Antibacterial Activity Of Serum Research Articles

The Impact of Graphite Oxide Nanocomposites on the Antibacterial Activity of Serum.

Nanoparticles can interact with the complement system and modulate the inflammatory response. The effect of these interactions on the complement activity strongly depends on physicochemical properties of nanoparticles. The interactions of silver nanoparticles with serum proteins (particularly with the complement system components) have the potential to significantly affect the antibacterial activity of serum, with serious implications for human health. The aim of the study was to assess the influence of graphite oxide (GO) nanocomposites (GO, GO-PcZr(Lys)2-Ag, GO-Ag, GO-PcZr(Lys)2) on the antibacterial activity of normal human serum (NHS), serum activity against bacteria isolated from alveoli treated with nanocomposites, and nanocomposite sensitivity of bacteria exposed to serum in vitro (using normal human serum). Additionally, the in vivo cytotoxic effect of the GO compounds was determined with application of a Galleria mellonella larvae model. GO-PcZr(Lys)2, without IR irradiation enhance the antimicrobial efficacy of the human serum. IR irradiation enhances bactericidal activity of serum in the case of the GO-PcZr(Lys)2-Ag sample. Bacteria exposed to nanocomposites become more sensitive to the action of serum. Bacteria exposed to serum become more sensitive to the GO-Ag sample. None of the tested GO nanocomposites displayed a cytotoxicity towards larvae.

Effects of safflower (Carthamus tinctorius) extract on serum antibacterial activity of rainbow trout (Oncorhynchus mykiss) against Aeromonas hydrophila, Streptococcus iniae and Yersinia ruckeri

In the present study, the effects of safflower ( Carthamus tinctorius) extract on serum antibacterial activity of rainbow trout ( Oncorhynchus mykiss ) against Aeromonas hydrophila , Streptococcus iniae and Yersinia ruckeri was studied. In this regard, 450 fish with average weight of 100±10 g were stocked into fifteen fiberglass tanks. This experiment consisted of 3 treatment groups (received 50, 100 and 200 mg/kg BW safflower extract via IP injection), one positive control group (just received normal saline) and one negative control group (with no injection). Blood samples were taken at the 3 th , 7 th and 10 th days after the injections, and antibacterial activity of serum were determined in vitro using CFU method. The results showed that safflower extract injection had no significant effects on serum anti-bacterial activity against A. hydrophyla and Y. rukeri during 10 days post injection. However, in the fish receiving 100 mg/kg safflower extract, serum bactericidal activity against S. iniae was significantly higher than the other groups. This study demonstrated that safflower extract at the doses of 50-200 mg/kg via IP injection did not cause significant changes in serum antibacterial activity against A. hydrophila and Y. ruckeri , but injection of 100 mg/kg extract led to an increase in the serum antibacterial activity against S. iniae , in rainbow trout.

Antibacterial activity in serum of the 3,5-diamino-piperidine translation inhibitors

Translation inhibitors of the 3,5-diamino-piperidine series act as aminoglycoside mimetics that inhibit bacterial growth. Here we show antibacterial SAR in the presence and absence of serum with a particular focus toward Pseudomonas aeruginosa.

Human serum activity of telithromycin, azithromycin and amoxicillin/clavulanate against common aerobic and anaerobic respiratory pathogens

Telithromycin is a new ketolide antimicrobial with a good in vitro activity against both aerobic and anaerobic respiratory pathogens. In this study, we evaluated the antibacterial activity over time of telithromycin (800 mg), azithromycin (500 mg), and amoxicillin/clavulanate (875/125 mg) in serum following single oral doses of these agents to 10 healthy subjects. Inhibitory and bactericidal titers were determined at 2, 6, 12, and 24 h after each dose and the median titer was used to determine antibacterial activity. Against two azithromycin-resistant strains of Streptococcus pneumoniae, both telithromycin (MIC = 0.25 and 0.5 μg/mL) and amoxicillin/clavulanate exhibited inhibitory and cidal activity for at least 6 h. All three antibiotics provided prolonged (≥12 h) inhibitory activity against strains of Hemophilus influenzae (telithromycin MIC = 4.0 μg/ml). Both telithromycin and amoxicillin/clavulanate exhibited rapid and prolonged inhibitory activity (≥12 h) against each of the anaerobes studied ( Finegoldia [Peptostreptococcus] magna Peptostreptococcus micros, Prevotella bivia, and Prevotella melaninogenica). Moreover, both agents provided bactericidal activity against both Prevotella species. In this ex vivo pharmacodynamic study, we found that telithromycin provided rapid and prolonged antibacterial activity in serum against macrolide-resistant strains of S. pneumoniae, beta-lactamase-positive and -negative strains of H. influenzae, and common respiratory anaerobic pathogens. These findings suggest that telithromycin could have clinical utility in the treatment of community-acquired mixed aerobic–anaerobic respiratory tract infections, including chronic sinusitis and aspiration pneumonia.

Sustained availability of trimethoprim in drinking water to achieve higher plasma sulphonamide–trimethoprim antibacterial activity in broilers

1. In order to make trimethoprim (TMP) available to broilers throughout the day, a sustained release formulation (SRF) of the drug in the form of granules was added to the water tank that supplies drinking water. 2. Broilers were initially dosed with sulphachloropiridazine–TMP (SCP–TMP 5:1) and then further medicated throughout the day, achieving in the end a dose of 30 mg/kg each of SCP and TMP (group A). Group B received a preparation with the same dose of SCP and TMP (1:1) as group A, but administered as a single dose without the SRF of TMP. Group C received the customary SCP–TMP 5:1 preparation (30 and 6 mg/kg, respectively). Water tanks were completely consumed in 3 to 4 h. 3. Broilers were bled at different times and concentration of antibacterial activity in serum determined by correlating the composite antibacterial activity of SCP and TMP with actual concentrations of these drugs by means of a microbiological agar diffusion assay. 4. Time vs serum concentrations of activity were higher in group B; the increments in the maximum serum concentration for group B over groups A and C being 39 and 67%, respectively. 5. However, the sustained concentration of activity over time, measured as the area under the curve, was highest in group A. Group B had higher values for area under the curve than group C. 6. An additional dose of TMP to achieve 30 mg/kg of both SCP and TMP improves the serum concentration of this combination over the customary 5:1 proportion. The best values for sustaining antibacterial activity were obtained using a 1:1 ratio as in group A. The use of a SRF as in group A may translate into better clinical results.

Inhibitors of lipopolysaccharide biosynthesis impair the virulence potential of Escherichia coli.

Inhibition of 3-deoxy-manno-octulosonate cytidylytransferase (CMP-KDO transferase; EC 2.7.7.38) by 8-amino-2,6-anhydro-3,8-dideoxy-D-glycero-D-talo-octonic acid (NH2dKDO) halts the growth of Gram-negative bacteria by depriving the cells of the 3-deoxy-D-manno-2-octulosonate required for the biosynthesis of the core region of the lipopolysaccharide components of the outer membrane. Low levels of this inhibitor increase the vulnerability of Escherichia coli to hydrophobic antibiotics, detergents, the complement-mediated antibacterial activity of serum, phagocytosis, and enhance the rate at which bacteria are cleared from the mouse bloodstream.

Influence of protein binding on therapeutic efficacy of cefoperazone.

The effect of protein binding of cefoperazone (89.3% bound to rabbit serum) on antibacterial activity in serum was tested in a model that simulated a closed-space infection in a neutropenic host. Four gram-negative bacilli were tested in the model with cefoperazone doses of 20 and 200 mg/kg administered intramuscularly every 6 h for 16 doses. Cefoperazone efficacy was measured at 92 h by determining the log10 decrease in bacterial count from that of the control for five paired studies with three isolates. A significantly better response was demonstrated when the free (non-protein-bound) drug concentration exceeded the MICs and MBCs for the infecting microorganisms at the infection site at all times (P less than 0.005). This supports the concept that free (unbound) drug is the active component in treating bacterial infections.

Cefotaxime: pharmacokinetics and in vitro antibacterial activity of serum and urine in normal human volunteers.

The pharmacokinetic and antibacterial properties of cefotaxime were determined in normal adult volunteers. Single doses of 250, 500, 1,000 and 2,000 mg were evaluated following 5- and 20-min intravenous (i.v.) infusions and intramuscular (i.m.) administration. Cefotaxime was well tolerated and mean peak serum levels exceeded the minimum inhibition concentration (MIC) values for a wide spectrum of potential bacterial pathogens. Approximately 48% of the i.v. doses was excreted renally; average volume of distribution was 30% of body weight and the t 1/2 was about 1 h. Cefotaxime was rapidly absorbed following i.m. injection with maximum serum concentrations occurring at approximately 0.6 h. Serum and urine antibacterial activity reflected the concentration of cefotaxime and MIC of the bacterial pathogens tested.

Treatment of Staphylococcal Endocarditis-Reply

Our intent in writing the LETTER TO THE EDITOR was to criticize Bryant and Alford's extrapolation from one patient with<i>S aureus</i>endocarditis who clearly relapsed after cefazolin therapy and one who was a very questionable failure to a general prohibition about use of this agent in<i>S aureus</i>endocarditis. We also questioned the validity of their second case and asked for studies of antibacterial activity in serum (usually considered standard procedure in managing endocarditis) to better evaluate their cases. These are not forthcoming in their answer to our letter. We also pointed out that<i>S aureus</i>endocarditis is a difficult disease to treat and that failures have been reported with every antistaphylococcal agent that has been evaluated. We certainly did not question the need to report both favorable and unfavorable results but only their interpretations. In the preceding letter, Bryant and Alford point out that there is

Antibacterial activity in serum and urine as a therapeutic guide in bacterial infections.

The peak and trough levels of bacteriostatic and bactericidal activity of the serum and the urine of 317 patients with cancer and a bacteriologically proven infection were measured, using the patient's microorganism and the serum or urine containing the given antibiotics. When the peak titer of bacteriostatic activity in serum was > 1:8, the infection was cured in > 80% of cases. The response to therapy of patients with urinary tract infections correlated best with the inhibitory level found in the urine; clinical cure was observed in at least 90% of the patients who had a titer of bacteriostatic activity in urine > 1:4. The antibacterial activity of serum was influenced by the in vitro sensitivity of the offending microorganism, and by the composition of the antimicrobial regimen; these two factors were shown to be related to the clinical outcome. It is suggested that the determination of the antimicrobial activity of the serum, early in the course of treated infection, might allow some adjustment of antibiotic therapy. Several authors have attempted to correlate the in vitro sensitivity tests of bacteria to antibiotics and concentrations of these drugs in the serum with clinical results [1, 2]. Organisms have been considered sensitive if they can be inhibited by levels of antibiotics that are easily attained in the bloodstream after administration of the usual doses. As a result of these studies, it has been stated that therapeutic blood levels should be maintained at two to five times the in vitro MIC. One

Evaluation of methods for determining antibacterial activity of serum and urine after colistimethate injection.

The purpose of this study was to evaluate methods for determining antibacterial activity in serum and urine following intramuscular administration of colistimethate sodium to man. The levels of actual antibacterial activity were determined by a serial dilution technique with the use of 30 minutes of incubation, and the results were compared with levels determined by an agar diffusion method and a serial dilution technique with 18 hours of incubation. The results indicate that colistimethate sodium itself has little antibacterial activity but that activation occurs rapidly in vivo. Antibacterial activity in serum was sustained for up to 12 hours after injection of colistimethate sodium. Levels derived with serial dilution methods with 18 hour incubation periods were falsely elevated, and levels obtained from agar diffusion techniques were falsely low. The inaccuracy of the agar diffusion results was, at least in part, related to a decrease in diffusibility of colistimethate sodium that occurs as the material is activated.

Serum antibacterial activity after oral suspensions and capsules of triacetyloleandomycin and erythromycin estolate.

Comparison of serum antibacterial activity against a beta-hemolytic streptococcus and a penicillin-resistant staphylococcus was made in a cross-over study in volunteers after ingestion of oral suspensions and capsules of triacetyloleandomycin and erythromycin estolate. Oral suspensions yielded earlier peak titers, but ultimate peak titers and duration of activity were similar to those observed after ingestion of capsules. Antibacterial activity of serum against both organisms was consistently greater with both erythromycin estolate preparations than with the triacetyloleandomycin preparations. These in vitro data were comparable to observations made previously in monkeys infected with the same organisms, although comparative clinical efficacy in monkeys did not reflect these implied therapeutic differences.

Serum Antibacterial Activity After Oral Suspensions and Capsules of Triacetyloleandomycin and Erythromycin Estolate

Comparison of serum antibacterial activity against a beta-hemolytic streptococcus and a penicillin-resistant staphylococcus was made in a cross-over study in volunteers after ingestion of oral suspensions and capsules of triacetyloleandomycin and erythromycin estolate. Oral suspensions yielded earlier peak titers, but ultimate peak titers and duration of activity were similar to those observed after ingestion of capsules. Antibacterial activity of serum against both organisms was consistently greater with both erythromycin estolate preparations than with the triacetyloleandomycin preparations. These in vitro data were comparable to observations made previously in monkeys infected with the same organisms, although comparative clinical efficacy in monkeys did not reflect these implied therapeutic differences.

Antibacterial activity of serum after oral doses of tetracycline, demethylchlortetracycline, and 6-methyleneoxytetracycline.

Studies in man indicate that tetracycline and 6‐methyleneoxytetracycline are absorbed more rapidly after oral administration than demethylchlortetracycline but that the antibacterial activity of the last is longer lasting. After 500 mg. of tetracycline and 300 mg. of the others, the amount in the blood stream is proportional to the dose; but when compared in terms of activity against Bacillus cereus, the effects of tetracycline are distinctly inferior to those of the other two, while the average antistreptococcal activity after demethylchlortetracycline is about the same as that after tetracycline and slightly greater than that after 6‐methyleneoxytetracycline. Plasma protein binding is about the same for demethylchlortetracycline and 6‐methyleneoxytetracycline but much less for tetracycline.

Sodium nitrofurantoin administered intravenously. A limited study to define its clinical indication.

NITROFURANTOIN is widely given by mouth for the treatment of bacterial infections of the urinary tract. After ingestion the drug is readily absorbed and excreted largely in the urine. The resulting high drug levels in urine are inhibitory or bactericidal for a majority of bacteria commonly found in urinary-tract infections.1 With daily doses of 600 mg. urinary concentrations of nitrofurantoin may reach 240 microgm. per milliliter determined as antibacterial activity against test micro-organisms.2 However, there is no antibacterial activity in serum or plasma, perhaps because the drug is firmly bound to blood protein.2 , 3 In spite of a few reports to . . .

Assay of antibacterial activity in serum. A useful guide for complex antimicrobial therapy.

Is the patient receiving the proper drugs? Is he being given sufficient amounts to eradicate the infection? Every physician asks himself these questions when faced with the antimicrobial treatment of a serious infection. In many well-defined bacterial infections, clinical experience alone can supply an adequate answer. However, with the changing behavior of microbes and the changing natural history of infectious processes, additional guidance is often welcome and sometimes essential for optimal therapy. It is the purpose of this communication to draw attention to a helpful laboratory test, the assay of antibacterial activity in serum of patients receiving antimicrobial drugs. The test is simple, inexpensive, can be learned by any laboratory in a short time and—if properly interpreted—can aid the physician in the management of severe infections. To be effective in systemic infections, orally or parenterally administered drugs must be absorbed and distributed, in active form, to tissues harboring microorganism. Blood