Inactivation of penicillin G in milk using hydrogen peroxide.

Milk antibiotic residues have been a public concern in recent years. The Grade A Pasteurized Milk Ordinance mandates that raw Grade A milk will test negative for beta-lactam antibiotic residues before processing. The purpose of this research was to investigate the ability of various levels of peroxide and heat to inactivate penicillin G in raw milk. Whole milk spiked to a mean of 436 +/- 15.1 (standard error of the mean) ppb of potassium penicillin G was treated with hydrogen peroxide at levels of 0.0, 0.09, 0.17, and 0.34%. Samples at each peroxide level (n = 6 per treatment) were treated as follows: 1) incubated at 54.4 degrees C for 3 h, 2) pasteurized at 62.8 degrees C for 30 min, 3) incubated and pasteurized as in treatments 1 and 2, or 4) received no further treatment. A beta-lactam competitive microbial receptor assay was used for quantification of penicillin G. Concentrations of penicillin in selected samples were determined by HPLC for a comparison of test methods. Treatments were evaluated relative to their ability to reduce milk penicillin G levels to below the safe level of 5 ppb. The 0.09% hydrogen peroxide level was ineffective for all treatments. Hydrogen peroxide at 0.17% lowered the mean penicillin G (+/- SEM) from 436 +/- 15.1 to 6 +/- 1.49 ppb using the incubated and pasteurized heat treatment. The 0.34% concentration of hydrogen peroxide was the most effective, inactivating penicillin G to a level well below the safe level of 5 ppb with the pasteurized heat treatment, with or without incubation.

Inhibitory effect of jujuboside A on penicillin sodium induced hyperactivity in rat hippocampal CA1 area in vitro.

AIM: To study the effect of jujuboside A (JuA), one constituent of Chinese herbal medicine Ziziphus jujuba Mill Var spinosa (Bunge) Hu,on the penicillin sodium induced hyperactivity in rat CA1 neurons in vitro. METHODS: Hippocampal slices were obtained from the Sprague-Dawley rat brain and populational signals were measured from CA1 neurons of hippocampal slices using the extracellular recording technique. RESULTS: Penicillin sodium of 500, 1000, and 2000 kU/L were found to excite hippocampal CA1 neurons in a concentration-dependent manner in vitro. This excitatory effect of penicillin sodium could be inhibited by phenobarbital sodium of 0.02 - 0.05 g/L and JuA of 0.05 - 0.10 g/L. CONCLUSION: A high dose of JuA can inhibit the hyperactivity of hippocampal CA1 area induced by penicillin sodium. The inhibition of the amplitude of the first population spike (PS) and the latency of PS are more pronounced than the slope of the field excitatory post-synaptic potential.

In vitro antimicrobial effect against Streptococcus pneumoniae of adding rifampin to penicillin, ceftriaxone, or 1-ofloxacin.

Adding rifampin to penicillin or l-ofloxacin diminished the rate at which these antibiotics killed 21 clinical isolates isolates of Streptococcus pneumoniae in vitro. A less pronounced inhibitory effect was observed when rifampin was added to ceftriaxone. Synergy was not observed for any bacterial isolate. The in vitro demonstration of indifference or antagonism using these antibiotic combinations argues against the empirical addition of rifampin to beta-lactams or fluoroquinolones in treating serious pneumococcal infections.

[Use of vilozen and ketotifen combination for increasing the effectiveness and prevention of complications of antibiotic therapy of streptococcal infections]. / Primenenie kombinatsii vilozena i ketotifena dlia povysheniia éffektivnosti i profilaktiki oslozhnenii antibiotikoterapii streptokokkovykh infektsii.

The clinical efficacy of a vilozen and ketotifen (zaditen) combination in the treatment of streptococcal infections along with the routine therapy was studied. The use of the combination was shown advisable in the complex therapy and prevention of relapses in patients with streptococcal infections. The combined pharmacotherapy promoted better clinical indices, normalization of the immune status and a reduction in the incidence of allergic reactions to antibiotics and a decrease in sensitization to bacterial allergens.

Suppression of penicillin-induced bacteriolysis of staphylococci by some anticoagulants.

Heparinoids and related negatively-charged substances caused suppression of the penicillin-induced bacteriolysis of staphylococci and a higher viability rate. Furthermore, the penicillin-induced release of cell wall material was reduced by these substances. The main reason for this suppression of bacteriolysis was an inhibition of the activity of cell wall autolytic enzymes while the penicillin-specific perturbations of wall morphogenesis were not affected.

Effects of anticonvulsants on K+-induced excitation and on penicillin-induced seizures.

Excitation induced in mice by intracerebral injection of KCl was antagonized by prior i.p. injection of phenytoin, chlordiazepoxide or phenobarbital, but was not significantly affected by muscimol, valproate, ethosuximide or trimethadione. In contrast, seizures induced by intracerebral injection of benzyl penicillin were antagonised by chlordiazepoxide, phenobarbital, valproate, ethosuximide and trimethadione, but not by phenytoin or muscimol. Implications with regard to mechanisms of action of the anticonvulsants and of penicillin are discussed.

Anticonvulsant actions of enflurane on epilepsy models in cats.

The effects of enflurane on three epilepsy models were studied in cats. The models used were seizures in amygdaloid kindled cats and those induced by bicuculline and penicillin. The authors found that not only a subconvulsive (1.5%) but a convulsive (3.5%) dose of enflurane suppressed the seizures in all models. There was no sign of activation by enflurane of the epileptic focal activities in the dose range studied: the penicillin-induced cortical seizure was suppressed completely, and the threshold dose of bicuculline required to induce seizure in normal cats and the threshold current required to induce seizure in amygdaloid-kindled cats were both increased by both the subconvulsive and convulsive dose of enflurane. The pattern of suppression was, however, dissimilar in each model. It was dose dependent in the case of penicillin-induced seizure, while it was biphasic in several aspects in the seizures of bicuculline-induced and amygdaloid kindled models. For the subconvulsive dose the degrees of increase in the thresholds required to induce seizure in bicuculline-induced and amygdaloid-kindled models were both greater than those for the convulsive dose of enflurane. In spite of such a definite suppression of the excitability of focus, the propagation of amygdaloid after-discharge was facilitated by the convulsive dose. The intensity of convulsion induced by suprathreshold dose of bicuculline was depressed in a dose-related manner. The intensity of the convulsion in the amygdaloid-kindled model was also suppressed when it was estimated by visual inspection of behavior and the degree of activation of the brain electrical activities. The authors conclude that there is little, if any, exacerbation by enflurane of preexisting epileptic foci, the only exception possibly being the case of certain myoclonic type epilepsies such as progressive myoclonic epilepsy and photosensitive epilepsy. This anesthetic probably can be used with a considerable degree of safety for epileptic patients.

Furosemide effect on penicillin induced convulsions.

Convulsions were induced in 20 cats by the administration of intravenous penicillin. Furosemide administered together and after penicillin failed to reduce the seizure activity. Penicillin brain concentrations were not reduced by furosemide. Penicillin induced seizures are not affected by furosemide.

Taurine- and penicillin-induced epileptic activity.

The present study has been performed to investigate the effect of i.v. administration of taurine on the electrical activity of the epileptogenic focus induced by penicillin applied to the right sensory motor cortex of adult rats. Taurine (100 mg/kg body weight) was administered 15, 30, 60, and 120 min before the application of penicillin. The EEG was unipolarly recorded by means of electrodes applied to the pia. Taurine caused a decrease of the frequency as well as the spike amplitude of epileptic discharge. The spread of epileptogenic foci to the opposite hemisphere was retarded when compared to that of control animals. The maximal antiepileptic effect of taurine was observed when the amino acid was administered 30-60 min previous to penicillin. It is suggested that high concentrations of taurine in the brain might be necessary to inhibit the epileptic activity.

Hydroxylamine inactivation of cephalosporins: nucleophilic attack on beta-lactam structures.

Cephalosporins are not degraded by hydroxylamine (NH2OH) in neutral and acidic solutions. Their reaction with NH2OH in slightly alkaline solutions leads to microbiological inactivation which seems to be a structure dependent phenomenon. In these experiments the mandelic acid-type compounds appear to be quite stable to the effect of NH2OH, whereas, cefazolin is gradually degraded and the straight chain-containing cephalosporins are variably inactivated. The phenylglycine-type oral cephalosporins were generally sensitive to the alkaline conditions used in these tests and apparently are not inactivated by NH2OH. On the contrary, the phenylglycine-type cephalosporins seem to be somewhat stabilized in the presence of NH2OH.

Response of Escherichia coli to Beta-lactam antibiotics: effect of the concomitant presence of staphylococci exhibiting inducible Beta-lactamase activity.

The response to Beta-lactam antibiotics of mixed cultures of Escherichia coli and Staphylococcus epidermidis was studied in static culture and in an in vitro model which simulates the dynamic conditions in which bacteria are exposed to antibiotics in the treatment of urinary infection. In static cultures, the concomitant presence of staphylococci exhibiting inducible Beta-lactamase activity substantially reduced the efficacy of benzylpenicillin and ampicillin (but not cefuroxime) against E. coli. In the conditions of the bladder model some interference with the activity of Beta-lactam antibiotics by Beta-lactamase producing staphylococci was also demonstrated. Nevertheless, relatively modest doses of ampicillin were still able to suppress growth of susceptible E. coli for periods exceeding the normal interdose interval, even in the presence of enzyme-producing staphylococci.

Prevention of penicillin-induced lysis of Staphylococcus aureus by cellular lipoteichoic acid.

The lysis of Staphylococcus aureus FDA 209P induced by benzylpenicillin was completely inhibited by cellular lipoteichoic acid isolated from an homologous organism. The cells prevented from penicillin-induced lysis were in static state and did not lose viability. The lipoteichoic acid inhibited either extracellular autolysin activity in culture supernatant or autolysis of whole cells in exponential phase of S. aureus. These results indicate that the prevention of penicillin-induced lysis of S. aureus by the lipoteichoic acid was brought about by the inhibition of autolytic activity of the organism.

Polymyxin B-penicillin antagonism in Proteus mirabilis.

Polymyxin B protects Proteus mirabilis from usually lethal penicillin concentrations.

[Deacylating activity of sera as a cause for the ineffectiveness of the treatment of experimental plaque in white mice with benzylpenicillin]. / Deatsiliruiushchaia aktivnost' syvorotok kak prichina neéffektiv-nosti lecheniia éksperimental'noi chumy belykh myshei benzilpenitsillinom

It was shown that serum of albino mice infected with plague microbe cells inactivated benzylpenicillin. Such deacetylating activity reached its peak by the 3rd day and after that decreased reaching by the 5th--7th day the level registered in non-infected animal and being apparently of non-specific character. Ampicillin proved to be 2 times more resistant to the effect of serum acylase as compared to benzylpenicillin. It was supposed that the ability of serum of infected animals to inactivate benzylpenicillin by splitting off phenylace acid was the cause of ineffective treatment of experimental plague of albino mice with comparatively low doses of the drug.

Penicillinase-producing Gonococci in Liverpool.

Gonococci, which had acquired a TEM-type of penicillinase widely distributed among gram-negative bacilli, appeared in February, 1976, and soon accounted for 9% of isolates at a clinic in Liverpool. In 45 patients infected by such gonococci, the frequency of complications did not suggest reduced communicability or invasiveness, and usual forms of treatment with penicillins always failed. Spectinomycin succeeded in 21 (95%) of 22 patients treated, blt tetracyclines succeeded in only 13 (68%) of 19. Appropriate laboratory tests for recognising penicillinase-producing gonococci must be used since such gonococci have already been transferred to other parts of the U.K. Penicillinase-stable cephalosporins were active in vitro and could prove to be the future treatment of choice.