The neonate is pharmacologically & physiologically distinctive, a fact that is most often overlooked when physicians prescribe antimicrobial drug therapy during the neonatal period.
As young infants are especially more receptive to staphylococcal infection, information concerning the effectiveness of oxacillin in treating such infections and the pharmacology of oxacillin sodium in such patients is highly required.
Moreover, over a past decade, the growing incidence of infections induced by multidrug-resistant Gram-positive bacteria, particularly staphylococci, pneumococci and enterococci, along with the spread of methicillin-resistant Staphylococcus aureus (MRSA) have instigated the development of new antibacterial drugs.
That said, Pharmacology, safety, clinical efficacy, and tolerability must be described for every drug prior to use in neonates and young infants — says Gian Maria Pacifici (Associate Professor of Pharmacology, Italy). Therefore the researcher reviewed the rrecommendations for dosage and frequency of administration for the most commonly used antibiotics named ‘OXACILLIN’ in newborns. These dosage schedules have been based on pharmacokinetic data and proved to be sound and safe in the treatment of neonatal bacterial infections.
The study conducted by Gian Maria provides information regarding 1.) The efficacy of the drug (OXACILLIN) as a therapy for severe staphylococcal infection in this age group (newborn and young children); 2.) The toxicity profile of the drug in neonates and in older infants ; 3.) The serum concentrations of oxacillin sodium obtained with differing dosage schedules in young infants.
The researcher conducted a multi center study wherein all infants receiving antibiotics were carefully examined for potency and possible toxic effects due to OXACILLIN. OXACILLIN SODIUM is a penicillin antibiotic which is used to treat certain kinds of bacterial infections. However it does not work for flu, colds, or other viral infections.
OXACILLIN has been indicated to effectively curb penicillin-sensitive and staphylococci resistant in vitro at concentrations readily achievable in vivo1 and together with other similar penicillinase-resistant penicillins, is regarded a drug of choice in staphylococcal infection.
Hypersensitivity reaction with renal tubular damage and interstitial nephritis has been reported occasionally along with rash, proteinuria, hematuria, eosinophilia, and renal insufficiency with the use of oxacillin. The reaction though generally relapses with termination of the drug. The researcher suggests to first assessing patients presenting with eosinophilia for likely drug-induced liver or kidney injury.
Moreover Gian Maria observed that though penicillin allergy has been delineated in up to 20% of patients in general population, up to 90% of those patients lack penicillin-particulate IgE antibodies and can safely accept the antibiotic. She advises on careful assessment of patients who report a true allergy to penicillin allergy since they may be at a greater risk for severe reactions upon re-exposure to a drug in the penicillin segment, such as oxacillin.
Oxacillin is a substitute treatment of choice for Coagulase-negative staphylococci infections; though, resistance to oxacillin can have a considerable effect on wellness by detrimentally affecting morbidity and mortality.
Newborns hospitalized at the neonatal ward of the University Hospital of the Faculty of Medicine of Botucatu were detected and defined with oxacillin-resistance Coagulase-negative staphylococci strains in blood cultures. A 100 of Coagulase-negative staphylococci strains when secluded led to detection of mecA gene in 69 of the Coagulase-negative staphylococci strains, including 85.7% of Staphylococcus haemolyticus strains, 73.2% of Staphylococcus epidermis strains, 50% of Staphylococcus lugdunensis strains and 28.6% of Staphylococcus hominis strains.
Additionally, an uppermost SCCmec profile of oxacillin-resistant Coagulase-negative Staphylococcus strains secluded from neonatal intensive care units was determined with a prevalence of SCCmec types found in hospital-obtained strains.
Furthermore, two infants reported to have developed watery diarrhea with blood-tinged strains when isolated the Clostridium difficile from the feces. One infant who had developed diarrhea after 5 days of parenteral oxacillin therapy reported to have relieved of diarrhea within 3 days of discontinuation of therapy. The other infant suffered diarrhea within next 4 days of oral dicloxacillin; the diarrhoea weakened within 2 days of discontinuation of therapy. During that time there were no traces of Clostridium difficile found in the stools of infants. Tissue culture assay presented the presence of preformed faecal toxin and displayed the toxigenicity of faecal seclusion of Clostridium difficile and reference strains.
These findings from the researcher’s review denote that Clostridium difficile may play a critical role in diarrhea linked with oxacillin and dicloxacillin in children.
Professor Gian Maria suggests that Oxacillin being penicillin should not be used in patients with penicillin hypersensitivity. Furthernore, Oxacillin should be prescribed cautiously in patients with cephalosporin hypersensitivity or carbapenem hypersensitivity because its structural similarity to the carbapenems and cephalosporins is capable of causing these patients to be more vulnerable to hypersensitivity reactions. Patients with allergies or allergic conditions including hay fever, hives, asthma, or, eczema may be positioned at a higher risk for hypersensitivity reactions to penicillins — stated Gian Maria.
The researcher through her review speaks confidently of oxacillin being significantly resistant to hydrolysis by staphylococcal penicillinase. Talking about the appropriate use of the penicillinase resistant isoxazolyl, professor Gian advices that penicillin should be confined to the treatment of infections that are known or supposed to be caused by staphylococci that adorn penicillinase.
The FDA-approved dosage of oxacillin is 25 mg/kg per dose IV or IM for mild to moderate infections. For meningitis, it is 50 mg/kg. Bloodstream infections are the most common and recurring nosocomial infections in neonatal intensive care units. The researcher displays that Oral administration of oxacillin is not an alternate for the parenteral route in the treatment of severe staphylococcal infections. Oxacillin helps in hampering the synthesis of bacterial cell wall, and is a powerful inhibitor of the growth of most penicillinase-producing staphylococci. It is mainly discharged unaltered in the urine, and has a good penetration in the pericardial, pleural, and synovial fluids.
After a single IM oxacillin dose of 20 mg/kg, the mean serum half-life of oxacillin is found to be 1.2 hours in 2 prematures aged 20 to 21 days and 1.6 hours in 8 premature infants aged 8 to 15 days (gestational age not reported). Using data from Infants and Children, A mean elimination half-life of 1.3 hours was reported from a small trial in 5 children (ages 7days to 2 years) receiving 25 mg/kg/dose IM every 6 hours.
The researcher concludes that relative immaturity of the pediatric patient and an ongoing state of development of body and organ functions regulates both drug absorption and drug disposition. The Daily dosage needs differ with age and weight. For many drugs, children require and accept much more of a drug, respective to their size, or weight for the same effect. She further submits that Newborns may require more or less of a drug for a relative effect.
This review provided a conceptual framework aiding in understanding the individuality of the pediatric patient's drug disposition processes based on variations in physiologic functions influencing drug absorption, distribution, and excretion.
Additional data is however required on drug disposition in children of all ages to maximize therapeutic drug usage with outright avoidance of toxicity.
Full Article link: http://www.oasispub.org/clinical-pharmacology-of-oxacillin-in-infants-and-children/
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