bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Trial of Trimethoprim-Sulfamethoxazole versus Pyrimethamine-Sulfadiazine for Therapy of Toxoplasmic Encephalitis in Patients with AIDS
Authors: Torre Donato , Casari Salvatore , Speranza Filippo , Donisi Alessandra , Gregis Giampietro , Poggio Antonio , Ranieri Sergio , Orani Anna , Angarano Gioacchino , Chiodo Francesco , Fiori GianPaolo , Carosi Giampiero ,   the Italian Collaborative Study Group
Published: October 2018

ABSTRACT
The aim of the present pilot study was to compare the efficacy and safety of trimethoprim (TMP) and sulfamethoxazole (SMX) with those of the standard therapy pyrimethamine (P)-sulfadiazine (S) for the treatment of toxoplasmic encephalitis in patients with AIDS. This was a pilot, multicenter, randomized, and prospective study. Patients were randomly assigned to receive TMP (10 mg/kg of body weight/day) and SMX (50 mg/kg/day) or P (50 mg daily) and S (60 mg/kg/day) as acute therapy (for 4 weeks) and then as maintenance therapy for 3 months at half of the original dosage. Seventy-seven patients were enrolled and randomized to the study: 40 patients were treated with TMP-SMX and 37 were treated with P-S. There was no statistically significant difference in clinical efficacy during acute therapy. In contrast, patients randomized to TMP-SMX appeared more likely to achieve a complete radiologic response after acute therapy. Adverse reactions were significantly more frequent in patients treated with P-S, and skin rash was the most common adverse event noted in these patients. In conclusion, the results of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in particular in patients with opportunistic bacterial infections.
Changes in MIC Alter Responses of
Pseudomonas aeruginosa
to Tobramycin Exposure
Authors: Ioannides-Demos L. L. , Liolios L. , Wood P. , Spicer W. J. , McLean A. J. 
Published: October 2018

ABSTRACT

The pharmacokinetic parameters determining antibiotic efficacy are peak concentrations (
C
max
), minimum (trough) concentrations (
C
min
), and area under the concentration-time curve (AUC). There is general agreement about the importance of
C
max
and AUC for aminoglycosides, but this is not so for maintenance of
C
min
. With in vitro exposures modelling in vivo administration,
Pseudomonas aeruginosa
reference strain ATCC 27853 (MIC, 1 mg/liter) and a higher-MIC (relatively resistant) clinical isolate (MIC, 4 mg/liter) were used to explore bacteriostatic and bactericidal outcomes. With
P. aeruginosa
ATCC 27853, kill followed a complete bolus profile with a 30-min postdistribution peak (
C
peak30
) of 10 mg/liter. The clinical isolate required a
C
peak30
bolus profile of 20 mg/liter for kill, and there was no difference between the efficacies of the bolus and infusion exposures. Bolus profiles that were truncated at 8.5 h and producing sublethal effects were then combined with a wide range of
C
min
s. With a
C
peak30
profile of 8 mg/liter,
P. aeruginosa
ATCC 27853 showed a graded bacteriostatic response until a
C
min
of ≥0.8 mg/liter, when complete kill resulted. In contrast, bactericidal effects on the clinical isolate required a
C
peak30
profile of 18 mg/liter with a
C
min
of ≥1.0 mg/liter. Therefore,
C
min
also contributes to the bactericidal effect of tobramycin, with requirements showing minor variation with change in MIC. Dosing principles for relatively resistant (higher-MIC) organisms are suggested from the data. Relatively higher aminoglycoside doses via infusion regimens are likely to be needed to generate higher peak concentrations and higher AUC values necessary for bactericidal effect in resistant organisms. Maintenance of trough concentrations on the order of 1.0 mg/liter during the interdose interval will tend to guard against the possibility of inadequate peak and AUC exposures for kill.
Comparison of In Vitro Antifungal Activities of Free and Liposome-Encapsulated Nystatin with Those of Four Amphotericin B Formulations
Authors: Johnson Elizabeth M. , Ojwang Joshua O. , Szekely Adrien , Wallace Thomas L. , Warnock David W. 
Published: October 2018

ABSTRACT

The in vitro activity of a multilamellar liposomal formulation of nystatin (Nyotran) was compared with those of free nystatin and four pharmaceutical preparations of amphotericin B. MICs for 200 isolates of two
Aspergillus
spp., seven
Candida
spp., and
Cryptococcus neoformans
were determined by a broth microdilution adaptation of the method recommended by the National Committee for Clinical Laboratory Standards. Minimum lethal concentrations (MLCs) of the six antifungal preparations were also determined. Both nystatin formulations possessed fungistatic and fungicidal activities against the 10 species tested. Liposomal nystatin appeared to be as active as free nystatin, with MICs and MLCs that were similar to, or lower than, those of the latter. Neither formulation of nystatin was as active as amphotericin B deoxycholate (Fungizone) or amphotericin B lipid complex (Abelcet), but both were more effective than liposomal amphotericin B (AmBisome). Our results suggest that further evaluation of liposomal nystatin is justified.
Antifungal Activity of 3′-Deoxyadenosine (Cordycepin)
Authors: Sugar Alan M. , McCaffrey Ronald P. 
Published: October 2018

ABSTRACT

The antifungal activity of the nucleoside analog 3′-deoxyadenosine (cordycepin) was studied in a murine model of invasive candidiasis. When protected from deamination by either deoxycoformycin or coformycin, both of which are adenosine deaminase inhibitors, cordycepin exhibited potent antifungal efficacy, as demonstrated by prolongation of survival and a decrease in CFU in the kidneys of mice treated with cordycepin plus an adenosine deaminase inhibitor. The antifungal effect was seen with three different
Candida
isolates:
Candida albicans
64, a relatively fluconazole-resistant clinical isolate of
C. albicans
(MIC, 16 μg/ml), and the fluconazole-resistant
Candida krusei
. Cordycepin and related compounds may provide another avenue for the discovery of clinically useful antifungal drugs.
Characterization of a Murine Monoclonal Antibody toCryptococcus neoformansPolysaccharide That Is a Candidate for Human Therapeutic Studies
Authors: Casadevall Arturo , Cleare Wendy , Feldmesser Marta , Glatman-Freedman Aharona , Goldman David L. , Kozel Thomas R. , Lendvai Nikoletta , Mukherjee Jean , Pirofski Liise-anne , Rivera Johanna , Rosas Angel L. , Scharff Matthew D. , Valadon Philippe , Westin Katherine , Zhong Zhaojing 
Published: October 2018

ABSTRACTThe murine monoclonal antibody (MAb) 18B7 [immunoglobulin G1(κ)] is in preclinical development for treatment ofCryptococcus neoformansinfections. In anticipation of its use in humans, we defined the serological and biological properties of MAb 18B7 in detail. Structural comparison to the related protective MAb 2H1 revealed conservation of the antigen binding site despite several amino acid differences. MAb 18B7 was shown by immunofluorescence and agglutination studies to bind to all four serotypes ofC. neoformans, opsonizeC. neoformansserotypes A and D, enhance human and mouse effector cell antifungal activity, and activate the complement pathway leading to deposition of complement component 3 (C3) on the cryptococcal capsule. Administration of MAb 18B7 to mice led to rapid clearance of serum cryptococcal antigen and deposition in the liver and spleen. Immunohistochemical studies revealed that MAb 18B7 bound to capsular glucuronoxylomannan in infected mouse tissues. No reactivity of MAb 18B7 with normal human, rat, or mouse tissues was detected. The results show that both the variable and constant regions of MAb 18B7 are biologically functional and support the use of this MAb in human therapeutic trials.
Ceftazidime and Aztreonam Resistance in
Providencia stuartii
: Characterization of a Natural TEM-Derived ExtendedSpectrum β-Lactamase, TEM-60
Authors: Franceschini Nicola , Perilli Mariagrazia , Segatore Bernardetta , Setacci Domenico , Amicosante Gianfranco , Mazzariol Annarita , Cornaglia Giuseppe 
Published: October 2018

ABSTRACT

A plasmid-encoded β-lactamase produced from a clinical strain of
Providencia stuartii
has been purified and characterized. The gene coding for the β-lactamase was cloned and sequenced. It appears to be a new natural TEM-derived enzyme, named TEM-60. Point mutations (Q39K, L51P, E104K, and R164S) are present with respect to the TEM-1 enzyme; the mutation L51P has never been previously reported, with the exception of the chromosomally encoded extended-spectrum β-lactamase PER-1. Kinetic parameters relative to penicillins, cephalosporins, and monobactams other than mechanism-based inactivators were related to the in vitro susceptibility phenotype.
In Vitro Activities of the New Ketolide Antibiotics HMR 3004 and HMR 3647 against
Streptococcus pneumoniae
in Germany
Authors: Reinert Ralf René , Bryskier André , Lütticken Rudolf 
Published: October 2018

ABSTRACT
The comparative in vitro activity of HMR 3004 and HMR 3647, new ketolide antibiotics, was tested by a standard agar dilution technique against 221 pneumococcal strains, including isolates with intermediate levels of resistance to penicillin and erythromycin-resistant isolates. The ketolides were more active than other macrolides and showed excellent activity against erythromycin-resistant strains. All the strains were inhibited by ≤2 μg of HMR 3004/ml or by ≤0.5 μg of HMR 3647/ml.
Famciclovir and Valaciclovir Differ in the Prevention of Herpes Simplex Virus Type 1 Latency in Mice: a Quantitative Study
Authors: Thackray Alana M. , Field Hugh J. 
Published: October 2018

ABSTRACT
Famciclovir (FCV) and valaciclovir (VACV) have previously been shown to be potent inhibitors of herpes simplex virus type 1 (HSV-1) in a murine cutaneous model. In the present study, mice were inoculated in the skin of the left ear pinna with herpes simplex virus (HSV) type 1. Antiviral therapy was started on different days postinoculation (p.i.), terminating at the end of day 10 p.i. The compounds were administered twice daily by oral gavage at 50 mg/kg of body weight/dose. Mice were sampled on day 5 p.i., during the acute phase of the infection, and the titers of infectious virus in the target tissues (ear, brain stem, and trigeminal ganglia) were determined. At 2 to 3 months p.i., the ipsilateral and contralateral trigeminal and cervical dorsal root ganglia were explanted, and four different methods were used to detect latent HSV. The methods were (i) conventional explant culture for 5 days followed by homogenization, (ii) long-term culture (up to 73 days) of whole ganglia, followed by homogenization, (iii) dissociation by enzymatic disaggregation and an infectious center assay, and (iv) in situ hybridization to detect latency-associated transcripts (LATs). The conventional explant culture method was the least sensitive method, while in situ staining for LAT was the most sensitive, and all mice, including those treated from early times with FCV, were shown to be latently infected. Significantly less latent virus was detected by all four methods, however, in ganglia obtained from mice that had been treated with FCV in comparison with the amount detected in ganglia from mice that had been treated with VACV. However, in no case was latency completely eliminated.
Antifungal Susceptibilities ofPaecilomycesSpecies
Authors: Aguilar C. , Pujol I. , Sala J. , Guarro J. 
Published: October 2018

ABSTRACTThe MICs and minimum fungicidal concentrations (MFCs) of amphotericin B, miconazole, itraconazole, ketoconazole, fluconazole, and flucytosine for 52 isolates ofPaecilomycesspecies were evaluated by the broth microdilution method, largely based on the recommendations of the National Committee for Clinical Laboratory Standards (document M27-A). The fungal isolates tested included 16P. variotii, 11P. lilacinus, 9P. marquandii, 6P. fumosoroseus, 4P. javanicus, and 2P. viridisisolates and 1 isolate of each of the following species:P. carneus,P. farinosus,P. fulvus, andP. niveus. The MFCs and the MICs at which 90% of isolates were inhibited (MIC90s) for the six antifungal agents were remarkably high; the MIC50s indicated that amphotericin B, miconazole, itraconazole, and ketoconazole had good activities, while fluconazole and flucytosine demonstrated poor efficacy. The ranges of the MICs were generally wider and lower than those of the MFCs. There were significant susceptibility differences among the species. All species with the exception ofP. variotiiwere highly resistant to fluconazole and flucytosine;P. variotiiwas susceptible to flucytosine. Amphotericin B and the rest of the azoles showed good activity againstP. variotii, while all the antifungal agents assayed showed low efficacy againstP. lilacinus.
In Vitro and In Vivo Activities of Levofloxacin against Biofilm-Producing
Pseudomonas aeruginosa
Authors: Ishida Hiroko , Ishida Yoshihisa , Kurosaka Yuichi , Otani Tsuyoshi , Sato Kenichi , Kobayashi Hiroyuki 
Published: October 2018

ABSTRACT

Interactions between biofilm cells of
Pseudomonas aeruginosa
and levofloxacin were studied.
P. aeruginosa
incubated for 6 days with Teflon sheets formed a biofilm on its surface. Against the biofilm bacteria, levofloxacin at an MIC determined by the standard method for the strain was highly bactericidal whereas gentamicin, ceftazidime, and ciprofloxacin showed no significant killing activity. Levofloxacin, ciprofloxacin, and gentamicin, but not ceftazidime, exhibited killing activity against nongrowing cells of the strain incubated in phosphate buffer. In addition, levofloxacin, ciprofloxacin, and ceftazidime, but not gentamicin, showed the ability to penetrate an agar containing alginate. These findings may explain the efficacy of levofloxacin and the ineffectiveness of gentamicin and ceftazidime against biofilm bacteria; however, the cause of the ineffectiveness of ciprofloxacin still remains to be determined. In experimental pneumonia in guinea pigs, in which the biofilm mode of growth of the strain was observed in the lung, only levofloxacin exhibited substantial therapeutic efficacy. These findings suggest the significant role of levofloxacin in therapy of biofilm bacterium-associated infectious diseases.
Differences in the Lipoprotein Distribution of Free and Liposome-Associated All-
trans
-Retinoic Acid in Human, Dog, and Rat Plasma Are Due to Variations in Lipoprotein Lipid and Protein Content
Authors: Wasan Kishor M. , Ramaswamy Manisha , Ng Samson P. , Wong Wesley , Parrott Steven C. , Ojwang Joshua O. , Wallace Thomas , Cossum Paul A. 
Published: October 2018

ABSTRACT

The objective of the proposed study was to determine the distribution in plasma lipoprotein of free all-
trans
retinoic acid (ATRA) and liposomal ATRA (Atragen; composed of dimyristoyl phosphatidylcholine and soybean oil) following incubation in human, rat, and dog plasma. When ATRA and Atragen at concentrations of 1, 5, 10, and 25 μg/ml were incubated in human and rat plasma for 5, 60, and 180 min, the majority of the tretinoin was recovered in the lipoprotein-deficient plasma fraction. However, when ATRA and Atragen were incubated in dog plasma, the majority of the tretinoin (>40%) was recovered in the high-density lipoprotein (HDL) fraction. No differences in the plasma distribution between ATRA and Atragen were found. These data suggest that a significant percentage of tretinoin associates with plasma lipoproteins (primarily the HDL fraction) upon incubation in human, dog, and rat plasma. Differences between the lipoprotein lipid and protein profiles in human plasma and in dog and rat plasma influenced the plasma distribution of ATRA and Atragen. Differences in lipoprotein distribution between ATRA and Atragen were not observed, suggesting that the drug’s distribution in plasma is not influenced by its incorporation into these liposomes.
Ceftazidime-Resistant
Klebsiella pneumoniae
and
Escherichia coli
Isolates Producing TEM-10 and TEM-43 β-Lactamases from St. Louis, Missouri
Authors: Yang Youjun , Bhachech Niraja , Bradford Patricia A. , Jett Bradley D. , Sahm Daniel F. , Bush Karen 
Published: October 2018

ABSTRACT

Ceftazidime-resistant
Escherichia coli
and
Klebsiella pneumoniae
(49 and 102 isolates, respectively) were collected from Barnes-Jewish Hospital, St. Louis, Mo., from 1992 to 1996. They were uniformly resistant to ceftazidime, generally resistant to aztreonam, and variably susceptible to cefotaxime. Four representative
E. coli
strains and 15
Klebsiella
strains were examined. From one to four β-lactamases were produced per strain, with three possible enzymes related to ceftazidime resistance: enzymes with pI values of 5.6, 6.1, or 7.6. By pulsed-field gel electrophoresis there were at least 13 different
Klebsiella
strain types and 3 different
E. coli
strain types, indicating that the outbreak was not clonal. After cloning and sequencing of the β-lactamase-encoding genes, the enzyme with a pI of 5.6 was identified as TEM-10. The enzyme with a pI of 6.1 was a novel TEM variant (TEM-43) with Lys at 104, His at 164, and Thr at 182. TEM-43 showed broad-spectrum hydrolytic activity against all penicillins, with the highest hydrolysis rate for ceftazidime compared to those for the other expanded-spectrum cephalosporins. Aztreonam was also a good substrate for TEM-43, with hydrolytic activity similar to that of ceftazidime and affinity higher than that of ceftazidime. The TEM-43 β-lactamase was well inhibited by clavulanic acid and tazobactam at concentrations of <10 nM. Sulbactam was less effective than the other inhibitors. The Thr182 mutation previously reported in an inhibitor-resistant β-lactamase did not cause the TEM-43 enzyme to become resistant to any of the inhibitors.
Evaluation of Moxifloxacin, a New 8-Methoxyquinolone, for Treatment of Meningitis Caused by a PenicillinResistant Pneumococcus in Rabbits
Authors: Østergaard Christian , Klitmøller Sørensen Tina , Dahl Knudsen Jenny , Frimodt-Møller Niels 
Published: October 2018

ABSTRACT

Moxifloxacin is a new 8-methoxyquinolone with high activity against gram-positive bacteria, including penicillin-resistant pneumococci. In an experimental meningitis model, we studied the pharmacokinetics of moxifloxacin in infected and uninfected rabbits and evaluated the antibiotic efficacies of moxifloxacin, ceftriaxone, and vancomycin against a penicillin-resistant
Streptococcus pneumoniae
strain (penicillin, ceftriaxone, vancomycin, and moxifloxacin MICs were 1, 0.5, 0.5, and 0.125 μg/ml, respectively). Moxifloxacin entered cerebrospinal fluid (CSF) readily, with peak values within 15 to 30 min after bolus intravenous infusion and with a mean percent penetration into normal and purulent CSF of approximately 50 and 80%, respectively. The bactericidal effect of moxifloxacin was concentration dependent, and regrowth was seen only when the concentration of moxifloxacin in CSF was below the minimal bactericidal concentration. All antibiotic-treated groups (moxifloxacin given in two doses of 40 mg/kg of body weight, moxifloxacin in two 20-mg/kg doses, ceftriaxone in one 125-mg/kg dose, and vancomycin in two 20-mg/kg doses) had significantly higher reductions in CSF bacterial concentration than the untreated group (
P
< 0.05). Moxifloxacin was as effective as vancomycin and ceftriaxone in reducing bacterial counts at all time points tested (3, 5, 10, and 24 h). Moreover, moxifloxacin given in two 40-mg/kg doses resulted in a significantly higher reduction in CSF bacterial concentration (in log
10
CFU per milliliter) than vancomycin within 3 h after the start of antibiotic treatment (3.49 [2.94 to 4.78] versus 2.50 [0.30 to 3.05];
P
< 0.05). These results indicate that moxifloxacin could be useful in the treatment of meningitis, including penicillin-resistant pneumococcal meningitis.
Pharmacokinetic Study of an Oral Cephalosporin, Cefdinir, in Hemodialysis Patients
Authors: Hishida Akira , Ohishi Kazuhisa , Nagashima Satoru , Kanamaru Mitsutaka , Obara Masao , Kitada Ayako 
Published: October 2018

ABSTRACT

The pharmacokinetics of cefdinir were investigated in six hemodialysis patients. For the present study, two tests were carried out, one with 4 h of hemodialysis and the other without hemodialysis. Cefdinir was given orally to each patient in a dose of 100 mg, and blood was collected serially for 48 h after dosing in the test without dialysis and for 72 h in the test with dialysis. In the test without dialysis, the maximum plasma concentration (
C
max
) was 2.36 ± 0.53 μg/ml (mean ± standard deviation) and the time to
C
max
was 9.00 ± 2.45 h. The terminal elimination half-life (
t
1/2
) and area under the concentration-time curve (AUC) were 16.95 ± 1.20 h and 69.05 ± 14.84 μg · h/ml, respectively. In the test with dialysis,
t
1/2
during hemodialysis decreased approximately to one-sixth of that obtained in the test without dialysis, although
t
1/2
in the latter elimination phase did not differ from that in the nondialysis test. AUC was reduced to 43% of that in the test without dialysis. The fractional removal of cefdinir by hemodialysis was 61%. These findings indicate that clearance of cefdinir is prolonged in patients with renal failure, and cefdinir is well removed by introduction of hemodialysis, although
t
1/2
(during hemodialysis) and AUC were two and eight times higher than the data previously reported for healthy volunteers, respectively. The pharmacokinetic data suggest that 100 mg of oral cefdinir once a day would result in a sufficient concentration in plasma in hemodialysis patients, but this remains to be confirmed by multiple-dose studies.
Comparisons between Antimicrobial Pharmacodynamic Indices and Bacterial Killing as Described by Using the Zhi Model
Authors: Corvaisier S. , Maire P. H. , Bouvier d’yvoire M. Y. , Barbaut X. , Bleyzac N. , Jelliffe R. W. 
Published: October 2018

ABSTRACTVarious suggestions have been made for empirical pharmacodynamic indices of antibiotic effectiveness, such as areas under the drug concentration-time curve in serum (AUC), AUC>MIC, AUC/MIC, area under the inhibitory curve (AUIC), AUC above MIC, and time above MIC (T>MIC). In addition, bacterial growth and killing models, such as the Zhi model, have been developed. The goal of the present study was to compare the empirical behavior of the Zhi model of bacterial growth and killing with the other empirical pharmacodynamic indices described above by using simulated clinical data analyzed with the USC*PACK PC clinical programs for adaptive control of drug therapy, with one model describing a concentration-dependent antibiotic (tobramycin) and another describing a concentration-independent antibiotic (ticarcillin). The computed relative number of CFU was plotted against each pharmacodynamic index, with each axis parameterized over time. We assumed that a good pharmacodynamic index should present a clear and continuous relationship between the time course of its values and the time course of the bacterial killing as seen with the Zhi model. Preliminary work showed that some pharmacodynamic indices were very similar. A good sensitivity to the change in the values of the MIC was shown for AUC/MIC and also forT>MIC. In addition, the time courses of some other pharmacodynamic indices were very similar. Since AUC/MIC is easily calculated and shows more sensitivity, it appeared to be the best of the indices mentioned above for the concentration-dependent drug, because it incorporated and used the MIC the best.T>MIC appeared to be the best index for a concentration-independent drug. We also propose a new composite index, weighted AUC (WAUC), which appears to be useful for both concentration-dependent and concentration-independent drugs.