bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in
Bartonella bacilliformis gyrB
Confer Resistance to Coumermycin A
1
Authors: Battisti James M. , Smitherman Laura S. , Samuels D. Scott , Minnick Michael F. 
Published: October 2018

ABSTRACT

This study describes the first isolation and characterization of spontaneous mutants conferring natural resistance to an antibiotic for any
Bartonella
species. The
Bartonella bacilliformis gyrB
gene, which encodes the B subunit of DNA gyrase, was cloned and sequenced. The
gyrB
open reading frame (ORF) is 2,079 bp and encodes a deduced amino acid sequence of 692 residues, corresponding to a predicted protein of ∼77.5 kDa. Sequence alignment indicates that
B. bacilliformis
GyrB is most similar to the GyrB protein from
Bacillus subtilis
(40.1% amino acid sequence identity) and that it contains the longest N-terminal tail (52 residues) of any GyrB characterized to date. The cloned
B. bacilliformis gyrB
was expressed in an
Escherichia coli
S30 cell extract and was able to functionally complement a temperature-sensitive
E. coli
Cou
r
gyrB
mutant (strain N4177). We isolated and characterized spontaneous mutants of
B. bacilliformis
resistant to coumermycin A
1
, an antibiotic that targets GyrB. Sequence analysis of
gyrB
from 12 Cou
r
mutants of
B. bacilliformis
identified single nucleotide transitions at three separate loci in the ORF. The predicted amino acid substitutions resulting from these transitions are Gly to Ser at position 124 (Gly124→Ser), Arg184→Gln, and Thr214→Ala or Thr214→Ile, which are analogous to mutated residues found in previously characterized resistant
gyrB
genes from
Borrelia burgdorferi
,
E. coli
,
Staphylococcus aureus
, and
Haloferax
sp. The Cou
r
mutants are three to five times more resistant to coumermycin A
1
than the wild-type parental strain.
Antimicrobial Susceptibility of Bacteria Isolated from Orthopedic Implants following Revision Hip Surgery
Authors: Tunney Michael M. , Ramage Gordon , Patrick Sheila , Nixon James R. , Murphy Philip G. , Gorman Sean P. 
Published: October 2018

ABSTRACT
The susceptibilities of 49 isolates recovered from orthopedic implants to seven antimicrobial agents were evaluated by the broth microdilution method. Ciprofloxacin and vancomycin were more active than gentamicin, representing aminoglycosides which are routinely incorporated into bone cement, and also more active than the peroperative antimicrobial agents cefamandole and erythromycin. The use of ciprofloxacin and vancomycin in vivo, therefore, warrants further evaluation.
Human Immunodeficiency Virus Protease Inhibitors Serve as Substrates for Multidrug Transporter Proteins MDR1 and MRP1 but Retain Antiviral Efficacy in Cell Lines Expressing These Transporters
Authors: Srinivas Ranga V. , Middlemas David , Flynn Pat , Fridland Arnold 
Published: October 2018

ABSTRACTThe human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs)—saquinavir, ritonavir, nelfinavir, and indinavir—interact with the ABC-type multidrug transporter proteins MDR1 and MRP1 in CEM T-lymphocytic cell lines. Calcein fluorescence was significantly enhanced in MDR1+CEM/VBL100 and MRP1+CEM/VM-1-5 cells incubated in the presence of various HIV PIs and calcein acetoxymethyl ester. HIV PIs also enhanced the cytotoxic activity of doxorubicin, a known substrate for MDR1 and MRP1, in both VBL100 and VM-1-5 CEM lines. Saquinavir, ritonavir, and nelfinavir enhanced doxorubicin toxicity in CEM/VBL100 cells by approximately three- to sevenfold. Saquinavir and ritonavir also enhanced doxorubicin toxicity in CEM/VM-1-5 cells. HIV-1 replication was effectively inhibited by the various PIs in all of the cell lines, and the 90% inhibitory concentration for a given compound was comparable between the different cell types. Therefore, overexpression of MDR1 or MRP1 by T lymphocytes is not likely to limit the antiviral efficacy of HIV PI therapy.
Expression of the
Pseudomonas aeruginosa
Gentamicin Resistance Gene
aacC3
in
Escherichia coli
Authors: van Boxtel Renée A. J. , van de Klundert Jos A. M. 
Published: October 2018

ABSTRACT

The
Pseudomonas aeruginosa aacC3
gene was expressed in
Escherichia coli
after cloning of the single gene behind the strong
tac
promoter. In the original
Pseudomonas
strain,
aacC3
is preceded by
cysC
; together they form a single transcription unit. The ribosome-binding site and start codon of
aacC3
are involved in a putative intercistronic hairpin, the stability of which interfered with the aminoglycoside resistance level. In Northern blots, full-length transcripts comprising both
cysC
and
aacC3
could not be detected either in the original
Pseudomonas
strain or in
E. coli
harboring a plasmid with the cloned operon. In contrast,
cysC
transcripts were abundant. Cloning of the operon between the
tac
promoter and a transcription termination signal resulted in higher mRNA levels and phenotypic expression in
E. coli
. The absence of a transcription termination signal in the wild-type
cysC-aacC3
sequence is associated with transcripts of heterogeneous size that were undetected in Northern blots. Our results shed more light on the expression of this gentamicin resistance determinant, although the discrepancies between its expression in
E. coli
and
Pseudomonas
are not fully solved.
No Interaction between Ciprofloxacin and an Oral Contraceptive
Authors: Scholten P. C. , Droppert R. M. , Zwinkels M. G. J. , Moesker H. L. , Nauta J. J. P. , Hoepelman I. M. 
Published: October 2018

ABSTRACT
Several antibiotics have been reported to lessen the ovarian suppression produced by oral contraceptive agents, as a result of drug interactions. The present investigation was designed to study the likelihood of the occurrence of any such interaction between the fluoroquinolone antibiotic ciprofloxacin (Ciproxin) at a dosage of 500 mg twice a day and the “low-dose” oral contraceptive Marvelon (30 μg of ethinyl estradiol [EE] plus 150 μg of desogestrel). Twenty-four healthy female volunteers were studied in a double-blind, placebo-controlled, randomized crossover trial. There were no significant differences between measurements of the area under the concentration-time curve of EE up to 24 h after oral contraceptive intake during placebo and ciprofloxacin administration on days 11 and 16 of the cycles, indicating the absence of pharmacokinetic interaction. Similarly, no clinically significant differences in the levels of sex hormone binding globulin were found between the placebo and ciprofloxacin cycles, indicating no major variation in EE levels during ciprofloxacin and placebo treatment. Ten subjects in each of the placebo and ciprofloxacin groups had early-follicular-phase levels of 17-β estradiol (<184 ng/liter) at one or more points during their cycles, but none had values above the early-follicular-phase range, indicating no significant ovarian activity. In addition, all subjects had progesterone levels of <2 ng/ml, indicating the absence of ovulation. Only two subjects, who received the placebo, had evidence of sustained follicular growth to a potentially ovulatory follicle (∼18 mm). We conclude that ciprofloxacin does not interfere with the ovarian suppression produced by the low-dose oral contraceptive Marvelon.
In Vitro and In Vivo Antibacterial Activities of CS-834, a New Oral Carbapenem
Authors: Yamaguchi Keizo , Domon Haruki , Miyazaki Shuichi , Tateda Kazuhiro , Ohno Akira , Ishii Kazuhiro , Matsumoto Tetsuya , Furuya Nobuhiko 
Published: October 2018

ABSTRACT

CS-834 is a prodrug of the carbapenem R-95867, developed by Sankyo Co., Ltd., Tokyo, Japan. To investigate the possibility that CS-834 may be the first carbapenem usable in an oral dosage form, its in vitro antibacterial activity (as R-95867) and in vivo antibacterial activity were compared with those of cefpodoxime proxetil, cefditoren pivoxil, cefdinir, ofloxacin, imipenem, and amoxicillin. R-95867 had high levels of activity against methicillin-susceptible staphylococci and streptococci, including penicillin-resistant
Streptococcus pneumoniae
, as well as
Neisseria gonorrhoeae
,
Moraxella catarrhalis
, the members of the family
Enterobacteriaceae
(with the exception of
Serratia marcescens
),
Haemophilus influenzae
, and
Bordetella pertussis
; for all these strains, the MICs at which 90% of tested strains are inhibited (MIC
90
s) were 1.0 μg/ml or less. Against methicillin-resistant staphylococci, enterococci,
Serratia marcescens
,
Brukholderia cepacia
,
Stenotrophomonas maltophilia
, and
Acinetobacter calcoaceticus
, R-95867 showed activity comparable to or slightly less than that of imipenem, with MIC
90
s ranging from 2 to >128 μg/ml. The in vivo efficacy of oral CS-834 against experimental mouse septicemia caused by gram-positive and gram-negative bacteria was better than that of comparative drugs. In murine respiratory infection models, the efficacy of CS-834 reflected not only its potent in vitro activity but also the high levels present in the lungs.
Prevalence of Antimicrobial-Resistant Pathogens in Middle Ear Fluid: Multinational Study of 917 Children with Acute Otitis Media
Authors: Jacobs Michael R. , Dagan Ron , Appelbaum Peter C. , Burch Daniel J. 
Published: October 2018

ABSTRACT

The management of acute otitis media is complicated by the emergence of resistance to β-lactam and other antibiotics among common pathogens. We conducted a large, international study of infants and children with acute otitis media to identify pathogens and susceptibility patterns. During the winter of 1994 to 1995, middle ear fluid samples were collected from 917 patients with acute otitis media in Bulgaria, the Czech Republic, Hungary, Romania, Slovakia, Israel, and the United States. A single reference laboratory performed in vitro susceptibility testing. Pathogens were isolated from 62% of the patients. For
Streptococcus pneumoniae
(30% of the patients), untypeable
Haemophilus influenzae
(17%), and
Moraxella catarrhalis
(4%), there was significant variation among geographic regions (
P
< 0.001). The composite susceptibilities of these three organisms to amoxicillin ranged from 62% in the United States to 89% in Eastern and Central Europe; the corresponding susceptibilities to amoxicillin-clavulanate ranged from 90% in Israel to 95% in Eastern and Central Europe. β-Lactamase was produced by 31 and 100% of the isolates of
H. influenzae
and
M. catarrhalis
, respectively. More isolates of
S. pneumoniae
were susceptible to amoxicillin (90%) or amoxicillin-clavulanate (90%) than to penicillin (70%;
P
= 0.002). The prevalence of resistant
S. pneumoniae
was highest in patients less than 12 months of age.
S. pneumoniae
,
H. influenzae
, and
M. catarrhalis
remain the most important bacterial pathogens in patients with acute otitis media; however, their prevalence is variable and resistance patterns are changing.
Susceptibilities of Penicillin- and Erythromycin-Susceptible and -Resistant Pneumococci to HMR 3647 (RU 66647), a New Ketolide, Compared with Susceptibilities to 17 Other Agents
Authors: Pankuch G. A. , Visalli M. A. , Jacobs M. R. , Appelbaum P. C. 
Published: October 2018

ABSTRACT

Susceptibility of 230 penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, was tested by agar dilution, and results were compared with those of erythromycin, azithromycin, clarithromycin, roxithromycin, rokitamycin, clindamycin, pristinamycin, ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. HMR 3647 was very active against all strains tested, with MICs at which 90% of the strains were inhibited (MIC
90
s) of 0.03 μg/ml for erythromycin-susceptible strains (MICs, ≤0.25 μg/ml) and 0.25 μg/ml for erythromycin-resistant strains (MICs, ≥1.0 μg/ml). All other macrolides yielded MIC
90
s of 0.03 to 0.25 and >64.0 μg/ml for erythromycin-susceptible and -resistant strains, respectively. The MICs of clindamycin for 51 of 100 (51%) erythromycin-resistant strains were ≤0.125 μg/ml. The MICs of pristinamycin for all strains were ≤1.0 μg/ml. The MIC
90
s of ciprofloxacin and sparfloxacin were 4.0 and 0.5 μg/ml, respectively, and were unaffected by penicillin or erythromycin susceptibility. Vancomycin and imipenem inhibited all strains at ≤1.0 μg/ml. The MICs of cefuroxime and cefotaxime rose with those of penicillin G. The MICs of trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol were variable but were generally higher in penicillin- and erythromycin-resistant strains. HMR 3647 had the best kill kinetics of all macrolides tested against 11 erythromycin-susceptible and -resistant strains, with uniform bactericidal activity (99.9% killing) after 24 h at two times the MIC and 99% killing of all strains at two times the MIC after 12 h for all strains. Pristinamycin showed more rapid killing at 2 to 6 h, with 99.9% killing of 10 of 11 strains after 24 h at two times the MIC. Other macrolides showed significant activity, relative to the MIC, against erythromycin-susceptible strains only.
Role of Superoxide in Catalase-Peroxidase-Mediated Isoniazid Action against Mycobacteria
Authors: Wang Jian-Ying , Burger Richard M. , Drlica Karl 
Published: October 2018

ABSTRACT

Isoniazid (INH) activation in vitro is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with O
2
to form an oxyferrous enzyme complex. Since this complex could also form directly via reaction of ferric KatG with superoxide, intracellular activation might be responsive to superoxide concentration. When
Mycobacterium smegmatis
carrying the
M. bovis katG
gene was treated with nontoxic levels of plumbagin, a generator of superoxide, the bacteriostatic activity of INH increased unless a plasmid-borne superoxide dismutase gene was also present. Thus, endogenous superoxide probably contributes to intracellular activation of INH.
Zidovudine Pharmacokinetics in Premature Infants Exposed to Human Immunodeficiency Virus
Authors: Mirochnick Mark , Capparelli Edmund , Dankner Wayne , Sperling Rhoda S. , van Dyke Russ , Spector Stephen A. 
Published: October 2018

ABSTRACT

We used population analysis techniques to determine zidovudine (ZDV) pharmacokinetic parameters in 15 preterm neonates (mean gestational age, 29.4 weeks; mean birth weight, 1,230 g) at a mean age of 5.5 days. The values of the pharmacokinetic parameters were as follows: clearance, 2.53 ± 0.44 ml/min/kg; volume of distribution, 1.59 ± 0.51 liters/kg; and half-life, 7.2 ± 1.5 h. For seven infants studied a second time, at a mean age of 17.7 days, an increase in the mean clearance (2.33 versus 4.35 ml/min/kg;
P
= 0.024) and a decrease in the half-life (7.3 versus 4.4 h;
P
= 0.003) were found. The ZDV clearance is low and the half-life is prolonged in premature neonates, but the clearance increases and the half-life decreases with postnatal age. Potentially toxic concentrations may accumulate in serum if the standard dosage for full-term infants is used. We suggest that initial ZDV dosing should be reduced to 1.5 mg every 12 h for preterm neonates.
Pharmacokinetics of Two Multiple-Dosing Regimens of D0870 in Human Immunodeficiency Virus-Positive Patients: a Phase I Study
Authors: De Wit S. , O’Doherty E. , Edwards J. , Yates R. , Smith R. P. , Clumeck A. N. 
Published: October 2018

ABSTRACT

D0870 is a triazole with a broad antifungal spectrum, and it has been shown to have both in vitro and in vivo activities against wild-type and fluconazole-resistant strains of
Candida albicans
. Twenty-two human immunodeficiency virus (HIV)-positive male subjects were enrolled in an open, nonrandomized trial investigating the pharmacokinetics of two different dosing regimens of D0870 and assessing the safety of multiple oral doses of D0870 in HIV-positive subjects and their ability to tolerate multiple oral doses. Nine subjects received an initial loading dose of 50 mg, followed by four once-daily maintenance doses of 10 mg. A further nine subjects received an initial 200-mg loading dose followed by four daily maintenance doses of 25 mg. All subjects were fasting. A single loading dose of 50 mg of D0870 resulted in a mean maximum concentration in serum (
C
max
) of 107 ± 32 ng/ml. Concentrations in plasma were maintained by the 10-mg once-daily dosing regimen as seen by the similar values of the area under the concentration-time curve from 0 to 24 h following dosing on days 1 and 5 and a mean accumulation ratio close to unity (0.90). The terminal plasma half-life of D0870 in plasma following dosing on day 5 ranged from 23 to 85 h (mean, 49 h). A single loading dose of 200 mg of D0870 resulted in a
C
max
of 431 ± 186 ng/ml. Concentrations in plasma were again maintained by the 25-mg daily dosing regimen, with the mean accumulation ratio being close to unity (1.17). The terminal half-life of D0870 in plasma following dosing on day 5 of phase II of the study ranged from 34 to 137 h (mean, 71 h). In addition, the concentrations achieved in the plasma of these HIV-positive subjects were similar to the values predicted from simulations based on data derived from normal, healthy subjects. D0870 was well tolerated. No serious adverse events were experienced during the course of the study, and all volunteers completed the trial. A total of 15 adverse events were reported, but none were considered to be related to the administration of D0870 and all had resolved by the end of the trial. No changes in the hematology, clinical chemistry, or urinalysis parameters were considered to be related to dosing with D0870. No clinically significant changes in the electrocardiogram parameters were noted during the trial. The data generated in this trial support further investigation of these regimens with HIV-positive subjects with fluconazole-susceptible or -resistant oropharyngeal candidosis.
Efficacy of LY333328 against Experimental Methicillin-Resistant
Staphylococcus aureus
Endocarditis
Authors: Kaatz Glenn W. , Seo Susan M. , Aeschlimann Jeffrey R. , Houlihan Heather H. , Mercier Renee-Claude , Rybak Michael J. 
Published: October 2018

ABSTRACT

The in vivo efficacy of LY333328, a new glycopeptide antibiotic, was compared with that of vancomycin by using the rabbit model of left-sided methicillin-resistant
Staphylococcus aureus
endocarditis. Animals received LY333328 or vancomycin (25 mg/kg of body weight every 24 or 8 h, respectively) for 4 days. These drugs were equally effective in clearing bacteremia and in reducing bacterial counts in vegetations and tissues. We conclude that in this model, LY333328 was microbiologically effective and may be a therapeutic alternative to vancomycin.
In Vitro Activities of Terbinafine against Cutaneous Isolates ofCandida albicansand Other Pathogenic Yeasts
Authors: Ryder Neil S. , Wagner Sonja , Leitner Ingrid 
Published: October 2018

ABSTRACTTerbinafine is active in vitro against a wide range of pathogenic fungi, including dermatophytes, molds, dimorphic fungi, and some yeasts, but earlier studies indicated that the drug had little activity againstCandida albicans. In contrast, clinical studies have shown topical and oral terbinafine to be active in cutaneous candidiasis andCandidanail infections. In order to define the anti-Candidaactivity of terbinafine, we tested the drug against 350 fresh clinical isolates and additional strains by using a broth dilution assay standardized according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) M27-A assay. Terbinafine was found to have an MIC of 1 μg/ml for referenceC. albicansstrains. For 259 clinical isolates, the MIC at which 50% of the isolates are inhibited (MIC50) of terbinafine was 1 μg/ml (fluconazole, 0.5 μg/ml), and the MIC90was 4 μg/ml (fluconazole, 1 μg/ml). Terbinafine was highly active againstCandida parapsilosis(MIC90, 0.125 μg/ml) and showed potentially interesting activity against isolates ofCandida dubliniensis,Candida guilliermondii,Candida humicola, andCandida lusitaniae. It was not active against theCandida glabrata,Candida krusei, andCandida tropicalisisolates in this assay.Cryptococcus laurentiiandCryptococcus neoformanswere highly susceptible to terbinafine, with MICs of 0.06 to 0.25 μg/ml. The NCCLS macrodilution assay provides reproducible in vitro data for terbinafine againstCandidaand other yeasts. The MICs forC. albicansandC. parapsilosisare compatible with the known clinical efficacy of terbinafine in cutaneous infections, while the clinical relevance of its activities against the other species has yet to be determined.
Activities of HMR 3004 (RU 64004) and HMR 3647 (RU 66647) Compared to Those of Erythromycin, Azithromycin, Clarithromycin, Roxithromycin, and Eight Other Antimicrobial Agents against Unusual Aerobic and Anaerobic Human and Animal Bite Pathogens Isolated from Skin and Soft Tissue Infections in Humans
Authors: Goldstein Ellie J. C. , Citron Diane M. , Gerardo Sharon Hunt , Hudspeth Marie , Merriam C. Vreni 
Published: October 2018

ABSTRACT

The activities of HMR 3004 and HMR 3647 and comparator agents, especially macrolides, were determined by the agar dilution method against 262 aerobic and 120 anaerobic strains isolated from skin and soft tissue infections associated with human and animal bite wounds. HMR 3004 and HMR 3647 were active against almost all aerobic and fastidious facultative isolates (MIC at which 90% of the isolates are inhibited [MIC
90
], ≤0.5 and 1 μg/ml, respectively) and against all anaerobes [
Bacteroides tectum
,
Porphyromonas macacae
(
salivosa
),
Prevotella heparinolytica
,
Porphyromonas
sp.,
Prevotella
sp., and peptostreptococci] at ≤0.25 and ≤0.5 μg/ml, respectively, except
Fusobacterium nucleatum
(HMR 3004, MIC
90
= 16 μg/ml; HMR 3647, MIC
90
= 8 μg/ml) and other
Fusobacterium
species (MIC
90
, 1 and 2 μg/ml, respectively). In general, HMR 3004 and HMR 3647 were more active than any of the macrolides tested. Azithromycin was more active than clarithromycin against all
Pasteurella
species, including
Pasteurella multocida
subsp.
multocida
,
Eikenella corrodens
, and
Fusobacterium
species, while clarithromycin was more active than azithromycin against
Corynebacterium
species,
Weeksella zoohelcum
,
B. tectum
, and
P. heparinolytica.
Mechanism of Resistance to Amikacin and Kanamycin in
Mycobacterium tuberculosis
Authors: Alangaden George J. , Kreiswirth Barry N. , Aouad Arlette , Khetarpal Minoo , Igno Felicitas R. , Moghazeh Soraya L. , Manavathu Elias K. , Lerner Stephen A. 
Published: October 2018

ABSTRACT

An A1400G mutation of the
rrs
gene was identified in
Mycobacterium tuberculosis
(MTB) strain ATCC 35827 and in 13 MTB clinical isolates resistant to amikacin-kanamycin (MICs, >128 μg/ml). High-level cross-resistance may result from such a mutation since MTB has a single copy of the
rrs
gene. Another mechanism(s) may account for high-level amikacin-kanamycin resistance in two mutants and lower levels of resistance in four clinical isolates, all lacking the A1400G mutation.