of enteric bacterial infections for which antibiotic therapy is indicated.
Pharmacokinetics and bacteriological effect of ceftazidime in experimental Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli meningitis
Authors: Sakata Y , Boccazzi A , McCracken G H
Published: June 2012

The pharmacokinetics and bacteriological effect of ceftazidime were evaluated in rabbits experimentally infected with Streptococcus pneumoniae, Haemophilus influenzae type b, and Escherichia coli K1. The mean penetration of ceftazidime into cerebrospinal fluid after single-dose or constant-infusion administration ranged from 7.8 to 14.9%. The median cerebrospinal fluid bactericidal titers were 1:64 against S. pneumoniae and H. influenzae and 1:128 against E. coli. The bacterial colony counts in cerebrospinal fluid were reduced by 58% to 100% (-2.3 to -3.9 log10 CFU/ml) in 3 h and by 100% (-3.2 to -5.1 log10 CFU/ml) in 9 h of constant infusion, whereas in untreated infected animals, bacterial counts increased from +1.4 to +2.1 log10 CFU/ml in 9 h. These data on ceftazidime compare favorably with those on penicillin, chloramphenicol, netilmicin, and moxalactam in this experimental meningitis model.
Ceftazidime therapy of serious bacterial infections
Authors: Eron L J , Goldenberg R I , Park C H , Poretz D M
Published: June 2012

Ceftazidime, a new broad-spectrum cephalosporin, was administered to 30 patients with serious bacterial infections in a randomized dosing trial with daily doses of 1.5 or 3 g. Both regimens were equally efficacious, with satisfactory clinical responses in 28 instances (93%) and microbiological eradication of 79% of initial bacterial isolates. The development of resistance to ceftazidime during therapy was observed in three cases (Enterobacter agglomerans, Enterobacter cloacae, and Pseudomonas aeruginosa) and superinfection by a resistant Enterobacter agglomerans strain occurred in one case. Adverse reactions of clinical significance included one case each of leukopenia, azotemia, diarrhea (Clostridium difficile toxin positive), and rash.
Unusual Mode of Inhibition of
Citrobacter freundii
β-Lactamases by Ceftriaxone
Authors: Arisawa Mikio , Ohshima Junko , Maruyama Hiromi B.
Published: June 2012

Several
Citrobacter freundii
β-lactamases, discernible by their substrate profiles and sensitivities to inhibition by newer cephalosporins, were inhibited by ceftriaxone in an unusual manner. Inhibition was noncompetitive at low concentrations of cephaloridine but became competitive at concentrations above 600 μM, which is close to the

K
m

(570 μM) for cephaloridine.
Selective Inhibitory Effect of Two 2-Nitronaphthofuran Derivatives on Growth and Induction of Transformation of Rous Sarcoma Virus-Infected Chicken Embryo Fibroblasts
Authors: Goldé Alice , Rouillard Danielle , Buisson Jean-Pierre , Royer René
Published: June 2012

Two 2-nitronaphthofuran derivatives exhibited a dose-dependent lethal effect on Rous sarcoma virus-tranformed chicken embryo fibroblasts. When they were added at time of infection, they prevented cell transformation, but not virus replication, in a dose-dependent manner. Since the two derivatives inhibited mainly the DNA sythesis, we assume that they altered some early DNA-dependent cell event required for cell transformation and not for the integration of provirus.