bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of Development of In Vitro Resistance to Amoxicillin, Clarithromycin, and Metronidazole inHelicobacter pylori
Authors: Sörberg Mikael , Hanberger Håkan , Nilsson Maud , Björkman Anders , Nilsson Lennart E. 
Published: October 2018

ABSTRACTWe have studied initial killing, morphological alterations, the frequency of occurrence, and the selective growth of resistant subpopulations ofHelicobacter pyloriduring exposure to amoxicillin, clarithromycin, or metronidazole by bioluminescence assay of intracellular ATP levels, microscopy, and a viable count assay. We found an induction of spheroplasts and a decrease in intracellular ATP levels after 21 h of exposure to high concentrations of amoxicillin. During clarithromycin exposure the onset of a decrease in intracellular ATP levels started after prolonged incubation, and with the highest concentration of clarithromycin an induction of coccoid forms was seen after 68 h. Metronidazole exposure resulted in the strongest initial decrease in intracellular ATP levels, and coccoid forms were seen after 21 h of exposure to high concentrations of metronidazole. Amoxicillin caused a low-level increase in resistant subpopulations, which indicates a need for surveillance of the amoxicillin susceptibility ofH. pyloriin order to detect decreasing susceptibility. No increase in the numbers of resistant subpopulations was demonstrated during clarithromycin exposure. Metronidazole selected resistant subpopulations, which caused high-level resistance inH. pylori.
Meropenem versus Cefuroxime plus Gentamicin for Treatment of Serious Infections in Elderly Patients
Authors: Jaspers C. A. J. J. , Kieft H. , Speelberg B. , Buiting A. , van Marwijk Kooij M. , Ruys G. J. H. M. , Vincent H. H. , Vermeulen M. C. A. , Olink A. G. , Hoepelman I. M. 
Published: October 2018

ABSTRACT

In this multicenter study, the efficacy of and tolerability for meropenem were compared with those for the combination of cefuroxime-gentamicin (±metronidazole) for the treatment of serious bacterial infections in patients ≥65 years of age. A total of 79 patients were randomized; thirty-nine received meropenem (1 g/8 h), and 40 received cefuroxime (1.5 g/8 h) plus gentamicin (4 mg/kg of body weight daily) for 5 to 10 days. Metronidazole (500 mg/6 h) could be added to the cefuroxime-gentamicin regimen for the treatment of intra-abdominal infections (
n
= 10). Seventy patients were evaluable for clinical efficacy; the primary diagnoses were as follows: pneumonia in 41 patients (20 treated with meropenem, 21 treated with cefuroxime-gentamicin), intra-abdominal infection in 10 patients (7 meropenem, 3 cefuroxime-gentamicin-metronidazole), urinary tract infection (UTI) in 11 patients (6 meropenem, 5 cefuroxime-gentamicin), sepsis syndrome in 7 patients (4 meropenem, 3 cefuroxime-gentamicin), and “other” in 1 patient (cefuroxime-gentamicin). The pathogens isolated from 18 patients with bacteremia were as follows:
Staphylococcus
spp. (
n
= 2),
Streptococcus
spp. (
n
= 2), members of the family
Enterobacteriaceae
(
n
= 11), and
Bacteroides
spp. (
n
= 3). A satisfactory clinical response at the end of therapy was achieved in 26 of 37 (70%) and 24 of 33 (73%) evaluable patients treated with meropenem and combination therapy, respectively. Clinical success was achieved in 23 of 31 (74%) and 21 of 28 (75%) evaluable patients with infections other than UTIs, respectively. A satisfactory microbiological response occurred in 15 of 22 (68%) patients in the meropenem group compared with 12 of 19 (63%) treated with combination therapy. Renal failure occurred during therapy in 2 of 39 (5%) meropenem recipients compared with 5 of 40 (13%) of those treated with combination therapy. The findings in this small study indicate that meropenem is as efficacious for and as well tolerated by elderly patients as the combination of cefuroxime-gentamicin (±metronidazole).
Sequence of the Gene Encoding a Plasmid-Mediated Cefotaxime-Hydrolyzing Class A β-Lactamase (CTX-M-4): Involvement of Serine 237 in Cephalosporin Hydrolysis
Authors: Gazouli Maria , Tzelepi Eva , Sidorenko Sergei V. , Tzouvelekis Leonidas S. 
Published: October 2018

ABSTRACT

The sequence of the gene encoding a novel cefotaxime-hydrolyzing β-lactamase (CTX-M-4) was determined. It was located in a plasmid harbored by a
Salmonella typhimurium
strain. CTX-M-4 was similar to the plasmidic cefotaxime-hydrolyzing β-lactamases CTX-M-2 and Toho-1 and related to the chromosomal β-lactamase of
Klebsiella oxytoca
. A Ser-237→Ala substitution, introduced by site-directed mutagenesis, caused minor alterations in the interaction of CTX-M-4 with β-lactams, reducing slightly the relative hydrolytic activity against cefotaxime and the susceptibility to inhibition by clavulanate.
A Triazine Dye, Cibacron Blue F3GA, Decreases Oxacillin Resistance Levels in Methicillin-Resistant
Staphylococcus aureus
Authors: Shirai Chiharu , Sugai Motoyuki , Komatsuzawa Hitoshi , Ohta Kouji , Yamakido Michio , Suginaka Hidekazu 
Published: October 2018

ABSTRACT

Cibacron blue F3GA (CB) was found to reduce the MIC of oxacillin for methicillin-resistant
Staphylococcus aureus
(MRSA). This effect was not observed with methicillin-susceptible
S. aureus
. CB alters the resistance level of MRSA through a factor(s) other than
mecA
-related products, major autolysins, or
femAB
products. The exact target(s) of CB in causing the effect is unknown.
Properties of Mutant SHV-5 β-Lactamases Constructed by Substitution of Isoleucine or Valine for Methionine at Position 69
Authors: Giakkoupi Panagiota , Miriagou Vivi , Gazouli Maria , Tzelepi Eva , Legakis Nicholas J. , Tzouvelekis Leonidas S. 
Published: October 2018

ABSTRACT

The effect of replacement of Met-69 by Ile or Val on the properties of the extended-spectrum β-lactamase SHV-5 was studied. Mutant enzymes were constructed by site-specific mutagenesis and expressed under isogenic conditions in
Escherichia coli
DH5α cells. Compared with SHV-5, the mutant β-lactamases conferred lower levels of β-lactam resistance and were less efficient in hydrolyzing ampicillin, cephalothin, and cefotaxime. The substitutions rendered SHV-5 less susceptible to inhibition by clavulanate, sulbactam, and tazobactam; however, the MICs of penicillin-inhibitor combinations remained similar, suggesting an attenuation of penicillinase activity.
In Vivo Efficacies of Amoxicillin and Cefuroxime against Penicillin-Resistant
Streptococcus pneumoniae
in a Gerbil Model of Acute Otitis Media
Authors: Cenjor Carlos , Ponte Carmen , Parra Araceli , Nieto Eva , García-Calvo Gloria , Giménez María José , Aguilar Lorenzo , Soriano Francisco 
Published: October 2018

ABSTRACT

The comparative efficacies of amoxicillin and cefuroxime against acute otitis media caused by a penicillin-resistant (MIC, 2 μg/ml)
Streptococcus pneumoniae
strain were assessed in a gerbil model by challenging each ear with 10
7
bacteria through transbullar instillation. Each antibiotic was tested at two doses (5 and 20 mg/kg of body weight) administered at 2, 10, and 18 h postinoculation. Samples were obtained from the middle ear (ME) on days 3 and 7 postinoculation for determination of bacterial counts. Only amoxicillin, at both doses, was able to significantly halt the weight loss in animals, reducing both the number of culture-positive animals and the bacterial concentration in ME samples versus the values for untreated animals. Comparison of the efficacies between the antibiotics, determined by their ability to achieve culture-negative ME specimens, showed that amoxicillin at 5 mg/kg was significantly more active than cefuroxime at the same dose. The use of higher doses of either amoxicillin or cefuroxime did not produce significantly better results than those obtained with the lower dose but caused a greater inflammatory response. The more favorable results obtained with amoxicillin compared with those obtained with cefuroxime could be related to the antimicrobial susceptibility of the pneumococcal strain (MICs and minimum bactericidal concentrations of 1 and 1 μg/ml and 4 and 4 μg/ml for amoxicillin and cefuroxime, respectively) as well as to the better pharmacokinetic parameters obtained with amoxicillin.
Assessment of Antifungal Activities of Fluconazole and Amphotericin B Administered Alone and in Combination against
Candida albicans
by Using a Dynamic In Vitro Mycotic Infection Model
Authors: Lewis Russell E. , Lund Brian C. , Klepser Michael E. , Ernst Erika J. , Pfaller Michael A. 
Published: October 2018

ABSTRACT

We evaluated the pharmacodynamic activities of fluconazole and amphotericin B given alone and in combination against
Candida albicans
by using an in vitro model of bloodstream infection that simulates human serum pharmacokinetic parameters for these antifungals. Fluconazole was administered as a bolus into the model to simulate regimens of 200 mg every 24 h (q24h) and 400 mg q24h. Amphotericin B was administered at doses producing the peak concentration (2.4 μg/ml) observed with a regimen of 1 mg/kg of body weight q24h. A combination regimen of fluconazole (400 mg q24h) and amphotericin B (1 mg/kg q24h) administered simultaneously and as a staggered regimen (amphotericin B bolus given 8 h after fluconazole bolus) was also simulated in the model to characterize possible antagonism between these agents. Fluconazole alone and amphotericin B alone demonstrated fungistatic (<99.9% reduction in numbers of CFU per milliliter from the starting inoculum) and fungicidal (>99.9% reduction) activity, respectively. When fluconazole and amphotericin B were administered simultaneously, fungicidal activity similar to that observed with amphotericin B alone was observed. Staggered administration of fluconazole and amphotericin B, however, resulted in a substantial reduction of the fungicidal activity of amphotericin B, producing fungistatic activity similar to that observed with noncombination fluconazole regimens. These results demonstrate the usefulness of this model for comparing the in vitro pharmacodynamic characteristics of different antifungal regimens and support the theory of azole-polyene antagonism. The effects of this antagonism on the in vivo activity and clinical usefulness of combination antifungal therapy, however, remain to be determined.
Novel Antibiotic Susceptibility Tests by the ATP-Bioluminescence Method Using Filamentous Cell Treatment
Authors: Hattori Noriaki , Nakajima Moto-O , O’Hara Koji , Sawai Tetsuo 
Published: October 2018

ABSTRACT

Antimicrobial susceptibility testing by the ATP-bioluminescence method has been noted for its speed; it provides susceptibility results within 2 to 5 h. However, several disagreements between the ATP method and standard methodology have been reported. The present paper describes a novel ATP method in a 3.5-h test which overcomes these deficiencies through the elimination of false-resistance discrepancies in tests on gram-negative bacteria with β-lactam agents. In our test model using
Pseudomonas aeruginosa
and piperacillin, it was shown that ATP in filamentous cells accounted for the false resistance. We found that 0.5% 2-amino-2-methyl-1,3-propanediol (AMPD) extracted ATP from the filamentous cells without affecting normal cells and that 0.3 U of adenosine phosphate deaminase (APDase)/ml simultaneously digested the extracted ATP. We used the mixture of these reagents for the pretreatment of cells in a procedure we named filamentous cell treatment, prior to ATP measurements. This novel ATP method with the filamentous cell treatment eliminated false-resistance discrepancies in tests on
P. aeruginosa
with β-lactam agents, including piperacillin, cefoperazone, aztreonam, imipenem-cilastatin, ceftazidime, and cefsulodin. Furthermore, this novel methodology produced results which agreed with those of the standard microdilution method in other tests on gram-negative and gram-positive bacteria, including
P. aeruginosa
,
Escherichia coli
,
Staphylococcus aureus
, and
Enterococcus faecalis
, for non-β-lactam agents, such as fosfomycin, ofloxacin, minocycline, and aminoglycosides. MICs obtained by the novel ATP method were also in agreement with those obtained by the agar dilution method of susceptibility testing. From these results, it was shown that the novel ATP method could be used successfully to test the activities of antimicrobial agents with the elimination of the previously reported discrepancies.
Analysis of the Pharmacokinetic Interaction between Cephalexin and Quinapril by a Nonlinear Mixed-Effect Model
Authors: Padoin C. , Tod M. , Perret G. , Petitjean O. 
Published: October 2018

ABSTRACT

Oligopeptidic drugs such as β-lactams and angiotensin-converting enzyme inhibitors share the same carriers in humans and animals, which results in possible pharmacokinetic interactions. To model such interactions, the effects of quinapril on cephalexin pharmacokinetics were investigated in rats. Blood cephalexin concentrations were measured by liquid chromatography, and the data were analyzed by a noncompartmental method and by fitting a bicompartmental model by a nonlinear mixed-effect modeling approach. Five groups of eight rats were examined. In the first three groups, cephalexin elimination kinetics after intra-arterial administration alone or in combination with quinapril given by the parenteral or the oral route were studied, and the occurrence of a pharmacokinetic interaction was not revealed. The absence of an effect of quinapril on cephalexin elimination after parenteral administration might be explained either by the higher affinity of cephalexin for the renal anionic transport system than that of quinapril or by the much higher concentrations of cephalexin than those of quinapril. In the last two groups, cephalexin was administered by the oral route alone or in combination with quinapril. The mean area under the concentration-time curve (AUC) for cephalexin was increased by ca. 30% by coadministration of quinapril (40.1 versus 31.4 mg · h/liter;
P
= 0.04). The mean elimination clearance of cephalexin was significantly decreased by quinapril, from 0.81 to 0.64 liter/h/kg of body weight (
P
< 0.05), probably by competitive inhibition of cephalexin secretion at the tubular level. The mean absorption rate constant of cephalexin was significantly lowered by quinapril (from 0.249 to 0.177 h
−1
;
P
< 0.01), without modification of the extent of absorption (89%). This pharmacokinetic interaction could be explained by competitive inhibition of cephalexin active transport by quinapril at the intestinal level.
Delivery of the Non-Membrane-Permeative Antibiotic Gentamicin into Mammalian Cells by Using
Shigella flexneri
Membrane Vesicles
Authors: Kadurugamuwa Jagath L. , Beveridge Terry J. 
Published: October 2018

ABSTRACT

We developed a model to test whether non-membrane-permeative therapeutic agents such as gentamicin could be delivered into mammalian cells by means of bacterial membrane vesicles. Many gram-negative bacteria bleb off membrane vesicles (MVs) during normal growth, and the quantity of these vesicles can be increased by brief exposure to gentamicin (J. L. Kadurugamuwa and T. J. Beveridge, J. Bacteriol. 177:3998–4008, 1995), which can be entrapped within the MVs. Gentamicin-induced MVs (g-MVs) were isolated from
Shigella flexneri
and contained 85 ± 2 ng of gentamicin per μg of MV protein. Immunogold electron microscopic labeling of thin sections with antibodies specific to
S. flexneri
lipopolysaccharide (LPS) demonstrated the adherence and subsequent engulfment of MVs by the human Henle 407 intestinal epithelial cell line. Further incubation of g-MVs with
S. flexneri
-infected Henle cells revealed that the g-MVs penetrated throughout the infected cells and reduced the intracellular pathogen by ∼1.5 log
10
CFU in the first hour of incubation. Antibiotic was detected in the cytoplasms of host cells, indicating the intracellular placement of the drug following the penetration of g-MVs. Soluble antibiotic, added as a fluid to the tissue culture growth medium, had no effect on intracellular bacterial growth, confirming the impermeability of the cell membranes of the tissue to gentamicin. Western blot analysis of MVs with
S. flexneri
Ipa-specific antibodies demonstrated that the invasion protein antigens IpaB, IpaC, and IpaD were present in MVs. Being bilayered, with outer faces composed of LPS and Ipa proteins, these MVs were readily engulfed by the otherwise impermeable membranes and eventually liberated their contents into the cytoplasmic substance of the host tissue.
Efficacies of Zinc-Finger-Active Drugs againstGiardia lamblia
Authors: Nash Theodore , Rice William G. 
Published: October 2018

ABSTRACTTwenty-nine of 34 (85%) Zn-finger-active compounds at 300 μM or less inhibited the growth ofGiardia lamblia. The most active compound, disulfiram (Antabuse), was cidal at 1.23 ± 0.32 μM. In the adult mouse model, significant in vivo activity was demonstrated by increased cure rates and decreased parasite burdens.
Oral Cimetidine Prolongs Clarithromycin Absorption
Authors: Amsden Guy W. , Cheng Kit L. , Peloquin Charles A. , Nafziger Anne N. 
Published: October 2018

ABSTRACT
The present study was conducted to identify any potential interaction between oral cimetidine and clarithromycin. Twelve healthy subjects were administered single doses of clarithromycin alone and with oral cimetidine dosed to steady state. Cimetidine prolonged the absorption of clarithromycin, as evidenced by decreased peak concentrations of both clarithromycin and 14-OH-clarithromycin (14OHC) in serum (46 and 43%, respectively), a delay in the formation of 14OHC (increase of 68%), and increases in both of their half-lives (75 and 82%, respectively), despite no changes in total oral clearance or area under the concentration-time curve for either compound. No mechanism for this interaction has been identified.
Urinary Excretion and Bactericidal Activities of a Single Oral Dose of 400 Milligrams of Fleroxacin versus a Single Oral Dose of 800 Milligrams of Pefloxacin in Healthy Volunteers
Authors: Naber Kurt G. , Theuretzbacher Ursula , Kinzig Martina , Savov Orlin , Sörgel Fritz 
Published: October 2018

ABSTRACT

Twelve healthy volunteers participated in this randomized crossover study to compare the concentrations and recovery levels of fleroxacin and pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs. The volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of pefloxacin. The mean cumulative renal excretion of unchanged fleroxacin,
N
-demethyl-fleroxacin, and
N
-oxide-fleroxacin accounted for 67, 7, and 6% of the total dose, respectively. The total urinary recovery of pefloxacin and the active metabolite norfloxacin was 34%. In the time-kill and the urinary bactericidal titer (UBT) studies, only the subjects’ urine not supplemented with broth was used. With most tested organisms and both quinolones it took more than 8 h to achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good correlation between UBTs and MICs for the strains. Against
Escherichia coli
ATCC 25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96 h; against the
E. coli
strain for which the MIC was 0.5 μg/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against
Klebsiella pneumoniae
were at least 1:16 for 72 h. The UBTs for
Staphylococcus aureus
(the MIC for which was 16 μg/ml) of both antibiotics were low, and in some of the samples, no bactericidal titers were observed. UBTs for
Proteus mirabilis
of pefloxacin are significantly higher than those of fleroxacin. For
Pseudomonas aeruginosa
the median UBTs were present for the 24-to-48-h interval. The same is true for
Enterococcus faecalis
. Against
Staphylococcus saprophyticus
, UBTs were present for at least 48 h with both quinolones. Overall, a single oral dose of 400 mg of fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin. Therefore, it may be expected that half of the dose of fleroxacin gives comparable results in the treatment of urinary tract infections; this should be substantiated in comparative clinical trials.
16S rRNA Mutation Associated with Tetracycline Resistance in a Gram-Positive Bacterium
Authors: Ross Jeremy I. , Eady E. Anne , Cove Jonathan H. , Cunliffe William J. 
Published: October 2018

ABSTRACT

A genetic basis for tetracycline resistance in cutaneous propionibacteria was suggested by comparing the nucleotide sequences of the 16S rRNA genes from 16 susceptible and 21 resistant clinical isolates and 6 laboratory-selected tetracycline-resistant mutants of a susceptible strain. Fifteen clinical isolates resistant to tetracycline were found to have cytosine instead of guanine at a position cognate with
Escherichia coli
16S rRNA base 1058 in a region important for peptide chain termination and translational accuracy known as helix 34. Cytosine at base 1058 was not detected in the laboratory mutants or the tetracycline-susceptible strains. The apparent mutation was recreated by site-directed mutagenesis in the cloned
E. coli
ribosomal operon,
rrnB
, encoded by pKK3535.
E. coli
strains carrying the mutant plasmid were more resistant to tetracycline than those carrying the wild-type plasmid both in MIC determinations and when grown in tetracycline-containing liquid medium. These data are consistent with a role for the single 16S rRNA base mutation in clinical tetracycline resistance in cutaneous propionibacteria.
Multidose Pharmacokinetics of Ritonavir and Zidovudine in Human Immunodeficiency Virus-Infected Patients
Authors: Cato Allen , Qian Jiang , Hsu Ann , Levy Benjamin , Leonard John , Granneman Richard 
Published: October 2018

ABSTRACT

The effect of coadministration of ritonavir and zidovudine (ZDV) on the pharmacokinetics of these drugs was investigated in a three-period, multidose, crossover study. Eighteen asymptomatic, human immunodeficiency virus-positive men were assigned randomly to six different sequences of the following three regimens: ZDV (200 mg every 8 h [q8h]) alone for 4 days, ritonavir (300 mg q6h) alone for 4 days, and ZDV with ritonavir for 4 days. Ritonavir pharmacokinetics were unaffected by coadministration with ZDV. However, ZDV exposure was reduced by about 26% (
P
< 0.05) in the presence of ritonavir. The maximum concentration in (
C
max
) of ZDV plasma decreased from 748 ± 375 (mean ± standard deviation) to 546 ± 296, and area under the concentration-time curve from 0 to 24 h (AUC
0–24
) decreased from 3,052 ± 1,007 to 2,261 ± 715 when coadministered with ritonavir. In contrast, the ZDV elimination rate constant was unaffected by ritonavir, suggesting that there was no change in ZDV systemic metabolism. Correspondingly, differences in ZDV-glucuronide
C
max
and AUC were not statistically significantly different between regimens (
P
> 0.31). Also, there were no apparent differences in the formation of 3′-amino-3′-deoxythymidine or in the adverse event profiles between the regimens. The lack of change in ritonavir pharmacokinetics suggests that dosage adjustment of ritonavir is unnecessary when it is administered concurrently with ZDV. The clinical relevance of a 26% reduction in ZDV exposure when ZDV is administered with ritonavir is unknown. In addition to other multidrug regimens, the long-term safety and efficacy of coadministration of ritonavir and ZDV is being investigated.