bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of plasmids determining high-level resistance to gentamicin in clinical isolates of Streptococcus faecalis
Authors: Zervos M J , Mikesell T S , Schaberg D R
Published: June 2012

Between November 1981 and October 1984, 48 of 3,458 clinical isolates of Streptococcus faecalis at the University of Michigan Hospital showed high-level (greater than 2,000 micrograms/ml) resistance to gentamicin, as well as to all other clinically available aminoglycosides. Thirteen percent of clinical isolates in the University of Michigan Hospital currently demonstrate this level of resistance. Transfer of resistance to a plasmid-free streptococcal recipient was observed in filter matings for 44 of 48 such isolates. Analysis of transconjugants by agarose gel electrophoresis showed that gentamicin resistance was transferred alone in 8 isolates and was combined with other antimicrobial resistances on the same plasmid in the other 36 isolates. There were seven isolates which transferred the property of horse blood beta-hemolysis along with gentamicin resistance. Transfer of gentamicin resistance was either by conjugative plasmids or by a nonconjugative but mobilizable plasmid. Transfer frequencies on filters ranged from 4.7 X 10(-2) to 4.1 X 10(-8). Based on donor and transconjugant antibiotic resistance markers, agarose gel electrophoresis, transfer properties, and restriction enzyme analysis, the plasmid content of transconjugants was heterogeneous and could be classified into at least seven different patterns. These findings argue against clonal dissemination as the cause of the increased frequency of resistant strains and suggest that resistance to gentamicin appears on a variety of physically distinct conjugative and nonconjugative plasmids in S. faecalis.
Concentration of ciprofloxacin in human prostatic tissue after oral administration
Authors: Dan M , Golomb J , Gorea A , Braf Z , Berger S A
Published: June 2012

Concomitant concentrations of ciprofloxacin in serum, urine, and prostatic tissue were determined in 15 patients after single oral doses of 750 mg. Levels in tissue ranged from 0.6 to 4.18 micrograms/g, and therapeutic concentrations were demonstrable for up to 9 h after administration. The mean ratio of tissue to serum concentration was 0.93 +/- 0.08 (standard error).
Imipenem-cilastatin as initial therapy for febrile cancer patients
Authors: Bodey G P , Alvarez M E , Jones P G , Rolston K V , Steelhammer L , Fainstein V
Published: June 2012

Imipenem-cilastatin was used to treat 79 febrile episodes in 71 cancer patients, most of whom had neutropenia. The overall response rate was 67%, and 76% of the 45 documented infections responded. The response rates for septicemias and pneumonias were 79 and 62%, respectively. Only 1 of the 17 infections caused by gram-negative bacilli failed to respond to this therapy. The most common side effects were skin rash, nausea, and diarrhea. Eight superinfections were detected during therapy.
Killing of Giardia lamblia by human milk is mediated by unsaturated fatty acids
Authors: Rohrer L , Winterhalter K H , Eckert J , Köhler P
Published: June 2012

Giardia lamblia trophozoites were killed in vitro by 1% fresh human milk in the presence of bile. A similar effect was achieved in the absence of bile with milk which had been stored for at least 24 h at 6 degrees C. This killing activity was found to be caused by unsaturated fatty acids. Depending on their chain length and the number of double bonds, the concentrations of unsaturated fatty acids required for a 50% killing effect varied between 15 and 36 microM. The saturated palmitic and stearic acids, as well as various substances related to fatty acids, showed only a slight killing effect. Bile enhanced and serum suppressed the action of fatty acids on the protozoan parasite. The possible site of interference of unsaturated fatty acids within G. lamblia and the reasons for the obvious inefficacy of dietary fatty acids in giardiasis are discussed.
Comparative trial of single-dose ciprofloxacin and ampicillin plus probenecid for treatment of gonococcal urethritis in men
Authors: Roddy R E , Handsfield H H , Hook E W
Published: June 2012

In a double-blind comparative trial, 100 men with uncomplicated gonorrhea caused by beta-lactamase-negative Neisseria gonorrhoeae were treated with a single 0.25-g dose of ciprofloxacin administered orally or with 3.5 g of ampicillin plus 1.0 g of probenecid administered orally. Urethral infection was eradicated in all 49 men treated with ciprofloxacin and in 47 (92%) of 51 men treated with ampicillin-probenecid (P = 0.12). The geometric mean MICs for pretreatment isolates were 0.008 microgram of ciprofloxacin per ml, 0.09 microgram of penicillin G per ml, 0.52 microgram of tetracycline per ml, and 23.5 micrograms of spectinomycin per ml. Chlamydia trachomatis infection persisted in 10 of 11 men treated with ciprofloxacin and in 11 of 14 men treated with ampicillin-probenecid. A single 0.25-g dose of ciprofloxacin was effective for treatment of uncomplicated urethral gonorrhea in men, but it did not eradicate coinfection with C. trachomatis.
Failure to detect ampicillin-resistant, non-beta-lactamase-producing Haemophilus influenzae by standard disk susceptibility testing
Authors: Mendelman P M , Chaffin D O , Clausen C , Stull T L , Needham C , Williams J D , Smith A L
Published: June 2012

We questioned whether the apparent rarity of ampicillin-resistant, non-beta-lactamase-producing (NBLP) Haemophilus influenzae was due to failure of detection. We identified ampicillin-resistant and ampicillin-susceptible H. influenzae by the agar dilution technique, using 10(5)- and 10(3)-CFU inocula. We compared the disk susceptibility of 18 ampicillin-resistant NBLP strains, 13 ampicillin-resistant, beta-lactamase-producing strains, and 10 ampicillin-susceptible strains by using standard 10- and 2-micrograms ampicillin disks on two different media. We also investigated the possibility that disks containing 10 micrograms of clavulanic acid and 2 micrograms of ampicillin could be used to distinguish between the two ampicillin-resistant populations. Using the disk containing 2 micrograms of ampicillin, we correctly differentiated all the ampicillin-resistant isolates from the ampicillin-susceptible isolates on both media (a zone diameter of less than or equal to 15 mm was considered resistant). In contrast, the 10-micrograms ampicillin disk failed to detect 44% (8 of 18) of the ampicillin-resistant NBLP strains (a zone diameter of less than or equal to 19 mm was considered resistant). The MIC of ampicillin with the 10(3)-CFU inoculum correlated better with zone diameters than with the 10(5)-CFU inoculum. A difference in zone diameters of greater than or equal to 8 mm between the disk containing 10 micrograms of clavulanic acid and 2 micrograms of ampicillin and the disk containing only 2 micrograms of ampicillin correctly identified all beta-lactamase-producing strains. We conclude that the 2-micrograms ampicillin disk tests more readily identify ampicillin resistance in H. influenzae than do the 10-micrograms ampicillin disk tests. Future investigation should determine whether this in vitro resistance correlates with clinical treatment failures.
Diversity of determinants encoding carbenicillin, gentamicin, and tobramycin resistance in nosocomial Pseudomonas aeruginosa
Authors: Mucha D K , Farrand S K
Published: June 2012

Plasmid pFMH1010, an 89-megadalton R plasmid, is endemic among members of the family Enterobacteriaceae at Hines Veterans Administration Hospital, Hines, Ill. It encodes resistance to nine antibiotics, including resistance to carbenicillin (Cb), gentamicin (Gm), and tobramycin (Tm). Pseudomonas aeruginosa strains resistant to carbenicillin, gentamicin, and tobramycin were isolated from five patients at Hines Veterans Administration Hospital from whom Serratia marcescens strains harboring pFMH1010 were also obtained. The P. aeruginosa strains were investigated to determine whether their Cb, Gm, and Tm characteristics derived from pFMH1010. One of the isolates, Ps559, was shown by Southern hybridization to contain approximately 76% of pFMH1010. Several lines of evidence suggested that the pFMH1010 sequences in Ps559 are integrated in the chromosome. Southern hybridization also demonstrated that the beta-lactam resistance of pFMH1010 is most probably due to the presence of sequences homologous with Tn3 and that these sequences are retained in Ps559. In two other Pseudomonas isolates, resistance to carbenicillin, gentamicin, tobramycin, and kanamycin was encoded by R plasmids unrelated to pFMH1010. In the last two isolates, resistance to gentamicin and tobramycin and several other antibiotics appeared to be chromosomally encoded, and it was rescuable from one of these strains by RP4-mediated mobilization.
Activity of compound G2 isolated from alfalfa roots against medically important yeasts
Authors: Polacheck I , Zehavi U , Naim M , Levy M , Evron R
Published: June 2012

An antimycotic agent was isolated from roots of alfalfa and further purified to yield a nonhemolytic, homogeneous compound (G2). This compound contained considerable activity against 10 medically important yeasts. MICs obtained by both agar and broth dilution methods ranged from 3 to 15 micrograms/ml. Compound G2 was fungicidal at a relatively low concentration for nine different species of yeasts tested (minimum fungicidal concentrations ranged between 6 and 24 micrograms/ml). The considerable stability of compound G2 and its strong inhibitory and fungicidal activity against a broad range of yeasts suggest that after further development it might be useful as an active agent in the treatment of mycotic infections.
Molecular cloning of amikacin resistance determinants from a Klebsiella pneumoniae plasmid
Authors: Tolmasky M E , Roberts M , Woloj M , Crosa J H
Published: June 2012

A multiresistant Klebsiella pneumoniae strain, JHCK1, harbored several plasmids. One of these, plasmid pJHCMW1, carried determinants for resistance to amikacin in addition to kanamycin, tobramycin, and ampicillin. The amikacin resistance determinant(s) was cloned and studied by restriction mapping, insertion, and deletion analysis. The amikacin resistance gene(s) was localized in a 1.5-kilobase DNA fragment. This pJHCMW1 DNA region was responsible for not only the resistance to amikacin but also the resistance to kanamycin and tobramycin. The cloned DNA fragment specified both an acetyltransferase activity and a low level of phosphotransferase activity. The two activities were absent from mutants that did not confer resistance to amikacin, kanamycin, and tobramycin.
Moxalactam in the treatment of typhoid fever
Authors: Uwaydah M , Vartivarian S , Shatila S , Raad I , Harakeh H , Nassar N T
Published: June 2012

Moxalactam therapy was evaluated in 25 patients with typhoid fever. A satisfactory initial response was observed in all cases. Treatment for 3 days resulted in a much higher relapse rate (three of five patients) than did treatment for 5 days (one of nine patients). None of the 11 patients treated for 10 to 11 days relapsed. Moxalactam is effective in typhoid fever, but its use is better restricted to special indications.
In vitro cytotoxicity and antibiotic activity of polymyxin B nonapeptide
Authors: Duwe A K , Rupar C A , Horsman G B , Vas S I
Published: June 2012

Polymyxin B nonapeptide, prepared by enzymic removal of the fatty acyl diaminobutyric acid side chain from polymyxin B, was about 100-fold less toxic to K562 cells than polymyxin B. MICs of polymyxin B nonapeptide against a test panel of bacteria were 2- to 64-fold lower than those of polymyxin B.
Efficacy of ciprofloxacin for experimental endocarditis caused by methicillin-susceptible or -resistant strains of Staphylococcus aureus
Authors: Carpenter T C , Hackbarth C J , Chambers H F , Sande M A
Published: June 2012

The efficacy of ciprofloxacin for experimental aortic valve endocarditis in rabbits infected by either a methicillin-susceptible or a methicillin-resistant strain of Staphylococcus aureus was compared with standard therapy of nafcillin or vancomycin, respectively. After 4 days of therapy, ciprofloxacin reduced the counts of organisms in aortic valve vegetations as effectively as the standard regimen for both susceptible and resistant strains. Mean concentrations of ciprofloxacin in serum achieved 1 h after a dose exceeded the MBC for each strain by twofold or less. In these experiments ciprofloxacin was as efficacious as standard regimens currently used to treat staphylococcal infections in humans.
Activity of fluconazole (UK 49,858) and ketoconazole against Candida albicans in vitro and in vivo
Authors: Rogers T E , Galgiani J N
Published: June 2012

Fluconazole (UK 49,858), a new orally administered bis-triazole, was compared with ketoconazole for activity in synthetic broth dilution susceptibility tests against Candida albicans and also in treatment of experimental systemic candidal infections in rats. In vitro studies indicated that fluconazole activity is less sensitive to acidic medium than is that of ketoconazole. At physiologic pH, fluconazole was approximately 16-fold less active than ketoconazole against 35 representative isolates of C. albicans. Two additional isolates (K-1 and K-3) recovered from patients who had failed ketoconazole therapy were 32- to 64-fold more resistant than the median of each drug for other isolates. In animal studies, fluconazole was very effective in prolonging survival of rats infected with a representative candidal strain. With an inoculum sufficient to kill 29 of 38 sham-treated animals, only 1 of 18 animals treated with 0.5 mg of fluconazole per kg per day died compared with 13 of 20 animals treated with 10.0 mg of ketoconazole per kg per day. However, when similar fluconazole treatment was administered to rats infected with the more resistant strain, K-1, no prolongation of survival was found. Thus, in vivo and in vitro results between strains correlated well for fluconazole. However, in comparing results between drugs, ketoconazole was 16-fold more active in vitro and fluconazole was 20-fold more active in vivo. This discrepancy may be due to drug distribution, modes of drug metabolism, or other pharmacologic differences between the two agents.
Dose ranging study and constant infusion evaluation of ciprofloxacin
Authors: Drusano G L , Plaisance K I , Forrest A , Standiford H C
Published: June 2012

We evaluated the pharmacokinetics of 100- and 200-mg doses of ciprofloxacin, with the 200-mg dose administered either as a 30-min infusion or as a 100-mg loading dose followed by a 4-h constant infusion of 25 mg/h in six normal volunteers. No significant differences were seen in the dose-normalized area under the curve when the 100- and 200-mg 30-min administrations were compared. Differences that approached statistical significance were seen when data from either of these trials were compared with data from the constant-infusion arm. Serum clearances averaged 23.0 +/- 9.1 liters/h per 1.73 m2 for the 100-mg dose and 23.7 +/- 5.1 liters/h per 1.73 m2 for the 200-mg dose. Renal clearance accounted for approximately two-thirds of the serum clearance in each instance. Half-lives were slightly longer than 4 h. For the constant-infusion arm, serum clearance was 28.9 +/- 2.7 liters/h per 1.73 m2, with renal clearance accounting for 58% of serum clearance. Although no nonlinearities were apparent in the 100- to 200-mg dose range, larger doses, particularly in the multiple-dosing situation, may uncover nonlinearity in the disposition of ciprofloxacin.
Inhibition of DNA replication initiation by aminoglycoside antibiotics
Authors: Matsunaga K , Yamaki H , Nishimura T , Tanaka N
Published: June 2012

The reinitiation of DNA replication induced by a temperature shift in a dnaC(Ts) mutant of Escherichia coli was markedly inhibited by aminoglycoside antibiotics around the MIC in a short period. Protein synthesis continued for several minutes after the addition of aminoglycosides but was immediately blocked by chloramphenicol, suggesting that the inhibition of initiation of replication by aminoglycosides is not a secondary effect due to the interruption of protein synthesis. Aminoglycosides did not significantly affect RNA synthesis, suggesting that primer RNA synthesis for DNA initiation is not blocked by the agents. The lethal action of habekacin was observed simultaneously with the inhibition of DNA reinitiation. DNA elongation demonstrated with a dnaE(Ts) mutant or toluene-treated cells of a polA mutant was not significantly affected by aminoglycosides. The oriC-membrane complex formation was markedly interrupted by habekacin in the dnaC(Ts) mutant, and the in vitro reconstitution of the oriC-membrane complex was completely blocked by aminoglycosides. The present studies show that aminoglycosides block initiation of DNA replication and suggest that the inhibition is caused by the interruption of oriC-membrane attachment.
Susceptibility of Campylobacter pyloridis to 20 antimicrobial agents
Authors: Lambert T , Mégraud F , Gerbaud G , Courvalin P
Published: June 2012

The susceptibility of 50 strains of Campylobacter pyloridis, isolated from human gastric biopsies, to 20 antimicrobial agents representing the different families of antibiotics was tested. The pattern of susceptibility was similar to that of the C. jejuni-C. coli group except for ampicillin, cephalothin, and rifampin. The relative resistance to cefsulodin was also noted.
In vitro activities of U-63366, a spectinomycin analog; roxithromycin (RU 28965), a new macrolide antibiotic; and five quinolone derivatives against Haemophilus ducreyi
Authors: Sanson-Le Pors M J , Casin I M , Thebault M C , Arlet G , Perol Y
Published: June 2012

The in vitro activities of the new spectinomycin analog U-63366, the new macrolide roxithromycin (RU 28965), and five new quinolone derivatives (pefloxacin, rosoxacin, norfloxacin, ofloxacin, and ciprofloxacin) were studied against 23 multiresistant strains of Haemophilus ducreyi (beta-lactamase producers) isolated in Paris and were compared with the activities of tetracycline, minocycline, chloramphenicol, streptomycin, kanamycin, gentamicin, spectinomycin, erythromycin, and nalidixic acid. All strains were uniformly susceptible to the seven new antibiotics tested. Ciprofloxacin had the greatest inhibitory effect in vitro (the MIC for 90% of the strains tested [MIC90] was 0.016 microgram/ml), and U-63366 was the most active aminoglycoside-aminocyclitol antibiotic (MIC90, 0.25 microgram/ml).
In vitro antiviral activity of the 6-substituted 2-(3',4'-dichlorophenoxy)-2H-pyrano[2,3-b]pyridines MDL 20,610, MDL 20,646, and MDL 20,957
Authors: Kenny M T , Dulworth J K , Bargar T M , Torney H L , Graham M C , Manelli A M
Published: June 2012

The 6-substituted 2-(3',4'-dichlorophenoxy)-2H-pyrano[2,3-b]pyridines MDL 20,610 (6-SO2CH3), MDL 20,646 (6-Br), and MDL 20,957 (6-Cl) are potent antirhinovirus compounds with median plaque 50% inhibitory concentrations (IC1/2s) of 0.03, 0.006, and 0.006 micrograms/ml, respectively, against the 32 serotypes evaluated. The 6-halogenated analogs produced 99% reductions in progeny virion yields at concentrations as low as 0.004 micrograms/ml. However, these analogs perturbated HeLa cell metabolism at lower concentrations (at or above 5 micrograms/ml) than did the 6-methylsulfonyl analog (at or above 20 micrograms/ml). Compound MDL 20,610 was also active against human, simian, and bovine rotaviruses (cytopathic effect IC1/2s of 0.8 to 1.5 micrograms/ml) and possessed variable enterovirus and paramyxovirus activity.
In vitro susceptibilities of four species of coagulase-negative staphylococci
Authors: Fass R J , Helsel V L , Barnishan J , Ayers L W
Published: June 2012

The in vitro susceptibilities of 260 strains of coagulase-negative staphylococci to penicillin G, oxacillin, nafcillin, methicillin, cephalothin, and seven non-beta-lactam antimicrobial agents were determined and compared with the susceptibilities of 54 strains of Staphylococcus aureus with known patterns of susceptibility. Penicillin G susceptibility for S. aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus hominis was readily determined by using beta-lactamase tests with induced cells and with a standardized microdilution test. MIC criteria for susceptibility used for S. aureus were applicable to the coagulase-negative species. Percentages of organisms susceptible were as follows: S. epidermidis, 7%; S. haemolyticus, 5%; and S. hominis, 47%. Oxacillin susceptibility for these four species was readily determined by using a modification of the microdilution test. MIC criteria for susceptibility used for S. aureus were applicable to S. haemolyticus and S. hominis, but alternate criteria were necessary for S. epidermidis. Percentages of organisms susceptible were as follows: S. epidermidis, 29%; S. haemolyticus, 36%; and S. hominis, 97%. Staphylococcus saprophyticus differed from the other staphylococcal species; all strains were beta-lactamase negative and were penicillin susceptible but had higher penicillin G MICs than did susceptible strains of the other species. There was total cross resistance among the penicillinase-resistant penicillins and cephalothin for the coagulase-negative staphylococci as well as for S. aureus; oxacillin MICs were more reliable than MICs of the other drugs or a standardized disk diffusion test for distinguishing resistant from susceptible strains. Vancomycin, rifampin, and ciprofloxacin were consistently active against all staphylococci. Erythromycin, clindamycin, gentamicin, and trimethoprim-sulfamethoxazole were more active against oxacillin-susceptible staphylococci than against oxacillin-resistant staphylococci.
In vitro activity of difloxacin hydrochloride (A-56619), A-56620, and cefixime (CL 284,635; FK 027) against selected genital pathogens
Authors: Bowie W R , Shaw C E , Chan D G , Boyd J , Black W A
Published: June 2012

Management of sexually transmitted diseases is facilitated by having antimicrobial agents with activity against all of the major genital pathogens. Newer quinolones show promise of being active against Neisseria gonorrhoeae and Chlamydia trachomatis. Two quinolones, difloxacin (A-56619) and A-56620, and an oral cephalosporin, cefixime (CL 284,635; FK 027), were evaluated in vitro. All three were highly active against 400 isolates of N. gonorrhoeae, including penicillinase-producing N. gonorrhoeae, N. gonorrhoeae with chromosomally mediated resistance, and isolates with penicillin MICs of less than 1 microgram/ml. Susceptibilities to one antimicrobial agent were usually strongly correlated with susceptibilities to the other antimicrobial agents evaluated, but isolates with increasing resistance to beta-lactams were least likely to show increasing resistance to quinolones. Difloxacin and, to a lesser extent, A-56620 were active against all 10 strains of C. trachomatis, and both had moderate activity against over 200 strains of Gardnerella vaginalis. Based on in vitro activity, difloxacin and A-56620 merit in vivo assessment for management of both C. trachomatis and N. gonorrhoeae infections, and cefixime shows considerable promise for treatment of N. gonorrhoeae infections.
Ciprofloxacin therapy for Mediterranean spotted fever
Authors: Raoult D , Gallais H , De Micco P , Casanova P
Published: June 2012

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.
Interferon in the prevention of genital herpes recurrence
Authors: Eron L J , Harvey L , Toy C , Santomauro D
Published: June 2012

Patients with genital herpes were treated three times weekly for 12 weeks with 3 X 10(6) IU of alpha 2b interferon (20 patients) or placebo (17 patients) administered by subcutaneous injection in a double-blind trial. Interferon had minimal effects on the suppression of recurrences and moderate toxicity (chills, fever, fatigue, and leukopenia), suggesting that this route and dosage of interferon may not be clinically useful for this indication.
In vitro activity of DQ-2556, a new cephalosporin
Authors: Fujimoto T , Otani T , Nakajima R , Une T , Osada Y
Published: June 2012

The in vitro antibacterial activity of DQ-2556, a new semisynthetic cephalosporin, was compared with that of ceftazidime and cefotaxime. The activity of DQ-2556 against members of the family Enterobacteriaceae was roughly comparable to that of cefotaxime. Against Pseudomonas aeruginosa, DQ-2556 was slightly less active than ceftazidime. DQ-2556 was more active than the reference cephalosporins against staphylococci. Haemophilus influenzae and Neisseria gonorrhoeae were also highly susceptible to DQ-2556.
Comparative study of cefoperazone and spectinomycin for treatment of uncomplicated gonorrhea in men
Authors: Hook E W , Judson F N , Verdon M S , Ehret J M , Handsfield H H
Published: June 2012

Beta-lactamase-negative Neisseria gonorrhoeae infections were treated with single-dose cefoperazone (0.5 or 1.0 g) or spectinomycin (2.0 g). Anogenital infections were cured in 36 (83%) of 43 volunteers given 0.5 g of cefoperazone, 61 of 61 volunteers given 1.0 g of cefoperazone, and 99 of 100 volunteers given spectinomycin. The cefoperazone geometric mean MIC for 242 isolates was 0.028 microgram/ml. Cefoperazone (1.0 g) and spectinomycin (2.0 g) are comparable for the therapy of anogenital gonorrhea in men.
Effect of medium, pH, and inoculum size on activity of ceftizoxime and Sch-34343 against anaerobic bacteria
Authors: Borobio M V , Pascual A , Dominguez M C , Perea E J
Published: June 2012

The effect of two media, three pH values, and three inoculum densities on the activity of ceftizoxime and Sch-34343 against anaerobic bacteria was evaluated. The activities of both antimicrobial agents were affected by medium composition, especially against Bacteroides fragilis. Changes in pH and inoculum size affected only the activity of ceftizoxime against anaerobic bacteria.
Beta-lactamase-mediated imipenem resistance in Bacteroides fragilis
Authors: Cuchural G J , Malamy M H , Tally F P
Published: June 2012

Imipenem has excellent antimicrobial activity owing in part to beta-lactamase stability. We found that only 2 of over 350 Bacteroides fragilis group clinical isolates were resistant to imipenem, with an MIC of more than 16 micrograms/ml. These two isolates from the Tufts Anaerobe Laboratory (TAL) were resistant to all other beta-lactam agents tested. The organisms were able to inactivate imipenem in broth cultures and contained similar beta-lactamases that were able to hydrolyze carbapenems, cephamycins, cephalosporins, and penicillins. The molecular sizes of the beta-lactamases in TAL2480 and TAL3636 were estimated to be 44,000 daltons. The novel beta-lactamase contained Zn2+ as a cofactor. An additional factor contributing to resistance was determined. The outer membranes of these two organisms were found to limit free diffusion of the drugs into the periplasm. This novel beta-lactamase, associated with a barrier to drug permeation, resulted in high-grade beta-lactam drug resistance.
Inhibition of Legionella pneumophila multiplication within human macrophages by antimicrobial agents
Authors: Vildé J L , Dournon E , Rajagopalan P
Published: June 2012

The activity of serial concentrations of different antimicrobial agents on the multiplication of Legionella pneumophila within human monocyte-derived macrophages was studied. The results led to the definition of a minimal extracellular concentration inhibiting intracellular multiplication (MIEC). According to the MIECs, the antimicrobial agents tested were classified in three groups: very active (MIEC less than or equal to 0.06 microgram/ml), such as erythromycin, rifampin, and pefloxacin; active (1 microgram/ml greater than or equal to MIEC greater than or equal to 0.1 microgram/ml), such as sulfamethoxazole-trimethoprim or doxycycline; and ineffective, such as cefoxitin, which was not active within macrophages at as high as 64 micrograms/ml despite a low MIC (0.2 microgram/ml) on bacterial charcoal-yeast extract agar. The activity of netilmicin was difficult to assess because of its effect on extracellular legionellae. Combinations of erythromycin with rifampin and pefloxacin with erythromycin, rifampin, doxycycline, or netilmicin showed an additive effect and no antagonism. These results obtained in a cellular model are in agreement with the efficacy of antimicrobial agents in experimental infections and in Legionnaires disease. They sustain clinical interest in the new quinolones, such as pefloxacin, and in combinations of antimicrobial agents for the treatment of Legionnaires disease.
Penicillin-induced effects on streptomycin uptake and early bactericidal activity differ in viridans group and enterococcal streptococci
Authors: Miller M H , el-Sokkary M A , Feinstein S A , Lowy F D
Published: June 2012

In vitro studies with penicillin and [3H]streptomycin in four strains of streptococci (S. faecalis, S. sanguis, and S. mitis) were performed by simultaneously measuring the rates of bacterial killing and uptake of streptomycin. In S. faecalis, penicillin stimulated streptomycin uptake, as has been shown by Moellering and Weinberg (R. C. Moellering, Jr., and A. N. Weinberg, J. Clin. Invest. 50:2580-2584, 1971). Moreover, the antibiotic combination was associated with an enhanced bactericidal rate which temporally correlated with beta-lactam-induced aminoglycoside uptake. In contrast, in viridans group streptococci (S. sanguis and S. mitis) penicillin had no effect on streptomycin uptake and a minimal effect on bactericidal rate when compared with either drug alone. These data suggested that the stimulation of streptomycin uptake in streptococci by penicillin is strain or species specific and that important differences exist between enterococci and viridans group streptococci regarding the mechanisms of beta-lactam-aminoglycoside potentiation.
Antimicrobial activity of U-70138F (paldimycin), roxithromycin (RU 965), and ofloxacin (ORF 18489) against Chlamydia trachomatis in cell culture
Authors: Stamm W E , Suchland R
Published: June 2012

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.
Tetracycline resistance and tetM in pathogenic urogenital bacteria
Authors: Roberts M C , Hillier S L , Hale J , Holmes K K , Kenny G E
Published: June 2012

Clinical isolates of Gardnerella vaginalis, Streptococcus agalactiae, Bacteroides spp., and Mobiluncus spp. were screened for resistance to tetracycline and for the presence of the streptococcal tetM determinant. The S. agalactiae and G. vaginalis strains contained DNA sequences homologous to the tetM determinant, while strains of the other two genera did not.
In vitro activity of imipenem against enterococci and staphylococci and evidence for high rates of synergism with teicoplanin, fosfomycin, and rifampin
Authors: Debbia E , Varaldo P E , Schito G C
Published: June 2012

The in vitro activities of imipenem alone and in combination with teicoplanin, fosfomycin, and rifampin were tested against clinical isolates of enterococci and staphylococci. In both groups of organisms, the three combinations demonstrated high rates of synergism in both checkerboard and time-kill studies.
Effect of antiviral agents on replication of herpes simplex virus type 1 in brain cultures
Authors: Pulliam L , Panitch H S , Baringer J R , Dix R D
Published: June 2012

An in vitro tissue culture system consisting of reaggregated embryonic brain cells was used to evaluate the inhibition of herpes simplex type 1 (HSV-1) by several antiviral compounds. The efficacy of acyclovir, vidarabine, bromovinyldeoxyuridine, and 9-(1,3-dihydroxy-2-propoxymethyl) guanine in HSV-1-infected Vero cell monolayer cultures was compared with that seen with brain cell aggregates. At a mean 50% inhibitory dose with Vero cells, acyclovir showed a 99% reduction of virus titer in brain cell aggregates. Vidarabine and 9-(1,3-dihydroxy-2-propoxymethyl) guanine gave a dose-dependent reduction in virus titer with Vero cells; however, in aggregate cultures treated with the same drugs a dose-dependent decrease at 24 h was followed by an increase to a point of no inhibition at 72 h postinfection. Pretreatment of brain cell aggregates with a hybrid human leukocyte interferon (Le IF-AD) reduced virus titers at 48 h postinfection but did not maintain this reduction at 72 h. In contrast, infected Vero cell monolayer cultures demonstrated a dose-dependent reduction in virus titers with Le IF-AD. Postinfection treatment with Le IF-AD did not reduce plaque formation in Vero cells but was effective in reducing virus titer in HSV-1-infected brain cell aggregates at 48 h postinfection. Antiviral concentrations of up to 200 micrograms or 200,000 IU/ml for interferon did not appear morphologically toxic to brain cells. Antiviral therapy of HSV-1-infected brain cell aggregates may more closely mimic in vivo responses than monolayer cultures.
Evaluation of a radiometric method for pyrazinamide susceptibility testing of Mycobacterium tuberculosis
Authors: Tarrand J J , Spicer A D , Gröschel D H
Published: June 2012

Pyrazinamide susceptibility testing of Mycobacterium tuberculosis requires an acid environment. By controlling the method of acidification and the quality and quantity of the inoculum, the test can be performed with the BACTEC radiometric system (Johnston Laboratories, Towson, Md.). We acidified BACTEC 7H12 medium with buffered phosphoric acid and adjusted the test inoculum to 1/10 of that usually employed in BACTEC protocols; after 5 days of growth we correctly identified 36 of 36 strains susceptible to 50 micrograms of pyrazinamide per ml. All 18 resistant strains were classified as pyrazinamide resistant. (Susceptibility or resistance had been determined by standard plate assays.) The test was able to detect small resistant populations in artificial mixtures of 1 or 2% resistant bacteria with a susceptible strain (10 mixtures each). We tested 70 M. tuberculosis strains in acidified BACTEC 7H12 medium and by the plate dilution test at pH 5.5. All strains grew in the BACTEC medium, but three strains failed to grow on plates and were not tested further; the results of both methods agreed for the remaining strains.
Genetics of resistance in a non-beta-lactamase-producing gonococcus with relatively high-level penicillin resistance
Authors: Faruki H , Sparling P F
Published: June 2012

A penicillin-resistant (Penr) non-penicillinase-producing Neisseria gonorrhoeae strain responsible for an outbreak affecting 199 persons in Durham, N.C., in 1983 was studied to determine the genetic basis of its unusually high-level (MIC, 2.0 micrograms/ml) Penr. Plasmid screening of the strain revealed no plasmids other than the 2.6-megadalton cryptic plasmid. Penr was found to be partially due to mutations genotypically and phenotypically similar to the previously characterized chromosomal loci penA, mtr, and penB. Resistance loci from the epidemic donor strain were transformed into susceptible recipients FA19 and F62 in a stepwise fashion; the combination of the three loci resulted in moderate levels of penicillin resistance (MIC, 0.5 micrograms/ml), but donor levels of resistance were not obtainable in either recipient, for uncertain reasons. Occurrence of an antibiotic-susceptible (env) mutation in a clinical isolate of the Penr epidemic strain also was documented.
Pharmacokinetics of ticarcillin and clavulanic acid (timentin) in relation to renal function
Authors: Jungbluth G L , Cooper D L , Doyle G D , Chudzik G M , Jusko W J
Published: June 2012

The disposition of coadministered ticarcillin (3 g/1.73 m2) and clavulanic acid (100 mg/1.73 m2) was examined after a 30-min infusion in 24 noninfected subjects with various degrees of renal function. Noncompartmental pharmacokinetic parameters for the individual compounds were determined from plasma concentrations and urinary excretion rates. All clearances (total, renal, and nonrenal) and urinary recoveries of unchanged drug were found to be linearly related to creatinine clearance (CLCR). The steady-state volume of distribution (9.9 and 12.9 liters for ticarcillin and clavulanic acid) approximated the extracellular fluid space and was not related to CLCR. The half-lives increased with reduced renal function and ranged from 56 to 392 min for ticarcillin and 26 to 266 min for clavulanic acid. The clearances of both drugs decreased proportionately with reduction in renal function, facilitating dosing adjustments based on CLCR. Calculations of expected steady-state maximum and minimum concentrations in plasma using constant doses and an extended dosing interval related to CLCR further rationalized use of the 30:1 drug combination ratio for all patients.
Ethambutol MICs and MBCs for Mycobacterium avium complex and Mycobacterium tuberculosis
Authors: Heifets L B , Iseman M D , Lindholm-Levy P J
Published: June 2012

We determined the MICs of ethambutol for both Mycobacterium avium and Mycobacterium tuberculosis strains by using broth dilution (7H12 broth, radiometric method) and agar dilution (7H11 agar) methods. We found the MICs to be much lower in liquid than in solid medium. The broth-determined MICs for susceptible M. tuberculosis and most of the M. avium strains were comparable to the levels in blood of patients, being lower than the peak levels. We propose that the MICs, determined radiometrically in in 7H12 broth, be considered as tentative criteria for susceptibility testing of M. avium isolates in future clinical trials. The use of these values instead of critical concentrations should also be considered as an alternative to the conventional susceptibility testing method in chemotherapy of tuberculosis. Ethambutol produced bactericidal effects against both M. tuberculosis and M. avium, and the MIC/MBC ratios were in the same range for both species when MICs and MBCs were tested in 7H12 broth by conventional sampling and plating.
Antistaphylococcal activity of a cyclic peptide, LY146032, and vancomycin
Authors: Knapp C C , Washington J A
Published: June 2012

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.
Relevance of in vitro antimicrobial susceptibility of Brucella melitensis to relapse rate in human brucellosis
Authors: Ariza J , Bosch J , Gudiol F , Liñares J , Viladrich P F , Martín R
Published: June 2012

The in vitro susceptibility of Brucella melitensis was examined vis-a-vis the clinical outcome in 75 patients with brucellosis. The initial MICs for Brucella isolates from patients who relapsed and from those who did not were similar. Furthermore, the MICs for isolates from patients whose infections relapsed were no different from those for original isolates. Our results clearly showed that neither initial nor subsequent antibiotic susceptibility plays a role in the likelihood of relapse of patients with brucellosis.
Amphotericin B or ketoconazole therapy of fungal infections in neutropenic cancer patients
Authors: Fainstein V , Bodey G P , Elting L , Maksymiuk A , Keating M , McCredie K B
Published: June 2012

Fungal infections in neutropenic cancer patients have increased in frequency and constitute an important cause of morbidity and mortality. Empiric antifungal therapy is often administered to those patients who have failed to respond to antibacterial antibiotics. We conducted a prospective, randomized trial of amphotericin B and ketoconazole for 172 neutropenic cancer patients with presumed or proven fungal infections. Overall, amphotericin B and ketoconazole were equally effective. Amphotericin B may have been more effective than ketoconazole for the treatment of pneumonia. Also, five of eight Candida tropicalis infections treated with amphotericin B responded, whereas all eight infections treated with ketoconazole failed to respond (P = 0.03). Response rates for localized fungal infections were similar with both drugs. Ketoconazole should not be used as empiric antifungal therapy at institutions where there is a high frequency of infections caused by Aspergillus spp. or C. tropicalis because this agent lacks activity in vitro against these species.
Activity of purine analogs against Leishmania donovani in vivo
Authors: Berman J D , Hanson W L , Lovelace J K , Waits V B , Jackson J E , Chapman W L , Klein R S
Published: June 2012

The dose of orally administered 9-deazainosine calculated to suppress 50% of Leishmania donovani amastigotes in hamster livers was 19 mg/kg (body weight) per day; 96 to 99% of Leishmania organisms were eliminated from the liver and spleen of squirrel monkeys by 50 mg/kg per day. Because these activities were greater than that of the experimental clinical agent allopurinol and comparable to that of the classical agent parenteral pentavalent antimony, 9-deazainosine should be considered for clinical development for visceral leishmaniasis.
Therapeutic implications of inhibition versus killing of Mycobacterium avium complex by antimicrobial agents
Authors: Yajko D M , Nassos P S , Hadley W K
Published: June 2012

Patients with the acquired immune deficiency syndrome (AIDS) with disseminated Mycobacterium avium infection have responded poorly to treatment with rifabutine (Ansamycin) and clofazimine, in spite of the good in vitro response of M. avium to these antimicrobial agents. We compared the ability of these and other antimicrobial agents to kill versus the ability to inhibit the growth of strains of the M. avium complex isolated from patients with AIDS. Killing curve experiments showed that the concentrations of rifabutine and clofazimine needed to kill two log units of M. avium are at least 32 times greater than the concentrations needed to inhibit growth. Little or no killing occurred at concentrations of these antimicrobial agents that are achievable in serum. In contrast, five of seven strains tested were killed by ciprofloxacin at concentrations that can be achieved in serum. Ciprofloxacin should be studied further for possible use in the treatment of M. avium infections.
In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium avium, Mycobacterium fortuitum, and Mycobacterium chelonae to ticarcillin in combination with clavulanic acid
Authors: Casal M J , Rodriguez F C , Luna M D , Benavente M C
Published: June 2012

The in vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium avium, Mycobacterium fortuitum, and Mycobacterium chelonae (M. chelonei) to ticarcillin in combination with calvulanic acid (CA) was studied by the agar dilution method. All the M. tuberculosis, M. bovis, and M. africanum strains were inhibited at a ticarcillin concentration of 32 micrograms/ml or lower in combination with 5 micrograms of CA. M. chelonae and M. avium strains proved resistant to more than 128 micrograms of ticarcillin plus 5 micrograms of CA per ml. M. fortuitum strains needed 128 micrograms of ticarcillin plus 5 micrograms of CA to inhibit approximately 30% of the isolates.
Inoculum effect with chloroquine and Plasmodium falciparum
Authors: Gluzman I Y , Schlesinger P H , Krogstad D J
Published: June 2012

In the studies reported here, we examined the inoculum effect observed with chloroquine and Plasmodium falciparum. The 50% effective doses observed with both chloroquine-susceptible and -resistant parasites increased five- to sevenfold from their baseline values as the inoculum was increased from 2 X 10(5) to 2 X 10(7) parasitized erythrocytes per ml (parasitemias of 0.1 to 10% with a hematocrit of 2%). Increasing the inoculum also decreased the chloroquine uptake per parasitized erythrocyte 15- to 20-fold with both chloroquine-susceptible and -resistant parasites. However, because of the 100-fold increase in the inoculum, the total amount of chloroquine taken up actually increased sufficiently to reduce the extracellular chloroquine concentration in vitro by 60 to 90%. These studies suggest that a chloroquine uptake of greater than or equal to 2.0 pmol/10(6) parasitized erythrocytes is necessary for chloroquine to inhibit parasite growth. More marked reductions in the amount of chloroquine uptake per parasitized erythrocyte were observed with a hematocrit of 40% using similar parasitemias of 0.1 to 10% (inocula of 4 X 10(6) to 4 X 10(8) parasitized erythrocytes per ml). Thin-layer chromatography of [3H]chloroquine taken up by chloroquine-resistant P. falciparum revealed no evidence of drug alteration by the parasite. These studies define the mechanism responsible for the inoculum effect observed with chloroquine and P. falciparum in vitro.
Successful treatment with aerosolized pentamidine of Pneumocystis carinii pneumonia in rats
Authors: Debs R J , Blumenfeld W , Brunette E N , Straubinger R M , Montgomery A B , Lin E , Agabian N , Papahadjopoulos D
Published: June 2012

We examined both the therapeutic efficacy and tissue distribution of aerosolized pentamidine in immunosuppressed rats with Pneumocystis carinii pneumonia. In rats immunosuppressed by 5 weeks of pretreatment with dexamethasone, a 2-week course of 5 mg of aerosolized pentamidine per kg per day, administered free or encapsulated in the drug carrier system (liposomes), eradicated P. carinii pneumonia in 75% of treated animals. At this dose, extrapulmonary drug uptake as measured by a sensitive high-pressure liquid chromatography assay was negligible. No significant differences in tissue distribution were noted between aerosolized free and liposome-encapsulated pentamidine. In rats receiving dexamethasone for 6 weeks prior to treatment with pentamidine, both lung uptake and therapeutic efficacy of aerosolized pentamidine (5 mg/kg per day) were substantially reduced. Aerosolized pentamidine appears to be an effective therapy for P. carinii pneumonia in rats and produces significantly lower extrapulmonary drug deposition than parenteral administration. The severity of P. carinii involvement at the time of treatment influences both the level of drug delivery to the lung and the response to aerosolized pentamidine therapy.
Novel type of plasmid-borne resistance to trimethoprim
Authors: Sundström L , Vinayagamoorthy T , Sköld O
Published: June 2012

A novel trait for transferable resistance to high concentrations of trimethoprim was found to dominate among enterobacteria collected from different parts of Sri Lanka. Drug resistance was a result of the production of dihydrofolate reductase with a decreased sensitivity to antifolates. By characterization of the partially purified enzyme and by restriction enzyme digestion analysis, the newly found gene was shown to be distinct from the earlier known plasmid-borne resistance genes which express dihydrofolate reductases of types I, II, and III. Cloning of fragments containing the resistance gene and further restriction enzyme digestion analysis showed that this gene was inserted very close to a sulfonamide resistance gene. Evolution of trimethoprim resistance in Sri Lanka thus seems to have taken a different route from that taken in the industrialized world, where transposon Tn7 seems to dominate. The close combination of the new trimethoprim resistance gene with sulfonamide resistance on the plasmids studied would effect an efficient spread of these genes, since trimethoprim has most often been used in combination with a sulfonamide.