bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ambulatory Treatment of Multidrug-Resistant
Staphylococcus
-Infected Orthopedic Implants with High-Dose Oral Co-trimoxazole (Trimethoprim-Sulfamethoxazole)
Authors: Stein Andreas , Bataille Jean Francois , Drancourt Michel , Curvale Georges , Argenson Jean Noel , Groulier Pierre , Raoult Didier 
Published: October 2018

ABSTRACT

We examined the effectiveness and safety of high-dose oral co-trimoxazole (trimethoprim-sulfamethoxazole) for the treatment of orthopedic implants infected with multidrug-resistant
Staphylococcus
species. The prospective study was conducted between 1989 and 1997 in a university medical center with ambulatory-care services. Patients eligible for the study consisted of those from whom multidrug-resistant
Staphylococcus
spp. organisms susceptible only to glycopeptides and co-trimoxazole were isolated from their orthopedic implants and for whom there was no contraindication to the treatment. All patients were treated orally with high-dose co-trimoxazole (trimethoprim, 20 mg/kg of body weight/day; sulfamethoxazole, 100 mg/kg/day). Patients with prosthetic hip infections were treated for 6 months, with removal of any unstable prosthesis after 5 months of treatment; patients with prosthetic knee infections were treated for 9 months, with removal of any unstable prosthesis after 6 months of treatment; and patients with infected osteosynthetic devices were treated for 6 months, with removal of the device after 3 months of treatment, if necessary. Monthly clinical evaluations were conducted until the completion of the treatment, and follow-up examinations were conducted regularly for up to 6 years. The overall treatment success rate was 66.7% (26 of 39 patients), with success rates of 62.5% for patients with prosthetic knee infections, 50% for those with prosthetic hip infections, and 78.9% for those with other device infections. Seventeen of the 28 (60.7%) patients who did not have any orthopedic material removed were cured. Eight patients stopped the treatment because of side effects, and one patient was not compliant. In three patients treatment failed because of the appearance of a resistant bacterium. Long-term oral ambulatory treatment with co-trimoxazole appears to be an effective alternative to the conventional medicosurgical treatment of chronic multidrug-resistant
Staphylococcus
-infected orthopedic implants which includes long-term intravenous antibiotic therapy combined with surgical debridement and removal of foreign material or its subsequent one- or two-stage replacement.
Efficacious Topical Treatment for Murine Cutaneous Leishmaniasis with Ethanolic Formulations of Amphotericin B
Authors: Frankenburg Shoshana , Glick Dvora , Klaus Sidney , Barenholz Yechezkel 
Published: October 2018

ABSTRACT
The goal of the present study was to evaluate the antileishmanial effects of topically applied lipid-based formulations containing amphotericin B (AmB) in CBA mice as a model for human cutaneous leishmaniasis. Such treatment, if efficacious, is expected to be superior to systemic treatments since, by acting in a localized manner, it will require lower, and therefore less toxic, drug dosages. Three preparations of AmB complexed to polar lipids were tested: Fungizone (mixed micelles composed of AmB and deoxycholate), Amphocil (AmB and cholesteryl sulfate complex), and ABPLC (AmB and phospholipid complex). All these formulations killed parasites in vitro with similar efficacies but were ineffective when they were applied topically. However, Amphocil and ABPLC, but not Fungizone, when dispersed in an aqueous solution containing 5 to 25% ethanol, induced a statistically significant improvement in lesion size from week 2 or 3 onward (a total of 15 mg of AmB per kg of body weight was applied over 3 weeks). AmB biodistribution measurements following topical application of Amphocil, determined by high-pressure liquid chromatography, showed that AmB was detectable in the skin but not in the internal organs. Application of at least 10 times more drug was necessary to obtain detectable levels of AmB in the internal organs. After application of therapeutic doses of ABPLC, very low levels of AmB were detected in the internal organs. These experiments show for the first time that AmB administered topically as a complex either with cholesteryl sulfate or with phospholipids and in the presence of ethanol can penetrate the skin and kill sensitive organisms in a localized manner by using very low total drug concentrations.
Possible Mechanism by Which the Carbapenem Antibiotic Panipenem Decreases the Concentration of Valproic Acid in Plasma in Rats
Authors: Kojima Saori , Nadai Masayuki , Kitaichi Kiyoyuki , Wang Li , Nabeshima Toshitaka , Hasegawa Takaaki 
Published: October 2018

ABSTRACT
There is evidence indicating that the carbapenem antibiotic panipenem decreases plasma concentrations of valproic acid (VPA) in epileptic patients during VPA therapy. The mechanism for panipenem-induced changes in the pharmacokinetics of VPA was investigated in rats with and without bile duct cannulation. The effect of panipenem on the pharmacokinetics of diclofenac, which undergoes extensive enterohepatic recirculation, was also examined. VPA (50 mg/kg of body weight) or diclofenac (10 mg/kg of body weight) was administered intravenously under the steady-state plasma panipenem concentration of 4 μg/ml, which had been achieved by a constant infusion rate. Panipenem decreased the plasma VPA concentrations in rats without bile duct cannulation but did not change the volume of the initial space and protein binding of VPA. However, panipenem had no effect on the plasma VPA concentrations and the biliary excretion of VPA in rats with bile duct cannulation. The secondary increase in plasma diclofenac concentration observed in the absence of panipenem was diminished in the presence of panipenem. These findings suggest that panipenem decreases plasma VPA concentrations by suppressing its enterohepatic recirculation, probably due to a panipenem-induced decrease in the numbers of enteric bacteria.
In Vitro Resistance to Thrombin-Induced Platelet Microbicidal Protein among Clinical Bacteremic Isolates of
Staphylococcus aureus
Correlates with an Endovascular Infectious Source
Authors: Bayer Arnold S. , Cheng Darwin , Yeaman Michael R. , Corey G. Ralph , McClelland R. Scott , Harrel Lizzie J. , Fowler Vance G. 
Published: October 2018

ABSTRACT

Platelet microbicidal proteins (PMPs), small cationic peptides released at sites of endovascular damage, kill common bloodstream pathogens in vitro. Our group previously showed that in vitro resistance of clinical staphylococcal and viridans group streptococcal bacteremic strains to PMPs correlated with the diagnosis of infective endocarditis (IE) (Wu et al., Antimicrob. Agents Chemother. 38:729–732, 1994). However, that study was limited by (i) the small number of
Staphylococcus aureus
isolates from IE patients, (ii) the retrospective nature of the case definitions, and (iii) the diverse geographic sources of strains. The present study evaluated the in vitro PMP susceptibility phenotype of a large number of staphylococcemic isolates (
n
= 60), collected at a single medical center and categorized by defined and validated clinical criteria. A significantly higher proportion of staphylococcemic strains from patients with IE was PMP resistant in vitro than the proportion of strains from patients with soft tissue sepsis (83% and 33%, respectively;
P
< 0.01). Moreover, the levels of PMP resistance (mean percent survival of strains after 2-h exposure to PMP in vitro) were significantly higher for isolates from patients with IE and with vascular catheter sepsis than for strains from patients with abscess sepsis (
P
< 0.005 and
P
< 0.01, respectively). These data further support the concept that bloodstream pathogens that exhibit innate or acquired PMP resistance have a survival advantage with respect to either the induction or progression of endovascular infections.
In Vitro Activities of Membrane-Active Peptides against Gram-Positive and Gram-Negative Aerobic Bacteria
Authors: Giacometti A. , Cirioni O. , Greganti G. , Quarta M. , Scalise G. 
Published: October 2018

ABSTRACT
Four peptides, cecropin P1, magainin II, indolicidin, and ranalexin, were evaluated against 202 clinical isolates of gram-positive and gram-negative aerobic bacteria by a microbroth dilution method. The gram-negative isolates were more susceptible to cecropin P1. Ranalexin was the most active compound against the gram-positive strains. The bactericidal activity of each peptide was equivalent to, or 1 dilution above, the MIC. In conclusion, the four peptides exhibited different in vitro activities and rapid time-dependent killing.
Inhibition of Acute-, Latent-, and Chronic-Phase Human Immunodeficiency Virus Type 1 (HIV-1) Replication by a Bistriazoloacridone Analog That Selectively Inhibits HIV-1 Transcription
Authors: Turpin Jim A. , Buckheit Robert W. , Derse David , Hollingshead Melinda , Williamson Karen , Palamone Carla , Osterling M. Clayton , Hill Shawn A. , Graham Lisa , Schaeffer Catherine A. , Bu Ming , Huang Mingjun , Cholody Wieslaw M. , Michejda Christopher J. , Rice William G. 
Published: October 2018

ABSTRACTNanomolar concentrations of temacrazine (1,4-bis[3-(6-oxo-6H-v-triazolo[4,5,1-de]acridin-5-yl)amino-propyl]piperazine) were discovered to inhibit acute human immunodeficiency virus type 1 (HIV-1) infections and suppress the production of virus from chronically and latently infected cells containing integrated proviral DNA. This bistriazoloacridone derivative exerted its mechanism of antiviral action through selective inhibition of HIV-1 transcription during the postintegrative phase of virus replication. Mechanistic studies revealed that temacrazine blocked HIV-1 RNA formation without interference with the transcription of cellular genes or with events associated with the HIV-1 Tat and Rev regulatory proteins. Although temacrazine inhibited the in vitro 3′ processing and strand transfer activities of HIV-1 integrase, with a 50% inhibitory concentration of approximately 50 nM, no evidence of an inhibitory effect on the intracellular integration of proviral DNA into the cellular genome during the early phase of infection could be detected. Furthermore, temacrazine did not interfere with virus attachment or fusion to host cells or the enzymatic activities of HIV-1 reverse transcriptase or protease, and the compound was not directly virucidal. Demonstration of in vivo anti-HIV-1 activity by temacrazine identifies bistriazoloacridones as a new class of pharmaceuticals that selectively blocks HIV-1 transcription.
Prophylactic Anti-Infective Activity of Poly-[1-6]-β-d-Glucopyranosyl-[1-3]-β-d-Glucopyranose Glucan in a Guinea Pig Model of Staphylococcal Wound Infection
Authors: Kernodle Douglas S. , Gates Hiriam , Kaiser Allen B. 
Published: October 2018

ABSTRACTThe judicious use of perioperative antibiotic prophylaxis reduces the infectious complications of surgery. However, increased bacterial resistance within hospitals may make antibiotic prophylaxis less effective in the future and alternative strategies are needed. New immunomodulatory agents might prevent wound infections by stimulation of the host immune system. To test this hypothesis, we administered poly-[1-6]-β-d-glucopyranosyl-[1-3]-β-d-glucopyranose glucan (PGG glucan), which enhances neutrophil microbicidal activity, intravenously to guinea pigs in doses ranging from 0.015 to 4 mg/kg of body weight on the day before, on the day of, and on the day after intermuscular inoculation with methicillin-resistant strains ofStaphylococcus aureusandStaphylococcus epidermidis. Abscesses were identified at 72 h, and median infective doses (ID50) and statistical significance were determined by logistic regression. Guinea pigs receiving PGG glucan and inoculated with methicillin-resistantS. aureusandS. epidermidisexhibited ID50of as much as 2.5- and 60-fold higher, respectively, than those of control guinea pigs not receiving PGG glucan. Maximal protection was observed with a dose of 1 mg of PGG glucan per kg, and efficacy was reduced at higher as well as at lower PGG glucan doses. Furthermore, a single dose of PGG glucan given 24 h following bacterial inoculation was found to be effective in preventing infection. We conclude that PGG glucan reduces the risk of staphylococcal abscess formation. Neutrophil-activating agents are a novel means of prophylaxis against surgical infection and may be less likely than antibiotics to be affected adversely by the increasing antibiotic resistance of nosocomial pathogens.
Treatment of Invasive Fungal Infections in Renally Impaired Patients with Amphotericin B Colloidal Dispersion
Authors: Anaissie Elias J. , Mattiuzzi Gloria N. , Miller Carole B. , Noskin Gary A. , Gurwith Marc J. , Mamelok Richard D. , Pietrelli Larry A. 
Published: October 2018

ABSTRACT
Amphotericin B colloidal dispersion (ABCD) is a new formulation of conventional amphotericin B designed to minimize drug distribution in the kidney and reduce nephrotoxicity. We studied the safety and efficacy of ABCD in 133 renally compromised patients with invasive fungal infections. Patients had either nephrotoxicity from amphotericin B or preexisting renal disease. Intravenous treatment with ABCD (4 mg/kg of body weight daily) was administered for up to 6 weeks. Evaluations included clinical response to treatment and adverse events, with emphasis on changes in serum creatinine levels. ABCD did not appear to have an adverse effect on renal function: mean serum creatinine level tended to decrease slightly with days on therapy, and increases were not dose related. Complete or partial response to treatment was reported for 50% of the 133 intent-to-treat patients and 67% of the 58 evaluable patients.
1,1,3-Trioxo-2
H
,4
H
-Thieno[3,4-
e
][1,2,4]Thiadiazine (TTD) Derivatives: a New Class of Nonnucleoside Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase Inhibitors with Anti-HIV-1 Activity
Authors: Witvrouw M. , Arranz M. E. , Pannecouque C. , Declercq R. , Jonckheere H. , Schmit J.-C. , Vandamme A.-M. , Diaz J. A. , Ingate S. T. , Desmyter J. , Esnouf R. , Van Meervelt L. , Vega S. , Balzarini J. , De Clercq E. 
Published: October 2018

ABSTRACT

We report the development of a new group of nonnucleoside reverse transcriptase inhibitors (NNRTIs). One of the most active congeners of this series of 1,1,3-trioxo-2
H
,4
H
-thieno[3,4-
e
][1,2,4]thiadiazine (TTD) derivatives, i.e., 2-(3-fluorobenzyl)-4-cyanomethylen-1,1,3-trioxo-2
H
,4
H
-thieno[3,4-
e
][1,2,4]thiadiazine) (QM96639) was found to inhibit human immunodeficiency virus (HIV) type 1 [HIV-1 (III
B
)] replication in MT-4 cells at a concentration of 0.09 μM. This compound was toxic for the host cells only at a 1,400-fold higher concentration. The TTD derivatives proved effective against a variety of HIV-1 strains, including those that are resistant to 3′-azido-3′-deoxythymidine (AZT), but not against HIV-2 (ROD) or simian immunodeficiency virus (SIV/MAC251). HIV-1 strains containing the L100I, K103N, V106A, E138K, Y181C, or Y188H mutations in their reverse transcriptase (RT) displayed reduced sensitivity to the compounds. Their cross-resistance patterns correlated with that of nevirapine. 2-Benzyl-4-cyanomethylen-1,1,3-trioxo-2
H
,4
H
-thieno[3,4-
e
][1,2,4]thiadiazine (QM96521) enhanced the anti-HIV-1 activity of AZT and didanosine in a subsynergistic manner. HIV-1-resistant virus containing the V179D mutation in the RT was selected after approximately six passages of HIV-1 (III
B
) in CEM cells in the presence of different concentrations of QM96521. From structure-activity relationship analysis of a wide variety of TTD derivatives, a number of restrictions appeared as to the chemical modifications that were compatible with anti-HIV activity. Modelling studies suggest that in contrast to most other NNRTIs, but akin to nevirapine, QM96521 does not act as a hydrogen bond donor in the RT-drug complex.
Identification of GS 4104 as an Orally Bioavailable Prodrug of the Influenza Virus Neuraminidase Inhibitor GS 4071
Authors: Li Weixing , Escarpe Paul A. , Eisenberg Eugene J. , Cundy Kenneth C. , Sweet Clive , Jakeman Kenneth J. , Merson James , Lew Willard , Williams Matt , Zhang Lijun , Kim Choung U. , Bischofberger Norbert , Chen Ming S. , Mendel Dirk B. 
Published: October 2018

ABSTRACT

GS 4071 is a potent carbocyclic transition-state analog inhibitor of influenza virus neuraminidase with activity against both influenza A and B viruses in vitro. GS 4116, the guanidino analog of GS 4071, is a 10-fold more potent inhibitor of influenza virus replication in tissue culture than GS 4071. In this study we determined the oral bioavailabilities of GS 4071, GS 4116, and their respective ethyl ester prodrugs in rats. Both parent compounds and the prodrug of the guanidino analog exhibited poor oral bioavailability (2 to 4%) and low peak concentrations in plasma (
C
max
s;
C
max
<0.06 μg/ml). In contrast, GS 4104, the ethyl ester prodrug of GS 4071, exhibited good oral bioavailability (35%) as GS 4071 and high
C
max
s of GS 4071 (C
max
= 0.47 μg/ml) which are 150 times the concentration necessary to inhibit influenza virus neuraminidase activity by 90%. The bioavailability of GS 4104 as GS 4071 was also determined in mice (30%), ferrets (11%), and dogs (73%). The plasma of all four species exhibited high, sustained concentrations of GS 4071 such that at 12 h postdosing the concentrations of GS 4071 in plasma exceeded those necessary to inhibit influenza virus neuraminidase activity by 90%. These results demonstrate that GS 4104 is an orally bioavailable prodrug of GS 4071 in animals and that it has the potential to be an oral agent for the prevention and treatment of influenza A and B virus infections in humans.
Neurotoxicodynamics of the Interaction between Ciprofloxacin and Foscarnet in Mice
Authors: Matsuo Hirotami , Ryu Miwako , Nagata Aya , Uchida Takahiro , Kawakami Jun-Ichi , Yamamoto Koujirou , Iga Tatsuji , Sawada Yasufumi 
Published: October 2018

ABSTRACT

The potential for convulsions induced by the coadministration of ciprofloxacin (CPFX) and foscarnet (PFA) may be due not to a change in the distribution of CPFX to the brain but to a potential CPFX-induced inhibition of γ-aminobutyric acid (GABA)-GABA
A
receptor binding in the presence of PFA.
Antimicrobial Activity of Novel Furanonaphthoquinone Analogs
Authors: Nagata Kumiko , Hirai Kei-Ichi , Koyama Junko , Wada Yasunao , Tamura Toshihide 
Published: October 2018

ABSTRACT

Analogs of furanonaphthoquinone (FNQ) from
Tecoma ipe
Mart had MICs ranging from 1.56 to 25 μg/ml against gram-positive bacteria. FNQ showed significantly lower MICs against methicillin-resistant
Staphylococcus aureus
than against methicillin-sensitive
S. aureus
. FNQ inhibited
Helicobacter pylori
with an MIC of 0.1 μg/ml. Fungi, including pathogenic species, were sensitive to FNQ with MICs similar to those of amphotericin B.
Thirteen-Year Evolution of Azole Resistance in Yeast Isolates and Prevalence of Resistant Strains Carried by Cancer Patients at a Large Medical Center
Authors: Boschman Cynthia R. , Bodnar Ulana R. , Tornatore Michelle A. , Obias Arlene A. , Noskin Gary A. , Englund Kristin , Postelnick Michael A. , Suriano Terra , Peterson Lance R. 
Published: October 2018

ABSTRACT

Drug resistance is emerging in many important microbial pathogens, including
Candida albicans
. We performed fungal susceptibility tests with archived isolates obtained from 1984 through 1993 and fresh clinical isolates obtained from 1994 through 1997 by testing their susceptibilities to fluconazole, ketoconazole, and miconazole and compared the results to the rate of fluconazole use. All isolates recovered prior to 1993 were susceptible to fluconazole. Within 3 years of widespread azole use, we detected resistance to all agents in this class. In order to assess the current prevalence of resistant isolates in our hematologic malignancy and transplant patients, we obtained rectal swabs from hospitalized, non-AIDS, immunocompromised patients between June 1995 and January 1996. The swabs were inoculated onto sheep’s blood agar plates containing 10 μg of vancomycin and 20 μg of gentamicin/ml of agar. One hundred one yeasts were recovered from 97 patients and were tested for their susceptibilities to amphotericin B, fluconazole, flucytosine, ketoconazole, and miconazole. The susceptibility pattern was then compared to those for all clinical isolates obtained throughout the medical center. The antifungal drug histories for each patient were also assessed. The yeasts from this surveillance study were at least as susceptible as the overall hospital strains. There did not appear to be a direct linkage between prior receipt of antifungal agent therapy and carriage of a new, drug-resistant isolate. Increased resistance to newer antifungal agents has occurred at our medical center, but it is not focal to any high-risk patient population that we studied. Monitoring of susceptibility to antifungal agents appears to be necessary for optimizing clinical therapeutic decision making.
Survey of Resistance of Herpes Simplex Virus to Acyclovir in Northwest England
Authors: Christophers Jacqueline , Clayton Julie , Craske John , Ward Rosemary , Collins Peter , Trowbridge Martin , Darby Graham 
Published: October 2018

ABSTRACT
Acyclovir (ACV) has been used for more than 15 years in the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) disease. The present survey was undertaken to assess the level of ACV resistance in the population. More than 2,000 HSV isolates from both immunocompetent and immunocompromised patients in northwest England were collected over a 2-year period and tested for sensitivity to ACV. These studies suggested a prevalence of resistance of approximately 0.1 to 0.6% in immunocompetent individuals, with no apparent difference in prevalence between treated and untreated groups. In line with previous studies, the prevalence of resistance in treated immunocompromised individuals was approximately 6%.