In vivo protection of penicillin-susceptible Bacteroides melaninogenicus from penicillin by facultative bacteria which produce beta-lactamase

1984 ◽  
Vol 30 (1) ◽  
pp. 98-104 ◽  
Author(s):  
Itzhak Brook ◽  
Garry Pazzaglia ◽  
James C. Coolbaugh ◽  
Richard I. Walker
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Clavulanic Acid ◽  
Single Agent ◽  
Mixed Infections ◽  
Beta Lactamase ◽  
Penicillin Therapy ◽  
And Staphylococcus Aureus ◽  
Antimicrobial Combinations

We investigated the possibility that beta-lactamase producing strains of Klebsiella pneumoniae and Staphylococcus aureus can protect organisms of the Bacteroides melaninogenicus group from penicillin. A mixed infection was induced in mice in the form of a subcutaneous abscess involving a penicillin-susceptible encapsulated B. melaninogenicus, and a beta-lactamase producing strain of either K. pneumoniae or S. aureus. The infected animals were treated for 7 days with single or combined antimicrobial therapy. The single agents used were penicillin, clavulanic acid, metronidazole, and gentamicin. The antimicrobial combinations were penicillin and clavulanic acid, penicillin and gentamicin, and metronidazole and gentamicin. Administration of a single agent was effective in treating abscesses caused by susceptible organisms. The only effective therapy for mixed infections was by combination therapy of penicillin and clavulanic acid or metronidazole and gentamicin. This study supports the hypothesis that beta-lactamase producing facultative bacteria may shield their anaerobic counterparts from penicillin therapy, thereby contributing to the persistence of the infection.

Cefotaxime and amikacin: results of in vitro and in vivo studies against Gram-negative bacteria and Staphylococcus aureus

1980 ◽  
Vol 6 (suppl A) ◽  
pp. 55-61 ◽  
Author(s):  
J. Klastersky ◽  
H. Gaya ◽  
S. H. Zinner ◽  
C. Bernard ◽  
J-C. Ryff ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
In Vivo Studies ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
And Staphylococcus Aureus

scholarly journals The Synergistic Effect of Nicotine and Staphylococcus aureus on Peri-Implant Infections

2021 ◽  
Vol 9 ◽  
Author(s):  
Yao Hu ◽  
Wen Zhou ◽  
Chengguang Zhu ◽  
Yujie Zhou ◽  
Qiang Guo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Synergistic Effects ◽  
Protein A ◽  
Treated Group ◽  
Combination Group ◽  
Staphylococcal Protein A ◽  
Receptor Activator ◽  
And Staphylococcus Aureus

Smoking is considered a key risk factor for implant survival; however, how it interacts with the pathogens in peri-implant infections is not clear. Here, we identified that nicotine, the key component of cigarette smoking, can interact with Staphylococcus aureus and synergistically induce peri-implant infections in a rat osteolysis model. The nicotine–S. aureus combination group increased the gross bone pathology, osteolysis, periosteal reactions, and bone resorption compared to the nicotine or S. aureus single treated group (p < 0.05). Nicotine did not promote the proliferation of S. aureus both in vitro and in vivo, but it can significantly upregulate the expression of staphylococcal protein A (SpA), a key virulence factor of S. aureus. The nicotine–S. aureus combination also synergistically activated the expression of RANKL (receptor activator of nuclear factor-kappa B ligand, p < 0.05) to promote the development of peri-implant infections. The synergistic effects between nicotine and S. aureus infection can be a new target to reduce the peri-implant infections.

Zidovudine and Didanosine Combination Therapy in Children With Human Immunodeficiency Virus Infection

PEDIATRICS ◽  
1994 ◽  
Vol 93 (2) ◽  
pp. 316-322 ◽  
Author(s):  
Robert N. Husson ◽  
Brigitta U. Mueller ◽  
Maureen Farley ◽  
Linda L. Lewis ◽  
Frank M. Balis ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Combination Therapy ◽  
Antiviral Activity ◽  
Hiv Infection ◽  
Geometric Mean ◽  
Single Agent ◽  
Nucleoside Analogues ◽  
Hematologic Toxicity ◽  
Immunodeficiency Virus

Objective. Zidovudine and didanosine are both beneficial for the treatment of human immunodeficiency virus (HIV) infection in children. Because disease progression and toxicity often limit their long-term use as single agents, new approaches to using nucleoside analogues are necessary to improve current antiretroviral therapy. Design. We conducted a phase I-II study to evaluate the tolerance, pharmacokinetics, and antiviral activity of the combination of zidovudine and didanosine in children with HIV infection. Sixty-eight children who were either previously untreated or who had manifested hematologic toxicity on full-dose zidovudine were enrolled. Eight dose combinations were studied in the previously untreated children, with doses of zidovudine ranging from 90 to 180 mg/m2 every 6 hours and doses of didanosine ranging from 90 to 180 mg/m2 every 12 hours. Results. Fifty-four previously untreated HIV-infected children were enrolled in this part of the study, of whom 49 remained in the study for a minimum of 24 weeks. For children with previous zidovudine-related hematologic toxicity, three dose levels with zidovudine at 60 mg/m2 every 6 hours orally and didanosine ranging from 90 to 180 mg/m2 every 12 hours orally were used. A total of 14 children were enrolled in this part of the study, and 12 remained on therapy for at least 24 weeks. No evidence of new or enhanced toxicity was observed in either group. After 24 weeks, the median CD4 cell count for all patients increased from 331 to 556 cells/mm3 (P = .01). For the previously untreated group, the median increase in CD4 counts was from 386 to 726 cells/mm3 (P = .003). The median p24 antigen concentration (in those with a detectable level at baseline) decreased from 95 to <31 pg/mL (P < .001). The geometric mean titer of HIV in plasma decreased from 83.1 to 2.7 tissue culture infectious doses/mL (P = .001). Conclusions. The combination of zidovudine and didanosine was well-tolerated at doses as high as those used in single agent therapy. Potent in vivo antiviral activity was observed. Combination therapy with nucleoside analogues may be an important approach to optimizing the use of these agents in the treatment of HIV infection.

Activity of a novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 to enhance antitumor activities of gemcitabine and EMAP II in pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 255-255
Author(s):  
N. Awasthi ◽  
P. L. Yen ◽  
M. A. Schwarz ◽  
R. Schwarz
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Antitumor Activity ◽  
Combination Therapy ◽  
Mtor Inhibitor ◽  
Single Agent ◽  
Percent Inhibition ◽  
Animal Survival

255 Background: Gemcitabine (Gem, G) has limited benefits as single agent or in combination for pancreatic ductal adenocarcinomas (PDACs). The phosphatidylinositol-3-kinase (PI3K)/AKT and mammalian target of rapamycin (mTOR) signaling pathways are frequently dysregulated in diverse human cancers including PDAC. NVP-BEZ235 (BEZ, B) is a novel dual PI3K/mTOR inhibitor that has been shown to have antitumor activity in multiple tumor types. Endothelial monocyte activating polypeptide II (EMAP, E) is an antiendothelial and antiangiogenic agent that enhances Gem and docetaxel activity in PDAC. We tested the combination benefits of BEZ and Gem in addition to EMAP in experimental PDAC. Methods: In vitro cell proliferation and protein expression were analyzed by WST-1 assay and Western blotting. In vivo animal survival experiments were performed in NOD-SCID PDAC xenografts. Results: Cultured cells of PDAC (AsPC-1), endothelial (HUVECs), and fibroblast origin (WI-38) all expressed AKT and mTOR protein. BEZ inhibited in vitro cell proliferation of AsPC-1 and HUVECs cells, with some additive effects in combination with Gem or EMAP, after 72 hours of incubation. In AsPC-1, treatment of BEZ (100 nM), Gem (100 nM) and EMAP (1 μM) caused 34, -7, -16, 62, 51, 3, and 59 percent inhibition in proliferation in the B, G, E, B+G, B+E, G+E and B+G+E groups. In HUVECs, percent inhibition in proliferation was 35, 33, 15, 55, 35, 31 and 53 in the B, G, E, B+G, B+E, G+E and B+G+E groups, respectively. Compared to controls (median survival: 16 days), an animal survival increase after BEZ and EMAP therapy alone (both 21 days) and Gem therapy alone (28 d) was observed. Further increases in survival occurred in combination therapy groups B+G (30 d, p=0.007), B+E (27 d, p=0.02), G+E (31 d, p=0.001) and B+G+E (33 d, p=0.004). Conclusions: Bez has experimental PDAC antitumor activity in vitro and in vivo that is further enhanced by combination of Gem and EMAP. These findings demonstrate advantages of combination therapy strategies targeting multiple pathways in pancreatic cancer treatment. No significant financial relationships to disclose.

Reliability of conventional ear swabs in tubotympanic CSOM

1990 ◽  
Vol 104 (6) ◽  
pp. 460-462 ◽  
Author(s):  
K. G. S. Raju ◽  
P. Unnykrishnan ◽  
R. C. Nayar ◽  
S. Dutt ◽  
R. Macaden
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistance ◽  
Otitis Media ◽  
Middle Ear ◽  
Single Agent ◽  
Chronic Suppurative Otitis Media ◽  
Mixed Infections ◽  
External Ear ◽  
Gram Positive ◽  
Suppurative Otitis Media

AbstractConventional external ear swab cultures were compared with cultures obtained from the middle ear, in 25 cases of tubotympanic type (‘safe’), chronic suppurative otitis media. These cultures were identical in 22 of the 25 cases.Anaerobic organisms were isolated in only one case. Mixed infections of both gram-positive and gramnegative organisms were seen in nine cases (36 per cent).Staphylococcus aureus was the commonest single agent isolated (16 cases). Multidrug resistance was seen in 12 of these isolates.

scholarly journals THE IN VIVO INTERACTION BETWEEN STAPHYLOCOCCUS BACTERIOPHAGE AND STAPHYLOCOCCUS AUREUS

1963 ◽  
Vol 118 (1) ◽  
pp. 13-26 ◽  
Author(s):  
P. F. Bartell ◽  
I. S. Thind ◽  
T. Orr ◽  
W. S. Blakemore
Keyword(s):  
Staphylococcus Aureus ◽  
Protective Effect ◽  
Host Defense ◽  
Defense Mechanisms ◽  
Protective Role ◽  
Protection Time ◽  
Determining Factors ◽  
Specific Bacteriophage ◽  
And Staphylococcus Aureus

Staphylococcus bacteriophage 81 is capable of in vivo interaction with Staphylococcus aureus, Type 80/81. This is immediately made evident by increased levels of bacteriophage and concomitant survival of 81 per cent infected mice. The reaction is dependent upon the use of active, type-specific bacteriophage. The maximal protective effect is observed at a bacteriophage to bacteria ratio of 1:2 and decreased quantities of bacteriophage result in decreased protection. Time and sequence of administration are also determining factors. It is evident that bacteriophage administered intravenously is capable of interaction with the infecting bacterial cell at the site of infection. In vivo produced bacteriophage is apparently eliminated or otherwise rendered nondetectable fairly rapidly, occurring within a period of 5 to 10 days. However, it appears that host defense mechanisms are stimulated in the process and actively play a protective role against subsequent challenge inocula administered up to 3 weeks later.

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