Effects of intravenous administration of polymyxin B in neonatal foals with experimental endotoxemia

Polymyxins are the last line potential antibiotics against multi-drug resistant gram-negative bacteria and consist of two sister antibiotics: Polymyxin B and colistin (polymyxin E). Intravenous use of polymyxins was started from a long ago in the treatment of serious gram-negative infections and once their uses were restricted due to potential adverse drug reactions, such as nephrotoxicity and neurotoxicity. Lack of in vivo clinical studies on polymyxins mostly, in human body makes the pharmacokinetics and pharmacodynamics of polymyxin B and colistin unclear in many aspects, such as the distribution of polymyxins in different compartments of lung. The nebulization of polymyxins is practicing very limitedly and lack of clinical evidence has not justified this administration technique yet properly to date. The main objective of this review study was to evaluate the pharmacokinetic and pharmacodynamic properties of intravenous and nebulized polymyxins and the related therapeutic potentialities. Aerosolized polymyxins directly administered to the respiratory tract was found with higher drug concentration in different subcompartments of lungs than the intravenous administration and sustainably meets the minimum inhibitory concentration locally with superior bactericidal properties in respiratory tract infections. In contrast, intravenous administration of polymyxins shows similar anti-infective superiority in other organs, such as blood, urinary tract etc. So, during this alarming situation of rapidly emerging multidrug-resistant organisms in human communities, therapeutic administration techniques of last resort polymyxins should be clinically evidence-based for achieving optimum therapeutic outcomes with minimum chance of adverse drug reactions.

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Respiratory Arrest Associated With Intravenous Administration of Polymyxin B Sulfate

JAMA ◽

10.1001/jama.1966.03100150127040 ◽

1966 ◽

Vol 196 (2) ◽

pp. 181 ◽

Cited By ~ 15

Author(s):

Guenther Pohlmann

Keyword(s):

Intravenous Administration ◽

Polymyxin B ◽

Respiratory Arrest

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Effects of polymyxin B on clinical signs, serum TNF-α, haptoglobin and plasma lactate concentrations in experimental endotoxaemia in sheep

Journal of Veterinary Research ◽

10.2478/jvetres-2018-0011 ◽

2018 ◽

Vol 62 (1) ◽

pp. 79-85 ◽

Cited By ~ 2

Author(s):

Ali Hajimohammadi ◽

Khalil Badiei ◽

Parviz Kheibari ◽

Meherdad Pourjafar ◽

Aliasghar Chalmeh

Keyword(s):

Intravenous Administration ◽

Clinical Signs ◽

Polymyxin B ◽

Positive Control ◽

Positive Control Group ◽

Control Group ◽

Plasma Lactate ◽

Serum Haptoglobin ◽

Tnf Α ◽

Significant Difference

AbstractIntroductionThe experiment evaluated the effects of intravenous administration of polymyxin B on experimental endotoxaemia in sheep.Material and MethodsTwenty clinically healthy fat-tailed sheep were randomly divided into: a group treated with 6,000 U/kg of polymyxin B, a group at 12,000 U/kg, and positive and negative controls. Endotoxaemia was induced by intravenous administration of lipopolysaccharide (LPS) fromE.coliserotype O55:B5 at 0.5 μg/kg. polymyxin was infused intravenously along with 2.5 L of isotonic intravenous fluids at 20 mL/kg/h. The positive control group received LPS and 2.5 L of isotonic fluids, the negatives receiving just 2.5 L of isotonic fluids. Clinical signs were evaluated before and at 1.5, 3, 4.5, 6, 24, and 48 h after LPS administration. Blood was also sampled at the denoted hours and serum haptoglobin, tumour necrosis factor-α (TNF-α), and plasma lactate concentrations were assayed.ResultsThe serum concentration of TNF-α in the positive control group increased significantly up to 48 h after LPS administration. The concentration of TNF-α was significantly different from those of the polymyxin B and positive control groups from 3 to 48 h; also, the concentrations of haptoglobin at different times in the polymyxin groups were lower than those of the positive control group and were significant at hours 3 to 48 (P < 0.05). Following the LPS administration, haptoglobin and TNF-α concentrations changed without significant difference between the two polymyxin B groups.ConclusionPolymyxin B (6,000 U/kg) restrained blood lactate concentrations. Furthermore, it significantly improved the clinical signs in endotoxaemic animals, including rectal temperature and heart and respiratory rates. Polymyxin B may be an antiendotoxic in fat-tailed sheep.

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Studies on the Fungal Pathogen of Dutch Elm Disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100098502 ◽

1981 ◽

Vol 39 ◽

pp. 400-401

Author(s):

H.M. Mazzone ◽

G. Wray ◽

R. Zerillo

Keyword(s):

Fungal Pathogen ◽

Fungal Growth ◽

Polymyxin B ◽

The United States ◽

Dutch Elm Disease ◽

Effective Control ◽

Sabouraud Agar ◽

Total Inhibition ◽

Zones Of Inhibition ◽

Control Plate

The fungal pathogen of the Dutch elm disease (DED), Ceratocystis ulmi (Buisman) C. Moreau, has eluded effective control since its introduction in the United States more than sixty years ago. Our studies on DED include establishing biological control agents against C. ulmi. In this report we describe the inhibitory action of the antibiotic polymyxin B on the causal agent of DED.In screening a number of antibiotics against C. ulmi, we observed that filter paper discs containing 300 units (U) of polymyxin B (Difco Laboratories) per disc, produced zones of inhibition to the fungus grown on potato dextrose agar or Sabouraud agar plates (100mm x 15mm), Fig. 1a. Total inhibition of fungal growth on a plate occurred when agar overlays containing fungus and antibiotic (polymyxin B sulfate, ICN Pharmaceuticals, Inc.) were poured on the underlying agar growth medium. The agar overlays consisted of the following: 4.5 ml of 0.7% agar, 0.5 ml of fungus (control plate); 4.0 ml of 0.7% agar, 0.5 ml of fungus, 0.5 ml of polymyxin B sulfate (77,700 U). Fig. 1, b and c, compares a control plate and polymyxin plate after seven days.

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Intravenous administration of furosemide in heart failure

JAMA ◽

10.1001/jama.200.10.824 ◽

1967 ◽

Vol 200 (10) ◽

pp. 824-829 ◽

Cited By ~ 4

Author(s):

M. Davidov

Keyword(s):

Heart Failure ◽

Intravenous Administration

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Scintigraphic Detection of Experimental Myocardial Infarction with 99mTc-2,3-Dimercaptosuccinic Acid

Nuklearmedizin ◽

10.1055/s-0038-1624263 ◽

1984 ◽

Vol 23 (06) ◽

pp. 317-319

Author(s):

J. Novák ◽

Y. Mazurová ◽

J. Kubíček ◽

J. Yižd’a ◽

P. Kafka ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Intravenous Administration ◽

Experimental Myocardial Infarction ◽

Myocardial Infarctions ◽

Clinical Use ◽

Scintigraphic Imaging ◽

Tissue Samples ◽

Scintigraphic Finding

SummaryAcute myocardial infarctions were produced by ligature of the left frontal descending coronary artery in 9 dogs. The possibility of scintigraphic imaging with 99mTc-DMSA 4 hrs after intravenous administration was studied. The infarctions were 4, 24 and 48 hrs old. The in vivo scan was positive in only one dog with a 4-hr old infarction. The in vivo scans were confirmed by the analysis of the radioactivity in tissue samples. The accumulation of the radiopharmaceutical increased slightly in 48-hr old lesions; however, this increase was not sufficient for a positive scintigraphic finding. Thus, we do not recommend 99mTc-DMSA for clinical use in acute lesions.

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Prevalence and Induction of Circulating Antibodies against Recombinant Staphylokinase

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642396 ◽

1994 ◽

Vol 71 (01) ◽

pp. 129-133 ◽

Cited By ~ 33

Author(s):

P J Declerck ◽

S Vanderschueren ◽

J Billiet ◽

H Moreau ◽

D Collen

Keyword(s):

Intravenous Administration ◽

Human Subjects ◽

Microtiter Plates ◽

Staphylococcus Aureus Bacteremia ◽

Alternative Agent ◽

Antibody Titers ◽

Potential Alternative ◽

Circulating Antibodies ◽

Low Levels ◽

Antibody Levels

SummaryStreptokinase (SK) is a routinely used thrombolytic agent but it is immunogenic and allergenic; staphylokinase (STA) is a potential alternative agent which is under early clinical evaluation. The comparative prevalence of antibodies against recombinant STA (STAR) and against SK was studied in healthy subjects and their induction with intravenous administration in small groups of patients.Enzyme-linked immunosorbent assays, using microtiter plates coated with STAR or SK and calibration with affinospecific human antibodies, revealed 2.1 to 65 μg/ml (median 11 μg/ml) anti-STAR antibodies and 0.9 to 370 μg/ml (median 18 μg/ml) anti-SK antibodies (p <0.001 vs anti-STAR antibodies) in plasma from 100 blood donors, with corresponding values of 0.6 to 100 μg/ml (median 7.1 μg/ml) and 0.4 to 120 μg/ml (median 7.3 μg/ml), respectively, in 104 patients with angina pectoris. Three out of 17 patients with Staphylococcus aureus bacteremia had significantly increased anti-STAR antibody levels (150, 75 and 75 μg/ml), and STAR neutralizing activities (2.2, 3.6 and 4.1 μg STAR neutralized per ml plasma, respectively). In 6 patients with acute myocardial infarction, given 10 mg STAR intravenously over 30 min, median anti-STAR antibody levels were 3.5 μg/ml at baseline, 2.9 μg/ml at 6 to 8 days and 1.2 μg/ml at 2 to 9 weeks, with median corresponding titers of STAR neutralizing activity at 2 to 9 weeks of 42 μg/ml plasma. Conversely, in 5 patients treated with 1,500,000 units SK over 60 min, median anti-SK antibodies increased from 2.9 μg/ml at baseline to 360 μg/ml at 5 to 10 days, with corresponding median SK neutralizing activities of 13 μg/ml. Antibodies against STAR did not cross-react with SK and vice versa.Plasma from human subjects contains low levels of circulating antibodies against recombinant staphylokinase, and intravenous administration of this compound boosts antibody titers. These antibodies do however not cross-react with streptokinase, whereby the use of these two immunogenic thrombolytic agents would not be mutually exclusive.

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Vampire Bat Salivary Plasminogen Activator Evokes Minimal Bleeding Relative to Tissue-Type Plasminogen Activator as Assessed by a Rabbit Cuticle Bleeding Time Model

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653800 ◽

1995 ◽

Vol 73 (03) ◽

pp. 478-483 ◽

Cited By ~ 7

Author(s):

Michael J Mellott ◽

Denise R Ramjit ◽

Inez I Stabilito ◽

Timothy R Hare ◽

Edith T Senderak ◽

...

Keyword(s):

Factor Viii ◽

Plasminogen Activator ◽

Intravenous Administration ◽

Bleeding Time ◽

Bleeding Risk ◽

Tissue Type ◽

Tissue Type Plasminogen Activator ◽

Type Plasminogen Activator ◽

Plasma Factor ◽

Vampire Bat

SummaryCuticle bleeding time (CBT) measurements in anesthetized rabbits were performed to assess the potential bleeding risks which may accompany the administration of tissue-type plasminogen activator (tPA) or vampire bat salivary plasminogen activator (BatPA). The dose of BatPA or tPA used in this study, 42 nmol/kg, was previously shown to be efficacious using a rabbit femoral artery thrombosis model (Gardell et al, Circulation 84:244, 1991). CBT was determined by severing the apex of the nail cuticle and monitoring the time to cessation of blood flow. CBT was minimally elevated (1.6-fold, p<NS) following bolus intravenous administration of BatPA; in contrast, bolus intravenous administration of tPA dramatically elevated CBT (6.2-fold, p<0.05). Rabbits treated with tPA, but not BatPA, displayed profound activation of systemic plasminogen and consequent degradation of Factor VIII and fibrinogen. Elevations in CBT after the administration of tPA were reversed by the replenishment of plasma Factor VIII activity to 40% of control, but were unaffected by complete replenishment of plasma fibrinogen. The results of this study suggest that the administration of BatPA, at a dose that promotes thrombolysis, may evoke a minimal bleeding risk, relative to an equi-efficacious dose of tPA. In addition, the tPA-provoked proteolytic consumption of Factor VIII may be a key contributor to the heightened bleeding risk.

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Intrathoracic Platelet Accumulation in the Guinea-Pig Induced by Intravenous Administration of Arachidonic Acid - Effect of Cyclooxygenase and Thromboxane Synthetase Inhibitors

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661674 ◽

1986 ◽

Vol 56 (03) ◽

pp. 311-317 ◽

Cited By ~ 1

Author(s):

P A Barrett ◽

K D Butler ◽

R A Shand ◽

R B Wallis

Keyword(s):

Arachidonic Acid ◽

Blood Volume ◽

Intravenous Administration ◽

Guinea Pigs ◽

Human Albumin ◽

Thromboxane Synthetase ◽

Acid Effect ◽

Rapid Accumulation ◽

Platelet Accumulation ◽

High Doses

SummaryIntravenous administration of arachidonic acid to guinea-pigs caused a dose-related, rapid accumulation of 51Cr-labelled platelets in the thorax. Inhibitors of cyclooxygenase inhibited the platelet accumulation, induced by arachidonic acid (30 mg/kg), at doses which did not alter the thoracic blood volume (as measured by 131I-labelled human albumin). Thromboxane synthetase inhibitors had different effects on platelet accumulation depending on the dose. CGS 12970 (3 mg/kg) and N(1-carboxyheptyl) imidazole (100 mg/kg) reduced platelet accumulation. High doses of CGS 12970 and CGS 13080 caused an apparent enhancement of platelet accumulation which was associated with pooling of blood in the thorax, as measured by either 131I-labelled human albumin or 51Cr-labelled erythrocytes. This increase in thoracic blood volume was abolished if the guinea-pigs were also pretreated with diclofenac (1 mg/kg) in addition to the thromboxane synthetase inhibitor. Increases in thoracic blood volume were also obtained following infusions of PGI2 but not PGD2 or PGE2.

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