Sulbactam/ampicillin, a new beta-lactamase inhibitor/beta-lactam antibiotic combination

Sulbactam/ampicillin is a combination of a beta-lactamase inhibitor with minimal intrinsic antibacterial activity (sulbactam sodium), and an aminopenicillin (ampicillin sodium). The addition of sulbactam to ampicillin has no effect on the chemical stability of ampicillin in aqueous solution, and the administration guidelines of the combination are the same as for ampicillin alone. Sulbactam acts primarily by irreversible inactivation of beta-lactamases from most beta-lactamase-producing organisms. The pharmacokinetics of sulbactam are similar to those of ampicillin with an elimination half-life of about one hour in most patients. One difference is that serum and tissue concentrations of sulbactam are usually twice those of ampicillin, at equivalent doses. The sulbactam/ampicillin combination has been approved for the treatment of adults with intraabdominal, skin and skin structure, and gynecological infections due to beta-lactamase-producing bacteria such as Staphylococcus aureus, Escherichia coli, and species of Klebsiella and Bacteroides. Clinical studies to date have also shown the combination to be effective for the treatment of meningitis, pneumonia, gonorrhea, epiglottis, urinary tract infections, cervical adenitis, and as prophylaxis for abdominal and gynecological surgeries. Many of these studies, however, have included small numbers of patients and/or had design flaws. Adverse effects have been minor with most being attributed to the ampicillin component. Sulbactam/ampicillin compares favorably with other antibiotic regimens in terms of acquisition costs and ease of administration.     

Dopamine and dobutamine in pediatric therapy

Dopamine hydrochloride is widely used to increase blood pressure, cardiac output, urine output, and peripheral perfusion in neonates, infants, and older children with shock and cardiac failure. Its pharmacologic effects are dose dependent, and at low, intermediate, and high dosages include dilation of renal, mesenteric, and cerebral vasculature; inotropic response in the myocardium; and increases in peripheral and renal vascular resistance, respectively. The inotropic response is diminished in neonates compared with older children and adults due to maturational differences in norepinephrine stores. The clearance of dopamine varies widely in the pediatric population, depending on age. Its elimination half-life is approximately 2 minutes in full-term neonates and older children, and may be as long as 4-5 minutes in preterm infants. Due to immaturity of the autonomic nervous system, the drug may produce some adverse respiratory responses at high dose in neonates, the most common being tachycardia and cardiac arrhythmias. Dobutamine resembles dopamine chemically and is an analog of isoproterenol. It is relatively cardioselective at dosages used in clinical practice, with its main action being on beta 1-adrenergic receptors. Unlike dopamine, it does not have any effect on specific dopaminergic receptors. Dobutamine is used to increase cardiac output in infants and children with circulatory failure. Its elimination half-life is about 2 minutes in adults and older children. No information is available about its pharmacokinetics in neonates and infants. Adverse effects such as an increase in heart rate usually occur at high dosages.     

Pharmacologic management of patent ductus arteriosus

The incidence, pathophysiology, and clinical findings of symptomatic patent ductus arteriosus (PDA) are reviewed, and the pharmacologic management of symptomatic PDA is discussed. Spontaneous closure of the ductus arteriosus (DA) usually occurs within four days after birth in most premature and full-term infants. The incidence of PDA is related to birth weight in premature infants and has been shown to decrease with an increase in birth weight. Clinical findings are reviewed. Prophylactic treatment in the first few hours after birth may not be needed in most premature infants. Treatment should be considered only if the ductus becomes symptomatic. Medical management consists of respiratory support, fluid restriction, diuretics, digoxin, and indomethacin. Respiratory support, fluid restriction, and diuretics are used as first-line treatment of symptomatic PDA. Digoxin cannot be recommended as part of first-line therapy, since its risks seem to outweigh the benefits in preterm infants. Indomethacin should be used only if other standard measures including fluid restriction and diuretic treatment fail. The mechanism of action, pharmacokinetics, adverse effects, and drug interactions of indomethacin are discussed. Symptomatic PDA can increase morbidity and mortality, especially in very low birth weight infants. Treatment of symptomatic PDA may decrease the morbidity associated with this condition.     

Haemophilus influenzae type B conjugate vaccines.

OBJECTIVE: To review the epidemiology of Haemophilus influenzae type b (Hib) disease, the first Hib vaccine and its limitations, the characteristics and clinical efficacy of the newer conjugate vaccines, and the current recommendations for administration of Hib vaccines. DATA SOURCES: Pertinent literature was identified via a MEDLINE search. Additionally, references cited in published articles were used as data sources. STUDY SELECTION: Studies describing the epidemiology of Hib disease and the efficacy and/or immunogenicity of the Hib vaccines are reviewed. DATA SYNTHESIS: Serious invasive disease secondary to Hib infection causes significant morbidity and mortality in children between the ages of three months and five years. The original Hib vaccine was found to be ineffective in stimulating an adequate immune response in children younger than two years of age. The new Hib conjugate vaccines provide superior efficacy and immunogenicity compared with the original unconjugated vaccine. They stimulate an immune response that is distinctly different from that elicited by the original vaccine. Two vaccine products are currently licensed for use in children as young as two months of age, thus conferring immunity to those children at highest risk for Hib disease. CONCLUSIONS: The new Hib conjugate vaccines provide excellent efficacy and, when used as recommended, may significantly reduce the incidence of invasive Hib disease and its sequelae.     

Treatment of irritable bowel syndrome

What is known and Objective: The complexity and diversity of irritable bowel syndrome’s (IBS) presentation make treatment difficult. Although there are reviews and guidelines for treating IBS, they focus on the efficacy of medications for IBS symptoms using high‐priority endpoints, leaving those of lower priority largely unreported. Therefore, the aim of this review is to provide a comprehensive evidence‐based review of the efficacy of medications to treat IBS symptoms, reported by IBS subtype, including secondary symptom endpoints that are often underreported. Methods: A review of PubMed for articles published through December 2009 using the keywords: ‘irritable bowel syndrome’, ‘therapeutics’, ‘antidiarrhoeals’, ‘laxatives’, ‘loperamide’, ‘dietary fibre’, ‘psyllium’, ‘calcium polycarbophil’, ‘bulking agents’, ‘lubiprostone’, ‘antidepressant agents, tricyclics’ and its representative entities, ‘serotonin reuptake inhibitors’ and its representative entities, ‘dicyclomine’, hyoscyamine’, ‘peppermint oil’, ‘parasympatholytics’ and its representative entities, ‘rifaximin’, ‘pregabalin’, ‘gabapentin’, ‘clonidine’, ‘octreotide’, ‘atropine’ and ‘probiotics’ is provided. Placebo‐controlled trials were evaluated for the strength of evidence supporting the efficacy of each medication for explicit IBS symptoms. The efficacy of each medication for the symptoms of abdominal pain, bloating, stool form, mucus, urgency, feeling of incomplete evacuation, flatulence, frequency, or borborgymi and overall symptoms are reported by IBS subtype. Results and Discussion: The literature search identified 58 placebo‐controlled trials of the efficacy of medications for treating IBS symptoms, which were critically evaluated and reported. The available studies suggest improvement in various IBS symptoms with loperamide, fibre supplements, lubiprostone, tricyclic antidepressants (TCAs), selective serotonin receptor inhibitors (SSRIs), antispasmotics, rifaximin, pregabalin, gabapentin, clonidine, octreotide and probiotic treatments. What is new and Conclusion: This review is the first to compile the available evidence on the efficacy of the various pharmacological treatments for IBS on the basis of IBS subtype and specific symptoms. This evidence is limited and more well‐designed studies are required to better inform therapeutic decision‐making in the management of this difficult syndrome.     

Decreased motility of the lower esophageal sphincter in a rat model of gastroesophageal reflux disease may be mediated by reductions of serotonin and acetylcholine signaling

To elucidate the altered function of the lower esophageal sphincter (LES) in gastroesophageal reflux disease (GERD), we evaluated the motility proximal to LES using force transducers, contraction and relaxation responses to neurotransmitters in LES strips, and gene expression of neurotransmitter receptors in GERD rats. Force transducers were applied to the proximal LES, and contraction of the LES was monitored during free moving. In addition, LES was isolated from sham-operated and GERD rats to investigate the LES function in an organ bath, and to determine gene expression. The in vivo motility proximal to LES (% motility index) in conscious rats was decreased by atropine treatment and increased by cisapride (5-HT(4) receptor agonist) treatment. Acetylcholine- and serotonin (5-HT)-induced LES contraction and sodium nitroprusside-induced relaxation in LES strips of GERD rats markedly decreased compared to sham-operated rats. The mRNA expressions of 5-HT(4) and muscarinic acetylcholine 3 receptors were significantly reduced in esophageal LES strips of GERD rats compared with sham-operated rats. Intraperitoneal administration of cisapride improves the erosive damage in the esophagus in GERD rats. It is suggested that the reduction of 5-HT-induced contraction in LES strips in GERD rats may be partly due to the decrease in 5-HT(4)-receptor activation. The reduction of LES function may be due to the decrease in neurotransmitters signal transduction, leading to the deterioration of histopathological damage in GERD.     

Atomoxetine hydrochloride for the treatment of attention-deficit/hyperactivity disorder

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) occurs in approximately 3% to 10% of the pediatric population. Most of the drugs typically used to treat ADHD are stimulants, which, because of their addictive properties and potential for abuse, are controlled substances. Although these drugs are the mainstay of treatment for ADHD, nearly one third of patients may not respond to or be able to tolerate them. Atomoxetine hydrochloride, a nonstimulant approved by the US Food and Drug Administration for the treatment of ADHD, may provide an alternative to the use of stimulants. OBJECTIVE: The goal of this review was to describe the chemistry, mechanism of action, pharmacokinetics, drug interactions, and efficacy and safety profiles of atomoxetine in pediatric and adult patients with ADHD, as well as relevant pharmacoeconomic considerations. METHODS: Relevant publications were identified through a search of the English-language literature indexed on PreMEDLINE and MEDLINE (1966-May 2003) using the search terms atomoxetine, tomoxetine, and LY139603. These terms were also applied to the Google search engine. All articles were reviewed for suitability for inclusion. The manufacturer of atomoxetine provided both published and unpublished data. RESULTS: In the data reviewed, atomoxetine was more efficacious than placebo in patients with ADHD (P<0.05 to P<0.01). Therapeutic doses ranged from 45 mg or placebo (P<0.05). These results add support to the hypothesis that atomoxetine may not cause the increase in dopamine concentrations in the nucleus accumbens that is associated with pleasurable effects and abuse potential.     

Influence of infusion methods on therapeutic drug monitoring in pediatric patients

The purpose of this article is to emphasize the importance of infusion method on therapeutic drug monitoring in pediatric patients. Although effective serum concentrations are anticipated after intravenous infusion of drugs, studies with chloramphenicol and tobramycin have shown that the infusion method can have a profound influence on peak serum concentration and time to achieve peak concentration during therapy. Factors including infusion rate, injection site, volume of drug and fluid to be infused in the tubing, and type of infusion system should be considered for accurate drug delivery. Specific guidelines for drug infusions should be available at each institution. Since serum concentration predictions are based on the dose infused and infusion time, meaningful therapeutic monitoring data can be generated only with the understanding of the influence of infusion method on serum concentration-time profile of drugs.