Elimination of oxacillin, its toxicity and antibacterial activity by using ionizing radiation.

The chemical changes caused by electron beam and γ irradiations and the biochemical characteristics of degradation products of a frequently used antibiotic oxacillin were investigated and compared with those of cloxacillin by applying pulse radiolysis, chemical and biochemical oxygen demand, total organic carbon content, oxygen uptake rate, toxicity and antibacterial activity measurements. Oxacillin was found to be non-toxic, but poorly biodegradable by the mixed microbial population of the activated sludge of a wastewater treatment plant. Therefore, it can significantly contribute to the spread of ß-lactam antibiotic resistant bacteria. However, the products formed by γ-irradiation were more easily biodegradable as they were utilized as nutrient source by the microbes of the activated sludge and the products did not show antibacterial activity. During irradiation treatment of aerated aqueous solutions mainly hydroxyl radicals induce the elimination of antimicrobial activity by making alterations at the bicyclic ß-lactam part of these antibiotics. Since the ß-lactam part is the same in oxacillin and cloxacillin, the biochemical characteristics of products of the two antibiotics are similar. The attack of hydrated electron takes place on the carbonyl groups. When the irradiation is made under anoxic conditions these reactions may also contribute considerably to alterations at the ß-lactam part and thereby to the loss of antibacterial activity.

Multiplex polymerase chain reaction for detection of genes for Staphylococcus aureus thermonuclease and methicillin resistance and correlation with oxacillin resistance.

A multiplex polymerase chain reaction (mPCR) was used for simultaneous amplification of the staphylococcal nuc gene, encoding the thermostable nuclease (TNase), and the mecA gene, encoding the penicillin-binding protein 2a which is associated with staphylococcal methicillin resistance. A total of 219 staphylococcal strains were tested and the mPCR data were compared with coagulase production and in vitro oxacillin susceptibility. The agreement was 100% for coagulase production and nuc amplification, and 97.7%, 96.8 and 97.3% for mecA amplification and oxacillin resistance tested with MIC determination, disk diffusion and agar screen methods, respectively. Discrepant results were due to non-S. aureus isolates with borderline MICs of oxacillin (1-8 micrograms/ml). In a pilot test the mPCR simultaneously amplified both genes of staphylococci in blood cultures. This mPCR is a rapid and reliable method for single-step identification of cultures of MRSA and may prove to be useful for direct application on clinical specimens.

Detecting methicillin-resistant Staphylococcus epidermidis--disc diffusion, broth breakpoint or polymerase chain reaction?

Growth conditions are important for the expression of resistance to methicillin among staphylococci. Consequently a phenotypic susceptibility test has to be chosen carefully to avoid false susceptible results. In this study we wanted to devise rapid and simple phenotypic tests whose results completely correlate with the presence of the methicillin resistance gene, mecA. A simplified polymerase chain reaction (PCR) method not needing separate DNA extraction from the tested bacteria was used to amplify a 449 bp region of the mecA gene. One hundred and ten strains of S. epidermidis were tested. The results were in complete agreement with those from a broth tube breakpoint test, known to identify more strains as resistant than does the method recommended by NCCLS. In disc diffusion test it was possible to clearly distinguish resistant from susceptible strains by using discs containing oxacillin, cephalexin and cephradine. A 5 micrograms cephradine disc was further analysed by testing another 441 consecutive clinical isolates of staphylococci. All resistant coagulase-negative staphylococci grew out to the edge of this disc, whereas susceptible strains showed an inhibition zone at least 10 mm in diameter. The 5 micrograms cephradine disc is recommended for routine work. The PCR method and broth tube breakpoint test are both reliable reference methods.

[Effect of ampicillin and oxacillin on fetal and neonatal development]. / Vliianie ampitsillina i oksatsillina na razvitie ploda i novorozhdennogo v éksperimente.

Ampicillin administration during pregnancy exerted no toxic effect on the developing fetus. However, it decreased the body weight of the progeny and the weight of the placenta. Oxacillin had an adverse effect on the pregnancy, labor, fetus and newborn. It is inferred that ampicillin can be used for treatment purposes at any time of the pregnancy whilst oxacillin administration might involve a high risk for the mother, fetus and newborn.

Intravitreal oxacillin in experimental staphylococcal endophthalmitis.

We compared combined intravitreal and systemic oxacillin to combined subconjunctival and systemic oxacillin in the treatment of experimental staphylococcal endophthalmitis. Intravitreal injection of 500 mcg was nontoxic to all intraocular structures and produced concentrations in the vitreous bactericidal to all susceptible strains of Staphylococcus aureus for almost 24 hours. In eyes treated 8, 10, and 12 hours after intravitreal inoculation of 10000 to 20000 penicillinase-producing S. aureus organisms, intravitreal injection of 500 mcg of oxacillin was superior to subconjunctival injection of 100 mg when each was combined with seven days of intensive intramuscular oxacillin.

Cerebral toxicity of penicillins in relation to their hydrophobic character.

The neurotoxic effects of ticarcillin, methicillin, phenthicillin, oxacillin, cloxacillin and dicloxacillin were studied in the conscious rabbit. During and after intravenous administration of 1.2 and 2.4 g/kg, resp., over 50 min the blood concentrations of the drugs were determined and the neurotoxicity assessed by continuous recording of the electroencephalogram. The hydrophobia of the penicillins was characterized by determination of their partition coefficients between isobutanol and buffer solution pH 7.4. The penicillins showed quite different neurotoxic properties. A close correlation (r = 0.928) was found between the neurotoxic potency of the penicillins and their partition coefficients. With increasing hydrophobia the neurotoxic potency increased in the following sequence: Ticarcillin, methicillin, oxacillin, phenethicillin, cloxacillin, dicloxacillin. It can be concluded, therefore, that determination of the partition coefficient of a penicillin gives valuable information on the neurotoxicity to be expected. The introduction of a neurotoxicity quotient revealed that penicillins may be divided into two groups: less neurotoxic penicillins with a partition coefficient below 1.0 and highly neurotoxic penicillins with a partition coefficient above 1.0.